Vitamin A Supplementation at Birth Might Prime the Response to Subsequent Vitamin A Supplements in Girls. Three Year Follow-Up of a Randomized Trial Tolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal. Safety of one 52-mumol (50,000 IU) oral dose of vitamin A administered to neonates. Childhood mortality after a high dose of vitamin A in a high risk population. Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial Integration of vitamin A supplementation with the Expanded Programme on Immunization: lack of impact on morbidity or infant growth Vitamin A and E Supplementation in Breast-Fed Newborns Mortality of infants < 6 mo of age supplemented with vitamin A: a randomized, double-masked trial in Nepal. Maternal vitamin A or beta-carotene supplementation in lactating bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency. Vitamin a supplementation does not affect infants' immune responses to polio and tetanus vaccines. Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal. Acute respiratory infections prevent improvement of vitamin A status in young infants supplemented with vitamin A. Vitamin A supplementation at birth delays pneumococcal colonization in South Indian infants. Effect of postpartum maternal or neonatal vitamin A supplementation on infant mortality among infants born to HIV-negative mothers in Zimbabwe. Simultaneous vitamin A administration at routine immunization contact enhances antibody response to diphtheria vaccine in infants younger than six months. Effect of early vitamin A supplementation on cell-mediated immunity in infants younger than 6 mo. Effect of maternal and neonatal vitamin A supplementation and other postnatal factors on anemia in Zimbabwean infants: a prospective, randomized study. High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant. Maternal night blindness increases risk of mortality in the first 6 months of life among infants in Nepal. Vitamin A supplementation enhances infants' immune responses to hepatitis B vaccine but does not affect responses to Haemophilus influenzae type b vaccine. Vitamin A supplementation of women postpartum and of their infants at immunization alters breast milk retinol and infant vitamin A status. Trends and mortality effects of vitamin A deficiency in children in 138 low-income and middle-income countries between 1991 and 2013: a pooled analysis of population-based surveys. Newborn vitamin A dosing reduces the case fatality but not incidence of common childhood morbidities in South India. Impact of a single megadose of vitamin A at delivery on breastmilk of mothers and morbidity of their infants A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol Effect of vitamin A administered at Expanded Program on Immunization contacts on antibody response to oral polio vaccine Vitamin A supplements are well tolerated with the pentavalent vaccine. The effects of maternal and infant vitamin A supplementation on vitamin A status: a randomised trial in Kenya. The effect of neonatal vitamin A supplementation on growth in the first year of life among low-birth-weight infants in Guinea-Bissau: two by two factorial randomised controlled trial Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania Neonatal vitamin A supplementation associated with a cluster of deaths and poor early growth in a randomised trial among low-birth-weight boys of vitamin A versus oral polio vaccine at birth Impact of supplementing newborn infants with vitamin A on early infant mortality: community based randomised trial in southern India Malaria Parasitaemia among Infants and Its Association with Breastfeeding Peer Counselling and Vitamin A Supplementation: A Secondary Analysis of a Cluster Randomized Trial Single megadose vitamin A supplementation of Indian mothers and morbidity in breastfed young infants Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi. Bulging fontanelle after supplementation with 25 000 IU of vitamin A in infancy using immunization contacts Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children. Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality. Effectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial No adverse events after simultaneous administration of 50 000 IU vitamin A and Bacille Calmette-Guerin vaccination to normal-birth-weight newborns in Guinea-Bissau Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial. [Impact on colostrum retinol levels of immediate postpartum supplementation with retinyl palmitate]. Effect on Infant Illness of Maternal Supplementation With 400 000 IU Vs 200 000 IU of Vitamin A Effect of vitamin A supplementation to mother and infant on morbidity in infancy. Effect of administration of 200,000 IU of vitamin A to women within 24 hrs after delivery on response to PPV administered to the newborn. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial Newborn Vitamin A Supplementation Reduced Infant Mortality in Rural Bangladesh Breast-feeding initiation time and neonatal mortality risk among newborns in South India Impact of neonatal vitamin A supplementation on infant morbidity and mortality. Enhancement in seroconversion to measles vaccine with simultaneous administration of vitamin A in 9-months-old Indian infants Randomised double-blind trial of the effect of vitamin A supplementation of Indonesian pregnant women on morbidity and growth of their infants during the first year of life Effect of vitamin A supplementation on measles vaccination in nine-month-old infants. Acute toxicity of vitamin A given with vaccines in infancy Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality No strong long-term effect of vitamin A supplementation in infancy on CD4 and CD8 T-cell subsets. A community study from Guinea-Bissau, West Africa Administration of 25,000 IU vitamin A doses at routine immunisation in young infants. Vitamin a status of pregnant women and effect of post partum vitamin a supplementation. Newborn vitamin A supplementation does not affect nasopharyngeal carriage of Streptococcus pneumoniae in Bangladeshi infants at age 3 months. Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group. The effect of high-dose vitamin A supplementation given with bacille Calmette-Guérin vaccine at birth on infant rotavirus infection and diarrhea: a randomized prospective study from Guinea-Bissau. The effect of newborn vitamin A supplementation on infant immune functions: trial design, interventions, and baseline data. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children
Objectives Within a r and omised trial of neonatal vitamin A supplementation ( VAS ) in Guinea-Bissau , neonatal VAS did not affect overall  infant mortality . We conducted a post-hoc analysis to test the hypothesis that neonatal VAS primes the response to subsequent vitamin A. Methods All trial children were offered VAS after follow-up ended at 1 year of age ( FU-VAS ) . We compared mortality between 1 and 3 years of age according to initial r and omization to neonatal VAS or placebo in Cox-regression models ; we expected that children r and omized to neonatal VAS compared with those r and omized to placebo would have lower mortality after reception of FU-VAS . Results Of 4345 infants enrolled in the original trial , 3646 lived in the study area at 1 year of age and 2958 received FU-VAS .  Between 1 and 3 years of age , 112 children died . After FU-VAS , neonatal VAS was associated with lower mortality than placebo : Mortality Rate Ratio ( MRR ) = 0.54 ( 95%CI : 0.31–0.94 ) . The effect was more pronounced in girls ( MRR = 0.37 ( 0.16–0.89 ) ) than boys ( MRR = 0.73 ( 0.35–1.51 ) ) . The beneficial effect of neonatal VAS may have been particularly strong for girls who received both VAS in a campaign and FU-VAS ( MRR = 0.15 ( 0.03–0.67 ) ) . Among children who had not received FU-VAS , mortality in the second and third year of life did not differ according to reception of neonatal VAS or placebo . Hence , in the second and third year of life the effect of neonatal VAS versus placebo was different in girls who had or had not received FU-VAS ( p for homogeneity = 0.01 ) . Conclusions The present results suggest that neonatal VAS primes the response in girls such that they get a beneficial effect after a subsequent dose of VAS . Trial Registration Clinical trials.gov A r and omized , double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age ) and infants aged 1 - 6 months who received a large , oral dose of vitamin A ( 15,000 retinol equivalents ( RE ) ( 50,000 IU ) and 30,000 RE ( 100,000 IU ) , respectively ) or placebo ( 75 RE ( 250 IU ) and 150 RE ( 500 IU ) , respectively ) in oil . Infants ( vitamin A group , n = 1461 ; controls , n = 1379 ) were assessed for vomiting , loose stools , fever , and irritability during the 24 hours before and after dosing . Fontanelles were palpated 24 hours after dosing . Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE . Compared with controls the older infants who ingested 30,000 RE had a 1.6 % excess rate of vomiting ( 95 % confidence interval ( CI ) : 0.2 - 3.0 % ) and a 0.5 % excess rate ( 95 % CI : -0.1 to 1.1 % ) in the occurrence of bulging fontanelles . There were no other significant differences in the older infants . The controlled , periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants ; a 30,000 RE dose is associated with a minimum risk of transient , acute side-effects A placebo-controlled trial was carried out among 2067 Indonesian neonates to assess the safety of administering one oral 52-mumol ( 50,000 IU ) dose of vitamin A.  Infants were assessed for potential acute side-effects before and throughout 48 hours after the dose . The first 965 infants were examined by cranial ultrasound before and at 24 hours after dosing to rule out intracranial haemorrhage and determine the resistive index ( RI ) of the anterior cerebral artery using duplex Doppler . Groups were comparable at the baseline . A bulging fontanelle occurred in the control and vitamin A groups , respectively , among 2.7 % and 4.6 % of the infants at 24 hours , and 2.4 % and 4.5 % of the infants at 48 hours . The groups did not differ in any other sign or symptom assessed . No infant developed intracranial haemorrhage . Mean RI values were normal and not different between groups at baseline or at 24 hours . Mean RI fell during the 24 hours , as normally occurs ; the mean decrease was nearly identical in the two groups . A bulging fontanelle was not associated with increased rates of any sign or symptom or with an increase in RI . The 52-mumol dose of oral vitamin A may cause a small increase in intracranial volume in a small proportion of infants , but no increase in intracranial pressure . Acute side-effects following this intervention were rare and mild OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation .  MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality . Design R and omised placebo controlled trial . Setting B and i m Health Project ’s demographic surveillance system in Guinea-Bissau , covering approximately 90 000 inhabitants . Participants 4345 infants due to receive BCG . Intervention Infants were r and omised to 50 000 IU vitamin A or placebo and followed until age 12 months . Main outcome measure Mortality rate ratios . Results 174 children  died during follow-up ( mortality=47/1000 person-years ) . Vitamin A supplementation was not significantly associated with mortality ; the mortality rate ratio was 1.07 ( 95 % confidence interval 0.79 to 1.44 ) . The effect was 1.00 ( 0.65 to 1.56 ) during the first four months and 1.13 ( 0.75 to 1.68 ) from 4 to 12 months of age . The mortality rate ratio in boys was 0.84 ( 0.55 to 1.27 ) compared with 1.39 ( 0.90 to 2.14 ) in girls ( P for interaction=0.10 ) . An explorative analysis revealed a strong interaction between vitamin A and season of administration . Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting . Although little doubt exists that vitamin A supplementation reduces mortality in older children , a global recommendation of supplementation for all newborn infants may not contribute to better survival . Trial registration Clinical trials NCT00168597 Vitamin A deficiency is associated with increased morbidity and mortality from diarrheal disease , measles , and malaria . It has been proposed that vitamin A supplementation could be linked with childhood immunization programs to improve child health . We conducted a r and omized , double‐blind , placebo‐controlled clinical trial to evaluate the impact of linking vitamin A supplementation with the Exp and ed Programme on Immunization on morbidity and child growth .  In West Java , Indonesia , 467 six‐week‐old infants were r and omized to receive 7.5 mg retinol equivalent ( RE ) , 15 mg RE , or placebo with childhood immunization contacts at 6 , 10 , and 14 wks and 9 mo of age . Child growth was assessed through anthropometry , and morbidity histories were obtained . Vitamin A supplementation had no apparent impact upon linear or ponderal growth or infectious disease morbidity in the first 15 mo of age when integrated with the Exp and ed Programme on Immunization Background Vitamins A and E are two potent antioxidant nutrients that play a significant role in immune function . In contrast to the numerous studies of vitamin A and E status in children , adolescents , and adults , information on term infants , particularly breast-fed infants , is scarce . The goals of the present investigation were to examine the vitamins A and E nutritional status of term breast-fed infants at birth and to assess retinol and tocopherol plasma levels during a 3-month supplementation trial . Methods The study was a prospect i ve , blinded comparison of a supplementation protocol with a placebo in a group of consecutively recruited term newborns . The supplemented group received 3000 IU vitamin A and 5 IU vitamin E orally . The placebo group received a solution of similar viscosity and organoleptic characteristics . Vitamin A and E were separated by reverse-phase high-performance liquid chromatography on a C18 Spectrasyl column and quantified by ultraviolet spectrophotometry . Results Vitamin A and E levels steadily increased with age in both groups of infants . However , levels at 3 months were higher in the supplemented than in the control group . Conclusion The data show that supplementation with 3000 IU vitamin A and 5 IU vitamin E for 3 months increases circulating vitamin levels in newborn term babies compared with those in nonsupplemented infants The effect of supplementing 11,918 infants < 1 mo and 1 - 5 mo of age with vitamin A ( 15,000 and 30,000 micrograms retinol equivalents or 50,000 and 100,000 IU , respectively ) or a placebo on subsequent 4-mo mortality was assessed in a r and omized , double-masked community trial in the rural plains of Nepal . There were 130 deaths ( 51.6/1000 child-y ) in the control group and 150 deaths ( 57.1/1000 child-y ) in the vitamin A group , yielding a relative risk of 1.11 ( 95 % CI : 0.86 , 1.42 ) , which is indicative of no overall effect on early infant mortality . There was a tendency for the relative risk of mortality among vitamin A recipients to rise with improved nutritional status . These results suggest that distribution of a large oral dose of vitamin A to infants < 5 - 6 mo of age may not benefit short-term survival . This is in contrast with the results of trials in which older infants and children in this same population were supplemented The effects of maternal postpartum vitamin A or beta-carotene supplementation  on  maternal and infant serum retinol concentrations , modified relative dose-response ( MRDR ) ratios and breast milk vitamin A concentrations were assessed during a community-based trial in Matlab , Bangladesh . At 1 - 3 wk postpartum , women were r and omly assigned to receive either ( 1 ) a single dose of 200,000 international units [ 60,000 retinol equivalents ( RE ) ] vitamin A followed by daily placebos ( n = 74 ) , ( 2 ) daily doses of beta-carotene [ 7.8 mg ( 1300 RE ) ] ( n = 73 ) or ( 3 ) daily placebos ( n = 73 ) until 9 mo postpartum . Compared to placebos , vitamin A supplementation result ed in lower maternal MRDR ratios ( i.e. , increased liver stores ) and higher milk vitamin A concentrations at 3 mo , but these improvements were not sustained . The beta-carotene supplementation acted more slowly , result ing in milk vitamin A concentrations higher than the placebo group only at 9 mo . Irrespective of treatment group , over 50 % of women produced milk with low vitamin A concentrations ( < /=1.05 micromol/L or < /=0.28 micromol/g fat ) throughout the study . Overall , mean maternal serum retinol concentrations were not affected by supplementation . Compared to the placebo group , the mean MRDR ratio of 6-mo-old infants was higher in the vitamin A group . Infants ( 33 % ) had serum retinol concentrations < 0.70 micromol/L and 88 % had MRDR ratios > /=0 . 06 . We conclude that while both interventions were beneficial , neither was sufficient to correct the underlying sub clinical vitamin A deficiency in these women nor to bring their infants into adequate vitamin A status It has been suggested that administering vitamin A with the measles vaccine may reduce the vaccine 's immunogenicity . This trial examined the effect of supplementing vitamin A during the early months of life on infants '  immune responses to tetanus and polio vaccines . Young infants ( n = 1085 ) were enrolled and individually r and omized into 1 of 4 groups in a factorial , double-blind , placebo-controlled trial . Three vitamin A supplementation strategies were investigated : 1 ) supplementation of breast-feeding mothers with 60 mg retinol equivalent ( RE ) vitamin A within 4 wk of delivery ; 2 ) Exp and ed Program on Immunization (EPI)-linked supplementation of infants with 7.5 mg RE vitamin A at 6 , 10 , and 14 wk ; and 3 ) combined mother and child supplementations . A 4th group in which mother and child were given placebos served as controls . Blood sample s were collected from each child at 6 wk and 6 mo of age to measure antipolio antibody titer , antitetanus toxoid antibodies , and avidity of antibodies to tetanus . Of the infants r and omized into the 4 arms of the study , 767 ( 71 % ) completed follow-up at 6 mo of age . Follow-up rates were similar in all 4 arms ( 69 - 72 % , P = 0.8 ) . Antibody titers were relatively high in all 4 groups at both 6 wk and 6 mo of age , with no differences among the groups . We found no evidence that vitamin A supplementation affects infants '  antibody responses to tetanus toxoid or oral polio vaccine delivered at EPI contacts BACKGROUND The effect of vitamin A supplementation on the survival of infants aged < 6 mo  is unclear . Because most infant deaths occur in the first few month of life , maternal supplementation may improve infant survival . OBJECTIVES The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants < 6 mo of age . DESIGN Married women of reproductive age in 270 wards of Sarlahi district , Nepal , were eligible to participate . Wards were r and omly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate ( vitamin A ) , 42 mg all-trans-beta-carotene , or placebo . Pregnancies were followed until miscarriage , stillbirth , maternal death , or live birth of one or more infants , who were followed through 24 wk of age . RESULTS A total of 43559 women were enrolled ; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial . The rate of fetal loss was 92.0/1000 pregnancies in the placebo group , comparable with rates in the vitamin A and beta-carotene groups , which had relative risks of 1.06 ( 95 % CI : 0.91 , 1.25 ) and 1.03 ( 95 % CI : 0.87 , 1.19 ) , respectively . The 24-wk mortality rate was 70.8/1000 live births in the placebo group , comparable with rates in the vitamin A and beta-carotene groups , which had relative risks of 1.05 ( 95 % CI : 0.87 , 1.25 ) and 1.03 ( 95 % CI : 0.86 , 1.22 ) , respectively . CONCLUSIONS Small weekly doses of vitamin A or beta-carotene given to women before conception , during pregnancy , and through 24 wk postpartum did not improve fetal or early infant survival in Nepal At immunization contact , 165 infants 2.5 mo old were r and omly assigned to receive either 15 mg vitamin A ( retinyl palmitate ) or placebo . Three doses were given at monthly intervals with each diphtheria , pertussis , tetanus and oral polio ( DPT/OPV ) immunization dose . The diarrhea and acute respiratory infection ( ARI ) morbidity was similar in the vitamin A and placebo groups . However , the duration ( days per child-year , mean + /- SD ) of ARI was less in the vitamin A group compared with placebo group ( 27.6 + /- 17.1 vs. 40.8 + /- 22.7 ; P = 0.005 ) . Fasting retinol concentrations were measured at entry and in 61 infants , the relative dose response ( RDR ) test was done 1 mo after the third dose of vitamin A. Eighty-five percent of the infants had serum retinol concentration < 0.70 mol/L at entry . After 3 mo the serum retinol levels improved significantly in both groups , and in the vitamin A-supplemented group the serum retinol concentration was significantly better than that in the placebo group ( P= 0.02 ) . However , 61 % of the infants remained deficient despite vitamin A supplementation . Among vitamin A-supplemented infants only , diarrhea and ARI morbidity during the 3-mo period were compared in children with normal versus children with abnormal RDR at the end of the supplementation period . The ARI episodes were more frequent in the supplemented infants who remained vitamin A deficient at the end of the 3 mo ( P = 0.027 ) . Also , the cumulative duration ( days , mean + /- SD ) of fever and cough was 5.0 + /- 2.8 in the normal versus 11.2 + /- 6.0 in the deficient group ( P = 0.04 ) . The results of this study suggest that a large proportion of infants remain vitamin A deficient even after large dose vitamin A supplementation because of frequent respiratory infections , particularly those accompanied by fever Nasopharyngeal colonization is a risk factor for pneumococcal disease , a leading cause of complications and death in infants . We assessed the impact of vitamin A supplementation in reducing pneumococcal colonization in infants from an area with endemic vitamin A deficiency . We recruited 464 2-mo-old infants from a rural area in South India . Infants were r and omly assigned to receive two 7000-microg retinol equivalent doses of vitamin A ( n = 239 ) or placebo ( n = 225 ) orally at birth , and nasopharyngeal specimens were collected at ages 2 , 4 and 6 mo . We studied the effect of vitamin A on culture-confirmed pneumococcal colonization and on the distribution of pneumococcal serotypes . Analyses were conducted by intention-to-treat . The risk of colonization among infants aged 4 mo who were not colonized by age 2 mo was significantly reduced in the vitamin A group compared with the placebo group [ odds ratio 0.51 ( 0.28 , 0.92 ) , P = 0.02 ) . The odds of colonization were 27 % lower in the treatment group than in the placebo group [ odds ratio 0.73 ( 0.48 , 1.1 ) , P = 0.13 ] . No differences were detected in the prevalence of invasive serotypes . The risk of colonization with penicillin-resistant isolates was 74 % lower in the vitamin A group than in the placebo group at 2 mo of age . However , the prevalence of penicillin-resistant isolates was only 4 % . Neonatal vitamin A supplementation may play a role in lowering morbidity rates associated with pneumococcal disease by delaying the age at which colonization occurs BACKGROUND Young infants are at risk of vitamin A deficiency . Supplementation of breastfeeding mothers improves the vitamin A status of their infants , but there are no data regarding its effect on infant mortality , and data on the effect of directly supplementing infants during the first few weeks of life are conflicting . OBJECTIVE The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single , large doses of vitamin A during the immediate postpartum period . DESIGN A r and omized , placebo-controlled , 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants ; 9208 of the mothers were HIV-negative at delivery , remained such during the postpartum year , and were retained in the current analysis . The infants were r and omly assigned within 96 h of delivery to 1 of 4 treatment groups : mothers and infants received vitamin A ( Aa ) , mothers received vitamin A and infants received placebo ( Ap ) , mothers received placebo and infants received vitamin A ( Pa ) , and both mothers and infants received placebo ( Pp ) . The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU . The mother-infant pairs were followed to 12 mo . RESULTS Hazard ratios ( 95 % CI ) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 ( 0.87 , 1.58 ) and 1.08 ( 0.80 , 1.46 ) , respectively . Hazard ratios ( 95 % CI ) for the Aa , Ap , and Pa groups compared with the Pp group were 1.28 ( 0.83 , 1.98 ) , 1.27 ( 0.82 , 1.97 ) , and 1.18 ( 0.76 , 1.83 ) , respectively . These data indicate no overall effect . Serum retinol concentrations among a sub sample of women were similar to reference norms . CONCLUSION Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women with an apparently adequate vitamin A status A r and omized , double-blind , placebo-controlled trial was conducted to evaluate the effect of simultaneous vitamin A supplementation and diphtheria , pertussis and tetanus ( DPT ) vaccination on the antibody levels .  Infants aged 6 - 17 wk ( n = 56 ) were r and omly given 15 mg oral vitamin A or placebo at the time of their DPT immunization . Three such doses were given at monthly intervals . Immunoglobulin ( Ig ) G antibodies to diphtheria , pertussis and tetanus were assayed on enrollment and 1 mo after the third dose . Baseline antibody concentrations to diphtheria , pertussis and tetanus did not differ between the vitamin A-supplemented and placebo-treated groups . The postdose antibody to diphtheria level was significantly greater in the vitamin A than in the placebo-treated group . The geometric mean + /- SEM antibody levels ( mg/L ) were 22.9 + /- 1.2 and 11.0 + /- 1.3 in the vitamin A and placebo groups , respectively ( P = 0.029 ) . The postsupplementation concentrations of antibodies to pertussis and tetanus did not differ between the two groups . These results suggest that antibody response to diphtheria vaccination was potentiated by simultaneous vitamin A administration and DPT immunization One hundred twenty infants were r and omly assigned to receive either 15 mg vitamin A or placebo with each of three DPT/OPV ( diphtheria , pertussis , tetanus/oral polio vaccine ) immunizations at monthly intervals . Sixty-two received vitamin A and 58 received placebo . One month after the third supplementation dose , the response to the delayed cutaneous hypersensitivity test [ multitest cell-mediated immunity ( CMI ) skin evaluation ] for tetanus , diphtheria , and tuberculin ( purified protein derivative , PPD ) was the same in the vitamin A and placebo infants . The number of anergic infants was 17 ( 27 % ) and 19 ( 33 % ) in the vitamin A and placebo groups , respectively . The number of positive tests among well-nourished infants was significantly higher than that in malnourished infants irrespective of supplementation ( P < 0.001 ) . Among the infants with adequate serum retinol concentrations ( > 0.7 mumol/L ) after supplementation , the vitamin A-supplemented infants had a significantly higher proportion of positive CMI tests than the placebo infants ( chi-square test : 8.99 , P = 0.008 ) . Among the infants with low serum retinol concentrations ( < 0.7 mumol/L ) after supplementation , vitamin A supplementation had no effect on CMI response . These results indicate that CMI in young infants was positively affected by vitamin A supplementation only in those infants whose vitamin A status was adequate ( ie , serum retinol > 0.7 mumol/L ) at the time of the CMI test . CMI was consistently better in well-nourished infants irrespective of supplementation BACKGROUND Anemia is prevalent in infants in developing countries . Its etiology is multifactorial and includes vitamin A deficiency . OBJECTIVE Our primary aim was to measure the effect of maternal or neonatal vitamin A supplementation ( or both ) on hemoglobin and anemia in Zimbabwean infants . Our secondary aim was to identify the underlying causes of postnatal anemia . DESIGN A r and omized , placebo-controlled trial was conducted in 14 110 mothers and their infants ; 2854 infants were r and omly selected for the anemia sub study , of whom 1592 were successfully observed for 8 - 14 mo and formed the study sample . Infants were r and omly assigned within 96 h of delivery to 1 of 4 treatment groups : mothers and infants received vitamin A ; mothers received vitamin A and infants received placebo ; mothers received placebo and infants received vitamin A ; and mothers and infants received placebo . The vitamin A doses were 400,000 and 50,000 IU in the mothers and infants , respectively . RESULTS Vitamin A supplementation had no effect on hemoglobin or anemia ( hemoglobin < 105 g/L ) in unadjusted or adjusted analyses . Infant HIV infection independently increased anemia risk > 6-fold . Additional predictors of anemia  in HIV-negative and -positive infants were male sex and lower total body iron at birth . In addition , in HIV-positive infants , the risk of anemia increased with early infection , low maternal CD4 + lymphocyte count at recruitment , and frequent morbidity . Six-month plasma ferritin concentrations < 12 microg/L were a risk factor in HIV-negative but not in HIV-positive infants . Maternal HIV infection alone did not cause anemia . CONCLUSION Prevention of infantile anemia should include efforts to increase the birth endowment of iron and prevent HIV infection For regions where vitamin A deficiency is common , high dose vitamin A supplementation of lactating mothers is currently recommended , but the effects of this intervention have not been carefully evaluated . We conducted a r and omized , double-blind trial in which 153 Indonesian mothers 1 - 3 wk postpartum received either a capsule containing 312 mumol of vitamin A as retinyl palmitate or a placebo .  Mothers ' serum retinol concentrations in the vitamin A group tended to be lower than in the placebo group at baseline but higher at 3 mo postpartum ( 1.39 vs. 1.24 mumol/L , P = 0.03 ) and 6 mo postpartum ( 1.23 vs. 1.08 mumol/L , P < 0.01 ) . The milk retinol concentrations of the vitamin A group were higher than those of the placebo group by 0.48 to 1.18 mumol/L at 1 - 8 mo postpartum ( P < 0.05 ) . Among the infants at 6 mo of age , the prevalences of low serum retinol concentration ( < 0.52 mumol/L ) were 36 and 15 % in the placebo and vitamin A groups , respectively ( P < 0.005 ) , and the prevalences of low vitamin A stores ( assessed by relative dose response ) were 23 and 10 % , respectively ( P < 0.03 ) . High dose vitamin A supplementation of lactating mothers is an efficacious way to improve the vitamin A status of both mother and breast-fed infant Night blindness occurs commonly among women during pregnancy in rural NEPAL : We examined the relationship between maternal night blindness and the risk of mortality occurring among infants in the first 6 mo of life . Stratified analysis by maternal night blindness status during pregnancy was done for 10,000 women participating in a r and omized , placebo-controlled trial of vitamin A and beta-carotene supplementation .  Mortality of infants of non-night blind women in all three supplementation groups was similar , and when combined , was 63/1000 live births . Relative to this , mortality was higher by 63 % [ 95 % confidence interval ( CI ) : 9 - 138 % ) and 50 % ( 95 % CI : -3 to 133 % ) among infants of night blind women receiving placebo and beta-carotene , respectively , but only by 14 % ( 95 % CI : -33 to 93 % ) among those receiving vitamin A. Thus , 6-mo mortality was higher among infants of women who had night blindness during pregnancy . Maternal receipt of vitamin A reduced this risk Vitamin A supplementation reduces child mortality and severe morbidity in less developed countries , and the Exp and ed Program on Immunization ( EPI ) offers an ideal opportunity to deliver supplements in developing countries . High-dose vitamin A supplementation has been shown to have no effect on the immunogenicity of oral polio vaccine , tetanus toxoid , pertussis , or on measles vaccine given at 9 mo , but a negative effect on measles vaccine administered at 6 mo and a potentiating effect on diphtheria vaccine . Its effect on the antibody response to hepatitis B and Haemophilus influenzae type b antigens has not yet been established . To assess these effects , the present trial was carried out in the Offinso district of Ghana ; 1077 infants were enrolled shortly after birth and r and omized either to receive or not to receive 15 mg retinol equivalent with vitamin A together with the pentavalent " diphtheria-polio-tetanus-Haemophilus influenzae b-hepatitis B " vaccine at 6 , 10 , and 14 wk of age . All mothers received a postpartum supplement of 120 mg retinol equivalent vitamin A as per national policy . Blood sample s were taken from infants at 6 and 18 wk of age . The results are based on 888 infants ( 82.4 % ) who completed the trial . The vitamin A supplementation did not affect the immune response to Haemophilus influenzae type b , but there was a significant improvement in the immune response to hepatitis B vaccine ( 93.9 vs. 90.2 % , P = 0.04 ) . However , given the high percentage of infants with seroprotection in the control group , it is doubtful that inclusion of vitamin A in the EPI would be justified on these grounds alone Vitamin A supplementation of lactating mothers and of infants at the time of diphtheria-pertussis-tetanus ( DPT ) and oral polio vaccine ( OPV ) immunizations have both been suggested as measures to prevent deficiency among infants . This multicenter r and omized , double-blind , placebo-controlled trial was conducted in Ghana , India and Peru to determine the effect of maternal vitamin A supplementation on breast milk retinol and of maternal and infant supplementation on infant vitamin A status .  Mothers in the intervention group received 60 mg vitamin A ( as retinol palmitate ) at 18 - 42 d postpartum ; their infants were given 7.5 mg three times , i.e. , at 6 , 10 and 14 wk of age with DPT and OPV immunizations . Mothers and infants in the comparison group received a placebo . Maternal supplementation result ed in higher breast milk retinol at 2 mo postpartum [ difference in means 7.1 , 95 % confidence interval ( CI ) , 3.4 , 10.8 nmol/g fat ] and lower proportion of mothers with breast milk retinol < or = 28 nmol/g fat ( 15.2 vs. 26.6 % , 95 % CI of difference -16.6 , -4.1 % ) . At 6 and 9 mo , maternal supplementation did not affect breast milk retinol or the proportion of mothers with low breast milk retinol .  Vitamin A supplementation of the mothers and their infants reduced the proportion of infants with serum retinol < or = 0.7 micro mol/L ( 30.4 vs. 37 % , 95 % CI of difference -13.7 , 0.6 % ) and that with low vitamin A stores as indicated by the modified relative dose response ( MRDR ) > 0.06 ( 44.2 vs. 52.9 % , 95 % CI of difference -16.6 , -0.9 % ) at 6 mo . Supplementation had no effect at 9 mo . The beneficial effect of supplementation on breast milk retinol and infants ' vitamin A status varied by site . It was greatest in India followed by Ghana and Peru . At the doses used , maternal supplementation improved breast milk retinol status at 2 mo ( P < 0.001 ) and maternal and infant supplementation modestly increased ( P = 0.03 ) infant vitamin A status at 6 mo of age . Additional strategies to improve vitamin A status of 6- to 9-mo-old infants must be considered BACKGROUND Vitamin A deficiency is a risk factor for blindness and for mortality from measles and diarrhoea in children aged 6 - 59 months . We aim ed to estimate trends in the prevalence of vitamin A deficiency between 1991 and 2013 and its mortality burden in low-income and middle-income countries . METHODS We collated 134 population -representative data sources from 83 countries with measured serum retinol concentration data . We used a Bayesian hierarchical model to estimate the prevalence of vitamin A deficiency , defined as a serum retinol concentration lower than 0·70 μmol/L. We estimated the relative risks ( RRs ) for the effects of vitamin A deficiency on mortality from measles and diarrhoea by pooling effect sizes from r and omised trials of vitamin A supplementation . We used information about prevalences of deficiency , RRs , and number of cause-specific child deaths to estimate deaths attributable to vitamin A deficiency . All analyses included a systematic quantification of uncertainty . FINDINGS In 1991 , 39 % ( 95 % credible interval 27 - 52 ) of children aged 6 - 59 months in low-income and middle-income countries were vitamin A deficient . In 2013 , the prevalence of deficiency was 29 % ( 17 - 42 ; posterior probability [ PP ] of being a true decline=0·81 ) . Vitamin A deficiency significantly declined in east and southeast Asia and Oceania from 42 % ( 19 - 70 ) to 6 % ( 1 - 16 ; PP>0·99 ) ; a decline in Latin America and the Caribbean from 21 % ( 11 - 33 ) to 11 % ( 4 - 23 ; PP=0·89 ) also occurred . In 2013 , the prevalence of deficiency was highest in sub-Saharan Africa ( 48 % ; 25 - 75 ) and south Asia ( 44 % ; 13 - 79 ) . 94 500 ( 54 200 - 146 800 ) deaths from diarrhoea and 11 200 ( 4300 - 20 500 ) deaths from measles were attributable to vitamin A deficiency in 2013 , which accounted for 1·7 % ( 1·0 - 2·6 ) of all deaths in children younger than 5 years in low-income and middle-income countries . More than 95 % of these deaths occurred in sub-Saharan Africa and south Asia . INTERPRETATION Vitamin A deficiency remains prevalent in south Asia and sub-Saharan Africa . Deaths attributable to this deficiency have decreased over time worldwide , and have been almost eliminated in regions other than south Asia and sub-Saharan Africa . This new evidence for both prevalence and absolute burden of vitamin A deficiency should be used to reconsider , and possibly revise , the list of priority countries for high-dose vitamin A supplementation such that a country 's priority status takes into account both the prevalence of deficiency and the expected mortality benefits of supplementation . FUNDIN Bill & Melinda Gates Foundation , Gr and Challenges Canada , UK Medical Research Council Vitamin A supplementation reduces mortality in young children in areas of endemic vitamin A deficiency . However , it has no impact on the incidence of common morbidities . This discrepancy has been explained by an impact on case fatality , although with the exception of hospitalized measles cases , there is little direct evidence to support this hypothesis . We assessed the impact of newborn dosing with vitamin A on the incidence and case fatality of common childhood morbidities in early infancy in a community-based , r and omized trial in South India . Morbidity for each day in the previous 2 wk was assessed for the first 6 mo of life . A total of 11,619 live-born infants were enrolled and r and omized to receive either 48,000 IU ( 50.4 micromol retinol ) of oral vitamin A or placebo following delivery . There was no difference between treatment groups in the incidence of acute or chronic diarrhea , dysentery , or fever but a small increased incidence of acute respiratory illness ( ARI ) . Case fatality for diarrhea and fever were significantly reduced in the vitamin A group compared with placebo ( relative case fatality [ 95 % CI ] of 0.50 [ 0.27 , 0.90 ] and 0.60 [ 0.40 , 0.88 ] , respectively ) . There was a trend in reduction of case fatality for various definitions of ARI , but the evidence for this effect was modest . Survival analysis among those with morbid episodes confirmed the case fatality analysis . This trial demonstrated that the reduction in overall mortality due to newborn vitamin A dosing was driven primarily by a reduction in case fatality among infants Objectives : To evaluate the effect of vitamin A supplementation 24 h after delivery on breastmilk retinol concentration . Methods : Fifty low income women were r and omly assigned to a single oral dose of 209 μmol of Vitamin A or none at delivery . Maternal serum and breastmilk retinol levels and infant morbidity and anthropometry were serially assessed . Results : Mean ( 95 % CI ) serum retinol levels increased in the supplemented mothers at 2.77 ( 2.3 , 3.2 ) compared to 1.15 ( 0.9 , 1.4 ) μmol/l in controls ( P<0.05 ) and remained at a significantly higher level of 1.59 ( 1.4 , 1.8 ) μmul/l compared to 1.33 ( 1.8 , 1.5 ) μmol/l in the control group ( P<0.001 ) up to a period of three months . Breastmilk retinol concentration was also greater at 24 h after supplementation , mean ( CI ) 11.34 ( 9.0 , 13.7 ) μmol/l , compared to 2.95 ( 2.3 , 3.6 ) μmol/l in the control group ( P<0.0001 ) , and remained higher for the next six months at 1.06 ( 0.9 , , 1.3 ) μmol/l compared to 0.73 ( 0.6 , 0.8 ) μmol/l in the control group ( P<0.02 ) . Infants of the supplemented mothers had reduced mean duration of respiratory tract infection of 3.1 ( 2.7 , 3.5 ) days compared to 3.7 ( 3.3 , 4.2 ) days ( P<0.03 ) and mean incidence of febrile illness 0.1 ( 0.1 , 0.1 ) compared to control infants 0.3 ( 0.3 , 0.3 ) days , ( P<0.002 ) . Conclusion : Vitamin A supplementation of malnourished mothers maintains higher breastmilk retinol concentration for at least six months and reduces the duration of respiratory tract infection and febrile illness in their breastfed infants . Sponsorship : The study was supported by the International Centre for Diarrhoeal Disease Research and the United States Agency for International Development Background Vitamin A supplementation significantly reduces all-cause mortality when given between 6–59 months of age , but has a null or detrimental effect when given between 1–5 months . Studies of  neonatal vitamin A supplementation  conducted across Africa and South Asia have produced conflicting findings . These age-pattern variations might result from immunological interactions between vitamin A supplementation and vaccines . Knowledge on the potential immunological sequelae of human neonatal vitamin A supplementation is so scarce that the foremost aim of this study is to seek indicative data on aspects of immunity likely to be affected by neonatal vitamin A supplementation . The objective of this trial is to test whether human neonatal vitamin A supplementation modulates immune function including improved thymic maturation in infancy and improved systemic immune responses to routine immunization . Methods / design In an area of moderate vitamin A deficiency in a peri-urban area of The Gambia , 200 mother – infant pairs were enrolled in a double-blind r and omised controlled trial . Within 48 hours of birth , neonates were r and omised with stratification by birth weight and sex to receive either an oral dose of 50,000 IU vitamin A or placebo . Exp and ed Programme of Immunisation birth vaccinations were administered after supplementation , with subsequent vaccinations administered at 8 , 12 and 16 weeks of age . A range of immunological outcomes were examined up to 17 weeks of age , with additional morbidity and anthropometry follow-up carried out throughout the first year of life . The primary endpoint of this trial is the frequency of circulating T regulatory ( Treg ) cells expressing gut homing receptors in infants at 17 week post-supplementation , with secondary outcomes including thymus maturation and B cell immune responses . Discussion Indicative immunological data from this trial ( and its Bangladeshi counterpart ) , will complement the larger r and omised controlled trials ( conducted in India , Tanzania and Ghana ) , on the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival . Combined these trials , in addition to the existing trials , will inform policy . Trial registration clinical trials.gov Objective : Vitamin A supplementation to mothers in the postpartum period and to their infants at routine immunization contacts is being considered to reduce vitamin A deficiency in infancy . This study was conducted to determine the impact of maternal and infant  vitamin A supplementation on antibody response to oral polio vaccine ( OPV ) . Design : R and omized , double blind , placebo-controlled trial . Interventions : Mothers in the intervention group received 60 mg retinol equivalent ( RE ) vitamin A 3–4 weeks after delivery and their infants 7.5 mg RE with each OPV dose at 6 , 10 and 14 weeks of age . The control group mothers and their infants received a placebo at each of these contacts . Main outcomes : Geometric mean ( GM ) titer of neutralizing antibodies and proportion of children with protective titer to the three polioviruses at 26 weeks of age . Results : Vitamin A supplementation increased the proportion of infants with protective antibody titer against poliovirus type 1 ( relative risk ( RR ) 1.15 , 95 % confidence interval ( CI ) 1.03–1.28 ) and the GM antibody titer ( ratio of GM 1.55 , 95 % CI 1.03–2.31 ) following immunization . The proportion of infants with protective antibody titer against poliovirus type 2 ( RR 0.99 , 95 % CI 0.94–1.05 ) or type 3 ( RR 1.05 , 95 % CI 0.96–1.15 ) was not significantly different in vitamin A and placebo groups . The GM antibody titer for poliovirus type 2 ( ratio of GM 0.99 , 95 % CI 0.64–1.54 ) or poliovirus type 3 ( ratio of GM 1.10 , 95 % CI 0.69–1.75 ) also did not differ across groups . Conclusions : Vitamin A given to the mothers in the postpartum period and their infants with OPV did not interfere with the antibody response to any of the three polioviruses and enhanced the response to poliovirus type 1.Sponsorship : Division of Child Health and Development , WHO , Geneva , Norwegian Universities Committee for Development and Research and Indian Council of Medical Research , Panacea Biotec Ltd , India ( provided the oral polio vaccine ) The Exp and ed Programme on Immunisation provides an opportunity to deliver vitamin A supplements to young infants in order to improve their vitamin A status . However , concerns have been raised about the safety of administering high dose vitamin A supplements to infants less than 6 months of age in developing countries . A r and omized controlled trial was carried out by the Kintampo Health Research Centre to assess the safety and immunogenicity of administering 15 mg retinol equivalent (RE)1 vitamin A alongside the pentavalent " diphtheria-polio-tetanus-Haemophilus influenzae b-hepatitis B vaccine " at 6 , 10 and 14 weeks of age . All mothers received a post-partum supplement of 120 mg RE vitamin A as per national policy . Mothers of infants who had been vaccinated were visited 24 h after vaccination to assess the side effects of the vaccine . They were also interviewed about adverse events which may have occurred in the past 4 weeks since the child was vaccinated . There were significantly fewer reports of illnesses and fever in infants who had been given vitamin A compared to infants in the control group . The pentavalent vaccine was found to be tolerable when administered with vitamin A according to the WHO/EPI schedule for infant immunisation at 6 , 10 and 14 weeks . There were few complaints made by the mothers of the children which were not thought to be related to giving vitamin A with the vaccines . There were six deaths in the trial , five in the intervention group and one in the control RR 4.65 ( 0.55 - 39.5 ) , p = 0.12 . Due to the high point estimate of 4.65 , we wish to urge caution in administering high doses of vitamin A to young infants with the pentavalent vaccine at 6 , 10 and 14 weeks of age Postpartum vitamin A supplementation of mothers and infants is recommended , but the efficacy has been question ed . In this double-blind , placebo-controlled trial , Kenyan mother-infant pairs were r and omised to maternal vitamin A ( 400,000 IU ) or placebo < 24 h postpartum , and infant vitamin A ( 100,000 IU ) or placebo at 14 weeks . Milk retinol was determined at weeks 4 , 14 and 26 , and maternal and infant serum retinol at weeks 14 and 26 . Infant retinol stores were assessed at week 26 , using a modified relative dose response ( MRDR ) test . Among 564 women , serum retinol at 36 weeks gestation was 0.81 ( SD 0.21 ) micromol/l , and 33.3 % were<0.7 micromol/l . Maternal serum retinol was not different between groups , but milk retinol was higher in the vitamin A group : ( 0.67 v. 0.60 micromol/l ; 0.52 v. 0.44 micromol/l ; 0.50 v. 0.44 micromol/l at 4 , 14 and 26 weeks , respectively ) . When expressed per gram fat , milk retinol was higher in the vitamin A group only at 4 weeks . Infant serum retinol was not different between groups . However , although most infants had deficient vitamin A stores ( MRDR>0.06 % ) at 26 weeks , vitamin A to infants , but not mothers , result ed in a lower proportion of infants with deficient vitamin A stores ( 69 v. 78 % ) . High-dose postpartum vitamin A supplementation failed to increase serum retinol and infant stores , despite modest effects on milk retinol . Infant supplementation , however , increased stores . There is a need for a better underst and ing of factors affecting absorption and metabolism of vitamin Background Vitamin A supplementation ( VAS ) may amplify the effect of vaccines . We therefore investigated if neonatal VAS given with and without Bacille Calmette-Guérin ( BCG ) vaccine to low-birth-weight ( LBW ) neonates had an effect on growth in the first year of life . We hypothesised that VAS would be particularly beneficial when provided with BCG . Methods We conducted a r and omised two-by-two factorial trial in Guinea-Bissau ; 1,717 LBW neonates were r and omly allocated to VAS or placebo at birth as well as early or the usual postponed BCG vaccination .  Anthropometric measurements were obtained at 2 , 6 , and 12 months after inclusion . Results Overall there was no effect of neonatal VAS on growth in the first year of life . By 2 months , VAS tended to have a beneficial effect on weight and head circumference when given with BCG but not when given without BCG ( interaction : weight-for-age p = 0.07 and head circumference-for-age : p = 0.06 ) . By 6 months , there was a beneficial effect of VAS on head circumference and weight among children who had not received DTP vaccine 2 months after inclusion ( weight : 0.18 ( 0.00 ; 0.36 ) and head circumference 0.27 ( 0.06 ; 0.48 ) ) , but no beneficial effect among those who had received DTP . Conclusion The results support other trials indicating that neonatal VAS does not have consistent effects on childhood growth and if anything the effects seem to be temporary . They also show that the effect may differ by vaccination status , being beneficial when given with BCG at birth and when DTP is delayed . Trial registration http://www . Clinical Trials.gov ( NCT00168610 BACKGROUND In HIV-1-infected women , poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes . We assessed the effects of vitamin A and multivitamins on birth outcomes in such women . METHODS In Tanzania , 1075 HIV-1-infected pregnant women at between 12 and 27 weeks ' gestation received placebo ( n=267 ) , vitamin A ( n=269 ) , multivitamins excluding vitamin A ( n=269 ) , or multivitamins including vitamin A ( n=270 ) in a r and omised , double-blind , placebo-controlled trial with a 2x2 factorial design . We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets . We did analyses by intention to treat . RESULTS 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins ( relative risk 0.61 [ 95 % CI 0.39 - 0.94 ] p=0.02 ) . Multivitamin supplementation decreased the risk of low birthweight ( < 2500 g ) by 44 % ( 0.56 [ 0.38 - 0.82 ] p=0.003 ) , severe preterm birth ( < 34 weeks of gestation ) by 39 % ( 0.61 [ 0.38 - 0.96 ] p=0.03 ) , and small size for gestational age at birth by 43 % ( 0.57 [ 0.39 - 0.82 ] p=0.002 ) . Vitamin A supplementation had no significant effect on these variables . Multivitamins , but not vitamin A , result ed in a significant increase in CD4 , CD8 , and CD3 counts . INTERPRETATION Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women . The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained Background The effect of oral polio vaccine administered already at birth ( OPV0 ) on child survival was not examined before being recommended in 1985 . Observational data suggested that OPV0 was harmful for boys , and trials have shown that neonatal vitamin A supplementation ( NVAS ) at birth may be beneficial for boys . We set out to test this research question in a r and omised trial . Methods The trial was carried out at the B and i m Health Project , Guinea-Bissau . We planned to enrol 900 low-birth weight ( LBW ) boys in a r and omised trial to investigate whether NVAS instead of OPV0 could lower infant mortality for LBW boys . At birth , the children were r and omised to OPV ( usual treatment ) or VAS ( intervention treatment ) and followed for 6 months for growth and 12 months for survival . Hazard Ratios ( HR ) for mortality were calculated using Cox regression . We compared the individual anthropometry measurements to the 2006 WHO growth reference . We compared differences in z-scores by linear regression . Relative risks ( RR ) of being stunted or underweight were calculated in Poisson regression models with robust st and ard errors . Results In the rainy season we detected a cluster of deaths in the VAS group and the trial was halted immediately with 232 boys enrolled . The VAS group had significantly higher mortality than the OPV0 group in the rainy season ( HR : 9.91 ( 1.23 – 80 ) ) . All deaths had had contact with the neonatal nursery ; of seven VAS boys enrolled during one week in September , six died within two months of age , whereas only one died among the six boys receiving OPV ( p = 0.05 ) . Growth ( weight and arm-circumference ) in the VAS group was significantly worse until age 3 months . Conclusion VAS at birth instead of OPV was not beneficial for the LBW boys in this study . With the premature closure of the trial it was not possible to answer the research question . However , the results of this study call for extra caution when testing the effect of NVAS in the future . Trial registration http://www . clinical trials.gov NCT00625482 . Registered 18 February 2008 Abstract Objective To assess the impact of supplementing newborn infants with vitamin A  on  mortality at age 6 months . Design Community based , r and omised , double blind , placebo controlled trial . Setting Two rural districts of Tamil Nadu , southern India . Participants 11 619 newborn infants allocated 24 000 IU  oral vitamin A or placebo on days 1 and 2 after delivery . Main outcome measure Primary outcome measure was mortality at age 6 months . Results Infants in the vitamin A group had a 22 % reduction in total mortality ( 95%confidence interval 4 % to 37 % ) compared with those in the placebo group . Vitamin A had an impact on mortality between two weeks and three months after treatment , with no additional impact after three months . Conclusion Supplementing newborn infants with vitamin A can significantly reduce early infant mortality Background Malaria is the second highest contributor to the disease burden in Africa and there is a need to identify low cost prevention strategies . The objectives of this study were to estimate the prevalence of malaria parasitaemia among infants and to measure the association between peer counselling for exclusive breastfeeding ( EBF ) , vitamin A supplementation , anthropometric status ( weight and length ) and malaria parasitaemia . Methods A cluster r and omized intervention trial was conducted between 2006 and 2008 where 12 of 24 clusters , each comprising one or two villages , in Eastern Ug and a were allocated to receive peer counselling for EBF .  Women in their third trimester of pregnancy ( based on the last normal menstrual period ) were recruited in all 24 clusters and followed up until their children 's first birthday . Blood was drawn from 483 infants between 3 and 12 months of age , to test for malaria parasitaemia .  Results The prevalence of malaria parasitaemia was 11 % in the intervention areas and 10 % in the control areas . The intervention did not seem to decrease the prevalence of malaria ( PR 1.7 ; 95 % CI : 0.9 , 3.3 ) . After controlling for potential confounders , infants not supplemented with Vitamin A had a higher prevalence for malaria compared to those who had been supplemented ( PR 6.1 ; 95 % CI : 2.1 , 17.6 ) . Among children supplemented with vitamin A , every unit increase in length-for-age Z ( LAZ ) scores was associated with a reduced prevalence in malaria ( PR 0.5 ; 95 % CI:0.4 , 0.6 ) . There was no association between LAZ scores and malaria among children that had not been supplemented . Conclusion Peer counselling for exclusive breastfeeding did not decrease the prevalence of malaria parasitaemia .  Children that had not received Vitamin A supplementation had a higher prevalence of malaria compared to children that had been supplemented . Trial registration Clinical trials.gov : NCT00397150 Background and objective : In developing countries low maternal vitamin A stores combined with increased dem and s of pregnancy and lactation may lead to its deficiency in breastfed infants . This study evaluates the effects of maternal supplementation with a high dose of vitamin A on the serum retinol levels of exclusively breastfed infants , and their morbidity in the first six months of life . Setting : Hospital based . Study design : R and omised controlled trial . Subjects and methods : Mothers of the test group ( n=150 ) were orally supplemented with a single dose of retinol ( 209 μmol ) soon after delivery and were advised exclusive breastfeeding for six months . Before supplementation retinol levels were estimated in the mothers ’ and newborns ’ blood , and in colostrum . On follow up , breastmilk and infants ’ serum retinol contents were assessed monthly for six months . Retinol level < 0.7 μmol/l indicated vitamin A deficiency . Morbidity patterns like vitamin A deficiency , diarrhoea , febrile illnesses , acute respiratory infection , measles , and ear infection were also studied and compared between the two groups . Results : Presupplement mean maternal serum retinol levels were 0.98 and 0.92 μmol/l and mean breastmilk levels were 3.85 and 3.92 μmol/l in the test and control groups respectively ( p>0.05 ) . Mean cord blood retinol levels were also comparable ( 0.68 v 0.64 μmol/l ) . After supplementation , the test group showed a rise in mean breastmilk retinol content ( 12.08 v 2.96 μmol/l ) which remained significantly higher for four months . The infants ’ mean serum retinol level , initially 322.06 % of the baseline value , was significantly higher for five months . In the control group , significant numbers of mothers and infants showed deficient breastmilk and serum retinol throughout the follow up ( p<0.01 ) . Decreased incidence and duration of various diseases were also found in the test group suggesting lesser morbidity . Conclusion : Maternal supplementation with single megadose vitamin A is an effective strategy for vitamin A prophylaxis of exclusively breastfed infants of 0–6 months Vitamin A is essential for immunity and growth . A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia , low birth weight , growth failure , HIV transmission , and mortality .  Women received daily doses of iron and folate , either alone or combined with vitamin A ( 3 mg retinol equivalent ) , from 18 - 28 weeks ' gestation until delivery . In the vitamin A and control groups , respectively , the mean ( + /-SE ) birth weights were 2895+/-31 g and 2805+/-32 g ( P=.05 ) , the proportions of low-birth-weight infants were 14.0 % and 21.1 % ( P=.03 ) , the proportions of anemic infants at 6 weeks postpartum were 23.4 % and 40.6 % ( P<.001 ) , and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6 % and 27.8 % ( P=.76 ) and 27.7 % and 32.8 % ( P=.21 ) . Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia , but it did not affect perinatal HIV transmission To evaluate the safety of vitamin A supplementation in early infancy using DPT/OPV immunization contracts , a double‐blind , r and omized , placebo‐controlled trial was conducted in Bangladesh . One hundred and sixty‐seven infants received three doses of either 25 000 IU of vitamin A or a placebo at about 6.5 , 11.8 and 17.0 weeks of age . Trained physicians examined each of the infants on days 1 , 2 , 3 and 8 after supplementation . Nine infants ( 10.5 % ) supplemented with vitamin A had episodes of bulging of the fontanelle compared with two infants ( 2.5 % ) in the placebo group ( p < 0.05 ) . Twelve of the 14 episodes occurred in infants supplemented with vitamin A. Of these 12 episodes , none occurred with the first dose , 3 occurred with the second and 9 with the third dose . The higher incidence of bulging of the fontanelle in the vitamin A group relative to the  placebo group and its temporal association with the vitamin A doses are suggestive of a causal association . The finding that increased numbers of vitamin A doses were associated with a higher probability of bulging of the fontanelle suggests a cumulative effect . Bulging fontanelle , clinical trial , safety , toxicity , vitamin The effects of vitamin A and vitamin E supplementation on the IgG response to tetanus toxoid after primary immunization were evaluated in a prospect i ve , r and omized controlled clinical trial involving 89 healthy infants with normal serum vitamin A and E levels at 2 months of age . Before the first dose of DPT vaccine , the infants were r and omly enrolled into four different study groups [ Group I ( n=24 ) : 30,000 IU vitamin A for 3 days just after each three doses of primary vaccination , Group II ( n=21 ) : 150 mg oral vitamin E for only 1 day after the injections for primary immunization , Group III ( n=21 ) : vitamins A and E together in the same order , Group IV ( n=23 ) no vitamin after DPT vaccines ] . Serum tetanus antitoxin ( IgG ) titres were measured three times ; initially at 2 months of age before the first dose of DPT , secondly at 5 months of age 1 month after primary immunization and thirdly at 16 - 18 months of age before the booster dose of DPT . Before the first dose of the DPT vaccine , 1 month after the third DPT injection and at 16 - 18 months before the booster dose of DPT , there was no significant difference in serum tetanus antitoxin levels between these four groups . A significant increase was observed in all the groups when serum tetanus antitoxin levels before ( 2 months ) and after ( 5 months ) primary immunization were compared . In addition , serum antibody levels against tetanus significantly decreased in the four groups before booster vaccination . Before the beginning of primary immunization , 15 infants ( 16.8 % ) had serum tetanus antitoxins ( IgG ) below protective level . After three doses of DPT , all the infants had protective antitoxin levels . At 16 - 18 months of age before booster dose , four infants ( 10 % ) also had serum tetanus antitoxins ( IgG ) below the protective level . No side-effects were observed except bulging fontanelle in two infants in Group BACKGROUND Low maternal serum retinol level is a risk factor for mother-to-child transmission ( MTCT ) of human immunodeficiency virus ( HIV ) . Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality . The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency ; neonatal dosing is under consideration . We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT , HIV-free survival , and mortality in HIV-exposed infants . METHODS A total of 14,110 mother-infant pairs were enrolled < or = 96 h after delivery , and both mother and infant , mother only , infant only , or neither received vitamin A supplementation in a r and omized , placebo-controlled trial with a 2 x 2 factorial design . All but 4 mothers initiated breast-feeding . A total of 4495 infants born to HIV-positive women were included in the present analysis . RESULTS Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months . However , the timing of infant HIV infection modified the effect that supplementation had on mortality .  Vitamin A supplementation had no effect in infants who were polymerase chain reaction ( PCR ) positive [ corrected ] for HIV at baseline . In infants who were PCR negative at baseline and PCR positive at 6 weeks , neonatal supplementation reduced mortality by 28 % ( P=.01 ) , but maternal supplementation had no effect . In infants who were PCR negative at 6 weeks , all 3 vitamin A regimens were associated with ~2-fold higher mortality ( P < or = .05 ) . CONCLUSIONS Targeted vitamin A supplementation of HIV-positive children prolongs their survival . However , postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks . These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas BACKGROUND Most developing countries have adopted a st and ard WHO dosing schedule for vitamin A supplementation . However , in 2002 the International Vitamin A Consultative Group ( IVACG ) Annecy Accord recommended a new high-dose regimen for mothers and infants . Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A , reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage , and improve infant gut epithelial integrity . METHODS In an area of moderate vitamin A deficiency in rural Gambia , 220 mother-infant pairs were enrolled in a r and omised double-blind trial between September , 2001 , and October , 2004 , that compared the IVACG high dose with the WHO dose . The primary endpoints were levels of maternal and infant plasma vitamin A , H pylori infection , pneumococcal carriage , and gut epithelial integrity . The trial is registered as IS RCT N 98554309 . FINDINGS 197 infants completed follow-up to 12 months ( 99 high dose and 98 WHO dose ) . There were no adverse events at dosing . No differences were found in the primary outcomes for high-dose versus WHO schedule : maternal vitamin A concentration at 2 months + 0.02 micromol/L ( 95 % CI -0.10 to 0.15 ) ; infant vitamin A at 5 months + 0.01 micromol/L ( -0.06 to 0.08 ) ; H pylori infection at 12 months -0.3 % ( -14.7 to 14.2 ) ; maternal pneumococcal carriage at 12 months -2.0 % ( -13.7 to 9.7 ) ; infant pneumococcal carriage at 12 months -4.1 % ( -15.8 to 7.6 ) ; infant gut mucosal damage at 12 months 5.2 % ( -8.7 to 19.2 ) . There were more clinic attendances by the high-dose group in the first 6 months of life ( p=0.018 ) . INTERPRETATION Our results do not lend support to the proposal to increase the existing WHO st and ard dosing schedule for vitamin A in areas of moderate vitamin A deficiency . Caution is urged for future studies because trials have shown possible adverse effects of higher doses of vitamin A , and potential negative interactions with the exp and ed programme on immunisation ( EPI ) vaccines Objective : To determine whether the combined intervention of 50 000 IU vitamin A administered together with Bacille Calmette-Guerin ( BCG ) vaccination at birth was associated with adverse events , in particular bulging fontanels and adverse reactions to BCG.Subjects/ Methods : From an ongoing trial , 2145 infants r and omized to 50 000 IU vitamin A or placebo with BCG vaccination were recruited .  Adverse events were monitored in two different ways : ( A ) daily clinical examinations by a medical doctor during the first 3 days post supplementation ; ( B ) weekly interviews by a trained assistant during the first month post supplementation . Results : In part A , 1271 infants were enrolled , in part B 2078 .  Vitamin A supplementation ( VAS ) was associated with a relative risk ( RR ) of bulging fontanels of 1.16 ( 95 % confidence interval (CI)=0.82–1.65 ) . The rate of health care contacts and various symptoms during the first month were comparable between the groups . VAS was associated with larger peak local reactions to BCG vaccination in boys , but not in girls ( P-value for test of interaction between VAS and sex=0.02 ) . Conclusion : 50 000 IU vitamin A with BCG was not associated with adverse events . The observed sex-differential effect of VAS on local reaction to BCG is in line with other observations of sex-differential effects of VAS Whether neonatal vitamin A supplementation ( NVAS ) should be policy in areas with vitamin A deficiency is debated . We observed that a smaller dose of vitamin A may decrease mortality more than a larger dose and conducted a r and omized , double-blind , placebo-controlled trial in Guinea-Bissau with the primary aim of comparing the effect of 50,000 with 25,000 IU neonatal vitamin A on infant mortality . The secondary aim was to study the effect of NVAS vs. placebo , including a combined analysis of NVAS trials . Between 2004 and 2007 , normal-birth-weight neonates were r and omly assigned in a 1:1:1 ratio to be administered 2 different doses of vitamin A ( 50,000 or 25,000 IU ) or placebo .  Infant mortality rates ( MRs ) were compared in Cox models providing MR ratios ( MRRs ) . Among 6048 children enrolled , there were 160 deaths in 4125 person-years ( MR = 39/1000 ) . There was no difference in mortality between the 2 dosage groups : the MRR for 25,000 vs. 50,000 IU was 0.96 ( 95 % CI : 0.67 , 1.38 ) . Neither dose of NVAS was associated with lower mortality than placebo ( MRR = 1.28 ; 95 % CI : 0.91 , 1.81 ) . In a combined analysis of the present trial and 2 previous NVAS trials in Guinea-Bissau , the effect of receiving NVAS ( any dose ) vs. placebo was 1.13 ( 95 % CI : 0.94 , 1.36 ) and differed significantly ( P = 0.01 ) between boys ( 0.80 ; 95 % CI : 0.58 , 1.09 ) and girls ( 1.35 ; 95 % CI : 1.04 , 1.75 ) . We could not confirm that a smaller dose of neonatal vitamin A reduces mortality more than a larger dose . We confirmed 2 other trials in Guinea-Bissau that showed no beneficial effect of NVAS . This trial was registered at clinical trials.gov as NCT00168610 OBJECTIVE To assess the effect of retinyl palmitate supplementation on colostrum retinol levels , investigating the influence of maternal variables ( age , type of delivery , and biochemical nutritional status ) on these levels . METHOD The study included 33 mothers receiving care at the Januário Cicco Maternity School , in the city of Natal , Rio Gr and e do Norte , Brazil . In the first hours after delivery , blood and colostrum sample s were collected . Another colostrum sample was collected six hours after maternal supplementation with 200,000 IU of retinyl palmitate .  Serum and colostrum retinol levels were determined by high-performance liquid chromatography . RESULTS The mean retinol level in colostrum before the supplementation was 110.8 + /- 82.3 microg/dL , and after supplementation it was 164.4 + /- 106.5 microg/dL ( P < 0.025 ) . Of the 33 mothers , 12 of them either did not respond to supplementation or had an increase of less than 10 % in colostrum retinol levels ; serum retinol in these women was significantly lower as compared to the responders ( P = 0.024 ) . In comparison to women with a normal delivery , the mothers who underwent cesarean delivery ( 64 % ) had lower serum retinol levels , but not lower colostrum retinol levels ( P = 0.036 ) . Maternal age did not influence retinol levels in either serum or colostrum . CONCLUSION The increase in colostrum retinol levels following vitamin A supplementation was sufficient to guarantee double the retinol requirements of a newborn infant BACKGROUND AND OBJECTIVE : Postpartum vitamin A supplementation is a strategy used to combat vitamin A deficiency and seems to reduce maternal/infant morbidity and mortality . However , studies have shown that a dose of 200 000 IU ( World Health Organization [ WHO ] protocol ) does not seem to provide adequate retinol levels in maternal breast milk , infant serum , and infant tissue . The objective of this study was to compare the effect of postpartum maternal supplementation with 400 000 IU ( International Vitamin A Consultative Group protocol ) compared with 200 000 IU of vitamin A on infant morbidity . METHODS : This was a r and omized controlled , triple-blinded clinical trial conducted at 2 public maternity hospitals in Recife in northeastern Brazil . There were 276 mother – child pairs that were allocated to 2 treatment groups : 400 000 IU or 200 000 IU of vitamin A. They were followed up for > 6 months to evaluate infant morbidity . RESULTS : Fever ( rate ratio [ RR ] : 0.92 [ 95 % confidence interval ( CI ) : 0.75–1.14 ] ) , diarrhea ( RR : 0.96 [ 95 % CI : 0.72–1.28 ] ) , otitis ( RR : 0.94 [ 95 % CI : 0.48–1.85 ] ) , acute respiratory infection ( RR : 1.03 [ 95 % CI : 0.88–1.21 ] ) , the need for intravenous rehydration ( RR : 2.08 [ 95 % CI : 0.64–2.07 ] ) , and the use of antibiotic treatment ( RR : 0.80 [ 95 % CI : 0.43–1.47 ] ) did not differ significantly between the 2 treatment groups . CONCLUSIONS : Our findings suggest that postpartum maternal supplementation with 400 000 IU of vitamin A does not provide any additional benefits in the reduction of illness in children aged < 6 months ; therefore , we do not support the proposal to increase the st and ard vitamin A dose in the existing WHO protocol OBJECTIVES To assess the impact of Vitamin A supplementation to the mother soon after delivery and to the infant at six months on morbidity in infancy . DESIGN R and omized double blind placebo controlled field trial . SETTING 51 villages in two contiguous Primary Health Centers in Villupuram Health Unit District of Tamil Nadu , South India . SUBJECTS 909 newly delivered mother- and -infant pairs . INTERVENTIONS Both mother and infant received Vitamin A ( 300,000 IU for mothers and 200,000 IU for children ) in 311 instances ( AA ) ; mother received Vitamin A but infant received Placebo in 301 instances ( AP ) ; and both mother and infant received Placebo in the remaining 297 instances ( PP ) . MAIN OUTCOME MEASURES Incidence of diarrhea and Acute Respiratory Infection ( ARI ) ; distributions of infants by frequency of episodes and number of infected days . RESULTS 233 in the AA Group and 228 each in the AP and PP Groups were followed up regularly . The incidence of diarrhea in these infants was 97.4 % , 96.9 % and 94.7 % in the three groups , mean number of diarrheal episodes was 4.4 , 4.6 and 4.2 and median number of days in infancy with diarrhea was 26 , 26 and 22 days , respectively . For ARI , the incidences were 96.6 % , 95.6 % and 96.1 % , means were 4.8 , 5.1 and 4.8 episodes , and the medians were 32 , 34 and 34 days , respectively . CONCLUSIONS Prophylactic administration of mega doses of Vitamin A to the mother soon after delivery and to the infant at six months do not have any beneficial impact on the incidence of diarrhea and ARI in infancy OBJECTIVE To explore the effect of maternal supplementation of vitamin A on the immune response to oral polio vaccine  in breastfed infants . DESIGN R and omized controlled trial . SETTING Hospital based . METHODS One hundred mothers having uncomplicated deliveries r and omly received either 200,000 IU vitamin A orally ( Experimental ) or placebo ( Control ) . All the newborns were given a dose of oral polio vaccine within 72 hours after birth and were breastfed . Type specific neutralizing antibodies to polio viruses in test sera diluted from 1:4 to 1:512 and serum retinol levels were determined from the cord blood and at the age of 6 weeks . Breast milk retinol levels were determined at 3 , 10 , 30 , 45 and 90 days of lactation . RESULTS Seroconversion to OPV and geometric means of antibody titers to the three types of polio viruses were comparable between the groups of infants belonging to the experimental and control mothers . Breast milk retinol levels were significantly higher in the experimental group upto 45 - 90 days of lactation . Majority of the infants at birth had serum retinol levels < 15 micrograms/dl which improved significantly by 6 weeks irrespective of the maternal supplementation status . CONCLUSIONS Maternal vitamin A supplementation soon after delivery improves vitamin A intakes of breastfed infants during the first 3 months and has no interference with the seroconversion to a neonatal dose of OPV . OPV administered to newborn in turn has no adverse effect on the vitamin A status of the breastfed infants Objective To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates . Design R and omised , placebo controlled , two by two factorial trial . Setting Bissau , Guinea-Bissau . Participants 1717 low birthweight neonates born at the national hospital . Intervention Neonates who weighed less than 2.5 kg were r and omly assigned to 25 000 IU vitamin A or placebo , as well as to early BCG vaccine or the usual late BCG vaccine , and were followed until age 12 months . Main outcome measure Mortality , calculated as mortality rate ratios ( MRRs ) , after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo . Results No interaction was observed between vitamin A supplementation and BCG vaccine allocation ( P=0.73 ) . Vitamin A supplementation at birth was not significantly associated with mortality : the MRR of vitamin A supplementation compared with placebo , controlled for r and omisation to “ early BCG ” versus “ no early BCG ” was 1.08 ( 95 % CI 0.79 to 1.47 ) . Stratification by sex revealed a significant interaction between vitamin A supplementation and sex ( P=0.046 ) , the MRR of vitamin A supplementation being 0.74 ( 95 % CI 0.45 to 1.22 ) in boys and 1.42 ( 95 % CI 0.94 to 2.15 ) in girls . When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau , the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 ( 95 % CI 0.87 to 1.33 ) ; 0.80 ( 95 % CI 0.58 to 1.10 ) in boys and 1.41 ( 95 % CI 1.04 to 1.90 ) in girls ( P=0.01 for interaction between neonatal vitamin A and sex ) . Conclusions The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that , overall , it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau . Worryingly , the trials show that vitamin A supplementation at birth can be harmful in girls . Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects . Trial registration Clinical Trials.gov NCT00168610 OBJECTIVES . We assessed the effect of supplementing newborns with 50000 IU of vitamin A on all-cause infant mortality  through 24 weeks of age . PATIENTS AND METHODS . This was a community-based , double-masked , cluster-r and omized , placebo-controlled trial conducted in 19 unions in rural northwest Bangladesh . The study was nested into and balanced across treatment arms of an ongoing placebo-controlled , weekly maternal vitamin A or β-carotene supplementation trial . Study -defined sectors ( N = 596 ) were evenly r and omized for newborns of participating mothers to receive a single , oral supplement of vitamin A ( 50000 IU ) or placebo as droplets of oil squeezed from a gelatinous capsule . Mothers provided informed consent for newborn participation at ∼28 weeks ' gestation . After birth , typically at home ( where > 90 % of births occurred ) , infants were supplemented and their vital status was followed through 24 weeks of age . The main outcome measure was mortality through 24 weeks of age . RESULTS . We obtained maternal consent to dose 17116 live-born infants ( 99.8 % of all eligible ) among whom 15937 ( 93.1 % ) were visited to be supplemented < 30 days after birth and for whom vital status at 24 weeks of age was known . Dosed infants ( n = 15902 [ 99.8 % ] ) received their study supplement at a median age of 7 hours . Relative to control subjects , the risk of death in vitamin A – supplemented infants was 0.85 , reflecting a 15 % reduction in all-cause mortality . Protective relative risks were indistinguishable by infant gender , gestational age , birth weight , age at dosing , maternal age , parity , or across the 3 treatment arms of the maternal supplementation trial . CONCLUSIONS . Newborn vitamin A dosing improved infant survival through the first 6 months of life in Bangladesh . These results corroborate previous findings from studies in Indonesia and India and provide additional evidence that vitamin A supplementation shortly after birth can reduce infant mortality in South Asia Objective : To examine the association between breast-feeding initiation time and  neonatal mortality in India , where breast-feeding initiation varies widely from region to region . Study Design : Data were collected as part of a community-based , r and omized , placebo-controlled trial of the impact of vitamin A supplementation  in rural villages of Tamil Nadu , India . Multivariate binomial regression analysis was used to estimate the association between neonatal mortality and breast-feeding initiation time ( < 12 h , 12 to 24 h , > 24 h ) among infants surviving a minimum of 48 h. Result : Among 10 464 newborns , 82.1 % were first breast-fed before 12 h , 13.8 % were breast-fed between 12 and 24 h , and 4.1 % were breast-fed after 24 h. After adjusting for birth weight , gestational age and other covariates , late initiators ( > 24 h ) were at ∼78 % higher risk of death ( relative risk=1.78 ( 95 % confidence interval (CI)=1.03 to 3.10 ) ) . There was no difference in mortality risk when comparing babies fed in the first 12 h compared with the second 12 h after birth . Conclusion : Late ( > 24 h ) initiation of breast-feeding is associated with a higher risk of neonatal mortality in Tamil Nadu . Emphasis on breast-feeding promotion programs in low-re source setting s of India where early initiation is low could significantly reduce neonatal mortality OBJECTIVE To determine whether vitamin A supplementation at birth could reduce  infant morbidity and mortality .  STUDY DESIGN We conducted a placebo-controlled trial among 2067 Indonesian neonates who received either 52 micromol ( 50,000 IU ) orally administered vitamin A or placebo on the first day of life . Infants were followed up at 1 year to determine the impact of this intervention on infant mortality . A subgroup ( n = 470 ) was also examined at 4 and 6 months of age to examine the impact on morbidity . RESULTS Vital status was confirmed in 89 % of infants in both groups at 1 year . There were 19 deaths in the control group and 7 in the vitamin A group ( relative risk = 0.36 ; 95 % confidence interval = 0.16 , 0.87 ) . The impact was stronger among boys , infants of normal compared with low birth weight , and those of greater ponderal index . Among infants examined at 4 months of age , the 1-week period prevalence of common morbidities was similar for vitamin A and control infants . However , during this same 4-month period , 73 % and 51 % more control infants were brought for medical treatment for cough ( p = 0.008 ) and fever ( p = 0.063 ) , respectively . CONCLUSIONS Neonatal vitamin A supplementation may reduce the infant mortality rate and the prevalence of severe respiratory infection among young infants The mutual interactions of measles vaccine and vitamin A dose when administered simultaneously to 9 month old infants are explored in this study . One hundred healthy infants of 9 months of age received EZ strain of measles vaccine  in the routine immunization clinic along with either 100,000 IU of vitamin A or a placebo orally . Blood sample s were collected before and 4 weeks after intervention . They were coded and analysed for serum retinol and Hemagglutination Inhibition ( HI ) antibodies to measles . Ninety five per cent of the infants were seronegative to measles prior to vaccination with a seroconversion rate of 63 % in the control group and a significantly higher percent of 83.7 % in the experimental group ( P < 0.01 ) . Seroconversion was not related to initial serum retinol levels in either of the groups . 42 % of infants had serum retinol levels less than 20 ug/dl before administration of the vaccine and both the groups showed improvement in vitamin A status following intervention , the increase being significant in the experimental group ( from 22.4 ± 1.32 to 26.0 ± 1.07 ; P < 0.05 ) . The results indicate that majority of the infants at 9 months of age were seronegative to measles . Seroconversion to measles vaccine in the routine immunization clinics was low . Simultaneous administration of vitamin A and measles vaccine had beneficial effects on vitamin A status as well as seroconversion rates to the vaccine in 9 months old infants Objective : To investigate whether supplementation with vitamin A together with iron of Indonesian pregnant women  decreases morbidity and improves growth of their infants during the first year of life . Design : Women from a rural area in West Java , Indonesia , were r and omly assigned on an individual basis to double-blind supplementation once weekly from ∼18 weeks of pregnancy until delivery . Supplementation comprised 120 mg iron and 500 µg folic acid with or without 4800 RE vitamin A. Their newborn infants were followed up during the first year of life : weight , length , morbidity and food intake were assessed monthly . Results : Infants whose mothers had taken vitamin A supplements during pregnancy had similar weight , length , weight gain and growth as their counterparts during the follow-up period . The proportions of infants with reported symptoms of morbidity were similar in the vitamin A plus iron group and the iron group . In addition immunisation coverage and feeding mode did not differ between the groups . All infants were breast-fed , but exclusive breast-feeding rapidly declined at 4 months of age . Infants with serum retinol concentrations > 0.70 µmol/l increased their weight and length more during the first 6 months of life and had higher weight-for-age Z-scores during the first year of life than infants with serum retinol concentrations ≤0.70 µmol/l . Serum retinol concentrations were not associated with morbidity . Conclusion : In this study , vitamin A supplementation in conjunction with iron supplementation of pregnant women did not improve growth or reduce morbidity of their infants during the first year of life . Sponsorship : Netherl and s Organization for Scientific Research -Netherl and s Foundation for the Advancement of Tropical Research ( NWO-WOTRO ) ( WV 93 - 280 ) , the Neys-van Hoogstraten Foundation ( IN 114 ) , The Netherl and s and the German Agency for Technical Cooperation (GTZ)/South East Asian Ministers of Education Organization , Tropical Medicine ( SEAMEO-TROPMED ) , Indonesia OBJECTIVE Childhood immunization programs have been suggested as an infrastructure to deliver vitamin A supplements to children in developing countries . The effects of giving vitamin A , a potent immune enhancer , with measles immunization to nine-month-old infants is unknown . METHODS A r and omized , double-masked , placebo-controlled clinical trial of vitamin A , 100,000 IU at the time of st and ard titer Schwarz measles immunization was conducted with nine-month-old infants in Bogor District , West Java , Indonesia .  Antibody titers to measles were measured at baseline and one and six months following immunization . RESULTS 394 infants received measles immunization , and 37 infants ( 9.4 % ) had baseline antibody titers > 1:120 , which is consistent with previous natural measles infection . Of the remaining infants , 98.8 % seroconverted to measles , and 99.3 % had titers consistent with protection against measles six months postimmunization . Seroconversion rates were similar in vitamin A and placebo treatment groups . CONCLUSION High dose vitamin A supplementation can be given without reducing seroconversion to st and ard titer Schwatz measles immunization in nine-month-old infants A double-blind , r and omised , placebo-controlled trial was conducted to evaluate the safety and toxicity of vitamin A supplementation within the Exp and ed Programme on Immunisation ( EPI ) in rural Bangladesh . 191 infants received 3 doses of either 50,000 IU of vitamin A or placebo  at about 1.5 , 2.5 , and 3.5 months and were examined on days 1 , 2 , 3 , and 8 after supplementation . 11 infants ( 11.5 % ) supplemented with vitamin A had episodes of bulging of the fontanelle as opposed to 1 ( 1 % ) in the placebo group . 16 of the 17 events occurred in the vitamin A supplemented group . No other side effects were noted . There was a tendency towards a cumulative effect of toxicity with increasing doses Background : HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status . Methods : A total of 1078 HIV-infected pregnant women from Tanzania were r and omly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks ’ gestation and throughout lactation . Results : Multivitamins excluding A had no effect on the total risk of HIV-1 transmission ( RR 1.04 , 95 % CI 0.82–1.32 , P = 0.76 ) . Vitamin A increased the risk of transmission ( RR 1.38 , 95 % CI 1.09–1.76 , P = 0.009 ) . Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding , and mortality by 24 months among those alive and not infected at 6 weeks . Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts ( RR 0.37 ; 95 % CI 0.16–0.85 , P = 0.02 ) compared with infants of mothers with higher counts ( RR 0.99 , 95 % CI 0.68–1.45 , P = 0.97 ; P-for-interaction 0.03 ) . Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate ( P-for-interaction 0.06 ) , low hemoglobin ( P-for-interaction 0.06 ) , and low birthweight babies ( P-for-interaction 0.04 ) . Multivitamins  reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status . Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months . Conclusion : Vitamin A increased the risk of HIV-1 transmission .  Multivitamin ( B , C , and E ) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women . The provision of these supplements to HIV-infected lactating women should be considered Summary The World Health Organization recommends that 100,000 IU of vitamin A be given to infants between 6 and 12 months of age at the same time as measles vaccination in order to prevent vitamin A deficiency . In the present study , our aim was to assess the effect of vitamin A supplementation on T-cell subsets in a r and omized factorial design , seeking a possible modifying effect of measles vaccination .  Three hundred children were allocated either to two doses of  measles vaccine at 6 and 9 months of age or  to  poliomyelitis vaccine at age 6 months and measles vaccine at age 9 months . Within each group , infants were to receive two doses of vitamin A or two doses of placebo at 6 and 9 months of age . We found no significant effect of vitamin A supplementation on CD4 and CD8 T-cell subsets at 3 and 9 months after supplementation . We found no effect of measles vaccine  and no interaction between vitamin A supplementation and measles vaccine .  Based on these observations , vitamin A supplementation does not seem to have a strong long-term effect on CD4 and CD8 T-cell subsets in infants without clinical vitamin A deficiency OBJECTIVE To investigate whether monthly administration of vitamin A at routine immunisation produces any side-effects , and to examine the effect of this supplementation on the vitamin A nutrition status of infants . DESIGN A double-blind r and omised  placebo-controlled clinical trial . SETTING Immunisation clinic of a large diarrhoea treatment centre . SUBJECTS Infants aged 6 - 17 weeks who will receive their first diphtheria-pertussis-tetanus/oral polio vaccine ( DPT/OPV ) dose . METHODS Infants were r and omly assigned to receive either  25,000 IU vitamin A or placebo . Three such doses were given with each immunisation dose at monthly intervals . Infants were examined by a physician before and during 24 h after the doses and any signs of toxicity were recorded . Venous blood was drawn at entry and 1 month after the 3rd dose for retinol assay . RESULTS One hundred and one infants received vitamin A and 98 received placebo .  Decreased feeding , irritability , diarrhoea , and vomiting were comparable between the two groups . In the vitamin A group five infants developed bulging fontanelle ; three of them developed it once ( after 1st , 2nd and 3rd dose respectively ) , one developed it twice ( after both the 2nd and 3rd dose ) , and the other infant after all three doses . In the placebo group a single child developed bulging fontanelle after the 3rd dose . In all the cases the bulging disappeared within 48 h of onset except in one infant , in whom it subsided at 60 h. The total bulging episodes in the vitamin A and placebo groups were 8 and 1 respectively ( RR = 7.7 ; P < 0.04 ) . However , none of these infants had irritability . At entry fasting retinol level was < 10 micrograms/dl in 35 % infants and in 87 % infants it was < 20 micrograms/dl . After the third dose fasting retinol level was marginally better in the vitamin A group ( mean + /- s.d . : 21.9 + /- 8.2 vs 19.2 + /- 7.8 ; P = 0.05 ) . However , 47 % infants receiving supplementation still had serum retinol level < 20 micrograms/dl . CONCLUSION The results suggest that administration of 25,000 IU of vitamin A in young infants along with routine immunisations , though associated with increased incidence of transient bulging fontanelle without any associated adverse signs or symptoms , may still be inadequate to prevent deficiency in this population . SPONSORSHIP This study was funded by the United States Agency for International Development ( USAID ) under grant no. DPE-5986-A-1009 - 00 with the International Centre for Diarrhoeal Disease Research , Bangladesh ( ICDDR , B ) . The ICDDR , B is supported by countries and agencies which share its concern for the health problems of developing countries OBJECTIVE To assess the Vitamin A status of pregnant women in their third trimester using maternal serum retinol levels as the indicator ; and ( ii ) To assess the impact of postpartum Vitamin A supplementation on the Vitamin A status of exclusively breastfed infants . DESIGN Prospect i ve r and omized single blind controlled study . SETTING Teaching Hospital . SUBJECTS 109 apparently healthy primi and second gravida women registered at the antenatal clinic were included in the study and followed up for three months postpartum . Serum retinol levels of pregnant mothers in their third trimester ( 35 - 37 weeks ) and cord blood levels after delivery were estimated . Mothers were then assigned to two groups . The experimental group included 53 mothers who received a single dose of 2 lakh units of Vitamin A  orally . The control group had 56 mothers who did not receive Vitamin A.  Mothers and infants were followed up for three months . The serum retinol of infants and the breast milk retinol levels were estimated at the end of three months and the results were compared . The growth of the infants was also monitored . RESULTS Sub clinical Vitamin A deficiency was seen in 29.67 % of pregnant women . At the end of three months , 69.6 % of mothers in the control group had breast milk retinol levels below 30 mg/dl , as opposed to 36.1 % in the experimental group . Forty five per cent of infants in the control group had sub clinical vitamin A deficiency compared to none in the experimental group . There was no difference in the growth of infants in the two groups . However , the infant serum and the breast milk retinol levels were significantly higher in the supplemented group . CONCLUSION There is a high prevalence of inapparent Vitamin A deficiency ( 29.7 % ) in pregnant women in their third trimester from lower socio-economic strata . Postpartum Vitamin A supplementation had a beneficial impact on the infant serum retional and the breast milk retinol level but no effect on infant growth Nasopharyngeal ( NP ) carriage of S. pneumoniae ( Spn ) is a risk factor for pneumococcal disease and its transmission . We assessed the impact of vitamin A ( VA ) supplementation shortly after birth in reducing Spn colonization in early infancy in rural Bangladesh . We recruited 500 infants participating in a cluster-r and omized trial that reported a 15 % reduction in mortality following receipt of an oral dose of VA ( 52.25 μmol ) compared to placebo . NP specimens were collected at the age of 3 mo to study the effect of VA on the prevalence of culture-confirmed Spn . Analyses were conducted by intention to treat . Spn carriage prevalence did not differ between VA and placebo recipients [ OR = 0.83 ( 95 % CI : 0.55 - 1.27 ) ; P = 0.390 ] . Spn carriage at the age of 3 mo was not lowered by VA given at birth . Results are similar to those from an Indian study in which impact on Spn carriage was assessed at the age of 4 mo [ OR = 0.73 ( 95 % CI : 0.48 - 1.10 ) ; P = 0.128 ] . The point estimate of the pooled effect size for the 2 studies is OR = 0.78 [ ( 95 % CI : 0.58 - 1.04 ) ; P = 0.095 ] , which may imply a modest impact on carriage . If so , then the evidence thus far would suggest that Spn carriage reduction is unlikely to be a primary ancillary benefit of newborn VA supplementation BACKGROUND A previous trial in Nepal showed that supplementation with vitamin A or its precursor ( betacarotene ) in women of reproductive age reduced pregnancy-related mortality by 44 % ( 95 % CI 16 - 63 ) . We assessed the effect of vitamin A supplementation in women in Ghana . METHODS ObaapaVitA was a cluster-r and omised , double-blind , placebo-controlled trial undertaken in seven districts in Brong Ahafo Region in Ghana . The trial area was divided into 1086 small geographical clusters of compounds with fieldwork areas consisting of four contiguous clusters . All women of reproductive age ( 15 - 45 years ) who gave informed consent and who planned to remain in the area for at least 3 months were recruited . Participants were r and omly assigned by cluster of residence to receive a vitamin A supplement ( 25 000 IU retinol equivalents ) or placebo capsule orally once every week . R and omisation was blocked and based on an independent , computer-generated list of numbers , with two clusters in each fieldwork area allocated to vitamin A supplementation and two to placebo . Capsules were distributed during home visits undertaken every 4 weeks , when data were gathered on pregnancies , births , and deaths . Primary outcomes were pregnancy-related mortality and all-cause female mortality . Cause of death was established by verbal post mortems . Analysis was by intention to treat ( ITT ) with r and om-effects regression to account for the cluster-r and omised design . Adverse events were synonymous with the trial outcomes . This trial is registered with Clinical Trials.gov , number NCT00211341 . FINDINGS 544 clusters ( 104 484 women ) were r and omly assigned to vitamin A supplementation and 542 clusters ( 103 297 women ) were assigned to placebo . The main reason for participant drop out was migration out of the study area . In the ITT analysis , there were 39 601 pregnancies and 138 pregnancy-related deaths in the vitamin A supplementation group ( 348 deaths per 100 000 pregnancies ) compared with 39 234 pregnancies and 148 pregnancy-related deaths in the placebo group ( 377 per 100 000 pregnancies ) ; adjusted odds ratio 0.92 , 95 % CI 0.73 - 1.17 ; p=0.51 . 1326 women died in 292 560 woman-years in the vitamin A supplementation group ( 453 deaths per 100 000 years ) compared with 1298 deaths in 289 310 woman-years in the placebo group ( 449 per 100 000 years ) ; adjusted rate ratio 1.01 , 0.93 - 1.09 ; p=0.85 . INTERPRETATION The body of evidence , although limited , does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies . FUNDING UK Department for International Development , and USAID OBJECTIVE Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome . We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1 . DESIGN AND METHODS In Durban , South Africa 728 pregnant HIV infected women received either vitamin A ( 368 ) or placebo ( 360 ) in a r and omized , double-blind trial . The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery . HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis . Results are reported on mother-to-child transmission rates up to 3 months of age . RESULTS There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [ 20.3 % ; 95 % confidence interval ( CI ) , 15.7 - 24.9 ] and placebo groups ( 22.3 % ; 95 % CI , 17.5 - 27.1 ) , nor were there differences in foetal or infant mortality rates between the two groups . Women receiving vitamin A supplement were , however , less likely to have a preterm delivery ( 11.4 % in the vitamin A and 17.4 % in the placebo group ; P = 0.03 ) and among the 80 preterm deliveries , those assigned to the vitamin A group were less likely to be infected ( 17.9 % ; 95 % CI , 3.5 - 32.2 ) than those assigned to the placebo group ( 33.8 % ; 95 % CI , 19.8 - 47.8 ) . CONCLUSION Vitamin A supplementation , a low-cost intervention , does not appear to be effective in reducing overall mother-to-child transmission of HIV ; however , its potential for reducing the incidence of preterm births , and the risk of mother-to-child transmission of HIV in these infants needs further investigation BACKGROUND Prophylactic vitamin A supplementation ( VAS ) reduces mortality and may reduce morbidity associated with diarrhea in children > 6 months of age . Rotavirus is the most common cause of acute dehydrating diarrhea among children worldwide . METHODS In a r and omized placebo-controlled study of 50,000 IU of vitamin A versus placebo given with bacille Calmette-Guérin vaccine at birth , 287 infants were followed up with weekly interviews and stool sample obtainment to test the hypothesis that VAS reduced the risk of rotavirus infection . RESULTS VAS was associated with increased risk of rotavirus infection and diarrhea ( incidence rate ratio [ IRR ] of infection , 1.72 [ 95 % confidence interval ( CI ) , 1.04 - 2.85 ] ; IRR of diarrhea , 3.74 [ 95 % CI , 1.40 - 9.98 ] ) among children < 6 months of age . There was no effect in older children . VAS had a beneficial effect on nonrotavirus diarrhea in boys < 6 months of age ( IRR , 0.51 ; 95 % CI , 0.27 - 0.95 ) and a detrimental effect in girls > 6 months of age ( IRR , 1.84 ; 95 % CI , 0.96 - 3.55 ) . CONCLUSION VAS at birth did not reduce rotavirus morbidity . The effect of VAS on nonrotavirus diarrhea may differ by sex , being more beneficial in boys . Clinical trials registration . NCT00168597 In recent years , neonatal vitamin A supplementation is considered as an essential infant-survival intervention but the evidence is not conclusive . This r and omized controlled clinical trial was conducted to evaluate the effect of vitamin A on immune competence in early infancy . Results would provide a mechanistic basis for underst and ing the effect of this intervention on infant survival . Within 2 days of birth , infants born at one maternity clinic located in a poor slum area of Dhaka city were supplemented with either 50,000 IU vitamin A or placebo . Live attenuated oral polio vaccine ( OPV ) and BCG vaccine were provided after supplementation . Infants also receive diphtheria , pertussis , tetanus ( TT ) , hepatitis B ( HBV ) and Haemophilus influenzae B vaccines ( pentavalent combination ) along with OPV at 6 , 10 and 14 weeks of age . Infant thymus size , anthropometry , feeding practice and morbidity data were collected at regular interval . Infant blood sample s were collected to determine T-cell-receptor excision circle ( TREC ) , total , naïve and memory T cells and mucosal targeting lymphocytes including Treg cells . TT- , HBV- , BCG- and OPV-specific T cell blastogenic , cytokine and plasma cell antibody responses were also measured . In 16 mo enrollment period , 306 newborns , equal number of boys and girls , were enrolled . ~95 % completed the 4-month follow-up period . Baseline characteristics are presented here . Anthropometry and immune assays with fresh blood sample s were completed immediately while stored sample s were analyzed in single batches at the end of the trial . Connecting different aspects of immunological data in early infancy will help eluci date immune competence for protecting infection . Trial registration Clinical Trials.gov : NCT01583972 Microbiota and infant development Malnutrition in children is a persistent challenge that is not always remedied by improvements in nutrition . This is because a characteristic community of gut microbes seems to mediate some of the pathology .  Human gut microbes  can be transplanted effectively into germ-free mice to recapitulate their associated phenotypes . Using this model , Blanton et al. found that the microbiota of healthy children relieved the harmful effects on growth caused by the microbiota of malnourished children . In infant mammals , chronic undernutrition results in growth hormone resistance and stunting . In mice , Schwarzer et al. showed that strains of Lactobacillus plantarum in the gut microbiota sustained growth hormone activity via signaling pathways in the liver , thus overcoming growth hormone resistance . Together these studies reveal that specific beneficial microbes could potentially be exploited to resolve undernutrition syndromes . Science , this issue p. 10.1126/science.aad3311 , p. 854 Microbes from healthy children protect mice from the detrimental effects of the microbiota of malnourished infants . INTRODUCTION As we come to appreciate how our microbial communities ( microbiota ) assemble following birth , there is an opportunity to determine how this facet of our developmental biology relates to the healthy or impaired growth of infants and children . Childhood undernutrition is a devastating global health problem whose long-term sequelae , including stunting , neurodevelopmental abnormalities , and immune dysfunction , remain largely refractory to current therapeutic interventions . RATIONALE To test the hypothesis that perturbations in the normal development of the gut microbiota are causally related to undernutrition , we first applied r and om forests ( RF ) , a machine learning method , to bacterial 16S ribosomal RNA data sets generated from fecal sample s that were collected serially from healthy Malawian infants and children during their first 3 postnatal years . Age-discriminatory bacterial taxa were identified with distinctive time-dependent changes in their relative abundances ; they were used to construct a sparse RF-derived model describing a program of normal postnatal gut microbiota development that is shared across biologically unrelated individuals . A metric based on this model ( microbiota-for-age Z-score ) was used to define the state of development ( maturation ) of fecal microbiota from infants and children with varying degrees of undernutrition . Fecal sample s obtained from 6- and 18-month-old children with healthy growth patterns or with varying degrees of undernutrition were transplanted into young germ-free mice that were fed a representative Malawian diet . The recipient animals ’ rate of lean body mass gain was characterized by serial quantitative magnetic resonance , their metabolic phenotypes were determined by targeted mass spectrometry , and their femoral bone morphologic features were delineated by microcomputed tomography . RESULTS Undernourished children in the Malawian birth cohort that we studied have immature gut microbiota . Unlike microbiota from healthy children , immature microbiota transmit impaired growth , altered bone morphology , and metabolic abnormalities in the muscle , liver , and brain to recipient gnotobiotic mice . The representation of several age-discriminatory taxa in the transplanted microbiota harbored by recipient animals correlated with their growth rates . Microbiota from 6-month-old infants produced greater effects on growth than did microbiota from 18-month-old children , although in each age bin , the growth effects produced by a healthy donor ’s community were greater than those produced by an undernourished donor ’s community . Cohousing coprophagic mice shortly after they received microbiota from healthy or severely stunted and underweight 6-month-old infants result ed in the invasion of age- and growth-discriminatory taxa from the former into the latter microbiota in the recipient animals , with associated prevention of growth impairments . Introducing cultured members from this group of invasive species ameliorated growth and metabolic abnormalities in recipients of microbiota from undernourished donors . CONCLUSION These pre clinical findings provide evidence that gut microbiota immaturity is causally related to childhood undernutrition . The age- and growth-discriminatory taxa that we identified should help direct studies of the effects of host and environmental factors on gut microbial community development , and they represent therapeutic targets for repairing or preventing gut microbiota immaturity . Pre clinical evidence that gut microbiota immaturity is causally related to childhood undernutrition . ( A ) A model of normal gut microbial community development in Malawian infants and children , based on the relative abundances of 25 bacterial taxa that provide a microbial signature defining the “ age , ” or state of maturation , of an individual ’s ( fecal ) microbiota . ( Hierarchical clusterings of operational taxonomic units are indicated on the left . ) ( B ) Fecal sample s from healthy ( H ) or stunted and underweight ( Un ) infants and children were transplanted into separate groups of young germ-free mice that were fed a Malawian diet . The immature microbiota of Un donors transmitted impaired growth phenotypes to the mice . ( C ) Evidence that a subset of age-discriminatory taxa are also growth-discriminatory . Cohousing mice shortly after they received microbiota from 6-month-old healthy or undernourished donors result ed in the invasion of taxa from the healthy donor ’s microbiota ( HCH ) into the undernourished donor ’s microbiota ( UnCH ) among recipient animals and prevented growth impairments . Adding cultured invasive growth-discriminatory taxa directly to the Un donor ’s microbiota ( Un+ ) improved growth .  Undernourished children exhibit impaired development of their gut microbiota .  Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children transmit impaired growth phenotypes . The representation of several age-discriminatory taxa in recipient animals correlated with lean body mass gain ; liver , muscle , and brain metabolism ; and bone morphology .  Mice were cohoused shortly after receiving microbiota from healthy or severely stunted and underweight infants ; age- and growth-discriminatory taxa from the microbiota of the former were able to invade that of the latter , which prevented growth impairments in recipient animals . Adding two invasive species , Ruminococcus gnavus and Clostridium symbiosum , to the microbiota from undernourished donors also ameliorated growth and metabolic abnormalities in recipient animals . These results provide evidence that microbiota immaturity is causally related to undernutrition and reveal potential therapeutic targets and agents
BACKGROUND Vitamin A deficiency is a significant public health problem in low- and middle-income countries .
Vitamin A supplementation provided to infants less than six months of age is one of the strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity .
OBJECTIVES To evaluate the effect of synthetic vitamin A supplementation in infants one to six months of age in low- and middle-income countries , irrespective of maternal antenatal or postnatal vitamin A supplementation status , on mortality , morbidity and adverse effects .