Rapid early growth is associated with increased risk of childhood type 1 diabetes in various European populations. Cow milk feeding in infancy: gastrointestinal blood loss and iron nutritional status. Association of consumption of products containing milk fat with reduced asthma risk in pre-school children: the PIAMA birth cohort study GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). Early infant feeding and type 1 diabetes Relationship of diet in the development of atopy in infancy Fecal alpha 1-antitrypsin and hemoglobin excretion in healthy human milk-, formula-, or cow's milk-fed infants. Environmental risk factors in prediction of childhood prediabetes. Iron status at 12 months of age — effects of body size, growth and diet in a population with high birth weight GRADE guidelines: 3. Rating the quality of evidence. Follow‐on formula in the prevention of iron deficiency: a multicentre study Development of atopic dermatitis according to age of onset and association with early-life exposures. Prevention of anaemia in inner city toddlers by an iron supplemented cows' milk formula. Different β-Casein Fractions in Icelandic Versus Scandinavian Cow's Milk May Influence Diabetogenicity of Cow's Milk in Infancy and Explain Low Incidence of Insulin-Dependent Diabetes Mellitus in Iceland Infant formulas and gastrointestinal illness. Environmental Factors in Childhood IDDM: A population-based, case-control study
OBJECTIVE To confirm that early growth is associated with type 1 diabetes risk in European children and eluci date any role of infant feeding . RESEARCH DESIGN AND METHODS Five centers participated , each with a population -based register of type 1 diabetes diagnosed at < 15 years of age . Control subjects were r and omly chosen from population registers , schools , or polyclinics . Growth data were obtained from routine records and infant feeding information from parental question naire or interview . Patient/control subject differences in mean st and ard deviation score ( SDS ) were obtained for each center and pooled . Odds ratios ( ORs ) were pooled by the Mantel-Haenszel method , and logistic regression was used to adjust for confounders . RESULTS Growth data were available for 499 patients and 1,337 control subjects .  Height and weight SDS were significantly increased among patients from 1 month after birth , the maximum differences of 0.32 ( 95 % CI 0.14 - 0.50 ) and 0.41 ( 0.26 - 0.55 ) , respectively , occurring between 1 and 2 years of age . Significant excesses in BMI SDS were observed from 6 months of age , with the largest difference of 0.27 ( 0.10 , 0.44 ) evident between 1 and 2 years . Breast-feeding was associated with reduced disease risk , OR 0.75 ( 0.58 - 0.96 ) . Introduction of cow 's milk , formula , or solid foods before 3 months was not associated with significant risk elevation . CONCLUSION Increased early growth is associated with disease risk in various European population s. Any role of infant feeding in this association remains unclear Eighty-one normal infants were studied between 112 and 196 days of age . Thirty-nine infants were fed pasteurized cow milk and the remainder were fed either Enfamil or heat-treated cow milk . During the age interval of 112 to 140 days , the proportion of infants with guaiac-positive stools was significantly ( P less than 0.01 ) greater among infants fed pasteurized cow milk than among those fed Enfamil or heat-treated cow milk . Similarly , infants fed cow milk had a significantly ( P less than 0.001 ) greater number of guaiac-positive stools than did the other infants . After 140 days of age , there was no difference between feeding groups in the number of guaiac-positive stools . No significant differences were observed in mean hemoglobin , hematocrit , serum iron , total iron-binding capacity , or transferrin saturation between feeding groups nor between infants with and those without guaiac-positive stools , It is concluded that pasteurized cow milk should not be fed before 140 days of age Background : Environment and lifestyle contribute to the development of asthma in children . Underst and ing the relevant factors in this relationship may provide methods of prevention . The role of diet in the development of asthma in pre-school children was investigated . Methods : Data from 2978 children participating in a prospect i ve birth cohort study were used . Food frequency data were collected at the age of 2 years and related to asthma symptoms reported at the age of 3 years . Results : The prevalence of recent asthma at age 3 was lower in children who consumed ( at age 2 ) full cream milk daily ( 3.4 % ) than in those who did not ( 5.6 % ) and in those who consumed butter daily ( 1.5 % ) than in those who did not ( 5.1 % ) . The prevalence of recent wheeze was lower in children who consumed milk products daily ( 13.7 % ) than in those who did not ( 18.4 % ) and in children who consumed butter daily ( 7.7 % ) than in those who did not ( 15.4 % ) . These effects remained in a logistic regression model including different foods and confounders ( adjusted odds ratio ( CI ) for recent asthma : full cream milk daily v rarely 0.59 ( 0.40 to 0.88 ) , butter daily v rarely 0.28 ( 0.09 to 0.88 ) ) . Daily consumption of brown bread was also associated with lower rates of asthma and wheeze , whereas no associations were observed with the consumption of fruits , vegetables , margarine , and fish . Conclusions : In pre-school children , frequent consumption of products containing milk fat is associated with a reduced risk of asthma symptoms In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Background Infant feeding practice s , particularly the type of milk feeding , have been associated with the development of type 1 diabetes . Aim of the study We studied the relationship between early infant feeding ( during the first year of life ) and diabetes in a large population -based cohort . Methods In 1994–1995 , 6,209 healthy full-term newborns participated in a study examining the effect of supplementary feeding , on development of allergy to cow ’s milk , in maternity hospitals . All supplements in the maternity hospitals were known . Mothers recorded the feeding of infants prospect ively at home . In August 2006 , from a nationwide diabetes registry , 45 children from our cohort were listed as having type 1 diabetes . Results The distribution of cases was similar in the r and omized feeding groups : 9/1,789 in the group that received adapted cow ’s milk-based formula ; 12/1,737 in those who received extensively hydrolyzed formula ; 16/1,859 in those who received banked human milk ; and 8 among those 824 exclusively breast-fed in the hospital . When children who had received cow ’s milk-based formula in the maternity hospital were compared with those without such exposure , less number of children in the former group had diabetes by age 8 ( P = 0.026 ) , but by the end of the follow-up ( 11.5 years ) the difference disappeared ( P = 0.16 ) . Length of breast-feeding and introduction of cereals and other solid foods were similar among those developing type 1 diabetes and those remaining healthy , while early regular daily feeding with cow ’s milk-based formula tended to associate with lower risk for type 1 diabetes ( OR 0.66 ; 95 % confidence interval 0.38–1.13 ; P = 0.08 ) . Conclusions In an extended , secondary analysis of a population -based cohort , very early exposure to cow ’s milk is not a risk factor for type 1 diabetes ; it may in fact diminish its appearance before age 8 We examined the relationship of diet to the development of atopic manifestations in a group of infants with an immediate family history of atopy , followed prospect ively from birth for up to 20 months of age . There was no relationship between the development of atopic dermatitis , rhinitis and wheeze and either 2 or 4 months exclusive breast feeding , or the introduction of cow 's milk or solids in the first 4 months of life . In addition there was no relationship between the introduction of milk , egg or wheat into the diet and the development of skin‐test positivity to these foods . In fact , five infants developed positive skin tests to the food prior to its introduction into the diet , suggesting exposure via maternal breast milk . Thus we have been unable to show a protective effect of either breast feeding or cow 's milk or solid avoidance on the development of atopic disease in infancy There is concern that whole cow 's milk feedings may be associated with intestinal abnormalities in infants . We studied this issue by measuring r and om fecal sample s for alpha 1-antitrypsin ( FA1AT ) and hemoglobin ( FH ) concentrations in 820 healthy infants up to 12 months of age . Subjects were fed either human milk , formula , or fresh whole cow 's milk . Solid foods were given ad libitum . Fecal sample s were also tested for occult blood with Hematest reagent tablets . None of the infants younger than 6 months of age were receiving fresh whole cow 's milk . We found small but statistically significant differences in mean FA1AT between the three feeding groups ( P less than .0001 ) : human milk ( n = 354 ) greater than formula ( n = 320 ) greater than cow 's milk ( n = 146 ) . The younger subjects fed either formula or human milk tended to have higher FA1AT concentrations than did the age-matched subjects who were not consuming solid foods ( P less than or equal to .005 ) . Daily FA1AT excretion , FA1AT concentration , and daily stool output were subsequently determined on a separate group of 40 infants 8 to 12 months of age to ascertain whether differences in total daily FA1AT excretion occur in children fed different types of milk . Total daily FA1AT excretion was similar in the three milk feeding groups . An inverse correlation between FA1AT concentration and daily stool output was also found ( P less than .001 ) . The overall rate of detectable FH in 792 stool smears was 2.1 % and unrelated to type of milk feeding . Of 705 stool smears , 3.5 % had positive Hematest reactions . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE The damage of beta cells occurs during the asymptomatic prodromal period called prediabetes before onset of diabetes mellitus . It is characterized by the presence of islet cell autoantibodies ( ICAs ) . The aim of this study was to find out what environmental factors predict ICA seroconversion in healthy schoolchildren in Lithuania . MATERIAL AND METHODS Sera from 3053 nondiabetic schoolchildren living in Lithuania were investigated for ICAs . ICAs were measured in undiluted sera by indirect immunofluorescence method . All ICA-positive and r and omly selected ICA-negative children were invited to participate in the study . Response rate in the families of ICA-positive children was 100 % and in ICA-negative-76.5 % . Data from 13 ICA-positive and 199 ICA-negative schoolchildren were included in the analysis . Information on the environmental factors was collected via question naires . RESULTS Proportions of breastfed children were similar in ICA-positive and ICA-negative schoolchildren . Full cow 's milk was introduced at one month of age or earlier more often in ICA-positive than ICA-negative schoolchildren ( 8.3 % and 1.1 % , respectively ; P=0.05 ) . Cereal before 3 months of age was introduced more often in ICA-positive than ICA-negative schoolchildren ( 7.7 % and 0.5 % , respectively ; P=0.01 ) . The mothers of cases took medicine during pregnancy more often than mothers of controls did ( 61.5 % and 14.1 % , respectively ; P<0.001 ) . More than half ( 53.8 % ) of ICA-positive children lived in homes where family members were smoking indoors , while this was recorded only for 26.6 % of controls ( P=0.04 ) . CONCLUSIONS Early introduction of cow 's milk and cereal , the intake of medicine during pregnancy , and indoor smoking of family members are risk factors that predict the development of prediabetes among Lithuanian children Objective : To investigate effects of growth and food intake in infancy on iron status at the age of 12 months in a population with high birth weight and high frequency of breast-feeding . Design : In a longitudinal observational study infants ' consumption and growth were recorded . Weighed 2 day food records at the ages of 6 , 9 and 12 months were used to analyse food and nutrient intake . Setting : Healthy-born participants were recruited from four maternity wards .  Blood sample s and growth data were collected from healthcare centres and food consumption data at home . Subjects : Newborn infants ( n=180 ) were selected r and omly according to the mother 's domicile and 77 % ( n=138 ) participated , of them , 83 % ( n=114 ) , or 63 % of original sample , came in for blood sampling . Results : Every fifth child was iron-deficient ( serum ferritin<12 µg/l and mean corpuscular volume<74 fl ) and 2.7 % were also anaemic ( Hb<105 g/l ) . Higher weight gain from 0 to 12 months was seen in infants who were iron-deficient at 12 months ( 6.7±0.9 kg ) than in non-iron-deficient infants ( 6.2±0.9 kg ) ( P=0.050 ) . Serum transferrin receptors at 12 months were positively associated with length gain from 0 to 12 months ( adjusted r 2=0.14 ; P=0.045 ) and mean corpuscular volume negatively to ponderal index at birth ( adjusted r 2=0.14 ; P=0.019 ) and 12 months ( adjusted r 2=0.17 ; P=0.006 ) . Iron-deficient infants had shorter breast-feeding duration ( 5.3±2.2 months ) than non-iron-deficient ( 7.9±3.2 months ; P=0.001 ) . Iron status indices were negatively associated with cow 's milk consumption at 9–12 months , significant above 460 g/day , but were positively associated with iron-fortified breakfast cereals , fish and meat consumption . Conclusions : In a population of high birth weight , iron deficiency at 12 months is associated with faster growth and shorter breast-feeding duration from 0 to 12 months of age . The results suggest that a diet of 9–12-month-olds should avoid cow 's milk above 500 g/day and include fish , meat and iron-fortified breakfast cereals to improve iron status . Sponsorship : The Icel and ic Research Council , Research Fund of the University of Icel and This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Abstract Six‐month‐old infants were recruited at 21 centres in the UK and Irel and and r and omly assigned to receive matching iron‐fortified ( 12.3 mg/l iron ) or non‐fortified ( 1.4 mg/l iron ) formula for 9 months . Infants already receiving cow 's milk continued this feed . Haematological indices and iron status were evaluated at age 6 months , 9–10 months and 15 months . Four hundred and six infants entered and 302 completed the study . There were no differences between the groups for increases in weight , head circumference or length . Significant differences between the groups were observed at 15 months for haemoglobin , serum ferritin , serum iron and total iron binding capacity . Haemoglobin levels were < 110 g/l in 33 % of infants fed cow 's milk compared with 13 % and 11 % in those receiving non‐iron‐fortified and iron‐fortified formula respectively . The corresponding figures for serum ferritin < 10 µg/l were 43 % , 22 % and 6 % . Follow‐on formula provides an acceptable vehicle for preventing iron deficiency in this vulnerable group BACKGROUND Environmental factors can affect the development of  atopic dermatitis  , and this was described to be already effective during pregnancy and in early life . An important early postnatal exposure is nutrition , although its association with allergic disease remains unclear . OBJECTIVE We sought to determine prospect ively whether early postnatal exposures , such as the introduction to complementary food in the first year of life , are associated with the development of atopic dermatitis , taking into account the reverse causality . METHODS One thous and forty-one children who participated in the Protection Against Allergy- Study in Rural Environments birth cohort study were included in the current study .  Atopic dermatitis  was defined by a doctor 's diagnosis reported by the parents of children up to 4 years of age , by question naires , and /or by positive SCORAD scores from 1 year of age and according to the age of onset within or after the first year of life . Feeding practice s were reported by parents in monthly diaries between the 3rd and 12th months of life . RESULTS The diversity of introduction of complementary food in the first year of life was associated with a reduction in the risk of having atopic dermatitis with onset after the first year of life ( adjusted odds ratio for atopic dermatitis with each additional major food item introduced , 0.76 ; 95 % CI , 0.65 - 0.88 ) . The introduction of yogurt in the first year of life also reduced the risk for atopic dermatitis ( adjusted odds ratio , 0.41 ; 95 % CI , 0.23 - 0.73 ) . CONCLUSION As early-life exposure , the introduction of yogurt and the diversity of food introduced in the first year of life might have a protective effect against atopic dermatitis There are few data to support the use of follow-on formulas in infants from the age of 6 months . In a prospect i ve trial in a deprived inner city area of Birmingham 100 infants who were already receiving pasteurised cows ' milk by 6 months of age were enrolled and r and omised either to receive a follow-on formula or to continue on cows ' milk from 6 months until 18 months . At 18 months of age the follow-on formula group returned to cows ' milk and both groups were followed up until 24 months . Iron status , growth , and nutritional status were analysed at intervals of six months . At enrollment , no differences in haematological status were evident . However , by 12 months of age , 31 % of the cows ' milk group were anaemic ( haemoglobin concentration < 110 g/l ) compared with only 3 % of those receiving follow-on formulas . At 18 months , 33 % of the cows ' milk group were anaemic compared with only 2 % of the follow-on formula group and by 24 months of age none of the follow-on formula group was anaemic , whereas 26 % in the cows ' milk group still had a haemoglobin of < 110 g/l . Mean corpuscular volume was significantly smaller and ferritin significantly lower in the cows ' milk group at 12 , 18 , and 24 months . Dietary iron intake was higher in the follow-on formula group at 12 and 18 months but not at 24 months , when both groups were back on cows ' milk . Infants and toddlers at high risk of iron deficiency are therefore unlikely to become anaemic if receiving a follow-on formula , although the relative merits of follow-on formula compared with an ordinary infant formula remain uncertain Objectives . To compare children with insulin-dependent diabetes mellitus ( IDDM ) with controls in Icel and regarding their consumption of  cow 's milk in infancy , and to investigate the β-casein fractions in Sc and inavian and Icel and ic cow 's milk . The A1 variant of β-casein has been shown to be diabetogenic in animal studies , and suggestions have been made that the B variant of β-casein acts similarly . Differences in the relative proportions of β-casein fractions might explain the lower incidence of IDDM in Icel and than in Sc and inavia . Methods . A retrospective case – control study on IDDM patients and matching controls was performed in Icel and to compare their diets in infancy . Fifty-five children with IDDM born in Icel and over a 16-year period and r and omly collected controls ( n = 165 ) were recruited to the study . Mothers of the children answered questions on breastfeeding habits and on when cow 's milk products were introduced . Sample s of cow 's milk from r and omly selected milk batches from the largest consumption areas in Icel and and Sc and inavia were collected . The milk sample s were freeze-dried and their β-casein fractions were analyzed using capillary electrophoresis . Results . No significant difference was found between IDDM patients and controls in the frequency and duration of breastfeeding or the first introduction of cow 's milk products . The analyses of milk sample s showed that the percentage of the A1 and B variants of β-casein in Icel and ic milk was significantly lower than in the milk from the Sc and inavian countries . Conclusions . Cow 's milk consumption in infancy is not related to IDDM in Icel and . The lower fraction of A1 and B β-caseins in Icel and ic cow 's milk may explain why there is a lower incidence of IDDM in Icel and than in Sc and inavia Infants under age one in a pediatric practice were followed prospect ively , and the determinants of acute gastrointestinal illness were evaluated in case-control pairs , matched by birth month . The risk of acute gastrointestinal illness in infants receiving formula  was six times greater than in infants receiving breast milk and 2.5 times greater than in infants receiving cow milk . In the second six months of life , infants on  formula had 0.38 more gastrointestinal illness episodes per child than infants on cow milk .  Episodes without rotavirus or bacterial agents accounted for most of the increased risk of formula . The increased risk could not be explained by iron fortification of the formulas , prescription of non-milk based formulas to high-risk infants , case ascertainment bias , control selection bias , or numerous control factors . Non-antibody anti-infection properties found in cow milk are one possible explanation for these findings OBJECTIVE To identify environmental factors involved in the etiology of  insulin-dependent diabetes mellitus ( IDDM ) . RESEARCH DESIGN AND METHODS An estimated 90 % of all incident cases of IDDM in patients 0–14 years of age in New South Wales , Australia , were ascertained over 18 months . For each IDDM patient , two age- and sex-matched control subjects were r and omly selected from the population . Past environmental exposures were determined with a question naire completed by the parents . Response rates were 92 % for the IDDM patients ( 217 of 235 ) and 55 % for the control subjects ( 258 of 470 ) . The relative risk associated with each exposure was estimated with the odds ratio ( OR ) adjusted for confounding factors using multiple logistic regression . RESULTS The introduction of cow 's milk-based infant formula into the diet before 3 months of age was associated with an increased risk ( OR 1.52 , 95 % confidence interval [ CI ] 1.04–2.24 ) . Exclusive breast-feeding for ≥3 months was associated with a protective effect ( OR 0.66 , 95 % CI 0.45–0.97 ) . High dietary intake of cow 's milk protein in the 12 months before the onset of diabetic symptoms was also associated with an increased risk ( OR 1.84 , 95 % CI 1.12–3.00 ) . A recent infection ( during the 3 months before onset of diabetic symptoms ) was more common in the patients than the control subjects ( OR 2.92 , 95 % CI 1.96–4.35 ) , as was day care attendance before the age of 3 ( OR 1.73 , 95 % CI 1.00–3.00 ) . When two age-groups , defined by the median age at onset of diabetes , were compared , the associations with early infant-feeding were stronger among the younger group ( < 9.2 years ) , and associations with recent diet and recent infection were stronger among the older group ( ≥9.2 years ) . CONCLUSIONS These results indicate an increased risk of IDDM associated with early dietary exposure to cow 's milk-containing formula , short duration of exclusive breast-feeding , high intake of cow 's milk protein in the recent diet , recent infection , and early attendance at day care
OBJECTIVE To summarize the best available evidence regarding the short- and long-term health effects of cow 's milk intake in healthy , full-term infants up to 3 years of age .