Effects of size at birth, gestational age and early growth in preterm infants on glucose and insulin concentrations at 9–12 years Multicentre trial on feeding low birthweight infants: effects of diet on early growth. Cardiovascular risk factors at age 30 following pre-term birth. Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies Low nutrient intake and early growth for later insulin resistance in adolescents born preterm IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMI. Low birth weight and later development of insulin resistance and biochemical/clinical features of polycystic ovary syndrome. Preterm birth and later insulin resistance: effects of birth weight and postnatal growth in a population based longitudinal study from birth into adult life Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Former small for gestational age (SGA) status is associated to changes of insulin resistance in obese children during weight loss.
Aims /hypothesis . To test the hypothesis that small size for gestation and poor postnatal growth in preterm infants is associated with higher fasting and post-load plasma glucose and insulin concentrations at 9–12 years of age.¶ Methods . Prospect i ve follow-up at 9–12 years of 385 preterm children with birth weight less than 1850 g , who had anthropometry recorded at birth , 18 months and 7 years .  Fasting plasma glucose , insulin , proinsulin and 32,33 split proinsulin concentrations and glucose and insulin concentrations 30 min after a st and ard glucose load were measured.¶ Results . Post-load glucose concentrations were negatively related to birth weight , independently of gestation or subsequent growth . Fasting split proinsulin and 30-min insulin concentrations were highest in children who showed the greatest increase in weight centile between birth and current follow-up , regardless of gestation . When weight during childhood was included , birthweight centile was , however , no longer statistically significant : concentrations of fasting , split , proinsulin and 30-min insulin were highest in those children who had shown the greatest increase in weight centile between 18 months of age and current follow-up , with no evidence of a greater effect in those who were smallest at 18 months.¶ Conclusion /interpretation . Our findings suggest that fetal growth influences plasma glucose 30 min after a glucose load in preterm children at 9–12 years . In contrast , childhood weight gain is the most important factor influencing insulin concentrations and this effect is the same regardless of early size . [ Diabetologia ( 2000 ) 43 : 714–717 A large multicentre study on the short and long term clinical and developmental outcome of infants r and omised to different diets is being undertaken . This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants ( gestation , mean ( SD ) 31 . 0 ( 2 . 9 ) weeks ; birthweight , mean ( SD ) 1364 ( 294 ) g ) , both ill and well , examined in two ( of four ) parallel trials . One trial compared banked breast milk with a new preterm formula ( primary trial ) ; the other compared these diets as supplements to maternal milk ( supplement trial ) . A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight , length , and head circumference was observed in the primary trial . Infants fed banked breast milk  and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula . A significant influence of diet on body proportions was seen in the relation between body weight , head circumference , and length . Similar though smaller differences in growth patterns were seen in the supplement trial . By the time they reach 2000 g , infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented ( as necessary ) with banked breast milk , fulfilled stringent criteria for failure to thrive ( weight less than 2 SD below the mean for age ) . Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital . The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised BACKGROUND Recent epidemiological evidence has shown increased rates of cardiovascular mortality and associated risk factors in those born small . However , scarce information exists concerning cardiovascular risk factors in adulthood following pre-term birth , or distinguishing the relative contributions of length of gestation and fetal growth to small size at birth . METHODS Prospect i ve follow-up of 458 30-year-olds whose mothers took part in a r and omized controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome ( 147 born at term , 311 born pre-term ) . Follow-up assessment s included anthropometry , blood pressure , blood lipids , early morning cortisol levels and  75 g oral glucose tolerance test .  RESULTS Gestational age at birth , pre-term birth , and birth weight z-score were not associated with serum cholesterol , triglyceride or cortisol at age 30 ( P > 0.1 for all ) . However , pre-term birth was associated with increased systolic blood pressure ( 3.5 mmHg , 95 % CI 0.9 - 6.1 mmHg , P = 0.009 ) and insulin resistance at age 30 [ Log ( Insulin area under the curve ) = 0.17 , 95 % CI 0.05 - 0.28 , P = 0.006 ] . Low gestational age at birth was also associated with these outcomes , whereas birth weight , adjusted for gestational age , was not . CONCLUSIONS Adults who were born moderately pre-term have increased blood pressure and insulin resistance at 30 years of age . Pre-term birth rather than poor fetal growth is the major determinant of this association . As both the incidence of pre-term birth and survival amongst those born pre-term are increasing , this group may contribute an increasing proportion to overall cardiovascular disease burden Objective To determine outcomes at age 3 years in babies born before 27 completed weeks ’ gestation in 2006 , and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks ’ gestation . Design Prospect i ve national cohort studies , EPICure and EPICure 2 . Setting Hospital and home based evaluations , Engl and . Participants 1031 surviving babies born in 2006 before 27 completed weeks ’ gestation . Outcomes for 584 babies born at 22 - 25 weeks ’ gestation were compared with those of 260 surviving babies of the same gestational age born in 1995 . Main outcome measures Survival to age 3 years , impairment ( 2008 consensus definitions ) , and developmental scores . Multiple imputation was used to account for the high proportion of missing data in the 2006 cohort . Results Of the 576 babies evaluated after birth in 2006 , 13.4 % ( n=77 ) were categorised as having severe impairment and 11.8 % ( n=68 ) moderate impairment . The prevalence of neurodevelopmental impairment was significantly associated with length of gestation , with greater impairment as gestational age decreased : 45 % at 22 - 23 weeks , 30 % at 24 weeks , 25 % at 25 weeks , and 20 % at 26 weeks ( P<0.001 ) . Cerebral palsy was present in 83 ( 14 % ) survivors . Mean developmental quotients were lower than those of the general population ( normal values 100 ( SD 15 ) ) and showed a direct relation with gestational age : 80 ( SD 21 ) at 22 - 23 weeks , 87 ( 19 ) at 24 weeks , 88 ( 19 ) at 25 weeks , and 91 ( 18 ) at 26 weeks . These results did not differ significantly after imputation . Comparing imputed outcomes between the 2006 and 1995 cohorts , the proportion of survivors born between 22 and 25 weeks ’ gestation with severe disability , using 1995 definitions , was 18 % ( 95 % confidence interval 14 % to 24 % ) in 1995 and 19 % ( 14 % to 23 % ) in 2006 . Fewer survivors had shunted hydrocephalus or seizures . Survival of babies admitted for neonatal care increased from 39 % ( 35 % to 43 % ) in 1995 to 52 % ( 49 % to 55 % ) in 2006 , an increase of 13 % ( 8 % to 18 % ) , and survival without disability increased from 23 % ( 20 % to 26 % ) in 1995 to 34 % ( 31 % to 37 % ) in 2006 , an increase of 11 % ( 6 % to 16 % ) . Conclusion Survival and impairment in early childhood are both closely related to gestational age for babies born at less than 27 weeks ’ gestation . Using multiple imputation to account for the high proportion of missing values , a higher proportion of babies admitted for neonatal care now survive without disability , particularly those born at gestational ages 24 and 25 weeks BACKGROUND In animals , acceleration of neonatal growth is thought to increase the later propensity to insulin resistance and non-insulin-dependent diabetes , whereas slow growth as a consequence of undernutrition is thought to have a beneficial effect . To test this hypothesis in people , we measured fasting concentrations of 32 - 33 split proinsulin , a marker of insulin resistance , in adolescents born preterm who had participated in r and omised intervention trials of neonatal nutrition , and in adolescents born at term . METHODS We determined fasting 32 - 33 split proinsulin concentration in participants aged 13 - 16 years born preterm and r and omised to receive a nutrient-enriched or lower-nutrient diet ( n=216 ) or in a reference group born at term ( n=61 ) . FINDINGS Fasting 32 - 33 split proinsulin concentration was greater in children given a nutrient-enriched diet ( geometric mean 7.2 pmol/L , 95 % CI 6.4 - 8.1 ) than in those given the lower-nutrient diet ( 5.9 pmol/L [ 5.2 - 6.4 ] ; mean difference 20.6 % [ 5.0 - 36.3 ] ; p=0.01 ) . Healthy babies born at term had similar fasting 32 - 33 split proinsulin concentrations ( 6.9 pmol/L ; 6.0 - 8.2 ) to the nutrient-enriched group . In non-r and omised analyses , fasting 32 - 33 split proinsulin concentration was associated with greater weight gain the first 2 weeks of life ( 13.2 % [ 5.4 - 20.9 ] change per 100 g weight increase ; p=0.001 ) independent of birthweight , gestation , neonatal morbidity , and demographic , anthropometric , and socioeconomic factors . INTERPRETATION Our results suggest that relative undernutrition early in life in children born preterm may have beneficial effects on insulin resistance OBJECTIVE Impaired fetal development may contribute to decreased insulin sensitivity . This study was design ed to characterize serum markers of insulin resistance in adults born small for date or born prematurely . STUDY DESIGN Fifty subjects , all women , were evaluated at a mean age + /- SD of 26 + /- 2 years ( range : 23 - 30 years ) . They were allocated to three groups : ( i ) born fullterm with birth weight < 2600 g ( n = 18 ) ( small for gestational age , SGA ) , ( ii ) born before gestational week 32 ( n = 15 ) ( ex-preterm ) , and ( iii ) controls , born fullterm with appropriate birth weight ( n = 17 ) .  Anthropometric data as well as  fasting serum sample s of plasma B-glucose , serum lipids , insulin , insulin-like growth factor-I ( IGF-I ) and insulin-like growth factor binding protein-1 ( IGFBP-1 ) levels were determined . RESULTS In the SGA group final height was lower and they weighed less compared with the controls . Fasting insulin and glucose levels did not differ amongst the groups . Triglycerides were lower in the SGA group and in the ex-preterm group compared with the controls ( P < 0.05 ) . The SGA group showed lower IGFBP-1 levels compared with the controls median 17 ( range 3 - 121 ) vs. 26 ( 7 - 67 ) microg L-1 ; P < 0.05 ] . The IGF-I levels in the SGA , ex-preterm and control groups were 212 + /- 58 , 259 + /- 37 and 216 + /- 32 microg L-1 , respectively , corresponding to a mean SD score of -0.8 + /- 1.0 , 0.1 + /- 0.6 and -0.6 + /- 0.6 . CONCLUSION As IGFBP-1 is a marker of insulin sensitivity , the low levels observed in adult women with normal BMI , born small for date , suggest relative insulin resistance in spite of normal BMI Reduced insulin sensitivity in adult life has been reported in subjects born at term small for gestational age ( SGA ) and in those born prematurely with very low birth weight ( LBW ) ( < 1,500 g ) . We assessed whether LBW ( < 2,500 g ) young women , irrespective of whether they were born SGA or adequate for gestational age ( premature AGA ) , exhibited a reduction in insulin sensitivity through a prospect i ve historical design . The risk of developing biochemical and clinical features of polycystic ovary syndrome was also investigated . The study population included 35 LBW women ( 19 SGA [ BW range , 1,000 - 2,400 g ] and 16 premature AGA [ BW range , 1,700 - 2,440 g ] ) aged 21.8 + /- 1.8 years and 35 term AGA controls , of similar age , recruited from a neonatal registry . All women underwent clinical , ultrasonographic , hormonal , and metabolic evaluations , including the composite insulin sensitivity index . Women under hormonal contraception ( 21.4 % ) were excluded from hormonal and metabolic analyses . Composite insulin sensitivity index was significantly lower in LBW women even when the 2 LBW subgroups , SGA and premature AGA , were analyzed separately ( 4.4 + /- 2.2 and 4.0 + /- 1.7 , respectively ) than in controls ( 6.9 + /- 4.4 ) . The LBW women showed a significantly higher incidence proportion of irregular menses ( 14/35 [ 40 % ] vs 2/35 [ 5.7 % ] ) and a significantly higher free and rogen index ( 5.8 + /- 3.5 vs 3.9 + /- 3.2 ) . They also showed a nonsignificantly higher proportion of hirsutism , acne , and polycystic ovaries . In conclusion , LBW ( < 2,500 g ) young women , irrespective of whether they were SGA and premature AGA , exhibited a reduction in insulin sensitivity as compared with born at term AGA women . Furthermore , they exhibited an increased risk of developing clinical and biochemical features of polycystic ovary syndrome Aims /hypothesisAn increased risk of type 2 diabetes mellitus is associated with low birthweight after full-term gestation , including amplification of this risk by weight gain during infancy and adult body composition . Premature birth is also associated with insulin resistance , but studies conducted so far have not provided follow-up into adulthood . We studied the effects of ( 1 ) lower birthweight ( as st and ard deviation score [ SDS ] ) and infancy weight gain on insulin resistance in 19-year-olds born before 32 weeks of gestation , and ( 2 ) the interaction between lower birthweight SDS and infancy weight gain , as well as between lower birthweight and adult body composition , on insulin resistance . Methods This was a prospect i ve follow-up study in 346 subjects from the Project on Preterm and Small-for-gestational-age infants cohort , in whom fasting glucose , insulin and C-peptide levels were measured at 19 years . Insulin resistance was calculated with homeostatic modelling ( homeostatic model assessment for insulin resistance index [ HOMA-IR ] ) . Results Birthweight SDS was unrelated to the outcomes . Rapid infancy weight gain until 3 months post-term was weakly associated with higher insulin level ( p=0.05 ) . Adult fatness was positively associated with insulin and C-peptide levels and HOMA-IR ( all p<0.001 ) . On these parameters , there was a statistical interaction between birthweight SDS and adult fat mass ( p=0.002 to 0.03 ) . Conclusions /interpretationIn subjects born very preterm , rapid infancy weight gain until 3 months predicted higher insulin levels at 19 years , but the association was weak . Adult obesity strongly predicted higher insulin and C-peptide levels as well as HOMA-IR . The effect of adult fat mass on these parameters was dependent on its interaction with birthweight SDS BACKGROUND Nutrient intakes meeting recommended dietary intakes ( RDIs ) take time to establish and once established are rarely maintained throughout hospital stay in preterm infants . A nutrient deficit , therefore , accrues . RDI are based on needs for maintenance and growth , with no provision to replace this deficit . We , therefore , hypothesized that postnatal malnutrition and growth retardation were inevitable in infants fed current RDI . METHODOLOGY Dietary intakes were prospect ively collected , by a single observer ( N.P. ) , on a daily basis in a group of preterm infants ( n = 105 ; birth weight < /=1750 g ; gestational age < /=34 weeks ) admitted to neonatal intensive care unit over a 6-month period . Actual was subtracted from recommended energy ( 120 kcal/kg/day ) and protein ( 3 g/kg/day ) intakes and nutritional deficits calculated . Infants were weighed on admission and throughout hospital stay . The data were analyzed using a combination of repeated measures analysis of variance and stepwise regression analysis . RESULTS Nutrient intakes meeting current RDIs were rarely achieved during early life . By the end of the first week , cumulative energy and protein deficits were 406 + /- 92 and 335 + /- 86 kcal/kg and 14 + /- 3 and 12 + /- 4 g/kg in infants < /=30 and those at > /=31 weeks . By the end of the fifth week , cumulative energy and protein deficits were 813 + /- 542 and 382 + /- 263 kcal/kg and 23 + /- 12 and 13 + /- 15 g/kg and the z scores were -1.14 + /-.6 and -.82 + /-.5 for infants at < /=30 and > /=31 weeks . Stepwise regression analysis indicated that variation in dietary intake accounted for 45 % of the variation in changes in z score . CONCLUSIONS Preterm infants inevitably accumulate a significant nutrient deficit in the first few weeks of life that will not be replaced when current RDIs are fed . This deficit can be directly related to subsequent postnatal growth retardation.postnatal growth retardation , preterm infants OBJECTIVE Former small for gestational age ( SGA ) children are at risk of both obesity and insulin resistance . Longitudinal studies are required to assess a possible relationship between former SGA status and insulin resistance independent of weight status . We hypothesized that obese children with former appropriate for gestational age ( AGA ) status improve their insulin resistance during weight loss more effectively compared to obese children with former SGA status . METHODS A 1-yr longitudinal follow-up study design was adopted in the primary care setting and 341 obese children [ 8 % SGA , mean age 10.5 + /- 0.1 yr , body mass index ( BMI ) 27.7 + /- 0.2 , BMI -st and ard deviation score ( SDS ) 2.47 + /- 0.02 ] were taken for the study . Outpatient 1-yr intervention was based on exercise , behavior and nutrition therapy . We measured insulin resistance index following the Homeostasis model assessment model ( HOMA ) , blood pressure , lipids , glucose , and insulin in all children before and after the 1-yr intervention . RESULTS In a multiple linear regression analysis adjusted for age , gender , and pubertal stage , changes of HOMA were significantly related to changes of BMI -SDS ( -2.55 per loss of 1 BMI -SDS unit ; p < 0.001 ) and SGA status ( + 2.05 for SGA children ; p < 0.001 ) . Changes of BMI -SDS together with gender and age explained 10 % of the variance of changes of HOMA , while SGA status explained an additional 4 % . After adjustment for age , sex , pubertal stage , and BMI -SDS , former SGA status was not significantly related to any other considered cardiovascular risk factor . CONCLUSIONS Change of weight status predicted change of HOMA in obese children participating in a lifestyle intervention . Changes of HOMA were also predicted by former SGA status supporting that former SGA status influences insulin resistance
OBJECTIVE The incidence of preterm birth is increasing worldwide .
Evidence suggests that in later life these children are at increased risk of ' metabolic syndrome ' , which is itself associated with reduced insulin sensitivity ( IS ) .
We carried out a systematic review to examine whether preterm birth is associated with later changes in IS and whether a difference exists between those born small-for-gestational age ( SGA ) and appropriate-for-gestational age ( AGA ) .