Human milk feeding and cognitive outcome in preterm infants: the role of infection and NEC reduction.

BACKGROUND: Breast milk has been associated with lower risk of infection and necrotising enterocolitis (NEC) and improved long-term cognitive outcomes in preterm infants but, if unsupplemented, does not meet the nutritional requirements of preterm infants. METHODS: Preterm infants were randomised to receive a high nutrient intervention diet: preterm formula (PTF) or the standard diet: term formula (TF) or banked donor breast milk (BBM), either as their sole diet or as supplement to maternal breast milk (MBM). IQ tests were performed at ages 7, 15, 20, and 30 years. RESULTS: An increase in MBM and BBM intake was associated with a lower chance of neonatal infection/NEC. Neonatal infection/NEC was associated with lower Full Scale IQ (FSIQ) and Performance IQ (PIQ) score at ages 7 and 30 years. The relationship between higher intake of MBM and PIQ at age 7 years was partly mediated by neonatal infection/NEC. The intervention diet was associated with higher Verbal IQ (VIQ) scores compared to the standard diet. There was no evidence that these effects changed from childhood through to adulthood. CONCLUSIONS: Neonatal diet is an important modifiable factor that can affect long-term cognitive outcome through a 'human milk' factor, protecting against infection/NEC, and a 'nutrient content' factor. IMPACT: This is the first study to demonstrate the effects of neonatal infection/necrotising enterocolitis (NEC) on IQ in the same cohort in childhood and adulthood. Diet can be a key factor in long-term cognitive outcome in people born preterm by preventing neonatal infection/NEC and providing adequate nutrients. Human milk, whether MBM or BBM, is associated with a reduced risk of infection/NEC. A higher nutrient diet is associated with better cognitive outcome in childhood. Performance IQ is particularly vulnerable to the effects of infection/NEC and verbal IQ to the quantity of (macro)nutrients in the diet.

An economic analysis of human milk supplementation for very low birth weight babies in the USA.

BACKGROUND: An exclusive human milk diet (EHMD) using human milk based products (pre-term formula and fortifiers) has been shown to lead to significant clinical benefits for very low birth weight (VLBW) babies (below 1250 g). This is expensive relative to diets that include cow's milk based products, but preliminary economic analyses have shown that the costs are more than offset by a reduction in the cost of neonatal care. However, these economic analyses have not completely assessed the economic implications of EHMD feeding, as they have not considered the range of outcomes affected by it. METHODS: We conducted an economic analysis of EHMD compared to usual practice of care amongst VLBW babies in the US, which is to include cow's milk based products when required. Costs were evaluated from the perspective of the health care payer, with societal costs considered in sensitivity analyses. RESULTS: An EHMD substantially reduces mortality and improves other health outcomes, as well as generating substantial cost savings of $16,309 per infant by reducing adverse clinical events. Cost savings increase to $117,239 per infant when wider societal costs are included. CONCLUSIONS: An EHMD is dominant in cost-effectiveness terms, that is it is both cost-saving and clinically beneficial, for VLBW babies in a US-based setting.

Diabetes Status and Race are Associated with Cardiovascular Risk Markers in Obese Adolescents.

OBJECTIVE: The objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies. METHODS: This was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children's of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM). RESULTS: There were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P<.0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (ß, 4.21; P<.0001) and non-HDL-C (ß, 4.3; P<.0001). CONCLUSION: Obese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA1c concentration.

DIABETES AND PREDIABETES ARE SIGNIFICANTLY HIGHER IN MORBIDLY OBESE CHILDREN COMPARED WITH OBESE CHILDREN.

OBJECTIVE: The objective of this study was to examine the prevalence and characteristics of comorbidities in obese and morbidly obese children with a comparison between the 2 sets of children. METHODS: This was a retrospective electronic chart review of obese and morbidly obese children and adolescents as defined by body mass index. We evaluated medical history of comorbid conditions, medication use, and cardiovascular risk markers, including blood pressure, lipid profile, and glycosylated hemoglobin. RESULTS: There were 1,111 subjects (African American = 635; non-Hispanic white = 364; Hispanic = 36; others = 86), of which 274 were obese and 837 were morbidly obese children with a mean age of 12.7 ± 3.37 years. Morbidly obese children had a higher prevalence of prediabetes (19.5% of obese versus 27.3% of morbidly obese; P<.0001) and type 2 diabetes (39.8% of obese versus 52.4% of morbidly obese; P<.0001). Use of medications for treatment of asthma was significantly higher in the morbidly obese group compared with the obese group (21% versus 14%; P = .01). CONCLUSION: Morbidly obese children have a higher prevalence of diabetes, prediabetes, and use of asthma medications compared with obese children.

Right ventricular systolic dysfunction in young adults born preterm.

BACKGROUND: Young adults born preterm have distinct differences in left ventricular mass, function, and geometry. Animal studies suggest that cardiomyocyte changes are evident in both ventricles after preterm birth; therefore, we investigated whether these young adults also have differences in their right ventricular structure and function. METHODS AND RESULTS: We studied 102 preterm-born young adults followed up prospectively since birth and 132 term-born control subjects born to uncomplicated pregnancies. We quantified right ventricular structure and function by cardiovascular magnetic resonance on a 1.5-T Siemens scanner using Argus and TomTec postprocessing software. Preterm birth was associated with a small right ventricle (end diastolic volume, 79.8±13.2 versus 88.5±11.8 mL/m(2); P<0.001) but greater right ventricular mass (24.5±3.5 versus 20.4±3.4 g/m2; P<0.001) compared with term-born controls, with the severity of differences proportional to gestational age (r=-0.47, P<0.001). Differences in right ventricular mass and function were proportionally greater than previously reported for the left ventricle. This was most apparent for systolic function; young adults born preterm had significantly lower right ventricular ejection fraction (57±8% versus 60±5%; P=0.006). Indeed, 21% had values below the lower limit observed in the term-born adults and 6% had mild systolic dysfunction (<45%). Postnatal ventilation accounted for some of the variation in mass but not function. CONCLUSIONS: Preterm birth is associated with global myocardial structural and functional differences in adult life, including smaller right ventricular size and greater mass. The changes are greater in the right ventricle than previously observed in the left ventricle, with potentially clinically significant impairment in right ventricular systolic function.

Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function.

BACKGROUND: Preterm birth leads to an early switch from fetal to postnatal circulation before completion of left ventricular in utero development. In animal studies, this results in an adversely remodeled left ventricle. We determined whether preterm birth is associated with a distinct left ventricular structure and function in humans. METHODS AND RESULTS: A total of 234 individuals 20 to 39 years of age underwent cardiovascular magnetic resonance. One hundred two had been followed prospectively since preterm birth (gestational age=30.3±2.5 week; birth weight=1.3±0.3 kg), and 132 were born at term to uncomplicated pregnancies. Longitudinal and short-axis cine images were used to quantify left ventricular mass, 3-dimensional geometric variation by creation of a unique computational cardiac atlas, and myocardial function. We then determined whether perinatal factors modify these left ventricular parameters. Individuals born preterm had increased left ventricular mass (66.5±10.9 versus 55.4±11.4 g/m(2); P<0.001) with greater prematurity associated with greater mass (r = -0.22, P=0.03). Preterm-born individuals had short left ventricles with small internal diameters and a displaced apex. Ejection fraction was preserved (P>0.99), but both longitudinal systolic (peak strain, strain rate, and velocity, P<0.001) and diastolic (peak strain rate and velocity, P<0.001) function and rotational (apical and basal peak systolic rotation rate, P =0.05 and P =0.006; net twist angle, P=0.02) movement were significantly reduced. A diagnosis of preeclampsia during the pregnancy was associated with further reductions in longitudinal peak systolic strain in the offspring (P=0.02, n=29). CONCLUSIONS: Individuals born preterm have increased left ventricular mass in adult life. Furthermore, they exhibit a unique 3-dimensional left ventricular geometry and significant reductions in systolic and diastolic functional parameters. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01487824.

Extraction of esophageal foreign bodies in children: rigid versus flexible endoscopy.

PURPOSE: Foreign body (FB) ingestion is a common and potentially serious problem in children. Both rigid (RE) and flexible (FE) endoscopic techniques are used for removal of esophageal FBs; however, there is no consensus amongst pediatric surgeons regarding the best method. This study reviewed our experience managing esophageal FBs using both techniques. METHODS: A 12-year retrospective review of children admitted with an esophageal FB between 1999 and 2012 was undertaken. Clinical data, management techniques, and complications were abstracted. Differences between these two groups were compared with standard statistical methods. RESULTS: 657 children were treated for esophageal FB ingestion, of which 366 (56%) were treated with FE. The most frequently ingested item was a coin (84%), and FBs were most commonly lodged in the upper third of the esophagus (78%). There was a slightly younger population in the FE group (4.0 vs. 3.3 years, p < 0.01), but otherwise no significant differences were found between the groups. The FB was successfully removed with the initially chosen technique in 97% of patients. CONCLUSIONS: Esophageal FBs may be successfully removed with either RE or FE. Since treatment failures were managed with conversion to the other technique, both procedures should be included in the training curriculum.

Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants.

OBJECTIVE: To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk. STUDY DESIGN: Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC). RESULTS: Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively (P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04. CONCLUSIONS: In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit.

Short-term exposure to exogenous lipids in premature infants and long-term changes in aortic and cardiac function.

OBJECTIVE: Intravenous lipid use is associated with an acute hyperlipidemia, but long-term consequences have not been studied. We investigated whether elevated lipids in humans during the critical period of preterm neonatal life have a long-term impact on aortic and myocardial function relevant to adult disease. METHODS AND RESULTS: We followed up 102 subjects born prematurely and now aged 23 to 28 years. Eighteen received intravenous lipids as neonates and were matched to controls with equivalent perinatal characteristics. Global and regional aortic stiffness and left ventricular function were assessed by cardiovascular magnetic resonance. Those who received intravenous lipids had greater aortic stiffness in early adulthood (P=0.0002), with greater stiffness in the abdominal aorta (P=0.012). The relationship was graded according to the elevation in neonatal cholesterol induced by intravenous lipids (P<0.0001) but not other metabolic parameters altered by the infusion. Peak systolic circumferential strain was also reduced in the lipid group (P=0.006), which, again, was proportional to neonatal cholesterol level (P<0.01). CONCLUSIONS: Aortic and myocardial function in young adulthood is associated with intralipid exposure during neonatal life for preterm infants, in a graded manner related to the rise in cholesterol. Circulating cholesterol during critical developmental periods may have long-term impacts on the human cardiovascular system.

Effect of nutritionally modified infant formula on academic performance: linkage of seven dormant randomised controlled trials to national education data.

OBJECTIVE: To compare differences in academic performance between adolescents who were randomised in infancy to modified or standard infant formula. DESIGN: Linkage of seven dormant randomised controlled trials to national education data. SETTING: Five hospitals in England, 11 August 1993 to 29 October 2001, and schools in England, September 2002 to August 2016. PARTICIPANTS: 1763 adolescents (425 born preterm, 299 born at term and small for gestational age, 1039 born at term) who took part in one of seven randomised controlled trials of infant formula in infancy. INTERVENTIONS: Nutrient enriched versus standard term formula (two trials), long chain polyunsaturated fatty acid (LCPUFA) supplemented versus unsupplemented formula (two trials), high versus low iron follow-on formula (one trial), high versus low sn-2 palmitate formula (one trial), and nucleotide supplemented versus unsupplemented formula (one trial). MAIN OUTCOME MEASURES: The primary outcome, determined by linkage of trial data to school data, was the mean difference in standard deviation scores for mandated examinations in mathematics at age 16 years. Secondary outcomes included differences in standard deviation scores in English (16 and 11 years) and mathematics (11 years). Analysis was by intention to treat with multiple imputation for participants missing the primary outcome. RESULTS: 1607 (91.2%) participants were linked to school records. No benefit was found for performance in mathematics examinations at age 16 years for any modified formula: nutrient enriched in preterm infants after discharge from hospital, standard deviation score 0.02 (95% confidence interval -0.22 to 0.27), and nutrient enriched in small for gestational age term infants -0.11 (-0.33 to 0.12); LCPUFA supplemented in preterm infants -0.19 (-0.46 to 0.08) and in term infants -0.14 (-0.36 to 0.08); iron follow-on formula in term infants -0.12 (-0.31 to 0.07); and sn-2 palmitate supplemented formula in term infants -0.09 (-0.37 to 0.19). Participants from the nucleotide trial were too young to have sat their General Certificate of Secondary Education (GCSE) examinations at the time of linkage to school data. Secondary outcomes did not differ for nutrient enriched, high iron, sn-2 palmitate, or nucleotide supplemented formulas, but at 11 years, preterm and term participants randomised to LCPUFA supplemented formula scored lower in English and mathematics. CONCLUSIONS: Evidence from these randomised controlled trials indicated that the infant formula modifications did not promote long term cognitive benefit compared with standard infant formulas.

The Preterm Heart-Brain Axis in Young Adulthood: The Impact of Birth History and Modifiable Risk Factors.

People born preterm are at risk of developing both cardiac and brain abnormalities. We aimed to investigate whether cardiovascular physiology may directly affect brain structure in young adulthood and whether cardiac changes are associated with modifiable biomarkers. Forty-eight people born preterm, followed since birth, underwent cardiac MRI at age 25.1 ± 1.4 years and brain MRI at age 33.4 ± 1.0 years. Term born controls were recruited at both time points for comparison. Cardiac left and right ventricular stroke volume, left and right ventricular end diastolic volume and right ventricular ejection fraction were significantly different between preterm and term born controls and associated with subcortical brain volumes and fractional anisotropy in the corpus callosum in the preterm group. This suggests that cardiovascular abnormalities in young adults born preterm are associated with potentially adverse future brain health. Associations between left ventricular stroke volume indexed to body surface area and right putamen volumes, as well as left ventricular end diastolic length and left thalamus volumes, remained significant when adjusting for early life factors related to prematurity. Although no significant associations were found between modifiable biomarkers and cardiac physiology, this highlights that cardiovascular health interventions may also be important for brain health in preterm born adults.

An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products.

OBJECTIVE: To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants. STUDY DESIGN: Infants fed their own mothers' milk were randomized to 1 of 3 study groups. Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor human milk if no mother's milk was available. Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother's milk was available. Outcomes included duration of parenteral nutrition, morbidity, and growth. RESULTS: The 3 groups (total n = 207 infants) had similar baseline demographic variables, duration of parenteral nutrition, rates of late-onset sepsis, and growth. The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis (NEC; P = .02) and NEC requiring surgical intervention (P = .007). CONCLUSIONS: For extremely premature infants, an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother's milk-based diet that also includes bovine milk-based products.

Impact of breast milk on intelligence quotient, brain size, and white matter development.

Although observational findings linking breast milk to higher scores on cognitive tests may be confounded by factors associated with mothers' choice to breastfeed, it has been suggested that one or more constituents of breast milk facilitate cognitive development, particularly in preterms. Because cognitive scores are related to head size, we hypothesized that breast milk mediates cognitive effects by affecting brain growth. We used detailed data from a randomized feeding trial to calculate percentage of expressed maternal breast milk (%EBM) in the infant diet of 50 adolescents. MRI scans were obtained (mean age=15 y 9 mo), allowing volumes of total brain (TBV) and white and gray matter (WMV, GMV) to be calculated. In the total group, %EBM correlated significantly with verbal intelligence quotient (VIQ); in boys, with all IQ scores, TBV and WMV. VIQ was, in turn, correlated with WMV and, in boys only, additionally with TBV. No significant relationships were seen in girls or with gray matter. These data support the hypothesis that breast milk promotes brain development, particularly white matter growth. The selective effect in males accords with animal and human evidence regarding gender effects of early diet. Our data have important neurobiological and public health implications and identify areas for future mechanistic study.

Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age--IPD meta-analysis of 4 large clinical trials.

OBJECTIVES: To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis. MATERIALS AND METHODS: Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups. RESULTS: There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were -0.8 (95% confidence interval -2.8 to 1.2) and -1.0 (-2.7 to 0.7), respectively. CONCLUSIONS: These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.

Preterm Infants Fed Cow's Milk-Derived Fortifier Had Adverse Outcomes Despite a Base Diet of Only Mother's Own Milk.

Objective: An increasingly common practice is to feed preterm infants a base diet comprising only human milk (HM), usually fortified with a cow's milk (CM)-derived fortifier (CMDF). We evaluated the safety of CMDF in a diet of 100% mother's own milk (MOM) against a HM-derived fortifier (HMDF). To date, this has received little research attention. Study Design: We reanalyzed a 12-center randomized trial, originally comparing exclusive HM feeding, including MOM, donor milk (DM), and HMDF, versus a CM exposed group fed MOM, preterm formula (PTF), and CMDF1. However, for the current study, we performed a subgroup analysis (n = 114) selecting only infants receiving 100% MOM base diet plus fortification, and fed no DM or PTF. This allowed for an isolated comparison of fortifier type: CMDF versus HMDF to evaluate the primary outcomes: necrotizing enterocolitis (NEC) and a severe morbidity index of NEC surgery or death; and several secondary outcomes. Results: CMDF and HMDF groups had similar baseline characteristics. CMDF was associated with higher risk of NEC; relative risk (RR) 4.2 (p = 0.038), NEC surgery or death (RR 5.1, p = 0.014); and reduced head circumference gain (p = 0.04). Conclusions: In neonates fed, as currently recommended with a MOM-based diet, the safety of CMDF when compared to HMDF has been little researched. We conclude that available evidence points to an increase in adverse outcomes with CMDF, including NEC and severe morbidity comprising NEC surgery or death.

Early diet and general cognitive outcome at adolescence in children born at or below 30 weeks gestation.

OBJECTIVE: To test the hypothesis that effects of early diet on cognition observed at age 8 years persist in adolescents born preterm at < or = 30 weeks gestational age. STUDY DESIGN: A subgroup from a preterm infant cohort recruited for a randomized trial studying the effects of early dietary intervention was assessed at age 16 years. IQ scores were compared between those assigned a high-nutrient diet (n = 49) or standard-nutrient diet (n = 46) in infancy at both 8 and 16 years. RESULTS: At age 8 years, the high-nutrient group had higher mean Verbal IQ (VIQ; P = .03), Performance IQ (P = .01), and Full-Scale IQ (P = .02) scores compared with the standard-nutrient group; the VIQ difference persisted at adolescence (P = .02). This effect was accounted for principally by a significant difference in the mean Verbal Comprehension Index score (P < .008). CONCLUSIONS: A brief period of dietary intervention after preterm birth, principally between 26 and 34 weeks of gestation, affected IQ at age 16 years. A standard-nutrient diet was associated with lower VIQ, accounted for mainly by differences in verbal comprehension, which persisted after control of social factors.

IPD meta-analysis shows no effect of LC-PUFA supplementation on infant growth at 18 months.

AIM: Clinical trials on the effects of long-chain polyunsaturated fatty acids (LC-PUFA) supplementation of formula milk on growth of term and preterm children have shown conflicting results. We examined the effects of LC-PUFAs-- especially docosahexaenoic acid (DHA) and arachidonic acid (AA)--on growth at 18 months. METHODS: We performed a meta-analysis based on individual patient data (IPD) of 901 children from four large, randomised clinical trials of formula milk with and without LC-PUFAs. Anthropometrics were assessed by z-scores based on weight for age, length for age, head circumference for age and body mass index (BMI) for age at 18 months. The studies differed in LC-PUFA composition and infant characteristics (two studies on preterm children, two on term children). RESULTS: Multivariate regression analyses including the possible confounders, sex, gestational age, birth weight, smoking in the last trimester and maternal age, as well as interaction terms showed no significant effects of LC-PUFA supplementation on any z-score. Subgroup analyses on trials with high amounts of DHA and on studies with duration of supplementation of at least 6 months yielded the same result. These findings cannot be explained by the lack of power. CONCLUSION: Our IPD meta-analysis shows no evidence that LC-PUFA supplementation affects children's growth at 18 months of age.

Early growth and body composition in infancy.

UNLABELLED: Examination of the relationship between early growth and body composition (BC) in infancy might provide clues about the mechanism of early nutrition programming. 150 healthy full-term infants (64 boys) born in Cambridge from 1985-1993 had BC measured using stable isotope at the age of 12 weeks as a part of infant nutrition studies. Fat mass index (FMI, FM/length(2)) and lean mass index (LMI, LM/length(2)) internal standard deviation scores (SDS) were calculated for boys and girls. Birth weight SDS was positively associated with length, BMI and FMI SDS at 12 weeks, but not LMI SDS; equivalent to 0.26 SDS increase in FMI per 1 SDS increase in birth weight (95% CI, 0.04-0.48). Weight SDS change from birth-12 weeks was positively correlated with FMI and LMI SDS at 12 weeks; equivalent to 0.68 SDS and 0.48 SDS increase in FMI and LMI per 1 SDS gain in weight (95% CI, 0.48-0.88 and 0.26-0.70, respectively). Associations were independent of gender, parity, infant diets, and, for weight gain, birth weight SDS. CONCLUSION: Higher birth weight was associated with higher fat mass at 3 months whereas rapid weight gain in the first 3 months was associated with both fat and lean mass. Our data do not support the hypothesis that lean mass tracks directly from fetal life to childhood.

Scientific Evidence for Breastfeeding.

The global drive to promote breastfeeding targeted at all 134 million infants born/year on the planet is one of the most pervasive public health interventions. It is, therefore, critical that the breastfeeding field is rooted in sound evidence. Three important scientific pillars of breastfeeding have been: (1) that human milk (HM) is the product of 200 million years of mammalian evolution; (2) that HM composition should be seen as the gold standard for infant nutritional requirements; and (3) that HM has numerous clinical benefits for the infant. I shall look carefully at these areas to help pave the way to a more solid basis for modern breastfeeding medicine. Firstly, I shall look at evolutionary theory for human breastfeeding and consider in general terms the implications for optimal nutritional care of breastfed infants. Secondly, I shall show how HM composition has been incorrectly translated into dietary intake in a large body of past flawed work that resulted in misleading data. Implementing such data as a model for infant formula appears to have increased the risk of obesity and cardiovascular disease (CVD) in formula-fed infants. Finally, most studies that examine the benefits of HM are observational and potentially confounded. So, this body of data needs to be backed by experimental evidence. Here, I shall use preterm infants as a model, since numerous RCTs and physiological studies over 40 years have compared exclusive HM feeding versus cow's milk exposure. Unexpectedly diverse immediate beneficial effects span the field of neonatology, and long-term programmed effects have been shown for cognition, brain structure, risk factors for CVD, structural development of the heart and lungs, bone health, and atopy. These data add much weight to the evidence, obtained in full-term infants using observational study designs, that HM feeding in early life may fundamentally and permanently change the biology of the organism. Breastfeeding is emerging as a major evidence-based field of medical and public health practice.