Human milk composition is variable. The identification of influencing factors and interdependencies of components may help to understand the physiology of lactation. In this study, we analyzed linear trends in human milk composition over time, the variation across different European countries and the influence of maternal celiac disease. Within a multicenter European study exploring potential prevention of celiac disease in a high-risk population (PreventCD), 569 human milk samples were donated by women from five European countries between 16 and 163 days postpartum. Some 202 mothers provided two samples at different time points. Protein, carbohydrates, fat and fatty acids, insulin, adiponectin, and insulin-like growth factor II (IGF-II) were analyzed. Milk protein and n-6 long chain polyunsaturated fatty acids decreased during the first three months of lactation. Fatty acid composition was significantly influenced by the country of residence. IGF-II and adiponectin concentrations correlated with protein content (r = 0.24 and r = 0.35), and IGF-II also correlated with fat content (r = 0.36), suggesting a possible regulatory role of IGF in milk macronutrient synthesis. Regarding the impact of celiac disease, only the level in palmitic acid was influenced by this disease, suggesting that breastfeeding by celiac disease mothers should not be discouraged.

BACKGROUND:Elevated stearoyl-CoA desaturase 1 (SCD-1) activity showed associations with obesity in cross-sectional studies. In non-pregnant populations, nutrition regulates SCD-1 transcription and activity.OBJECTIVE:To investigate the longitudinal associations of maternal and fetal SCD-1 activity markers with infant anthropometry up to 2 years of age, and to explore how selected dietary intakes modulate SCD-1 activity in pregnancy.METHODS:As a secondary analysis from the ROLO intervention study, which was conducted in a population at risk for macrosomia, non-esterified fatty acids (NEFA) from maternal plasma at 13 and 28 weeks' gestation and in cord blood were measured via liquid-chromatography-mass-spectrometry. Fatty acid ratios 18:1/18:0 and 16:1/16:0 were used as markers for SCD-1 activity ('desaturation indices', DIs). Relationships of DIs with infant anthropometry up to 2 years of age and maternal dietary parameters during pregnancy were investigated using adjusted linear regression models and p-values correction for multiple testing.RESULTS:18:1/18:0, but not 16:1/16:0, was associated with measures of infant anthropometry at birth (maternal and fetal markers) and up to 2 years of age (maternal markers only). Dietary intakes did not show strong associations with 18:1/18:0, but 16:1/16:0 was associated with absolute and relative dietary intakes.CONCLUSIONS:In a population at risk for macrosomia, maternal SCD-1 activity measured via 18:1/18:0 was involved in the fetal programming of infant obesity, but could not be substantially modulated by short-term diet in pregnancy.CLINICAL TRIAL REGISTRATION:ISRCTN Registration number: ISRCTN54392969 (http://www.isrctn.com/ISRCTN54392969).

Objectives A high dairy protein intake in infancy, maternal pre-pregnancy BMI, and delivery mode are documented early programming factors that modulate the later risk of obesity and other health outcomes, but the mechanisms of action are not understood. Methods The Childhood Obesity Project is a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants. Participating infants were either breastfed (BF) or randomized to receive higher (HP) or lower protein (LP) content formula in the first year of life. At the ages 5.5 years ( n = 276) and 8 years ( n = 232), we determined plasma metabolites by liquid chromatography tandem-mass-spectrometry of which 226 and 185 passed quality control at 5.5 years and 8 years, respectively. We assessed the effects of infant feeding, maternal pre-pregnancy BMI, smoking in pregnancy, delivery mode, parity, birth weight and length, and weight gain (0–24 months) on the metabolome at 5.5 and 8 years. Results At 5.5 years, plasma alpha-ketoglutarate and the acylcarnitine/BCAA ratios tended to be higher in the HP than in the LP group, but no metabolite reached statistical significance ( P bonferroni >0.09). There were no group differences at 8 years. Quantification of the impact of early programming factors revealed that the intervention group explained 0.6% of metabolome variance at both time points. Except for country of residence that explained 16% and 12% at 5.5 years and 8 years, respectively, none of the other factors explained considerably more variance than expected by chance. Conclusions Plasma metabolome was largely unaffected by feeding choice and other early programming factors and we could not prove the existence of a long term programming effect of the plasma metabolome.

Today, awareness has been raised regarding high consumption of n-6 polyunsaturated fatty acids (PUFA) in western diets. A comprehensive analysis of total and individual postprandial fatty acids profiles would provide insights into metabolic turnover and related health effects. After an overnight fast, 9 healthy adults consumed a mixed meal comprising 97 g carbohydrate and 45 g fat, of which 26.4 g was linoleic acid (LA). Nonesterified fatty acids (NEFA), phospholipid fatty acids (PL-FA) and triacylglycerol fatty acids (TG-FA) were monitored in plasma samples, at baseline and hourly over a 7-h postprandial period. Total TG-FA concentration peaked at 2 h after the meal and steadily decreased thereafter. LA from TG18:2n-6 and behenic acid from TG22:0 showed the highest response among TG-FA, with a biphasic response detected for the former. PL-FA exhibited no change. Total NEFA initially decreased to nadir at 1 h, then increased to peak at 7 h. The individual NEFA showed the same response curve except LA and some very-long-chain saturated fatty acids (VLCSFA, ≥20 carbon chain length) that markedly increased shortly after the meal intake. The similarities and dissimilarities in lipid profiles between study subjects at different time points were visualized using nonmetric multi-dimensional scaling. Overall, the results indicate that postprandial levels of LA and VLCSFA, either as NEFA or TG, were most affected by the test meal, which might provide an explanation for the health effects of this dietary lifestyle characterized by high intake of mixed meals rich in n-6 PUFA.

Childhood obesity prevalence is rising in countries worldwide. A variety of etiologic factors contribute to childhood obesity but little is known about underlying biochemical mechanisms. We performed an individual participant meta-analysis including 1,020 pre-pubertal children from three European studies and investigated the associations of 285 metabolites measured by LC/MS-MS with BMI z-score, height, weight, HOMA, and lipoprotein concentrations. Seventeen metabolites were significantly associated with BMI z-score. Sphingomyelin (SM) 32:2 showed the strongest association with BMI z-score (P = 4.68 × 10 −23 ) and was also closely related to weight, and less strongly to height and LDL, but not to HOMA. Mass spectrometric analyses identified SM 32:2 as myristic acid containing SM d18:2/14:0. Thirty-five metabolites were significantly associated to HOMA index. Alanine showed the strongest positive association with HOMA (P = 9.77 × 10 −16 ), while acylcarnitines and non-esterified fatty acids were negatively associated with HOMA. SM d18:2/14:0 is a powerful marker for molecular changes in childhood obesity. Tracing back the origin of SM 32:2 to dietary source in combination with genetic predisposition will path the way for early intervention programs. Metabolic profiling might facilitate risk prediction and personalized interventions in overweight children.

Objectives: Fetal and early life represent a period of developmental plasticity during which metabolic pathways are modified by environmental and nutritional cues. Little is known on the pathways underlying this multifactorial complex. We explored whether 6 months old breast-fed infants could be clustered into metabolically similar groups and that those metabotypes could be used to predict later obesity risk. Methods: Plasma samples were obtained from 183 breast-fed infants aged 6 months participating in the European multicenter Childhood Obesity Project study. We measured amino acids along with polar lipid concentrations (acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins). We determined the metabotypes using a Bayesian agglomerative clustering method and investigated the properties of these clusters with respect to clinical, programming, and metabolic factors up to 6 years of age. Results: We identified 20 metabolite clusters comprising 1 to 39 children. Phosphatidylcholines predominantly influenced the clustering process. In the largest clusters (n ≥ 14), large differences existed for birth length (unadjusted P < 0.0001) and length and weight at 6 months (unadjusted P < 0.0001 and P = 0.012, respectively). Infants tended to cluster together by country (unadjusted P < 0.001). The body mass index (BMI) z score at 6 years of age tended to differ (unadjusted P = 0.07). Conclusions: Our exploratory study provided evidence that breast-fed infants are not metabolically homogeneous and that variation in metabolic profiles among infants may provide insight into later development and health. This work highlights the potential of metabotypes for identifying inter-individual differences that may form the basis for developing personalized early preventive strategies.

SCOPE:The fetal programming paradigm posits that the origins of obesity can be traced, in part, to the intrauterine period of life. However, the mechanisms underlying fetal programming are not well understood, and few studies have measured offspring adiposity in the neonatal period. The aim of this study is to identify maternal metabolites, and their determinants, that are associated with neonatal adiposity.METHODS AND RESULTS:A targeted metabolomics approach is applied to analyze plasma samples collected across gestation from a well-characterized cohort of 253 pregnant women participating in a prospective study at the University of California, Irvine. Whole-body dual X-ray absorptiometry (DXA) imaging of body composition is obtained in N = 121 newborns. Statistical models are adjusted for potential confounders and multiple testing. The authors identify six alkyl-linked phosphatidylcholines (PCae), containing fatty acid 20:4, that are significantly and negatively associated with neonatal body fat percentage. Factors indicating higher socioeconomic status, non-Hispanic ethnicity, and higher nonesterified fatty acid percentages are positively associated with these PCae.CONCLUSIONS:The polyunsaturated fatty acid 20:4 contained in PCae may exert a beneficial effect with respect to future propensity for obesity development. Prepregnancy and early pregnancy factors are determinants of these PCae, highlighting the importance of addressing preconceptional conditions for fetal programming of newborn adiposity.

BACKGROUND & AIMS:Breastfeeding is beneficial for mothers and infants. Underlying mechanisms and biochemical mediators thus need to be investigated to develop and support improved infant nutrition practices promoting the child health. We analysed the relation between maternal breast milk composition and infant metabolism.METHODS:196 pairs of mothers and infants from a European research project (PreventCD) were studied. Maternal milk samples collected at month 1 and month 4 after birth were analysed for macronutrient classes, hormone, and fatty acid (FA) content. Phospholipids, acylcarnitines, and amino acids were measured in serum samples of 4-month old infants. Associations between milk components and infant metabolites were analysed with spearman correlation and linear mixed effect models (LME). P-values were corrected for multiple testing (PLME).RESULTS:Month 1 milk protein content was strongly associated with infant serum lyso-phosphatidylcholine (LPC) 14:0 (PLME = 0.009). Month 1 milk insulin was associated to infant acetylcarnitine (PLME = 0.01). There were no associations between milk protein content and serum amino acids and milk total fat content and serum polar lipids. Middle- and odd-chain FA% in breast milk at both ages were significantly related to serum LPC and sphingomyelins (SM) species in infant serum (all PLME<0.05), while FA% 20:5n-3 and 22:6n-3 percentages were significantly associated to serum LPC 22:6 (PLME = 1.91×10-4/7.93×10-5) in milk only at month 4. Other polyunsaturated fatty acids and hormones in milk showed only weak associations with infant serum metabolites.CONCLUSIONS:Infant serum LPC are influenced by breast milk FA composition and, intriguingly, milk protein content in early but not late lactation. LPC 14:0, previously found positively associated with obesity risk, was the serum metabolite which was the most strongly associated to milk protein content. Thus, LPC 14:0 might be a key metabolite not only reflecting milk protein intake in infants, but also relating high protein content in milk or infant formula to childhood obesity risk.

Growth characteristics during periods of early developmental plasticity are linked with later health outcomes and with disease risks. Infant growth is modulated by genetic and exogenous factors including nutrition. We try to explore their underlying mechanisms using targeted metabolomic profiling of small molecules in biological samples using high-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) to quantify hundreds of molecules in small biosamples, e.g., 50 µL plasma. In the large German LISA birth cohort study, cord blood lysophosphatidylcholines and fatty acids were closely associated with infant birth weight, with a nonsignificant trend towards an association with infant weight gain and later BMI. Studies in infants randomized to different protein intakes in the European CHOP Study show conventional high protein intakes to markedly increase plasma-indispensable amino acids (AA), particularly branched-chain AA (BCAA), while exceeding the infant's capacity of BCAA breakdown, and an increase in the dispensable AA tyrosine previously associated with insulin resistance. In a path model analysis of the relationship of infant plasma AA, growth factors, and infant growth, AA were generally found to induce a stronger response of insulin than IGF-I although effects of individual AA were very different. We conclude that targeted improvement in nutrient supply in pregnancy and infancy may offer large opportunities for promoting desirable child growth patterns and long-term health.

Context Offspring exposed in utero to maternal obesity have an increased risk of later obesity; however, the underlying mechanisms remain unknown. Objective To assess the effect of an antenatal lifestyle intervention in obese women on the offspring's cord blood metabolic profile and to examine associations of the cord blood metabolic profile with maternal clinical characteristics and offspring anthropometry at birth and age 6 months. Design Randomized controlled trial and cohort study. Setting The UK Pregnancies Better Eating and Activity Trial. Participants Three hundred forty-four mother-offspring pairs. Intervention Antenatal behavioral lifestyle (diet and physical activity) intervention. Main Outcome Measures Targeted cord blood metabolic profile, including candidate hormone and metabolomic analyses. Results The lifestyle intervention was not associated with change in the cord blood metabolic profile. Higher maternal glycemia, specifically fasting glucose at 28 weeks gestation, had a linear association with higher cord blood concentrations of lysophosphatidylcholines (LPCs) 16.1 (β = 0.65; 95% confidence interval: 0.03 to 0.10) and 18.1 (0.52; 0.02 to 0.80), independent of the lifestyle intervention. A principal component of cord blood phosphatidylcholines and LPCs was associated with infant z scores of birth weight (0.04; 0.02 to 0.07) and weight at age 6 months (0.05; 0.00 to 0.10). Cord blood insulin growth factor (IGF)-1 and adiponectin concentrations were positively associated with infant weight z score at birth and at 6 months. Conclusions Concentrations of LPCs and IGF-1 in cord blood are related to infant weight. These findings support the hypothesis that susceptibility to childhood obesity may be programmed in utero, but further investigation is required to establish whether these associations are causally related.

The relationships between nutrition, metabolic response, early growth and later body weight have been investigated in human studies. The aim of this follow-up study was to assess the long-term effect of infant feeding on growth and to study whether the infant metabolome at the age of 4 months might predict anthropometry at 4 years of age. The Belgrade-Munich infant milk trial (BeMIM) was a randomized controlled trial in which healthy term infants received either a protein-reduced infant formula (1.89 g protein/100 kcal) containing alpha-lactalbumin enriched whey and long-chain polyunsaturated fatty acids (LC-PUFA), or a standard formula (2.2 g protein/100 kcal) without LC-PUFA, focusing on safety and suitability. Non-randomized breastfed infants were used as a reference group. Of the 259 infants that completed the BeMIM study at the age of 4 months (anthropometry assessment and blood sampling), 187 children participated in a follow-up visit at 4 years of age. Anthropometry including weight, standing height, head circumference, and percent body fat was determined using skinfolds (triceps, subscapular) and bioelectrical impedance analysis. Plasma metabolite concentration, collected in samples at the age of 4 months, was measured using flow-injection tandem mass spectrometry. A linear regression model was applied to estimate the associations between each metabolite and growth with metabolites as an independent variable. At 4 years of age, there were no significant group differences in anthropometry and body composition between formula groups. Six metabolites (Asn, Lys, Met, Phe, Trp, Tyr) measured at 4 months of age were significantly associated with changes in weight-for-age z-score between 1 to 4 months of age and BMI-for-age z-score (Tyr only), after adjustment for feeding group. No correlation was found between measured metabolites and long-term growth (up to 4 years of age). No long-term effects of early growth patterns were shown on anthropometry at 4 years of age. The composition of infant formula influences the metabolic profile and early growth, while long-term programming effects were not observed in this study.

Background Leptin and adiponectin communicate with organ systems in order to regulate energetic and metabolic homeostasis. Their different points of action have been well characterized; however, no study has investigated their interrelationship with the metabolism at the molecular level in vivo. Objective To examine the associations of leptin and adiponectin with the metabolic profile reflecting the intercellular and interorgan communication as well as activated metabolic pathways. Patients/Methods We measured plasma concentrations of leptin, adiponectin, and insulin along with concentrations of 196 metabolites in 400 healthy, fasting 8-years old German children who participated in the German Ulm Birth Cohort Study (UBCS). Using multiple linear mixed models, we evaluated the associations between hormones and metabolites. Results Leptin levels increased exponentially with increasing BMI. Leptin was furthermore strongly associated with alanine and aspartate (Bonferroni corrected P[PBF] = 5.7×10−8 and 1.7×10−6, respectively), and negatively associated to the sum of the non-esterified fatty acids (NEFA) and the sum of the long-chain acylcarnitines C12–C18 (PBF = 0.009 and 0.0001, respectively). Insulin showed a similar association pattern, although the associations were less strong than for leptin. Adiponectin was neither related to BMI nor to any metabolite. Conclusion Although children were presumably metabolically similar, we found strong associations of insulin and leptin with the metabolite profile. High alanine concentrations and the lower concentrations of NEFA in children with high fasting leptin concentrations might arise from an increased gluconeogenesis and from the disinhibiting effect of leptin on the carnitine-palmitoyltransferase-1, respectively. As insulin had the same trend towards these associations, both hormones seem to be related to processes that provide the body with energy in fasting state.

Background/Aims: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. Methods: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA), polar lipids, non-esterified fatty acids (NEFA), and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. Results: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. Conclusion: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.

During pregnancy, pro-inflammatory cytokines such as Interleukin (IL)-6 are secreted from the placenta, but may also be released from adipocytes and circulating levels increase in response to stress. Elevated prenatal IL-6 has been previously associated with increased neonatal adiposity, possibly driven by enhanced insulin resistance and excess fetal fuel supply. This study aims to investigate the association of prenatal IL-6 with plasma amino acid and lipid metabolites in order to identify potential biochemical pathways for fetal programming of obesity risk. Ninety-three pregnant women were followed prospectively across pregnancy with fasting blood samples collected in each trimester. Serum high-sensitivity IL-6 was determined enzymatically and plasma amino acid and lipid metabolites were assessed by liquid chromatography-gas spectrometry, targeted metabolomics techniques. As IL-6 levels remained stable across gestation, mean pregnancy values were calculated and used in subsequent analysis. Metabolites were converted to Z-scores within each trimester and their linear association with IL-6 was determined, after accounting for any variation explained by maternal pre-pregnancy body mass index, age or ethnicity. Mean gestational IL-6 was not associated with metabolites in trimesters 1 and 2. In trimester 3, a weak positive association was observed for several plasma non-esterified fatty acids, however, stronger inverse associations were noted for 8 out of 20 amino acids profiled. Alanine, the primary gluconeogenic amino acid, was most significantly reduced in response to raised IL-6 (B=-0.4, p=0.001), independent of maternal characteristics. This study provides novel insight into potential inflammatory pathways contributing to fetal programming of obesity. Raised IL-6 may decrease maternal plasma amino acids in late gestation via increased gluconeogenesis, generating increased glucose supply to the fetus. IL-6 may also stimulate placental uptake of amino acids via system transporter A, the activity of which has been previously associated with higher infant birthweight among obese women. The impact of these findings on infant adiposity and the factors influencing higher maternal IL-6 are worthy of further investigation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

There are differences in the prevalence and severity of diseases between males, females not taking hormonal contraceptives (non-HC females) and females taking hormonal contraceptives (HC females). The aim of this study was to identify sex-specific differences in the metabolome and its relation to components of the metabolic syndrome in a young adult population.

ObjectiveNoncommunicable diseases such as obesity have become a serious global public health epidemic. This study aimed to examine whether there was an association between early life factors (with a special focus on breastfeeding) BMI, waist circumference, and the metabolome in offspring at 20 years.MethodsData from the Western Australian Pregnancy Cohort (Raine) Study were analyzed using 1,024 plasma samples from the 20-year follow-up. A liquid chromatography, tandem mass spectrometry metabolomics approach was used to measure metabolites. Multiple linear regression models were performed and adjusted for relevant confounders. Inverse probability weighting was used to adjust the 20-year data for differences in socioeconomic variables between participants and nonparticipants since the commencement of the study.ResultsAn inverse association between breastfeeding and BMI or waist circumference at 20 years was lost after adjusting for parental prepregnancy BMI and maternal smoking during pregnancy. There was no significant effect of breastfeeding on metabolite concentrations at 20 years.ConclusionsAlthough other studies have shown associations between breastfeeding, obesity, and metabolite concentrations at younger ages, this was not evident in our study in young adults. We found no association of metabolites previously associated with waist circumference at 20 years and breastfeeding in early life.

BackgroundA male dizygotic twin was delivered at a gestational age of 36 weeks in the Children's Hospital of the Helios Medical Centre Wuppertal, Witten/Herdecke University Hospital.Contrary to his brother the boy presented dystrophic at birth (1.715 g birth weight; 150 g below 3rd percentile) and developed adverse gastrointestinal conditions within the first 2 months of life.These included chronic mucosal inflammation and oedematous lamina propria in the intestine, which contributed to intractable diarrhoea.At an age of 7 months the infant eventually died of enteral haemorrhages and liver failure.Further anamnesis revealed several similar fatalities in the familial clan with reportedly frequent parental consanguinity.Intractable chronic diarrhoea in infancy are heterogeneous disorders challenging for diagnostics and therapy.Despite extensive diagnostic approaches the etiology of many cases remains elusive.Investigating putatively underlying genetic disorders might clarify many cases. ResultsTo contribute to the diagnosis we performed whole exome sequencing of the affected infant as well as his twin brother and parents.We identified a suspicious nonsynonymous single nucleotide polymorphism (SNP) in the integrin beta-6 gene (ITGB6G1312A) entailing a V438M substitution.This SNP is very rare in the G1000 cohort and predicted being potentially harmful.The allelic distribution in the genotyped family members fit well with an autosomal recessive inheritance scheme.We performed computational biological and molecular biological analyses on the α V β6 integrin receptor function suggesting that the integrin α V β6 dimerization could be impaired, potentially causing a loss of α V β6 function in wound healing and epithelial tissue integrity. ConclusionsOur study provides a starting point for elucidating integrin α V β6 function and for understanding a pathomechanistical relevance of ITGB6V438M.

The fetal programming paradigm posits that the origins of childhood obesity may be traced back to intrauterine life. In order to elucidate potential biochemical targets responsible for the intergenerational transfer of obesity, this study utilizes metabolomics technology to investigate the prenatal plasma fatty acid profiles associated with both maternal obesity and neonatal adiposity. This longitudinal prospective mother-infant cohort study recruited non-diabetic pregnant women in early pregnancy (N=160). Pre-pregnancy weight was self-reported and height measured to determine pre-pregnancy body mass index (pBMI). Women were followed-up in each trimester for weight measurement, dietary intake assessment, and fasting bloods were collected for targeted metabolomics analysis of plasma lipid metabolites. At 2-4 weeks postnatal, a subset of infants underwent body composition analysis by dual x-ray absorptiometry (DXA) whole-body imaging (N=77). Bonferroni correction was applied to analyses for multiple outcome testing. Mean (SD) pBMI was 25.9 (6.0)kg/m2; 42% of women were classified as overweight or obese. All women delivered healthy term neonates with mean birthweight of 3.36kg. pBMI was significantly positively associated with concentrations of several non-esterified fatty acids (NEFA) across gestation, particularly the long-chain omega-6 NEFA C20:3 and C20:4 (Figure 1), and the monounsaturated NEFA C16:1, C17:1, C18:1, independent of maternal age, ethnicity, dietary intake or gestational weight gain. The long-chain omega-3 polyunsaturated NEFA, C20:5 and C22:6, were not influenced by pBMI in any trimester. Neonatal fat mass and percent body fat were significantly inversely associated with trimester 3 levels of phospholipids containing long-chain omega-3 polyunsaturated fatty acids. The association remained after adjusting for pBMI, ethnicity and sex. The results of this study underscore the importance of preconception health status. Raised maternal pBMI may adversely influence gestational fatty acid profiles regardless of weight gain or dietary intake, with preponderance for elevated omega-6 and monounsaturated fatty acids. Meanwhile, suboptimal maternal omega-3 fatty acid status in late gestation may contribute to fetal programming of adiposity.