Maternal Pre-pregnancy Obesity Research Articles

Inter-generational link of obesity in term and preterm births: role of maternal plasma acylcarnitines.

BACKGROUND/OBJECTIVESAcylcarnitines, intermediates of fatty acid oxidation, are known to be involved in obesity and insulin resistance. Since maternal prepregnancy overweight or obesity (OWO) is a recognized major risk factor for offspring OWO, we hypothesized that maternal plasma acylcarnitines may play a role in inter-generational OWO.SUBJECTS/METHODSThis study included 1402 mother-child pairs (1043 term, 359 preterm) recruited at birth from 1998–2013 and followed prospectively up to age 18 years at the Boston Medical Center. The primary outcomes were child OWO defined as BMI≥85th percentile for age and sex. The primary exposures were maternal prepregnancy OWO defined as BMI≥25 and maternal acylcarnitine levels measured in plasma samples collected soon after delivery using liquid chromatography–tandem mass spectrometry (LC-MS) in a targeted manner.RESULTSApproximately 40% of the children in this study were OWO by age 5. Maternal OWO had a significant association with childhood OWO, both in term and preterm births. β-hydroxybutyryl-carnitine (C4-OH) levels were significantly and positively associated with child OWO among term births after adjustment for potential confounders and multiple-comparisons. Children born to OWO mothers in the top tertile C4-OH levels were at highest risk of OWO: OR=3.78 (95%: 2.47, 5.79) as compared with those born to non-OWO mothers in the lowest tertile (P for interaction of maternal OWO and C4-OH= 0.035). In a four-way decomposition of mediation/interaction analysis, we estimated that C4-OH levels explained about 27% (se=0.08) of inter-generational OWO risk (P=0.001). In contrast, these associations were not observed in preterm births.CONCLUSIONSIn this U.S. urban low-income birth cohort, we provide further evidence of the inter-generational link of OWO and reveal the differential role of C4-OH in explaining the inter-generational obesity between term and preterm births. Further investigations are warranted to better understand and prevent the inter-generational transmission of OWO.

Survival of infants with spina bifida and the role of maternal prepregnancy body mass index.

To investigate first-year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality. This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan-Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (≥30). Infant mortality risk among infants with spina bifida was (4.4% [3.52, 5.60%]). Infants with multiple co-occurring defects, very preterm delivery, multiple gestation, high-level spina bifida lesions, or non-Hispanic Black mothers had an elevated risk of infant mortality. Maternal prepregnancy underweight and obesity were associated with higher infant mortality (15.7% [7.20, 32.30%] and 5.82% [3.60, 9.35%], respectively). Adjusted HR estimates showed underweight and obese mothers had greater hazard of infant mortality compared to normal weight mothers (HR: 4.5 [1.08, 16.72] and 2.6 [1.36, 8.02], respectively). The overall risk of infant mortality for infants born with spina bifida was lower than most previously reported estimates. Infants born with spina bifida to mothers who were underweight or obese prepregnancy were at higher risk of infant mortality. This study provides additional evidence of the importance of healthy maternal weight prior to pregnancy.

Maternal pre-pregnancy obesity and timing of puberty in sons and daughters: a population-based cohort study.

BackgroundIn many countries, an increased prevalence of obesity in pregnancy has coincided with a declining pubertal age. We aimed to explore the potential effect of maternal pre-pregnancy overweight and obesity on timing of puberty in sons and daughters.MethodsBetween 2012 and 2018, 15 819 of 22 439 invited children from the Danish National Birth Cohort, born 2000–03, provided half-yearly information from the age of 11 years on the pubertal milestones: Tanner stages, voice break, first ejaculation, menarche, acne and axillary hair. We estimated adjusted mean monthly differences (with 95% confidence intervals) in age at attaining the pubertal milestones for children exposed to maternal pre-pregnancy obesity [body mass index (BMI) ≥30.0 kg/m2] or overweight (BMI 25.0 to 29.9 kg/m2) with normal weight (BMI 18.5 to 24.9 kg/m2) as reference. In mediation analysis, we explored whether childhood BMI at age 7 years mediated the associations.ResultsMaternal pre-pregnancy obesity was associated with earlier age at attaining most pubertal milestones in sons, and pre-pregnancy overweight and obesity were associated with earlier age at attaining all pubertal milestones in daughters. When combining all pubertal milestones, pre-pregnancy obesity [sons: −1.5 (−2.5, −0.4) months; daughters: −3.2 (−4.2, −2.1) months] and overweight [daughters only: −2.6 (−3.3, −1.8) months] were associated with earlier timing of puberty. The associations in sons were completely mediated by higher childhood BMI and partly so in daughters.ConclusionsMaternal pre-pregnancy obesity appears to lower timing of puberty through childhood obesity in sons and mainly through other mechanisms in daughters.

Prenatal Risk Predicts Preschooler Executive Function: A Cascade Model.

Little research has considered whether prenatal experience contributes to executive function (EF) development above and beyond postnatal experience. This study tests direct, mediated, and moderated associations between prenatal risk factors and preschool EF and IQ in a longitudinal sample of 1,292 children from the Family Life Project. A composite of prenatal risk factors (i.e., low birth weight, prematurity, maternal emotional problems, maternal prepregnancy obesity, and obstetric complications) significantly predicted EF and IQ at age 3, above quality of the postnatal environment. This relationship was indirect, mediated through infant general cognitive abilities. Quality of the postnatal home and child-care environments did not moderate the cascade model. These findings highlight the role of prenatal experience as a contributor to individual differences in cognitive development.

Maternal dyslipidemia during early pregnancy and epigenetic ageing of the placenta

ABSTRACTDisruption of physiological ageing of the placenta is associated with obstetric complications. Altered lipid metabolism is a known trigger of tissue ageing, but the effect of maternal dyslipidemia on placental ageing is not clearly understood. We examined the relationship between maternal dyslipidemia and placental age acceleration (PAA), an epigenetic ageing measure derived from the difference between DNA methylation age and chronological gestational age. We also assessed whether the association varies by maternal pre-pregnancy obesity status and fetal sex. Placental data were obtained as part of the NICHD Fetal Growth Studies that involved participants from four race/ethnic groups. Placental DNA methylation age was estimated using 62 CpGs that have previously been found to have high placental age prediction accuracy. We used multivariable linear regression to test associations between maternal dyslipidemia during early gestation (i.e., high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), total cholesterol (TChol), and triglycerides) and PAA adjusting for fetal sex and socio-demographic factors. Among normal-weight women, low HDLc, compared to high HDLc, was associated with 0.82 (95% CI: 0.00, 1.64) weeks higher PAA. Among women with female neonates, low HDLc, compared to high HDLc, was associated with 1.20 (95% CI: 0.17, 2.24) weeks higher PAA. High TChol was associated with 1.28 (95% CI: 0.12, 2.45) weeks higher PAA among Whites. In all, the study found that maternal dyslipidemia due to low HDLc was associated with accelerated epigenetic ageing of the placenta among mothers with normal pre-pregnancy weight and a female fetus.

Maternal Prenatal Psychosocial Stress and BMI Predict Lower Fetal Iron Status in a Mexico City Cohort (FS01-07-19)

ObjectivesInsufficient iron in utero may impair neurocognitive development. Prenatal physiological stress, as in obesity, inhibits fetal iron accumulation. Emerging evidence suggests prenatal psychosocial stress may similarly suppress fetal iron, a novel potential mechanism linking prenatal stress and child neuro-cognition. In a pregnancy cohort in Mexico City, Mexico, we investigated associations between maternal prenatal stress and psychological function, pre-pregnancy BMI and fetal iron at delivery. We hypothesized that maternal prenatal psychosocial stress and psychological dysfunction and pre-pregnancy BMI would be associated with lower cord blood Hb and ferritin. MethodsPsychosocial stress and psychological function were assessed with validated questionnaires in mid-pregnancy: depression symptoms (CES-D), trait anxiety (STI), perceived stress (PSS-4), lifetime exposure to violence (ETV), and negative life events (NLEs, CRISYS). Pre-pregnancy BMI was calculated from self-reported height and weight. Cord blood was collected at delivery and ferritin (ferr.) and hemoglobin (Hb) measured. Regression models were developed for Hb and log-transformed ferr. as functions of dichotomized stress scores (CES-D ≥ 13, STI > median, PSS-4 > 4th quartile, ETV > 0.5, CRISYS > 1st quartile) and pre-pregnancy overweight and obesity in separate models, each adjusted for maternal age, SES, child sex and maternal prenatal iron supplementation (yes/no). ResultsIn 455 dyads with complete data, median (IQR) ferr. and Hb were 186 μg/L (125, 265) and 16 g/dL (14.7, 17), respectively. In adjusted models, lower ferr. was associated with prenatal depression symptoms (11%, 95% CI: –0.26, 0.01), elevated perceived stress (23%, –0.35, –0.09), high lifetime violence (21%, –0.33, –0.06) and high NLEs count (10%, –0.22, 0.02), as well as maternal pre-pregnancy obesity (17%, –0.31, –0.00). Interaction models suggested possible stronger prenatal stressor effects among overweight and obese mothers. No associations with cord blood Hb were observed. ConclusionsIn Mexico City pregnant women, excess pre-pregnancy BMI and multiple prenatal psychosocial stressors were each associated with fetal iron stores at birth. Insufficient fetal iron accrual may explain links between maternal prenatal stress and child neurocognitive development, but more research is needed. Funding SourcesNational Institutes of Health, Office of the Director; National Institute of Environmental Health Sciences.

Maternal Prenatal Psychosocial Stress and BMI Predict Lower Fetal Iron Status in a Mexico City Cohort (FS01-07-19)

ObjectivesInsufficient iron in utero may impair neurocognitive development. Prenatal physiological stress, as in obesity, inhibits fetal iron accumulation. Emerging evidence suggests prenatal psychosocial stress may similarly suppress fetal iron, a novel potential mechanism linking prenatal stress and child neuro-cognition. In a pregnancy cohort in Mexico City, Mexico, we investigated associations between maternal prenatal stress and psychological function, pre-pregnancy BMI and fetal iron at delivery. We hypothesized that maternal prenatal psychosocial stress and psychological dysfunction and pre-pregnancy BMI would be associated with lower cord blood Hb and ferritin. MethodsPsychosocial stress and psychological function were assessed with validated questionnaires in mid-pregnancy: depression symptoms (CES-D), trait anxiety (STI), perceived stress (PSS-4), lifetime exposure to violence (ETV), and negative life events (NLEs, CRISYS). Pre-pregnancy BMI was calculated from self-reported height and weight. Cord blood was collected at delivery and ferritin (ferr.) and hemoglobin (Hb) measured. Regression models were developed for Hb and log-transformed ferr. as functions of dichotomized stress scores (CES-D ≥ 13, STI > median, PSS-4 >4th quartile, ETV >0.5, CRISYS >1st quartile) and pre-pregnancy overweight and obesity in separate models, each adjusted for maternal age, SES, child sex and maternal prenatal iron supplementation (yes/no). ResultsIn 455 dyads with complete data, median (IQR) ferr. and Hb were 186 μg/L (125, 265) and 16 g/dL (14.7, 17), respectively. In adjusted models, lower ferr. was associated with prenatal depression symptoms (11%, 95% CI: -0.26, 0.01), elevated perceived stress (23%, -0.35, -0.09), high lifetime violence (21%, -0.33, -0.06) and high NLEs count (10%, -0.22, 0.02), as well as maternal pre-pregnancy obesity (17%, -0.31, -0.00). Interaction models suggested possible stronger prenatal stressor effects among overweight and obese mothers. No associations with cord blood Hb were observed. ConclusionsIn Mexico City pregnant women, excess pre-pregnancy BMI and multiple prenatal psychosocial stressors were each associated with fetal iron stores at birth. Insufficient fetal iron accrual may explain links between maternal prenatal stress and child neurocognitive development, but more research is needed. Funding SourcesNational Institutes of Health, Office of the Director; National Institute of Environmental Health Sciences.

Metabolic analysis of adipose tissues in a rodent model of pre-pregnancy maternal obesity combined with offsprings on high-carbohydrate diet

Maternal obesity is associated with adverse effects on the health of offsprings. Consumption of a high-carbohydrate (HC) diet has been found to promote abnormal fatty acid metabolism in adipose tissue. Therefore, we hypothesised that maternal obesity combined with an offspring HC diet would alter the fatty acid metabolism of adipose tissue and subsequently contribute to offspring obesity. Leprdb/+ mice were used to model pre-pregnancy maternal obesity and the C57BL/6 wildtype were used as a control group. Offspring were fed either HC diet or a normal-carbohydrate (NC) diet after weaning. Brown adipose tissue (BAT) and white adipose tissue (WAT) were collected from offspring at 20 weeks of age and their fatty acid metabolome was characterized using gas chromatography-mass spectrometry. We found that HC diet increased the body weight of offspring (males increased by 14.70% and females increased by 1.05%) compared to control mothers. However, maternal obesity alone caused a 7.9% body weight increase in female offspring. Maternal obesity combined with an offspring HC diet resulted in dynamic alterations of the fatty acid profiles of adipose tissue in male offspring. Under the impact of a HC diet, the fatty acid metabolome was solely elevated in female WAT, whereas, the fatty acid metabolites in BAT showed a similar trend in the male and female offsprings. 6,9-octadecadienoic acid and 12,15-cis-octadecatrienoic acid were significantly affected in female WAT, in response to offspring consumption of a HC diet. Our study demonstrated that maternal obesity and offspring HC diet have different metabolic effects on adipose tissue in male and female offsprings.

Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study

ABSTRACTPre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4–5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: −0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: −0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity.

Michigan cohorts to determine associations of maternal pre-pregnancy body mass index with pregnancy and infant gastrointestinal microbial communities: Late pregnancy and early infancy.

BackgroundAbout 25% of women in the United States are obese prior to becoming pregnant. Although there is some knowledge about the relationship between the gastrointestinal microbiota and obesity, little is known about the relationship between pre-pregnancy obesity and the gastrointestinal microbiota in pregnancy or its impact on infant gut microbiota. However, the composition of the gut microbiota early in life may influence childhood health. Thus, the objective of this research was to identify associations between maternal pre-pregnancy obesity and the pregnancy (n = 39) or early infancy (n = 39) microbiotas.ResultsFecal bacterial communities from overweight women had lower microbiota diversity (Chao1: p = 0.02; inverse Simpson: p = 0.05; Shannon: p = 0.02) than communities from normal weight or obese women. The within-group microbiota composition of overweight women differed from those of normal and obese women at the genus and phylum levels (p = 0.003 and p = 0.02, respectively). Pre-pregnancy overweight women had higher abundances of Bacteroides and lower Phascolarctobacterium than women who were normal weight or obese prior to becoming pregnant. Normal weight women had lower abundances of Acidaminococcus and Dialister than overweight and obese women. Infant community composition tended to differ in membership (Sorensen index) by maternal pre-pregnancy BMI category, and significantly differed by delivery mode and breastfeeding exclusivity (p = 0.06, p = 0.001, p = 0.008, respectively). Infants from normal weight women had lower abundances of Megasphaera than infants from overweight or obese women. Streptococcus was lowest in infants from overweight women, and Staphylococcus was lowest in infants from obese women.ConclusionMaternal and infant microbiotas are associated with and might be affected by maternal pre-pregnancy BMI. Future work should determine if there are also functional differences in the infant microbiome, if those functional differences are related to maternal pre-pregnancy BMI, and whether differences in composition or traits persist over time.

Sex Differences in Nutrition, Growth, and Metabolism in Preterm Infants.

Biological differences between the sexes are apparent even from the early part of the pregnancy. The crown-rump length is larger in male fetuses compared to females in the first trimester. Placentae of male and female fetuses have different protein and gene expressions, especially in adverse conditions. Even within the intrauterine milieu, the same extracellular micro RNA may show upregulation in females and downregulation in male fetuses. There appears to be a natural survival advantage for females. Maternal glucocorticoids (GC) play an important role in fetal growth and organ maturation. However, excess glucocorticoids can not only affect growth but the response may be sex-specific and probably mediated through glucocorticoid receptors (GR) in the placenta. Mild pre-eclampsia and asthma are associated with normal growth pattern in males, but in female fetuses, they are associated with a slowing of growth rate without causing IUGR probably as an adaptive response for future adverse events. Thus, female fetuses survive while male fetuses exhibit IUGR, preterm delivery and even death in the face of another adverse event. It is thought that the maternal diet may not influence growth but may influence the programming for adult disease. There is growing evidence that maternal pre-pregnancy overweight or obesity status is directly associated with a higher risk of obesity in a male child, but not in a female child, at 1 year of age. It is observed that exposure to gestational diabetes is a risk factor for childhood overweight in boys but not in girls. It is fascinating that male and female fetuses respond differently to the same intrauterine environment, and this suggests a fundamental biological variation most likely at the cellular and molecular level.

Maternal metabolic factors during pregnancy predict early childhood growth trajectories and obesity risk: the CANDLE Study.

BackgroundWe investigated the individual and additive effects of three modifiable maternal metabolic factors, including pre-pregnancy overweight/obesity, gestational weight gain (GWG), and gestational diabetes mellitus (GDM), on early childhood growth trajectories and obesity risk.MethodsA total of 1 425 mother-offspring dyads (953 black and 472 white) from a longitudinal birth cohort were included in this study. Latent class growth modeling was performed to identify the trajectories of body mass index (BMI) from birth to four years in children. Poisson regression models were used to examine the associations between the maternal metabolic risk factors and child BMI trajectories and obesity risk at four years.ResultsWe identified three discrete BMI trajectory groups, characterized as rising-high-BMI (12.6%), moderate-BMI (61.0%), or low-BMI (26.4%) growth. Both maternal pre-pregnancy obesity (adjusted relative risk [adjRR] = 1.96; 95% CI: 1.36–2.83) and excessive GWG (adjRR = 1.71, 95% CI: 1.13–2.58) were significantly associated with the rising-high-BMI trajectory, as manifested by rapid weight gain during infancy and a stable but high BMI until four years. All three maternal metabolic indices were significantly associated with childhood obesity at age four years (adjRR for pre-pregnancy obesity = 2.24, 95% CI: 1.62–3.10; adjRR for excessive GWG = 1.46, 95% CI: 1.01–2.09; and adjRR for GDM = 2.14, 95% = 1.47–3.12). In addition, risk of rising-high BMI trajectory or obesity at age four was stronger among mothers with more than one metabolic risk factor. We did not observe any difference in these associations by race.ConclusionMaternal pre-pregnancy obesity, excessive GWG, and GDM individually and jointly predict rapid growth and obesity at age four in offspring, regardless of race. Interventions targeting maternal obesity and metabolism may prevent or slow the rate of development of childhood obesity.

The contribution of maternal characteristics and cesarean delivery to an increasing trend of severe maternal morbidity

BackgroundSevere maternal morbidity – life-threatening childbirth complications – has more than doubled in the United States over the past 15 years, affecting more than 50,000 women (1.4% of deliveries) annually. During this time period, maternal age, obesity, comorbidities, and cesarean delivery also increased and may be related to the rise in severe maternal morbidity. We sought to evaluate: (1) the association of advanced maternal age, pre-pregnancy obesity, pre-pregnancy comorbidities, and cesarean delivery with severe maternal morbidity, and (2) whether changes in the prevalence of these risk factors affected the trend of severe maternal morbidity.MethodsThis population-based cohort study used linked birth record and patient discharge data from live births in California during 2007–2014 (n = 3,556,206). We used multivariable logistic regression models to assess the association of advanced maternal age (≥35 years), pre-pregnancy obesity (body mass index ≥30 kg/m2), pre-pregnancy comorbidity (index of 12 conditions), and cesarean delivery with severe maternal morbidity prevalence and trends. Severe maternal morbidity was identified by an index of 18 diagnosis and procedure indicators. We estimated odds ratios, predicted prevalence, and population attributable risk percentages.ResultsThe prevalence of severe maternal morbidity increased by 65% during 2007–2014. Advanced maternal age, pre-pregnancy obesity, and pre-pregnancy comorbidity also increased during this period, but cesarean delivery did not. None of these risk factors affected the increasing trend of severe maternal morbidity. However, the pre-pregnancy risk factors together were estimated to contribute to 13% (95% confidence interval: 12, 14%) of severe maternal morbidity cases in the study population overall, and cesarean delivery was estimated to contribute to 37% (95% confidence interval: 36, 38%) of cases.ConclusionsPre-pregnancy health and cesarean delivery are important risk factors for severe maternal morbidity but do not explain an increasing trend of severe maternal morbidity in California during 2007–2014. Investigation of other potential contributors is needed in order to identify ways to reverse the trend of severe maternal morbidity.

Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study

Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study

Placenta Microbiome Diversity Is Associated with Maternal Pre-Pregnancy Obesity and Placenta Biogeography

Placenta Microbiome Diversity Is Associated with Maternal Pre-Pregnancy Obesity and Placenta Biogeography

Maternal prepregnancy body mass index and offspring white matter microstructure: results from three birth cohorts.

Prepregnancy maternal obesity is a global health problem and has been associated with offspring metabolic and mental ill-health. However, there is a knowledge gap in understanding potential neurobiological factors related to these associations. This study explored the relation between maternal prepregnancy body mass index (BMI) and offspring brain white matter microstructure at the age of 6, 10, and 26 years in three independent cohorts. The study used data from three European birth cohorts (n = 116 children aged 6 years, n = 2466 children aged 10 years, and n = 437 young adults aged 26 years). Information on maternal prepregnancy BMI was obtained before or during pregnancy and offspring brain white matter microstructure was measured at age 6, 10, or 26 years. We used magnetic resonance imaging-derived fractional anisotropy (FA) and mean diffusivity (MD) as measures of white matter microstructure in the brainstem, callosal, limbic, association, and projection tracts. Linear regressions were fitted to examine the association of maternal BMI and offspring white matter microstructure, adjusting for several socioeconomic and lifestyle-related confounders, including education, smoking, and alcohol use. Maternal BMI was associated with higher FA and lower MD in multiple brain tracts, for example, association and projection fibers, in offspring aged 10 and 26 years, but not at 6 years. In each cohort maternal BMI was related to different white matter tract and thus no common associations across the cohorts were found. Maternal BMI was associated with higher FA and lower MD in multiple brain tracts in offspring aged 10 and 26 years, but not at 6 years of age. Future studies should examine whether our observations can be replicated and explore the potential causal nature of the findings.

Maternal Pre-Pregnancy Obesity Attenuates Response to Omega-3 Fatty Acids Supplementation During Pregnancy.

Maternal obesity is associated with adverse offspring outcomes. Inflammation and deficiency of anti-inflammatory nutrients like omega(n)-3 polyunsaturated fatty acids (PUFA) may contribute to these associations. Fetal supply of n-3 PUFA is dependent on maternal levels and studies have suggested that improved offspring outcomes are associated with higher maternal intake. However, little is known about how maternal obesity affects the response to n-3 supplementation during pregnancy. We sought to determine (1) the associations of obesity with PUFA concentrations and (2) if the systemic response to n-3 supplementation differs by body mass index (BMI). This was a secondary analysis of 556 participants (46% lean, 28% obese) in the Maternal-Fetal Medicine Units Network trial of n-3 (Docosahexaenoic acid (DHA) + Eicosapentaenoic acid (EPA)) supplementation, in which participants had 2g/day of n-3 (n = 278) or placebo (n = 278) from 19 to 22 weeks until delivery. At baseline, obese women had higher plasma n-6 arachidonic acid concentrations (β: 0.96% total fatty acids; 95% Confidence Interval (CI): 0.13, 1.79) and n-6/n-3 ratio (β: 0.26 unit; 95% CI: 0.05, 0.48) compared to lean women. In the adjusted analysis, women in all BMI groups had higher n-3 concentrations following supplementation, although obese women had attenuated changes (β = −2.04%, CI: −3.19, −0.90, interaction p = 0.000) compared to lean women, resulting in a 50% difference in the effect size. Similarly, obese women also had an attenuated reduction (β = 0.94 units, CI: 0.40, 1.47, interaction p = 0.046) in the n-6/n-3 ratio (marker of inflammatory status), which was 65% lower compared to lean women. Obesity is associated with higher inflammation and with an attenuated response to n-3 supplementation in pregnancy.

Obesity and abnormal glucose tolerance in the offspring of mothers with diabetes.

Type 2 diabetes and obesity during childhood, puberty, and adulthood have become more common. This trend presents a global problem in terms of public health and health economics. Associations between intrauterine exposure to hyperglycemia, obesity, and abnormal glucose tolerance (AGT) in offspring have been reported in populations at high risk of diabetes such as Pima Indians, but these associations have not been established in other groups. In this review, we summarize the evidence on obesity and AGT in the offspring of mothers with diabetes. Although there are many reports indicating that the incidence of obesity or overweight is higher in the offspring of mothers with gestational diabetes, there is no consensus on whether maternal prepregnancy obesity has a larger impact than intrauterine exposure to hyperglycemia. While the risk of AGT or type 2 diabetes in the offspring of mothers with gestational diabetes is thought to increase after puberty, the incidence of AGT is elevated by the age of 7 years in the offspring of mothers with untreated gestational diabetes. Maternal gestational diabetes is a risk factor for AGT or type 2 diabetes independent of maternal prepregnancy BMI. When the offspring of women who had gestational diabetes and received therapeutic intervention in two randomized controlled studies were followed, the prevalence of obesity and impaired fasting glucose was lower in some 7-year-old girls, but the effect of maternal intervention was limited. The risk of obesity or overweight is higher in the offspring of mothers with type 1 diabetes, even after adjustment for maternal prepregnancy BMI. The risk of type 2 diabetes in such offspring is also higher. Although the offspring of mothers with type 2 diabetes are likely to be at high risk for type 2 diabetes, there are only limited reports supporting this hypothesis. Intrauterine exposure to hyperglycemia is associated with obesity and AGT among offspring. The present review suggests that these associations might depend on the type of maternal diabetes, that is, the timing and degree of exposure to hyperglycemia. There are only a small number of studies on the effect of therapeutic interventions for maternal diabetes on metabolism in the offspring.

Maternal Prepregnancy Overweight and Obesity Are Associated with Reduced Physical Fitness But Do Not Affect Physical Activity in Childhood: The Amsterdam Born Children and Their Development Study.

Maternal overweight/obesity during pregnancy increases offspring's risks of obesity and cardiovascular disease (CVD). A possible pathway is by reduced physical fitness and physical activity (PA) levels in children of overweight/obese mother. We assessed whether maternal prepregnancy overweight/obesity independently determines cardiorespiratory fitness (CRF), muscular strength, moderate-to-vigorous physical activity (MVPA), and sedentary behavior (SB) in 8- to 9-year-old children. We also assessed whether child's fat mass (FM) mediates these associations. One hundred ninety-four children of Dutch ethnicity aged 8.6 (± 0.4) years were randomly selected from a prospective birth cohort, the Amsterdam Born Children and their Development (ABCD) study. CRF was assessed by the 20-m multistage shuttle run test (20-m MSRT), muscular strength by hand dynamometry, and MVPA and SB by accelerometry. The association of prepregnancy body mass index (BMI) ≥ 25 kg/m2 with these outcome measures was assessed by multivariable linear regressions. Mean (± standard deviation) attained 20-m MSRT stage was 5.3 (± 1.7). Compared with children from normal weight women, children of women with prepregnancy overweight/obesity attained a 0.80 (95% confidence interval: 0.15-1.50) lower stage, adjusted for child's sex and MVPA. This association was not mediated by birthweight or child's FM at age 5 years. Maternal prepregnancy overweight/obesity was not associated with child's muscular strength, MVPA, or SB. Maternal prepregnancy overweight/obesity was associated with reduced childhood CRF, but not with muscular strength, PA, or SB. Birthweight and FM at age 5 years did not mediate this association. Reduced CRF may partly explain the increased CVD risk in children of overweight/obese women.

OP02.04: The association between maternal prepregnancy obesity and congenital malformations in offspring

OP02.04: The association between maternal prepregnancy obesity and congenital malformations in offspring