Pre-pregnancy Obesity Research Articles

Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4–12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7–65.6%, and hence the predictive significance of the model, and mediated 60.8–75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.

Exploring weight bias internalization in pregnancy

BackgroundRecent research has shown that pregnant individuals experience weight stigma throughout gestation, including negative comments and judgement associated with gestational weight gain (GWG). Weight bias internalization (WBI) is often a result of exposure to weight stigma and is detrimental to biopsychological health outcomes. The purpose of this study was to explore WBI in pregnancy and compare scores based on maternal weight-related factors including pre-pregnancy body mass index (BMI), obesity diagnosis and excessive GWG.MethodsPregnant individuals in Canada and USA completed a modified version of the Adult Weight Bias Internalization Scale. Self-reported pre-pregnancy height and weight were collected to calculate and classify pre-pregnancy BMI. Current weight was also reported to calculate GWG, which was then classified as excessive or not based on Institute of Medicine (2009) guidelines. Participants indicated if they were diagnosed with obesity by a healthcare provider. Inferential analyses were performed comparing WBI scores according to pre-pregnancy BMI, excessive GWG, and obesity diagnosis. Significance was accepted as p < 0.05 and effect sizes accompanied all analyses.Result336 pregnant individuals completed the survey, with an average WBI score of 3.9 ± 1.2. WBI was higher among those who had a pre-pregnancy BMI of obese than normal weight (p = 0.04, η2 = 0.03), diagnosed with obesity than not diagnosed (p < 0.001, Cohen’s d = 1.3), and gained excessively versus not (p < 0.001, Cohen’s d = 1.2).ConclusionsPregnant individuals who have a higher BMI, obesity and gain excessively may experience WBI. Given that weight stigma frequently occurs in pregnancy, effective person-oriented strategies are needed to mitigate stigma and prevent and care for WBI.

Associations Between State-Level Severe Maternal Morbidity and Other Perinatal Indicators

This cross-sectional study examines state-level associations between severe maternal morbidity and other perinatal indicators, including prepregnancy hypertension, prepregnancy diabetes, prepregnancy obesity, low-risk cesarean delivery, preterm birth, and maternal and infant mortality.

The interactive effects of pre-pregnancy body mass index, thyroid function, and blood lipid levels on the risk of gestational diabetes mellitus: a crossover analysis

BackgroundStudies have demonstrated the associations between pre-pregnancy obesity, thyroid dysfunction, dyslipidemia, and increased risk of gestational diabetes mellitus (GDM) in pregnant women. This study was designed to investigate whether and to what extent, the interactions between these factors contribute to the risk of GDM.MethodsA case–control study of 232 GDM cases and 696 controls was conducted among pregnant women from Hangzhou, China. Multiple logistic regression analysis was applied to identify independent risk factors of GDM. Crossover analysis was performed to assess the interactive effects of pre-pregnancy body mass index (pBMI), thyroid hormones, and blood lipid profiles on the risk of GDM. The indexes including attributable proportion (AP) to the interaction and the relative excess risk due to interaction (RERI) were calculated.ResultsChinese pregnant women with pBMI > 23 kg/m2 (adjusted: OR = 4.162, p < 0.001), high triglyceride levels (> 2.30 mmol/L) (adjusted: OR = 1.735, p < 0.001), and the free triiodothyronine/free thyroxine (FT3/FT4) ratio ≥ 0.502 (OR = 4.162, p < 0.001) have significantly increased risk of GDM. Crossover analysis indicated that there were significant interactions between pre-pregnancy overweight/obesity and FT3/FT4 ≥ 0.502 (AP = 0.550, p < 0.001; RERI = 7.586, p = 0.009), high TG levels and FT3/FT4 ≥ 0.502 (AP = 0.348, 95%CI = 0.081–0.614, P = 0.010; RERI = 2.021, 95%CI = 0.064–3.978, p = 0.043) on the risk of GDM.ConclusionThe interactions between pBMI and FT3/FT4 ratio, TG level and FT3/FT4 ratio may have significant impacts on the risk of GDM in pregnant women. Such findings may help improve our understanding of the pathogenesis of GDM as well as develop comprehensive strategies for the management of GDM.

Maternal pre-pregnancy BMI and offspring hyperactivity-inattention trajectories from 3 to 8years in the EDEN birth cohort study.

Evidence suggests obesity during pregnancy is associated with offspring attention-deficit hyperactivity disorder. However, studies have been limited to evaluating the association at a single age with inadequate data on important maternal lifestyle confounders and unmeasured familial confounding. The objective of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 3, 5 and 8years. Data came from the EDEN mother-child cohort. Maternal pre-pregnancy BMI status (kg/m2) was calculated using pre-pregnancy weight and height (self-reported by mothers or measured by midwives). HIS were assessed by parental-report on the Strengths and Difficulties Questionnaire at 3, 5 and 8years of age and used to derive developmental trajectories of HIS (n = 1428). Multivariate models were adjusted for confounders including socioeconomic status, maternal lifestyle behaviours (exercise, diet, smoking, alcohol), childcare and a stimulating home environment. Paternal BMI was used as a negative control. Compared to a normal pre-pregnancy BMI, pre-pregnancy maternal obesity was positively associated with increased odds of a high HIS trajectory between 3 and 8years old in both unadjusted and adjusted logistic regression (adjusted odds ratio [aOR] 1.87 [95% CI 1.12, 3.12]). Pre-pregnancy overweight was not significantly associated after adjustment for confounders (aOR 1.32 [0.87, 2.01]). Maternal pre-pregnancy obesity, but not overweight, was associated with increased likelihood of a high HIS trajectory in children from 3 to 8years old. This association persisted despite controlling for many important maternal lifestyle factors and paternal BMI. Further research is warranted to identify possible mediators involved.

Interactive Affection of Pre-Pregnancy Overweight or Obesity, Excessive Gestational Weight Gain and Glucose Tolerance Test Characteristics on Adverse Pregnancy Outcomes Among Women With Gestational Diabetes Mellitus.

PurposeTo examine the combined effect of pre-pregnancy overweight or obesity, excessive gestational weight gain, and glucose tolerance status on the incidence of adverse pregnancy outcomes among women with gestational diabetes mellitus.MethodsA observational study including 5529 gestational diabetes mellitus patients was performed. Logistic regression were used to assess the independent and multiplicative interactions of overweight or obese, excessive gestational weight gain, abnormal items of oral glucose tolerance test and adverse pregnancy outcomes. Additive interactions were calculated using an Excel sheet developed by Anderson to calculate relative excess risk.ResultsOverall 1076(19.46%) study subject were overweight or obese and 1858(33.60%) women gained weight above recommended. Based on IADPSG criteria, more than one-third women with two, or three abnormal glucose values. Preconception overweight or obesity, above recommended gestational weight gain, and two or more abnormal items of oral glucose tolerance test parameters significantly increased the risk of adverse pregnancy outcomes, separately. After accounting for confounders, each two of overweight or obesity, excessive gestational weight gain, two or more abnormal items of OGTT parameters, the pairwise interactions on adverse pregnancy outcomes appear to be multiplicative. Coexistence of preconception overweight or obesity, above recommended gestational weight gain and two or more abnormal items of oral glucose tolerance test parameters increased the highest risk for adverse pregnancy outcomes. No additive interaction was found.ConclusionsPre-pregnancy overweight or obesity, excessive gestational weight gain, two or more abnormal items of OGTT parameters contribute to adverse pregnancy outcomes independently among women with gestational diabetes mellitus. Additionally, the combined effect between these three factors and adverse pregnancy outcomes appear to be multiplicative. Interventions focus on maternal overweight or obesity and gestational weight gain should be offered to improve pregnancy outcomes.

Association between gestational abnormal glucose tolerance and maternal-fetal outcomes.

To investigate the relationship between abnormal glucose tolerance during pregnancy and maternal-fetal outcomes, after categorizing women into groups with different levels of gestational abnormal glucose tolerance. A total of 1858 pregnant women who received two-step screening for gestational diabetes mellitus (GDM) at Fooyin University Hospital were categorized into four groups, according to their glucose abnormalities, and their maternal-fetal outcomes were investigated from October 2015 to June 2020. Among the groups having different levels of abnormal glucose tolerance, there were significant differences and trends in mother's age, currently married status, and prepregnancy overweight or obesity, incidences of cesarean section, preterm, and gestational hypertension or preeclampsia; and with respect to neonatal incidence of large for gestational age (LGA), average weight, and average height (p < 0.05). After adjusting for potential factors, there were higher incidences of cesarean section (AOR=1.71; 95% confidence interval [CI]: 1.12-2.61), preterm (AOR=2.20; 95% CI: 1.23-3.91), neonatal LGA (AOR=4.94; 95% CI: 2.87-8.51), and neonatal intensive care unit (NICU) admission (AOR=2.66; 95% CI: 1.14-6.24) in the GDM group, relative to the control group. Furthermore, the women in the oral glucose tolerance test (OGTT)-1 group had a higher incidence of neonatal LGA when compared with the women in the normal group (AOR=2.31; 95% CI: 1.02-5.33). We found higher incidences of cesarean section, preterm, and neonatal LGA and NICU admission in the GDM women, and a higher incidence of neonatal LGA in the OGTT-1 group, relative to control group.

Sex Discrepancy Observed for Gestational Metabolic Syndrome Parameters and Polygenic Risk Associated With Preschoolers' BMI Growth Trajectory: The Ma'anshan Birth Cohort Study.

BackgroundFew studies have investigated the associations of childhood growth trajectories with the prenatal metabolic risks of mothers and their interaction with children’s genetic susceptibility.ObjectiveTo investigate the effects of gestational metabolic syndrome (GMS) risks and children’s polygenic risk scores (PRSs), and their interaction effect on the BMI trajectory and obesity risk of offspring from birth to 6 years of age.MethodsA total of 2,603 mother-child pairs were recruited from the Ma’anshan birth cohort (Anhui Province of China) study. Data on maternal prepregnancy obesity, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP) were used to evaluate maternal GMS risk. In addition, 1,482 cord blood samples were used to genotype 11 candidate single-nucleotide polymorphisms (SNPs) to calculate children’s PRSs. The latent class growth model using the longitudinal BMI-for-age z scores (BMIz) was applied to validly capture the BMIz growth trajectory.ResultsMaternal GMS status was associated with higher BMIz scores and with an increased risk of overweight/obesity. Positive relationships were revealed between PRS and the risk of overweight/obesity among girls. Additionally, maternal GMS significantly interacted with the child’s PRS on BMIz scores and the risk of overweight/obesity among girls. Hierarchical BMI trajectory graphs by different exposure groups showed consistent findings, and both boys’ and girls’ BMIz trajectories were divided into three groups. Among girls, the higher the GMS risk or PRS they had, the higher the probability of being in the high BMIz trajectory group.ConclusionsMaternal GMS status increased BMIz scores and the risk of obesity in both boys and girls and elevated the child’s BMI trajectory from birth to 6 years of age among girls. PRSs were significantly associated with children’s BMI trajectory and the risk of obesity and modified the associations between maternal GMS status and obesity biomarkers only among girls. Thus, regarding childhood obesity, steps should be taken to decrease maternal metabolic risks before and during pregnancy, and sex discrepancies should be noted to identify high-risk populations after birth to hierarchically manage them.

Association of Prepregnancy Body Mass Index With Risk of Severe Maternal Morbidity and Mortality Among Medicaid Beneficiaries

The association between body mass index (BMI, which is calculated as weight in kilograms divided by height in meters squared) and severe maternal morbidity (SMM) and/or mortality is uncertain, judging from the current evidence. To examine the association between prepregnancy BMI and SMM and/or mortality through 1 year post partum and to identify both the direct and indirect implications of maternal obesity for SMM and/or mortality by examining hypertensive disorders and pregestational diabetes as potential mediators. This population-based cohort study was conducted from March to October 2021 using the vital records and linked Medicaid claims data in the state of Ohio from January 1, 2012, through December 31, 2017. The cohort comprised pregnant Medicaid beneficiaries who delivered at 20 weeks' gestation or later and had prepregnancy BMI information. The primary exposure was maternal prepregnancy BMI, which was categorized as follows: underweight (<18.5), healthy weight (18.5-24.9), overweight (25.0-29.9), class 1 obesity (30.0-34.9), class 2 obesity (35.0-39.9), and class 3 obesity (≥40.0). The primary outcome was a composite of SMM (defined using Centers for Disease Control and Prevention criteria) and/or maternal mortality between 20 weeks' gestation and 1 year post partum. Additional periods were assessed, including 20 weeks' gestation through delivery hospitalization and 20 weeks' gestation through 42 days post partum. Generalized estimating equation models were used to estimate adjusted relative risks (aRRs) for the primary outcome according to BMI category. Maternal hypertensive diseases and pregestational diabetes were assessed as potential meditators. In a cohort of 347 497 pregnancies among 276 691 Medicaid beneficiaries (median [IQR] maternal age at delivery, 25 [21-29] years; 210 470 non-Hispanic White individuals [60.6%]), the prevalence of maternal obesity was 30.5% (n = 106 031). Composite SMM and/or mortality outcome occurred in 5.3% of pregnancies (n = 18 398). Overweight (aRR, 1.07; 95% CI, 1.03-1.11) and obesity (class 1: aRR, 1.19 [95% CI, 1.14-1.24]; class 2: aRR, 1.37 [95% CI, 1.30-1.44]; class 3: aRR, 1.71 [95% CI, 1.63-1.80]) were associated with an elevated risk of SMM and/or mortality during pregnancy to 1 year post partum compared with healthy BMI. Similar findings were observed when the follow-up period was shortened to 42 days post partum or the delivery hospitalization. Hypertension mediated 65.1% (95% CI, 64.6%-65.6%) of the association between obesity and the primary outcome. Results of this study showed that maternal prepregnancy obesity was associated with an elevated risk of SMM and/or mortality. Hypertensive disorders appeared to mediate this association, suggesting that improved prevention and management of hypertensive disorders in pregnancy may reduce morbidity and mortality in individuals with obesity.

Effect of an antenatal diet and lifestyle intervention and maternal BMI on cord blood DNA methylation in infants of overweight and obese women: The LIMIT Randomised Controlled Trial.

To investigate the effect of an antenatal diet and lifestyle intervention, and maternal pre-pregnancy overweight or obesity, on infant cord blood DNA methylation. We measured DNA methylation in 645 cord blood samples from participants in the LIMIT study (an antenatal diet and lifestyle intervention for women with early pregnancy BMI ≥25.0 kg/m2) using the Illumina 450K BeadChip array, and tested for any differential methylation related to the intervention, and to maternal early pregnancy BMI. We also analysed differential methylation in relation to selected candidate genes. No CpG sites were significantly differentially methylated in relation to either the diet and lifestyle intervention, or with maternal early pregnancy BMI. There was no significant differential methylation in any of the selected genes related to the intervention, or to maternal BMI. We found no evidence of an effect of either antenatal diet and lifestyle, or of maternal early pregnancy BMI, on cord blood DNA methylation. ACTRN12607000161426.

Factors Associated with Hospitalization with Symptomatic COVID-19 Illness Among Pregnant Individuals: A Multi-Center Retrospective Cohort Study

BackgroundPregnant individuals are at increased risk of COVID-19 hospitalization and death, and primary and booster COVID-19 vaccination is recommended for this population.MethodsAmong a cohort of pregnant individuals who received prenatal care at three healthcare systems in the United States, we estimated the cumulative incidence of hospitalization with symptomatic COVID-19 illness. We also identified factors associated with COVID-19 hospitalization using a multivariable Cox proportional-hazards model with pregnancy weeks as the timescale and a time-varying adjustor that accounted for SARS-CoV-2 circulation; model covariates included site, age, race, ethnicity, insurance status, pre-pregnancy weight status, and selected underlying medical conditions. Data were collected primarily through medical record extraction.ResultsAmong 19,456 pregnant individuals with an estimated due date March 1, 2020-February 28, 2021, 75 (0.4%) were hospitalized with symptomatic COVID-19. Factors associated with hospitalization for symptomatic COVID-19 were Hispanic ethnicity (aHR: 2.7; 95% CI: 1.3,5.5), native Hawaiian or Pacific Islander race (aHR: 12; 95% CI: 3.2,45.5), age <25 years (aHR: 3.1; 95% CI: 1.3,7.6), pre-pregnancy obesity (aHR: 2.1; 95% CI: 1.1,3.9), diagnosis of a metabolic disorder (aHR: 2.2; 95% CI: 1.2,3.8), lung disease excluding asthma (aHR: 49; 95% CI: 28,84) and cardiovascular disease (aHR: 2.6; 95% CI: 1.5,4.7).ConclusionAlthough hospitalization with symptomatic COVID-19 was uncommon, pregnant individuals should be aware of risk factors associated with severe illness when considering COVID-19 vaccination.

Maternal Pre-Pregnancy Obesity and Gestational Diabetes Mellitus Increase the Risk of Childhood Obesity.

Previous studies have shown inconsistent results regarding the effects of maternal gestational diabetes mellitus (GDM) and pre-pregnancy obesity (PPO) on childhood obesity. This study aimed to determine the risk for early childhood obesity based on maternal GDM and PPO. This nationwide study used data obtained from the National Health Information Database in South Korea. The participants were divided into four groups based on maternal GDM and PPO, and 1:1 matching was performed. Each group had 1319 participants. A generalized estimating equation model was used to analyze the changes in body mass index percentile of children with age, and simple and multiple conditional logistic regression models were used to compare the prevalence of childhood obesity at 5 years. Children whose mothers had both PPO and GDM, only PPO, or only GDM had a 4.46 (95% CI: 3.28–6.05, p < 0.001), 3.11 (95% CI: 2.27–4.26, p < 0.001), or 1.58 (95% CI: 1.12–2.23, p = 0.010) times higher risk, respectively, of developing childhood obesity than children whose mothers had neither PPO nor GDM. Maternal PPO increases the risk for childhood obesity to a higher degree than maternal GDM, and the presence of both increases the risk even further.

Prevalence and characteristics of macrosomia in the first and subsequent pregnancy: a multi-center retrospective study.

Prevalence and characteristics of macrosomia in the first and subsequent pregnancy: a multi-center retrospective study.

Three trajectories of gestational weight gain identified in an Australian twin study

ObjectivesGestational weight gain (GWG) has been associated with maternal and child health outcomes, but knowledge of appropriate GWG for twin gestations is limited. Study designThe Peri/Postnatal Epigenetic Twins Study is a prospective twin cohort study of 250 women and their twin children in Melbourne, Australia. We modeled trajectories of GWG using group-based growth modeling and compared these trajectories to GWG categories (within, above, or below current GWG recommendations for twin pregnancy). We fitted robust linear and Poisson regression models to assess associations of maternal pre-pregnancy and gestational exposures with risk of gaining weight outside the recommendations. ResultsOf the 250 women enrolled in the PETS, GWG measures were available for 172 women. Forty-seven percent of women had GWG within the current recommendations. We identified three GWG trajectories – 23.6% of women had low GWG throughout pregnancy, 34.5% had average GWG throughout pregnancy, and 42.0% had average initial GWG, followed by high GWG from trimester two until delivery. Gestational diabetes mellitus (GDM) was associated with increased risk of inadequate GWG (RR: 2.40, 95%CI: 1.53, 3.75). Pre-pregnancy obesity (RR: 1.88, 95%CI: 1.09, 3.26) and hypertensive disorders of pregnancy (RR: 2.64, 95%CI: 1.20, 5.81) were associated with increased risk of excessive GWG. ConclusionsMore than half of the women in the PETS did not meet the current GWG recommendations. Women with GDM or hypertensive disorders were more likely to gain weight outside these guidelines. More research is needed to establish comprehensive guidelines for twin pregnancies.

Maternal and Perinatal Outcomes Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy, Florida, 2020-2021: A Retrospective Cohort Study.

BackgroundThe objective was to estimate risk of SARS-CoV-2 infection in pregnancy and assess adverse maternal and perinatal outcomes.MethodsWe used a population-based, retrospective cohort of all pregnancies with a live birth or fetal death in Florida from March 1, 2020 to April 30, 2021. COVID-19 case reports were matched to vital registries. Outcomes assessed were risk of infection in pregnancy, preterm birth, maternal or neonatal admission to an intensive care unit (ICU), perinatal or fetal death, and maternal death. Modified Poisson and multinomial logistic regression models were used to derive relative risk estimates.ResultsOf 234,492 women with a live birth or fetal death during the study period, 12,976 (5.5%) were identified with COVID-19 during pregnancy. Risk factors for COVID-19 in pregnancy included Hispanic ethnicity (relative risk [RR] = 1.89), Black race (RR = 1.34), being unmarried (RR = 1.04), and being overweight or obese pre-pregnancy (RR = 1.08-1.32). COVID-19 during pregnancy was associated with preterm birth (RR = 1.31), Cesarean delivery (RR = 1.04), and neonatal (RR = 1.17) and maternal (RR = 3.10) ICU admission; no association was found with increased risk of perinatal (RR = 0.72) or fetal death (RR = 0.86). Women infected during any trimester showed increased risk of preterm birth. Fourteen maternal deaths were identified among COVID-19 cases; of those who died 12 were obese. The death rate per 10,000 was 22.09 among obese and 1.22 among non-obese gravida with COVID-19 during pregnancy (RR = 18.99, P = 0.001).ConclusionsObesity is a risk factor for SARS-CoV-2 infection in pregnancy and for more severe COVID-19 illness among pregnant women. SARS-CoV-2 infection is associated with preterm birth.

Pre-pregnancy overweight and obesity prevalence and relation to maternal and perinatal outcomes

ObjectiveTo identify the prevalence of pre-pregnancy overweight/obesity in pregnant women and its relationship with socio-demographic factors and to describe the maternal and perinatal outcomes in a Barcelona hospital (Spain). MethodA descriptive cross-association study, with retrospective data collection, was performed Barcelona Hospital. The data of 5447 pregnant women who delivered at >=23 weeks of gestation were included. Body Mass Index (BMI) data were categorised into World Health Organization classifications. p values <.05 (two-tailed) were considered significant. Logistic regression models were performed. ResultsThe prevalence of pre-pregnancy obesity was 8.4% and 18.9% for overweight. Gestational diabetes was more frequent in pre-pregnancy overweight/obesity (OR 1.92: 95% CI 1.54–2.40 and OR 3.34: 95% CI 2.57–4.33), as were preeclampsia (OR 2.08: 95% CI 1.55–2.79 and OR 3.35: 95% CI 2.38–4.71), induction of labour (OR 1.19: 95% CI 1.02–1.38 and OR 1.94: 95% CI 1.57–2.10), caesarean section (OR 1.41: 95% CI 1.21–1.65 and OR 2.68: 95% CI 2.18–3.29), prematurity (OR 1.28: 95% CI 1–1.65 and OR 1.79: 95% CI 1.32–2.44) and macrosomia (OR 1.87: 95% CI 1.43–2.46 and OR 2.03: 95% CI 1.40–2.93). ConclusionsOne in four pregnant women had pre-pregnancy overweight or obesity. This study shows the relationship between pre-pregnancy overweight or obesity with adverse maternal and perinatal outcomes.

247-OR: Maternal Prepregnancy Obesity and Gestational Diabetes Are Associated with Epigenetic Gestational Aging in the Placenta

Pregnancy conditions like maternal pre-pregnancy obesity and gestational diabetes (GDM) have been linked with the development of placenta, a critical organ required for maternal-fetal interface during gestation, and can lead to adverse health outcomes in both mother and fetus. However, the molecular signatures associated with these conditions are not fully understood. Epigenetic clocks, which are based upon DNA methylation of age-related CpGs, are thought to better reflect biological age compared to chronological age and have been used in different tissues as potential biomarkers. In the present study, we hypothesized that altered placental epigenetic gestational aging is associated with pre-pregnancy obesity and GDM. We explored these relationships by leveraging data from three diverse cohorts in the Environmental influences on Child Health Outcomes (ECHO) program (overall N=830) . First, we investigated associations between maternal pre-pregnancy obesity and GDM and estimated placental epigenetic gestational age acceleration (eGAA) . Next, we examined associations between these two conditions and methylation of each CpG site within the robust placental clock (558 CpGs) . Significant associations were not observed between pre-pregnancy obesity and GDM and eGAA. Interestingly, pre-pregnancy obesity was associated with methylation levels at 28 placental clock CpGs (q&amp;lt;0.1) . These sites were annotated to 17 unique genes that enrich processes like circadian entrainment and cellular response to glucagon stimulus (GNAS, GNG2) . Additionally, GDM was associated with methylation levels at 22 CpGs that mapped to 14 genes related to apoptosis (TNFRSF10B, TRADD) and neurological development (CACNA1G, ATXN1) . Overall, findings suggest that maternal pre-pregnancy obesity and GDM are associated with CpG methylation of the placental epigenetic clock, revealing potential markers vital for healthy pregnancy and fetal development. Disclosure K.Huff: None. C.Marsit: None. S.Niemiec: None. H.Volk: None. T.M.O'shea: None. R.Fry: None. K.Roell: None. C.Bulka: None. K.E.Boyle: None. C.Breton: None. A.Burt: None. D.Dabelea: None. L.Kahn: None. M.R.Karagas: None. Funding National Institutes of Health (UH3OD023348)

Pre-pregnancy Obesity Associated With Lower Odds of Meeting Breastfeeding Recommendations When Controlling for Prenatal Intentions

ObjectivesThe American Academy of Pediatrics (AAP) recommends exclusive breastfeeding (EBF) to 6 months of age, with continued breastfeeding (any BF) for at least 1 year. Maternal obesity has been associated with reduced duration of any and exclusive BF. However, few studies have incorporated degree of obesity or controlled for prenatal BF intentions when comparing BF outcomes. We calculated odds of meeting AAP BF recommendations by pre-pregnancy BMI category while controlling for prenatal BF intentions and demographics in PREVAIL, a CDC-funded birth cohort in Cincinnati, OH.MethodsPrenatally, enrolled subjects completed a 3rd trimester questionnaire including demographics, pre-pregnancy weight and height, and EBF intention to 6 months. BMI (kg/m2) was categorized as healthy (18.5–24.9), overweight (25–29.9), obesity 1 (30–34.9), or obesity 2+ (≥35). Postnatally, mothers self-reported BF initiation, exclusivity, and duration via quarterly study questionnaires. Logistic regression compared EBF to 6 months and ABF to 1 year across BMI categories among those who initiated BF. All models were adjusted for maternal race, education, income and intention to EBF to 6 months.ResultsOf N = 245 enrolled subjects, the pre-pregnancy maternal obesity prevalence was 41% (n = 100), with 23% (n = 57) meeting Obesity 2 + criteria. There were no significant differences between BMI categories in intention to EBF to 6 months or BF initiation, with high (84–87%) initiation rates. Healthy BMI mothers reported the highest (40%) and mothers with obesity 2 + the lowest (4%), rates of EBF to 6 months (aOR 0.13 (CI 0.02–0.57)). Although only 26% of mothers provided any BF at the 1 year mark, healthy BMI mothers (49%) were more likely to achieve this recommendation than mothers with overweight (13%, aOR 0.11 (CI: 0.04, 0.34)), obesity 1 (16%, aOR 0.11 (CI 0.03, 0.33) and obesity 2+ (10%, aOR 0.15 (CI 0.04, 0.46)).ConclusionsDespite high BF initiation rates, increasing BMI category was associated with decreasing odds of meeting AAP BF recommendations after adjustment for demographics and prenatal EBF intention in the PREVAIL Cohort. Whether these findings can be explained by physiologic barriers associated with higher BMI merits further attention.Funding SourcesCenters for Disease Control and Prevention.

Maternal Periconceptional Stressors, Mediterranean Diet Adherence, and Child Outcomes

ObjectivesTo evaluate the relationships between maternal periconceptional Mediterranean diet adherence and 1) maternal periconceptional BMI, 2) subsequent maternal depression during pregnancy, 3) prenatal inflammatory cytokine IL-17A, 4) child birthweight, and 5) child weight-for-height at ages 0–8 years in African American, Hispanic and White mother-child dyads from the Newborn Epigenetics STudy (NEST).MethodsFood frequency questionnaires were used to estimate periconceptional Mediterranean diet adherence in mothers. Maternal depression during pregnancy was assessed using the Centers for Epidemiological Studies Depression scale. Weight and height were measured in children between birth and age 8 years. Linear and logistic regression models were used to examine associations between maternal adherence to a Mediterranean diet, inflammatory cytokines and pregnancy and postnatal outcomes, adjusted for education, maternal age at delivery, maternal smoking, gestational age, age and sex of child, breastfeeding, parity, maternal BMI.ResultsAdherence to a Mediterranean diet varied widely by ethnicity with > 55% of White mothers reporting high adherence during the periconceptional period, compared to 22% of Hispanic mothers, and 18% of African American mothers (P < 0.05). Higher adherence to this diet was associated with lower risk of depressive mood (β = −0.45, p = 0.02) and pre-pregnancy obesity (β = −0.29, p = 0.05). Higher maternal adherence to this diet pattern was also associated with lower body weight at birth, that was maintained to ages 3–5 and 6–8 years—these associations were most apparent in White children (3–5 years: β = −2.9, p = 0.02; 6–8 years: β = −3.99, p = 0.01). Higher diet adherence was associated with lower levels of prenatal IL-17A levels in African American mother-child dyads (β = 0.21, p = 0.03).ConclusionsOur data suggest that maternal Mediterranean diet adherence provides a potent avenue by which effects of prenatal stressors on maternal and fetal outcomes can be mitigated to reduce ethnic disparities in childhood obesity.Funding SourcesThis research was funded by grants from the National Institute of Minority Health and Health Disparities and the National Institute of Environmental Health Sciences, and supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

Association of maternal obesity with preterm birth phenotype and mediation effects of gestational diabetes mellitus and preeclampsia: a prospective cohort study

BackgroundThe association between maternal obesity and preterm birth remains controversial and inconclusive, and the effects of gestational diabetes mellitus (GDM) and preeclampsia (PE) on the relationship between obesity and preterm birth have not been studied. We aimed to clarify the relationship between prepregnancy body mass index (BMI) and the phenotypes of preterm birth and evaluate the mediation effects of GDM and PE on the relationship between prepregnancy BMI and preterm birth.MethodsWe conducted a prospective cohort study of 43,056 women with live singleton births from 2017 through 2019. According to the WHO International Classification, BMI was classified as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5–25 kg/m2), overweight (BMI 25–30 kg/m2) and obese (BMI ≥30 kg/m2). Preterm birth was defined as gestational age less than 37 weeks (extremely, < 28 weeks; very, 28–31 weeks; and moderately, 32–36 weeks). The clinical phenotypes of preterm birth included spontaneous preterm birth (spontaneous preterm labor and premature rupture of the membranes) and medically indicated preterm birth. We further analyzed preterm births with GDM or PE. Multivariable logistic regression analysis and causal mediation analysis were performed.ResultsRisks of extremely, very, and moderately preterm birth increased with BMI, and the highest risk was observed for obese women with extremely preterm birth (OR 3.43, 95% CI 1.07–10.97). Maternal obesity was significantly associated with spontaneous preterm labor (OR 1.98; 95% CI 1.13–3.47), premature rupture of the membranes (OR 2.04; 95% CI 1.08–3.86) and medically indicated preterm birth (OR 2.05; 95% CI 1.25–3.37). GDM and PE mediated 13.41 and 36.66% of the effect of obesity on preterm birth, respectively. GDM mediated 32.80% of the effect of obesity on spontaneous preterm labor and PE mediated 64.31% of the effect of obesity on medically indicated preterm birth.ConclusionsMaternal prepregnancy obesity was associated with all phenotypes of preterm birth, and the highest risks were extremely preterm birth and medically indicated preterm birth. GDM and PE partially mediated the association between obesity and preterm birth.