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Background Physical activity (PA) prior to and during pregnancy may have intergenerational effects on offspring health through placental epigenetic modifications. We are unaware of epidemiologic studies on longitudinal PA and placental DNA methylation. Objectives We evaluated the association between PA before and during pregnancy and placental DNA methylation. Methods Placental tissues were obtained at delivery and methylation was measured using HumanMethylation450 Beadchips for participants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singletons among 298 participants. Using the Pregnancy Physical Activity Questionnaire, women recalled periconception PA (past 12 mo) at 8–13 wk of gestation and PA since last visit at 4 follow-up visits at 16–22, 24–29, 30–33, and 34–37 wk. We conducted linear regression for associations of PA at each visit with methylation controlling for false discovery rate (FDR). Top 100 CpGs were queried for enrichment of functional pathways using Ingenuity Pathway Analysis. Results Periconception PA was significantly associated with 1 CpG site. PA since last visit for visits 1–4 was associated with 2, 2, 8, and 0 CpGs (log fold changes ranging from –0.0319 to 0.0080, after controlling for FDR). The largest change in methylation occurred at a site in TIMP2 , which is known to encode a protein critical for vasodilation, placentation, and uterine expansion during pregnancy (log fold change: –0.05; 95% CI: –0.06, –0.03 per metabolic equivalent of task–h/wk at 30–33 wk). Most significantly enriched pathways include cardiac hypertrophy signaling, B-cell receptor signaling, and netrin signaling. Significant CpGs and enriched pathways varied by visit. Conclusions Recreational PA in the year prior and during pregnancy was associated with placental DNA methylation. The associated CpG sites varied based on timing of PA. If replicated, the findings may inform the mechanisms underlying the impacts of PA on placenta health. This study was registered at clinicaltrials.gov as NCT00912132. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to describe the overall quantity and type of supplements and medications used during pregnancy in a low-risk cohort and to examine any racial/ethnic differences in intake. Study Design  We used data from 2,164 racially/ethnically diverse, nonobese, and low-risk pregnant women participating without pre-pregnancy chronic conditions in a prospective cohort study at 12 sites across the United States. Medication data were self-reported as free text in enrollment, follow-up visit questionnaires, and abstracted from medical records at delivery. Supplements and medications data were mapped to their active ingredients and categorized into corresponding classes using the Slone Drug Dictionary. The total number and classes of supplements and medications consumed during pregnancy were calculated. Modified Poisson regression models were used to estimate the racial/ethnic differences in supplements and medications intake. All models were adjusted for maternal sociodemographic factors and study site. Results  98% of women took at least one supplement during pregnancy, with prenatal vitamins/multivitamins being most common. While only 31% reported taking no medications during pregnancy, 23% took one, 18% took two, and 28% took three or more. The percentage of women taking at least one medication during pregnancy was highest among non-Hispanic white women and lowest among Asians (84 vs. 55%, p  < 0.001). All racial/ethnic groups reported taking the same top four medication classes including central nervous system agents, gastrointestinal drugs, anti-infective agents, and antihistamines. Compared with non-Hispanic white women, Hispanic (adjusted relative risk [aRR]: 0.84, 95% confidence interval [CI]: 0.71–0.98), and Asian women (aRR: 0.83, 95% CI: 0.70–0.98) were less likely to take central nervous system agents, as well as gastrointestinal drugs (Hispanics aRR: 0.79, 95% CI: 0.66–0.94; Asians aRR = 0.75, 95% CI: 0.63–0.90), and antihistamines (Hispanics aRR: 0.65, 95% CI: 0.47–0.92). Conclusion  Supplement intake was nearly universal. Medication use was also common among this low-risk pregnancy cohort and differed by race/ethnicity. ClinicalTrials.gov Identifier  NCT00912132. Key Points In women without chronic conditions, medication use is common. Racial/ethnic differences exist in prenatal medications use. Almost all women use supplements during pregnancy. [ABSTRACT FROM AUTHOR]

Background Epigenetic mechanisms may underlie associations between maternal caffeine consumption and adverse childhood metabolic outcomes. However, limited studies have examined neonate DNA methylation (DNAm) patterns in the context of preconception or prenatal exposure to caffeine metabolites. Objectives We examined preconception and pregnancy caffeine exposure with DNAm alterations in neonate cord blood (n  = 378). Methods In a secondary analysis of the Effects of Aspirin in Gestation and Reproduction Trial (EAGeR), we measured maternal caffeine, paraxanthine, and theobromine concentrations from stored serum collected preconception (on average 2 months before pregnancy) and at 8 weeks of gestation. In parallel, self-reported caffeinated beverage intake was captured via administration of questionnaires and daily diaries. We profiled DNAm from the cord blood buffy coat of singletons using the MethylationEPIC BeadChip. We assessed associations of maternal caffeine exposure and methylation β values using multivariable robust linear regression. A false discovery rate (FDR) correction was applied using the Benjamini-Hochberg method. Results In preconception, the majority of women reported consuming 1 or fewer servings/day of caffeine on average, and caffeine and paraxanthine metabolite levels were 88 and 36 µmol/L, respectively. Preconception serum caffeine metabolites were not associated with individual cytosine-guanine (CpG) sites (FDR >5%), though pregnancy theobromine was associated with DNAm at cg09460369 near RAB2A (β = 0.028; SE = 0.005; FDR P  = 0.012). Preconception self-reported caffeinated beverage intake compared to no intake was associated with DNAm at cg09002832 near GLIS3 (β = –0.013; SE = 0.002; FDR P  = 0.036). No associations with self-reported intake during pregnancy were found. Conclusions Few effects of maternal caffeine exposure on neonate methylation differences in leukocytes were identified in this population with relatively low caffeine consumption. [ABSTRACT FROM AUTHOR]

Background: The American Academy of Pediatrics recommends that if parents choose to introduce juice, they wait until ≥12 months, citing concerns of obesity and dental caries.Objectives: We sought to identify correlates of early juice introduction (<6 months) and determine whether early introduction establishes a pattern of sugary beverage intake in childhood.Methods: Upstate KIDS is a prospective birth cohort study with follow-up through 7 years (n = 4989). The age of juice introduction was assessed from responses on periodic questionnaires from 4-18 months and categorized as <6,  6 to <12, and ≥12 months. Sociodemographic information was reported using vital records or maternal questionnaires. At 24, 30, and 36 months and 7 years, mothers reported their child's regular juice, soda, water, and milk intakes. The analysis was restricted to singletons and 1 randomly selected twin from each pair with information on juice introduction (n = 4067). We assessed associations of sociodemographic correlates with juice introduction using Cox proportional hazard models. The relations of juice introduction with beverage intake were evaluated using Poisson or logistic regression for adjusted risk ratios (aRR) or ORs, adjusting for sociodemographic covariates and total beverage intake.Results: Of the mothers, 25% and 74% introduced juice prior to 6 and 12 months, respectively. Younger maternal age; black or Hispanic race/ethnicity; lower educational attainment; Special Supplemental Nutrition Program for Women, Infants, and Children participation (yes); smoking during pregnancy; a higher pre-pregnancy BMI; a lower household income; and living in a townhouse/condominium or mobile home were associated with earlier juice introduction. Earlier juice introduction was related to a higher childhood juice intake, any soda intake, and lower water intake, holding total beverage intake constant [aRR, 1.5 (95% CI: 1.3-1.7; P-trend < 0.0001); adjusted OR 1.6 (95% CI: 1.0-2.4; P-trend = 0.01); aRR 0.9 (95% CI: 0.8-0.9; P-trend < 0.0001), respectively].Conclusions: Markers of lower socioeconomic status are strongly associated with earlier juice introduction, which, in turn, relates to sugary beverage intake in childhood, potentially replacing water. [ABSTRACT FROM AUTHOR]

Objective  The aim of this study is to model the association between gestational age at birth and early child development through 3 years of age. Study Design  Development of 5,868 children in Upstate KIDS (New York State; 2008–2014) was assessed at 7 time points using the Ages and Stages Questionnaire (ASQ). The ASQ was implemented using gestational age corrected dates of birth at 4, 8, 12, 18, 24, 30, and 36 months. Whether children were eligible for developmental services from the Early Intervention Program was determined through linkage. Gestational age was based on vital records. Statistical models adjusted for covariates including sociodemographic factors, maternal smoking, and plurality. Results  Compared with gestational age of 39 weeks, adjusted odds ratios (aOR) and 95% confidence intervals of failing the ASQ for children delivered at <32, 32–34, 35–36, 37, 38, and 40 weeks of gestational age were 5.32 (3.42–8.28), 2.43 (1.60–3.69), 1.38 (1.00–1.90), 1.37 (0.98–1.90), 1.29 (0.99–1.67), 0.73 (0.55–0.96), and 0.51 (0.32–0.82). Similar risks of being eligible for Early Intervention Program services were observed (aOR: 4.19, 2.10, 1.29, 1.20, 1.01, 1.00 [ref], 0.92, and 0.78 respectively for <32, 32–34, 37, 38, 39 [ref], 40, and 41 weeks). Conclusion  Gestational age was inversely associated with developmental delays for all gestational ages. Evidence from our study is potentially informative for low-risk deliveries at 39 weeks, but it is notable that deliveries at 40 weeks exhibited further lower risk. [ABSTRACT FROM AUTHOR]

We examined whether cesarean delivery (CD) increased the risk of wheeze or food allergy in early childhood compared with vaginal delivery and whether these associations were mediated by breastfeeding. The study population was the Upstate KIDS cohort (2008–2010) of mothers and infants from the State of New York (excluding New York City). Infant's wheeze was reported by questionnaire every 4–6 months until 3 years of age, as were food allergies beginning at 8 months. Modified Poisson regression was used to compare risks of the outcomes according to mode of delivery (MOD). Potential confounders were identified a priori using directed acyclic graphs. Emergency CD (n = 1,356) was associated with elevated risk of wheeze, adjusting for pregnancy complications, maternal atopy, gestational age, birth weight, and smoking during pregnancy (risk ratio = 2.47, 95% confidence interval: 1.31, 4.66), and an increased risk of food allergy, adjusting for maternal atopy, prepregnancy body mass index, smoking during pregnancy, and parity (risk ratio = 3.02, 95% confidence interval: 1.26, 7.25). Neither outcome was significantly associated with planned CD (n = 1,565 infants). Breastfeeding mediated the association between MOD and wheeze but not food allergy. Other factors not associated with early-life microbial transfer, but relating to the development of the outcomes, might contribute to the association between MOD and wheeze/food allergy. [ABSTRACT FROM AUTHOR]

Background: Postpartum weight retention (PPWR) can contribute to obesity development in women of reproductive age. Few studies have examined the association between postnatal diet and PPWR. Objective: We examined both PPWR and substantial PPWR (≥4.55 kg) in association with the following dietary patterns: the alternate Mediterranean Diet Score (aMED) and the Alternative Healthy Eating Index-2010 (AHEI-2010). Design: Women (n = 1136) in the Infant Feeding Practices Study II (2005-2007) self-reported their prepregnancy and postpartum weights at ~4, 7, 10, and 14 mo. Dietary patterns were calculated from a food-frequency questionnaire administered ~4 mo postpartum. Linear mixed models and generalized estimating equations for repeated measurements were used to examine PPWR and substantial PPWR, respectively, in association with the dietary patterns with adjustment for energy intake, breastfeeding, age, education, smoking, and marital status. Results: At 14 mo postpartum, the mean (±SD) PPWR was 1.1 ± 6.7 kg, and 22.4% of women had substantial PPWR. Although the change in PPWR over time seemed to differ by diet quality 4-7 mo postpartum, no differences were ultimately observed in the total mean PPWR or probability of substantial PPWR across aMED and AHEI-2010 categories during the rest of the follow-up (P > 0.12). Instead, PPWR and substantial PPWR were associated with total energy intake (at ~7-14 mo postpartum: 0.97 kg/1000 kcal (95% CI: 0.40, 1.55 kg/1000 kcal); OR: 1.25/1000 kcal (95% CI: 1.03, 1.52/1000 kcal), respectively]. Conclusions: Postpartum diet quality assessed by 2 patterns was not associated with weight retention. Total energy intake, regardless of the diet composition, plays a more important role in weight retention. [ABSTRACT FROM AUTHOR]

Carbon isotopic signatures (“δ13C”) might reflect consumption of corn- and cane-based sweeteners. The authors hypothesized that the δ13C value of human serum is higher for individuals with high versus low intakes of corn- and cane-based sweeteners (measured as sweetened beverage intake). They conducted a cross-sectional study within the Atherosclerosis Risk in Communities Magnetic Resonance Imaging study (Maryland, 2005–2006). Diet was assessed by food frequency questionnaire, and blinded serum samples were assayed by natural abundance stable isotope mass spectroscopy. Studied were 186 participants (53% male; mean age, 71 years; mean body mass index, 30 kg/m2). Serum δ13C values for individuals with high sweetened beverage intakes were significantly higher than for those with low intakes (−19.15‰ vs. −19.47‰, P < 0.001). Serum δ13C value increased 0.20‰ for every serving/day of sweetened beverages (P < 0.01). The association between sweetened beverages and serum δ13C value remained significant after adjustment for confounding by corn-based product intake (P < 0.001). Serum δ13C values were also associated with waist circumference, body mass index, and waist-to-hip ratio. This study provides the first known evidence that the δ13C value of human serum differs between persons consuming low and high amounts of sweets. Within the proper framework, serum δ13C value could be developed into an objective biomarker promoting more reliable assessment of dietary sweets intake. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. METHODS: Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at ~4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8,12,18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with ≥1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). RESULTS: Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI ≥30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI ≥35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85). CONCLUSIONS: Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether data obtained from maternal self-report for assisted reproductive technology treatment parameters and reproductive history are accurate for use in research studies.Objectives: We evaluated the accuracy of self-reported in assisted reproductive technology treatment and reproductive history from the Upstate KIDS study in comparison with clinical data reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System.Study Design: Upstate KIDS maternal questionnaire data from deliveries between 2008 and 2010 were linked to data reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System. The 617 index deliveries were compared as to treatment type (frozen embryo transfer and donor egg or sperm) and use of intracytoplasmic sperm injection and assisted hatching. Use of injectable medications, self-report for assisted reproductive technology, or frozen embryo transfer prior to the index deliveries were also compared. We report agreement in which both sources had yes or both no and sensitivity of maternal report using Society for Assisted Reproductive Technology Clinic Outcome Reporting System as the gold standard. Significance was determined using χ(2) at P < 0.05.Results: Universal agreement was not reached on any parameter but was best for treatment type of frozen embryo transfer (agreement, 96%; sensitivity, 93%) and use of donor eggs (agreement, 97%; sensitivity, 82%) or sperm (agreement, 98%; sensitivity, 82%). Use of intracytoplasmic sperm injection (agreement, 78%: sensitivity, 78%) and assisted hatching (agreement, 57%; sensitivity, 38%) agreed less well with self-reported use (P < .0001). In vitro fertilization (agreement, 82%) and frozen embryo transfer (agreement, 90%) prior to the index delivery were more consistently reported than was use of injectable medication (agreement, 76%) (P < .0001).Conclusion: Women accurately report in vitro fertilization treatment but are less accurate about procedures handled in the laboratory (intracytoplasmic sperm injection or assisted hatching). Clinics might better communicate with patients on the use of these procedures, and researchers should use caution when using self-reported treatment data. [ABSTRACT FROM AUTHOR]

Objective: To study the associations between maternal polycystic ovary syndrome (PCOS) and hirsutism with offspring attention-deficit/hyperactivity disorder (ADHD), anxiety, conduct disorder, and behavioral problems.Design: Prospective birth cohort study.Setting: Not applicable.Patient(s): A total of 1,915 mother-child dyads.Intervention(s): None.Main Outcome Measure(s): Maternal report of offspring ADHD, anxiety, or conduct disorder diagnosis at 7 to 8 years; emotional symptoms, behavioral problems (including peer relationship, conduct, hyperactivity/inattention), and prosocial problems measured with the Strengths and Difficulties Questionnaire (SDQ) at 7 years.Result(s): Prevalence of PCOS and hirsutism were 12.0% and 3.9%; 84% of women with hirsutism had PCOS. After adjustment for sociodemographic covariates, prepregnancy body mass index, and parental history of affective disorders, children born to mothers with PCOS had higher risk of anxiety (adjusted risk ratio [aRR] 1.62; 95% confidence interval [CI], 1.02-2.57) and borderline emotional symptoms (aRR 1.66; 95% CI, 1.18-2.33) compared with children born to mothers without PCOS. The associations between maternal PCOS and offspring ADHD were positive but imprecise. Maternal hirsutism was related to a higher risk of children's ADHD (aRR 2.33; 95% CI, 1.28-4.24), conduct disorder (aRR 2.54; 95% CI 1.18-5.47), borderline emotional symptoms, peer relationship problems, and conduct problems (aRRs 2.61; 95% CI, 1.69-4.05; 1.92; 95% CI, 1.16-3.17; and 2.22; 95% CI, 1.30-3.79, respectively).Conclusion(s): Maternal PCOS was associated with offspring anxiety, and hirsutism was related to other offspring behavioral problems. These findings should be interpreted with caution as replication is needed in prospective cohort studies that assess PCOS and hirsutism diagnoses using medical records. [ABSTRACT FROM AUTHOR]