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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: To evaluate whether children conceived using assisted reproductive technology (ART) or ovulation induction (OI) have greater cardiometabolic risk than children conceived without treatment.Design: Clinical assessments in 2018-2019 in the Upstate KIDS cohort.Setting: Clinical sites in New York.Patient(s): Three hundred thirty-three singletons and 226 twins from 448 families.Intervention(s): Mothers reported their use of fertility treatment and its specific type at baseline and approximately 4 months after delivery. High validity of the self-reported use of ART was previously confirmed. The children were followed up from infancy through 8-10 years of age. A subgroup was invited to participate in clinic visits.Main Outcome Measure(s): The measurements of blood pressure (BP), arterial stiffness using pulse wave velocity, anthropometric measures, and body fat using bioelectrical impedance analysis were performed (n = 559). The levels of plasma lipids, C-reactive protein, and hemoglobin A1c were measured using blood samples obtained from 263 children.Result(s): The average age of the children was 9.4 years at the time of the clinic visits Approximately 39% were conceived using fertility treatment (18% using ART and 21% using OI). Singletons conceived using fertility treatment (any type or using ART or OI specifically) did not statistically differ in systolic or diastolic BP, heart rate, or pulse wave velocity. Singletons conceived using OI were smaller than singletons conceived without treatment, but the average body mass index of the latter was higher (z-score: 0.41 [SD, 1.24]) than the national norms. Twins conceived using either treatment had lower BP than twins conceived without treatment. However, twins conceived using OI had significantly higher arterial stiffness (0.59; 95% CI, 0.03-1.15 m/s), which was attenuated after accounting for maternal BP (0.29; 95% CI, -0.03 to 0.46 m/s). Twins did not significantly differ in size or fat measures across the groups. The mode of conception was not associated with the levels of lipids, C-reactive protein, or glycosylated hemoglobin.Conclusion(s): Clinical measures at the age of 9 years did not indicate greater cardiometabolic risk in children conceived using ART or OI compared with that in children conceived without treatment.Clinical Trial Registration Number: ClinicalTrials.gov #NCT03106493. [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: To investigate whether deoxyribonucleic acid (DNA) methylation at birth and in childhood differ by conception using assisted reproductive technologies (ART) or ovulation induction compared with those in children conceived without fertility treatment.Design: Upstate KIDS is a matched exposure cohort which oversampled on newborns conceived by treatment.Setting: New York State (excluding New York City).Patient(s): This analysis included 855 newborns and 152 children at approximately 9 years of age.Intervention(s): None.Main Outcome Measure(s): DNA methylation levels were measured using the Illumina EPIC platform. Single CpG and regional analyses at imprinting genes were conducted.Result(s): Compared to no fertility treatment, ART was associated with lower mean DNA methylation levels at birth in 11 CpGs (located in/near SYCE1, SPRN, KIAA2013, MYO1D, GET1/WRB-SH4BGR, IGF1R, SORD, NECAB3/ACTL10, and GET1) and higher mean methylation level in 1 CpG (KLK4; all false discovery rate P<.05). The strongest association (cg17676129) was located at SYCE1, which codes for a synaptonemal complex that plays a role in meiosis and therefore infertility. This CpG remained associated with newborn hypomethylation when the analysis was limited to those conceived with ICSI, but this may be because of underlying male infertility. In addition, nine regions in maternally imprinted genes (IGF1R, PPIEL, SVOPL GNAS, L3MBTL, BLCAP, HYMAI/PLAGL1, SNU13, and MEST) were observed to have decreased mean DNA methylation levels among newborns conceived by ART. In childhood, hypomethylation of the maternally imprinted gene, GNAS, persisted. No CpGs or regions were associated with ovulation induction.Conclusion(s): ART but not ovulation induction was associated with hypomethylation at birth, but only one difference at an imprinting region appeared to persist in childhood. [ABSTRACT FROM AUTHOR]

Despite diet being a first-line strategy for preventing cardiovascular disease, the optimal macronutrient profile remains unclear. We studied the effects of macronutrient profile on subclinical cardiovascular injury and inflammation. OmniHeart was a randomized 3-period, crossover feeding study in 164 adults with high blood pressure or hypertension (SBP 120–159 or DBP 80–99 mm Hg). Participants were fed each of 3 diets (emphasizing carbohydrate (CARB), protein (PROT), or unsaturated fat (UNSAT)) for 6-weeks, with feeding periods separated by a washout period. Weight was held constant. Fasting serum was collected at baseline while participants ate their own diets and after each feeding period. High-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity C-reactive protein (hs-CRP) were measured in stored specimens. The average age was 53.6 years, 55% were African American, and 45% were women. At baseline, the median (25th-percentile, 75th-percentile) hs-cTnI was 3.3 ng/L (1.9, 5.6) and hs-CRP was 2.2 mg/L (1.1, 5.2). Compared to baseline, all 3 diets reduced hs-cTnI: CARB –8.6% (95%CI: −16.1, −0.4), PROT –10.8% (−18.4, −2.5), and UNSAT −9.4% (−17.4, −0.5). Hs-CRP was similarly changed by −13.9 to −17.0%. Hs-cTnI and hs-CRP reductions were of similar magnitudes as SBP and low-density lipoprotein cholesterol (LDLc) but were not associated with these risk-factor reductions (P - values = 0.09). There were no between-diet differences in hs-cTnI and hs-CRP reductions. Healthy diet, regardless of macronutrient emphasis, directly mitigated subclinical cardiac injury and inflammation in a population at risk for cardiovascular disease. These findings support dietary recommendations emphasizing healthy foods rather than any one macronutrient. Trial Registration : This trial is registered at clinicaltrials.gov , number: NCT00051350 ; URL: https://clinicaltrials.gov/ct2/show/NCT00051350. • Three healthy diets led to reduction in high-sensitivity troponin, a marker of subclinical cardiac injury. • Inflammation, measured by high-sensitivity CRP, was also reduced by all three healthy diets. • These changes were not explained alone by improvement in hypertension or hyperlipidemia. • All three healthy diets can be recommended to help reduce cardiovascular risk. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether family history of cardiovascular disease (CVD) is a risk factor for pregnancy loss, given potential shared etiology, including vascular mechanisms involved in reproduction and placentation.Methods: In a prospective study, first-degree family histories were self-reported before pregnancy among women with 1-2 previous losses. Women were followed for up to 6 menstrual cycles while attempting pregnancy and through pregnancy. Pregnancies were ascertained by urinary human chorionic gonadotropin and confirmed by ultrasound. Risk ratios and 95% confidence intervals for pregnancy loss were estimated using weighted Poisson regression models with robust standard errors adjusted for covariates including prepregnancy body mass index and sociodemographics.Results: Of 1228 women enrolled, 742 had a clinically confirmed pregnancy, and of these, 18% experienced a clinical pregnancy loss. Forty six percent of women reported family history of CVD, diabetes, hypertension, or hypercholesterolemia/dyslipidemia. Family history of CVD was not associated with the risk of pregnancy loss overall (1.01; 95% confidence interval: 0.64, 1.59) or among women with 2 previous losses (1.05; 0.51, 2.17). Family history of hypertension was also not associated with pregnancy loss (0.98; 0.65, 1.46).Conclusions: Family history of CVD is not providing additional information helpful in determining the risk of subsequent pregnancy loss in an at-risk group. [ABSTRACT FROM AUTHOR]

Abstract Background Novel methodologies to quantify infant exposures to endocrine disrupting chemicals (EDCs) for population-based studies are needed. Objectives We used newborn dried blood spots to quantify three EDCs and their associations with infant outcomes in the Upstate KIDS Cohort. Methods We measured bisphenol A (BPA), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in 2071 singleton and 1040 twin infants born to mothers in New York State. We log transformed concentrations after rescaling by their standard deviations and modeled each in relation to gestational age, birthweight, length, head circumference and Ponderal Index (PI) using linear regression techniques. All models were adjusted for maternal age, body mass index, education, infertility treatment and parity. Generalized estimating equations with robust standard errors were used to assess the associations for twins. Results Chemicals were largely quantified above the limits of detection (>99% for PFOS and PFOA; 90% for BPA). Overall, we observed no significant associations between PFASs and birth size irrespective of plurality of birth. However, among twins, BPA was associated with decreases in gestational age (adjusted β = −0.09 weeks; 95% Confidence Interval (CI): −0.16, −0.02) and birthweight (adjusted β = −32.52 g; 95% CI: −60.99, −4.05), head circumference (adjusted β = −0.18 cm; 95% CI: −0.38, −0.02) and increased PI in singletons (adjusted β = 0.02 cm; 95% CI: 0.004, 0.04). Conclusion We observed negative associations between BPA and birth size in twins. Our findings demonstrate the feasibility of newborn dried blood spots for quantifying neonatal exposure at the population level. Highlights • Used newborn dried blood spots to quantify BPA, PFOS and PFOA • Observed inverse association between BPA and birth size in twins • No observed association between BPA and birth size in singletons • No observed association with PFOS and PFOA and birth size, regardless of plurality [ABSTRACT FROM AUTHOR]

To evaluate whether underlying infertility and mode of conception are associated with childhood behavioral disorders. Oversampling on fertility treatment exposure using vital records, the Upstate KIDS Study followed 2057 children (of 1754 mothers) from birth to 11 years. Type of fertility treatment and time to pregnancy (TTP) were self-reported. Mothers completed annual questionnaires reporting symptomology, diagnoses, and medications at 7–11 years of age. The information identified children with probable attention-deficit/hyperactivity disorder, anxiety or depression, and conduct or oppositional defiant disorders. We estimated adjusted relative risks (aRR) for disorders by underlying infertility (TTP > 12 months) or treatment exposure groups compared to children born to parents with TTP ≤ 12 months. Children conceived with fertility treatment (34%) did not have an increased risk of attention-deficit/hyperactivity disorder (aRR): 1.21; 95% CI: 0.88, 1.65), or conduct or oppositional defiant disorders (aRR: 1.31; 0.91, 1.86), but did have an increased risk of anxiety or depression (aRR: 1.63; 1.18, 2.24), which remained elevated even after adjusting for parental mood disorders (aRR: 1.40; 0.99, 1.96). Underlying infertility without the use of treatment was also associated with a risk of anxiety or depression (aRR: 1.82; 95% CI: 0.96, 3.43). Underlying infertility or its treatment was not associated with risk of attention-deficit/hyperactivity disorder. Observations of increased anxiety or depression require replication. [ABSTRACT FROM AUTHOR]

Background: The relation between breastfeeding and early motor development is difficult to characterize because of the problems in existing studies such as incomplete control for confounding, retrospective assessment of infant feeding, and even the assessment of some motor skills too early. Objective: We sought to estimate associations between infant feeding and time to achieve major motor milestones in a US cohort. Design: The Upstate New York Infant Development Screening Program (Upstate KIDS Study) enrolled mothers who delivered live births in New York (2008-2010). Mothers of 4270 infants (boys: 51.7%) reported infant motor development at 4, 8, 12, 18, and 24 mo postpartum; information on infant feeding was reported at 4 mo. Accelerated failure time models were used to compare times to standing or walking across feeding categories while adjusting for parental characteristics, daycare, region, and infant plurality, sex, rapid weight gain, and baseline neurodevelopmental test results. Main models were stratified by preterm birth status. Results: The prevalence of exclusive breastfeeding in preterm infants was lower than in term infants at 4 mo postpartum (8% compared with 19%). After adjustment for confounders, term infants who were fed solids in addition to breast milk at 4 mo postpartum achieved both standing [acceleration factor (AF): 0.93; 95% CI: 0.87, 0.99] and walking (AF: 0.93; 95% CI: 0.88, 0.98) 7% faster than did infants who were exclusively breastfed, but these findings did not remain statistically significant after correction for multiple testing. We did not identify feeding-associated differences in motor milestone achievement in preterm infants. Conclusion: Our results suggest that differences in feeding likely do not translate into large changes in motor development. [ABSTRACT FROM AUTHOR]

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking. Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM). Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors. Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P-trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth. Conclusions: Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with off-spring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

Background: Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications. Objective: We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status. Design: FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offspring's ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors. Results: At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (β = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (β = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo. Conclusion: Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI. [ABSTRACT FROM AUTHOR]

Objectives: To assess the association between age of juice introduction and child anthropometry after the American Academy of Pediatrics changed their guidelines in 2017 to recommend delaying juice introduction until at least 12 months of age (previously 6 months), citing concerns of weight gain.Study Design: Upstate KIDS is a prospective birth cohort with follow-up through 9 years of age. Juice introduction was assessed on parental questionnaires at 4-18 months and categorized as <6, 6-<12, and ≥12 months. Child height and weight were recorded at 2-3 and 7-9 years of age. Weight-, height-, and body mass index (BMI)-for-age and sex z scores were calculated using the Centers for Disease Control and Prevention reference. Overweight/obese and obese status were categorized as BMI-for-age z score ≥85th and ≥95th percentiles. Controlling for sociodemographic characteristics and parental BMI, we assessed the associations of age of juice introduction with child anthropometry.Results: Prevalence of childhood obesity was 16.4% at 2-3 (n = 1713) and 22.8% at 7-9 years of age (n = 1283). Juice introduction at <6 vs ≥12 months was associated with higher weight-for-age z score at 2-3 years of age (mean difference = 0.21; 95% CI 0.04-0.37). At 7-9 years of age, juice introduction at <6 vs ≥12 months was related to higher BMI-for-age (0.38; 0.12-0.64) and weight-for-age z scores (0.27; 0.06-0.49). Risk of developing overweight/obesity and obesity was 1.54 (0.99-2.38) and 2.17 (1.11-4.23) times higher among children with juice introduced at <6 months. No associations were found with juice introduced at 6-<12 vs ≥12 months.Conclusions: Risk of developing overweight/obesity or obesity is higher among children introduced to juice before 6 months of age compared with ≥12 months. [ABSTRACT FROM AUTHOR]

Isoflavones have been associated with lower cardiovascular disease risk, but existing research focused on very high isoflavone intakes, as seen in Asian populations, as well as on risk factor reductions primarily in postmenopausal women. We investigated whether habitual low isoflavone intake among premenopausal women was associated with serum C-reactive protein (CRP) concentration, a commonly used biomarker associated with prediction of cardiovascular disease risk in healthy women. Between 2005 and 2007, 259 healthy, regularly menstruating women were enrolled in the BioCycle Study, and followed for up to 2 menstrual cycles. CRP was measured in serum at up to 16 clinic visits, timed to phases of the women's menstrual cycle. Diet was assessed up to 4 times per cycle by using 24-h recalls. Marginal structural models with inverse probability of exposure weights estimated the association between CRP and quartiles of isoflavone intake adjusted for age, race, BMI, cycle phase, total energy intake, total fiber, total whole grains, and phase-specific hormone concentrations including estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone. Compared with the lowest quartile of total isoflavone intake, women in the highest quartile had, on average, 27% lower serum CRP concentrations (95% CI: -35, -21%). Our results suggest that dietary isoflavone intakes at levels characteristic of the U.S. population are associated with decreased serum CRP concentrations, a factor associated with beneficial effects on inflammation, and subsequently may have the potential to improve health status among young women. [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]

Background: Consumption of high-fructose corn syrup, as well as cane sugar, has been implicated in the rise of the obesity and diabetes epidemics. To date, however, no reliable biomarker for the consumption of these sweeteners is available. Objective: The objective of the study was to determine the natural abundance stable-carbon-isotope signature of commonly consumed foods of plant origin. Design: Samples from ≈100 plant-derived food products purchased from local grocery stores were analyzed for 13C content by using stable-isotope mass spectroscopy. Results: Measurement of natural abundance ratios of 13C to 12C in ≈100 off-the-shelf foods found a distinct range of values for corn and sugar cane- derived foods, particularly those rich in high fructose corn syrup. Conclusion: A new technique, in which consumption of these foods may be estimated in humans by measuring the natural abundance stable-carbon-isotope profile of corn- and sugar cane-sweetened or sugar-containing foods as tracked in tissue or blood, could potentially provide an objective assessment of dietary intake and offer new opportunities for the study of diet-disease relations. [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]

Maternal antenatal depression experienced around conception or during pregnancy may adversely affect child development. This study explores three potential mechanisms of the effects of antenatal depression on children's developmental delays at 2–3 years: gestational age of the child, continued depressive symptoms postnatally, and interrupted breastfeeding practices. Mothers (N = 2888) of 3450 children, including 2303 singletons and 1147 multiples from the Upstate KIDS cohort provided data. Linked hospital discharge data was combined with mothers' reports to identify women with moderate to severe antenatal depression. Gestational age was extracted from birth certificates. Mothers completed a depression screener at 4 months postpartum, reported about their breastfeeding practices from 4 to 12 months postpartum, and completed a developmental delay screener when children were 24, 30, and 36 months. In unadjusted path analysis models, mothers with antenatal depression had more postnatal depressive symptoms and breastfed fewer months, which translated into children being more likely to have developmental delays. Gestational age was not a mediator. Effects were similar across girls and boys and singletons and twins, and largely held when adjusting for covariates. Main limitations were the relatively advantaged sample and reliance on maternal report. Maternal antenatal depression may impact child development through continued depressive symptoms in the postpartum period and through reduced breastfeeding duration suggesting additional targets for intervention. • This study explored 3 potential mechanisms of antenatal depression's effects on children's developmental delays at 2-3 years. • Associations were partially mediated by postnatal depression symptoms and breastfeeding duration, but not gestational age. • Models were similar across singletons and twins as well as girls and boys. • Beyond treating depression, this study suggests that breastfeeding may be a viable target for intervention. [ABSTRACT FROM AUTHOR]

The cardiometabolic health of children conceived by assisted reproductive technologies (ART) compared with children conceived without medical assistance is unclear. Although the majority of published studies evaluating height, weight, and body mass index have not found differences by method of conception, some studies have indicated differences in adiposity by more direct measures such as skinfolds and dual X-ray absorptiometry. Far fewer studies have investigated other cardiometabolic characteristics, such as blood pressure and measures of lipid and glucose metabolism. Of these studies, some indications of increased blood pressure and recent findings of vascular dysfunction among children conceived by ART compared with children conceived without ART warrant further investigation. Epigenetic differences may be the global mechanism at work, resulting from different aspects of ART treatment, such as ovarian stimulation, in vitro culture, and manipulation of sperm, among other considerations. Fetal growth and placental development may serve as mediators of these effects. Future studies should consider recruiting sufficient numbers of ART and non-ART conceived multiples and collect information on indicators of cardiometabolic health in the parents. Despite some advantages of sibling cohorts in developmental origins research, its feasibility and utility for investigating health of children conceived by ART remains debatable. [ABSTRACT FROM AUTHOR]

Single-pollutant models have linked prenatal PM 2.5 exposure to lower birthweight. However, analyzing air pollutant mixtures better captures pollutant interactions and total effects. Unfortunately, strong correlations between pollutants restrict traditional methods. We explored the association between exposure to a mixture of air pollutants during different gestational age windows of pregnancy and birthweight. We included 4,635 mother-infant dyads from a New York State birth cohort born 2008–2010. Air pollution data were sourced from the EPA's Community Multiscale Air Quality model and matched to the census tract centroid of each maternal home address. Birthweight and gestational age were extracted from vital records. We applied linear regression to study the association between prenatal exposure to PM 2.5 , PM 10 , NO X , SO 2 , and CO and birthweight during six sensitive windows. We then utilized Bayesian kernel machine regression to examine the non-linear effects and interactions within this five-pollutant mixture. Final models adjusted for maternal socio-demographics, infant characteristics, and seasonality. Single-pollutant linear regression models indicated that most pollutants were associated with a decrement in birthweight, specifically during the two-week window before birth. An interquartile range increase in PM 2.5 exposure (IQR: 3.3 µg/m3) from the median during this window correlated with a 34 g decrement in birthweight (95 % CI: −54, −14), followed by SO 2 (IQR: 2.0 ppb; β: −31), PM 10 (IQR: 4.6 µg/m3; β: −29), CO (IQR: 60.8 ppb; β: −27), and NO X (IQR: 7.9 ppb; β: −26). Multi-pollutant BKMR models revealed that PM 2.5 , NO X , and CO exposure were negatively and non-linearly linked with birthweight. As the five-pollutant mixture increased, birthweight decreased until the median level of exposure. Prenatal exposure to air pollutants, notably PM 2.5 , during the final two weeks of pregnancy may negatively impact birthweight. The non-linear relationships between air pollution and birthweight highlight the importance of studying pollutant mixtures and their interactions. [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]

Purpose: Examine associations between interpregnancy body mass index (BMI) change (difference in the pre-pregnancy BMIs of two consecutive pregnancies) and gestational diabetes mellitus (GDM), pre-eclampsia (PE), gestational hypertension (GHtn), primary cesarean delivery, and vaginal birth after cesarean delivery (VBAC).Methods: Modified Poisson regression models estimated adjusted associations.Results: Every 1-unit increase in interpregnancy BMI increased risks of GDM (relative risk [RR]: 1.09; 95% confidence interval [CI], 1.07-1.11), PE (RR: 1.06; 95% CI, 1.04-1.09), GHtn (RR: 1.08; 95% CI, 1.06-1.10), and primary cesarean delivery (RR: 1.03; 95% CI, 1.01-1.05) and decreased the risk of a successful VBAC (RR: 0.98; 95% CI: 0.97-0.997) in the second pregnancy. A BMI increase of ≥3 units increased risks of GDM (RR: 1.71, 95% CI, 1.52-1.93), PE (RR: 1.60, 95% CI, 1.33-1.94), GHtn (RR: 1.66, 95% CI, 1.42-1.94), and primary cesarean delivery (RR: 1.29, 95% CI, 1.12-1.49) and decreased the risk of a successful VBAC (RR: 0.89; 95% CI, 0.80-0.99) compared to women with interpregnancy BMI change within -1 and +1 unit. GDM was also increased among women increasing their BMI by ≥2 but <3 units (RR: 1.40; 95% CI, 1.21-1.61) and among those gaining ≥1 but <2 units (RR: 1.23; 95% CI, 1.08-1.40).Conclusion: An interpregnancy BMI increase of ≥3 units is associated with an increased risk of all outcomes. These findings emphasize the importance of interpregnancy weight management. [ABSTRACT FROM AUTHOR]

Prune belly syndrome (PBS), also known as Eagle-Barrett syndrome, is a rare congenital disorder characterized by absence or hypoplasia of the abdominal wall musculature, urinary tract anomalies, and cryptorchidism in males. The etiology of PBS is largely unresolved, but genetic factors are implicated given its recurrence in families. We examined cases of PBS to identify novel pathogenic copy number variants (CNVs). A total of 34 cases (30 males and 4 females) with PBS identified from all live births in New York State (1998–2005) were genotyped using Illumina HumanOmni2.5 microarrays. CNVs were prioritized if they were absent from in-house controls, encompassed ≥10 consecutive probes, were ≥20 Kb in size, had ≤20% overlap with common variants in population reference controls, and had ≤20% overlap with any variant previously detected in other birth defect phenotypes screened in our laboratory. We identified 17 candidate autosomal CNVs; 10 cases each had one CNV and four cases each had two CNVs. The CNVs included a 158 Kb duplication at 4q22 that overlaps the BMPR1B gene; duplications of different sizes carried by two cases in the intron of STIM1 gene; a 67 Kb duplication 202 Kb downstream of the NOG gene, and a 1.34 Mb deletion including the MYOCD gene. The identified rare CNVs spanned genes involved in mesodermal, muscle, and urinary tract development and differentiation, which might help in elucidating the genetic contribution to PBS. We did not have parental DNA and cannot identify whether these CNVs were de novo or inherited. Further research on these CNVs, particularly BMP signaling is warranted to elucidate the pathogenesis of PBS. [ABSTRACT FROM AUTHOR]

Objective: To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women. Design: Prospective cohort study. Setting: University. Patient(s): Participants included 259 healthy regularly menstruating women aged 18–44 years. Intervention(s): None. Main Outcome Measure(s): Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women. Result(s): Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6–78.8 mg/d) was significantly associated with greater SHBG concentrations (β = 0.09; 95% confidence interval [CI] 0.02–0.16), compared with the first quartile (Q1: 0.0–0.3 mg/d). Conclusion(s): Isoflavone intake was not associated with sporadic anovulation (Q4 vs. Q1: odds ratio 0.87, 95% CI 0.32–1.66). Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility. [Copyright &y& Elsevier]

Objective: To identify associations between fertility treatment use (assisted reproductive technologies, ovulation induction, and artificial insemination) and subsequent infant feeding practices.Design: The Upstate KIDS population-based cohort enrolled mothers who delivered live births in New York (2008-2010), sampling on fertility treatment and plurality.Setting: Not applicable.Patient(s): Data regarding singletons and one randomly selected infant between twins were used.Intervention(s): Not applicable.Main Outcome Measure(s): Mothers reported breast feeding and formula feeding practices at 4, 8, and 12 months postpartum. Modified Poisson regression was used to compare risks for feeding practices by mode of conception. Marginal structural models were used to estimate the controlled direct effects of fertility treatment on feeding, independent of preterm birth.Result(s): Among 4,591 mothers, 1,361 (30%) conceived with the use of fertility treatments. Mothers who used fertility treatments were less likely to breast feed to 12 months after birth and were more likely to provide formula, solids, and juice by 4 months than mothers who did not conceive with treatments. Fertility treatment remained associated with breast feeding cessation and formula feeding in mediation analyses, suggesting that preterm birth does not fully explain these associations.Conclusion(s): Women who conceived with the use of fertility treatments were less likely to breast feed later in infancy and were more likely to provide formula, solids, and juice earlier in infancy. Our analyses accounted for confounding and preterm birth, but other contributing factors may include difficulties feeding twins or workplace breast feeding accommodations. [ABSTRACT FROM AUTHOR]