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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]

Objectives We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research. Methods Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4 months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic ( k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates with either maternal self-report or SPARCS. Results GHD was under-ascertained on birth certificates (5.7 %) and more frequently indicated by maternal report (11 %) and discharge data (8.2 %). PROM was indicated more on birth certificates (7.4 %) than maternal report (4.5 %) or discharge data (5.7 %). Confirmation across data sources for some outcomes varied by maternal age, race/ethnicity, prenatal care utilization, preterm delivery, parity, mode of delivery, infant sex, use of infertility treatment and for multiple births. Agreement between maternal report and discharge data with birth certificates was generally poor ( kappa < 0.4) to moderate (0.4 ≤ kappa < 0.75) but was excellent between discharge data and birth certificates for GDM among women who underwent infertility treatment ( kappa = 0.79, 95 % CI 0.74, 0.85). Conclusions for Practice Prevalence and agreement of conditions varied across sources. Condition-specific variations in reporting should be considered when designing studies that investigate associations between preexisting maternal medical and pregnancy-related conditions with health outcomes over the life-course. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We examined the longitudinal associations of age at achieving gross motor milestones and children's development in a US cohort of singletons and twins. METHODS: In the Upstate KIDS study, a population-based study of children born between 2008 and 2010, information on age at achievement of motor milestones and developmental skills was available in 599 children (314 singletons, 259 twins, and 26 triplets). Mothers reported their children's major motor milestones at ~4, 8, 12, 18, and 24 months. At age 4 years, children's development was clinically assessed by using the Battelle Developmental Inventory, Second Edition (BDI-2). Primary analyses by using multivariate linear regressions were conducted in singletons. We also examined the associations in twins. RESULTS: Later achievement of standing with assistance predicted lower BDI-2 scores in singletons in adjusted models (B per SD of age at achievement, -21.9 [95% confidence interval (CI), -41.5 to -2.2]). Post hoc analysis on age of standing with assistance showed that associations were driven by differences in adaptive skills (B = -5.3 [95% CI, -9.0 to -1.6]) and cognitive skills (B = -5.9 [95% CI, -11.5 to -0.4]). Analyses restricted to twins suggested no association between the age at achievement of milestones and total BDI-2 score after adjustment for gestational age and birth weight. CONCLUSIONS: This study provides evidence that the age of achieving motor milestones may be an important basis for various aspects of later child development. In twins, key predictors of later development (eg, perinatal factors) overshadow the predictive role of milestones in infancy. [ABSTRACT FROM AUTHOR]

Aim: We examined whether children of mothers with a medical condition diagnosed before or during pregnancy took longer to achieve gross motor milestones up to age 24 months.Method: We obtained information on medical conditions using self-reports, birth certificates, and hospital records in 4909 mothers participating in Upstate KIDS, a population-based birth cohort. Mothers reported on their children's motor milestone achievement at 4, 8, 12, 18, and 24 months of age.Results: After adjustment for covariates (including pre-pregnancy body mass index), children of mothers with gestational diabetes took longer to achieve sitting without support (hazard ratio [HR]=0.84, 95% confidence interval [CI] 0.75-0.93), walking with assistance (HR=0.88, 95% CI 0.77-0.98), and walking alone (HR=0.88, 95% CI 0.77-0.99) than children of females with no gestational diabetes. Similar findings emerged for maternal diabetes. Gestational hypertension was associated with a longer time to achieve walking with assistance. These associations did not change after adjustment for gestational age or birthweight. Severe hypertensive disorders of pregnancy were related to a longer time to achieve milestones, but not after adjustment for perinatal factors.Interpretation: Children exposed to maternal diabetes, gestational or pre-gestational, may take longer to achieve motor milestones than non-exposed children, independent of maternal obesity. [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]

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]

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]

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]

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]

Abstract: Trace exposures to metals may affect female reproductive health. To assess the relation between trace concentrations of blood metals and female fecundity, 99 non-pregnant women discontinuing contraception for the purpose of becoming pregnant were prospectively followed. Participants completed a baseline interview and daily diaries until pregnant, or up to 12 menstrual cycles at risk for pregnancy; home pregnancy test kits were used. For 80 women, whole blood specimens were analyzed for arsenic, cadmium, lead, magnesium, nickel, selenium and zinc using inductively coupled plasma mass spectrometry (ICP–MS). Time to pregnancy was estimated using Cox proportional hazards models for discrete time. Metal concentrations were generally within population reference intervals. Adjusted models suggest a 51.5% increase in the probability for pregnancy per 3.60μg/L increase in Mg (P =0.062), and a 27.7% decrease per 0.54μg/L increase in Zn (P =0.114). Findings indicate that Mg and Zn may impact female fecundity, but in varying directions. [Copyright &y& Elsevier]