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High weight gain in pregnancy is associated with greater postpartum weight retention, yet long-term implications remain unknown. We aimed to assess whether gestational weight change was associated with mortality more than 50 years later.

ABSTRACTResearch suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation β-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [β(SE): −0.080 (0.010); FDR p = 0.009], cg08471713 [β(SE):0.077 (0.014); FDR p = 0.016] and cg17897916 [β(SE):0.050 (0.009); FDR p = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR p = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.

Carney complex (CNC), is an autosomal dominant multiple neoplasia and lentiginosis syndrome. We aimed to identify risk factors associated with the occurrence and recurrence of cardiac myxomas, the predominant cause of death in CNC patients.

IMPORTANCE: Prenatal exposure to persistent organic pollutants (POPs) has been associated with birth size, but data on fetal growth and among racially/ethnically diverse pregnant women remain scarce. OBJECTIVES: To assess the association between maternal plasma POPs in early pregnancy and fetal growth and by infant sex and maternal race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the National Institute of Child Health and Human Development Fetal Growth Studies–Singleton cohort, which recruited nonobese, low-risk pregnant women before 14 weeks’ gestation between July 1, 2009, and January 31, 2013, in 12 community-based clinics throughout the United States. Participants self-identified their race/ethnicity, self-reported their behavioral risk factors, and were followed up throughout their pregnancy. Data were analyzed from July 31, 2018, to June 3, 2019. EXPOSURES: Levels of 76 POPs in early gestation plasma were measured: 11 perfluoroalkyl and polyfluoroalkyl substances, 1 polybrominated biphenyl, 9 polybrominated diphenyl ethers (PBDEs), 44 polychlorinated biphenyls (PCBs), and 11 organochlorine pesticides (OCPs). The bayesian kernel machine regression method was used to examine chemical class mixtures, and generalized additive mixed model was used to analyze individual chemicals. MAIN OUTCOMES AND MEASURES: Fourteen fetal biometrics were measured, including head circumference, abdominal circumference, and femur length, within 5 ultrasonography appointments. RESULTS: A total of 2284 low-risk pregnant women were included: 606 women (26.5%) self-identified as white with a mean (SD) age of 30.3 (4.4) years, 589 (25.8%) as black with a mean (SD) age of 25.5 (5.5) years, 635 (27.8%) as Hispanic with a mean (SD) age of 27.1 (5.5) years, and 454 (19.9%) as Asian with a mean (SD) age of 30.5 (4.5) years. A comparison between the 75th and 25th percentile of exposure revealed that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% CI, −6.7 to −2.8 mm) in head circumference, 3.5 mm (95% CI, −4.7 to −2.2 mm) in abdominal circumference, and 0.6 mm (95% CI, −1.1 to −0.2 mm) in femur length. Higher exposure to the PBDE mixture was associated with reduced abdominal circumference (–2.4 mm; 95% CI, −4.0 to −0.5 mm) and femur length (−0.5 mm; 95% CI, −1.0 to −0.1 mm), and the dioxin-like PCB mixture was associated with reduced head circumference (–6.4 mm; 95% CI, −8.4 to −4.3 mm) and abdominal circumference (–2.4 mm; 95% CI, −3.9 to −0.8 mm). Associations with individual chemicals were less consistent. There were some interactions by fetal sex, although most of the results did not vary by maternal race/ethnicity. For example, oxychlordane (–0.98 mm; 95% CI, –1.60 to –0.36 mm; P for interaction <.001), trans-nonachlor (–0.31 mm; 95% CI, –0.54 to –0.08 mm; P for interaction = .005), and p,p’-dichlorodiphenyldichloroethylene (–0.19 mm; 95% CI, –0.22 to –0.09 mm; P for interaction = .006) were associated with shorter femur length among boys only. CONCLUSIONS AND RELEVANCE: This study found that, among pregnant women with low POP levels, a mixture of OCPs was negatively associated with most fetal growth measures and that mixtures of PBDEs and dioxin-like PCBs were associated with reduced abdominal circumference. These findings suggested that, although exposures may be low, associations with fetal growth are apparent.

IMPORTANCE: Many children begin interacting with screen media as early as infancy. Although screen time is associated with negative developmental consequences, few longitudinal studies in the United States have examined covariates of screen time among children under 3 years of age. OBJECTIVES: To identify trajectories of screen time among children aged 1 to 3 years, to examine their association with screen use at 8 years of age, and to assess potential determinants of screen time. DESIGN, SETTING, AND PARTICIPANTS: This prospective birth cohort study included 3895 children (3083 singletons and 812 unrelated multiples) in New York State who had screen time data available for at least 1 time point from 1 to 3 years of age; 1156 children had data at 8 years. The study spanned September 4, 2007, through June 12, 2014, in the first phase, and August 29, 2014, through November 15, 2019, in the second phase. Data analysis for the present study was conducted from September 28, 2018, to July 15, 2019. MAIN OUTCOMES AND MEASURES: Maternal reports of children’s television, movie, and computer game times were summed for total daily screen time at 12, 18, 24, 30, and 36 months of age. Two screen time trajectories (low and increasing use) were classified by cluster analysis, and logistic regression was used to model risk factors for the increasing trajectory. Children exhibiting the highest 10th percentile of screen use at each point were examined, and linear mixed models were used to identify risk factors of this high exposure category. RESULTS: Among the 3895 children included in the analysis (2031 boys [52.1%] and 1864 girls [47.9%]), median daily screen time increased from 30 (interquartile range, 0-60) minutes at 12 months of age to 120 (interquartile range, 75-200) minutes at 36 months of age. Of 1045 children with complete data at all 5 time points, 279 (26.7%) had an increasing screen time trajectory. Female child sex (adjusted odds ratio [aOR], 0.90; 95% CI, 0.81-0.99) and graduate school levels of paternal (aOR, 0.73; 95% CI, 0.56-0.95) and maternal (aOR, 0.60; 95% CI, 0.47-0.77) education, compared with having completed college, were associated with lower risk of increasing trajectory. Maternal nulliparity was associated with higher risk of increasing trajectory (aOR, 1.14; 95% CI, 1.00-1.30). Children with an increasing trajectory from 1 to 3 years of age had an additional 22 (95% CI, 11-33) minutes per day of screen time at 8 years of age. Covariates associated with the highest 10th percentile of screen exposure included paterman graduate school education compared with college (aOR, 0.63; 95% CI, 0.39-0.99), maternal graduate school education compared with college (aOR, 0.55; 95% CI, 0.37-0.82), maternal nulliparity (aOR, 1.98; 95% CI, 1.50-2.61), twins compared with singletons (aOR, 1.41; 95% CI, 1.05-1.91), non-Hispanic black compared with non-Hispanic white race/ethnicity (aOR, 4.77; 95% CI, 2.25-10.10), and type of care (home-based care aOR, 2.17 [95% CI, 1.38-3.41]; parental care aOR, 2.11 [95% CI, 1.41-3.15]) compared with center-based care. CONCLUSIONS AND RELEVANCE: These findings suggest that a range of parental and child characteristics are associated with screen time. Screen time habits appear to track from as early as infancy, emphasizing the need for earlier interventions.

In the present prospective cohort study with preconception enrollment and daily follow-up of couples, seafood intake in both partners was associated with a higher SIF and greater fecundity.

BackgroundPolycystic ovarian syndrome (PCOS) is the most common cause of female infertility and is associated with higher levels of circulating androgens. Exposure to higher levels of androgens in utero may be a risk factor for obesity among children of women with PCOS.MethodsWe examined whether maternal PCOS was associated with differences in offspring growth and obesity in the Upstate KIDS study, a prospective cohort study of infants born in New York State (excluding New York City) oversampled for fertility treatments and multiple births. Measurements of offspring length/height and weight were recorded at doctor’s visits through 3 years of age. PCOS diagnosis was self-reported by mothers at baseline. We used linear mixed models with robust SEs to estimate differences in growth by maternal PCOS exposure. We used logistic regression to examine whether infants experienced rapid weight gain at 4, 9 and 12 months. Growth measures were reported by 4098 mothers for 4949 children (1745 twins). Of these, 435 mothers (10.6%) had a diagnosis of PCOS.ResultsCompared with children born to mothers without PCOS, children of mothers with PCOS did not have significant differences in weight (4.81 g, 95% CI −95.1 to 104.7), length/height (0.18 cm, 95% CI −0.16 to 0.52) and body mass index (−0.14 kg/m2, 95% CI −0.30 to 0.01) through 3 years of age. We also observed no association between maternal PCOS and offspring rapid weight gain.ConclusionsOverall, we found little evidence to suggest that maternal PCOS influences early childhood growth in this large, prospective cohort study.

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Adverse childhood experiences (ACEs) can have lasting effects on adult health and survival. In this study, we aimed to examine how the cumulative number and clustering patterns of ACEs were related to premature mortality.

IMPORTANCE: An increasing percentage of births are conceived with assisted reproductive technology (ART) and other infertility treatment. Despite findings that such treatments may be associated with diminished gestation and birth size, scarce data exist regarding infertility treatments and children’s development in the United States. OBJECTIVE: To assess the use and type of infertility treatment in relation to children’s development through age 36 months. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (conducted 2008-2014) that sampled based on infertility treatment and plurality. Included in the study were infants born between 2008 and 2010 in New York state (excluding New York City) whose parents completed developmental screening instruments through 36 months of age. A total of 4824 mothers (97% of 4989) completed 1 or more developmental screening instruments for 5841 children, including 1830 conceived with infertility treatment and 2074 twins. EXPOSURES: Maternal self-report of any infertility treatment was further categorized into ART and ovulation induction/intrauterine insemination. Assisted reproductive technology use was previously validated by linkage with the Society for Assisted Reproductive Technology–Clinical Outcome Reporting System. MAIN OUTCOMES AND MEASURES: Five developmental domains (fine motor, gross motor, communication, personal-social functioning, and problem-solving ability), as measured by the parental completion of the Ages and Stages Questionnaires at 4, 8, 12, 18, 24, 30, and 36 months of age. Generalized linear mixed modeling techniques estimated adjusted odds ratios (aORs) and 95% CIs for use and type of infertility treatment in relation to failing a developmental domain. Data were stratified by plurality and weighted for the sampling scheme. RESULTS: There were 1422 mothers (29.5%; mean [SD], age, 34.1 [5.2] years) who underwent infertility treatment. Infertility treatment was not associated with risk of their children failing any developmental domain (aOR, 1.33; 95% CI, 0.94-1.89). Assisted reproductive technology was associated with increased risk for failing any developmental domain but only when singletons and twins were evaluated together (aOR, 1.81; 95% CI, 1.21-2.72). Adjustment for birth weight further attenuated this estimate (aOR, 1.26; 95% CI, 0.82-1.93). After stratifying by plurality, type of treatment also was not significantly associated with failing any developmental domain for ovulation induction/intrauterine insemination (aOR, 1.00; 95% CI, 0.57-1.77 for singletons and aOR, 1.30; 95% CI, 0.76-2.21 for twins) or ART (aOR, 1.38; 95% CI, 0.78-2.43 for singletons and aOR, 1.58; 95% CI, 0.94-2.65 for twins). CONCLUSIONS AND RELEVANCE: After considering plurality, children’s development through age 3 years was similar irrespective of infertility treatment or specific type. To our knowledge, these findings are among the first to focus on non-ART treatments in the United States.

Maternal obesity may affect offspring asthma and atopic disease risk by altering fetal immune system development. However, few studies examine gestational weight gain (GWG).

Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues.

The reliability of retrospective time to pregnancy (TTP) has been established, but its validity has been assessed in only 1 study, which had a short follow-up.

In mammals, the rate of somatic growth is rapid in early postnatal life but then slows with age, approaching zero as the animal approaches adult body size. To investigate the underlying changes in cell-cycle kinetics, [methyl-3H]thymidine and 5'-bromo-2'deoxyuridine were used to double-label proliferating cells in 1-, 2-, and 3-wk-old mice for four weeks. Proliferation of renal tubular epithelial cells and hepatocytes decreased with age. The average cell-cycle time did not increase in liver and increased only 1.7 fold in kidney. The fraction of cells in S-phase that will divide again declined approximately 10 fold with age. Concurrently, average cell area increased approximately 2 fold. The findings suggest that somatic growth deceleration primarily results not from an increase in cell-cycle time but from a decrease in growth fraction (fraction of cells that continue to proliferate). During the deceleration phase, cells appear to reach a proliferative limit and undergo their final cell divisions, staggered over time. Concomitantly, cells enlarge to a greater volume, perhaps because they are relieved of the size constraint imposed by cell division. In conclusion, a decline in growth fraction with age causes somatic growth deceleration and thus sets a fundamental limit on adult body size.

In mammals, the rate of somatic growth is rapid in early postnatal life but then slows with age, approaching zero as the animal approaches adult body size. To investigate the underlying changes in cell-cycle kinetics, methyl-3Hthymidine and 5′-bromo-2′deoxyuridine were used to double-label proliferating cells in 1-, 2-, and 3-wk-old mice for four weeks. Proliferation of renal tubular epithelial cells and hepatocytes decreased with age. The average cell-cycle time did not increase in liver and increased only 1.7 fold in kidney. The fraction of cells in S-phase that will divide again declined approximately 10 fold with age. Concurrently, average cell area increased approximately 2 fold. The findings suggest that somatic growth deceleration primarily results not from an increase in cell-cycle time but from a decrease in growth fraction (fraction of cells that continue to proliferate). During the deceleration phase, cells appear to reach a proliferative limit and undergo their final cell divisions, staggered over time. Concomitantly, cells enlarge to a greater volume, perhaps because they are relieved of the size constraint imposed by cell division. In conclusion, a decline in growth fraction with age causes somatic growth deceleration and thus sets a fundamental limit on adult body size.

IMPORTANCE: Higher caffeine consumption during pregnancy has been associated with lower birth weight. However, associations of caffeine consumption, based on both plasma concentrations of caffeine and its metabolites, and self-reported caffeinated beverage intake, with multiple measures of neonatal anthropometry, have yet to be examined. OBJECTIVE: To evaluate the association between maternal caffeine intake and neonatal anthropometry, testing effect modification by fast or slow caffeine metabolism genotype. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal cohort study, the National Institute of Child Health and Human Development Fetal Growth Studies–Singletons, enrolled 2055 nonsmoking women at low risk for fetal growth abnormalities with complete information on caffeine consumption from 12 US clinical sites between 2009 and 2013. Secondary analysis was completed in 2020. EXPOSURES: Caffeine was evaluated by both plasma concentrations of caffeine and paraxanthine and self-reported caffeinated beverage consumption measured/reported at 10-13 weeks gestation. Caffeine metabolism defined as fast or slow using genotype information from the single nucleotide variant rs762551 (CYP1A2*1F). MAIN OUTCOMES AND MEASURES: Neonatal anthropometric measures, including birth weight, length, and head, abdominal, arm, and thigh circumferences, skin fold and fat mass measures. The ß coefficients represent the change in neonatal anthropometric measure per SD change in exposure. RESULTS: A total of 2055 participants had a mean (SD) age of 28.3 (5.5) years, mean (SD) body mass index of 23.6 (3.0), and 580 (28.2%) were Hispanic, 562 (27.4%) were White, 518 (25.2%) were Black, and 395 (19.2%) were Asian/Pacific Islander. Delivery occurred at a mean (SD) of 39.2 (1.7) gestational weeks. Compared with the first quartile of plasma caffeine level (=28 ng/mL), neonates of women in the fourth quartile (>659 ng/mL) had lower birth weight (ß?=?-84.3 g; 95% CI, -145.9 to -22.6 g; P?=?.04 for trend), length (ß?=?-0.44 cm; 95% CI, -0.78 to -0.12 cm; P?=?.04 for trend), and head (ß?=?-0.28 cm; 95% CI, -0.47 to -0.09 cm; P?<?.001 for trend), arm (ß?=?-0.25 cm; 95% CI, -0.41 to -0.09 cm: P?=?.02 for trend), and thigh (ß?=?-0.29 cm; 95% CI, -0.58 to -0.04 cm; P?=?.07 for trend) circumference. Similar reductions were observed for paraxanthine quartiles, and for continuous measures of caffeine and paraxanthine concentrations. Compared with women who reported drinking no caffeinated beverages, women who consumed approximately 50 mg per day (~?1/2 cup of coffee) had neonates with lower birth weight (ß?=?-66 g; 95% CI, -121 to -10 g), smaller arm (ß?=?-0.17 cm; 95% CI, -0.31 to -0.02 cm) and thigh (ß?=?-0.32 cm; 95% CI, -0.55 to -0.09 cm) circumference, and smaller anterior flank skin fold (ß?=?-0.24 mm; 95% CI, -0.47 to -0.01 mm). Results did not differ by fast or slow caffeine metabolism genotype. CONCLUSIONS AND RELEVANCE: In this cohort study, small reductions in neonatal anthropometric measurements with increasing caffeine consumption were observed. Findings suggest that caffeine consumption during pregnancy, even at levels much lower than the recommended 200 mg per day of caffeine, are associated with decreased fetal growth.

Recurrent events are often encountered in medical follow up studies. In addition, such recurrences have other quantities associated with them that are of considerable interest, for instance medical costs of the repeated hospitalizations and tumor size in cancer recurrences. These processes can be viewed as point processes, i.e. processes with arbitrary positive jump at each recurrence. An analysis of the mean function for such point processes have been proposed in the literature. However, such point processes are often skewed, leading to median as a more appropriate measure than the mean. Furthermore, the analysis of recurrent event data is often complicated by the presence of death. We propose a semiparametric model for assessing the effect of covariates on the quantiles of the point processes. We investigate both the finite sample as well as the large sample properties of the proposed estimators. We conclude with a real data analysis of the medical cost associated with the treatment of ovarian cancer.

The inability to reduce the climbing rate of cesarean delivery worldwide is due, in part, to an inadequate understanding of the normal labor process, especially the first stage of labor. Improved diagnostic and interventional procedures are needed to manage women who labor slowly. This multicenter, prospective, observational study investigated patterns of labor in a large population, and assessed an alternative diagnostic approach for abnormal labor progression. The first stage of labor was studied using data from the National Collaborative Perinatal Project collected from 1959 to 1966. A total of 26,836 singleton term pregnancies delivered at 20 weeks or later were included in the final analysis. Other inclusion criteria were spontaneous onset of labor, a vertex fetal presentation at admission, and a normal perinatal outcome. To assess labor progression among nulliparous and multiparous pregnancies, a repeated-measures analysis with an eighth-degree polynomial model was used to construct average labor curves. An interval-censored regression assessed the duration of labor stratified by cervical dilation at admission, and the time for progression centimeter by centimeter.