Association of Maternal Fish Consumption and Omega-3 Supplement Use During Pregnancy With Child Autism-Related Outcomes: Results from a Cohort Consortium Analysis.

BACKGROUND: Prenatal fish intake is a key source of omega-3 polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: To examine associations of prenatal fish intake and omega-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and omega-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-Second Edition (n=3939 and n=3609 for fish intake analyses, respectively; n=4537 and n=3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (OR=0.84, 95% CI 0.77 to 0.92), and a modest reduction in raw total SRS scores (b=-1.69, 95% CI -3.3 to -0.08). Estimates were similar across categories of fish consumption from "any" or "less than once per week" to "more than twice per week." For omega-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (ß=1.98, 95% CI 0.33-3.64). CONCLUSIONS: These results extend prior work by suggesting that prenatal fish intake, but not omega-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low fish intake in the U.S. general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.

Prevalence and correlates of diagnosed and probable polycystic ovary syndrome (PCOS) in a cohort of parous women.

OBJECTIVES: To assess correlates of diagnosed and probable polycystic ovary syndrome (PCOS) among parous women. METHODS: This study includes 557 women recruited from multi-specialty clinics in eastern Massachusetts. We categorized women as "diagnosed PCOS" based on medical records and self-reported clinician-diagnoses. Next, we constructed a category of "probable PCOS" for women without a diagnosis but with ≥2 of the following: ovulatory dysfunction (cycle length<21 or ≥35 days), hyperandrogenism (free testosterone>75th percentile), or elevated anti-Müllerian hormone (>75th percentile). We classified the remaining as "no PCOS," and compared characteristics across groups. RESULTS: 9.7% had diagnosed and 9.2% had probable PCOS. The frequency of irregular cycles was similar for diagnosed and probable PCOS. Free testosterone and AMH were higher for probable than diagnosed PCOS. Frequency of irregular cycles and both hormones were higher for the two PCOS groups vs. the no PCOS group. Obesity prevalence for diagnosed PCOS was twice that of probable PCOS (43.9% vs. 19.6%), yet the two groups had similar HbA1c and adiponectin. CONCLUSIONS: Women with probable PCOS are leaner but have comparable glycemic traits to those with a formal diagnosis, highlighting the importance of assessing biochemical profiles among women with irregular cycles, even in the absence of overweight/obesity.

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion.

BACKGROUND: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. OBJECTIVE: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. METHODS: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999-2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n=269-314) and cytokine secretion (n=217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. RESULTS: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. CONCLUSIONS: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.

Associations of gestational exposure to air pollution with maternal vitamin D levels: a meta-analysis.

OBJECTIVE: Maternal vitamin D level is an important determinant of pregnancy and child health outcomes. Exposure to air pollution is suspected to increase the risk of vitamin D deficiency, but the evidence is scarce. We investigated the association between air pollution during pregnancy and maternal vitamin D levels. METHODS: A total of 15,935 pregnant women from 5 birth cohorts in Europe and U.S were included. Averaged concentrations of nitrogen oxides, fine and coarse particles, and composition of fine particles from conception until vitamin D measurement were estimated at participants' residential addresses using land-use regression or other spatiotemporal models. Cohorts measured vitamin D as 25(OH)D or 25(OH)D3 levels in serum or plasma at early or mid-pregnancy. We defined suboptimal vitamin D levels as levels below 20 ng/mL. We performed logistic regression models for each cohort to estimate the association between air pollution exposure and suboptimal vitamin D levels and pooled cohort-specific estimates in a random-effect meta-analysis. Models were adjusted for sociodemographic and lifestyle characteristics and month of conception. RESULTS: We found an association between PM2.5 and higher odds of suboptimal vitamin D levels (i.e., below 20 ng/mL) (odds ratio per 5 µg/m3 increase in PM2.5, 1.43 95%CI: 1.02, 1.99). There was no association between other air pollutant exposure and vitamin D levels. CONCLUSIONS: PM2.5 exposure might contribute to suboptimal levels of vitamin D in pregnancy. Reducing air pollution exposure should be a priority because vitamin D deficiency may adversely influence offspring development.

Lifetime History of Low Birth Weight Delivery and Cognitive Function in Middle-Aged Parous Women.

BACKGROUND AND OBJECTIVES: Pregnancy outcomes such as low birth weight (LBW) delivery may reflect vascular or metabolic dysfunction in mothers and presage future cognitive impairment and dementia. However, the evidence is currently limited. Our objective was to examine the extent to which a lifetime history of LBW delivery was associated with cognitive function in parous middle-aged women. METHODS: We studied participants from the Nurses' Health Study II, an ongoing longitudinal cohort of female nurses enrolled in 1989. In 2009, participants completed a reproductive history questionnaire. Participants who completed at least one of 2 post-traumatic stress disorder questionnaires were invited to participate in a cognition substudy with 2 waves of baseline data collection (2014 or 2018). We restricted the analysis to participants with one valid cognitive assessment who reported ≥1 birth at 18 years and older. We defined LBW delivery history as having delivered offspring with a birth weight <2,500 g (<5.5 lbs) in any pregnancy. The outcome was a single assessment of cognitive function evaluated with the self-administered Cogstate Brief Battery. The battery comprises 4 tasks, which we used to create 2 composite z-scores measuring psychomotor speed/attention and learning/working memory (higher z-scores = better cognitive function). We used multivariable linear regression models. RESULTS: The analysis included 15,323 participants with a mean age of 62 (standard deviation: 4.9 years) at cognitive assessment. Among them, 1,224 (8%) had a history of LBW delivery. After adjusting for age at cognitive assessment, race, and ethnicity, participants' education, wave of baseline cognitive assessment, socioeconomic status, and prepregnancy characteristics, women with a history of LBW delivery had lower z-scores in the psychomotor speed/attention (ß, -0.06; 95% CI -0.12 to -0.01) and learning/working memory (ß, -0.05; 95% CI -0.09 to -0.01) composites than parous women without a history of LBW delivery. We observed a gradient of lower z-scores with an increasing number of LBW deliveries. DISCUSSION: History of LBW delivery may be marker of future poorer cognition. If confirmed, our findings support future investigations into the value of early preventive efforts targeting women with a history of LBW delivery to reduce the burden of cognitive impairment in women.

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence.

OBJECTIVE: To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. STUDY DESIGN: Project Viva is a prospective prebirth cohort (n = 2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n = 1107), early adolescence (n = 1027), and mid-adolescence (n = 693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). RESULTS: In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n = 27) had a higher BMI z-score (ß; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. CONCLUSION: Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Relative humidity, temperature, and hypertensive disorders of pregnancy: Findings from the Project Viva cohort.

BACKGROUND: Preeclampsia is a multi-system hypertensive disorder of pregnancy that is a leading cause of maternal and fetal morbidity and mortality. Prior studies disagree on the cause and even the presence of seasonal patterns in its incidence. Using unsuitable time windows for seasonal exposures can bias model results, potentially explaining these inconsistencies. OBJECTIVES: We aimed to investigate humidity and temperature as possible causes for seasonal trends in preeclampsia in Project Viva, a prebirth cohort in Boston, Massachusetts, considering only exposure windows that precede disease onset. METHODS: Using the Parameter-elevation Relationships on Independent Slopes Model (PRISM) Climate Dataset, we estimated daily residential temperature and relative humidity (RH) exposures during pregnancy. Our primary multinomial regression adjusted for person-level covariates and season. Secondary analyses included distributed lag models (DLMs) and adjusted for ambient air pollutants including fine particulates (PM2.5). We used Generalized Additive Mixed Models (GAMMs) for systolic blood pressure (SBP) trajectories across hypertensive disorder statuses to confirm exposure timing. RESULTS: While preeclampsia is typically diagnosed late in pregnancy, GAMM-fitted SBP trajectories for preeclamptic and non-preeclamptic women began to diverge at around 20 weeks' gestation, confirming the need to only consider early exposures. In the primary analysis with 1776 women, RH in the early second trimester, weeks 14-20, was associated with significantly higher odds of preeclampsia (OR per IQR increase: 1.81, 95% CI: 1.10, 2.97). The DLM corroborated this window, finding a positive association from weeks 12-20. There were no other significant associations between RH or temperature and preeclampsia or gestational hypertension in any other time period. DISCUSSION: The association between preeclampsia and RH in the early second trimester was robust to model choice, suggesting that RH may contribute to seasonal trends in preeclampsia incidence. Differences between these results and those of prior studies could be attributable to exposure timing differences.

Metabolomic signatures for blood pressure from early to late adolescence: findings from a U.S. cohort.

INTRODUCTION: Metabolite signatures for blood pressure (BP) may reveal biomarkers, elucidate pathogenesis, and provide prevention targets for high BP. Knowledge regarding metabolites associated with BP in adolescence remains limited. OBJECTIVES: Investigate the associations between metabolites and adolescent BP, both cross-sectionally (in early and late adolescence) and prospectively (from early to late adolescence). METHODS: Participants are from the Project Viva prospective cohort. During the early (median: 12.8 years; N = 556) and late (median: 17.4 years; N = 501) adolescence visits, we conducted untargeted plasma metabolomic profiling and measured systolic (SBP) and diastolic BP (DBP). We used linear regression to identify metabolites cross-sectionally associated with BP at each time point, and to assess prospective associations of changes in metabolite levels from early to late adolescence with late adolescence BP. We used Weighted Gene Correlation Network Analysis and Spearman's partial correlation to identify metabolite clusters associated with BP at each time point. RESULTS: In the linear models, higher androgenic steroid levels were consistently associated with higher SBP and DBP in early and late adolescence. A cluster of 59 metabolites, mainly composed of androgenic steroids, correlated with higher SBP and DBP in early adolescence. A cluster primarily composed of fatty acid lipids was marginally associated with higher SBP in females in late adolescence. Multiple metabolites, including those in the creatine and purine metabolism sub-pathways, were associated with higher SBP and DBP both cross-sectionally and prospectively. CONCLUSION: Our results shed light on the potential metabolic processes and pathophysiology underlying high BP in adolescents.

First trimester plasma PER- AND Polyfluoroalkyl Substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnancy

BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.

Evaluation of the Prime Diet Quality Score from Early Childhood Through Mid-Adolescence.

BACKGROUND: Few diet quality indices have been developed and validated for use among children and adolescents. Additionally, many available indices require completion of burdensome dietary assessments. OBJECTIVES: We aimed to calculate and evaluate the performance of a modified version of the food-based Prime Diet Quality Score (PDQS) derived from different diet assessment methods conducted at 4 time points in a single study population from childhood through adolescence. METHODS: Among 1460 child participants in the Project Viva cohort, we calculated the PDQS in early and mid-childhood and early and mid-adolescence using dietary data obtained from food frequency questionnaire (early childhood: parent report), PrimeScreen (mid-childhood: parent report; early adolescence: self-report) and 24-h recall (mid-adolescence: self-report). We evaluated construct and relative validity and internal reliability of the score in each life stage. RESULTS: The PDQS showed a range of scores at all life stages and higher scores were associated with intake of many health-promoting macronutrients and micronutrients (e.g., protein, fiber, and vitamins) in early childhood and mid-adolescence. The PDQS performed similarly to the Youth Healthy Eating Index/Healthy Eating Index (Spearman r = 0.63-0.85) in various assessments. Higher PDQS was associated with expected characteristics including more frequent breakfast eating, family dinners, and vigorous physical activity; with less frequent TV viewing and fast food intake; and with more sleep and higher maternal diet scores during pregnancy. Cross-sectional associations of the PDQS with various anthropometric measurements and biomarkers were inconsistent but generally in the expected directions (e.g., higher PDQS associated with lower triglycerides and insulin and higher HDL cholesterol). Internal reliability was consistent with what has been found for other diet quality indices. CONCLUSIONS: The PDQS can be calculated from data collected using different and brief dietary assessment methods and appears to be a valid and useful measure of overall diet quality in children and adolescents. Project Viva was registered at clinicaltrials.gov as NCT02820402.

Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh.

BACKGROUND: There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. METHODS: Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1ß, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders. RESULTS: 248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants, elevated concentrations (>75%) of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevated IL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1ß with lower expressive communication and motor z-scores. CONCLUSIONS: In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetal growth restriction. IMPACT: Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh. 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants. Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

Associations of Childhood Adiposity and Cardiometabolic Biomarkers With Adolescent PCOS.

OBJECTIVE: Polycystic Ovary Syndrome (PCOS) is common among females, with significant metabolic and reproductive comorbidities. We describe PCOS development in a pediatric population. METHODS: We assessed cardiometabolic biomarkers and adiposity at the midchildhood (mean 7.9 y), early teen (mean 13.1 y), and midteen (mean 17.8 y) visits among 417 females in the prospective Project Viva cohort. We defined PCOS via self-reported diagnosis or ovulatory dysfunction with hyperandrogenism in midlate adolescence. We used multivariable logistic regression to assess associations of metabolic and adiposity markers at each visit with PCOS. RESULTS: Adolescents with PCOS (n = 56, 13%) versus without had higher mean (SD) BMI z-score and truncal fat mass at the midchildhood (0.66 [0.99] vs 0.30 [1.04]; 3.5 kg [2.6] vs 2.7 [1.5]), early teen (0.88 [1.01] vs 0.25 [1.08]; 9.4 kg [6.7] vs 6.1 [3.4]), and midteen (0.78 [1.03] vs 0.33 [0.97]; 11.6 kg [7.2] vs 9.1 [4.9]) visits as well as lower adiponectin to leptin ratio at the early (0.65 [0.69] vs 1.04 [0.97]) and midteen (0.33 [0.26] vs 0.75 [1.21]) visits. In models adjusted for maternal PCOS, education and child race and ethnicity (social factors), we found higher odds of PCOS per 1-SD increase in truncal fat at midchildhood (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.03-1.95) and early teen visits (OR 1.61; 95% CI 1.14-2.28) and lower odds per 1-SD increase in adiponectin/leptin ratio at the midteen visit (OR 0.14; 95% CI 0.03-0.58). CONCLUSIONS: Childhood excess adiposity and adipose tissue dysfunction may be a first signs of later PCOS risk.

Associations of gestational weight gain with the long-term postpartum weight gain, body mass index, waist circumference and abdominal obesity: A 27-year prospective cohort study.

BACKGROUND: This prospective cohort study aimed to investigate the associations between gestational weight gain (GWG) and long-term postpartum maternal weight gain, body mass index (BMI), waist circumference (WC), and the risk of general and abdominal obesity, beyond motherhood (some 27 y after childbirth). METHODS: Participants were 1953 women enrolled in the Mater-University of Queensland Study of Pregnancy cohort study that started in the early 1980 s, with the most recent follow-up at 27 y postpartum. We examined the prospective associations of GWG in pregnancy with weight, BMI, and WC and the risk of adiposity 27 y after the index pregnancy. We used linear and multinomial logistic regressions to examine the independent effect of GWG on each outcome, adjusting for potential confounders and mediators. RESULTS: The average GWG during pregnancy was 14.88 kg (SD 5.24). One in four women (25.50%) gained below the Institute of Medicine (IOM) recommendations and one in three (34.00%) gained excess weight during pregnancy. Every 100 g/week increment of GWG was associated with 2.0 (95% CI: 1.5, 2.6) kg, 0.7 (0.5, 0.9) kg/m2, 1.3 (0.8, 1.8) cm greater body weight, BMI, and WC, respectively 27 y postpartum. Women who gained inadequate weight in pregnancy had significantly lower odds of general obesity (OR; 0.70, 95% CI:0.53,0.94) or abdominal obesity (0.73; 0.56,0.96), whereas those who gained excess gestational weight had much higher odds of general obesity (4.49; 3.36,6.00) and abdominal obesity (3.09; 2.29,4.16). These associations were independent of potential confounders. CONCLUSION: Maternal GWG in pregnancy independently and strongly predicted beyond motherhood weight gain trajectory. GWG within IOM recommendation may prevent long-term development of both general and central obesity.

Associations of anti-Müllerian hormone levels among women in their mid-30s with menopausal symptoms ~14 years later.

OBJECTIVE: The aim of this study was to examine associations of anti-Müllerian hormone (AMH) levels in gravid women in their mid-30s with menopausal symptoms ~14 years later and age at natural menopause. METHODS: In this prospective analysis, 474 participants in Project Viva, a longitudinal cohort, were enrolled during pregnancy between 1999 and 2002. AMH levels were determined using plasma samples collected 3 years postpartum. Participants completed the Menopause Rating Scale (MRS) and self-reported age at and reason for menopause at the 17 years postpartum visit (Mid-Life Visit). Primary outcomes were individual MRS item responses and total MRS score. To examine associations between AMH levels and menopausal outcomes, we performed linear and logistic regressions, and survival analyses, adjusting for confounding variables. RESULTS: Mean (SD) AMH level was 2.80 (2.74) ng/mL, measured at 38.2 (3.9) years. At the Mid-Life Visit, mean (SD) age was 52.3 (3.9) years and total MRS score was 8.0 (5.7). During follow-up, 50% had experienced natural menopause, and self-reported mean (SD) age at natural menopause was 50.4 (3.6) years. AMH in the lowest tertile (mean [SD]: 0.47 [0.32] ng/mL) was associated with higher odds of moderate to severe vaginal dryness (adjusted odds ratio: 2.58; 95% CI: 1.16 to 5.73), a lower MRS psychological subscale (adjusted ß: -0.71; 95% CI: -1.35 to -0.07), and earlier attainment of natural menopause (adjusted hazards ratio: 7.1; 95% CI: 4.6 to 11.0) compared with AMH in the highest tertile (mean [SD]: 6.01 [2.37] ng/mL). CONCLUSIONS: Lower AMH in the mid-30s was associated with earlier menopause and increased odds of vaginal dryness but fewer psychological symptoms ~14 years later.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Birth outcomes in relation to neighborhood food access and individual food insecurity during pregnancy in the Environmental Influences on Child Health Outcomes (ECHO)-wide cohort study.

BACKGROUND: Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. OBJECTIVES: We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. METHODS: We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. RESULTS: Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [ß -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. CONCLUSIONS: Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.

Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO programme.

OBJECTIVE: n-3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or n-3 supplement intake. DESIGN: Pooled pregnancy cohort studies. SETTING: Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020. PARTICIPANTS: A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use. RESULTS: Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1-2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever (v. never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35-40 v. <29 years), were other than non-Hispanic White (1·13, 95 % CI 1·08, 1·18 for non-Hispanic Black; 1·05, 95 % CI 1·01, 1·10 for non-Hispanic Asian; 1·06, 95 % CI 1·02, 1·10 for Hispanic) or used tobacco (1·04, 95 % CI 1·01, 1·08). The RR was lower in those with overweight v. healthy weight (0·97, 95 % CI 0·95, 1·0). Only 16·2 % reported n-3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1·5, 95 % CI 1·23, 1·82 for twice-weekly v. never). CONCLUSIONS: One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and n-3 supplement use was uncommon, even among those who did not consume fish.

Acute exposure to pollen and airway inflammation in adolescents.

INTRODUCTION: Pollen exposure is known to exacerbate allergic asthma and allergic rhinitis symptoms, yet few studies have investigated if exposure to pollen affects lung function or airway inflammation in healthy children. METHODS: We evaluated the extent to which higher pollen exposure was associated with differences in airway inflammation and lung function among 490 early adolescent participants (mean age of 12.9 years) in Project Viva, a prebirth cohort based in Massachusetts. We obtained regional daily total pollen counts, including tree, grass, and weed pollen, from a Rotorod pollen counter. We evaluated associations of 3- and 7-day moving averages of pollen with fractional exhaled nitric oxide (FeNO) and lung function using linear regression models and evaluated the linearity of associations with penalized splines. We tested if associations of pollen with FeNO and lung function were modified by current asthma diagnosis, history of allergic rhinitis, aeroallergen sensitivity, temperature, precipitation, and air pollution. RESULTS: Three- and 7-day median pollen concentrations were 19.0 grains/m3 (IQR: 73.4) and 20.9 grains/m3 (IQR: 89.7). In main models, higher concentrations of total pollen over the preceding 3 and 7 days were associated with a 4.6% (95% CI: 0.1,9.2) and 7.4% (95% CI: 0.9,14.3) higher FeNO per IQR of pollen, respectively. We did not find associations of pollen with lung function in main models. Asthma, allergic rhinitis, precipitation, and air pollution (nitrogen dioxide and ozone) modified associations of pollen with lung function (Pinteraction < 0.1), while temperature, sex, and aeroallergen sensitization did not. CONCLUSION: Short-term exposure to pollen was associated with higher FeNO in early adolescents, even in the absence of allergic sensitization and asthma.

Associations of prenatal one-carbon metabolism nutrients and metals with epigenetic aging biomarkers at birth and in childhood in a US cohort.

Epigenetic gestational age acceleration (EGAA) at birth and epigenetic age acceleration (EAA) in childhood may be biomarkers of the intrauterine environment. We investigated the extent to which first-trimester folate, B12, 5 essential, and 7 non-essential metals in maternal circulation are associated with EGAA and EAA in early life. Bohlin EGAA and Horvath pan-tissue and skin and blood EAA were calculated using DNA methylation measured in cord blood (N=351) and mid-childhood blood (N=326; median age = 7.7 years) in the Project Viva pre-birth cohort. A one standard deviation increase in individual essential metals (copper, manganese, and zinc) was associated with 0.94-1.2 weeks lower Horvath EAA at birth, and patterns of exposures identified by exploratory factor analysis suggested that a common source of essential metals was associated with Horvath EAA. We also observed evidence nonlinear associations of zinc with Bohlin EGAA, magnesium and lead with Horvath EAA, and cesium with skin and blood EAA at birth. Overall, associations at birth did not persist in mid-childhood; however, arsenic was associated with greater EAA at birth and in childhood. Prenatal metals, including essential metals and arsenic, are associated with epigenetic aging in early life, which might be associated with future health.

Associations of parental preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-a concentrations with child eating behaviors.

BACKGROUND: Eating behaviors are controlled by the neuroendocrine system. Whether endocrine disrupting chemicals have the potential to affect eating behaviors has not been widely studied in humans. We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-A (BPA) concentrations were associated with children's eating behaviors. METHODS: We used data from mother-father-child triads in the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-13 years whose parent(s) previously enrolled in a fertility clinic-based prospective preconception study. We quantified urinary concentrations of 11 phthalate metabolites and BPA in parents' urine samples collected preconceptionally and during pregnancy. Parents rated children's eating behavior using the Child Eating Behavior Questionnaire (CEBQ). Using multivariable linear regression, accounting for correlation among twins, we estimated covariate-adjusted associations of urinary phthalate biomarkers and BPA concentrations with CEBQ subscale scores. RESULTS: This analysis included 195 children (30 sets of twins), 160 mothers and 97 fathers; children were predominantly non-Hispanic white (84%) and 53% were male. Paternal and maternal preconception monobenzyl phthalate (MBzP) concentrations and maternal preconception mono-n-butyl phthalate (MnBP) were positively associated with emotional overeating, food responsiveness, and desire to drink scores in children (ß's= 0.11 [95% CI: 0.01, 0.20]-0.21 [95% CI: 0.10, 0.31] per loge unit increase in phthalate biomarker concentration). Paternal preconception BPA concentrations were inversely associated with scores on food approaching scales. Maternal pregnancy MnBP, mono-isobutyl phthalate (MiBP) and MBzP concentrations were associated with increased emotional undereating scores. Maternal pregnancy monocarboxy-isononyl phthalate concentrations were related to decreased food avoiding subscale scores. CONCLUSIONS: In this cohort, higher maternal and paternal preconception urinary concentrations of some phthalate biomarkers were associated with increased food approaching behavior scores and decreased food avoiding behavior scores, which could lead to increased adiposity in children.