Dietary Intake of Nutrients Involved in Serotonin and Melatonin Synthesis and Prenatal Maternal Sleep Quality and Affective Symptoms.

Poor sleep quality and psychological distress in pregnancy are important health concerns. Serotonin and melatonin levels may underlie variation in these adverse outcomes. In this study, we examined dietary nutrients involved in serotonin and melatonin synthesis in relation to maternal sleep quality and affective symptoms during pregnancy. Pregnant women at no greater than normal medical risk at enrollment completed 24-hour dietary recalls in mid-late pregnancy. Usual intakes of vitamin B6, vitamin D, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and tryptophan were estimated from dietary intake of foods and supplements using the National Cancer Institute (NCI) method. Sleep quality, depression, and anxiety were measured using validated questionnaires. Associations between nutrient intakes, sleep quality, and affective symptoms were estimated using generalized estimating equation models adjusting for potential confounding factors. In minimally adjusted models, EPA + DHA and tryptophan intakes were associated with a lower score indicating better sleep quality (b: -1.07, 95% CI: -2.09, -0.05) and (b: -12.40, 95% CI: -24.60, -0.21), respectively. EPA + DHA and tryptophan intakes were also associated with a lower odds of shorter sleep duration and sleep disturbances. In addition, tryptophan was associated with a lower odds of higher sleep latency. However, associations were attenuated and nonsignificant after adjustment for demographic and lifestyle factors. In conclusion, intakes of EPA + DHA and tryptophan were associated with improved sleep quality, but these associations were confounded by maternal demographic and lifestyle characteristics. This study highlights the need to consider dietary intake and pregnancy health in the context of demographic characteristics and lifestyle behaviors.

Association of maternal fish consumption and ω-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 (ω-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: This study aimed to examine associations of prenatal fish intake and ω-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 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 ω-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 v3609 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 (odds ratio: 0.84; 95% confidence interval [CI]: 0.77, 0.92), and a modest reduction in raw total SRS scores (ß: -1.69; 95% CI: -3.3, -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 ω-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 previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States 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.

Systemic oxidative stress levels during the course of pregnancy: Associations with exposure to air pollutants.

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 µg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Associations between mycoestrogen exposure and sex steroid hormone concentrations in maternal serum and cord blood in the UPSIDE pregnancy cohort.

Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17ß-estradiol (E2), they interact with estrogen receptors α/ß earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (n = 297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health.

Combining developmental and sleep health measures for autism spectrum disorder screening: an ECHO study.

BACKGROUND: Sleep problems are reported for up to 80% of autistic individuals. We examined whether parsimonious sets of items derived from the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the Brief Infant Sleep Questionnaire (BISQ) are superior to the standard M-CHAT-R in predicting subsequent autism spectrum disorder (ASD) diagnoses. METHODS: Participants from 11 Environmental influences on Child Health Outcomes (ECHO) cohorts were included. We performed logistic LASSO regression models with 10-fold cross-validation to identify whether a combination of items derived from the M-CHAT-R and BISQ are superior to the standard M-CHAT-R in predicting ASD diagnoses. RESULTS: The final sample comprised 1552 children. The standard M-CHAT-R had a sensitivity of 44% (95% CI: 34, 55), specificity of 92% (95% CI: 91, 94), and AUROC of 0.726 (95% CI: 0.663, 0.790). A higher proportion of children with ASD had difficulty falling asleep or resisted bedtime during infancy/toddlerhood. However, LASSO models revealed parental reports of sleep problems did not improve the accuracy of the M-CHAT-R in predicting ASD diagnosis. CONCLUSION: While children with ASD had higher rates of sleep problems during infancy/toddlerhood, there was no improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. IMPACT: Parental-reported sleep problems are common in autism spectrum disorder (ASD). We investigated whether the inclusion of parental-reports of infant/toddler sleep patterns enhanced the effectiveness of developmental screening for autism. We reported higher rates of difficulty falling asleep and resisting bedtime during infancy and toddlerhood among children later diagnosed with ASD; however, we did not find an improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. In our sample, the standard M-CHAT-R had a sensitivity of 39% among children of mothers with government insurance compared with a sensitivity of 53% among children of mothers with employer-based insurance.

Age of Juice Introduction and Cardiometabolic Outcomes in Middle Childhood.

BACKGROUND: The American Academy of Pediatrics recommends juice introduction after 12 months of age. Juice consumption has been linked to childhood obesity and cardiometabolic risk. OBJECTIVES: To examine the prospective relationship between the age of juice introduction and primary and secondary cardiometabolic outcomes in middle childhood. METHODS: Parents reported the age of juice introduction on Upstate KIDS questionnaires completed between 4 and 18 months. The quantity and type of juice introduced were not measured. Anthropometry, blood pressure (BP), and arterial stiffness by pulse wave velocity (PWV) were measured for 524 children (age, 8-10 y) at study visits (2017-2019). Age- and gender-adjusted z-scores were calculated using the Centers for Disease Control and Prevention reference for anthropometrics. Plasma lipids, hemoglobin A1c (HbA1c), and C-reactive protein (CRP) in a subset of children were also measured (n = 248). Associations between age at juice introduction (categorized as <6, 6 to <12, ≥12 months), and outcomes were estimated using mean differences and odds ratios, applying generalized estimating equations to account for correlations between twins. RESULTS: Approximately 18% of children were introduced to juice at <6 months, 52% between 6 and <12 months, and 30% ≥ 12 months of age. Children who were introduced to juice before 6 months had higher systolic BP (3.13 mmHg; 95% confidence interval [CI]: 0.52, 5.74), heart rate (4.46 bpm; 95% CI: 1.05, 7.87), and mean arterial pressure (2.08 mmHg; 95% CI: 0.15, 4.00) compared with those introduced ≥12 months after covariate adjustment including sociodemographic factors and maternal prepregnancy body mass index. No adjusted differences in anthropometry, lipids, HbA1c, and CRP levels were found. CONCLUSIONS: Early juice introduction during infancy was associated with higher systolic BP, heart rate, and mean arterial pressure in middle childhood. This trial was registered at clinicaltrials.gov as NCT03106493 (https://clinicaltrials.gov/study/NCT03106493?term=upstate%20KIDS&rank=1).

Maternal affective symptoms and sleep quality have sex-specific associations with placental topography.

BACKGROUND: The impacts of prenatal maternal affective symptoms on the placental structure are not well-established. Employing Geographic Information System (GIS) spatial autocorrelation, Moran's I, can help characterize placental thickness uniformity/variability and evaluate the impacts of maternal distress on placental topography. METHODS: This study (N = 126) utilized cohort data on prenatal maternal affective symptoms and placental 2D and 3D morphology. Prenatal maternal depression, stress, anxiety and sleep quality were scored for each trimester using the Edinburgh Postnatal Depression Scale (EPDS), Stressful Life Event Scale (SLE), Penn State Worry Questionnaire (PSWQ), and Pittsburgh Sleep Quality Index (PSQI), respectively. Placental shape was divided into Voronoi cells and thickness variability among these cells was computed using Moran's I for 4-nearest neighbors and neighbors within a 10 cm radius. Sex-stratified Spearman correlations and linear regression were used to study associations between mean placental thickness, placental GIS variables, placental weight and the average score of each maternal variable. RESULTS: For mothers carrying boys, poor sleep was associated with higher mean thickness (r = 0.308,p = 0.035) and lower placental thickness uniformity (r = -0.36,p = 0.012). Lower placental weight (r = 0.395,p = 0.003), higher maternal depression (r = -0.318,p = 0.019) and worry/anxiety (r = -0.362,p = 0.007) were associated with lower placental thickness uniformity for mothers carrying girls. LIMITATIONS: The study is exploratory and not all GIS models were developed. Excluding high-risk pregnancies prevented investigating pregnancy complications related hypotheses. A larger sample size is needed for greater confidence for clinical application. CONCLUSIONS: Placental topography can be studied using GIS theory and has shown that prenatal maternal affective symptoms and sleep have sex-specific associations with placental thickness.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

BACKGROUND: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. OBJECTIVES: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-(hCGα) and beta-subunits (hCGß), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. METHODS: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. RESULTS: Perfluorohexane sulfonic acid (PFHxS) [hCGß: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: -0.09; 95% CI: -0.16, -0.02) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with hCGα and positively with hCGß. Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with hCGß only in Black participants (-0.23; 95% CI: -0.37, -0.09) and in participants with high school education or less (-0.14; 95% CI: -0.26, -0.02); conversely, perfluorononanoic acid (PFNA) was negatively associated with hCGα only in White participants (-0.15; 95% CI: -0.27, -0.03) and with hCGß only in participants with a college education or greater (-0.19; 95% CI: -0.36, -0.01). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was <100%. Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with hCGα, and PFNA with h-hCG. CONCLUSIONS: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with hCGα and hCGß differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Prenatal maternal immune activation predicts observed fearfulness in infancy.

Fear reactivity is an early emerging temperament trait that predicts longer term behavioral and health outcomes. The current analysis tests the hypothesis, an extension of prior research on maternal immune activation (MIA), that the prenatal maternal immune system is a reliable predictor of observed fear reactivity in infancy. The analysis is based on a prospective longitudinal cohort study that collected data from the first trimester and conducted observational assessments of temperament at approximately 12 months of age (n = 281 infants). MIA was assessed from immune biomarkers measured in maternal blood at each trimester; infant temperament was assessed using the Laboratory Temperament Assessment Battery assessment at 12 months; covariates included family and sociodemographic factors. Patterns of inflammatory markers across gestation reliably predicted observed temperament: elevated prenatal MIA was associated with high fear reactivity to novel stimuli. The findings provide novel evidence of prenatal origins of fear reactivity and suggest developmental mechanisms that may underlie early emerging individual differences in child temperament. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PFAS alters placental arterial vasculature in term human placentae: A prospective pregnancy cohort study.

INTRODUCTION: Perfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function. OBJECTIVES: The objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes. METHODS: Using data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image. RESULTS: In both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (ß = -0.23, 95% CI: -0.41, -0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (ß = -0.19, 95% CI: -0.34, -0.051). There were no reliable differences in effect by fetal sex. DISCUSSION: The findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks.

Segmenting hypothalamic subunits in human newborn magnetic resonance imaging data.

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary analyses (mean postmenstrual age = 44.3 ± 3.5 weeks, nmale /nfemale = 110/106). The outputs of FreeSurfer's hypothalamic subunit segmentation tools designed for adults (segFS) were compared against those of a novel registration-based pipeline developed here (segATLAS) and against manually edited segmentations (segMAN) as reference. Comparisons were made using Dice Similarity Coefficients (DSCs) and through expected associations with postmenstrual age at scan. In addition, we aimed to demonstrate the validity of the segATLAS pipeline by testing for the stability of inter-individual variation in hypothalamic volume across the first year of life (n = 41 longitudinal datasets available). SegFS and segATLAS segmentations demonstrated a wide spread in agreement (mean DSC = 0.65 ± 0.14 SD; range = {0.03-0.80}). SegATLAS volumes were more highly correlated with postmenstrual age at scan than segFS volumes (n = 215 infants; RsegATLAS 2 = 65% vs. RsegFS 2 = 40%), and segATLAS volumes demonstrated a higher degree of agreement with segMAN reference segmentations at the whole hypothalamus (segATLAS DSC = 0.89 ± 0.06 SD; segFS DSC = 0.68 ± 0.14 SD) and subunit levels (segATLAS DSC = 0.80 ± 0.16 SD; segFS DSC = 0.40 ± 0.26 SD). In addition, segATLAS (but not segFS) volumes demonstrated stability from near birth to ~1 years age (n = 41; R2 = 25%; p < 10-3 ). These findings highlight segATLAS as a valid and publicly available (https://github.com/jerodras/neonate_hypothalamus_seg) pipeline for the segmentation of hypothalamic subunits using human newborn MRI up to 3 months of age collected at resolutions on the order of 1 mm isotropic. Because the hypothalamus is traditionally understudied due to a lack of high-quality segmentation tools during the early life period, and because the hypothalamus is of high biological relevance to human growth and development, this tool may stimulate developmental and clinical research by providing new insight into the unique role of the hypothalamus and its subunits in shaping trajectories of early life health and disease.

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.

Psychosocial Risk Exposure Limits Routine Pediatric Oral Health Care.

Introduction: This study aimed to identify social, psychological, and contextual factors that influenced attendance at routine oral health visits in a cohort of 189 preschool children who were followed over a 2-year period. Methods: Generalized estimating equation was used to examine the association between clinic attendance and the predictors. ORs and 95% CIs were reported in the multiple logistic regression models. The study was conducted in Rochester, New York, between February 2016 and February 2021. Results: Prior to the COVID-19 pandemic declaration, the rate of canceled and no-show appointments was greater for routine clinic visits (20% and 24%, respectively) than for research visits (14% and 9%, respectively) for the same participants; these rates increased during the pandemic. After adjusting for sociodemographic factors, the likelihood of a canceled or no-show appointment was associated with parental depression (OR=1.06, CI=1.03, 1.09), regardless of the type or occurrence of the visit. Conclusions: Findings from this study demonstrate that attendance to oral health care in young children is reliably reduced with parental depression and that this may provide one mechanism for early emerging health inequalities of oral health.

Molecular pathways in placental-fetal development and disruption.

The first trimester of pregnancy ranks high in priority when minimizing harmful exposures, given the wide-ranging types of organogenesis occurring between 4- and 12-weeks' gestation. One way to quantify potential harm to the fetus in the first trimester is to measure a corollary effect on the placenta. Placental biomarkers are widely present in maternal circulation, cord blood, and placental tissue biopsied at birth or at the time of pregnancy termination. Here we evaluate ten diverse pathways involving molecules expressed in the first trimester human placenta based on their relevance to normal fetal development and to the hypothesis of placental-fetal endocrine disruption (perturbation in development that results in abnormal endocrine function in the offspring), namely: human chorionic gonadotropin (hCG), thyroid hormone regulation, peroxisome proliferator activated receptor protein gamma (PPARγ), leptin, transforming growth factor beta, epiregulin, growth differentiation factor 15, small nucleolar RNAs, serotonin, and vitamin D. Some of these are well-established as biomarkers of placental-fetal endocrine disruption, while others are not well studied and were selected based on discovery analyses of the placental transcriptome. A literature search on these biomarkers summarizes evidence of placenta-specific production and regulation of each biomarker, and their role in fetal reproductive tract, brain, and other specific domains of fetal development. In this review, we extend the theory of fetal programming to placental-fetal programming.

Maternal social support during and after pregnancy and child cognitive ability: examining timing effects in two cohorts.

BACKGROUND: Maternal anxiety, depression, and stress during and after pregnancy are negatively associated with child cognitive development. However, the contribution of positive maternal experiences, such as social support, to child cognitive development has received less attention. Furthermore, how maternal experience of social support during specific developmental periods impacts child cognitive development is largely unknown. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 5784) and the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study (PREDO; n = 420), we investigated the associations between maternal perceived social support during and after pregnancy and child's general cognitive ability at 8 years of age, assessed with the Wechsler Intelligence Scale for Children (WISC). Bayesian relevant life course modeling was used to investigate timing effects of maternal social support on child cognitive ability. RESULTS: In both cohorts, higher maternal perceived social support during pregnancy was associated with higher performance on the WISC, independent of sociodemographic factors and concurrent maternal symptoms of depression and anxiety. In ALSPAC, pregnancy emerged as a sensitive period for the effects of perceived social support on child cognitive ability, with a stronger effect of social support during pregnancy than after pregnancy on child cognitive ability. CONCLUSIONS: Our findings, supported from two prospective longitudinal cohorts, suggest a distinct role of maternal perceived social support during pregnancy for cognitive development in children. Our study suggests that interventions aimed at increasing maternal social support during pregnancy may be an important strategy for promoting maternal and child well-being.

Prenatal sleep health and risk of offspring ADHD symptomatology and associated phenotypes: a prospective analysis of timing and sex differences in the ECHO cohort.

Background: Sleep difficulties are common in pregnancy, yet poor prenatal sleep may be related to negative long-term outcomes for the offspring, including risk for attention-deficit/hyperactivity disorder (ADHD). Existing studies are few and have not examined timing of exposure effects or offspring sex moderation. We thus aimed to test the hypotheses that poor sleep health in pregnancy is associated with increased risk for ADHD symptoms and offspring sleep problems at approximately 4 years of age. Methods: Participants were 794 mother-child dyads enrolled in the NIH Environmental Influences on Child Health Outcomes Study (ECHO). Participants self-reported on sleep duration, quality, and disturbances during pregnancy and on children's ADHD symptoms and sleep problems on the Child Behaviour Checklist. Findings: Pregnant participants were 32.30 ± 5.50 years and children were 46% female. 44 percent of pregnant participants identified as Hispanic or Latine; 49% identified as White. Second-trimester sleep duration was associated with offspring ADHD symptoms (b = -0.35 [95% CI = -0.57, -0.13], p = 0.026), such that shorter duration was associated with greater symptomatology. Poorer sleep quality in the second trimester was also associated with increased ADHD symptomatology (b = 0.66 [95% CI = 0.18, 1.14], p = 0.037). Greater sleep disturbances in the first trimester were associated with offspring ADHD (b = 1.03 [95% CI = 0.32, 1.03], p = 0.037) and in the second trimester with sleep problems (b = 1.53 [95% CI = 0.42, 2.92], p = 0.026). We did not document substantial offspring sex moderation. Interpretation: Poor prenatal sleep health, particularly quality and duration in the second trimester, may be associated with offspring risk of neurodevelopmental disorders and sleep problems in early childhood. Further research is needed to understand mechanisms, yet our study suggests that prenatal maternal sleep may be a modifiable target for interventions aimed at optimizing early neurodevelopment. Funding: NIH grants U2COD023375, U24OD023382, U24OD023319, UH3OD023320, UH3OD023305, UH3OD023349, UH3OD023313, UH3OD023272, UH3OD023328, UH3OD023290, K08MH117452 and NARSAD Young Investigator Award 28545.

Associations between COVID-19-related family hardships/distress and children's Adverse Childhood Experiences during the pandemic: The Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: Economic hardships imposed by the pandemic could have implications for children's experiences of adversity in the home, or Adverse Childhood Experiences (ACEs). OBJECTIVE: This observational cohort study examined associations between COVID-19-related hardships and distress (e.g., job loss, caregiver stress) and the cumulative number of child ACEs reported by caregivers during the pandemic (i.e., March 1, 2020-February 28, 2022). PARTICIPANTS AND SETTING: The study included children (N = 4345; median age = 6.0 years, interquartile range = 4-9 years) and their parents/caregivers who participated in the NIH-funded Environmental influences in Child Health Outcomes (ECHO) Program. METHODS: We described socio-demographic characteristics and pandemic-related family hardships/distress and cumulative child ACE scores reported during pre-pandemic and pandemic periods. We used negative binomial regression models to evaluate associations between pandemic-related family hardships and cumulative child ACE scores reported during the pandemic. RESULTS: Each caregiver-reported hardship/distress was associated with higher child ACE scores reported during the pandemic. After accounting for pre-pandemic child ACE scores, moderate and severe symptoms of pandemic-related traumatic stress among caregivers were associated with 108 % and 141 % higher child ACE scores reported during the pandemic, respectively, compared with no or low caregiver symptoms. In addition, finance-related stress during the pandemic was associated with 47 % higher child ACE scores. After adjusting for pre-pandemic child experiences of neglect, most sources of stress remained significantly associated with higher child ACE scores reported during the pandemic, particularly severe/very severe symptoms of pandemic-related traumatic stress among caregivers. Findings held for children with no known pre-pandemic ACEs. CONCLUSIONS: This research suggests that caregivers experiencing financial hardships and those with severe pandemic-related traumatic stress may require additional support systems during stressful events.

Opportunities for Examining Child Health Impacts of Early-Life Nutrition in the ECHO Program: Maternal and Child Dietary Intake Data from Pregnancy to Adolescence.

Background: Longitudinal measures of diet spanning pregnancy through adolescence are needed from a large, diverse sample to advance research on the effect of early-life nutrition on child health. The Environmental influences on Child Health Outcomes (ECHO) Program, which includes 69 cohorts, >33,000 pregnancies, and >31,000 children in its first 7-y cycle, provides such data, now publicly available. Objectives: This study aimed to describe dietary intake data available in the ECHO Program as of 31 August, 2022 (end of year 6 of Cycle 1) from pregnancy through adolescence, including estimated sample sizes, and to highlight the potential for future analyses of nutrition and child health. Methods: We identified and categorized ECHO Program dietary intake data, by assessment method, participant (pregnant person or child), and life stage of data collection. We calculated the number of maternal-child dyads with dietary data and the number of participants with repeated measures. We identified diet-related variables derived from raw dietary intake data and nutrient biomarkers measured from biospecimens. Results: Overall, 66 cohorts (26,941 pregnancies, 27,103 children, including 22,712 dyads) across 34 US states/territories provided dietary intake data. Dietary intake assessments included 24-h recalls (1548 pregnancies and 1457 children), food frequency questionnaires (4902 and 4117), dietary screeners (8816 and 23,626), and dietary supplement use questionnaires (24,798 and 26,513). Repeated measures were available for ∼70%, ∼30%, and ∼15% of participants with 24-h recalls, food frequency questionnaires, and dietary screeners, respectively. The available diet-related variables describe nutrient and food intake, diet patterns, and breastfeeding practices. Overall, 17% of participants with dietary intake data had measured nutrient biomarkers. Conclusions: ECHO cohorts have collected longitudinal dietary intake data spanning pregnancy through adolescence from a geographically, socioeconomically, and ethnically diverse US sample. As data collection continues in Cycle 2, these data present an opportunity to advance the field of nutrition and child health.