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This report provides recommendations to improve both preconception health and care. The goal of these recommendations is to improve the health of women and couples, before conception of a first or subsequent pregnancy. Since the early 1990s, guidelines have recommended preconception care, and reviews of previous studies have assessed the evidence for interventions and documented the evidence for specific interventions.CDC has developed these recommendations based on a review of published research and the opinions of specialists from the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. The 10 recommendations in this report are based on preconception health care for the U.S. population and are aimed at achieving four goals to 1) improve the knowledge and attitudes and behaviors of men and women related to preconception health; 2) assure that all women of childbearing age in the United States receive preconception care services (i.e., evidence-based risk screening, health promotion, and interventions) that will enable them to enter pregnancy in optimal health; 3) reduce risks indicated by a previous adverse pregnancy outcome through interventions during the interconception period, which can prevent or minimize health problems for a mother and her future children; and 4) reduce the disparities in adverse pregnancy outcomes.The recommendations focus on changes in consumer knowledge, clinical practice, public health programs, health-care financing, and data and research activities. Each recommendation is accompanied by a series of specific action steps and, when implemented, can yield results within 2--5 years. Based on implementation of the recommendations, improvements in access to care, continuity of care, risk screening, appropriate delivery of interventions, and changes in health behaviors of men and women of childbearing age are expected to occur. The implementation of these recommendations will help achieve Healthy People 2010 objectives. The recommendations and action steps are a strategic plan that can be used by persons, communities, public health and clinical providers, and governments to improve the health of women, their children, and their families. Improving preconception health among the approximately 62 million women of childbearing age will require multistrategic, action-oriented initiatives. [ABSTRACT FROM AUTHOR]

Problem/Condition: High vaccination levels in the population are necessary to decrease disease transmission and prevent disease; therefore, an important component of the U.S. vaccination program is the assessment of vaccination coverage. Current goals are for >/=90% coverage with recommended vaccines during the first 2 years of life. Reporting Period: January-December 1998. Description of Systems: The National Immunization Survey (NIS) is an ongoing, random-digit-dialed telephone survey that gathers vaccination coverage data for children aged 19-35 months in all 50 states and 28 urban areas. Vaccination coverage rates derived from NIS data are adjusted statistically for households with multiple telephone lines, household nonresponse, the proportion of households without telephones, and vaccination provider nonresponse. The results were also adjusted to match the known total population of children in each survey area. Results: On the basis of NIS data, national coverage was >/=90% for three doses of poliovirus vaccine (Polio), three doses of Haemophilus influenzae type b vaccine (Hib), and one dose of measles-containing vaccine (MCV). Coverage was the highest ever reported for four doses of any diphtheria and tetanus toxoids and pertussis vaccine (DTP) (i.e., diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids [DT], or diphtheria and tetanus toxoids and acellular pertussis vaccine [DTaP]) (83.9%), three doses of hepatitis B vaccine (Hep B, 87.0%), and one dose of varicella vaccine (43.2%). The number of states achieving the >/=90% goal was 47 for three doses of Hib, 40 for three doses of Polio, 40 for one dose of MCV, nine for three doses of Hep B, and seven for four doses of DTP. Proportionally fewer urban areas achieved the >/=90% goal: 23 of 28 for three doses of Hib, 13 for three doses of Polio, 16 for one dose of MCV, five for three doses of Hep B, and one for four doses of DTP. No state or urban area has yet achieved the >/=90% goal for varicella. Interpretation: Findings from the 1998 NIS indicate that national vaccination coverage levels for routinely recommended childhood vaccines are at the highest levels ever reported. However, substantial variation in coverage remains at the state and urban area levels. Public Health Actions: The public health community and vaccination providers in areas with low coverage should intensify their efforts to implement recommended strategies for increasing vaccination coverage to ensure that children are equally well protected throughout the United States. [ABSTRACT FROM AUTHOR]

Folate and vitamin B12 deficiencies represent important and evolving global health challenges that contribute to the global burden of anemia, neurologic conditions, neurodevelopmental disorders, and birth defects. We present a review of population-based programs designed to increase consumption of folates and vitamin B12. A folic acid supplementation program targeting couples prior to marriage in China has led to optimal consumption of supplements containing folic acid and a significant reduction of neural tube defects (NTD). Supplementation programs that use mass community education show some promise, but have not been shown to be as effective as targeted education. The success of supplementation programs hinges on a strong and persistent educational component and access to the supplements. Fortification with folic acid has been shown to reduce the prevalence of NTD in the countries where it has been implemented. Challenges to fortification programs include identifying the appropriate delivery vehicles, setting the optimal fortification level, sustaining the quality assurance of the fortification level, and addressing regulatory challenges and trade barriers of commercially fortified flours. Supplementation and fortification are cost-effective and viable approaches to reducing the burden of NTD, anemia, and other conditions resulting from folate deficiency. The experience with interventions involving folic acid could provide a model for the subsequent development of supplementation and fortification programs involving vitamin B12. [ABSTRACT FROM AUTHOR]

Although phthalate exposure has been linked with multiple adverse pregnancy outcomes, their underlying biological mechanisms are not fully understood. We examined associations between biomarkers of phthalate exposures and metabolic alterations using untargeted metabolomics in 99 pregnant women and 86 newborns [mean (SD) gestational age = 39.5 (1.5) weeks] in the PROTECT cohort. Maternal urinary phthalate metabolites were quantified using isotope dilution high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), while metabolic profiles in maternal and cord blood plasma were characterized via reversed-phase LC-MS. Multivariable linear regression was used in metabolome-wide association studies (MWAS) to identify individual metabolic features associated with elevated phthalate levels, while clustering and correlation network analyses were used to discern the interconnectedness of biologically relevant features. In the MWAS adjusted for maternal age and prepregnancy BMI, we observed significant associations between specific phthalates, namely, di(2-ethylhexyl) phthalate (DEHP) and mono(3-carboxypropyl) phthalate (MCPP), and 34 maternal plasma metabolic features. These associations predominantly included upregulation of fatty acids, amino acids, purines, or their derivatives and downregulation of ceramides and sphingomyelins. In contrast, fewer significant associations were observed with metabolic features in cord blood. Correlation network analysis highlighted the overlap of features associated with phthalates and those identified as differentiating markers for preterm birth in a previous study. Overall, our findings underscore the complex impact of phthalate exposures on maternal and fetal metabolism, highlighting metabolomics as a tool for understanding associated biological processes. Future research should focus on expanding the sample size, exploring the effects of phthalate mixtures, and validating identified metabolic features in larger, more diverse populations.

Background: Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures., Objectives: To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association., Method: Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression modeling was performed for each sleep outcome, adjusting for maternal age at delivery and education and child sex, gestational age at birth, and age at outcome ascertainment, with random intercepts for cohorts., Results: Prenatal PSS score was associated with both CBCL (B = 0.09, 95% confidence interval [CI]: 0.06, 0.11; p < 0.01) and PSD4a (B = 0.07, 95% CI: 0.03, 0.12; p < 0.01) scores. Postnatal perceived stress mediated a proportion of the total effect of prenatal stress in both CBCL (66.3%) and PSD4a (95.9%) samples., Conclusions: Both pre- and postnatal maternal perceived stress appear to influence sleep quality during early life., Impact: Prenatal stress significantly associates with child sleep problems and disturbances at ages 4-8 years; postnatal maternal stress is a significant mediator of these associations. Research suggests a range of prenatal affective/distress exposures associated with child sleep problems, but the conclusions remain in doubt due to the mixture of exposures and outcomes employed. Ours is the first US-based effort to explore associations between perceived maternal stress during pregnancy and child sleep problems and disturbance in early and middle childhood. Even a small effect of a prevalent issue like psychosocial stress may have important public health implications at the population level., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants produced through the combustion of organic matter, with sources ranging from traffic pollution to diet. Although PAH exposure has been associated with adverse health effects, few studies have examined its impact on neurodevelopmental delay (NDD). Thus, our study aims to investigate the effect of prenatal PAH exposure on the odds of NDD. We measured 7 hydroxylated PAH metabolites in spot urine samples collected up to three times during pregnancy in the PROTECT birth cohort. NDD was identified using score cutoffs from the Ages and Stages Questionnaire, 3rd edition offered in Spanish, across five domains at 12, 24, 36, and 48 months. We utilized logistic regression and mixed effects logistic regression models to assess associations between prenatal PAH concentrations and NDD. Our results showed mostly lower odds of NDD with higher PAH exposure (p < 0.05). However, male children showed higher odds of NDD in relation to PAH exposure, particularly in the Fine Motor domain. For example, 1-hydroxypyrene was associated with 1.11 (1.01, 1.23) times odds of delay in fine motor function in male children versus 0.91 (0.82, 1.00) times odds in female children. Our preliminary sex-specific results suggest that PAH exposure may impact neurodevelopment in male children and prompt further investigation into the potential sex-specific mechanisms of PAHs on motor function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The objective of this study was to evaluate the racial and ethnic disparities in delivery hospitalizations involving severe maternal morbidity (SMM) by location of residence and community income. We used the 2016 to 2019 Healthcare Cost and Utilization Project National Inpatient Sample. International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to identify delivery hospitalizations with SMM. Using logistic regression models, we examined the association between race and ethnicity and delivery hospitalizations involving SMM. In adjusted analyses, the models were stratified by location of residence and community income and adjusted for patient and hospital characteristics. In rural areas, non-Hispanic Black women (AOR 1.50; 95% CI 1.25-1.79) and women of other races (AOR 1.32; 95% CI 1.03-1.69) had an increased odds of experiencing a delivery hospitalization involving SMM when compared to non-Hispanic White women. In micropolitan areas, non-Hispanic Black women (AOR 1.88; 95% CI 1.79-1.97), non-Hispanic Asian/Pacific Islander women (AOR 1.54; 95% CI 1.16-2.05), and women of other races (AOR 1.31; 95% CI 1.03-1.67) had an increased odds of experiencing a delivery hospitalization involving SMM when compared to non-Hispanic White women. Non-Hispanic Black women also had increased odds of experiencing a delivery hospitalization involving SMM in communities with the lowest income (quartile 1) (AOR 1.59; 95% CI 1.49-1.66), middle income (quartiles 2 and 3) (AOR 1.81; 95% CI 1.72-1.91), and highest income (AOR 2.09; 95% CI 1.90-2.29) when compared to non-Hispanic White women. We found that location of residence and community income are associated with racial and ethnic differences in SMM in the United States. These factors, outside of individual factors assessed in previous studies, provide a better understanding of some of the structural and systemic factors that may contribute to SMM., (© 2024. The Author(s).)

Preterm birth is a leading cause of neonatal mortality and presents significant public health concerns. Environmental chemical exposures during pregnancy may be partially to blame for disrupted delivery timing. Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion, exposure to which occurs via inhalation of cigarette smoke and automobile exhaust, and ingestion of charred meats. Exposure to PAHs in the US population is widespread, and pregnant women represent a susceptible population to adverse effects of PAHs. We aimed to investigate associations between gestational exposure to PAHs and birth outcomes, including timing of delivery and infant birth size. We utilized data from the PROTECT birth cohort where pregnant women provided spot urine samples at up to three study visits (median 16, 20, and 24 weeks gestation). Urine samples were assayed for eight hydroxylated PAH concentrations. Associations between PAHs and birth outcomes were calculated using linear/logistic regression models, with adjustment for maternal age, education, pre-pregnancy BMI, and daily exposure to environmental tobacco smoke. Models accounted for urine dilution using specific gravity. We also explored effect modification by infant sex. Interquartile range (IQR) increases in all averaged PAH exposures during the second trimester were associated with reduced gestational age at delivery and increased odds of overall PTB, although these associations were not statistically significant (p > 0.05). Most PAHs at the second study visit were most strongly associated with earlier delivery and increased odds of overall and spontaneous PTB, with visit 2 2-hydroxynapthalene (2-NAP) being significantly associated with increased odds of overall PTB (OR:1.55; 95 %CI: 1.05,2.29). Some PAHs resulted in earlier timing of delivery among only female fetuses, specifically 2-NAP on overall PTB (female OR:1.52 95 %CI: 1.02,2.27; male OR:0.78, 95 %CI: 0.53,1.15). Future work should more deeply investigate differential physiological impacts of PAH exposure between pregnancies with male and female fetuses, and on varying developmental processes occurring at different points through pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background/aim: Heavy metals are known to induce oxidative stress and inflammation, and the association between metal exposure and adverse birth outcomes is well established. However, there lacks research on biomarker profiles linking metal exposures and adverse birth outcomes. Eicosanoids are lipid molecules that regulate inflammation in the body, and there is growing evidence that suggests associations between plasma eicosanoids and pregnancy outcomes. Eicosanoids may aid our understanding of etiologic birth pathways. Here, we assessed associations between maternal blood metal concentrations with eicosanoid profiles among 654 pregnant women in the Puerto Rico PROTECT birth cohort., Methods: We measured concentrations of 11 metals in whole blood collected at median 18 and 26 weeks of pregnancy, and eicosanoid profiles measured in plasma collected at median 26 weeks. Multivariable linear models were used to regress eicosanoids on metals concentrations. Effect modification by infant sex was explored using interaction terms., Results: A total of 55 eicosanoids were profiled. Notably, 12-oxoeicosatetraenoic acid (12-oxoETE) and 15-oxoeicosatetraenoic acid (15-oxoETE), both of which exert inflammatory activities, had the greatest number of significant associations with metal concentrations. These eicosanoids were associated with increased concentrations of Cu, Mn, and Zn, and decreased concentrations of Cd, Co, Ni, and Pb, with the strongest effect sizes observed for 12-oxoETE and Pb (β:-33.5,95 %CI:-42.9,-22.6) and 15-oxoETE and Sn (β:43.2,95 %CI:11.4,84.1). Also, we observed differences in metals-eicosanoid associations by infant sex. Particularly, Cs and Mn had the most infant sex-specific significant associations with eicosanoids, which were primarily driven by female fetuses. All significant sex-specific associations with Cs were inverse among females, while significant sex-specific associations with Mn among females were positive within the cyclooxygenase group but inverse among the lipoxygenase group., Conclusion: Certain metals were significantly associated with eicosanoids that are responsible for regulating inflammatory responses. Eicosanoid-metal associations may suggest a role for eicosanoids in mediating metal-induced adverse birth outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA ( p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA ( q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: We sought to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on perinatal outcomes while accounting for maternal depression or perceived stress and to describe COVID-specific stressors, including changes in prenatal care, across specific time periods of the pandemic., Study Design: Data of dyads from 41 cohorts from the National Institutes of Health Environmental influences on Child Health Outcomes Program ( N  = 2,983) were used to compare birth outcomes before and during the pandemic ( n  = 2,355), and a partially overlapping sample ( n  = 1,490) responded to a COVID-19 questionnaire. Psychosocial stress was defined using prenatal screening for depression and perceived stress. Propensity-score matching and general estimating equations with robust variance estimation were used to estimate the pandemic's effect on birth outcomes., Results: Symptoms of depression and perceived stress during pregnancy were similar prior to and during the pandemic, with nearly 40% of participants reporting mild to severe stress, and 24% reporting mild depression to severe depression. Gestations were shorter during the pandemic ( B  =  - 0.33 weeks, p  = 0.025), and depression was significantly associated with shortened gestation ( B  =  - 0.02 weeks, p  = 0.015) after adjustment. Birth weights were similar ( B  =  - 28.14 g, p  = 0.568), but infants born during the pandemic had slightly larger birth weights for gestational age at delivery than those born before the pandemic ( B  = 0.15 z-score units, p  = 0.041). More women who gave birth early in the pandemic reported being moderately or extremely distressed about changes to their prenatal care and delivery (45%) compared with those who delivered later in the pandemic. A majority (72%) reported somewhat to extremely negative views of the impact of COVID-19 on their life., Conclusion: In this national cohort, we detected no effect of COVID-19 on prenatal depression or perceived stress. However, experiencing the COVID-19 pandemic in pregnancy was associated with decreases in gestational age at birth, as well as distress about changes in prenatal care early in the pandemic., Key Points: · COVID-19 was associated with shortened gestations.. · Depression was associated with shortened gestations.. · However, stress during the pandemic remained unchanged.. · Most women reported negative impacts of the pandemic.., Competing Interests: C.M. served as Chair of the Data Safety Monitoring Board (DSMB) for an Aerogen-supported trial: A Partially-Blind, Randomized, Controlled, Parallel-Group Dose Ranging Study to Determine the Efficacy, Safety and Tolerability of AeroFactTM (SF-RI 1 surfactant for inhalation combined with a dedicated drug delivery system) in Preterm Infants at Risk for Worsening Respiratory Distress Syndrome; Chair of the DSMB for the NIH RCT evaluating Sildenafil in Preterm Infants with Pulmonary Hypertension. J.N. served on the Advisory Board for the Twin Life Study (Germany); received royalties or licenses from Macmillan and consulting fees from the University of Southern California. J.H. served on the New York State Drinking Water Quality Council. The other authors have no conflicts of interest to disclose., (Thieme. All rights reserved.)

Exposure to phenols and parabens may contribute to increased maternal inflammation and adverse birth outcomes, but these effects are not well-studied in humans. This study aimed to investigate relationships between concentrations of 8 phenols and 4 parabens with 6 inflammatory biomarkers (C-reactive protein (CRP); matrix metalloproteinases (MMP) 1, 2, and 9; intercellular adhesion molecule-1 (ICAM-1); and vascular cell adhesion molecule-1 (VCAM-1)) measured at two time points in pregnancy in the PROTECT birth cohort in Puerto Rico. Linear mixed models were used, adjusting for covariates of interest. Results are expressed as the percent change in outcome per interquartile range (IQR) increase in exposure. Particularly among phenols, numerous significant negative associations were found, for example, between benzophenone-3 and CRP (-11.21 %, 95 % CI: -17.82, -4.07) and triclocarban and MMP2 (-9.87 %, 95 % CI: -14.05, -5.5). However, significant positive associations were also detected, for instance, between bisphenol-A (BPA) and CRP (9.77 %, 95 % CI: 0.67, 19.68) and methyl-paraben and MMP1 (10.78 %, 95 % CI: 2.17, 20.11). Significant interactions with female fetal sex and the later study visit (at 24-28 weeks gestation) showed more positive associations compared to male fetal sex and the earlier study visit (16-20 weeks gestation). Our results suggest that phenols and parabens may disrupt inflammatory processes pertaining to uterine remodeling and endothelial function, with important implications for pregnancy outcomes. More research is needed to further understand maternal inflammatory status in an effort to improve reproductive and developmental outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Financial support was provided by the Superfund Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH; grant numbers P42ES017198 and R01ES03220). Additional support was provided from grants P30ES017885 and T32ES007062 from the NIEHS, NIH, and the Environmental influences on Child Health Outcomes (ECHO) program grant number UH3OD023251. ECHO is a nationwide research program supported by the NIH, Office of the Director to enhance child health., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: N-(phosphonomethyl)glycine, or glyphosate, is a non-selective systemic herbicide widely used in agricultural, industrial, and residential settings since 1974. Glyphosate exposure has been inconsistently linked to neurotoxicity in animals, and studies of effects of gestational exposure among humans are scarce. In this study we investigated relationships between prenatal urinary glyphosate analytes and early childhood neurodevelopment., Methods: Mother-child pairs from the PROTECT-CRECE birth cohort in Puerto Rico with measures for both maternal urinary glyphosate analytes and child neurodevelopment were included for analysis (n = 143). Spot urine samples were collected 1-3 times throughout pregnancy and analyzed for glyphosate and aminomethylphosphonic acid (AMPA), an environmental degradant of glyphosate. Child neurodevelopment was assessed at 6, 12, and 24 months using the Battelle Developmental Inventory, 2nd edition Spanish (BDI-2), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. We used multivariable linear regression to examine associations between the geometric mean of maternal urinary glyphosate analytes across pregnancy and BDI-2 scores at each follow-up. Results were expressed as percent change in BDI-2 score per interquartile range increase in exposure., Results: Prenatal AMPA concentrations were negatively associated with communication domain at 12 months (%change = -5.32; 95%CI: 9.04, -1.61; p = 0.007), and communication subdomain scores at 12 and 24 months. At 24 months, four BDI-2 domains were associated with AMPA: adaptive (%change = -3.15; 95%CI: 6.05, -0.25; p = 0.038), personal-social (%change = -4.37; 95%CI: 7.48, -1.26; p = 0.008), communication (%change = -7.00; 95%CI: 11.75, -2.26; p = 0.005), and cognitive (%change = -4.02; 95%CI: 6.72, -1.32; p = 0.005). Similar trends were observed with GLY concentrations, but most confidence intervals include zero. We found no significant associations at 6 months., Conclusions: Our results suggest that gestational exposure to glyphosate is associated with adverse early neurodevelopment, with more pronounced delays at 24 months. Given glyphosate's wide usage, further investigation into the impact of gestational glyphosate exposure on neurodevelopment is warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John D. Meeker reports a relationship with University of Michigan that includes: paid expert testimony. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

In the summer of 2020, SARS-CoV-2 infection rates among the U.S. population aged 20-39 years exceeded other age groups, with the largest increases occurring in the southern US. As many colleges reopened for in-person instruction in August and September, these trends continued among campuses across the country. Our study aimed to identify risk factors (demographic and behavioral) associated with SARS-CoV-2 infection among college students. We used data from a survey administered to students at a southern university in the US. The survey had a total of 765 respondents and this study included the 679 (88.8%) who responded about their SARS-CoV-2 infection status. We examined associations between population characteristics and reported SARS-CoV-2 infection and calculated prevalence ratios along with 95% confidence intervals. SARS-CoV-2 infection was 2.5 times more likely among current users of electronic nicotine delivery systems (ENDS) compared to those who do not use ENDS (95% confidence interval [CI]: (1.76-3.4)) and 2.8 times more likely among those who reported a high frequency of binge drinking compared to those who did not report binge drinking (95% CI: (1.81-4.36)). Current high frequency ENDS users were 2.76 (1.79-4.25) more likely to report SARS-CoV-2 infection than non-users. Current low frequency users of ENDS were 2.27 (1.53-3.37) times more likely to report SARS-CoV-2 infection than nonusers. A trend analysis among ENDS use frequency and SARS-CoV-2 infection was statistically significant, showing a significant dose response with increasing ENDS use. The results of this analysis may assist in providing guidance on policies as well as may serve as a steppingstone for future research concerning SAR-CoV-2 infection among university populations.

Nutritional approaches to optimize cattle health and performance during the receiving period are warranted. This experiment evaluated the impacts of supplementing organic complexed Cu, Co, Mn, and Zn on productive and health responses of high-risk beef cattle during a 60-day backgrounding phase. Crossbred steers (120) were purchased at auction and transported to the experimental facility, where BW was recorded (day-1; initial shrunk BW = 227.7 ± 1.3 kg). On day 0, steers were ranked by BW and allocated to one of eight groups and housed in drylot pens equipped with GrowSafe automated feeding systems (Model 8000; two bunks/pen). Groups were randomly assigned to receive a total mixed ration containing: (1) sulfate sources of Cu, Co, Mn, and Zn (INR; n = 40); (2) organic complexed sources of the same minerals (AAC; Zinpro Availa 4 based on a metal:amino acid complex ratio of 1:1 for Zn, Cu, and Mn in addition to cobalt glucoheptonate; Zinpro Corp., Eden Prairie, MN; n = 40); or (3) AAC and an organic complexed trace mineral drench (APF; 30 mL/hd; Zinpro ProFusion, Zinpro Corp.) on day 0 and with morbidity treatment (n = 40). Diets provided the same daily amount of all nutrients and minerals based on 7 g/steer daily of Zinpro Availa 4. Steers were assessed for bovine respiratory disease (BRD) signs daily. Liver biopsies were performed on days 0, 28 and 60. Blood samples were collected on days 0, 2, 6, 10, 13, 21, 28 and 45. No treatment differences were detected (P ≥ 0.23) for feed intake, final BW, average daily gain, or BRD incidence. Mean liver Co concentrations were greater (P = 0.02) in AAC and APF compared to INR steers. Mean liver Cu was greater (P = 0.02) in APF compared to AAC steers. Liver Zn tended to be greater (P = 0.10) on day 28 but less (P = 0.05) on day 60 for INR compared to AAC and APF steers. Plasma cortisol was lowest (P = 0.05) for AAC steers on day 6, whereas AAC steers tended to have greater (P = 0.09) plasma cortisol on day 13 compared with APF. Plasma haptoglobin tended to be greater (P ≤ 0.10) for INR steers on days 28 and 45 compared to AAC and APF. While supplementing cattle with AAC or INR results in similar animal performance and clinical disease, AAC and APF reduce stress and acute phase protein responses., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility., Objective: The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework., Methods: We used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure., Results: Only 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P < 0.05) with offspring BMI z-scores at age 2 years in a meta-analytic framework including at least two studies: arabinose (Coef meta  = 0.40 [95% CI 0.10,0.70], P meta  = 9.7 × 10 -3 ), guanidinoacetate (Coef meta  = - 0.28 [- 0.54, - 0.02], P meta  = 0.033), 3-ureidopropionate (Coef meta  = 0.22 [0.017,0.41], P meta  = 0.033), 1-methylhistidine (Coef meta  = - 0.18 [- 0.33, - 0.04], P meta  = 0.011), serine (Coef meta  = - 0.18 [- 0.36, - 0.01], P meta  = 0.034), and lysine (Coef meta  = - 0.16 [- 0.32, - 0.01], P meta  = 0.044). No associations were robust to multiple testing correction., Conclusions: Despite including three cohorts with large sample sizes (N > 100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth., Objectives: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a ) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b ) exposure-response models stratified by race and ethnicity., Methods: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth., Results: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): - 34 % , 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: - 19 % , 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono- n -butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants., Conclusions: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Matrix metalloproteinases (MMPs) are major extracellular matrix (ECM) remodeling proteinases and regulate uterine remodeling, which is a critical process for healthy pregnancies. The goal of this study was to investigate associations between maternal blood MMPs during pregnancy and birth outcomes among 898 pregnant women in the Puerto Rico PROTECT birth cohort. MMPs (MMP1, MMP2, and MMP9) were quantified using a customized Luminex assay in blood samples collected at two gestational study visits (around 18 and 26 weeks gestation). Linear and logistic regression models were used to regress continuous and binary birth outcomes, respectively, on MMPs at each study visit separately. Sensitivity analyses were conducted to test for effect modification by fetal sex on associations between MMPs and birth outcomes. We observed significant associations between MMP2 at visit 1 and newborn length that were in the opposite direction from the associations between MMP9 at visit 3 and newborn length. MMPs were associated with increased odds of preeclampsia and gestational diabetes mellitus, though case numbers were low. We also observed significant inverse associations with gestational age for MMP9 and MMP2 at visit 1 and visit 3, respectively, and these associations were observed only in mothers carrying male fetuses. Further, MMP2 was associated with heavier female fetuses, whereas MMP9 was associated with lighter female fetuses. We observed significant associations between birth outcomes and MMPs, and the majority of these associations differed by fetal sex. This study highlighted significant MMPs-birth outcomes associations that may provide a basis to explore the impact of MMPs on endometrium health and physiology., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Importance: Few population-based studies in the US collected individual-level data from families during the COVID-19 pandemic., Objective: To examine differences in COVID-19 pandemic-related experiences in a large sociodemographically diverse sample of children and caregivers., Design, Setting, and Participants: The Environmental influences on Child Health Outcomes (ECHO) multi-cohort consortium is an ongoing study that brings together 64 individual cohorts with participants (24 757 children and 31 700 caregivers in this study) in all 50 US states and Puerto Rico. Participants who completed the ECHO COVID-19 survey between April 2020 and March 2022 were included in this cross-sectional analysis. Data were analyzed from July 2021 to September 2022., Main Outcomes and Measures: Exposures of interest were caregiver education level, child life stage (infant, preschool, middle childhood, and adolescent), and urban or rural (population <50 000) residence. Dependent variables included COVID-19 infection status and testing; disruptions to school, child care, and health care; financial hardships; and remote work. Outcomes were examined separately in logistic regression models mutually adjusted for exposures of interest and race, ethnicity, US Census division, sex, and survey administration date., Results: Analyses included 14 646 children (mean [SD] age, 7.1 [4.4] years; 7120 [49%] female) and 13 644 caregivers (mean [SD] age, 37.6 [7.2] years; 13 381 [98%] female). Caregivers were racially (3% Asian; 16% Black; 12% multiple race; 63% White) and ethnically (19% Hispanic) diverse and comparable with the US population. Less than high school education (vs master's degree or more) was associated with more challenges accessing COVID-19 tests (adjusted odds ratio [aOR], 1.88; 95% CI, 1.06-1.58), lower odds of working remotely (aOR, 0.04; 95% CI, 0.03-0.07), and more food access concerns (aOR, 4.14; 95% CI, 3.20-5.36). Compared with other age groups, young children (age 1 to 5 years) were least likely to receive support from schools during school closures, and their caregivers were most likely to have challenges arranging childcare and concerns about work impacts. Rural caregivers were less likely to rank health concerns (aOR, 0.77; 95% CI, 0.69-0.86) and social distancing (aOR, 0.82; 95% CI, 0.73-0.91) as top stressors compared with urban caregivers., Conclusions: Findings in this cohort study of US families highlighted pandemic-related burdens faced by families with lower socioeconomic status and young children. Populations more vulnerable to public health crises should be prioritized in recovery efforts and future planning.

Humans are exposed to complex mixtures of phthalates. Gestational exposure to phthalates has been linked to preeclampsia and preterm birth through potential pathways such as endocrine disruption, oxidative stress, and inflammation. Eicosanoids are bioactive signaling lipids that are related to a variety of homeostatic and inflammatory processes. We investigated associations between urinary phthalates and their mixtures with plasma eicosanoid levels during pregnancy using the PROTECT cohort in Puerto Rico (N = 655). After adjusting for covariates, we estimated pair-wise associations between the geometric mean of individual phthalate metabolite concentrations across pregnancy and eicosanoid biomarkers using multivariable linear regression. We used bootstrapping of adaptive elastic net regression (adENET) to evaluate phthalate mixtures associated with eicosanoids and subsequently create environmental risk scores (ERS) to represent weighted sums of phthalate exposure for each individual. After adjusting for false-discovery, in single-pollutant analysis, 14 of 20 phthalate metabolites or parent compound indices showed significant and primarily negative associations with multiple eicosanoids. In our mixture analysis, associations with several metabolites of low molecular weight phthalates - DEP, DBP, and DIBP - became prominent. Additionally, MEHHTP and MECPTP, metabolites of a new phthalate replacement, DEHTP, were selected as important predictors for determining the concentrations of multiple eicosanoids from different pathway groups. A unit increase in phthalate ERS derived from bootstrapping of adENET was positively associated with several eicosanoids mainly from Cytochrome P450 pathway. For example, an increase in ERS was associated with 11(S)-HETE (β = 1.6, 95% CI: 0.020, 3.180), (±)11,12-DHET (β = 2.045, 95% CI: 0.250, 3.840), 20(S)-HETE (β = 0.813, 95% CI: 0.147, 1.479), and 9 s-HODE (β = 2.381, 95% CI: 0.657, 4.104). Gestational exposure to phthalates and phthalate mixtures were associated with eicosanoid levels during pregnancy. Results from the mixture analyses underscore the complexity of physiological impacts of phthalate exposure and call for further in-depth studies to examine these relationships., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse., Objectives: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history., Methods: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE., Results: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46)., Conclusions: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States., Objective: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin., Study Design: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F 2α , 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F 2α (F 2 -IsoP-M; the major 8-iso-prostaglandin-F 2α metabolite), and prostaglandin-F 2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models., Results: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F 2 -IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F 2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis., Conclusion: Here, oxidative stress, as measured by 8-iso-prostaglandin-F 2α , F 2 -IsoP-M, and prostaglandin-F 2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm., Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term., Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022., Exposures: Premature birth (<37 weeks' gestation)., Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion., Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78)., Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models.

Background: This study examined the relationship between prenatal maternal stress (PREMS) and non-nutritive suck (NNS) and tested its robustness across 2 demographically diverse populations., Methods: The study involved 2 prospective birth cohorts participating in the national Environmental influences on Child Health Outcomes (ECHO) Program: Illinois Kids Development Study (IKIDS) and ECHO Puerto Rico (ECHO-PROTECT). PREMS was measured during late pregnancy via the 10-item Perceived Stress Scale (PSS-10). NNS was sampled from 1- to 8-week-olds using a custom pacifier for ~5 min., Results: Overall, 237 mother-infant dyads completed this study. Despite several significant differences, including race/ethnicity, income, education, and PREMS levels, significant PREMS-NNS associations were found in the 2 cohorts. In adjusted linear regression models, higher PREMS, measured through PSS-10 total scores, related to fewer but longer NNS bursts per minute., Conclusions: A significant association was observed between PREMS and NNS across two diverse cohorts. This finding is important as it may enable the earlier detection of exposure-related deficits and, as a result, earlier intervention, which potentially can optimize outcomes. More research is needed to understand how NNS affects children's neurofunction and development., Impact: In this double-cohort study, we found that higher maternal perceived stress assessed in late pregnancy was significantly associated with fewer but longer sucking bursts in 1- to 8-week-old infants. This is the first study investigating the association between prenatal maternal stress (PREMS) and infant non-nutritive suck (NNS), an early indicator of central nervous system integrity. Non-nutritive suck is a potential marker of increased prenatal stress in diverse populations. Non-nutritive suck can potentially serve as an early indicator of exposure-related neuropsychological deficits allowing for earlier interventions and thus better prognoses., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Individual symptoms and signs of infectious mononucleosis (IM) are of limited value for diagnosis., Objective: To develop and validate risk scores based on signs and symptoms with and without haematologic parameters for the diagnosis of IM., Design and Setting: Data were extracted from electronic health records of a university health centre and were divided into derivation (9/1/2015-10/31/2017) and a prospective temporal internal validation (11/1/2017-1/31/2019) cohort., Method: Independent predictors for the diagnosis of IM were identified in univariate analysis using the derivation cohort. Logistic regression models were used to develop 2 risk scores: 1 with only symptoms and signs (IM-NoLab) and 1 adding haematologic parameters (IM-Lab). Point scores were created based on the regression coefficients, and patients were grouped into risk groups. Primary outcomes were area under the receiver operating characteristic curve (AUROCC) and classification accuracy., Results: The IM-NoLab model had 4 predictors and identified a low-risk group (7.9% with IM) and a high-risk group (22.2%) in the validation cohort. The AUROCC was 0.75 in the derivation cohort and 0.69 in the validation cohort. The IM-Lab model had 3 predictors and identified a low-risk group (3.6%), a moderate-risk group (12.5%), and a high-risk group (87.6%). The AUROCC was 0.97 in the derivation cohort and 0.93 in the validation cohort., Conclusion: We derived and internally validated the IM-NoLab and IM-Lab risk scores. The IM-Lab score in particular had very good discrimination and have the potential to reduce the need for diagnostic testing for IM., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To describe the importance of community engagement from research projects and research centers in times of disasters or emergencies, using the case of Puerto Rico in recent years (2017 - 2022) as an example., Methods: First, research participants and stakeholders from local community and health organizations were contacted via email and phone calls after each emergency to assess their immediate needs. Second, needs were classified in categories (materials, educational resources, service referrals, and collaborations). Finally, delivery of support was coordinated in a timely manner whether in person or online., Results: Activities were conducted such as handing out materials, providing educational resources, contacting participants, and stakeholders, as well as coordinating collaboration with community and organizations., Conclusion: Several lessons were learned from our experiences related to Puerto Rico's recent emergencies as well as some relevant recommendations for future disasters. The efforts presented illustrate the importance of community engagement from academic institutions in disasters. Research centers and research projects, particularly those with community engagement components, should consider providing support in the preparedness phase as well as the recovery phase if necessary. Community engagement in emergencies is crucial to recovery efforts as well as fostering empowerment and making an impact on individual and societal levels.

Background: The PROTECT Center is a multi-project initiative that studies the relationship between exposure to environmental contaminants and preterm births during the prenatal and postnatal period among women living in Puerto Rico. PROTECT's Community Engagement Core and Research Translation Coordinator (CEC/RTC) play a key role in building trust and capacity by approaching the cohort as an engaged community that provides feedback about processes, including how personalized results of their exposure to chemicals should be reported back. The goal of the Mi PROTECT platform was to create a mobile-based application of DERBI (Digital Exposure Report-Back Interface) for our cohort that provides tailored, culturally appropriate information about individual contaminant exposures as well as education on chemical substances and approaches to exposure reduction., Methods: Participants (N = 61) were presented with commonly used terms in environmental health research related to collected samples and biomarkers, followed by a guided training on accessing and exploring the Mi PROTECT platform. Participants evaluated the guided training and Mi PROTECT platform answering a Likert scale in separated surveys that included 13 and 8 questions, respectively., Results: Participants provided overwhelmingly positive feedback on the clarity and fluency of presenters in the report-back training. Most participants reported that the mobile phone platform was both accessible and easy to navigate (83% and 80%, respectively) and that images included in the platform facilitated comprehension of the information. Overall, most participants (83%) reported that language, images, and examples in Mi PROTECT strongly represented them as Puerto Ricans., Conclusions: Findings from the Mi PROTECT pilot test informed investigators, community partners and stakeholders by demonstrating a new way to promote stakeholder participation and foster the "research right-to-know.", Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cardona Cordero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother−child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. Phthalate metabolites were measured in multiple maternal urine collected during pregnancy. Neurodevelopment was measured at 6, 12, and 24 months of age using the Battelle Developmental Inventory-2nd edition (BDI), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. Multivariable linear regression was used to examine associations between phthalate metabolite concentrations and BDI scores, adjusting for maternal age, maternal education, child age, and specific gravity. Sex-specificity was assessed with sex X exposure interaction terms and stratified models. Results show that all five domains were significantly associated with mono-3-carboxypropyl phthalate (MCPP) at age 24 months, suggesting a holistic developmental delay related to this metabolite. Sex-specificity existed for all timepoints (p-interaction < 0.2), in general, showing stronger associations among boys. For example, metabolites of a recent phthalate replacement, di-2-ethylhexyl terephthalate (DEHTP), were differentially associated with the adaptive domain (boys −7.53%/IQR, 95% CI: −14.58, −0.48 vs. girls −0.85%/IQR, 95% CI: −5.08, 3.37), and the cognitive domain (boys −6.05%/IQR, 95% CI: −10.88, −1.22 vs. girls −1.93%/IQR, 95%CI: −4.14, 0.28) at 6 months. To conclude, gestational exposure to phthalates and phthalate replacements was associated with neurodevelopmental delay across multiple domains, with differences by sex and child age.

Phthalates are ubiquitous environmental exposures that may be implicated in inflammatory processes, as demonstrated by previous in vivo and in vitro studies. Few human studies have substantiated these observations. This study sought to examine whether maternal phthalate exposures impact inflammatory processes, as measured by circulating inflammatory biomarkers, in the PROTECT cohort in northern Puerto Rico. Inflammatory biomarkers included matrix metalloproteinases 1, 2, and 9 (MMPs), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM), and intercellular cell adhesion molecule-1 (ICAM). Biomarkers were measured in maternal serum samples collected during pregnancy. 19 phthalate metabolites were assessed in urinary samples collected at three study visits across pregnancy. Phthalates with <50 % of measurements above the limit of detection were excluded from analysis. We utilized linear mixed effect models to estimate associations between interquartile range increases in phthalate metabolite concentrations and percent changes in inflammatory biomarkers. Our results revealed significant associations between mono-n-butyl phthalate (MBP) and higher MMP1 by 7.86 % (95 % CI: 0.49, 15.76) and between mono oxononyl phthalate (MONP) and higher MMP2 by 8.30 % (95 % CI: 2.22, 14.75). We observed negative or null associations between phthalate metabolites and MMP2, MMP9, ICAM, VCAM, and CRP. Many results were significantly modified by fetal sex, particularly those between di-2-ethylhexyl phthalate (DEHP) metabolites and MMP1 (p-interaction: MEHHP = 0.01, MEOHP = 0.04, MECPP = 0.01) and MMP2 (p-interaction: MEHHP = 0.03, MEOHP = 0.01, MECPP = 0.01), for which associations were positive among only women carrying female fetuses. MMPs have been previously associated with preeclampsia and hypertensive pregnancy disorders as mediators of artery remodeling. Hence, our findings suggest a potential role for phthalates in mediating the maternal inflammatory response, as well as significant sexual dimorphism in these relationships, which has implications for several adverse pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background/aim: Infant non-nutritive suck (NNS) has been used as an early marker of neonatal brain function. Although there is an established relationship between prenatal exposure to certain metals and brain development, the association between metal exposure and NNS has not been explored. Therefore, in this study we assessed associations between maternal urinary metal(loid) concentrations and NNS measurements among infants from the Puerto Rico PROTECT birth cohort. We hypothesized that maternal urinary metal(loid) concentrations are significantly associated with infant NNS measures in a sex-dependent manner., Methods: We measured urinary concentrations of 14 metal(loid)s in pregnant women at up to three time points in pregnancy. The geometric mean of each metal(loid) for each pregnant woman was calculated and used as an exposure measurement across gestation. NNS measurements (duration, frequency, amplitude, bursts/min, cycles/burst, cycles/min) were collected from infants between 4 and 6 (±2 weeks) weeks of age using our custom research pacifier. Linear regression was used to estimate associations between urinary metal(loid) concentrations across pregnancy and continuous NNS variables. Sex-specific effects were estimated using interaction terms between NNS variables and infant sex., Results: We observed significant positive associations between mercury, manganese, and tin with NNS duration (mercury: %Δ = 1.08, 95% CI: 0.42, 1.74; manganese: %Δ = 0.67, 95% CI: 0.15, 1.20; tin: %Δ = 0.83, 95% CI: 0.17, 1.49) and NNS cycles/burst (mercury: %Δ = 1.85, 95% CI: 0.58, 3.11; manganese: (%Δ = 1.37, 95% CI: 0.40, 2.34; tin: %Δ = 1.68, 95% CI: 0.46, 2.91). Furthermore, the association between NNS cycles/min with cadmium (%Δ = 8.06, 95% CI: 3.33, 12.78), manganese (%Δ = 4.44, 95% CI: 1.40, 7.47), and tin (%Δ = 4.50, 95% CI: 0.81, 8.18) were in the opposite direction from its association with zinc (%Δ = -9.30, 95% CI: -14.71, -3.89), as well as with copper (%Δ = -6.58, 95% CI: -12.06, -1.10). For the sex-stratified analysis, the negative associations between metal(loid)s and NNS duration were predominantly driven by male infants; however, the negative associations between metal(loid)s and NNS bursts/min were mainly driven by female infants., Conclusion: We observed significant associations between prenatal metal(loid) exposure and NNS measurements among infants from the ongoing Puerto Rico PROTECT cohort. Similar to previous studies that have demonstrated associations between NNS and subsequent neurodevelopment, this study highlights the potential of NNS as a quantitative index to measure altered neurodevelopment from prenatal metal(loid) exposures. We believe this study will inform future efforts aimed at reducing health risks related to early life metal exposures, such as developing early identification of metal-induced adverse outcomes in child neurodevelopment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Kim, Zimmerman, Huerta-Montañez, Rosario-Pabón, Vélez-Vega, Alshawabkeh, Cordero, Meeker and Watkins.)

This study examined the relationship between maternal food source and preparation during pregnancy and the duration of breastfeeding among 751 mother-child dyads in the United States. The data collected from the Environmental influences on Child Health Outcomes (ECHO) Program included twelve cohorts of mothers (age ≥ 18) who delivered infant(s). Three categories of maternal food source and preparation including, High, Moderate, or Low Food Source Quality were derived from the mother report. The mean duration of breastfeeding differed strongly across the three categories. The High Food Source Quality group breastfed an average of 41 weeks, while shorter durations were observed for the Moderate (26 weeks) and Low (16 weeks) Food Source Quality groups. Cox proportional hazards models were used to estimate the relative hazard of time to breastfeeding cessation for each participant characteristic. The full model adjusted for clustering/cohort effect for all participant characteristics, while the final model adjusted for the subset of characteristics identified from variable reduction modeling. The hazard of breastfeeding cessation for those in the High Food Source Quality group was 24% less than the Moderate group (RH = 0.76; 95% CI, 0.63-0.92). Pregnant women in the High Food Source Quality group breastfed longer than the Moderate and Low groups. We encourage more detailed studies in the future to examine this relationship longitudinally.

Objectives: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11., Materials and Methods: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools., Results: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11., Conclusion: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations., (© 2021 Wiley Periodicals LLC.)

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth., Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US., Design, Setting, and Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included., Exposures: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated., Main Outcomes and Measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth., Results: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively., Conclusions and Relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

Background: Lower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers., Methods: Leveraging four pregnancy cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program spanning multiple geographic regions across the United States (U.S.) (N = 2082), we measured biomarkers of oxidative stress in urine samples at up to three time points during pregnancy, including 8-isoprostane-prostaglandin F 2α (8-isoPGF 2α ), its major metabolite, 2,3-dinor-5,6-dihydro-15-F 2t -isoprostane, and prostaglandin F 2α (PGF 2α ). Maternal age, pre-pregnancy body mass index, marital/partnered status, parity, and smoking status were included as biological and behavioral factors while race/ethnicity, maternal education, and stressful life events were considered social factors. We examined associations between each individual biological, behavioral, and social factor with oxidative stress biomarkers using multivariable-adjusted linear mixed models., Results: Numerous biological, behavioral, and social factors were associated with elevated levels of 8-isoPGF 2α , its major metabolite, and PGF 2α . Pregnant people who were current smokers relative to non-smokers or had less than a high school education relative to a college degree had 11.04% (95% confidence interval [CI] = -1.97%, 25.77%) and 9.13% (95% CI = -1.02%, 20.32%) higher levels of 8-isoPGF 2α , respectively., Conclusions: Oxidative stress biomarkers are elevated among pregnant people with higher socioeconomic disadvantage and may represent one pathway linking biological, behavioral, and social factors to adverse pregnancy and child health outcomes, which should be explored in future work., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To examine postpartum depressive symptom trajectories from birth to age 5 and their risk factors in a national sample of mothers of preterm and full-term infants. The racially and ethnically diverse sample comprised 11,320 maternal participants (M age  = 29; SD = 5.9) in the Environmental influences on Child Health Outcomes (ECHO) Program in the USA with data on newborn gestational age at birth (≥ 22 weeks) and maternal depression symptoms during the first 5 years following childbirth. Growth mixture models determined the number and trajectory of postpartum depression classes among women in the preterm and full-term groups, and we examined predictors of class membership. Five trajectories described depressive symptoms for both groups; however, notable differences were observed. One in 5 mothers of preterm infants developed clinically relevant depressive symptoms over time compared with 1 in 10 mothers of full-term infants. Among women who delivered preterm compared with those who delivered full-term, symptoms were more likely to increase over time and become severe when offspring were older. Distinct subgroups describe mothers' depressive symptom trajectories through 5 years following childbirth. Mild to moderate depressive symptoms may onset or persist for many women beyond the initial postpartum period regardless of newborn gestational age at birth. For women with preterm infants, initially mild symptoms may increase to high levels of severity during the preschool and toddler years., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)