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BackgroundThere are few data on tenofovir-diphosphate (TFV-DP) concentrations in pregnant and postpartum women on Tenofovir Disoproxil Fumarate-Emtricitabine (TDF-FTC) or Tenofovir Alafenamide-Emtricitabine (TAF-FTC).MethodsEligible pregnant women were randomized to TDF-FTC or TAF-FTC and followed for 16 weeks (8-weeks pregnant, 8-weeks postpartum) with weekly collection of dried blood spot (DBS) and 4-weekly peripheral blood mononuclear cells (PBMC). PrEP dosing was observed daily via asynchronous videos sent via cell phone. We report geometric means (GM) and their ratios (GMR) with 95% confidence intervals (CIs) for TFV-DP in PBMC and DBS from pregnancy and postpartum.ResultsWe enrolled N = 39 participants (n = 19 TDF-FTC, n = 20 TAF-FTC): median age was 28 years (IQR:25-34); median gestational age was 24-weeks (IQR:21-28). For TDF-FTC, TFV-DP DBS concentrations at 8-weeks did not differ significantly between pregnancy (GM: 675; 95%CI:537-849) and postpartum (GM: 583; 95%CI:471-722; GMR-TDF = 1.16; 95%CI:0.74-1.80). For TAF-FTC, TFV-DP DBS concentrations at 8-weeks were 44% higher in postpartum (GM: 1199; 95%CI:929-1549) versus pregnancy (GM: 832; 95%CI:751-922; GMR-TAF = 1.44; 95% CI: 1.01-2.06). In PBMC analysis of TDF-FTC, 8-week median TFV-DP (pmol/10^6 cell) was 71 (IQR 44-112) in pregnancy and 73 (IQR 50-102) in postpartum (GMR = 1.04; 95%CI:0.44-2.44). In TAF-FTC, median PBMC at 8-weeks was 580 (IQR:341-985) in pregnancy and 666 (IQR:396-1123) in postpartum (GMR = 1.15; 95%CI:0.30-2.49).ConclusionTFV-DP concentrations were overall lower during pregnancy than postpartum for TAF-FTC. We found high concentrations of TFV-DP in PBMC in pregnancy and postpartum on TAF-FTC, suggesting PrEP efficacy is maintained. Efficacy and safety studies are warranted to evaluate TAF-FTC for PrEP in pregnant and postpartum women.

Pregnancy is a time of high metabolic coordination, as maternal metabolism adapts to support the growing fetus. Many of these changes are coordinated by the placenta, a critical fetal endocrine organ and the site of maternal-fetal crosstalk. Dysregulation in maternal and placental metabolism during pregnancy has been linked to adverse outcomes, including altered neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder linked to metabolic alterations in both children and their mothers. Prenatal environmental exposures have been linked to risk of ASD through dysregulated maternal, placental, and fetal metabolism. In this review, we focus on recent studies investigating the associations between prenatal metabolism in the maternal-placental-fetal unit and the impact of prenatal environmental exposures to phthalates and micronutrients on ASD risk. By identifying the mechanisms through which phthalates and other ubiquitous endocrine disrupting chemicals influence development, and how nutritional interventions can impact those mechanisms, we can identify promising ways to prevent suboptimal neurodevelopment.

Purpose of reviewDepression during the perinatal or antenatal period affects at least 1 in 10 women worldwide, with long term health implications for the mother and child. Concurrently, there is increasing evidence associating maternal exposure to per- and poly-fluoroalkyl substances (PFAS) to adverse pregnancy outcomes. We reviewed the body of evidence examining both the associations between PFAS exposure and perturbations in the maternal metabolome, and the associations between the maternal metabolome and perinatal/antenatal depression. Through this, we sought to explore existing evidence of the perinatal metabolome as a potential mediation pathway linking PFAS exposure and perinatal/antenatal depression.Recent findingsThere are few studies examining the metabolomics of PFAS exposure-specifically in pregnant women-and the metabolomics of perinatal/antenatal depression, let alone studies examining both simultaneously. Of the studies reviewed (N = 11), the majority were cross sectional, based outside of the US, and conducted on largely homogenous populations. Our review identified 23 metabolic pathways in the perinatal metabolome common to both PFAS exposure and perinatal/antenatal depression. Future studies may consider findings from our review to conduct literature-derived hypothesis testing focusing on fatty acid metabolism, alanine metabolism, glutamate metabolism, and tyrosine metabolism when exploring the biochemical mechanisms conferring the risk of perinatal/antenatal depression due to PFAS exposure. We recommend that researchers also utilize heterogenous populations, longitudinal study designs, and mediation approaches to elucidate key pathways linking PFAS exposures to perinatal/antenatal depression.

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

BackgroundGestational nutrition can protect against adverse neurodevelopmental outcomes.ObjectivesWe developed a short tool for collecting maternal nutritional intake during pregnancy to facilitate research in this area and compared its retrospective use to prospectively-collected food frequency questionnaires (FFQ).MethodsMaternal nutritional intake was retrospectively assessed using three versions (full interview, full self-administered online, and shortened interview) of the Early Life Exposure Assessment Tool (ELEAT) among participants of the MARBLES pregnancy cohort study of younger siblings of autistic children. Retrospective responses were compared with responses to supplement questions and the validated 2005 Block FFQ prospectively collected in MARBLES during pregnancies 2-7 years prior. ELEAT nutrient values were calculated using reported food intake frequencies and nutrient values from the USDA nutrient database. Correlations between retrospectively- and prospectively-reported intake were evaluated using Kappa coefficients, Youden's J, and Spearman Rank Correlation Coefficients (rs).ResultsMARBLES FFQ dietary intakes were compared among 54 women who completed the ELEAT full form including 12 online, and among 23 who completed the ELEAT short form. Correlations across most foods were fair to moderate. Most ELEAT quantified nutrient values were moderately correlated (rs = 0.3-0.6) with those on the Block FFQ. Supplement questions in both MARBLES and the ELEAT were completed by 114 women. Kappas were moderate for whether or not supplements were taken, but modest for timing. Correlations varied by version and child diagnosis or concerns, and were higher when mothers completed the ELEAT when their child was 4 years old or younger.ConclusionsWith recall up to several years, ELEAT dietary and supplement module responses were modestly to moderately reliable and produced nutrient values moderately correlated with prospectively-collected measures. The ELEAT dietary and vitamin supplements modules can be used to rank participants in terms of intake of several nutrients relevant for neurodevelopment.

BackgroundTubal sterilization is the most commonly used method of contraception in the United States. Because contraceptive effectiveness influences contraceptive selection, we examined typical use failure rates after tubal sterilization in the United States.MethodsWe estimated rates of pregnancy after tubal sterilization using data from four waves of the National Survey of Family Growth (NSFG), representative samples of U.S. women aged 15 to 44 years, collected in 2002, 2006 to 2010, 2011 to 2013, and 2013 to 2015. Survey weighting was used in survival analysis to examine time to first pregnancy after tubal sterilization. Data from these participants were censored after a tubal reversal procedure, infertility treatment, hysterectomy, or bilateral oophorectomy. Reported pregnancy rates after tubal sterilization procedures were examined by using Kaplan-Meier curves and then multivariable Cox proportional-hazards models to examine the effects of age at tubal sterilization, race/ethnicity, education, Medicaid funding, and postpartum versus interval procedures.ResultsPregnancy after tubal sterilization was reported by 2.9 to 5.2% of participants across NSFG waves. In the most recent survey wave (2013 to 2015), the estimated percentage of participants with pregnancies within the first 12 months after a tubal sterilization procedure was 2.9%; at 120 months after tubal sterilization, the estimated percentage with a pregnancy was 8.4%. At all the time points examined, pregnancy after tubal sterilization was less common after postpartum procedures than after interval procedures; however, this difference was not evident in multivariable models. In multivariable models, chance of pregnancy decreased with age at time of tubal sterilization. Race/ethnicity, education, and Medicaid funding were not consistently associated with pregnancy after tubal sterilization.ConclusionsThese data suggest that there may be nontrivial rates of pregnancy after tubal sterilization.

We conducted a cluster-randomized hybrid effectiveness-implementation study of CyberRwanda, a digital family planning and reproductive health intervention for Rwandan adolescents. Sixty schools were randomized 1:1:1 to control or to one of two implementation models-self-service (self-guided access on tablets) or facilitated (peer-led clubs plus tablet access) with no masking. Eligible participants were aged 12-19 years, in secondary school levels 1 or 2, and willing to provide consent or assent/parental consent and contact information for follow-up. In 2021, 6,078 randomly selected adolescents were enrolled. At 24 months, 91.3% of participants were retained and included in the primary intention-to-treat analyses (control, n = 1,845; self-service, n = 1,849 and facilitated, n = 1,858). There were no adverse events related to the study. CyberRwanda did not affect the primary outcomes of modern contraceptive use (prevalence ratio (PR) = 1.04; 95% confidence interval (CI) = 0.76, 1.42), childbearing (PR = 1.33; 95% CI = 0.71, 2.50) and HIV testing (PR = 1.00; 95% CI = 0.91, 1.11) in the full sample. Significantly higher modern contraceptive use observed in the CyberRwanda facilitated arm in a prespecified analysis of sexually active participants suggests that longer-term evaluation is needed to examine effects as more of the study population becomes sexually active and has increased demand for contraception. ClinicalTrials.gov registration: NCT04198272 .

Prior research has produced mixed findings regarding whether women feel more attractive during the fertile phase of the menstrual cycle. Here, we analyzed cycle phase and hormonal predictors of women's self-perceived attractiveness (SPA) assessed within a daily diary study. Forty-three women indicated their SPA, sexual desire, and interest in their own partners or other potential mates each day across 1-2 menstrual cycles; saliva samples collected on corresponding days were assayed for estradiol, progesterone, and testosterone; and photos of the women taken at weekly intervals were rated for attractiveness. Contrary to some prior studies, we did not find a significant increase in SPA within the estimated fertile window (i.e., cycle days when conception is possible). However, within-cycle fluctuations in progesterone were significantly negatively associated with shifts in SPA, with a visible nadir in SPA in the mid-luteal phase. Women's sexual desire and SPA were positively associated, and the two variables fluctuated in very similar ways across the cycle. Third-party ratings of women's photos provided no evidence that women's SPA simply tracked actual changes in their visible attractiveness. Finally, for partnered women, changes in SPA correlated with shifts in attraction to own partners at least as strongly as it did with shifts in fantasy about extra-pair partners. Our findings provide preliminary evidence for the idea that SPA is a component of women's sexual motivation that may change in ways similar to other hormonally regulated shifts in motivational priorities. Additional large-scale studies are necessary to test replication of these preliminary findings.

IntroductionContraceptive counseling during the perinatal period is an important component of comprehensive perinatal care. We synthesized research about contraceptive counseling during the perinatal period, which has not previously been systematically compiled.MethodsWe developed search criteria to identify articles listed in PubMed, Embase, and Popline databases published between 1992 and July 2022 that address patients' preferences for, and experiences of, perinatal contraceptive counseling, as well as health outcomes associated with this counseling. Search results were independently reviewed by multiple reviewers to assess relevance for the present review. Methods were conducted in accordance with PRISMA guidelines.ResultsThirty-four articles were included in the final full text review. Of the included articles, 10 included implementation and evaluation of a contraceptive counseling method or protocol, and 24 evaluated preferences for or experiences of existing contraceptive counseling in the perinatal period. Common themes included the acceptability of contraceptive counseling in the peripartum and postpartum periods, and a preference for contraceptive counseling at some point during the antenatal period and before the inpatient hospital experience, and direct provider-patient discussion instead of video or written material. Multiple studies suggest that timing, content, and modality should be individualized. In general, avoiding actual or perceived directiveness and providing multi-modal counseling that includes both written educational materials and patient-provider conversations was desired.DiscussionThe perinatal period constitutes a critical opportunity to provide contraceptive counseling that can support pregnant and postpartum people's management of their reproductive futures. The reviewed studies highlight the importance of patient-centered approach to providing this care, including flexibility of timing, content, and modality to accommodate individual preferences.

PurposeThe aim of this study is to prospectively evaluate whether women with copper-containing intrauterine devices (Cu-IUD), currently listed as MR conditional, can safely undergo 3.0 Tesla (3 T) magnetic resonance imaging (MRI).Methods73 women, age 18-54 years old, with a Cu-IUD who were undergoing MRI for any reason were included consecutively. Pre- and post-MRI standard pelvic ultrasound examinations were completed to determine the appropriate pre- and post-MRI positioning of the Cu-IUD. Displaced IUDs were defined by IUD crossbars not in the fundal portion of the endometrial cavity, a visualized tip in the mid or lower uterus, any part of the device located in the cervical canal or outside of the endometrial canal, a fractured device, or a non-visualized IUD. Additionally, a questionnaire was completed by participants to determine the level of pre- and post-MRI pelvic pain.ResultsThere were zero observed displaced Cu-IUDs on post-MRI pelvic ultrasounds (p = 0/70, 95% CI 0, .043). Three participants were dropped from the study due to malpositioned IUDs on pre-MRI pelvic ultrasound. Six patients reported new or worsening pelvic pain/discomfort during or after their MRI examination.ConclusionOur results suggest that performing 3 T MRI using a low SAR setting does not cause displacement of Cu-IUDs, with zero out of 70 patients demonstrating IUD displacement.

ImportanceResearch on fetal epigenetic programming suggests that the intrauterine environment can have long-term effects on offspring disease susceptibility.ObjectiveTo examine the association between prenatal maternal occupation and child epigenetic age acceleration (EAA) among a farmworker community.Design, setting, and participantsThis cohort study included participants in the Center for the Health Assessment of Mothers and Children of Salinas, a prospective, Latino, prebirth cohort. Pregnant women were recruited from October 1, 1999, to October 1, 2000, from 6 community clinics in California's Salinas Valley agricultural region. Participants were 18 years or older, English or Spanish speaking, Medicaid eligible, and at 20 weeks' gestation or earlier at enrollment. Mother-child pairs who had blood DNA methylation measured at the ages of 7, 9, and 14 years were included. Data were analyzed from July 2021 to November 2023.ExposuresPrenatal maternal occupation was ascertained through study interviews conducted during prenatal visits and shortly after delivery.Main outcomes and measuresChild EAA at 7, 9, and 14 years of age was estimated using DNA methylation-based epigenetic age biomarkers. Three EAA measures were calculated: the Horvath EAA, skin and blood EAA, and intrinsic EAA. Linear mixed-effects models were used to estimate longitudinal associations of prenatal maternal occupation and child EAA, adjusting for confounders and prenatal organophosphate pesticide exposure.ResultsAnalyses included 290 mother-child pairs (mean [SD] maternal age at delivery, 26.5 [5.2] years; 152 [52.4%] female infants); 254 mothers (87.6%) were born in Mexico, 33 (11.4%) in the US, and 3 (1.0%) in other countries; and 179 families (61.7%) were below the federal poverty line during pregnancy. Mothers reported engaging in several types of work during pregnancy, including agricultural fieldwork (90 [31.0%]), other agricultural work (40 [13.8%]), nonagricultural work (53 [18.3%]), or no work (107 [36.9%]). Children whose mothers worked in agricultural fields during pregnancy had a mean of 0.66 (95% CI, 0.17-1.15) years of greater Horvath EAA, 0.62 (95% CI, 0.31-0.94) years of greater skin and blood EAA, and 0.45 (95% CI, 0.07-0.83) years of greater intrinsic EAA compared with children whose mothers did not work during pregnancy.Conclusions and relevanceIn this cohort study, prenatal maternal agricultural fieldwork was associated with accelerated childhood epigenetic aging independent of organophosphate pesticide exposure. Future research on which factors related to agricultural fieldwork accelerate aging in the next generation can inform targeted prevention programs and policies that protect children's health.

In vitro gametogenesis (IVG), the reconstitution of germ cell development in vitro, is an emerging stem cell-based technology with profound implications for reproductive science. Despite researchers' long-term goals for future clinical applications, little is currently known about the views of IVG held by the stakeholders potentially most affected by its introduction in humans. We conducted focus groups and interviews with 80 individuals with lived experience of infertility and/or LGBTQ+ family formation in the US, two intersecting groups of potential IVG users. Respondents expressed hope that IVG would lead to higher reproductive success than current assisted reproductive technology (ART), alleviate suffering associated with ART use, and promote greater social inclusion, while expressing concerns predominantly framed in terms of equity and safety. These findings underscore the importance of sustained engagement with stakeholders with relevant experience to anticipate the implications of IVG for research and clinical translation.

The prevalence and progression of cancer differ in males and females, and thus, sexual dimorphism in tumor development directly impacts clinical research and medicine. Long non-coding RNAs (lncRNAs) are increasingly recognized as important players in gene expression and various cellular processes, including cancer development and progression. In recent years, lncRNAs have been implicated in the differences observed in cancer incidence, progression, and treatment responses between men and women. Here, we present a brief overview of the current knowledge regarding the role of lncRNAs in cancer sex dimorphism, focusing on how they affect epigenetic processes in male and female mammalian cells. We discuss the potential mechanisms by which lncRNAs may contribute to sex differences in cancer, including transcriptional control of sex chromosomes, hormonal signaling pathways, and immune responses. We also propose strategies for studying lncRNA functions in cancer sex dimorphism. Furthermore, we emphasize the importance of considering sex as a biological variable in cancer research and the need to investigate the role lncRNAs play in mediating these sex differences. In summary, we highlight the emerging link between lncRNAs and cancer sex dimorphism and their potential as therapeutic targets.

The relative risk of pregnancy with the levonorgestrel 52 mg IUD is 3 times lower than with optimal combined oral contraceptive use.

Background: The Addressing Reproductive Coercion in Health Settings (ARCHES) intervention trains existing providers to address reproductive coercion (RC) and intimate partner violence (IPV) within routine family planning counseling. This study evaluated the effectiveness of a single ARCHES counseling session as adapted for use with abortion clients in Bangladesh. Methods: In this cluster-randomized controlled trial conducted between January 2019 and January 2021, health facilities with an abortion clinic with infrastructure for private counseling and onsite violence support services were eligible. Six facilities in Bangladesh met inclusion criteria, and matched pairs randomization with parallel assignment and a 1:1 allocation ratio was used to randomize three facilities to ARCHES and three facilities to control, which implemented standard counseling. Blinding was not possible as providers in intervention facilities participated in a three-day ARCHES training. Participants were abortion clients aged 18–49 years who could provide safe recontact information and be interviewed privately. The primary outcome was past three-month modern contraceptive use without interruption or interference. The trial was registered on clinicaltrials.gov (NCT03539315) on 29 May 2018. Findings: A total of 1492 intervention participants and 1237 control participants were enrolled. Available data were analyzed at each follow-up period: 1331 intervention and 1069 control participants at the three-month follow-up, and 1269 intervention and 1050 control participants at the twelve-month follow-up. ARCHES was associated with higher likelihood of modern contraceptive use at the three-month follow-up (adjusted RR = 1.08, 95% CI: 1.06–1.10) and the twelve-month follow-up (adjusted RR = 1.06, 95% CI: 1.02–1.10). ARCHES was also associated with decreased incident pregnancy, decreased IPV, and increased knowledge of IPV support services. Interpretation: The ARCHES intervention is effective in increasing post-abortion modern contraceptive use and decreasing incident pregnancy and IPV among abortion clients in Bangladesh. Implementation of ARCHES should be considered in facilities with sufficient privacy for counseling. Funding: Society of Family Planning (#SFPRF11-07) and Ipas.

ObjectiveHIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD.Design/methodsA nested 1 : 1 case-control study ( N  = 362) was conducted within a multicountry randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (

BackgroundChildhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks.ObjectiveThis population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring.MethodsData on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers.ResultsOffspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth.ConclusionsIn this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

IntroductionAdverse sexual and reproductive health (SRH) outcomes, such as unplanned pregnancies and HIV infection, disproportionately affect adolescent girls and young women (AGYW; aged 15-24 years) in east Africa. Increasing uptake of preventive SRH services via innovative, youth-centred interventions is imperative to addressing disparities in SRH outcomes.Methods and analysisFrom 2018 to 2019, we used human-centred design to co-develop a theoretically driven HIV and pregnancy prevention intervention for AGYW at private drug shops called Accredited Drug Dispensing Outlets (ADDOs) in Tanzania. The result, Malkia Klabu (Queen Club), was a customer loyalty programme designed to strengthen ADDOs' role as SRH providers while encouraging uptake of critical SRH prevention products among AGYW. Malkia Klabu members had access to free contraceptives and oral HIV self-test (HIVST) kits and earned punches on a loyalty card for other shop purchases; punches were redeemable for small prizes. Our pilot among 40 shops showed that intervention ADDOs had higher AGYW patronage and distributed more HIVST kits and contraceptives to AGYW relative to business-as-usual (ie, client purchasing) comparison shops. We will conduct a cluster-randomised controlled trial (c-RCT) among 120-140 ADDOs in 40 health catchment areas in Shinyanga and Mwanza Regions (Lake Zone), Tanzania. ADDO shop recruitment includes a 1-month run-in with a tablet-based electronic inventory management system for tracking shop transactions, followed by enrolment, randomisation and a 24-month trial period. Our c-RCT evaluating the human-centred design-derived intervention will assess population impact on the primary outcomes of HIV diagnoses and antenatal care registrations, measured with routine health facility data. We will also assess secondary outcomes focusing on mechanisms of action, evaluate programme exposure and AGYW behaviour change in interviews with AGYW, and assess shop-level implementation strategies and fidelity.Ethics and disseminationEthical approval was granted from both the University of California, San Francisco and the Tanzanian National Institute for Medical Research. Study progress and final outcomes will be posted annually to the National Clinical Trials website; study dissemination will occur at conferences, peer-reviewed manuscripts and local convenings of stakeholders.Trial registration numberNCT05357144.

BackgroundMaternal cigarette smoking during pregnancy (MSDP) is associated with numerous adverse health outcomes in infants and children with potential lifelong consequences. Negative effects of MSDP on placental DNA methylation (DNAm), placental structure, and function are well established.ObjectiveOur aim was to develop biomarkers of MSDP using DNAm measured in placentas (N=96), collected as part of the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function double-blind, placebo-controlled randomized clinical trial conducted between 2012 and 2016. We also aimed to develop a digital polymerase chain reaction (PCR) assay for the top ranking cytosine-guanine dinucleotide (CpG) so that large numbers of samples can be screened for exposure at low cost.MethodsWe compared the ability of four machine learning methods [logistic least absolute shrinkage and selection operator (LASSO) regression, logistic elastic net regression, random forest, and gradient boosting machine] to classify MSDP based on placental DNAm signatures. We developed separate models using the complete EPIC array dataset and on the subset of probes also found on the 450K array so that models exist for both platforms. For comparison, we developed a model using CpGs previously associated with MSDP in placenta. For each final model, we used model coefficients and normalized beta values to calculate placental smoking index (PSI) scores for each sample. Final models were validated in two external datasets: the Extremely Low Gestational Age Newborn observational study, N=426; and the Rhode Island Children's Health Study, N=237.ResultsLogistic LASSO regression demonstrated the highest performance in cross-validation testing with the lowest number of input CpGs. Accuracy was greatest in external datasets when using models developed for the same platform. PSI scores in smokers only (n=72) were moderately correlated with maternal plasma cotinine levels. One CpG (cg27402634), with the largest coefficient in two models, was measured accurately by digital PCR compared with measurement by EPIC array (R2=0.98).DiscussionTo our knowledge, we have developed the first placental DNAm-based biomarkers of MSDP with broad utility to studies of prenatal disease origins. https://doi.org/10.1289/EHP13838.

Neonatal seizures are common among patients with acute brain injury or critical illness and can be difficult to diagnose and treat. The most common etiology of neonatal seizures is hypoxic-ischemic encephalopathy, with other common causes including ischemic stroke and intracranial hemorrhage. Neonatal clinicians can use a standardized approach to patients with suspected or confirmed neonatal seizures that entails laboratory testing, neuromonitoring, and brain imaging. The primary goals of management of neonatal seizures are to identify the underlying cause, correct it if possible, and prevent further brain injury. This article reviews recent evidence-based guidelines for the treatment of neonatal seizures and discusses the long-term outcomes of patients with neonatal seizures.

BackgroundAutoimmune diseases have been linked to an increased risk of pregnancy-related complications. A family history of autoimmune diseases may be related to the risk of childhood cancer based on similar histocompatibility antigens. We utilized data from national registries in Denmark to examine associations between maternal autoimmune disease and cancer in their offspring.MethodsWe linked data from several national registries in Denmark to identify childhood cancer cases in children

BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer.MethodsThe present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy.Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74).ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

In South Africa, alcohol use during pregnancy is prevalent and associated with increased HIV risk. Developing locally sensitive and contextually appropriate evidence-based interventions to address alcohol use among pregnant and breastfeeding women in South Africa requires comprehensive understanding of the context of perinatal alcohol use and how relationships and lived environments may serve as barriers or supports for alcohol reduction. We conducted twenty in-depth qualitative interviews with isiXhosa speaking women who reported alcohol use during their recent pregnancy and/or recent intimate partner violence in Cape Town, South Africa between September and November 2022. We describe patterns and drivers of ongoing alcohol use during pregnancy and map them onto levels of the socioecological model. Data were analyzed utilizing the interpretivist paradigm and interpretive thematic analysis. Eight women reported alcohol use during pregnancy, sixteen reported experiencing recent IPV, and four women reported both alcohol use during pregnancy and recent IPV. In interviews, commonly cited reasons for continued alcohol use in pregnancy included stress (e.g., due to financial concerns), peer pressure, the central role of alcohol use in socialization and the persistence of misconceptions regarding the safety of alcohol use in pregnancy. Still, despite women reporting social norms that supported continued alcohol use in pregnancy, many altered who they drank with due to fear of judgement from close friends and family, leaving them isolated from their social support system. Interventions aimed at increasing interpersonal support, such as the use of peer mentors, could prove beneficial. Although the clinic provides messaging around the harms of alcohol use in pregnancy, these messages conflict with messaging received from their peers, limiting their impact on behavior. Locally sensitive tailored, relevant programming that intervenes on barriers to reducing alcohol use in pregnancy at multiple levels of the socioeconomic model are vital to effectively addressing this public health issue.

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.

Pregnancy is a period of profound hormonal and physiological change experienced by millions of women annually, yet the neural changes unfolding in the maternal brain throughout gestation have not been studied in humans. Leveraging precision imaging, we mapped neuroanatomical changes in an individual from preconception through two years postpartum. Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, which stand in contrast to increases in white matter microstructural integrity, ventricle volume, and cerebrospinal fluid, with few regions untouched by the transition to motherhood. This dataset serves as the first comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to stimulate further exploration and discovery.

ObjectiveWe 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 designData 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.ResultsSymptoms 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.ConclusionIn 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..

BackgroundLabor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns.MethodsIn this prospective cohort study, parturients aged 25-35 years with a gestational age of 37-42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models.ResultsWe showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and β-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (β = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (β = -449.36, adjusted P = 0.015), P. aeruginosa (β = -192.55, adjusted P = 0.008), or S. maltophilia (β = -142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (β = -2702.77, adjusted P = 0.003) in neonates.ConclusionLEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.

BackgroundPregnant and postpartum women in Sub-Saharan Africa are at high risk of HIV acquisition. We evaluated a person-centered dynamic choice intervention for HIV prevention (DCP) among women attending antenatal and postnatal care.SettingRural Kenya and Uganda.MethodsWomen (aged 15 years or older) at risk of HIV acquisition seen at antenatal and postnatal care clinics were individually randomized to DCP vs. standard of care (SEARCH; NCT04810650). The DCP intervention included structured client choice of product (daily oral pre-exposure prophylaxis or postexposure prophylaxis), service location (clinic or out of facility), and HIV testing modality (self-test or provider-administered), with option to switch over time and person-centered care (phone access to clinician, structured barrier assessment and counseling, and provider training). The primary outcome was biomedical prevention coverage-proportion of 48-week follow-up with self-reported pre-exposure prophylaxis or postexposure prophylaxis use, compared between arms using targeted maximum likelihood estimation.ResultsBetween April and July 2021, we enrolled 400 women (203 intervention and 197 control); 38% were pregnant, 52% were aged 15-24 years, and 94% reported no pre-exposure prophylaxis or postexposure prophylaxis use for ≥6 months before baseline. Among 384/400 participants (96%) with outcome ascertained, DCP increased biomedical prevention coverage 40% (95% CI: 34% to 47%; P < 0.001); the coverage was 70% in intervention vs. 29% in control. DCP also increased coverage during months at risk of HIV (81% in intervention, 43% in control; 38% absolute increase; 95% CI: 31% to 45%; P < 0.001).ConclusionA person-centered dynamic choice intervention that provided flexibility in product, testing, and service location more than doubled biomedical HIV prevention coverage in a high-risk population already routinely offered access to biomedical prevention options.

IntroductionPostpartum health is in crisis in the United States, with rising pregnancy-related mortality and worsening racial inequities. The World Health Organization recommends four postpartum visits during the 6 weeks after childbirth, yet standard postpartum care in the United States is generally one visit 6 weeks after birth. We present community midwifery postpartum care in the United States as a model concordant with World Health Organization guidelines, describing this model of care and its potential to improve postpartum health for birthing people and babies.MethodsWe conducted semi-structured interviews with 34 community midwives providing care in birth centers and home settings in Oregon and California. A multidisciplinary team analyzed data using reflexive thematic analysis.ResultsA total of 24 participants were Certified Professional Midwives; 10 were certified nurse-midwives. A total of 14 midwives identified as people of color. Most spoke multiple languages. We describe six key elements of the community midwifery model of postpartum care: (1) multiple visits, including home visits; typically five to eight over six weeks postpartum; (2) care for the parent-infant dyad; (3) continuity of personalized care; (4) relationship-centered care; (5) planning and preparation for postpartum; and (6) focus on postpartum rest.ConclusionThe community midwifery model of postpartum care is a guideline-concordant approach to caring for the parent-infant dyad and may address rising pregnancy-related morbidity and mortality in the United States.

Data from Bering-Chukchi-Beaufort Seas bowhead whales (Balaena mysticetus), harvested during 1973–2021 by aboriginal subsistence hunters, were used to estimate reproductive parameters: length at sexual maturity (LSM), age at sexual maturity (ASM), pregnancy rate (PR), and calving interval. Sexual maturity (N = 187 females) was determined from the presence/absence of corpora in the ovaries, or a fetus. Using sampling bias-corrected logistic regression, LSM was estimated at 13.5 m, 95% CI [13.0, 13.8]. There was a downward trend in LSM over time, statistically significant with one method but marginal with another. A growth model translated this estimate to an ASM estimate of 23.5 years, 95% CI [20.4, 26.7]. Pregnancy rate was determined from mature females (N = 125), and from a subset limited to certain autumn-caught whales (n = 37) to reduce bias. The PR was estimated at 0.46 globally, 95% CI [0.36, 0.55] and 0.38 for the autumn sample, 95% CI [0.20, 0.51]. Both estimated PRs are consistent with a 3-year calving interval, because the larger estimate includes two cohorts of pregnant whales harvested in spring, and bowhead whale gestation is longer than 12 months. These analyses represent the most conclusive empirical estimates of ASM, LSM, and PR for this bowhead whale stock from the largest available data sets to date.

IntroductionIn South Asia, younger women have high rates of unmet need for family planning and low empowerment. Life skills interventions can equip young women with agency, but the effectiveness of these interventions in reproductive and sexual autonomy and contraception has not been examined.Methods and analysisA two-arm, parallel, cluster randomised controlled trial will evaluate the impact of TARANG (Transforming Actions for Reaching and Nurturing Gender Equity and Empowerment), a life skills and reproductive health empowerment group-based intervention for newly married women, compared with usual services in the community in rural and tribal Rajasthan, India. TARANG will also provide light-touch sessions to husbands and mothers-in-law of newly married women. We will test the impact of TARANG in 80 village clusters among 800 eligible households comprising newly married women aged 18-25 years who are at risk of pregnancy but do not want a pregnancy within 1 year at the time of enrolment, their husbands and mothers-in-law who consent to participate. Women in the intervention villages will receive 14 sessions over a 6-month period, while husbands and mothers-in-law will receive 1 and 4 sessions (respectively) each. Three rounds of surveys will be collected over 18 months. Control villages will receive the intervention after the endline surveys. Primary outcomes include rate of unintended pregnancy and modern contraceptive use. We plan to start recruitment of participants and data collection in April 2024. We will estimate unadjusted and adjusted intention-to-treat effects using survival analysis and mixed models.Ethics and disseminationStudy protocols have been reviewed and approved by the human subjects review boards at the University of California, San Francisco, and the Centre for Media Studies, India (IRB00006230) and ACE Independent Ethics Committee, Bangalore (NET0062022). Results will be disseminated in international peer-reviewed journals and conferences, to stakeholders including local government and non-governmental organisations, and directly to the communities and individuals that participated in the intervention.Trial registration numberNCT06024616.

ObjectivesTo explore the relevance of pregnancy intention as a screen for contraceptive needs among postpartum individuals.Study designWe surveyed 234 postpartum individuals to assess the alignment between pregnancy intentions in the next year and current desire to prevent pregnancy.ResultsMost individuals (87%) desired pregnancy prevention now, including 73% of individuals who desired or were ambivalent about pregnancy in the next year.ConclusionA majority of individuals considering pregnancy in the next year desired pregnancy prevention now. Directly assessing current desire to prevent pregnancy may be more specific for contraceptive needs in postpartum individuals.ImplicationsOur ability to ensure that all individuals who want to prevent pregnancy have access to contraception depends on the use of effective screening questions. These findings prompt consideration of broader clinical implementation of screening for desire to prevent pregnancy in lieu of questions about pregnancy intention in the next year.

ObjectiveThe vast majority of the 300 000 pregnancy-related deaths every year occur in South Asia and sub-Saharan Africa. Increased access to quality antepartum and intrapartum care can reduce pregnancy-related morbidity and mortality worldwide. We used a population-based cross-sectional cohort design to: (1) examine the sociodemographic risk factors and structural barriers associated with pregnancy care-seeking and institutional delivery, and (2) investigate the influence of residential distance to the nearest primary health facility in a rural population in Mali.MethodsA baseline household survey of Malian women aged 15-49 years was conducted between December 2016 and January 2017, and those who delivereda baby in the 5 years preceding the survey were included. This study leverages the baseline survey data from a cluster-randomised controlled trial to conduct a secondary analysis. The outcomes were percentage of women who received any antenatal care (ANC) and institutional delivery; total number of ANC visits; four or more ANC visits; first ANC visit in the first trimester.ResultsOf the 8575 women in the study, two-thirds received any ANC in their last pregnancy, one in 10 had four or more ANC visits and among those that received any ANC, about one-quarter received it in the first trimester. For every kilometre increase in distance to the nearest facility, the likelihood of the outcomes reduced by 5 percentage points (0.95; 95% CI 0.91 to 0.98) for any ANC; 4 percentage points (0.96; 95% CI 0.94 to 0.98) for an additional ANC visit; 10 percentage points (0.90; 95% CI 0.86 to 0.95) for four or more ANC visits; 6 percentage points (0.94; 95% CI 0.94 to 0.98) for first ANC in the first trimester. In addition, there was a 35 percentage points (0.65; 95% CI 0.56 to 0.76) decrease in likelihood of institutional delivery if the residence was within 6.5 km to the nearest facility, beyond which there was no association with the place of delivery. We also found evidence of increase in likelihood of receiving any ANC care and its intensity increased with having some education or owning a business.ConclusionThe findings suggest that education, occupation and distance are important determinants of pregnancy and delivery care in a rural Malian context.Trial registration numberNCT02694055.

ObjectiveEvaluate reduction in progressively motile sperm per high power field (HPF) in midcycle cervical mucus after intercourse with Ovaprene: an investigational monthly non-hormonal vaginal contraceptive consisting of a vaginal ring and mechanical barrier, releasing spermiostatic ferrous gluconate.Study designOpen-label, multicenter study enrolling heterosexually-active women with previous permanent contraception. Participants underwent a baseline postcoital test cycle with no device to confirm the presence of sperm, followed by one diaphragm postcoital test cycle, one Ovaprene safety cycle, and two Ovaprene postcoital test cycles. In each postcoital test cycle, participants underwent a midcycle cervical mucus evaluation to confirm an Insler score ≥10 and absence of sperm, and then returned two to four hours after vaginal intercourse for repeat cervical mucus evaluation. We considered

Background: Scabies infections of the breast in lactating individuals are not well described, especially how maternal infection can impact human milk feeding of hospitalized infants in the intensive care setting. Methods: This case report presents a critically ill female infant with a complex surgical history whose mother had an active scabies infection around the breast postpartum and wished to provide expressed human milk. Results: In this case report, human milk was recommended despite maternal scabies infection. Conclusion: Given the limited information that is known about the risk of scabies transmission in human milk for critically ill infants, this case adds to the knowledge base and supports the call for further research.

From 1965-2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary syndrome (PCOS). The author reviews the critical discoveries of this era from his perspective investigating these disorders, commencing with his early discoveries of the unique pattern of plasma androgens in premature adrenarche and the elevation of an index of the plasma free testosterone concentration in most hirsute women. The molecular genetic basis, though not the developmental biologic basis, for adrenarche is now known and 11-oxytestosterones shown to be major bioactive adrenal androgens. The evolution of the lines of research into the pathogenesis of PCOS is historically traced: research milestones are cited in the areas of neuroendocrinology; insulin resistance, hyperinsulinism, type 2 diabetes mellitus; folliculogenesis; androgen secretion; obesity; phenotyping, prenatal androgenization, epigenetics, and complex genetics. Large scale genome-wide association studies led to the 2014 discovery of an unsuspected steroidogenic regulator DENND1A (differentially expressed in normal and neoplastic development). The splice variant DENND1A.V2 is constitutively overexpressed in PCOS theca cells in long-term culture and accounts for their PCOS-like phenotype. The genetics are complex, however: DENND1A intronic variant copy number is related to phenotype severity, and recent data indicates that rare variants in a DENND1A regulatory network and other genes are related to PCOS. Obesity exacerbates PCOS manifestations via insulin resistance and pro-inflammatory cytokine excess; excess adipose tissue also forms testosterone. Polycystic ovaries in one-quarter of apparently normal women lie on the PCOS functional spectrum. Much remains to be learned.

PurposeTo determine whether a diagnosis of a perinatal mood and anxiety disorder (PMAD) is associated with adverse perinatal outcomes.MethodsMental health symptom screening and diagnostic data from 82 women with single gestation in the Healthy Babies Before Birth study conducted from 2013 to 2018 were obtained by clinic interview. If a woman scored over 10 on the Patient Health Questionnaire (PHQ-9) or endorsed the suicidality item; or scored over 7 on the Overall Anxiety Severity and Impairment Scale (OASIS), a Structured Clinical Interview for DSM-IV (SCID) Axis I Disorders was administered. An adverse perinatal outcome was operationalized as a diagnosis of gestational diabetes mellitus, intrauterine growth restriction, preeclampsia, chorioamnionitis, hemorrhage, fetal death, preterm birth, or a low birthweight baby, and abstracted from the medical records.ResultsWomen were between 22.0 and 45.0 years old (Mean age = 33.1 ± 4.3). Mean BMI was 24.7 ± 5.6 (Range 16.8 to 47.1). Nineteen percent (16) of the 82 women had a SCID diagnosis of a PMAD. Thirty-seven percent (30) had a diagnosed adverse perinatal outcome. Multiple logistic regression was conducted with these predictors: SCID diagnosis of a PMAD, maternal age, BMI. All predictors were significant with respective odds ratios as follows: OR = 3.58, 95% CI 1.03-12.44, p = .045; OR = 2.30, 95% CI 1.21-4.38, p = .011; OR = 1.69, 95% CI 1.06-2.69, p = .027.ConclusionsA PMAD diagnosis was associated with 3.5 times higher odds of having an adverse perinatal outcome. For every 5 years a woman aged or every five units her BMI increased her odds of having an adverse perinatal outcome increased. Older age and increased BMI are well established adverse perinatal outcome risk factors. These results suggest that mental illness risk should also be consistently assessed in obstetric settings.

BackgroundInfants with hypoxic-ischemic encephalopathy are often treated with therapeutic hypothermia and high-frequency ventilation. Fluctuations in PaCO2 during therapeutic hypothermia are associated with poor neurodevelopmental outcomes. Transcutaneous CO2 monitors offer a noninvasive estimate of PaCO2 represented by transcutaneously measured partial pressure of carbon dioxide (PtcCO2 ). We aimed to assess the precision between PtcCO2 and PaCO2 values in neonates undergoing therapeutic hypothermia.MethodsThis was a retrospective chart review of 10 neonates who underwent therapeutic hypothermia requiring respiratory support over 2 y. A range of 2-27 simultaneous PtcCO2 and PaCO2 pairs of measurements per neonate were analyzed via linear mixed models and a Bland-Altman plot for multiple observations per neonate.ResultsA linear mixed-effect model demonstrated that PtcCO2 and PaCO2 (controlling for sex) were similar. The 95% CI of the mean difference ranged from -2.3 to 5.7 mm Hg (P = .41). However, precision was poor as the PtcCO2 ranged from > 18 mm Hg to < 13 mm Hg than PaCO2 values for 95% of observations.ConclusionsThe neonates' PtcCO2 was as much as 18 mm Hg higher to 13 mm Hg lower than the PaCO2 95% of the time. Transcutaneous CO2 monitoring may not be a good trending tool, nor is it appropriate for estimating PaCO2 in patients undergoing therapeutic hypothermia.

ObjectivePregnant and postpartum women (PPW) in Southern Africa are at increased risk of acquiring HIV and curable sexually transmitted infections (STIs). Oral pre-exposure prophylaxis (PrEP) is safe and effective to use during pregnancy to reduce HIV acquisition and vertical transmission. Point-of-care (POC) STI testing can identify PPW at risk of HIV and facilitate risk-differentiated and person-centred counselling to improve PrEP initiation, persistence and adherence. We evaluated the impact of POC STI testing compared with STI syndromic management on PrEP outcomes among PPW in Cape Town, South Africa.MethodsThe STI and PrEP in Pregnancy Study enrolled PPW without HIV and ≤34 weeks pregnant at their regular antenatal care visit with follow-up after 1 month. PPW were randomised to receive POC STI testing or STI syndromic management. PPW randomised to POC STI testing self-collected vaginal swabs for Chlamydia trachomatis, Neisseria gonorhoeae and Trichomonas vaginalis (Cepheid GeneXpert) testing and were offered same-day treatment if diagnosed. We compared PrEP initiation at baseline, PrEP prescription refill at 1 month (persistence) and adherence through tenofovir-diphosphate detection in dried blood spots by randomisation arm. In a secondary analysis, we evaluated the association between an STI diagnosis (positive STI test or reporting STI symptoms) with PrEP outcomes.ResultsWe enrolled and randomised 268 pregnant women. Twenty-eight per cent of women were diagnosed with ≥1 STI. Overall, 65% of women initiated and 79% persisted on PrEP with no significant differences by randomisation arm. Secondary analysis demonstrated that an STI diagnosis (positive STI test or reporting STI symptoms) was associated with higher PrEP initiation (adjusted relative risk=1.28; 95% CI 1.08 to 1.52), controlling for arm, maternal and gestational age.ConclusionsPOC STI testing was not associated with PrEP initiation or persistence relative to syndromic management. However, improving STI diagnosis by supplementing syndromic management with POC STI testing could improve PrEP initiation among PPW.Trial registration numberNCT03902418; Clinical Trials.gov; 1 April 2019.

IntroductionReproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.MethodsParticipants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).ResultsYounger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.DiscussionSeveral aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to

IntroductionTo describe and compare intervention rates and experiences of respectful care when Hungarian women opt to give birth in the community.MethodsWe conducted a cross-sectional online survey (N = 1257) in 2014. We calculated descriptive statistics comparing obstetric procedure rates, respectful care indicators, and autonomy (MADM scale) across four models of care (public insurance; chosen doctor or chosen midwife in the public system; private midwife-led community birth). We used an intention-to-treat approach. After adjusting for social and clinical covariates, we used logistic regression to estimate the odds of obstetric procedures and disrespectful care and linear regression to estimate the level of autonomy (MADM scale).FindingsIn the sample, 99 (7.8%) saw a community midwife for prenatal care. Those who planned community births had the lowest rates of cesarean at 9.1% (public: 30.4%; chosen doctor: 45.2%; chosen midwife 16.5%), induced labor at 7.1% (public: 23.1%; chosen doctor: 26.0%; chosen midwife: 19.4%), and episiotomy at 4.44% (public: 62.3%; chosen doctor: 66.2%; chosen midwife: 44.9%). Community birth clients reported the lowest rates of disrespectful care at 25.5% (public: 64.3%; chosen doctor: 44.3%; chosen midwife: 38.7%) and the highest average MADM score at 31.5 (public: 21.2; chosen doctor: 25.5; chosen midwife: 28.6). In regression analysis, community midwifery clients had significantly reduced odds of cesarean (0.35, 95% CI 0.16-0.79), induced labor (0.27, 95% CI 0.11-0.67), episiotomy (0.04, 95% CI 0.01-0.12), and disrespectful care (0.36, 95% CI 0.21-0.61), while also having significantly higher average MADM scores (5.71, 95% CI 4.08-7.36).ConclusionsHungarian women who plan to give birth in the community have low obstetric procedure rates and report greater respect, in line with international data on the effects of place of birth and model of care on experiences of perinatal care.

Adverse pregnancy outcomes are common among pregnant individuals and are associated with long-term risk of cardiovascular disease. Individuals with adverse pregnancy outcomes also have an increased incidence of cardiovascular disease risk factors after delivery. Despite this, evidence-based approaches to managing these patients after pregnancy to reduce cardiovascular disease risk are lacking. In this scientific statement, we review the current evidence on interpregnancy and postpartum preventive strategies, blood pressure management, and lifestyle interventions for optimizing cardiovascular disease using the American Heart Association Life's Essential 8 framework. Clinical, health system, and community-level interventions can be used to engage postpartum individuals and to reach populations who experience the highest burden of adverse pregnancy outcomes and cardiovascular disease. Future trials are needed to improve screening of subclinical cardiovascular disease in individuals with a history of adverse pregnancy outcomes, before the onset of symptomatic disease. Interventions in the fourth trimester, defined as the 12 weeks after delivery, have great potential to improve cardiovascular health across the life course.

Mollusc and crustacean consumption in the first 1000 d may improve maternal and child health by providing essential nutrients. However, in some contexts, molluscs and crustaceans have been associated with allergies and environmental contamination, potentially leading to adverse health and development outcomes. It is unclear whether the health benefits of consuming molluscs and crustaceans, collectively classified as shellfish in nutrition, are outweighed by the potential risks to pregnant women and children. We conducted a scoping review (PROSPERO: CRD42022320454) in PubMed, Scopus and EBSCO Global Health of articles published between January 2000 and March 2022 that assessed shellfish consumption during pregnancy, lactation or childhood (0-2 years) in relation to maternal health, child health or child development. A total of forty-six articles were included in this review. Overall, shellfish consumption was associated with higher biomarkers of environmental contaminants, with mercury being the most studied and having the strongest evidence base. The limited research on nutritional biomarker status shows an association between shellfish consumption and iodine status. Preterm birth was not associated with shellfish consumption, but newborn anthropometry showed mixed results, with several studies reporting lower birth weight with higher shellfish consumption. The few studies that examined child development and maternal health outcomes reported no significant associations. This review revealed trade-off health risks and benefits with inclusion of molluscs and crustaceans in the dietary patterns of mothers and young children. More research is needed to understand how these aquatic animal-source foods may be safely consumed and leveraged for improving human nutrition.

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

PurposeMiscarriage, often resulting from a variety of genetic factors, is a common pregnancy outcome. Preconception genetic carrier screening (PGCS) identifies at-risk partners for newborn genetic disorders; however, PGCS panels currently lack miscarriage-related genes. In this study, we evaluated the potential impact of both known and candidate genes on prenatal lethality and the effectiveness of PGCS in diverse populations.MethodsWe analyzed 125,748 human exome sequences and mouse and human gene function databases. Our goals were to identify genes crucial for human fetal survival (lethal genes), to find variants not present in a homozygous state in healthy humans, and to estimate carrier rates of known and candidate lethal genes in various populations and ethnic groups.ResultsThis study identified 138 genes in which heterozygous lethal variants are present in the general population with a frequency of 0.5% or greater. Screening for these 138 genes could identify 4.6% (in the Finnish population) to 39.8% (in the East Asian population) of couples at risk of miscarriage. This explains the cause of pregnancy loss in approximately 1.1-10% of cases affected by biallelic lethal variants.ConclusionThis study has identified a set of genes and variants potentially associated with lethality across different ethnic backgrounds. The variation of these genes across ethnic groups underscores the need for a comprehensive, pan-ethnic PGCS panel that includes genes related to miscarriage.

IntroductionWe assessed awareness of the maternal health benefits of lactation among a sample of nulliparous pregnant individuals in the United States, identified variables associated with awareness of these benefits, and examined whether awareness of these benefits impacts breastfeeding attitudes or intentions.MethodsWe administered a web-based survey to nulliparous U.S.-born individuals carrying a singleton gestation of at least 28 weeks. We assessed awareness of the maternal health benefits of lactation using 10 items to create a summative score. We examined variation in awareness of these benefits by demographic characteristics, health insurance, and personal or family health history and used multivariable models to estimate associations between awareness of the maternal health benefits of lactation and breastfeeding intentions.ResultsOf the 675 individuals invited to complete surveys, 451 (67%) responded. Only 50% were aware that breastfeeding lowers maternal risk of breast cancer; fewer were aware that breastfeeding lowers the risk of ovarian cancer (35%), diabetes (27%), and hypertension and heart disease (26%). Awareness of the maternal benefits of lactation did not vary by age or race/ethnicity. However, significant regional variation was noted. In multivariable models, scores of awareness of the maternal health benefits of breastfeeding were significantly associated with intentions to breastfeed for at least 12 months (adjusted odds ratio, 1.23; 95% confidence interval, 1.11, 1.37).ConclusionsEfforts to increase awareness of the maternal health benefits of lactation are still needed. Increasing awareness of the maternal health benefits of lactation may strengthen intentions to breastfeed as recommended.