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Aflatoxin exposure has been implicated in adverse human health outcomes in areas where the toxin is prevalent in foods [1]. Consequently, many people may be chronically exposed to large amounts [...]

Background Antenatal care (ANC) is an essential platform to improve maternal and newborn health (MNH). While several articles have described the content of ANC in low- and middle-income countries (LMICs), few have investigated the quality of detection and management of pregnancy risk factors during ANC. It remains unclear whether women with pregnancy risk factors receive targeted management and additional ANC. Methods and findings This observational study uses baseline data from the MNH eCohort study conducted in 8 sites in Ethiopia, India, Kenya, and South Africa from April 2023 to January 2024. A total of 4,068 pregnant women seeking ANC for the first time in their pregnancy were surveyed. We built country-specific ANC completeness indices that measured provision of 16 to 22 recommended clinical actions in 5 domains: physical examinations, diagnostic tests, history taking and screening, counselling, and treatment and prevention. We investigated whether women with pregnancy risks tended to receive higher quality care and we assessed the quality of detection and management of 7 concurrent illnesses and pregnancy risk factors (anemia, undernutrition, obesity, chronic illnesses, depression, prior obstetric complications, and danger signs). ANC completeness ranged from 43% in Ethiopia, 66% in Kenya, 73% in India, and 76% in South Africa, with large gaps in history taking, screening, and counselling. Most women in Ethiopia, Kenya, and South Africa initiated ANC in second or third trimesters. We used country-specific multivariable mixed-effects linear regression models to investigate factors associated with ANC completeness. Models included individual demographics, health status, presence of risk factors, health facility characteristics, and fixed effects for the study site. We found that some facility characteristics (staffing, patient volume, structural readiness) were associated with variation in ANC completeness. In contrast, pregnancy risk factors were only associated with a 1.7 percentage points increase in ANC completeness (95% confidence interval 0.3, 3.0, p-value 0.014) in Kenya only. Poor self-reported health was associated with higher ANC completeness in India and South Africa and with lower ANC completeness in Ethiopia. Some concurrent illnesses and risk factors were overlooked during the ANC visit. Between 0% and 6% of undernourished women were prescribed food supplementation and only 1% to 3% of women with depression were referred to a mental health provider or prescribed antidepressants. Only 36% to 73% of women who had previously experienced an obstetric complication (a miscarriage, preterm birth, stillbirth, or newborn death) discussed their obstetric history with the provider during the first ANC visit. Although we aimed to validate self-reported information on health status and content of care with data from health cards, our findings may be affected by recall or other information biases. Conclusions In this study, we observed gaps in adherence to ANC standards, particularly for women in need of specialized management. Strategies to maximize the potential health benefits of ANC should target women at risk of poor pregnancy outcomes and improve early initiation of ANC in the first trimester., Author(s): Catherine Arsenault 1,*, Nompumelelo Gloria Mfeka-Nkabinde 2, Monica Chaudhry 3, Prashant Jarhyan 3, Tefera Taddele 4, Irene Mugenya 5, Shalom Sabwa 6, Katherine Wright 6, Beatrice Amboko 5, Laura [...]

Background Following a decline in perinatal HIV transmission from 20% to 10% between 2010 and 2017 in Kenya, rates have since plateaued with an estimated 8% transmission rate in 2021. Between October 2016 and September 2021, Family AIDS Care & Education Services (FACES) supported HIV care and treatment services across 61 facilities in Kisumu County, Kenya with an emphasis on service strengthening for pregnant and postpartum women living with HIV to reduce perinatal HIV transmission. This included rigorous implementation of national HIV guidelines and implementation of 3 locally adapted evidence-based interventions targeted to the unique needs of women and their infants. We examined whether these person-centered program enhancements were associated with changes in perinatal HIV transmission at FACES-supported sites over time. Methods and findings We conducted a repeated cross-sectional study of annually aggregated routinely collected documentation of perinatal HIV transmission risk through the end of breastfeeding at FACES-supported facilities between October 2016 and September 2021. Data included 12,599 women living with HIV with baseline antenatal care metrics, and, a separate data set of 11,879 mother-infant pairs who were followed from birth through the end of breastfeeding (overlapping with those in antenatal care 2 years prior). FACES implemented 3 interventions for pregnant and postpartum women living with HIV in 2019: (1) high-risk clinics; (2) case management; and (3) a mobile app to support treatment engagement. Our primary outcome was infant HIV acquisition by the end of breastfeeding (18 to 24 months). We compared infant HIV acquisition risk in the final year of the FACES program (2021) to the year before intervention scale-up and following implementation of the 'Treat All' policy (2018). Mother-infant pair loss to follow-up was a secondary outcome. Program data were aggregated by year and site, thus in multivariable regression, we adjusted for site-level characteristics, including facility type, urban versus rural, number of women with HIV in antenatal care each year, and the proportion among them under 25 years of age. Between October 2016 and September 2021, 81,172 pregnant women received HIV testing at the initiation of antenatal care, among whom 12,599 (15.5%) were living with HIV, with little variation in HIV prevalence over time. The risk of infant HIV acquisition by 24 months of age declined from 4.9% (101/2,072) in 2018 to 2.2% (48/2,156) in 2021 (adjusted risk difference -2.6% [95% confidence interval (CI): -3.7, -1.6]; p < 0.001). Loss to follow-up declined from 9.9% (253/2,556) in 2018 to 2.5% (59/2,393) in 2021 (risk difference -7.5% [95% CI: -8.8, -6.2]; p < 0.001). During the same period, UNAIDS estimated rates of perinatal transmission in the broader Nyanza region and in Kenya as a whole did not decline. The main limitation of this study is that we lacked a comparable control group. Conclusions These findings suggest that implementation of person-centered interventions was associated with significant declines in perinatal HIV transmission and loss to follow-up of pregnant and postpartum women., Author(s): Francesca Odhiambo 1,*, Raphael Onyango 1, Edwin Mulwa 1, Maurice Aluda 1, Linda Otieno 1, Elizabeth A. Bukusi 1,2, Craig R. Cohen 2,3,4, Pamela M. Murnane 3,4,5 Introduction Elimination [...]

Background The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. Methods and findings A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. Conclusions In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term. Trial registration The trial is registered with ISRCTN (41918550)., Author(s): Maryam de Brun 1, Anders Magnuson 2, Scott Montgomery 2,3,4, Snehal Patil 2, David Simmons 5,6, Kerstin Berntorp 7, Stefan Jansson 8, Ulla-Britt Wennerholm 9, Anna-Karin Wikström 10, Helen [...]

Metabolomics--the comprehensive characterization of an organism's metabolites from endogenous and exogenous substances (1,2)--is an integral tool in environmental health research. (3) A study recently published in Environmental Health Perspectives demonstrates [...]

* Context.--Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. Objective.--To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. Design.--We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. Results.--Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. Conclusions.--For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype-guided management of Rh immune globulin therapy and RBC transfusions., In the United States and Canada, 0.06% to 2.2% of patients have red blood cells (RBCs) that type weakly reactive for RhD, termed 'serologic weak D phenotype.' (1-6) In past [...]

Background The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies. Methods and findings Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB Conclusions Emergency cerclage for cervical dilation or short cervical length, Author(s): Francesco D'Antonio 1, Nashwa Eltaweel 2, Smriti Prasad 3, Maria Elena Flacco 4, Lamberto Manzoli 5, Asma Khalil 3,6,7,8,* Introduction Twin pregnancies are at increased risk of perinatal morbidity [...]

Background: Amniogenesis is a key event in biochemical pregnancy, and its failure may result in human embryonic death. However, whether and how environmental chemicals affect amniogenesis remain largely unknown. OBJECTIVES: The objective of the present study was to screen chemicals that may disrupt amniogenesis in an amniotic sac embryoid model and to investigate the potential mechanism of amniogenesis failure, with a focus on organophosphate flame retardants (OPFRs). Methods: This study developed a high-throughput toxicity screening assay based on transcriptional activity of octamer- binding transcription factor 4 (Oct4). For the two positive OPFR hits with the strongest inhibitory activity, we used time-lapse and phase- contrast imaging to assess their effects on amniogenesis. Associated pathways were explored by RNA-sequencing and western blotting, and potential binding target protein was identified through a competitive binding experiment. Results: Eight positive hits exhibiting Oct4 expression were identified, with 2-ethylhexyl-diphenyl phosphate (EHDPP) and isodecyl diphenyl phosphate (IDDPP) showing the strongest inhibitory activity. EHDPP and IDDPP were found to disrupt the rosette-like structure of the amniotic sac or inhibit its development. Functional markers of squamous amniotic ectoderm and inner cell mass were also found disrupted in the EHDPP- and IDDPP-exposed embryoids. Mechanistically, embryoids exposed to each chemical exhibited abnormal accumulation of phosphorylated nonmuscle myosin (p-MLC-II) and were able to bind to integrin [beta]1 (ITG[beta]1). Conclusion: The amniotic sac embryoid models suggested that OPFRs disrupted amniogenesis likely by inhibiting the ITG[beta]1 pathway, thus providing direct in vitro evidence associating OPFRs with biochemical miscarriage. https://doi.org/10.1289/EHP11958, Introduction Miscarriage has been recognized as the most noticeable complication during human pregnancy (1) and has sharply increased globally over the past decades. (2,3) About 23 million miscarriages occurred annually [...]

Globally, about 1 in 10 people will experience a miscarriage at some point during their childbearing years. (1) These traumatic events are associated with risk factors such as infections, fetal [...]

The worldwide prevalence of gestational hypertension and preeclampsia is estimated at 10% and 2%-8%, respectively. (1) In the United States alone, the incidence of preeclampsia--a leading cause of maternal mortality--increased [...]

Introduction The impact on research findings that use pregnancy data from surveys with underreported abortions is not well-established. We estimate the percent of all pregnancies missing from women's self-reported pregnancy histories because of abortion underreporting. Methods We obtained abortion and fetal loss data from the 2006-2015 National Survey of Family Growth (NSFG), annual counts of births from US vital statistics, and external abortion counts from the Guttmacher Institute. We estimated the completeness of abortion reporting in the NSFG as compared to the external counts, the proportion of pregnancies resolving in abortion, and the proportion of pregnancies missing in the NSFG due to missing abortions. Each measure was examined overall and by age, race/ethnicity, union status, and survey period. Results Fewer than half of abortions (40%, 95% CI 36-44) that occurred in the five calendar years preceding respondents' interviews were reported in the NSFG. In 2006-2015, 18% of pregnancies resolved in abortion, with significant variation across demographic groups. Nearly 11% of pregnancies (95% CI 10-11) were missing from the 2006-2015 NSFG due to abortion underreporting. The extent of missing pregnancies varied across demographic groups and was highest among Black women and unmarried women (18% each); differences reflect both the patterns of abortion underreporting and the share of pregnancies ending in abortion. Discussion Incomplete reporting of pregnancy remains a fundamental shortcoming to the study of US fertility-related experiences. Efforts to improve abortion reporting are needed to strengthen the quality of pregnancy data to support maternal, child, and reproductive health research., Author(s): Sheila Desai [sup.1] , Laura D. Lindberg [sup.1] , Isaac Maddow-Zimet [sup.1] , Kathryn Kost [sup.1] Author Affiliations: (1) grid.417837.e, 0000 0001 1019 058X, Guttmacher Institute, , 125 Maiden [...]

Objectives Prepregnancy body mass index (BMI) and gestational weight gain (GWG) are known determinants of maternal and child health; calculating both requires an accurate measure of prepregnancy weight. We compared self-reported prepregnancy weight to measured weights to assess reporting bias by maternal and clinical characteristics. Methods We conducted a retrospective cohort study among pregnant women using electronic health records (EHR) data from Kaiser Permanente Northwest, a non-profit integrated health care system in Oregon and southwest Washington State. We identified women age [greater than or equal to] 18 years who were pregnant between 2000 and 2010 with self-reported prepregnancy weight, [greater than or equal to] 2 measured weights between [less than or equal to] 365-days-prior-to and [less than or equal to] 42-days-after conception, and measured height in their EHR. We compared absolute and relative difference between self-reported weight and two 'gold-standards': (1) weight measured closest to conception, and (2) usual weight (mean of weights measured 6-months-prior-to and [less than or equal to] 42-days-after conception). Generalized-estimating equations were used to assess predictors of misreport controlling for covariates, which were obtained from the EHR or linkage to birth certificate. Results Among the 16,227 included pregnancies, close agreement (± 1 kg or [less than or equal to] 2%) between self-reported and closest-measured weight was 44% and 59%, respectively. Overall, self-reported weight averaged 1.3 kg (SD 3.8) less than measured weight. Underreporting was higher among women with elevated BMI category, late prenatal care entry, and pregnancy outcome other than live/stillbirth (p < .05). Using self-reported weight, BMI was correctly classified for 91% of pregnancies, but ranged from 70 to 98% among those with underweight or obesity, respectively. Results were similar using usual weight as gold standard. Conclusions for Practice Accurate measure of prepregnancy weight is essential for clinical guidance and surveillance efforts that monitor maternal health and evaluate public-health programs. Identification of characteristics associated with misreport of self-reported weight can inform understanding of bias when assessing the influence of prepregnancy BMI or GWG on health outcomes., Author(s): Andrea J. Sharma [sup.1] [sup.3] , Joanna E. Bulkley [sup.2] , Ashley B. Stoneburner [sup.2] , Padmavati Dandamudi [sup.2] , Michael Leo [sup.2] , Williams M. Callaghan [sup.1] , [...]

Background: Perfluoroalkyl acids (PFAA) have been measured in ovarian follicular fluid from women using in vitro fertilization (IVF), although associations between follicular fluid PFAA and IVF outcomes have been inconsistent. Objectives: We investigated the association between follicular fluid PFAA and embryo quality in women undergoing IVF. Methods: We prospectively enrolled 729 women undergoing IVF treatment in Guangxi province, China, from July 2018 to December 2018. We measured 32 PFAA, including branched isomers, in follicular fluid using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We applied restricted cubic splines, linear regression, and log-binominal regression models to investigate associations between follicular fluid PFAA and embryo quality, adjusting for confounding variables and investigated oocyte maturity as an intervening variable using causal mediation analysis. We further estimated the overall effect of the PFAA mixture on outcomes using Bayesian kernel machine regression (BKMR). Results: We detected 8 of 32 measured PFAA in >85% of follicular fluid samples. Higher PFAA concentrations were associated with fewer high-quality embryos from IVF. The high-quality embryo rates at the 50th percentile of linear perfluoro-1-octanesulfonate acid (n-PFOS), all branched PfOS isomers (Br-PFOS) and linear perfluoro-n-octanoic acid (n-PFOA) were -6.34% [95% confidence interval (CI): - 9.45, -3.32%], -16.78% (95% CI: -21.98, -11.58%) and -8.66% (95% CI: -11.88, -5.43%) lower, respectively, than the high quality embryo rates at the reference 10th percentile of PFAA. Oocyte maturity mediated 11.76% (95% CI: 3.18, 31.80%) and 14.28% (95% CI: 2.95, 31.27%) of the n- PFOS and n-PFOA associations, respectively. The results of the BKMR models showed a negative association between the PFAA mixture and the probability of high-quality embryos, with branched PFOS isomers having posterior inclusion probabilities of 1 and accounting for the majority of the association. Discussion: Exposure to higher PFAA concentrations in follicular fluid was associated with poorer embryo quality during IVF. Branched PFOS isomers may have a stronger effect than linear PFOS isomers. More studies are needed to confirm these findings and to directly estimate the effects on pregnancy and live-birth outcomes. https://doi.org/10.1289/EHP10857, Introduction Infertility, defined as 12 months of unprotected heterosexual intercourse without a successful pregnancy according to the International Committee for Monitoring Assisted Reproductive Technology, (1) affects approximately 48.5 million reproductive-age [...]

Preimplantation embryo arrest (PREMBA) is a common cause of female infertility and recurrent failure of assisted reproductive technology. However, the genetic basis of PREMBA is largely unrevealed. Here, using whole-exome sequencing data from 606 women experiencing PREMBA compared with 2,813 controls, we performed a population and gene-based burden test and identified a candidate gene, karyopherin subunit [alpha]7 (KPNA7). In vitro studies showed that identified sequence variants reduced KPNA7 protein levels, impaired KPNA7 capacity for binding to its substrate ribosomal L1 domain-containing protein 1 (RSL1D1), and affected KPNA7 nuclear transport activity. Comparison between humans and mice suggested that mouse KPNA2, rather than mouse KPNA7, acts as an essential karyopherin in embryonic development. [Kpna2.sup.-/-] female mice showed embryo arrest due to zygotic genome activation defects, recapitulating the phenotype of human PREMBA. In addition, female mice with an oocyte-specific knockout of Rsl1d1 recapitulated the phenotype of [Kpna2.sup.-/-] mice, demonstrating the vital role of substrate RSL1D1. Finally, complementary RNA (cRNA) microinjection of human KPNA7, but not mouse Kpna7, was able to rescue the embryo arrest phenotype in [Kpna2.sup.-/-] mice, suggesting mouse KPNA2 might be a homologue of human KPNA7. Our findings uncovered a mechanistic understanding for the pathogenesis of PREMBA, which acts by impairing nuclear protein transport, and provide a diagnostic marker for PREMBA patients., Introduction Successful human reproduction requires normal embryonic development. Preimplantation embryo arrest (PREMBA) is a common reason for recurrent failure of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and [...]

Maternal adverse childhood experiences (ACEs) and intimate partner violence (IPV) are temporally distinct risk factors that negatively impact mothers and their offspring. Risk associated with ACEs and IPV begin during pregnancy, a period of increased physical and psychological demands. The current study examined a person-centered method to empirically identify profiles of pregnant women based on type and severity of ACEs and past-year IPV. Profiles were then differentiated on psychosocial functioning indicators. A primarily Latinx, low socioeconomic sample of women (n = 225) completed measures assessing ACEs and past-year IPV, perceived and experienced stress, emotion regulation, and trauma-related symptoms during their third trimester. Latent profile analysis (LPA) was used to identify unique profiles of women based on seven dimensional indicators reflecting threat- and deprivation-based ACEs and IPV. A 4-class solution best fit the data: (1) low probability of ACEs or IPV (64.9%), (2) childhood neglect-only (20.4%), (3) childhood abuse/neglect (10.2%), and (4) polytrauma characterized by a combination of childhood abuse, neglect, and IPV (4.4%). Women with the 'childhood abuse/neglect' or 'polytrauma' profiles reported more stress and symptoms than women with the 'low exposure' profile. Women in the 'childhood neglect-only' profile were generally similar to women in the 'low exposure' profile, but did report greater difficulties in emotion regulation. These results suggest that childhood abuse and IPV, exposure types involving threat, are potent correlates of stress, emotion regulation, and mental health difficulties during pregnancy. However, exposure characterized by deprivation alone generally did not increase difficulties., Author(s): Brandon L. Goldstein [sup.1] , Margaret J. Briggs-Gowan [sup.1] , Damion J. Grasso [sup.1] Author Affiliations: (1) grid.208078.5, 0000000419370394, Department of Psychiatry, University of Connecticut School of Medicine, , [...]