Maternal heat exposure has been linked to adverse pregnancy outcomes. The impact of high ambient temperature exposure on inflammation during human pregnancy remains largely unknown. Determine the associations between preconception/ trimester-wise exposure to excessive heat stress (HS) and α1-acid glycoprotein (AGP) or C-Reactive Protein (CRP) at 12 and 34 weeks of gestation. This secondary analysis included women with serum concentrations of AGP (n = 160), and CRP (n = 143) collected at 12 and 34 weeks of pregnancy from Women First Preconception Maternal Nutrition Trial in Thatta, Pakistan. Excessive HS was categorically defined as > 20 days with average maximal daily temperature >39 °C in each period: 90 days preconception (PreC), trimester 1 (T1), or trimester 2 (T2). Multiple linear regression was used to assess relationships between HS and each inflammatory marker in separate models for 12 and 34-weeks assessments, including adjustment for maternal characteristics, intervention arm, cluster, maternal anemia status, PM2.5 levels, and 12-week AGP or CRP (for 34-week outcomes). Exposure to HS during PreC increased 34-week AGP by 0.10 µg/mL compared to no HS exposure (p = 0.045). Exposure to HS compared to no exposure was positively associated with 34-week CRP (mg/L) during PreC (ß= 1.90, p = 0.015), T1 (ß= 2.06, p = 0.009), and T2 (ß= 1.93, p = 0.020). No significant associations were observed between exposure to HS and inflammatory markers at 12 weeks. Findings suggest that preconception and early pregnancy HS may contribute to late-gestation inflammation.

Recent literature suggests that climate change can impact sexual and reproductive health and rights (SRHR) outcomes, especially since climate-related events may exacerbate persistent inequalities based on gender, disability status, sexual orientation, and age, among others. Climate change can also impact health infrastructure with an impact on SRHR access and outcomes. However, data are scarce when it comes to certain topical areas, types of evidence, and in using an intersectional approach. Based on a prior expert consultation exercise, we conducted a consensus and priority setting process to develop a list of priority research questions at the intersection of climate change and SRHR. For this, in 2024, we completed an iterative process over three rounds consisting of online surveys and consultations, following modified Delphi and Child Health and Nutrition Research Initiative (CHNRI) methodologies for which 100 people were included. For round one, 56 people responded to the 17-question survey framed around topical areas in SRHR, research methodologies, and intersectionality; 39 people participated in the online consultation. The round two survey had 36 respondents and 41 participants to the online consultation. The third round included a survey with a list of 31 questions that respondents were asked to prioritize. A final list of ten questions emerged which highlighted important areas where there continue to be gaps in evidence, including maternal and perinatal health, contraception and abortion access, and gender-based violence. Other critical areas include intersectional issues regarding gender and poverty and comprehensive sex education. The list can serve as a starting point to guide the SRHR research community to generate the evidence needed for policy action.

OBJECTIVE:A multi-centre international trial (A-PLUS), demonstrated that a single dose of 2 g oral azithromycin in labour reduced the risk of maternal sepsis or death, but not neonatal mortality. We aimed to determine whether the efficacy of azithromycin in prevention of any maternal infection or neonatal infection varied by time interval from azithromycin administration to delivery. DESIGN:This is a secondary analysis of a randomized controlled trial. SETTING:Multi-centre international randomized controlled trial. POPULATION:Pregnant patients ≥ 28 weeks gestation (singleton or multiple gestation) presenting in labour for planned vaginal delivery. OUTCOMES:The primary outcome for this secondary analysis was maternal infection and the secondary outcome was any neonatal infection. METHODS:The estimated relative risks (and 95% confidence interval) of any maternal or neonatal infection comparing azithromycin to placebo were obtained by fitting a Poisson model adjusting for site, treatment arm, hours between drug administration and delivery (as continuous measure, and ≤ 12 or > 12 h for maternal and ≤ 9 or > 9 h for neonatal), and the two-way interaction between treatment arm and hours between drug administration and delivery. RESULTS:Included in the analysis were n = 14 569 randomized to azithromycin and n = 14 667 to placebo. There was no evidence that the benefit of azithromycin on reducing the risk of any maternal infection varied by time from dose to delivery (RR 0.71 (0.64-0.79) and RR 0.71 (0.54-0.94) for ≤ 12 and > 12 h respectively, interaction p = 0.987), although there was an observed interaction in Sub-Saharan Africa subgroup with reduced risk observed with administration > 12 vs. ≤ 12 (RR 0.21 (0.08-0.54) vs. RR 0.52 (0.41-0.66), interaction p = 0.03). There was no benefit observed in prevention of infant infection regardless of time from dose to delivery (≤ 9 or > 9 h) (RR 1.00 (0.95-1.06) and RR 1.01 (0.88-1.15) interaction p = 0.997). CONCLUSION:The benefit observed with a single intrapartum dose of azithromycin for prevention of any maternal infection in the setting of planned vaginal delivery was not observed to vary by time interval from azithromycin administration to delivery, although in some populations there may be greater benefit with delivery > 12 h from administration. Pregnant patients presenting for planned vaginal birth benefit from a single dose of 2 g azithromycin regardless of how soon delivery is anticipated.

Importance Scalable interventions are urgently needed to mitigate the adverse effects of heat on pregnancy and newborn health. Objective To evaluate whether low-dose aspirin modifies the association between heat exposure and preterm birth. Design, Setting, and Participants This secondary analysis of the Global Network for Women’s and Children’s Health Research Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) randomized, double-blinded, placebo-controlled clinical trial was conducted from March 2016 to June 2018. Statistical analyses were performed from June 2024 to June 2025. The study settings included the Democratic Republic of Congo, Zambia, Kenya, Guatemala, Pakistan, and Belagavi and Nagpur, India. Participants included nulliparous individuals between 6 and 13 weeks’ gestation recruited through local clinics and communities, with delivery at 20 or more weeks’ gestation. Exposures Prenatal care site–specific daily maximum humid heat averaged across gestation and by gestational week, and randomization to aspirin or placebo. Main Outcome and Measure The main outcome was preterm birth (delivery between 20 and <37 weeks’ gestation) with gestational age confirmed by enrollment ultrasonography. Results Of 11 558 participants (mean [SD] age, 20.9 [3.3] years), 5787 were randomized to receive aspirin and 5771 to receive placebo. Preterm birth occurred among 754 placebo recipients (13.1%) and 668 aspirin recipients (11.6%). In mixed-effects pooled logistic regression, each 1 °C increase in mean daily maximum shaded wet-bulb globe temperature across gestation was associated with a 5% increased odds of preterm birth (adjusted odds ratio, 1.05; 95% CI, 1.01-1.10). In stratified analyses, this increased risk was observed only among placebo recipients (adjusted odds ratio [AOR], 1.07; 95% CI, 1.02-1.13), not among aspirin recipients (AOR, 1.03; 95% CI, 0.97-1.10). In pooled mixed-effects logistic distributed lag models, increased odds of preterm birth were observed 17 to 19 weeks before delivery among individuals whose daily maximum shaded wet-bulb globe temperature exceeded the site-specific 75th percentile compared with the lowest 3 quartiles. This vulnerability was not observed among aspirin recipients. In contrast, the association of heat with perinatal mortality was observed only among those receiving aspirin (AOR, 1.15; 95% CI, 1.05-1.26) and not among those receiving placebo (AOR, 1.03; 95% CI, 0.96-1.11). Conclusions and Relevance The findings of this secondary analysis of the Global Network ASPIRIN trial suggest that low-dose aspirin initiated early in pregnancy among nulliparous individuals may mitigate the effects of heat exposure on preterm birth. The increasing global prevalence of heat stress warrants testing its efficacy more broadly among pregnant people as well as its safety with respect to perinatal mortality. Trial Registration ClinicalTrials.gov Identifier: NCT02409680

OBJECTIVES:Fetal death is a major pregnancy complication, with rates of 5.5 per 1,000 births in the United States and substantially higher in India (24.7/1,000) and Pakistan (44.5/1,000). Maternal vascular malperfusion (MVM) is the most frequent placental lesion associated with fetal death, occurring in 58 % of fetal deaths and 31 % of preterm neonatal deaths in South Asia. Angiogenic imbalance, characterized by a low placental growth factor (PlGF) to soluble fms-like tyrosine kinase-1 (sFlt-1) ratio, has been associated with MVM and fetal death in high-income countries. We examined whether maternal serum concentrations of PlGF, sFlt-1, and their ratio differ between mothers with and without MVM among stillbirths and preterm neonatal deaths in India and Pakistan. METHODS:This retrospective cohort analysis used data from the PURPOSe study (Project to Understand and Research Preterm Pregnancy Outcomes and Stillbirths in South Asia). Maternal blood was collected at delivery, and placental histopathology was classified according to the Amsterdam criteria. Serum PlGF and sFlt-1 were measured using Elecsys® immunoassays, with analyses stratified by gestational age. RESULTS:Placental MVM was present in 44-57 % of stillbirths and 31-38 % of preterm neonatal deaths. Between 28 and 36 weeks, women with MVM had significantly lower PlGF and higher sFlt-1 and sFlt-1/PlGF ratios (p<0.001). A tenfold decrease in PlGF or increase in the ratio was associated with MVM (OR 0.5 and 1.7, respectively). CONCLUSIONS:The maternal sFlt-1/PlGF ratio identifies pregnancies with fetal or neonatal death associated with placental MVM, particularly between 28 and 36 weeks' gestation.

Abstract Background The UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) has a mandate to lead in sexual and reproductive health and rights research and to support research capacity strengthening. Starting in 2016, it did so through supporting the latter through a large network of research institutions called the HRP Alliance. This commentary highlights the work of the HRP Alliance in response to the coronavirus disease (COVID-19) pandemic. Main body The onset of the COVID-19 pandemic prompted the HRP Alliance to adapt the way they had been working. HRP Alliance research capacity strengthening hubs actively contributed to developing a research agenda based on WHO’s research and development blueprint and country-specific needs. They also took on leading roles in developing, adapting to each country/setting, and implementing research projects aimed at understanding how the COVID-19 pandemic was affecting SRHR in different contexts and income settings. These studies provided opportunities for early career researchers and students to lead in project management, study implementation, training, and data analysis. Through a network of nimble research institutions, the HRP Alliance collaborated to generate evidence on the impact of COVID-19 on pregnancy, pregnancy outcomes, access to SRHR services, gender-based violence, and abortion care. The success of implementing these research response mechanisms and developing global networks of research and healthcare institutions, provided solid ground upon which to build SRHR research responses to future pandemics and other emerging diseases. Conclusion Adequate readiness and response to global health emergencies require high quality and timely evidence generation. Global networks of research partner institutions, brought together through research capacity strengthening initiatives, can provide a fruitful platform ready and able to swiftly respond. However, inherent power imbalances and challenges to equitable partnerships need to be considered to ensure sustainable ways of working together.

OBJECTIVE:To identify risk factors for bag and mask ventilation (BMV) and compare mortality outcomes between infants who did and did not receive BMV. STUDY DESIGN:Secondary analysis of data from the seven sites of the Global Network Maternal Newborn Health registry, including fresh stillbirths and live births ≥ 1500 grams from 2017 to 2023. RESULTS:A total of 171 279 births (98.9% live births, 1.1% fresh stillbirths) were included. BMV was administered in 3.9% of cases. Maternal education, labor complications, delivery location, and prematurity were identified as major risk factors for receiving BMV. Adjusted relative risks (95% CI) for very early neonatal mortality with BMV was 26.18 (23.02-29.79), early neonatal mortality 19.08 (17.40-20.93), neonatal mortality 14.23 (13.08,15.49, mortality < 42 days 12.86 (11.84,13.97) and asphyxia-related deaths was and 2.42 (2.11, 2.77). CONCLUSION:These finding underscore the importance of early identification of maternal and perinatal factors associated with receiving BMV to improve neonatal outcomes.

OBJECTIVE:To evaluate the association between 2 g of intrapartum azithromycin given to laboring mothers and neurodevelopmental outcomes after birth asphyxia. METHODS:This was a neurodevelopmental follow-up study of children born at 34 weeks of gestation or later who had concern for asphyxia and whose mothers were enrolled in A-PLUS (the Azithromycin Prevention in Labor Use Study). Mothers in A-PLUS were randomized to receive a single oral dose of azithromycin (2 g) or placebo during labor. This follow-up to A-PLUS spanned six sites across five countries (India [two sites], Pakistan, Zambia, Democratic Republic of Congo, and Guatemala). Asphyxia was defined as 5-minute Apgar score less than 7 or the need for bag-and-mask ventilation at birth. The primary outcome was the CCS (Cognitive Composite Score) of the BSID-III (Bayley Scales of Infant and Toddler Development, 3rd Edition) at a corrected age of 24±1 months. Secondary outcomes included the LCS (Language Composite Score) and MCS (Motor Composite Score) of the BSID-III at a corrected age of 24±1 months. Masked examiners administered the BSID-III and the ASQ-3 (Ages & Stages Questionnaires, 3 rd Edition). Outcomes were analyzed using a generalized linear model and were adjusted for site, gestational age at delivery, and maternal and child baseline characteristics that differed between treatment groups. RESULTS:Of 529 eligible mother-child dyads screened, 403 (197 in the azithromycin arm and 206 in the placebo arm) were enrolled and completed the neurodevelopmental follow-up at a corrected age of 24±1 months. The primary outcome, the CCS of the BSID-III, did not differ significantly between groups (azithromycin: 90.9±11.2 vs placebo: 90.9±11.7; mean difference: 0.29; 95% CI, -1.77 to 2.34). No significant differences were observed between treatment arms in the BSID-III's LCS and MCS or in the total scores of the ASQ-3's five domains. Subgroup analysis by region (sub-Saharan Africa vs South Asia) also showed no differences in BSID-III or ASQ-3 scores between the azithromycin and placebo groups. CONCLUSION:In this follow-up study, a single oral dose of azithromycin given to laboring mothers who delivered neonates with birth asphyxia did not improve neurodevelopmental outcomes at 2 years of age. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT03871491.

Introduction:Family planning (FP) services are essential for reproductive health and women's empowerment, yet quality gaps persist in low-income urban areas of Pakistan. This study explores women's perspectives on FP service quality in the underserved communities of Malir Town, Karachi. Methods:Using a phenomenological qualitative design, in-depth interviews and focus group discussions were conducted with current and past users of modern contraceptives from three Union Councils: Saudabad, Khokhrapar and Kala Board. Data were collected through 12 in-depth interviews and four focus group discussions (n=25 participants). Data were analysed thematically using Judith Bruce's 'Quality of Care' framework. Results:Participants reported inadequate contraceptive options, poor counselling, lack of follow-up and limited decision-making autonomy. Respectful provider interactions, clear communication and community health worker support were identified as key facilitators. Structural issues, such as fragmented service delivery and poor integration, hindered consistent contraceptive use. Conclusion:Improving FP service quality in poor urban settings requires a client-centred approach that strengthens counselling, ensures method availability, integrates services and leverages community-based support. Further research should include non-users to inform scalable, equity-focused interventions.

OBJECTIVE:The randomized trial of azithromycin to reduce maternal and neonatal sepsis (the A-PLUS Trial) found substantial reduction in maternal sepsis among women receiving azithromycin and substantial non-study antibiotic use. This secondary analysis explored the effect modification of non-study antibiotics on azithromycin versus placebo on maternal and newborn infection among A-PLUS participants. METHODS:Women ≥28 weeks gestation in labor and planning a vaginal delivery at a study hospital in seven low- and middle-income countries (Bangladesh, India [two sites], Pakistan, Guatemala, Kenya, Democratic Republic of Congo, and Zambia) were eligible for inclusion. Non-study antibiotic use was collected prospectively. We estimated the interaction of non-study antibiotics with azithromycin versus placebo on maternal and newborn sepsis. RESULTS:A total of 29 287 participants were randomized (14 590 to azithromycin; 14 688 to placebo). Maternal infection was reduced among the azithromycin group compared to placebo among those who did not receive non-study antibiotics, with estimated relative risk (RR) 0.58 (95% confidence interval [CI] 0.48, 0.70), and among those who received non-study antibiotics, with RR 0.80 (95% CI 0.70, 0.91). Similar results were observed for maternal sepsis. Neonatal infection was not significantly reduced in any group. These results were similar when stratified by African and Asian region but not statistically significant. CONCLUSION:Our results suggest a benefit of azithromycin in reducing maternal infection or sepsis across all groups, with a larger reduction in risk among participants who had not received other antibiotics. Given the concerns of inappropriate use of antibiotics, further research is warranted to determine the most effective strategies of reducing risk of infection.

OBJECTIVE:A single oral dose of azithromycin (AZM) given during labor to women planning a vaginal delivery reduced maternal infections including sepsis, with a stronger effect in sub-Saharan Africa than South Asia. Since maternal infection contributes to labor dysfunction and postpartum hemorrhage (PPH), we evaluated the effect of AZM on the risk of PPH and blood transfusion. METHODS:This was an unplanned secondary analysis of the Azithromycin Prevention in Labor Use Study (A-PLUS) randomized controlled trial at eight sites in seven low- and middle-income countries in sub-Saharan Africa, South Asia, and Latin America. The population consisted of pregnant women in labor at ≥28 weeks' gestation in health facilities randomized to either 2 g AZM or placebo. Based on an intent-to-treat analysis, the risk of PPH and blood transfusion was compared between AZM and placebo arms using Poisson regression adjusting for arm and site as fixed effects. The main outcome measures were (1) PPH (500 mL or greater) after delivery; and (2) postpartum blood transfusion after delivery. RESULTS:A total of 29 278 participants were randomized to APLUS; 14 590 to AZM and 14 688 to placebo. The risk of PPH did not significantly differ between AZM and placebo arms (1.4% in AZM; 1.6% in placebo; relative risk [RR] = 0.88; 95% confidence interval [CI]: 0.73, 1.07). The risk of blood transfusion also did not significantly differ between AZM and placebo arms (0.5% in AZM; 0.5% in placebo; RR = 0.90; 95% CI: 0.65, 1.25). There was also evidence indicating that the effect of AZM on the risk of blood transfusion, but not PPH, was beneficial in sub-Saharan Africa but not in South Asia (P value for two-way interaction = 0.002). CONCLUSION:A single intrapartum oral dose of AZM did not significantly reduce the overall risk of PPH or blood transfusion. CLINICALTRIALS:gov Identifier: NCT03871491.

ABSTRACT Objectives Limited population‐based data have evaluated COVID‐19 infections during pregnancy in low‐ and middle‐income countries (LMICs). We updated COVID‐19 antibody positivity rates and relationships to pregnancy outcomes in unvaccinated women in LMICs. Design COVID‐19 antibody testing was conducted for pregnant women at delivery. We evaluated pregnancy outcomes using data collected in a prospective registry. Setting The Maternal and Newborn Health Registry (MNHR) is a prospective, population‐based study in specific geographic communities in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Bangladesh, Pakistan, India, and Guatemala. Methods From October 2020 to October 2021, we conducted COVID‐19 antibody testing at delivery among women enrolled in the MNHR ( n = 14 015). Results include women delivering from November 2021 to July 2022 ( n = 8204). Outcomes among women who were COVID‐19 positive versus negative at delivery were compared among women unvaccinated for COVID‐19. Outcome Measures COVID‐19 antibody positivity rates, stillbirth, neonatal mortality, maternal mortality, and morbidity. Results Vaccination among pregnant women increased from < 1% (October 2020–October 2021) to 30.4% (November 2021–June 2022). In the final period, COVID‐19 vaccination rates ranged from 0.1% in DRC to 67.4% in Guatemala. Among unvaccinated women, the antibody positivity rate overall was 14.0% (October 2020–December 2020), increasing to 69.5% during May–July 2022. Over time, antibody positivity rates increased until January 2022 for women in all sites, when the positivity rates remained relatively stable through July 2022. In the final period, antibody positivity rates ranged from 59.4% (DRC) to 88.0% (India). After adjusting for site and maternal characteristics, antibody positivity was not associated with any adverse fetal/neonatal outcome. Conclusions In the pregnant populations across seven LMICs, COVID‐19 infections occurred in over 50% of unvaccinated women overall. Adverse pregnancy outcomes, including preterm birth, low birthweight, stillbirth, neonatal death, and antepartum hemorrhage, were not increased in women who were antibody positive compared to women who were antibody negative in either time period.

BackgroundProphylactic oral azithromycin vs. placebo reduced maternal, but not neonatal, mortality/sepsis in the A-PLUS Randomized Trial. While prophylactic intrapartum azithromycin reduces maternal mortality/sepsis, it may promote antimicrobial resistance (AMR) in commensal bacteria,.MethodsRandomly selected women and their infants participating in A-PLUS were enrolled in a longitudinal cross-sectional sub-study to assess the presence of azithromycin resistance in selected bacteria in nasal cultures. Staphylococcus aureus and Streptococcus pneumoniae were cultured on selective agar, then azithromycin-containing agar to select for azithromycin resistant bacteria, identified biochemically. Azithromycin susceptibility was assessed by E-test. Nasal cultures were collected from women and infants between August 11, 2021 and September 18, 2023 during labor/day 1, day 7, 6 weeks, and 3, 6 and 12 months after delivery.ResultsThe study enrolled 911 women and 915 liveborn infants at 8 sites in 7 countries. Azithromycin resistance in S aureus was higher and azithromycin susceptibility was lower in women receiving azithromycin compared with those receiving placebo on day 7 (P < 0.001), 6 weeks (P < 0.001) and 3 months (P = 0.009) after delivery. Azithromycin resistance in S aureus was also higher and azithromycin susceptibility was lower 6 weeks after delivery (P < 0.001) in infants born to women receiving azithromycin, Azithromycin resistance in S. pneumoniae was too sparse to interpret.ConclusionsThere was an increase in prevalence of azithromycin resistance (or reduction in azithromycin susceptibility) in commensal nasal S. aureus between day 7, 6 weeks and 3 months in women exposed to azithromycin vs. placebo and only at 6 weeks in infants exposed to azithromycin vs. placebo. These differences between the azithromycin and placebo groups were no longer detected at 6 and 12 months post-partum in the women and after 6 weeks through 12 months in the infants.

INTRODUCTION:The Women First (WF) Preconception Maternal Nutrition trial found greater benefits of small-quantity lipid-based nutrient supplements (SQ-LNS) for intrauterine growth among anaemic versus non-anaemic women at preconception. We investigated whether the benefits of SQ-LNS in improving markers of intrauterine growth occurred evenly across the mild to moderate spectrum of pre-pregnancy anaemia. METHODS:We analysed WF data (n=2443 maternal-newborn dyads) from Pakistan, India, Guatemala and the Democratic Republic of Congo. Women received SQ-LNS either ≥3 months preconception through pregnancy (Arm 1); starting in the late first trimester (Arm 2); or not at all (Arm 3: control), with all supplementations discontinued at delivery. The outcomes were infant weight, length and head circumference measured within 48 hours of birth, expressed as Z-scores. For each site, adjusted mean differences in the Z-scores were computed across six pre-pregnancy haemoglobin (Hb) categories (80-89, 90-99, 100-109, 110-119, 120-129, and ≥130 g/L) and pooled using meta-analysis. RESULTS:The effect of SQ-LNS on birth weight, length and head circumference varied by pre-pregnancy Hb categories. No significant differences in pooled mean Z-scores were observed for any Hb category >110 g/L, and no differences were found for Arm 1 vs Arm 2 across any Hb categories. For women with Hb 90-99 g/L pooled mean differences (95% CI) in the Z-scores for length (0.60 (0.03 to 1.23)), weight (0.50 (0.11 to 0.89)) and head circumference (0.26 (0.02 to 0.51)) were greatest for Arm 1 versus Arm 3. For women with Hb 100-109 g/L in Arm 1 versus Arm 3, pooled mean difference (95% CI) in birth weight Z-scores was significantly greater (0.33 (0.24 to 0.42)). Arm 2 vs Arm 3 women with Hb 90-99 g/L had greater birth weight Z-scores (0.14 (0.05 to 0.22)). CONCLUSION:The findings highlight the importance of identifying women preconception for whom nutrition interventions may have the greatest impact on fetal growth.

Importance:Scalable interventions are urgently needed to mitigate the adverse effects of heat on pregnancy and newborn health. Objective:To evaluate whether low-dose aspirin modifies the association between heat exposure and preterm birth. Design, Setting, and Participants:This secondary analysis of the Global Network for Women's and Children's Health Research Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) randomized, double-blinded, placebo-controlled clinical trial was conducted from March 2016 to June 2018. Statistical analyses were performed from June 2024 to June 2025. The study settings included the Democratic Republic of Congo, Zambia, Kenya, Guatemala, Pakistan, and Belagavi and Nagpur, India. Participants included nulliparous individuals between 6 and 13 weeks' gestation recruited through local clinics and communities, with delivery at 20 or more weeks' gestation. Exposures:Prenatal care site-specific daily maximum humid heat averaged across gestation and by gestational week, and randomization to aspirin or placebo. Main Outcome and Measure:The main outcome was preterm birth (delivery between 20 and <37 weeks' gestation) with gestational age confirmed by enrollment ultrasonography. Results:Of 11 558 participants (mean [SD] age, 20.9 [3.3] years), 5787 were randomized to receive aspirin and 5771 to receive placebo. Preterm birth occurred among 754 placebo recipients (13.1%) and 668 aspirin recipients (11.6%). In mixed-effects pooled logistic regression, each 1 °C increase in mean daily maximum shaded wet-bulb globe temperature across gestation was associated with a 5% increased odds of preterm birth (adjusted odds ratio, 1.05; 95% CI, 1.01-1.10). In stratified analyses, this increased risk was observed only among placebo recipients (adjusted odds ratio [AOR], 1.07; 95% CI, 1.02-1.13), not among aspirin recipients (AOR, 1.03; 95% CI, 0.97-1.10). In pooled mixed-effects logistic distributed lag models, increased odds of preterm birth were observed 17 to 19 weeks before delivery among individuals whose daily maximum shaded wet-bulb globe temperature exceeded the site-specific 75th percentile compared with the lowest 3 quartiles. This vulnerability was not observed among aspirin recipients. In contrast, the association of heat with perinatal mortality was observed only among those receiving aspirin (AOR, 1.15; 95% CI, 1.05-1.26) and not among those receiving placebo (AOR, 1.03; 95% CI, 0.96-1.11). Conclusions and Relevance:The findings of this secondary analysis of the Global Network ASPIRIN trial suggest that low-dose aspirin initiated early in pregnancy among nulliparous individuals may mitigate the effects of heat exposure on preterm birth. The increasing global prevalence of heat stress warrants testing its efficacy more broadly among pregnant people as well as its safety with respect to perinatal mortality. Trial Registration:ClinicalTrials.gov Identifier: NCT02409680.

OBJECTIVE:To evaluate if the effect of low-dose aspirin (LDA) commenced between 6 and 13 weeks of gestational age (GA) on preterm delivery (PTD) is modified by total exposure. DESIGN:Post hoc analysis of a randomized controlled trial. SETTING:Hospitals in low-resource settings in Africa, Asia and Latin America. POPULATION:Outcomes were obtained for 11 908/11943 women at 6 0/7 to 13 6/7 weeks' GA randomized. METHODS:Women received prepackaged two-week medication allotments. Adherence was assessed by pill counts every 2 weeks. Estimated relative risk and 95% confidence interval data for each outcome at each GA of treatment initiation weeks were obtained by fitting a Poisson model to each outcome, adjusting for site, treatment arm and GA at treatment initiation. MAIN OUTCOMES MEASURES:The primary outcome was PTD. Secondary outcomes included PTD < 34 weeks and perinatal mortality including analysis by region. RESULTS:The median gestational age at treatment initiation was 10.1 weeks (IQR 8.6, 12.0). 85.5% of the mothers had over 90% adherence to treatment. For each 1 week increase of GA at treatment initiation, the treatment risk ratio did not change for PTD [RR 0.97 (95% CI, 0.93, 1.02)], PTD < 34 weeks [< 0.98 (0.89, 1.07)] or perinatal mortality [1.04 (0.96, 1.12)], with no evidence of effect modification. For each 5% increase in adherence, the treatment risk ratio did not change for PTD [1.01 (0.99, 1.04)], PTD < 34 weeks [< 0.99 (0.95, 1.03)] or perinatal mortality [1.02 (0.98, 1.06)], indicating no meaningful interaction with adherence. There was no effect modification by region. CONCLUSIONS:This analysis shows that the results of PTD, PTD < 34 weeks and perinatal mortality were not dependent on the timing of the initiation or adherence to treatment. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02409680.

The UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) has a mandate to lead in sexual and reproductive health and rights research and to support research capacity strengthening. Starting in 2016, it did so through supporting the latter through a large network of research institutions called the HRP Alliance. This commentary highlights the work of the HRP Alliance in response to the coronavirus disease (COVID-19) pandemic. The onset of the COVID-19 pandemic prompted the HRP Alliance to adapt the way they had been working. HRP Alliance research capacity strengthening hubs actively contributed to developing a research agenda based on WHO’s research and development blueprint and country-specific needs. They also took on leading roles in developing, adapting to each country/setting, and implementing research projects aimed at understanding how the COVID-19 pandemic was affecting SRHR in different contexts and income settings. These studies provided opportunities for early career researchers and students to lead in project management, study implementation, training, and data analysis. Through a network of nimble research institutions, the HRP Alliance collaborated to generate evidence on the impact of COVID-19 on pregnancy, pregnancy outcomes, access to SRHR services, gender-based violence, and abortion care. The success of implementing these research response mechanisms and developing global networks of research and healthcare institutions, provided solid ground upon which to build SRHR research responses to future pandemics and other emerging diseases. Adequate readiness and response to global health emergencies require high quality and timely evidence generation. Global networks of research partner institutions, brought together through research capacity strengthening initiatives, can provide a fruitful platform ready and able to swiftly respond. However, inherent power imbalances and challenges to equitable partnerships need to be considered to ensure sustainable ways of working together.

INTRODUCTION:This study examined associations between information sources and COVID-19 vaccination behavior among pregnant and postpartum women in Brazil, Ghana, Kenya, and Pakistan. METHODS:This mixed methods study involved concurrent in-depth interviews and cross-sectional surveys. RESULTS:A total of 1797 women participated in the study. Overall, participants were more likely to be vaccinated if they believed that they knew enough about safety to make a decision (aOR: 1.51; CI: 1.04-2.20) and trusted the information they received from healthcare providers (aoR: 1.74; CI: 1.19-2.54). Odds of vaccination were higher among those who trusted information provided by scientists (aoR:1.86; CI: 1.31-2.63) and among those who believed that leaders in their community recommended the COVID-19 vaccine (aOR: 1.4; CI: 1.01-1.92). Higher odds of vaccination were observed among participants in Pakistan who had the information they needed to make a decision (aOR: 2.58; CI: 1.35-4.94), knew enough about safety to make a decision (aOR: 3.82; CI: 1.85-7.89), trusted the information they received from healthcare providers (aOR: 3.20; CI: 1.39-7.34), and believed that community leaders recommended the COVID-19 vaccine (aOR: 2.53; CI: 1.22-5.25). Participants in Brazil who trusted information provided by scientists (aOR: 4.70; CI: 1.23-18.05); participants in Kenya who trusted information from the media (aOR: 1.94; CI: 1.10-3.44); and participants in Ghana who trusted recommendations from their government (aOR: 2.66; CI: 1.42-5.0) had higher odds of vaccination. Interviewed women noted that they felt overwhelmed with the amount of information and misinformation related to COVID-19 and the vaccine specifically. DISCUSSION:Trusted COVID-19 vaccine information sources reported by pregnant and postpartum women vary by country, suggesting the need to identify sources across different target populations to improve vaccine acceptability and uptake with the goal of realizing the population level benefits of vaccination.

INTRODUCTION:There are many factors associated with maternal immunization decision making. This study aimed to describe COVID-19 vaccination attitudes, beliefs, behaviors, and intentions among pregnant women across four countries within the context of varying and changing policy recommendations related to COVID-19 vaccination for pregnant women. METHODS:This cross-sectional quantitative study surveyed pregnant women in antenatal care facilities serving mostly urban or peri-urban populations in Campinas, Brazil; Accra, Ghana; Nairobi, Kenya; and Karachi, Pakistan. Potential participants were approached in clinic waiting rooms, and if eligible, enrolled after informed consent was obtained. RESULTS:A total of 1603 women were surveyed, with 64 % overall reporting they received a COVID-19 vaccine, ranging from 46 % in Pakistan to 97 % in Brazil. Among those ever vaccinated, 15 % received a COVID-19 vaccine during pregnancy, most received only one dose during pregnancy and the majority (53 %) reported they were vaccinated in their first trimester. The top two reasons for vaccination were the same across all countries: protecting themselves and protecting their baby. Among those not vaccinated against COVID-19, the majority of participants (68 %) indicated that they did not intend to be vaccinated, and fears that the vaccine was not safe was the highest rank among all countries as the primary reason for not getting vaccinated. In adjusted models, higher disease risk perception (aOR: 1.88; CI: 1.35-2.62), higher beliefs in vaccine effectiveness for the pregnant women (aOR: 1.75; CI: 1.19-2.55), belief in the safety of the vaccine for their baby (aOR: 2.30; CI: 1.46-3.64), and believing that peers were taking the vaccine (aOR: 1.54; CI: 1.14-2.08) were associated with vaccination status. Holding views consistent with vaccine hesitancy was associated with lower odds of vaccination (aOR: 0.28; CI: 0.20-0.40). DISCUSSION:Enhancing risk perception of COVID-19 in pregnancy, knowledge about safety and benefits of the vaccine compared to the risks, and promoting supportive environments where vaccines are perceived as normative behavior can help increase vaccine uptake among pregnant women.