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.

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.

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.

BACKGROUND:In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin reduces maternal sepsis or death in women with planned vaginal delivery in low-resource settings, but whether it reduces maternal infection is unknown. We aimed to evaluate the effectiveness of intrapartum azithromycin in reducing maternal infection. METHODS:We performed a post-hoc analysis of the multicentre, facility-based, randomised, double-blind, placebo-controlled A-PLUS trial. This trial compared prophylactic intrapartum single oral dose of 2 g azithromycin versus placebo on maternal morbidity and mortality in low-resource settings in southeast Asia and Africa from Sept 9, 2020, to Aug 18, 2022. The trial enrolled women in labour at 28 weeks' gestation (or later) at eight sites in the Democratic Republic of the Congo, Kenya, Zambia, Bangladesh, India, Pakistan, and Guatemala and found that azithromycin reduced the incidence of maternal sepsis or death. The primary outcome of the present analysis was the incidence of any maternal infection in the azithromycin versus placebo groups, which was defined as one or more of these infections after randomisation: chorioamnionitis, endometritis, perineal or caesarean wound infection, abdominopelvic abscess, mastitis or breast abscess, and other infections. Any neonatal infection was also analysed. All analyses were by intention to treat in all those with data available for that outcome. Relative risks (RRs) and 95% CIs were estimated with a Poisson model adjusted for treatment group and site. Subgroup analyses included a two-way interaction test between intervention group and subgroup. A-PLUS was registered at ClinicalTrials.gov, number NCT03871491. FINDINGS:29 278 women were randomly assigned to groups: 14 590 to receive azithromycin, 14 688 to receive placebo. Baseline characteristics were similar between the azithromycin and placebo groups (43·3% vs 43·4% primiparous, 8·5% vs 8·7% high risk for infection). The presence of any maternal infection occurred less often in the azithromycin group (580 [4·0%] of 14 558) compared with the placebo group (824 [5·6%] of 14 661 women; RR 0·71, 95% CI 0·64-0·79, p<0·0001). Any neonatal infection did not differ between treatment groups. Adverse events were not detected. INTERPRETATION:Among women planning vaginal delivery, this analysis provides evidence indicating that intrapartum azithromycin is associated with a lower incidence of maternal infections than placebo. FUNDING:The Eunice Kennedy Shriver National Institute of Child Health and Human Development and Bill and Melinda Gates Foundation via Foundation of National Institutes of Health. TRANSLATIONS:For the French and Spanish translations of the abstract see Supplementary Materials section.

Background The Azithromycin Prevention in Labor Use Study (A-PLUS), a large, multi-national randomized trial, was performed to evaluate the improvement of maternal and newborn outcomes following a single dose of azithromycin (AZ) given during labor. However, the immediate and long-term impact of this single dose on the microbiome and the development or prevalence of antimicrobial resistance are unknown. We designed a sub-study to assess AZ resistance of bacterial isolates from clinical infections and of three target bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli) from the serial surveillance of the nasopharynx and rectum. Additionally, the serially surveilled samples will be evaluated for changes to the microbiome and the resistome of the nasopharynx and rectum. Methods and Analysis As part of the large, randomized APLUS trial, maternal and neonatal clinical infections were monitored for up to 42 days postpartum, and samples collected for culture using site-specific routine methods. For this sub-study, cultured bacterial isolates will be assessed for AZ resistance using an antibiotic susceptibility method. Additionally, a random subset of maternal-neonatal dyads from the main trial will be selected for serial surveillance with aseptic swab collections of the nasopharynx and the rectum at baseline, and subsequently at 1-week, 6-weeks, 3-months, 6-months, and 12-months postpartum. The serial samples will undergo selective culturing of sentinel bacterial species and screened for AZ resistance. An additional set of serial samples will be stored for future microbiome and resistome analyses. Ethics and Dissemination The study protocol was reviewed, and ethics approval obtained from all the relevant ethical review boards at each research site. All participants will provide informed written consent prior to their enrollment. Results of the trial will be disseminated through peer-reviewed publications, presentations at relevant conferences, and at dissemination meetings with the ministries of health and local stakeholders at each research site. Trial Registration NCT03871491.

BACKGROUND:Sepsis is one of the leading causes of maternal mortality globally. In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin for women planning a vaginal birth reduced the risk of maternal sepsis or death and infection. We aimed to evaluate the cost-effectiveness of intrapartum azithromycin for pregnant people planning a vaginal birth in low-income and middle-income countries (LMICs) using A-PLUS trial data. METHODS:We compared the benefits and costs of intrapartum azithromycin versus standard care across 100 000 model simulations using data from the A-PLUS trial and a probabilistic decision tree model that included 24 mutually exclusive scenarios. A-PLUS was a randomised, double-blind, placebo-controlled trial that enrolled 29 278 women in labour at 28 weeks' gestation or more at eight sites in the Democratic Republic of the Congo, Kenya, Zambia, Bangladesh, India, Pakistan, and Guatemala. Women randomly assigned to azithromycin received a single intrapartum 2 g oral dose. In this cost-effectiveness analysis, we considered the cost of azithromycin treatment and its effects on a composite outcome of maternal infection, sepsis, or death and its individual components, and health-care use. Our analysis had a health-care sector perspective. We summarised results as an average and 95% CI of the model simulations. We also conducted sensitivity analyses. A-PLUS was registered at ClinicalTrials.gov, number NCT03871491. FINDINGS:In model simulations, intrapartum azithromycin resulted in 1592·0 (95% CI 1139·7 to 2024·1) cases of maternal infection, sepsis, or death averted per 100 000 pregnancies, yielding 248·5 (95·3 to 403·7) facility readmissions averted, 866·8 (537·8 to 1193·2) unplanned clinic visits averted, and 1816·2 (1324·5 to 2299·7) antibiotic regimens averted. Using mean health-care costs across the A-PLUS sites, intrapartum azithromycin resulted in net savings of US$32 661 (-52 218 to 118 210) per 100 000 pregnancies and 13·2 (8·3 to 17·9) disability-adjusted life-years averted. The cost of facility readmission, cost of azithromycin, and probability of infection had the greatest impact on the incremental cost. INTERPRETATION:In most cases, intrapartum azithromycin is a cost-saving intervention for the prevention of maternal infection, sepsis, or death in LMICs. This evidence supports global consideration of intrapartum azithromycin as an economically efficient preventive therapy to reduce infection, sepsis, or death among women planning a vaginal birth in LMICs. FUNDING:Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Foundation for the National Institutes of Health through the Maternal, Newborn, and Child Health Discovery and Tools Initiative of the Bill & Melinda Gates Foundation TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Improving neonatal resuscitation practices reduces neonatal mortality. In low- and middle-income countries (LMICs), granular details about provider actions during resuscitation are largely unknown; therefore, identifying targets for improvement is difficult. The International Liaison Committee on Resuscitation (ILCOR) recognizes the importance of uniform reporting of clinical neonatal resuscitation studies and published a guideline recommending specific variables to include. We established an open cohort study for newborn resuscitation in the Democratic Republic of the Congo (DRC) as a platform for developing and evaluating novel strategies to improve newborn resuscitation. We included all in-born neonates at two health facilities in Kinshasa, DRC. We gathered data on all enrollees via delivery registry and medical record abstraction. Using the Liveborn Observation app, we directly observed care at birth for a convenience sample. We collected heart rate data when providers used NeoBeat, a battery-operated heart rate meter. From September 2022 to August 2023, we abstracted delivery registry and medical record data for 6,414 newborns and gathered observational data on the infant's breathing status and provider actions for 3,166 (49%). Our dataset includes 85% of ILCOR's recommended core variables applicable to this setting, and 50% of ILCOR's applicable supplemental variables. Our registry also contains variables beyond those recommended by ILCOR that are contextually important for evaluating resuscitation care in LMICs such as duration of suctioning, pauses in positive pressure ventilation and fresh stillbirth. Our experience establishing a resuscitation registry with novel tools in the DRC serves as a model for resuscitation research in low-resource settings. Our cohort study provides important insight to inform subsequent versions of ILCOR's guideline on uniform reporting of neonatal resuscitations studies globally.

ObjectiveTo describe the intrapartum and postpartum use of non-study antibiotics in low- and middle-income countries (LMICs) during the double-blinded NICHD Global Network Azithromycin in Labor (A-PLUS) trial.DesignThe antibiotic use sub-study was a planned prospective, observational sub-study of the A-PLUS trial.SettingsThe study was carried out in hospitals or health centres affiliated with eight sites of the Global Network for Women's and Children's Health Research (Global Network) in seven countries: Bangladesh, Pakistan, India (two sites), Kenya, Zambia, The Democratic Republic of the Congo (DRC) and Guatemala.PopulationTotally, 29 278 pregnant women enrolled in the A-PLUS trial.MethodsWe collected data on 29 278 pregnant women admitted to a facility for delivery related to non-study antibiotic use overall and during three time periods: (1) in the facility prior to delivery, (2) after delivery until facility discharge and (3) after discharge to 42 days post-partum.Main Outcome MeasuresNon-study antibiotic use overall and for treatment or prophylaxis by the site during the three time periods.ResultsOf the 29 278 women in the study, 5020 (17.1%; 95% CI 16.7%-17.6%) received non-study antibiotics in the facility prior to delivery, 11 956 (40.8%; 95% CI 40.3%-41.4%) received non-study antibiotics in the facility after delivery, and 13 390 (47.6%; 95% CI 47.0%-48.2%) women received non-study antibiotics after delivery and after facility discharge. Antibiotics were prescribed more often among women in the Asian and Guatemalan sites than in the African sites. In the three time-periods, among those receiving antibiotics, prophylaxis was the indication in 82.3%, 97.7% and 90.7% of the cases, respectively. The type of antibiotics used varied substantially by time-period and site, but generally, penicillin-type drugs, cephalosporin-type drugs and metronidazole were used more frequently than other types.ConclusionsAcross the eight sites of the Global Network, in the facility before delivery, and in the post-partum periods before and after facility discharge, antibiotics were used frequently, but use was highly variable by site and time-period.

Background The Azithromycin Prevention in Labor Use Study (A-PLUS), a large, multi-national randomized trial, was performed to evaluate the improvement of maternal and newborn outcomes following a single dose of azithromycin (AZ) given during labor. However, the immediate and long-term impact of this single dose on the microbiome and the development or prevalence of antimicrobial resistance are unknown. We designed a sub-study to assess AZ resistance of bacterial isolates from clinical infections and of three target bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli) from the serial surveillance of the nasopharynx and rectum. Additionally, the serially surveilled samples will be evaluated for changes to the microbiome and the resistome of the nasopharynx and rectum. Methods and Analysis As part of the large, randomized APLUS trial, maternal and neonatal clinical infections were monitored for up to 42 days postpartum, and samples collected for culture using site-specific routine methods. For this sub-study, cultured bacterial isolates will be assessed for AZ resistance using an antibiotic susceptibility method. Additionally, a random subset of maternal-neonatal dyads from the main trial will be selected for serial surveillance with aseptic swab collections of the nasopharynx and the rectum at baseline, and subsequently at 1-week, 6-weeks, 3-months, 6-months, and 12-months postpartum. The serial samples will undergo selective culturing of sentinel bacterial species and screened for AZ resistance. An additional set of serial samples will be stored for future microbiome and resistome analyses. Ethics and Dissemination The study protocol was reviewed, and ethics approval obtained from all the relevant ethical review boards at each research site. All participants will provide informed written consent prior to their enrollment. Results of the trial will be disseminated through peer-reviewed publications, presentations at relevant conferences, and at dissemination meetings with the ministries of health and local stakeholders at each research site. Trial Registration NCT03871491.

Background Neonatal infections are a major public health concern worldwide, particularly in low- and middle-income countries, where most of the infection-related deaths in under-five children occur. Sub-Saharan Africa has the highest mortality rates, but there is a lack of data on the incidence of sepsis from this region, hindering efforts to improve child survival. We aimed to determine the incidence of possible serious bacterial infection (PSBI) in young infants in three high-burden countries in Africa. Methods This is a secondary analysis of data from the African Neonatal Sepsis (AFRINEST) trial, conducted in the Democratic Republic of the Congo (DRC), Kenya, and Nigeria between 15 March 2012 and 15 July 2013. We recorded baseline characteristics, the incidence of PSBI (as defined by the World Health Organization), and the incidence of local infections among infants from 0-59 days after birth. We report descriptive statistics. Results The incidence of PSBI among 0-59-dayold infants across all three countries was 11.2% (95% confidence interval (CI) = 11.0-11.4). The DRC had the highest incidence of PSBI (19.0%; 95% CI = 18.2-19.8). Likewise, PSBI rates were higher in low birth weight infants (24.5%; 95% CI = 23.1-26.0) and infants born to mothers aged <20 years (14.1%; 95% CI = 13.4-14.8). The incidence of PSBI was higher among infants delivered at home (11.7%; 95% CI = 11.4-12.0). Conclusions The high burden of PSBI among young infants in DRC, Kenya, and Nigeria demonstrates the importance of addressing PSBI in improving child survival in sub-Saharan Africa to reach the Sustainable Development Goals (SDGs). These data can support government authorities, policymakers, programme implementers, non-governmental organisations, and international partners in reducing preventable under-five deaths. Registration Australian New Zealand Clinical Trials Registry: ACTRN12610000286044.

BackgroundFew studies have assessed the impact of first-trimester malaria infection during pregnancy. We estimated this impact on adverse maternal and pregnancy outcomes.MethodsIn a convenience sample of women from the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial in Kenya, Zambia, and the Democratic Republic of the Congo, we tested for first-trimester Plasmodium falciparum infection using quantitative polymerase chain reaction. We estimated site-specific effects on pregnancy outcomes using parametric g-computation.ResultsCompared to uninfected women, we observed the adjusted site-specific prevalence differences (PDs) among women with first-trimester malaria of the following pregnancy outcomes: preterm birth among Congolese (aPD = 0.06 [99% CI: -0.04, 0.16]), Kenyan (0.03 [-0.04, 0.09]), and Zambian (0.00 [-0.10, 0.20]) women; low birth weight among Congolese (0.07 [-0.03, 0.16]), Kenyan (0.01 [-0.04, 0.06]) and Zambian (-0.04 [-0.13, 0.16]) women; spontaneous abortion among Congolese (0.00 [-0.05, 0.04]), Kenyan (0.00 [-0.04, 0.04]), and Zambian (0.02 [-0.07, 0.24]) women, and anemia later in pregnancy among Congolese (0.04 [-0.09, 0.16]), Kenyan (0.05 [-0.06, 0.17]), and Zambian (0.07 [-0.12, 0.36]) women. The pooled PD for anemia later in pregnancy (26-30 weeks) was 0.08 [99% CI: 0.00, 0.16].ConclusionsFirst-trimester malaria was associated with increased prevalence of anemia later in pregnancy. We identified areas for further investigation including effects of first-trimester malaria on preterm birth and low birth weight.

Multiple factors influence infant and child neurodevelopment in low resource settings. In offspring of participants in the preconception maternal nutrition trial, Women First (WF), we examined the impact of providing a preconception (Arm 1) or prenatal (Arm 2) nutrient supplement (compared to controls, Arm 3) on neurodevelopmental outcomes at 24 months; predictors of neurodevelopment scores; and associations of infant anthropometrics with neurodevelopmental scores. Follow‐up visits for anthropometry were conducted at 6‐, 12‐, 18‐ and 24‐month of age. At 24‐months, in a randomized subset, the Bayley Scales of Infant Development, 3rd edition (BSID‐III), including cognitive, motor and social‐emotional subscales, and the Family Care Indicators (FCI) questionnaire, assessing family and home environment, were completed. Multiple covariates (intervention arm, site, maternal sociodemographic characteristics, FCI subscales, birthweight and 6–24 months' change in anthropometry z‐scores, (e.g., ΔLAZ6–24) were evaluated by linear regression to predict BSID‐III outcomes and to assess associations of anthropometric changes with BSID‐III scores. The analysis consisted of 1386 infants (n = 441, 486, 459 for Arms 1, 2 and 3, respectively). None of the domain‐specific BSID‐III subscale scores differed by maternal intervention arm. Four covariates significantly predicted (p ≤ 0.01) all 3 BSID‐III subscales: secondary maternal education, ΔLAZ6–24, birthweight >2500 g, and FCI play materials. Linear growth was associated with all domains of neurodevelopment. The results underscore the multi‐dimensional aspects of child development represented by the nurturing care framework, including prenatal maternal nutrition, post‐natal growth, maternal education for responsive caregiving and opportunities for early learning.

OBJECTIVE: Because low-dose aspirin is now commonly prescribed in pregnancy, we sought to assess the association between early antenatal exposure and child neurodevelopment. METHODS: We performed a noninferiority, masked, neurodevelopmental follow-up study of children between age 33 and 39 months whose mothers had been randomized to daily low-dose aspirin (81 mg) or placebo between 6 0/7 and 13 6/7 weeks of gestation through 37 weeks. Neurodevelopment was assessed with the Bayley-III (Bayley Scales of Infant and Toddler Development, 3rd Edition) and the ASQ-3 (Ages and Stages Questionnaire, 3rd Edition). The primary outcome was the Bayley-III cognitive composite score with a difference within 4 points demonstrating noninferiority. RESULTS: A total of 640 children (329 in the low-dose aspirin group, 311 in the placebo group) were evaluated between September 2021 and June 2022. The Bayley-III cognitive composite score was noninferior between the two groups (−1, adjusted mean −0.8, 95% CI, −2.2 to 0.60). Significant differences were not seen in the language composite score (difference 0.7, 95% CI, −0.8 to 2.1) or the motor composite score (difference −0.6, 95% CI, −2.5 to 1.2). The proportion of children who had any component of the Bayley-III score lower than 70 did not differ between the two groups. Similarly, the communication, gross motor, fine motor, problem-solving, and personal–social components of the ASQ-3 did not differ between groups. Maternal characteristics, delivery outcomes, breastfeeding rates, breastfeeding duration, and home environment as measured by the Family Care Indicators were similar. CONCLUSION: Antenatal low-dose aspirin exposure was not associated with altered neurodevelopmental outcomes at age 3 years. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04888377.