Zinc supplementation initiated prior to or during pregnancy modestly impacted maternal status and high prevalence of hypozincemia in pregnancy and lactation: the Women First Preconception Maternal Nutrition Trial.

BACKGROUND: Data regarding effects of small quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: Evaluate the effect of preconception vs prenatal zinc supplementation (vs control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low resource settings, and to assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, Pakistan) of the Women First Preconception Nutrition trial, we compared SZC at 12- and 34-weeks gestation (n=651 and 838, respectively) and 3-months postpartum (n=742) in women randomized to daily SQ-LNS containing 15 mg zinc from ≥3 months prior to conception (preconception, Arm 1), from ∼12 weeks gestation through delivery (early pregnancy, Arm 2) or not at all (control, Arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point. RESULTS: At 12-weeks gestation and 3-months postpartum, no statistical differences in mean SZC were observed among arms. At 34-weeks, mean SZC for Arms 1 and 2 were significantly higher than Arm 3 (50.3, 50.8, 47.8 µg/dL respectively; P=0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-weeks (<56 µg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 weeks (<50 µg/dL) 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-months postpartum (<66 µg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-weeks was associated with lower birth length-for-age Z-scores (all sites P=0.013, Pakistan P=0.008) and weight-for-age Z-scores (all sites P=0.017, Pakistan P=0.022). CONCLUSIONS: Despite daily zinc supplementation for ≥7 months, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. CLINICAL TRIAL REGISTRATION: The study protocol is registered at ClinicalTrials.gov #NCT01883193 at https://clinicaltrials.gov/ct2/show/NCT01883193?term=01883193&rank=1 and the protocol is available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000057/.

Exploring gestational age, and birth weight assessment in Thatta district, Sindh, Pakistan: Healthcare providers' knowledge, practices, perceived barriers, and the potential of a mobile app for identifying preterm and low birth weight.

INTRODUCTION: Reliable methods for identifying prematurity and low birth weight (LBW) are crucial to ending preventable deaths in newborns. This study explored healthcare providers' (HCPs) knowledge, practice, perceived barriers in assessing gestational age and birth weight and their referral methods for preterm and LBW infants. The study additionally assessed the potential of using a mobile app for the identification and referral decision of preterm and LBW. METHODS: This qualitative descriptive study was conducted in Thatta District, Sindh, Pakistan. Participants, including doctors, nurses, lady health visitors, and midwives, were purposefully selected from a district headquarter hospital, and private providers in the catchment area of Global Network's Maternal and Newborn Health Registry (MNHR). Interviews were conducted using an interview guide after obtaining written informed consent. Audio recordings of the interviews were transcribed and analyzed using NVIVO® software with an inductive approach. RESULTS: The HCPs had extensive knowledge about antenatal and postnatal methods for assessing gestational age. They expressed a preference for antenatal ultrasound due to the perceived accuracy, though accept practical barriers including workload, machine malfunctions, and cost. Postnatal assessment using the Ballard score was only undertaken sparingly due to insufficient training and subjectivity. All HCPs preferred electronic weighing scales for birth weight Barriers encountered included weighing scale calibration and battery issues. There was variation in the definition of prematurity and LBW, leading to delays in referral. Limited resources, inadequate education, and negative parent past experiences were barriers to referral. Foot length measurements were not currently being used. While mobile apps are felt to have potential, unreliable electricity supply and internet connectivity are barriers. CONCLUSION: The HCPs in this study were knowledgeable in terms of potential tools, but acknowledged the logistical and parental barriers to implementation.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Predictors of Preterm Neonatal Mortality in India and Pakistan: A Secondary Analysis of Data from PURPOSe Study.

Objective. To create a prediction model for preterm neonatal mortality. Methods. A secondary analysis was conducted using data from a prospective cohort study, the Project to Understand and Research Preterm Pregnancy Outcome South Asia. The Cox proportional hazard model was used and adjusted hazard ratios (AHR) with 95% confidence intervals (95% CI) were reported. Results. Overall, 3446 preterm neonates were included. The mean age of preterm neonates was 0.65 (1.25) hours and 52% were female. The preterm neonatal mortality rate was 23.3%. The maternal factors predicting preterm neonatal death was any antepartum hemorrhage, AHR 1.99 (1.60-2.47), while neonatal predictors were preterm who received positive pressure ventilation AHR 1.30 (1.08-1.57), temperature <35.5°C AHR 1.18 (1.00-1.39), and congenital malformations AHR 3.31 (2.64-4.16). Conclusion. This study identified key maternal and neonatal predictors of preterm neonatal mortality, emphasizing the need for targeted interventions and collaborative public health efforts to address disparities and regional variations.

Diagnostic accuracy of foot length measurement for identification of preterm newborn in rural Sindh, Pakistan.

INTRODUCTION: Assessing gestational age accurately is crucial for saving preterm newborns. In low and middle-income countries, such as Pakistan, where access to antenatal ultrasonography (A-USG) is limited, alternative methods are needed. This study evaluated the diagnostic accuracy of foot length (FL) measurement for identifying preterm newborns in rural Pakistan using A-USG as the reference standard. METHODS: A test validation study was conducted between January and June 2023 in rural Sindh, Pakistan, within the catchment area of the Global Network for Maternal Newborn Health Registry, Thatta. Singleton newborns whose mothers had an A-USG before 20 weeks of gestation were enrolled. A research assistant measured FL three times using a rigid transparent plastic ruler within 48 hours of birth and the average FL was reported. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) and likelihood ratios were calculated. The optimal FL cut-off for the identification of preterm newborns was determined using the Youden Index. RESULTS: A total of 336 newborns were included in the final analysis, of whom 75 (22.3%) were born before 37 weeks of gestation. The median gestational age of the newborns was 38.2 weeks, and the median FL was 7.9 cm. The area under the curve was 97.6%. The optimal FL cut-off for identifying preterm newborns was considered as ≤7.6 cm with a sensitivity of 90.8%, specificity of 96.0%, PPV of 86.7% and NPV of 97.3%. A lower cut-off of ≤7.5 cm had a sensitivity of 95.4%, specificity of 84.0%, PPV of 63.1% and NPV of 98.5%. CONCLUSION: In conclusion, this study highlights the utility of FL measurement for identifying preterm newborns in rural settings where A-USG is unavailable before 20 weeks of gestation. Optimal cut-offs of ≤7.6 and ≤7.5 cm provide a simple, cost-effective and reliable tool for clinicians and frontline healthcare providers in rural areas, respectively. TRIAL REGISTRATION NUMBER: NCT05515211.

International progress on stillbirth reduction: Changes in Stillbirth Rates in Selected Low and Middle-Income Countries from 2000 to 2021.

In this paper, we attempted to determine if there were reductions in low and middle - income country stillbirth rates since 2000 - focusing on sub-Saharan Africa, Asia and Latin America and the Caribbean. We used data made available by the United Nations Inter-agency Group for Child Mortality Estimation and the World Health Organization as well as the National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research.. Overall, nearly every country evaluated had at least a small reduction in stillbirth rate from the year 2000 to 2021, but the reductions varied substantially between regions. Asia and Latin America/Caribbean had similar levels of reductions with a number of countries in each of those regions having rates in 2021 that were 40 % or more lower than those documented in 2000. No country in Africa documented a reduction in stillbirths of 40 % and many had stillbirth reductions of less than 15 %.

Neurodevelopment of Children Whose Mothers Were Randomized to Low-Dose Aspirin During Pregnancy.

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.

Neonatal Respiratory Support Utilization in Low- and Middle-Income Countries: A Registry-Based Observational Study.

BACKGROUND: Newborns with hypoxemia often require life-saving respiratory support. In low-resource settings, it is unknown if respiratory support is delivered more frequently to term infants or preterm infants. We hypothesized that in a registry-based birth cohort in 105 geographic areas in seven low- and middle-income countries, more term newborns received respiratory support than preterm newborns. METHODS: This is a hypothesis-driven observational study based on prospectively collected data from the Maternal and Newborn Health Registry of the NICHD Global Network for Women's and Children's Health Research. Eligible infants enrolled in the registry were live-born between 22 and 44 weeks gestation with a birth weight ≥400 g and born from January 1, 2015, to December 31, 2018. Frequency data were obtained to report the number of term and preterm infants who received treatment with oxygen only, CPAP, or mechanical ventilation. Test for trends over time were conducted using robust Poisson regression. RESULTS: 177,728 (86.3%) infants included in this study were term, and 28,249 (13.7%) were preterm. A larger number of term infants (n = 5,108) received respiratory support compared to preterm infants (n = 3,287). Receipt of each mode of respiratory support was more frequent in term infants. The proportion of preterm infants who received respiratory support (11.6%) was higher than the proportion of term infants receiving respiratory support (2.9%, p < 0.001). The rate of provision of respiratory support varied between sites. CONCLUSIONS: Respiratory support was more frequently used in term infants expected to be at low risk for respiratory disorders compared to preterm infants.

Understanding the Mechanisms of Change in the Supportive and Respectful Maternity Care Intervention in Sindh, Pakistan: Provider Perspectives.

INTRODUCTION: We conducted this qualitative investigation to explore the mechanisms of change in providing respectful care resulting from the supportive and respectful maternity care intervention (S-RMC) in Sindh, Pakistan. METHODS: We applied the principles of realist evaluation methodology with a descriptive explanatory research design. We conducted in-depth interviews with 36 maternity care providers at secondary-level public health facilities where S-RMC was implemented for 6 months. The S-RMC broad components included capacity-building of maternity teams and systemic changes for improvements in governance and accountability within public health facilities. Data were analyzed using a deductive content analysis approach. RESULTS: We identified mechanisms of change, categorized by the S-RMC components: (1) S-RMC training: insight into women's feelings and rights, realization of the value that nonclinical staff can play, understanding of team coordination, orientation in psychosocial components of maternity care; (2) assessment of women's psychosocial vulnerabilities: identification of women's differential needs beyond routine care to provide woman-centered care; (3) psychosocial support: effective engagement with women and within maternity teams and the customization of woman- and companion-focused care; (4) care coordination: improved coordination among clinical and nonclinical staff to provide personalized care and psychosocial support and proper handover to ensure continuity of care; (5) assessment of quality of care: identification of service gaps from women's feedback; and (6) performance review and accountability: monthly performance review meetings to establish team member communication, systematic awareness of the maternity team's performance and challenges, and implementation of collective corrective actions. CONCLUSION: Our findings pointed to S-RMC working along multiple pathways-and concertedly with various health system components-to enable positive processes and behavioral change in maternity teams.

Maternal age extremes and adverse pregnancy outcomes in low-resourced settings.

Introduction: Adolescent (<20 years) and advanced maternal age (>35 years) pregnancies carry adverse risks and warrant a critical review in low- and middle-income countries where the burden of adverse pregnancy outcomes is highest. Objective: To describe the prevalence and adverse pregnancy (maternal, perinatal, and neonatal) outcomes associated with extremes of maternal age across six countries. Patients and methods: We performed a historical cohort analysis on prospectively collected data from a population-based cohort study conducted in the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia between 2010 and 2020. We included pregnant women and their neonates. We describe the prevalence and adverse pregnancy outcomes associated with pregnancies in these maternal age groups (<20, 20-24, 25-29, 30-35, and >35 years). Relative risks and 95% confidence intervals of each adverse pregnancy outcome comparing each maternal age group to the reference group of 20-24 years were obtained by fitting a Poisson model adjusting for site, maternal age, parity, multiple gestations, maternal education, antenatal care, and delivery location. Analysis by region was also performed. Results: We analyzed 602,884 deliveries; 13% (78,584) were adolescents, and 5% (28,677) were advanced maternal age (AMA). The overall maternal mortality ratio (MMR) was 147 deaths per 100,000 live births and increased with advancing maternal age: 83 in the adolescent and 298 in the AMA group. The AMA groups had the highest MMR in all regions. Adolescent pregnancy was associated with an adjusted relative risk (aRR) of 1.07 (1.02-1.11) for perinatal mortality and 1.13 (1.06-1.19) for neonatal mortality. In contrast, AMA was associated with an aRR of 2.55 (1.81 to 3.59) for maternal mortality, 1.58 (1.49-1.67) for perinatal mortality, and 1.30 (1.20-1.41) for neonatal mortality, compared to pregnancy in women 20-24 years. This pattern was overall similar in all regions, even in the <18 and 18-19 age groups. Conclusion: The maternal mortality ratio in the LMICs assessed is high and increased with advancing maternal age groups. While less prevalent, AMA was associated with a higher risk of adverse maternal mortality and, like adolescence, was associated with adverse perinatal mortality with little regional variation.

Maternal and perinatal outcomes of women with vaginal birth after cesarean section compared to repeat cesarean birth in select South Asian and Latin American settings of the global network for women's and children's health research.

OBJECTIVE: Our objective was to analyze a prospective population-based registry including five sites in four low- and middle-income countries to observe characteristics associated with vaginal birth after cesarean versus repeat cesarean birth, as well as maternal and newborn outcomes associated with the mode of birth among women with a history of prior cesarean. HYPOTHESIS: Maternal and perinatal outcomes among vaginal birth after cesarean section will be similar to those among recurrent cesarean birth. METHODS: A prospective population-based study, including home and facility births among women enrolled from 2017 to 2020, was performed in communities in Guatemala, India (Belagavi and Nagpur), Pakistan, and Bangladesh. Women were enrolled during pregnancy, and delivery outcome data were collected within 42 days after birth. RESULTS: We analyzed 8267 women with a history of prior cesarean birth; 1389 (16.8%) experienced vaginal birth after cesarean, and 6878 (83.2%) delivered by a repeat cesarean birth. Having a repeat cesarean birth was negatively associated with a need for curettage (ARR 0.12 [0.06, 0.25]) but was positively associated with having a blood transfusion (ARR 3.74 [2.48, 5.63]). Having a repeat cesarean birth was negatively associated with stillbirth (ARR 0.24 [0.15, 0.49]) and, breast-feeding within an hour of birth (ARR 0.39 [0.30, 0.50]), but positively associated with use of antibiotics (ARR 1.51 [1.20, 1.91]). CONCLUSIONS: In select South Asian and Latin American low- and middle-income sites, women with a history of prior cesarean birth were 5 times more likely to deliver by cesarean birth in the hospital setting. Those who delivered vaginally had less complicated pregnancy and labor courses compared to those who delivered by repeat cesarean birth, but they had an increased risk of stillbirth. More large scale studies are needed in Low Income Country settings to give stronger recommendations. TRIAL REGISTRATION: NCT01073475, Registered February 21, 2010, https://clinicaltrials.gov/ct2/show/record/NCT01073475 .

Factors associated with continuation of hormonal contraceptives among married women of reproductive age in Gilgit, Pakistan: a community-based case-control study.

OBJECTIVE: This study aimed to determine the factors associated with continuation of hormonal contraceptive methods among married women of Gilgit, Pakistan at least 6 months after their initiation. DESIGN: Unmatched case-control study. SETTING: Community settings of Gilgit, Pakistan from 1 April 2021 to 30 July 2021. PARTICIPANTS: The cases were married women of reproductive age who, at the time of interview, were using a hormonal method of contraception for at least 6 months continuously, and controls were married women of reproductive age who had used a hormonal method in the past and currently were using a non-hormonal method for at least 6 months. PRIMARY AND SECONDARY OUTCOME MEASURES: OR for continuation of hormonal contraceptive. RESULTS: The factors significantly associated with continuous use of hormonal contraceptive methods for our sample from Gilgit were the family planning centre's distance from home (adjusted OR (AOR) 6.33, 95% CI 3.74 to 10.71), satisfaction with current method used (AOR 3.64, 95% CI 2.06 to 6.44), visits to the family planning centre to avail services (AOR 1.86, 95% CI 1.07 to 3.45) and relatively older age of women (AOR 1.07, 95% CI 1.02 to 1.12). In addition, women with formal education (AOR 0.27, 95% CI 0.12 to 0.6) were less likely to use a modern contraceptive method. CONCLUSION: Continuation of using a hormonal method was associated with easy access to family planning centres, satisfaction with the current method and frequent visits to the family planning centres. Continuation of using a hormonal method was also seen in women with low education status. The importance of the presence of family planning centres near residential areas cannot be emphasised more. This does not only provide easy access to family planning methods, but also reassure women of continuation of modern methods when they face any unpleasant effects while using these.

An approach to determining the most common causes of stillbirth in low and middle-income countries: A commentary.

Stillbirth, one of the most common adverse pregnancy outcomes, is especially prevalent in low and middle-income countries (LMICs). Understanding the causes of stillbirth is crucial to developing effective interventions. In this commentary, investigators working across several LMICs discuss the most useful investigations to determine causes of stillbirths in LMICs. Useful data were defined as 1) feasible to obtain accurately and 2) informative to determine or help eliminate a cause of death. Recently, new tools for LMIC settings to determine cause of death in stillbirths, including minimally invasive tissue sampling (MITS) - a method using needle biopsies to obtain internal organ tissue from deceased fetuses for histology and pathogen identification in those tissues have become available. While placental histology has been available for some time, the development of the Amsterdam Criteria in 2016 has provided a useful framework to categorize placental lesions. The authors recommend focusing on the clinical history, the placental evaluation, the external examination of the fetus, and, when available, fetal tissue obtained by MITS, especially of the lung (focused on histology and microbiology) and brain/cerebral spinal fluid (CSF) and fetal blood (focused on microbiological analysis). The authors recognize that this approach may not identify some causes of stillbirth, including some genetic abnormalities and internal organ anomalies, but believe it will identify the most common causes of stillbirth, and most of the preventable causes.

Placental inflammation and pregnancy outcomes: A prospective, observational study in South Asia: The PURPOSe study.

OBJECTIVE: To examine inflammatory lesions in placentas of stillbirths, preterm neonatal deaths and term controls in India and Pakistan. DESIGN: Prospective, observational study. SETTING: Three hospitals in India and a large maternity hospital in Pakistan. POPULATION: The enrolled participants with placentas available for histology evaluation included stillbirths (n = 814), preterm live births who died within 28 days of birth (n = 618) and term live birth controls (n = 201). From this same population, polymerase chain reaction (PCR) analysis for pathogens was performed on 809 stillbirth placentas, 614 neonatal death placentas and the placentas of 201 term controls. Placentas from preterm infants who lived beyond day 28 (n = 1432) were only available from India. METHODS: A prospective observational study of placental inflammatory lesions defined by the Amsterdam criteria and on the same placentas, multiplex PCR evaluation for 75 pathogens using TaqMan Array Cards. MAIN OUTCOME MEASURES: Any placental inflammatory lesions, including chorioamnionitis, funisitis, villitis and intervillitis and their association with various pathogens. RESULTS: In the Indian liveborn preterm infants, placental inflammation of any kind was present in 26.2% of those who died versus 16.6% of those who lived (p = 0.0002). Chorioamnionitis was present in 25.8% of those who died versus 16.3% of those who lived (p = 0.0002) and funisitis was present in 4.1% of those who died versus 1.5% of those who lived, (p = 0.005). Across all three sites, in the placentas of the 201 term controls, 18.9% had any inflammation, 16.9% had chorioamnionitis, 5.5% had funisitis, 0.5% had intervillitis and none had villitis. Overall, for stillbirths, any inflammation was observed in 30.2%, chorioamnionitis in 26.9%, funisitis in 5.7%, intervillitis in 6.0% and villitis in 2.2%. For the neonatal deaths, any inflammation was present in 24.9%, chorioamnionitis in 23.3%, funisitis in 8.1%, intervillitis in 1.9% and villitis in 0.5%. Compared with the placentas of term controls, in neonatal deaths, only chorioamnionitis was significantly increased (23.3% versus 16.9%, p = 0.05). Among stillbirths, the rates of any inflammation, chorioamnionitis, intervillitis and villitis were similar across the birthweight groups. However, funisitis was more common in the placentas of stillborn fetuses weighing 2500 g or more (13.8%) compared with 1.0% for those weighing less than 1000 g and 4.8% for stillborn fetuses weighing 1000-2499 g. In the PCR studies, Ureaplasma spp. were by far the most common pathogens found and generally were more commonly found in association with inflammatory lesions. CONCLUSIONS: Chorioamnionitis was the most common type of placental inflammatory lesion regardless of whether the placentas evaluated were from term controls, stillbirths or neonatal deaths. For stillbirths, inflammation in each inflammation category was more common than in the term controls and significantly more so for any inflammation, chorioamnionitis, intervillitis and villitis. For neonatal deaths, compared with the placentas of term controls, all inflammation categories were more common, but only significantly so for chorioamnionitis. Ureaplasma spp. were the most common organisms found in the placentas and were significantly associated with inflammation.

Can the date of last menstrual period be trusted in the first trimester? Comparisons of gestational age measures from a prospective cohort study in six low-income to middle-income countries.

OBJECTIVES: We examined gestational age (GA) estimates for live and still births, and prematurity rates based on last menstrual period (LMP) compared with ultrasonography (USG) among pregnant women at seven sites in six low-resource countries. DESIGN: Prospective cohort study SETTING AND PARTICIPANTS: This study included data from the Global Network's population-based Maternal and Newborn Health Registry which follows pregnant women in six low-income and middle-income countries (Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan and Zambia). Participants in this analysis were 42 803 women, including their 43 230 babies, who registered for the study in their first trimester based on GA estimated either by LMP or USG and had a live or stillbirth with an estimated GA of 20-42 weeks. OUTCOME MEASURES: GA was estimated in weeks and days based on LMP and/or USG. Prematurity was defined as GA of 20 weeks+0 days through 36 weeks+6 days, calculated by both USG and LMP. RESULTS: Overall, average GA varied ≤1 week between LMP and USG. Mean GA for live births by LMP was lower than by USG (adjusted mean difference (95% CI) = -0.23 (-0.29 to -0.17) weeks). Among stillbirths, a higher GA was estimated by LMP than USG (adjusted mean difference (95% CI)= 0.42 (0.11 to 0.72) weeks). Preterm birth rates for live births were significantly higher when dated by LMP (adjusted rate difference (95% CI)= 4.20 (3.56 to 4.85)). There was no significant difference in preterm birth rates for stillbirths. CONCLUSION: The small differences in GA for LMP versus USG in the Guatemalan and Indian sites suggest that LMP may be a useful alternative to USG for GA dating during the first trimester until availability of USG improves in those areas. Further research is needed to assess LMP for first-trimester GA dating in other regions with limited access to USG. TRIAL REGISTRATION NUMBER: NCT01073475.

Building a predictive model of low birth weight in low- and middle-income countries: a prospective cohort study.

BACKGROUND: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants. METHODS: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine. RESULTS: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) and approximately 20% (in each Asian site). Of the five models tested, the logistic regression model performed best with an area under the curve of 0.72, an accuracy of 61% and a recall of 72%. All of the top performing models identified clinical site, maternal weight, hypertensive disorders, severe antepartum hemorrhage and antenatal care as key variables in predicting LBW. CONCLUSIONS: Predictive modeling can identify women at high risk for delivering a LBW infant with good sensitivity using clinical variables available prior to delivery in LMICs. Such modeling is the first step in the development of a clinical decision support tool to assist providers in decision-making regarding referral of these women prior to delivery. Consistent referral of women at high-risk for delivering a LBW infant could have extensive public health consequences in LMICs by directing limited resources for advanced neonatal care to the infants at highest risk.

The impact of risk factors on aspirin's efficacy for the prevention of preterm birth.

BACKGROUND: The Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial was a landmark study that demonstrated a reduction in preterm birth and hypertensive disorders of pregnancy in nulliparous women who received low-dose aspirin. All women in the study had at least 1 moderate-risk factor for preeclampsia (nulliparity). Unlike current US Preventative Service Task Force guidelines, which recommend low-dose aspirin for ≥2 moderate-risk factors, women in this study were randomized to receive low-dose aspirin regardless of the presence or absence of an additional risk factor. OBJECTIVE: This study aimed to compare how low-dose aspirin differentially benefits nulliparous women with and without additional preeclampsia risk factors for the prevention of preterm birth and hypertensive disorders of pregnancy. STUDY DESIGN: This was a non-prespecified secondary analysis of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial that randomized nulliparous women with singleton pregnancies from 6 low-middle-income countries to receive low-dose aspirin or placebo. Our primary exposure was having an additional preeclampsia risk factor beyond nulliparity. Our primary outcome was preterm birth before 37 weeks of gestation, and our secondary outcomes included preterm birth before 34 weeks of gestation, preterm birth before 28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality. RESULTS: Among 11,558 nulliparous women who met the inclusion criteria, 66.8% had no additional risk factors. Low-dose aspirin similarly reduced the risk of preterm birth at <37 weeks of gestation in women with and without additional risk factors (relative risk: 0.75 vs 0.85; P=.35). Additionally for our secondary outcomes, low-dose aspirin similarly reduced the risk of preterm birth at <28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality in women with and without additional risk factors. The reduction of preterm birth at <34 weeks of gestation with low-dose aspirin was significantly greater in women without additional risk factors than those with an additional risk factor (relative risk: 0.69 vs 1.04; P=.04). CONCLUSION: Low-dose aspirin's ability to prevent preterm birth, hypertensive disorders of pregnancy, and perinatal mortality was similar in nulliparous women with and without additional risk factors. Professional societies should consider recommending low-dose aspirin to all nulliparous women.

Prevention of maternal and neonatal death/infections with a single oral dose of azithromycin in women in labour in low-income and middle-income countries (A-PLUS): a study protocol for a multinational, randomised placebo-controlled clinical trial.

INTRODUCTION: Maternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in preventing many of these deaths. A randomised clinical trial conducted in a single site in The Gambia showed that treatment with an oral dose of 2 g azithromycin versus placebo for all women in labour reduced certain maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. In a large, multinational randomised trial, we will evaluate the impact of azithromycin given in labour to improve maternal and newborn outcomes. METHODS AND ANALYSIS: This randomised, placebo-controlled, multicentre clinical trial includes two primary hypotheses, one maternal and one neonatal. The maternal hypothesis is to test whether a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labour will reduce maternal death or sepsis. The neonatal hypothesis will test whether this intervention will reduce intrapartum/neonatal death or sepsis. The intervention is a single, prophylactic intrapartum oral dose of 2 g azithromycin, compared with a single intrapartum oral dose of an identical appearing placebo. A total of 34 000 labouring women from 8 research sites in sub-Saharan Africa, South Asia and Latin America will be randomised with a one-to-one ratio to intervention/placebo. In addition, we will assess antimicrobial resistance in a sample of women and their newborns. ETHICS AND DISSEMINATION: The study protocol has been reviewed and ethics approval obtained from all the relevant ethical review boards at each research site. The results will be disseminated via peer-reviewed journals and national and international scientific forums. TRIAL REGISTRATION NUMBER: NCT03871491 (https://clinicaltrials.gov/ct2/show/NCT03871491?term=NCT03871491&draw=2&rank=1).