Factors influencing the participation of pregnant and lactating women in clinical trials: A mixed-methods systematic review.

BACKGROUND: Poor representation of pregnant and lactating women and people in clinical trials has marginalised their health concerns and denied the maternal-fetal/infant dyad benefits of innovation in therapeutic research and development. This mixed-methods systematic review synthesised factors affecting the participation of pregnant and lactating women in clinical trials, across all levels of the research ecosystem. METHODS AND FINDINGS: We searched 8 databases from inception to 14 February 2024 to identify qualitative, quantitative, and mixed-methods studies that described factors affecting participation of pregnant and lactating women in vaccine and therapeutic clinical trials in any setting. We used thematic synthesis to analyse the qualitative literature and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. We compared quantitative data against the thematic synthesis findings to assess areas of convergence or divergence. We mapped review findings to the Theoretical Domains Framework (TDF) and Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to inform future development of behaviour change strategies. We included 60 papers from 27 countries. We grouped 24 review findings under 5 overarching themes: (a) interplay between perceived risks and benefits of participation in women's decision-making; (b) engagement between women and the medical and research ecosystems; (c) gender norms and decision-making autonomy; (d) factors affecting clinical trial recruitment; and (e) upstream factors in the research ecosystem. Women's willingness to participate in trials was affected by: perceived risk of the health condition weighed against an intervention's risks and benefits, therapeutic optimism, intervention acceptability, expectations of receiving higher quality care in a trial, altruistic motivations, intimate relationship dynamics, and power and trust in medicine and research. Health workers supported women's participation in trials when they perceived clinical equipoise, had hope for novel therapeutic applications, and were convinced an intervention was safe. For research staff, developing reciprocal relationships with health workers, having access to resources for trial implementation, ensuring the trial was visible to potential participants and health workers, implementing a woman-centred approach when communicating with potential participants, and emotional orientations towards the trial were factors perceived to affect recruitment. For study investigators and ethics committees, the complexities and subjectivities in risk assessments and trial design, and limited funding of such trials contributed to their reluctance in leading and approving such trials. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. CONCLUSIONS: This systematic review highlights diverse factors across multiple levels and stakeholders affecting the participation of pregnant and lactating women in clinical trials. By linking identified factors to frameworks of behaviour change, we have developed theoretically informed strategies that can help optimise pregnant and lactating women's engagement, participation, and trust in such trials.

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: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk 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-wk gestation and 3-mo postpartum, no statistical differences in mean SZC were observed among arms. At 34-wk, mean SZC for arms 1 and 2 were significantly higher than for 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-wk (<56 µg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 wk (<50 µg/dL), 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-mo postpartum (<66 µg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-wk 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 mo, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. This trial is registered at clinicaltrials.gov as #NCT01883193.

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.

Maternal and perinatal health research during emerging and ongoing epidemic threats: a landscape analysis and expert consultation.

INTRODUCTION: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner. METHODS: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of Science, Google Scholar and PubMed augmented by key informant interviews. Findings were reviewed and Quid analysis was performed to identify clusters and connectors across research networks followed by two expert consultations. These formed the basis for the development of an operational framework for maternal and perinatal research during epidemics. RESULTS: Ninety-four relevant research efforts were identified. Although well suited to generating epidemiological data, the entire infrastructure to support a robust research response remains insufficient, particularly for use of medical products in pregnancy. Limitations in global governance, coordination, funding and data-gathering systems have slowed down research responses. CONCLUSION: Leveraging current research efforts while engaging multinational and regional networks may be the most effective way to scale up maternal and perinatal research preparedness and response. The findings of this landscape analysis and proposed operational framework will pave the way for developing a roadmap to guide coordination efforts, facilitate collaboration and ultimately promote rapid access to countermeasures and clinical care for pregnant women and their offspring in future epidemics.

Tranexamic acid to reduce blood loss in women at high risk of postpartum hemorrhage undergoing cesarean delivery-a randomized controlled trial.

BACKGROUND: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. Tranexamic acid has proven to be useful in treating hemorrhage from acute blood loss. However, its role in preventing blood loss in women at high risk of postpartum hemorrhage undergoing cesarean delivery is not well studied. OBJECTIVE: This study aimed to assess the role of tranexamic acid in reducing blood loss during elective and unscheduled cesarean deliveries in women at high risk of postpartum hemorrhage. STUDY DESIGN: This was a prospective, placebo-controlled, randomized controlled trial from March 2021 to February 2022 at the Karnatak Lingayat Education Society Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, India. Women at a high risk of postpartum hemorrhage undergoing cesarean delivery were recruited and randomized to receive either tranexamic acid or placebo (1:1) at least 10 minutes before skin incision. High-risk factors for postpartum hemorrhage included obesity, hypertension, multiparity, previous cesarean delivery, multiple pregnancy, abnormally implanted placenta, placenta previa, abruption, uterine leiomyomas, polyhydramnios, and fetal macrosomia. The primary outcome was blood loss, calculated by a formula using pre- and postoperative hematocrit levels. In addition, gravimetrically measured blood loss was measured and compared between the 2 groups. RESULTS: A total of 212 women met the inclusion criteria and were randomized (tranexamic acid [n=106] and placebo [n=106]). The mean blood loss estimates were 400.9 mL in the tranexamic acid group and 597.9 mL in the placebo group (P<.001). The mean gravimetrically measured blood loss estimates were 379.2 mL in the tranexamic acid group and 431.1 mL in the placebo group (P<.001). In addition, there was a significant difference in the fall in hemoglobin levels (1.04 vs 1.61 g/dL) and change in hematocrit levels (3.20% vs 4.95%) from the pre- to postoperative period between the 2 groups (P<.001). No difference in the need for additional uterotonics (P=.26) or the need for postoperative parental iron (P=.18) was noted. No woman was transfused in either group. CONCLUSION: High-risk women receiving tranexamic acid had significantly less blood loss than women receiving placebo during cesarean delivery.

An integrated buoy-satellite based coastal water quality nowcasting system: India's pioneering efforts towards addressing UN ocean decade challenges.

The Indian coastal waters are stressed due to a multitude of factors, such as the discharge of industrial effluents, urbanization (municipal sewage), agricultural runoff, and river discharge. The coastal waters along the eastern and western seaboard of India exhibit contrasting characteristics in terms of seasonality, the magnitude of river influx, circulation pattern, and degree of anthropogenic activity. Therefore, understanding these processes and forecasting their occurrence is highly necessary to secure the health of coastal waters, habitats, marine resources, and the safety of tourists. This article introduces an integrated buoy-satellite based Water Quality Nowcasting System (WQNS) to address the unique challenges of water quality monitoring in Indian coastal waters and to boost the regional blue economy. The Indian National Centre for Ocean Information Services (INCOIS) has launched a first-of-its-kind WQNS, and positioned the buoys at two important locations along the east (Visakhapatnam) and west (Kochi) coast of India, covering a range of environmental conditions and tourist-intensive zones. These buoys are equipped with different physical-biogeochemical sensors, data telemetry systems, and integration with satellite-based observations for real-time data transmission to land. The sensors onboard these buoys continuously measure 22 water quality parameters, including surface current (speed and direction), salinity, temperature, pH, dissolved oxygen, phycocyanin, phycoerythrin, Coloured Dissolved Organic Matter, chlorophyll-a, turbidity, dissolved methane, hydrocarbon (crude and refined), scattering, pCO2 (water and air), and inorganic macronutrients (nitrite, nitrate, ammonium, phosphate, silicate). This real-time data is transmitted to a central processing facility at INCOIS, and after necessary quality control, the data is disseminated through the INCOIS website. Preliminary results from the WQNS show promising outcomes, including the short-term changes in the water column oxic and hypoxic regimes within a day in coastal waters off Kochi during the monsoon period, whereas effluxing of high levels of CO2 into the atmosphere associated with the mixing of water, driven by local depression in the coastal waters off Visakhapatnam. The system has demonstrated its ability to detect changes in the water column properties due to episodic events and mesoscale processes. Additionally, it offers valuable data for research, management, and policy development related to coastal water quality.

Infant and young child feeding indicators are positively associated with length and family care indicators in the children of the Women First trial participants.

This research describes the proportion of children in four low- and middle-income countries with adequate dietary practices at 6, 12, 18 and 24 months of age and how these practices changed over time using the World Health Organisation and UNICEF's infant young child feeding (IYCF) indicators. The associations between the IYCF indicators and anthropometric z-scores from 6 to 24 months, and between the IYCF indicators and the family care indicators (FCIs) at 24 months are described. This was a longitudinal study of offspring from participants in the Women First Preconception Maternal Nutrition Trial conducted in Sud-Ubangi, Democratic Republic of Congo; Chimaltenango, Guatemala; Belagavi, North Karnataka, India; and Thatta, Sindh Province, Pakistan. The frequency of the minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum adequate diet (MAD) increased between 6 and 24 months, but even at 24 months MAD remained below 50% at all sites. MDD (ß = 0.12; 95% CI = 0.04-0.22) and MMF (ß = 0.10; 95% CI = 0.03-0.17) were positively associated with length-for-age z-score at 24 months. All IYCF indicators were positively associated with mean total FCI score: MDD (proportion ratio [PR] = 1.04; 95% CI = 1.02-1.07), MMF (PR = 1.02; 95% CI = 1.01-1.04), MAD (PR = 1.05; 95% CI = 1.02-1.08). Although there are multiple barriers to young children having an adequate diet, our results support a positive association between familial interactions and improved IYCF feeding practices.

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.

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.

RAPIDIRON Trial follow-up study - the RAPIDIRON-KIDS Study: protocol of a prospective observational follow-up study.

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India's National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India Fact Sheet). In 2021, the parent RAPIDIRON Trial (Derman et al., Trials 22:649, 2021) was initiated in two states in India, with the goal of assessing whether a dose of intravenous (IV) iron given to anemic women during early pregnancy results in a greater proportion of participants with normal hemoglobin concentrations in the third trimester and a lower proportion of participants with LBW deliveries compared to oral iron. As a follow-up to the RAPIDIRON Trial, the RAPIDIRON-KIDS Study will follow the offspring of previously randomized mothers to assess, neurobehavioral, hematological, and health outcomes. METHODS: This prospective observational cohort study will follow a subset of participants previously randomized as part of the RAPIDIRON Trial and their newborns. Study visits occur at birth, 6 weeks, 4 months, 12 months, 24 months, and 36 months and include blood sample collection with both maternal and infant participants and specific neurobehavioral assessments conducted with the infants (depending on the study visit). The primary outcomes of interest are (1) infant iron status as indicated by both hemoglobin and ferritin (a) at birth and (b) at 4 months of age and (2) the developmental quotient (DQ) for the cognitive domain of the Bayley Scales of Infant Development Version IV (BSID-IV) at 24 months of age. DISCUSSION: This RAPIDIRON-KIDS Study builds upon its parent RAPIDIRON Trial by following a subset of the previously randomized participants and their offspring through the first 3 years of life to assess neurodevelopmental and neurobehavioral (infants, children), hematological, and health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05504863 , Registered on 17 August 2022. Clinical Trials Registry - India CTRI/2022/05/042933 . Registered on 31 May 2022.

The CryoPop study: Screening for high-grade cervical dysplasia in Karnataka, India.

OBJECTIVE: To describe our experience of screening with visual inspection with acetic acid (VIA) and colposcopy to identify women with high-grade precancerous cervical lesions who were candidates for cryotherapy. Women were screened to determine eligibility for a clinical trial testing the safety and efficacy of a new, simple and inexpensive cryotherapy device (CryoPop®) targeted for use in low and middle-income countries (LMICs). DESIGN: Prospective cohort study. SETTING: Primary and urban health centres in Belagavi, Hubballi and Vijayapur, India. POPULATION: Women in the age-group 30-49 years, premenopausal, with no prior hysterectomy and no known HIV infection were eligible for screening. METHODS: Visual inspection with acetic acid was performed on eligible women following informed consent. VIA-positive women were referred for colposcopy and biopsy. Biopsies were read by two pathologists independently, with a third pathologist acting as tie-breaker if needed. MAIN OUTCOME MEASURES: The primary outcome measures were the number/proportion of women screening positive by VIA and the number/proportion of those women screening VIA-positive found to have high-grade cervical lesions on biopsy (cervical intraepithelial neoplasia 2/3 [CIN 2/3]). Demographic variables were compared between women who screened VIA-positive and those who screened VIA-negative; a separate comparison of demographic and limited reproductive variables was performed between women who had CIN 2/3 on biopsy and those without CIN 2/3 on biopsy. Chi-square or Fisher's exact tests for categorical data and t-tests or analysis of variance for numeric data were used with all tests two-sided and performed at an alpha 0.05 level of statistical significance. RESULTS: A total of 9130 women were screened with VIA between 4 July 2020 and 31 March 2021. The mean age of all women screened was 37 years (standard deviation = 5.6 years) with 6073 of the women (66.5%) in the 30-39 year range. Only 1% of women reported prior cervical cancer screening. A total of 501 women (5.5%) were VIA-positive; of these, 401 women underwent colposcopy. Of those who had colposcopy, 17 (4.2%) had high-grade lesions on biopsy, an additional 164 (40.9%) had low-grade cervical lesions on biopsy or endocervical curettage and one woman (0.2%) was found to have invasive cancer. VIA-positive women were younger and had higher levels of education and income; however, women who were VIA-positive and found to have CIN 2/3 were older, were more likely to be housewives and had higher household income than those without CIN 2/3. CONCLUSION: Despite the COVID-19 pandemic, over 9100 women were screened with VIA for precancerous lesions. However, only 17 (4.2%) were found to have biopsy-proven high-grade cervical lesions, underscoring the subjective performance of VIA as a screening method. Given that this is significantly lower than rates reported in the literature, it is possible that the prevalence of high-grade lesions in this population was impacted by screening a younger and more rural population. This study demonstrates that screening is feasible in an organised fashion and can be scaled up rapidly. However, while inexpensive and allowing for same-day treatment, VIA may be too subjective and have insufficient accuracy clearly to identify lesions requiring treatment, particularly in low-prevalence and low-risk populations, calling into question its overall cost-effectiveness.

Facilitators, barriers, and key influencers of breastfeeding among low birthweight infants: a qualitative study in India, Malawi, and Tanzania.

BACKGROUND: Low birthweight (LBW) infants are at increased risk of morbidity and mortality. Exclusive breastfeeding up to six months is recommended to help them thrive through infection prevention, growth improvements, and enhancements in neurodevelopment. However, limited data exist on the feeding experiences of LBW infants, their caregivers and key community influencers. The qualitative component of the Low Birthweight Infant Feeding Exploration (LIFE) study aimed to understand practices, facilitators, and barriers to optimal feeding options in the first six months for LBW infants in low-resource settings. METHODS: This study was conducted in four sites in India, Malawi, and Tanzania from July 2019 to August 2020. We conducted 37 focus group discussions with mothers and family members of LBW infants and community leaders and 142 in-depth interviews with healthcare providers, government officials, and supply chain and donor human milk (DHM) experts. Data were analyzed using a framework approach. RESULTS: All participants believed that mother's own milk was best for LBW infants. Direct breastfeeding was predominant and feeding expressed breast milk and infant formula were rare. DHM was a new concept for most. Adequate maternal nutrition, lactation support, and privacy in the facility aided breastfeeding and expression, but perceived insufficient milk, limited feeding counseling, and infant immaturity were common barriers. Most believed that DHM uptake could be enabled through community awareness by overcoming misconceptions, safety concerns, and perceived family resistance. CONCLUSION: This study fills an evidence gap in LBW infant feeding practices and their facilitators and barriers in resource-limited settings. LBW infants face unique feeding challenges such as poor latching and tiring at the breast. Similarly, their mothers are faced with numerous difficulties, including attainment of adequate milk supply, breast pain and emotional stress. Lactation support and feeding counseling could address obstacles faced by mothers and infants by providing psychosocial, verbal and physical support to empower mothers with skills, knowledge and confidence and facilitate earlier, more and better breast milk feeding. Findings on DHM are critical to the future development of human milk banks and highlight the need to solicit partnership from stakeholders in the community and health system.

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.

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.

Correction: Short-Term Outcomes of Uncemented Bipolar Hemiarthroplasty Using Stainless Steel Fully Hydroxyapatite-Coated Stem in Transcervical Fracture of the Femur.

[This corrects the article DOI: 10.1007/s43465-023-00942-2.].

The Global Network COVID-19 studies: a review.

With the paucity of data available regarding COVID-19 in pregnancy in low- and middle-income countries (LMICs), near the start of the pandemic, the Global Network for Women's and Children's Health Research, funded by the National Institute of Child Health and Human Development (NICHD), initiated four separate studies to better understand the impact of the COVID-19 pandemic in eight LMIC sites. These sites included: four in Asia, in Bangladesh, India (two sites) and Pakistan; three in Africa, in the Democratic Republic of the Congo (DRC), Kenya and Zambia; and one in Central America, in Guatemala. The first study evaluated changes in health service utilisation; the second study evaluated knowledge, attitudes and practices of pregnant women in relationship to COVID-19 in pregnancy; the third study evaluated knowledge, attitude and practices related to COVID-19 vaccination in pregnancy; and the fourth study, using antibody status at delivery, evaluated changes in antibody status over time in each of the sites and the relationship of antibody positivity with various pregnancy outcomes. Across the Global Network, in the first year of the study there was little reduction in health care utilisation and no apparent change in pregnancy outcomes. Knowledge related to COVID-19 was highly variable across the sites but was generally poor. Vaccination rates among pregnant women in the Global Network were very low, and were considerably lower than the vaccination rates reported for the countries as a whole. Knowledge regarding vaccines was generally poor and varied widely. Most women did not believe the vaccines were safe or effective, but slightly more than half would accept the vaccine if offered. Based on antibody positivity, the rates of COVID-19 infection increased substantially in each of the sites over the course of the pandemic. Most pregnancy outcomes were not worse in women who were infected with COVID-19 during their pregnancies. We interpret the absence of an increase in adverse outcomes in women infected with COVID-19 to the fact that in the populations studied, most COVID-19 infections were either asymptomatic or were relatively mild.