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Background Due to high fertility rates in some low and lower-middle income countries, the interval between pregnancies can be short, which may lead to adverse maternal and neonatal outcomes. Methods We analyzed data from women enrolled in the NICHD Global Network Maternal Newborn Health Registry (MNHR) from 2013 through 2018. We report maternal characteristics and outcomes in relationship to the inter-delivery interval (IDI, time from previous delivery [live or stillborn] to the delivery of the index birth), by category of 6–17 months (short), 18–36 months (reference), 37–60 months, and 61–180 months (long). We used non-parametric tests for maternal characteristics, and multivariable logistic regression models for outcomes, controlling for differences in baseline characteristics. Results We evaluated 181,782 women from sites in the Democratic Republic of Congo, Zambia, Kenya, Guatemala, India, and Pakistan. Women with short IDI varied by site, from 3% in the Zambia site to 20% in the Pakistan site. Relative to a 18–36 month IDI, women with short IDI had increased risk of neonatal death (RR = 1.89 [1.74, 2.05]), stillbirth (RR = 1.70 [1.56, 1.86]), low birth weight (RR = 1.38 [1.32, 1.44]), and very low birth weight (RR = 2.35 [2.10, 2.62]). Relative to a 18–36 month IDI, women with IDI of 37–60 months had an increased risk of maternal death (RR 1.40 [1.05, 1.88]), stillbirth (RR 1.14 [1.08, 1.22]), and very low birth weight (RR 1.10 [1.01, 1.21]). Relative to a 18–36 month IDI, women with long IDI had increased risk of maternal death (RR 1.54 [1.10, 2.16]), neonatal death (RR = 1.25 [1.14, 1.38]), stillbirth (RR = 1.50 [1.38, 1.62]), low birth weight (RR = 1.22 [1.17, 1.27]), and very low birth weight (RR = 1.47 [1.32,1.64]). Short and long IDIs were also associated with increased risk of obstructed labor, hemorrhage, hypertensive disorders, fetal malposition, infection, hospitalization, preterm delivery, and neonatal hospitalization. Conclusions IDI varies by site. When compared to 18–36 month IDI, women with both short IDI and long IDI had increased risk of adverse maternal and neonatal outcomes. Trial registration The MNHR is registered at NCT01073475.

OBJECTIVE: To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6 months postnatal age. STUDY DESIGN: The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation-initiated preconception (Arm 1) vs at ~11 weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6 months. We fitted longitudinal models on growth from birth to 6 months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates. RESULTS: Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15–0.35; P < .001) and 0.19 (95% CI 0.09–0.28; P < .001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ

Objective Approximately 10% of stillbirths are attributed to fetal anomalies, but anomalies are also common in live births. We aimed to assess the relationship between anomalies, by system and stillbirth. Design Secondary analysis of a prospective, case-control study. Setting Multicentre, 59 hospitals in five regional catchment areas in the USA. Population or sample All stillbirths and representative live birth controls. Methods Standardised postmortem examinations performed in stillbirths, medical record abstraction for stillbirths and live births. Main outcome measures Incidence of major anomalies, by type, compared between stillbirths and live births with univariable and multivariable analyses using weighted analysis to account for study design and differential consent. Results Of 465 singleton stillbirths included, 23.4% had one or more major anomalies compared with 4.3% of 1871 live births. Having an anomaly increased the odds of stillbirth; an increasing number of anomalies was more highly associated with stillbirth. Regardless of organ system affected, the presence of an anomaly increased the odds of stillbirth. These relationships remained significant if stillbirths with known genetic abnormalities were excluded. After multivariable analyses, the adjusted odds ratio (aOR) of stillbirth for any anomaly was 4.33 (95% CI 2.80-6.70) and the systems most strongly associated with stillbirth were cystic hygroma (aOR 29.97, 95% CI 5.85-153.57), and thoracic (aOR16.18, 95% CI 4.30-60.94) and craniofacial (aOR 35.25, 95% CI 9.22-134.68) systems. Conclusions In pregnancies affected by anomalies, the odds of stillbirth are higher with increasing numbers of anomalies. Anomalies of nearly any organ system increased the odds of stillbirth even when adjusting for gestational age and maternal race. Tweetable abstract Stillbirth risk increases with anomalies of nearly any organ system and with number of anomalies seen.

BackgroundAnemia is a major public health concern among women of reproductive age leading to high maternal mortality in low- and middle-income countries. Of the prior studies conducted in Pakistan, most focused on large urban areas and did not explore the determinants of anemia among women of reproductive age (WRA) across socio-demographic, dietary, reproductive, and biological domains. Thus, we aimed to study the prevalence and determinants of anemia among WRA in rural Pakistan.MethodsWe conducted a cross-sectional study in the Thatta district of Pakistan from September 2018 to January 2019 and enrolled 150 non-pregnant, married women. Data collectors administered a structured questionnaire to collect sociodemographic, reproductive and dietary data from women, who also provided stool and blood samples. We classified all WRA as anemic if their hemoglobin was ResultsIn our study, 61.3% of the enrolled women were anemic. In the multivariable analysis, we found that factors such as serum iron levels of less than 50 μg/dl (aOR: 7.17; 95% CI (2.94, 17.47)), history of breastfeeding (aOR: 2.43; 95% CI (1.04, 5.72)), living in a katcha house (aOR: 6.61; 95% CI (2.21, 19.87)), no consumption of meat (aOR: 4.18; 95% CI (1.66, 9.96)) were significantly associated with anemia among WRA. A history of more than one abortion (aOR: 0.06; 95% CI (0.01, 0.33) appeared protective for its association with anemia.ConclusionOur findings demonstrate a high burden of anemia and its complex determinants among WRA in rural Pakistan. A combination of nutritional and educational strategies should be designed to encourage rural women to consume iron-rich foods in their diet with an access to adequate food. Breastfeeding women should be encouraged to consume extra calories with sufficient intake of the food to continue exclusive breastfeeding and reserve the iron stores through amenorrhea to prevent themselves from becoming anemic.

Objective. To determine the hematologic profile of preterm infants with regard to different diseases. Methods. A prospective, cross-sectional, observational study, conducted in 5 hospitals in Ethiopia from July 2016 to May 2018. Preterm babies 3, and 159 340 cells/mm3, respectively. Early onset neonatal sepsis (EONS) 1433 (37%), asphyxia 266 (6.9%), and respiratory distress syndrome (RDS) 1738 (45.3%) were common reasons for admission. The WBC count was 3 for 8.8%, 9.0%, and 11.1% of neonates with EONS, asphyxia and RDS, respectively. The hemoglobin value was 3 for 16.8%, 17.7%, and 19.8% of preterms admitted with a diagnosis of EONS, asphyxia, and RDS, respectively. Conclusion. WBC and platelet counts were the most common to be associated with EONS, asphyxia, and RDS. Further study is recommended to determine the effect of abnormal hematologic profile on the outcome of preterm babies.

Background In Pakistan, there is a dearth of literature on the perceptions of anemia among women of reproductive age (WRA). This study was undertaken to explore the perceptions of women, their husbands, and healthcare providers about anemia, its possible causes, and how anemia impacts maternal and child health in Thatta, Pakistan. Methods A qualitative study was conducted in Thatta, Pakistan from September to December 2018. Using a pre-tested semi-structured interview (SSI), we collected data to understand their definitions of anemia through ten focus group discussions (FGDs) with women and their partners and ten primary informant interviews (KIIs) with healthcare providers. We identified six major themes: (I) Knowledge and awareness of anemia, (II) Causes and consequences of Anemia, (III) Dietary practices, (IV) Knowledge and practices regarding the use of iron-folic acid supplements, (V) Factors influencing prevention and control of anemia and (VI) Women’s health behavior. We analyzed the data through thematic analysis using NVivo 10 software. Results Most community members were not aware of the term anemia but described anemia as a condition characterized by ‘blood deficiency’ in the body. All study participants perceived anemia as an important health problem tending to cause adverse outcomes among WRA and their children. Study participants perceived gutka (chewable tobacco) consumption as an important cause of anemia. Healthcare providers identified short inter-pregnancy intervals, lack of family planning, poor health-seeking behavior, and consumption of unhealthy food as causes of anemia in the district. Consumption of unhealthy food might not be related to related to a poorer knowledge of iron-deficient foods, but economic constraints. This was further endorsed by the healthcare providers who mentioned that most women were too poor to afford iron-rich foods. All men and women were generally well versed with the sources of good nutrition to be consumed by WRA to prevent anemia. Conclusion The findings suggest that the government should plan to develop strategies for poverty-stricken and vulnerable rural women and plan health awareness programs to improve dietary practices, compliance with supplements, and health-seeking behavior among women of reproductive age. There is a need to develop effective counseling strategies and context-specific health education sessions to improve the health-seeking behavior of women and men in the Thatta district of Pakistan. Besides, there is need to address social determinants of health such as poverty that pushes women of poorer socioeconomic strata to eat less nutritious foods and have more anaemia. Therefore, a comprehensive and robust strategic plan need to be adopted by government that focuses not only on the awareness programs, but also aim to reduce inequities that lead to pregnant women eat iron-poor foods, which, in turn, forces them to become anemic.

BackgroundPreterm infants have high risk of developing growth restriction and long-term complications. Enteral feeding is often delayed in neonatal intensive care units (NICUs) for the fear of feeding intolerance and the associated necrotising enterocolitis, and recent advances in nutritional support are unavailable in low-income countries.ObjectiveThe aim of this study was to assess the incidence and associated factors of extrauterine growth restriction (EUGR) among preterm infants in selected NICUs in Ethiopia.MethodThis was a cross-sectional study involving a subgroup analysis of preterm infants admitted to hospitals, from a multicentre descriptive study of cause of illness and death in preterm infants in Ethiopia, conducted from 2016 to 2018. EUGR was defined as weight at discharge Z-scores ResultFrom 436 preterm infants included in the analysis, 223 (51%) were male, 224 (51.4%) very low birth weight (VLBW) and 185 (42.4%) small for gestational age (SGA). The mean (SD) of weight for corrected age Z-score at the time of discharge was −2.5 (1.1). The incidence of EUGR was 86.2%. Infants who were SGA, VLBW and longer hospital stay over 21 days had increased risk of growth restriction (p-valueConclusionThe majority of the infants had EUGR at the time of discharge from the hospital, which indicates suboptimal nutrition. Revision of national guidelines for preterm infants feeding and improvement in clinical practice is highly required.

In this issue of The Journal , Gibson, et al have demonstrated that certain subscales of the Multidimensional Health Assessment Questionnaire (MDHAQ) can be combined to provide clues to the diagnosis of comorbid fibromyalgia (FM) in patients with rheumatic diseases1. An FM assessment screening tool (FAST) compared favorably to the 2011 self-report FM criteria, developed for clinical and epidemiologic studies2, and both agreed moderately with the clinical diagnosis of FM. The authors suggest that because MDHAQ is already frequently used in rheumatology centers, adapting the FAST indices can alert clinicians to concurrent FM without adding new self-administered screening instruments. This paper also reconsiders a number of important issues involving rheumatologists and FM. First, rheumatologists have become more aware of the frequency and effect of FM in every rheumatic disease. Whether using the FAST indices, the 2011 FM criteria, or the gold standard (Dr. Gibson’s clinical diagnosis), FM was present in about 20–30% of patients with rheumatic disease. This is consistent with reports of FM in 13–40% of cases of rheumatoid arthritis (RA)3,4, 10–20% of osteoarthritis (OA)5, 10–30% with psoriatic arthritis or a spondyloarthropathy [SpA; such … Address correspondence to Dr. D.L. Goldenberg, 1125 NW 12th Ave., Unit 107, Portland, Oregon 97209, USA. E-mail: dongoldenberg44{at}gmail.com

The novel coronavirus, COVID-19, proliferates as a contagious psychological threat just like the physical disease itself. Due to the growing death toll and constant coverage this pandemic gets, it is likely to activate mortality awareness, to greater or lesser extents, depending on a variety of situational factors. Using terror management theory and the terror management health model, we outline reactions to the pandemic that consist of proximal defences aimed at reducing perceived vulnerability to (as well as denial of) the threat, and distal defences bound by ideological frameworks from which symbolic meaning can be derived. We provide predictions and recommendations for shifting reactions to this pandemic towards behaviours that decrease, rather than increase, the spread of the virus. We conclude by considering the benefits of shifting towards collective mindsets to more effectively combat COVID-19 and to better prepare for the next inevitable pandemic.

PurposeThe aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age.MethodWe compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study ‘Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)’. Data were analysed using SPSS V.23. ORs and 95% CIs and χ2tests were done, p value of ResultThe majority of the infants (1194, 89%) were moderate to late preterm (32–36 weeks of gestation), 763 (57%) were females. Male preterm infants had higher risk of being SGA than female infants (pConclusionNeonatal complications such as hypoglycaemic, NEC, LOS, polycythaemia and prolonged hospitalisation are more common in SGA infants, while rates of RDS and mortality are similar in SGA and AGA groups. Early recognition of SGA status, high index of suspicion and screening for complications associated and timely intervention to prevent complications need due consideration.

Uncertainty about the causes of neonatal deaths impedes achieving global health targets to reduce mortality. Complete diagnostic autopsy (CDA) is the gold standard to determine cause of death. However, it is often difficult to perform in high-burden, low-income settings. Validations of more feasible methods to determine cause of death are needed. This prospective, multi-center study in Ethiopia assessed the validity of the minimally invasive tissue sampling (MITS) approach to contribute to causes of death in preterm neonates compared to CDA. The MITS and CDA of 105 cases were reviewed. The MITS sampling success for lungs and liver was 100% and 84%, respectively. The kidney and brain had sampling successes of 58% each. MITS showed good agreement with CDA for the diagnosis of hyaline membrane disease (kappa = 0.78), and moderate to substantial agreement for pneumonia and pulmonary hemorrhage (kappa = 0.59 and 0.68, respectively). Even though CDA is the gold standard in identifying the cause of death, we believe that the MITS method can be a useful alternative method in supporting determination of cause of death in low-resource settings.

Objective Umbilical cord abnormalities are commonly cited as a cause of stillbirth, but details regarding these stillbirths are rare. Our objective was to characterize stillbirths associated with umbilical cord abnormalities using rigorous criteria and to examine associated risk factors. Methods The Stillbirth Collaborative Research Network conducted a case-control study of stillbirth and live births from 2006 to 2008. We analyzed stillbirths that underwent complete fetal and placental evaluations and cause of death analysis using the INCODE (Initial Causes of Fetal Death) classification system. Umbilical cord abnormality was defined as cord entrapment (defined as nuchal, body, shoulder cord accompanied by evidence of cord occlusion on pathologic examination); knots, torsions, or strictures with thrombi, or other obstruction by pathologic examination; cord prolapse; vasa previa; and compromised fetal microcirculation, which is defined as a histopathologic finding that represents objective evidence of vascular obstruction and can be used to indirectly confirm umbilical cord abnormalities when suspected as a cause for stillbirth. We compared demographic and clinical factors between women with stillbirths associated with umbilical cord abnormalities and those associated with other causes, as well as with live births. Secondarily, we analyzed the subset of pregnancies with a low umbilical cord index. Results Of 496 stillbirths with complete cause of death analysis by INCODE, 94 (19%, 95% CI 16-23%) were associated with umbilical cord abnormality. Forty-five (48%) had compromised fetal microcirculation, 27 (29%) had cord entrapment, 26 (27%) knots, torsions, or stricture, and five (5%) had cord prolapse. No cases of vasa previa occurred. With few exceptions, maternal characteristics were similar between umbilical cord abnormality stillbirths and non-umbilical cord abnormality stillbirths and between umbilical cord abnormality stillbirths and live births, including among a subanalysis of those with hypo-coiled umbilical cords. Conclusion Umbilical cord abnormalities are an important risk factor for stillbirth, accounting for 19% of cases, even when using rigorous criteria. Few specific maternal and clinical characteristics were associated with risk.

Background Oligohydramnios is a condition of abnormally low amniotic fluid volume that has been associated with poor pregnancy outcomes. To date, the prevalence of this condition and its outcomes has not been well described in low and low-middle income countries (LMIC) where ultrasound use to diagnose this condition in pregnancy is limited. As part of a prospective trial of ultrasound at antenatal care in LMICs, we sought to evaluate the incidence of and the adverse maternal, fetal and neonatal outcomes associated with oligohydramnios. Methods We included data in this report from all pregnant women in community settings in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo (DRC) who received a third trimester ultrasound as part of the First Look Study, a randomized trial to assess the value of ultrasound at antenatal care. Using these data, we conducted a planned secondary analysis to compare pregnancy outcomes of women with to those without oligohydramnios. Oligohydramnios was defined as measurement of an Amniotic Fluid Index less than 5 cm in at least one ultrasound in the third trimester. The outcomes assessed included maternal morbidity and fetal and neonatal mortality, preterm birth and low-birthweight. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models using general estimating equations to account for the correlation of outcomes within cluster. Results Of 12,940 women enrolled in the clusters in Guatemala, Pakistan, Zambia and the DRC in the First Look Study who had a third trimester ultrasound examination, 87 women were diagnosed with oligohydramnios, equivalent to 0.7% of those studied. Prevalence of detected oligohydramnios varied among study sites; from the lowest of 0.2% in Zambia and the DRC to the highest of 1.5% in Pakistan. Women diagnosed with oligohydramnios had higher rates of hemorrhage, fetal malposition, and cesarean delivery than women without oligohydramnios. We also found unfavorable fetal and neonatal outcomes associated with oligohydramnios including stillbirths (OR 5.16, 95%CI 2.07, 12.85), neonatal deaths Conclusions Oligohydramnos was associated with worse neonatal, fetal and maternal outcomes in LMIC. Further research is needed to assess effective interventions to diagnose and ultimately to reduce poor outcomes in these settings. Trial registration NCT01990625.

Objectives To assess deviations in longitudinally measured cytokines with preterm birth (PTB). Methods Prospective longitudinal study targeting 80 subjects. Phlebotomy specimens for broad panel of cytokine analysis were obtained at three time (T) intervals: first trimester (T1: 8–14 weeks’ gestation), second trimester (T2: 18–22 weeks’ gestation), and third trimester (T3: 28–32 weeks’ gestation). Important demographics and outcomes were tracked. Data were stratified and the target groups were analyzed as follows: “Uncomplicated” (delivered ≥37 weeks) or “Preterm Birth” ( Results Complete data replete with phlebotomy at all three visits were obtained on 80 women. Birth outcomes were as follows: 11 Uncomplicated Term Birth (UTB), 28 PTB, 4 low birth weight (LBW), 16 OB complications (OBC), 11 current infections (IFN), and 10 mixed complications (MC=2 or more of the above). 28 PTB were compared to 11 uncomplicated term deliveries. In both groups, T helper type 1 (TH1) cytokine (IL-1β), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over gestation, but rates of change in IL-1β, IL-6, and IL-10 were significantly different. Stratification of women by smoking status additionally demonstrated significant variance in immune status over the course of pregnancy Conclusions Women delivering PTB demonstrated significant differences in cytokine trajectory over pregnancy; these data further validate key role played by immune regulation in directing pregnancy outcome. Likewise, smoking impacts longitudinal trajectory of cytokines over pregnancy.

Globally, more than 5 million stillbirths and neonatal deaths occur annually. For many, the cause of death (CoD) is unknown. Minimally invasive tissue sampling (MITS) has been increasingly used in postmortem examinations for ascertaining the CoD in stillbirths and neonates. Our study compared the counseling and consent methods used in MITS projects in five countries in Africa and south Asia. Key informant interviews were conducted with researchers to describe the characteristics and backgrounds of counselors, the environment and timing of consent and perceived facilitators and barriers encountered during the consent process. Counselors at all sites had backgrounds in social science, psychology and counseling or clinical expertise in obstetrics/gynecology or pediatrics. All counsellors received training about techniques for building rapport and offering emotional support to families; training duration and methods differed across sites. Counselling environments varied significantly; some sites allocated a separate room, others counselled families at the bedside or nursing stations. All counsellors had a central role in explaining the MITS procedure to families in their local languages. Most sites did not use visual aids during the process, relying solely on verbal descriptions. In most sites, parents were approached within one hour of death. The time needed for decision making by families varied from a few minutes to 24 h. In most sites, extended family took part in the decision making. Because many parents wanted burial as soon as possible, counsellors ensured that MITS would be conducted promptly after receiving consent. Barriers to consent included decreased comprehension of information due to the emotional and psychological impact of grief. Moreover, having more family members engaged in decision-making increased the complexity of counselling and achieving consensus to consent for the procedure. While each site adapted their approach to fit the context, consistencies and similarities across sites were observed.

BackgroundTo determine the gender differences in neonatal mortality, stillbirths, and perinatal mortality in south Asia using the Global Network data from the Maternal Newborn Health Registry.MethodsThis study is a secondary analysis of prospectively collected data from the three south Asian sites of the Global Network. The maternal and neonatal demographic, clinical characteristics, rates of stillbirths, early neonatal mortality (1–7 days), late neonatal mortality (8–28 days), mortality between 29–42 days and the number of infants hospitalized after birth were compared between the male and female infants.ResultsBetween 2010 and 2018, 297,509 births [154,790 males (52.03%) and 142,719 females (47.97%)] from two Indian sites and one Pakistani site were included in the analysis [288,859 live births (97.1%) and 8,648 stillbirths (2.9%)]. The neonatal mortality rate was significantly higher in male infants (33.2/1,000 live births) compared to their female counterparts (27.4/1,000, p ConclusionThe risks of stillbirths, and early neonatal mortality were higher among male infants than their female counterparts. However, there was no gender difference in mortality after 7 days of age. Our results highlight the importance of stratifying neonatal mortality into early and late neonatal period to better understand the impact of gender on neonatal mortality. The information from this study will help in developing strategies and identifying measures that can reduce differences in sex-specific mortality.

Background. Globally, prematurity is the leading cause of neonatal mortality, and hypothermia is one of its contributing factors. The goal of this study was to determine the association between hypothermia and mortality. Methods. A prospective, multi-center, descriptive clinical study was conducted in 5 hospitals in Ethiopia. Axillary temperatures were taken at the time of admission to the newborn intensive care units (NICU) and followed during the NICU stay. Results. A total of 3852 premature neonates (

Background The objectives of this analysis were to document trends in and risk factors associated with the cesarean birth rate in low- and middle-income country sites participating in the Global Network for Women’s and Children’s Health Research (Global Network). Methods This is a secondary analysis of a prospective, population-based study of home and facility births conducted in the Global Network sites. Results Cesarean birth rates increased uniformly across all sites between 2010 and 2018. Across all sites in multivariable analyses, women younger than age twenty had a reduced risk of cesarean birth (RR 0.9 [0.9, 0.9]) and women over 35 had an increased risk of cesarean birth (RR 1.1 [1.1, 1.1]) compared to women aged 20 to 35. Compared to women with a parity of three or more, less parous women had an increased risk of cesarean (RR 1.2 or greater [1.2, 1.4]). Four or more antenatal visits (RR 1.2 [1.2, 1.3]), multiple pregnancy (RR 1.3 [1.3, 1.4]), abnormal progress in labor (RR 1.1 [1.0, 1.1]), antepartum hemorrhage (RR 2.3 [2.0, 2.7]), and hypertensive disease (RR 1.6 [1.5, 1.7]) were all associated with an increased risk of cesarean birth, p Conclusion Cesarean birth rates continue to rise within the Global Network. The proportions of cesarean birth are higher among women with no history of cesarean birth in the African sites and among women with primary elective cesarean, primary cesarean after induction, and repeat cesarean in the non-African sites.

Background Nulliparity has been associated with lower birth weight (BW) and other adverse pregnancy outcomes, with most of the data coming from high-income countries. In this study, we examined birth weight for gestational age z-scores and neonatal (28-day) mortality in a large prospective cohort of women dated by first trimester ultrasound from multiple sites in low and middle-income countries. Methods Pregnant women were recruited during the first trimester of pregnancy and followed through 6 weeks postpartum from Maternal Newborn Health Registry (MNHR) sites in the Democratic Republic of Congo (DRC), Guatemala, Belagavi and Nagpur, India, and Pakistan from 2017 and 2018. Data related to the pregnancy and its outcomes were collected prospectively. First trimester ultrasound was used for determination of gestational age; (BW) was obtained in grams within 48 h of delivery and later transformed to weight for age z-scores (WAZ) adjusted for gestational age using the INTERGROWTH-21st standards. Results 15,121 women were eligible and included. Infants of nulliparous women had lower mean BWs (males: 2676 gr, females: 2587 gr, total: 2634 gr) and gestational age adjusted weight for age z-scores (males: − 0.73, females: − 0.77, total: − 0.75,) than women with one or more previous pregnancies. The largest differences were between zero and one previous pregnancies among female infants. The associations of parity with BW and z-scores remained even after adjustment for maternal age, maternal height, maternal education, antenatal care visits, hypertensive disorders, and socioeconomic status. Nulliparous women also had a significantly higher Conclusions In this large sample from diverse settings, nulliparity was independently associated with both lower BW and WAZ scores as well as higher neonatal mortality compared to multiparity.

South Asia has >50% of the global burden of low birth weight (LBW). The objective was to determine the extent to which maternal nutrition interventions commenced before conception or in the 1st trimester improved fetal growth in this region. This was a secondary analysis of combined newborn anthropometric data for the South Asian sites (India and Pakistan) in the Women First Preconception Maternal Nutrition Trial. Participants were 972 newborn of mothers who were poor, rural, unselected on basis of nutritional status, and had been randomized to receive a daily lipid-based micronutrient supplement commencing ≥3 months prior to conception (Arm 1), in the 1st trimester (Arm 2), or not at all (Arm 3). An additional protein-energy supplement was provided if BMI

Placental surface area is often estimated using diameter measurements. However, as many placentas are not elliptical, we were interested in the validity of these estimates. We compared placental surface area from images for 491 singletons from the Stillbirth Collaborative Research Network (SCRN) Study (416 live births, 75 stillbirths) to estimates obtained using diameter measurements. Placental images and diameters were obtained from pathologic assessments conducted for the SCRN Study and images were analyzed using ImageJ software. On average, diameter-based measures underestimated surface area by −5.58% (95% confidence interval: −30.23, 19.07); results were consistent for normal and abnormal shapes. The association between surface area and birthweight was similar for both measures. Thus, diameter-based surface area can be used to estimate placental surface area.

OBJECTIVE: To better characterize infection stillbirth in terms of pathogenesis and microbiology. METHODS: We conducted a secondary analysis of 512 stillbirths in a prospective, multisite, geographically, racially and ethnically diverse, population-based study of stillbirth in the United States. Cases underwent evaluation that included maternal interview, chart abstraction, biospecimen collection, fetal autopsy, and placental pathology. Recommended evaluations included syphilis and parvovirus serology. Each case was assigned probable and possible causes of death using the INCODE Stillbirth Classification System. Cases where infection was assigned as a probable or possible cause of death were reviewed. For these cases, clinical scenario, autopsy, maternal serology, culture results and placental pathology were evaluated. RESULTS: For 66 (12.9%) cases of stillbirth, infection was identified as a probable or possible cause of death. Of these, 36% (95% CI 35% - 38%) were categorized as a probable and 64% (95% CI 62% - 65%) as a possible cause of death. Infection-related stillbirth occurred earlier than non-infection related stillbirth (median gestational age 22 weeks vs 28 weeks, p= 0.001). Fetal bacterial culture results were available in 47 cases (71%), of which 35 (53%) grew identifiable organisms. The predominant species were Escherichia coli (19; 29%), group B streptococcus (8; 12%), and enterococcus (8; 12%). Placental pathology revealed chorioamnionitis in 50 (76%), funisitis in 27 (41%), villitis in 11 (17%), deciduitis in 35 (53%), necrosis in 27 (41%), and viral staining in 7 (11%) cases. Placental pathology found inflammation or evidence of infection in 65 (99%) cases and fetal autopsy in 26 (39%) cases. In infection stillbirth cases, the likely causative non-bacterial organisms identified were parvovirus in 2 (3%) cases, syphilis in 1 (2%) case, cytomegalovirus in 5 (8%) cases and herpes in 1 (2%) case. CONCLUSIONS: Of infection-related stillbirth cases in a large U.S. cohort, E. coli, group B streptococcus and enterococcus were the most common bacterial pathogens and cytomegalovirus the most common viral pathogen.

Accurate knowledge regarding cause of death (COD) for stillbirths and neonatal deaths is crucial, especially in low-income countries, in order for public health and medical officials to choose appropriate interventions likely to reduce these deaths. To date, many of the COD studies in these areas have relied only on obstetric or neonatal clinical information and the determination of COD is likely to be inaccurate. Information related to infectious COD is especially lacking. Thus, without more sophisticated testing, data as currently collected only provide a very weak approximation of the COD and may well lead to adoption of interventions of limited usefulness. In this commentary, we propose recommendations regarding the type of data needed to determine with reasonable accuracy the COD for stillbirths and neonatal deaths in low-resource settings. Using these data, and a method to determine the degree of certainty, we then propose definitions for the most common COD. Our goal is to reduce subjectivity and provide more specificity for the tests used in existing classification systems so that the methodology of COD determination is transparent and able to be replicated over time and from location to location.

Background There is limited information on potentially modifiable risk factors for stillbirth, such as gestational weight gain (GWG). Our purpose was to explore the association between GWG and stillbirth using the GWG z−score. Methods We analyzed 479 stillbirths and 1601 live births from the Stillbirth Collaborative Research Network case−control study. Women with triplets or monochorionic twins were excluded from analysis. We evaluated the association between GWG z−score (modeled as a restricted cubic spline with knots at the 5th, 50th, and 95th percentiles) and stillbirth using multivariable logistic regression with generalized estimating equations, adjusting for pre − pregnancy body mass index (BMI) and other confounders. In addition, we conducted analyses stratified by pre − pregnancy BMI category (normal weight, overweight, obese). Results Mean GWG was 18.95 (SD 17.6) lb. among mothers of stillbirths and 30.89 (SD 13.3) lb. among mothers of live births; mean GWG z−score was − 0.39 (SD 1.5) among mothers of cases and − 0.17 (SD 0.9) among control mothers. In adjusted analyses, the odds of stillbirth were elevated for women with very low GWG z−scores (e.g., adjusted odds ratio (aOR) and 95% Confidence Interval (CI) for z−score − 1.5 SD versus 0 SD: 1.52 (1.30, 1.78); aOR (95% CI) for z−score − 2.5 SD versus 0 SD: 2.36 (1.74, 3.20)). Results differed slightly by pre − pregnancy BMI. The odds of stillbirth were slightly elevated among women with overweight BMI and GWG z−scores ≥1 SD (e.g., aOR (95% CI) for z−score of 1.5 SD versus 0 SD: 1.84 (0.97, 3.50)). Conclusions GWG z−scores below − 1.5 SD are associated with increased odds of stillbirth.

The placenta plays a critical role in regulating fetal growth. Recent studies suggest that there may be sex-specific differences in placental development. The purpose of our study was to evaluate the associations between birthweight and placental morphology in models adjusted for covariates and to assess sex-specific differences in these associations. We analyzed data from the Stillbirth Collaborative Research Network's population-based case–control study conducted between 2006 and 2008, which recruited cases of stillbirth and population-based controls in 5 states. Our analysis was restricted to singleton live births with a placental examination (n = 1229). Characteristics of placental morphology evaluated include thickness, surface area, difference in diameters, shape, and umbilical cord insertion site. We used linear regression to model birthweight as a function of placental morphology and covariates. Surface area had the greatest association with birthweight; a reduction in surface area of 83 cm2, which reflects the interquartile range, is associated with a 260.2-g reduction in birthweight (95% confidence interval, −299.9 to −220.6), after adjustment for other features of placental morphology and covariates. Reduced placental thickness was also associated with lower birthweight. These associations did not differ between males and females. Our results suggest that reduced placental thickness and surface area are independently associated with lower birthweight and that these relationships are not related to sex.

Background Participation in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) has been associated with lower risk of stillbirth. We hypothesized that such an association would differ by race/ethnicity because of factors associated with WIC participation that confound the association. Methods We conducted a secondary analysis of the Stillbirth Collaborative Research Network’s population-based case-control study of stillbirths and live-born controls, enrolled at delivery between March 2006 and September 2008. Weighting accounted for study design and differential consent. Five nested models using multivariable logistic regression examined whether the WIC participation/stillbirth associations were attenuated after sequential adjustment for sociodemographic, health, healthcare, socioeconomic, and behavioral factors. Models also included an interaction term for race/ethnicity x WIC. Results In the final model, WIC participation was associated with lower adjusted odds (aOR) of stillbirth among non-Hispanic Black women (aOR: 0.34; 95% CI 0.16, 0.72) but not among non-Hispanic White (aOR: 1.69; 95% CI: 0.89, 3.20) or Hispanic women (aOR: 0.91; 95% CI 0.52, 1.52). Conclusions Contrary to our hypotheses, control for potential confounding factors did not explain disparate findings by race/ethnicity. Rather, WIC may be most beneficial to women with the greatest risk factors for stillbirth. WIC-eligible, higher-risk women who do not participate may be missing the potential health associated benefits afforded by WIC. Electronic supplementary material The online version of this article (10.1186/s12884-018-1920-0) contains supplementary material, which is available to authorized users.

Antenatal corticosteroids are standard of care for pregnancies at risk of preterm delivery between 24-34 weeks' gestational age. Recent trials demonstrate modest benefits from antenatal corticosteroids for late preterm and elective cesarean deliveries, and antenatal corticosteroids for periviable deliveries should be considered with family discussion. However, many women with threatened preterm deliveries receive antenatal corticosteroids but do not deliver until >34 weeks or at term. The net effect is that a substantial fraction of the delivery population will be exposed to antenatal corticosteroids. There are gaps in accurate assessments of benefits of antenatal corticosteroids because the randomized controlled trials were performed prior to about 1990 in pregnancies generally >28 weeks. The care practices for the mother and infant survival were different than today. The randomized controlled trial data also do not strongly support the optimal interval from antenatal corticosteroid treatment to delivery of 1-7 days. Epidemiology-based studies using large cohorts with >85% of at-risk pregnancies treated with antenatal corticosteroids probably overestimate the benefits of antenatal corticosteroids. Although most of the prematurity-associated mortality is in low-resource environments, the efficacy and safety of antenatal corticosteroids in those environments remain to be evaluated. The short-term benefits of antenatal corticosteroids for high-risk pregnancies in high-resource environments certainly justify antenatal corticosteroids as few risks have been identified over many years. However, cardiovascular and metabolic abnormalities have been identified in large animal models and cohorts of children exposed to antenatal corticosteroids that are consistent with fetal programming for adult diseases. These late effects of antenatal corticosteroids suggest caution for the expanded use of antenatal corticosteroids beyond at-risk pregnancies at 24-34 weeks. A way forward is to develop noninvasive fetal assessments to identify pregnancies across a wider gestational age that could benefit from antenatal corticosteroids.

Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation.ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970.From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups.In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality.Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The objective of this secondary analysis was to identify maternal characteristics that modified the effect of maternal supplements on newborn size. Participants included 1465 maternal&ndash, newborn dyads in Guatemala, India, and Pakistan. Supplementation commenced before conception (Arm 1) or late 1st trimester (Arm 2), Arm 3 received usual care. Characteristics included body mass index (BMI), stature, anemia, age, education, socio-economic status (SES), parity, and newborn sex. Newborn outcomes were z-scores for length (LAZ), weight (WAZ), and weight to length ratio-for-age (WLRAZ). Mixed-effect regression models included treatment arm, effect modifier, and arm * effect modifier interaction as predictors, controlling for site, characteristics, and sex. Parity (para-0 vs. para &ge, 1), anemia (anemia/no anemia), and sex were significant effect modifiers. Effect size (95% CI) for Arm 1 vs. 3 was larger for para-0 vs. &ge, 1 for all outcomes (LAZ 0.56 (0.28, 0.84, p &lt, 0.001), WAZ 0.45 (0.20, 0.07, p &lt, WLRAZ 0.52 (0.17, 0.88, p &lt, 0.01) but only length for Arm 2 vs. 3. Corresponding effects for para &ge, 1 were &gt, 0.02. Arm 3 z-scores were all very low for para-0, but not para &ge, 1. Para-0 and anemia effect sizes for Arm 1 were &gt, Arm 2 for WAZ and WLRAZ, but not LAZ. Arm 1 and 2 had higher WAZ for newborn boys vs. girls. Maternal nulliparity and anemia were associated with impaired fetal growth that was substantially improved by nutrition intervention, especially when commenced prior to conception.

The Jawaharlal Nehru Medical College (JNMC) Women’s and Children’s Health Research Unit (WCHRU) of the Karnataka Lingayat Education (KLE) Academy of Higher Education and Research Deemed-to-be-University and its collaborators convened the ‘2nd International Conference on Maternal and Newborn Health -Translating Research Evidence to Practice’ to address the common theme of improving maternal and newborn health in low- and middle- income countries (LMIC). This supplement, including 16 manuscripts, reflects much of the research presented at the conference, including analyses of the state of knowledge, as well as completed, ongoing and planned research in these areas conducted by the WCHRU in India together with many collaborators across high-income and LMIC. The first paper reviews maternal, fetal and neonatal mortality in low-income countries, considers their causes, as well as evidence for potential interventions to reduce mortality. A second paper addresses near miss maternal mortality. Several manuscripts address the research conducted by WCHRU and their colleagues in a multi-center research network. One study examines rates of miscarriage and medically terminated pregnancy in India and the risk factors for these occurrences. Another paper addresses stillbirth and its risk factors, both in India as well as in other LMIC. Haemorrhage and preeclampsia/eclampsia, important causes of maternal mortality, stillbirth and neonatal morbidity in LMIC, are addressed in a series of papers summarizing trials of interventions to reduce improve outcomes associated with these conditions. Poor maternal and infant nutritional status, which contribute to adverse outcomes, are addressed through papers which describe a number of important studies that the WCHRU and their colleagues have conducted to attempt to improve nutritional status. Another paper describes a study to investigate causes of stillbirth and deaths among preterm births, which will utilize new techniques to investigate the infectious causes of these deaths. Finally, the supplement addresses the process for dissemination of research results to inform public policy. Together these manuscripts represent a body of research to inform interventions to reduce maternal, fetal and newborn mortality and illustrates what a dedicated research group together with institutional support can accomplish.

Background Stillbirth rates remain high, especially in low and middle-income countries, where rates are 25 per 1000, ten-fold higher than in high-income countries. The United Nations’ Every Newborn Action Plan has set a goal of 12 stillbirths per 1000 births by 2030 for all countries. Methods From a population-based pregnancy outcome registry, including data from 2010 to 2016 from two sites each in Africa (Zambia and Kenya) and India (Nagpur and Belagavi), as well as sites in Pakistan and Guatemala, we evaluated the stillbirth rates and rates of annual decline as well as risk factors for 427,111 births of which 12,181 were stillbirths. Results The mean stillbirth rates for the sites were 21.3 per 1000 births for Africa, 25.3 per 1000 births for India, 56.9 per 1000 births for Pakistan and 19.9 per 1000 births for Guatemala. From 2010 to 2016, across all sites, the mean stillbirth rate declined from 31.7 per 1000 births to 26.4 per 1000 births for an average annual decline of 3.0%. Risk factors for stillbirth were similar across the sites and included maternal age 35 years. Compared to parity 1–2, zero parity and parity > 3 were both associated with increased stillbirth risk and compared to women with any prenatal care, women with no prenatal care had significantly increased risk of stillbirth in all sites. Conclusions At the current rates of decline, stillbirth rates in these sites will not reach the Every Newborn Action Plan goal of 12 per 1000 births by 2030. More attention to the risk factors and treating the causes of stillbirths will be required to reach the Every Newborn Action Plan goal of stillbirth reduction. Trial registration NCT01073475.

Objective To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. Design A population-based, prospective observational study. Setting Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. Population All deaths among pregnant women resident in the study sites from 2014 to December 2016. Methods For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. Main outcome measures Assigned causes of maternal mortality. Results Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. Conclusions The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. Tweetable abstract An algorithmic system for determining maternal cause of death in low-resource settings is described.

The terror management health model suggests targeting sources of self-esteem or identity, in conjunction with mortality salience, offers a pathway for health behavior promotion. To date, however, experimental evidence has been limited to single time point studies. Two studies assessed whether similar processes impact behavior over time. In Study 1, mortality salience was paired with exercise (i.e., riding a recumbent bike); two weeks later, individuals primed with mortality reported more exercise than those not primed with death, and this increased fitness-contingent self-esteem and exercise intentions. In Study 2, when smokers visualized a prototypical unhealthy (vs. typical) smoker after mortality salience, they reported more attempts to quit smoking (over three weeks) than participants not primed with mortality. This facilitated continued quit attempts and decreased smoker identification three weeks later. Implications are discussed for a longitudinal process model in which mortality salience c...

Women are objectified through overt sexualization and through a focus on physical appearance, but empirical research has not yet made this distinction. In three studies, we found evidence consistent with the hypothesis that although both forms of objectification strip women of their humanness, there are unique dehumanizing signatures associated with each. When women were objectified by a focus on their sexual features or functions ( sexual objectification), they were perceived as lacking uniquely human attributes (i.e., animalistic dehumanization). Conversely, when women were objectified by an emphasis on their beauty or physical appearance ( appearance-focused objectification), they were perceived as lacking human nature (i.e., mechanistic dehumanization). In Study 3, we also examined an outcome associated with women’s risk of harm and found that mechanistic dehumanization, in response to appearance-focused objectification, uniquely promoted the perception that a woman was less capable of feeling pain. Implications for objectification research are discussed.

Background Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. Objective This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. Study Design White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. Results A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m2) categorized as normal (18.5–24.9), overweight (25.0–29.9), or obese (30.0 + ). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14–1.94) and obese women (COR, 1.60; 95% CI: 1.23–2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p Conclusion Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.

Objective The objective of this study was to describe the relationship between early pregnancy body mass index (BMI) and maternal, perinatal, and neonatal outcomes in rural India and Pakistan. Study Design In a prospective, population-based pregnancy registry implemented in communities in Thatta, Pakistan and Nagpur and Belagavi, India, we obtained women's BMI prior to 12 weeks' gestation (categorized as underweight, normal, overweight, and obese following World Health Organization criteria). Outcomes were assessed 42 days postpartum. Results The proportion of women with an adverse maternal outcome increased with increasing maternal BMI. Less than one-third of nonoverweight/nonobese women, 47.2% of overweight women, and 56.0% of obese women experienced an adverse maternal outcome. After controlling for site, maternal age and parity, risks of hypertensive disease/severe preeclampsia/eclampsia, cesarean/assisted delivery, and antibiotic use were higher among women with higher BMIs. Overweight women also had significantly higher risk of perinatal and early neonatal mortality compared with underweight/normal BMI women. Overweight women had a significantly higher perinatal mortality rate. Conclusion High BMI in early pregnancy was associated with increased risk of adverse maternal, perinatal, and neonatal outcomes in rural India and Pakistan. These findings present an opportunity to inform efforts for women to optimize weight prior to conception to improve pregnancy outcomes.

Background: Effectively monitoring the coverage and quality of data in low-resource settings is challenging. Lot quality assurance sampling (LQAS) is a method to classify coverage as adequate or inadequate. The aim of this pilot study is sought to determine the coverage and quality of a birth registry in a rural district in Pakistan. Methods: This survey was conducted in 14 clusters of Thatta, Pakistan. LQAS methodology was used to monitor the birth registry from December 2015 to February 2016. We randomly selected 19 villages from each cluster. We used a short questionnaire to review the quality of data collection for select variables. Frequency and percentages were reported for categorical variables. For data validation, Kappa statistics (κ) were applied to assess the agreement between categorical observations, and the Bland–Altman test was used to assess agreement for continuous data. Results: Of the 14 clusters sampled, 12 clusters had adequate coverage. Agreement of hemoglobin performance between the women's response and information in birth registry data was good (κ = 0.718) (95% confidence interval [CI]: 0.58–0.82); agreement on birth outcome recorded by the workers in the registry and as mentioned by women was very good (κ = 1.0); and agreement whether birth weight was assessed within 48 h of delivery was good (κ = 0.648) (0.37–0.92). Conclusion: LQAS is a powerful tool to monitor coverage and data quality of the birth registry maintained by the global network for women's and children's health in Pakistan and potentially for data from other surveillance systems.

Background Fetal death is one of the major adverse pregnancy outcomes and is common in low- and middle-income countries. Placental lesions may play an important role in the etiology of fetal and neonatal deaths. Previous research relating placental lesions to fetal death causation was hindered by a lack of agreement on a placental classification scheme. The Amsterdam consensus statement that was published in 2016 focused its attention on malperfusions in the maternal and fetal placental circulations. Objective This study aimed to investigate the relationships of placental maternal and fetal vascular malperfusions in fetal and neonatal deaths, focusing on the most important maternal clinical conditions in the pathway to fetal and neonatal deaths, such as maternal hypertension, antepartum hemorrhage, and decreased fetal growth. Study Design This was a prospective, observational cohort study conducted at 2 Asian sites. The data collected included clinical history, gross and histologic evaluations of the placenta, and several other investigations and were used to determine the cause of death. The placenta was evaluated at both sites using the Amsterdam consensus framework. We estimated the risk of placental maternal and fetal vascular malperfusions in fetal and neonatal deaths. Results Between July 2018 and January 2020 in India and Pakistan, 1633 women with placentas available for the study provided consent. Of these women, 814 had fetal deaths, 618 had preterm live births and subsequent neonatal deaths, and 201 had term live births. The prevalence of maternal vascular malperfusion was higher in the placentas associated with fetal deaths (58.4%) and preterm neonatal deaths (31.1%) than in the placentas associated with term live births (15.4%). Adjusting for site, maternal vascular malperfusion had a relative risk of 3.88 (95% confidence interval, 2.70–5.59) in fetal deaths vs term live births and a relative risk of 2.07 (95% confidence interval, 1.41–3.02) in preterm neonatal deaths vs term live births. Infarcts and distal villous hypoplasia were the most common histologic components of maternal vascular malperfusion. Compared with maternal vascular malperfusion (58.4%), fetal vascular malperfusion was less common in the placentas associated with fetal deaths (19.0%). However, there were higher frequencies of fetal vascular malperfusion in the placentas associated with fetal deaths (19.0%) than in placentas associated with neonatal deaths (8.3%) or term live birth (5.0%). Adjusting for site, fetal vascular malperfusion had a relative risk of 4.09 (95% confidence interval, 2.15–7.75) in fetal deaths vs term live births and a relative risk of 1.77 (95% confidence interval, 0.90–3.49) in preterm neonatal deaths vs term live births. Furthermore, there was a higher incidence of maternal vascular malperfusion in cases of maternal hypertension (71.4%), small for gestational age (69.9%), and antepartum hemorrhage (59.1%) than in cases of fetal deaths with none of these conditions (43.3%). There was no significant difference in the occurrence of fetal vascular malperfusion in the 4 clinical categories. Conclusion Histologic examination of the placenta, especially for malperfusion disorders, is crucial in elucidating pathways to fetal and neonatal deaths in preterm infants. In particular, focusing on placental maternal and fetal vascular malperfusions during pregnancy is a means to identify fetuses at risk of fetal death and is an important strategy to reduce the risk of fetal death early delivery. We hope that the increased risk of fetal and neonatal deaths in these pregnancies can be reduced by the development of an intervention that reduces the likelihood of developing maternal and fetal vascular malperfusion.

MANDATE is a mathematical model designed to estimate the relative impact of different interventions on maternal, fetal, and neonatal lives saved in sub-Saharan Africa and India. A key advantage is that it allows users to explore the contribution of preventive interventions, diagnostics, treatments, and transfers to higher levels of care to mortality reductions, and at different levels of penetration, utilization, and efficacy., Maternal, fetal, and neonatal mortality disproportionately impact low- and middle-income countries, and many current interventions that can save lives are often not available nor appropriate for these settings. Maternal and Neonatal Directed Assessment of Technologies (MANDATE) is a mathematical model designed to evaluate which interventions have the greatest potential to save maternal, fetal, and neonatal lives saved in sub-Saharan Africa and India. The MANDATE decision-support model includes interventions such as preventive interventions, diagnostics, treatments, and transfers to different care settings to compare the relative impact of different interventions on mortality outcomes. The model is calibrated and validated based on historical and current rates of disease in sub-Saharan Africa and India. In addition, each maternal, fetal, or newborn condition included in MANDATE considers disease rates specific to sub-Saharan Africa and India projected to intervention rates similar to those seen in high-income countries. Limitations include variance in quality of data to inform the estimates and generalizability of findings of the effectiveness of the interventions. The model serves as a valuable resource to compare the potential impact of multiple interventions, which could help reduce maternal, fetal, and neonatal mortality in low-resource settings. The user should be aware of assumptions in evaluating the model and interpret results accordingly.

Objective To investigate whether associations between pain and the additional symptoms associated with fibromyalgia are different in persons with chronic widespread pain (CWP) compared to multisite pain (MSP), with or without joint areas. Methods Six studies were used: 1958 British birth cohort, Epidemiology of Functional Disorders, Kid Low Back Pain, Managing Unexplained Symptoms (Chronic Widespread Pain) in Primary Care: Involving Traditional and Accessible New Approaches, Study of Health and its Management, and Women's Health Study (WHEST; females). MSP was defined as the presence of pain in ≥8 body sites in adults (≥10 sites in children) indicated on 4-view body manikins, conducted first to include joints (positive joints) and second without (negative joints). The relationship between pain and fatigue, sleep disturbance, somatic symptoms, and mood impairment was assessed using logistic regression. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results There were 34,818 participants across the study populations (adults age range 42–56 years, male 43–51% [excluding WHEST], and CWP prevalence 12–17%). Among those reporting MSP, the proportion reporting CWP ranged between 62% and 76%. Among those reporting the symptoms associated with fibromyalgia, there was an increased likelihood of reporting pain, the magnitude of which was similar regardless of the definition used. For example, within WHEST, reporting moderate/severe fatigue (Chalder fatigue scale 4–11) was associated with a >5-fold increase in likelihood of reporting pain (CWP OR 5.2 [95% CI 3.9–6.9], MSP–positive joints OR 6.5 [95% CI 5.0–8.6], and MSP–negative joints OR 6.5 [95% CI 4.7–9.0]). Conclusion This large-scale study demonstrates that regardless of the pain definition used, the magnitude of association between pain and other associated symptoms of fibromyalgia is similar. This finding supports the continued collection of both when classifying fibromyalgia, but highlights the fact that pain may not require to follow the definition outlined within the 1990 American College of Rheumatology criteria.

We consider a new version of the nonadiabatic system for the formation of a helical electron beam in a gyrotron, in which electrons acquire initial oscillatory velocities when a rectilinear beam is injected at an angle to the magnetic field. In such an electron gun, the influence of thermal electron velocities and roughness of the emitting surface can be decreased, as compared with the conventional electron-optical systems of gyrotrons. This makes it possible to increase significantly the system efficiency. The main factors affecting the quality of the formed beam are considered.

Research on terror management theory demonstrates that people respond to reminders of mortality with defenses aimed at maintaining their self-esteem and defending cultural worldviews. We posited that being open to experience should allow individuals to process death more receptively (i.e., with curiosity), attenuating the need to bolster self-esteem or defend worldviews, because death is a novel experience. Across three studies, dispositional openness moderated reactions to mortality salience. Individuals low in openness to experience responded to mortality salience with increased self-esteem striving (Study 1) and worldview defense (Study 2), and this functioned to decrease the subsequent availability of death-related thought (Study 2). Individuals high in openness to experience did not exhibit these same defense tendencies. Study 3 examined a possible mechanism for the attenuated effects observed among high openness individuals: increased curiosity in response to mortality salience was found to decrease worldview defense, but only for those high in openness. Together this research depicts openness as a resource facilitating reduced defensiveness following mortality salience.

Persistent global disparities in maternal and neonatal outcomes and the emergence of compact ultrasound technology as an increasingly viable technology for low-resource settings provided the genesis of the First Look Ultrasound study. Initiated in 2014 in 5 low- and middle-income countries and completed in June 2016, the study's intervention included the training of health personnel to perform antenatal ultrasound screening and to refer women identified with high-risk pregnancies to hospitals for appropriate care. This article examines the challenges that arose in implementing the study, with a particular focus on the site in Equateur Province of the Democratic Republic of the Congo (DRC) where the challenges were greatest and the efforts to meet these challenges most illuminating. During the study period, we determined that with resources and dedicated staff, it was possible to leverage the infrastructure and implement ultrasound at antenatal care across a variety of remote sites, including rural DRC. However, numerous technical and logistical challenges had to be addressed including security of the equipment, electricity requirements, and integration of the intervention into the health system. To address security concerns, in most of the countries field sonographers were hired and dispatched each day with the equipment to the health centers. At the end of each day, the equipment was locked in a secure, central location. To obtain the required power source, the DRC health centers installed solar panels bolted on adjacent poles since the thatch roofs of the centers prohibited secure roof-top installation. To realize the full value of the ultrasound intervention, women screened with high-risk pregnancies had to seek a higher level of care at the referral hospital for a definitive diagnosis and appropriate care. While the study did provide guidance on referral and systems management to health center and hospital administration, the extent to which this resulted in the necessary structural changes varied depending on the motivation of the stakeholders. In order for such an intervention to be scaled up and sustained as part of a health system's general services, it would require considerable effort, political will, and financial and human resources. Preliminary results from the study indicate that taking routine antenatal ultrasound screening to scale is not warranted. Lessons learned in implementing the study, however, can help inform future studies or programs that are considering use of ultrasound or other imaging technology for other applications in low-resource settings.

Objective To describe the Global Network Near-Miss Maternal Mortality System and its application in seven sites. Methods In a population-based study, pregnant women eligible for enrollment in the Maternal and Newborn Health Registry at seven sites (Democratic Republic of the Congo; Guatemala; Belagavi and Nagpur, India; Kenya; Pakistan; and Zambia) between January 2014 and April 2016 were screened to identify those likely to have a near-miss event. The WHO maternal near-miss criteria were modified for low-resource settings. The ratio of near-miss events to maternal deaths was calculated. Results Among 122 707 women screened, 18 307 (15.0%) had a potential near-miss event, of whom 4866 (26.6%; 4.0% of all women) had a near-miss maternal event. The overall maternal mortality ratio was 155 per 100 000 live births. The ratio of near-miss events to maternal deaths was 26 to 1. The most common factors involved in near-miss cases were the hematologic/coagulation system, infection, and cardiovascular system. Conclusion By using the Global Network Near-Miss Maternal Mortality System, large numbers of women were screened for near-miss events, including those delivering at home or a low-level maternity clinic. The 4.0% incidence of near-miss maternal mortality is similar to previously reported data. The ratio of 26 near-miss cases to 1 maternal death suggests that near miss might evaluate the impact of interventions more efficiently than maternal mortality. This article is protected by copyright. All rights reserved.

Pregnancy results in alterations in coagulation processes, which may increase the risk of thrombosis. Inherited thrombophilia mutations may further increase this risk, possibly through alterations in the placenta, which may result in pregnancy complications such as poor fetal growth. The purpose of our study is to evaluate the association of fetal growth, approximated by birth weight for gestational age percentile, with genetic markers of thrombophilia and placental characteristics related to vascular malperfusion. We analyzed data from the Stillbirth Collaborative Research Network's population-based case–control study conducted in 2006–2008. Study recruitment occurred in five states: Rhode Island and counties in Massachusetts, Georgia, Texas, and Utah. The analysis was restricted to singleton, nonanomalous live births ≤42 weeks' gestation with a complete placental examination and successful testing for ≥1 thrombophilia marker (858 mothers, 902 infants). Data were weighted to account for oversampling, differential consent, and availability of placental examination. We evaluated five thrombophilia markers: factor V Leiden, factor II prothrombin, methylenetetrahydrofolate reductase A1298C and C677T, and plasminogen activator inhibitor type 1 in both maternal blood and placenta/cord blood. We modeled maternal and fetal thrombophilia markers separately using linear regression. Maternal factor V Leiden mutation was associated with a 13.16-point decrease in adjusted birth weight percentile (95% confidence interval: −25.50, −0.82). Adjustment for placental abnormalities related to vascular malperfusion did not affect the observed association. No other maternal or fetal thrombophilia markers were significantly associated with birth weight percentile. Maternal factor V Leiden may be associated with fetal growth independent of placental characteristics.

Aim To determine which interventions would have the greatest impact on reducing neonatal mortality in sub-Saharan Africa in 2012. Methods We used MANDATE, a mathematical model, to evaluate scenarios for the impact of available interventions on neonatal deaths from primary causes, including: (i) for birth asphyxia – obstetric care preventing intrapartum asphyxia, newborn resuscitation and treatment of asphyxiated infants; (ii) for preterm birth – corticosteroids, oxygen, continuous positive air pressure and surfactant; and, (iii) for serious newborn infection – clean delivery, chlorhexidine cord care and antibiotics. Results Reductions in infection-related mortality have occurred. Between 80 and 90% of deaths currently occurring from infections and asphyxia can be averted from available interventions, as can 58% of mortality from preterm birth. More than 200 000 neonatal deaths can each be averted from asphyxia, preterm birth and infections. Using available interventions, more than 80% of the neonatal deaths occurring today could be prevented in sub-Saharan Africa. Conclusion Reducing neonatal deaths from asphyxia require improvements in infrastructure and obstetric care to manage maternal conditions such as obstructed labour and preeclampsia. Reducing deaths from preterm birth would also necessitate improved infrastructure and training for preterm infant care. Reducing infection-related mortality requires less infrastructure and lower-level providers.

Aim This study estimated the causes of neonatal death using an algorithm for low-resource areas, where 98% of the world's neonatal deaths occur. Methods We enrolled women in India, Pakistan, Guatemala, the Democratic Republic of Congo, Kenya and Zambia from 2014 to 2016 and tracked their delivery and newborn outcomes for up to 28 days. Antenatal care and delivery symptoms were collected using a structured questionnaire, clinical observation and/or a physical examination. The Global Network Cause of Death algorithm was used to assign the cause of neonatal death, analysed by country and day of death. Results One-third (33.1%) of the 3068 neonatal deaths were due to suspected infection, 30.8% to prematurity, 21.2% to asphyxia, 9.5% to congenital anomalies and 5.4% did not have a cause of death assigned. Prematurity and asphyxia-related deaths were more common on the first day of life (46.7% and 52.9%, respectively), while most deaths due to infection occurred after the first day of life (86.9%). The distribution of causes was similar to global data reported by other major studies. Conclusion The Global Network algorithm provided a reliable cause of neonatal death in low-resource settings and can be used to inform public health strategies to reduce mortality.