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Background: The Global Network for Women's and Children's Health Research (Global Network) supports and conducts clinical trials in resource-limited countries by pairing foreign and U.S. investigators, with the goal of evaluating low-cost, sustainable interventions to improve the health of women and children. Accurate reporting of births, stillbirths, neonatal deaths, maternal mortality, and measures of obstetric and neonatal care is critical to efforts to discover strategies for improving pregnancy outcomes in resource-limited settings. Because most of the sites in the Global Network have weak registration within their health care systems, the Global Network developed the Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnancies at the Global Network sites to provide precise data on health outcomes and measures of care. Methods: Pregnant women are enrolled in the MNHR if they reside in or receive healthcare in designated groups of communities within sites in the Global Network. For each woman, demographic, health characteristics and major outcomes of pregnancy are recorded. Data are recorded at enrollment, the time of delivery and at 42 days postpartum. Results: From 2010 through 2013 Global Network sites were located in Argentina, Guatemala, Belgaum and Nagpur, India, Pakistan, Kenya, and Zambia. During this period, 283,496 pregnant women were enrolled in the MNHR; this number represented 98.8% of all eligible women. Delivery data were collected for 98.8% of women and 42-day follow-up data for 98.4% of those enrolled. In this supplement, there are a series of manuscripts that use data gathered through the MNHR to report outcomes of these pregnancies. Conclusions: Developing public policy and improving public health in countries with poor perinatal outcomes is, in part, dependent upon understanding the outcome of every pregnancy. Because the worst pregnancy outcomes typically occur in countries with limited health registration systems and vital records, alternative registration systems may prove to be highly valuable in providing data. The MNHR, an international, multicenter, populationbased registry, assesses pregnancy outcomes over time in support of efforts to develop improved perinatal healthcare in resource-limited areas. [ABSTRACT FROM AUTHOR]

Abstract: Little evidence is available to document that mechanical ventilation is an antecedent of systemic inflammation in preterm humans. We obtained blood on postnatal day 14 from 726 infants born before the 28thweek of gestation and measured the concentrations of 25 inflammation-related proteins. We created multivariable models to assess the relationship between duration of ventilation and protein concentrations in the top quartile. Compared to newborns ventilated for fewer than 7days (N =247), those ventilated for 14days (N =330) were more likely to have elevated blood concentrations of pro-inflammatory cytokines (IL-1β, TNF-α), chemokines (IL-8, MCP-1), an adhesion molecule (ICAM-1), and a matrix metalloprotease (MMP-9), and less likely to have elevated blood concentrations of two chemokines (RANTES, MIP-1β), a matrix metalloproteinase (MMP-1), and a growth factor (VEGF). Newborns ventilated for 7–13days (N =149) had systemic inflammation that approximated the pattern of newborns ventilated for 14days. These relationships were not confounded by chorioamnionitis or antenatal corticosteroid exposure, and were not altered appreciably among infants with and without bacteremia. These findings suggest that 2weeks of ventilation are more likely than shorter durations of ventilation to be accompanied by high blood concentrations of pro-inflammatory proteins indicative of systemic inflammation, and by low concentrations of proteins that might protect from inflammation-mediated organ injury. [Copyright &y& Elsevier]

OBJECTIVE. Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bronchopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS. Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of ⩾0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation. RESULTS. Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%); no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality. CONCLUSIONS.There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation. [ABSTRACT FROM AUTHOR]

Patent ductus arteriosus (PDA) is a common diagnosis among extremely premature infants, especially in those with lung disease. Treatments are often used to close the PDA. Despite nearly three decades of research, the question of whether the benefits of treatments to prevent ductal patency or promote closure outweigh the risks of these treatments remains unanswered. The authors rarely use treatments designed to close the PDA. This article reviews three considerations in support of this restrained approach: rates of spontaneous closure of the ductus arteriosus; adverse effect of persistent ductal patency; and benefits and risks of treatments for closure. [ABSTRACT FROM AUTHOR]

OBJECTIVE. The goals were to identify the blood pressures of extremely low gestational age newborns that prompt intervention, to identify other infant characteristics associated with receipt of therapies intended to increase blood pressure, and to assess the interinstitutional variability in the use of these therapies. METHODS. The cohort included 1507 extremely low gestational age newborns born at 23 weeks to 27 6/7 weeks of gestation, at 14 institutions, between March 2002 and August 2004; 1387 survived the first postnatal week. Blood pressures were measured as clinically indicated. Interventions were grouped as any treatment (ie, vasopressor and/or fluid boluses of > 10 mL/kg) and vasopressor treatment, and logistic regression analyses were performed. RESULTS. At each gestational age, the lowest mean arterial pressures in treated and untreated infants tended to increase with advancing postnatal age. Infants who received any therapy tended to have lower mean arterial pressures than infants who did not, but uniform thresholds for treatment were not apparent. The proportion of infants receiving any treatment decreased with increasing gestational age from 93% at 23 weeks to 73% at 27 weeks. Treatment nearly always began during the first 24 hours of life. Lower gestational age, lower birth weight, male gender, and higher Score for Neonatal Acute Physiology-II values were associated with any treatment and vasopressor treatment. Institutions varied greatly in their tendency to offer any treatment and vasopressor treatment. Neither the lowest mean arterial pressure on the day of treatment nor other characteristics of the infants accounted for center differences in treatment. CONCLUSIONS. Blood pressure in extremely premature infants not treated for hypotension increased directly with both increasing gestational age and postnatal age. The decision to provide treatment was associated more strongly with the center where care was provided than with infant attributes. [ABSTRACT FROM AUTHOR]

Abstract. Neonatal back transport is defined as the return of previously critically ill neonates from Level III newborn intensive care units to Level II and Level I nurseries for intermediate and/or convalescing care. During 1980, 172 infants (65% of eligible infants) were back transported from a Level III nursery to both Level I and Level II community hospitals. Infants who were returned to Level II hospitals tended to be smaller at the time of transfer, were less frequently nipple fed, and more frequently required oxygen supplementation compared with infants returned to Level I hospitals. Back transport permitted physicians to defer 3,892 days of hospitalization for these infants to community hospitals, an equivalent savings of approximately ten hospital beds at full occupancy. This resulted in a 44% reduction in the need for services in the newborn intensive care unit. Back transport is an efficient means of dealing with overcrowding of Level III nurseries. [ABSTRACT FROM AUTHOR]

Abstract. Relactation, the induction of lactation at any time beyond the immediate postpartum period, has received minimal scientific investigation. In this study, one adoptive mother and six mothers ten to 150 days postpartum, who for a variety of reasons did not initiate or maintain lactation after delivery, attempted relactation. Each suckled her infant at regular feeding intervals. Prior to milk production, formula was provided during suckling through an artificial device. Serum prolactin responses to thyrotropin-releasing hormone infusion and to suckling were measured at the start of the study and to suckling at approximately weekly intervals thereafter. All mothers produced milk; three completely nourished their infants and two others provided at least haft of their infants' nutritional needs. The adoptive mother and one other failed to provide significant quantities of milk. Mothers reached their maximum potential for milk production in varying periods of time (eight to 58 days). Shorter postpartum interval and less postpartum breast involution correlated with the likelihood of successful relactation and the rapidity of the onset of lactation. Basal prolactin levels and stimulation tests were of no additional predictive value. Each mother, regardless of milk production, expressed positive feelings about nurturing her infant in this manner. We conclude that relactation frequently is possible and may offer the mother of a sick or premature infant who desires to breast-feed an alternative ff she does not maintain lactation in the immediate postpartum period. Pediatrics 67:565-569, 1980; relactation, breast-feeding, lactation, prolactin. [ABSTRACT FROM AUTHOR]

Background: Malaria can have deleterious effects early in pregnancy, during placentation. However, malaria testing and treatment are rarely initiated until the second trimester, leaving pregnancies unprotected in the first trimester. To inform potential early intervention approaches, we sought to identify clinical and demographic predictors of first-trimester malaria.Methods: We prospectively recruited women from sites in the Democratic Republic of the Congo (DRC), Kenya, and Zambia who participated in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial. Nulliparous women were tested for first-trimester Plasmodium falciparum infection by quantitative polymerase chain reaction. We evaluated predictors using descriptive statistics.Results: First-trimester malaria prevalence among 1513 nulliparous pregnant women was 6.3% (95% confidence interval [CI], 3.7%-8.8%] in the Zambian site, 37.8% (95% CI, 34.2%-41.5%) in the Kenyan site, and 62.9% (95% CI, 58.6%-67.2%) in the DRC site. First-trimester malaria was associated with shorter height and younger age in Kenyan women in site-stratified analyses, and with lower educational attainment in analyses combining all 3 sites. No other predictors were identified.Conclusions: First-trimester malaria prevalence varied by study site in sub-Saharan Africa. The absence of consistent predictors suggests that routine parasite screening in early pregnancy may be needed to mitigate first-trimester malaria in high-prevalence settings. [ABSTRACT FROM AUTHOR]

Abstract. Percutaneous insertion of a very narrow (0.635-mm outside diameter) Silastic catheter for delivery of central hyperalimentation was performed on infants in the Newborn Intensive Care Center. Insertion of the catheter into the external jugular or basilic vein was successful in 15/17 (88%) infants, including four weighing less than 1,000 gm. Catheters remained in place for 446 patient-days (mean 24.8 +/- 15.9 days). Culture-proven infection, thrombophlebitis, or caval obstruction did not occur. Percutaneously placed central Silastic catheters proved to be a safe and effective alternative to surgically placed catheters. [ABSTRACT FROM AUTHOR]

The article reports on an evaluation of implementation of Helping Babies Breathe (HBB), a simulation-based educational program on newborn resuscitation, in Tanzania as a strategy to reduce neonatal mortality. Topics discussed include the importance of educating providers and for education to be supplemented by strategies to maintain knowledge and skills and barriers to input.

Approximately 15% of infants worldwide are born with low birthweight (<2500 g). These children are at risk for growth failure. The aim of this umbrella review is to assess the relationship between infant milk type, fortification and growth in low‐birthweight infants, with particular focus on low‐ and lower middle–income countries. We conducted a systematic review in PubMed, CINAHL, Embase and Web of Science comparing infant milk options and growth, grading the strength of evidence based on standard umbrella review criteria. Twenty‐six systematic reviews qualified for inclusion. They predominantly focused on infants with very low birthweight (<1500 g) in high‐income countries. We found the strongest evidence for (1) the addition of energy and protein fortification to human milk (donor or mother's milk) leading to increased weight gain (mean difference [MD] 1.81 g/kg/day; 95% confidence interval [CI] 1.23, 2.40), linear growth (MD 0.18 cm/week; 95% CI 0.10, 0.26) and head growth (MD 0.08 cm/week; 95% CI 0.04, 0.12) and (2) formula compared with donor human milk leading to increased weight gain (MD 2.51 g/kg/day; 95% CI 1.93, 3.08), linear growth (MD 1.21 mm/week; 95% CI 0.77, 1.65) and head growth (MD 0.85 mm/week; 95% CI 0.47, 1.23). We also found evidence of improved growth when protein is added to both human milk and formula. Fat supplementation did not seem to affect growth. More research is needed for infants with birthweight 1500–2500 g in low‐ and lower middle–income countries. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Focuses on the status of research into the treatment of chronic lung disease (CLD) in neonates. Scarcity of effective therapies for the prevention or treatment of neonatal CLD; Highlights of the results of a study conducted by Doyle et. al; Manifestations of CLD.

The National Institute of Child Health and Human Development created and continues to support the Global Network for Women's and Children's Health Research, a partnership between research institutions in the US and low-middle income countries. This commentary describes a series of 15 papers emanating from the Global Network's Maternal and Newborn Health Registry. Using data from 2010 to 2013, the series of papers describe nearly 300,000 pregnancies in 7 sites in 6 countries -- India (2 sites), Pakistan, Kenya, Zambia, Guatemala and Argentina. These papers cover a wide range of topics including several dealing with efforts made to ensure data quality, and others reporting on specific pregnancy outcomes including maternal mortality, stillbirth and neonatal mortality. Topics ranging from antenatal care, adolescent pregnancy, obstructed labor, factors associated with early initiation of breast feeding and maintenance of exclusive breast feeding and contraceptive usage are presented. In addition, case studies evaluating changes in mortality over time in 3 countries - India, Pakistan and Guatemala - are presented. In order to make progress in improving pregnancy outcomes in low-income countries, data of this quality are needed. [ABSTRACT FROM AUTHOR]

The National Institute of Child Health and Human Development created and continues to support the Global Network for Women's and Children's Health Research, a partnership between research institutions in the US and low-middle income countries. This commentary describes a series of 15 papers emanating from the Global Network’s Maternal and Newborn Health Registry. Using data from 2010 to 2013, the series of papers describe nearly 300,000 pregnancies in 7 sites in 6 countries – India (2 sites), Pakistan, Kenya, Zambia, Guatemala and Argentina. These papers cover a wide range of topics including several dealing with efforts made to ensure data quality, and others reporting on specific pregnancy outcomes including maternal mortality, stillbirth and neonatal mortality. Topics ranging from antenatal care, adolescent pregnancy, obstructed labor, factors associated with early initiation of breast feeding and maintenance of exclusive breast feeding and contraceptive usage are presented. In addition, case studies evaluating changes in mortality over time in 3 countries - India, Pakistan and Guatemala - are presented. In order to make progress in improving pregnancy outcomes in low-income countries, data of this quality are needed. [ABSTRACT FROM AUTHOR]

Objective: On a population basis, we assessed medical care for pregnant women in specific geographic regions of six countries before and during the first year of the COVID-19 pandemic in relationship to pregnancy outcomes.Design: Prospective, population-based study.Setting: Communities in Kenya, Zambia, the Democratic Republic of the Congo, Pakistan, India, and Guatemala.Population: Pregnant women enrolled in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry METHODS: Pregnancy/delivery care services and pregnancy outcomes in the pre-COVID-19 time-period (March 2019-February 2020) were compared to the COVID-19 time-period (March 2020-February 2021).Main Outcome Measures: Stillbirth, neonatal mortality, preterm birth, low birth weight, maternal mortality RESULTS: Across all sites, a small but statistically significant increase in home births occurred between the pre-COVID and COVID periods. (18.9% vs 20.3%, aRR 1.12 95% CI 1.05, 1.19). Also, a small but significant decrease in the mean number of antenatal care visits (4.1 - 4.0, p= <0.0001) was seen during the COVID-19 period. Of outcomes evaluated, overall, a small but significant decrease in low-birthweight in the COVID-19 period occurred (15.7% vs 14.6%, aRR 0.94 (0.89, 0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites.Conclusions: Small but significant increases in home births and decreases in the ANC services were observed during the initial COVID-19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birth weight or preterm birth rates during the COVID-19 period as compared to the prior year. Further research should help elucidate the relationship between access to and use of pregnancy-related medical services and birth outcomes over an extended period. [ABSTRACT FROM AUTHOR]

Introduction: Neonates with serious bacterial infections should be treated with injectable antibiotics after hospitalization, which may not be feasible in many low resource settings. In 2015, the World Health Organization (WHO) launched a guideline for the management of young infants (0–59 days old) with possible serious bacterial infection (PSBI) when referral for hospital treatment is not feasible. We evaluated the feasibility of the WHO guideline implementation in the Democratic Republic of the Congo (DRC) to achieve high coverage of PSBI treatment. Methods: From April 2016 to March 2017, in a longitudinal, descriptive, mixed methods implementation research study, we implemented WHO PSBI guideline for sick young infants (0–59 dyas of age) in the public health programme setting in five health areas of North and South Ubangi Provinces with an overall population of about 60,000. We conducted policy dialogue with national and sub-national level government planners, decision-makers, academics and other stakeholders. We established a Technical Support Unit to provide implementation support. We built the capacity of health workers and managers and ensured the availability of necessary medicines and commodities. We followed infants with PSBI signs up to 14 days. The research team systematically collected data on adherence to treatment and outcomes. Results: We identified 3050 live births and 285 (9.3%) young infants with signs of PSBI in the study area, of whom 256 were treated. Published data have reported 10% PSBI incidence rate in young infants. Therefore, the estimated coverage of treatment was 83.9% (256/305). Another 426 from outside the study catchment area were also identified with PSBI signs by the nurses of a health centre within the study area. Thus, a total of 711 young infants with PSBI were identified, 285 (40%) 7–59 days old infants had fast breathing (pneumonia), 141 (20%) 0–6 days old had fast breathing (severe pneumonia), 233 (33%) had signs of clinical severe infection (CSI), and 52 (7%) had signs of critical illness. Referral to a hospital was advised to 426 (60%) infants with CSI, critical illness or severe pneumonia. The referral was refused by 282 families who accepted simplified antibiotic treatment on an outpatient basis at the health centres. Treatment failure among those who received outpatient treatment occurred in 10/128 (8%) with severe pneumonia, 25/147 (17%) with CSI, including one death, and 2/7 (29%) young infants with a critical illness. Among 285 infants with pneumonia, 257 (90%) received oral amoxicillin treatment, and 8 (3%) failed treatment. Adherence to outpatient treatment was 98% to 100% for various PSBI sub-categories. Among 144 infants treated in a hospital, 8% (1/13) with severe pneumonia, 23% (20/86) with CSI and 40% (18/45) with critical illness died. Conclusion: Implementation of the WHO PSBI guideline when a referral was not possible was feasible in our context with high coverage. Without financial and technical input to strengthen the health system at all levels, including the community and the referral level, it may not be possible to achieve and sustain the same high treatment coverage. [ABSTRACT FROM AUTHOR]

Objective To determine if antenatal treatment of maternal periodontitis affects early childhood neurodevelopment. Study Design We evaluated neurodevelopment of 331 24-month-old children born to women who participated in a randomized trial of antenatal (167) or postpartum (164) treatment of periodontitis. Children within groups defined by maternal treatment were designated as high risk for abnormal neurodevelopment (n = 96; birth at ≤34 6/7 weeks' gestation or small for gestational age following birth at term) or low risk (n = 235; appropriate birth weight and ≥37 weeks' gestation). We measured neurodevelopment using the Bayley Scale of Infant and Toddler Development III (BSID III) and neurological examination. Treatment effect was analyzed using a chi-square or Fisher exact test. Between-group mean scores were compared using Student t test. Results There were no differences in the incidence of neuromotor or sensory (visual or hearing) impairment or scores on the BSID III between groups. Low-risk children in the antenatal treatment group had higher language scores than those in the postpartum treatment group (92.9 versus 89.2; p = 0.05). Conclusion Antenatal treatment of maternal periodontitis does not appear to affect neurodevelopment at 24 months of age. The slight improvement in language development in low-risk children may be an artifact or not clinically relevant. [ABSTRACT FROM AUTHOR]

BACKGROUND. Pulmonary disease among infants of <28 weeks' gestation (extremely low gestational age newborns) often has the following pattern: the infant Starts out with little need for supplemental oxygen and ventilatory support in the first postnatal week but then has pulmonary deterioration in the second postnatal week, with an increased need for supplemental oxygen and respiratory support. We evaluated the antecedents and correlates of patterns of early lung disease, with particular emphasis on pulmonary deterioration, in a large cohort study (the Extremely Low Gestational Age Newborn [ELGANI study). PATIENTS AND METHODS. We examined data collected prospectively on 1340 infants born between 2002 and 2004 at 23 to 27 completed weeks of gestation and who survived to 14 days. Pulmonary deterioration was defined as receipt of fraction of inspired oxygen < 0.23 on any day between days 3 and 7 and receipt of fraction of inspired oxygen ⩾ 0.25 on day 14. RESULTS. One fifth (20%) of the infants had consistently low fraction of inspired oxygen, approximately two fifths (38%) had pulmonary deterioration, and the remaining approximately two fifths (43%) had consistently high fraction of inspired oxygen (early and persistent lung dysfunction). Compared with infants who had consistently low fraction of inspired oxygen, infants who experienced pulmonary deterioration had lower gestational ages and lower birth weights, had higher scores for neonatal acute physiology, and received more intensive modes of respiratory support. Gender, multifetal pregnancy, cesarean delivery, antenatal steroids, chorioamnionitis, and funisitis were not associated with pulmonary deterioration. The incidence of chronic lung disease, defined as oxygen therapy at 36 weeks' postmenstrual age, was 17% in the consistently low fraction of inspired oxygen group, 51% in the pulmonary deterioration group, and 67% in the early and persistent pulmonary dysfunction group. The incidence of death in these 3 groups before 36 weeks' postmenstrual age was 1%, 3%, and 5%, respectively. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of resuscitation training and continuous electronic heart rate (HR) monitoring of non-breathing newborns on identification of stillbirth.Methods: We conducted a pre-post interventional trial in three health facilities in the Democratic Republic of the Congo. We collected data on a retrospective control group of newborns that reflected usual resuscitation practice (Epoch 1). In the prospective, interventional group, skilled birth attendants received resuscitation training in Helping Babies Breathe and implemented continuous electronic HR monitoring of non-breathing newborns (Epoch 2). Our primary outcome was the incidence of stillbirth with secondary outcomes of fresh or macerated stillbirth, neonatal death before discharge and perinatal death. Among a subset, we conducted expert review of electronic HR data to estimate misclassification of stillbirth in Epoch 2. We used a generalized estimating equation, adjusted for variation within-facility, to compare risks between EPOCHs.Results: There was no change in total stillbirths following resuscitation training and continuous electronic HR monitoring of non-breathing newborns (aRR 1.15 [0.95, 1.39]). We observed an increased rate of macerated stillbirth (aRR 1.58 [1.24, 2.02]), death before discharge (aRR 3.31 [2.41, 4.54]), and perinatal death (aRR 1.61 [1.38, 1.89]) during the intervention period. In expert review, 20% of newborns with electronic HR data that were classified by SBAs as stillborn were liveborn.Conclusion: Resuscitation training and use of continuous electronic HR monitoring did not reduce stillbirths nor eliminate misclassification. [ABSTRACT FROM AUTHOR]

BackgroundInhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease.MethodsWe did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age [< or =]34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age.FindingsThe two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%).InterpretationLow-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury. [ABSTRACT FROM AUTHOR]

Abstract. The convalescent course of 55 infants transported from a Level III hospital back to the community hospitals from which they were originally transported was compared with the course of 58 infants who convalesced in the tertiary center nurseries. The events in their prenatal course and acute neonatal course were similar, thus making comparisons of their convalescent course possible. Weight gain was greater among the transported infants for infants with birth weights is greater than or equal to 2,000 g and comparable if birth weight was <2,000 g. Transported infants received fewer transfusions than their nontransported counterparts. Tolerance of feedings, the occurrence of apnea and bradycardia, and use and discontinuance of supplemental oxygen were similar in both groups. Major new health problems occurred in 27% of all subjects, 20% of transported infants and 32% of nontransported infants. Readmission to the tertiary center or a change in status to more intensive care in the tertiary center occurred in 10% of all infants, 7% of transported and 14% of nontransported infants. It was concluded that convalescing infants often presented new clinical problems, in similar numbers and severity whether convalescing in the tertiary center or after back transport to community hospitals. Community hospital care givers were considered alert to these new problems and to have provided appropriate care, including retransfer to the tertiary center when necessary. [ABSTRACT FROM AUTHOR]

Objective: Legal, ethical, and regulatory requirements of medical research uniformly call for informed consent. We aimed to characterize and compare consent rates for neonatal randomized controlled trials in low- and lower middle-income countries versus high-income countries, and to evaluate the influence of study characteristics on consent rates. Methods: In this systematic review, we searched MEDLINE, EMBASE and Cochrane for randomized controlled trials of neonatal interventions in low- and lower middle-income countries or high-income countries published 01/01/2013 to 01/04/2018. Our primary outcome was consent rate, the proportion of eligible participants who consented amongst those approached, extracted from the article or email with the author. Using a generalised linear model for fractional dependent variables, we analysed the odds of consenting in low- and lower middle-income countries versus high-income countries across control types and interventions. Findings: We screened 3523 articles, yielding 300 eligible randomized controlled trials with consent rates available for 135 low- and lower middle-income country trials and 65 high-income country trials. Median consent rates were higher for low- and lower middle-income countries (95.6%; interquartile range (IQR) 88.2–98.9) than high-income countries (82.7%; IQR 68.6–93.0; p<0.001). In adjusted regression analysis comparing low- and lower middle-income countries to high-income countries, the odds of consent for no placebo-drug/nutrition trials was 3.67 (95% Confidence Interval (CI) 1.87–7.19; p = 0.0002) and 6.40 (95%CI 3.32–12.34; p<0.0001) for placebo-drug/nutrition trials. Conclusion: Neonatal randomized controlled trials in low- and lower middle-income countries report consistently higher consent rates compared to high-income country trials. Our study is limited by the overrepresentation of India among randomized controlled trials in low- and lower middle-income countries. This study raises serious concerns about the adequacy of protections for highly vulnerable populations recruited to clinical trials in low- and lower middle-income countries. [ABSTRACT FROM AUTHOR]

Background While trends in caesarean birth by maternal request in low- and middle-income countries are unclear, age, education, multiple gestation and hypertensive disease appear associated with the indication when compared with caesarean birth performed for medical indications. Methods We performed a secondary analysis of a prospectively collected population-based study of home and facility births using descriptive statistics, bivariate comparisons and multilevel mixed-effects logistic regression. Results Of 28 751 patients who underwent caesarean birth and had a documented primary indication for the surgery, 655 (2%) were attributed to caesarean birth by maternal request. The remaining 98% were attributed to maternal and foetal indications and prior caesarean birth. In a multilevel mixed effects logistic regression adjusted for site and cluster of birth, when compared with caesareans performed for medical indications, caesarean birth performed for maternal request had a higher odds of being performed among women ≥35 y of age, with a university or higher level of education, with multiple gestations and with pregnancies complicated by hypertension (P < 0.01). Caesarean birth by maternal request was associated with a two-times increased odds of breastfeeding within 1 h of delivery, but no adverse outcomes (when compared with women who underwent caesarean birth for medical indications; P < 0.01). Conclusion Caesarean performed by maternal request is more common in older and more educated women and those with multifoetal gestation or hypertensive disease. It is also associated with higher rates of breastfeeding within 1 h of delivery. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Gastroschisis is a congenital anomaly that has been reported to be increasing in frequency. The objective of this study was to determine the birth prevalence of gastroschisis using two large databases. STUDY DESIGN: We reviewed data from a statewide database and a national database from a neonatal health care provider, abstracting cases of gastroschisis. RESULTS: In North Carolina, the birth prevalence of gastroschisis increased from 1.96 per 10,000 births in 1997 to 4.49 per 10,000 births in 2000 (p = 0.0007). The overall increase was almost entirely because of the increase in infants born to mothers less than 20 years old. Among infants receiving care from the national neonatal provider, the prevalence of gastroschisis increased from 2.9 per 1000 patients in 1997 to five per 1000 patients in 2001 (p = 0.044). CONCLUSION: The birth prevalence of gastroschisis is increasing in North Carolina, and this trend may be occurring nationally. The rapid change in the birth prevalence in the subset of population most at risk for gastroschisis implicates environmental or pharmacologic teratogens rather than changing population characteristics as a causal factor in the development of gastroschisis. [ABSTRACT FROM AUTHOR]

Background: Preterm birth continues to be a major public health problem contributing to 75% of the neonatal mortality worldwide. Low birth weight (LBW) is an important but imperfect surrogate for prematurity when accurate assessment of gestational age is not possible. While there is overlap between preterm birth and LBW newborns, those that are both premature and LBW are at the highest risk of adverse neonatal outcomes. Understanding the epidemiology of preterm birth and LBW is important for prevention and improved care for at risk newborns, but in many countries, data are sparse and incomplete. Methods: We conducted data analyses using the Global Network's (GN) population-based registry of pregnant women and their babies in rural communities in six low- and middle-income countries (Democratic Republic of Congo, Kenya, Zambia, Guatemala, India and Pakistan). We analyzed data from January 2014 to December 2018. Trained study staff enrolled all pregnant women in the study catchment area as early as possible during pregnancy and conducted follow-up visits shortly after delivery and at 42 days after delivery. We analyzed the rates of preterm birth, LBW and the combination of preterm birth and LBW and studied risk factors associated with these outcomes across the GN sites. Results: A total of 272,192 live births were included in the analysis. The overall preterm birth rate was 12.6% (ranging from 8.6% in Belagavi, India to 21.8% in the Pakistani site). The overall LBW rate was 13.6% (ranging from 2.7% in the Kenyan site to 21.4% in the Pakistani site). The overall rate of both preterm birth and LBW was 5.5% (ranging from 1.2% in the Kenyan site to 11.0% in the Pakistani site). Risk factors associated with preterm birth, LBW and the combination were similar across sites and included nulliparity [RR − 1.27 (95% CI 1.21–1.33)], maternal age under 20 [RR 1.41 (95% CI 1.32–1.49)] years, severe antenatal hemorrhage [RR 5.18 95% CI 4.44–6.04)], hypertensive disorders [RR 2.74 (95% CI − 1.21–1.33], and 1–3 antenatal visits versus four or more [RR 1.68 (95% CI 1.55–1.83)]. Conclusions: Preterm birth, LBW and their combination continue to be common public health problems at some of the GN sites, particularly among young, nulliparous women who have received limited antenatal care services. Trial registration The identifier of the Maternal and Newborn Health Registry at ClinicalTrials.gov is NCT01073475.Trial registration: The identifier of the Maternal and Newborn Health Registry at ClinicalTrials.gov is NCT01073475. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic status (SES) is an important determinant of health globally and an important explanatory variable to assess causality in epidemiological research. The 10th Sustainable Development Goal is to reduce disparities in SES that impact health outcomes globally. It is easier to study SES in high-income countries because household income is representative of the SES. However, it is well recognized that income is poorly reported in low- and middle- income countries (LMIC) and is an unreliable indicator of SES. Therefore, there is a need for a robust index that will help to discriminate the SES of rural households in a pooled dataset from LMIC. Methods: The study was nested in the population-based Maternal and Neonatal Health Registry of the Global Network for Women's and Children's Health Research which has 7 rural sites in 6 Asian, sub-Saharan African and Central American countries. Pregnant women enrolling in the Registry were asked questions about items such as housing conditions and household assets. The characteristics of the candidate items were evaluated using confirmatory factor analyses and item response theory analyses. Based on the results of these analyses, a final set of items were selected for the SES index. Results: Using data from 49,536 households of pregnant women, we reduced the data collected to a 10-item index. The 10 items were feasible to administer, covered the SES continuum and had good internal reliability and validity. We developed a sum score-based Item Response Theory scoring algorithm which is easy to compute and is highly correlated with scores based on response patterns (r = 0.97), suggesting minimal loss of information with the simplified approach. Scores varied significantly by site (p < 0.001). African sites had lower mean SES scores than the Asian and Central American sites. The SES index demonstrated good internal consistency reliability (Cronbach's alpha = 0.81). Higher SES scores were significantly associated with formal education, more education, having received antenatal care, and facility delivery (p < 0.001). Conclusions: While measuring SES in LMIC is challenging, we have developed a Global Network Socioeconomic Status Index which may be useful for comparisons of SES within and between locations. Next steps include understanding how the index is associated with maternal, perinatal and neonatal mortality. Trial Registration NCT01073475 Plain English summary: Socioeconomic status (SES) is an important determinant of health globally, and improving SES is important to reduce disparities in health outcomes. It is easier to study SES in high-income countries because it can be measured by income and what income is spent on, but this concept does not translate easily to low and middle income countries. We developed a questionnaire that includes 10 items to determine SES in low-resource settings that was added to an ongoing Maternal and Neonatal Health Registry that is funded by the National Institutes of Child Health and Human Development's Global Network. The Registry includes sites that collect outcomes of pregnancies in women and their babies in rural areas in 6 countries in South Asia, sub-Saharan Africa and Central America. The Registry is population based and tracks women from early in pregnancy to day 42 post-partum. The questionnaire is easy to administer and has good reliability and validity. Next steps include understanding how the index is associated with maternal, fetal and neonatal mortality. [ABSTRACT FROM AUTHOR]

Background: Pakistan has among the poorest pregnancy outcomes worldwide, significantly worse than many other low-resource countries. The reasons for these differences are not clear. In this study, we compared pregnancy outcomes in Pakistan to other low-resource countries and explored factors that might help explain these differences. Methods: The Global Network (GN) Maternal Newborn Health Registry (MNHR) is a prospective, population-based observational study that includes all pregnant women and their pregnancy outcomes in defined geographic communities in six low-middle income countries (India, Pakistan, Democratic Republic of Congo, Guatemala, Kenya, Zambia). Study staff enroll women in early pregnancy and follow-up soon after delivery and at 42 days to ascertain delivery, neonatal, and maternal outcomes. We analyzed the maternal mortality ratios (MMR), neonatal mortality rates (NMR), stillbirth rates, and potential explanatory factors from 2010 to 2018 across the GN sites. Results: From 2010 to 2018, there were 91,076 births in Pakistan and 456,276 births in the other GN sites combined. The MMR in Pakistan was 319 per 100,000 live births compared to an average of 124 in the other sites, while the Pakistan NMR was 49.4 per 1,000 live births compared to 20.4 in the other sites. The stillbirth rate in Pakistan was 53.5 per 1000 births compared to 23.2 for the other sites. Preterm birth and low birthweight rates were also substantially higher than the other sites combined. Within weight ranges, the Pakistani site generally had significantly higher rates of stillbirth and neonatal mortality than the other sites combined, with differences increasing as birthweights increased. By nearly every measure, medical care for pregnant women and their newborns in the Pakistan sites was worse than at the other sites combined. Conclusion: The Pakistani pregnancy outcomes are much worse than those in the other GN sites. Reasons for these poorer outcomes likely include that the Pakistani sites' reproductive-aged women are largely poorly educated, undernourished, anemic, and deliver a high percentage of preterm and low-birthweight babies in settings of often inadequate maternal and newborn care. By addressing the issues highlighted in this paper there appears to be substantial room for improvements in Pakistan's pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Few studies have shown how the move toward institutional delivery in low and middle-income countries (LMIC) impacts stillbirth and newborn mortality. Objectives: The study evaluated trends in institutional delivery in research sites in Belagavi and Nagpur India, Guatemala, Kenya, Pakistan, and Zambia from 2010 to 2018 and compared them to changes in the rates of neonatal mortality and stillbirth. Methods: We analyzed data from a nine-year interval captured in the Global Network (GN) Maternal Newborn Health Registry (MNHR). Mortality rates were estimated from generalized estimating equations controlling for within-cluster correlation. Cluster-level analyses were performed to assess the association between institutional delivery and mortality rates. Results: From 2010 to 2018, a total of 413,377 deliveries in 80 clusters across 6 sites in 5 countries were included in these analyses. An increase in the proportion of institutional deliveries occurred in all sites, with a range in 2018 from 57.7 to 99.8%. In 2010, the stillbirth rates ranged from 19.3 per 1000 births in the Kenyan site to 46.2 per 1000 births in the Pakistani site and by 2018, ranged from 9.7 per 1000 births in the Belagavi, India site to 40.8 per 1000 births in the Pakistani site. The 2010 neonatal mortality rates ranged from 19.0 per 1000 live births in the Kenyan site to 51.3 per 1000 live births in the Pakistani site with the 2018 neonatal mortality rates ranging from 9.2 per 1000 live births in the Zambian site to 50.2 per 1000 live births in the Pakistani site. In multivariate modeling, in some but not all sites, the reductions in stillbirth and neonatal death were significantly associated with an increase in the institutional deliveries. Conclusions: There was an increase in institutional delivery rates in all sites and a reduction in stillbirth and neonatal mortality rates in some of the GN sites over the past decade. The relationship between institutional delivery and a decrease in mortality was significant in some but not all sites. However, the stillbirth and neonatal mortality rates remain at high levels. Understanding the relationship between institutional delivery and stillbirth and neonatal deaths in resource-limited environments will enable development of targeted interventions for reducing the mortality burden. Trial registration: The study is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475. [ABSTRACT FROM AUTHOR]

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 < 0.001. For multiparous women with a history of prior cesarean birth, rates of vaginal birth after cesarean were about 20% in the Latin American and Southeast Asian sites and about 84% at the sub-Saharan African sites. In the African sites, proportions of cesarean birth in the study were highest among women without a prior cesarean and a single, cephalic, term pregnancy. In the non-African sites, groups with the greatest proportion of cesarean births were nulliparous women with a single, cephalic, term pregnancy and all multiparous women with at least one previous uterine scar with a term, cephalic pregnancy. 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. [ABSTRACT FROM AUTHOR]

Achieving the ambitious reduction in global neonatal mortality targeted in the Sustainable Development Goals and Every Newborn Action Plan will require reducing geographic disparities in newborn deaths through targeted implementation of evidence-based practices. Helping Babies Survive, a suite of educational programs targeting the 3 leading causes of neonatal mortality, has been commonly used to educate providers in evidence-based practices in low-resource settings. Quality improvement (QI) can play a pivotal role in translating this education into improved care. Measurement of key process and outcome indicators, derived from the algorithms ("Action Plans") central to these training programs, can assist health care providers in understanding the baseline quality of their care, identifying gaps, and assessing improvement. Helping Babies Survive has been the focus of QI programs in Kenya, Nepal, Honduras, and Ethiopia, with critical lessons learned regarding the challenge of measurement, necessity of facility-based QI mentorship and multidisciplinary teams, and importance of systemic commitment to improvement in promoting a culture of QI. Complementing education with QI strategies to identify and close remaining gaps in newborn care will be essential achieving the Sustainable Development Goals and Every Newborn Action Plan targets in the coming decade. [ABSTRACT FROM AUTHOR]

Ninety percent of intrapartum-related neonatal deaths are attributable to respiratory depression, with the vast majority of these deaths occurring in low- and lower-middle--income countries. Neonatal resuscitation training with Helping Babies Breathe (HBB) decreases mortality from respiratory depression. Cardiorespiratory monitoring in conjunction with HBB can provide valuable resuscitation feedback for both training and bedside purposes. In this article, we discuss 3 innovations that couple cardiorespiratory monitoring with HBB: NeoNatalie Live, the Augmented Infant Resuscitator, and NeoBeat. NeoNatalie Live is a high-fidelity manikin that facilitates bag mask ventilation training through case scenarios of varying difficulty. The Augmented Infant Resuscitator is added in-line between a face mask and ventilation bag during bag mask ventilation training to provide users with real-time feedback on ventilation quality. NeoBeat is a battery-operated heart rate meter that digitally displays the newborn heart rate during bedside resuscitations. For each innovation, we review details of the device, implementation in the field, and areas for further research. Using early experience implementing these devices, we suggest building blocks for effective translation of training into improved care. We also highlight general challenges in implementation of devices in facilities in low- and lower-middle--income countries including considerations for training, adaptations to existing workflow, and integration into the ecosystem. Although the devices highlighted in this article hold promise, more data are needed to understand their impact on newborn outcomes. [ABSTRACT FROM AUTHOR]

Helping Babies Breathe (HBB) addresses a major cause of newborn mortality by teaching basic steps of neonatal resuscitation and improving survival rates of infants affected by intrapartum-related events or asphyxia. Addressing the additional top causes of mortality (infection and prematurity) requires more comprehensive education, including content on thermal and nutritional support, breastfeeding, and alternative feeding strategies, as well as recognition and treatment of infection. Essential Care for Every Baby (ECEB) and Essential Care for Small Babies (ECSB) use educational principles developed with HBB as a model for teaching basic newborn care. These programs complement the content provided with HBB, further integrate counseling of families, and advance the agenda of providing quality care to all infants at birth. ECEB and ECSB have further demonstrated that engagement of individuals through active participation in their education empowers providers at all levels. With added experience teaching and implementing ECEB and ECSB, the next generation of newborn educational programs will likely incorporate bedside teaching and clinical exposure, multimedia platforms for demonstrating clinical content, and added efforts toward quality improvement. Through ECEB and ECSB, the attention brought to the newborn health agenda with HBB has only grown. Although current global health issues pose new challenges in implementing this agenda, these programs together provide a critical framework to both educate and advocate for optimal care of every newborn. [ABSTRACT FROM AUTHOR]

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 < 28 days (OR 3.18, 95% CI 1.18, 8.57), low birth weight (OR 2.10, 95% CI 1.44, 3.07) and preterm births (OR 2.73, 95%CI 1.76, 4.23). The mean birth weight was 162 g less (95% CI -288.6, − 35.9) with oligohydramnios. 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. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Findings: 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.Interpretation: 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.Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development. [ABSTRACT FROM AUTHOR]

Introduction: Uncertainty exists regarding the impact of malpresentation on pregnancy outcomes and the optimal mode of delivery in low- and middle-income countries. We sought to compare outcomes between cephalic and non-cephalic pregnancies.Material and Methods: Using the NICHD Global Network's prospective, population-based registry of pregnancy outcomes from 2010 to 2016, we studied outcomes in 436 112 singleton pregnancies. Robust Poisson regressions were used to estimate the risk of adverse outcomes associated with malpresentation. We examined rates of cesarean delivery for malpresentation and compared outcomes between cesarean and vaginal delivery by region.Results: Across all regions, stillbirth and neonatal mortality rates were higher among deliveries with malpresentation. In adjusted analysis, malpresentation was significantly associated with stillbirth (adjusted relative risk [aRR] 4.0, 95% confidence interval [CI] 3.7-4.5) and neonatal mortality (aRR 2.3, 95% CI 2.1-2.6). Women with deliveries complicated by malpresentation had higher rates of morbidity and mortality. Rates of cesarean delivery for malpresentation ranged from 27% to 87% among regions. Compared with cesarean delivery, vaginal delivery for malpresentation was associated with increased maternal risk, especially postpartum hemorrhage (aRR 5.0, 95% CI; 3.6-7.1).Conclusions: In a cohort of deliveries in low- and middle-income countries, malpresentation was associated with increased perinatal and maternal risk. Further research is needed to determine the best management of these pregnancies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Maternal stature and body mass indices (BMI) of non-pregnant women (NPW) of child bearing age are relevant to maternal and offspring health. The objective was to compare anthropometric indices of NPW in four rural communities in low- to low-middle income countries (LMIC).Methods: Anthropometry and maternal characteristics/household wealth questionnaires were obtained for NPW enrolled in the Women First Preconception Maternal Nutrition Trial. Body mass index (BMI, kg/m2) was calculated. Z-scores were determined using WHO reference data.Results: A total of 7268 NPW participated in Equateur, DRC (n = 1741); Chimaltenango, Guatemala (n = 1695); North Karnataka, India (n = 1823); and Thatta, Sindh, Pakistan (n = 2009). Mean age was 23 y and mean parity 1.5. Median (P25-P75) height (cm) ranged from 145.5 (142.2-148.9) in Guatemala to 156.0 (152.0-160.0) in DRC. Median weight (kg) ranged from 44.7 (39.9-50.3) in India to 52.7 (46.9-59.8) in Guatemala. Median BMI ranged from 19.4 (17.6-21.9) in India to 24.9 (22.3-28.0) in Guatemala. Percent stunted (<-2SD height for age z-score) ranged from 13.9% in DRC to 80.5% in Guatemala; % underweight (BMI <18.5) ranged from 1.2% in Guatemala to 37.1% in India; % overweight/obese (OW, BMI ≥25.0) ranged from 5.7% in DRC to 49.3% in Guatemala. For all sites, indicators for higher SES and higher age were associated with BMI. Lower SES women were underweight more frequently and higher SES women were OW more frequently at all sites. Younger women tended to be underweight, while older women tended to be OW.Conclusions: Anthropometric data for NPW varied widely among low-income rural populations in four countries located on three different continents. Global comparisons of anthropometric measurements across sites using standard reference data serve to highlight major differences among populations of low-income rural NPW and assist in evaluating the rationale for and the design of optimal intervention trials.Trial Registration: ClinicalTrials.gov # NCT01883193 (18 June 2013, retrospectively registered). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) may substantially reduce the rate of PTB.Methods: Hypothesis: LDA initiated in the first trimester reduces the risk of preterm birth. Study Design Type: Prospective randomized, placebo-controlled, double-blinded multi-national clinical trial conducted in seven low and middle income countries. Trial will be individually randomized with one-to-one ratio (intervention/control) Population: Nulliparous women between the ages of 14 and 40, with a singleton pregnancy between 6 0/7 weeks and 13 6/7 weeks gestational age (GA) confirmed by ultrasound prior to enrollment, no more than two previous first trimester pregnancy losses, and no contraindications to aspirin.Intervention: Daily administration of low dose (81 mg) aspirin, initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA, compared to an identical appearing placebo. Compliance and outcomes will be assessed biweekly.Outcomes: Primary outcome: Incidence of PTB (birth prior to 37 0/7 weeks GA). Secondary outcomes Incidence of preeclampsia/eclampsia, small for gestational age and perinatal mortality.Discussion: This study is unique as it will examine the impact of LDA early in pregnancy in low-middle income countries with preterm birth as a primary outcome. The importance of developing low-cost, high impact interventions in low-middle income countries is magnified as they are often unable to bear the financial costs of treating illness.Trial Registration: ClinicalTrials.gov identifier: NCT02409680 Date: March 30, 2015. [ABSTRACT FROM AUTHOR]

Background: Infants of women with lower education levels are at higher risk for perinatal mortality. Objectives: We explored the impact of training birth attendants and pregnant women in the Essential Newborn Care (ENC) Program on fresh stillbirths (FSBs) and early (7-day) neonatal deaths (END) by maternal education level in developing countries. Methods: A train-the-trainer model was used with local instructors in rural communities in six countries (Argentina, Democratic Republic of the Congo, Guatemala, India, Pakistan, and Zambia). Data were collected using a pre-/postactive baseline controlled study design. Results: A total of 57,643 infants/mothers were enrolled. The follow-up rate at 7 days of age was 99.2%. The risk for FSB and END was higher for mothers with 0-7 years of education than for those with ≥ 8 years of education during both the pre- and post- ENC periods in unadjusted models and in models adjusted for confounding. The effect of ENC differed as a function of maternal education for FSB (interaction p = 0.041) without evidence that the effect of ENC differed as a function of maternal education for END. The model-based estimate of FSB risk was reduced among mothers with 0-7 years of education (19.7/1,000 live births pre-ENC, CI: 16.3, 23.0 vs. 12.2/1,000 live births post-ENC, CI: 16.3, 23.0, p < 0.001), but was not significantly different for mothers with ≥ 8 years of education, respectively. Conclusion: A low level of maternal education was associated with higher risk for FSB and END. ENC training was more effective in reducing FSB among mothers with low education levels. [ABSTRACT FROM AUTHOR]

Journal of Perinatology (2002) 22, 306–307 DOI: 10.1038/sj/jp/7210696 [ABSTRACT FROM AUTHOR]

Micronutrient deficiency is an important cause of growth stunting. To avoid micronutrient deficiency, the World Health Organization recommends complementary feeding with animal‐source foods. However, animal‐source foods are not readily available in many parts of the Democratic Republic of Congo (DRC). In such areas, caterpillars are a staple in adult diets and may be suitable for complementary feeding for infants and young children. We developed a cereal made from dried caterpillars and other locally available ingredients (ground corn, palm oil, sugar and salt), measured its macro‐ and micronutrient contents and evaluated for microbiologic contamination. Maternal and infant acceptability was evaluated among 20 mothers and their 8–10‐month‐old infants. Mothers were instructed in the preparation of the cereal and asked to evaluate the cereal in five domains using a Likert scale. Mothers fed their infants a 30‐g portion daily for 1 week. Infant acceptability was based on cereal consumption and the occurrence of adverse events. The caterpillar cereal contained 132 kcal, 6.9‐g protein, 3.8‐mg iron and 3.8‐mg zinc per 30 g and was free from microbiologic contamination. Mothers’ median ratings for cereal characteristics were (5 = like very much): overall impression = 4, taste = 5, smell = 4, texture = 4, colour = 5, and consistency = 4. All infants consumed more than 75% of the daily portions, with five infants consuming 100%. No serious adverse events were reported. We conclude that a cereal made from locally available caterpillars has appropriate macro‐ and micronutrient contents for complementary feeding, and is acceptable to mothers and infants in the DRC. [ABSTRACT FROM AUTHOR]

ObjectiveWe conducted a cluster-randomized controlled trial to assess the efficacy of a cereal made from caterpillars, a micronutrient-rich, locally available alternative animal-source food, on reducing stunting and anaemia in infants in the Democratic Republic of Congo.DesignSix-month-old infants were cluster randomized to receive either caterpillar cereal daily until 18 months of age or the usual diet. At 18 months of age, anthropometric measurements and biological samples were collected.SettingThe rural Equateur Province in the Democratic Republic of Congo.SubjectsOne hundred and seventy-five infants followed from 6 to 18 months of age.ResultsStunting was common at 6 months (35 %) and the prevalence increased until 18 months (69 %). There was no difference in stunting prevalence at 18 months between the intervention and control groups (67 % v. 71 %, P=0·69). Infants in the cereal group had higher Hb concentration than infants in the control group (10·7 v. 10·1 g/dl, P=0·03) and fewer were anaemic (26 v. 50 %, P=0·006), although there was no difference in estimates of body Fe stores (6·7 v. 7·2 mg/kg body weight, P=0·44).ConclusionsSupplementation of complementary foods with caterpillar cereal did not reduce the prevalence of stunting at 18 months of age. However, infants who consumed caterpillar cereal had higher Hb concentration and fewer were anaemic, suggesting that caterpillar cereal might have some beneficial effect. The high prevalence of stunting at 6 months and the lack of response to this micronutrient-rich supplement suggest that factors other than dietary deficiencies also contribute to stunting. [ABSTRACT FROM AUTHOR]

Background: Health centers in low-income countries often depend on donations to provide appropriate diagnostic equipment. However, donations are sometimes made without an understanding of the recipient's needs, practical constraints or sustainability of supplies. Methods:We donated a set of physical diagnostic equipment, non-invasive instrument tests and laboratory supplies to a rural health center in the Democratic Republic of Congo. We collected information on the usage and durability of equipment and supplies for each patient encounter over a 1-year period. Results:We recorded 913 patient encounters. The most commonly used physical diagnostic equipment were the stethoscope (98.9%; 903/913), thermometer (81.7%; 746/913), adult scale (81.4%; 744/913), stop watch (62.6%; 572/913), adult sphygmomanometer (55.8%; 510/913), infant scale (24.9%; 228/913), measuring tape (24.3%; 222/913) and fetoscope (23.8%; 218/913). The most commonly used laboratory tests were the blood smear for malaria (53.7%; 491/913), hematocrit (23.5%; 215/913), urinalysis (20.1%; 184/913) and sputum stain for TB (13.3%; 122/913). With the exception of a penlight and solar lantern, all equipment remained functional. Conclusions: This study adds valuable information about the utility and durability of equipment supplied to a health center in the Democratic Republic of Congo. Our results might aid in determining the appropriateness of donated medical equipment in similar settings. The selection of donated goods should be made with knowledge of the context in which it will be used, and utilization should be monitored. [ABSTRACT FROM AUTHOR]

Background: Stillbirth rates remain nearly ten times higher in low-middle income countries (LMIC) than high income countries. In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented characteristics or care for mothers with stillbirths. Non-macerated stillbirths, those occurring around delivery, are generally considered preventable with appropriate obstetric care. Methods: We undertook a prospective, population-based observational study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Results: From 2010 through 2013, 269,614 enrolled women had 272,089 births, including 7,865 stillbirths. The overall stillbirth rate was 28.9/1000 births, ranging from 13.6/1000 births in Argentina to 56.5/1000 births in Pakistan. Stillbirth rates were stable or declined in 6 of the 7 sites from 2010-2013, only increasing in Pakistan. Less educated, older and women with less access to antenatal care were at increased risk of stillbirth. Furthermore, women not delivered by a skilled attendant were more likely to have a stillbirth (RR 2.8, 95% CI 2.2, 3.5). Compared to live births, stillbirths were more likely to be preterm (RR 12.4, 95% CI 11.2, 13.6). Infants with major congenital anomalies were at increased risk of stillbirth (RR 9.1, 95% CI 7.3, 11.4), as were multiple gestations (RR 2.8, 95% CI 2.4, 3.2) and breech (RR 3.0, 95% CI 2.6, 3.5). Altogether, 67.4% of the stillbirths were non-macerated. 7.6% of women with stillbirths had cesarean sections, with obstructed labor the primary indication (36.9%). Conclusions: Stillbirth rates were high, but with reductions in most sites during the study period. Disadvantaged women, those with less antenatal care and those delivered without a skilled birth attendant were at increased risk of delivering a stillbirth. More than two-thirds of all stillbirths were non-macerated, suggesting potentially preventable stillbirth. Additionally, 8% of women with stillbirths were delivered by cesarean section. The relatively high rate of cesarean section among those with stillbirths suggested that this care was too late or not of quality to prevent the stillbirth; however, further research is needed to evaluate the quality of obstetric care, including cesarean section, on stillbirth in these low resource settings. [ABSTRACT FROM AUTHOR]

Background: Research directed to optimizing maternal nutrition commencing prior to conception remains very limited, despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy. Methods/Study design: This is an individually randomized controlled trial of the impact on birth length (primary outcome) of the time at which a maternal nutrition intervention is commenced: Arm 1: = 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none. 192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) <20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites. Discussion: Positive results of this trial will support a paradigm shift in attention to nutrition of all females of child-bearing age. [ABSTRACT FROM AUTHOR]

Background: In high-resource settings, obstetric ultrasound is a standard component of prenatal care used to identify pregnancy complications and to establish an accurate gestational age in order to improve obstetric care. Whether or not ultrasound use will improve care and ultimately pregnancy outcomes in low-resource settings is unknown. Methods/Design: This multi-country cluster randomized trial will assess the impact of antenatal ultrasound screening performed by health care staff on a composite outcome consisting of maternal mortality and maternal near-miss, stillbirth and neonatal mortality in low-resource community settings. The trial will utilize an existing research infrastructure, the Global Network for Women's and Children's Health Research with sites in Pakistan, Kenya, Zambia, Democratic Republic of Congo and Guatemala. A maternal and newborn health registry in defined geographic areas which documents all pregnancies and their outcomes to 6 weeks post-delivery will provide population-based rates of maternal mortality and morbidity, stillbirth, neonatal mortality and morbidity, and health care utilization for study clusters. A total of 58 study clusters each with a health center and about 500 births per year will be randomized (29 intervention and 29 control). The intervention includes training of health workers (e.g., nurses, midwives, clinical officers) to perform ultrasound examinations during antenatal care, generally at 18-22 and at 32-36 weeks for each subject. Women who are identified as having a complication of pregnancy will be referred to a hospital for appropriate care. Finally, the intervention includes community sensitization activities to inform women and their families of the availability of ultrasound at the antenatal care clinic and training in emergency obstetric and neonatal care at referral facilities. Discussion: In summary, our trial will evaluate whether introduction of ultrasound during antenatal care improves pregnancy outcomes in rural, low-resource settings. The intervention includes training for ultrasound-naïve providers in basic obstetric ultrasonography and then enabling these trainees to use ultrasound to screen for pregnancy complications in primary antenatal care clinics and to refer appropriately. [ABSTRACT FROM AUTHOR]

Aim. To determine among infants born before the 28th week of gestation to what extent blood gas abnormalities during the first three postnatal days provide information about the risk of bronchopulmonary dysplasia (BPD). Methods. We studied the association of extreme quartiles of blood gas measurements (hypoxemia, hyperoxemia, hypocapnea, and hypercapnea) in the first three postnatal days, with bronchopulmonary dysplasia, among 906 newborns, using multivariable models adjusting for potential confounders. We approximated NIH criteria by classifying severity of BPD on the basis of the receipt of any O2 on postnatal day 28 and at 36 weeks PMA and assisted ventilation. Results. In models that did not adjust for ventilation, hypoxemia was associated with increased risk of severe BPD and very severe BPD, while infants who had hypercapnea were at increased risk of very severe BPD only. In contrast, infants who had hypocapnea were at reduced risk of severe BPD. Including ventilation for 14 or more days eliminated the associations with hypoxemia and with hypercapnea and made the decreased risk of very severe BPD statistically significant. Conclusions. Among ELGANs, recurrent/persistent blood gas abnormalities in the first three postnatal days convey information about the risk of severe and very severe BPD. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility of introducing a simple indicator of quality of obstetric and neonatal care and to determine the proportion of potentially avoidable perinatal deaths in hospitals in low-income countries.Methods: Between September 1, 2011, and February 29, 2012, data were collected from consecutive women who were admitted to the labor ward of 1 of 6 hospitals in 4 low-income countries. Fetal heart tones on admission were monitored, and demographic and birth data were recorded.Results: Data were obtained for 3555 women and 3593 neonates (including twins). The doptone was used on 97% of women admitted. The overall perinatal mortality rate was 34 deaths per 1000 deliveries. Of the perinatal deaths, 40%-45% occurred in the hospital and were potentially preventable by better hospital care.Conclusion: The results demonstrated that it is possible to accurately determine fetal viability on admission via a doptone. Implementation of doptone use, coupled with a concise data record, might form the basis of a low-cost and sustainable program to monitor and evaluate efforts to improve quality of care and ultimately might help to reduce the in-hospital component of perinatal mortality in low-income countries. [ABSTRACT FROM AUTHOR]