Exclusive Breastfeeding and Developmental and Behavioral Status in Early Childhood

Breastfeeding during infancy may have beneficial effects on various developmental outcomes in childhood. In this study, exclusively breastfed infants were randomly assigned to receive complementary foods from the age of 4 months in addition to breast milk (CF, n = 60), or to exclusively breastfeed to 6 months (EBF, n = 59). At 18 months and again at 30–35 months of age, the children were evaluated with the Parent’s Evaluation of Developmental Status questionnaire (PEDS) and the Brigance Screens-II. The parents completed the PEDS questionnaire at both time intervals and the children underwent the Brigance Screens-II at 30–35 months. At 30–35 months, no significant differences were seen in developmental scores from the Brigance screening test (p = 0.82). However, at 30–35 months a smaller percentage of parents in group CF (2%) had concerns about their children’s gross motor development compared to those in group EBF (19%; p = 0.01), which remained significant when adjusted for differences in pre-randomization characteristics (p = 0.03). No sustained effect of a longer duration of exclusive breastfeeding was seen on selected measures of developmental and behavioral status at 18 months, although at 30–35 months, a smaller percentage of parents of children introduced to complementary foods at four months of age expressed concerns about their gross motor development

The relationship between birth intervals and adverse maternal and neonatal outcomes in six low and lower-middle income countries

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

Neonatal deaths in infants born weighing ≥ 2500 g in low and middle-income countries

Background: Babies born weighing ≥ 2500 g account for more than 80% of the births in most resource-limited locations and for nearly 50% of the 28-day neonatal deaths. In contrast, in high-resource settings, 28-day neonatal mortality among this group represents only a small fraction of the neonatal deaths. Yet mortality risks for birth weight of ≥ 2500 g is limited. Knowledge regarding the factors associated with mortality in these babies will help in identifying interventions that can reduce mortality.Methods: The Global Network\u27s 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 that has been conducted in research sites in six low-middle income countries (India, Pakistan, Democratic Republic of Congo, Guatemala, Kenya and Zambia). Study staff enroll all pregnant women as early as possible during pregnancy and conduct follow-up visits to ascertain delivery and 28-day neonatal outcomes. We analyzed the neonatal mortality rates (NMR) and risk factors for deaths by 28 days among all live-born babies with a birthweight ≥ 2500 g from 2010 to 2018 across the Global Network sites.Results: Babies born in the Global Network sites from 2010 to 2018 with a birthweight ≥ 2500 g accounted for 84.8% of the births and 45.4% of the 28-day neonatal deaths. Among this group, the overall NMR was 13.1/1000 live births. The overall 28-day NMR for ongoing clusters was highest in Pakistan (29.7/1000 live births) and lowest in the Zambian/Kenyan sites (9.3/1000) for ≥ 2500 g infants. ≥ 2500 g NMRs declined for Zambia/Kenya and India. For Pakistan and Guatemala, the NMR remained almost unchanged over the period. The ≥ 2500 g risks related to maternal, delivery and newborn characteristics varied by site. Maternal factors that increased risk and were common for all sites included nulliparity, hypertensive disease, previous stillbirth, maternal death, obstructed labor, severe postpartum hemorrhage, and abnormal fetal presentation. Neonatal characteristics including resuscitation, hospitalization, congenital anomalies and male sex, as well as lower gestational ages and birthweights were also associated with increased mortality.Conclusions: Nearly half of neonatal deaths in the Global Network sites occurred in infants born weighing ≥ 2500 g. The NMR for those infants was 13.1 per 1000 live births, much higher than rates usually seen in high-income countries. The changes in NMR over time varied across the sites. Even among babies born ≥ 2500 g, lower gestational age and birthweight were largely associated with increased risk of mortality. Since many of these deaths should be preventable, attention to preventing mortality in these infants should have an important impact on overall NMR.Trial registration: https://ClinicalTrials.gov Identifier: NCT01073475

The global network maternal newborn health registry: A multi-country, community-based registry of pregnancy outcomes

Background: The Global Network for Women\u27s and Children\u27s Health Research (Global Network) conducts clinical trials in resource-limited countries through partnerships among U.S. investigators, international investigators based in in low and middle-income countries (LMICs) and a central data coordinating center. The Global Network\u27s objectives include evaluating low-cost, sustainable interventions to improve women\u27s and children\u27s health in LMICs. Accurate reporting of births, stillbirths, neonatal deaths, maternal mortality, and measures of obstetric and neonatal care is critical to determine strategies for improving pregnancy outcomes. In response to this need, the Global Network developed the Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnant women, fetuses and neonates receiving care in defined catchment areas at the Global Network sites. This publication describes the MNHR, including participating sites, data management and quality and changes over time.Methods: Pregnant women who reside in or receive healthcare in select communities are enrolled in the MNHR of the Global Network. For each woman and her offspring, sociodemographic, health care, and the major outcomes through 42-days post-delivery are recorded. Study visits occur at enrollment during pregnancy, at delivery and at 42 days postpartum.Results: From 2010 through 2018, the Global Network MNHR sites were located in Guatemala, Belagavi and Nagpur, India, Pakistan, Democratic Republic of Congo, Kenya, and Zambia. During this period at these sites, 579,140 pregnant women were consented and enrolled in the MNHR, nearly 99% of all eligible women. Delivery data were collected for 99% of enrolled women and 42-day follow-up data for 99% of those delivered. In this supplement, the trends over time and assessment of differences across geographic regions are analyzed in a series of 18 manuscripts utilizing the MNHR data.Conclusions: Improving maternal, fetal and newborn health in countries with poor outcomes requires an understanding of the characteristics of the population, quality of health care and outcomes. 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, population-based registry, assesses pregnancy outcomes over time in support of efforts to develop improved perinatal healthcare in resource-limited areas. Trial Registration The Maternal Newborn Health Registry is registered at Clinicaltrials.gov (ID# NCT01073475). Registered February 23, 2019. https://clinicaltrials.gov/ct2/show/NCT01073475

Regional trends in birth weight in low- and middle-income countries 2013-2018

Background: Birth weight (BW) is a strong predictor of neonatal outcomes. The purpose of this study was to compare BWs between global regions (south Asia, sub-Saharan Africa, Central America) prospectively and to determine if trends exist in BW over time using the population-based maternal and newborn registry (MNHR) of the Global Network for Women\u27sand Children\u27s Health Research (Global Network).Methods: The MNHR is a prospective observational population-based registryof six research sites participating in the Global Network (2013-2018), within five low- and middle-income countries (Kenya, Zambia, India, Pakistan, and Guatemala) in threeglobal regions (sub-Saharan Af rica, south Asia, Central America). The birth weights were obtained for all infants born during the study period. This was done either by abstracting from the infants\u27 health facility records or from direct measurement by the registry staff for infants born at home. After controlling for demographic characteristics, mixed-effect regression models were utilized to examine regional differences in birth weights over time.Results: The overall BW meanswere higher for the African sites (Zambia and Kenya), 3186 g (SD 463 g) in 2013 and 3149 g (SD 449 g) in 2018, ascompared to Asian sites (Belagavi and Nagpur, India and Pakistan), 2717 g (SD450 g) in 2013 and 2713 g (SD 452 g) in 2018. The Central American site (Guatemala) had a mean BW intermediate between the African and south Asian sites, 2928 g (SD 452) in 2013, and 2874 g (SD 448) in 2018. The low birth weight (LBW) incidence was highest in the south Asian sites (India and Pakistan) and lowest in the African sites (Kenya and Zambia). The size of regional differences varied somewhat over time with slight decreases in the gap in birth weights between the African and Asian sites and slight increases in the gap between the African and Central American sites.Conclusions: Overall, BWmeans by global region did not change significantly over the 5-year study period. From 2013 to 2018, infants enrolled at the African sites demonstrated the highest BW means overall across the entire study period, particularly as compared to Asian sites. The incidence of LBW was highest in the Asian sites (India and Pakistan) compared to the African and Central American sites. Trial registration The study is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475

Association of parity with birthweight and neonatal death in five sites: The global network\u27s maternal newborn health registry study

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 \u3c 28-day neonatal mortality rate (27.7 per 1,000 live births) than parous women (17.2 and 20.7 for parity of 1-3 and ≥ 4 respectively). Risk of preterm birth was higher among women with ≥ 4 previous pregnancies (15.5%) compared to 11.3% for the nulliparous group and 11.8% for women with one to three previous pregnancies (p = 0.0072).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

Gender variations in neonatal and early infant mortality in India and Pakistan: A secondary analysis from the global network maternal newborn health registry

Background: To 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.Methods: This 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.Results: Between 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 \u3c 0.001). The rates of stillbirths (31.0 vs. 26.9/1000 births) and early neonatal mortality (27.1 vs 21.6/1000 live births) were also higher in males. However, there were no significant differences in late neonatal mortality (6.3 vs. 5.9/1000 live births) and mortality between 29-42 days (2.1 vs. 1.9/1000 live births) between the two groups. More male infants were hospitalized within 42 days after birth (1.8/1000 vs. 1.3/1000 live births, p \u3c 0.001) than females.Conclusion: The 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

Hemoglobin concentrations and adverse birth outcomes in south Asian pregnant women: Findings from a prospective maternal and neonatal health registry

Background: While the relationship between hemoglobin (Hb) concentrations and pregnancy outcomes has been studied often, most reports have focused on a specific Hb cutoff used to define anemia. Fewer studies have evaluated pregnancy outcomes across the entire range of Hb values. Moreover, to date, most studies of the relationship of Hb concentrations to pregnancy outcomes have been done in high-income countries. Thus, we have sought to determine the relationship between the range of maternal Hb concentrations and adverse birth outcomes among South Asian pregnant women.Methods: For this study, we used data collected from two South Asian countries (Pakistan - Sindh Province and two sites in India - Belagavi and Nagpur) in a prospective maternal and newborn health registry study. To assess the association between Hb concentrations and various maternal and fetal outcomes, we classified the Hb concentrations into seven categories. Regression analyses adjusting for multiple potential confounders were performed to assess adverse pregnancy outcomes across the range of Hb concentrations.Findings: Between January 2012 and December 2018, 130,888 pregnant women were enrolled in the South Asian sites had a Hb measurement available, delivered and were included in the analyses. Overall, the mean Hb concentration of pregnant women from the sites was 9.9 g/dL, 10.0 g/dL in the Indian sites and 9.5 g/dL in the Pakistan site. Hb concentrations \u3c 7 g/dL were observed in 6.9% of the pregnant Pakistani women and 0.2% of the Indian women. In both the Pakistani and Indian sites, women with higher parity and women with no formal education had lower Hb concentrations. In the Pakistani site, women \u3e 35 years of age, women with ≥4 children and those who enrolled in the third trimester were more likely to have Hb concentrations of \u3c 7 g/dL but these associations were not found for the Indian sites. When adjusting for potential confounders, for both India and Pakistan, lower Hb concentrations were associated with stillbirth, preterm birth, lower mean birthweight, and increased risk of low birthweight. In the Pakistani site, there was evidence of a U-shaped relationship between Hb concentrations and low birth weight, and neonatal mortality, and in India with hypertensive disease.Interpretation: This study documented the relationship between maternal Hb concentrations and adverse pregnancy outcomes in women from the Pakistani and Indian sites across the range of Hb values. Both low and high Hb concentrations were associated with risk of at least some adverse outcomes. Hence, both low and high values of Hb should be considered risk factors for the mother and fetus

Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings

BACKGROUND: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network´s (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs). METHODS: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013. RESULTS: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time. CONCLUSION: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health.Fil: Goudar, Shivaprasad S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Stolka, Kristen B.. Research Triangle Institute International; Estados UnidosFil: Koso Thomas, Marion. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Honnungar, Narayan V.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Mastiholi, Shivanand C.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Ramadurg, Umesh Y.. S. Nijalingappa Medical College; IndiaFil: Dhaded, Sangappa M.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Pasha, Omrana. Aga Khan University; PakistánFil: Patel, Archana. Indira Gandhi Government Medical College and Lata Medical Research Foundation; IndiaFil: Esamai, Fabian. University School of Medicine; KeniaFil: Chomba, Elwyn. University of Zambia; ZambiaFil: Garces, Ana. Universidad de San Carlos; GuatemalaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Carlo, Waldemar A.. University of Alabama at Birmingahm; Estados UnidosFil: Goldenberg, Robert L.. Columbia University; Estados UnidosFil: Hibberd, Patricia L.. Massachusetts General Hospital for Children; Estados UnidosFil: Liechty, Edward A.. Indiana University; Estados UnidosFil: Krebs, Nancy F.. University of Colorado School of Medicine; Estados UnidosFil: Hambidge, Michael K.. University of Colorado School of Medicine; Estados UnidosFil: Moore, Janet L.. Research Triangle Institute International; Estados UnidosFil: Wallace, Dennis D.. Research Triangle Institute International; Estados UnidosFil: Derman, Richard J. Christiana Care Health Services; Estados UnidosFil: Bhalachandra, Kodkany S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Bose, Carl L.. University of North Carolina; Estados Unido