Birth weight and gestational age distributions in a rural Kenyan population.

BACKGROUND: With the increased availability of access to prenatal ultrasound in low/middle-income countries, there is opportunity to better characterize the association between fetal growth and birth weight across global settings. This is important, as fetal growth curves and birthweight charts are often used as proxy health indicators. As part of a randomized control trial, in which ultrasonography was utilized to establish accurate gestational age of pregnancies, we explored the association between gestational age and birthweight among a cohort in Western Kenya, then compared our results to data reported by the INTERGROWTH-21st study. METHODS: This study was conducted in 8 geographical clusters across 3 counties in Western Kenya. Eligible subjects were nulliparous women carrying singleton pregnancies. An early ultrasound was performed between 6 + 0/7 and 13 + 6/7 weeks gestational age. At birth, infants were weighed on platform scales provided either by the study team (community births), or the Government of Kenya (public health facilities). The 10th, 25th, median, 75th, and 90th BW percentiles for 36 to 42 weeks gestation were determined; resulting percentile points were plotted, and curves determined using a cubic spline technique. A signed rank test was used to quantify the comparison of the percentiles generated in the rural Kenyan sample with those of the INTERGROWTH-21st study. RESULTS: A total of 1291 infants (of 1408 pregnant women randomized) were included. Ninety-three infants did not have a measured birth weight. The majority of these were due to miscarriage (n = 49) or stillbirth (n = 27). No significant differences were found between subjects who were lost to follow-up. Signed rank comparisons of the observed median of the Western Kenya data at 10th, 50th, and 90th birthweight percentiles, as compared to medians reported in the INTERGROWTH-21st distributions, revealed close alignment between the two datasets, with significant differences at 36 and 37 weeks. Limitations of the current study include small sample size, and detection of potential digit preference bias. CONCLUSIONS: A comparison of birthweight percentiles by gestational age estimation, among a sample of infants from rural Kenya, revealed slight differences as compared to those from the global population (INTERGROWTH-21st). TRIAL REGISTRATION: This is a single site sub-study of data collected in conjunction with the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN) Trial, which is listed at  ClinicalTrials.gov ,  NCT02409680 (07/04/2015).

Development and implementation of the National Heart, Lung, and Blood Institute COVID-19 common data elements.

Background: Coronavirus Disease 2019 (COVID-19) instigated a flurry of clinical research activity. The unprecedented pace with which trials were launched left an early void in data standardization, limiting the potential for subsequent data pooling. To facilitate data standardization across emerging studies, the National Heart, Lung, and Blood Institute (NHLBI) charged two groups with harmonizing data collection, and these groups collaborated to create a concise set of COVID-19 Common Data Elements (CDEs) for clinical research. Methods: Our iterative approach followed three guiding principles: 1) draw from existing multi-center COVID-19 clinical trials as precedents, 2) incorporate existing data elements and data standards whenever possible, and 3) alignment to data standards that facilitate data sharing and regulatory submission. We also supported rapid implementation of the CDEs in NHLBI-funded studies and iteratively refined the CDEs based on feedback from those study teams. Results: The NHLBI COVID-19 CDEs are publicly available and being used for current COVID-19 clinical trials. CDEs are organized into domains, and each data element is classified within a three-tiered prioritization system. The CDE manual is hosted publicly at https://nhlbi-connects.org/common_data_elements with an accompanying data dictionary and implementation guidance. Conclusions: The NHLBI COVID-19 CDEs are designed to aid data harmonization across studies to achieve the benefits of pooled analyses. We found that organizing CDE development around our three guiding principles focused our efforts and allowed us to adapt as COVID-19 knowledge advanced. As these CDEs continue to evolve, they could be generalized for use in other acute respiratory illnesses.

Safety of daily low-dose aspirin use during pregnancy in low-income and middle-income countries.

BACKGROUND: The daily use of low-dose aspirin may be a safe, widely available, and inexpensive intervention for reducing the risk of preterm birth. Data on the potential side effects of low-dose aspirin use during pregnancy in low- and middle-income countries are needed. OBJECTIVE: This study aimed to assess differences in unexpected emergency medical visits and potential maternal side effects from a randomized, double-blind, multicountry, placebo-controlled trial of low-dose aspirin use (81 mg daily, from 6 to 36 weeks' gestation). STUDY DESIGN: This study was a secondary analysis of data from the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial, a trial of the Global Network for Women's and Children's Health conducted in India (2 sites), Pakistan, Guatemala, Democratic Republic of the Congo, Kenya, and Zambia. The outcomes for this analysis were unexpected emergency medical visits and the occurrence of the following potential side effects-overall and separately-nausea, vomiting, rash or hives, diarrhea, gastritis, vaginal bleeding, allergic reaction, and any other potential side effects. Analyses were performed overall and by geographic region. RESULTS: Between the aspirin (n=5943) and placebo (n=5936) study groups, there was no statistically significant difference in the risk of unexpected emergency medical visits or the risk of any potential side effect (overall). Of the 8 potential side effects assessed, only 1 (rash or hives) presented a different risk by treatment group (4.2% in the aspirin group vs 3.5% in the placebo group; relative risk, 1.20; 95% confidence interval, 1.01-1.43; P=.042). CONCLUSION: The daily use of low-dose aspirin seems to be a safe intervention for reducing the risk of preterm birth and well tolerated by nulliparous pregnant women between 6 and 36 weeks' gestation in low- and middle-income countries.

A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers.

PT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150's safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic interactions between ethanol and PT150 in healthy subjects. This single-site, Phase I pilot trial consisted of community-recruited, healthy, alcohol-experienced participants aged 21-64 years. Of 32 participants screened, 11 were enrolled and randomized, one of which withdrew before intervention. PT150 (900 mg/day) was administered orally to all participants for five days. All participants received two beverage challenges on Day 1 (before PT150 administration) and Day 5 (after PT150 administration). On challenge days, they received both alcohol (16% ethanol) and placebo (1% ethanol) beverages in random order. Primary outcomes included breath alcohol level, blood pressure, heart rate, adverse events, and electrocardiogram changes. There were no statistically significant differences in vital signs or estimated blood alcohol concentrations between PT150 non-exposed and exposed groups during the ethanol challenge. There were no clinically significant abnormal electrocardiograms or serious adverse events. These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol.Trial Registration ClinicalTrials.gov Identifier: NCT03548714.

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's 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 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 .

Understanding the impact of mild traumatic brain injury on veteran service-connected disability: results from Chronic Effects of Neurotrauma Consortium.

OBJECTIVES: Disability evaluation is complex. The association between mild traumatic brain injury (mTBI) history and VA service-connected disability (SCD) ratings can have implications for disability processes in the civilian population. We examined the association of VA SCD ratings with lifetime mTBI exposure in three models: any mTBI, total mTBI number, and blast-related mTBI. METHODS: Participants were 492 Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans from four US VA Medical Centers enrolled in the Chronic Effects of Neurotrauma Consortium study between January 2015 and August 2016. Analyses entailed standard covariate-adjusted linear regression models, accounting for demographic, military, and health-related confounders and covariates. RESULTS: Unadjusted and adjusted results indicated lifetime mTBI was significantly associated with increased SCD, with the largest effect observed for blast-related mTBI. Every unit increase in mTBI was associated with an increase in 3.6 points of percent SCD. However, hazardous alcohol use was associated with lower SCD. CONCLUSIONS: mTBI, especially blast related, is associated with higher VA SCD ratings, with each additional mTBI increasing percent SCD. The association of hazardous alcohol use with SCD should be investigated as it may impact veteran health services access and health outcomes. These findings have implications for civilian disability processes.

Is balance performance reduced after mild traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multi-centre study.

OBJECTIVES: Determine if mild traumatic brain injury (mTBI) history is associated with balance disturbances. SETTING: Chronic Effects of Neurotrauma Consortium (CENC) centres. PARTICIPANTS: The CENC multi-centre study enrols post-9/11 era Service Members and Veterans with combat exposure. This sample (n = 322) consisted of enrolees completing initial evaluation by September 2016 at the three sites conducting computerized dynamic post-urography (CDP) testing. DESIGN: Observational study with cross-sectional analyses using structural equation modelling. MAIN MEASURES: Comprehensive structured interviews were used to diagnose all lifetime mild traumatic brain injuries (mTBIs). The outcome, Sensory Organization Test (SOT), was measured on CDP dual-plate force platform. Other studied variables were measured by structured interviews, record review and questionnaires. RESULTS: The overall positive/negative mTBI classification did not have a significant effect on the composite equilibrium score. However, the repetitive mTBI classification showed lower scores for participants with ≥ 3 mTBI versus 1-2 lifetime mTBIs. For repetitive mTBI, pain interference acted as a mediator for the indirect effect, and a direct effect was evident on some sensory condition equilibrium scores. CONCLUSION: These findings show that repeated mTBI, partially mediated by pain, may lead to later balance disturbances among military combatants. Further study of CDP outcomes within this accruing cohort is warranted.

Effects of virus infection on pollen production and pollen performance: Implications for the spread of resistance alleles.

PREMISE OF STUDY: Studies over the past 25 years have shown that environmental stresses adversely affect male function, including pollen production and pollen performance (germination and pollen tube growth rate). Consequently, genetic variation among plants in resistance to a stress has the potential to impact pollen donation to conspecifics and, if deposited onto a stigma, the ability of the pollen to achieve fertilization. We examined the effects of a nonlethal virus epidemic on pollen production and pollen performance in a population of susceptible and resistant (transgenic) wild squash (Cucurbita pepo subsp. texana). METHODS: We grew 135 susceptible and 45 virus-resistant wild squash plants in each of two 0.4-ha fields, initiated a zucchini yellow mosaic virus (ZYMV) epidemic, and recorded staminate and pistillate flower production per plant over the field season and the total number of mature fruit. We also assessed pollen production per flower on ZYMV-infected and non-infected plants and the ability of pollen from flowers on infected and non-infected plants to achieve fertilization under competitive conditions. KEY RESULTS: ZYMV infection reduced flower and fruit production per plant and pollen production per flower. Pollen from infected plants was also less likely to sire a seed under competitive conditions. CONCLUSIONS: ZYMV infection adversely impacts the amount of pollen that can be donated to conspecifics, and pollen competition within the styles increases the probability that the ovules are fertilized by pollen from plants that are thriving when challenged by a viral disease.