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Background: Although the official age of fetal viability in Nigeria is 28 weeks, there are pockets of reports some anecdotal, of survival of babies delivered at younger gestational age (GA) from different parts of the country. The routine resuscitation and management of premature infants born before the official age of fetal viability (28 weeks) is likely to generate important ethical and medical concerns that are bound to influence our approach to the management of such infants. Aim: To determine the GA- specific neonatal mortality and survival among preterm deliveries at the National Hospital Abuja. Subjects and Methods: A retrospective review of relevant data from the National Hospital Neonatal Registry Database based on the Research Electronic Data Capture software (REDCap) was undertaken to determine the mortality rate of preterm babies managed in the neonatal intensive care unit (NICU) from January 2017 to February 2018. Disaggregated GA specific mortality rates were also computed to determine the fetal age at which extra uterine neonatal survival rate was at least 50%. Gestational age estimation was based on mothers’ last menstrual period (LMP) in over 96% of cases. Results: Sixty-three (63) of 305 preterm babies admitted died during hospitalization giving a mortality rate of 20.7%. This was significantly higher than the mortality rate among term babies (7.5%, P=0.01) hospitalized over the same period. Antenatal corticosteroid use was low (11.2%), 188 (25.8%) received CPAP for Respiratory Distress Syndrome (RDS), and none of the babies received surfactant or mechanical ventilation. There were no survivors among babies delivered at GA of 22-25 weeks (11, 3.6%). However, the survival rate at 26 weeks gestation was 53.8%, and this subsequently increased, reaching a peak of 96.5% survival at 35 weeks. RDS accounted for 53.9% of all deaths. Conclusion: It is concluded that the survival rate (53.8%) of babies at GA of 26 weeks despite minimal antenatal interventions and limited postnatal respiratory support was reasonably high, and this could serve the basis for discussions for a downward review of the age of fetal viability in Nigeria.

Background: Few studies have assessed the impact of first-trimester malaria infection during pregnancy. We estimated this impact on adverse maternal and pregnancy outcomes., Methods: In a convenience sample of women from the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial in Kenya, Zambia, and the Democratic Republic of the Congo, we tested for first-trimester Plasmodium falciparum infection using quantitative polymerase chain reaction. We estimated site-specific effects on pregnancy outcomes using parametric g-computation., Results: Compared to uninfected women, we observed the adjusted site-specific prevalence differences (PDs) among women with first-trimester malaria of the following pregnancy outcomes: preterm birth among Congolese (aPD = 0.06 [99% CI: -0.04, 0.16]), Kenyan (0.03 [-0.04, 0.09]), and Zambian (0.00 [-0.10, 0.20]) women; low birth weight among Congolese (0.07 [-0.03, 0.16]), Kenyan (0.01 [-0.04, 0.06]) and Zambian (-0.04 [-0.13, 0.16]) women; spontaneous abortion among Congolese (0.00 [-0.05, 0.04]), Kenyan (0.00 [-0.04, 0.04]), and Zambian (0.02 [-0.07, 0.24]) women, and anemia later in pregnancy among Congolese (0.04 [-0.09, 0.16]), Kenyan (0.05 [-0.06, 0.17]), and Zambian (0.07 [-0.12, 0.36]) women. The pooled PD for anemia later in pregnancy (26-30 weeks) was 0.08 [99% CI: 0.00, 0.16]., Conclusions: First-trimester malaria was associated with increased prevalence of anemia later in pregnancy. We identified areas for further investigation including effects of first-trimester malaria on preterm birth and low birth weight., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Apnoea of prematurity (AOP) is a common complication among preterm infants (< 37 weeks gestation), globally. However, access to caffeine citrate (CC) that is a proven safe and effective treatment in high-income countries is largely unavailable in low- and-middle income countries, where most preterm infants are born. Therefore, the overall aim of this study was to describe the demand, policies, and supply factors affecting the availability and clinical use of CC in LMICs. A mixed methods approach was used to collect data from diverse settings in LMICs including Ethiopia, Kenya, Nigeria, South Africa, and India. Qualitative semi-structured interviews and focus group discussions were conducted with 107 different health care providers, and 21 policymakers and other stakeholders from industry. Additional data was collected using standard questionnaires. A thematic framework approach was used to analyze the qualitative data and descriptive statistics were used to summarize the quantitative data. The findings indicate that there is variation in in-country policies on the use of CC in the prevention and treatment of AOP and its availability across the LMICs. As a result, the knowledge and experience of using CC also varied with clinicians in Ethiopia having no experience of using it while those in India have greater knowledge and experience of using it. This, in turn, influenced the demand, and our findings show that only 29% of eligible preterm infants are receiving CC in these countries. There is an urgent need to address the multilevel barriers to accessing CC for managing AOP in Africa. These include cost, lack of national policies, and, therefore, lack of demand stemming from its clinical equivalency with aminophylline. Practical ways to reduce the cost of CC in LMICs could potentially increase its availability and use., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ekhaguere et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Adolescent (<20 years) and advanced maternal age (>35 years) pregnancies carry adverse risks and warrant a critical review in low- and middle-income countries where the burden of adverse pregnancy outcomes is highest., Objective: To describe the prevalence and adverse pregnancy (maternal, perinatal, and neonatal) outcomes associated with extremes of maternal age across six countries., Patients and Methods: We performed a historical cohort analysis on prospectively collected data from a population-based cohort study conducted in the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia between 2010 and 2020. We included pregnant women and their neonates. We describe the prevalence and adverse pregnancy outcomes associated with pregnancies in these maternal age groups (<20, 20-24, 25-29, 30-35, and >35 years). Relative risks and 95% confidence intervals of each adverse pregnancy outcome comparing each maternal age group to the reference group of 20-24 years were obtained by fitting a Poisson model adjusting for site, maternal age, parity, multiple gestations, maternal education, antenatal care, and delivery location. Analysis by region was also performed., Results: We analyzed 602,884 deliveries; 13% (78,584) were adolescents, and 5% (28,677) were advanced maternal age (AMA). The overall maternal mortality ratio (MMR) was 147 deaths per 100,000 live births and increased with advancing maternal age: 83 in the adolescent and 298 in the AMA group. The AMA groups had the highest MMR in all regions. Adolescent pregnancy was associated with an adjusted relative risk (aRR) of 1.07 (1.02-1.11) for perinatal mortality and 1.13 (1.06-1.19) for neonatal mortality. In contrast, AMA was associated with an aRR of 2.55 (1.81 to 3.59) for maternal mortality, 1.58 (1.49-1.67) for perinatal mortality, and 1.30 (1.20-1.41) for neonatal mortality, compared to pregnancy in women 20-24 years. This pattern was overall similar in all regions, even in the <18 and 18-19 age groups., Conclusion: The maternal mortality ratio in the LMICs assessed is high and increased with advancing maternal age groups. While less prevalent, AMA was associated with a higher risk of adverse maternal mortality and, like adolescence, was associated with adverse perinatal mortality with little regional variation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Nyongesa, Ekhaguere, Marete, Tenge, Kemoi, Bann, Bucher, Patel, Hibberd, Naqvi, Saleem, Goldenberg, Goudar, Derman, Krebs, Garces, Chomba, Carlo, Mwenechanya, Lokangaka, Tshefu, Bauserman, Koso-Thomas, Moore, McClure, Liechty and Esamai.)

Introduction: Maternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in preventing many of these deaths. A randomised clinical trial conducted in a single site in The Gambia showed that treatment with an oral dose of 2 g azithromycin versus placebo for all women in labour reduced certain maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. In a large, multinational randomised trial, we will evaluate the impact of azithromycin given in labour to improve maternal and newborn outcomes., Methods and Analysis: This randomised, placebo-controlled, multicentre clinical trial includes two primary hypotheses, one maternal and one neonatal. The maternal hypothesis is to test whether a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labour will reduce maternal death or sepsis. The neonatal hypothesis will test whether this intervention will reduce intrapartum/neonatal death or sepsis. The intervention is a single, prophylactic intrapartum oral dose of 2 g azithromycin, compared with a single intrapartum oral dose of an identical appearing placebo. A total of 34 000 labouring women from 8 research sites in sub-Saharan Africa, South Asia and Latin America will be randomised with a one-to-one ratio to intervention/placebo. In addition, we will assess antimicrobial resistance in a sample of women and their newborns., Ethics and Dissemination: The study protocol has been reviewed and ethics approval obtained from all the relevant ethical review boards at each research site. The results will be disseminated via peer-reviewed journals and national and international scientific forums., Trial Registration Number: NCT03871491 (https://clinicaltrials.gov/ct2/show/NCT03871491?term=NCT03871491&draw=2&rank=1)., Competing Interests: Competing interests: None declared., (Link or Companion Paper: bmjopen-2022-067581"Copyright may not be established in the United States for works of government employees (17 U.S.C. § 105). The NIH Public Access Policy requires NIH authors to submit final, peer-reviewed journal manuscripts to the digital archive PubMed Central upon acceptance for publication but no later than 12 months after publication.''.)

Aim: We aimed to describe in-hospital mortality, and its predictors, in very low birthweight (VLBW) infants managed in tertiary centres in a low- to middle-income country., Methods: This was a retrospective cohort study of VLBW infants (birthweight 500 to 1500 grams) admitted within 72 h of life to the neonatal intensive care units (NICUs) of three tertiary centres in Nigeria from July 2017 to March 2021. We describe in-hospital mortality rates, causes and when they died. The independent predictors of in-hospital mortality were determined using multivariate logistic analysis., Results: Of the 6187 NICU admissions, 1161 met the inclusion criteria: 545 (47%) VLBW infants died, including 309 (57%) from respiratory distress syndrome, and 55% occurred within 72 h of life. The adjusted odds (aOR) for mortality increased with each extra Downes respiratory distress score (aOR 1.27) with a 95% confidence interval (CI) of 1.14-1.41. Study site 3 had a higher aOR for mortality than site 1 (aOR 2.78, 95% CI 1.72-4.48) and site 2 (aOR 2.29, 95% CI 1.45-3.61)., Conclusion: Nearly half (47%) of all VLBW infants admitted to three tertiary referral hospitals in Nigeria died during hospitalisation. Mortality varied significantly by site and both the centre and respiratory distress independently predicted mortality., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Nasal continuous positive airway pressure (NCPAP) is a strategy to maintain positive airway pressure throughout the respiratory cycle through the application of a bias flow of respiratory gas to an apparatus attached to the nose. Early treatment with NCPAP is associated with decreased risk of mechanical ventilation exposure and might reduce chronic lung disease. Nasal intermittent positive pressure ventilation (NIPPV) is a form of noninvasive ventilation delivered through the same nasal interface during which patients are exposed to short inflations, along with background end-expiratory pressure., Objectives: To examine the risks and benefits of early (within the first six hours after birth) NIPPV versus early NCPAP for preterm infants at risk of or with respiratory distress syndrome (RDS). Primary endpoints are respiratory failure and the need for intubated ventilatory support during the first week of life. Secondary endpoints include the incidence of mortality, chronic lung disease (CLD) (oxygen therapy at 36 weeks' postmenstrual age), pneumothorax, duration of respiratory support, duration of oxygen therapy, and intraventricular hemorrhage (IVH)., Search Methods: Searches were conducted in January 2023 in CENTRAL, MEDLINE, Embase, Web of Science, and Dissertation Abstracts. The reference lists of related systematic reviews and of studies selected for inclusion were also searched., Selection Criteria: We considered all randomized and quasi-randomized controlled trials. Eligible studies compared NIPPV versus NCPAP treatment, starting within six hours after birth in preterm infants (< 37 weeks' gestational age (GA))., Data Collection and Analysis: We collected and analyzed data using the recommendations of the Cochrane Neonatal Review Group., Main Results: We included 17 trials, enrolling 1958 infants in this review. NIPPV likely reduces the rate of respiratory failure (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.78; risk difference (RD) -0.08, 95% CI -0.12 to -0.05; 17 RCTs, 1958 infants; moderate-certainty evidence) and needing endotracheal tube ventilation (RR 0.67, 95% CI 0.56 to 0.81; RD -0.07, 95% CI -0.11 to -0.04; 16 RCTs; 1848 infants; moderate-certainty evidence) amongst infants treated with early NIPPV compared with early NCPAP. The meta-analysis demonstrated that NIPPV may reduce the risk of developing CLD compared to CPAP (RR 0.70, 95% CI 0.52 to 0.92; 12 RCTs, 1284 infants; low-certainty evidence) slightly. NIPPV may result in little to no difference in mortality (RR 0.82, 95% CI 0.62 to 1.10; 17 RCTs; 1958 infants; I 2 of 0%; low-certainty evidence), the incidence of pneumothorax (RR 0.92, 95% CI 0.60 to 1.41; 16 RCTs; 1674 infants; I 2 of 0%; low-certainty evidence), and rates of severe IVH (RR 0.98, 95% CI 0.53 to 1.79; 8 RCTs; 977 infants; I 2 of 0%; low-certainty evidence)., Authors' Conclusions: When applied within six hours after birth, NIPPV likely reduces the risk of respiratory failure and the need for intubation and endotracheal tube ventilation in very preterm infants (GA 28 weeks and above) with respiratory distress syndrome or at risk for RDS. It may also decrease the rate of CLD slightly. However, most trials enrolled infants with a gestational age of approximately 28 to 32 weeks with an overall mean gestational age of around 30 weeks. As such, the results of this review may not apply to extremely preterm infants that are most at risk of needing mechanical ventilation or developing CLD. Additional studies are needed to confirm these results and to assess the safety of NIPPV compared with NCPAP alone in a larger patient population., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death., Methods: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit., Results: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events., Conclusions: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.)., (Copyright © 2023 Massachusetts Medical Society.)

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 10 th , 25 th , median, 75 th , and 90 th 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 10 th , 50 th , and 90 th 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-21 st )., 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)., (© 2023. The Author(s).)

Purpose: Newborn respiratory support using Bubble Continuous positive airway pressure (bCPAP) has become acceptable in Nigeria as many centers are increasingly reporting its usefulness. There is increasing access to CPAP devices although the use of 100% oxygen for bCPAP administration is on the rise as oxygen/air blenders are not commonly available or insufficient. The cost of oxygen has become a significant contributor to hospital bills. The oxygen concentrator driven bCPAP device with blending capacity is expected to save lives and reduce cost of care., Objective: To compare the cost saving benefit of the use of oxygen concentrator bCPAP devices for CPAP administration to oxygen based devices in a resource limited setting., Methods: This prospective cross sectional study was done between February and December 2019. The oxygen use by CPAP devices-Improvised (IbCPAP), Fisher and Paykel and T-piece were quantified, costed, documented and compared with the same duration of use of concentrator CPAP-Diamedica., Results: CPAP services was accessed by 357 babies, 154 males and 203 females of GA range from 22 to 42 weeks and Birthweights range from 264 to 4400 grams. The main indication for CPAP was respiratory distress syndrome 201(56.3%). Oxygen supply were by oxygen pipeline 250 (70%), cylinders 39 (10.9%), concentrator CPAP 44 (12.3%) mixed source 24 (6.7%). Mean duration on the CPAP devices was 5.4 days, mean cost ₦37,645 ($104) or ₦6,971 ($20)/day, highest with IbCPAP, non-existent with concentrator bCPAP., Conclusion: The high running cost implication of CPAP use in low resource settings could deter transitioning to quality devices hence the need for non-oxygen dependent devices.

The complications of prematurity are the leading cause of neonatal mortality worldwide, with the highest burden in the low- and middle-income countries of South Asia and Sub-Saharan Africa. A major driver of this prematurity-related neonatal mortality is respiratory distress syndrome due to immature lungs and surfactant deficiency. The World Health Organization's Every Newborn Action Plan target is for 80% of districts to have resources available to care for small and sick newborns, including premature infants with respiratory distress syndrome. Evidence-based interventions for respiratory distress syndrome management exist for the peripartum, delivery and neonatal intensive care period- however, cost, resources, and infrastructure limit their availability in low- and middle-income countries. Existing research and implementation gaps include the safe use of antenatal corticosteroid in non-tertiary settings, establishing emergency transportation services from low to high level care facilities, optimized delivery room resuscitation, provision of affordable caffeine and surfactant as well as implementing non-traditional methods of surfactant administration. There is also a need to optimize affordable continuous positive airway pressure devices able to blend oxygen, provide humidity and deliver reliable pressure. If the high prematurity-related neonatal mortality experienced in low- and middle-income countries is to be mitigated, a concerted effort by researchers, implementers and policy developers is required to address these key modalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a shared committee with one of the authors MB., (Copyright © 2022 Ekhaguere, Okonkwo, Batra and Hedstrom.)

Competing Interests: Competing interests: None declared.

The wait time clients spend during immunization clinic visits in low- and middle-income countries is a not well-understood reported barrier to vaccine completion. We used a prospective, observational design to document the total time from client arrival-to-discharge and all sequential provider-client activities in 1 urban, semi-urban, and rural immunization clinic in Nigeria. We also conducted caregiver and provider focus group discussions to identify perceived determinants of long clinic wait times. Our findings show that the time from arrival-to-discharge varied significantly by the clinic and ranged between 57 and 235 minutes, as did arrival-to-all providers-client activities. Focus group data attributed workflow delays to clinic staff waiting for a critical mass of clients to arrive for their immunization appointment before starting the essential health education talk or opening specific vaccine vials. Additionally, respondents indicated that complex documentation processes caused system delays. Research on clinic workflow transformation and simplification of immunization documentation is needed., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Caffeine is the preferred pharmacologic treatment for apnea of prematurity. Little is known about the availability and affordability of caffeine in the low and middle-income countries of sub-Saharan Africa (SSA). We conducted an online survey in 2020 of newborn physicians in SSA to determine their access to caffeine. Of 90 invited participants, 55 responded (61%). They worked in 13 SSA countries and 48 hospitals. Caffeine was used in 6 countries. In 5 of these countries, the price of caffeine was reported and ranged from US $1.73 in Ghana to US $73.63 in Kenya per 3 mL vial. High drug prices and lack of drug availability for purchase were identified most frequently as primary barriers. Some respondents believed that other methylxanthines are adequate substitutes for caffeine. Only 31 of 53 (58%) respondents knew that caffeine is included in the essential drug list of the World Health Organization (WHO)., (© 2020 Published by Elsevier Ltd.)

Background/aims: Noninferiority clinical trials are susceptible to false confirmation of noninferiority when the intention-to-treat principle is applied in the setting of incomplete trial protocol adherence. The risk increases as protocol adherence rates decrease. The objective of this study was to compare protocol adherence and hypothesis confirmation between superiority and noninferiority randomized clinical trials published in three high impact medical journals. We hypothesized that noninferiority trials have lower protocol adherence and greater hypothesis confirmation., Methods: We conducted an observational study using published clinical trial data. We searched PubMed for active control, two-arm parallel group randomized clinical trials published in JAMA: The Journal of the American Medical Association, The New England Journal of Medicine, and The Lancet between 2007 and 2017. The primary exposure was trial type, superiority versus noninferiority, as determined by the hypothesis testing framework of the primary trial outcome. The primary outcome was trial protocol adherence rate, defined as the number of randomized subjects receiving the allocated intervention as described by the trial protocol and followed to primary outcome ascertainment (numerator), over the total number of subjects randomized (denominator). Hypothesis confirmation was defined as affirmation of noninferiority or the alternative hypothesis for noninferiority and superiority trials, respectively., Results: Among 120 superiority and 120 noninferiority trials, median and interquartile protocol adherence rates were 91.5 [81.4-96.7] and 89.8 [83.6-95.2], respectively; P = 0.47. Hypothesis confirmation was observed in 107/120 (89.2%) of noninferiority and 64/120 (53.3%) of superiority trials, risk difference (95% confidence interval): 35.8 (25.3-46.3), P < 0.001., Conclusion: Protocol adherence rates are similar between superiority and noninferiority trials published in three high impact medical journals. Despite this, we observed greater hypothesis confirmation among noninferiority trials. We speculate that publication bias, lenient noninferiority margins and other sources of bias may contribute to this finding. Further study is needed to identify the reasons for this observed difference.

Objective: The use of acid suppression therapies in newborns lacks efficacy and is associated with adverse effects. Point-of-care (POC) assessment of gastric aspirate pH may provide an objective, noninvasive measure of gastric acidity in tube fed infants. We conducted the present study to characterize the POC gastric pH levels in gastric tube fed infants before and after initiation of enteral omeprazole or ranitidine., Study Design: Retrospective cohort study of infants with gastric aspirate pH levels determined by POC pH strips. Gastric pH levels recorded during 7 days before and 14 days after medication initiation were compared using Wilcoxon's sign-rank tests., Results: Among 307 evaluated infants, 284 (92%) had a median gastric pH level ≥4 in 7 days prior to ranitidine or omeprazole. In 14 days after medication initiation, the median gastric pH of infants with pretreatment median gastric pH < 4 increased to 4.5 and 5 ( p  < 0.01) in the ranitidine and omeprazole groups, respectively. There was no change in infants with pretreatment median gastric pH ≥4., Conclusion: Among infants receiving gastric tube feedings and enteral omeprazole or ranitidine, only those with a pretreatment gastric pH level <4 demonstrated a significant increase in gastric pH. Validation of our findings against esophageal pH multichannel intraluminal impedance testing is needed., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Aim: This research presents the radiogenic components in thirteen limestone samples from a quarry site in Ewekoro, southwestern Nigeria., Methods: The distributions of natural radionuclides ( 238 U, 232 Th and 40 K) in the limestone samples were determined by gamma spectroscopy using a well-type thallium-doped sodium iodide detector. Also, estimated associated radiological hazards are presented and compared with the standard threshold values., Results: The activity concentrations for 238 U, 232 Th and 40 K radionuclides range 18.09 ± 3.43-239.50 ± 25.74 Bqkg-1, 8.33 ± 0.83 - 360.01 ± 21.33 Bqkg-1 and 11.28 ± 0.81-735.26 ± 0.95 Bqkg-1 respectively. The radium equivalent activity concentration in the samples ranges 58.857-758.832 Bqkg-1 with samples S3, S4 and S11 values higher than the threshold limit of 370 Bqkg-1. Estimated dose rate and annual effective dose rate (AEDE) from the samples have ranges 28.754-330.917 nGyh-1 and 35.26-405.84 μSvy-1 respectively greater than the standard limit of 59 nGyh-1 and 70 μSvy-1 respectively for all samples except S9. The estimated external and internal indices are ranging 0.16 - 2.05 and 0.21 - 2.68 respectively, greater than permissible unity in some limestone samples such as S3, S4, S8, S11 and S13. Excess lifetime cancer risk was also computed using a life expectancy of 54.5 years. The results of higher radiological parameters in the limestone samples revealed that the miners have a high probability of contracting induced cancer., Conclusion: A regular check-up is recommended for the miners and staffs within the quarry site. Also, the residents within the environs should be relocated far away from the quarry site, as the particulates from the limestone rock blasting could contaminate the air in the study area., (Copyright: © 2019 Kehinde David Oyeyemi, Ahzegbobor Phillips Aizebeokhai, Osagie Ayo Ekhaguere, Douglas Emeka Chinwuba, Charity Ada Onumejor.)

Background: Sub-Saharan Africa has high under-5 mortality and low childhood immunisation rates. Vaccine-preventable diseases cause one-third of under-5 deaths. Text messaging reminders improve immunisation completion in urban but not rural settings in sub-Saharan Africa. Low adult literacy may account for this difference. The feasibility and impact of combined automated voice and text reminders on immunisation completion in rural sub-Saharan Africa is unknown., Methods: We randomised parturient women at the Mother and Child Hospitals Ondo State, Nigeria, owning a mobile phone and planning for child immunisation at these study sites to receive automated call and text immunisation reminders or standard care. We assessed the completion of the third pentavalent vaccine (Penta-3) at 18 weeks of age, immunisation completion at 12 months and within 1 week of recommended dates. We assessed selected demographic characteristics associated with completing immunisations at 12 months using a generalised binomial linear model with 'log' link function. Feasibility was assessed as proportion of reminders received., Results: Each group had 300 mother-baby dyads with similar demographic characteristics. At 18 weeks, 257 (86%) and 244 (81%) (risk ratio (RR) 1.05, 95% CI 0.98 to 1.13; p=0.15) in the intervention and control groups received Penta-3 vaccine. At 12 months, 220 (74%) and 196 (66%) (RR 1.12, 95% CI 1.01 to 1.25; p=0.04) in the intervention and control groups received the measles vaccine. Infants in the intervention group were more likely to receive Penta-3 (84% vs 78%, RR 1.09, 95% CI 1.01 to 1.17; p=0.04), measles (73% vs 65%, RR 1.13, 95% CI 1.02 to 1.26; p=0.02) and all scheduled immunisations collectively (57% vs 47%, RR 1.13, 95% CI 1.02 to 1.26; p=0.01) within 1 week of the recommended date. No demographic character predicted immunisation completion. In the intervention group, 92% and 86% reported receiving a verification reminder and at least one reminder during the study period, respectively., Conclusion: Paired automated call and text reminders significantly improved immunisation completion and timeliness., Trial Registration Number: NCT02819895., Competing Interests: Competing interests: None declared.

Over 80% of the global burden of childhood deaths occur in Low- and Middle-Income Countries (LMIC). Of the leading causes of death, respiratory failure is common to the top three. Bubble Continuous Positive Airway Pressure (bCPAP) is a standard therapy considered safe and cost effective in high resource settings. Although high-quality trials from LMIC are few, pooled available trial data considered alongside studies from high-income countries suggest that bCPAP: (i) reduces mortality; (ii) reduces the need for mechanical ventilation; and (iii) prevents extubation failure. Wider availability and optimal use at all levels of the health care system in LMIC are important steps to improve childhood survival. Studies aimed at effectively implementing, and sustaining safe use of bCPAP in the resource limited setting of LMIC are required., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Steroid 3-beta hydroxysteroid dehydrogenase type II (3β-HSD2) deficiency is a rare autosomal recessive form of congenital adrenal hyperplasia (CAH). We report the genetic basis of 3β-HSD2 deficiency arising from uniparental isodisomy (UPD) of chromosome 1. We describe a term undervirilized male whose newborn screen indicated borderline CAH. The patient presented on the 7 th day of life in salt-wasting adrenal crisis. Steroid hormone testing revealed a complex pattern suggestive of 3β-HSD deficiency. Chromosomal microarray and single nucleotide polymorphism analysis revealed complete UPD of chromosome 1. Sanger sequencing of HSD3B2 revealed a previously described missense mutation, c.424G>A (p.E142K) in homozygous state, thus confirming the diagnosis of 3β-HSD2 deficiency. We provide evidence of the existence of an uncommon mechanism for HSD3B2 gene-related CAH arising from UPD of chromosome 1.

Background: Red blood cell (RBC) transfusions in very-low-birth-weight (VLBW) infants, while common, carry risk. Our objective was to determine clinical predictors of and trends in RBC transfusions among VLBW infants., Methods: RBC transfusion practice and its clinical predictors in 1,750 VLBW (≤1,500 g) infants were analyzed in a single-center cohort across sequential epochs: 2000-2004 (Epoch 1), 2005-2009 (Epoch 2), and 2010-2013 (Epoch 3)., Results: Overall, 1,168 (67%) infants received ≥1 transfusions. The adjusted likelihood of ≥1 transfusions decreased for each 1-g/dl increment in initial hemoglobin concentration following birth, for females, and for each 100-g increment in birth weight. The adjusted likelihood of ≥1 transfusions increased with infants receiving mechanical ventilation, with increasing length of hospital stay, necrotizing enterocolitis, and nonlethal congenital anomalies requiring surgery. The adjusted mean (SEM) number of transfusions per patient was decreased in Epoch 3, compared with Epoch 1 and Epoch 2. For an initial hemoglobin of ≥16.5 g/dl, the predicted probability of being transfused was ≤50%., Conclusion: Adjusted RBC transfusions declined and female sex conferred an unexplained protection over the study period. Modest increases in initial hemoglobin by placentofetal transfusion at delivery may reduce the need for RBC transfusion.

Orofacial clefts are the most common malformations of the head and neck. In Africa, orofacial clefts are underascertained, with little or no surveillance system in most parts for clefts and other birth defects. A Nigerian craniofacial anomalies study, NigeriaCRAN, was established in 2006 to support cleft research specifically for epidemiological studies, treatment outcomes, and studies into etiology and prevention. We pooled data from seven of the largest Smile Train treatment centers in the six geopolitical zones in Nigeria. Data from September 2006 to June 2011 were analyzed and clefts compared between sides and genders using the Fisher exact test. A total of 2197 cases were identified during the study period, with an estimated prevalence rate of 0.5 per 1000. Of the total number of orofacial clefts, 54.4% occur in males and 45.6% in females. There was a significant difference (P = .0001) between unilateral left clefts and unilateral right clefts, and there was a significant difference (P = .0001) between bilateral clefts and clefts on either the left or right side. A significant gender difference (P = .03) was also observed for cleft palate, with more females than males. A total of 103 (4.7%) associated anomalies were identified. There were nine syndromic cleft cases, and 10.4% of the total number of individuals with clefts have an affected relative. The significant difference between unilateral clefts and the gender differences in the proportion of cleft palate only are consistent with the literature. The present study emphasizes the need for birth defects registries in developing countries in order to estimate the exact prevalence of birth defects including orofacial clefts.