Cycled Phototherapy Dose-Finding Study for Extremely Low-Birth-Weight Infants: A Randomized Clinical Trial.

Importance: Cycled (intermittent) phototherapy (PT) might adequately control peak total serum bilirubin (TSB) level and avoid mortality associated with usual care (continuous PT) among extremely low-birth-weight (ELBW) infants (401-1000 g). Objective: To identify a cycled PT regimen that substantially reduces PT exposure, with an increase in mean peak TSB level lower than 1.5 mg/dL in ELBW infants. Design, Setting, and Participants: This dose-finding randomized clinical trial of cycled PT vs continuous PT among 305 ELBW infants in 6 US newborn intensive care units was conducted from March 12, 2014, to November 14, 2018. Interventions: Two cycled PT regimens (≥15 min/h and ≥30 min/h) were provided using a simple, commercially available timer to titrate PT minutes per hour against TSB level. The comparator arm was usual care (continuous PT). Main Outcomes and Measures: Mean peak TSB level and total PT hours through day 14 in all 6 centers and predischarge brainstem auditory-evoked response wave V latency in 1 center. Mortality and major morbidities were secondary outcomes despite limited power. Results: Consent was requested for 452 eligible infants and obtained for 305 (all enrolled) (mean [SD] birth weight, 749 [152] g; gestational age, 25.7 [1.9] weeks; 81 infants [27%] were multiple births; 137 infants [45%] were male; 112 [37%] were black infants; and 107 [35%] were Hispanic infants). Clinical and demographic characteristics of the groups were similar at baseline. After a preplanned interim analysis of 100 infants, the regimen of 30 min/h or more was discontinued, and the study proceeded with 2 arms. Comparing 128 infants receiving PT of 15 min/h or more with 128 infants receiving continuous PT among those surviving to 14 days, mean peak TSB levels were 7.1 vs 6.4 mg/dL (adjusted difference, 0.7; 95% CI, 0.4-1.1 mg/dL) and mean total PT hours were 34 vs 72 (adjusted difference, -39; 95% CI, -45 to -32). Wave V latency adjusted for postmenstrual age was similar in 37 infants receiving 15 min/h or more of PT and 33 infants receiving continuous PT: 7.42 vs 7.32 milliseconds (difference, 0.10; 95% CI, -0.11 to 0.30 millisecond). The relative risk for death was 0.79 (95% CI, 0.40-1.54), with a risk difference of -4.5% (95% CI, -10.9 to 2.0). Morbidities did not differ between groups. Conclusions and Relevance: Cycled PT can substantially reduce total PT with little increase in peak TSB level. A large, randomized trial is needed to assess whether cycled PT would increase survival and survival without impairment in small, preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT01944696.

How to Save 1 Million Lives in a Year in Low- and Middle-Income Countries.

Despite major improvements in reducing childhood mortality worldwide, over 5 million pregnancies per year end in stillbirths or neonatal deaths. The vast majority of these deaths occur in low- and middle-income countries. Many of these deaths are preventable with readily available evidence-based care practices. This review focuses on educational programs developed to reduce preventable deaths in newborn infants in low- and middle-income countries, including Essential Newborn Care and Helping Babies Breathe, a simplified version of the Neonatal Resuscitation Program. Innovative pragmatic large-scale trials conducted in the Global Network for Women's and Children's Health Research of the National Institutes of Health in the USA have evaluated these programs in low-resource settings. The results of these studies and the implications for future programs designed to decrease childhood mortality are reviewed.

Short versus Extended Duration of Trophic Feeding to Reduce Time to Achieve Full Enteral Feeding in Extremely Preterm Infants: An Observational Study.

BACKGROUND: Trophic feeding compared to no enteral feeding prevents atrophy of the gastrointestinal tract. However, the practice of extending the duration of trophic feeding often delays initiation of full enteral feeding in extremely preterm infants. We hypothesized that a short duration of trophic feeding (3 days or less) is associated with early initiation of full enteral feeding. METHODS: A total of 192 extremely preterm infants (23-28 weeks' gestation) born between 2013 and 2015 were included. Infants were divided into 2 groups according to the duration of trophic feeding (short vs. extended). The primary outcome was time to achieve full enteral feeding and the safety outcome was necrotizing enterocolitis (NEC) and/or death. RESULTS: A short duration of trophic feeding was associated with a reduction in time to achieve full enteral feeding after adjustment for birth weight, gestational age, race, sex, type of enteral nutrition, and day of initiation of trophic feeding (mean difference favoring a short duration of trophic feeding: -4.1 days; 95% CI: -2.3 to -5.8; p < 0.001). A short duration of trophic feeding was not associated with a higher risk of NEC and/or death after achieving full enteral feeding (AOR: 0.91; 95% CI: 0.30-2.77; p = 0.87). CONCLUSIONS: A short duration of trophic feeding is associated with early initiation of full enteral feeding. A short duration of trophic feeding is not associated with a higher risk of NEC, but our study was underpowered for this safety outcome. Randomized trials are needed to test this study hypothesis.

Effects of Essential Newborn Care Training on Fresh Stillbirths and Early Neonatal Deaths by Maternal Education.

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-/post-active 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.

Two million intrapartum-related stillbirths and neonatal deaths: where, why, and what can be done?

BACKGROUND: Intrapartum-related neonatal deaths ("birth asphyxia") are a leading cause of child mortality globally, outnumbering deaths from malaria. Reduction is crucial to meeting the fourth Millennium Development Goal (MDG), and is intimately linked to intrapartum stillbirths as well as maternal health and MDG 5, yet there is a lack of consensus on what works, especially in weak health systems. OBJECTIVE: To clarify terminology for intrapartum-related outcomes; to describe the intrapartum-related global burden; to present current coverage and trends for care at birth; and to outline aims and methods for this comprehensive 7-paper supplement reviewing strategies to reduce intrapartum-related deaths. RESULTS: Birth is a critical time for the mother and fetus with an estimated 1.02 million intrapartum stillbirths, 904,000 intrapartum-related neonatal deaths, and around 42% of the 535,900 maternal deaths each year. Most of the burden (99%) occurs in low- and middle-income countries. Intrapartum-related neonatal mortality rates are 25-fold higher in the lowest income countries and intrapartum stillbirth rates are up to 50-fold higher. Maternal risk factors and delays in accessing care are critical contributors. The rural poor are at particular risk, and also have the lowest coverage of skilled care at birth. Almost 30,000 abstracts were searched and the evidence is evaluated and reported in the 6 subsequent papers. CONCLUSION: Each year the deaths of 2 million babies are linked to complications during birth and the burden is inequitably carried by the poor. Evidence-based strategies are urgently needed to reduce the burden of intrapartum-related deaths particularly in low- and middle-income settings where 60 million women give birth at home.