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To report stillbirth and early neonatal mortality and to quantify the relative importance of different primary obstetric causes of perinatal mortality in 171 perinatal deaths from 7993 pregnancies that ended after 28 weeks in nulliparous women. A review of all stillbirths and early newborn deaths reported in the WHO calcium supplementation trial for the prevention of pre-eclampsia conducted at seven WHO collaborating centres in Argentina, Egypt, India, Peru, South Africa and Viet Nam. We used the Baird-Pattinson system to assign primary obstetric causes of death and classified causes of early neonatal death using the International classification of diseases and related health problems, Tenth revision (ICD-10). Stillbirth rate was 12.5 per 1000 births and early neonatal mortality rate was 9.0 per 1000 live births. Spontaneous preterm delivery and hypertensive disorders were the most common obstetric events leading to perinatal deaths (28.7% and 23.6%, respectively). Prematurity was the main cause of early neonatal deaths (62%). Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries.

Objective Neonatal sepsis is a global public health concern in general and causes a massive burden in developing countries particularly in sub-Saharan Africa. Though it is mostly preventable, neonatal sepsis remained the leading cause of mortality in developing countries. This study was conducted to determine the current proportion and identify factors associated with neonatal sepsis to suggest directions. Results In this study 504 randomly selected neonatal charts were reviewed. The proportion of overall neonatal sepsis was 63.69% (95% CI 59.38, 67.79), where early-onset sepsis was 59.33% (95% CI 54.96, 63.55) and late-onset sepsis was 4.17% (95% CI 2.73, 6.31). Maternal intra-partum fever, season of birth and admission, vaginal mode of delivery and preterm gestational age at birth increased the likelihood of overall and early-onset neonatal sepsis. In conclusion of this study, neonatal sepsis remaining the leading cause of morbidity among younger infants. Intra-partum conditions were major contributors to neonatal sepsis. Thus, providing emphasis on associated factors in particular and universal safe obstetric care in general is recommended.

Purpose Antenatal corticosteroids have been shown to decrease neonatal respiratory morbidity in singleton pregnancies when given during the late-preterm period (34 0/7 –36 6/7 weeks). Whether these findings also apply to late-preterm twins, who account for approximately one-third of infants born at 34 0/7 –35 6/7 weeks, is currently unclear. The answer to this question depends, in part, on whether the risk of respiratory morbidity among late-preterm twin infants is similar to that observed in late-preterm singletons. We aimed to assess the rate of respiratory morbidity among late-preterm twin infants using a secondary analysis of prospectively collected data from a large international multicenter trial, and to compare that rate with previous studies that used the same definition of respiratory morbidity. Study design This was a secondary analysis of the twin birth study. In the current study, we limited the analysis to women who gave birth during the late preterm period. The primary outcomes were the same primary composite respiratory morbidity variables that were used in the randomized controlled trial of Gyamfi-Bannerman et al., on the administration of betamethasone during the late preterm period in singletons (ALPS trial). The risk of respiratory morbidity among late preterm twins was stratified by gestational week at birth. Results A total of 1163 women who gave birth to 2324 late preterm twin infants met the inclusion criteria. The rates of respiratory morbidity and severe respiratory morbidity were 16.5% and 8.9%, respectively. The risk of respiratory morbidity was highly dependent on gestational week at birth, being more than fourfold for infants born at 34 0/7 –34 6/7 weeks (aOR 4.30, 95%–CI 3.01–6.14) and more than twofold for infants born at 35 0/7 –35 6/7 weeks (aOR 2.12, 95%–CI 1.51–2.98) compared with infants born at 36 0/7 –36 6/7 weeks. The rate of respiratory morbidity and the theoretical number of women needed to be treated with betamethasone to prevent a single case of respiratory morbidity in the current study were similar to those reported in the APLS trial (16.5% vs. 14.4%, p  = 0.103, and NNT 31 vs. 34, respectively). Conclusions The risk–benefit ratio of betamethasone with regard to neonatal respiratory morbidity in women with twins at risk of late-preterm birth is expected to be similar to that observed in singletons.

Background Magnesium sulphate is currently recommended for neuroprotection of preterm infants for women at risk of preterm birth at less than 30 weeks’ gestation, based on high quality evidence of benefit. However there remains uncertainty as to whether these benefits apply at higher gestational ages. The aim of this randomised controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks’ gestation reduces the risk of death or cerebral palsy in their children at two years’ corrected age. Methods/design Design: Randomised, multicentre, placebo controlled trial. Inclusion criteria: Women, giving informed consent, at risk of preterm birth between 30 to 34 weeks’ gestation, where birth is planned or definitely expected within 24 hours, with a singleton or twin pregnancy and no contraindications to the use of magnesium sulphate. Trial entry & randomisation: Eligible women will be randomly allocated to receive either magnesium sulphate or placebo. Treatment groups: Women in the magnesium sulphate group will be administered 50 ml of a 100 ml infusion bag containing 8 g magnesium sulphate heptahydrate [16 mmol magnesium ions]. Women in the placebo group will be administered 50 ml of a 100 ml infusion bag containing isotonic sodium chloride solution (0.9%). Both treatments will be administered through a dedicated IV infusion line over 30 minutes. Primary study outcome: Death or cerebral palsy measured in children at two years’ corrected age. Sample size : 1676 children are required to detect a decrease in the combined outcome of death or cerebral palsy, from 9.6% with placebo to 5.4% with magnesium sulphate (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). Discussion Given the magnitude of the protective effect in the systematic review, the ongoing uncertainty about benefits at later gestational ages, the serious health and cost consequences of cerebral palsy for the child, family and society, a trial of magnesium sulphate for women at risk of preterm birth between 30 to 34 weeks’ gestation is both important and relevant for clinical practice globally. Trial registration Australian New Zealand Clinical Trials Registry - ACTRN12611000491965

Background Three million babies are stillborn each year and 3.6 million die in the first month of life. In India, early neonatal deaths make up four-fifths of neonatal deaths and infant mortality three-quarters of under-five mortality. Information is scarce on cause-specific perinatal and neonatal mortality in urban settings in low-income countries. We conducted verbal autopsies for stillbirths and neonatal deaths in Mumbai slum settlements. Our objectives were to classify deaths according to international cause-specific criteria and to identify major causes of delay in seeking and receiving health care for maternal and newborn health problems. Methods Over two years, 2005–2007, births and newborn deaths in 48 slum areas were identified prospectively by local informants. Verbal autopsies were collected by trained field researchers, cause of death was classified by clinicians, and family narratives were analysed to investigate delays on the pathway to mortality. Results Of 105 stillbirths, 65 were fresh (62%) and obstetric complications dominated the cause classification. Of 116 neonatal deaths, 87 were early and the major causes were intrapartum-related (28%), prematurity (23%), and severe infection (22%). Bereavement was associated with socioeconomic quintile, previous stillbirth, and number of antenatal care visits. We identified 201 individual delays in 121/187 birth narratives (65%). Overall, delays in receiving care after arrival at a health facility dominated and were mostly the result of referral from one institution to another. Most delays in seeking care were attributed to a failure to recognise symptoms of complications or their severity. Conclusions In Mumbai’s slum settlements, early neonatal deaths made up 75% of neonatal deaths and intrapartum-related complications were the greatest cause of mortality. Delays were identified in two-thirds of narratives, were predominantly related to the provision of care, and were often attributable to referrals between health providers. There is a need for clear protocols for care and transfer at each level of the health system, and an emphasis on rapid identification of problems and communication between health facilities. Trial registration ISRCTN96256793

Background Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births. Methods We hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1) diffusing recommendations for antenatal corticosteroids use to health providers, (2) training health providers on identification of women at high risk of preterm birth, (3) providing reminders to health providers on the use of the kits, and (4) using a color-coded tape to measure uterine height to estimate gestational age in women with unknown gestational age. In both intervention and control clusters , health providers will be trained in essential newborn care for low birth weight babies. The primary outcome is neonatal mortality at 28 days of life in preterm infants. Trial registration ClinicalTrials.gov. Identifier: NCT01084096

In 2006, the Nuffield Council on Bioethics convened a working group to explore the ethical, social, economic and legal issues around clinical decisions made in fetal and neonatal medicine1; in response to their report, the British Association of Perinatal Medicine (BAPM), in conjunction with other professional groups, developed a Framework for Clinical Practice for the management of babies born extremely preterm at less than 26 weeks of gestation. In the current era, the outcomes for babies actively managed at 22 weeks of gestation appear similar to those of babies at 23 weeks of gestation at the time of the 2008 BAPM Framework for Clinical Practice.5–8 Reports from other countries confirm increasing survival and improving neurodevelopmental outcome for babies born before 27 weeks of gestation.9–12 Although internationally there remain differences in practice, there is increasing willingness to consider stabilisation at birth and subsequent intensive care for the most extremely preterm babies,13–15 accompanied by greater acknowledgement of the importance of involving parents in perinatal decision-making.16 Reported outcomes are, of course, impacted by willingness to consider active interventions before and after birth.17 This updated Framework for Practice has been developed by consensus, taking into account the most recent available outcome data both from the UK and internationally, and follows wide consultation. The scope has been extended to include births up to 26+6 weeks of gestation, better to align with national recommendations and published data, and we refer to new RCPCH and other national guidance on palliative care of babies as well as guidance on bereavement care for parents who experience loss of a baby.18 19 Prevention of preterm birth is now a national priority and all maternity services should ensure that measures are in place to realise this ambition. Risk-based approach to decision-making A key ethical consideration for decisions about instituting life-sustaining treatment for an extremely preterm baby is the baby’s prognosis—the risk of an acceptable (or unacceptable) outcome if active (survival focused) management is undertaken.

Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate. Trials in which women considered at risk of preterm birth (<37 weeks' gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1-9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0-12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5-3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1-8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8-20.2) versus 9.8% (95% Cl 9.6-11.0) for neonatal death and 29.6% (96% CI 28.5-30.6) versus 17.5% (95% CI 15.7-18.3) for very preterm births, respectively). Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health.

Background The first month is the most crucial period for child survival. Neonatal mortality continues to remain high with little improvement over the years in Sub-Saharan Africa, including Ethiopia. This region shows the least progress in reducing neonatal mortality and continues to be a significant public health issue. In this study setting, the causes and predictors of neonatal death in the neonatal intensive care units are not well documented. Hence, this study aimed to determine the causes and predictors of neonatal mortality among infants admitted to neonatal intensive care units in eastern Ethiopia. Methods A facility-based in prospective follow-up study was conducted among neonates admitted to neonatal intensive care units of public hospitals of eastern Ethiopia from November 1 to December 30, 2018. Data were collected using a pre-tested structured questionnaire and a follow-up checklist. The main outcomes and causes of death were set by pediatricians and medical residents. EpiData 3.1 and Statistical Package for Social Sciences Version 25 software were used for data entry and analysis, respectively. Multivariable logistic regression was used to identify the predictors of facility-based neonatal mortality. Results The proportion of facility-based neonatal mortality was 20% (95% CI:16.7–23.8%). The causes of death were complications of preterm birth (28.58%), birth asphyxia (22.45%), neonatal infection (18.36%), meconium aspiration syndrome (9.18%), respiratory distress syndrome (7.14%), and congenital malformation (4.08%). Low birth weight, preterm births, length of stay of the neonatal intensive care unit, low 5 min APGAR score, hyperthermia, and initiation of feeding were predictors of neonatal death among infants admitted to the neonatal intensive care units of public hospitals in eastern Ethiopia. Conclusions The proportion of facility-based neonatal deaths was unacceptably high. The main causes of death were preventable and treatable. Hence, improving the timing and quality of antenatal care is essential for early detection, anticipating high-risk newborns, and timely interventions. Furthermore, early initiation of feeding and better referral linkage to tertiary health facilities could lead to a reduction in neonatal death in this setting.