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In this Series paper, we review trends since the 2005 Lancet Series on Neonatal Survival to inform acceleration of progress for newborn health post-2015. On the basis of multicountry analyses and multi-stakeholder consultations, we propose national targets for 2035 of no more than 10 stillbirths per 1000 total births, and no more than 10 neonatal deaths per 1000 livebirths, compatible with the under-5 mortality targets of no more than 20 per 1000 livebirths. We also give targets for 2030. Reduction of neonatal mortality has been slower than that for maternal and child (1–59 months) mortality, slowest in the highest burden countries, especially in Africa, and reduction is even slower for stillbirth rates. Birth is the time of highest risk, when more than 40% of maternal deaths (total about 290 000) and stillbirths or neonatal deaths (5·5 million) occur every year. These deaths happen rapidly, needing a rapid response by health-care workers. The 2·9 million annual neonatal deaths worldwide are attributable to three main causes: infections (0·6 million), intrapartum conditions (0·7 million), and preterm birth complications (1·0 million). Boys have a higher biological risk of neonatal death, but girls often have a higher social risk. Small size at birth—due to preterm birth or small-for-gestational-age (SGA), or both—is the biggest risk factor for more than 80% of neonatal deaths and increases risk of post-neonatal mortality, growth failure, and adult-onset non-communicable diseases. South Asia has the highest SGA rates and sub-Saharan Africa has the highest preterm birth rates. Babies who are term SGA low birthweight (10·4 million in these regions) are at risk of stunting and adult-onset metabolic conditions. 15 million preterm births, especially of those younger than 32 weeks' gestation, are at the highest risk of neonatal death, with ongoing post-neonatal mortality risk, and important risk of long-term neurodevelopmental impairment, stunting, and non-communicable conditions. 4 million neonates annually have other life-threatening or disabling conditions including intrapartum-related brain injury, severe bacterial infections, or pathological jaundice. Half of the world's newborn babies do not get a birth certificate, and most neonatal deaths and almost all stillbirths have no death certificate. To count deaths is crucial to change them. Failure to improve birth outcomes by 2035 will result in an estimated 116 million deaths, 99 million survivors with disability or lost development potential, and millions of adults at increased risk of non-communicable diseases after low birthweight. In the post-2015 era, improvements in child survival, development, and human capital depend on ensuring a healthy start for every newborn baby—the citizens and workforce of the future.

This second paper in the Born Too Soon supplement presents a review of the epidemiology of preterm birth, and its burden globally, including priorities for action to improve the data. Worldwide an estimated 11.1% of all livebirths in 2010 were born preterm (14.9 million babies born before 37 weeks of gestation), with preterm birth rates increasing in most countries with reliable trend data. Direct complications of preterm birth account for one million deaths each year, and preterm birth is a risk factor in over 50% of all neonatal deaths. In addition, preterm birth can result in a range of long-term complications in survivors, with the frequency and severity of adverse outcomes rising with decreasing gestational age and decreasing quality of care. The economic costs of preterm birth are large in terms of immediate neonatal intensive care, ongoing long-term complex health needs, as well as lost economic productivity. Preterm birth is a syndrome with a variety of causes and underlying factors usually divided into spontaneous and provider-initiated preterm births. Consistent recording of all pregnancy outcomes, including stillbirths, and standard application of preterm definitions is important in all settings to advance both the understanding and the monitoring of trends. Context specific innovative solutions to prevent preterm birth and hence reduce preterm birth rates all around the world are urgently needed. Strengthened data systems are required to adequately track trends in preterm birth rates and program effectiveness. These efforts must be coupled with action now to implement improved antenatal, obstetric and newborn care to increase survival and reduce disability amongst those born too soon. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report \"Born Too Soon: the global action report on preterm birth\" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health 's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format.

Preterm birth is the second largest direct cause of child deaths in children younger than 5 years. Yet, data regarding preterm birth (<37 completed weeks of gestation) are not routinely collected by UN agencies, and no systematic country estimates nor time trend analyses have been done. We report worldwide, regional, and national estimates of preterm birth rates for 184 countries in 2010 with time trends for selected countries, and provide a quantitative assessment of the uncertainty surrounding these estimates. We assessed various data sources according to prespecified inclusion criteria. National Registries (563 datapoints, 51 countries), Reproductive Health Surveys (13 datapoints, eight countries), and studies identified through systematic searches and unpublished data (162 datapoints, 40 countries) were included. 55 countries submitted additional data during WHO's country consultation process. For 13 countries with adequate quality and quantity of data, we estimated preterm birth rates using country-level loess regression for 2010. For 171 countries, two regional multilevel statistical models were developed to estimate preterm birth rates for 2010. We estimated time trends from 1990 to 2010 for 65 countries with reliable time trend data and more than 10 000 livebirths per year. We calculated uncertainty ranges for all countries. In 2010, an estimated 14·9 million babies (uncertainty range 12·3–18·1 million) were born preterm, 11·1% of all livebirths worldwide, ranging from about 5% in several European countries to 18% in some African countries. More than 60% of preterm babies were born in south Asia and sub-Saharan Africa, where 52% of the global livebirths occur. Preterm birth also affects rich countries, for example, USA has high rates and is one of the ten countries with the highest numbers of preterm births. Of the 65 countries with estimated time trends, only three (Croatia, Ecuador, and Estonia), had reduced preterm birth rates 1990–2010. The burden of preterm birth is substantial and is increasing in those regions with reliable data. Improved recording of all pregnancy outcomes and standard application of preterm definitions is important. We recommend the addition of a data-quality indicator of the per cent of all live preterm births that are under 28 weeks' gestation. Distinguishing preterm births that are spontaneous from those that are provider-initiated is important to monitor trends associated with increased caesarean sections. Rapid scale up of basic interventions could accelerate progress towards Millennium Development Goal 4 for child survival and beyond. Bill & Melinda Gates Foundation through grants to Child Health Epidemiology Reference Group (CHERG) and Save the Children's Saving Newborn Lives programme; March of Dimes; the Partnership for Maternal Newborn and Childe Health; and WHO, Department of Reproductive Health and Research.

Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard.Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated.Setting CHERG birth cohorts from 14 population based sites in low and middle income countries.Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%.Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (<2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700).Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries

With increasing adverse cardiovascular disease (CVD) outcomes in HIV/AIDS patients, the possible contribution of antiretroviral therapy (ART) to the prevailing CVD epidemic in sub-Saharan Africa (SSA) through its effect on CVD risk factors has rather been under investigated. This study aimed to assess the extent to which ART is associated with hypertension, diabetes mellitus (DM) and dyslipidemia in SSA. This is a systematic review and meta-analysis of studies from SSA, published between January 1946 and December 2017, from Medline, Embase, Africa-wide Information, the Cochrane library, African Index and Medicus databases. Both observational and interventional studies with comparable ART-treated and ART-naïve populations were selected and data was extracted from eligible studies. Pooled estimates of the effect of ART on the outcomes of interest (hypertension, diabetes and abnormal lipid profiles) were obtained using random effects meta-analysis, and meta-regression analysis was used to explore between-study heterogeneity. Twenty cross-sectional studies were included involving 5386 participants. There was no association between ART use and hypertension (OR: 1.9, 95%CI: 0.96-3.76, n = 8, I2 = 73.8%) and DM (OR: 2.53, 95%CI: 0.87-7.35, n = 8, I2 = 73.8%). ART use was associated with high total cholesterol (OR: 3.85, 95%CI: 2.45-6.07, n = 8, I2 = 67.0%), high triglycerides (OR: 1.46, 95%CI: 1.21-1.75, n = 14, I2 = 10.0%) and high LDL-cholesterol (OR: 2.38, 95%CI: 1.43-3.95, n = 11, I2 = 87.6%). ART was associated with rather lower odds of having low HDL-cholesterol (OR: 0.53, 95%CI: 0.32-0.87, n = 8, I2 = 78.2%). There was evidence of between-study heterogeneity for all outcomes except high triglycerides. ART appears to be associated with CVD risk in HIV/AIDS patients in SSA only through dyslipidemia but not through hypertension and DM, however, high quality and robust research in SSA is mandated to accurately ascertain the actual contribution of ART to the CVD burden in this part of the world. Nevertheless, HIV/AIDS patients should still benefit from systematic CVD screening alongside their regular care services. Prospero Registration - CRD42016042306.

Background Globally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity. Objectives This review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality. Methods We conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken. Results Moderate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 – 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 – 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 – 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 – 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong. Conclusion Detection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.

The Malaria Vaccine Implementation Program, coordinated by the World Health Organization, intended to initiate the roll-out of the RTS, S/AS01 malaria vaccine in 3 sub-Saharan African countries in 2018. With sub-optimal implementation, the effectiveness of this vaccine in routine clinical use could be significantly lower than its measured efficacy in randomized trials. This study had as objectives to systematically review and summarize published studies addressing the challenges faced during the implementation phase of malaria vaccination programs and randomized trials conducted in sub-Saharan Africa. The review also sought to report proposed solutions to the challenges identified. This was a systematic review of studies published between 1947 and 2017. Medline, Embase and the Cochrane library databases were searched. Of the 365 studies retrieved, 8 eligible studies reported on challenges of implementing a malaria vaccine in sub-Saharan Africa and possible solutions to these challenges. Data were abstracted from the eligible studies and a qualitative synthesis was done. The 8 studies included in the review had a total of 6189 participants and used a variety of methodologies (3 qualitative, 1 quantitative, 3 mixed method studies and 1 clinical trial review). There was an overall positive acceptance towards the new malaria vaccine (n = 6/8 studies), with a mean acceptance rate of 86.1% (95% CI: 62.0-110.2, n = 2). The main challenges to vaccine receptivity were: inadequate community engagement due to lack of information about the vaccine (n = 6), fear of the vaccine's side effects (n = 5), inefficient delivery of vaccination services to children (n = 4), and sub-optimal quality of the health services (n = 3). Main themes identified from the proposed solutions consisted of the following: using dynamic communication models and trusted sources for delivering vaccine-related health information to the communities (n = 6), community engagement at both national and district level (n = 6), implementing the new vaccine services alongside the existing health services already delivered (n = 6). Effective implementation of the malaria vaccine program requires careful consideration of the socio-cultural context of each community. The RTS, S/AS01 malaria vaccine acceptance and uptake may be significantly enhanced if caregivers' perceptions about vaccines and their importance are adequately fine-tuned. In order to achieve these, community participation and the provision of adequate information in an acceptable form via reliable communication channels seem to be imperative.

Every year, 1·1 million babies die from prematurity, and many survivors are disabled. Worldwide, 15 million babies are born preterm (<37 weeks' gestation), with two decades of increasing rates in almost all countries with reliable data. The understanding of drivers and potential benefit of preventive interventions for preterm births is poor. We examined trends and estimate the potential reduction in preterm births for countries with very high human development index (VHHDI) if present evidence-based interventions were widely implemented. This analysis is to inform a rate reduction target for Born Too Soon. Countries were assessed for inclusion based on availability and quality of preterm prevalence data (2000–10), and trend analyses with projections undertaken. We analysed drivers of rate increases in the USA, 1989–2004. For 39 countries with VHHDI with more than 10 000 births, we did country-by-country analyses based on target population, incremental coverage increase, and intervention efficacy. We estimated cost savings on the basis of reported costs for preterm care in the USA adjusted using World Bank purchasing power parity. From 2010, even if all countries with VHHDI achieved annual preterm birth rate reductions of the best performers for 1990–2010 (Estonia and Croatia), 2000–10 (Sweden and Netherlands), or 2005–10 (Lithuania, Estonia), rates would experience a relative reduction of less than 5% by 2015 on average across the 39 countries. Our analysis of preterm birth rise 1989–2004 in USA suggests half the change is unexplained, but important drivers include non-medically indicated labour induction and caesarean delivery and assisted reproductive technologies. For all 39 countries with VHHDI, five interventions modelling at high coverage predicted a 5% relative reduction of preterm birth rate from 9·59% to 9·07% of livebirths: smoking cessation (0·01 rate reduction), decreasing multiple embryo transfers during assisted reproductive technologies (0·06), cervical cerclage (0·15), progesterone supplementation (0·01), and reduction of non-medically indicated labour induction or caesarean delivery (0·29). These findings translate to roughly 58 000 preterm births averted and total annual economic cost savings of about US$3 billion. We recommend a conservative target of a relative reduction in preterm birth rates of 5% by 2015. Our findings highlight the urgent need for research into underlying mechanisms of preterm births, and development of innovative interventions. Furthermore, the highest preterm birth rates occur in low-income settings where the causes of prematurity might differ and have simpler solutions such as birth spacing and treatment of infections in pregnancy than in high-income countries. Urgent focus on these settings is also crucial to reduce preterm births worldwide. March of Dimes, USA, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institutes of Health, USA.

IntroductionThe COVID-19 pandemic has substantially impacted maternity care provision worldwide. Studies based on modelling estimated large indirect effects of the pandemic on services and health outcomes. The objective of this study was to prospectively document experiences of frontline maternal and newborn healthcare providers.MethodsWe conducted a global, cross-sectional study of maternal and newborn health professionals via an online survey disseminated through professional networks and social media in 12 languages. Information was collected between 24 March and 10 April 2020 on respondents’ background, preparedness for and response to COVID-19 and their experience during the pandemic. An optional module sought information on adaptations to 17 care processes. Descriptive statistics and qualitative thematic analysis were used to analyse responses, disaggregating by low-income and middle-income countries (LMICs) and high-income countries (HICs).ResultsWe analysed responses from 714 maternal and newborn health professionals. Only one-third received training on COVID-19 from their health facility and nearly all searched for information themselves. Half of respondents in LMICs received updated guidelines for care provision compared with 82% in HICs. Overall, 47% of participants in LMICs and 69% in HICs felt mostly or completely knowledgeable in how to care for COVID-19 maternity patients. Facility-level responses to COVID-19 (signage, screening, testing and isolation rooms) were more common in HICs than LMICs. Globally, 90% of respondents reported somewhat or substantially higher levels of stress. There was a widespread perception of reduced use of routine maternity care services, and of modification in care processes, some of which were not evidence-based practices.ConclusionsSubstantial knowledge gaps exist in guidance on management of maternity cases with or without COVID-19. Formal information-sharing channels for providers must be established and mental health support provided. Surveys of maternity care providers can help track the situation, capture innovations and support rapid development of effective responses.

Background In 2021, Uganda had an estimated 25,855 stillbirths and 32,037 newborn deaths. Many Adverse Pregnancy Outcomes (APOs) go unreported despite causing profound grief and other mental health effects. This study explored psychosocial effects of APOs and their influence on reporting these events during surveys and surveillance settings in Uganda. Methods A qualitative cross-sectional study was conducted in September 2021 in Iganga Mayuge health and demographic surveillance system site, eastern Uganda. Narratives were held with 44 women who had experienced an APO (miscarriage, stillbirth or neonatal death) and 7 men whose spouses had undergone the same. Respondents were purposively selected and the sample size premised on the need for diverse respondents. Reflexive thematic analysis was undertaken, supported by NVivo software. Results 60.8% of respondents had experienced neonatal deaths, 27.4% stillbirths, 11.8% miscarriages and almost half had multiple APOs. Theme one on psychosocial effects showed that both women and men suffered disbelief, depression, shame and thoughts of self-harm. In theme two on reactions to interviews, most respondents were reminded about their loss. Indeed, some women cried and a few requested termination of the interview. However, many said they eventually felt better, especially where interviewers comforted and advised them. In theme three about why people consent to such interviews, it was due to the respondents’ need for sensitization on causes of pregnancy loss and danger signs, plus the expectation that the interview would lead to improved health services. Theme four on suggestions for improving interviews highlighted respondents’ requests for a comforting and encouraging approach by interviewers. Conclusion Psychosocial effects of APOs may influence respondents’ interest and ability to effectively engage in an interview. Findings suggest that a multi-pronged approach, including interviewer training in identifying and dealing responsively with grieving respondents, and meeting needs for health information and professional counselling could improve reporting of APOs in surveys and surveillance settings. More so, participants need to understand the purpose of the interview and have realistic expectations.