Preterm pigs for preterm birth research: reasonably feasible

Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.

Summary Background Preterm birth is the leading cause of death in children younger than 5 years worldwide. Although preterm survival rates have increased in high-income countries, preterm newborns still die because of a lack of adequate newborn care in many low-income and middle-income countries. We estimated global, regional, and national rates of preterm birth in 2014, with trends over time for some selected countries. Methods We systematically searched for data on preterm birth for 194 WHO Member States from 1990 to 2014 in databases of national civil registration and vital statistics (CRVS). We also searched for population-representative surveys and research studies for countries with no or limited CRVS data. For 38 countries with high-quality data for preterm births in 2014, data are reported directly. For countries with at least three data points between 1990 and 2014, we used a linear mixed regression model to estimate preterm birth rates. We also calculated regional and global estimates of preterm birth for 2014. Findings We identified 1241 data points across 107 countries. The estimated global preterm birth rate for 2014 was 10·6% (uncertainty interval 9·0–12·0), equating to an estimated 14·84 million (12·65 million–16·73 million) live preterm births in 2014. 12· 0 million (81·1%) of these preterm births occurred in Asia and sub-Saharan Africa. Regional preterm birth rates for 2014 ranged from 13·4% (6·3–30·9) in North Africa to 8·7% (6·3–13·3) in Europe. India, China, Nigeria, Bangladesh, and Indonesia accounted for 57·9 million (41×4%) of 139·9 million livebirths and 6·6 million (44×6%) of preterm births globally in 2014. Of the 38 countries with high-quality data, preterm birth rates have increased since 2000 in 26 countries and decreased in 12 countries. Globally, we estimated that the preterm birth rate was 9×8% (8×3–10×9) in 2000, and 10×6% (9×0–12×0) in 2014. Interpretation Preterm birth remains a crucial issue in child mortality and improving quality of maternal and newborn care. To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting. Funding WHO and the March of Dimes.

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. Copyright © 2012 Elsevier Ltd. All rights reserved.