HMGB1: a double-edged sword and therapeutic target in the female reproductive system

Summary This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12–13% in the USA and 5–9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM—together called spontaneous preterm births—are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.

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.

Hyperglycaemia that develops during pregnancy and resolves after birth has been recognized for over 50 years, but uniform worldwide consensus is lacking about threshold hyperglycaemic levels that merit a diagnosis of 'gestational diabetes mellitus' (GDM) and thus treatment during pregnancy. GDM is currently the most common medical complication of pregnancy, and prevalence of undiagnosed hyperglycaemia and even overt diabetes in young women is increasing. Maternal overweight and obesity, later age at childbearing, previous history of GDM, family history of type 2 diabetes mellitus and ethnicity are major GDM risk factors. Diagnosis is usually performed using an oral glucose tolerance test (OGTT), although a non-fasting, glucose challenge test (GCT) is used in some parts of the world to screen women for those requiring a full OGTT. Dietary modification and increased physical activity are the primary treatments for GDM, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved. Oral hypoglycaemic agents, principally metformin and glibenclamide (glyburide), are also used in some countries. Treatment improves immediate pregnancy outcomes, reducing excess fetal growth and adiposity and pregnancy-related hypertensive disorders. GDM increases the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease, in both the mother and infant. Optimal management of mother and infant during long-term follow-up remains challenging, with very limited implementation of preventive strategies in most parts of the world.