Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970-2019: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Meeting the contraceptive needs of women of reproductive age is beneficial for the health of women and children, and the economic and social empowerment of women. Higher rates of contraceptive coverage have been linked to the availability of a more diverse range of contraceptive methods. We present estimates of the contraceptive prevalence rate (CPR), modern contraceptive prevalence rate (mCPR), demand satisfied, and the method of contraception used for both partnered and unpartnered women for 5-year age groups in 204 countries and territories between 1970 and 2019. METHODS: We used 1162 population-based surveys capturing contraceptive use among women between 1970 and 2019, in which women of reproductive age (15-49 years) self-reported their, or their partner's, current use of contraception for family planning purposes. Spatiotemporal Gaussian process regression was used to generate estimates of the CPR, mCPR, demand satisfied, and method mix by age and marital status. We assessed how age-specific mCPR and demand satisfied changed with the Socio-demographic Index (SDI), a measure of social and economic development, using the meta-regression Bayesian, regularised, trimmed method from the Global Burden of Diseases, Injuries, and Risk Factors Study. FINDINGS: In 2019, 162·9 million (95% uncertainty interval [UI] 155·6-170·2) women had unmet need for contraception, of whom 29·3% (27·9-30·6) resided in sub-Saharan Africa and 27·2% (24·4-30·3) resided in south Asia. Women aged 15-19 years (64·8% [62·9-66·7]) and 20-24 years (71·9% [68·9-74·2]) had the lowest rates of demand satisfied, with 43·2 million (95% UI 39·3-48·0) women aged 15-24 years with unmet need in 2019. The mCPR and demand satisfied among women aged 15-19 years were substantially lower than among women aged 20-49 years at SDI values below 60 (on a 0-100 scale), but began to equalise as SDI increased above 60. Between 1970 and 2019, the global mCPR increased by 20·1 percentage points (95% UI 18·7-21·6). During this time, traditional methods declined as a proportion of all contraceptive methods, whereas the use of implants, injections, female sterilisation, and condoms increased. Method mix differs substantially depending on age and geography, with the share of female sterilisation increasing with age and comprising more than 50% of methods in use in south Asia. In 28 countries, one method was used by more than 50% of users in 2019. INTERPRETATION: The dominance of one contraceptive method in some locations raises the question of whether family planning policies should aim to expand method mix or invest in making existing methods more accessible. Lower rates of demand satisfied among women aged 15-24 years are also concerning because unintended pregnancies before age 25 years can forestall or eliminate education and employment opportunities that lead to social and economic empowerment. Policy makers should strive to tailor family planning programmes to the preferences of the groups with the most need, while maintaining the programmes used by existing users. FUNDING: Bill & Melinda Gates Foundation.

The State of US Health, 1990-2016: Burden of Diseases, Injuries, and Risk Factors Among US States.

Introduction: Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective: To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting: A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures: Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results: Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95% UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95% UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), and West Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5% (95% UI, 42.8% to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5% of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance: There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.

National and regional trends in the prevalence of polycystic ovary syndrome since 1990 within Europe: the modeled estimates from the Global Burden of Disease Study 2016.

INTRODUCTION: The exact prevalence of polycystic ovary syndrome (PCOS) is difficult to assess due to the clinical heterogeneity of this condition, the lack of a universal definition as well as the lack of studies comparing differences within and between ethnic groups across geographical regions. MATERIAL AND METHODS: Using a modeling approach, we analyzed the data from Global Burden of Disease Study 2016 and extracted the national and regional estimates on PCOS prevalence since 1990 in females aged 15-49 years by country and three major European regions: Western, Central, and Eastern. RESULTS: The average prevalence of PCOS in Europe was 276.4 cases per 100,000 (95% uncertainty interval (UI): 207.8-363.2). The estimates varied markedly across countries and regions, with the highest rates per 100,000 in the Czech Republic (460.6) and the lowest in Sweden (34.10); other Nordic countries, Germany, and the UK had relatively low rates as well. The rates in Central and Eastern Europe were more than three times higher than those in Western countries. They were comparable among Eastern countries, ranging from 406.4 in Lithuania to 443.1 in Russia. Within Central Europe, PCOS prevalence was lowest in Turkey and Albania, while in the majority of the remaining countries, the prevalence ranged between 420 and 440 per 100,000. Between 1990 and 2016, the rates across European regions were relatively stable. CONCLUSIONS: We found highly variable national and regional prevalence of PCOS among European females. Our estimates encourage the search at the population level for new environmental and genetic determinants of PCOS.

High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children.

BACKGROUND: Monocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children. SETTING: Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial (NCT00428116) and extended cohort study in Kenya. METHODS: HIV-infected infants (N = 67) initiated antiretroviral therapy (ART) at age <5 months. Plasma soluble (s) CD163 (sCD163), sCD14, and neopterin were measured before ART (entry) and 6 months later. Milestone attainment was ascertained monthly during 24 months, and neuropsychological tests were performed at 5.8-8.2 years after initiation of ART (N = 27). The relationship between neurodevelopment and sCD163, sCD14, and neopterin at entry and 6 months after ART was assessed using Cox proportional hazards models and linear regression. RESULTS: Infants with high entry sCD163 had unexpected earlier attainment of supported sitting (5 vs 6 months; P = 0.006) and supported walking (10 vs 12 months; P = 0.02) with trends in adjusted analysis. Infants with high 6-month post-ART sCD163 attained speech later (17 vs 15 months; P = 0.006; adjusted hazard ratio, 0.47; P = 0.02), threw toys later (18 vs 17 months; P = 0.01; adjusted hazard ratio, 0.53; P = 0.04), and at median 6.8 years after ART, had worse neuropsychological test scores (adj. mean Z-score differences, cognition, -0.42; P = 0.07; short-term memory, -0.52; P = 0.08; nonverbal test performance, -0.39, P = 0.05). CONCLUSIONS: Before ART, monocyte activation may reflect transient neuroprotective mechanisms in infants. After ART and viral suppression, monocyte activation may predict worse short- and long-term neurodevelopment outcomes.

Diseases, Injuries, and Risk Factors in Child and Adolescent Health, 1990 to 2017: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2017 Study.

Importance: Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies. Objective: To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories. Design, Setting, and Participants: This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018. Exposures: Being under the age of 20 years between 1990 and 2017. Main Outcomes and Measures: Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability. Results: Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle-SDI locations experiencing 82.2% (95% UI, 81.6%-82.9%) of deaths, up from 70.9% (95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile. Conclusions and Relevance: Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years.

Trichloroethylene perturbs HNF4a expression and activity in the developing chick heart.

Exposure to trichloroethylene (TCE) is linked to formation of congenital heart defects in humans and animals. Prior interactome analysis identified the transcription factor, Hepatocyte Nuclear Factor 4 alpha (HNF4a), as a potential target of TCE exposure. As a role for HNF4a is unknown in the heart, we examined developing avian hearts for HNF4a expression and for sensitivity to TCE and the HNF4a agonist, Benfluorex. In vitro analysis using a HNF4a reporter construct showed both TCE and HFN4a to be antagonists of HNF4a-mediated transcription at the concentrations tested. HNF4a mRNA is expressed transiently in the embryonic heart during valve formation and cardiac development. Embryos were examined for altered gene expression in the presence of TCE or Benfluorex. TCE altered expression of selected mRNAs including HNF4a, TRAF6 and CYP2C45. There was a transition between inhibition and induction of marker gene expression in embryos as TCE concentration increased. Benfluorex was largely inhibitory to selected markers. Echocardiography of exposed embryos showed reduced cardiac function with both TCE and Benfluorex. Cardiac contraction was reduced by 29% and 23%, respectively at 10 ppb. The effects of TCE and Benfluorex on autocrine regulation of HNF4a, selected markers and cardiac function argue for a functional interaction of TCE and HNF4a. Further, the dose-sensitive shift between inhibition and induction of marker expression may explain the nonmonotonic-like dose response observed with TCE exposure in the heart.

Bariatric Surgery in Women of Childbearing Age, Timing Between an Operation and Birth, and Associated Perinatal Complications.

Importance: Metabolic changes after maternal bariatric surgery may affect subsequent fetal development. Many relevant perinatal outcomes have not been studied in this postoperative population, and the risks associated with short operation-to-birth (OTB) intervals have not been well examined. Objective: To examine the risk for perinatal complications in women with a history of bariatric surgery (postoperative mothers [POMs]) by comparing them with mothers without operations (nonoperative mothers [NOMs]) and examining the association of the OTB interval with perinatal outcomes. Design, Setting, and Participants: This investigation was a population-based retrospective cohort study (January 1, 1980, to May 30, 2013) at hospitals in Washington State. Data were collected from birth certificates and maternally linked hospital discharge data. Participants were all POMs and their infants (n = 1859) and a population-based random sample of NOMs and their infants frequency matched by delivery year (n = 8437). Exposures: Bariatric operation before birth or categories of OTB intervals. Main Outcomes and Measures: The primary outcomes were prematurity, neonatal intensive care unit (NICU) admission, congenital malformation, small for gestational age (SGA), birth injury, low Apgar score (≤8), and neonatal mortality. Poisson regression was used to compute relative risks (RRs) and 95% CIs, with adjustments for maternal body mass index, delivery year, socioeconomic status, age, parity, and comorbid conditions. Results: A total of 10 296 individuals were included in the analyses for this study. In the overall cohort, the median age was 29 years (interquartile range, 24-33 years). Compared with infants from NOMS, infants from POMs had a higher risk for prematurity (14.0% vs 8.6%; RR, 1.57; 95% CI, 1.33-1.85), NICU admission (15.2% vs 11.3%; RR, 1.25; 95% CI, 1.08-1.44), SGA status (13.0% vs 8.9%; RR, 1.93; 95% CI, 1.65-2.26), and low Apgar score (17.5% vs 14.8%; RR, 1.21; 95% CI, 1.06-1.37). Compared with infants from mothers with greater than a 4-year OTB interval, infants from mothers with less than a 2-year interval had higher risks for prematurity (11.8% vs 17.2%; RR, 1.48; 95% CI, 1.00-2.19), NICU admission (12.1% vs 17.7%; RR, 1.54; 95% CI, 1.05-2.25), and SGA status (9.2% vs 12.7%; RR, 1.51; 95% CI, 0.94-2.42). Conclusions and Relevance: Infants of mothers with a previous bariatric operation had a greater likelihood of perinatal complications compared with infants of NOMs. Operation-to-birth intervals of less than 2 years were associated with higher risks for prematurity, NICU admission, and SGA status compared with longer intervals. These findings are relevant to women with a history of bariatric surgery and could inform decisions regarding the optimal timing between an operation and conception.