Dexamethasone versus betamethasone for preterm birth: a systematic review and network meta-analysis.

OBJECTIVE: This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth. DATA SOURCES: The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov, and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted. STUDY ELIGIBILITY CRITERIA: Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study. METHODS: Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability. RESULTS: A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62-1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80-1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56-1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, -49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45-1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24-2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72-6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96-2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis. CONCLUSION: Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies.

Pregnancy Loss and Carotid Intima-Media Thickness in Mexican Women.

BACKGROUND: Cardiovascular disease in women often develops without conventional risk factors. Prenatal loss is a common pregnancy outcome that may result in physiological changes can increase the potential future risk of cardiovascular disease. Insufficient information exists regarding the impact of pregnancy loss on early markers of cardiovascular disease risk. METHODS AND RESULTS: Cross-sectional analysis of 1767 disease-free women from the MTC (Mexican Teachers' Cohort) who had been pregnant was used to evaluate the relationship between pregnancy loss and carotid intima-media thickness (IMT). Participants responded to a questionnaire regarding their reproductive history, risk factors, and medical conditions. We defined pregnancy loss as history of miscarriage and/or stillbirth. Trained neurologists measured IMT using ultrasound. We log-transformed IMT and defined subclinical carotid atherosclerosis (SCA) as IMT ≥0.8 mm and/or plaque. We used multivariable linear and logistic regression models to assess the relation of pregnancy loss, IMT, and SCA. The mean age of participants was 49.8±5.1 years. The prevalence of pregnancy loss was 22%, and we observed SCA in 23% of participants. Comparing participants who reported a pregnancy loss and those who did not, the multivariable-adjusted odds ratio for SCA was 1.52 (95% confidence interval, 1.12-2.06). Women who experienced a stillbirth had 2.32 higher odds (95% confidence interval, 1.03-5.21) of SCA than those who did not. Mean IMT appeared to be higher in women who reported a pregnancy loss relative to those who did not; nevertheless, this was not statistically significant. CONCLUSIONS: Pregnancy loss could be linked to cardiovascular disease later in life. The key findings of our study await confirmation and further investigation of the potential underlying mechanisms for this association is required.

Beyond too little, too late and too much, too soon: a pathway towards evidence-based, respectful maternity care worldwide.

On the continuum of maternal health care, two extreme situations exist: too little, too late (TLTL) and too much, too soon (TMTS). TLTL describes care with inadequate resources, below evidence-based standards, or care withheld or unavailable until too late to help. TLTL is an underlying problem associated with high maternal mortality and morbidity. TMTS describes the routine over-medicalisation of normal pregnancy and birth. TMTS includes unnecessary use of non-evidence-based interventions, as well as use of interventions that can be life saving when used appropriately, but harmful when applied routinely or overused. As facility births increase, so does the recognition that TMTS causes harm and increases health costs, and often concentrates disrespect and abuse. Although TMTS is typically ascribed to high-income countries and TLTL to low-income and middle-income ones, social and health inequities mean these extremes coexist in many countries. A global approach to quality and equitable maternal health, supporting the implementation of respectful, evidence-based care for all, is urgently needed. We present a systematic review of evidence-based clinical practice guidelines for routine antenatal, intrapartum, and postnatal care, categorising them as recommended, recommended only for clinical indications, and not recommended. We also present prevalence data from middle-income countries for specific clinical practices, which demonstrate TLTL and increasing TMTS. Health-care providers and health systems need to ensure that all women receive high-quality, evidence-based, equitable and respectful care. The right amount of care needs to be offered at the right time, and delivered in a manner that respects, protects, and promotes human rights.

The Antenatal Corticosteroids Trial (ACT): a secondary analysis to explore site differences in a multi-country trial.

BACKGROUND: The Antenatal Corticosteroid Trial (ACT) assessed the feasibility, effectiveness, and safety of a multifaceted intervention to increase the use of antenatal corticosteroids (ACS) in mothers at risk of preterm birth at all levels of care in low and middle-income countries. The intervention effectively increased the use of ACS but had no overall impact on neonatal mortality in the targeted <5(th) percentile birth weight infants. Being in the intervention clusters was also associated with an overall increase in neonatal deaths. We sought to explore plausible pathways through which this intervention increased neonatal mortality. METHODS: We conducted secondary analyses to assess site differences in outcome and potential explanations for the differences in outcomes if found. By site, and in the intervention and control clusters, we evaluated characteristics of the mothers and care systems, the proportion of the <5(th) percentile infants and the overall population that received ACS, the rates of possible severe bacterial infection (pSBI), determined from clinical signs, and neonatal mortality rates. RESULTS: There were substantial differences between the sites in both participant and health system characteristics, with Guatemala and Argentina generally having the highest levels of care. In some sites there were substantial differences in the health system characteristics between the intervention and control clusters. The increase in ACS in the intervention clusters was similar among the sites. While overall, there was no difference in neonatal mortality among <5(th) percentile births between the intervention and control clusters, Guatemala and Pakistan both had significant reductions in neonatal mortality in the <5(th) percentile infants in the intervention clusters. The improvement in neonatal mortality in the Guatemalan site in the <5(th) percentile infants was associated with a higher level of care at the site and an improvement in care in the intervention clusters. There was a significant increase overall in neonatal mortality in the intervention clusters compared to the control. Across sites, this increase in neonatal mortality was statistically significant and most apparent in the African sites. This increase in neonatal mortality was accompanied by a significant increase in pSBI in the African sites. CONCLUSIONS: The improvement in neonatal mortality in the Guatemalan site in the <5(th) percentile infants was associated with a higher level of care and an improvement in care in the intervention clusters. The increase in neonatal mortality in the intervention clusters across all sites was largely driven by the poorer outcomes in the African sites, which also had an increase in pSBI in the intervention clusters. We emphasize that these results come from secondary analyses. Additional prospective studies are needed to assess the effectiveness and safety of ACS on neonatal health in low resource settings. TRIAL REGISTRATION: clinicaltrials.gov (NCT01084096).

mHealth Interventions in Low-Income Countries to Address Maternal Health: A Systematic Review.

BACKGROUND: The wide availability and relative simplicity of mobile phones make them a promising instrument for delivering a variety of health-related interventions. Mobile health (mHealth) interventions have been tested in a variety of health delivery areas, but research has been restricted to pilot and small studies with limited generalizability. The aim of this review was to explore the current evidence on the use of mHealth for maternal health interventions in low- and low middle-income countries. METHODS: Peer-reviewed papers were identified from Medline/PubMed, Web of Science, and Cochrane Library via a combination of search terms. Quantitative or mixed-methods papers published in the English language between January 2000 and July 2015 were included. RESULTS: Three hundred and seventy papers were found in the literature search. We assessed the full text of 57 studies, and included 19 in the review. Study designs included were 5 randomized controlled trials, 9 before and after comparisons, 1 study with endline assessment only, 3 postintervention assessments, and 1 cohort study. Quality assessment elucidated 9 low-quality, 5 moderate, and 5 high studies. Five studies supported the use of mobile phones for data collection, 3 for appointment reminders, and 4 for both appointment reminders and health promotion. Six studies supported the use of mHealth for provider-to-provider communication and 1 for clinical management. CONCLUSIONS: Studies demonstrated promise for the use of mHealth in maternal health; however, much of the evidence came from low- and moderate-quality studies. Pilot and small programs require more rigorous testing before allocating resources to scaling up this technology.

Barriers to providing quality emergency obstetric care in Addis Ababa, Ethiopia: Healthcare providers' perspectives on training, referrals and supervision, a mixed methods study.

BACKGROUND: Increasing women's access to and use of facilities for childbirth is a critical national strategy to improve maternal health outcomes in Ethiopia; however coverage alone is not enough as the quality of emergency obstetric services affects maternal mortality and morbidity. Addis Ababa has a much higher proportion of facility-based births (82%) than the national average (11%), but timely provision of quality emergency obstetric care remains a significant challenge for reducing maternal mortality and improving maternal health. The purpose of this study was to assess barriers to the provision of emergency obstetric care in Addis Ababa from the perspective of healthcare providers by analyzing three factors: implementation of national referral guidelines, staff training, and staff supervision. METHODS: A mixed methods approach was used to assess barriers to quality emergency obstetric care. Qualitative analyses included twenty-nine, semi-structured, key informant interviews with providers from an urban referral network consisting of a hospital and seven health centers. Quantitative survey data were collected from 111 providers, 80% (111/138) of those providing maternal health services in the same referral network. RESULTS: Respondents identified a lack of transportation and communication infrastructure, overcrowding at the referral hospital, insufficient pre-service and in-service training, and absence of supportive supervision as key barriers to provision of quality emergency obstetric care. CONCLUSIONS: Dedicated transportation and communication infrastructure, improvements in pre-service and in-service training, and supportive supervision are needed to maximize the effective use of existing human resources and infrastructure, thus increasing access to and the provision of timely, high quality emergency obstetric care in Addis Ababa, Ethiopia.

Prepregnancy and early adulthood body mass index and adult weight change in relation to fetal loss.

OBJECTIVE: To examine prospectively the relationships of prepregnancy body mass index (BMI), BMI at age 18 years, and weight change since age 18 years with risk of fetal loss. METHODS: Our prospective cohort study included 25,719 pregnancies reported by 17,027 women in the Nurses' Health Study II between 1990 and 2009. In 1989, height, current weight, and weight at age 18 years were self-reported. Current weight was updated every 2 years thereafter. Pregnancies were self-reported, with case pregnancies lost spontaneously and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. RESULTS: Incident fetal loss was reported in 4,494 (17.5%) pregnancies. Compared with those of normal BMI, the multivariate relative risks of fetal loss were 1.07 (95% CI [confidence interval] 1.00-1.15) for overweight women, 1.10 (95% CI 0.98-1.23) for class I obese women, and 1.27 (95% CI 1.11-1.45) for class II and class III obese women (P trend ≤ .001). Body mass index at age 18 years was not associated with fetal loss (P trend=.59). Compared with women who maintained a stable weight (± 4 kg) between age 18 years and before pregnancy, women who lost weight had a 20% (95% CI 9-29%) lower risk of fetal loss. This association was stronger among women who were overweight at age 18 years. CONCLUSION: Being overweight or obese before pregnancy was associated with higher risk of fetal loss. In women overweight or obese at age 18 years, losing 4 kg or more was associated with a lower risk of fetal loss. LEVEL OF EVIDENCE: : II.

Semen quality in relation to antioxidant intake in a healthy male population.

OBJECTIVE: To assess the relationship between dietary antioxidant intake and semen quality in young healthy males. DESIGN: Cross-sectional study. SETTING: University and college campuses in the Rochester, New York, area. PATIENT(S): One hundred eighty-nine university-aged men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen volume, total sperm count, concentration, motility, total motile count, and morphology. RESULT(S): Progressive motility was 6.5 (95% confidence interval [CI], 0.6, 12.3) percentage units higher among men in the highest quartile of ß-carotene intake compared with men in the lowest quartile. Similar results were observed for lutein intake. Lycopene intake was positively related to sperm morphology. The adjusted percentages (95% CI) of morphologically normal sperm in increasing quartiles of lycopene intake were 8.0 (6.7, 9.3), 7.7 (6.4, 9.0), 9.2 (7.9, 10.5), and 9.7 (8.4, 11.0). There was a nonlinear relationship between vitamin C intake and sperm concentration, with men in the second quartile of intake having, on average, the highest sperm concentrations and men in the top quartile of intake having the lowest concentrations. CONCLUSION(S): In a population of healthy young men, carotenoid intake was associated with higher sperm motility and, in the case of lycopene, better sperm morphology. Our data suggest that dietary carotenoids may have a positive impact on semen quality.

Men's body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization.

OBJECTIVE: To evaluate the association between men's body mass index (BMI), early embryo quality, and clinical outcomes in couples undergoing in vitro fertilization (IVF). DESIGN: Prospective cohort study. SETTING: Fertility clinic in an academic medical center. PATIENT(S): 114 couples who underwent 172 assisted reproduction cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization rate, embryo quality, implantation rate, clinical pregnancy rate, and live birth rate. RESULT(S): The fertilization rate was higher among obese men than among normal weight men in conventional IVF cycles. No statistically significant associations were found between men's BMI and the proportion of poor-quality embryos on day 3, slow embryo cleavage rate, or accelerated embryo cleavage rate. Men's BMI was unrelated to positive ß-human chorionic gonadotropin rate, clinical pregnancy rate, or live-birth rate per embryo transfer. Among couples undergoing intracytoplasmic sperm injection, the odds of live birth in couples with obese male partners was 84% lower than the odds in couples with men with normal BMI. CONCLUSION(S): Our data suggest a possible deleterious effect of male obesity on the odds of having a live birth among couples undergoing intracytoplasmic sperm injection.

Dietary patterns and semen quality in young men.

STUDY QUESTION: Are different dietary patterns associated with semen parameters in young men? STUDY ANSWER: The consumption of a Prudent dietary pattern was significantly associated with higher progressive sperm motility and unrelated to sperm concentration and morphology. The consumption of a Western dietary pattern was unrelated to conventional semen quality parameters. WHAT IS KNOWN ALREADY: Over the past decades there has been evidence of a concomitant decline in sperm and diet quality. Yet whether diet composition influences semen quality remains largely unexplored. STUDY DESIGN, SIZE, DURATION: The Rochester Young Men's Study (n= 188) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS, SETTING, METHODS: Men aged 18-22 years were included in this analysis. Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns and conventional semen quality parameters (sperm concentration, progressive motility and morphology) adjusting for abstinence time, multivitamin use, race, smoking status, BMI, recruitment period, moderate-to-intense exercise and total calorie intake. RESULTS: Two dietary patterns were identified by factor analysis. The 'Western' pattern was characterized by high intake of red and processed meat, refined grains, pizza, snacks, high-energy drinks and sweets. The 'Prudent' pattern was characterized by high intake of fish, chicken, fruit, vegetables, legumes and whole grains. The Prudent pattern was positively associated with percent progressively motile sperm in multivariate models (P-trend = 0.04). Men in the highest quartile of the Prudent diet had 11.3% (95% CI 1.3, 21.3) higher % progressively motile sperm compared with men in the lowest quartile. The Prudent pattern was unrelated to sperm concentration and morphology. The Western pattern was not associated with any semen parameter. LIMITATIONS: This was a cross-sectional and observational study, which limited our ability to determine causality of diet on semen quality parameters. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support the suggestion that a diet rich in fruits, vegetables, chicken, fish and whole grains may be an inexpensive and safe way to improve at least one measure of semen quality. STUDY FUNDING/COMPETING INTERESTS: The authors are supported by NIH grant T32DK007703-16 and P30DK46200 and European Union DEER Grant 212844. The authors have no competing interests to declare.

Body mass index and short-term weight change in relation to treatment outcomes in women undergoing assisted reproduction.

OBJECTIVE: To assess the relation between body mass index (BMI) and short-term weight change with assisted reproductive technology (ART) outcomes. DESIGN: Prospective cohort study. SETTING: Fertility center. PATIENT(S): A total of 170 women undergoing 233 ART cycles. INTERVENTION(S): Baseline BMI and short-term weight change were related to ART outcomes. Regression models accounting for repeated observations were used to adjust data for potential confounders. MAIN OUTCOME MEASURE(S): Peak E2 levels, oocyte yield, MII yield, fertilization rate, embryo quality, postive [beta]-hCH, clinical pregnancy and live birth rates. RESULT(S): Overweight and obesity were associated with lower live birth rates. The adjusted live birth rate (95% confidence interval) was 42% (28%-58%) among women with a BMI between 20 and 22.4 kg/m(2) and 23% (14%-36%) among overweight or obese women. Short-term weight loss was associated with a higher proportion of metaphase II (MII) oocytes retrieved. The adjusted proportion of MII eggs was 91% (87%-94%) for women who lost 3 kg or more and 86% (81%-89%) for women whose weight remained stable. This association was stronger among women who were overweight or obese at baseline. Short-term weight loss was unrelated to positive ß-hCG, clinical pregnancy, or live birth rates. CONCLUSION(S): Overweight and obesity were related to lower live birth rates in women undergoing ART. Short-term weight loss was related to higher MII yield, particularly among overweight and obese women, but unrelated to clinical outcomes.