Iron intake in relation to ovarian reserve among women seeking infertility treatment.

STUDY QUESTION: Is there an association between iron intake and ovarian reserve among women seeking fertility care? SUMMARY ANSWER: Supplemental iron intake above 45 mg/day is associated with lower ovarian reserve among women seeking fertility care. WHAT IS KNOWN ALREADY: Although the literature regarding iron intake in relation to ovarian reserve is scant and inconsistent, some evidence suggests that iron may have gonadotoxic effects. STUDY DESIGN, SIZE, DURATION: This observational study included 582 female participants attending the Massachusetts General Hospital Fertility Center (2007-2019) enrolled in the Environment and Reproductive Health (EARTH) Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Iron intake was estimated using a validated food frequency questionnaire. Markers of ovarian reserve included antral follicle count (AFC) (assessed via transvaginal ultrasound) and Day 3 FSH, both obtained during the course of an infertility evaluation. MAIN RESULTS AND THE ROLE OF CHANCE: Participants had a median age of 35 years and median total iron intake of 29 mg/day. Total iron intake was inversely related to AFC and this association was driven by intake of supplemental iron. Compared to women with a supplemental iron intake of ≤20 mg/day, women consuming 45-64 mg/day of supplemental iron had a 17% (-35%, 0.3%) lower AFC and women consuming ≥65 mg/day of supplemental iron had a 32% (-54%, -11%) lower AFC after adjusting for potential confounders (P, linear trend = 0.003). Similarly, in a multivariable-adjusted analysis, Day 3 FSH levels were 0.9 (0.5, 1.3) IU/ml higher among women with a supplemental iron intake of ≥65 mg/day when compared to women with a supplemental iron intake of ≤20 mg/day (P, linear trend = 0.02). LIMITATIONS, REASONS FOR CAUTION: Iron intake was estimated using a method that relies on self-report and we had no biomarkers of iron status in our participants; only 36 women consumed ≥45 mg/day of supplemental iron. WIDER IMPLICATIONS OF THE FINDINGS: Since all study participants were seeking fertility treatment, our findings may not apply to women in the general population. Although our findings are consistent with studies of women with iron overload, given the paucity of literature on this topic, it is essential that this question is revisited in studies designed to better understand the dose-response relation of this association across the entire distribution of ovarian reserve and the risk-benefit balance of pre-conceptional iron supplementation given its many positive effects on pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by Grants R01ES022955, R01ES033651, R01ES009718, P30ES000002, and P30DK046200 from the National Institutes of Health. N.J.-C. was supported by a Fulbright Scholarship. N.J.-C., M.M., L.M.-A., E.O.-P., S.W., I.S., and J.E.C. declare no conflict of interest related to the work in the manuscript. R.H. has received grants from the National Institute of Environmental Health Sciences. TRIAL REGISTRATION NUMBER: N/A.

Diabetes is associated with a higher risk of mortality among women in a middle-income country: Results form the Mexican Teacher's cohort study.

AIMS: In Mexico City, the mortality rate among patients with diabetes appears to be four times that of people without diabetes. Our study aimed to refine analyses of the impact of diabetes on mortality in a large cohort of women from different areas in Mexico with healthcare insurance. METHODS: Our study followed 111,299 women with comprehensive healthcare coverage from the Mexican Teachers' Cohort. After a median follow-up of 7.8years, 5514 (5%) prevalent self-reported diabetes cases and 4023 incident cases were identified, while deaths were identified through employers' databases and next-of-kin reports, with dates and causes of death for 1121 women obtained from mortality databases. Hazard ratios (HRs) for total and cause-specific mortality were estimated by Cox regression models, using follow-up time as the time scale and allowing for time-variable diabetes status after adjusting for age, socioeconomic status, use of health services, and anthropometric and lifestyle variables. RESULTS: In multivariable-adjusted models, the HR for all-cause mortality was 3.28 (95% CI: 2.86-3.75) in women with vs. without diabetes. The impact of diabetes on mortality was higher in rural vs. urban areas (HR: 4.72 vs. 2.98, respectively). HRs were 1.57 and 23.44 for cancer and renal disease mortality, respectively. CONCLUSION: In women with healthcare coverage in Mexico, the magnitude of the association between diabetes and all-cause mortality was higher than that observed in high-income countries, but less than what has previously been reported for Mexico. Such elevated mortality suggests a lack of adequate access to quality diabetes care in the population despite comprehensive healthcare coverage.

Circulating leptin and adiponectin, and breast density in premenopausal Mexican women: the Mexican Teachers' Cohort.

PURPOSE: Leptin and adiponectin are produced by the adipose tissue. Mammographic density (MD) is one of the strongest predictors of breast cancer (BC) and is highly influenced by adiposity. How the interplay between MD, obesity, and obesity-related biomarkers influences BC risk, however, is still unknown, especially in premenopausal women, where adiposity seems to be protective for BC. The aim of the present study was to explore the association between circulating leptin, adiponectin, and their ratio, with MD in Mexican premenopausal women who are part of the large Mexican Teachers' Cohort (MTC). METHODS: A subsample of 2,084 women from the MTC participated in a clinical evaluation. Of them, 574 premenopausal women were randomly selected, from four MD strata. Serum leptin and adiponectin concentrations were measured by immunoassays. Multivariate regression analyses were performed to compare means of MD by quartiles of adipokines and their ratio. RESULTS: High leptin and leptin/adiponectin ratio levels were significantly associated with lower percentage MD and higher absolute and non-absolute dense tissue areas. High adiponectin levels were significantly associated with lower absolute dense and non-dense tissue areas, but not with percentage MD. After adjustment for BMI, only the associations between percentage MD and absolute non-dense tissue area with leptin remained statistically significant. CONCLUSIONS: Leptin, adiponectin, and their ratio were associated with MD; however, only the positive association with leptin seemed to be independent from overall obesity.

A global reference for caesarean section rates (C-Model): a multicountry cross-sectional study.

OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems.

Maternal complications and perinatal mortality: findings of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: We aimed to determine the prevalence and risks of late fetal deaths (LFDs) and early neonatal deaths (ENDs) in women with medical and obstetric complications. DESIGN: Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS). SETTING: A total of 359 participating facilities in 29 countries. POPULATION: A total of 308 392 singleton deliveries. METHODS: We reported on perinatal indicators and determined risks of perinatal death in the presence of severe maternal complications (haemorrhagic, infectious, and hypertensive disorders, and other medical conditions). MAIN OUTCOME MEASURES: Fresh and macerated LFDs (defined as stillbirths ≥ 1000 g and/or ≥28 weeks of gestation) and ENDs. RESULTS: The LFD rate was 17.7 per 1000 births; 64.8% were fresh stillbirths. The END rate was 8.4 per 1000 liveborns; 67.1% occurred by day 3 of life. Maternal complications were present in 22.9, 27.7, and 21.2% [corrected] of macerated LFDs, fresh LFDs, and ENDs, respectively. The risks of all three perinatal mortality outcomes were significantly increased with placental abruption, ruptured uterus, systemic infections/sepsis, pre-eclampsia, eclampsia, and severe anaemia. CONCLUSIONS: Preventing intrapartum-related perinatal deaths requires a comprehensive approach to quality intrapartum care, beyond the provision of caesarean section. Early identification and management of women with complications could improve maternal and perinatal outcomes.

Mode and timing of twin delivery and perinatal outcomes in low- and middle-income countries: a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To describe the mode and timing of delivery of twin pregnancies at ≥34 weeks of gestation and their association with perinatal outcomes. DESIGN: Secondary analysis of a cross-sectional study. POPULATION: Twin deliveries at ≥34 weeks of gestation from 21 low- and middle-income countries participating in the WHO Multicountry Survey on Maternal and Newborn Health. METHODS: Descriptive analysis and effect estimates using multilevel logistic regression. MAIN OUTCOME MEASURES: Stillbirth, perinatal mortality, and neonatal near miss (use of selected life saving interventions at birth). RESULTS: The average length of gestation at delivery was 37.6 weeks. Of all twin deliveries, 16.8 and 17.6% were delivered by caesarean section before and after the onset of labour, respectively. Prelabour caesarean delivery was associated with older maternal age, higher institutional capacity and wealth of the country. Compared with spontaneous vaginal delivery, lower risks of neonatal near miss (adjusted odds ratio, aOR, 0.63; 95% confidence interval, 95% CI, 0.44-0.94) were found among prelabour caesarean deliveries. A lower risk of early neonatal mortality (aOR 0.12; 95% CI 0.02-0.56) was also observed among prelabour caesarean deliveries with nonvertex presentation of the first twin. The week of gestation with the lowest rate of prospective fetal death varied by fetal presentation: 37 weeks for vertex-vertex; 39 weeks for vertex-nonvertex; and 38 weeks for a nonvertex first twin. CONCLUSIONS: The prelabour caesarean delivery rate among twins varied largely between countries, probably as a result of overuse of caesarean delivery in wealthier countries and limited access to caesarean delivery in low-income countries. Prelabour delivery may be beneficial when the first twin is nonvertex. International guidelines for optimal twin delivery methods are needed.