Chronicling menstrual cycle patterns across the reproductive lifespan with real-world data.

The intricate hormonal and physiological changes of the menstrual cycle can influence health on a daily basis. Although prior studies have helped improve our understanding of the menstrual cycle, they often lack diversity in the populations included, sample size, and the span of reproductive and life stages. This paper aims to describe the dynamic differences in menstrual cycle characteristics and associated symptoms by age in a large global cohort of period-tracking application users. This work aims to contribute to our knowledge and understanding of female physiology at varying stages of reproductive aging. This cohort study included self-reported menstrual cycle and symptom information in a sample of Flo application users aged 18-55. Cycle and period length and their variability, and frequency of menstrual cycle symptom logs are described by the age of the user. Based on data logged by over 19 million global users of the Flo app, the length of the menstrual cycle and period show clear age-associated patterns. With higher age, cycles tend to get shorter (Cycle length: D ¯ = 1.85 days, Cohen's D = 0.59) and more variable (Cycle length SD: D ¯ = 0.42 days, Cohen's D = 0.09), until close to the chronological age (40-44) suggesting menopausal transition, when both cycles and periods become longer (Cycle length: D ¯ = 0.86 days, t = 48.85, Cohen's D = 0.26; Period length: D ¯ = 0.08, t = 15.6, Cohen's D = 0.07) and more variable (Cycle length SD: D ¯ = 2.80 days, t = 111.43, d = 0.51; Period length SD: D ¯ = 0.23 days, t = 67.81, Cohen's D = 0.31). The proportion of individuals with irregular cycles was highest in participants aged 51-55 (44.7%), and lowest in the 36-40 age group (28.3%). The spectrum of common menstrual cycle-related symptoms also varies with age. The frequency of logging of cramps and acne is lower in older participants, while logs of headache, backache, stress, and insomnia are higher in older users. Other symptoms show different patterns, such as breast tenderness and fatigue peaking between the ages of 20-40, or mood swings being most frequently logged in the youngest and oldest users. The menstrual cycle and related symptoms are not static throughout the lifespan. Understanding these age-related differences in cycle characteristics and symptoms is essential in understanding how best to care for and improve the daily experience for menstruators across the reproductive life span.

Prevalence, Incidence, and Reversal Pattern of Childhood Stunting From Birth to Age 2 Years in Ethiopia.

Importance: Although there has been a reduction in stunting (low-height-for-age and low-length-for-age), a proxy of malnutrition, the prevalence of malnutrition in Ethiopia is still high. Child growth patterns and estimates of stunting are needed to increase awareness and resources to improve the potential for recovery. Objective: To estimate the prevalence, incidence, and reversal of stunting among children aged 0 to 24 months. Design, Setting, and Participants: This population-based cohort study of the Birhan Maternal and Child Health cohort in North Shewa Zone, Amhara, Ethiopia, was conducted between December 2018 and November 2020. Eligible participants included children aged 0 to 24 months who were enrolled during the study period and had their length measured at least once. Data analysis occurred from Month Year to Month Year. Main Outcomes and Measures: The primary outcome of this study was stunting, defined as length-for-age z score (LAZ) at least 2 SDs below the mean. Z scores were also used to determine the prevalence, incidence, and reversal of stunting at each key time point. Growth velocity was determined in centimeters per month between key time points and compared with global World Health Organization (WHO) standards for the same time periods. Heterogeneity was addressed by excluding outliers in sensitivity analyses using modeled growth trajectories for each child. Results: A total of 4354 children were enrolled, out of which 3674 (84.4%; 1786 [48.7%] female) had their length measured at least once and were included in this study. The median population-level length was consistently below WHO growth standards from birth to 2 years of age. The observed prevalence of stunting was highest by 2 years of age at 57.4% (95% CI, 54.8%-9 60.0%). Incidence of stunting increased over time and reached 51.0% (95% CI, 45.3%-56.6%) between ages 12 and 24 months. Reversal was 63.5% (95% CI, 54.8%-71.4%) by age 6 months and 45.2% (95% CI, 36.0%-54.8%) by age 2 years. Growth velocity point estimate differences were slowest compared with WHO standards during the neonatal period (-1.4 cm/month for girls and -1.6 cm/month for boys). There was substantial heterogeneity in anthropometric measurements. Conclusions and Relevance: The evidence from this cohort study highlights a chronically malnourished population with much of the burden associated with growth faltering during the neonatal periods as well as after 6 months of age. To end all forms of malnutrition, growth faltering in populations such as that in young children in Amhara, Ethiopia, needs to be addressed.

Antenatal care coverage in a low-resource setting: Estimations from the Birhan Cohort.

Antenatal care (ANC) coverage estimates commonly rely on self-reported data, which may carry biases. Leveraging prospectively collected longitudinal data from the Birhan field site and its pregnancy and birth cohort, the Birhan Cohort, this study aimed to estimate the coverage of ANC, minimizing assumptions and biases due to self-reported information and describing retention patterns in ANC in rural Amhara, Ethiopia. The study population were women enrolled and followed during pregnancy between December 2018 and April 2020. ANC visits were measured by prospective facility chart abstraction and self-report at enrollment. The primary study outcomes were the total number of ANC visits attended during pregnancy and the coverage of at least one, four, or eight ANC visits. Additionally, we estimated ANC retention patterns. We included 2069 women, of which 150 (7.2%) women enrolled <13 weeks of gestation with complete prospective facility reporting. Among these 150 women, ANC coverage of at least one visit was 97.3%, whereas coverage of four visits or more was 34.0%. Among all women, coverage of one ANC visit was 92.3%, while coverage of four or more visits was 28.8%. No women were found to have attended eight or more ANC visits. On retention in care, 70.3% of participants who had an ANC visit between weeks 28 and <36 of gestation did not return for a subsequent visit. Despite the high proportion of pregnant women who accessed ANC at least once in our study area, the coverage of four visits remains low. Further efforts are needed to enhance access to more ANC visits, retain women in care, and adhere to the most recent Ethiopian National ANC guideline of at least eight ANC visits. It is essential to identify the factors that lead a large proportion of women to discontinue ANC follow-up.

Development of Prediction Models for Antenatal Care Attendance in Amhara Region, Ethiopia.

Importance: Antenatal care prevents maternal and neonatal deaths and improves birth outcomes. There is a lack of predictive models to identify pregnant women who are at high risk of failing to attend antenatal care in low-resource settings. Objective: To develop a series of predictive models to identify women who are at high risk of failing to attend antenatal care in a rural setting in Ethiopia. Design, Setting, and Participants: This prognostic study used data from the Birhan Health and Demographic Surveillance System and its associated pregnancy and child cohort. The study was conducted at the Birhan field site, North Shewa zone, Ethiopia, a platform for community- and facility-based research and training, with a focus on maternal and child health. Participants included women enrolled during pregnancy in the pregnancy and child cohort between December 2018 and March 2020, who were followed-up in home and facility visits. Data were analyzed from April to December 2022. Exposures: A wide range of sociodemographic, economic, medical, environmental, and pregnancy-related factors were considered as potential predictors. The selection of potential predictors was guided by literature review and expert knowledge. Main Outcomes and Measures: The outcome of interest was failing to attend at least 1 antenatal care visit during pregnancy. Prediction models were developed using logistic regression with regularization via the least absolute shrinkage and selection operator and ensemble decision trees and assessed using the area under the receiving operator characteristic curve (AUC). Results: The study sample included 2195 participants (mean [SD] age, 26.8 [6.1] years; mean [SD] gestational age at enrolment, 25.5 [8.8] weeks). A total of 582 women (26.5%) failed to attend antenatal care during cohort follow-up. The AUC was 0.61 (95% CI, 0.58-0.64) for the regularized logistic regression model at conception, with higher values for models predicting at weeks 13 (AUC, 0.68; 95% CI, 0.66-0.71) and 24 (AUC, 0.66; 95% CI, 0.64-0.69). AUC values were similar with slightly higher performance for the ensembles of decision trees (conception: AUC, 0.62; 95% CI, 0.59-0.65; 13 weeks: AUC, 0.70; 95% CI, 0.67-0.72; 24 weeks: AUC, 0.67; 95% CI, 0.64-0.69). Conclusions and Relevance: This prognostic study presents a series of prediction models for antenatal care attendance with modest performance. The developed models may be useful to identify women at high risk of missing their antenatal care visits to target interventions to improve attendance rates. This study opens the possibility to develop and validate easy-to-use tools to project health-related behaviors in settings with scarce resources.

Estimates of Stillbirths, Neonatal Mortality, and Medically Vulnerable Live Births in Amhara, Ethiopia.

Importance: Data on birth outcomes and early mortality are scarce, especially in settings with limited resources. Total births, both stillbirths and live births, are often not counted, yet such data are critical to allocate resources and target interventions to improve survival. Objective: To estimate the prevalence of stillbirths, neonatal deaths, and medically vulnerable phenotypes, such as preterm births, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and low-birth-weight (LBW) births, in a setting where these key indicators remain largely unknown. Design, Setting, and Participants: This prospective pregnancy cohort study of women and their newborns was conducted between December 12, 2018, and November 5, 2020. The study was conducted in North Shewa Zone, Amhara, Ethiopia. Data were analyzed from July 2021 to May 2022. Main Outcomes and Measures: Pregnancy status, gestational age, birth weight, and vital status were measured to estimate the prevalence of stillbirths, live births, and medically vulnerable live births (ie, preterm, SGA, LGA, and LBW births). For mortality outcomes, the prevalence of neonatal (overall, early, and late) and perinatal mortality were estimated. Results: Among the 2801 enrolled women, the median (IQR) age at conception was 26.5 (22.2-31.0) years, and the median (IQR) gestational age at enrollment was 24 (17-31) weeks. Of the 2628 women (93.8%) with outcome data, 101 pregnancies (3.8%) resulted in an early loss (<28 gestational weeks). Among the 2527 remaining pregnant women, there were 2518 births between 28 and less than 46 weeks' gestation; 2459 (97.7%; 95% CI, 97.0%-98.2%) were live births and 59 (2.3%; 95% CI, 1.8%-3.0%) were stillbirths. Many newborns (41.7%) were born preterm, SGA, LGA, or LBW. The estimated prevalence was 15.1% (95% CI, 13.7%-16.6%) for preterm births, 23.1% (95% CI, 21.3%-25.1%) for SGA births, 10.6% (95% CI, 9.3%-12.1%) for LGA births, and 9.4% (95% CI, 8.2%-10.8%) for LBW births. Among live births, the overall prevalence of neonatal mortality was 3.1% (95% CI, 2.5%-3.9%); mortality was higher among preterm births (7.2%; 95% CI, 4.9%-10.4%), LBW births (12.2%; 95% CI, 8.2%-17.7%), and SGA births (4.1%; 95% CI, 2.6%-6.5%). The prevalence of early neonatal mortality was almost twice as high as the prevalence of late neonatal mortality. The perinatal mortality prevalence was 4.3% (95% CI, 3.6%-5.2%), with a 1.2:1 ratio of stillbirths to first-week deaths. Conclusions and Relevance: These findings have important implications for newborn health and survival. For policy makers and programmers, accurate data on key indicators of neonatal health provide information for resource allocation and to evaluate progress. For researchers, the findings underlie the importance for further research to develop and deliver interventions that improve health outcomes.

Birhan maternal and child health cohort: a study protocol.

INTRODUCTION: Reliable estimates on maternal and child morbidity and mortality are essential for health programmes and policies. Data are needed in populations, which have the highest burden of disease but also have the least evidence and research, to design and evaluate health interventions to prevent illnesses and deaths that occur worldwide each year. METHODS AND ANALYSIS: The Birhan Maternal and Child Health cohort is an open prospective pregnancy and birth cohort nested within the Birhan Health and Demographic Surveillance System. An estimated 2500 pregnant women are enrolled each year and followed through pregnancy, birth and the postpartum period. Newborns are followed through 2 years of life to assess growth and development. Baseline medical data, signs and symptoms, laboratory test results, anthropometrics and pregnancy and birth outcomes (stillbirth, preterm birth, low birth weight) are collected from both home and health facility visits. We will calculate the period prevalence and incidence of primary morbidity and mortality outcomes. ETHICS AND DISSEMINATION: The cohort has received ethical approval. Findings will be disseminated at scientific conferences, peer-reviewed journals and to relevant stakeholders including the Ministry of Health.

Effective Demand for In-Line Chlorination Bundled with Rental Housing in Dhaka, Bangladesh.

Delivering safe water in cities of lower- and middle-income countries remains elusive even where there is a piped supply. Passive, in-line chlorination upstream of the point of water collection reduces child diarrhea without the behavior change required for point-of-use water treatment products or manual chlorine dispensers. We conducted a price experiment to measure effective demand (willingness and ability to pay) for an in-line chlorination service using tablet chlorinators among 196 landlords of rental housing properties in Dhaka, Bangladesh. We offered a 12-month subscription using Becker-DeGroot-Marschak auctions with real money payments. The service consistently delivered chlorinated water and satisfied tenants. Landlords' effective demand for in-line chlorination was similar to or greater than that for point-of-use treatment products and manual chlorine dispensers previously documented among Dhaka households. Over the service period, landlords renting to low-income households had lower effective demand than those renting to middle-income households despite similar initial rates of payment across both groups. Making in-line chlorination financially viable for the lowest-income consumers would likely require service cost reductions, subsidies, or both. Our findings suggest that even revealed preference experiments may overestimate the effective demand needed to sustain water supply improvements, especially in low-income populations, if they only measure demand once.

Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis.

INTRODUCTION: Newborn sepsis accounts for more than a third of neonatal deaths globally and one in five neonatal deaths in Ethiopia. The first-line treatment recommended by WHO is the combination of gentamicin with ampicillin or benzylpenicillin. Gram-negative bacteria (GNB) are increasingly resistant to previously effective antibiotics. OBJECTIVES: Our goal was to estimate the prevalence of antibiotic-resistant gram-negative bacteremia and identify risk factors for antibiotic resistance, among newborns with GNB sepsis. METHODS: At a tertiary hospital in Ethiopia, we enrolled a cohort pregnant women and their newborns, between March and December 2017. Newborns who were followed up until 60 days of life for clinical signs of sepsis. Among the newborns with clinical signs of sepsis, blood samples were cultured; bacterial species were identified and tested for antibiotic susceptibility. We described the prevalence of antibiotic resistance, identified newborn, maternal, and environmental factors associated with multidrug resistance (MDR), and combined resistance to ampicillin and gentamicin (AmpGen), using multivariable regression. RESULTS: Of the 119 newborns with gram-negative bacteremia, 80 (67%) were born preterm and 82 (70%) had early-onset sepsis. The most prevalent gram-negative species were Klebsiella pneumoniae 94 (79%) followed by Escherichia coli 10 (8%). Ampicillin resistance was found in 113 cases (95%), cefotaxime 104 (87%), gentamicin 101 (85%), AmpGen 101 (85%), piperacillin-tazobactam 47 (39%), amikacin 10 (8.4%), and Imipenem 1 (0.8%). Prevalence of MDR was 88% (n = 105). Low birthweight and late-onset sepsis (LOS) were associated with higher risks of AmpGen-resistant infections. All-cause mortality was higher among newborns treated with ineffective antibiotics. CONCLUSION: There was significant resistance to current first-line antibiotics and cephalosporins. Additional data are needed from primary care and community settings. Amikacin and piperacillin-tazobactam had lower rates of resistance; however, context-specific assessments of their potential adverse effects, their local availability, and cost-effectiveness would be necessary before selecting a new first-line regimen to help guide clinical decision-making.

Faecal contamination of the environment and child health: a systematic review and individual participant data meta-analysis.

BACKGROUND: Exposure to faecal contamination is believed to be associated with child diarrhoea and possibly stunting; however, few studies have explicitly measured the association between faecal contamination and health. We aimed to assess individual participant data (IPD) across multiple trials and observational studies to quantify the relationship for common faecal-oral transmission pathways. METHODS: We did a systematic review and meta-analysis of IPD from studies identified in an electronic search of PubMed, Web of Science, and Embase on May 21, 2018. The search was done in English, but full texts published in French, Portuguese, and Spanish were also reviewed. Eligible studies quantified (1) household-level faecal indicator bacteria concentrations along common faecal-oral transmission pathways of drinking water, soil, or food, on children's hands or fomites, or fly densities in food preparation areas; and (2) individual-level diarrhoea or linear growth measures for children younger than 5 years in low-income and middle-income countries. For the diarrhoea analysis, all definitions of diarrhoea were eligible but studies were excluded if they used a recall period longer than 7 days. For the linear growth analysis (using height-for-age Z scores [HAZ]), cross-sectional studies were excluded, because of the absence of longitudinal environmental contamination data measured before the growth outcomes. We used multilevel generalised mixed-effects models to estimate the odds ratio (OR) for diarrhoea and the difference in HAZ scores for individual studies associated with a 1-log10 higher measure of faecal contamination. Estimates from each study were combined under a random-effects meta-analysis framework. The study protocol was pre-registered with PROSPERO (CRD42018102114). FINDINGS: From 72 eligible studies, we included IPD for 20 studies in the meta-analyses, totalling 54 225 diarrhoea or linear growth observations matched to faecal indicator bacteria concentrations in drinking water, and a further 35 010 observations with faecal contamination data for the other transmission pathways. Child diarrhoea was associated with 1-log10 higher faecal indicator bacteria concentrations in drinking water (OR 1·09, 95% CI 1·04 to 1·13; p=0·0002, I2=34%, 95% CI 0 to 62) and on children's hands (1·11, 1·02 to 1·22; p=0·021, I2=0%, 0 to 71). Lower HAZ scores were associated with 1-log10 higher median faecal indicator bacteria concentrations in drinking water (HAZ -0·04, 95% CI -0·06 to -0·01; p=0·0054; I2=19%, 95% CI 0 to 63) and on fomites (-0·06, -0·12 to 0·00; p=0·044, I2=57%, 0 to 90). INTERPRETATION: Although summary measures from individual studies often report little or no effect of measured faecal contamination on child health, this multi-study IPD analysis indicates that household faecal indicator bacteria concentrations are associated with important adverse health outcomes in young children. Improved direct measures of exposure and enteric pathogens could help to better characterise the relationship and inform intervention design in future studies. FUNDING: None.

Measuring Environmental Exposure to Enteric Pathogens in Low-Income Settings: Review and Recommendations of an Interdisciplinary Working Group.

Infections with enteric pathogens impose a heavy disease burden, especially among young children in low-income countries. Recent findings from randomized controlled trials of water, sanitation, and hygiene interventions have raised questions about current methods for assessing environmental exposure to enteric pathogens. Approaches for estimating sources and doses of exposure suffer from a number of shortcomings, including reliance on imperfect indicators of fecal contamination instead of actual pathogens and estimating exposure indirectly from imprecise measurements of pathogens in the environment and human interaction therewith. These shortcomings limit the potential for effective surveillance of exposures, identification of important sources and modes of transmission, and evaluation of the effectiveness of interventions. In this review, we summarize current and emerging approaches used to characterize enteric pathogen hazards in different environmental media as well as human interaction with those media (external measures of exposure), and review methods that measure human infection with enteric pathogens as a proxy for past exposure (internal measures of exposure). We draw from lessons learned in other areas of environmental health to highlight how external and internal measures of exposure can be used to more comprehensively assess exposure. We conclude by recommending strategies for advancing enteric pathogen exposure assessments.

Child Salivary SIgA and Its Relationship to Enteric Infections and EED Biomarkers in Maputo, Mozambique.

Characterizing child immunological responses to enteric infections with antibody detection in serum can be challenging in resource-constrained field settings, because sample collection requires trained individuals and its invasive procedure may lead to low response rates, especially among children. Saliva may present a promising non-invasive alternative. The objectives of this research were to compare salivary antibody levels in children to enteric infections and biomarkers of environmental enteric dysfunction (EED). We collected saliva samples from children aged one to six years enrolled in a sanitation trial in Maputo, Mozambique, and characterized salivary secretory immunoglobulin A (SIgA) concentrations with enzyme-linked immunosorbent assays. We used multilevel linear models to analyze cross-sectional associations between salivary SIgA and the number of concurrent enteric pathogen infections, as well as EED biomarkers in matched stool samples. Median salivary SIgA concentrations in this study population were 54 µg/mL (inter-quartile range (IQR): 34, 85 µg/mL), and SIgA levels were similar between children of different ages. SIgA was lower in children experiencing a higher number of concurrent infections -0.04 log µg/mL (95% confidence interval (CI): -0.08 to -0.005 log µg/mL), but was not associated with any of the included EED biomarkers. Contrary to evidence from high-income countries that suggests salivary SIgA increases rapidly with age in young children, the high prevalence of enteric infections may have led to a suppression of immunological development in this study sample and could in part explain the similar SIgA levels between children of different ages.

Quantifying user preferences for sanitation construction and use: Application of discrete choice experiments in Amhara, Ethiopia.

OBJECTIVE: To quantify stated preferences for latrine use and construction in Amhara, Ethiopia, using Discrete Choice Experiments (DCEs). METHODS: We conducted image-based DCEs to assess preferences for latrine use (stratified by gender) and construction (among men only) in Amhara, Ethiopia. Preference was quantified using a conditional logistic model to estimate utilities and corresponding odds ratios associated with a set of latrine attributes. RESULTS: For latrine use, tin roof, handwashing stations and clean latrines had the highest relative utility coefficients. Tin roof was preferred to no roof for use (Women: OR: 3.68, 95% CI: 3.18-4.25; Men: OR: 3.75, 95% CI: 3.21-4.39) and new latrine construction (5.92, 5.04-6.95). Concrete slabs, a critical aspect of improved sanitation, was not preferred to dirt floors for use (Women: 0.87, 0.75-1.00; Men: 1.03, 0.88-1.20), but was preferred for new construction (1.52, 1.30-1.78). We did not observe any trends in preference for direct (monetary) or indirect cost (labour days), so we were not able to elicit trade-offs between latrine attributes and these costs for the construction of new latrines. CONCLUSION: Our findings suggest similar latrine use preferences between men and women. We found that tin roofs are the most strongly preferred latrine characteristic, but concrete slabs, commonly promoted in sanitation programmes, were not preferred for use. We demonstrate the utility of DCEs to elicit stated preferences for latrine use and construction among community members who have myriad motivations for using and making improvements to their sanitation facilities, including the ease of cleaning and hygiene, durability, or privacy and comfort.