Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) - a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health.

PURPOSE: Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health. PARTICIPANTS: Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at <15 weeks of gestation from Boston, Massachusetts area hospitals. Participants completed ≤4 prenatal study visits (median: 12, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks), during which we collected biospecimens, health histories, demographic and behavioural data, and vitals and anthropometric measurements. Participants completed a postpartum fasting 2-hour 75 g oral glucose tolerance test. Clinical data were abstracted from electronic medical records. Ongoing (as of 2024) extended post-pregnancy follow-up visits occur annually following similar data collection protocols. FINDINGS TO DATE: We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight. FUTURE PLANS: Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study.

Indoor Temperature and Energy Insecurity: Implications for Prenatal Health Disparities in Extreme Heat Events.

BACKGROUND: Extreme heat events are a major public health concern and are only expected to increase in intensity and severity as climate change continues to accelerate. Pregnant people are physiologically more vulnerable to the effects of extreme heat, and exposure can induce harm on both the pregnant person and the fetus. OBJECTIVES: This commentary argues that there is a need for greater epidemiological research on indoor heat exposure and energy insecurity as potential drivers of maternal and child environmental health disparities. DISCUSSION: While there is substantial evidence linking ambient (outdoor) high temperature to pregnancy-related outcomes, there is a lack of epidemiological evidence to date on pregnant people's exposure to high indoor temperature and adverse maternal and/or child health outcomes. Energy insecurity is disproportionately experienced by people with low incomes and/or people of color, and indoor temperature may play a role in shaping socioeconomic and racial/ethnic disparities in maternal and child health in the United States. Further research is needed to understand the relationship between indoor heat exposure, energy insecurity, and pregnancy outcomes in both parents and children and to inform potential policies and practices to enhance resilience and reduce maternal/child health disparities. https://doi.org/10.1289/EHP13706.

Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: An ecological study.

OBJECTIVE: To investigate associations between air particulate matter of ≤2.5 µm in diameter (PM2.5 ) and ovarian cancer. DESIGN: County-level ecological study. SETTING: Surveillance, epidemiology, and end results from a collection of state-level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5- and 10-year PM2.5 county-level values. County-level data on demographic characteristics were obtained from the American Community Survey. POPULATION: A total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016. METHODS: Generalised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5- and 10-year periods of exposure, and ovarian cancer risk, after accounting for county-level covariates. MAIN OUTCOME MEASURES: Risk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels. RESULTS: For the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 µg/m3 (SD = 3.7) and the average PM10 level was 22.7 µg/m3 (SD = 5.7). After adjusting for county-level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5-year PM2.5 (RR = 1.11 per 10 units (µg/m3 ) increase, 95% CI 1.06-1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county-level covariates there was a significant association with trailing 5-year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08-1.17). Likewise, 10-year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer. CONCLUSIONS: Higher county-level ambient PM2.5 levels are associated with 5- and 10-year incidences of ovarian cancer, as measurable in an ecological study.

Predictors of Phthalate Metabolites Exposure among Healthy Pregnant Women in the United States, 2010-2015.

Phthalate use and the concentrations of their metabolites in humans vary by geographic region, race, ethnicity, sex, product use and other factors. Exposure during pregnancy may be associated with detrimental reproductive and developmental outcomes. No studies have evaluated the predictors of exposure to a wide range of phthalate metabolites in a large, diverse population. We examined the determinants of phthalate metabolites in a cohort of racially/ethnically diverse nulliparous pregnant women. We report on urinary metabolites of nine parent phthalates or replacement compounds-Butyl benzyl phthalate (BBzP), Diisobutyl phthalate (DiBP), Diethyl phthalate (DEP), Diisononyl phthalate (DiNP), D-n-octyl phthalate (DnOP), Di-2-ethylhexyl terephthalate (DEHTP), Di-n/i-butyl phthalate (DnBP), Di-isononyl phthalate (DiNP) and Di-(2-ethylhexyl) phthalate (DEHP) from urine collected up to three times from 953 women enrolled in the Nulliparous Mothers To Be Study. Phthalate metabolites were adjusted for specific gravity. Generalized estimating equations (GEEs) were used to identify the predictors of each metabolite. Overall predictors include age, race and ethnicity, education, BMI and clinical site of care. Women who were Non-Hispanic Black, Hispanic or Asian, obese or had lower levels of education had higher concentrations of selected metabolites. These findings indicate exposure patterns that require policies to reduce exposure in specific subgroups.

Vector-borne disease, climate change and perinatal health.

Vector-borne diseases (VBDs) are caused by infectious pathogens that spread from an infected human or animal reservoir to an uninfected human via a vector (mosquito, tick, rodent, others) and remain an important cause of morbidity and mortality worldwide. Pregnant individuals and their fetuses are especially at risk, as certain pathogens, such as Zika virus, have specific implications in pregnancy and for neonatal health. Global climate change is affecting the incidence and geographic spread of many VBDs. Thus, it is important for clinicians in the fields of obstetrics/gynecology and newborn medicine, regardless of geographic location, to familiarize themselves with a basic understanding of these conditions and how climate change is altering their distributions. In this chapter, we review the incidence, clinical presentation, implications during pregnancy and intersection with climate change for four of the most important VBDs in pregnancy: malaria, Zika, dengue and Chagas disease. Although not exhaustive of all VBDs, a more extensive table is included for reference, and our discussion provides a helpful framework for understanding other vector-borne pathogens and perinatal health.

Associations between ambient temperature and pregnancy outcomes from three south Asian sites of the Global Network Maternal Newborn Health Registry: A retrospective cohort study.

OBJECTIVE: Growing evidence suggests that environmental heat stress negatively influences fetal growth and pregnancy outcomes. However, few studies have examined the impact of heat stress on pregnancy outcomes in low-resource settings. We combined data from a large multi-country maternal-child health registry and meteorological data to assess the impacts of heat stress. DESIGN: Retrospective cohort study. SETTING: Three sites based in south Asia as part of the Global Network for Women's and Children's Health research in India (Belagavi and Nagpur) and Pakistan (Thatta). POPULATION OR SAMPLE: Data from women enrolled between 2014 and 2020 in the Global Network's Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnancies, were used. METHODS: A total of 126 273 pregnant women were included in this analysis. Daily maximal air temperatures (Tmax ) were acquired from local meteorological records. Associations between averages of daily maximal temperatures for each trimester and main outcomes were analysed using a modified Poisson regression approach. MAIN OUTCOMES MEASURES: Incidence of stillbirth, preterm birth, low birthweight (<2500 g) or evidence of pregnancy hypertension or pre-eclampsia. RESULTS: In the overall cohort, risk of preterm birth was positively associated with greater temperature in the second trimester (relative risk [RR] 1.05, 95% CI 1.02-1.07, p = 0.0002). Among individual sites, the risk of preterm birth was greatest in Nagpur (RR 1.07, 95% CI 1.03-1.11, p = 0.0005) and associated with second-trimester temperature. The overall risk of low birthweight was associated with ambient temperature in second trimester (RR 1.02, 95% CI 1.01-1.04, p = 0.01). The risk for LBW was associated with first-trimester heat in Thatta and with second-trimester heat in Nagpur. Finally, the overall risk of gestational hypertensive disease was associated with greater temperature in the third trimester among all sites (RR 1.07, 95% CI 1.02-1.12, p = 0.005) and was particularly significant for Nagpur (RR 1.13, 95% CI 1.05-1.23, p = 0.002). These findings highlight the increased risk of detrimental obstetric and neonatal outcomes with greater temperature. CONCLUSION: In a multi-country, community-based study, greater risk of adverse outcomes was observed with increasing temperature. The study highlights the need for deeper understanding of covarying factors and intervention strategies, especially in regions where high temperatures are common.

Identifying sensitive windows of prenatal household air pollution on birth weight and infant pneumonia risk to inform future interventions.

BACKGROUND: Prenatal household air pollution impairs birth weight and increases pneumonia risk however time-varying associations have not been elucidated and may have implications for the timing of public health interventions. METHODS: The Ghana Randomized Air Pollution and Health Study (GRAPHS) enrolled 1,414 pregnant women from Kintampo, Ghana and measured personal carbon monoxide (CO) exposure four times over pregnancy. Birth weight was measured within 72-hours of birth. Fieldworkers performed weekly pneumonia surveillance and referred sick children to study physicians. The primary pneumonia outcome was one or more physician-diagnosed severe pneumonia episode in the first year of life. We employed reverse distributed lag models to examine time-varying associations between prenatal CO exposure and birth weight and infant pneumonia risk. RESULTS: Analyses included n = 1,196 mother-infant pairs. In models adjusting for child sex; maternal age, body mass index (BMI), ethnicity and parity at enrollment; household wealth index; number of antenatal visits; and evidence of placental malaria, prenatal CO exposures from 15 to 20 weeks gestation were inversely associated with birth weight. Sex-stratified models identified a similar sensitive window in males and a window at 10-weeks gestation in females. In models adjusting for child sex, maternal age, BMI and ethnicity, household wealth index, gestational age at delivery and average postnatal child CO exposure, CO exposure during 34-39 weeks gestation were positively associated with severe pneumonia risk, especially in females. CONCLUSIONS: Household air pollution exposures in mid- and late- gestation are associated with lower birth weight and higher pneumonia risk, respectively. These findings support the urgent need for deployment of clean fuel stove interventions beginning in early pregnancy.

Use of personal care products during pregnancy and birth outcomes - A pilot study.

Prenatal exposure to endocrine disrupting chemicals (EDCs) from personal care products may be associated with birth outcomes including preterm birth and low birth weight. There is limited research examining the role of personal care product use during pregnancy on birth outcomes. Our pilot study consisted of 164 participants in the Environmental Reproductive and Glucose Outcomes (ERGO) study (Boston, MA), with data on self-reported personal care product use at four study visits throughout pregnancy (product use in the 48 h before a study visit and hair product use in the month before a study visit). We used covariate-adjusted linear regression models to estimate differences in mean gestational age at delivery, birth length, and sex-specific birth weight-for-gestational age (BW-for-GA) Z-score based on personal care product use. Hair product use in the past month prior to certain study visits was associated with decreased mean sex-specific BW-for-GA Z-scores. Notably, hair oil use in the month prior to study visit 1 was associated with a lower mean BW-for-GA Z-score (V1: -0.71, 95% confidence interval: -1.12, -0.29) compared to non-use. Across all study visits (V1-V4), increased mean birth length was observed among nail polish users vs. non-users. In comparison, decreased mean birth length was observed among shave cream users vs. non-users. Liquid soap, shampoo, and conditioner use at certain study visits were significantly associated with higher mean birth length. Suggestive associations were observed across study visits for other products including hair gel/spray with BW-for-GA Z-score and liquid/bar soap with gestational age. Overall, use of a variety of personal care products throughout pregnancy was observed to be associated with our birth outcomes of interest, notably hair oil use during early pregnancy. These findings may help inform future interventions/clinical recommendations to reduce exposures linked to adverse pregnancy outcomes.

Persistent hypertension at 3 months postpartum among women with hypertensive disorders of pregnancy at a tertiary hospital in Southwestern Uganda.

BACKGROUND: Hypertension is a key contributor to the global epidemic of cardiovascular disease and is responsible for more deaths worldwide than any other cardiovascular risk factor. Hypertensive disorders of pregnancy, of which preeclampsia and eclampsia are the most common forms, have been shown to be a female-specific risk factor for chronic hypertension. OBJECTIVE: This study aimed to determine the proportion and risk factors for persistent hypertension at 3 months after delivery among women with hypertensive disorders of pregnancy in Southwestern Uganda. STUDY DESIGN: This was a prospective cohort study of pregnant women with hypertensive disorders of pregnancy admitted for delivery at Mbarara Regional Referral Hospital in Southwestern Uganda from January 2019 to December 2019; however, women with chronic hypertension were excluded from the study. The participants were followed up for 3 months after delivery. Participants with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg or receiving antihypertension therapy at 3 months after delivery were considered to have persistent hypertension. Multivariable logistic regression was used to determine independent risk factors associated with persistent hypertension. RESULTS: A total of 111 participants with hypertensive disorders of pregnancy diagnosed at hospital admission were enrolled with a follow-up rate of 49% (54/111) at 3 months after delivery. Of these women, 21 of 54 (39%) had persistent hypertension 3 months after delivery. In the adjusted analyses, an elevated serum creatinine level (>106.08 µmol/L [≤1.2 mg/dL]) at admission for delivery was the only independent risk factor for persistent hypertension at 3 months after delivery (adjusted relative risk, 1.93; 95% confidence interval, 1.08-3.46; P=.03), controlling for age, gravidity, and eclampsia. CONCLUSION: Approximately 4 of 10 women presenting with hypertensive disorders of pregnancy at our institution remained hypertensive 3 months after delivery. Innovative strategies are needed to identify these women and provide long-term care to optimize blood pressure control and reduce future cardiovascular disease after hypertensive disorders of pregnancy.

Traffic-Related Air Pollution and Ultrasound Parameters of Fetal Growth in Eastern Massachusetts.

Previous studies have examined the association between prenatal nitrogen dioxide (NO2)-a traffic emissions tracer-and fetal growth based on ultrasound measures. Yet, most have used exposure assessment methods with low temporal resolution, which limits the identification of critical exposure windows given that pregnancy is relatively short. Here, we used NO2 data from an ensemble model linked to residential addresses at birth to fit distributed lag models that estimated the association between NO2 exposure (resolved weekly) and ultrasound biometric parameters in a Massachusetts-based cohort of 9,446 singleton births from 2011-2016. Ultrasound biometric parameters examined included biparietal diameter (BPD), head circumference, femur length, and abdominal circumference. All models adjusted for sociodemographic characteristics, time trends, and temperature. We found that higher NO2 was negatively associated with all ultrasound parameters. The critical window differed depending on the parameter and when it was assessed. For example, for BPD measured after week 31, the critical exposure window appeared to be weeks 15-25; 10-parts-per-billion higher NO2 sustained from conception to the time of measurement was associated with a lower mean z score of -0.11 (95% CI: -0.17, -0.05). Our findings indicate that reducing traffic emissions is one potential avenue to improving fetal and offspring health.

Association between malaria and household air pollution interventions in a predominantly rural area of Ghana.

BACKGROUND: Though anecdotal evidence suggests that smoke from HAP has a repellent effect on mosquitoes, very little work has been done to assess the effect of biomass smoke on malaria infection. The study, therefore, sought to investigate the hypothesis that interventions to reduce household biomass smoke may have an unintended consequence of increasing placental malaria or increase malaria infection in the first year of life. METHODS: This provides evidence from a randomized controlled trial among 1414 maternal-infant pairs in the Kintampo North and Kintampo South administrative areas of Ghana. Logistic regression was used to assess the association between study intervention assignment (LPG, Biolite or control) and placental malaria. Finally, an extended Cox model was used to assess the association between study interventions and all episodes of malaria parasitaemia in the first year of infant's life. RESULTS: The prevalence of placental malaria was 24.6%. Out of this, 20.8% were acute infections, 18.7% chronic infections and 60.5% past infections. The study found no statistical significant association between the study interventions and all types of placental malaria (OR = 0.88; 95% CI 0.59-1.30). Of the 1165 infants, 44.6% experienced at least one episode of malaria parasitaemia in the first year of life. The incidence of first and/or only episode of malaria parasitaemia was however found to be similar among the study arms. CONCLUSION: The findings suggest that cookstove interventions for pregnant women and infants, when combined with additional malaria prevention strategies, do not lead to an increased risk of malaria among pregnant women and infants.

Ambient temperature during pregnancy and fetal growth in Eastern Massachusetts, USA.

BACKGROUND: Left unabated, rising temperatures pose an escalating threat to human health. The potential effects of hot temperatures on fetal health have been under-explored. Here, we examined the association between prenatal ambient temperature exposure and fetal growth measures in a Massachusetts-based pregnancy cohort. METHODS: We used ultrasound measurements of biparietal diameter (BPD), head circumference (HC), femur length and abdominal circumference (AC), in addition to birthweight (BW), from 9446 births at Beth Israel Deaconess Medical Center from 2011 to 2016. Ultrasound scans were classified into three distinct gestational periods: 16-23 weeks, 24-31 weeks, 32+ weeks; and z-scores were created for each fetal growth measure using the INTERGROWTH-21st standards. We fitted distributed lag models to estimate the time-varying association between weekly temperature and fetal growth, adjusting for sociodemographic characteristics, seasonal and long-term trends, humidity and particulate matter (PM2.5). RESULTS: Higher ambient temperature was associated with smaller fetal growth measures. The critical window of exposure appeared to be Weeks 1-20 for ultrasound parameters, and high temperatures throughout pregnancy were important for BW. Associations were strongest for head parameters (BPD and HC) in early to mid-pregnancy, AC late in pregnancy and BW. For example, a 5ºC higher cumulative temperature exposure was associated with a lower mean AC z-score of -0.26 (95% CI: -0.48, -0.04) among 24-31-Week scans, and a lower mean BW z-score of -0.32 (95% CI: -0.51, -0.12). CONCLUSION: Higher temperatures were associated with impaired fetal growth. This has major health implications given that extreme temperatures are more common and escalating.

Racial and ethnic disparities in preterm birth: a mediation analysis incorporating mixtures of polybrominated diphenyl ethers.

Background: Racial and ethnic disparities persist in preterm birth (PTB) and gestational age (GA) at delivery in the United States. It remains unclear whether exposure to environmental chemicals contributes to these disparities. Objectives: We applied recent methodologies incorporating environmental mixtures as mediators in causal mediation analysis to examine whether racial and ethnic disparities in GA at delivery and PTB may be partially explained by exposures to polybrominated diphenyl ethers (PBDEs), a class of chemicals used as flame retardants in the United States. Methods: Data from a multiracial/ethnic US cohort of 2008 individuals with low-risk singleton pregnancies were utilized, with plasma PBDE concentrations measured during early pregnancy. We performed mediation analyses incorporating three forms of mediators: (1) reducing all PBDEs to a weighted index, (2) selecting a PBDE congener, or (3) including all congeners simultaneously as multiple mediators, to evaluate whether PBDEs may contribute to the racial and ethnic disparities in PTB and GA at delivery, adjusted for potential confounders. Results: Among the 2008 participants, 552 self-identified as non-Hispanic White, 504 self-identified as non-Hispanic Black, 568 self-identified as Hispanic, and 384 self-identified as Asian/Pacific Islander. The non-Hispanic Black individuals had the highest mean ∑PBDEs, the shortest mean GA at delivery, and the highest rate of PTB. Overall, the difference in GA at delivery comparing non-Hispanic Black to non-Hispanic White women was -0.30 (95% CI: -0.54, -0.05) weeks. This disparity reduced to -0.23 (95% CI: -0.49, 0.02) and -0.18 (95% CI: -0.46, 0.10) weeks if fixing everyone's weighted index of PBDEs to the median and the 25th percentile levels, respectively. The proportion of disparity mediated by the weighted index of PBDEs was 11.8%. No statistically significant mediation was found for PTB, other forms of mediator(s), or other racial and ethnic groups. Conclusion: PBDE mixtures may partially mediate the Black vs. White disparity in GA at delivery. While further validations are needed, lowering the PBDEs at the population level might help reduce this disparity.

Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study: protocol of a pragmatic clinical effectiveness study to improve birth outcomes in Ethiopia.

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.

Measurement of symphysis fundal height for gestational age estimation in low-to-middle-income countries: A systematic review and meta-analysis.

In low- and middle-income countries (LMIC), measurement of symphysis fundal height (SFH) is often the only available method of estimating gestational age (GA) in pregnancy. This systematic review aims to summarize methods of SFH measurement and assess the accuracy of SFH for the purpose of GA estimation. We searched PubMed, EMBASE, Cochrane, Web of Science, POPLINE, and WHO Global Health Libraries from January 1980 through November 2021. For SFH accuracy, we pooled the variance of the mean difference between GA confirmed by ultrasound versus SFH. Of 1,003 studies identified, 37 studies were included. Nineteen different SFH measurement techniques and 13 SFH-to-GA conversion methods were identified. In pooled analysis of five studies (n = 5838 pregnancies), 71% (95% CI: 66-77%) of pregnancies dated by SFH were within ±14 days of ultrasound confirmed dating. Using the 1 cm SFH = 1wk assumption, SFH underestimated GA compared with ultrasound-confirmed GA (mean bias: -14.0 days) with poor accuracy (95% limits of agreement [LOA]: ±42.8 days; n = 3 studies, 2447 pregnancies). Statistical modeling of three serial SFH measurements performed better, but accuracy was still poor (95% LOA ±33 days; n = 4 studies, 4391 pregnancies). In conclusion, there is wide variation in SFH measurement and SFH-to-GA conversion techniques. SFH is inaccurate for estimating GA and should not be used for GA dating. Increasing access to quality ultrasonography early in pregnancy should be prioritized to improve gestational age assessment in LMIC.