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).

Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing.

BACKGROUND: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform. OBJECTIVE: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features. STUDY DESIGN: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death). RESULTS: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values. CONCLUSION: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks.

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.

Polybrominated diphenyl ethers and gestational weight gain: a multi-center prospective cohort study.

OBJECTIVE: To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG). DESIGN: Prospective cohort study. SETTING: US-based, multicentre cohort of pregnant women. POPULATION: We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies - Singleton Cohort, with first-trimester plasma PBDE concentrations and weight measurements throughout pregnancy. METHODS: We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders. MAIN OUTCOME MEASURES: Total GWG (kg), total and trimester-specific GWG velocities (kg/week), and GWG categories and trajectory groups. RESULTS: Mean pre-pregnancy BMIs were 23.6 and 34.5 kg/m2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log-transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39-3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01-0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group. CONCLUSIONS: PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms.

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.

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.

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.

Risk-Factor Based Lead Screening and Correlation with Blood Lead Levels in Pregnancy.

OBJECTIVES: Lead exposure has devastating neurologic consequences for children and may begin in utero. The American College of Obstetricians and Gynecologists recommends prenatal lead screening using a risk factor-based approach rather than universal blood testing. The clinical utility of this approach has not been studied. We evaluated a risk-factor based questionnaire to detect elevated blood lead levels in pregnancy. METHODS: We performed a secondary analysis of a cohort of parturients enrolled to evaluate the association of lead with hypertensive disorders of pregnancy. We included participants in this analysis if they had a singleton pregnancy ≥ 34 weeks' gestation with blood lead levels recorded. Participants completed a lead risk factor survey modified for pregnancy. We defined elevated blood lead as ≥ 2 µg/dL, as this was the clinically reportable level. RESULTS: Of 102 participants enrolled in the cohort, 92 had blood lead measured as part of the study. The vast majority (78%) had 1 or more risk factor for elevated lead using the questionnaire yet none had clinical blood lead testing during routine visits. Only two participants (2.2%) had elevated blood lead levels. The questionnaire had high sensitivity but poor specificity for predicting detectable lead levels (sensitivity 100%, specificity 22%). CONCLUSIONS FOR PRACTICE: Prenatal risk-factor based lead screening appears underutilized in practice and does not adequately discriminate between those with and without elevated blood levels. Given the complexity of the risk factor-based approach and underutilization, the benefit and cost-effectiveness of universal lead testing should be further explored.

Regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP).

OBJECTIVES: To describe regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP). METHODS: Retrospective cohort study of a large, US commercial managed care plan claims database with pharmacy coverage from 2008 to 2018. Singleton pregnancies with at least one prior spontaneous preterm birth (sPTB) were included. Regional and state-based differences in 17-OHP use were compared. Data were analyzed using t-tests and Fisher's exact tests. RESULTS: Of the 4,514 individuals with an indication for 17-OHP, 580 (12.8%) were prescribed 17-OHP. Regional and state-based differences in 17-OHP utilization were identified; Northeast 15.7%, Midwest 13.7%, South 12.0%, and West 10.4% (p=0.003). CONCLUSIONS: While significant regional differences in 17-OHP utilization were demonstrated, 17-OHP utilization remained low despite this cohort having insurance through a US commercial managed care plan. Suboptimal utilization demonstrates a disconnect between research and uptake in clinical practice. This underscores a need for implementation science in obstetrics to translate updated recommendations more effectively and efficiently into clinical practice.

Prolonged Second Stage of Labor and Anal Sphincter Injury in a Contemporary Cohort of Term Nulliparas.

OBJECTIVE: This study aimed to assess whether a prolonged second stage of labor is an independent predictor of obstetric anal sphincter injury (OASI) in a contemporary cohort of nulliparous and term parturients, and to evaluate whether predelivery factors can accurately predict OASI. STUDY DESIGN: This was a nested case-control study within a cohort of consecutive nulliparous term parturients with a singleton gestation who underwent a vaginal delivery at a single institution between January 2014 and January 2015. Cases were defined as women with a third- or fourth-degree laceration at the time of delivery, and controls were women without a third- or fourth-degree laceration. A prolonged second stage was defined as a second stage of ≥3 hours. Univariable and multivariable regression analyses were performed to examine the relationship between prolonged second stage of labor and third- or fourth-degree lacerations. Receiver operator curves were developed to assess the predictive capacity of predelivery information for third- and fourth-degree lacerations. RESULTS: Of 1,197 births, 63 women had third- or fourth-degree lacerations (5.3%). With each additional hour of the second stage, the rate of OASI increased, with 2.9% of women with a second stage of <1 hour with OASI, 3.5% between 1 and 2 hours, 5.7% between 2 and 3 hours, 7.8% between 3 and 4 hours, 16.1% between 4 and 5 hours, and 28.6% among women with a second stage length >5 hours (p < 0.001). In multivariable regression analysis, operative vaginal delivery (adjusted odds ratio [aOR] = 5.92, 95% confidence interval [CI]: 3.17-11.07) and a prolonged second stage (aOR = 1.92, 95% CI: 1.06-3.51) were independent predictors of third- and fourth-degree lacerations. A predictive model was developed from these results (area under the curve [AUC] = 0.75, 95% CI: 0.68-0.81). CONCLUSION: Prolonged second stage of labor is a predictor of OASI, after adjustment for operative vaginal delivery. A model using predelivery risk factors has a reasonable prediction of OASI. KEY POINTS: · Prolonged second stage labor is associated with obstetric anal sphincter injury in term nulliparas.. · Predelivery risk factors reasonably predict obstetric anal sphincter injury in term nulliparas.. · Improved models are needed for clinical risk-stratification..

Effect of birthweight measurement quality improvement on low birthweight prevalence in rural Ethiopia.

BACKGROUND: Low birthweight (LBW) (< 2500 g) is a significant determinant of infant morbidity and mortality worldwide. In low-income settings, the quality of birthweight data suffers from measurement and recording errors, inconsistent data reporting systems, and missing data from non-facility births. This paper describes birthweight data quality and the prevalence of LBW before and after implementation of a birthweight quality improvement (QI) initiative in Amhara region, Ethiopia. METHODS: A comparative pre-post study was performed in selected rural health facilities located in West Gojjam and South Gondar zones. At baseline, a retrospective review of delivery records from February to May 2018 was performed in 14 health centers to collect birthweight data. A birthweight QI initiative was introduced in August 2019, which included provision of high-quality digital infant weight scales (precision 5 g), routine calibration, training in birth weighing and data recording, and routine field supervision. After the QI implementation, birthweight data were prospectively collected from late August to early September 2019, and December 2019 to June 2020. Data quality, as measured by heaping (weights at exact multiples of 500 g) and rounding to the nearest 100 g, and the prevalence of LBW were calculated before and after QI implementation. RESULTS: We retrospectively reviewed 1383 delivery records before the QI implementation and prospectively measured 1371 newborn weights after QI implementation. Heaping was most frequently observed at 3000 g and declined from 26% pre-initiative to 6.7% post-initiative. Heaping at 2500 g decreased from 5.4% pre-QI to 2.2% post-QI. The percentage of rounding to the nearest 100 g was reduced from 100% pre-initiative to 36.5% post-initiative. Before the QI initiative, the prevalence of recognized LBW was 2.2% (95% confidence interval [CI]: 1.5-3.1) and after the QI initiative increased to 11.7% (95% CI: 10.1-13.5). CONCLUSIONS: A QI intervention can improve the quality of birthweight measurements, and data measurement quality may substantially affect estimates of LBW prevalence.

Endocrine disrupting chemical-associated hair product use during pregnancy and gestational age at delivery: a pilot study.

BACKGROUND: Prenatal endocrine disrupting chemical (EDC) exposure has been associated with increased risk of preterm birth. Non-Hispanic Black women have higher incidence of preterm birth compared to other racial/ethnic groups and may be disproportionately exposed to EDCs through EDC-containing hair products. However, research on the use of EDC-associated hair products during pregnancy and risk of preterm birth is lacking. Therefore, the objective of this pilot study was to estimate associations of prenatal hair product use with gestational age at delivery in a Boston, Massachusetts area pregnancy cohort. METHODS: The study population consisted of a subset of participants enrolled in the Environmental Reproductive and Glucose Outcomes (ERGO) Study between 2018 and 2020. We collected self-reported data on demographics and hair product use using a previously validated questionnaire at four prenatal visits (median: 12, 19, 26, 36 weeks' gestation) and abstracted gestational age at delivery from medical records. We compared gestational age and hair product use by race/ethnicity and used linear regression to estimate covariate-adjusted associations of product use and frequency of use at each study visit with gestational age at delivery. Primary models were adjusted for maternal age at enrollment and delivery method. RESULTS: Of the 154 study participants, 7% delivered preterm. Non-Hispanic Black participants had lower mean gestational age at delivery compared to non-Hispanic White participants (38.2 vs. 39.2 weeks) and were more likely to report ever and more frequent use of hair products. In regression models, participants reporting daily use of hair oils at visit 4 had lower mean gestational age at delivery compared to non-users (ß: -8.3 days; 95% confidence interval: -14.9, -1.6). We did not find evidence of associations at earlier visits or with other products. CONCLUSIONS: Frequent use of hair oils during late pregnancy may be associated with shorter gestational duration. As hair oils are more commonly used by non-Hispanic Black women and represent potentially modifiable EDC exposure sources, this may have important implications for the known racial disparity in preterm birth.

Ambient PM gross ß-activity and glucose levels during pregnancy.

BACKGROUND: Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient particulate matter (PM) gross ß-activity and gestational diabetes mellitus (GDM) among pregnant women, we examined pregnancy glucose levels in relation to PM gross ß-activity to better understand this pathway. METHODS: Our study included 103 participants receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA. PM gross ß-activity was obtained from US Environmental Protection Agency's RadNet program monitors, and blood glucose levels were obtained from the non-fasting glucose challenge test performed clinically as the first step of the 2-step GDM screening test. For each exposure window we examined (i.e., moving average same-day, one-week, first-trimester, and second-trimester PM gross ß-activity), we fitted generalized additive models and adjusted for clinical characteristics, socio-demographic factors, temporal variables, and PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5). Subgroup analyses by maternal age and by body mass index were also conducted. RESULTS: An interquartile range increase in average PM gross ß-activity during the second trimester of pregnancy was associated with an increase of 17.5 (95% CI: 0.8, 34.3) mg/dL in glucose concentration. Associations were stronger among younger and overweight/obese participants. Our findings also suggest that the highest compared to the lowest quartile of one-week exposure was associated with 17.0 (95% CI: - 4.0, 38.0) mg/dL higher glucose levels. No associations of glucose were observed with PM gross ß-activity during same-day and first-trimester exposure windows. PM2.5 was not associated with glucose levels during any exposure window in our data. CONCLUSIONS: Exposure to higher levels of ambient PM gross ß-activity was associated with higher blood glucose levels in pregnant patients, with implications for how this novel environmental factor could impact pregnancy health.

Wireless versus routine physiologic monitoring after cesarean delivery to reduce maternal morbidity and mortality in a resource-limited setting: protocol of type 2 hybrid effectiveness-implementation study.

BACKGROUND: Women in sub-Saharan Africa have the highest rates of morbidity and mortality during childbirth globally. Despite increases in facility-based childbirth, gaps in quality of care at facilities have limited reductions in maternal deaths. Infrequent physiologic monitoring of women around childbirth is a major gap in care that leads to delays in life-saving interventions for women experiencing complications. METHODS: We will conduct a type-2 hybrid effectiveness-implementation study over 12 months to evaluate using a wireless physiologic monitoring system to detect and alert clinicians of abnormal vital signs in women for 24 h after undergoing emergency cesarean delivery at a tertiary care facility in Uganda. We will provide physiologic data (heart rate, respiratory rate, temperature and blood pressure) to clinicians via a smartphone-based application with alert notifications if monitored women develop predefined abnormalities in monitored physiologic signs. We will alternate two-week intervention and control time periods where women and clinicians use the wireless monitoring system during intervention periods and current standard of care (i.e., manual vital sign measurement when clinically indicated) during control periods. Our primary outcome for effectiveness is a composite of severe maternal outcomes per World Health Organization criteria (e.g. death, cardiac arrest, jaundice, shock, prolonged unconsciousness, paralysis, hysterectomy). Secondary outcomes include maternal mortality rate, and case fatality rates for postpartum hemorrhage, hypertensive disorders, and sepsis. We will use the RE-AIM implementation framework to measure implementation metrics of the wireless physiologic system including Reach (proportion of eligible women monitored, length of time women monitored), Efficacy (proportion of women with monitoring according to Uganda Ministry of Health guidelines, number of appropriate alerts sent), Adoption (proportion of clinicians utilizing physiologic data per shift, clinical actions in response to alerts), Implementation (fidelity to monitoring protocol), Maintenance (sustainability of implementation over time). We will also perform in-depth qualitative interviews with up to 30 women and 30 clinicians participating in the study. DISCUSSION: This is the first hybrid-effectiveness study of wireless physiologic monitoring in an obstetric population. This study offers insights into use of wireless monitoring systems in low resource-settings, as well as normal and abnormal physiologic parameters among women delivering by cesarean. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04060667 . Registered on 08/01/2019.

Impact of an educational intervention on WHO surgical safety checklist and pre-operative antibiotic use at a referral hospital in southwestern Uganda.

INTRODUCTION: The World Health Organization (WHO) recommends adherence to its surgical safety checklist (SSC) to optimize patient safety and reduce cesarean surgical site infection (SSI). Educational interventions combined with audit and feedback mechanisms on the checklist use by clinicians have the potential to improve adherence and clinical outcomes. Despite the increase in cesarean delivery rates, there is a paucity of data on how such interventions can improve adherence in resource-limited settings. OBJECTIVE: We performed a quality improvement project to measure the impact of an educational intervention with daily audit and feedback procedures on rates of WHO SSC adherence, including pre-operative antibiotic administration and SSI at Mbarara Regional Referral Hospital maternity ward in Uganda. METHODS: The study involved chart abstraction of WHO SSC and pre-operative antibiotic use during cesarean deliveries and signs of subsequent SSI in three phases. First, we conducted a retrospective review of all charts from May to June 2018 (pre-intervention phase). Second, we instituted an educational intervention on the WHO SSC and pre-operative antibiotics use, followed by a daily audit of charts and feedback to clinicians from July to August 2018 (the intervention phase). Third, we reviewed charts from September to October 2018 (the post-intervention phase). The WHO SSC adherence, pre-operative antibiotic administration and SSI rates were measured as the proportion of the total cesarean deliveries per study phase and then compared across the three phases. RESULTS: We reviewed 678 patients' charts (200 in the pre-intervention phase, 230 in the intervention phase and 248 in the post-intervention phase). The mean patient age was 25 years. The use of the WHO SSC was 7% in the pre-intervention phase compared to 92% in the intervention phase (P < 0.001), and 77% in the post-intervention phase (P < 0.001). Pre-intervention antibiotic receipt was 18% compared to 90% in the intervention phase (P < 0.001) and 84% in the post-intervention phase (P < 0.001). The documented SSI rate in the pre-intervention phase was 15% compared to 7% in the intervention phase (P = 0.02) and 11% in the post-intervention phase (P = 0.20). CONCLUSIONS: An educational intervention, daily audit and feedback to clinicians increased the use of the WHO SSC and prophylactic antibiotics for cesarean delivery-although the rates waned with time. Research to understand factors influencing the checklist use and antibiotic prophylaxis including prescriber knowledge, motivation and clinical process is required. Implementation interventions to sustain usage and impact on clinical outcomes need to be explored.

Effectiveness of 17-OHP for Prevention of Recurrent Preterm Birth: A Retrospective Cohort Study.

OBJECTIVE: 17-α-hydroxyprogesterone caproate (17-OHP) has been recommended by professional societies for the prevention of recurrent preterm birth, but subsequent clinical studies have reported conflicting efficacy results. This study aimed to contribute to the evidence base regarding the effectiveness of 17-OHP in clinical practice using real-world data. STUDY DESIGN: A total of 4,422 individuals meeting inclusion criteria representing recurrent spontaneous preterm birth (sPTB) were identified in a database of insurance claims, and 568 (12.8%) received 17-OHP. Crude and propensity score-matched recurrence rates and risk ratios (RRs) for the association of receiving 17-OHP on recurrent sPTB were calculated. RESULTS: Raw sPTB recurrence rates were higher among those treated versus not treated; after propensity score matching, no association was detected (26.3 vs. 23.8%, RR = 1.1, 95% CI: 0.9-1.4). CONCLUSION: We failed to identify a beneficial effect of 17-OHP for the prevention of spontaneous recurrent preterm birth in our observational, U.S. based cohort. KEY POINTS: · •We observed higher risk for sPTB in the group receiving 17-OHP in the unmatched analysis. · •After propensity-score matching, we still failed to identify a beneficial effect of 17-OHP on sPTB. · •Sensitivity analyses demonstrated robustness to the inclusion criteria and modeling assumptions..

Placenta accreta spectrum: biomarker discovery using plasma proteomics.

BACKGROUND: Many cases of placenta accreta spectrum are not diagnosed antenatally, despite identified risk factors and improved imaging methods. Identification of plasma protein biomarkers could further improve the antenatal diagnosis of placenta accreta spectrum . OBJECTIVE: The purpose of this study was to determine if women with placenta accreta spectrum have a distinct plasma protein profile compared with control subjects. STUDY DESIGN: We obtained plasma samples before delivery from 16 participants with placenta accreta spectrum and 10 control subjects with similar gestational ages (35.1 vs 35.5 weeks gestation, respectively). We analyzed plasma samples with an aptamer-based proteomics platform for alterations in 1305 unique proteins. Heat maps of the most differentially expressed proteins (T test, P<.01) were generated with matrix visualization and analysis software. Principal component analysis was performed with the use of all 1305 proteins and the top 21 dysregulated proteins. We then confirmed dysregulated proteins using enzyme-linked immunosorbent assay and report significant differences between placenta accreta spectrum and control cases (Wilcoxon-rank sum test, P<.05). RESULTS: Many of the top 50 proteins that significantly dysregulated in participants with placenta accreta spectrum were inflammatory cytokines, factors that regulate vascular remodeling, and extracellular matrix proteins that regulate invasion. Placenta accreta spectrum, with the use of the top 21 proteins, distinctly separated the placenta accreta spectrum cases from control cases (P<.01). Using enzyme-linked immunosorbent assay, we confirmed 4 proteins that were dysregulated in placenta accreta spectrum compared with control cases: median antithrombin III concentrations (240.4 vs 150.3 mg/mL; P=.002), median plasminogen activator inhibitor 1 concentrations (4.1 vs 7.1 ng/mL; P<.001), soluble Tie2 (13.5 vs 10.4 ng/mL; P=.02), soluble vascular endothelial growth factor receptor 2 (9.0 vs 5.9 ng/mL; P=.003). CONCLUSION: Participants with placenta accreta spectrum had a unique and distinct plasma protein signature.

Prenatal Household Air Pollution Is Associated with Impaired Infant Lung Function with Sex-Specific Effects. Evidence from GRAPHS, a Cluster Randomized Cookstove Intervention Trial.

RATIONALE: Approximately 2.8 billion people are exposed daily to household air pollution from polluting cookstoves. The effects of prenatal household air pollution on lung development are unknown. OBJECTIVES: To prospectively examine associations between prenatal household air pollution and infant lung function and pneumonia in rural Ghana. METHODS: Prenatal household air pollution exposure was indexed by serial maternal carbon monoxide personal exposure measurements. Using linear regression, we examined associations between average prenatal carbon monoxide and infant lung function at age 30 days, first in the entire cohort (n = 384) and then stratified by sex. Quasi-Poisson generalized additive models explored associations between infant lung function and pneumonia. MEASUREMENTS AND MAIN RESULTS: Multivariable linear regression models showed that average prenatal carbon monoxide exposure was associated with reduced time to peak tidal expiratory flow to expiratory time (ß = -0.004; P = 0.01), increased respiratory rate (ß = 0.28; P = 0.01), and increased minute ventilation (ß = 7.21; P = 0.05), considered separately, per 1 ppm increase in average prenatal carbon monoxide. Sex-stratified analyses suggested that girls were particularly vulnerable (time to peak tidal expiratory flow to expiratory time: ß = -0.003, P = 0.05; respiratory rate: ß = 0.36, P = 0.01; minute ventilation: ß = 11.25, P = 0.01; passive respiratory compliance normalized for body weight: ß = 0.005, P = 0.01). Increased respiratory rate at age 30 days was associated with increased risk for physician-assessed pneumonia (relative risk, 1.02; 95% confidence interval, 1.00-1.04) and severe pneumonia (relative risk, 1.04; 95% confidence interval, 1.00-1.08) in the first year of life. CONCLUSIONS: Increased prenatal household air pollution exposure is associated with impaired infant lung function. Altered infant lung function may increase risk for pneumonia in the first year of life. These findings have implications for future respiratory health. Clinical trial registered with www.clinicaltrials.gov (NCT 01335490).