Spatial Patterning of Spontaneous and Medically Indicated Preterm Birth in Philadelphia.

Preterm birth (PTB) remains a key public health issue that disproportionately affects Black individuals. Since spontaneous PTB (sPTB) and medically indicated PTB (mPTB) may have different causes and interventions, we quantified racial disparities for sPTB and mPTB, and we characterized the geographic patterning of these phenotypes, overall and according to race/ethnicity. We examined a pregnancy cohort of 83,952 singleton births at 2 Philadelphia hospitals from 2008-2020, and classified each PTB as sPTB or mPTB. We used binomial regression to quantify the magnitude of racial disparities between non-Hispanic Black and non-Hispanic White individuals, then generated small area estimates by applying a Bayesian model that accounts for small numbers and smooths estimates of PTB risk by borrowing information from neighboring areas. Racial disparities in both sPTB and mPTB were significant (relative risk of sPTB = 1.83, 95% confidence interval: 1.70, 1.98; relative risk of mPTB = 2.20, 95% confidence interval: 2.00, 2.42). The disparity was 20% greater in mPTB than sPTB. There was substantial geographic variation in PTB, sPTB, and mPTB risks and racial disparity. Our findings underscore the importance of distinguishing PTB phenotypes within the context of public health and preventive medicine. Future work should consider social and environmental exposures that may explain geographic differences in PTB risk and disparities.

Maternal blood arsenic levels and associations with birth weight-for-gestational age.

BACKGROUND: Among highly exposed populations, arsenic exposure in utero may be associated with decreased birth weight, however less is known about potential effects of arsenic exposure in urban communities without contaminated sources such as drinking water. OBJECTIVE: Investigate the association of blood arsenic levels with birth weight-for-gestational age categories within a prospective birth cohort study. DESIGN/METHODS: We analyzed 730 mother-infant dyads within the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Total arsenic was measured in maternal blood samples from the 2nd and 3rd trimesters, at delivery, as well as from infant umbilical cord blood samples. Multivariable, multinomial logistic regression models adjusting for maternal age at enrollment, pre-pregnancy body mass index, parity, infant sex, socioeconomic position, and prenatal environmental tobacco smoke exposure were used to calculate odds ratios of small-for-gestational age (<10th percentile, SGA) and large-for-gestational age (>90th percentile, LGA) compared to appropriate-for-gestational age (AGA) per unit increase of log-transformed arsenic. RESULTS: Median (IQR) blood arsenic levels for maternal second trimester were 0.72 (0.33) µg/L, maternal third trimester 0.75 (0.41) µg/L, maternal at delivery 0.85 (0.70) µg/L, and infant cord 0.78 (0.65) µg/L. Maternal delivery and infant cord blood samples were most strongly correlated (spearman r = 0.65, p < 0.0001). Maternal arsenic levels at delivery were associated with significantly higher odds of both SGA (adj. OR = 1.44, 95% CI: 1.08-1.93) and LGA (adj. OR = 2.03, 95% CI: 1.12-3.67) compared to AGA. Results were similar for cord blood. There were 130 SGA infants and 22 LGA infants. Earlier in pregnancy, there were no significant associations of arsenic and birth weight-for-gestational age. However, we observed non-significantly higher odds of LGA among women with higher arsenic levels in the 3rd trimester (adj. OR = 1.46, 95% CI: 0.67-3.12). CONCLUSION: We found that in a Mexico City birth cohort, higher maternal blood arsenic levels at delivery were associated with higher odds of both SGA and LGA. However, sources and species of arsenic were not known and the number of LGA infants was small, limiting the interpretation of this finding and highlighting the importance of future large studies to incorporate arsenic speciation. If our findings were confirmed in studies that addressed these limitations, determining modifiable factors that could be mitigated, such as sources of arsenic exposure, may be important for optimizing fetal growth to improve long-term health of children.

Giving Birth With a Midwife in Attendance: Associations of Race and Insurance Status With Continuity of Midwifery Care in Philadelphia.

INTRODUCTION: From 2013 to 2019, Black women comprised 73% of pregnancy-related deaths in Philadelphia. There is currently a dearth of research on the continuity of midwifery care from initiation of prenatal care through birth in relation to characteristics such as race/ethnicity and income. The aim of this study was to investigate whether race/ethnicity and insurance status were associated with the likelihood of a pregnant person who begins prenatal care with a midwife to remain in midwifery care for birth attendance. METHODS: This was a retrospective cohort study of a diverse population of pregnant patients who gave birth in a large tertiary care hospital and had their first prenatal visit with a certified nurse-midwife (CNM) between June 2, 2009, and June 30, 2020 (n = 5121). We used multivariable, log-binomial regression models to calculate risk ratios of transferring to physician care (vs remaining within CNM care), adjusted for age, race/ethnicity, prepregnancy body mass index, insurance type, and comorbidities. RESULTS: After adjusting for pregnancy-related risk factors, non-Hispanic Black patients (adjusted relative risk [aRR], 1.14; 95% CI, 1.04-1.24) and publicly insured patients (aRR, 1.11; 95% CI, 1.01-1.22) were at higher risk of being transferred to physician care compared with non-Hispanic White and privately insured patients. Secondary analysis revealed that non-Hispanic Black patients had higher risk of transferring and having an operative birth (aRR, 1.35; 95% CI, 1.18-1.55), whereas publicly insured patients were at higher risk of being transferred for reasons other than operative births (aRR, 1.35; 95% CI, 1.18-1.54). DISCUSSION: These findings indicate that Black and publicly insured patients were more likely than White and privately insured patients to transfer to physician care even after adjustment for comorbid conditions. Thus, further research is needed to identify the factors that contribute to racial and economic disparity in continuity of midwifery care.

Neighborhood Walkability as a Risk Factor for Preterm Birth Phenotypes in Two Philadelphia Hospitals from 2013-2016.

A total of one in ten infants is born preterm in the U.S. with large racial disparities. Recent data suggest that neighborhood exposures may play a role. Walkability-how easily individuals can walk to amenities-may encourage physical activity. We hypothesized that walkability would be associated with a decreased risk of preterm birth (PTB) and that associations would vary by PTB phenotype. PTB can be spontaneous (sPTB) from conditions such as preterm labor and preterm premature rupture of membranes, or medically indicated (mPTB) from conditions such as poor fetal growth and preeclampsia. We analyzed associations of neighborhood walkability (quantified by their Walk Score® ranking) with sPTB and mPTB in a Philadelphia birth cohort (n = 19,203). Given racial residential segregation, we also examined associations in race-stratified models. Walkability (per 10 points of Walk Score ranking) was associated with decreased odds of mPTB (aOR 0.90, 95% CI: 0.83, 0.98), but not sPTB (aOR 1.04, 95% CI: 0.97, 1.12). Walkability was not protective for mPTB for all patients; there was a non-significant protective effect for White (aOR 0.87, 95% CI: 0.75, 1.01), but not Black patients (aOR 1.05, 95% CI: 0.92, 1.21) (interaction p = 0.03). Measuring health effects of neighborhood characteristics across populations is key for urban planning efforts focused on health equity.

Neighborhood Deprivation and Racial Disparities in Early Pregnancy Impaired Glucose Tolerance.

OBJECTIVE: There is mounting evidence that neighborhoods contribute to perinatal health inequity. We aimed (1) to determine whether neighborhood deprivation (a composite marker of area-level poverty, education, and housing) is associated with early pregnancy impaired glucose intolerance (IGT) and pre-pregnancy obesity and (2) to quantify the extent to which neighborhood deprivation may explain racial disparities in IGT and obesity. STUDY DESIGN: This was a retrospective cohort study of non-diabetic patients with singleton births ≥ 20 weeks' gestation from 1 January 2017-31 December 2019 in two Philadelphia hospitals. The primary outcome was IGT (HbA1c 5.7-6.4%) at <20 weeks' gestation. Addresses were geocoded and census tract neighborhood deprivation index (range 0-1, higher indicating more deprivation) was calculated. Mixed-effects logistic regression and causal mediation models adjusted for covariates were used. RESULTS: Of the 10,642 patients who met the inclusion criteria, 49% self-identified as Black, 49% were Medicaid insured, 32% were obese, and 11% had IGT. There were large racial disparities in IGT (16% vs. 3%) and obesity (45% vs. 16%) among Black vs. White patients, respectively (p < 0.0001). Mean (SD) neighborhood deprivation was higher among Black (0.55 (0.10)) compared with White patients (0.36 (0.11)) (p < 0.0001). Neighborhood deprivation was associated with IGT and obesity in models adjusted for age, insurance, parity, and race (aOR 1.15, 95%CI: 1.07, 1.24 and aOR 1.39, 95%CI: 1.28, 1.52, respectively). Mediation analysis revealed that 6.7% (95%CI: 1.6%, 11.7%) of the Black-White disparity in IGT might be explained by neighborhood deprivation and 13.3% (95%CI: 10.7%, 16.7%) by obesity. Mediation analysis also suggested that 17.4% (95%CI: 12.0%, 22.4%) of the Black-White disparity in obesity may be explained by neighborhood deprivation. CONCLUSION: Neighborhood deprivation may contribute to early pregnancy IGT and obesity-surrogate markers of periconceptional metabolic health in which there are large racial disparities. Investing in neighborhoods where Black patients live may improve perinatal health equity.

Benzene and NO2 Exposure during Pregnancy and Preterm Birth in Two Philadelphia Hospitals, 2013-2017.

Infants born preterm are at risk of neonatal morbidity and mortality. Preterm birth (PTB) can be categorized as either spontaneous (sPTB) or medically indicated (mPTB), resulting from distinct pathophysiologic processes such as preterm labor or preeclampsia, respectively. A growing body of literature has demonstrated the impacts of nitrogen dioxide (NO2) and benzene exposure on PTB, though few studies have investigated how these associations may differ by PTB subtype. We investigated the associations of NO2 and benzene exposure with sPTB and mPTB among 18,616 singleton live births at two Philadelphia hospitals between 2013 and 2017. Residential NO2 exposure was estimated using a land use regression model and averaged over the patient's full pregnancy. Benzene exposure was estimated at the census tract level using National Air Toxics Assessment (NATA) exposure data from 2014. We used logistic mixed-effects models to calculate odds ratios for overall PTB, sPTB, and mPTB separately, adjusting for patient- and tract-level confounders. Given the known racial segregation and PTB disparities in Philadelphia, we also examined race-stratified models. Counter to the hypothesis, neither NO2 nor benzene exposure differed by race, and neither were significantly associated with PTB or PTB subtypes. As such, these pollutants do not appear to explain the racial disparities in PTB in this setting.

Changes in preterm birth during the COVID-19 pandemic by duration of exposure and race and ethnicity.

OBJECTIVE: We aimed to determine whether coronavirus-disease-2019 (COVID-19) pandemic exposure duration was associated with PTB and if the pandemic modified racial disparities. STUDY DESIGN: We analyzed Philadelphia births and replicated in New Haven. Compared to matched months in two prior years, we analyzed overall PTB, specific PTB phenotypes, and stillbirth. RESULTS: Overall, PTB was similar between periods with the following exceptions. Compared to pre-pandemic, early pregnancy (<14 weeks') pandemic exposure was associated with lower risk of PTB < 28 weeks' (aRR 0.60 [0.30-1.10]) and later exposure with higher risk (aRR 1.77 [0.78-3.97]) (interaction p = 0.04). PTB < 32 weeks' among White patients decreased during the pandemic, resulting in non-significant widening of the Black-White disparity from aRR 2.51 (95%CI: 1.53-4.16) to aRR 4.07 (95%CI: 1.56-12.01) (interaction P = 0.41). No findings replicated in New Haven. CONCLUSION: We detected no overall pandemic effects on PTB, but potential indirect benefits for some patients which could widen disparities remains possible.

Neighborhood Characteristics and Racial Disparities in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seropositivity in Pregnancy.

OBJECTIVE: To quantify the extent to which neighborhood characteristics contribute to racial and ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity in pregnancy. METHODS: This cohort study included pregnant patients who presented for childbirth at two hospitals in Philadelphia, Pennsylvania from April 13 to December 31, 2020. Seropositivity for SARS-CoV-2 was determined by measuring immunoglobulin G and immunoglobulin M antibodies by enzyme-linked immunosorbent assay in discarded maternal serum samples obtained for clinical purposes. Race and ethnicity were self-reported and abstracted from medical records. Patients' residential addresses were geocoded to obtain three Census tract variables: community deprivation, racial segregation (Index of Concentration at the Extremes), and crowding. Multivariable mixed effects logistic regression models and causal mediation analyses were used to quantify the extent to which neighborhood variables may explain racial and ethnic disparities in seropositivity. RESULTS: Among 5,991 pregnant patients, 562 (9.4%) were seropositive for SARS-CoV-2. Higher seropositivity rates were observed among Hispanic (19.3%, 104/538) and Black (14.0%, 373/2,658) patients, compared with Asian (3.2%, 13/406) patients, White (2.7%, 57/2,133) patients, and patients of another race or ethnicity (5.9%, 15/256) (P<.001). In adjusted models, per SD increase, deprivation (adjusted odds ratio [aOR] 1.16, 95% CI 1.02-1.32) and crowding (aOR 1.15, 95% CI 1.05-1.26) were associated with seropositivity, but segregation was not (aOR 0.90, 95% CI 0.78-1.04). Mediation analyses revealed that crowded housing may explain 6.7% (95% CI 2.0-14.7%) of the Hispanic-White disparity and that neighborhood deprivation may explain 10.2% (95% CI 0.5-21.1%) of the Black-White disparity. CONCLUSION: Neighborhood deprivation and crowding were associated with SARS-CoV-2 seropositivity in pregnancy in the prevaccination era and may partially explain high rates of SARS-CoV-2 seropositivity among Black and Hispanic patients. Investing in structural neighborhood improvements may reduce inequities in viral transmission.

A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia.

BackgroundAntibody-based strategies for COVID-19 have shown promise in prevention and treatment of early disease. COVID-19 convalescent plasma (CCP) has been widely used but results from randomized trials supporting its benefit in hospitalized patients with pneumonia are limited. Here, we assess the efficacy of CCP in severely ill, hospitalized adults with COVID-19 pneumonia.MethodsWe performed a randomized control trial (PennCCP2), with 80 adults hospitalized with COVID-19 pneumonia, comparing up to 2 units of locally sourced CCP plus standard care versus standard care alone. The primary efficacy endpoint was comparison of a clinical severity score. Key secondary outcomes include 14- and 28-day mortality, 14- and 28-day maximum 8-point WHO ordinal score (WHO8) score, duration of supplemental oxygenation or mechanical ventilation, respiratory SARS-CoV-2 RNA, and anti-SARS-CoV-2 antibodies.ResultsEighty hospitalized adults with confirmed COVID-19 pneumonia were enrolled at median day 6 of symptoms and day 1 of hospitalization; 60% were anti-SARS-CoV-2 antibody seronegative. Participants had a median of 3 comorbidities, including risk factors for severe COVID-19 and immunosuppression. CCP treatment was safe and conferred significant benefit by clinical severity score (median [MED] and interquartile range [IQR] 10 [5.5-30] vs. 7 [2.75-12.25], P = 0.037) and 28-day mortality (n = 10, 26% vs. n = 2, 5%; P = 0.013). All other prespecified outcome measures showed weak evidence toward benefit of CCP.ConclusionTwo units of locally sourced CCP administered early in hospitalization to majority seronegative participants conferred a significant benefit in clinical severity score and 28-day mortality. Results suggest CCP may benefit select populations, especially those with comorbidities who are treated early.Trial RegistrationClinicalTrials.gov NCT04397757.FundingUniversity of Pennsylvania.