Publications

  • Racial and Ethnic Disparities in Anemia and Severe Maternal Morbidity. Obstetrics and gynecology Igbinosa, I. I., Leonard, S. A., Noelette, F., Davies-Balch, S., Carmichael, S. L., Main, E., Lyell, D. J. 2023

    Abstract

    To evaluate antepartum anemia prevalence by race and ethnicity, to assess whether such differences contribute to severe maternal morbidity (SMM), and to estimate the contribution of antepartum anemia to SMM and nontransfusion SMM by race and ethnicity.We conducted a population-based cohort study using linked vital record and birth hospitalization data for singleton births at or after 20 weeks of gestation in California from 2011 through 2020. Pregnant patients with hereditary anemias, out-of-hospital births, unlinked records, and missing variables of interest were excluded. Antepartum anemia prevalence and trends were estimated by race and ethnicity. Centers for Disease Control and Prevention criteria were used for SMM and nontransfusion SMM indicators. Multivariable logistic regression modeling was used to estimate risk ratios (RRs) for SMM and nontransfusion SMM by race and ethnicity after sequential adjustment for social determinants, parity, obstetric comorbidities, delivery, and antepartum anemia. Population attributable risk percentages were calculated to assess the contribution of antepartum anemia to SMM and nontransfusion SMM by race and ethnicity.In total, 3,863,594 births in California were included. In 2020, Black pregnant patients had the highest incidence of antepartum anemia (21.5%), followed by Pacific Islander (18.2%), American Indian-Alaska Native (14.1%), multiracial (14.0%), Hispanic (12.6%), Asian (10.6%), and White pregnant patients (9.6%). From 2011 to 2020, the prevalence of anemia increased more than100% among Black patients, and there was a persistent gap in prevalence among Black compared with White patients. Compared with White patients, the adjusted risk for SMM was high among most racial and ethnic groups; adjustment for anemia after sequential modeling for known confounders decreased SMM risk most for Black pregnant patients (approximated RR 1.47, 95% CI 1.42-1.53 to approximated RR 1.27, 95% CI 1.22-1.37). Compared with White patients, the full adjusted nontransfusion SMM risk remained high for most groups except Hispanic and multiracial patients. Within each racial and ethnic group, the population attributable risk percentage for antepartum anemia and SMM was highest for multiracial patients (21.4%, 95% CI 17.5-25.0%), followed by Black (20.9%, 95% CI 18.1-23.4%) and Hispanic (20.9%, 95% CI 19.9-22.1%) patients. The nontransfusion SMM population attributable risk percentages for Asian, Black, and White pregnant patients were less than 8%.Antepartum anemia, most prevalent among Black pregnant patients, contributed to disparities in SMM by race and ethnicity. Nearly one in five to six SMM cases among Black, Hispanic, American Indian-Alaska Native, Pacific Islander, and multiracial pregnant patients is attributable in part to antepartum anemia.

    View details for DOI 10.1097/AOG.0000000000005325

    View details for PubMedID 37678935

  • Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population-based case-control study of women meeting the folic acid recommendations. The American journal of clinical nutrition Petersen, J. M., Smith-Webb, R. S., Shaw, G. M., Carmichael, S. L., Desrosiers, T. A., Nestoridi, E., Darling, A. M., Parker, S. E., Politis, M. D., Yazdy, M. M., Werler, M. M. 2023; 118 (3): 720-728

    Abstract

    Neural tube defects (NTDs) still occur among some women who consume 400 μg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs.To investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations.Data were from the National Birth Defects Prevention Study (United States population-based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 μg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center.NTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake.Our findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.

    View details for DOI 10.1016/j.ajcnut.2023.05.034

    View details for PubMedID 37661108

  • Neighborhood gentrification, displacement, and severe maternal morbidity in California. Social science & medicine (1982) Gao, X., Thomas, T. A., Morello-Frosch, R., Allen, A. M., Snowden, J. M., Carmichael, S. L., Mujahid, M. S. 2023; 334: 116196

    Abstract

    Gentrification, a racialized and profit-driven process in which historically disinvested neighborhoods experience an influx of development that contributes to the improvement of physical amenities, increasing housing costs, and the dispossession and displacement of existing communities, may influence the risk of severe maternal morbidity (SMM). Leveraging a racially diverse population-based sample of all live hospital births in California between 2006 and 2017, we examined associations between neighborhood-level gentrification and SMM. SMM was defined as having one of 21 procedures and diagnoses, as described in the SMM index developed by Centers for Disease Control and Prevention. We compared three gentrification measures to determine which operationalization best captures aspects of gentrification most salient to SMM: Freeman, Landis 3-D, and Urban Displacement Project Gentrification and Displacement Typology. Descriptive analysis assessed bivariate associations between gentrification and birthing people's characteristics. Overall and race and ethnicity-stratified mixed-effects logistic models assessed associations between gentrification and SMM, adjusting for individual sociodemographic and pregnancy factors while accounting for clustering by census tract. The study sample included 5,256,905 births, with 72,718 cases of SMM (1.4%). The percentage of individuals living in a gentrifying neighborhood ranged from 5.7% to 11.7% across exposure assessment methods. Net of individual and pregnancy-related factors, neighborhood-level gentrification, as measured by the Freeman method, was protective against SMM (OR = 0.89, 95% CI: 0.86-0.93); in comparison, gentrification, as measured by the Gentrification and Displacement Typology, was associated with greater risk of SMM (OR = 1.18, 95% CI: 1.14-1.23). These associations were significant among non-Hispanic White, non-Hispanic Black, and Hispanic individuals. Findings demonstrate that gentrification plays a role in shaping the risk of SMM among birthing people in California. Differences in how gentrification is conceptualized and measured, such as an emphasis on housing affordability compared to a broader characterization of gentrification's multiple aspects, may explain the heterogeneity in the directions of observed associations.

    View details for DOI 10.1016/j.socscimed.2023.116196

    View details for PubMedID 37678111

  • Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors? Birth defects research Neo, D. T., Martin, C. L., Carmichael, S. L., Gucsavas-Calikoglu, M., Conway, K. M., Evans, S. P., Feldkamp, M. L., Gilboa, S. M., Insaf, T. Z., Musfee, F. I., Shaw, G. M., Shumate, C., Werler, M. M., Olshan, A. F., Desrosiers, T. A. 2023

    Abstract

    Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations.We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction.Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3).Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors.

    View details for DOI 10.1002/bdr2.2224

    View details for PubMedID 37439400

  • Oxidative balance scores and neural crest cell-related congenital anomalies. Birth defects research Carmichael, S. L., Yang, W., Ma, C., Desrosiers, T. A., Weber, K., Collins, R. T., Nestoridi, E., Shaw, G. M. 2023

    Abstract

    Oxidative stress and redox imbalance adversely affect embryonic development. We developed two oxidative balance scores (OBS) that include dietary and nondietary exposures. We hypothesized that higher scores (i.e., lower oxidative stress) would be associated with lower risk of neural tube defects, orofacial clefts, conotruncal heart defects, and limb deficiencies. We used data from the National Birth Defects Prevention Study to create a dietary OBS based on intake of 13 nutrients and an overall OBS that included the 13 nutrients and eight additional nondietary factors related to oxidative balance (e.g., smoking). We used logistic regression to examine odds ratios associated with having low or high scores (i.e., <10th or >90th percentiles). Continuous models indicated reduced odds associated with high versus low scores (i.e., comparing odds at the 90th versus 10th percentile values of the distribution) on the overall OBS for cleft lip with or without cleft palate [adjusted odds ratio (aOR) 0.72, 95% confidence interval (CI) 0.63-0.82], longitudinal limb deficiency (aOR 0.73, CI 0.54-0.99), and transverse limb deficiency (aOR 0.74, CI 0.58-0.95); increased odds for anencephaly (aOR 1.40, CI 1.07-1.84); and primarily nonsignificant associations with conotruncal heart defects. Results for the dietary OBS were similar. This study provides some evidence that oxidative stress contributes to congenital anomalies related to neural crest cell development.

    View details for DOI 10.1002/bdr2.2211

    View details for PubMedID 37309307

  • Early postpartum hospital encounters among patients with genitourinary and wound infections during hospitalization for birth. American journal of perinatology Leonard, S. A., Girsen, A., Trepman, P., Carmichael, S. L., Darmawan, K., Butwick, A., Gibbs, R. 2023

    Abstract

    To assess the associations between genitourinary and wound infections during the birth hospitalization and early postpartum hospital encounters, and to evaluate clinical risk factors for early postpartum hospital encounters among patients with a genitourinary or wound infection during the birth hospitalization.We conducted a population-based cohort study of births in California during 2016-2018 and postpartum hospital encounters. We identified genitourinary and wound infections using diagnosis codes. Our main outcome was early postpartum hospital encounter, defined as a readmission or ED visit within 3 days after discharge from the birth hospitalization. We evaluated the association of genitourinary and wound infections (overall and subtypes) with early postpartum hospital encounter using logistic regression, adjusting for sociodemographic factors and comorbidities and stratified by mode of birth. We then evaluated factors associated with early postpartum hospital encounter among patients with genitourinary and wound infections.Among 1,217,803 birth hospitalizations, 5.5% were complicated by genitourinary and wound infections and 1.8% resulted in an early postpartum hospital encounter. Genitourinary or wound infection was associated with an early postpartum hospital encounter among patients with both vaginal births (aRR 1.26, 95% CI 1.17, 1.36) and cesarean births (aRR 1.23, 95% CI 1.15, 1.32). Major puerperal infection, followed by wound infection, among patients with a cesarean birth conferred the highest risk of an early postpartum hospital encounter (6.4% and 4.3%, respectively). Among patients with genitourinary and wound infections at birth hospitalization, factors associated with an early postpartum hospital encounter included severe maternal morbidity, major mental health condition, prolonged postpartum hospital stay, and, among cesarean births, postpartum hemorrhage (P-value < 0.05).Genitourinary and wound infections during hospitalization for birth may increase risk of a readmission or ED visit within the first few days after discharge, particularly among patients who have a major puerperal infection or wound infection.

    View details for DOI 10.1055/a-2097-1584

    View details for PubMedID 37216972

  • Racial and Ethnic Disparities in Primary Cesarean Birth and Adverse Outcomes Among Low-Risk Nulliparous People. Obstetrics and gynecology Carmichael, S. L., Snowden, J. 2023; 141 (5): 1024

    View details for DOI 10.1097/AOG.0000000000005158

    View details for PubMedID 37103537

  • Neighborhood-level socioeconomic position during early pregnancy and risk of gastroschisis. Epidemiology (Cambridge, Mass.) Neo, D. T., Desrosiers, T. A., Martin, C. L., Carmichael, S. L., Gucsavas-Calikoglu, M., Conway, K. M., Evans, S. P., Feldkamp, M. L., Gilboa, S. M., Insaf, T. Z., Musfee, F. I., Shaw, G. M., Shumate, C. J., Werler, M. M., Olshan, A. F. 2023

    Abstract

    Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the understudied association between neighborhood-level socioeconomic position during early pregnancy and risk of gastroschisis, an abdominal birth defect of increasing prevalence.We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997 - 2011). To characterize neighborhood-level socioeconomic position, we conducted principal component analysis to construct two indices - Neighborhood Deprivation Index (NDI) and Neighborhood Socioeconomic Position Index (nSEPI). We created neighborhood-level indices using census socioeconomic indicators corresponding to census tracts associated with addresses where mothers lived the longest during the periconceptional period. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with multiple imputation for missing data and adjustment for maternal race-ethnicity, household income, education, birth year, and duration of residence.Mothers residing in moderate (NDI Tertile 2 aOR: 1.2; 95% CI: 1.0, 1.5 and nSEPI Tertile 2 aOR: 1.2; 95% CI: 1.0, 1.5) or low socioeconomic neighborhoods (NDI Tertile 3 aOR: 1.3; 95% CI: 1.01, 1.6 and nSEPI Tertile 3 aOR: 1.3, 95% CI: 1.1, 1.6) were more likely to deliver an infant with gastroschisis compared with mothers residing in high socioeconomic neighborhoods.Our findings suggest that lower neighborhood-level socioeconomic position during early pregnancy is associated with elevated odds of gastroschisis. Additional epidemiologic studies may aid in confirming this finding and evaluating potential mechanisms linking neighborhood-level socioeconomic factors and gastroschisis.

    View details for DOI 10.1097/EDE.0000000000001621

    View details for PubMedID 36976718

  • Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants. American journal of medical genetics. Part A Sok, P., Sabo, A., Almli, L. M., Jenkins, M. M., Nembhard, W. N., Agopian, A. J., Bamshad, M. J., Blue, E. E., Brody, L. C., Brown, A. L., Browne, M. L., Canfield, M. A., Carmichael, S. L., Chong, J. X., Dugan-Perez, S., Feldkamp, M. L., Finnell, R. H., Gibbs, R. A., Kay, D. M., Lei, Y., Meng, Q., Moore, C. A., Mullikin, J. C., Muzny, D., Olshan, A. F., Pangilinan, F., Reefhuis, J., Romitti, P. A., Schraw, J. M., Shaw, G. M., Werler, M. M., Harpavat, S., Lupo, P. J. 2023

    Abstract

    The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex.

    View details for DOI 10.1002/ajmg.a.63185

    View details for PubMedID 36942736

  • Neighborhood Deprivation and Severe Maternal Morbidity in the State of California: An Examination of Effect Modification by Race/Ethnicity. American journal of obstetrics & gynecology MFM Mujahid, M. S., Wall-Wieler, E., Hailu, M. E., Berkowitz, R. L., Gao, M. X., Morris, M. C., Abrams, B., Lyndon, A., Carmichael, S. L. 2023: 100916

    Abstract

    Social determinants of health, including neighborhood context, may be a key driver of severe maternal morbidity and its related racial/ethnic inequities, but investigations remain limited.We examined associations between neighborhood socioeconomic characteristics and severe maternal morbidity and whether associations were modified by race/ethnicity.This study leveraged a California statewide data resource on all hospital births ≥20 weeks (1997-2018). Severe maternal morbidity was defined as having at least one of 21 diagnoses and procedures (for example, blood transfusion, hysterectomy) as outlined by the Centers for Disease Control and Prevention. Neighborhoods were defined as residential census tracts (N=8,022; average of 1,295 births per neighborhood), and neighborhood deprivation index was a summary measures of 8 census indicators (for example, percent poverty, unemployment, public assistance). Mixed-effects logistic regression models (individuals nested within neighborhoods) were used to compare odds of severe maternal morbidity across quartiles (Quartile 1= least deprived; Quartile 4 = most deprived) of neighborhood deprivation index before and after adjustment for maternal sociodemographic and pregnancy-related factors and co-morbidities. We also created cross-product terms to determine if associations were modified by race/ethnicity.Of 10,384,976 births, the prevalence of severe maternal morbidity was 1.2% (N=120,487). In fully adjusted mixed-effects models, odds of severe maternal morbidity increased with increasing neighborhood deprivation index (Odds Ratios and 95% Confidence Intervals, with Quartile 1 as reference: Quartile 4 =1.23 (1.20-1.26), Quartile 3=1.13 (1.10-1.16), Quartile 2=1.06 (1.03-1.08). Associations were modified by race/ethnicity such that associations (Quartile 4 vs. Quartile 1, 95% C.I.) were strongest among individuals in the "Other" racial/ethnic category (1.39, 1.03-1.86) and weakest among Black individuals (1.07, 0.98-1.16).These findings suggest that neighborhood deprivation contributes to an increased risk of severe maternal morbidity. Future research should examine which aspects of neighborhood environments matter most across racial/ethnic groups.

    View details for DOI 10.1016/j.ajogmf.2023.100916

    View details for PubMedID 36905984