Risk of adverse perinatal outcomes among African-born Black women in California, 2011-2020.

BACKGROUND: African-born women have a lower risk of preterm birth and small for gestational age (SGA) birth compared to United States (US)-born Black women, however variation by country of origin is overlooked. Additionally, the extent that nativity disparities in adverse perinatal outcomes to Black women are explained by individual-level factors remains unclear. METHODS: We conducted a population-based study of non-anomalous singleton live births to US- and African-born Black women in California from 2011-2020 (n=194,320). We used age-adjusted Poisson regression models to estimate risk of preterm birth and SGA, and reported risk ratios (RR) and 95% confidence intervals (CI). Decomposition using Monte Carlo integration of the g-formula computed the percentage of disparities in adverse outcomes between US- and African-born women explained by individual-level factors. RESULTS: Eritrean women (RR 0.4; 95%CI: 0.3, 0.5) had the largest differences in risk of preterm birth and Cameroonian women (RR 0.5; 95% CI: 0.3, 0.6) in SGA birth, compared to US-born Black women. Ghanaian women had smaller differences in risk of preterm birth (RR 0.8; 95%CI: 0.7, 1.0) and SGA (RR 0.9; 95% CI 0.8, 1.1) compared to US-born women. Overall, we estimate that absolute differences in socio-demographic and clinical factors contributed to 32% of nativity-based disparities in the risk of preterm birth and 26% of disparities in SGA. CONCLUSIONS: We observed heterogeneity in risk of adverse perinatal outcomes for African- compared to US-born Black women, suggesting that nativity disparities in adverse perinatal outcomes were not fully explained by differences in individual-level factors.

Prenatal cannabis use disorder and gastroschisis in California, 2007-19.

BACKGROUND: Gastroschisis is a congenital anomaly of the abdominal wall with an unknown aetiology. Recent trends in the prevalence of gastroschisis suggest that changing environmental or behavioural factors may contribute. We examined whether prenatal cannabis use disorder was associated with gastroschisis. METHODS: The Study of Outcomes of Mothers and Infants is a population-based cohort compiled of California birth records that have been linked to Department of Health Care Access and Information hospitalization, emergency department and ambulatory surgery records. We included 2007-19 singleton live births (n = 5 774 656). Cannabis use disorder was measured by diagnosis codes at any visit during pregnancy or at birth. Gastroschisis was measured by diagnosis or surgical repair procedure codes at birth or during the first year of life. RESULTS: The prevalence of cannabis use disorder was about 1%. The prevalence of gastroschisis was 0.14% and 0.06% among those with and without cannabis use disorder, respectively. There were positive associations between cannabis use disorder and gastroschisis when using a multivariable model [adjusted risk ratio (aRR) = 1.3, 95% confidence interval (CI) 1.0, 1.7) and a matched sample approach (aRR = 1.5, 95% CI 1.1, 2.1). The association varied by maternal age and was largest among people aged >34 years (aRR = 2.5, 95% CI 1.0, 5.8). CONCLUSIONS: We confirm findings of a positive association between cannabis exposure and gastroschisis and add that it is strongest when maternal age is greater than 34 years. More investigation into whether the association is causal, and why the association varies by maternal age, is encouraged.

Impact of being underweight before pregnancy on preterm birth by race/ethnicity and insurance status in California: an analysis of birth records.

BACKGROUND: The US still has a high burden of preterm birth (PTB), with important disparities by race/ethnicity and poverty status. There is a large body of literature looking at the impact of pre-pregnancy obesity on PTB, but fewer studies have explored the association between underweight status on PTB, especially with a lens toward health disparities. Furthermore, little is known about how weight, specifically pre-pregnancy underweight status, and socio-economic-demographic factors such as race/ethnicity and insurance status, interact with each other to contribute to risks of PTB. OBJECTIVES: The objective of this study was to measure the association between pre-pregnancy underweight and PTB and small for gestational age (SGA) among a large sample of births in the US. Our secondary objective was to see if underweight status and two markers of health disparities - race/ethnicity and insurance status (public vs. other) - on PTB. STUDY DESIGN: We used data from all births in California from 2011 to 2017, which resulted in 3,070,241 singleton births with linked hospital discharge records. We ran regression models to estimate the relative risk of PTB by underweight status, by race/ethnicity, and by poverty (Medi-cal status). We then looked at the interaction between underweight status and race/ethnicity and underweight and poverty on PTB. RESULTS: Black and Asian women were more likely to be underweight (aRR = 1.0, 95% CI: 1.01, 1.1 and aRR = 1.4, 95% CI: 1.4, 1.5, respectively), and Latina women were less likely to be underweight (aRR = 0.7, 95% CI: 0.7, 0.7). Being underweight was associated with increased odds of PTB (aRR = 1.3, 95% CI 1.3-1.3) and, after controlling for underweight, all nonwhite race/ethnic groups had increased odds of PTB compared to white women. In interaction models, the combined effect of being both underweight and Black, Indigenous and People of Color (BIPOC) statistically significantly reduced the relative risk of PTB (aRR = 0.9, 95% CI: 0.8, 0.9) and SGA (aRR = 1.0, 95% CI: 0.9, 1.0). The combined effect of being both underweight and on public insurance increased the relative risk of PTB (aRR = 1.1, 95% CI: 1.1, 1.2) but there was no additional effect of being both underweight and on public insurance on SGA (aRR = 1.0, 95% CI: 1.0, 1.0). CONCLUSIONS: We confirm and build upon previous findings that being underweight preconception is associated with increased risk of PTB and SGA - a fact often overlooked in the focus on overweight and adverse birth outcomes. Additionally, our findings suggest that the effect of being underweight on PTB and SGA differs by race/ethnicity and by insurance status, emphasizing that other factors related to inequities in access to health care and poverty are contributing to disparities in PTB.

Racial and Ethnic Inequities in Therapeutic Hypothermia and Neonatal Hypoxic-Ischemic Encephalopathy: A Retrospective Cohort Study.

OBJECTIVE: To investigate racial inequities in the use of therapeutic hypothermia (TH) and outcomes in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We queried an administrative birth cohort of mother-baby pairs in California from 2010 through 2019 using International Classification of Diseases codes to evaluate the association between race and ethnicity and the application of TH in infants with HIE. We identified 4779 infants with HIE. Log-linear regression was used to calculate risk ratios (RR) for TH, adjusting for hospital transfer, rural location, gestational age between 35 and 37 weeks, and HIE severity. Risk of adverse infant outcome was calculated by race and ethnicity and stratified by TH. RESULTS: From our identified cohort, 1338 (28.0%) neonates underwent TH. White infants were used as the reference sample, and 410 (28.4%) received TH. Black infants were significantly less likely to receive TH with 74 (20.0%) with an adjusted risk ratio (aRR) of 0.7 (95% CI 0.5-0.9). Black infants with any HIE who did not receive TH were more likely to have a hospital readmission (aRR 1.36, 95% CI 1.10-1.68) and a tracheostomy (aRR 3.07, 95% CI 1.19-7.97). Black infants with moderate/severe HIE who did not receive TH were more likely to have cerebral palsy (aRR 2.72, 95% CI 1.07-6.91). CONCLUSIONS: In this study cohort, Black infants with HIE were significantly less likely to receive TH. Black infants also had significantly increased risk of some adverse outcomes of HIE. Possible reasons for this inequity include systemic barriers to care and systemic bias.

Disparities in the impact of heat wave definitions on emergency department visits during the first year of life among preterm and full-term infants in California.

INTRODUCTION: Heat waves will be aggravated due to climate change, making this a critical public health threat. However, heat wave definitions to activate alert systems can be ambiguous, highlighting the need to assess a range of definitions to identify those that contribute to the most adverse health outcomes. Additionally, children are highly susceptible to the impacts of heat waves, especially infants, despite the lack of focus on this subpopulation. We aimed to assess the relationship between 30 heat wave definitions and the first all-cause emergency department (ED) visits for California infants. We also examined modification of this relationship by preterm birth status and demographic characteristics to identify possible health disparities. METHODS: Live-born, singleton deliveries from the Study of Outcomes in Mothers and Infants born in 2014-2018 were included. Thirty heat wave definitions were assessed based on temperature metrics (minimum/maximum temperatures), thresholds (90th; 92.5th; 95th; 97.5th; 99th percentiles), and duration (1-; 2-; 3-days). A time-stratified case-crossover design assessed heat wave impacts on ED visits using infants with a warm season ED visit (May-October) within the first year of life (n = 228,250). Effect modification by preterm birth status, age, sex, race/ethnicity, education, and delivery payment type was also investigated. RESULTS: Infants demonstrated increased risk of an ED visit with exposure to all heat definitions. The 3-day minimum temperature 99th percentile definition had the highest adjusted odds ratio (AOR: 1.14; 95% CI: 1.05-1.23) for the total population. Term infants were more affected by some heat waves than preterm infants. Effect modification was additionally identified, such as by maternal education. DISCUSSION: This study provides insight on the heat wave definitions that lead to adverse health outcomes and the identification of the most susceptible infants to these impacts, which has implications on heat-related interventions.

Racial Disparities in Cesarean Delivery Rates: Do Hospital-Level Factors Matter?

OBJECTIVE: This study aimed to assess whether racial disparities in nulliparous, term, singleton, vertex cesarean delivery rates vary among hospitals of different type (academic vs. nonacademic), setting (urban vs. rural), delivery volume, and patient population. STUDY DESIGN: This is a retrospective cohort study including singleton term vertex live births in nulliparous Black and non-Hispanic White birthing people in California between 2011 and 2017. Cesarean delivery rates were obtained using birth certificate data and International Classification of Diseases, 9th/10th Revision codes. Risk of cesarean delivery was compared among Black versus White birthing people by hospital type (academic, nonacademic), setting (rural, suburban, urban), volume (< 1,200, 1,200-2,300, 2,400-3,599, ≥3,600 deliveries annually), and patient population (proportion Black-serving). Federal Information Processing codes were used to designate hospital setting. Risks were calculated using univariable and multivariable logistic regression and adjusted for birthing person age, body mass index, medical comorbidities, gestational age, labor type (spontaneous vs. induction), and infant birthweight. RESULTS: The sample included 59,441 Black (cesarean delivery rate: 30.2%) and 363,624 White birthing people (cesarean delivery rate: 26.1%). Black birthing people were significantly more likely than White birthing people to have a cesarean delivery across nearly all hospital-level factors considered with adjusted relative risks ranging from 1.1 to 1.3. The only exception was rural settings in which the adjusted relative risk was 1.3 but did not reach statistical significance. CONCLUSION: Black-White disparities in nulliparous, term, singleton, vertex cesarean delivery rates were persistent across all hospital-level factors we considered: academic status, rurality, delivery volume, and patient population. Furthermore, disparities existed at roughly the same magnitude regardless of hospital characteristics. These global increased risks likely reflect structural inequities in care, which contribute to disparities in pregnancy-related morbidity and mortality. These data should encourage providers, hospital systems, and quality collaboratives to further investigate racial disparities in cesarean delivery rates and develop strategies for eliminating them. KEY POINTS: · Nulliparous Black birthing people are more likely than White to undergo cesarean delivery.. · This persists across hospitals of all academic status, rurality, delivery volume, and patient population.. · These findings likely reflect structural rather than institutional inequities in obstetric care..

Resuscitation, survival and morbidity of extremely preterm infants in California 2011-2019.

OBJECTIVE: To describe changes over time in resuscitation, survival, and morbidity of extremely preterm infants in California. STUDY DESIGN: This population-based, retrospective cohort study includes infants born ≤28 weeks. Linked birth certificates and hospital discharge records were used to evaluate active resuscitation, survival, and morbidity across two epochs (2011-2014, 2015-2019). RESULTS: Of liveborn infants, 0.6% were born ≤28 weeks. Active resuscitation increased from 16.9% of 22-week infants to 98.1% of 25-week infants and increased over time in 22-, 23-, and 25-week infants (p-value ≤ 0.01). Among resuscitated infants, survival to discharge increased from 33.2% at 22 weeks to 96.1% at 28 weeks. Survival without major morbidity improved over time for 28-week infants (p-value < 0.01). CONCLUSION: Among infants ≤28 weeks, resuscitation and survival increased with gestational age and morbidity decreased. Over time, active resuscitation of periviable infants and morbidity-free survival of 28-week infants increased. These trends may inform counseling around extremely preterm birth.

Pregnancy characteristics and outcomes among birthing individuals with a diagnosis of fetal alcohol syndrome.

BACKGROUND: Fetal alcohol syndrome (FAS) can have adverse effects on health outcomes throughout the life course. Adults with FAS have an increased risk of chronic and infectious diseases. Although these conditions can affect reproductive health, few have described perinatal outcomes among individuals with an FAS diagnosis. METHODS: We analyzed data from the Study of Mothers and Infants, an administrative birth cohort derived from California birth certificates linked with a hospital discharge database. The cohort consisted of 7.3 million singleton, live births between 2005 and 2021. FAS was identified by International Classification of Diseases (ICD) codes in maternal hospital discharge records. Pregnancy and birth outcomes were captured via ICD codes in maternal or infant records. We performed descriptive analyses for pregnancy and birth outcomes by maternal FAS diagnosis. RESULTS: There were 35 babies born to 30 individuals with an FAS diagnosis between 2005 and 2021 (0.5/100,000 live births). The prevalence of births to individuals with an FAS diagnosis increased over the period. Individuals with an FAS diagnosis were more likely to identify as non-Hispanic White, or "other/multiple" race, and less likely to be Hispanic than those without FAS. They were also more likely to be publicly insured and less than 18 years old. Birthing individuals with FAS were also more likely to use nicotine during pregnancy and to have diagnoses of mental health disorders, epilepsy, substance use disorders, preexisting or gestational hypertension, and sexually transmitted infections or other infections complicating pregnancy. Infants of individuals with FAS were more likely to be born prematurely or small for gestational age and be admitted to the neonatal intensive care unit. CONCLUSIONS: These findings highlight the need for improved recognition of FAS among birthing people. The results suggest that individuals with FAS would benefit from early and sustained medical care prior to pregnancy to optimize perinatal outcomes.

Maternal Mental Health Diagnoses and Infant Emergency Department Use, Hospitalizations, and Death.

BACKGROUND: The period surrounding childbirth is a uniquely vulnerable time for women and their mental health. We sought to describe the association between maternal mental health diagnoses in the year prior and after birth and infant Emergency Department (ED) utilization, hospitalization, and death. METHODS: We studied mothers who gave singleton live birth in California (2011-2017) and their infants using linked infant birth and death certificates and maternal and infant discharge records. Maternal mental health diagnoses in the year before and after birth were identified using International Classification of Diseases (ICD) codes. We abstracted infant ED visits, hospitalizations, discharge diagnoses, deaths, and causes of death. Log-linear regression was used to compare relative risks of infant outcomes between mothers with and without mental health diagnoses, adjusting for maternal variables. RESULTS: Of the 3,067,069 mother-infant pairs, 85,047 (2.8%) mothers had at least one mental health diagnosis in the year before and after birth. Infants of mothers with mental health diagnoses were more likely to visit the ED (aRR 1.2, CI:1.1-1.2), have three or more ED visits (aRR 1.4, CI:1.3-1.4), be hospitalized (aRR 1.1, CI:1.04-1.1), and die (aRR 1.7, CI:1.6-1.8) in the first year of life. These infants were also more likely to be diagnosed with accidental injuries, nonaccidental trauma, and non-specific descriptive diagnosis (fussiness/fatigue/brief resolved unexplained event). CONCLUSION: This large administrative cohort study showed associations between maternal mental health diagnoses and infant acute ED visits, hospitalization, and death. This study underscores the urgent need to understand what is driving these findings and how to mitigate this risk.

Structural racism, nativity and risk of adverse perinatal outcomes among Black women.

BACKGROUND: Black women in the United States (US) have the highest risk of preterm birth (PTB) and small for gestational age (SGA) births, compared to women of other racial groups. Among Black women, there are disparities by nativity whereby foreign-born women have a lower risk of PTB and SGA compared to US-born women. Differential exposure to racism may confer nativity-based differences in adverse perinatal outcomes between US- and foreign-born Black women. This remains unexplored among US- and African-born women in California. OBJECTIVES: Evaluate the relationship between structural racism, nativity, PTB and SGA among US- and African-born Black women in California. METHODS: We conducted a population-based study of singleton births to US- and African-born Black women in California from 2011 to 2017 (n = 131,424). We examined the risk of PTB and SGA by nativity and neighbourhoods with differing levels of structural racism, as measured by the Index of Concentration at the Extremes. We fit crude and age-adjusted Poisson regression models, estimated using generalized estimating equations, with risk ratios (RR) and 95% confidence intervals (CI) as the effect measure. RESULTS: The proportions of PTB and SGA were 9.7% and 14.5%, respectively, for US-born women, while 5.6% and 8.3% for African-born women. US-born women (n = 24,782; 20.8%) were more likely to live in neighbourhoods with high structural racism compared to African-born women (n = 1474; 11.6%). Structural racism was associated with an elevated risk of PTB (RR 1.19, 95% CI 1.12, 1.26) and SGA (RR 1.19, 95% CI 1.13, 1.25) for all Black women, however, there was heterogeneity by nativity, with US-born women experiencing a higher magnitude of effect than African-born women. CONCLUSIONS: Among Black women in California, exposure to structural racism and the impacts of structural racism on the risk of PTB and SGA varied by nativity.

Assessing for prenatal risk factors associated with infant neurologic morbidity using a multivariate analysis.

OBJECTIVE: To characterize the biochemical and demographic profiles of pregnant people with maternal immune activation (MIA) and identify the prenatal characteristics associated with neurologic morbidity in offspring. STUDY DESIGN: This was a retrospective cohort study of 602 mother-infant dyads with births between 2009 and 2010 in California. Multivariable logistic regression was used to build a MIA vulnerability profile including mid-pregnancy biochemical markers and maternal demographic characteristics, and its relationship with infant neurologic morbidity was examined. RESULTS: Of the 602 mother-infant dyads, 80 mothers and 61 infants had diagnoses suggestive of MIA and neurologic morbidity, respectively. Our model, including two demographic and seven biochemical characteristics, identified mothers with MIA with good performance (AUC:0.814; 95% CI:0.7-0.8). Three demographic and five inflammatory markers together identified 80% of infants with neurological morbidity (AUC:0.802, 95% CI:0.7-0.8). CONCLUSION: Inflammatory environment in mothers with pre-existing risk factors like obesity, poverty, and prematurity renders offspring more susceptible to neurologic morbidities.

Adverse live-born pregnancy outcomes among pregnant people with anorexia nervosa.

BACKGROUND: Previous findings related to the association of adverse pregnancy outcomes with anorexia nervosa are mixed. OBJECTIVE: This study aimed to investigate the association of adverse live-born pregnancy outcomes with anorexia nervosa using adjustment modeling accounting for confounding factors, and a mediation analysis addressing the contribution of underweight prepregnancy body mass index and gestational weight gain to those outcomes. STUDY DESIGN: The sample included California live-born singletons with births between 2007 and 2021. The administrative data set contained birth certificates linked to hospital discharge records. Anorexia nervosa diagnosis during pregnancy was obtained from International Classification of Diseases codes on hospital discharge records. Adverse pregnancy outcomes examined included gestational diabetes, gestational hypertension, preeclampsia, anemia, antepartum hemorrhage, premature rupture of membranes, premature labor, cesarean delivery, oligohydramnios, placenta previa, chorioamnionitis, placental abruption, severe maternal morbidity, small for gestational age, large for gestational age, low birthweight, and preterm birth (by timing and indication). Risk of each adverse outcome was calculated using Poisson regression models. Unadjusted risk of each adverse outcome was calculated, and then the risks were adjusted for demographic factors. The final adjusted model included demographic factors, anxiety, depression, substance use, and smoking. A mediation analysis was performed to estimate the excess risk of adverse outcomes mediated by underweight prepregnancy body mass index and gestational weight gain below the American College of Obstetricians and Gynecologists recommendation. RESULTS: The sample included 241 pregnant people with a diagnosis of anorexia nervosa and 6,418,236 pregnant people without an eating disorder diagnosis. An anorexia nervosa diagnosis during pregnancy was associated with many adverse pregnancy outcomes in unadjusted models (relative risks ranged from 1.65 [preeclampsia] to 3.56 [antepartum hemorrhage]) in comparison with people without an eating disorder diagnosis. In the final adjusted models, birthing people with an anorexia nervosa diagnosis were more likely to have anemia, preterm labor, oligohydramnios, severe maternal morbidity, a small for gestational age or low-birthweight infant, and preterm birth between 32 and 36 weeks with spontaneous preterm labor (adjusted relative risks ranged from 1.43 to 2.55). Underweight prepregnancy body mass index mediated 7.78% of the excess in preterm births and 18.00% of the excess in small for gestational age infants. Gestational weight gain below the recommendation mediated 38.89% of the excess in preterm births and 40.44% of the excess in low-birthweight infants. CONCLUSION: Anorexia nervosa diagnosis during pregnancy was associated with a number of clinically important adverse pregnancy outcomes in comparison with people without an eating disorder diagnosis. Adjusting for anxiety, depression, substance use, and smoking during pregnancy decreased this risk. A substantial percentage of the excess risk of adverse outcomes was mediated by an underweight prepregnancy body mass index, and an even larger proportion of excess risk was mediated by gestational weight gain below the recommendation. This information is important for clinicians to consider when caring for patients with anorexia nervosa. Considering and treating anorexia nervosa and comorbid conditions and counseling patients about mediating factors such as preconception weight and gestational weight gain may improve live-born pregnancy outcomes among people with anorexia nervosa.

Estimating the effect of timing of earned income tax credit refunds on perinatal outcomes: a quasi-experimental study of California births.

BACKGROUND: The largest poverty alleviation program in the US is the earned income tax credit (EITC), providing $60 billion to over 25 million families annually. While research has shown positive impacts of EITC receipt in pregnancy, there is little evidence on whether the timing of receipt may lead to differences in pregnancy outcomes. We used a quasi-experimental difference-in-differences design, taking advantage of EITC tax disbursement each spring to examine whether trimester of receipt was associated with perinatal outcomes. METHODS: We conducted a difference-in-differences analysis of California linked birth certificate and hospital discharge records. The sample was drawn from the linked CA birth certificate and discharge records from 2007-2012 (N = 2,740,707). To predict eligibility, we created a probabilistic algorithm in the Panel Study of Income Dynamics and applied it to the CA data. Primary outcome measures included preterm birth, small-for-gestational age (SGA), gestational diabetes, and gestational hypertension/preeclampsia. RESULTS: Eligibility for EITC receipt during the third trimester was associated with a lower risk of preterm birth compared with preconception. Eligibility for receipt in the preconception period resulted in improved gestational hypertension and SGA. CONCLUSION: This analysis offers a novel method to impute EITC eligibility using a probabilistic algorithm in a data set with richer sociodemographic information relative to the clinical and administrative data sets from which outcomes are drawn. These results could be used to determine the optimal intervention time point for future income supplementation policies. Future work should examine frequent income supplementation such as the minimum wage or basic income programs.

What drives outcomes in infants of mothers with congenital heart disease? A mediation analysis.

OBJECTIVE: Infants of mothers with adult congenital heart disease (ACHD) are at increased risk for adverse pregnancy and neonatal outcomes. We aim to identify mediators in the relationship between ACHD and pregnancy and infant outcomes. STUDY DESIGN: Case-control study using linked maternal and infant hospital records. Structural equation modeling was performed to assess for potential mediators of pregnancy and infant outcomes. RESULT: We showed an increased risk of multiple adverse infant and pregnancy outcomes among infants born to mothers with ACHD. Maternal placental syndrome and congestive heart failure were mediators of prematurity. Prematurity and critical congenital heart disease in the infant were mediators of infant outcomes. However, the direct effect of ACHD on outcomes beyond that explained by these mediators remained significant. CONCLUSION: While significant mediators of infant and pregnancy outcomes were identified, there was a large direct effect of maternal ACHD. Further studies should aim to identify more factors that explain these infants' vulnerability.

Adverse Perinatal Outcomes and Postpartum Suicidal Behavior in California, 2013-2018.

Background: The objectives of this study were to describe trends in the prevalence of postpartum suicidal behaviors in California, 2013-2018, and to estimate associations between adverse perinatal outcomes and suicidal behaviors. Materials and Methods: We used data from a population-based cohort derived from all birth and fetal death certificates. Records were individually linked to maternal hospital discharge records for the years before and after delivery. We estimated the prevalence of postpartum suicidal ideation and attempt by year. Then, we estimated crude and adjusted associations between adverse perinatal outcomes and these suicidal behaviors. The sample included 2,563,288 records. Results: The prevalence of postpartum suicidal ideation and attempt increased from 2013 to 2018. People with postpartum suicidal behavior were younger, had less education, and were more likely to live in rural areas. A greater proportion of those with postpartum suicidal behavior were Black and publicly insured. Severe maternal morbidity, neonatal intensive care unit admission, and fetal death were associated with greater risk of ideation and attempt. Major structural malformation was not associated with either outcome. Conclusions: The burden of postpartum suicidal behavior has increased over time and is unequally distributed across population subgroups. Adverse perinatal outcomes may help identify individuals that could benefit from additional care during the postpartum period.

Reclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing.

Importance: Understanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood. Objective: To determine the association of genetic diseases with infant mortality. Design, Setting, and Participants: This cohort study was conducted at a large pediatric hospital system in San Diego County (California) and included 546 infants (112 infant deaths [20.5%] and 434 infants [79.5%] with acute illness who survived; age, 0 to 1 year) who underwent diagnostic whole-genome sequencing (WGS) between January 2015 and December 2020. Data analysis was conducted between 2015 and 2022. Exposure: Infants underwent WGS either premortem or postmortem with semiautomated phenotyping and diagnostic interpretation. Main Outcomes and Measures: Proportion of infant deaths associated with single-locus genetic diseases. Results: Among 112 infant deaths (54 girls [48.2%]; 8 [7.1%] African American or Black, 1 [0.9%] American Indian or Alaska Native, 8 [7.1%] Asian, 48 [42.9%] Hispanic, 1 [0.9%] Native Hawaiian or Pacific Islander, and 34 [30.4%] White infants) in San Diego County between 2015 and 2020, single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Thirty-nine (83%) of these diseases had been previously reported to be associated with childhood mortality. Twenty-eight death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology. Treatments that can improve outcomes were available for 14 (30%) of the genetic diseases. In 5 of 7 infants in whom genetic diseases were identified postmortem, death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission. Conclusions and Relevance: In this cohort study of 112 infant deaths, the association of genetic diseases with infant mortality was higher than previously recognized. Strategies to increase neonatal diagnosis of genetic diseases and immediately implement treatment may decrease infant mortality. Additional study is required to explore the generalizability of these findings and measure reduction in infant mortality.

Scalable, high quality, whole genome sequencing from archived, newborn, dried blood spots.

Universal newborn screening (NBS) is a highly successful public health intervention. Archived dried bloodspots (DBS) collected for NBS represent a rich resource for population genomic studies. To fully harness this resource in such studies, DBS must yield high-quality genomic DNA (gDNA) for whole genome sequencing (WGS). In this pilot study, we hypothesized that gDNA of sufficient quality and quantity for WGS could be extracted from archived DBS up to 20 years old without PCR (Polymerase Chain Reaction) amplification. We describe simple methods for gDNA extraction and WGS library preparation from several types of DBS. We tested these methods in DBS from 25 individuals who had previously undergone diagnostic, clinical WGS and 29 randomly selected DBS cards collected for NBS from the California State Biobank. While gDNA from DBS had significantly less yield than from EDTA blood from the same individuals, it was of sufficient quality and quantity for WGS without PCR. All samples DBS yielded WGS that met quality control metrics for high-confidence variant calling. Twenty-eight variants of various types that had been reported clinically in 19 samples were recapitulated in WGS from DBS. There were no significant effects of age or paper type on WGS quality. Archived DBS appear to be a suitable sample type for WGS in population genomic studies.