Vaginal microbiomes show ethnic evolutionary dynamics and positive selection of Lactobacillus adhesins driven by a long-term niche-specific process.

The vaginal microbiome's composition varies among ethnicities. However, the evolutionary landscape of the vaginal microbiome in the multi-ethnic context remains understudied. We perform a systematic evolutionary analysis of 351 vaginal microbiome samples from 35 multi-ethnic pregnant women, in addition to two validation cohorts, totaling 462 samples from 90 women. Microbiome alpha diversity and community state dynamics show strong ethnic signatures. Lactobacillaceae have a higher ratio of non-synonymous to synonymous polymorphism and lower nucleotide diversity than non-Lactobacillaceae in all ethnicities, with a large repertoire of positively selected genes, including the mucin-binding and cell wall anchor genes. These evolutionary dynamics are driven by the long-term evolutionary process unique to the human vaginal niche. Finally, we propose an evolutionary model reflecting the environmental niches of microbes. Our study reveals the extensive ethnic signatures in vaginal microbial ecology and evolution, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective.

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

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.

Sub-optimal maternal gestational gain is associated with shorter leukocyte telomere length at birth in a predominantly Latinx cohort of newborns.

OBJECTIVE: To assess in utero exposures associated with leukocyte telomere length (LTL) at birth and maternal LTL in a primarily Latinx birth cohort. STUDY DESIGN: Mothers and newborns were recruited postnatally before 24 h of life. Newborn LTL was collected via heelstick at birth and maternal LTL was collected postnatally. LTL was determined by quantitative PCR. Using a longitudinal design, we evaluated associations between neonatal and maternal LTL and appropriate maternal gestational gain as indicated by the American College of Obstetrics and Gynecology (ACOG). RESULT: Mean infant LTL was 2.02 ± 0.30 T/S (n = 386) and maternal LTL was 1.54 ± 0.26 T/S (n = 58). Independent risk factors for shorter LTL at birth included longer gestational duration (Coeff:-0.03, 95%CI: -0.05-0.01;p < 0.01) and maternal gestational weight gain below ACOG recommendations (Coeff:-0.10, 95%CI: -0.18 - -0.02; p = 0.01). CONCLUSION: Gestational weight gain below ACOG recommendations may adversely impact neonatal health in Latinx infants as indicated by shorter LTL at birth.

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.

Addressing anti-black racism in an academic preterm birth initiative: perspectives from a mixed methods case study.

BACKGROUND: Growing recognition of racism perpetuated within academic institutions has given rise to anti-racism efforts in these settings. In June 2020, the university-based California Preterm Birth Initiative (PTBi) committed to an Anti-Racism Action Plan outlining an approach to address anti-Blackness. This case study assessed perspectives on PTBi's anti-racism efforts to support continued growth toward racial equity within the initiative. METHODS: This mixed methods case study included an online survey with multiple choice and open-ended survey items (n = 27) and key informant interviews (n = 8) of leadership, faculty, staff, and trainees working within the initiative. Survey and interview questions focused on perspectives about individual and organizational anti-racism competencies, perceived areas of initiative success, and opportunities for improvement. Qualitative interview and survey data were coded and organized into common themes within assessment domains. RESULTS: Most survey respondents reported they felt competent in all the assessed anti-racism skills, including foundational knowledge and responding to workplace racism. They also felt confident in PTBi's commitment to address anti-Blackness. Fewer respondents were clear on strategic plans, resources allocated, and how the anti-racism agenda was being implemented. Suggestions from both data sources included further operationalizing and communicating commitments, integrating an anti-racism lens across all activities, ensuring accountability including staffing and funding consistent with anti-racist approaches, persistence in hiring Black faculty, providing professional development and support for Black staff, and addressing unintentional interpersonal harms to Black individuals. CONCLUSIONS: This case study contributes key lessons which move beyond individual-level and theoretical approaches towards transparency and accountability in academic institutions aiming to address anti-Black racism. Even with PTBi's strong commitment and efforts towards racial equity, these case study findings illustrate that actions must have sustained support by the broader institution and include leadership commitment, capacity-building via ongoing coaching and training, broad incorporation of anti-racism practices and procedures, continuous learning, and ongoing accountability for both short- and longer-term sustainable impact.

Cultural considerations and beliefs surrounding preterm birth in Kenya and South Africa.

BACKGROUND: Preterm birth (PTB) is a global health epidemic, sub-Saharan Africa is severely impacted due to its limited healthcare resources. Pregnancy knowledge, cultural beliefs and practices play a role in the identification of risk and management of PTB. This study explored knowledge, understandings, cultural beliefs and attitudes to pregnancy and PTB, as well as cultural considerations for the introduction of an intravaginal device which could be used to identify PTB risk. METHODS: Qualitative research was conducted in South Africa and Kenya. In-depth interviews were conducted using semi-structured guides with women with a history of PTB (n = 10), healthcare providers (n = 16) and health systems experts (n = 10); and 26 focus group discussions with pregnant women seeking antenatal care (n = 132) and community male partners/fathers (n = 54). Interviews/discussions were transcribed, translated, and analysed thematically. RESULTS: Pregnancy knowledge, especially for first time pregnancies was poor, with many reporting late entry to antenatal care. Knowledge about PTB was understood in terms of gestational age, weight or small size of baby, with concerns about long term health and stigma. Various risk factors for PTB were described, including those related to traditions and beliefs of witchcraft/curses. Cultural practices, such as the use of traditional medicines and pica, and religion and its impact on health seeking behaviour were also viewed as risk factors. Although insertion of intravaginal devices was not widely acceptable in traditional communities, especially during pregnancy, it was felt that the use of one to detect risk of PTB would be accepted if proven effective in reducing PTB risk. CONCLUSIONS: Various culturally-informed beliefs exist which explain understandings of and attitudes toward pregnancy, pregnancy risk, and PTB. An inclusive exploratory process is critical to facilitate an understanding of the beliefs and traditions which could impact the introduction and design of a product to detect the risk of PTB.

Adverse infant outcomes among women with sleep apnea or insomnia during pregnancy: A retrospective cohort study.

OBJECTIVE: To evaluate whether sleep apnea or insomnia among pregnant people is associated with increased risk for adverse infant outcomes. DESIGN: Retrospective cohort study SETTING: California PARTICIPANTS: The sample included singleton live births. Sleep apnea and insomnia were defined based on ICD-9 and -10 codes. A referent group was selected using exact propensity score matching on maternal characteristics, obstetric factors, and infant factors among individuals without a sleep disorder. MEASUREMENTS: Adverse infant outcomes were obtained from birth certificate, hospital discharge, and death records (eg, Apgar scores, neonatal intensive care unit (NICU) stay, infant death, long birth stay, etc.). Logistic regression was used to calculate odds of an adverse infant outcome by sleep disorder type. RESULTS: Propensity-score matched controls were identified for 69.9% of the 3371 sleep apnea cases and 68.8% of the 3213 insomnia cases. Compared to the propensity-matched referent group, individuals with a diagnosis of sleep apnea (n = 2357) had infants who were more likely to have any adverse outcome, low 1-min Apgar scores, NICU stay, and an emergency room visit in the first year of life. Infants born to mothers with a diagnosis of insomnia (n = 2212) were at increased risk of few negative outcomes relative to the propensity matched referent group, with the exception of an emergency room visit. CONCLUSIONS: In unadjusted analyses, infants born to individuals with a diagnosis of sleep apnea or insomnia were at increased risk of several adverse outcomes. These were attenuated when using propensity score matching, suggesting these associations were driven by other comorbidities.

Using Community-Based Participatory Research to Design a Patient and Practitioner-Centered Group Prenatal Care Model.

In response to disproportionately high rates of infant mortality and preterm birth among women of color and women in poverty in Fresno County, California, community and academic partners coordinated a community-based participatory research (CBPR) project with local residents. Social isolation and stress, inaccessible prenatal care, and dissatisfaction with care experiences were identified as leading predictors of poor birth outcomes. The PRECEDE-PROCEED framework was used to lead the CBPR effort that resulted in the development of a model of group prenatal care, named Glow! Group Prenatal Care Program (Glow! Program). Group prenatal care (GPNC), which focuses on pregnancy health assessments, education, and peer support, has the potential to address the health and social priorities of women during pregnancy. As a result of the employed CBPR process and the extensive participation from stakeholders, this modified GPNC model responds to the unique needs of the at-risk community members, the agencies aiming to improve maternal-child health experiences and outcomes, and the prenatal care providers offering it to their patients. The methods from this study can be applied in the design and implementation of community-based health care interventions. Returning to community partners throughout the design, implementation, and evaluation phases underscored that health care interventions cannot be designed in silos, and require flexibility to respond to factors that promote improved maternal and infant outcomes, which affect the end goal for the intervention.

Toward an intravaginal device to detect risk of preterm labor: a user-centered design approach in Sub-Saharan Africa.

BACKGROUND: Prematurity and its complications are the leading cause of death and disability in children under five in Africa and North America, affecting as many as one in ten pregnancies. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. In parallel with early-stage U.S.-based testing of a novel self-placed intravaginal device to predict PTB risk, we elicited key stakeholder input from two sub-Saharan African countries to ensure local contextual factors inform future development of the device and its acceptability. METHODS: A qualitative study was conducted in Kiambu County, Kenya and KwaZulu-Natal Province, South Africa. We conducted 26 focus group discussions with pregnant women (n = 132) and males from the community (n = 54); in-depth interviews with women who had a history of PTB (n = 10), healthcare providers (n = 16), and health system experts (n = 10). Interviews were transcribed and thematic analysis was performed using an iterative coding technique. In addition, we facilitated user-centered design sessions to generate prototype preferences. RESULTS: Women with a personal history of PTB were almost unanimous in support of the proposed device, whereas those with no experience of PTB expressed the greatest degree of reservation. Healthcare providers anticipated that women with a history of PTB would accept the device. However, various potential challenges were identified, including potential discomfort with device insertion, hygiene, and sexual activity, as well as need for provider training, and attention to country-specific regulatory processes. Both community participants and providers expressed a preference for a provider inserted device. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. CONCLUSIONS: Use of an intravaginal device to detect risk of PTB was generally acceptable, however stakeholders expressed a notable preference for insertion by providers. This reflects the significance of end-user consultation in device design and use. Recommended device modifications as well as educational messaging and provider technical assistance may facilitate utilization.

Prematurity and its complications are the leading cause of death and disability in children under 5 years of age. Up to ten percent of pregnancies in North America and Africa are affected. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. A U.S.-based study has developed an intravaginal device to detect preterm labor. In order to assess acceptability and guide development for a low-resource setting, a qualitative study was conducted in Kenya and South Africa. We conducted focus group discussions and interviews with pregnant women, male community members, health care providers and health systems experts. Participants with a personal history of PTB were almost unanimous in support of the proposed device; women with no experience of PTB expressed the greatest degree of reservation. Various potential challenges were identified: discomfort, hygiene, and sexual activity, the need for provider training and attention to country-specific regulatory processes. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. Stakeholders expressed a strong preference for insertion by providers. These findings reflect the significance of end-user consultation in device design and use.

Risk of early birth by body mass index in a propensity score-matched sample: A retrospective cohort study.

OBJECTIVE: Evaluate the risk of preterm (<37 weeks) or early term birth (37 or 38 weeks) by body mass index (BMI) in a propensity score-matched sample. DESIGN: Retrospective cohort analysis. SETTING: California, USA. POPULATION: Singleton live births from 2011-2017. METHODS: Propensity scores were calculated for BMI groups using maternal factors. A referent sample of women with a BMI between 18.5 and <25.0 kg/m2 was selected using exact propensity score matching. Risk ratios for preterm and early term birth were calculated. MAIN OUTCOME MEASURES: Early birth. RESULTS: Women with a BMI <18.5 kg/m2 were at elevated risk of birth of 28-31 weeks (relative risk [RR] 1.2, 95% CI 1.1-1.4), 32-36 weeks (RR 1.3, 95% CI 1.2-1.3), and 37 or 38 weeks (RR 1.1, 95% CI 1.1-1.1). Women with BMI ≥25.0 kg/m2 were at 1.2-1.4-times higher risk of a birth <28 weeks and were at reduced risk of a birth between 32 and 36 weeks (RR 0.8-0.9) and birth during the 37th or 38th week (RR 0.9). CONCLUSION: Women with a BMI <18.5 kg/m2 were at elevated risk of a preterm or early term birth. Women with BMI ≥25.0 kg/m2 were at elevated risk of a birth <28 weeks. Propensity score-matched women with BMI ≥30.0 kg/m2 were at decreased risk of a spontaneous preterm birth with intact membranes between 32 and 36 weeks, supporting the complexity of BMI as a risk factor for preterm birth. TWEETABLE ABSTRACT: Propensity score-matched women with BMI ≥30 kg/m2 were at decreased risk of a late spontaneous preterm birth.

NAFTNet retrospective report on the treatment of anti-Ro/SSA mediated fetal heart block with dexamethasone.

BACKGROUND: Complete atrioventricular block (CAVB) is a complication of maternal antibody positivity and treatment of fetal disease is controversial in terms of efficacy and safety. We hypothesized that dexamethasone treatment for fetal anti-Ro/SSA antibody-mediated cardiac disease leads to better pregnancy outcomes than expectant management. METHODS: A retrospective multi-center cohort study of anti-Ro/SSA antibody positive pregnancies with fetal conduction disease reported by participating North American Fetal Therapy Network (NAFTNet) centers between January 2010 and December 2018. The primary outcomes included: fetal death, oligohydramnios, growth restriction, preterm delivery, and new maternal comorbidities. Secondary outcomes included: pacemaker prior to 28 days, transplantation, and neonatal death in maternal/fetal dyads treated with dexamethasone versus not. RESULTS: In 127 anti-Ro/SSA positive pregnancies, 98 were treated with dexamethasone and 29 were not. Of those treated, 61/96 (63.5%) met the primary outcome including 45/91 (49.4%) premature deliveries; 20 mothers developed comorbidities during treatment (fetal death 5, 10 growth restriction, 14 oligohydramnios, two new/worsening gestational diabetes). In the untreated group, 15/25 (60%) met the primary outcome including 11/22 (50%) premature deliveries and four mothers developing comorbidities during their pregnancy (fetal death 3, one growth restriction, one new onset maternal hypertension). Regarding secondary outcomes, 37/96 (43%) treated fetuses required a pacemaker or died by 28 days, while untreated 13/25 (52%) required pacemaker placement, died prior to 28 days or required listing for transplantation. Excluding terminations, survival without transplant was 17 (68%) in untreated and 85 (89%) in treated patients (p<.01). CONCLUSIONS: While the use of dexamethasone in anti-Ro/SSA positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was an unexpected similarly high rate in untreated positive pregnancies. This suggests that the maternal disease itself is influencing pregnancy complications independent of dexamethasone. Our data, which show that treatment decreases neonatal morbidity and overall mortality without increasing overall pregnancy complications, warrant further study.

Racial disparities in emergency mental healthcare utilization among birthing people with preterm infants.

BACKGROUND: Birthing people of color are more likely to deliver low birthweight and preterm infants, populations at significant risk of morbidity and mortality. Birthing people of color are also at higher risk for mental health conditions and emergency mental healthcare utilization postpartum. Although this group has been identified as high risk in these contexts, it is not known whether racial and ethnic disparities exist in mental healthcare utilization among birthing people who have delivered preterm. OBJECTIVE: We sought to determine if racial and ethnic disparities exist in postpartum mental healthcare-associated emergency department visits or hospitalizations for birthing people with preterm infants in a large and diverse population. STUDY DESIGN: This population-based historic cohort study used a sample of Californian live-born infants born between 2011 and 2017 with linked birth certificates and emergency department visit and hospital admission records from the California Statewide Health Planning and Development database. The sample was restricted to preterm infants (<37 weeks' gestation). Self-reported race and ethnicity groups included Hispanic, non-Hispanic Black, non-Hispanic Asian, non-Hispanic White, and non-Hispanic others. Mental health diagnoses were identified from the International Classification of Diseases Ninth and Tenth revision codes recorded in emergency department and hospital discharge records. Logistic regression analysis was used to estimate the association between mental health-related emergency department visits and rehospitalizations by race or ethnicity compared with non-Hispanic White birthing people and controlling for the following characteristics and health condition covariates: age, parity, previous preterm birth, body mass index, smoking, alcohol use, hypertension, diabetes, previous mental health diagnosis, and prenatal care. RESULTS: Of 204,539 birthing people who delivered preterm infants in California, 1982 visited the emergency department and 836 were hospitalized in the first year after preterm birth for a mental health-related illness. Black birthing people were more likely to have a mental health-related emergency department visit and hospitalization (risk ratio, 1.8; 95% confidence interval, 1.5-2.0 and risk ratio, 1.9; 95% confidence interval, 1.5-2.3, respectively) within the first postpartum year than White birthing people. Hispanic and Asian birthing people were less likely to have mental health-related emergency department visits (adjusted risk ratio, 0.7; 95% confidence interval, 0.7-0.8 and adjusted risk ratio, 0.2; 95% confidence interval, 0.2-0.3, respectively) and hospitalizations (adjusted risk ratio, 0.6; 95% confidence interval, 0.5-0.7 and adjusted risk ratio, 0.2; 95% confidence interval, 0.1-0.3, respectively). When controlling for birthing people with a previous mental health diagnosis and those without, the disparities remained the same. CONCLUSION: Racial and ethnic disparities exist in emergency mental healthcare escalation among birthing people who have delivered preterm infants. Our findings highlight a need for further investigation into disparate mental health conditions, exacerbations, access to care, and targeted hospital and legislative policies to prevent emergency mental healthcare escalation and reduce disparities.

Systematic review of transcriptome and microRNAome associations with gestational diabetes mellitus.

Purpose: Gestational diabetes (GDM) is associated with increased risk for preterm birth and related complications for both the pregnant person and newborn. Changes in gene expression have the potential to characterize complex interactions between genetic and behavioral/environmental risk factors for GDM. Our goal was to summarize the state of the science about changes in gene expression and GDM. Design: The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: PubMed articles about humans, in English, from any date were included if they described mRNA transcriptome or microRNA findings from blood samples in adults with GDM compared with adults without GDM. Results: Sixteen articles were found representing 1355 adults (n=674 with GDM, n=681 controls) from 12 countries. Three studies reported transcriptome results and thirteen reported microRNA findings. Identified pathways described various aspects of diabetes pathogenesis, including glucose and insulin signaling, regulation, and transport; natural killer cell mediated cytotoxicity; and fatty acid biosynthesis and metabolism. Studies described 135 unique miRNAs that were associated with GDM, of which eight (miR-16-5p, miR-17-5p, miR-20a-5p, miR-29a-3p, miR-195-5p, miR-222-3p, miR-210-3p, and miR-342-3p) were described in 2 or more studies. Findings suggest that miRNA levels vary based on the time in pregnancy when GDM develops, the time point at which they were measured, sex assigned at birth of the offspring, and both the pre-pregnancy and gestational body mass index of the pregnant person. Conclusions: The mRNA, miRNA, gene targets, and pathways identified in this review contribute to our understanding of GDM pathogenesis; however, further research is warranted to validate previous findings. In particular, longitudinal repeated-measures designs are needed that control for participant characteristics (e.g., weight), use standardized data collection methods and analysis tools, and are sufficiently powered to detect differences between subgroups. Findings may be used to improve early diagnosis, prevention, medication choice and/or clinical treatment of patients with GDM.

The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California.

INTRODUCTION: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic medical conditions is limited. METHODS: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB. FINDINGS: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI [1.4, 1.9]), PTB (aRR 1.4, 95% CI [1.3, 1.4]), and early term birth (aRR 1.1, 95% CI [1.1, 1.2]). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity. INTERPRETATION: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons. FUNDING: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) [K12 HD052163] and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.

Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Selenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations. METHODS: Gestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis. FINDINGS: In all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi. INTERPRETATION: While our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered.

Mortality and Major Neonatal Morbidity in Preterm Infants with Serious Congenital Heart Disease.

OBJECTIVE: To investigate the trends of 1-year mortality and neonatal morbidities in preterm infants with serious congenital heart disease (CHD). STUDY DESIGN: This cohort study used a population-based administrative dataset of all liveborn infants of 26-36 weeks gestational age with serious CHD born in California between 2011 and 2017. We assessed 1-year mortality and major neonatal morbidities (ie, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage grade >2, and periventricular leukomalacia) across the study period and compared these outcomes with those in infants without CHD. RESULTS: We identified 1921 preterm infants with serious CHD. The relative risk (RR) of death decreased by 10.6% for each year of the study period (RR, 0.89; 95% CI, 0.84-0.95), and the RR of major neonatal morbidity increased by 8.3% for each year (RR, 1.08; 95% CI, 1.02-1.15). Compared with preterm neonates without any CHD (n = 234 522), the adjusted risk difference (ARD) for mortality was highest at 32 weeks of gestational age (9.7%; 95% CI, 8.3%-11.2%), that for major neonatal morbidity was highest at 28 weeks (21.9%; 95% CI, 17.0%-26.9%), and that for the combined outcome was highest at 30 weeks (26.7%; 95% CI, 23.3%-30.1%). CONCLUSIONS: Mortality in preterm neonates with serious CHD decreased over the last decade, whereas major neonatal morbidities increased. Preterm infants with a gestational age of 28-32 weeks have the highest mortality or morbidity compared with their peers without CHD. These results support the need for specialized and focused medical neonatal care in preterm neonates with serious CHD.

Maternal nativity and risk of adverse perinatal outcomes among Black women residing in California, 2011-2017.

OBJECTIVE: Examine the risk of adverse perinatal outcomes among the United States (US)-born and foreign-born Black women in California. STUDY DESIGN: The study comprised all singleton live births to Black women in California between 2011 and 2017. We defined maternal nativity as US-born or foreign-born. Using Poisson regression, we computed risk ratios (RR) and 95% confidence intervals (CI) for three adverse perinatal outcomes: preterm birth, small for gestational age deliveries, and infant mortality. RESULTS: Rates of adverse perinatal outcomes were significantly higher among US-born Black women. In adjusted models, US-born Black women experienced an increased risk of preterm birth (RR 1.51, 95% CI 1.39, 1.65) and small for gestational age deliveries (RR 1.52, 95% CI 1.41, 1.64), compared to foreign-born Black women. CONCLUSIONS: Future studies should consider experiences of racism across the life course when exploring heterogeneity in the risk of adverse perinatal outcomes by nativity among Black women in the US.

Association of Maternal Immune Activation during Pregnancy and Neurologic Outcomes in Offspring.

OBJECTIVE: To evaluate neurologic morbidity among offspring during their first year of life in association with prenatal maternal immune activation (MIA), using an inclusive definition. STUDY DESIGN: This retrospective cohort study included singletons born in California between 2011 and 2017. MIA was defined by International Classification of Diseases diagnosis of infection, autoimmune disorder, allergy, asthma, atherosclerosis, or malignancy during pregnancy. Neurologic morbidity in infants was defined by International Classification of Diseases diagnosis of intraventricular hemorrhage, periventricular leukomalacia, seizures, abnormal neurologic examination, or abnormal neurologic imaging. Outcomes of delayed developmental milestones during the first year of life were also explored. Risk of neurologic morbidity in offspring was approximated for women with and without MIA using log link binary regression. RESULTS: Demographic characteristics among 3 004 166 mother-infant dyads with or without MIA were similar in both groups. Rate of preterm delivery in mothers with MIA (9.4%) was significantly higher than those without MIA (5.6%). Infants of mothers with MIA were more likely to experience neurologic morbidities across all gestational ages. Adjusted relative risk (95% CI) in the exposed infants was 2.0 (1.9-2.1) for abnormal neurologic examination; 1.6 (1.5-1.7) for seizures, and 1.6 (1.4-1.8) for periventricular leukomalacia. CONCLUSIONS: Our results demonstrate that MIA during pregnancy may be associated with considerably higher risk of neurologic morbidity in offspring.

The association between preterm birth and postpartum mental healthcare utilization among California birthing people.

BACKGROUND: While mental health conditions such as postpartum depression are common, little is known about how mental healthcare utilization varies after term versus preterm delivery. OBJECTIVE: This study aimed to determine whether preterm birth is associated with postpartum inpatient and emergency mental healthcare utilization. STUDY DESIGN: The study sample was obtained from a database of live-born neonates delivered in California between the years of 2011 and 2017. The sample included all people giving birth to singleton infants between the gestational age of 20 and 44 weeks. Preterm birth was defined as <37 weeks' gestation. Emergency department visits and hospitalizations with a mental health diagnosis within 1 year after birth were identified using International Classification of Diseases codes. Logistic regression was used to compare relative risks of healthcare utilization among people giving birth to preterm infants vs term infants, adjusting for the following covariates: age, race or ethnicity, parity, previous preterm birth, body mass index, tobacco use, alcohol or drug use, hypertension, diabetes mellitus, adequacy of prenatal care, education, insurance payer, and the presence of a mental health diagnosis before birth. Results were then stratified by mental health diagnosis before birth to determine whether associations varied based on mental health history. RESULTS: Of our sample of 3,067,069 births, 6.7% were preterm. In fully adjusted models, compared with people giving birth to term infants, people giving birth to preterm infants had a 1.5 times (relative risk; 95% confidence interval, 1.4-1.7) and 1.3 times (relative risk; 95% confidence interval, 1.2-1.4) increased risk of being hospitalized with a mental health diagnosis within 3 months and 1 year after delivery, respectively. People giving birth to preterm infants also had 1.4 times (95% confidence interval, 1.3-1.5) and 1.3 times (95% confidence interval, 1.2-1.4) increased risk of visiting the emergency department for a mental health diagnosis within 3 months and 1 year after birth, respectively. Stratifying by preexisting mental health diagnosis, preterm birth was associated with an elevated risk of mental healthcare utilization for people with and without a previous mental health diagnosis. CONCLUSION: We found that preterm birth is an independent risk factor for postpartum mental healthcare utilization. Our findings suggest that screening for and providing mental health resources to birthing people after delivery are crucial, particularly among people giving birth to preterm infants, regardless of mental health history.