Search

Background: Perinatal mental health conditions are the most common complication of pregnancy and childbirth (1 in 8 women). When left untreated, perinatal depression and anxiety adversely affects the entire family with pregnancy complications and negative outcomes including preterm birth, impaired mother-infant bonding, impaired lactation, substance abuse, divorce, suicide, and infanticide. Significant disparities persist in the diagnosis and treatment of perinatal depression and anxiety and these inequities are often intersectional. Preliminary research with stakeholders including community advisory boards, underrepresented and minority birthing people, and state departments of health, demonstrates the importance of social support as a mechanism for reducing disparities in perinatal depression, particularly in rural geographies. Home visiting programs (HVPs) can provide the social support needed to improve mental health outcomes in pregnant and postpartum women. Our project aims to explore the impact of context on the implementation of a mental health intervention, focusing on the lived experiences of diverse populations served by HVPs to reduce disparities in adverse maternal outcomes. Methods: Using implementation facilitation, our study will engage multilevel stakeholders (e.g., policymakers, front-line implementers, and intervention recipients) to adapt facilitation to integrate a maternal mental health intervention (i.e., Mothers and Babies) across two midwestern, rural states (Iowa and Indiana) with multiple HVP models. Given the complexity and heterogeneity of the contexts in which Mothers and Babies will be integrated, a three variable hybrid implementation-effectiveness-context trial will test the adapted facilitation strategy compared with implementation as usual (i.e., standard education) and will assess contextual factors related to the outcomes. Using an evidence-based implementation strategy that tailors implementation delivery to the needs of the specific populations and context may improve fidelity and adoption, particularly in rural states where residents have limited access to care. Discussion: The immediate impact of this research will be to show whether adapted facilitation can improve the uptake and fidelity of Mothers and Babies across multiple HVP models and thus positively affect depressive symptoms and perceived stress of recipients. Our implementation protocol may be used by researchers, practitioners, and policy makers to better integrate evidence-based interventions into diverse contexts, leading to more equitable implementation and improved health outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT06575894, registered on August 29, 2024 https://clinicaltrials.gov/study/NCT06575894?id=NCT06575894&rank=1. [ABSTRACT FROM AUTHOR]

Introduction Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (1) the characteristics of smokers who begin using electronic cigarettes (ECs) during pregnancy, (2) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (3) the risk for neonatal health complications among smokers who initiate ECs during pregnancy. Aims and Methods Pregnant women using CCs exclusively during prepregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified as dual users (used both ECs and CCs) or EC replacers (used ECs exclusively). Results Of 29 505 pregnant smokers, 1.5% reported using ECs during the last three pregnancy months. Among them, 29.7% became EC-exclusive users. EC initiators were disproportionately non-Hispanic White. Relative to quitters, EC initiators had lower income, were less likely to be married, have intended pregnancies, receive first-trimester prenatal care, and participate in a federal assistance program. Compared to CC-exclusive users, EC initiators overall, and dual users specifically, were more likely to reduce pre- and post-natal CC usage relative to prepregnancy levels. EC initiators' risk for neonatal health complications fell between quitters and CC-exclusive users, though the differences were not statistically significant. Conclusions Although EC initiators reduced CC use more than CC-exclusive users, only 29.7% reported complete CC cessation, and there was insufficient evidence of reduction in neonatal health complications relative to CC-exclusive users. Currently, ECs should not be considered a viable gestational smoking cessation strategy. Implications Health agencies have identified a critical need for research evaluating the use of e-cigarettes in supporting prenatal smoking cessation. Using the U.S. Pregnancy Risk Assessment Monitoring System surveillance study data, we provide real-world evidence that prenatal e-cigarette initiation as a smoking cessation tool is used infrequently among pregnant CCs smokers. Most using e-cigarettes in the last 3 months of pregnancy also used CCs. [ABSTRACT FROM AUTHOR]

PURPOSE Currently, 40% of counties in the United States do not have an obstetrician or midwife, and in rural areas the likelihood of childbirth being attended to by a family medicine (FM) physician is increasing. We sought to characterize the effect of the FM presence on unit culture and a key perinatal quality metric in Iowa hospital intrapartum units. METHODS Using a cross-sectional design, we surveyed Iowa physicians, nurses, and midwives delivering intrapartum care at hospitals participating in a quality improvement initiative to decrease the incidence of cesarean delivery. We linked respondents with their hospital characteristics and outcomes data. The primary outcome was the association between FM physician, obstetrician (OB), or both disciplines’ presence on labor and delivery and hospital low-risk, primary cesarean delivery rate. Unit culture was compared by hospital type (FMonly, OB-only, or Both). RESULTS A total of 849 clinicians from 39 hospitals completed the survey; 13 FM-only, 11 OB-only, and 15 hospitals with both. FM-only hospitals were all rural, with <1,000 annual births. Among hospitals with <1,000 annual births, births at FM-only hospitals had an adjusted 34.3% lower risk of cesarean delivery (adjusted incident rate ratio = 0.66; 95% CI, 0.52-.0.98) compared with hospitals with both. Nurses endorsed unit norms more supportive of vaginal birth and stronger safety culture at FM-only hospitals (P <.05). CONCLUSIONS Birthing hospitals staffed exclusively by FM physicians were more likely to have lower cesarean rates and stronger nursing-rated safety culture. Both access and quality of care provide strong arguments for reinforcing the pipeline of FM physicians training in intrapartum care. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with Turner syndrome (TS) are at increased risk of developing diabetes mellitus (DM). Currently, annual DM screening with hemoglobin A1c (HbA1c) with or without fasting blood glucose (FBG) is recommended starting at age 10. However, the optimal DM screening for individuals with TS is not known. The purpose of this study was to evaluate the correlation between HbA1c, FBG, and the 2-h oral glucose tolerance test (OGTT). A second goal was to query whether optimal HbA1c and FBG cut points for TS-associated DM and impaired glucose tolerance (IGT), as defined by the OGTT 2-h blood glucose (BG), might differ from those for the general population. Methods: Individuals with TS ≥ age 10 from the TS: Genotype Phenotype study in the National Institute of Child Health and Human Development's Data and Specimen Hub (DASH) who had 2-h OGTT BG, HbA1c, and FBG were included. Correlations between HbA1c, FBG, and 2-h OGTT BG were evaluated. Areas under the receiver operative characteristic (ROC-AUC) curves were generated. Optimal cut points for predicting TS-associated IGT (2-h BG ≥7.77 mmol/L) and DM (2-h BG ≥11.10 mmol/L) were determined. Results: 348 individuals had complete data (2-h OGTT BG <7.77 mmol/L, n = 239; TS-associated IGT, n = 79; DM, n = 30). ROC-AUC was poor for HbA1c to predict IGT (0.57, 0.49–0.65) but better for DM (0.81, 0.71–0.90). ROC-AUC was also poor for FBG to predict IGT (0.63, 0.56–0.70) but better for DM (0.85, 0.77–0.93). At a cut point of 38 mmol/mol (5.6%), HbA1c had 67% sensitivity (95% CI: 47–83%) and 86% specificity (95% CI: 82–90%) for identifying TS-associated DM defined by 2-h OGTT BG. Conclusions: The correlation of HbA1c and 2-h OGTT BG is lower in TS than in other published studies regarding type 2 DM. HbA1c is fairly specific for DM in TS but lacks sensitivity, especially at currently utilized levels. Future research should focus on characterizing individuals with TS whose glycemic status is discordant, as this may provide additional insights into the pathophysiology of glucose metabolism in TS. Longitudinal assessment of glycemia as it relates to micro- and macrovascular complications in individuals with TS will further inform DM screening in this population. [ABSTRACT FROM AUTHOR]

Newborn metabolite perturbations may identify potential biomarkers or mechanisms underlying adverse, smoking-related childhood health outcomes. We assessed associations between third-trimester smoking and newborn metabolite concentrations using the Tennessee Pregnancy Risk Assessment Monitoring System (PRAMS, 2009–2019) as the discovery cohort and INSPIRE (2012–2014) as the replication cohort. Children were linked to newborn screening metabolic data (33 metabolites). Third-trimester smoking was ascertained from birth certificates (PRAMS) and questionnaires (INSPIRE). Among 8600 and 1918 mother–child dyads in PRAMS and INSPIRE cohorts, 14% and 13% of women reported third-trimester smoking, respectively. Third-trimester smoking was associated with higher median concentrations of free carnitine (C0), glycine (GLY), and leucine (LEU) at birth (PRAMS: C0: adjusted fold change 1.11 [95% confidence interval (CI) 1.08, 1.14], GLY: 1.03 [95% CI 1.01, 1.04], LEU: 1.04 [95% CI 1.03, 1.06]; INSPIRE: C0: 1.08 [95% CI 1.02, 1.14], GLY: 1.05 [95% CI 1.01, 1.09], LEU: 1.05 [95% CI 1.01, 1.09]). Smoking cessation (vs. continued smoking) during pregnancy was associated with lower median metabolite concentrations, approaching levels observed in infants of non-smoking women. Findings suggest potential pathways underlying fetal metabolic programming due to in utero smoke exposure and a potential reversible relationship of cessation. [ABSTRACT FROM AUTHOR]

Background: Research on health effects and potential harms of electronic cigarette (EC) use during pregnancy is limited. We sought to determine the risks of pregnancy EC use on pregnancy-related adverse birth outcomes and assess whether quitting ECs reduces the risks. Methods: Women with singleton live births who participated in the US Pregnancy Risk Assessment Monitoring System (PRAMS) survey study 2016–2020 were classified into four mutually exclusive groups, by their use of ECs and combustible cigarettes (CCs) during pregnancy: non-use, EC only use, CC only use, and dual use. We determined the risk of preterm birth, low birth weight, and small-for-gestational-age (SGA) by comparing cigarette users to non-users with a modified Poisson regression model adjusting for covariates. In a subset of women who all used ECs prior to pregnancy, we determined whether quitting EC use reduces the risk of preterm birth, low birth weight, and SGA by comparing to those who continued its use. All analyses were weighted to account for the PRAMS survey design and non-response rate. Results: Of the 190,707 women (weighted N = 10,202,413) included, 92.1% reported cigarette non-use, 0.5% EC only use, 6.7% CC only use, and 0.7% dual use during pregnancy. Compared with non-use, EC only use was associated with a significantly increased risk of preterm birth (adjusted risk ratio [aRR]: 1.29, 95% confidence interval [CI]: 1.00, 1.65) and low birth weight (aRR: 1.38, 95%CI: 1.09, 1.75), but not SGA (aRR: 1.04, 95%CI: 0.76, 1.44). Among 7,877 (weighted N = 422,533) women EC users, quitting use was associated with a significantly reduced risk of low birth weight (aRR: 0.76, 95%CI: 0.62, 0.94) and SGA (aRR: 0.77, 95%CI: 0.62, 0.94) compared to those who continued to use ECs during pregnancy. Conclusions: Pregnancy EC use, by itself or dual use with CC, is associated with preterm birth and low birth weight. Quitting use reduces that risk. ECs should not be considered as a safe alternative nor a viable gestational smoking cessation strategy. [ABSTRACT FROM AUTHOR]

Objective: In a large multi-racial/ethnic cohort of women, we examined racial/ethnic disparities in preterm birth (PTB) risk stratified by autoimmune rheumatic disease (ARD) type, which included systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: Birth records linked to hospital discharge data of singleton births in California from 2007 to 2012 were leveraged for a retrospective cohort study including women with SLE or RA. The relative risk of PTB (< 37 versus ≥ 37 weeks' gestation) was compared among different racial/ethnic groups (Asian, Hispanic, Non-Hispanic (NH) Black, and NH White) and stratified by ARD type. Results were adjusted for relevant covariates using Poisson regression. Results: We identified 2874 women with SLE and 2309 women with RA. NH Black, Hispanic, and Asian women with SLE were 1.3 to 1.5 times more likely to have PTB compared to NH White women. NH Black women with RA were 2.0 to 2.4 times more likely to have PTB compared to Asian, Hispanic, or NH White women. The NH Black-NH White and NH Black-Hispanic disparity in PTB risk was significantly higher in women with RA compared to SLE or the general population. Conclusion: Our findings highlight the racial/ethnic disparities for risk of PTB among women with SLE or RA and highlight that several of the disparities are higher for women with RA compared to those with SLE or the general population. These data may provide important public health information for addressing racial/ethnic disparities in the risk of preterm birth, particularly among women with RA. Key Points • There is an unmet need for studies that evaluate racial/ethnic disparities in birth outcomes specifically in women with RA or SLE. • This is one of the first studies describing racial/ethnic disparities in PTB risk for women with RA, and to draw conclusions regarding Asian women in the USA with rheumatic diseases and PTB. • These data provide important public health information for addressing racial/ethnic disparities in the risk of preterm birth among women with autoimmune rheumatic diseases. [ABSTRACT FROM AUTHOR]

Purpose: Closure of rural Labor & Delivery (L&D) units can impact timely access to hospital‐based obstetrical care. Iowa has lost over a quarter of its L&D units in the previous decade. Assessing the effect of these closures on prenatal care in those rural communities is important to understanding the full effect of unit closures on maternal health care. Methods: Using birth certificate data in Iowa from 2017 to 2019, the initiation of prenatal care and adequacy of prenatal visits were assessed for 47 rural counties in Iowa. Of these, 7 experienced a closure of the only L&D unit between 1/1/2018 and 1/1/2019. The impact of these closures is modeled for all birthing parents and compared for Medicaid versus non‐Medicaid recipients. Findings: All 7 counties that experienced the loss of their only L&D unit continued to have prenatal care services available. Experiencing a closure of an L&D unit was associated with a lower likelihood of overall adequate prenatal care but not significantly associated with a lower rate of first‐trimester prenatal care utilization. Among Medicaid recipients of the communities where an L&D unit closed, there was an association of closure with both a lower likelihood of adequate prenatal care and entry to prenatal care after the first trimester. Conclusions: Utilization of prenatal care is lower in rural communities following L&D unit closure, especially among Medicaid recipients. This suggests that the overall maternal health systems were disrupted by the closure of the L&D unit, impacting the utilization of services that remained available to the community. [ABSTRACT FROM AUTHOR]

We aimed first to assess associations between maternal health characteristics and newborn metabolite concentrations and second to assess associations between metabolites associated with maternal health characteristics and child body mass index (BMI). This study included 3492 infants enrolled in three birth cohorts with linked newborn screening metabolic data. Maternal health characteristics were ascertained from questionnaires, birth certificates, and medical records. Child BMI was ascertained from medical records and study visits. We used multivariate analysis of variance, followed by multivariable linear/proportional odds regression, to determine maternal health characteristic-newborn metabolite associations. Significant associations were found in discovery and replication cohorts of higher pre-pregnancy BMI with increased C0 and higher maternal age at delivery with increased C2 (C0: discovery: aβ 0.05 [95% CI 0.03, 0.07]; replication: aβ 0.04 [95% CI 0.006, 0.06]; C2: discovery: aβ 0.04 [95% CI 0.003, 0.08]; replication: aβ 0.04 [95% CI 0.02, 0.07]). Social Vulnerability Index, insurance, and residence were also associated with metabolite concentrations in a discovery cohort. Associations between metabolites associated with maternal health characteristics and child BMI were modified from 1–3 years (interaction: p < 0.05). These findings may provide insights on potential biologic pathways through which maternal health characteristics may impact fetal metabolic programming and child growth patterns. [ABSTRACT FROM AUTHOR]

Patient decisions to bypass the closest labor & delivery (L&D) facility in favor of other birthing locations can have consequences for the provision of health care in rural and micropolitan areas as patient volumes decline and payer mixes change. Among 220 589 uncomplicated births in Iowa, we document characteristics of birth parents who bypass their closest birthing facility, show how this bypassing behavior results in changed travel times to delivery facilities across the rural/urban divide, and indicate the parts of the state where bypassing behavior is most prevalent. From 2013 to 2019, 55.2% of deliveries occurred in facilities that were further from birthing parents' residences than the closest L&D facility. Bypassing is associated with White, non‐Hispanic race/ethnicity, and private insurance status. Although bypassing is least common among micropolitan birth parents, this group has the greatest travel burden to birthing facilities and exhibits increasing rates of bypassing over time. Perinatal quality improvement programs can target locations and populations where low‐risk birthing parents can be encouraged to deliver close to home if medically appropriate, particularly in small towns and rural areas. This can potentially alleviate the risk of obstetric deserts by ensuring L&D units maintain patient volumes necessary to continue operations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Continued closure of rural hospitals and labor & delivery units can impact timely access to care. Iowa has lost over a quarter of its labor & delivery units in the previous decade. Calculating how travel times to labor & delivery services have changed, and where in the state the largest travel times take place, are important for understanding access to this critical service. Methods: Using parental address and facility location from birth certificate data in Iowa from 2013 to 2019, travel times to birth facility are assessed for rural, micropolitan, and metropolitan parents, as well as for complicated versus noncomplicated births and Medicaid versus non‐Medicaid recipients. Findings: Parts of the state have travel times that are consistently greater than 30 minutes over the duration of the study. The largest increases in travel times are found among micropolitan residents, particularly those experiencing complicated births. Travel times are consistently the longest for rural residents but increased only slightly over the study time period. Conclusions: These findings suggest that access to hospital‐based obstetric care is most changed for residents of small towns rather than rural or larger city residents. [ABSTRACT FROM AUTHOR]

Background: Neonatal risk factors, such as preterm birth and low birth weight, have been robustly linked to neurodevelopmental deficits, yet it is still unclear why some infants born preterm and/or low birth weight experience neurodevelopmental difficulties while others do not. The current study investigated this heterogeneity in neurodevelopmental abilities by examining additional neonatal morbidities as risk factors, utilizing latent class analysis to classify neonates into groups based on similar neonatal risk factors, and including neonates from the full spectrum of gestational age. Methods: Neonates who received neonatal care at an academic public hospital during an almost 10‐year period (n = 19,951) were included in the latent class analysis, and 21 neonatal indicators of health were used. Neonatal class, sex, and the interaction between neonatal class and sex were used to examine differences in neurodevelopment at 18 months of age in a typically developing population. Results: The best fitting model included five infant classes: healthy, hypoxic, critically ill, minorly ill, and complicated delivery. Scores on the parent‐rated neurodevelopmental measure differed by class such that infants in the critically ill, minorly ill, and complicated delivery classes had lower scores. There was no main effect of sex on the neurodevelopmental measure scores, but the interaction between sex and neonatal class was significant for three out of five neurodevelopmental domains. Conclusions: The current study extends the understanding of risk factors in neurodevelopment by including several neonatal medical conditions that are often overlooked and by using a person‐centered, as opposed to variable‐centered, approach. Future work should continue to examine risk factors, such as maternal health during pregnancy and medical interventions for newborns, in relation to neonatal risks and neurodevelopment by using a person‐centered approach. [ABSTRACT FROM AUTHOR]

Objective: Leukemia and lymphoma are top cancers affecting children, adolescents and young adults with high five-year survival rates. Late effects of these cancers are a concern in reproductive-age patients, including pregnancy outcomes such as preterm birth. Our study aimed to evaluate whether diagnosis of leukemia or lymphoma prior to pregnancy was associated with preterm birth (<37 weeks gestation). Methods: We conducted a cross-sectional study using a population-based dataset from California with linked birth certificates to hospital discharge records and an Iowa-based sample that linked birth certificates to Surveillance, Epidemiology, and End Results (SEER) cancer registry data. Preterm birth was defined using birth certificates. We ascertained history of leukemia and lymphoma using discharge diagnosis data in California and SEER registry in Iowa. Results: Prevalence of preterm birth in California and Iowa was 14.6% and 12.0%, respectively, in women with a history of leukemia/lymphoma compared to 7.8% and 8.2%, respectively, in women without a cancer history. After adjusting for maternal age, race, education, smoking, and plurality, Women with history of leukemia/lymphoma were at an increased risk of having a preterm birth in California (odds ratio (OR) 1.89; 95% confidence interval (CI) 1.56–2.28) and Iowa (OR 1.61; 95% CI 1.10–2.37) compared to those with no cancer history. Conclusion: In both California and Iowa, women with a history of leukemia or lymphoma were at increased risk for preterm birth. This suggests the importance of counseling with a history of leukemia/lymphoma prior to pregnancy and increased monitoring of women during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether socioeconomic status (SES) and small birthweight for gestational age (SGA) exhibit independent or joint effects on infant levels of 42 metabolites. Study design: Population-based retrospective cohort of metabolic newborn screening information linked to hospital discharge data. SGA infants defined by birthweight <10th percentile for gestational age by sex. SES was determined by a combined metric including education level, participation in the WIC nutritional assistance program, and receiving California MediCal insurance. We performed linear regression to determine the effects of SES independently, SGA independently, and the interaction of SGA and SES on 42 newborn metabolite levels. Results: 736,435 California infants born in 2005–2011 were included in the analysis. SGA was significantly associated with 36 metabolites. SES was significantly associated with 41 of 42 metabolites. Thirty-eight metabolites exhibited a dose-response relationship between SGA and metabolite levels as SES worsened. Fourteen metabolites showed significant interaction between SES and SGA. Eight metabolites showed significant individual and joint effects of SES and SGA: alanine, glycine, free carnitine, C-3DC, C-5DC, C-16:1, C-18:1, and C-18:2. Conclusions: SES and SGA exhibited independent effects on a majority of metabolites and joint effects on select metabolites. A better understanding of how SES and SGA status are related to infant metabolites may help identify maternal and newborn interventions that can lead to better outcomes for infants born SGA. [ABSTRACT FROM AUTHOR]

Background: Leukemia and lymphoma are cancers affecting children, adolescents, and young adults and may affect reproductive outcomes and maternal metabolism. We evaluated for metabolic changes in newborns of mothers with a history of these cancers. Methods: A cross-sectional study was conducted on California births from 2007 to 2011 with linked maternal hospital discharge records, birth certificate, and newborn screening metabolites. History of leukemia or lymphoma was determined using ICD-9-CM codes from hospital discharge data and newborn metabolite data from the newborn screening program. Results: A total of 2,068,038 women without cancer history and 906 with history of leukemia or lymphoma were included. After adjusting for differences in maternal age, infant sex, age at metabolite collection, gestational age, and birthweight, among newborns born to women with history of leukemia/lymphoma, several acylcarnitines were significantly (p < .001 – based on Bonferroni correction for multiple testing) higher compared to newborns of mothers without cancer history: C3-DC (mean difference (MD) = 0.006), C5-DC (MD = 0.009), C8:1 (MD = 0.008) C14 (MD = 0.010), and C16:1 (MD = 0.011), whereas citrulline levels were significantly lower (MD = 0.581) among newborns born to mothers with history of leukemia or lymphoma compared to newborns of mothers without a history of cancer. Conclusion: The varied metabolite levels suggest history of leukemia or lymphoma has metabolic impact on newborn offspring, which may have implications for future metabolic consequences such as necrotizing enterocolitis and urea cycle enzyme disorders in children born to mothers with a history of leukemia or lymphoma. [ABSTRACT FROM AUTHOR]

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. Propensity score‐matched women with BMI ≥30 kg/m2 were at decreased risk of a late spontaneous preterm birth. Propensity score‐matched women with BMI ≥30 kg/m2 were at decreased risk of a late spontaneous preterm birth. [ABSTRACT FROM AUTHOR]

Background: We conducted a meta‐analysis of observational epidemiological studies to evaluate the association between periconceptional use of vitamin A and the risk of giving birth to a child with nonsyndromic orofacial clefts (NSOFCs). Methods: We carried out a systematic literature search of Embase, PubMed, Web of Science, Google Scholar, and OpenGrey from inception to June 30, 2021. Two reviewers independently evaluated the studies that met the inclusion criteria and filled out an abstraction form for each study. Study quality was assessed using the Newcastle‐Ottawa Assessment Scale (NOS). Adjusted estimates were pooled with an inverse variance weighting using a random‐effects model. Heterogeneity and publication bias were assessed using the Cochran's Q test and funnel plot, respectively. Results: A total of six case–control studies with moderate risk of bias were included. The pooled OR showed a 20% reduction in the risk of NSOFCs for periconceptional use of vitamin A which was not statistically significant (OR =.80; 95% CI.54–1.17, p =.25). For nonsyndromic cleft lip with or without cleft palate (NSCL/P), the studies were homogenous, and the pooled estimate showed a 13% risk reduction, which was significant (OR =.87; 95% CI.77–.99, p =.03). For nonsyndromic cleft palate only (NSCPO), the pooled estimate showed a 33% lower likelihood, which was not statistically significant (OR =.67; 95% CI.42–1.08, p =.10). Conclusion: Our results suggest a possible protective effect for the periconceptional use of vitamin A on the risk of NSCL/P. This finding should be investigated further in prospective studies across multiple populations. [ABSTRACT FROM AUTHOR]

To determine the prevalence of virus in a previously uncharacterized matched maternal-infant preterm cohort and test if viral presence or viral load correlate with histologic chorioamnionitis, spontaneous preterm labor or pre-eclampsia. Using qRT-PCR/qPCR we tested plasma or whole blood samples from 56 matched maternal and premature infant dyads for: adenovirus, anellovirus (alphatorquevirus and betatorquevirus), cytomegalovirus (CMV), Epstein-Barr virus (EBV), enterovirus, human herpesvirus 6 (HHV6), parechovirus, and parvovirus B19. Viral detection was more common in maternal samples 29/56 (52%) than in cord blood from their infants (4/56 (7%)) (p ≤.0001). No significant difference in viral load or viral prevalence was identified between pregnancies with and without histologic chorioamnionitis, spontaneous preterm labor or pre-eclampsia. Despite frequent detection of virus in maternal samples, virus was less frequently detected in the infants. Additionally, there was no association of presence or quantity of virus in maternal blood with histologic chorioamnionitis, spontaneous preterm labor or pre-eclampsia in this small, but well-defined cohort. Future studies are necessary to further characterize the role of virus in placental inflammatory states and pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies that used traditional multivariable and sibling matched analyses to investigate interpregnancy interval (IPI) and birth outcomes have reached mixed conclusions about a minimum recommended IPI, raising concerns about confounding. Our objective was to isolate the contribution of interpregnancy interval to the risk for adverse birth outcomes using propensity score matching. Methods: For this retrospective cohort study, data were drawn from a California Department of Health Care Access and Information database with linked vital records and hospital discharge records (2007–2012). We compared short IPIs of < 6, 6–11, and 12–17 months to a referent IPI of 18–23 months using 1:1 exact propensity score matching on 13 maternal sociodemographic and clinical factors. We used logistic regression to calculate the odds of preterm birth, early-term birth, and small for gestational age (SGA). Results: Of 144,733 women, 73.6% had IPIs < 18 months, 5.5% delivered preterm, 27.0% delivered early-term, and 6.0% had SGA infants. In the propensity matched sample (n = 83,788), odds of preterm birth were increased among women with IPI < 6 and 6–11 months (OR 1.89, 95% CI 1.71–2.0; OR 1.22, 95% CI 1.13–1.31, respectively) and not with IPI 12–17 months (OR 1.01, 95% CI 0.94–1.09); a similar pattern emerged for early-term birth. The odds of SGA were slightly elevated only for intervals < 6 months (OR 1.10, 95% CI 1.00–1.20, p <.05). Discussion: This study demonstrates a dose response association between short IPI and adverse birth outcomes, with no increased risk beyond 12 months. Findings suggest that longer IPI recommendations may be overly proscriptive. [ABSTRACT FROM AUTHOR]

Background Knowledge of gestational age is critical for guiding preterm neonatal care. In the last decade, metabolic gestational dating approaches emerged in response to a global health need; because in most of the developing world, accurate antenatal gestational age estimates are not feasible. These methods initially developed in North America have now been externally validated in two studies in developing countries, however, require shipment of samples at sub-zero temperature. Methods A subset of 330 pairs of heel prick dried blood spot samples were shipped on dry ice and in ambient temperature from field sites in Tanzania, Bangladesh and Pakistan to laboratory in Iowa (USA). We evaluated impact on recovery of analytes of shipment temperature, developed and evaluated models for predicting gestational age using a limited set of metabolic screening analytes after excluding 17 analytes that were impacted by shipment conditions of a total of 44 analytes. Results With the machine learning model using all the analytes, samples shipped in dry ice yielded a Root Mean Square Error (RMSE) of 1.19 weeks compared to 1.58 weeks for samples shipped in ambient temperature. Out of the 44 screening analytes, recovery of 17 analytes was significantly different between the two shipment methods and these were excluded from further machine learning model development. The final model, restricted to stable analytes provided a RMSE of 1.24 (95% confidence interval (CI) = 1.10-1.37) weeks for samples shipped on dry ice and RMSE of 1.28 (95% CI = 1.15-1.39) for samples shipped at ambient temperature. Analysis for discriminating preterm births (gestational age <37 weeks), yielded an area under curve (AUC) of 0.76 (95% CI = 0.71-0.81) for samples shipped on dry ice and AUC of 0.73 (95% CI = 0.67-0.78) for samples shipped in ambient temperature. Conclusions In this study, we demonstrate that machine learning algorithms developed using a sub-set of newborn screening analytes which are not sensitive to shipment at ambient temperature, can accurately provide estimates of gestational age comparable to those from published regression models from North America using all analytes. If validated in larger samples especially with more newborns <34 weeks, this technology could substantially facilitate implementation in LMICs. [ABSTRACT FROM AUTHOR]

Background: Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1-2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings.Methods: This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed.Results: Overall model estimated GA had MAE of 5.2 days (95% CI 4.6-6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6-6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31-94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0-99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5-23.7; p = 0.002).Conclusions: Machine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation. [ABSTRACT FROM AUTHOR]

Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has a significant genetic predisposition, our objective was to identify genetic and transcriptomic evidence of heat shock proteins and nuclear hormone receptors that may affect risk for SPTB. We investigated all 97 genes encoding members of the heat shock protein families and all 49 genes encoding nuclear hormone receptors for their potential role in SPTB susceptibility. We used multiple genetic and genomic datasets including genome-wide association studies (GWASs), whole-exome sequencing (WES), and placental transcriptomics to identify SPTB predisposing factors from the mother, infant, and placenta. There were multiple associations of heat shock protein and nuclear hormone receptor genes with SPTB. Several orthogonal datasets supported roles for SEC63, HSPA1L, SACS, RORA, and AR in susceptibility to SPTB. We propose that suppression of specific heat shock proteins promotes maintenance of pregnancy, whereas activation of specific heat shock protein mediated signaling may disturb maternal–fetal tolerance and promote labor. [ABSTRACT FROM AUTHOR]

Background: A growing amount of evidence indicates in utero and early life growth has profound, long-term consequences for an individual's health throughout the life course; however, there is limited data in preterm infants, a vulnerable population at risk for growth abnormalities. Objective: To address the gap in knowledge concerning early growth and its determinants in preterm infants. Methods: A retrospective cohort study was performed using a population of preterm (< 37 weeks gestation) infants obtained from an electronic medical record database. Weight z-scores were acquired from discharge until roughly two years corrected age. Linear mixed effects modeling, with random slopes and intercepts, was employed to estimate growth trajectories. Results: Thirteen variables, including maternal race, hypertension during pregnancy, preeclampsia, first trimester body mass index, multiple status, gestational age, birth weight, birth length, head circumference, year of birth, length of birth hospitalization stay, total parenteral nutrition, and dextrose treatment, were significantly associated with growth rates of preterm infants in univariate analyses. A small percentage (1.32% - 2.07%) of the variation in the growth of preterm infants can be explained in a joint model of these perinatal factors. In extremely preterm infants, additional variation in growth trajectories can be explained by conditions whose risk differs by degree of prematurity. Specifically, infants with periventricular leukomalacia or retinopathy of prematurity experienced decelerated rates of growth compared to infants without such conditions. Conclusions: Factors found to influence growth over time in children born at term also affect growth of preterm infants. The strength of association and the magnitude of the effect varied by gestational age, revealing that significant heterogeneity in growth and its determinants exists within the preterm population. [ABSTRACT FROM AUTHOR]

Background Globally, 15 million infants are born preterm and another 23.2 million infants are born small for gestational age (SGA). Determining burden of preterm and SGA births, is essential for effective planning, modification of health policies and targeting interventions for reducing these outcomes for which accurate estimation of gestational age (GA) is crucial. Early pregnancy ultrasound measurements, last menstrual period and post-natal neonatal examinations have proven to be not feasible or inaccurate. Proposed algorithms for GA estimation in western populations, based on routine new-born screening, though promising, lack validation in developing country settings. We evaluated the hypothesis that models developed in USA, also predicted GA in cohorts of South Asia (575) and Sub-Saharan Africa (736) with same precision. Methods Dried heel prick blood spots collected 24-72 hours after birth from 1311 newborns, were analysed for standard metabolic screen. Regression algorithm based, GA estimates were computed from metabolic data and compared to first trimester ultrasound validated, GA estimates (gold standard). Results Overall Algorithm (metabolites + birthweight) estimated GA to within an average deviation of 1.5 weeks. The estimated GA was within the gold standard estimate by 1 and 2 weeks for 70.5% and 90.1% newborns respectively. Inclusion of birthweight in the metabolites model improved discriminatory ability of this method, and showed promise in identifying preterm births. Receiver operating characteristic (ROC) curve analysis estimated an area under curve of 0.86 (conservative bootstrap 95% confidence interval (CI) = 0.83 to 0.89); P < 0.001) and Youden Index of 0.58 (95% CI = 0.51 to 0.64) with a corresponding sensitivity of 80.7% and specificity of 77.6%. Conclusion Metabolic gestational age dating offers a novel means for accurate population-level gestational age estimates in LMIC settings and help preterm birth surveillance initiatives. Further research should focus on use of machine learning and newer analytic methods broader than conventional metabolic screen analytes, enabling incorporation of region-specific analytes and cord blood metabolic profiles models predicting gestational age accurately. [ABSTRACT FROM AUTHOR]

Background Limited ultrasound capacity in low-resource settings makes correct gestational age (GA) dating difficult. Previous work demonstrated that newborn metabolic profiles can accurately determine gestational age, but this relationship has not been evaluated in low-income countries. The objective of this study was to validate and adapt a metabolic GA dating model developed using newborn blood spots for use in a low-resource setting in rural Uganda. Methods A cohort of pregnant women was followed prospectively and heel stick blood spots were collected from 666 newborns in Busia, Uganda at the time of delivery. They were dried, frozen, and shipped to the US where they were tested for 47 metabolites. Metabolic model performance was assessed using early ultrasound determined GA as the standard. Models tested included previously built multivariable models and models specifically adapted to the Busia population. Results The previously built model successfully dated 81.2% of newborns within two weeks of their ultrasound GA. Only 4.8% of GAs were off by greater than three weeks. In the model adapted to the local population, 89.2% of GAs matched their corresponding ultrasound to within two weeks. The model-derived preterm birth rate was 7.2% compared to 5.9% by ultrasound. Conclusions These results suggest that metabolic dating is a reliable method to determine GA in a low-income setting. Metabolic dating offers the potential to better elucidate preterm birth rates in low-resource settings, which is important for assessing population-level patterns, tailoring clinical care, and understanding the developmental trajectories of preterm infants. [ABSTRACT FROM AUTHOR]

Background and Objectives: Postpartum women represent a large population with opioid exposure who also have an increased risk of experiencing mood and anxiety disorders. However, the effect that mood and anxiety disorders have on opioid use postpartum has received little attention in the literature. Therefore, the objective of this study was to examine the association of mood and anxiety disorders with filling opioid prescriptions within the first 3 months postpartum.Methods: A retrospective cohort study (n = 25 279) was completed using claims data for a sample of privately insured women who gave birth in the state of Iowa. The interactive effects of mood and anxiety disorders and delivery mode on filling at least one and two or more opioid prescriptions were examined in logistic regression models.Results: The presence of mood and anxiety disorders among women who delivered vaginally increased their odds of filling at least one opioid fill by nearly 50% (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.35-1.63) and by 20% (OR: 1.20, 95% CI: 1.00-1.43) among women with cesarean delivery.Discussion and Conclusion: Postpartum women with mood and anxiety disorders were more likely to fill opioid prescriptions postpartum compared to women without these conditions.Scientific Significance: This study extends prior research by examining the intersection of risk of mood and anxiety disorders and opioid use postpartum. Findings from this study support the need for future research to identify the drivers of increased opioid use among postpartum women with mood and anxiety disorders. (Am J Addict 2020;29:463-470). [ABSTRACT FROM AUTHOR]

Background: Most of the women who smoke before pregnancy continue smoking during pregnancy, and some start to quit smoking after being pregnant, although existing guidelines for pregnancy recommend that women who smoke should quit smoking before pregnancy. Findings about the timing and intensity of maternal smoking, especially low-intensity smoking (1-9 cigarettes per day), and preterm birth are still inconsistent and ambiguous. This study aimed to examine the association of the timing of smoking and doses of smoking before pregnancy and during the first or second trimester of pregnancy with preterm birth in a large-scale population-based retrospective cohort study.Methods and Findings: We used nationwide birth certificate data from singleton mother-infant pairs in the United States National Vital Statistics System, 2011-2018. All adult women with live singleton births, without preexisting hypertension or diabetes, and with complete data on smoking and gestational age at delivery were included. Participants reported their smoking status (yes or no) and daily number of cigarettes consumed before and during each trimester of pregnancy. The outcome of interest was preterm birth, defined as a birth before 37 weeks of gestation. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence intervals (CIs) of preterm birth associated with smoking status and the number of cigarettes consumed, adjusting for maternal age, race/ethnicity, parity, education levels, prepregnancy BMI, previous history of preterm birth, marital status, infant sex, and initiation of prenatal care. This study included 25,623,479 women, with a mean age of 29 years (range 20-50 years); 13,742,486 (53.6%) participants were of non-Hispanic white ancestry, 5,971,598 (23.3%) of Hispanic ancestry, and 3,417,456 (13.34%) of non-Hispanic black ancestry. The prevalence of preterm birth was 9.3% (n = 2,378,398). We found that maternal smoking during pregnancy, even at a very low level of intensity, was associated with an increased risk of preterm delivery. The adjusted ORs (95% CI) of preterm birth for mothers who smoked 1-2, 3-5, 6-9, 10-19, and ≥20 cigarettes per day during the first trimester compared with mothers who did not smoke were 1.31 (1.29-1.33), 1.31 (1.30-1.32), 1.33 (1.31-1.35), 1.44 (1.43-1.45), and 1.53 (1.52-1.55), respectively (all P values < 0.001), whereas for those who smoked during the second trimester, the corresponding ORs were 1.37 (1.35-1.39), 1.36 (1.35-1.38), 1.36 (1.34-1.38), 1.48 (1.47-1.49), and 1.59 (1.58-1.61), respectively (all P values < 0.001). Furthermore, smokers who quit before pregnancy, regardless of smoking intensity, had a comparable risk of preterm birth with nonsmokers, although this was not the case when cessation occurred in the first or second trimester of pregnancy. The major limitation of this study is the self-reported information about smoking, which may be subject to information bias. In addition, we cannot rule out the possibility of residual confounding caused by unmeasured factors in an observational research design.Conclusions: In this study, we observed that low-intensity cigarette consumption during either the first or second trimester of pregnancy, even as low as 1-2 cigarettes per day, was associated with an increased risk of preterm birth. These findings suggest that there is no safe level or safe trimester for maternal smoking during pregnancy. Women of reproductive age who smoke should be strongly encouraged and supported to quit smoking before pregnancy. [ABSTRACT FROM AUTHOR]

Objective To determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth. Design Case control. setting California hospitals. Participants 868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010. Methods Logistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes. Primary outcome Preterm delivery status. results Adjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ² differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686. Conclusion Traditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women. [ABSTRACT FROM AUTHOR]

Background: Preterm infants suffer from respiratory morbidity especially during the first year of life.Objective: To investigate the association of air quality and sociodemographic indicators on hospital admission rates for respiratory causes.Methods: This is a retrospective cohort study. We identified all live-born preterm infants in California from 2007 to 2012 in a population-based administrative data set and linked them to a data set measuring several air quality and sociodemographic indicators at the census tract level. All sociodemographic and air quality predictors were divided into quartiles (first quartile most favourable to the fourth quartile least favourable). Mixed effect logistic models to account for clustering at the census tract level were used to investigate associations between chronic air quality and sociodemographic indicators respiratory hospital admission during the first year of life.Results: Of 205 178 preterm infants, 5.9% (n = 12 033) were admitted to the hospital for respiratory causes during the first year. In the univariate analysis, comparing the first to the fourth quartile of chronic ozone (risk ratio [RR] 1.29, 95% confidence interval [CI] 1.21, 1.37), diesel (RR 1.10, 95% CI 1.02, 1.17) and particulate matter 2.5 (RR 1.07, 95% CI 1.01, 1.14) exposure were associated with hospital admission during the first year. Following adjustment for confounders, the risk ratios for hospital admission during the first year were 1.53 (95% CI 1.37, 1.72) in relation to educational attainment (per cent of the population over age 25 with less than a high school education) and 1.23 (95% CI 1.09, 1.38) for poverty (per cent of the population living below two times the federal poverty level).Conclusions: Among preterm infants, respiratory hospital admissions in the first year in California are associated with socioeconomic characteristics of the neighbourhood an individual is living in. [ABSTRACT FROM AUTHOR]

Objective: Autoimmune conditions are associated with an increased risk of adverse pregnancy complications and outcomes, suggesting that pregnancy complications may mediate the excess risk. We performed a causal mediation analysis to quantify the mediated effects of autoimmune conditions on adverse pregnancy outcomes.Methods: We queried a California birth cohort created from linked birth certificates and hospital discharge summaries. From 2,963,888 births, we identified women with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, and inflammatory bowel disease (IBD). Pregnancy complications included preeclampsia/hypertension, gestational diabetes mellitus, and infection in pregnancy. Adverse pregnancy outcomes were preterm birth, cesarean delivery, and small for gestational age. We performed a mediation analysis to estimate the total effects of each autoimmune condition and adverse pregnancy outcome and the indirect effects through pregnancy complications.Results: All 4 autoimmune conditions were associated with preterm birth and cesarean delivery, and RA, SLE, and IBD were associated with offspring that were small for gestational age. The strongest mediator of RA, SLE, and psoriasis was preeclampsia/hypertension, accounting for 20-33% of the excess risk of preterm births and 10-19% of excess cesarean deliveries. Gestational diabetes mellitus and infections generally mediated <10% of excess adverse pregnancy outcomes. Of the 4 autoimmune conditions, selected pregnancy complications mediated the least number of adverse pregnancy outcomes among women with IBD.Conclusion: We found evidence that some excess risk of adverse pregnancy outcomes is mediated through pregnancy complications, particularly preeclampsia/hypertension. Quantifying excess risk and associated pathways provides insight into the underlying etiologies of adverse pregnancy outcomes and can inform intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Donor human milk supplementation for healthy newborns has increased. Racial-ethnic disparities in supplementation have been described in the neonatal intensive care unit but not in the well newborn setting. Research aim: The aim of this study was to identify maternal characteristics associated with donor human milk versus formula supplementation in the well newborn unit. Methods: This retrospective cohort study includes dyads of well newborns and their mothers (N = 678) who breastfed and supplemented with formula (n = 372) or donor human milk (n = 306) during the birth hospitalization at a single hospital in the midwestern United States. Maternal characteristics and infant feeding type were extracted from medical records. Chi-square and logistic regression were used to examine associations between maternal characteristics and feeding type. Results: Nonwhite women were less likely to use donor human milk. Compared to non-Hispanic white women, the largest disparity was with Hispanic (adjusted odds ratio [OR] = 0.28, 95% CI [0.12, 0.65]), then non-Hispanic black (adjusted OR = 0.32, 95% CI [0.13, 0.76]) and Asian women (adjusted OR = 0.34, 95% CI [0.16, 0.74]). Lower donor human milk use was associated with primary language other than English and public versus private insurance. Conclusion: The goal of improving public health through breastfeeding promotion may be inhibited without targeting donor human milk programs to these groups. Identifying the drivers of these disparities is necessary to inform person-centered interventions that address the needs of women with diverse backgrounds. [ABSTRACT FROM AUTHOR]

Introduction: Reproductive health advantages have been reported among selected immigrants, but few studies have included new immigrants and refugees, nor simultaneously adjusted for socioeconomic, behavioral, and medical disparities. Methods: We examined the risk of preterm birth (PTB, < 37 weeks' gestation) among singleton live births in San Diego County from 2007 to 2012. Multivariable regression was used to compare PTB (1) by nativity within racial/ethnic groups and (2) among immigrants compared to United States (US) born Whites, while adjusting for sociodemographic, behavioral, reproductive and medical variables. Results: Among 230,878 singleton live births, overall PTB prevalence was highest among parturient women who were US-born Blacks (10.9%), Philippine (10.8%) and US-born Filipinas (10.7%), and US-born Asians (8.6%) despite differences in socioeconomic and maternal risk factors, and lowest among Somali (5.5%) migrants. Blacks born in Somalia or outside of the US, had significantly lower overall PTB prevalence compared to US-born Blacks (5.5% vs 7.6% vs 10.9%). Compared to US-born Whites, spontaneous PTB risk was significantly lower among Somali migrants (4.8% vs 3.7%, adjusted relative risk, aRR 0.7 [95% Confidence Intervals 0.5–0.9]), but higher among Philippine migrants (4.8% vs 7.7%, aRR 1.4 [1.3–1.6]). The strongest risk factor for overall PTB among nulliparous US-born Blacks was preexisting diabetes (aRR 3.81 [2.05–7.08]), and preexisting hypertension among Filipinas (aRR: 3.27 [2.36–4.54] and US-born Asians (aRR: 3.64 [1.61–8.24]). Conclusion: Black migrants had lower PTB prevalence compared to US-born Blacks, but this immigrant advantage was not observed in other racial/ethnic groups. Compared to US-born Whites, Somali migrants had significantly lower risk of spontaneous PTB while Filipinas had elevated risk. [ABSTRACT FROM AUTHOR]

Objective: Rural populations may experience more frequent and intense risk factors for perinatal depression than their urban counterparts. However, research has yet to examine rural versus urban differences in a population‐based study in the United States. Therefore, this study examined differences in risk of perinatal depression between women living in rural versus urban areas in the United States. Method: Using 2016 data from the Pregnancy Risk Assessment Monitoring System, we examined the association between rural‐urban status and the risk of depression during the perinatal time period. The total analytical sample included 17,229 women from 14 states. The association between rural‐urban status and risk of perinatal depression was estimated using logistic regression, adjusting for race/ethnicity, maternal age, and state of residence. A second model adjusted for maternal education, health insurance status, and Women, Infants, and Children Special Supplemental Nutrition Program (WIC). Results: Odds of perinatal depression risk were higher by 21% among rural versus urban women (OR = 1.21, 95% CI: 1.05‐1.41) adjusted for race, ethnicity, and maternal age. This risk difference became smaller and not significant when adding maternal education, health insurance coverage, and WIC participation. Conclusion: Findings suggest a rural‐urban inequality in perinatal depression risk. Reducing this inequality may require improving socioeconomic conditions and reducing associated risk factors among rural women. [ABSTRACT FROM AUTHOR]

Objective: Examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. Methods: The study population was drawn from singleton live births in California from 2007 to 2012 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes linked birth certificate and mother and infant hospital discharge records. The sample was restricted to infants delivered between 20 and 44 weeks gestation. Logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) for factors influencing late entry into prenatal care. Maternal age, education, smoking, drug or alcohol abuse/dependence, mental illness, participation in the Women, Infants and Children's program and rural residence were evaluated for women entering prenatal care > sixth month of gestation compared with women entering < fourth month. Backwards stepwise logistic regression was used to create final multivariable models of risk and protective factors for late prenatal care entry for each race or ethnicity and insurance payer. Results: The sample included 2,963,888 women. The percent of women with late entry into prenatal care was consistently higher among women with public versus private insurance. Less than 1% of white non-Hispanic and Asian women with private insurance entered prenatal care late versus more than 4% of white non-Hispanic and black women with public insurance. After stratifying by race or ethnicity and insurance status, women less than 18 years of age were more likely to enter prenatal care late, with young Asian women with private insurance at the highest risk (15.6%; adjusted RR 7.4, 95%CI 5.3-10.5). Among all women with private insurance, > 12-year education or age >34 years at term reduced the likelihood of late prenatal care entry (adjusted RRs 0.5-0.7). Drugs and alcohol abuse/dependence and residing in a rural county were associated with increased risk of late prenatal care across all subgroups (adjusted RRs 1.3-3.8). Participation in the Women, Infants, and Children's program was associated with decreased risk of late prenatal care for women with public insurance (adjusted RRs 0.6-0.7), but increased risk for women with private insurance (adjusted RRs 1.4-2.1). Conclusions: The percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. Participation in the Women, Infants, and Children's program and maternal age >34 years at delivery increased the likelihood of late prenatal care for some subgroups of women and decreased the likelihood for others. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care. Rationale: Optimal prenatal care includes initiation before the 14th week of gestation. Beginning care in the first trimester provides an opportunity for sonographic pregnancy dating or confirmation with best accuracy, which can later prove critical for management of preterm labor, maternal or fetal complications, or prolonged pregnancy. In order to improve maternal and infant health by increasing the number of women seeking prenatal care in the first trimester, it is important to examine the drivers for late entry. Here, we examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. We found the percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care. [ABSTRACT FROM AUTHOR]

Maternal lipid profiles are associated with risk for preterm birth (PTB), although the lipid component and effect size are inconsistent between studies. It is also unclear whether these associations are the result of excessive changes in lipid metabolism during pregnancy or genetic variability in genes controlling basal lipid metabolism. This study investigates the association between genetic risk scores (GRS) for four lipid components (high‐density lipoprotein [HDL‐C], low‐density lipoprotein [LDL‐C], triacylglycerols [TAG], and total cholesterol [TC]) with risk for PTB. Subjects included 954 pregnant women from California for whom second trimester serum samples were available, of which 479 gave birth preterm and 475 gave birth at term. We genotyped 96 single‐nucleotide polymorphisms, which were selected from genome‐wide association studies of lipid levels in adult populations. Lipid‐specific GRS were constructed for HDL‐C, LDL‐C, TAG, and TC. The associations between GRS and PTB were analyzed using logistic regression. A higher HDL‐C GRS was associated with increased risk for PTB overall and spontaneous PTB. Higher TAG and TC GRS were associated with decreased risk for PTB overall and spontaneous PTB. This study identifies counter‐intuitive associations between lipid GRS and spontaneous PTB. Further replication studies are needed to confirm these findings, but they suggest that our current scientific understanding of the relationship between lipid metabolism, PTB, and genetics is incomplete. [ABSTRACT FROM AUTHOR]

Background: The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored. Methods: We performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted meta-analysis. Results: We identified six loci associated with QRS (P<5x10-8), including two novel loci: MYOCD, a nuclear protein expressed in the heart, and SYT1, an integral membrane protein. The top SNP in the MYOCD locus, intronic SNP rs16946539, was found in Hispanics/Latinos with a minor allele frequency (MAF) of 0.04, but is monomorphic in European and African descent populations. The most significant QRS duration association was with intronic SNP rs3922344 (P = 1.19x10-24) in SCN5A/SCN10A. Three other previously identified loci, CDKN1A, VTI1A, and HAND1, also exceeded the GWAS significance threshold among Hispanics/Latinos. A total of 27 of 32 previously identified QRS duration SNPs were shown to generalize in Hispanics/Latinos. Conclusions: Our QRS duration GWAS, the first in Hispanic/Latino populations, identified two new loci, underscoring the utility of extending large scale genomic studies to currently under-examined populations. [ABSTRACT FROM AUTHOR]

Deregulation of the circadian system in humans and animals can lead to various adverse reproductive outcomes due to genetic mutations and environmental factors. In addition to the clock, lipid metabolism may also play an important role in influencing reproductive outcomes. Despite the importance of the circadian clock and lipid metabolism in regulating birth timing few studies have examined the relationship between circadian genetics with lipid levels during pregnancy and their relationship with preterm birth (PTB). In this study we aimed to determine if single nucleotide polymorphisms (SNPs) in genes from the circadian clock and lipid metabolism influence 2nd trimester maternal lipid levels and if this is associated with an increased risk for PTB. We genotyped 72 SNPs across 40 genes previously associated with various metabolic abnormalities on 930 women with 2nd trimester serum lipid measurements. SNPs were analyzed for their relationship to levels of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides (TG) using linear regression. SNPs were also evaluated for their relationship to PTB using logistic regression. Five SNPs in four genes met statistical significance after Bonferroni correction (p < 1.8 × 10-4) with one or more lipid levels. Of these, four SNPs were in lipid related metabolism genes: rs7412 in APOE with total cholesterol, HDL and LDL, rs646776 and rs599839 in C ELSR2-PSRC1-SORT1 gene cluster with total cholesterol, HDL and LDL and rs738409 in PNPLA3 with HDL and TG and one was in a circadian clock gene: rs228669 in PER3 with TG. Of these SNPs only PER3 rs228669 was marginally associated with PTB (p = 0.02). In addition, PER3 rs228669 acts as an effect modifier on the relationship between TG and PTB. [ABSTRACT FROM AUTHOR]

Implementation of dietary and lifestyle interventions prior to and early in pregnancy in high risk women has been shown to reduce the risk of gestational diabetes mellitus (GDM) development later in pregnancy. Although numerous risk factors for GDM have been identified, the ability to accurately identify women before or early in pregnancy who could benefit most from these interventions remains limited. As nulliparous women are an under-screened population with risk profiles that differ from their multiparous counterparts, development of a prediction model tailored to nulliparous women may facilitate timely preventive intervention and improve maternal and infant outcomes. We aimed to develop and validate a model for preconception and early pregnancy prediction of gestational diabetes mellitus based on clinical risk factors for nulliparous women. A risk prediction model was built within a large California birth cohort including singleton live birth records from 2007–2012. Model accuracy was assessed both internally and externally, within a cohort of women who delivered at University of Iowa Hospitals and Clinics between 2009–2017, using discrimination and calibration. Differences in predictive accuracy of the model were assessed within specific racial/ethnic groups. The prediction model included five risk factors: race/ethnicity, age at delivery, prepregnancy body mass index, family history of diabetes, and pre-existing hypertension. The area under the curve (AUC) for the California internal validation cohort was 0.732 (95% confidence interval (CI) 0.728, 0.735), and 0.710 (95% CI 0.672, 0.749) for the Iowa external validation cohort. The model performed particularly well in Hispanic (AUC 0.739) and Black women (AUC 0.719). Our findings suggest that estimation of a woman’s risk for GDM through model-based incorporation of risk factors accurately identifies those at high risk (i.e., predicted risk >6%) who could benefit from preventive intervention encouraging prompt incorporation of this tool into preconception and prenatal care. [ABSTRACT FROM AUTHOR]