Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells.

Background: Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations. Method: This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways. Results: Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta. Conclusion: Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta. Supplementary Information: The online version contains supplementary material available at 10.1186/s43682-024-00027-7.

IL-1 and TNF mediates IL-6 signaling at the maternal-fetal interface during intrauterine inflammation.

Introduction: IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP). Methods: Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation. Results: IUI induced a robust expression of IL6 mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of IL6 mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, ADAM17 (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and IL6R mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced IL6 mRNAs in the AMC and variably decreased elements of IL6 trans-signaling. Discussion: These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.

Influence of Pregnancy Intention on Postpartum Contraceptive Choice at an Urban Academic Medical Center.

OBJECTIVE: This study aimed to describe postpartum contraception preferences in the context of pregnancy intention (PI). STUDY DESIGN: A prospective cohort study analyzing postpartum contraceptive choice (PCC) in 431 postpartum women who delivered at a single academic medical center. PCC in women with an unintended or mistimed pregnancy was compared to contraceptive choice in women with an intended pregnancy using the adapted National Survey of Family Growth categorization. Mistimed and unintended pregnancies were grouped for analysis. Generalized linear modeling estimated the relative influence of PI on PCC adjusting for maternal age, race, and parity. RESULTS: Nearly three out of four (71.9%) pregnancies were mistimed or unintended. These pregnancies were more likely in women who were non-Hispanic Black (62.3%), unmarried (86.3%), 18 to 24 years (51.3%), and insured by Medicaid or Medicare (82.1%), compared to women with an intended pregnancy, p-value <0.001. Women with mistimed or unintended pregnancy were 83% more likely to choose highly effective, user-independent methods compared to any other or no method, adjusted relative risk (aRR) = 1.83 (95% confidence interval [CI]: 1.36, 2.47), and more likely to desire voluntary sterilization, aRR = 2.70 (95% CI: 1.58, 4.59). Additionally, women with these pregnancies were 56% more likely to use user-independent methods compared to user-dependent methods, aRR = 1.56 (95% CI: 1.18, 2.06). CONCLUSION: Women with mistimed or unintended pregnancies are 83% more likely to choose highly effective postpartum contraception or voluntary sterilization, and thus initiatives are necessary to increase access and affordability to these methods before hospital discharge after delivery. KEY POINTS: · Nearly three out of four pregnancies in this study were mistimed or unintended.. · Women with mistimed or unintended pregnancies are more likely to choose highly effective postpartum contraception or voluntary sterilization.. · Public health initiatives to improve access to family planning services and postpartum contraception, including surgery for bilateral tubal ligation before discharge from the hospital postdelivery, are important areas of focus to help attenuate the rates of unintended pregnancy in the United States..

Endemic Coronavirus Infections are Associated with Strong Homotypic Immunity in a US Cohort of Children from Birth to 4 Years.

BACKGROUND: The endemic coronaviruses OC43, HKU1, NL63, and 229E cause cold-like symptoms and are related to SARS-CoV-2, but their natural histories are poorly understood. In a cohort of children followed from birth to 4 years, we documented all coronavirus infections, including SARS-CoV-2, to understand protection against subsequent infections with the same virus (homotypic immunity) or a different coronavirus (heterotypic immunity). METHODS: Mother-child pairs were enrolled in metropolitan Cincinnati during the third trimester of pregnancy in 2017-2018. Mothers reported their child's sociodemographics, risk factors, and weekly symptoms. Mid-turbinate nasal swabs were collected weekly. Blood was collected at 6 weeks, 6, 12, 18, 24 months, and annually thereafter. Infections were detected by testing nasal swabs by an RT-PCR multi-pathogen panel and by serum IgG responses. Health care visits were documented from pediatric records. Analysis was limited to 116 children with high sample adherence. Reconsent for monitoring SARS-CoV-2 infections from June 2020 through November 2021 was obtained for 74 (64%) children. RESULTS: We detected 345 endemic coronavirus infections (1.1 infections/child-year) and 21 SARS-CoV-2 infections (0.3 infections/child-year). Endemic coronavirus and SARS-CoV-2 infections were asymptomatic or mild. Significant protective homotypic immunity occurred after a single infection with OC43 (77%) and HKU1 (84%) and after two infections with NL63 (73%). No heterotypic protection against endemic coronaviruses or SARS-CoV-2 was identified. CONCLUSIONS: Natural coronavirus infections were common and resulted in strong homotypic immunity but not heterotypic immunity against other coronaviruses, including SARS-CoV-2. Endemic coronavirus and SARS-CoV-2 infections in this US cohort were typically asymptomatic or mild.

Factors Associated with Maternal Morbidity among Black Women in the United States.

OBJECTIVE: Non-Hispanic Black people (NHBP) have a three-fold higher rate of maternal mortality compared to other racial groups. Racial disparities in maternal morbidity are well-described; however, there are substantial differences in cultural, economic, and social determinants of health among racial groups. We thus sought to study the at-risk, non-Hispanic Black population as its own cohort to identify factors most associated with severe maternal morbidity (SMM). STUDY DESIGN: This is a population-based retrospective case-control study of all live births in the United States between 2017 and 2019 using birth records obtained from the National Center for Health Statistics. The primary outcome for this study was to determine demographic, social, medical, and obstetric factors associated with maternal morbidity among NHBP who did and did not experience an SMM event. Multivariable logistic regression was used to estimate the adjusted odds ratio between each individual factor and the outcome of SMM among NHBP. RESULTS: Of the 1,624,744 NHBP who delivered between 2017 and 2019, 1.1% experienced an SMM event defined as a composite of blood product transfusion, eclamptic seizure, intensive care unit admission, unplanned hysterectomy, and uterine rupture. The rates of these individual SMM events per 10,000 deliveries were 50, 40, 20, 5, and 4 among NHBP, respectively. Among NHBP, factors associated in multivariable regression analysis with SMM in order of strength of association included cesarean delivery, earlier gestational age at delivery, preeclampsia, induction of labor, chronic hypertension, prior preterm birth, lower educational attainment, multifetal gestation, advanced maternal age, pregestational diabetes, and cigarette smoking. The population attributable fraction for cesarean delivery, preterm birth, and pregnancy-induced hypertensive disease for the outcome of SMM were 0.46, 0.23, and 0.07, respectively. CONCLUSION: The three factors most associated with SMM among NHBP are potentially avoidable or modifiable by aggressive screening, prevention, and treatment of preeclampsia and preterm birth as well as reducing cesarean rates in this population. KEY POINTS: · The rate of SMM in NHBP may be modifiable.. · NHBP have a three-fold higher rate of maternal mortality.. · Preeclampsia, preterm birth, and cesarean sections are most associated with maternal morbidity..

Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants.

BACKGROUND AND OBJECTIVES: Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS: Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS: Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS: Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.

The Combined Influence of Maternal Medical Conditions on the Risk of Primary Cesarean Delivery.

Background Common maternal medical comorbidities such as hypertensive disorders, diabetes, tobacco use, and extremes of maternal age, body mass index, and gestational weight gain are known individually to influence the rate of cesarean delivery. Numerous studies have estimated the risk of individual conditions on cesarean delivery. Objective To examine the risk for primary cesarean delivery in women with multiple maternal medical comorbidities to determine the cumulative risk they pose on mode of delivery. Study Design In this population-based retrospective cohort study, we analyzed data from Ohio live birth records from 2006 to 2015 to estimate the influence of individual and combinations of maternal comorbidities on rates of singleton primary cesarean delivery. The exposures were individual and combinations of maternal medical conditions (chronic hypertension [CHTN], gestational hypertension, pregestational diabetes, gestational diabetes, tobacco use, advanced maternal age, and maternal obesity) and outcomes were rates and adjusted relative risk (aRR) of primary cesarean delivery. Results There were 1,463,506 live births in Ohio during the study period, of which 882,423 (60.3%) had one or more maternal medical condition, and of those 243,112 (27.6%) had primary cesarean delivery. The range of rates and aRR range of primary cesarean delivery were 13.9 to 29.3% (aRR 0.78-1.68) in singleton pregnancies with a single medical condition, and this increased to 21.9 to 48.6% (aRR 1.34-3.87) in pregnancies complicated by multiple medical comorbidities. The highest risk for primary cesarean occurred in advanced maternal age, obese women with pregestational diabetes, and CHTN. Conclusion A greater number of maternal medical comorbidities during pregnancy is associated with increasing cumulative risk of primary cesarean delivery. These data may be useful in counseling patients on risk of cesarean during pregnancy.

Cardiac Abnormalities in Hispanic/Latina Women With Prior De Novo Hypertensive Disorders of Pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with long-term maternal risks for cardiovascular disease for reasons that remain incompletely understood. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a multi-center community-based cohort of Hispanic/Latino adults recruited 2008 to 2011, was used to evaluate the associations of history of de novo HDP (gestational hypertension, preeclampsia, eclampsia) with echocardiographic measures of cardiac structure and function in Hispanic/Latina women with ≥1 prior pregnancy and the proportion of association mediated by current hypertension (>140/90 mm Hg or antihypertensive therapy). RESULTS.: The study cohort included 5168 Hispanic/Latina women with an average age (SD) of 58.7 (9.7) years at time of echocardiogram. Prior de novo HDP was reported by 724 (14%) of the women studied and was associated with lower left ventricle (LV) ejection fraction -0.66 (95% confidence interval [CI], -1.21 to -0.11), higher LV relative wall thickness 0.09 (95% CI, 0-0.18), and 1.39 (95% CI, 1.02-1.89) higher risk of abnormal LV geometry after adjusting for blood pressure and other confounders. The proportion of the association mediated by current hypertension between HDP and LV ejection fraction was 0.09 (95% CI, 0.03-0.45), LV relative wall thickness was 0.28 (95% CI, 0.16-0.51), abnormal LV geometry was 0.14 (95% CI, 0.12-0.48), concentric left ventricular hypertrophy was 0.31 (95% CI, 0.19-0.86), and abnormal LV diastolic dysfunction was 0.58 (95% CI, 0.26-0.79). CONCLUSIONS.: In a large cohort of Hispanic/Latina women those with history of de novo HDP had detectable and measurable subclinical alterations in cardiac structure and both systolic and diastolic dysfunction that were only partially mediated by current hypertension.

Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases.

Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate "human-like" obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more "human-like" approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.

Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach.

INTRODUCTION: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. METHOD: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. RESULTS: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. CONCLUSION: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.

Social determinants among Black people during pregnancy following a short interpregnancy interval.

BACKGROUND: Short interpregnancy interval has been shown to be a key contributor to infant mortality. Black pregnant people have a higher incidence of short interpregnancy interval than people of other races and ethnicities, as well as higher rates of infant mortality. Understanding the factors related to racial disparities in short interpregnancy interval and infant mortality are a public health priority. OBJECTIVE: This study aimed to examine the relationship between social determinants of health and interpregnancy interval in Black pregnant people by comparing those with a short interpregnancy interval defined as <18 months with those with a referent interpregnancy interval defined as ≥18 months. STUDY DESIGN: This was a nested case-control study from a prospective cohort analyzing social determinants of health in 576 postpartum patients at an urban medical center, 2011-2021. Sociodemographic, pregnancy, and maternal characteristic data were collected from participants' medical records. Structured interviews measured participants' health behaviors, physical environment, social support, health literacy, and structural drivers. Differences in social determinants of health among Black study participants were compared between those with a short interpregnancy interval (<18 months) and those with a referent interpregnancy interval (≥18 months). The odds ratios were calculated to assess the association between short interpregnancy interval and social determinants. Factors with significant differences between the short interpregnancy interval and referent interpregnancy interval groups in Black participants were compared with that of White groups for social context. RESULTS: Black participants with a short interpregnancy interval were more likely to report financial support from the Special Supplemental Nutrition Program for Women, Infants, and Children (odds ratio, 2.4; 95% confidence interval, 1.2-5.1), negative feelings toward the pregnancy (odds ratio, 2.4; 95% confidence interval, 1.2-4.9), choosing not to breastfeed because they do not like it (odds ratio ,12.0; 95% confidence interval, 1.5-543.1), not receiving prenatal care as early as desired (odds ratio, 3.4; 95% confidence interval, 1.6-7.2) because of consid- eration of pregnancy termination (odds ratio, 5.2; 95% confidence interval, 1.2-30.5) and less likely to report low levels of social support (odds ratio, 0.3; 95% confidence interval, 0.1-0.8) than Black participants with a referent interpregnancy interval. CONCLUSION: Social determinants of health that differed between participants with a short interpregnancy interval and those with a referent interpregnancy interval were Special Supplemental Nutrition Program for Women, Infants, and Children support, feelings toward the pregnancy, social support, breastfeeding intent, and delayed prenatal care because of consideration of abortion. Previous studies examining infant mortality risk factors used White people as the referent group when analyzing social determinants. Our study focused specifically on understanding the lives of Black pregnant people so that future public health initiatives focused on social determinants may attenuate the racial disparity of infant mortality in the United States.

Antigen-specific decidual CD8+ T cells include distinct effector memory and tissue-resident memory cells.

Maternal decidual CD8+ T cells must integrate the antithetical demands of providing immunity to infection while maintaining immune tolerance for fetal and placental antigens. Human decidual CD8+ T cells were shown to be highly differentiated memory T cells with mixed signatures of dysfunction, activation, and effector function. However, no information is present on how specificity for microbial or fetal antigens relates to their function or dysfunction. In addition, a key question, whether decidual CD8+ T cells include unique tissue-resident memory T cells (Trm) or also effector memory T cell (Tem) types shared with peripheral blood populations, is unknown. Here, high-dimensional flow cytometry of decidual and blood CD8+ T cells identified 2 Tem populations shared in blood and decidua and 9 functionally distinct Trm clusters uniquely found in decidua. Interestingly, fetus- and virus-specific decidual CD8+ Trm cells had similar features of inhibition and cytotoxicity, with no significant differences in their expression of activation, inhibitory, and cytotoxic molecules, suggesting that not all fetus-specific CD8+ T cell responses are suppressed at the maternal-fetal interface. Understanding how decidual CD8+ T cell specificity relates to their function and tissue residency is crucial in advancing understanding of their contribution to placental inflammation and control of congenital infections.

The SunBEAm birth cohort: Protocol design.

Background: Food allergy (FA) and atopic dermatitis (AD) are common conditions that often present in the first year of life. Identification of underlying mechanisms and environmental determinants of FA and AD is essential to develop and implement effective prevention and treatment strategies. Objectives: We sought to describe the design of the Systems Biology of Early Atopy (SunBEAm) birth cohort. Methods: Funded by the National Institute of Allergy and Infectious Diseases (NIAID) and administered through the Consortium for Food Allergy Research (CoFAR), SunBEAm is a US population-based, multicenter birth cohort that enrolls pregnant mothers, fathers, and their newborns and follows them to 3 years. Questionnaire and biosampling strategies were developed to apply a systems biology approach to identify environmental, immunologic, and multiomic determinants of AD, FA, and other allergic outcomes. Results: Enrollment is currently underway. On the basis of an estimated FA prevalence of 6%, the enrollment goal is 2500 infants. AD is defined on the basis of questionnaire and assessment, and FA is defined by an algorithm combining history and testing. Although any FA will be recorded, we focus on the diagnosis of egg, milk, and peanut at 5 months, adding wheat, soy, cashew, hazelnut, walnut, codfish, shrimp, and sesame starting at 12 months. Sampling includes blood, hair, stool, dust, water, tape strips, skin swabs, nasal secretions, nasal swabs, saliva, urine, functional aspects of the skin, and maternal breast milk and vaginal swabs. Conclusions: The SunBEAm birth cohort will provide a rich repository of data and specimens to interrogate mechanisms and determinants of early allergic outcomes, with an emphasis on FA, AD, and systems biology.

Gestational Age and Birth Outcomes in Term Singleton Pregnancies Conceived With Infertility Treatment.

Importance: Despite the increased perinatal risks associated with pregnancies conceived with infertility treatment, there are no recommendations for timing of delivery among this at-risk population. Objective: To identify the gestational age at which the ongoing risks of stillbirth are optimally balanced with the risks of neonatal comorbidities and infant deaths in term singleton pregnancies conceived with infertility treatment. Design, Setting, and Participants: This cohort study used birth and death data from January 1, 2014, to December 31, 2018, in the US obtained from the National Center for Health Statistics. Singleton pregnancies conceived with infertility treatment delivered at term (37-42 weeks' gestation) were eligible for inclusion. The exclusion criteria were deliveries at less than 37 weeks' or at least 43 weeks' gestation and pregnancies with unknown history of infertility treatment, congenital anomalies, pregestational diabetes, pregestational hypertension, gestational hypertension, and preeclampsia. Data were analyzed from July 22, 2022, to June 24, 2023. Exposure: Gestational age at delivery between 37 and 42 weeks. Main Outcomes and Measures: The primary outcome was optimal timing of delivery. To ascertain this timing, the risk of delivery (rate of neonatal morbidity and infant death) at a given gestational week was compared with the risk of delivery in the subsequent week of gestation for an additional week (rate of stillbirth during the given week per 10 000 ongoing pregnancies plus rate of neonatal morbidity and infant death in the subsequent week of gestation per 10 000 deliveries). The rates of stillbirth, neonatal morbidity, and infant death (within 1 year of life) were compared at each week. Neonatal morbidity included an Apgar score of 3 or lower at 5 minutes, requirement of ventilation for 6 hours or more, neonatal intensive care unit admission, and seizures. Results: Of the 178 448 singleton term pregnancies conceived with infertility treatment (maternal mean [SD] age, 34.2 [5.2] years; mean [SD] gestational age, 39.2 [1.2] weeks; 130 786 [73.5%] were non-Hispanic White patients). The risk of delivery in the subsequent week of gestation was lower than the risk of delivery at both 37 weeks (628 [95% CI, 601-656] vs 1005 [95% CI, 961-1050] per 10 000 live births) and 38 weeks (483 [95% CI, 467-500 vs 625 [95% CI, 598-652] per 10 000 live births). The risks of delivery in subsequent week of gestation significantly exceeded the risk of delivery at 39 weeks (599 [95% CI, 576-622] vs 479 [95% CI, 463-495] per 10 000 live births) and were not significant at 40 weeks (639 [95% CI, 605-675] vs 594 [95% CI, 572-617] per 10 000 live births) and 41 weeks (701 [95% CI, 628-781] vs 633 [95% CI, 599-669] per 10 000 live births). Conclusions and Relevance: Results of this study suggest that, in pregnancies conceived with infertility treatment, delivery at 39 weeks provided the lowest perinatal risk when comparing risk of delivery at this week of gestation vs the subsequent week of gestation.

Influence of social determinants of health on breastfeeding intent in the United States.

BACKGROUND: Breastfeeding rates in the United States are suboptimal despite public health recommendations that infants are fed breastmilk for their first year of life. This study aimed to characterize the influence of social determinants of health on intended breastfeeding duration. METHODS: This case-control study analyzed breastfeeding intent in 421 postpartum women. Data on social determinants and medical history were obtained from medical records and participant self-report. Logistic regression estimated the influence of demographic factors and social determinants on intent to breastfeed for durations of <6 months, 6-12 months, and at least 1 year. RESULTS: Thirty-five percent of mothers intended to breastfeed for at least 6 months, and 15% for 1 year. Social determinants that negatively predicted breastfeeding intent included not owning transportation and living in a dangerous neighborhood (p < 0.05). Women were more likely to intend to breastfeed for 12 months if they had knowledge of breastfeeding recommendations (adjusted odds ratio [aOR] 6.19, 95% confidence interval [CI 2.67-14.34]), an identifiable medical provider (aOR 2.64 [CI 1.22-5.72]), familial support (aOR 2.80 [CI 1.01-7.80]), or were married (aOR 2.55 [CI 1.01-6.46]). Sociodemographic factors that negatively influenced breastfeeding intent included non-Hispanic Black race, no high school diploma, cigarette use, income below $20,000, fewer than five prenatal visits, and WIC or Medicaid enrollment (p < 0.05). CONCLUSIONS: Women who lack familial support, an identifiable healthcare provider, or knowledge of breastfeeding guidelines are less likely to intend to breastfeed. Public health initiatives should address these determinants to improve breastfeeding and infant outcomes.

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn.

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44-0.88 log10 higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55-1.77 for IgG, 1.00-1.78 for live virus nAb and 1.79-2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.

Twin-twin transfusion syndrome recipient with arterial calcification and heterozygous variant in ABCC6: Evidence of a gene-environment interaction?

We report a case of a twin-twin transfusion syndrome (TTTS) recipient who, after successful fetoscopic surgery, developed a large pericardial effusion and calcifications of the aorta and main pulmonary artery. The donor fetus never had cardiac strain and never developed cardiac calcifications. A heterozygous likely pathogenic variant in ABCC6 (c.2018T > C, p.Leu673Pro) was identified in the recipient twin. While TTTS recipient twins are at risk of arterial calcifications and right heart failure secondary to the disease, calcifications of the great vessels are also observed in generalized arterial calcification of infancy, a Mendelian genetic disorder with associated biallelic pathogenic variations in ABCC6 or ENPP1, which can result in significant pediatric morbidity or mortality. The recipient twin in this case had some degree of cardiac strain prior to TTTS surgery; however, the progressive calcification of the aorta and pulmonary trunk occurred weeks after TTTS resolution. This case raises the possibility of a gene-environment interaction and emphasizes the need for genetic evaluation in the setting of TTTS and calcifications.

Neonatal Depression Is Associated With 1-Year Mortality in Critical Congenital Heart Disease.

Background Low 5-minute Apgar scores (AS) are predictive of term and preterm neonatal mortality but have not been well studied in the critical congenital heart disease (CCHD) population. We analyzed US national vital statistics data to evaluate the association between neonatal depression (AS 0-3) and 1-year mortality in CCHD. Methods and Results We performed a retrospective cohort study using 2014 to 2018 Centers for Disease Control and Prevention cohort-linked birth certificate and infant death records. Five-minute AS were categorized as ≤3, 4 to 6, or ≥7. We calculated birth rates and associated mortality rates by AS group in infants with and without CCHD. Multivariable logistic regression analyzed neonatal, maternal, and pregnancy-related risk factors for neonatal depression and 1-year mortality. Of 11 642 neonates with CCHD (0.06% of all births), the 5.8% with AS 0 to 3 accounted for 23.3% of all 1-year CCHD mortality, with 69.9% of deaths occurring within 1 month of life. Gestational age at birth, growth restriction, extracardiac defects, race, and low maternal education were associated with an increased odds of AS 0 to 3 in neonates with CCHD relative to those with AS 7 to 10 on multivariable analysis. AS 0 to 3 was associated with 1-year CCHD mortality after adjusting for these factors, prenatal care, and delivery location (adjusted odds ratio, 14.57 [95% CI, 11.73-18.10]). Conclusions The AS is a routine clinical measure providing important prognostic information in CCHD. These findings suggest that prenatal and perinatal factors, beyond those included in current risk stratification tools, are important for CCHD outcomes. Multidisciplinary collaboration to understand the pathophysiology underlying neonatal depression may help identify interventions to improve CCHD mortality rates.

Influence of the COVID-19 pandemic on social determinants of health among an inner-city obstetrical population.

BACKGROUND: Social determinants of health are a well-described influencer of pregnancy-related morbidity and mortality. It is unclear how societal changes secondary to the COVID-19 pandemic altered the social determinants of health among pregnant patients. OBJECTIVE: This study aimed to investigate differences in the social determinants of health among patients who experienced pregnancy before and during the COVID-19 pandemic. STUDY DESIGN: This was a secondary analysis of an ongoing prospective cohort study examining the social determinants of health in postpartum patients at a single inner-city academic medical center. The planned secondary analysis was to compare the social determinants of health between patients that experienced societal changes before the pandemic and patients that experienced societal changes during the pandemic. Patients were included in the pandemic group if they delivered on or after March 30, 2020; moreover, patients in the pandemic group were compared with those who delivered before March 30, 2020 (referent group). Medical records were used to collect sociodemographic, pregnancy, and infant outcome data. The study participants were interviewed to collect detailed information regarding their perceived social, emotional, and physical environment as indicators of social determinants of health. Generalized linear modeling estimated the influence of social determinants of health  on births during the COVID-19 pandemic. RESULTS: Overall, 577 patients were enrolled in the study, of which 452 (78%) delivered before the COVID-19 pandemic and 125 (22%) delivered during the pandemic. Patients who delivered during the pandemic were more likely to report limited social or emotional support (relative risk, 1.62; 95% confidence interval, 1.02-2.59) and higher race-based discrimination (relative risk, 1.59; 95% confidence interval, 1.00-2.53). Mothers in the prepandemic group were more likely to have used federally funded programs, such as Medicaid, food stamps, and the Special Supplemental Nutrition Program for Women, Infants, and Children, during their pregnancy. Furthermore, the referent group reported more limited access to transportation. In addition, mothers in the prepandemic group were more likely to initiate prenatal care at a later gestational age and have fewer total prenatal care visits. CONCLUSION: The COVID-19 pandemic created unprecedented changes in pregnancy care, and these were reflected in social determinants of health. It is imperative that we focus on the social determinants of health that were mitigated during this time and their effects on maternal and infant health.