Discovery of a multipotent cell type from the term human placenta.

We report a unique population of multipotent cells isolated from the term human placenta, for the first time, that can differentiate into cardiomyocytes and vascular cells with clonal proliferative ability, migratory ability, and trancriptomic evidence of immune privilege. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development but has not previously been implicated in developmentally conserved regenerative mechanisms. We had earlier reported that Cdx2 lineage cells in the mouse placenta are capable of restoring cardiac function after intravenous delivery in male mice with experimental cardiac injury (myocardial infarction). Here we demonstrate that CDX2-expressing cells are prevalent in the human chorion and are poised for cardiovascular differentiation. We examined the term placentas from 106 healthy patients and showed that isolated CDX2 cells can spontaneously differentiate into cardiomyocytes, functional vascular cells, and retain homing ability in vitro. Functional annotation from transcriptomics analysis supports enhanced cardiogenesis, vasculogenesis, immune modulation, and chemotaxis gene signatures in CDX2 cells. CDX2 cells can be clonally propagated in culture with retention of cardiovascular differentiation. Our data supports further use of this accessible and ethically feasible cell source in the design of therapeutic strategies for cardiovascular disease.

Evaluation of 2-year outcomes in infants born to mothers with and without NAFLD in pregnancy.

Nonalcoholic fatty liver disease (NAFLD) affects an estimated 17% of pregnant patients in the USA. However, there are limited data on the impact of maternal NAFLD on pediatric outcomes. We prospectively evaluated outcomes in infants born to mothers with and without NAFLD in pregnancy over their first 2 years of life. Maternal subjects were identified through an ongoing prospective study in which pregnant individuals were screened for NAFLD. Pediatric outcomes of infants born to these mothers-including adverse neonatal outcomes and weight and weight-for-length percentile at 6, 12, 18, and 24 months-were prospectively evaluated. Multivariate logistic regression was performed to evaluate the association of maternal NAFLD with pediatric outcomes, as well as to adjust for potentially confounding maternal characteristics. Six hundred thirty-eight infants were included in our cohort. The primary outcomes assessed were weight and growth throughout the first 2 years of life. Maternal NAFLD was also not associated with increased infant birth weight or weight-for-gestational-age percentile or weight or weight-for-length percentile over the first 2 years of life. Maternal NAFLD was significantly associated with very premature delivery before 32 weeks, even after adjustment for confounding maternal characteristics (aOR = 2.83, p = 0.05). Maternal NAFLD was also significantly associated with neonatal jaundice, including after adjusting for maternal race (aOR = 1.67, p = 0.03). However, maternal NAFLD was not significantly associated with any other adverse neonatal outcomes.    Conclusion: Maternal NAFLD may be independently associated with very premature birth and neonatal jaundice but was not associated with other adverse neonatal outcomes. Maternal NAFLD was also not associated with any differences in infant growth over the first 2 years of life. What is Known: • Maternal NAFLD in pregnancy may be associated with adverse pregnancy and neonatal outcomes, but the findings are inconsistent across the literature. What is New: • Maternal NAFLD is not associated with any differences in weight at birth or growth over the first 2 years of life. • Maternal NAFLD is associated with very premature delivery and neonatal jaundice, but is not associated with other adverse neonatal outcomes.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Titer Levels in Pregnant Individuals After Infection, Vaccination, or Both.

We examined differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses in pregnant individuals with natural, vaccine-induced, or combined immunity. Participants had live or nonlive births between 2020 and 2022, were seropositive (SARS-CoV-2 spike protein, anti-S), and had available mRNA vaccination and infection information (n=260). We compared titer levels among three immunity profiles: 1) natural immunity (n=191), 2) vaccine-induced immunity (n=37), and 3) combined immunity (ie, natural and vaccine-induced immunity; n=32). We applied linear regression to compare anti-S titers between the groups, controlling for age, race and ethnicity, and time between vaccination or infection (whichever came last) and sample collection. Anti-S titers were 57.3% and 94.4% lower among those with vaccine-induced and natural immunity, respectively, compared with those with combined immunity ( P <.001, P =.005).

Unique Profile of Inflammation and Immune Activation in Pregnant People With HIV in the United States.

BACKGROUND: Little is known about inflammation/immune activation during pregnancy in people with HIV (PWH) and growth in their children who are HIV-exposed and uninfected (CHEU). METHODS: Using data from the Pediatric HIV/AIDS Cohort Study and an HIV-seronegative comparison group, we assessed associations of (1) HIV status, mode of HIV acquisition (perinatally vs nonperinatally acquired), and type of antiretroviral therapy (ART) with inflammation/immune activation in pregnancy; and (2) inflammation/immune activation in pregnancy with growth of CHEU at 12 months. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble(s) TNF-α receptor 1 and 2 (sTNFR1, sTNFR2), sCD14, and sCD163 were measured between 13 and 27 weeks' gestation. Linear regression models were fit to estimate differences between groups for each log-transformed biomarker, adjusted for confounders. RESULTS: Pregnant PWH (188 total, 39 perinatally acquired, 149 nonperinatally acquired) and 76 HIV-seronegative persons were included. PWH had higher IL-6, sTNFR1, sCD14, and sCD163 and lower sTNFR2 compared to HIV-seronegative persons in adjusted models. Among PWH, sCD163 was higher in those with perinatally versus nonperinatally acquired HIV and on PI-based versus INSTI-based ART. Higher maternal concentrations of IL-6, sTNFR2, and hs-CRP were associated with poorer growth at 12 months. CONCLUSIONS: Maternal HIV status is associated with a distinct profile of inflammation/immune activation during pregnancy, which may influence child growth.

Impact of prenatal COVID-19 vaccination on delivery and neonatal outcomes: Results from a New York City cohort.

Research suggest prenatal vaccination against coronavirus disease-19 (COVID-19) is safe. However, previous studies utilized retrospectively collected data or examined late pregnancy vaccinations. We investigated the associations of COVID-19 vaccination throughout pregnancy with delivery and neonatal outcomes. We included 1,794 mother-neonate dyads enrolled in the Generation C Study with known prenatal COVID-19 vaccination status and complete covariate and outcome data. We used multivariable quantile regressions to estimate the effect of prenatal COVID-19 vaccination on birthweight, delivery gestational age, and blood loss at delivery; and Poisson generalized linear models for Caesarean delivery (CD) and Neonatal Intensive Care Unit (NICU) admission. Using the above methods, we estimated effects of trimester of vaccine initiation on these outcomes. In our sample, 13.7% (n = 250) received at least one prenatal dose of any COVID-19 vaccine. Vaccination was not associated with birthweight (ß = 12.42 g [-90.5, 114.8]), gestational age (ß = 0.2 days [-1.1, 1.5]), blood loss (ß = -50.6 ml [-107.0, 5.8]), the risks of CD (RR = 0.8; [0.6, 1.1]) or NICU admission (RR = 0.9 [0.5, 1.7]). Trimester of vaccine initiation was also not associated with these outcomes. Our findings suggest that there is no associated risk between prenatal COVID-19 vaccination and adverse delivery and neonatal outcomes in a cohort sample from NYC.

Prevalence of elevated alanine aminotransferase (ALT) in pregnancy: A cross-sectional labor and delivery-based assessment.

Since liver tests are not routinely checked in pregnancy, the prevalence of abnormal liver tests and liver-related abnormalities in pregnancy in a US-based population is not known. We sought to determine the prevalence of abnormal alanine aminotransferase (ALT) among pregnant Individuals who present to labor and delivery for evaluation and to evaluate prevalence of underlying diagnosed liver conditions. Prospective study evaluating liver tests in consecutive samples obtained on the labor and delivery unit. Patient characteristics were compared between those with and without abnormal ALT and those with and without abnormal ALT without a liver-related diagnosis made in clinical practice, using t tests for continuous measures and χ2 or Fisher's exact tests as appropriate for categorical measures. Logistic regression was utilized to identify factors associated with abnormal ALT in this subcohort to determine predictors of abnormal ALT in those without a known liver-related diagnosis. We collected 1024 laboratory specimens from 996 patients. Of these patients, 131 of 996 (13.2%) had elevated ALT ≥25 IU/L; 20 (2%) had ALT ≥50, 6 (0.6%) had ALT ≥125 and 3 (0.3%) had ALT ≥250. 61/131 (46.6%) of patients with ALT ≥25 IU/L had not had LTs checked during routine pregnancy care. 20 (15%) of individuals with abnormal LT had preeclampsia; 5 (4%) had cholestasis of pregnancy; 1 (0.8%) had hepatitis C; there were no other chronic liver diseases diagnosed. There were no significant demographic or clinical differences between those with and without ALT ≥25, whether liver disease diagnosis was made or not. We identified an over 10% prevalence of abnormal LTs in consecutive pregnant individuals who presented to L&D, most of whom did not have a liver-related condition diagnosed in clinical practice. Among those with liver-related diagnoses, PE and ICP were the most common among individuals with ALT≥25 IU/mL, with chronic liver disease rarely diagnosed. Further evaluation of the role of ALT testing as part of routine prenatal care is needed, particularly in establishing a baseline prevalence of liver test abnormalities in pregnancy and independent association with pregnancy outcomes.

SARS-CoV-2 during pregnancy and associated outcomes: Results from an ongoing prospective cohort.

BACKGROUND: The COVID-19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Questions remain about how SARS-CoV-2 impacts pregnant individuals and their children. OBJECTIVE: To expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. METHODS: The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT-PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. RESULTS: The SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS-CoV-2 RT-PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. CONCLUSION: Seropositivity for SARS-CoV-2 without RT-PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

Distinct cord blood C-peptide, adipokine, and lipidomic signatures by in utero HIV exposure.

BACKGROUND: Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported. METHODS: Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011 to 2015. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) newborns using ELISA and metabolites, lipid subspecies, and eicosanoids via liquid chromatography/mass spectrometry. Linear regression was employed to assess the association of intrauterine HIV/ART with insulin and C-peptide. Graphical lasso regression was used to identify differences between metabolite/lipid subspecies networks associated with C-peptide. RESULTS: Of 118 infants, 56 were HEU, ART exposed. In adjusted analyses, mean cord insulin (ß = 0.295, p = 0.03) and C-peptide (ß = 0.522, p < 0.01) were significantly higher in HEU vs. HUU newborns. HEU neonates exhibited primarily positive associations between complex lipids and C-peptide, indicative of fuel storage, and augmented associations between cord eicosanoids and cytokines. HUU neonates exhibited negative associations with lipids and C-peptide indicative of increased fuel utilization. CONCLUSION: Higher cord insulin and C-peptide in HEU vs. HUU newborns as well as differences in cord metabolites, metabolic-related cytokines, and eicosanoids may reflect a propensity for fuel storage and an inflammatory milieu suggestive of fetal metabolic changes associated with in utero HIV/ART exposure. IMPACT: There is a paucity of studies assessing cord blood and neonatal metabolic health in HIV-exposed uninfected (HEU) newborns, an increasing population worldwide. Compared to HIV-unexposed uninfected (HUU) newborns, HEU newborns exhibit alterations in fuel homeostasis and an inflammatory milieu associated with in utero HIV/antiretroviral therapy (ART) exposure. The long-term implications of these neonatal findings are as yet unknown, but merit continued evaluation as this important and growing population ages into adulthood.

Corrigendum to: Hepatitis C Seroprevalence Among Consecutive Labor and Delivery Admissions in Two New York City Hospitals.

[This corrects the article DOI: 10.1093/ofid/ofaa514.].