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.

Objective: Women with systemic lupus erythematosus (SLE) may experience adverse perinatal outcomes in the years before an SLE diagnosis. Overall, there is limited research on perinatal outcomes among African American women with SLE. We undertook this study to examine the risk of preterm and small-for-gestational age births among African American women with SLE compared to the general population of African American women in a large metropolitan area. Methods: Information about women with SLE was identified from the Georgia Lupus Registry and the Georgians Organized Against Lupus Cohort and was linked with birth certificates by the Georgia Department of Public Health. Births were categorized into occurring more than 3 years before SLE diagnosis, 0–3 years before SLE diagnosis, 0–3 years after SLE diagnosis, or more than 3 years after SLE diagnosis. Comparison birth certificates to African American women in the same geographic area were obtained from the National Center for Health Statistics. We used log-risk models to compare the risk of preterm or small-for-gestational age births among SLE births in each diagnosis timing category to the general population, adjusting for maternal age and education and parity. Results: Births to women with SLE were more likely to occur preterm at 0–3 years before SLE diagnosis (risk ratio [RR] 1.71, 95% confidence interval [95% CI] 1.24–2.35), 0–3 years after SLE diagnosis (RR 2.29, 95% CI 1.70–3.09), and 3 or more years after SLE diagnosis (RR 2.83, 95% CI 2.36–3.38), but not 3 or more years before SLE diagnosis compared to the general population (RR 1.03, 95% CI 0.77–1.38). Similar results were observed for small-for-gestational age births. Conclusion: Our analysis, conducted among African American women, demonstrates an increased risk of adverse perinatal outcomes even before a clinical diagnosis of SLE.

Importance: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad. Objective: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy. Design, Setting, and Participants: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic acid or antigen test, and for whom ECMO was initiated for respiratory failure from March 1, 2020, to October 1, 2022. Exposures: ECMO in the setting of COVID-19 respiratory failure. Main outcome and measures: The primary outcome was maternal mortality. Secondary outcomes included serious maternal morbidity, obstetrical outcomes, and neonatal outcomes. Outcomes were compared by timing of infection during pregnancy or post partum, timing of ECMO initiation during pregnancy or post partum, and periods of circulation of SARS-CoV-2 variants. Results: From March 1, 2020, to October 1, 2022, 100 pregnant or postpartum individuals were started on ECMO (29 [29.0%] Hispanic, 25 [25.0%] non-Hispanic Black, 34 [34.0%] non-Hispanic White; mean [SD] age: 31.1 [5.5] years), including 47 (47.0%) during pregnancy, 21 (21.0%) within 24 hours post partum, and 32 (32.0%) between 24 hours and 6 weeks post partum; 79 (79.0%) had obesity, 61 (61.0%) had public or no insurance, and 67 (67.0%) did not have an immunocompromising condition. The median (IQR) ECMO run was 20 (9-49) days. There were 16 maternal deaths (16.0%; 95% CI, 8.2%-23.8%) in the study cohort, and 76 patients (76.0%; 95% CI, 58.9%-93.1%) had 1 or more serious maternal morbidity events. The largest serious maternal morbidity was venous thromboembolism and occurred in 39 patients (39.0%), which was similar across ECMO timing (40.4% pregnant [19 of 47] vs 38.1% [8 of 21] immediately postpartum vs 37.5% postpartum [12 of 32]; P > .99). Conclusions and Relevance: In this multicenter US cohort study of pregnant and postpartum patients who required ECMO for COVID-19-associated respiratory failure, most survived but experienced a high frequency of serious maternal morbidity.

Background:This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples.Setting:A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children.Methods:Intensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Atazanavir and cobicistat were measured in plasma by validated high-performance liquid chromatography-ultraviolet and liquid chromatography-tandem mass spectrometry assays, respectively. A 2-tailed Wilcoxon signed-rank test (α = 0.10) was used for paired within-participant comparisons.Results:A total of 11 pregnant women enrolled in the study. Compared with paired postpartum data, atazanavir AUC0-24was 26% lower in the second trimester [n = 5, P = 0.1875, geometric mean of ratio (GMR) = 0.739, 90% CI: 0.527 to 1.035] and 54% lower in the third trimester (n = 6, GMR = 0.459, P = 0.1563, 90% CI: 0.190 to 1.109), whereas cobicistat AUC0-24was 35% lower in the second trimester (n = 5, P = 0.0625, GMR = 0.650, 90% CI: 0.493 to 0.858) and 52% lower in the third trimester (n = 7, P = 0.0156, GMR = 0.480, 90% CI: 0.299 to 0.772). The median (interquartile range) 24-hour atazanavir trough concentration was 0.21 g/mL (0.16-0.28) in the second trimester, 0.21 g/mL (0.11-0.56) in the third trimester, and 0.61 g/mL (0.42-1.03) in postpartum. Placental transfer of atazanavir and cobicistat was limited.Conclusions:Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission.

BACKGROUND: Pregnant patients with SARS-CoV-2 infection are at increased risk for severe disease including hospitalization, intensive care admission, ventilatory support, and death. Although pregnant patients were excluded from investigational trials for pharmacologic treatments for COVID-19 illness, the National Institutes of Health treatment guidelines state that efficacious treatments should not be withheld from pregnant patients. An infusion of casirivimab and imdevimab (REGEN-COV), a monoclonal antibody therapy, was shown to reduce the risk of COVID-19–related hospitalization or death from any cause and resolved symptoms and reduced SARS-CoV-2 viral load more rapidly than placebo. In July of 2021, the Food and Drug Administration released an Emergency Use Authorization for REGEN-COV. Although pregnant persons were not included in the original trials, given the higher risk of morbidity and mortality in the pregnant population, our institution offered REGEN-COV to our pregnant patients beginning in August of 2021. Side effects after REGEN-COV administration are rare and thought to be secondary to COVID-19 rather than REGEN-COV. OBJECTIVE: This study aimed to track safety and clinical outcomes in unvaccinated pregnant patients who received REGEN-COV and to compare these outcomes with those of a contemporary cohort of patients who tested positive for SARS-CoV-2 and were eligible but did not receive REGEN-COV. Our hypothesis was that REGEN-COV administration during pregnancy is safe, and that pregnant persons who received REGEN-COV would experience less severe COVID-19 respiratory illness, with decreased length of hospital stay, rates of intensive care unit admission, and need for oxygen and other COVID-19 therapeutics. STUDY DESIGN: This is a retrospective cohort study of pregnant patients who either tested positive for SARS-CoV-2 or had a known exposure to a COVID-19–positive person, and were therefore eligible for REGEN-COV at our institution. Within this cohort, we compared those who received REGEN-COV with those who did not between March and October of 2021 at Grady Memorial Hospital in Atlanta, Georgia. The main outcomes studied were perinatal outcomes, safety data, and the clinical course of SARS-CoV-2 infection. RESULTS: From March to October of 2021, 86 pregnant people tested positive for SARS-CoV-2 via real-time polymerase chain reaction or had a confirmed exposure. In this group, 36 received REGEN-COV and 50 did not. There were no instances of infusion rate adjustment or discontinuation, anaphylaxis, or death among individuals who received REGEN-COV. One individual experienced worsening shortness of breath >24 hours after administration, which was classified as an infusion-related reaction. There were no significant differences in perinatal outcomes, length of hospitalization, rates of intensive care unit admission, additional pharmacologic treatment for COVID-19, or oxygen requirement between the 2 groups. CONCLUSION: Administration of REGEN-COV is safe in pregnancy and did not increase adverse maternal, neonatal, or obstetrical outcomes. There was not a statistically significant difference in COVID-19–related outcomes in our high-risk population. Given the likely safety of this drug in pregnancy and its known benefits in the nonpregnant population, we advocate for the continued use of this therapy and encourage the development of future studies to enroll a larger and more diverse cohort to explore its efficacy further.

Pregnancy is an independent risk factor for severe covid-19. Vaccination is the best way to reduce the risk for SARS-CoV-2 infection and limit its morbidity and mortality. The current recommendations from the World Health Organization, Centers for Disease Control and Prevention, and professional organizations are for pregnant, postpartum, and lactating women to receive covid-19 vaccination. Pregnancy specific considerations involve potential effects of vaccination on fetal development, placental transfer of antibodies, and safety of maternal vaccination. Although pregnancy was an exclusion criterion in initial clinical trials of covid-19 vaccines, observational data have been rapidly accumulating and thus far confirm that the benefits of vaccination outweigh the potential risks. This review examines the evidence supporting the effectiveness, immunogenicity, placental transfer, side effects, and perinatal outcomes of maternal covid-19 vaccination. Additionally, it describes factors associated with vaccine hesitancy in pregnancy. Overall, studies monitoring people who have received covid-19 vaccines during pregnancy have not identified any pregnancy specific safety concerns. Additional information on non-mRNA vaccines, vaccination early in pregnancy, and longer term outcomes in infants are needed. To collect this information, vaccination during pregnancy must be prioritized in vaccine research.

Pregnant people and minorities are at increased risk for severe COVID-19 infection, including hospitalization, ICU admission and death.1, 2, 3 Early research on the maternal and fetal implications of SARS-CoV-2 infection in pregnancy focused on maternal outcomes and was limited by lack of patient diversity and biospecimen data to answer questions related to maternal immunity and passive immunity.4 The Grady Memorial Hospital obstetrics service, which is a large publicly supported hospital in Atlanta (970 beds, approximately 2500 deliveries per year), a tertiary referral hospital, and a safety net institution, is uniquely poised to address this literature gap. Despite this, an infrastructure did not previously exist for biologic sample collection.

Preeclampsia (PE) is a prevalent pregnancy disorder that leads to high maternal and fetal morbidity and mortality. While defective vascular development and angiogenesis in placenta are known as crucial pathological findings, its pathophysiological mechanism remains elusive. To better understand the effects of PE on angio-vasculogenesis and inflammatory networks in the fetus and to identify their biological signatures, we investigated the quantitative and functional characteristics of cord blood-derived mononuclear cells (CB-MNCs) and CD31-positive MNCs. Flow cytometry analysis demonstrated that the CB-MNCs from the severe PE group had significantly decreased number of cells expressing CD3, CD11b, CD14, CD19, KDR, and CD31 compared with the normal group. Quantitative real time PCR (qRT-PCR) shows down-regulation of the major angiogenic factor VEGFA in MNCs and CD31+ MNCs in severe PE. The major inflammatory cytokines IL1 was highly upregulated in CD31+ CB-MNCs in the severe PE patients. Mild PE patients, however, did not display any significant difference in expression of all measured angiogenic genes and most inflammatory genes. These findings show distinct angiogenic and inflammatory signatures from severe PE, and they may play a significant role in the pathogenesis of vascular defects in placenta of severe PE.

Introduction: Although rare, perinatal HIV transmission still occurs in the United States and most transmissions are preventable. We aim to identify patient barriers to antiretroviral therapy (ART) adherence during pregnancy and assess patient understanding of perinatal transmission. Methods: This cross-sectional survey recruited HIV positive postpartum women at a large safety net hospital in Atlanta, Georgia, between January 2016 and February 2018. Survey questions included demographic characteristics, HIV history, knowledge of perinatal transmission, and ART adherence. Perinatal and HIV outcomes were assessed using chart abstraction. Results: Of the 70 HIV infected postpartum women delivered at a large safety net hospital in Atlanta, GA, 45 women were eligible and consented to participate. Participating women were aged 18 to 40 years with an average age of 29 years old, 93% of participants were African-American, and 68% had ≥3 pregnancies. The majority of participants (75%) reported daily ART adherence. "Forgetting" was the most frequent reason for missing pills (57%). Thirteen women had a detectable viral load at the time of delivery and nine of those women had a viral load greater than 1000 copies/mL. Approximately 85% of women who correctly stated ART medications decrease perinatal transmission risk reported daily adherence compared with 50% of women without that knowledge (OR 5.6, 95% CI 1.17, 26.7). Almost half of women (40%) either did not know or believed a vaginal delivery, regardless of viral load, would increase their risk of perinatal transmission. Conclusion: Overall, women who were diagnosed with HIV during the current pregnancy, those with planned pregnancies, and those who were on medications prior to pregnancy were more likely to report daily ART adherence. Detectable viral load at delivery is the greatest risk factor for perinatal transmission; therefore strategies to increase ART adherence are needed.

The use of frozen embryo transfer in assisted reproductive technology (ART) has steadily increased since development in the early 1980’s. While there are many benefits to delayed frozen embryo transfer, certain adverse perinatal outcomes are noted to be more common in these transfers when compared to fresh transfers, specifically hypertensive disorders of pregnancy. Frozen embryo transfers require coordination between the embryo’s developmental stage and the endometrial environment and can occur in either ovulatory or programmed cycles. Though there is no consensus on the ideal method of endometrial preparation prior to frozen embryo transfer, emerging data suggests differences in maternal and neonatal outcomes, specifically increased rates of hypertensive disorders of pregnancy in programmed cycles. Other reported differences include an increased risk of cesarean delivery, placenta accreta, postpartum hemorrhage, low birthweight, preterm birth, post term delivery, macrosomia, large for gestational age, and premature rupture of membranes in programmed cycles. The mechanism by which these differences exist could reflect inherent differences in groups selected for each type of endometrial preparation, the role of super physiologic hormone environments in programmed cycles, or the unique contributions of the corpus luteum in ovulatory cycles that are not present in programmed cycles. Given that existing studies are largely retrospective and have several key limitations, further investigation is needed. Confirmation of these findings has implications for current practice patterns and could enhance understanding of the mechanisms behind important adverse perinatal outcomes in those pursuing assisted reproduction.