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This study describes the largest cohort to date (n=147) of pregnant patients living with HIV on bictegravir (BIC). BIC in pregnancy was associated with high levels of viral suppression and similar perinatal outcomes to published literature. These findings support consideration for use of BIC in management of HIV during pregnancy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.9% in the United States, with >25,000 infants born annually at risk for chronic infection due to perinatal transmission. Given the burden of disease associated with chronic hepatitis B infection, recent national guidance has expanded both the indications for screening for hepatitis B infection and immunity and the indications for vaccination. The purpose of this document is to aid clinicians caring for pregnant patients in screening for hepatitis B infection and immunity status, discuss the perinatal risks of hepatitis B infection in pregnancy, determine whether treatment is indicated for maternal or perinatal indications, and recommend hepatitis B vaccination among susceptible patients. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend triple-panel testing (hepatitis B surface antigen screening, antibody to hepatitis B surface antigen, and total antibody to hepatitis B core antigen) at the initial prenatal visit if not previously documented or known to have been performed (GRADE 1C); (2) we recommend universal hepatitis B surface antigen screening alone at the initial prenatal care visit for all pregnancies where there has been a previously documented negative triple-panel test (GRADE 1B); (3) we recommend that individuals with unknown hepatitis B surface antigen screening status be tested on any presentation for care in pregnancy; we also recommend that those with clinical hepatitis or those with risk factors for acute hepatitis B infection be tested at the time of admission to a birthing facility when delivery is anticipated (GRADE 1B); (4) we do not recommend altering routine intrapartum care in individuals chronically infected with hepatitis B; administration of neonatal immunoprophylaxis is standard of care in these situations (GRADE 1B); (5) we do not recommend cesarean delivery for the sole indication of reducing perinatal hepatitis B virus transmission (GRADE 1B); (6) we recommend that individuals with HBV infection can breastfeed as long as the infant has received immunoprophylaxis at birth (GRADE 1C); (7) we suggest individuals with hepatitis B infection who desire invasive testing may have the procedure performed after an informed discussion on risks and benefits in the context of shared decision-making and in the context of how testing will affect clinical care (GRADE 2C); (8) in individuals with hepatitis viral loads >200,000 IU/mL (>5.3 log 10 IU/mL), we recommend antiretroviral therapy with tenofovir (tenofovir alafenamide at 25 mg daily or tenofovir disoproxil fumarate at 300 mg daily) in the third trimester (initiated at 28-32 weeks of gestation) as an adjunctive strategy to immunoprophylaxis to reduce perinatal transmission (GRADE 1B); (9) we recommend administering hepatitis B vaccine and hepatitis B immunoglobin within 12 hours of birth to all newborns of hepatitis B surface antigen-positive pregnant patients or those with unknown or undocumented hepatitis B surface antigen status, regardless of whether antiviral therapy has been given during the pregnancy to the pregnant patient (GRADE 1B); and (10) we recommend hepatitis B vaccination in pregnancy for all individuals without serologic evidence of immunity or documented history of vaccination (GRADE 1C)., (Copyright © 2023. Published by Elsevier Inc.)

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., (Copyright © 2024 by the American Academy of Pediatrics.)

Persons with HIV can receive mixed messages about the safety of breastfeeding. We sought to assess if they felt coerced to formula feed when counseled about practices to reduce HIV transmission. Persons with HIV who had given birth were eligible to complete a survey to describe their experiences with infant feeding counseling and if they felt coerced to formula feed. An Iowa Infant Feeding Attitude Scale (IIFAS) assessed attitudes towards breastfeeding. Qualitative analyses were performed on narrative responses. One hundred surveys were collected from sites in Georgia, North Carolina, Pennsylvania, and South Carolina. The mean IIFAS score ( n , 85) was 47 (SD 9.2), suggesting relatively favorable attitudes toward breastfeeding. Thirteen persons reported feeling coerced to formula feed. When controlling for choosing to give any breast milk, persons with any college education were more likely to report feeling coerced (aOR 9.8 [95% CI 1.8-52.5]). Qualitative analyses revealed three themes: perceiving breastfeeding as unsafe, engaging in shared decision-making, and resisting advice to formula feed. Persons with HIV desire to be counseled about safe infant feeding practices and have their questions answered without judgement. We highlight experiences of persons with HIV that reflect a need for a nuanced approach to infant feeding counseling.

Problem: In pregnancy, lower socioeconomic status (SES) is associated with adverse outcomes, which is partly attributed to chronic inflammation. Our study compared the maternal serum cytokine profiles in patients with low and high SES., Method of Study: This retrospective cohort study compared maternal serum cytokine profiles between Medicaid-insured patients who delivered at an urban safety-net hospital (low SES) and privately-insured patients who delivered at a community-based academic hospital (high SES) in Atlanta, GA (n = 32-33/group). Serum samples were obtained during prenatal venipuncture from 13 to 38 weeks' gestation and the cohorts were matched by gestational age. Interferon (IFN)-γ, Interleukin (IL)-10, IL-1β, IL-4, IL-6, IL-8, and Tumor Necrosis Factor (TNF)-α were assayed from maternal serum samples using a standard ELISA assay., Results: Median concentrations of IL-6, a promotor of chronic inflammation, were higher in the low SES group (0.85 vs. 0.49 pg/mL, p < .001), while median levels of IL-1β, a potent monocyte activator, and TNF-α, a master regulator of acute inflammation, were lower in the low SES group (0.09 vs. 0.46 pg/mL, p < .001, and 1.23 vs. 1.58 pg/mL, p = .002, respectively) as compared to the high SES group. After adjusting for maternal age, obesity, hypertensive disorders, and gestational age at delivery, the differences in IL-6 and IL-1β by SES persisted (p = .0002 and p < .0001, respectively)., Conclusions: In this retrospective cohort study, there were significant differences in levels of pro-inflammatory cytokines during pregnancy for groups defined by SES, even after adjustment for confounding variables. Our data are foundational for further research to investigate SES-associated inflammation that may contribute to adverse pregnancy outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Pregnant patients face greater morbidity and mortality from COVID-19 related illness than their non-pregnant peers. Previous research in non-pregnant patients established that poor clinical outcomes in SARS-CoV-2 positive patients admitted to the ICU were correlated with a significant increase in the proinflammatory markers interleukin (IL)-1β, IL-6, IL-8, and IL-10. Importantly, high levels of these inflammatory markers have also been associated with adverse pregnancy outcomes, including spontaneous preterm birth, preeclampsia, and severe respiratory disease., Study Design: This was a retrospective cohort study that compared the serum inflammatory cytokine profiles of pregnant patients with acute/post-acute SARS-CoV-2 infection to those with previous exposure. All subjects in both cohorts tested positive for SARS-CoV-2 antibodies; however, those in the acute/post-acute infection cohort had a documented positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 30 days of serum sample collection. Serum samples were obtained during prenatal venipuncture from 13 to 39 weeks' gestation and the cohorts were matched by gestational age. The inflammatory cytokines interferon (IFN)-γ, IL-10, IL-1β, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α were assayed from maternal serum using a standard ELISA assay and median cytokine concentrations were compared using the Mann-Whitney test., Results and Discussion: We enrolled 50 non-Hispanic Black patients with confirmed COVID-19 infection who received prenatal care at Grady Memorial Hospital in Atlanta, Georgia. Those with acute/post-acute infection (n = 22) had significantly higher concentrations of SARS-CoV-2 antibody, IL-10, IL-1β, and IL-8, while patients with previous exposure (n = 28) had significantly higher concentrations of IL-4. There were no significant inter-group differences in medical comorbidities. Pregnant patients with acute/post-acute SARS-CoV-2 infection had significantly higher serum concentrations of pro-inflammatory cytokines as compared to those with previous exposure, suggesting that, like in the non-pregnant population, SARS-CoV-2 infection alters the levels of circulating proinflammatory markers during pregnancy. The increased levels of cytokines may contribute to the adverse obstetric outcomes observed with COVID-19 illness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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 log 10 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F.M.M. is an investigator of pediatric studies of COVID-19 vaccines for Pfizer and for a pediatric remdesivir study conducted by Gilead Sciences, Inc; serves as investigator on projects supported by an NIH contract for a Vaccine Treatment and Evaluation Unit (VTEU), serves as member of the Data Safety monitoring Board (DSMB) for clinical trials conducted by Pfizer, Moderna, Meissa Vaccines, Virometix, and the NIH; and is a member of the American Academy of Pediatrics Section of Infectious Diseases (SOID), the Immunization Expert Group of the American College of Obstetrics and Gynecology (ACOG), and was co-Chair of the COVAX-CEPI Maternal Immunization Working Group. K.M.N. is a member of the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization, serves as co-investigator on an NIH contract for a Vaccine Treatment and Evaluation Unit (VTEU), serves as Co-Chair of the NIH COVID Prevention Network (CoVPN), and served as an investigator for Phase I/II Pfizer COVID-19 vaccine grant, with a grant to the institution, but no salary support. M.J.M. conducts laboratory research and clinical trials with contract funding for vaccines or MABs vs SARS-CoV-2 with Lilly, Pfizer, and Sanofi and receives personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. M.S.S. served as an advisor for Moderna (ended December 2021) and is currently serving as an advisor for Ocugen, Inc. B.A.R. currently holds a position on a DSMB for clinical trials at Gilead Sciences, Inc. R.C.B. at Cincinnati Children’s Hospital receives research grant support for clinical trials from PATH, Astra Zeneca and Pfizer on which she serves as co-investigator. B.B. owns shares in HDT Bio Corp. J.S.G. receives research funds from NIH for Moderna KidCOVE study. R.M.N. is a paid advisor to Gilead and an investigator on NIH-funded trials of Moderna, Pfizer and Janssen vaccines. J.R-K is a medical speaker for Abbott Nutrition with the UIC team. A.R.F. holds research grants from Pfizer, Janssen, Merck, Cyanvac, Biofire Diagnostics and serves on the DSMB for Novavax. N.R. receives funds to conduct industry trials from Pfizer, Merck, and Sanofi-Pasteur and serves as a safety consultant for EMMES and ICON. R.W.F. Jr., MD has received funds to conduct industry trials from Pfizer, Moderna and Astra Zeneca, serves on advisory boards for Merck, Sanofi-Pasteur, Johnson and Johnson and Seqirus and serves on an ICON-sponsored DSMB for a C difficile study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To improve our understanding of the immune response, including the neutralization antibody response, following COVID-19 vaccination in pregnancy., Methods: This was a prospective cohort study comprising patients with PCR-confirmed SARS-CoV-2 infection and patients who received both doses of mRNA COVID-19 vaccine (mRNA-1273, BNT162b2) in pregnancy recruited from two hospitals in Atlanta, GA, USA. Maternal blood and cord blood at delivery were assayed for anti-receptor binding domain (RBD) IgG, IgA and IgM, and neutralizing antibody. The detection of antibodies, titers, and maternal to fetal transfer ratios were compared., Results: Nearly all patients had detectable RBD-binding IgG in maternal and cord samples. The vaccinated versus infected cohort had a significantly greater proportion of cord samples with detectable neutralizing antibody (94% vs. 28%, P < 0.001) and significantly higher transfer ratios for RBD-specific IgG and neutralizing antibodies with a transfer efficiency of 105% (vs. 80%, P < 0.001) and 110% (vs. 90%, P < 0.001), respectively. There was a significant linear decline in maternal and cord blood RBD-specific IgG and neutralizing antibody titers as time from vaccination to delivery increased., Conclusions: Those who receive the mRNA COVID-19 vaccine mount an immune response that is equivalent to-if not greater than-those naturally infected by SARS-CoV-2 during pregnancy., (© 2023 International Federation of Gynecology and Obstetrics.)

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.

The majority of pediatric human immunodeficiency virus (HIV) infections are the result of vertical transmissions that occur during pregnancy, childbirth, and breastfeeding. The treatment of all pregnant persons living with HIV remains a global health initiative. Early and consistent use of antiretroviral therapy throughout pregnancy and childbirth drastically reduces the risk of perinatal transmission of HIV, resulting in fewer children living with the disease worldwide. Given that the maternal HIV viral load is the strongest predictor of perinatal transmission, suppressive antiretroviral treatment during pregnancy is the principal means to eliminate transmission of HIV from mother to child. With the use of combined antiretroviral therapy, typically with dual-nucleoside reverse transcriptase inhibitors plus an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, HIV-infected mothers can now achieve virologic suppression to undetectable levels and yield a perinatal transmission rate of less than 2%. Important considerations of HIV treatment in pregnancy include the safety and efficacy of antiretroviral drugs, altered pregnancy-related pharmacokinetics, potential for birth defects or adverse neonatal outcomes, and individualized delivery planning based on maternal viral load. This practical review article summarizes the options, considerations, and recommendations for antiretroviral treatment in pregnancy to reduce perinatal HIV transmission and optimize health outcomes for mothers and infants worldwide., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: We examined the relationship between placental histopathology and transplacental antibody transfer in pregnant patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: Differences in plasma concentrations of anti-receptor biding domain (RBD) immunoglobulin (Ig)G antibodies in maternal and cord blood were analyzed according to presence of placental injury., Results: Median anti-RBD IgG concentrations in cord blood with placental injury (n = 7) did not differ significantly from those without injury (n = 16) (median 2.7 [interquartile range {IQR}, 1.8-3.6] vs 2.7 [IQR, 2.4-2.9], P = 0.59). However, they were associated with lower transfer ratios (median 0.77 [IQR, 0.61-0.97] vs 0.97 [IQR, 0.80-1.01], P = 0.05)., Conclusions: SARS-CoV-2 placental injury may mediate reduced maternal-fetal antibody transfer., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For cipermissions, please e-mail: journals.permissions@oup.com.)

Viral infections pose unique threats to pregnant persons and their infants. As the frequency of epidemics caused by novel pathogens increases, understanding pregnancy-specific considerations for antiviral treatments is critical for obstetric and nonobstetric providers alike. The use of pharmacologic therapeutics in pregnancy, which include antivirals, pathogen-specific antibodies, and vaccines, is limited due to the lack of purposeful, methodologic, pharmacometrics analyses in this special population. Our current understanding regarding dosing, safety, and efficacy stems from our knowledge of potential maternal or neonatal risks, observational data, and rarely clinical trials. In this review, we provide an overview on the use of antivirals during pregnancy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Historically, individuals with HIV have reported feeling coerced during contraceptive counseling or experienced forced sterilization. The purpose of this study was to assess perceptions of coercion related to counseling and influence on postpartum contraceptive choice among individuals with HIV., Methods: This is a mixed methods study conducted in Georgia, North Carolina, Pennsylvania, and South Carolina between March 2020 and June 2021. Participants completed a survey to assess their experiences with contraception counseling and perceived coercion. An Interpersonal Quality of Family Planning (IQFP) care score was calculated to assess quality of counseling. Qualitative analyses were performed on narrative responses. Bivariate and regression analyses were used to evaluate factors associated with perceived coercion and IQFP scores., Results: 100 surveys were collected. The median age of respondents was 29 (IQR 24-35). The median IQFP score was 53 (IQR 44-55) and 45 % of individuals had a maximum IQFP score of 55. Most individuals (96 %) report that a provider "did a good job" explaining contraceptive options and 26 % report their provider's preference affected their contraceptive choice to some degree. Few (11 %) respondents felt pressured to use long-acting reversible contraception postpartum. This perceived coercion was more likely when a provider suggested a specific contraceptive method, aOR 6.1 [95 % CI 1.1-33.1] and such specific provider suggestions were reported by one-third of respondents., Conclusion: While perceived coercion was reported by few individuals with HIV, it was strongly associated with the provider making a specific method suggestion. Disproportionate provider influence in the final contraceptive decision occurred in one-quarter of individuals. More research is needed to discern to what extent provider preference compromises patient autonomy in shared decision-making., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Gestational weight gain above Institute of Medicine recommendations is associated with increased risk of pregnancy complications. The goal was to analyze the association between newer HIV antiretroviral regimens (ART) on gestational weight gain., Methods: A retrospective cohort study of pregnant women with HIV-1 on ART. The primary outcome was incidence of excess gestational weight gain. Treatment effects were estimated by ART regimen type using log-linear models for relative risk (RR), adjusting for prepregnancy BMI and presence of detectable viral load at baseline., Results: Three hundred three pregnant women were included in the analysis. Baseline characteristics, including prepregnancy BMI, viral load at prenatal care entry, and gestational age at delivery were similar by ART, including 53% of the entire cohort had initiated ART before pregnancy (P = nonsignificant). Excess gestational weight gain occurred in 29% of the cohort. Compared with non-integrase strand transfer inhibitor (-INSTI) or tenofovir alafenamide fumarate (TAF)-exposed persons, receipt of INSTI+TAF showed a 1.7-fold increased RR of excess gestational weight gain (95% CI: 1.18-2.68; P < .01), while women who received tenofovir disoproxil fumarate had a 0.64-fold decreased RR (95% CI: .41-.99; P = .047) of excess gestational weight gain. INSTI alone was not significantly associated with excess weight gain in this population. The effect of TAF without INSTI could not be inferred from our data. There was no difference in neonatal, obstetric, or maternal outcomes between the groups., Conclusions: Pregnant women receiving ART with a combined regimen of INSTI and TAF have increased risk of excess gestational weight gain., Competing Interests: Potential conflicts of interest. M. L. B. reports the following contracts/support: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Pediatric and Adolescent HIV/AIDS research program at Emory University School of Medicine–International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network site co-investigator; National Institutes of Health (NIH), Emory Vaccine and Treatment Evaluation Unit—DMID 21-004-MOMI-Vax: An Observational, Prospective Cohort Study of the Immunogenicity and Safety of SARS-CoV-2 Vaccines Administered during Pregnancy or Postpartum and Evaluation of Antibody Transfer and Durability in Infants (3UM1AI148576-02S5, site principal investigator); NIH/Mental Health (MH)—The Effects of Pregnancy on Post Traumatic Symptoms and Fear Physiology in Traumatized African American Women–Impacts of COVID-19 and Racial Discrimination on Mental, Physical, and Psychophysiological Health in Black Pregnant and Postpartum Persons (3R01MH115174-04W1, site co-investigator). G. A. S. and N. T. J. report royalties for the following UpToDate articles: “Disaster Settings: Care of Pregnant People,” and “Disaster Settings: Care of Gynecologic Problems.” All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare: MLB and CMD receive NIH grant funding for DMID 21-0004, an observational, prospective cohort study of the immunogenicity and safety of SARS-CoV-2 vaccines administered during pregnancy or post partum and evaluation of antibody transfer and durability in infants., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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 AUC0-24 was 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 AUC0-24 was 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 μg/mL (0.16-0.28) in the second trimester, 0.21 μg/mL (0.11-0.56) in the third trimester, and 0.61 μg/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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022. The Author(s).)

Objective: To characterize maternal immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and quantify the efficiency of transplacental antibody transfer., Methods: We conducted a prospective cohort study of pregnant patients who tested positive for SARS CoV-2 infection at any point in pregnancy and collected paired maternal and cord blood samples at the time of delivery. An enzyme-linked immunosorbent assay (ELISA) and neutralization assays were performed to measure maternal plasma and cord blood concentrations and neutralizing potency of immunoglobulin (Ig)G, IgA, and IgM antibodies directed against the SARS-CoV-2 spike protein. Differences in concentrations according to symptomatic compared with asymptomatic infection and time from positive polymerase chain reaction (PCR) test result to delivery were analyzed using nonparametric tests of significance. The ratio of cord to maternal anti-receptor-binding domain IgG titers was analyzed to assess transplacental transfer efficiency., Results: Thirty-two paired samples were analyzed. Detectable anti-receptor-binding domain IgG was detected in 100% (n=32) of maternal and 91% (n=29) of cord blood samples. Functional neutralizing antibody was present in 94% (n=30) of the maternal and 25% (n=8) of cord blood samples. Symptomatic infection was associated with a significant difference in median (interquartile range) maternal anti-receptor-binding domain IgG titers compared with asymptomatic infection (log 3.2 [3.5-2.4] vs log 2.7 [2.9-1.4], P=.03). Median (interquartile range) maternal anti-receptor-binding domain IgG titers were not significantly higher in patients who delivered more than 14 days after a positive PCR test result compared with those who delivered within 14 days (log 3.3 [3.5-2.4] vs log 2.67 [2.8-1.6], P=.05). Median (range) cord/maternal antibody ratio was 0.81 (0.67-0.88)., Conclusions: These results demonstrate robust maternal neutralizing and anti-receptor-binding domain IgG response after SARS-CoV-2 infection, yet a lower-than-expected efficiency of transplacental antibody transfer and a significant reduction in neutralization between maternal blood and cord blood. Maternal infection does confer some degree of neonatal antibody protection, but the robustness and durability of protection require further study., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

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.

We conducted a cohort study to determine sociodemographic risk factors for severe acute respiratory syndrome coronavirus 2 infection among obstetric patients in 2 urban hospitals in Atlanta, Georgia, USA. Prevalence of infection was highest among women who were Hispanic, were uninsured, or lived in high-density neighborhoods.

Preeclampsia (PE) yields a spectrum of phenotypic expression, leading to varying degrees of hypertension, maternal renal dysfunction and placental insufficiency with resultant maternal and neonatal morbidity. Increased sFLT1 expression contributing to angiogenic factor imbalance, placental hypoxia, failed immune adaptation to the fetus and defective decidualization are among the commonly proposed theories of PE pathogenesis. Recently researchers have focused their attention on the events that occur at the maternal fetal interface as potential contributors to PE pathogenesis. Decidual stromal cells (DSC) isolated from preeclamptic women show diminished ability to decidualize upon stimulation and reduced capacity to downregulate sFlt-1 levels. In this study, we sought to gain insight into the molecular mechanism(s) involved in the aberrant decidualization capacity of PE DSC. Our findings using qRT-PCR show that PE DSCs have 6-fold higher basal levels of transcription factor AP2A (TFAP2A) RNA compared to women without PE and that expression of TFAP2A increases during decidualization but only in DSCs of normotensive (NT) women. Silencing of TFAP2A using Trilencer siRNA upregulated sFLT1 expression only in NT-DSCs but suppressed the expression of decidualization markers PRL, IGFBP1 and their regulator FOXO1 in cells from both groups. Collectively, our observations suggest that TFAP2A acts as a repressor of sFLT1 and plays a necessary role in decidualization possibly through interacting with another factor that is aberrantly expressed in PE DSCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Decidual stromal cells (DSC) from women with preeclampsia (PE) show defective decidualization upon in vitro treatment with cAMP. Decidualization is associated with a multitude of gene expression changes and is a prerequisite for embryo implantation. We reason that the process of decidualization involves a cascade of changes in transcriptional regulators. Our prior studies have found defective decidualization of PE-DSCs as reflected by low prolactin (PRL) levels and other decidualization markers. Transcription factor array analysis identified inhibitor of DNA binding (ID1) and FOXO1 as top differentially expressed genes during decidualization. Unlike ID1, FOXO1 involvement in decidualization has been established. We hypothesized that ID1 plays a major role in regulating stromal cell decidualization. Our data shows basal ID1 mRNA expression is significantly higher in PE DSCs. Cyclic AMP-mediated decidualization significantly upregulates ID1 mRNA expression in DSCs and siRNA-mediated knockdown of ID1 significantly interferes with decidualization as shown by a reduction in PRL and FOXO1 expression, and morphologic criteria. Thus ID1 may serve as a master regulator of stromal cell differentiation and defects in ID1 expression may affect decidualization as seen in PE-DSCs., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Fetal pleural effusions are a rare fetal anomaly that may result from congenital chylothorax. Severe cases lead to chest compression with resulting pulmonary hypoplasia and possible neonatal demise. Fetal thoracoamiontic shunt (TAS) placement may decrease the amount of pleural effusion and improve lung expansion., Case: A 30-year-old primigravida at 29 2/7 weeks' gestation presented with fetal bilateral pleural effusions with no identifiable genetic or structural abnormalities. TAS placement accomplished decompression of the left fetal chest. The neonate was delivered at 33 3/7 weeks and required minimal respiratory support with no apparent long term complications at discharge., Conclusion: This case demonstrated that fetal intervention with TAS placement can improve neonatal outcomes. Referral to an MFM specialist capable of TAS should be considered for isolated fetal bilateral pleural effusion.

Objective: To compare the incidence of hypertensive disorders of pregnancy among women living with human immunodeficiency virus (HIV) on combination antiretroviral therapy (ART) to women without HIV, and to evaluate the association of hypertensive disorders of pregnancy with ART regimens or timing of ART initiation., Methods: We conducted a retrospective cohort study among two overlapping pregnancy cohorts using preexisting databases at a single tertiary care hospital: all pregnant women who delivered during years 2016-2018 (cohort 1) and all women living with HIV who delivered during years 2011-2018 (cohort 2). The primary outcome for both cohorts was any hypertensive disorder of pregnancy; gestational hypertension and preeclampsia were also examined separately. The primary exposure variables were HIV status for cohort 1 and ART regimen (integrase strand transfer inhibitor-containing, protease inhibitor-containing, or non-nucleoside reverse transcriptase inhibitor-containing) for cohort 2. For estimation of risk ratios (RRs), we used a modified Poisson regression with robust error variances. Multivariate models among the women living with HIV in cohort 2 were tested for a statistical interaction between ART regimen and timing of initiation., Results: In cohort 1, among 80 women living with HIV compared with 3,464 women without HIV, there was no difference in the risk of hypertensive disorders of pregnancy (29% in women living with HIV vs 30% in women without HIV, adjusted RR 0.9, 95% CI 0.6-1.3). In cohort 2, among 265 women living with HIV, integrase strand transfer inhibitor-containing regimens were associated with an increased risk for any hypertensive disorder of pregnancy (25% among integrase strand transfer inhibitor vs 10% among protease inhibitor, adjusted RR 2.8, 95% CI 1.5-5.1) and gestational hypertension (20% among integrase strand transfer inhibitor vs 8% among protease inhibitor, adjusted RR 2.8, 95% CI 1.3-5.9) compared with protease inhibitor-containing regimens. Timing of ART initiation was not associated with hypertensive disorders of pregnancy, nor did it significantly alter the associations between ART regimen and hypertensive disorders of pregnancy outcomes., Conclusion: Overall the risk of hypertensive disorders of pregnancy was similar among women living with HIV on ART and women without HIV. With greater integrase strand transfer inhibitor use, the greater frequency of hypertensive disorders of pregnancy with these regimens compared with protease inhibitor-containing regimens warrants future evaluation using cohorts with greater sample size.

Background: There is limited information on potentially modifiable risk factors for stillbirth, such as gestational weight gain (GWG). Our purpose was to explore the association between GWG and stillbirth using the GWG z-score., Methods: We analyzed 479 stillbirths and 1601 live births from the Stillbirth Collaborative Research Network case-control study. Women with triplets or monochorionic twins were excluded from analysis. We evaluated the association between GWG z-score (modeled as a restricted cubic spline with knots at the 5th, 50th, and 95th percentiles) and stillbirth using multivariable logistic regression with generalized estimating equations, adjusting for pre - pregnancy body mass index (BMI) and other confounders. In addition, we conducted analyses stratified by pre - pregnancy BMI category (normal weight, overweight, obese)., Results: Mean GWG was 18.95 (SD 17.6) lb. among mothers of stillbirths and 30.89 (SD 13.3) lb. among mothers of live births; mean GWG z-score was - 0.39 (SD 1.5) among mothers of cases and - 0.17 (SD 0.9) among control mothers. In adjusted analyses, the odds of stillbirth were elevated for women with very low GWG z-scores (e.g., adjusted odds ratio (aOR) and 95% Confidence Interval (CI) for z-score - 1.5 SD versus 0 SD: 1.52 (1.30, 1.78); aOR (95% CI) for z-score - 2.5 SD versus 0 SD: 2.36 (1.74, 3.20)). Results differed slightly by pre - pregnancy BMI. The odds of stillbirth were slightly elevated among women with overweight BMI and GWG z-scores ≥1 SD (e.g., aOR (95% CI) for z-score of 1.5 SD versus 0 SD: 1.84 (0.97, 3.50))., Conclusions: GWG z-scores below - 1.5 SD are associated with increased odds of stillbirth.

sFLT1 (soluble VEGF [vascular endothelial growth factor] receptor-1) levels are increased in preeclampsia-a pathological condition of pregnancy. The mechanism of sFLT1 overexpression by gestational tissues, particularly the decidua, remains unknown. Mass spectrometry measurement of the active retinoid metabolite, all-trans retinoic acid (RA), showed significantly lower levels of RA in preeclamptic versus normotensive decidua. In this study, we investigated the involvement of RA in regulating decidual sFLT1 expression. When decidual stromal cells (DSCs) isolated from the decidua basalis of normotensive and preeclampsia placentas were treated with BMS493-a pan-RAR (RA nuclear receptor) antagonist-upregulation of sFLT1 expression was observed. Conversely, treatment with RA resulted in downregulation of sFLT1 in normotensive DSCs and preeclampsia DSCs. Unlike treatment with cAMP, which induces decidualization while downregulating sFLT1, RA treatment did not alter DSC expression of prolactin-a marker of decidualization-or FOXO1 (forkhead box protein 01)-a transcription factor required for prolactin upregulation. TFAP2A (transcription factor AP-2-alpha [activating enhancer-binding protein 2 alpha]), a different transcription factor was upregulated in normotensive DSCs but not in preeclampsia DSCs after RA treatment. Collectively, our data show that RA suppresses sFLT1 expression in DSCs independently of cellular decidualization. These findings suggest that reduced decidual RA levels may contribute to preeclampsia pathogenesis by allowing sFLT1 accumulation at the maternal-fetal interface.

In a high-volume clinic in the Southeastern United States, pregnant women living with human immunodeficiency virus (HIV) had improved HIV outcomes up to 6 months after delivery following the introduction of a multidisciplinary perinatal care coordination team.

Background: There is a knowledge gap on the clinical use of elvitegravir (EVG) during pregnancy and maternal viral suppression. Our objective was to evaluate the effects of EVG use in pregnancy on rates of HIV virologic suppression and perinatal outcomes., Methods: We conducted a retrospective, multicenter study of pregnant women living with HIV (WLHIV) who used EVG-containing antiretroviral therapy (ART) between January 2014 and March 2017 at 9 tertiary care centers in the United States. WLHIV were included if they took EVG at any time during pregnancy. We described the characteristics of the WLHIV using EVG during the study period and evaluated the rates of HIV suppression and perinatal outcomes., Results: Among 134 pregnant WLHIV who received EVG at any time during pregnancy, viral suppression at delivery (HIV-1 RNA < 40 copies/mL) occurred in 81.3%. In WLHIV who initiated EVG before pregnancy and continued through delivery (n = 68), the rate of viral suppression at delivery was 88.2%. The average gestational age at the time of delivery was 37 weeks 6 days, and the overall rate of preterm birth was 20%. No cases of open neural tube defects were noted in women on EVG at the time of conception (n = 82). The perinatal HIV transmission rate was 0.8%., Conclusions: EVG use was associated with high sustained levels of HIV suppression during pregnancy and a low rate of perinatal HIV transmission.

Uterine stromal cell decidualization of maternal tissue is essential for implantation of and local adaptation to the fetal allograft, as well as growth and maintenance of the placenta in healthy pregnancies. Maternal defects in decidualization have been suggested as a possible driver of preeclampsia. Preeclampsia (PE) pregnancies demonstrate shallow implantation, inadequate spiral artery remodeling, and elevated levels of the anti-angiogenic protein, sFlt1. To test whether stromal cells (DSCs) isolated from PE placentas exhibit inadequate re-decidualization and increased expression of sFlt1, DSCs from normotensive (NT-DSCs) and PE (PE-DSCs) placentas were treated for 8 days (D8) with cAMP to induce decidualization and levels of decidualization markers (PRL, IGFBP1, VEGF) and sFlt1 were measured at day 0 (D0), D8, and after reversal of treatment. NT-DSCs achieved statistically significant elevations in PRL and IFGBP1 expression (25.72 [5.78-50.04], p = 0.0008 and 92.09 [1.79-543.10], p = 0.005). PE-DSCs increased PRL and IFGBP1 expression to 6.15 [2.30-10.73] (p = 0.18) and 8.67 [1.64-376.10] (p = 0.04). NT-DSCs reduced sFlt1 expression at D8 to 0.25 [0.17-0.49] (p = 0.0021) compared to 0.31 [0.25-0.82] (p = 0.087) in PE-DSCs. These results show that, when induced to decidualize, PE-DSCs fail to increase expression of decidualization markers to levels achieved by NT-DSCs. sFlt1 expression is higher in PE-DSCs during decidualization, suggesting inadequate suppression during the crucial implantation period. These defects at the maternal fetal interface may lead to the failed spiral artery modification, decreased placental invasion of the uterus, and elevated circulating sFlt1 levels seen in PE pathology., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery., Design: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the United States., Methods: Intensive steady-state 24-h pharmacokinetic profiles after 150 mg of elvitegravir and 150 mg of cobicistat given orally in fixed dose combination once-daily were performed during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Elvitegravir and cobicistat were measured in plasma by a validated liquid chromatography with tandem mass spectrometry assay with a lower quantitation limit of 10 ng/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons., Results: Thirty pregnant women taking elvitegravir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, elvitegravir AUC0-24 was 24% lower in the second trimester [n = 14, P = 0.058, geometric mean ratios (GMR) = 0.76, 90% confidence interval (CI) 0.57-1.0] and 44% lower in the third trimester (n = 24, P = 0.0001, GMR = 0.56, 90% CI 0.42-0.73), while cobicistat AUC0-24 was 44% lower in the second trimester (n = 14, P = 0.0085, GMR = 0.56, 90% CI 0.37-0.85) and 59% lower in the third trimester (n = 24, P < 0.0001, GMR = 0.41, 90% CI 0.30-0.57). Median cord blood elvitegravir concentration was 540.6 ng/ml and the median ratio of cord blood to maternal plasma elvitegravir concentrations was 0.91., Conclusion: Standard elvitegravir and cobicistat dosing during pregnancy results in significantly lower exposure which may increase the risk of virologic failure and mother-to-child transmission. Additional studies are needed to optimize elvitegravir and cobicistat dosing regimens in pregnant women.

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.

Infertility is a disease that affects up to 15.5% of reproductive-aged couples. Until the birth of the first neonate born from in vitro fertilization (IVF) in 1978, many infertile couples did not have an opportunity to conceive a biological child. Over the past 40 years, access to and effectiveness of IVF have increased; currently 1.7% of births in the United States result from IVF. As with any medical intervention, potential risk exists. In the case of IVF, both maternal risks (ovarian stimulation, oocyte retrieval, and subsequent pregnancy) and fetal risks that vary based on maternal age and fetal number must be considered. Importantly, risk quantification varies by comparison group, which is typically either spontaneous conception in a fertile couple or assisted non-IVF conception in an infertile couple. It must also be considered compared with the alternative of not undergoing IVF, which may mean not having a biological child. Although increased compared with spontaneous conception, absolute maternal-fetal-assisted reproductive technology risks are low and can be minimized by optimizing ovarian stimulation and transferring a single embryo. In this article, we aim to summarize maternal and fetal risk associated with use of assisted reproductive technology. The review focuses on ovarian stimulation and procedural risks as well as adverse perinatal outcomes among resultant singleton and twin pregnancies in young women and women of advanced maternal age.

Objective: Our goal was to evaluate the infrastructure of programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) in major delivery units in the Atlanta, Georgia, metropolitan statistical area and to assess the knowledge, attitude, and practice of providers in these facilities around PMTCT., Methods: Hospital assessments and individual knowledge and practices were surveyed among 71 healthcare providers from March 2015 to March 2016 in 11 hospitals that deliver 40000 infants annually, which represents 70% of all deliveries in the Atlanta metropolitan statistical area. Included were questions about HIV testing for mother-infant pairs, test result turnaround times, policies and procedures for PMTCT, opt-out versus opt-in testing, availability of rapid point-of-care testing on labor and delivery units, and postnatal prophylaxis., Results: Seventy-three percent (8 of 11) of the hospitals had limitations in their PMTCT infrastructure, and 36% (4 of 11) reported no standardized policies for care of HIV-infected women. Three labor and delivery units used opt-in HIV testing of women. Only 27% (3 of 11) of the hospitals reported nucleic acid testing of HIV-exposed infants. Oral zidovudine for infant prophylaxis was available in all the hospitals, but 64% (7 of 11) of them did not stock nevirapine. Fifty-nine percent (24 of 44) of the obstetricians did not routinely offer rapid testing at delivery without a third-trimester HIV test, and 78% (n = 32 of 41) of them did not offer testing at delivery if the woman declined antenatal testing. The facility with the most annual births in Georgia did not offer rapid testing at delivery for women with an unknown HIV status., Conclusion: We identified several limitations in PMTCT infrastructure that might have contributed to perinatal HIV transmissions. The need to address these healthcare gaps to eliminate mother-to-child transmission of HIV in the United States is urgent.

The World Health Organization's Millennium Development Goals 6 includes eliminating human immunodeficiency virus (HIV) in children as a top priority. Many states in the United States report maternal-to-child transmission rates less than 1% using the current recommendations for the management of HIV-infected pregnant women. This review article summarizes the most current management guidelines in caring for HIV-infected women and their infants to prevent maternal-to-child transmission., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether elective induction of labor between 39 through 41 weeks of gestation, as compared with expectant management, is associated with reduced cesarean delivery and other adverse outcomes among obese women and their offspring., Methods: We conducted a retrospective cohort study using the 2007-2011 California Linked Patient Discharge Data-Birth Cohort File of 165,975 singleton, cephalic, nonanomalous deliveries to obese women. For each gestational week (39-41), we used multivariable logistic regression models, stratified by parity, to assess whether elective induction of labor or expectant management was associated with lower odds of cesarean delivery and other adverse outcomes., Results: At 39 and 40 weeks of gestation, cesarean delivery was less common in obese nulliparous women who were electively induced compared with those who were expectantly managed (at 39 weeks of gestation, frequencies were 35.9% vs 41.0%, respectively [P<.05]; adjusted odds ratio [OR] 0.82, 95% CI 0.77-0.88). Severe maternal morbidity was less frequent among electively induced obese nulliparous patients (at 39 weeks of gestation, 5.6% vs 7.6% [P<.05]; adjusted OR 0.75, 95% CI 0.65-0.87). Neonatal intensive care unit admission was less common among electively induced obese nulliparous women (at 39 weeks of gestation, 7.9% vs 10.1% [P<.05]; adjusted OR 0.79, 95% CI 0.70-0.89). Patterns were similar among obese parous women at 39 weeks of gestation (crude frequencies and adjusted ORs [95% CIs] were as follows: for cesarean delivery, 7.0% vs 8.7% [P<.05] and 0.79 [0.73-0.86]; for severe maternal morbidity, 3.3% vs 4.0% [P<.05] and 0.83 [0.74-0.94]; for neonatal intensive care unit admission: 5.3% vs 7.4% [P<.05] and 0.75 [0.68-0.82]). Similarly, elective induction at 40 weeks of gestation was associated with reduced odds of cesarean delivery, maternal morbidity, and neonatal intensive care unit admission among both obese nulliparous and parous patients., Conclusion: Elective labor induction after 39 weeks of gestation was associated with reduced maternal and neonatal morbidity among obese women. Further prospective investigation is necessary.

Background: Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed., Methods: We searched Global Health, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Medline databases from inception to May 2015 for studies published on botulism or botulinum antitoxin use during pregnancy and the postpartum period, as well as the Centers for Disease Control and Prevention National Botulism Surveillance database. Our search identified 4517 citations., Results: Sixteen cases of botulism during pregnancy (11 in the third trimester) and 1 case during the postpartum period were identified. Ten cases were associated with confirmed or likely foodborne exposure; 2 cases were attributed to wound contamination related to heroin use, and the source of 5 cases was unknown. Eleven women with botulism had progressive neurologic deterioration and respiratory failure, requiring intensive care unit admission. Four women had adverse outcomes, including 2 deaths and 2 women who remained in a persistent vegetative state. No neonatal losses or cases of congenital botulism were reported. Among the 12 cases that reported neonatal data, 6 neonates were born preterm. No adverse maternal or neonatal events were identified as associated with botulinum antitoxin therapy among 11 patients who received it., Conclusions: Our review of 17 cases of botulism in pregnant/postpartum women found that more than half required ventilator support, 2 women died, and 6 infants were born prematurely. A high level of clinical suspicion is key for early diagnosis and treatment of botulism. Care of pregnant women or new mothers with botulism can include preparation for possible intubation., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Effective treatment for botulism requires early clinical recognition. Diagnosis of botulism, including during outbreaks, can be challenging. We assessed combinations of signs and symptoms among confirmed cases and identified sensitive clinical criteria to trigger suspicion. We produced a tool that may facilitate rapid identification of sporadic and outbreak-associated cases., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: To evaluate fetal ultrasound and magnetic resonance imaging findings among a series of pregnant women with confirmed Zika virus infection to evaluate the signs of congenital Zika syndrome with respect to timing of infection., Methods: We conducted a retrospective case series of pregnant women referred to two perinatal clinics in Barranquilla and Ibagué, Colombia, who had findings consistent with congenital Zika syndrome and Zika virus infection confirmed in maternal, fetal, or neonatal samples. Serial ultrasound measurements, fetal magnetic resonance imaging results, laboratory results, and perinatal outcomes were evaluated., Results: We describe 17 cases of confirmed prenatal maternal Zika virus infection with adverse fetal outcomes. Among the 14 symptomatic women, the median gestational age for maternal Zika virus symptoms was 10 weeks (range 7-14 weeks of gestation). The median time between Zika virus symptom onset and microcephaly (head circumference less than 3 standard deviations below the mean) was 18 weeks (range 15-24 weeks). The earliest fetal head circumference measurement consistent with microcephaly diagnosis was at 24 weeks of gestation. The earliest sign of congenital Zika syndrome was talipes equinovarus, which in two patients was noted first at 19 weeks of gestation. Common findings on fetal magnetic resonance imaging were microcephaly, ventriculomegaly, polymicrogyria, and calcifications., Conclusion: Our analysis suggests a period of at least 15 weeks between maternal Zika virus infection in pregnancy and development of microcephaly and highlights the importance of serial and detailed neuroimaging.