Provider confidence in counseling preconception, pregnant, and postpartum patients regarding COVID-19 vaccination: A cross-sectional survey study.

Background and Aims: Healthcare provider counseling surrounding COVID-19 vaccine in pregnancy and lactation is essential to vaccination uptake in this population; however, provider knowledge and confidence are not well characterized. We aimed to assess knowledge and confidence in COVID-19 vaccine counseling among practitioners who provide care to pregnant persons and to describe factors associated with confidence in counseling. Methods: A web-based anonymous survey was distributed via email to a cross-sectional convenience sample of Obstetrics and Gynecology, Primary Care, and Internal Medicine faculty at three hospitals in a single healthcare network in Massachusetts, United States. Individual demographics and institution-specific variables were included in the survey along with questions assessing both attitudes toward COVID-19 illness and confidence in counseling regarding the use of the vaccine in pregnancy. Results: Almost all providers (151, 98.1%) reported that they received a COVID-19 vaccine, and most (111, 72.1%) reported that they believe the benefits of the vaccine in pregnancy outweigh the risks. Forty-one (26.6%) reported feeling very confident in counseling patients who primarily speak English about the evidence for messenger ribonucleic acid vaccination in pregnancy, and 36 (23%) reported feeling very confident in counseling patients who are not primarily English-speaking. Forty-three providers (28.1%) expressed strong confidence in their comfort talking to individuals with vaccine hesitancy based on historic and continued racism and systemic injustices. The sources that survey respondents most used to find information regarding COVID-19 vaccination in pregnancy were the Centers for Disease Control (112, 74.2%), hospital-specific resources (94, 62.3%), and the American College of Obstetricians and Gynecologists (82, 54.3%). Conclusion: Ensuring that providers feel comfortable bridging the gap between their belief that the vaccine is beneficial for pregnant patients and their comfort with holding conversations with patients regarding vaccination is paramount to ensure equitable access to vaccines for pregnant patients.

Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy.

Importance: Prior studies using large registries have suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific. Objective: To determine whether in utero exposure to SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared with unexposed offspring born during or prior to the COVID-19 pandemic period. Design, Setting, and Participants: This retrospective cohort study included the live offspring of all mothers who delivered between January 1 and December 31, 2018 (born and followed up before the COVID-19 pandemic), between March 1 and December 31, 2019 (born before and followed up during the COVID-19 pandemic), and between March 1, 2020, and May 31, 2021 (born and followed up during the COVID-19 pandemic). Offspring were born at any of 8 hospitals across 2 health systems in Massachusetts. Exposures: Polymerase chain reaction evidence of maternal SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures: Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to neurodevelopmental disorders. Results: The COVID-19 pandemic cohort included 18 355 live births (9399 boys [51.2%]), including 883 (4.8%) with maternal SARS-CoV-2 positivity during pregnancy. The cohort included 1809 Asian individuals (9.9%), 1635 Black individuals (8.9%), 12 718 White individuals (69.3%), and 1714 individuals (9.3%) who were of other race (American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, more than 1 race); 2617 individuals (14.3%) were of Hispanic ethnicity. Mean maternal age was 33.0 (IQR, 30.0-36.0) years. In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs community), maternal age, and preterm status, maternal SARS-CoV-2 positivity was associated with a statistically significant elevation in risk for neurodevelopmental diagnoses at 12 months among male offspring (adjusted OR, 1.94 [95% CI 1.12-3.17]; P = .01) but not female offspring (adjusted OR, 0.89 [95% CI, 0.39-1.76]; P = .77). Similar effects were identified using matched analyses in lieu of regression. At 18 months, more modest effects were observed in male offspring (adjusted OR, 1.42 [95% CI, 0.92-2.11]; P = .10). Conclusions and Relevance: In this cohort study of offspring with SARS-CoV-2 exposure in utero, such exposure was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring at 12 months following birth. As with prior studies of maternal infection, substantially larger cohorts and longer follow-up will be required to reliably estimate or refute risk.

Change in Emergency Medical Services-Attended Out-of-Hospital Deliveries during COVID-19 in the United States.

BACKGROUND: The COVID-19 pandemic disrupted access to routine in-person prenatal care, potentially leading to higher risk of out-of-hospital deliveries. Unplanned out-of-hospital deliveries pose a substantial risk of morbidity and mortality for pregnant patients and newborns. Our objective was to determine the change in rate of emergency medical services (EMS)-attended out-of-hospital deliveries during the COVID-19 pandemic. We hypothesized that COVID-19-related stay-at-home orders were associated with a higher rate of out-of-hospital deliveries during the initial wave of COVID-19. METHODS: We conducted an interrupted time series analysis using the 2019 and 2020 National EMS Information System datasets. We included 9-1-1 scene activations for patients 12-50 years old with out-of-hospital deliveries who were treated and transported by EMS. We calculated the weekly rate of deliveries per 100,000 EMS emergency activations each year overall, and for each census division. The interruption modeled was the enactment of stay-at-home orders, with March 25-31 selected as when most orders had been enacted. We fit ordinary least squares regression models with Newey-West standard errors to adjust for autocorrelation, testing for a change in level and slope overall and by census division. RESULTS: A total of 10,778 out-of-hospital deliveries were included, 58% (n = 6,254) in 2020. The mean weekly rate of out-of-hospital deliveries in 2019 was 29.4 per 100,000 activations (95% CI: 28.4 to 30.4) versus 33.0 (95% CI: 31.8 to 34.1) in 2020. There was an immediate increase of 6.3 deliveries per 100,000 activations (95% CI: 3.3 to 9.3) after the week of March 25-31, with a subsequent decrease of 0.3 deliveries per 100,000 per week after (95% CI: -0.4 to -0.2). There were also statistically significant immediate increases in out-of-hospital deliveries after March 25-31 in the New England, East North Central, West South Central, and Mountain divisions. CONCLUSION: EMS-attended out-of-hospital deliveries remained rare during the COVID-19 pandemic, but there was an immediate increase during the initial wave of the pandemic with evidence of geographic variation. Large-scale disruptions in the health care system may result in increases in uncommon patient presentations to EMS.

Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy.

Importance: Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring. Objective: To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth. Design, Setting, and Participants: This retrospective cohort study examined live offspring of all mothers who delivered between March and September 2020 at any of 6 Massachusetts hospitals across 2 health systems. Statistical analysis was performed from October to December 2021. Exposures: Maternal SARS-CoV-2 infection confirmed by a polymerase chain reaction test during pregnancy. Main Outcomes and Measures: Neurodevelopmental disorders determined from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes over the first 12 months of life; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record. Results: The cohort included 7772 live births (7466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean (SD) maternal age of 32.9 (5.0) years; offspring were 9.9% Asian (772), 8.4% Black (656), and 69.0% White (5363); 15.1% (1134) were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers: 14.4% (32) vs 8.7% (654) (P = .003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models (odds ratio [OR], 2.17 [95% CI, 1.24-3.79]; P = .006) as well as those adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR, 1.86 [95% CI, 1.03-3.36]; P = .04). Third-trimester infection was associated with effects of larger magnitude (adjusted OR, 2.34 [95% CI, 1.23-4.44]; P = .01). Conclusions and Relevance: This cohort study of SARS-CoV-2 exposure in utero found preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these associations.

Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?

BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.

Compromised SARS-CoV-2-specific placental antibody transfer.

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection. Design, Setting, and Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. Main Outcomes and Measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted. Conclusions and Relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

COVID-19 is associated with traumatic childbirth and subsequent mother-infant bonding problems.

BACKGROUND: Knowledge of women's experience of childbirth in the outbreak of the coronavirus (COVID-19) pandemic and associated maternal health outcomes is scarce. METHODS: A sample of primarily American women who gave birth around the height of COVID-19 (n = 1,611) and matched controls, i.e., women who gave birth before COVID-19 (n = 640), completed an anonymous Internet survey about recent childbirth, birth-related traumatic stress (peritraumatic distress inventory; PTSD-checklist), maternal bonding (maternal attachment inventory; mother-to-infant bonding scale) and breastfeeding status. Groups (n = 637 in each) were matched on demographics, prior mental health/trauma and childbirth factors to determine the unique contribution of COVID-19 to the psychological experience of childbirth. RESULTS: Mothers in COVID-19-exposed communities endorsed more clinically acute stress response to childbirth than matched controls (Z = 2.65, p = .008, OR= 1.38). A path mediation model revealed that acute stress mediated the relationship between study group and postpartum outcomes. Specifically, higher acute stress response in birth was associated with more childbirth-related posttraumatic stress disorder symptoms (ß = .42, p < .001) and less bonding with the infant (ß = .26, p < .001), including breastfeeding problems (ß = .10, p < .01). LIMITATIONS: Use of a convenient internet sample introduces bias towards more educated women and reliance on retrospective self-report assessments may entail recall bias. CONCLUSIONS: COVID-19 is a major stressor for delivering women. It can heighten traumatic childbirth experiences and interfere with successful postpartum adjustment. Clinical attention to traumatic stress in childbirth and problems with caring for the young during this pandemic is important.

Rapid establishment of a COVID-19 perinatal biorepository: early lessons from the first 100 women enrolled.

BACKGROUND: Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from research. We describe the establishment of a COVID-19 perinatal biorepository, the unique challenges imposed by the COVID-19 pandemic, and strategies used to overcome them. METHODS: A transdisciplinary approach was developed to maximize the enrollment of pregnant women and their newborns into a COVID-19 prospective cohort and tissue biorepository, established on March 19, 2020 at Massachusetts General Hospital (MGH). The first SARS-CoV-2 positive pregnant woman was enrolled on April 2, and enrollment was expanded to SARS-CoV-2 negative controls on April 20. A unified enrollment strategy with a single consent process for pregnant women and newborns was implemented on May 4. SARS-CoV-2 status was determined by viral detection on RT-PCR of a nasopharyngeal swab. Wide-ranging and pregnancy-specific samples were collected from maternal participants during pregnancy and postpartum. Newborn samples were collected during the initial hospitalization. RESULTS: Between April 2 and June 9, 100 women and 78 newborns were enrolled in the MGH COVID-19 biorepository. The rate of dyad enrollment and number of samples collected per woman significantly increased after changes to enrollment strategy (from 5 to over 8 dyads/week, P < 0.0001, and from 7 to 9 samples, P < 0.01). The number of samples collected per woman was higher in SARS-CoV-2 negative than positive women (9 vs 7 samples, P = 0.0007). The highest sample yield was for placenta (96%), umbilical cord blood (93%), urine (99%), and maternal blood (91%). The lowest-yield sample types were maternal stool (30%) and breastmilk (22%). Of the 61 delivered women who also enrolled their newborns, fewer women agreed to neonatal blood compared to cord blood (39 vs 58, P < 0.0001). CONCLUSIONS: Establishing a COVID-19 perinatal biorepository required patient advocacy, transdisciplinary collaboration and creative solutions to unique challenges. This biorepository is unique in its comprehensive sample collection and the inclusion of a control population. It serves as an important resource for research into the impact of COVID-19 on pregnant women and newborns and provides lessons for future biorepository efforts.