Impact of asymptomatic and mild COVID-19 infection on fetal growth during pregnancy.

BACKGROUND: During pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR). STUDY DESIGN: This is a single institution, retrospective cohort study of patients ages 16-55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy. RESULTS: Among 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend). CONCLUSION: Asymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection.

Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives.

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.

Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with significant maternal morbidity and increased rates of preterm birth. For this reason, COVID-19 vaccination in pregnancy has been endorsed by multiple professional societies, including the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, despite the exclusion of pregnant women from initial clinical trials of vaccine safety and efficacy. However, to date, little data exist regarding the outcomes of pregnant patients after COVID-19 vaccination. OBJECTIVE: To assess the safety and efficacy of COVID-19 vaccines in pregnant patients. STUDY DESIGN: A comprehensive vaccine registry was combined with a delivery database for an integrated healthcare system to create a delivery cohort that included vaccinated patients. Maternal sociodemographic data were examined to identify factors associated with COVID-19 vaccination. Pregnancy and birth outcomes were analyzed, including a composite measure of maternal and neonatal pregnancy complications, the Adverse Outcome Index. RESULTS: Of 2002 patients in the delivery cohort, 140 (7.0%) received a COVID-19 vaccine during pregnancy, and 212 (10.6%) experienced a COVID-19 infection during pregnancy. The median gestational age at first vaccination was 32 weeks (range, 13 6/7-40 4/7 weeks), and patients vaccinated during pregnancy were less likely than unvaccinated patients to experience COVID-19 infection before delivery (2/140 [1.4%] vs 210/1862 [11.3%]; P<.001). No maternal COVID-19 infection occurred after the vaccination of pregnant patients. Factors significantly associated with increased likelihood of vaccination in a multivariable logistic regression model included older age, higher level of maternal education, being a nonsmoker, use of infertility treatment for the current pregnancy, and lower gravidity. Compared with unvaccinated patients, no significant difference in the composite adverse outcome (7/140 [5.0%] vs 91/1862 [4.9%]; P=.95) or other maternal or neonatal complications, including thromboembolic events and preterm birth, was observed in vaccinated patients. CONCLUSION: In this birth cohort, vaccinated pregnant women were less likely than unvaccinated pregnant patients to experience COVID-19 infection, and COVID-19 vaccination during pregnancy was not associated with increased pregnancy or delivery complications. The cohort was skewed toward late pregnancy vaccination, and thus, findings may not be generalizable to vaccination during early pregnancy.

SARS-CoV-2 Infection and COVID-19 During Pregnancy: A Multidisciplinary Review.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has been associated with worse outcomes in several patient populations, including the elderly and those with chronic comorbidities. Data from previous pandemics and seasonal influenza suggest that pregnant women may be at increased risk for infection-associated morbidity and mortality. Physiologic changes in normal pregnancy and metabolic and vascular changes in high-risk pregnancies may affect the pathogenesis or exacerbate the clinical presentation of COVID-19. Specifically, SARS-CoV-2 enters the cell via the angiotensin-converting enzyme 2 (ACE2) receptor, which is upregulated in normal pregnancy. Upregulation of ACE2 mediates conversion of angiotensin II (vasoconstrictor) to angiotensin-(1-7) (vasodilator) and contributes to relatively low blood pressures, despite upregulation of other components of the renin-angiotensin-aldosterone system. As a result of higher ACE2 expression, pregnant women may be at elevated risk for complications from SARS-CoV-2 infection. Upon binding to ACE2, SARS-CoV-2 causes its downregulation, thus lowering angiotensin-(1-7) levels, which can mimic/worsen the vasoconstriction, inflammation, and pro-coagulopathic effects that occur in preeclampsia. Indeed, early reports suggest that, among other adverse outcomes, preeclampsia may be more common in pregnant women with COVID-19. Medical therapy, during pregnancy and breastfeeding, relies on medications with proven safety, but safety data are often missing for medications in the early stages of clinical trials. We summarize guidelines for medical/obstetric care and outline future directions for optimization of treatment and preventive strategies for pregnant patients with COVID-19 with the understanding that relevant data are limited and rapidly changing.

SARS-CoV-2 in Pregnancy: A Comprehensive Summary of Current Guidelines.

Since the declaration of the global pandemic of COVID-19 by the World Health Organization on 11 March 2020, we have continued to see a steady rise in the number of patients infected by SARS-CoV-2. However, there is still very limited data on the course and outcomes of this serious infection in a vulnerable population of pregnant patients and their fetuses. International perinatal societies and institutions including SMFM, ACOG, RCOG, ISUOG, CDC, CNGOF, ISS/SIEOG, and CatSalut have released guidelines for the care of these patients. We aim to summarize these current guidelines in a comprehensive review for patients, healthcare workers, and healthcare institutions. We included 15 papers from 10 societies through a literature search of direct review of society's websites and their journal publications up till 20 April 2020. Recommendations specific to antepartum, intrapartum, and postpartum were abstracted from the publications and summarized into Tables. The summary of guidelines for the management of COVID-19 in pregnancy across different perinatal societies is fairly consistent, with some variation in the strength of recommendations. It is important to recognize that these guidelines are frequently updated, as we continue to learn more about the course and impact of COVID-19 in pregnancy.