key: cord-0721933-750fcxp1 authors: Jamieson, Denise J.; Rasmussen, Sonja A. title: An Update on Coronavirus Disease 2019 (COVID-19) and Pregnancy date: 2021-09-14 journal: Am J Obstet Gynecol DOI: 10.1016/j.ajog.2021.08.054 sha: 86f63106e28472235acd575a5e4441503d7d34ca doc_id: 721933 cord_uid: 750fcxp1 Physiologic, mechanical and immunologic alterations in pregnancy could potentially affect susceptibility to and severity of COVID-19 during pregnancy. Due to lack of comparable incidence data and challenges with disentangling differences in susceptibility from different exposure risks, data are insufficient to determine whether pregnancy increases susceptibility to SARS-CoV-2 infection. Data support pregnancy as a risk factor for severe disease associated with COVID-19; some of the best evidence comes from the Centers for Disease Control and Prevention’s (CDC’s) COVID-19 surveillance system, which reported that pregnant persons were more likely to be admitted to an intensive care unit (ICU), require invasive ventilation, require extracorporeal membrane oxygenation, and die compared with nonpregnant women of reproductive age. Although intrauterine transmission of SARS-CoV-2 has been documented, it appears to be rare, possibly related to low levels of SARS-CoV-2 viremia and decreased co-expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) needed for SARS-CoV-2 entry into cells in the placenta. Evidence is accumulating that SARS-CoV-2 infection during pregnancy is associated with a number of adverse pregnancy outcomes including preeclampsia, preterm birth, and stillbirth, especially among pregnant persons with severe COVID-19 disease. In addition to the direct impact of COVID-19 on pregnancy outcomes, there is evidence that the pandemic and its effects on healthcare systems have had adverse effects on pregnancy outcomes, such as increased stillbirths and maternal deaths. These trends may represent widening disparities and an alarming reversal of recent improvements in maternal and infant health. All three COVID-19 vaccines currently available under an Emergency Use Authorization by the United States Food and Drug Administration can be administered to pregnant or lactating persons, with no preference for vaccine type. Although safety data in pregnancy are rapidly accumulating and no safety signals in pregnancy have been detected, additional information about birth outcomes, particularly among persons vaccinated earlier in pregnancy, are needed. CoV-2 transmission have been carefully documented, 19 transmission appears to be rare. 18 Several 143 factors may help explain why transmission appears to be rare. For intrauterine transmission of a 144 viral pathogen to occur, the pathogen needs to reach and cross the placenta, 20 and SARS-CoV-2 145 infection is not associated with high levels of viremia. 21 In addition, the placenta may not co-146 express high levels of the primary factors that facilitate SARS-CoV-2 entry into cells, 147 angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) [21] [22] [23] 148 although data regarding expression of these factors is not entirely consistent. 24, 25 149 Most SARS-CoV-2 infections identified among infants after birth are due to exposure to 150 infected caregivers. However, data on the safety of a SARS-CoV-2-infected mother 151 breastfeeding are reassuring. Replication-competent SARS-CoV-2 has not been detected in 152 breastmilk, 26 although breastmilk samples are occasionally PCR-positive. 27 An observational 153 cohort of 116 SARS-CoV-2-infected mothers who reported consistent use of surgical masks, 154 hand hygiene, and breast cleansing all safely breastfed without SARS-CoV-2 transmission. 28 In 155 addition, a systematic review found no increase in late postnatal transmission (defined as 156 occurring after 72 hours of life) associated with breastfeeding; however, an increased risk of late Although it appears that SARS-CoV-2 rarely is transmitted transplacentally to the fetus, 164 evidence is accumulating that SARS-CoV-2 infection during pregnancy is associated with a 165 number of adverse pregnancy outcomes. A systematic review and meta-analysis of relatively 166 high-quality studies with appropriate comparison groups found an increased risk of 167 preeclampsia, preterm birth, and stillbirth among pregnant persons with SARS-CoV-2 infection 168 compared with those without SARS-CoV-2 infection. 32 Among pregnant persons with COVID-169 19, severe disease was associated with preeclampsia, preterm birth, gestational diabetes, and low 170 birth weight compared to those with mild disease. 32 Two studies published after the meta-171 analysis found similar findings. A multi-national cohort study found pregnant persons with 172 COVID-19 were at increased risk for preeclampsia/eclampsia and preterm birth compared to 173 pregnancies without In an observational study of 1219 pregnant patients testing 174 positive for SARS-CoV-2, those with severe disease were at increased of cesarean delivery, 175 hypertensive disorders of pregnancy, and preterm birth compared to asymptomatic patients. 14 In addition to the direct impact of COVID-19 on pregnancy outcomes, there is evidence 177 that the pandemic and its effects on healthcare systems have had adverse effects on pregnancy 178 outcomes, even among those not infected with SARS-CoV-2. In a global systematic review, 179 increases in stillbirths and maternal deaths, declines in maternal mental health (as measured by 180 mean Edinburgh Postnatal Depression Scale scores), and an increased rate of ruptured ectopic 181 pregnancies representing a delay in appropriate care were observed during the pandemic 182 compared to before the pandemic. 34 This deterioration in several maternal health measures,, 183 which was more pronounced in low-resource compared to high-resource settings, may represent lockdown periods in some [36] [37] [38] [39] [40] but not all 41,42 high-resource settings, largely due to reductions in 187 extreme prematurity. Although these trends could represent a shift in deliveries from liveborn 188 premature infants to stillborn infants, alternatively, these may represent true improvements in 189 birth outcomes in some settings. Since our efforts over many decades to prevent preterm birth 190 have been largely unsuccessful, these findings are intriguing and could potentially hold clues to 191 long-standing challenges to preventing preterm births. (Table) . CDC specifies that any of the currently authorized vaccines can be administered to Clinicians should ensure that women younger than 50 years old are aware of the risk for this rare 293 adverse event and that other COVID-19 vaccines for which this risk has not been seen are 294 available. Although the overall risk of thrombosis is increased during pregnancy and postpartum, 295 the mechanism of TTS is distinct from the pregnancy-associated thrombosis and therefore there 296 is no specific concern for pregnant persons distinct from those who are not pregnant. 43 However, American College of Obstetricians and Gynecologists. COVID-19 Vaccination Considerations for Obstetric-Gynecologic Care COVID-19 Vaccination During Pregnancy: Coverage and Safety Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine COVID-19 vaccine response in pregnant and lactating women: A cohort study Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices -United States Pregnancy Registry Team. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons COVID-19 vaccination in pregnancy: Early experience from a single institution * A preprint publication (not yet peer reviewed) reporting updated data from v-safe confirms that receipt of mRNA vaccine preconception or during pregnancy is not associated with an increased risk of spontaneous abortion + A preprint publication (not yet peer reviewed) reports no increased risk of a composite adverse outcome (includes maternal death, uterine rupture, ICU admission, return to operating room, postpartum hemorrhage, perineal laceration, fetal or neonatal death, neonatal encephalopathy, low Apgar, NICU admission, low birthweight, neonatal birth trauma) among pregnant persons who received Pfizer (n=127), Moderna (n=12), or Janssen (n=1) (vaccines analyzed together) American College of Obstetricians and Gynecologists. COVID-19 Vaccination Considerations for Obstetric-Gynecologic Care COVID-19 Vaccination During Pregnancy: Coverage and Safety Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine COVID-19 vaccine response in pregnant and lactating women: A cohort study Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices -United States Pregnancy Registry Team. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons COVID-19 vaccination in pregnancy: Early experience from a single institution * A preprint publication (not yet peer reviewed) reporting updated data from v-safe confirms that receipt of mRNA vaccine preconception or during pregnancy is not associated with an increased risk of spontaneous abortion + A preprint publication (not yet peer reviewed) reports no increased risk of a composite adverse outcome (includes maternal death, uterine rupture, ICU admission, return to operating room, postpartum hemorrhage, perineal laceration, fetal or neonatal death, neonatal encephalopathy, low Apgar, NICU admission, low birthweight, neonatal birth trauma) among pregnant persons who received Pfizer (n=127), Moderna (n=12), or Janssen (n=1) (vaccines analyzed together) Astra Zeneca (n=13) (vaccines analyzed together ; No evidence of increased risk of adverse perinatal outcomes among 13 pregnant persons who received mRNA vaccine; type not specified. ; No concerning trends in perinatal outcome among 65 pregnant persons who received Pfizer vaccine Guillain-Barre syndrome -7.8 cases per 1,000,000 doses administered -highest rate in males aged 50-64 years large Ebola vaccination trial. +