SARS-CoV-2 Infection during Pregnancy in a Rural Midwest All-delivery Cohort and Associated Maternal and Neonatal Outcomes.

OBJECTIVE: This study aimed to estimate the prevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) among pregnant patients at the time of delivery in a rural Midwest tertiary care hospital and to examine demographics, clinical factors, and maternal and neonatal outcomes associated with SARS-CoV-2 infection during pregnancy. STUDY DESIGN: This prospective cohort study included all delivering patients between May 1 and September 22, 2020 at the University of Iowa Hospitals and Clinics. Plasma SARS-CoV-2 antibody testing was performed. SARS-CoV-2 viral reverse-transcription polymerase chain reaction (RT-PCR) results and maternal and neonatal outcomes were collected from the electronic medical record. Data were analyzed using univariate statistical methods with clustering for multiple births. RESULTS: In total, 1,000 patients delivered between May 1 and September 22, 2020. Fifty-eight (5.8%) were SARS-CoV-2 antibody positive. Twenty-three also tested viral positive during pregnancy. Three of 1,000 (0.3%) were viral positive on admission but antibody negative. The median age was 30 years (interquartile range [IQR]: 26-33 years) and body mass index was 31.75 kg/m2 (IQR 27.7-37.5 kg/m2). The cesarean delivery rate was 34.0%. The study population was primarily white (71.6%); however, 41.0% of SARS-CoV-2 infected patients identified as Black, 18.0% as Hispanic/Latino, 3.3% as Native Hawaiian/Pacific Islander, and only 27.9% as White (p < 0.0001). SARS-CoV-2 infection was more likely in patients without private insurance (p = 0.0243). Adverse maternal and/or neonatal outcomes were not more likely in patients with evidence of infection during pregnancy. Two SARS-CoV-2 infected patients were admitted to the intensive care unit. There were no maternal deaths during the study period. CONCLUSION: In this largely rural Midwest population, 6.1% of delivering patients had evidence of past or current SARS-CoV-2 infection. Rates of SARS-CoV-2 during pregnancy were higher among racial and ethnic minorities and patients without private insurance. The SARS-CoV-2 infected patients and their neonates were not found to be at increased risk for adverse outcomes. KEY POINTS: · SARS-CoV-2 seroprevalence rate in pregnant population in Iowa is 5.8%.. · Infections are higher among minorities, non-English speakers, and patients without private insurance.. · No increased adverse maternal/neonatal outcomes observed for SARS-CoV-2 infected mothers..

Maternal and Infant Outcomes Associated with Maternity Practices Related to COVID-19: The COVID Mothers Study.

Background: Maternity care practices such as skin-to-skin care, rooming-in, and direct breastfeeding are recommended, but it is unclear if these practices increase the risk of clinically significant COVID-19 in newborns, and if disruption of these practices adversely affects breastfeeding. Methods: We performed a retrospective cohort study of 357 mothers and their infants <12 months who had confirmed or suspected COVID-19. Subjects came from an anonymous worldwide online survey between May 4 and September 30, 2020, who were recruited through social media, support groups, and health care providers. Using multivariable logistic regression, Fisher's exact test, and summary statistics, we assessed the association of skin-to-skin care, feeding, and rooming-in with SARS-CoV-2 outcomes, breastfeeding outcomes, and maternal distress. Results: Responses came from 31 countries. Among SARS-CoV-2+ mothers whose infection was ≤3 days of birth, 7.4% of their infants tested positive. We found a nonsignificant decrease in risk of hospitalization among neonates who roomed-in, directly breastfed, or experienced uninterrupted skin-to-skin care (p > 0.2 for each). Infants who did not directly breastfeed, experience skin-to-skin care, or who did not room-in within arms' reach, were significantly less likely to be exclusively breastfed in the first 3 months, adjusting for maternal symptoms (p ≤ 0.02 for each). Nearly 60% of mothers who experienced separation reported feeling "very distressed," and 29% who tried to breastfeed were unable. Presence of maternal symptoms predicted infant transmission or symptoms (adjusted odds ratio = 4.50, 95% confidence interval = 1.52-13.26, p = 0.006). Conclusion: Disruption of evidence-based quality standards of maternity care is associated with harm and may be unnecessary.

Maternal, fetal and neonatal outcomes of large series of SARS-CoV-2 positive pregnancies in peripartum period: A single-center prospective comparative study.

OBJECTIVE: To describe the proportions of asymptomatic, mild and severe diseases in infected pregnant women admitted for delivery. To compare maternal, fetal and neonatal outcomes of SARS-CoV-2 infected pregnant women with those of non-infected patients. STUDY DESIGN: Through an universal PCR testing for SARS-COV-2 at admission (not symptoms-based), this prospective cohort study enrolled all pregnant women admitted for delivery between 16th of June and the 16th of August 2020 in the West French Guiana Hospital Center. RESULTS: 507 pregnant women were included during the study period, of which 137 (27 %) were infected with SARS-COV-2. On admission, only 34/137 (24.8 %) of these patients presented with clinical symptoms. Among asymptomatic women, 16 /103 (15 %) became symptomatic after diagnosis. Throughout the delivery hospitalization and follow-up, 87/137 (63.5 %) remained always asymptomatic, 45/137 (32.8 %) developed a mild COVID-19 and 5/137 (3.6 %) developed a severe infection. SARS-CoV-2 infected patients were more likely to have post-partum hemorrhage >500 mL (14.2 % vs 7.2 %, RR 2.0 [95 %CI 1.1-3.4]), to be transfused (5.5 % vs 1.1 %, RR 4.9 [1.5-16.6]), and to be hospitalized in ICU (3.6 % vs 0.8 %, RR 4.5 [95 %CI 1.1-18.6] than uninfected ones. Intra-uterine fetal demises were more common in infected mothers compared to controls (5.1 % vs 1.1 %, RR 4.7 [95 % CI 1.4-45.9). Among 108 neonates from infected mothers tested at birth, none tested positive (0/108). When tested between 25 and 42 h after delivery, 4/29 (13.7 %) were positive for SARS-CoV-2 RT-PCR on nasopharyngeal swabs and remained asymptomatic. CONCLUSION: Pregnant women admitted for delivery and diagnosed with a SARS-COV-2 infection through an universal screening were symptomatic in only a quarter of cases. Their risks of post-partum hemorrhage, transfusion and admission to ICU were higher than those of uninfected patients. They also presented a higher risk of intra-uterine fetal demise. There were no other differences in maternal, obstetrical or neonatal outcomes.

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study.

Background: The coronavirus disease 2019 pandemic has had an impact on healthcare systems around the world with 3 million people contracting the disease and 208,000 cases resulting in death as of this writing. Information regarding coronavirus infection in pregnancy is still limited. Objective: This study aimed to describe the clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnant women with positive laboratory testing for severe acute respiratory syndrome coronavirus 2. Study Design: This is a cohort study of pregnant women with severe or critical coronavirus disease 2019 hospitalized at 12 US institutions between March 5, 2020, and April 20, 2020. Severe disease was defined according to published criteria as patient-reported dyspnea, respiratory rate >30 per minute, blood oxygen saturation ≤93% on room air, ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen <300 mm Hg, or lung infiltrates >50% within 24-48 hours on chest imaging. Critical disease was defined as respiratory failure, septic shock, or multiple organ dysfunction or failure. Women were excluded from the study if they had presumed coronavirus disease 2019, but laboratory testing was negative. The primary outcome was median duration from hospital admission to discharge. Secondary outcomes included need for supplemental oxygen, intubation, cardiomyopathy, cardiac arrest, death, and timing of delivery. The clinical courses are described by the median disease day on which these outcomes occurred after the onset of symptoms. Treatment and neonatal outcomes are also reported. Results: Of 64 hospitalized pregnant women with coronavirus disease 2019, 44 (69%) had severe disease, and 20 (31%) had critical disease. The following preexisting comorbidities were observed: 25% had a pulmonary condition, 17% had cardiac disease, and the mean body mass index was 34 kg/m2. Gestational age was at a mean of 29±6 weeks at symptom onset and a mean of 30±6 weeks at hospital admission, with a median disease day 7 since first symptoms. Most women (81%) were treated with hydroxychloroquine; 7% of women with severe disease and 65% of women with critical disease received remdesivir. All women with critical disease received either prophylactic or therapeutic anticoagulation during their admission. The median duration of hospital stay was 6 days (6 days [severe group] and 10.5 days [critical group]; P=.01). Intubation was usually performed around day 9 on patients who required it, and peak respiratory support for women with severe disease was performed on day 8. In women with critical disease, prone positioning was required in 20% of cases, the rate of acute respiratory distress syndrome was 70%, and reintubation was necessary in 20%. There was 1 case of maternal cardiac arrest, but there were no cases of cardiomyopathy or maternal death. Thirty-two of 64 (50%) women with coronavirus disease 2019 in this cohort delivered during their hospitalization (34% [severe group] and 85% [critical group]). Furthermore, 15 of 17 (88%) pregnant women with critical coronavirus disease 2019 delivered preterm during their disease course, with 16 of 17 (94%) pregnant women giving birth through cesarean delivery; overall, 15 of 20 (75%) women with critical disease delivered preterm. There were no stillbirths or neonatal deaths or cases of vertical transmission. Conclusion: In pregnant women with severe or critical coronavirus disease 2019, admission into the hospital typically occurred about 7 days after symptom onset, and the duration of hospitalization was 6 days (6 [severe group] vs 12 [critical group]). Women with critical disease had a high rate of acute respiratory distress syndrome, and there was 1 case of cardiac arrest, but there were no cases of cardiomyopathy or maternal mortality. Hospitalization of pregnant women with severe or critical coronavirus disease 2019 resulted in delivery during the clinical course of the disease in 50% of this cohort, usually in the third trimester. There were no perinatal deaths in this cohort.

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.

Objective: The aim of this systematic review was to report pregnancy and perinatal outcomes of coronavirus spectrum infections, and particularly coronavirus 2019 (COVID-19) disease because of severe acute respiratory syndrome-coronavirus-2 infection during pregnancy. Data Sources: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for coronavirus or severe acute respiratory syndrome or SARS or Middle East respiratory syndrome or MERS or COVID-19 and pregnancy. The search and selection criteria were restricted to English language. Study Eligibility Criteria: Inclusion criteria were hospitalized pregnant women with a confirmed coronavirus related-illness, defined as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), or COVID-19. Study Appraisal and Synthesis Methods: We used meta-analyses of proportions to combine data and reported pooled proportions, so that a pooled proportion may not coincide with the actual raw proportion in the results. The pregnancy outcomes observed included miscarriage, preterm birth, preeclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score <7 at 5 minutes, neonatal asphyxia, admission to a neonatal intensive care unit, perinatal death, and evidence of vertical transmission. Results: Nineteen studies including 79 hospitalized women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8%, and the most common symptoms were fever (82.6%), cough (57.1%), and dyspnea (27.0%). For all coronavirus infections, the pooled proportion of miscarriage was 64.7% (8/12; 95% confidence interval, 37.9-87.3), although reported only for women affected by SARS in two studies with no control group; the pooled proportion of preterm birth <37 weeks was 24.3% (14/56; 95% confidence interval, 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (6/34; 95% confidence interval, 9.5-34.9), preeclampsia in 16.2% (2/19; 95% confidence interval, 4.2-34.1), and fetal growth restriction in 11.7% (2/29; 95% confidence interval, 3.2-24.4), although reported only for women affected by SARS; 84% (50/58) were delivered by cesarean; the pooled proportion of perinatal death was 11.1% (5/60; 95% confidence interval, 84.8-19.6), and 57.2% of newborns (3/12; 95% confidence interval, 3.6-99.8) were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth <37 weeks, occurring in 41.1% of cases (14/32; 95% confidence interval, 25.6-57.6), while the pooled proportion of perinatal death was 7.0% (2/41; 95% confidence interval, 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. Conclusion: In hospitalized mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, preterm birth is the most common adverse pregnancy outcome. COVID-19 infection was associated with higher rate (and pooled proportions) of preterm birth, preeclampsia, cesarean, and perinatal death. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy, although they should be interpreted with caution in view of the very small number of included cases.

Pregnancy and neonatal outcomes in COVID-19: study protocol for a global registry of women with suspected or confirmed SARS-CoV-2 infection in pregnancy and their neonates, understanding natural history to guide treatment and prevention.

INTRODUCTION: Previous novel COVID-19 pandemics, SARS and middle east respiratory syndrome observed an association of infection in pregnancy with preterm delivery, stillbirth and increased maternal mortality. COVID-19, caused by SARS-CoV-2 infection, is the largest pandemic in living memory.Rapid accrual of robust case data on women in pregnancy and their babies affected by suspected COVID-19 or confirmed SARS-CoV-2 infection will inform clinical management and preventative strategies in the current pandemic and future outbreaks. METHODS AND ANALYSIS: The pregnancy and neonatal outcomes in COVID-19 (PAN-COVID) registry are an observational study collecting focused data on outcomes of pregnant mothers who have had suspected COVID-19 in pregnancy or confirmed SARS-CoV-2 infection and their neonates via a web-portal. Among the women recruited to the PAN-COVID registry, the study will evaluate the incidence of: (1) miscarriage and pregnancy loss, (2) fetal growth restriction and stillbirth, (3) preterm delivery, (4) vertical transmission (suspected or confirmed) and early onset neonatal SARS-CoV-2 infection.Data will be centre based and collected on individual women and their babies. Verbal consent will be obtained, to reduce face-to-face contact in the pandemic while allowing identifiable data collection for linkage. Statistical analysis of the data will be carried out on a pseudonymised data set by the study statistician. Regular reports will be distributed to collaborators on the study research questions. ETHICS AND DISSEMINATION: This study has received research ethics approval in the UK. For international centres, evidence of appropriate local approval will be required to participate, prior to entry of data to the database. The reports will be published regularly. The outputs of the study will be regularly disseminated to participants and collaborators on the study website (https://pan-covid.org) and social media channels as well as dissemination to scientific meetings and journals. STUDY REGISTRATION NUMBER: ISRCTN68026880.

Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. METHODS: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. DISCUSSION: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies at Delivery in Women, Partners, and Newborns.

OBJECTIVE: To investigate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in parturient women, their partners, and their newborns and the association of such antibodies with obstetric and neonatal outcomes. METHODS: From April 4 to July 3, 2020, in a single university hospital in Denmark, all parturient women and their partners were invited to participate in the study, along with their newborns. Participating women and partners had a pharyngeal swab and a blood sample taken at admission; immediately after delivery, a blood sample was drawn from the umbilical cord. The swabs were analyzed for SARS-CoV-2 RNA by polymerase chain reaction, and the blood samples were analyzed for SARS-CoV-2 antibodies. Full medical history and obstetric and neonatal information were available. RESULTS: A total of 1,313 parturient women (72.5.% of all women admitted for delivery at the hospital in the study period), 1,188 partners, and 1,206 newborns participated in the study. The adjusted serologic prevalence was 2.6% in women and 3.5% in partners. Seventeen newborns had SARS-CoV-2 immunoglobulin G (IgG) antibodies, and none had immunoglobulin M antibodies. No associations between SARS-CoV-2 antibodies and obstetric or neonatal complications were found (eg, preterm birth, preeclampsia, cesarean delivery, Apgar score, low birth weight, umbilical arterial pH, need for continuous positive airway pressure, or neonatal admission), but statistical power to detect such differences was low. Full serologic data from 1,051 families showed an absolute risk of maternal infection of 39% if the partner had antibodies. CONCLUSION: We found no association between SARS-CoV-2 infection and obstetric or neonatal complications. Sixty-seven percent of newborns delivered by mothers with antibodies had SARS-CoV-2 IgG antibodies. A limitation of our study is that we lacked statistical power to detect small but potentially meaningful differences between those with and without evidence of infection.

Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to conduct a systematic review of the current literature to determine estimates of vertical transmission of coronavirus disease 2019 based on early RNA detection of severe acute respiratory syndrome coronavirus 2 after birth from various neonatal or fetal sources and neonatal serology. DATA SOURCES: Eligible studies published until May 28, 2020, were retrieved from PubMed, EMBASE, medRxiv, and bioRxiv collection databases. STUDY ELIGIBILITY CRITERIA: This systematic review included cohort studies, case series, and case reports of pregnant women who received a coronavirus disease 2019 diagnosis using severe acute respiratory syndrome coronavirus 2 viral RNA test and had reported data regarding the testing of neonates or fetuses for severe acute respiratory syndrome coronavirus 2 immediately after birth and within 48 hours of birth. A total of 30 eligible case reports describing 43 tested neonates and 38 cohort or case series studies describing 936 tested neonates were included. STUDY APPRAISAL AND SYNTHESIS METHODS: The methodological quality of all included studies was evaluated by a modified version of the Newcastle-Ottawa scale. Quantitative synthesis was performed on cohort or case series studies according to the neonatal biological specimen site to reach pooled proportions of vertical transmission. RESULTS: Our quantitative synthesis revealed that of 936 neonates from mothers with coronavirus disease 2019, 27 neonates had a positive result for severe acute respiratory syndrome coronavirus 2 viral RNA test using nasopharyngeal swab, indicating a pooled proportion of 3.2% (95% confidence interval, 2.2-4.3) for vertical transmission. Of note, the pooled proportion of severe acute respiratory syndrome coronavirus 2 positivity in neonates by nasopharyngeal swab in studies from China was 2.0% (8/397), which was similar to the pooled proportion of 2.7% (14/517) in studies from outside of China. Severe acute respiratory syndrome coronavirus 2 viral RNA testing in neonatal cord blood was positive in 2.9% of samples (1/34), 7.7% of placenta samples (2/26), 0% of amniotic fluid (0/51), 0% of urine samples (0/17), and 9.7% of fecal or rectal swabs (3/31). Neonatal serology was positive in 3 of 82 samples (3.7%) (based on the presence of immunoglobulin M). CONCLUSION: Vertical transmission of severe acute respiratory syndrome coronavirus 2 is possible and seems to occur in a minority of cases of maternal coronavirus disease 2019 infection in the third trimester. The rates of infection are similar to those of other pathogens that cause congenital infections. However, given the paucity of early trimester data, no assessment can yet be made regarding the rates of vertical transmission in early pregnancy and potential risk for consequent fetal morbidity and mortality.

Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore.

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION: The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.

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.

Rates of Maternal and Perinatal Mortality and Vertical Transmission in Pregnancies Complicated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2) Infection: A Systematic Review.

OBJECTIVE: To ascertain the frequency of maternal and neonatal complications, as well as maternal disease severity, in pregnancies affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DATA SOURCES: MEDLINE, Ovid, ClinicalTrials.gov, MedRxiv, and Scopus were searched from their inception until April 29, 2020. The analysis was limited to reports with at least 10 pregnant patients with SARS-CoV-2 infection that reported on maternal and neonatal outcomes. METHODS OF STUDY SELECTION: Inclusion criteria were pregnant women with a confirmed diagnosis of SARS-CoV-2 infection. A systematic search of the selected databases was performed by implementing a strategy that included the MeSH terms, key words, and word variants for "coronavirus," "SARS-CoV-2," "COVID-19," and "pregnancy.r The primary outcomes were maternal admission to the intensive care unit (ICU), critical disease, and death. Secondary outcomes included rate of preterm birth, cesarean delivery, vertical transmission, and neonatal death. Categorical variables were expressed as percentages with number of cases and 95% CIs. TABULATION, INTEGRATION, AND RESULTS: Of the 99 articles identified, 13 included 538 pregnancies complicated by SARS-CoV-2 infection, with reported outcomes on 435 (80.9%) deliveries. Maternal ICU admission occurred in 3.0% of cases (8/263, 95% CI 1.6-5.9) and maternal critical disease in 1.4% (3/209, 95% CI 0.5-4.1). No maternal deaths were reported (0/348, 95% CI 0.0-1.1). The preterm birth rate was 20.1% (57/284, 95% CI 15.8-25.1), the cesarean delivery rate was 84.7% (332/392, 95% CI 80.8-87.9), the vertical transmission rate was 0.0% (0/310, 95% CI 0.0-1.2), and the neonatal death rate was 0.3% (1/313, 95% CI 0.1-1.8). CONCLUSION: With data from early in the pandemic, it is reassuring that there are low rates of maternal and neonatal mortality and vertical transmission with SARS-CoV-2. The preterm birth rate of 20% and the cesarean delivery rate exceeding 80% seems related to geographic practice patterns. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020181497.

COVID-19: neonatal-perinatal perspectives.

The coronavirus disease 2019 (COVID-19) pandemic, resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused severe and widespread illness in adults, including pregnant women, while rarely infecting neonates. An incomplete understanding of disease pathogenesis and viral spread has resulted in evolving guidelines to reduce transmission from infected mothers to neonates. Fortunately, the risk of neonatal infection via perinatal/postnatal transmission is low when recommended precautions are followed. However, the psychosocial implications of these practices and racial/ethnic disparities highlighted by this pandemic must also be addressed when caring for mothers and their newborns. This review provides a comprehensive overview of neonatal-perinatal perspectives of COVID-19, ranging from the basic science of infection and recommendations for care of pregnant women and neonates to important psychosocial, ethical, and racial/ethnic topics emerging as a result of both the pandemic and the response of the healthcare community to the care of infected individuals.

Vertical Transmission of COVID-19 to the Neonate.

Objective: To estimate the incidence rate of vertical transmission of coronavirus disease 2019 (COVID-19) to the neonate during the third trimester. Study Design. We conducted a retrospective observational study of pregnant women diagnosed with COVID-19 during the third trimester, who delivered at Flushing Hospital Medical Centre (FHMC) or Jamaica Hospital Medical Centre (JHMC) between March 20, 2020, and April 30, 2020. The study participants were symptomatic pregnant women diagnosed with COVID-19 via positive SARS-CoV-2 RNA, real-time reverse transcription-polymerase chain reaction (SARS-CoV-2 rRT-PCR) test. Evidence of vertical transmission was assessed in the neonate via a SARS-CoV-2 rRT-PCR test, with nasopharyngeal swab samples collected on the neonates after 24 hours of birth. The exclusion criteria for this study were maternal or neonate records without SARS-CoV-2 rRT-PCR test results, neonates not delivered at FHMC or JHMC, and foetuses with suspected foetal anomalies or incomplete medical records. Results: We identified 19 symptomatic pregnant women diagnosed with COVID-19, including two women with twin pregnancies. Seven patients (36.8%) were delivered via cesarean. 12 patients (63.1%) presented in spontaneous labour, and 8 (38.1%) had preterm delivery. No maternal intensive care unit admission, maternal sepsis, or maternal mortality was observed. Twenty-one neonates were evaluated for COVID-19 after birth. SARS-CoV-2 rRT-PCR test results were negative in 100% of the neonates. Thirteen neonates (61.9%) were admitted to the neonatal intensive care unit. Prematurity was the most common cause of NICU admission 6 (46.1%), with a length of stay of 5.5 ± 6.4 days. No invasive mechanical ventilation, neonatal sepsis, or neonatal mortality was observed. Conclusion: In our cohort, symptomatic COVID-19 during the third trimester of pregnancy was not associated with vertical transmission to the neonate.

Clinical characteristics and outcomes of pregnant women with COVID-19 and the risk of vertical transmission: a systematic review.

PURPOSE: This systematic review summarizes the clinical features and maternal-infant outcomes of 230 pregnant women (154 patients gave birth) infected with COVID-19 and their 156 infants, including the possibility and evidence of vertical transmission. METHODS: An electronic search of PubMed, Embase, Medline, MedRxiv, CNKI, and the Chinese Medical Journal Full Text Database following PRISMA guidelines was performed through April 18, 2020. Search terms included COVID-19, SARS-CoV-2, pregnant women, infants, and vertical transmission. RESULTS: A total of 230 women with COVID-19 (154 deliveries, 66 ongoing pregnancies, and 10 abortions) and 156 newborns from 20 eligible studies were included in this systematic review. A total of 34.62% of the pregnant patients had obstetric complications, and 59.05% of patients displayed fever. Lymphopenia was observed in 40.71% of patients. A total of 5.19% of women received mechanical ventilation. Seven women were critically ill. One mother and two newborns died. A total of 24.74% of newborns were premature. Five newborns' throat swab tests of SARS-CoV-2 were positive, all of which were delivered by cesarean section. For eight newborns with negative throat swab tests, three had both elevated IgM and IgG against SARS-CoV-2. Nucleic acid tests of vaginal secretions, breast milk, amniotic fluid, placental blood, and placental tissues were negative. CONCLUSION: Most pregnant patients were mildly ill. The mortality of pregnant women with COVID-19 was lower than that of overall COVID-19 patients. Cesarean section was more common than vaginal delivery for pregnant women with COVID-19. Premature delivery was the main adverse event for newborns. The vertical transmission rate calculated by SARS-CoV-2 nucleic acid tests was 3.91%. Serum antibodies against SARS-CoV-2 should be tested more frequently, and multiple samples should be included in pathogenic testing.

Pregnancy Outcomes Among Women With and Without Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Importance: Published data suggest that there are increased hospitalizations, placental abnormalities, and rare neonatal transmission among pregnant women with coronavirus disease 2019 (COVID-19). Objectives: To evaluate adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and to describe clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes. Design, Setting, and Participants: This observational cohort study of maternal and neonatal outcomes among delivered women with and without SARS-CoV-2 during pregnancy was conducted from March 18 through August 22, 2020, at Parkland Health and Hospital System (Dallas, Texas), a high-volume prenatal clinic system and public maternity hospital with widespread access to SARS-CoV-2 testing in outpatient, emergency department, and inpatient settings. Women were included if they were tested for SARS-CoV-2 during pregnancy and delivered. For placental analysis, the pathologist was blinded to illness severity. Exposures: SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures: The primary outcome was a composite of preterm birth, preeclampsia with severe features, or cesarean delivery for abnormal fetal heart rate among women delivered after 20 weeks of gestation. Maternal illness severity, neonatal infection, and placental abnormalities were described. Results: From March 18 through August 22, 2020, 3374 pregnant women (mean [SD] age, 27.6 [6] years) tested for SARS-CoV-2 were delivered, including 252 who tested positive for SARS-CoV-2 and 3122 who tested negative. The cohort included 2520 Hispanic (75%), 619 Black (18%), and 125 White (4%) women. There were no differences in age, parity, body mass index, or diabetes among women with or without SARS-CoV-2. SARS-CoV-2 positivity was more common among Hispanic women (230 [91%] positive vs 2290 [73%] negative; difference, 17.9%; 95% CI, 12.3%-23.5%; P < .001). There was no difference in the composite primary outcome (52 women [21%] vs 684 women [23%]; relative risk, 0.94; 95% CI, 0.73-1.21; P = .64). Early neonatal SARS-CoV-2 infection occurred in 6 of 188 tested infants (3%), primarily born to asymptomatic or mildly symptomatic women. There were no placental pathologic differences by illness severity. Maternal illness at initial presentation was asymptomatic or mild in 239 women (95%), and 6 of those women (3%) developed severe or critical illness. Fourteen women (6%) were hospitalized for the indication of COVID-19. Conclusions and Relevance: In a large, single-institution cohort study, SARS-CoV-2 infection during pregnancy was not associated with adverse pregnancy outcomes. Neonatal infection may be as high as 3% and may occur predominantly among asymptomatic or mildly symptomatic women. Placental abnormalities were not associated with disease severity, and hospitalization frequency was similar to rates among nonpregnant women.

Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance.

BACKGROUND: Babies differ from older children with regard to their exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data describing the effect of SARS-CoV-2 in this group are scarce, and guidance is variable. We aimed to describe the incidence, characteristics, transmission, and outcomes of SARS-CoV-2 infection in neonates who received inpatient hospital care in the UK. METHODS: We carried out a prospective UK population-based cohort study of babies with confirmed SARS-CoV-2 infection in the first 28 days of life who received inpatient care between March 1 and April 30, 2020. Infected babies were identified through active national surveillance via the British Paediatric Surveillance Unit, with linkage to national testing, paediatric intensive care audit, and obstetric surveillance data. Outcomes included incidence (per 10 000 livebirths) of confirmed SARS-CoV-2 infection and severe disease, proportions of babies with suspected vertically and nosocomially acquired infection, and clinical outcomes. FINDINGS: We identified 66 babies with confirmed SARS-CoV-2 infection (incidence 5·6 [95% CI 4·3-7·1] per 10 000 livebirths), of whom 28 (42%) had severe neonatal SARS-CoV-2 infection (incidence 2·4 [1·6-3·4] per 10 000 livebirths). 16 (24%) of these babies were born preterm. 36 (55%) babies were from white ethnic groups (SARS-CoV-2 infection incidence 4·6 [3·2-6·4] per 10 000 livebirths), 14 (21%) were from Asian ethnic groups (15·2 [8·3-25·5] per 10 000 livebirths), eight (12%) were from Black ethnic groups (18·0 [7·8-35·5] per 10 000 livebirths), and seven (11%) were from mixed or other ethnic groups (5·6 [2·2-11·5] per 10 000 livebirths). 17 (26%) babies with confirmed infection were born to mothers with known perinatal SARS-CoV-2 infection, two (3%) were considered to have possible vertically acquired infection (SARS-CoV-2-positive sample within 12 h of birth where the mother was also positive). Eight (12%) babies had suspected nosocomially acquired infection. As of July 28, 2020, 58 (88%) babies had been discharged home, seven (11%) were still admitted, and one (2%) had died of a cause unrelated to SARS-CoV-2 infection. INTERPRETATION: Neonatal SARS-CoV-2 infection is uncommon in babies admitted to hospital. Infection with neonatal admission following birth to a mother with perinatal SARS-CoV-2 infection was unlikely, and possible vertical transmission rare, supporting international guidance to avoid separation of mother and baby. The high proportion of babies from Black, Asian, or minority ethnic groups requires investigation. FUNDING: UK National Institute for Health Research Policy Research Programme.

Birth and Infant Outcomes Following Laboratory-Confirmed SARS-CoV-2 Infection in Pregnancy - SET-NET, 16 Jurisdictions, March 29-October 14, 2020.

Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness and might be at risk for preterm birth (1-3). The full impact of infection with SARS-CoV-2, the virus that causes COVID-19, in pregnancy is unknown. Public health jurisdictions report information, including pregnancy status, on confirmed and probable COVID-19 cases to CDC through the National Notifiable Diseases Surveillance System.* Through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET), 16 jurisdictions collected supplementary information on pregnancy and infant outcomes among 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29-October 14, 2020. Among 3,912 live births with known gestational age, 12.9% were preterm (<37 weeks), higher than the reported 10.2% among the general U.S. population in 2019 (4). Among 610 infants (21.3%) with reported SARS-CoV-2 test results, perinatal infection was infrequent (2.6%) and occurred primarily among infants whose mother had SARS-CoV-2 infection identified within 1 week of delivery. Because the majority of pregnant women with COVID-19 reported thus far experienced infection in the third trimester, ongoing surveillance is needed to assess effects of infections in early pregnancy, as well the longer-term outcomes of exposed infants. These findings can inform neonatal testing recommendations, clinical practice, and public health action and can be used by health care providers to counsel pregnant women on the risks of SARS-CoV-2 infection, including preterm births. Pregnant women and their household members should follow recommended infection prevention measures, including wearing a mask, social distancing, and frequent handwashing when going out or interacting with others or if there is a person within the household who has had exposure to COVID-19.†.