Initial review of pregnancy and neonatal outcomes of pregnant women with COVID-19 infection

Study design and participants

We conducted a retrospective cohort study of patients from four large, acute care hospitals in the Nuvance Health System. The study received exempt determination from the Biomedical Research Alliance of New York Institutional Review Board and the Vassar Brothers Medical Center Institutional Review Board.

The study included pregnant women 18 years or older with a diagnosis of COVID-19 (ICD 10 codes B97.29, J12.89, J18.9, U07.1) between March 17, 2020 and June 4, 2020 who were evaluated in several units (emergency department, outpatient clinic, inpatient, or labor and delivery). Pregnancy status was defined as a documented current ‘pregnant’ status in the problem list. Patients were excluded if they did not have a documented positive lab result for COVID-19. Women were identified by a data analytics weekly report in the Nuvance Health medical record system with a quality assurance review completed by a third-party research assistant. Testing for SARS-CoV-2 was performed using polymerase chain reaction (PCR) of a nasopharyngeal or nasal swab by either the hospital internal lab or Sunrise Laboratory. Testing was performed on admission to the labor and delivery unit, outpatient setting, and/or inpatient hospitalization.

Variables

Data were obtained through medical record abstraction. The variables included age, race, body mass index (BMI), positive COVID-19 status before delivery, rapid testing upon admission for delivery, retest COVID-19 information, known negative COVID-19 tests, viral symptoms, respiratory symptoms, COVID-19 related medications and illness complications, imaging results and obstetrics history. Race/ethnicity was defined as White, Black or African American, Hispanic, or other (undefined in medical chart). Treatment-related variables included the need for hospital admission, mechanical ventilation, oxygen requirements, biologic infusions, and treatment with antibiotics. For patients who delivered, we collected data regarding the mode of delivery, delivery course, neonatal birth weight, Apgar score, and neonatal SARS-CoV-2 test results.

Statistics

We computed descriptive statistics as percentages of the total for dichotomous and categorical variables and mean with standard deviation for continuous variables

Obstetrical outcomes

Of the 40 pregnant women who were positive for SARS-CoV-2, 25 delivered during the study time frame, with one woman having no labor and delivery information available (Table 3). Of the 25 women that delivered, 80% were COVID-19 positive at the time of admission. While the remaining 20% had a recent history of a positive COVID-19 test, however they tested negative during their labor hospitalization. Eighteen out of the 25 (72%) women were asymptomatic on admission to the labor and delivery unit. On admission for delivery, 7 (28%) women experienced active symptoms of SARS-CoV-2 and 21 of the 25 women (84%) delivered after 37 and 0/7 weeks gestation. One patient delivered between 34 and 0/7 weeks and 36 and 6/7 weeks. Three patients delivered under 33 and 6/7 weeks. Two patients had spontaneous second trimester fetal loss. The cases included fetal demise at 17 and 4/7 weeks and demise of twins at 20 and 4/7 weeks.

Seventeen of the 25 women (68%) had vaginal deliveries. The remaining eight women (32%) had cesarean deliveries. Of the women with cesarean deliveries, 4 (50%) women tested positive on admission, 2 (25%) experienced symptoms at the time of admission, and one needed supplemental oxygen due to the risk of respiratory decompensation. The indication for cesarean delivery was primarily due to non-reassuring fetal heart tracing (NRFHT) (37.5%) and history of previous cesarean delivery (50%). One patient had cesarean section for risk of respiratory decompensation. All three patients who had a cesarean delivery for NRFHT were asymptomatic during their labor. Furthermore, the modes of delivery were similar between the women that had symptoms and those without symptoms at the time of delivery. There were 9 (36%) women that had a vaginal delivery and were symptomatic while there were 8 (32%) women who were asymptomatic with a vaginal delivery. Alternatively, 6 (24%) of the women who had a cesarean section were symptomatic, while 2 (8%) women were asymptomatic at the time of the cesarean section. Two patients were reported to have deliveries complicated by postpartum hemorrhage.

Neonatal outcomes

Of the 25 women who had a live birth, 23 had viable neonates (Table 4). The mean 1 and 5 min Apgar scores were 8 and 8.8, respectively. The mean birth weight was 3212 g. Of the 23 neonates, 20 were tested for SARS-CoV-2 and were all found to be negative. Three of the neonates were not tested. Preterm delivery at 28 and 2/7 weeks with apnea of prematurity and hyperbilirubinemia requiring phototherapy were the two neonatal complications noted.

Clinical features of COVID-19 infection in all pregnancies

Current evidence on the impact of COVID-19 in pregnant women and on neonatal outcomes is limited by the emergent nature of the pandemic and the comparatively limited number of SARS-CoV-2 positive patients as demonstrated in our study. Notable patient characteristics in our study of pregnant women with COVID-19 infection include young maternal age, high BMI, and Hispanic ethnicity. About one third of the pregnant women identified as Hispanic were COVID-19 positive. The CDC also reported similar rates in which 5,141 of the 12,969 (39.6%) pregnant women with COVID-19 in the nation were Hispanic or Latino [3]. The high prevalence may be related to inequities in social determinants of health and essential work occupations in the Hispanic population. Furthermore, half of the patients were less than 30 years old, which is likely due to average childbearing age in our study population. Large-scale empirical research will lead to the identification of risk factors for poor outcomes for pregnant women.

The most commonly reported symptom was dry cough, fever, and shortness of breath, which was similar to symptoms reported by Yan et al [7]. Several of the women with respiratory distress received hydroxychloroquine and two women received convalescent plasma. Hydroxychloroquine was used in this study prior to the recent recommendation to avoid use of the medication unless in a hospital or clinical trial because the efficacy is unclear at this time and due to the adverse effects of arrhythmia. In our study, two of the patients’ symptoms improved after starting hydroxychloroquine and lopinavir/ritonavir and there were no arrhythmias noted on electrocardiogram (EKG). Additionally, evidence for convalescent plasma therapy is emerging. A systematic review showed that convalescent plasma use may decrease viral load and increase levels of neutralizing antibodies [8].

Previous case series have noted that the clinical course of patients with COVID-19 infection were similar to their non-pregnant counterparts [7]. In one of the largest expanded case series on pregnant patients with COVID-19, 8 of 116 patients developed severe pneumonia requiring ICU admission and two of these patients required mechanical ventilation [7]. There were no maternal deaths in this study. In our study, we noted no cases of severe COVID-19 infection requiring ICU admission and no patients required mechanical ventilation. The women presenting with respiratory distress were treated promptly with oxygen and plasma therapy leading to avoidance of admission to the ICU. Furthermore, lymphocytopenia was a common finding, and additionally there were elevated levels of C-reactive protein (CRP) in a similar number of patients. Lymphopenia may be due to viral infection of lymphocytes or apoptosis by inflammatory cytokines [9]. CRP is a marker of inflammation and has been found to be elevated in patients with COVID-19 infection which may be a biomarker for disease severity [10].

Obstetrical outcomes of patients who delivered

A total of 25 patients with COVID-19 infection delivered. Two of the patients had preterm deliveries at 28 and 2/7 weeks and 35 and 0/7 weeks. Two of the patients had a spontaneous second trimester loss. It cannot be confirmed if the loss of the fetuses was related to COVID-19. Both patients were asymptomatic and the fetuses were not tested. Furthermore, one of the patients had no prenatal care. A study by Schwartz reported cases of preterm delivery in COVID-19 patients; however, there is no current evidence that COVID-19 increases risk of miscarriages [11]. In regard to the mode of delivery, most patients in our study had vaginal deliveries while 32% of the patients had cesarean deliveries. The indications for cesarean delivery were primarily for non-reassuring fetal heart tracing and previous cesarean delivery. One patient had a cesarean delivery secondary to acute hypoxic respiratory failure requiring supplemental oxygenation and convalescent plasma therapy. This patient was nulliparous and presented at 37 and 3/7 weeks with eight days shortness of breath, fever along with significant transaminitis, and the chest X-ray showed bilateral opacifications. Fetal status was reassuring at the time, however cesarean delivery was performed due to worsening dyspnea and remote from delivery. Plasma therapy was initiated due to hypoxia and concern for respiratory decompensation especially given risk factors including morbid obesity and diabetes. In a study of seven pregnant women with COVID-19 pneumonia in Wuhan, China all patients had cesarean deliveries [12]. The indication for cesarean delivery in that study is unclear however all the patients required oxygen and antiviral therapy. The Society of Maternal Fetal Medicine (SMFM) recommends that mode of delivery should be based on routine indications [5]. However, cesarean delivery may be warranted if maternal status is deteriorating and the patient is remote from delivery. Currently, there is no data comparing obstetrical complications between pregnant women with COVID-19 and pregnant women without COVID-19 infection. However, there’s no evidence at this time that pregnant women are susceptible to severe pneumonia in comparison to non-pregnant women [7]. However, pregnant women are more likely to be hospitalized than non-pregnant women and the risk of death is similar for both [3].

Neonatal outcomes

There is limited data on the effect of COVID-19 on neonates. To date, there is no evidence of vertical transmission of COVID-19. There is one case report of a woman with COVID-19 whose neonate tested positive for SARS-CoV-2 [13]. However, the neonate was swabbed at about 30 hours old. It is unclear if horizontal transmission occurred via exposure to respiratory droplets while breastfeeding. Also, there was no testing of cord blood or placenta therefore intrauterine transmission cannot be confirmed. Our study demonstrated that all 20 neonates tested negative which is similar to prior studies [14], [15]. Furthermore, placental pathology did not detect COVID-19 infection. At this time, vertical transmission is unlikely, however it is inconclusive and further efforts are needed to analyze amniotic fluid, breast milk, and umbilical cord for the presence of SARS-CoV-2.

The Apgar scores and birth weights of the neonates in our study were reassuring and within normal limits. Neonatal complications were also minimal which included apnea of prematurity and hyperbilirubinemia. Both of the neonates with complications were born by women who were asymptomatic. It is unclear if these complications are associated with COVID-19 infection or are unrelated events. A case report of pregnant women with COVID-19 infection showed that none of the three infants developed serious symptoms [16]. Two infants had a rash that spontaneously resolved and one had mild dyspnea. Overall, the neonates in our study had similarly good outcomes.