Obstetrical and Newborn Outcomes Among Patients With SARS-CoV-2 During Pregnancy.

We report on the perinatal outcomes of pregnant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 2 hospitals in Montréal, Québec. Outcomes of 45 patients with SARS-CoV-2 during pregnancy were compared with those of 225 patients without infection. Sixteen percent of patients with SARS-CoV-2 delivered preterm, compared with 9% of patients without (P = 0.28). Median gestational age at delivery (39.3 (interquartile range [IQR] 37.7-40.4) wk vs. 39.1 [IQR 38.3-40.1] wk) and median birth weight (3250 [IQR 2780-3530] g vs. 3340 [IQR 3025-3665] g) were similar between groups. The rate of cesarean delivery was 29% for patients with SARS-CoV-2. Therefore, we did not find important differences in outcomes associated with SARS-CoV-2. Our findings may be limited to women with mild COVID-19 diagnosed in the third trimester.

M.-J. Trahan

INTRODUCTION

Despite mounting evidence demonstrating the increased susceptibility of pregnant women to severe manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effects of the virus on perinatal outcomes remain incompletely understood. Among pregnant patients with coronavirus disease 2019 (COVID-19), high rates of preterm delivery (up to 39%) and cesarean delivery (CD) (33%–96%) have been reported.2, 3, 4, 5 Concerns regarding maternal status and potential fetal compromise may influence obstetrical management, including timing and mode of delivery. Thus, more information regarding obstetrical and newborn outcomes associated with COVID-19 is urgently needed to guide clinical decision making. We conducted a multicentre retrospective matched cohort study aiming to (1) report on obstetrical and newborn outcomes among patients with SARS-CoV-2 during pregnancy and (2) evaluate whether testing positive for SARS-CoV-2 is associated with any major adverse pregnancy outcomes that could be identified in a cohort of limited size.

METHODS

All pregnant women who delivered between March 22 and July 31, 2020, at the 2 study sites were eligible for inclusion. Pregnant patients with SARS-CoV-2 were identified according to a prospective log of admitted obstetrical patients who tested positive. At both centres, testing was initially restricted to at-risk patients, as identified through a screening questionnaire. Starting in May 2020, universal testing was implemented for all pregnant patients admitted to both hospitals. In all cases, SARS-CoV-2 testing was performed using polymerase chain reaction on nasopharyngeal swabs. Women who tested positive for SARS-CoV-2 were matched to patients who did not test positive for SARS-CoV-2 during pregnancy and who delivered within 1 day and at the same centre, in a ratio of 1:5.

Data were extracted from electronic medical records using a standardized data collection form. Data on maternal baseline characteristics included age, ethnicity, parity, current pregnancy plurality, and presence of underlying medical and pregnancy-associated conditions. Ethnicity was extracted from the electronic medical record when available, or from the antenatal record. Underlying medical conditions of interest included asthma and other respiratory conditions, diabetes mellitus (pre-gestational), cardiac conditions, chronic hypertension, and obesity (defined as pre-pregnancy or first obstetrical visit body mass index ≥30 kg/m2). Pregnancy-associated conditions of interest included gestational diabetes, hypertensive disorders (gestational hypertension and preeclampsia), and intrauterine growth restriction. Adverse maternal and newborn outcomes evaluated included preterm delivery, preterm premature rupture of membranes (PPROM), intrapartum complications, CD, low birth weight (<2500 g), very low birth weight (<1500 g), and neonatal intensive care admission. Preterm delivery was considered “medically indicated” or “iatrogenic” if it occurred as a result of obstetrical intervention, as opposed to preterm labour or PPROM. Intrapartum complications included major intrapartum fetal heart rate tracing abnormalities and emergency CD. Major intrapartum fetal heart rate tracing abnormalities were defined as requiring either cessation of oxytocin or performance of an instrumental vaginal delivery or CD. Indications for emergency CD included failure to progress, failed trial of labour after cesarean, fetal distress, or worsening maternal clinical status.

Maternal demographic characteristics were described using mean, median, standard deviation, and interquartile range (IQR), as appropriate. Obstetrical and newborn outcomes were compared between exposed (with SARS-CoV-2) and unexposed (without SARS-CoV2) groups using the Mann-Whitney test for continuous variables and the chi-square or Fisher test for categorical variables. P values were considered statistically significant if ≤0.05. Because sample size was limited by the number of available cases, an a priori power calculation was not performed. Instead, post hoc power calculations were assessed for 2 of the outcomes reported: preterm delivery and median gestational age (GA). Obstetrical and newborn outcomes among patients with severe COVID-19 were also reported. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS, version 27, 2020; IBM, NY).

This study was conducted in accordance with the TCPS 2, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2018). Research ethics board approval was obtained (CIUSSS West-Central Montreal REB, Project #2021-2346).

RESULTS

Of 2253 patients who delivered during the study period at both centres, we identified 45 patients with SARS-CoV-2 during pregnancy. These patients were matched to 225 patients who did not test positive for SARS-CoV-2. Maternal demographic and baseline characteristics are summarized in Table 1 and are similar between groups. Nearly all patients with SARS-CoV-2 (44 of 45; 98%) were diagnosed in the third trimester. The majority of patients with SARS-CoV-2 reported experiencing symptoms (32 of 44; 72%), with 13% (6 of 45) requiring antepartum hospital admission for COVID-19. Four of 45 patients (9%) met World Health Organization criteria for severe COVID-19, and 1 patient (2%) required mechanical ventilation. There were no maternal deaths.

Table 1

Maternal characteristics of patients with SARS-CoV-2 during pregnancy

	Group; no (%)
	Patients who tested positive for SARS-CoV-2 during pregnancy; n = 45	Patients who did not test positive for SARS-CoV-2 during pregnancy; n = 225
Delivery hospital
A	37 (82)	185 (82)
B	8 (18)	40 (18)
Maternal age, y
<25	9 (20)	19 (8)
25–34	20 (44)	119 (53)
≥35	16 (36)	87 (39)
Ethnicity
White	29 (64)	114 (51)
Asian	4 (9)	27 (12)
Black	8 (18)	31 (14)
Hispanic	2 (4)	12 (5)
Biracial/multiracial	1 (2)	5 (2)
First Nations	0 (0)	6 (3)
Not reported	1 (2)	30 (13)
Parity
0	15 (33)	85 (38)
1	12 (27)	62 (28)
≥2	18 (40)	78 (35)
Twin pregnancy	2 (4)	2 (1)
Underlying medical conditions
Asthma	3 (7)	10 (4)
Diabetes mellitus	0 (0)	5 (2)
Chronic hypertension	2 (4)	8 (4)
Cardiac condition	3 (7)	0 (0)
Obesity (pre-pregnancy BMI ≥30 kg/m2)	4 (9)	5 (2)
Pregnancy-associated conditions
Gestational diabetes	1 (2)	24 (11)
Gestational hypertension or preeclampsia	3 (7)	17 (8)
IUGR	1 (2)	7 (3)
Severe COVID-19	8 (18)	—
Mechanical ventilation	1 (2)	—
ECMO	0 (0)	—

BMI: body mass index; COVID-19: coronavirus disease 2019; ECMO: extracorporeal membranous oxygenation; IUGR: intrauterine growth restriction; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Obstetrical and newborn outcomes are summarized in Table 2 . Among patients with SARS-CoV-2, 16% (7 of 45) delivered preterm, compared to 9% (21 of 225) of unexposed patients (P = 0.28). Median GA at delivery was 39.3 weeks (IQR 37.7–40.4) among exposed patients, compared to 39.1 weeks (IQR 38.3–40.1) among unexposed patients. Among patients with SARS-CoV-2, 3 preterm deliveries were medically indicated (worsening maternal clinical status [n = 2] and preeclampsia with adverse conditions [n = 1]), 2 were spontaneous preterm deliveries, and 2 deliveries occurred after PPROM.

Table 2

Pregnancy outcomes and mode of delivery among patients with SARS-COV-2 during pregnancy

	Group; no (%)a		P value
	Patients who tested positive for SARS-CoV-2 during pregnancy; n = 45	Patients who did not test positive for SARS-CoV-2 during pregnancy; n = 225
Obstetrical outcomes
GA at delivery, mean ± SD, wk	38.9 ± 2.2	38.8 ± 2.5	0.74
GA at delivery, median (IQR), wk	39.3 (37.7–40.4)	39.1 (38.3–40.1)
Preterm delivery <37 wk	7 (16)	21 (9)	0.28
Preterm delivery <34 wk	2 (4)	10 (5)	1.0
PPROM	2 (4)	9 (4)	1.0
Intrapartum complications
Major intrapartum FHRT abnormalities requiring intervention	13/40 (33)	39/192 (20)	0.09
Mode of delivery
Instrumental vaginal delivery	4/40 (10)	12/192 (6)	0.73
Cesarean delivery (overall)	13 (29)	76 (34)	0.45
Emergency cesarean delivery	8/40 (20)	43/192 (22)	0.74
Newborn outcomes
Birth weight, median (IQR), g	3250 (2780–3530)	3340 (3025–3665)	0.08
Low birth weight	5/47 (11)	22/227 (10)	0.79
Very low birth weight	0/47 (0)	5/227 (2)	—
NICU admission	6/47 (13)	22/227 (10)	0.60

Unless otherwise specified.

FHRT: fetal heart rate tracing; GA: gestational age; IQR: interquartile range; NICU: neonatal intensive care unit; PPROM: preterm premature rupture of membranes; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Overall rates of CD and emergency CD were, respectively, 29% (13 of 45) and 20% (8 of 40) among patients with SARS-CoV-2, compared to 34% (76 of 225) and 22% (43 of 192) among patients without SARS-CoV-2 (P = 0.45 and P = 0.74). Among patients with SARS-CoV-2 who underwent an emergency CD, indications for CD included worsening maternal clinical status (n = 2), fetal distress (n = 2), failure to progress (n = 3), and failed trial of labour after cesarean (n = 1).

In total, 13% of infants (6 of 47) born to women with SARS-CoV-2 had a neonatal intensive care admission, compared to 10% (22 of 227) born to women without SARS-CoV-2 (P = 0.60). Infants born to women with SARS-CoV-2 had a median birth weight of 3250 g (IQR 2780–3530), compared to 3340 g (IQR 3025–3665) for infants born to women without SARS-CoV-2 (P = 0.08).

Pregnancy outcomes among patients with severe COVID-19 are presented in the online Appendix Table. The small number of patients with severe COVID-19 in this cohort precluded a comparative subanalysis among these patients.

Table

Pregnancy Outcomes and Mode of Delivery Among Patients with Severe COVID-19 During Pregnancy

Characteristics	Patients with severe COVID-19 during pregnancy; n = 4a
GA at delivery, mean ± SD, wk	34.8 ± 3.9
GA at delivery, median (IQR), wk	34.5 (31.3–38.5)
Preterm delivery <37 wk	2 (50)
Preterm delivery <34 wk	2 (50)
PPROM	1 (25)
Major intrapartum FHRT abnormalities requiring intervention	2 (50)
Instrumental vaginal delivery	0 (0)
Cesarean delivery (overall)	2 (50)
Emergency cesarean delivery	2 (50)
Birth weight, median (IQR), g	1945 (1748–3458)
Low birth weight	4/6 (67)
Very low birth weight	0/6 (0)
NICU admission	4/6 (67)

Unless otherwise specified.

FHRT: fetal heart rate tracing; GA: gestational age; IQR: interquartile range; NICU: neonatal intensive care unit; PPROM: preterm premature rupture of membranes.

DISCUSSION

Summary of Findings

Patients in our cohort who tested positive for SARS-CoV-2 in pregnancy had a 16% rate of preterm delivery. Median GA at delivery was similar between exposed and unexposed patients. We did not find an increased risk of CD among patients with SARS-CoV-2. Median birth weight was similar for infants born to exposed versus unexposed mothers. As such, in our patient population, we did not find significant differences in pregnancy and newborn outcomes among women with and without SARS-CoV-2.

Interpretation

Previous studies have reported rates of preterm delivery among patients with COVID-19 of up to 39%.2, 3, 4, 5 The U.S. Centers for Disease Control and Prevention reported a 12.6% rate of preterm delivery among pregnant patients with SARS-CoV-2 in the United States. Preterm delivery was 3 times more common among symptomatic patients than among asymptomatic patients (23% vs. 8%; P < 0.05). In our study, 16% of patients with SARS-CoV-2 delivered preterm, most of whom were symptomatic at time of delivery. Moreover, median GA was similar between groups, and post hoc analysis revealed that we were sufficiently powered to detect a 3-week difference in GA at delivery had there been one. In our cohort, 2 patients delivered preterm for worsening maternal status (2 of 7; 30%); therefore, these deliveries can be considered iatrogenic preterm deliveries for reasons related to COVID-19. The absence of a difference between groups in median GA at delivery may reflect a non-interventionalist approach to avoid iatrogenic preterm delivery among patients with COVID-19 at our institutions. Indeed, we previously reported that most patients (6 of 8; 75%) with severe COVID-19 treated at our institutions were discharged from the hospital undelivered, including 2 patients who had required mechanical ventilation.

Although COVID-19 is not an indication for CD, high rates of CD among SARS-CoV-2–positive patients are reported.2, 3, 4, 5 In a systematic review of 33 studies from 10 countries, which included 252 patients with SARS-CoV-2, 69% delivered by cesarean. In our study, we found that the overall rate of CD among patients with SARS-CoV-2 during pregnancy was similar to our institutional rates (30%). In addition, the rate of emergency CD among patients with SARS-CoV-2 was comparable to that among controls, with 2 emergency CDs performed for reasons related to COVID-19 among patients with SARS-CoV-2.

Owing to the association between low birth weight and other respiratory viruses, such as other coronaviruses and influenza, there is concern that SARS-CoV-2 infection during pregnancy may affect fetal growth. In our study, median birth weight among infants born to mothers with SARS-CoV-2 was similar to that of infants born to unexposed mothers, with the difference of 90 g between groups unlikely to be of clinical significance.

Strengths and Limitations

Because this study was performed at designated COVID-19 hospitalization centres in Canada's epicenter for COVID-19 during the first wave of infection, it provides valuable data on the initial Canadian experience in treating pregnancies complicated by SARS-CoV-2. Importantly, we were able to discern whether COVID-19 influenced obstetrical management, including timing and mode of delivery.

Because of our small sample size, our study was underpowered to demonstrate statistically significant differences for some of our findings. Nevertheless, no major signal suggesting a link between SARS-CoV-2 and adverse perinatal outcomes was detected. However, most patients in this cohort had mild disease diagnosed in the third trimester. Therefore, results may not be generalizable to patients with severe disease or those diagnosed earlier in pregnancy.

CONCLUSION

We did not find a major difference in the frequency of adverse obstetrical or newborn outcomes between women with and without SARS-CoV-2. However, our cohort was limited by a small sample size, and more subtle differences may be highlighted by larger cohorts. Our reported findings are important because they will contribute to future meta-analyses, which will provide a better understanding of the population effect of SARS-CoV-2 during pregnancy. Until further data become available, heightened surveillance for pregnancies affected by SARS-CoV-2 remains warranted.

SUPPLEMENTARY DATA

Supplementary data related to this article can be found at 10.1016/j.jogc.2021.03.012.