Pregnancy outcomes in patients with suspected SARS-CoV-2 infection before delivery

Abstract

The SARS-CoV-2 virus has led to over 700 million COVID-19 cases worldwide, with over six million deaths.1 A revised report from the CDC determined that 6.6% of SARS-CoV-2 positive cases in women of childbearing age were pregnant at the time of testing.2 Data on infection in pregnancy primarily comes from symptomatic cases or routine hospital screening, revealing associations with adverse outcomes like preeclampsia, preterm birth, and stillbirth. However, many infections are subclinical or undiagnosed. Without population screening and seroprevalence studies, cases during pregnancy may be undetected or misclassified. Few studies examined the impact of SARS-CoV-2 seroprevalence on pregnancy outcomes.3,4 Two studies focused on unvaccinated pregnant individuals in pandemic-affected areas, finding most seroconverted individuals asymptomatic and no adverse effects on mothers or neonates.3,5 However, these studies had small sample sizes (n=100, n=528) and lacked statistical power.5 At the beginning of the pandemic, we instituted universal screening for SARS-CoV-2 immunoglobulin G (IgG) in pregnant individuals during the routine third-trimester blood draw. This study aimed to evaluate outcomes in patients with prior COVID-19 infection, as evidenced by positive antibody screening, that usual testing eligibility criteria would not have detected. In this IRB-approved retrospective cohort study at a single academic center, we conducted universal antepartum SARS-CoV-2 IgG screening during the third-trimester blood draw at 32 weeks gestation from June 2020 to January 2022. All pregnant women presenting for admission for delivery were tested for SARS-CoV-2 nucleic acid via nasopharyngeal swabs. Those with SARS-CoV-2 IgG screening in the third trimester and negative SARS-CoV-2 PCR testing on admission for delivery from June 2020 to January 2022 were eligible for analysis. Those with a history of SARS-CoV-2 infection or vaccination were excluded. Relevant patient characteristics and maternal and neonatal outcomes were collected. Outcomes were then compared among those with positive versus negative antepartum IgG screens. Our primary outcome was a neonatal composite, including NICU admission, arterial cord pH < 7.1, and various neonatal complications. Secondary outcomes included individual neonatal composite components and adverse maternal outcomes, such as cesarean delivery, preterm delivery, and preeclampsia. We compared primary and secondary outcomes between groups using univariable and multivariable analyses. A total of 8,551 patients were delivered in the study period, with 4,414 eligible for this analysis. Of these, 3,138 (71%) had a negative IgG, and 1,276 (29%) had a positive IgG screen (Figure 1). The only difference in baseline characteristics was a higher BMI in the IgG-positive group. There were no differences in the neonatal composite or maternal outcomes between groups (Table 2). Results were unchanged after adjusting for BMI (aRR 0.89; 95%CI 0.76-1.03 for neonatal composite).Table 1Patient characteristics and maternal and neonatal outcomes.COVID IgG (-)N=3138COVID IgG (+)N=1276RR [95%CI] or MD [95%CI]Age (years)27 ± 6.127 ± 6.20.2 [-0.2-0.6]Ethnicity Hispanic2043 (65.3)1071 (84.1)2.8 [2.4-3.3]Race White2611 (83.2)1142 (89.5)1.7 [1.4-2.1] Black416 (13.3)114 (8.9)0.6 [0.5-0.8] Asian83 (2.7)16 (1.3)0.5 [0.3-0.8] American Indian/Alaskan23 (0.7)2 (0.2)0.2 [0.1-0.9] Native Hawaiian4 (0.1)2 (0.2)1.2 [0.2-6.7]BMI (kg/m2)32 (18-94)33 (19-68)-0.4 [-0.8-0.1]Gravida2 (1-23)3 (1-11)0.0 [-0.1-0.1]Para1 (0-9)1 (0-10)-0.1 [-0.1-0.0]Gestational age at delivery (weeks)39 (35-43)39 (34-42)-0.0 [-0.1-0.1]Birth weight (g)3250 (1765-4885)3270 (1665-5060)-11.4 [-39.1-16.4]Arterial cord pH7.29 ± 1.47.26 ± 0.070.03 [-0.06-0.12]Neonatal composite803/3105 (26)302/1273 (24)0.9 [0.8-1.0] Arterial cord pH < 7.141/2198 (1.9)20/938 (2.1)1.1 [0.7-2.0] APGAR < 7 at 5 minutes17/3105 (0.5)4/1273 (0.3)0.6 [0.2-1.7] Neonatal hypoglycemia222/3105 (7.1)72/1273 (5.7)0.8 [0.6-1.0] Hypotension requiring pressors13/3105 (0.4)5/1273 (0.4)0.9 [0.3-3] NICU admission214/3105 (6.9)81/1273 (6.4)0.9 [0.7-1.2] Meconium aspiration syndrome6/3105 (0.2)3/1273 (0.2)1.2 [0.3-4.9] Sepsis7/3105 (0.2)3/1273 (0.2)1.0 [0.3-4.1] Seizures3/3105 (0.1)5/1273 (0.4)4.1 [1.0-17.1] Hyperbilirubinemia178/3105 (5.7)75/1273 (5.9)1.0 [0.8-1.4] Bronchopulmonary dysplasia0 (0)0 (0)- Retinopathy0 (0)0 (0)- Hypoxic-ischemic encephalopathy2/3105 (0.1)4/1273 (0.3)4.9 [0.9-26.7] Necrotizing enterocolitis1/3105 (0.03)1/1273 (0.1)2.4 [0.2-39.0] Respiratory support479/3105 (15.4)182/1273 (14.3)0.9 [0.8-1.1] Perinatal death9/3105 (0.3)1/1273 (0.1)0.3 [0.1-2.1]Maternal Outcomes Cesarean section1098/3100 (35.4)418/1273 (32.8)0.9 [0.8-1.0] Live birth > 37 weeks3019/3100 (97.4)1233/1273 (96.9)0.8 [0.6-1.2] Diagnosis of preeclampsia after admission182/3100 (5.9)69/1273 (5.4)0.9 [0.7-1.2] Maternal ICU admission7/3100 (0.2)1/1273 (0.1)0.3 [0.1-2.8] Maternal death0 (0)0 (0)-Continuous data are presented as median (range) or mean ± standard deviation and categorical data are presented as n/N (%)ICU: intensive care unit; NICU: neonatal intensive care unit. RR: relative risk ratio; MD: mean difference. Open table in a new tab Continuous data are presented as median (range) or mean ± standard deviation and categorical data are presented as n/N (%) ICU: intensive care unit; NICU: neonatal intensive care unit. RR: relative risk ratio; MD: mean difference. The COVID-19 pandemic has affected millions globally, including pregnant individuals.6,7 Data on pregnancy effects mainly comes from symptomatic cases, but many infections are subclinical or undiagnosed. Few studies have evaluated undiagnosed COVID-19 infections during pregnancy, with limitations in reporting outcomes or statistical power.4,5 COVID-19 can pose serious health risks for pregnant people and their neonates. Most published reports include symptomatic patients or those with positive/negative routine nucleic acid tests at hospital admission. Without universal screening, asymptomatic cases are missed or misclassified. To address this issue, we leveraged our universal screening policy to evaluate outcomes in patients with prior COVID-19 infection, evidenced by antibody screening, that usual testing eligibility criteria would not have detected. All these patients had negative nucleic acid testing on admission and did not report any COVID symptoms, infection, or vaccination before admission for delivery. We found no differences in the neonatal composite or maternal outcomes between patients with positive and negative antepartum IgG screens, indicating that previously undiagnosed COVID-19 infections are not significantly associated with pregnancy outcomes. Our study has limitations, such as its retrospective nature and potential selection bias, and lacks information on infection timing. However, it is the largest study of undetected COVID-19 infection effects on pregnancy outcomes, a difficult analysis to replicate as most pregnant people now have positive antibody screens from natural exposure or vaccination. In conclusion, undiagnosed COVID-19 infections do not significantly affect immediate pregnancy outcomes. Further research is needed to understand long-term effects, and adherence to public health guidelines remains crucial to protect pregnant individuals and their neonates. 1World Health Organization. Coronavirus (COVID-19) Dashboard. Available at: https://covid19.who.int/.2Overton EE, Goffman D, Friedman AM. The Epidemiology of COVID-19 in Pregnancy. Clin Obstet Gynecol. 2022 Mar 1;65(1):110-122. doi: 10.1097/GRF.0000000000000674. PMID: 35045034; PMCID: PMC8767915.3Accurti V, Gambitta B, Iodice S, et al. SARS-CoV-2 Seroconversion and Pregnancy Outcomes in a Population of Pregnant Women Recruited in Milan, Italy, between April 2020 and October 2020. Int J Environ Res Public Health. 2022 Dec; 19(24):16720.4Gupta P, Kumar S, Sharma SS. SARS-CoV-2 prevalence and maternal-perinatal outcomes among pregnant women admitted for delivery: Experience from COVID-19-dedicated maternity hospital in Jammu, Jammu and Kashmir (India). J Med Virol. 2021 Sep; 93(9):5505-5514.5Zambrano H, Anchundia K, Aviles D, et al. Seroprevalence of SARS-CoV-2 immunoglobulins in pregnant women and neonatal cord blood from a highly impacted region. Placenta. 2021 Nov; 115:146-150.6Pierce-Williams RAM, Burd J, Felder L, et al. Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study. Am J Obstet Gynecol MFM. 2020;2(3):100134.7Savasi VM, Parisi F, Patane L, et al. Clinical findings and disease severity in hospitalized pregnant women with coronavirus disease 2019 (COVID-19). Obstet Gynecol. 2020 Jul;136(1):252-258.