COVID-19 in pregnancy associated with substantially increased maternal and neonatal morbidity and mortality

1. COVID-19 infection during pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications compared to non-infected pregnancies, especially in symptomatic individuals presenting or those with co-morbidities.

2. Women with COVID-19 were at increased risk of severe pregnancy complications including pre-eclampsia/eclampsia, intensive care unit (ICU) admission, and preterm birth.

Evidence Rating Level: 2 (Good)

Study Rundown: To date, the extent of maternal and neonatal risks and adverse outcomes associated with COVID-19 infection in pregnant women remains largely unclear. Similar coronavirus infections including severe acute respiratory syndrome and Middle East respiratory syndrome have been known to cause deleterious effects during pregnancy. Thus, the question posed by this study remains an important and relevant one as nations continue to treat and control the pandemic. This prospective cohort study (INTERCOVID) sought to assess the association between COVID-19 and maternal and neonatal outcomes in pregnant women with COVID-19 diagnosis, compared with concomitantly enrolled pregnant women without COVID-19. The primary outcome measures were indices of morbidity and mortality (maternal and neonatal) and the individual components of these indices were secondary outcomes of the study. In total, 706 pregnant women with COVID-19 and 1,424 pregnant women without COVID-19 were enrolled, all with similar demographic characteristics. The study found that women with COVID-19 were at increased risk of severe pregnancy complications including preeclampsia/eclampsia/HELLP syndrome, ICU admission, infections requiring antibiotics, preterm birth, and low birth weight. The risk of maternal mortality was 1.6% – 22 times higher than non-infected pregnant individuals. Reassuringly, asymptomatic COVID-19 patients had similar outcomes to non-infected women, except for an elevated risk of preeclampsia. Furthermore, the study found the presence of any COVID-19 symptoms was associated with increased morbidity and mortality, especially in women presenting with fever and shortness of breath. The risks of severe neonatal complications including NICU stay were also higher with COVID-19. Lastly, 12.1% of neonates born to test-positive women also tested positive, with the highest rate among cesarean deliveries at 72.2%. Breastfeeding was not associated with any increase in the rate of test-positive neonates. A limitation of this study was the risk of reporting bias relating to maternal and neonatal morbidity as women with COVID-19 diagnosis and their newborns may have been more carefully evaluated, tested, and have more events reported than non-infected individuals. A major strength, however, was being one of the first of its kind to report the deleterious effects of COVID-19 on pregnancy in a large cohort study.

Click to read the study in JAMA Pediatrics

Click to read an editorial in JAMA Pediatrics

Relevant Reading: Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study

In-Depth [prospective cohort]: This prospective, longitudinal, observational study took place from March to October 2020, involving 43 institutions in 18 countries. Two unmatched, consecutive, non-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care in order to minimize bias. Women and neonates were followed up until hospital discharge. Models for the study outcomes were then adjusted for country, month entering study, maternal age, and history of morbidity in the analysis. A total of 706 pregnant women with a COVID-19 diagnosis and 1,424 pregnant women without COVID-19 were enrolled (mean [SD] age, 30.2 [6.1] years). The COVID-19 positive cohort was at increased risk for preeclampsia/eclampsia (RR, 1.76; 95%CI, 1.27-2.43), severe infections (RR, 3.38; 95%CI, 1.63-7.01), ICU admission (RR, 5.04; 95%CI, 3.13-8.10), maternal mortality (RR, 22.3; 95%CI, 2.88-172), preterm birth (RR, 1.59; 95%CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95%CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95%CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95%CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95%CI, 2.11-11.69). However, asymptomatic COVID-19 positive women remained at higher risk only for maternal morbidity (RR, 1.24; 95%CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95%CI, 1.01-2.63). Among women who tested positive via real-time polymerase chain reaction testing, 54 (13%) of their neonates also tested positive. Cesarean delivery (RR, 2.15; 95%CI, 1.18-3.91) was associated with increased risk for neonatal test positivity, however, breastfeeding was not (RR, 1.10; 95%CI, 0.66-1.85).

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