The COVID-19 pandemic is continuing to cause huge social, economic, and health-related costs throughout the world, especially in Spain. Clinicians are still coming to terms with the range of health conditions wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A new study published on the preprint server medRxiv* in September 2020 shows that this infection results in fetal and maternal complications.
Screening for COVID-19 in Pregnancy
Due to the intense exposure in Spain, the country set up a universal screening program for all pregnant women to detect the actual rate of COVID-19-induced pregnancy complications in this cohort. The current study utilized the data from this screening program to evaluate the effect of obstetric intervention on pregnancy outcomes.
While over 80% of non-pregnant women have mild illness with COVID-19, some do show signs of severe inflammation and respiratory impairment requiring mechanical ventilation. Some earlier research has shown that this trend is also seen among pregnant patients.
Adverse Outcomes in Pregnancy
Prior studies have shown that the cytokines found to be elevated to tremendously high levels in progressive COVID-19, like IL-6, are linked to a poor perinatal prognosis in pregnant patients. Therefore, the researchers tried to identify whether COVID-19 leads to adverse outcomes in pregnancy. They focused on indicators like preterm birth, premature rupture of membranes, and increased neonatal intensive care unit (NICU) admissions.
The study involved over 1,000 patients who gave birth between March 23 and May 31, 2020. Of these, about a were COVID-19-positive. Of the pregnant women with COVID-19, almost 90% were asymptomatic at the time of delivery, but 20% had reported symptoms earlier. That is, almost 80% of this group remained asymptomatic throughout.
Most Infected Pregnant Women are Asymptomatic
Among the pregnant women who were symptomatic during childbirth, the vast majority, almost 86%, had mild symptoms like cough and anosmia, tiredness, fever, and mild shortness of breath. About 7% developed mild or moderate pneumonia, and another 7% had severe pneumonia. Not a single pregnant woman died or went into septic shock.
Reviewing the demographics of the study, it is seen that Latin American women in this group were almost three times as likely to be infected. In contrast, White European women were at only half the risk.
Risk of Preterm Birth Doubled
The researchers found that despite the majority of infections being asymptomatic, there were twice as many preterm births among these women, at ~14% vs 7% in the healthy group. This difference was found even though prior screening by ultrasound and clinical examination had shown no significant variation in risk factors between the groups.
Iatrogenic Preterm Deliveries
Iatrogenic preterm deliveries that were not the result of premature rupture of membranes (PROM) were four times more common in this group, at 5% vs. 1%, but not spontaneous preterm deliveries, which had the same incidence in both groups. This could have been due to the presence of severe pre-eclampsia and pneumonia, leading to the induction of labor in order to end the pregnancies.
Symptomatic COVID-19 was observed to be present in over 40% of iatrogenic preterm deliveries, but only a fifth of spontaneous preterm births. Both PROM and preterm premature rupture of the membranes (PPROM) were found to be increased in the exposed group as compared to the unexposed group, by 70%.
Though no mothers died in this cohort, the proportion of intrauterine fetal deaths was higher among the patient group compared to the healthy mothers, by over ten times, at 1.2% vs. 0.1%. NICU admissions were more than 4.5 times higher among babies born to infected mothers, mainly due to premature birth and respiratory distress. Not a single baby required care due to COVID-19.
Unique Positioning and Limitations
This is the first prospective cohort study to examine the link between exposure to COVID-19 and obstetric outcomes related to this infection. The incidence of PROM, PPROM, prematurity and its complications were significantly higher in the group of pregnant women with COVID-19, and the rate of intrauterine fetal death was also significantly higher.
The researchers point out that this is a preliminary report. Even so, more work is necessary to pinpoint the reason for this increase in premature labor, especially because of its robust link with PROM.
The study is also limited in that the infected cohort could not be compared with healthy mothers from the start due to the emergency situation in which the study took place and the acute shortage of diagnostic testing. By the time of this screening set-up, severely symptomatic COVID-19 had become less common, which reduced the power of the study to analyze some of these effects.
The researchers also point out that many obstetric crises, including severe pre-eclampsia, pulmonary thromboembolism, and placental abruption, occurred in March and April when many hospitals were not prepared with this screening program. Thus, clinical outcomes have been lumped together without differential analysis.
Serological testing was also not available or offered at that time to patients who were PCR negative. The study also focused on the perinatal outcomes, omitting other periods of pregnancy, including late abortions. Thus, the risk of transmission to the baby, or the reasons for intrauterine death, are not examined here. The role of IL-6 needs to be examined since this cytokine is present at a higher level in amniotic fluid in pregnant women who suffer miscarriage without COVID-19.
Implications and Future Directions
The researchers sum up, “We did find an increase in obstetric pathology in these patients, which in our opinion indicates that in the pregnant woman with asymptomatic COVID-19, there is a specific obstetric pathology that needs to be recognized.” The unique finding here is that PROM is associated with COVID-19, possibly due to the increased levels of cytokines like IL-6 that are already known to be common to both preterm delivery, PROM, and COVID-19. In fact, IL-6 is established to be a risk factor for preterm delivery.
Further work is required to trace the effect of genetic and ethnic susceptibility, as well as of socioeconomic deprivation impacting on obstetric care, on the demographic divide observed in this study.
The study concludes, “Pregnant COVID-19 patients are a population at risk of suffering preterm deliveries, and the disease has an impact on NICU admissions. Premature rupture of membranes at term and preterm are more frequent in patients with COVID-19.’
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.