Pregnancy may increase the risk of COVID-19 severity

Against the background of the coronavirus disease 2019 (COVID-19) pandemic, the impact of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pregnancy has been a subject of much controversy.

In order to help answer the question as to whether this infection causes significant harm in pregnancy, a new study, released as a medRxiv* preprint, reports on the disease outcomes of this infection in pregnant women.

Study aims

The study included 66 systematic reviews of observational studies. Earlier studies indicate a 10% rate of COVID-19 in pregnant women in hospital, which is not above the rate of infection in other groups.

However, severe COVID-19 is apparently more likely in pregnant or recently pregnant women with advanced age, high body weight, and with chronic health conditions like hypertension or diabetes, according to the World Health Organization (WHO). Breastfeeding is largely considered to be safe, even if the mother is COVID-19 positive.

The researchers aimed to provide a panoramic view of the information gathered through multiple systematic reviews of COVID-19 in pregnancy.

Study details

The systematic reviews used here were assessed for eligibility, including a comprehensive search, data synthesis and avoiding bias. These were evaluated thereafter for quality, taking only the review and not the primary study into mind.

The systematic reviews chosen for inclusion were those that best answered any given question specifically and comprehensively, as well as most recently to a high-quality standard.

Presentation

The researchers showed that fever and mild breathing symptoms (40% and 20% respectively) predominated among symptoms. At the same time, an increased C-reactive protein level, lymphopenia, a high white cell count and high procalcitonin were the most common positive laboratory findings. Chest X-rays or CT (computerized tomography) also frequently showed evidence of pneumonia in 65% or more of cases.

Pregnancy was associated with ~55-60% lower chances of fever and myalgia.  

Maternal outcomes

Maternal mortality, in the selected representative review, occurred in 0.6% of SARS-CoV-2-positive mothers, while severe COVID-19 occurred in 13% of cases. Less than five in a hundred required intensive care unit (ICU) admission or invasive ventilation.

Compared to non-pregnant infected women of comparable age, the odds of ICU admission were 62% higher, with odds of ventilation up by 88%.

Risk factors associated with severe disease included age, high body mass, high blood pressure, and diabetes existing before pregnancy. These increased the chances of severe COVID-19 to almost double that of non-pregnant women.

Presentation in the newborn

The most frequent presentations in babies just before or following their birth to mothers infected with the virus included respiratory distress syndrome (RDS), breathing problems, and fetal distress. Most commonly, increased immunoglobulin (Ig) M and IgG antibodies to the virus, and signs of pneumonia on chest imaging were also found.

The best review in this area found almost one in five of these babies were admitted to the neonatal ICU, while complications due to preterm birth, RDS, and birth defects all occurred in less than 5% each. A little less than two-thirds were hospitalized as newborns, but for less than two days. Only just more than a tenth were in the hospital for over a week.

Outcomes in newborns

The scientists also report that the most common adverse neonatal outcomes following maternal SARS-CoV-2 infection included low birth weight and preterm birth. According to the most reliable study, about 0.3% of babies died, but about a fourth were admitted to the NICU. The odds of death were three-fold higher compared to those born to uninfected mothers. Preterm birth occurred in 17% of deliveries among women reported to have COVID-19.

Transmission to the fetus/infant

Most studies reporting on viral transmission from mother to child looked at neonatal test positivity but not transmission via breast milk or perinatal transmission, except for some small studies.

In the best study covering this area, among 72 mothers with positive tests for the virus in their breast milk, only 14 infants tested positive. This includes eight of 23 breastfed infants, two of 18 infants fed on a substitute, and two of four infants fed with both breast milk and a substitute. Of the 23 babies where feeding history was unknown, two were positive for the virus.

Another review described three positive neonatal tests out of 90 tested. The occurrence of IgG antibodies in two-thirds of these babies indicates vertical transmission is unlikely on any large scale.

What are the implications?

Most of the systematic reviews included here were highly unreliable in their confidence level, as assessed by the AMSTAR tool. Thus, the evidence from these studies cannot be treated as certain in most cases.

A small increase in risk for ICU admission or invasive ventilation may be associated with COVID-19 in pregnancy, as well as of having a Cesarean section, of preterm delivery, and of neonatal ICU admission.

Preterm delivery seems to be iatrogenic, with spontaneous preterm births having a similar prevalence in women with and without COVID-19. The rate of Cesarean sections is also up by three-fold the global rate, the reasons for which are not mentioned.

Some risk factors for severe and critical COVID-19 and for maternal death have been pointed out, which are not unique to the pregnant population. These include chronic hypertension and diabetes preceding pregnancy.

Fetal or neonatal mortality is hardly higher, despite the three-fold higher odds of NICU admission.

The takeaways include the need to be aware of the often asymptomatic or mildly symptomatic nature of COVID-19 in pregnancy compared to the general population; the increase in the risk of ICU admission and ventilator use; added risk with specific comorbid conditions which will require interdisciplinary management; and the low risk of vertical transmission.

Further systematic reviews should be high-quality to ensure that guidelines are based on sound evidence. This mandates careful data retrieval, analysis and reporting, to maintain the quality of the study.

*Important Notice

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.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.