Covid-19 During Pregnancy: Increased Risk Of Preterm Delivery And Infant Neurodevelopmental Issues

Pregnant Woman and Gynecologist Doctor at Hospital

Doctor examine pregnant belly for baby and mother healthcare check up.



During pregnancy, a mother’s body suppresses parts of the immune system to help tolerate the growing fetus. This means pregnant women are at an especially high risk of contracting disease, including Covid-19. The risk they face is two-fold: first, towards their own health, and second, towards the health of their unborn child. Still, not much is known about the impacts of SARS-CoV-2 infection during pregnancy. In a previous article, I summarized some of the key findings thus far. Since then, two new studies have been published, offering additional insights into the dangers of Covid-19 exposure during pregnancy. The first findings come from researchers at the University College London. Their work suggests that mothers who catch Covid-19 during their first trimester are more likely to have an early miscarriage. The second study, led by a group at Harvard Medical School, found that infants born to mothers who had Covid-19 during pregnancy are more likely to receive a neurodevelopmental diagnosis in the first 12 months following delivery. The good news? Maternal vaccination can help cut down many of the risks associated with SARS-CoV-2 infection during pregnancy.

Covid-19 Raises the Risk of Early Miscarriage 

Between May and December of 2020, Balachandren et al. recruited 3500 women via social media to help participate in the COVID-19 Contraception and Pregnancy Study (CAP-COVID). All women had conceived during the pandemic and were within the first 12 weeks of pregnancy. The team of researchers asked the women to report on any current or prior pregnancy complications and their medical history. The participants were also asked every trimester whether they or anyone in their household had been diagnosed with SARS-CoV-2 infection. Depending on their answer, the women were filtered into one of three groups: those who self-reported a SARS-CoV-2 infection within the first trimester (“presumed infected”), those who had symptoms or were exposed to household contacts with symptoms but had no official diagnosis (“uncertain”), and those who had neither symptoms nor household contacts with symptoms (“presumed uninfected”).

After accounting for age, body mass index (BMI), number of previous miscarriages, ethnicity, and smoking status, Baachandren and his colleagues discovered that the risk of early miscarriage was around 1.7 times higher in the “presumed infected” group — a rate of 14%, compared to 8% in the “presumed uninfected” group and 5% in the “uncertain” group.

How SARS-CoV-2 infection during the first trimester contributes to early miscarriage is not entriely clear. Dimitrios Mavrelos, co-lead author of the study and Honorary Associate Professor, proposed that cytokines may be involved: “Coronaviruses have also been shown to induce a pro-inflammatory cytokine storm in the body. Cytokines are thought the play a role in the development of recurrent pregnancy loss, which could explain the increased risk of early miscarriage in women infected with COVID-19.”

The researchers stress that they have not established a strict causal relationship between Covid-19 and early miscarriage, but rather a correlation between the two. Further research will be needed to prove that SARS-CoV-2 is directly at fault.

It is worth noting that the study suffers from a few limitations. For one, the sample size was too small to establish statistical significance, the standard by which results are deemed “real” rather than simply a byproduct of chance or sample bias. Second, Balachandren et al. mention that the use of self-reported data always runs the risk of inaccuracy, since there’s no way of guaranteeing validity. Some of the participants in the “presumed uninfected” group may have simply been asymptomatic, for example.

Still, the results are concrete enough to warrant the recommendation that women in their first 12 weeks of pregnancy take extra precautions to avoid SARS-CoV-2 infection.

Covid-19 Raises the Risk of Neurodevelopmental Issues 

Andrea et al., based at the Massachusetts General Hospital in Boston, set out to study whether infants born to mothers who caught Covid-19 during pregnancy are at a higher risk for neurodevelopmental disorders within their first 12 months of life.

They followed a cohort of 7800 infants born at the height of the early pandemic, between March and September of 2020. Of these, 222 infants were born to mothers who had caught Covid-19 at some point during their pregnancy. Maternal SARS-CoV-2 infection was confirmed via polymerase chain reaction (PCR) test, the gold standard for diagnosis.

Their findings confirmed prior research: Covid-19 during pregnancy increases the risk of preterm delivery. In this particular case, 14.4% of mothers who suffered from Covid-19 delivered early. The likelihood of preterm delivery in the control group, on the other hand, stood at around 8%.

Andrea and colleagues also got an answer to their primary question. The odds of suffering from neurodevelopmental disorders are twice as high for infants born to mothers who tested positive for SARS-CoV-2 during pregnancy. Of the 222 exposed infants, 14 went on to receive a neurodevelopmental diagnosis within their first year of life — around 6%. In comparison, only 227 of the 7550 —roughly 3%— of the exposed infants went on to receive a diagnosis.

The same trend holds true when adjusting the model for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status. Under the adjusted model, maternal SARS-CoV-2 positivity still correlates with an 80% increase in the odds of neurodevelopmental issues in infants. Maternal Covid-19 during the third trimester of pregnancy was associated with an especially steep increase in the odds of infant neurodevelopmental disorders — almost two and a half times the odds.

Most of the diagnosed neurodevelopmental disorders reflected issues with motor function or of speech and language.

Take-home Message

As much of the world seems to want to forget the pandemic, these two studies stress the importance of continued caution on behalf of expecting mothers. Measures such as social distancing, avoidance of crowded and poorly ventilated spaces, and masking with N95/KN95 masks are still the best strategies for the prevention of Covid-19.

At this point, there is also a wealth of safety data on vaccination during pregnancy; all of it suggests that vaccination against Covid-19 significantly reduces risks for both the mother and the child. For one, the risk of developing Covid-19 in the first place is lower in vaccinated mothers. The likelihood of stillbirth is markedly lower in vaccinated mothers as well — 15% lower, compared to unvaccinated mothers. The rate of adverse effects in vaccinated mothers —including the risk of miscarriage— mirrors that of mothers who gave birth before the pandemic, confirming the safety of vaccination.

Maternal vaccination even protects the baby. Antibodies developed by the mother in response to vaccination can pass through the placenta to the fetus, transferring on immunity against SARS-CoV-2. These elevated antibody levels can persist up to 6 months after birth. The result? Infants born to vaccinated mothers are much less likely to require hospitalization for Covid-19. mRNA vaccines are 52% effective at preventing Covid-19-related hospitalization in infants. This number jumps up to 70% when looking at effectiveness against admission to an intensive care unit. Spreading out vaccine delivery so that the second dose is administered at some point after the first 20 months of pregnancy is particularly effective at preventing infant hospitalization.


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© William A. Haseltine, PhD. All Rights Reserved.