Multiple studies show COVID-19’s impact on pregnancy, yet some question it
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Numerous studies have shown that COVID-19 poses significant health risks to pregnant women and their offspring — with increased rates of preeclampsia, preterm birth and even perinatal death, for example.
However, other research suggests that there might not be any difference in outcomes between pregnant and nonpregnant women with COVID-19. Researchers acknowledge that more work is needed to uncover the health effects of the disease.
To make sense of the data, Healio spoke with experts about the latest research on COVID-19 during pregnancy.
Evolution of research
Early studies exploring how COVID-19 impacted pregnancy were mixed about whether there were adverse outcomes tied to the disease.
For example, a September 2020 study found that pregnant women with COVID-19 were more likely to experience preterm birth than those without COVID-19. But a December 2020 study found no significant differences in preterm birth in these populations, as well as no differences in preeclampsia with severe features or cesarean delivery for fetal indication.
“Pregnant patients seemed to be doing okay. I was one of those people looking at the original data and saying ‘Hey, don’t sweat it. It seems that people are doing well,’” Mary Jane Minkin, MD, clinical professor in the department of obstetrics, gynecology and reproductive sciences at the Yale School of Medicine, told Healio.
“It wasn’t until a few months into the pandemic that people really started noticing that maybe this is not so good,” said Minkin, who also is a Healio Women’s Health & OB/GYN Peer Perspective Board Member.
The researchers in the December 2020 study are now evaluating pregnancy outcomes from patients diagnosed in 2021, and they plan to present their findings to the Society for Maternal-Fetal Medicine’s Pregnancy Meeting later this month.
“We know and have published that the risks of severe or critical COVID-19 illness were significantly higher for pregnant women infected during the delta variant surge than we had seen previously,” author Emily H. Adhikari, MD, assistant professor of obstetrics and gynecology at University of Texas Southwestern Medical Center, told Healio.
In 2021, more evidence that COVID-19 had significant impacts on pregnancy began to emerge.
A January 2021 study by the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHHD) found increased risks for cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy and preterm birth.
In July 2021, the NICHHD published a review of 28 studies involving 15,524 pregnant women diagnosed with SARS-CoV-2 infection, finding an increased risk for preeclampsia among these patients.
“That really raised people’s awareness that these preeclampsia risks are real,” Minkin said. “These are not women who were necessarily at high risk for preeclampsia, but they were sick with COVID-19, and they got really sick.”
Additionally, a study published in The Journal of Infectious Diseases in December that included 2,655 pregnancies with a documented SARS-CoV-2 infection found a two- to threefold higher risk for induced abortion, cesarean section, clinician-initiated preterm birth, fetal growth restriction and postpartum hemorrhage.
Despite the increasing number of studies showing an association between SARS-CoV-2 infection and poor pregnancy outcomes further into the pandemic, there was still some research in 2021 that failed to demonstrate a connection. For example, patients with rheumatic diseases who had COVID-19 while pregnant had favorable pregnancy and infection outcomes in a study of 39 women. In fact, according to the study, 32 of these patients did not receive any specific medication for COVID-19.
A much larger study published in October 2021 that evaluated the outcomes of 838,489 women who gave birth found no significant differences in the frequency of preterm birth, stillbirth, small for gestational age, large for gestational age, hypertensive disorders of pregnancy, placental abruption, cesarean birth or postpartum hemorrhage between those who tested positive and negative for SARS-CoV-2.
“There may be a few reasons for the differences between our study and other studies,” author Moeun Son, MD, MSCI, FACOG, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the Yale School of Medicine, told Healio.
The study by Son and colleagues was based on a large U.S. population and is more appropriately comparable to other U.S. studies with similarly large sample sizes, which are few in number, said Son. Also, the study used data from the Epic system, and it included 465 hospitals across all four U.S. Census Bureau regions.
“With access to detailed data including laboratory data, we were able to compare women who had confirmed SARS-CoV-2 infection versus those who were tested and tested negative,” Son said.
Other studies have been limited by using only the presence or absence of diagnosis codes for COVID-19 infection, not confirmed positive vs. negative, or small numbers of women with confirmed SARS-CoV-2 infections, Son continued.
“This is important because women who have a COVID-19 diagnosis code in databases may be women who are more likely to be symptomatic or have more significant disease, which may increase their risk for pregnancy complications,” Son said.
“It is important, however, to keep in mind that the data are ever-evolving, and there may be different pregnancy complication risks for different variants of SARS-CoV-2,” Son said. “Our data [spanned] March 1, 2020, to December 31, 2020, when it was predominantly the alpha variant, and before vaccination availability.”
COVID-19 may exacerbate existing problems
Minkin said greater risks for negative outcomes — if eventually confirmed in the literature over time — can be traced to the physiology of both pregnancy and COVID-19.
“You have to breathe. Oxygen is good. But what happens is when you have this kid sitting in your pelvis, your abdomen is then pushing up on your diaphragm. And it’s harder for the lungs to expand,” she said. “A pregnant woman has some degree of respiratory compromise just from being pregnant. Then you have SARS-CoV-2 sitting in her lungs, which makes it extra hard for her.”
Pregnant women also face greater metabolic demands, with fluid volume up 50% over baseline.
“If you’re a young, healthy person, you can handle it. But if someone is compromised with COVID-19, with extra metabolic demands, that person will be set up for a potential problem no matter what,” Minkin said.
Diabetes and obesity are risk factors in both pregnancy and COVID-19 as well, setting up even greater potential for complications.
“The body wants sugar always to be available for the baby. The placenta makes a hormone called HPL, which drives the pancreas and raises blood sugars,” Minkin said. “This driver is challenging your pancreas beyond its normal capacities, so pregnancy already is a diabetogenic state. You have that exacerbating the whole picture as well.”
When perinatal death occurs, Minkin says that hypoxia is a key factor.
“You need oxygen. Unfortunately, the fetus is well sheltered, and it needs to get oxygen through the placenta,” she said. “Anything that is going to compromise placental function is going to compromise oxygen flow to the fetus.”
Importance of vaccination
COVID-19 vaccines became widely available in the spring of 2021. A study published in April of that year showed that the incidences of adverse outcomes among 35,691 pregnant patients who received an mRNA vaccine and their infants were similar to those reported before the pandemic.
But by Sept. 18, only 31% of pregnant women in the U.S. had been fully vaccinated, according to data from the COVID-19-Associated Hospitalization Surveillance Network. Many women were concerned about the vaccines’ impact on reproductive health.
“We had plenty of clinical data that the vaccine did not cause miscarriage, and there really is no reason to assume that it causes infertility. There’s no physiologic reason to show that it does. There’s no increase in people not getting pregnant,” Minkin said.
In fact, three separate studies presented at the American Society for Reproductive Medicine Scientific Congress & Expo last October demonstrated that COVID-19 vaccination did not impair fertility, early pregnancy outcomes or sperm quality.
On Sept. 29, the CDC issued an urgent health advisory recommending that women who are pregnant; women who were recently pregnant, including women who are breastfeeding; and women who are trying to conceive or who may become pregnant in the future get vaccinated against COVID-19.
A more recent study published in January 2022 demonstrated the vaccines’ ability to protect women and their offspring against adverse outcomes. The study included 87,694 women who gave birth in Scotland between December 2020 and October 2021. According to the researchers, 16.6% of babies born within 28 days of their mother developing COVID-19 were delivered more than 3 weeks before their due date, compared with 7.9% of babies born to mothers who had not been infected with SARS-CoV-2.
Additionally, the perinatal death rate among babies born within 28 days of their mother developing COVID-19 was 22.6 per 1,000 births, compared with 4.3 per 1,000 births among mothers who were vaccinated within 28 days of giving birth.
The study also suggested that risk for complications stemming from COVID-19 was greater if women developed the disease later in their pregnancy.
“The findings support other data that show vaccination is the safest and most effective way for pregnant women to protect themselves and their babies against COVID-19,” author Sarah Stock, MD, PhD, a reader in maternal and fetal health and an honorary consultant and subspecialist in maternal and fetal medicine at the University of Edinburgh Usher Institute, told Healio.
Although the study covered May through November 2021 — when the delta variant was dominant in Scotland — Stock and colleagues are mindful of the omicron variant.
“Although omicron may cause milder symptoms in many, it is still a dangerous virus, especially in the unvaccinated,” she said.
Most of the data so far on omicron come from nonpregnant populations, so its effects on pregnancy, including complications such as preterm births and neonatal deaths, are still unknown. However, its levels of transmissibility make it a concern, again highlighting the importance of vaccination, Stock said.
Next, Stock said she and her colleagues will use the COVID-19 in Pregnancy in Scotland dataset to examine the effects of SARS-CoV-2 on early pregnancy outcomes such as miscarriage, while further studying vaccine safety and efficacy.
Other researchers agree that vaccination is effective in protecting mothers and their offspring.
“Vaccination has been shown to decrease morbidity and hospitalization for severe COVID-19, but unfortunately, vaccination rates for pregnant patients have lagged behind rates for the general population,” said Adhikari, noting that all but one pregnant patient admitted to the hospital in her evaluation of the delta surge were unvaccinated.
“We do not know all of the effects of this virus on pregnancy or on the long-term health of the mother or neonate, so there is urgency to prevent infections using evidence-based vaccination recommendations, including boosters for those who are eligible,” she said.
Plus, a study from September 2021 suggests that pregnant women who get vaccinated against COVID-19 pass that protection on to their babies, with 100% of these infants carrying high levels of protective anti-SARS-CoV-2 spike immunoglobulin G antibodies.
Minkin cautions that it is too soon to tell if the vaccine is keeping these babies from getting COVID-19, however.
“We certainly have data that the antibodies are there,” she said. “As far as clinical outcomes of developing the infection, fortunately, moms are pretty good about trying to shield their kids. I don’t know how much data we have yet accumulated about incidence of newborns coming down with COVID-19. I hope we’re trying to keep it as low as possible.”
References:
- Adhikari EH, et al. JAMA Netw Open. 2020;doi:10.1001/jamanetworkopen.2020.29256.
- Allotey J, et al. BMJ. 2020;doi:10.1136/bmj.m3320.
- Bermas BL, et al. J Rheumatol. 2021;doi:10.3899/jrheum.210480.
- Conde-Agudelo A, et al. Am J Obstet Gynecol. 2021;doi:10.1016/j.ajog.2021.07.009.
- Gonzalez D, et al. P-453. Presented at: American Society of Reproductive Medicine Scientific Congress & Expo; Oct. 17-20, 2021; Baltimore (hybrid meeting).
- Lee JA, et al. O-177. Presented at: American Society of Reproductive Medicine Scientific Congress & Expo; Oct. 17-20, 2021; Baltimore (hybrid meeting).
- Media Advisory: Severe COVID-19 in pregnancy associated with preterm birth, other complications. https://www.nichd.nih.gov/newsroom/news/012821-GRAVID. Published Jan. 28, 2021. Accessed Jan. 18, 2022.
- Morris AJ, et al. O-190. Presented at: American Society of Reproductive Medicine Scientific Congress & Expo; Oct. 17-20, 2021; Baltimore (hybrid meeting).
- Regan AK, et al. J Infect Dis. 2021;doi:10.1093/infdis/jiab626.
- Shimabukuro TT, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2104983.
- Son M, et al. Obstet Gynecol. 2021;doi:10.1097/AOG.0000000000004547.
- Stock SJ, et al. Nat Med. 2022;doi:10.1038/s41591-021-01666-2.
- Trostle ME, et al. Am J Obstet Gynecol MFM. 2021;doi:10.1016/j.ajogmf.2021.100481.
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