Does COVID-19 cause adverse pregnancy and neonatal outcomes?

Early in the coronavirus disease 2019 (COVID-19) pandemic, pregnant women were thought to be at unusually high risk from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to the general population or non-pregnant women. However, later studies failed to agree on the extent and nature of the danger posed by the infection. A recent study reports on the adverse effects of SARS-CoV-2 infection on the mother and baby during pregnancy.

Study: Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis. Image Credit: ESB Professional / Shutterstock

Introduction

Earlier studies showed contradictory results on the effects of this condition during pregnancy. One extensive 2021 review showed an association between COVID-19 in pregnancy and a higher risk of dying, being admitted to the intensive care unit (ICU), of babies being born prematurely, and of stillbirths and admission to the neonatal care unit. A significant flaw of this study was that there were less than ten studies reviewed per outcome in most cases.

Other more recent studies indicated increased chances of hypertensive disorders of pregnancy, as well as for Cesarean section and adverse neonatal outcomes. Nevertheless, these conclusions remain controversial due to the heterogeneous study design, faulty selection of subjects and controls, and methodological flaws. Moreover, these were often not generalizable because they contained little data from low-income countries.

The current study, published in BMJ Global Health, aimed to produce more definitive conclusions. The researchers undertook a collaborative effort using high-quality individual participant data from 12 studies that are currently underway. These were conducted in a dozen countries and involved over 13,000 pregnant women.

The present study attempted to perform a sequential prospective meta-analysis (sPMA) to identify the outcomes of COVID-19 during pregnancy in a prospective manner. The researchers used data from almost a thousand pregnancies (ongoing or within seven days of childbirth) with COVID-19 (confirmed or probable). All the women were negative for the virus and/or antibody at the time of delivery.

The mean age of the women was 31 years, with obesity prevalence being 10% to 15%.  

What did the study show?

Based on three studies that recorded deaths during the study period (the others had no deaths), the researchers demonstrated an increased risk of maternal death among pregnant women with SARS-CoV-2 infection, with the maternal mortality risk increasing eight-fold. Similarly, they were at almost fourfold higher risk for admission to the intensive care unit (ICU), at an absolute risk of 3%.

Their risk for mechanical ventilation was increased 15-fold, while they were at a 5.5-fold higher risk of receiving any kind of critical care, at 4%. The risk of a pneumonia diagnosis was 32-5-fold higher, while that of thromboembolic complications was increased 5.5-fold.

Hypertensive disease risk increased by ~25%, while pre-eclampsia/eclampsia risk increased by ~40%. The underlying reasons could be linked to the difference in the expression of angiotensin-converting enzyme 2 (ACE2), with its vascular effects; systemic inflammation and hypercoagulability due to COVID-19; or the common risk factors for COVID-19 and hypertensive disorders of pregnancy. Alternatively, these cases may not all be true eclampsia or pre-eclampsia but rather similar syndromes caused by concurrent COVID-19.

In this study, newborns were twice as likely to be admitted to a neonatal care unit if they were born to SARS-CoV-2-infected mothers. In addition, the risk of preterm or moderately preterm birth went up 1.7-fold and 2.9-fold, respectively, following a history of SARS-CoV-2 during pregnancy.

When only symptomatic infections were included vs. pregnant women without COVID-19, the results were similar but stronger, such as a higher risk of maternal death, critical care, ventilation, and other maternal/neonatal complications. The infants were more likely to be small for gestational age and very low birth weight or preterm.

Interestingly, there were no associations between SARS-CoV-2 infection in pregnancy with stillbirths or intrauterine growth restriction (low birth weight). However, earlier studies have shown such a link with a doubled risk of stillbirth. The reasons for this inconsistency remain unexplained.

What are the implications?

The findings of this study support those of other recent reviews and multinational studies.

These results may strengthen the case for vaccinating pregnant women with effective and safe COVID-19 vaccines, but even more, indicate the need to strengthen healthcare systems globally to provide preventive and therapeutic care for COVID-19 in pregnancy.

Journal reference

Smith, E. R. et al. (2023). Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis. BMJ Global Health. doi:10.1136/bmjgh-2022-009495. https://gh.bmj.com/content/8/1/e009495

Early in the coronavirus disease 2019 (COVID-19) pandemic, pregnant women were thought to be at unusually high risk from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to the general population or non-pregnant women. However, later studies failed to agree on the extent and nature of the danger posed by the infection. A recent study reports on the adverse effects of SARS-CoV-2 infection on the mother and baby during pregnancy.

Introduction

Earlier studies showed contradictory results on the effects of this condition during pregnancy. One extensive 2021 review showed an association between COVID-19 in pregnancy and a higher risk of dying, being admitted to the intensive care unit (ICU), of babies being born prematurely, and of stillbirths and admission to the neonatal care unit. A significant flaw of this study was that there were less than ten studies reviewed per outcome in most cases.

Other more recent studies indicated increased chances of hypertensive disorders of pregnancy, as well as for Cesarean section and adverse neonatal outcomes. Nevertheless, these conclusions remain controversial due to the heterogeneous study design, faulty selection of subjects and controls, and methodological flaws. Moreover, these were often not generalizable because they contained little data from low-income countries.

The current study, published in BMJ Global Health, aimed to produce more definitive conclusions. The researchers undertook a collaborative effort using high-quality individual participant data from 12 studies that are currently underway. These were conducted in a dozen countries and involved over 13,000 pregnant women.

The present study attempted to perform a sequential prospective meta-analysis (sPMA) to identify the outcomes of COVID-19 during pregnancy in a prospective manner. The researchers used data from almost a thousand pregnancies (ongoing or within seven days of childbirth) with COVID-19 (confirmed or probable). All the women were negative for the virus and/or antibody at the time of delivery.

The mean age of the women was 31 years, with obesity prevalence being 10% to 15%.  

What did the study show?

Based on three studies that recorded deaths during the study period (the others had no deaths), the researchers demonstrated an increased risk of maternal death among pregnant women with SARS-CoV-2 infection, with the maternal mortality risk increasing eight-fold. Similarly, they were at almost fourfold higher risk for admission to the intensive care unit (ICU), at an absolute risk of 3%.

Their risk for mechanical ventilation was increased 15-fold, while they were at a 5.5-fold higher risk of receiving any kind of critical care, at 4%. The risk of a pneumonia diagnosis was 32-5-fold higher, while that of thromboembolic complications was increased 5.5-fold.

Hypertensive disease risk increased by ~25%, while pre-eclampsia/eclampsia risk increased by ~40%. The underlying reasons could be linked to the difference in the expression of angiotensin-converting enzyme 2 (ACE2), with its vascular effects; systemic inflammation and hypercoagulability due to COVID-19; or the common risk factors for COVID-19 and hypertensive disorders of pregnancy. Alternatively, these cases may not all be true eclampsia or pre-eclampsia but rather similar syndromes caused by concurrent COVID-19.

In this study, newborns were twice as likely to be admitted to a neonatal care unit if they were born to SARS-CoV-2-infected mothers. In addition, the risk of preterm or moderately preterm birth went up 1.7-fold and 2.9-fold, respectively, following a history of SARS-CoV-2 during pregnancy.

When only symptomatic infections were included vs. pregnant women without COVID-19, the results were similar but stronger, such as a higher risk of maternal death, critical care, ventilation, and other maternal/neonatal complications. The infants were more likely to be small for gestational age and very low birth weight or preterm.

Interestingly, there were no associations between SARS-CoV-2 infection in pregnancy with stillbirths or intrauterine growth restriction (low birth weight). However, earlier studies have shown such a link with a doubled risk of stillbirth. The reasons for this inconsistency remain unexplained.

What are the implications?

“This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction.”

The findings of this study support those of other recent reviews and multinational studies.

These results may strengthen the case for vaccinating pregnant women with effective and safe COVID-19 vaccines, but even more, indicate the need to strengthen healthcare systems globally to provide preventive and therapeutic care for COVID-19 in pregnancy.