Maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of poor neonatal outcomes, including neonatal death, according to a population-based retrospective cohort study from Canada.
Compared with infants who were not exposed to the COVID vaccine, those who were exposed to one or more doses in utero had lower risks of:
- Severe neonatal morbidity: 7.3% vs 8.3% (adjusted risk ratio RR [aRR] 0.86, 95% CI 0.83-0.90)
- Neonatal death: 0.09% vs 0.16% (aRR 0.47, 95% CI 0.33-0.65)
- Neonatal intensive care unit (NICU) admission: 11.4% vs 13.1% (aRR 0.86, 95% CI 0.83-0.89)
There were no associations between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted HR 1.03, 95% CI 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; aHR 1.01, 95% CI 0.96-1.05), reported Jeffrey Kwong, MD, MSc, of the University of Toronto, and colleagues in JAMA Pediatrics.
The study “provides further reassurance on the safety of maternal mRNA COVID-19 vaccination during all trimesters of pregnancy for newborns and infants,” the authors wrote, noting that “uncertainty about vaccine safety for the infant is one of the most frequently reported reasons for lack of intent to get vaccinated during pregnancy.”
“Lower risks of adverse neonatal outcomes among infants of vaccinated mothers would be consistent with the well-documented association between severe COVID-19 during pregnancy and increased neonatal morbidity, together with evidence suggesting that COVID-19 vaccination reduces the risk of severe COVID-19 in pregnant populations,” they continued.
In an accompanying editorial, Catherine Mary Healy, MD, of Baylor College of Medicine in Houston, and Laura Riley, MD, of Weill Cornell Medicine in New York City, noted that the findings paint a compelling picture of the benefits of maternal vaccination, especially when combined with data on maternal immunization against respiratory syncytial virus (RSV) and influenza.
“Safe and effective vaccines such as the COVID-19 vaccine should provide confidence in the maternal vaccination program where maternal vaccines provide protection for mothers and neonates against potentially devastating infections,” they wrote. “At the same time, concerns about vaccine adverse effects such as birth defects, spontaneous abortion, preterm labor, and other adverse pregnancy outcomes are not observed.”
The challenge, Healy and Riley stressed, is getting pregnant women vaccinated.
“Although influenza vaccine has been recommended to protect pregnant persons and their newborns against influenza for decades, vaccination rates in pregnancy hover at approximately 50%,” the editorialists pointed out. “Reasons for these poor vaccination rates include safety concerns despite years of safety data, lack of awareness of risk for severe morbidity and mortality associated with influenza in pregnancy, and lack of knowledge that maternal vaccination protects the newborn when the newborn is most vulnerable before vaccination at 6 months of age.”
“Recent data show that maternal vaccination uptake is low for all recommended vaccines, suggesting that greater efforts are needed to provide education about the harmful effect of these diseases on pregnancy specifically as well as to broadly message the safety data that emerges from real-world use,” they added.
“Studies consistently demonstrate … that the single most important factor in vaccination uptake in all populations is receiving a strong recommendation from a trusted health care professional, and for pregnant women, this patient-clinician relationship is particularly strong,” they wrote. “When this recommendation is combined with easy access, preferably on-site but at least convenient for uptake during a visit, vaccine administration in pregnancy is most likely to occur.”
For this study, Kwong and colleagues used multiple linked health administrative databases in Ontario, Canada, looking at singleton live births with an expected delivery date between May 1, 2021, and Sept. 2, 2022.
In total, 142,006 infants (mean gestational age at birth 38.7 weeks, 51% boys) were included, and 60% were exposed in utero to at least one mRNA COVID vaccine dose. Mean age of mothers was 31.7.
Among the vaccinated mothers, 48.6% had received one dose, 49.6% had received two doses, and 1.8% had received three doses. About a third had received at least one dose during the first trimester, 53.6% received at least one dose during the second trimester, and 44.5% received at least one dose during the third trimester.
Of these women, 68% received the Pfizer/BioNTech (Comirnaty) vaccine for all doses.
The primary endpoint of severe neonatal morbidity was a composite of 15 poor neonatal outcomes, including gestational age less than 32 weeks and low birth weight; respiratory problems; neurological problems; birth trauma; and the need for resuscitation, ventilation, transfusion, and intercostal, central venous, or arterial catheter placement, as well as death.
This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care, in addition to multiple other sources.
Kwong reported grants from the Public Health Agency of Canada and the Canadian Institutes of Health Research. One co-author reported employment by Pfizer. Others reported relationships with the Canadian Immunization Research Network, CERobs, the Public Health Agency of Canada, CANImmunize, and Medicago Moderna.
Healy reported participation in a data safety monitoring committee for a vaccine trial for Emmes Corporation and participation in an advisory board meeting for Moderna, but declined payment for both. She receives stock options from Vapotherm, Quidel Diagnostics, Intuitive, and Dexcom, and writer/contributor fees from UpToDate. Riley reported receiving consultant fees from Pfizer and GSK, writer/contributor fees from UpToDate, lecture fees from Medscape, and participating on the editorial board of the New England Journal of Medicine.
Source Reference: Jorgensen SCJ, et al “Newborn and early infant outcomes following maternal COVID-19 vaccination during pregnancy” JAMA Pediatr 2023; DOI: 10.1001/jamapediatrics.2023.4499.
Source Reference: Healy CM, Riley LE “Safety and benefits of COVID-19 vaccination in pregnancy — implications for the maternal vaccination platform” JAMA Pediatr 2023; DOI: 10.1001/jamapediatrics.2023.4496.