Maternal vaccination against COVID-19 lowered risk of preterm births, Stanford study finds
Peer-Reviewed PublicationSTANFORD UNIVERSITY
During the first two years of the pandemic, a COVID-19 infection during pregnancy increased the risk of preterm birth and NICU hospitalizations. However, by 2022, when COVID-19 vaccines were readily available in the United States, this effect disappeared – suggesting that vaccination against the coronavirus may have prevented thousands of preterm births, according to a new study led by Stanford sociologist Florencia Torche.
The study’s findings, published Nov. 27 in the journal Proceedings of the National Academy of Sciences, show how vaccination against COVID-19 may have helped a generation of U.S. children avoid the long-term health issues and costs associated with premature delivery. As previous studies have shown, children who are born prematurely are more likely to encounter educational and economic setbacks later in life.
“The effects of COVID-19 on infant health may be among the most enduring legacies of the pandemic,” said Torche, the Dunlevie Family Professor in the School of Humanities and Sciences. “I hope the study provides strong evidence supporting the benefits of vaccination for the health of the next generation.”
Studying the effects of COVID-19 infection
Torche, along with Jenna Nobles at the University of Wisconsin-Madison, based their study on natality data for California, a diverse and populous state that accounts for 12% of all U.S. births.
In June 2020, California began recording confirmed or presumed cases of COVID-19 infection for all mothers giving birth. This is also when the researchers began their analysis, focusing on facilities with documented, universal testing.
The researchers identified infants with siblings in the California birth records, which allowed them to compare “treated” infants exposed to COVID-19 infection in utero with their “untreated” siblings who did not experience a COVID infection.
The researchers also took into consideration the zip code of the mother’s residence to compare areas that had low and high uptakes of vaccination against COVID-19.
Some of Torche and Nobles’ key findings include:
- Maternal COVID-19 infection increases the probability of preterm delivery, defined as a birth that occurs before 37 weeks of gestation, by 1.2 percentage points, from 7.1 to 8.3%. “This effect is roughly equivalent to in utero exposure to a 9 percentage point increase in the area-level unemployment rate – or to high-intensity wildfire smoke for 20 days – an enormous impact,” the researchers write.
- Maternal COVID-19 infection also led to higher rates of premature delivery before 32 weeks of gestation, resulting in infants facing the highest risk of mortality, morbidity, and developmental difficulties later in life.
- By January 2022, the impacts of COVID-19 on preterm births dropped to zero, but zip codes that had high vaccination rates saw the harmful effects disappear a year earlier than areas with a slower vaccination uptake.
How COVID-19 may exacerbate inequality
Torche and Nobles’ study is one of the first to offer a causal estimate of the impact of maternal COVID-19 infection on neonatal health.
With vaccine rates for the most recent booster hovering at about 7% of U.S. adults, Torche hopes the study emphasizes the importance of staying protected against the virus.
“Unfortunately, even if the adverse impact of COVID-19 infection on preterm birth has plummeted to zero, this adverse impact is likely to emerge again as the virus continues to evolve and mutate, and as vaccine-driven immunity wanes,” Torche said.
The study builds on Torche and Nobles’ previous work that looked at the socioeconomic disparities of the COVID-19 pandemic and its impacts on inequality in the U.S. – an issue Torche is concerned about here, too.
“Barriers to vaccination are higher in disadvantaged and racialized populations, including people with less education and those living in rural areas, i.e. populations that experience much worse infant health even in absence of COVID-19,” Torche said. “This suggests COVID-19 will further exacerbate disparities in infant health in the United States.”
This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and by the National Science Foundation (NSF).
METHOD OF RESEARCH
Observational study
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Vaccination, immunity, and the changing impact of COVID-19 on infant health
ARTICLE PUBLICATION DATE
27-Nov-2023
MADISON, Wis. — COVID-19 caused an alarming surge in premature births, but vaccines were key to returning the early birth rate to pre-pandemic levels, according to a new analysis of California birth records.
“The effect of maternal COVID infection from the onset of the pandemic into 2023 is large, increasing the risk of preterm births over that time by 1.2 percentage points,” says Jenna Nobles, a University of Wisconsin–Madison sociology professor. “To move the needle on preterm birth that much is akin to a disastrous environmental exposure, like weeks of breathing intense wildfire smoke.”
But the first two years of the pandemic alone were far worse for many pregnancies, according to findings Nobles and co-author Florencia Torche, a Stanford University sociology professor, published today in the Proceedings of the National Academy of Sciences.
The virus that causes COVID-19 endangers pregnancies by causing immune and inflammation responses, and via deterioration of the placenta. One consequence is early interruption of the pregnancy and birth well in advance of the end of the expected 39- to 40-week gestation.
As the virus spread from July to November of 2020, the likelihood that a mother with COVID-19 in California would give birth more than three weeks before the due date was 5.4 percentage points higher than anticipated — 12.3% instead of 6.9% — according to the new study.
The researchers measured the impact of the pandemic with the help of birth records for California’s nearly 40 million people, using information on birth timing and the comparison of sibling births to help control for the pandemic’s disparate impacts on different demographic groups. They found the excess risk of preterm birth fell slightly in early 2021 before dropping steeply in 2022, at which point maternal COVID-19 infection in pregnancy caused no excess risk of preterm birth for infants.
Vaccines contributed to that decrease, the researchers say, an effect that jumps out when the birth records are divided up geographically.
“In ZIP codes with the highest vaccination rates, the excess risk of preterm birth declines much faster. By summer 2021, having COVID-19 in pregnancy had no effect on preterm birth risk in these communities. It takes almost a year longer for that to happen in the ZIP codes with the lowest vaccine uptake,” Nobles says. “That highlights how protective COVID vaccines have been. By increasing immunity faster, early vaccination uptake likely prevented thousands of preterm births in the U.S.”
Preterm birth is associated with a host of short- and long-term health problems and deficiencies for the children and their families. It’s the leading contributor to infant mortality, and cutting short development in the womb can require additional medical attention that costs, on average, more than $80,000 per child. Preterm birth by even just a few weeks reduces expected educational attainment, health and earnings as an adult.
“And we found similar increases, of about 38%, in the risk of very preterm birth — that is pre-32 weeks — when a child is likely to need neonatal intensive care, with the possibility of developmental delays and serious implications for their families as well,” Nobles said.
The evidence showing the positive effects of vaccination in preventing premature births could help allay some of the most prominent concerns voiced as COVID-19 vaccines became available to pregnant patients.
“One big contributor to vaccine hesitancy is that people are worried about safety for the fetus and about the ability to get pregnant,” Nobles says. “We already know there is very little evidence of adverse effects of vaccination on fetal development. The results here are compelling evidence that what will actually harm the fetus is not getting vaccinated. That’s a message practitioners can share with concerned patients.”
The results should be a compelling argument in favor of getting vaccinations and boosters, according to the researchers, even after COVID-related premature birth risk ebbed in California.
“This is still an evolving epidemic, and the rate of vaccine boosters among pregnant people right now is very low,” Nobles says. “The question is, how many more iterations of viral evolution does this need to escape the immunity that we have? It’s miraculous and incredible that we're now down to essentially zero additional preterm births, but it does not indicate that it’s going to be that way in perpetuity.”
This research was supported in part by grants from the National Science Foundation (NSF2049529) and the National Institutes of Health (R21 HD105361-01).
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— Chris Barncard, barncard@wisc.edu
JOURNAL
Proceedings of the National Academy of Sciences
METHOD OF RESEARCH
Data/statistical analysis
SUBJECT OF RESEARCH
People
Reducing the dose of a widely used COVID-19 booster vaccine produces a similar immune response in adults to a full-dose with fewer side effects, according to a new study.
The research, led by Murdoch Children's Research Institute (MCRI) and the National Centre for Communicable Diseases in Mongolia, found that a half dose of a Pfizer COVID-19 booster vaccine elicited a non-inferior immune response to a full dose in Mongolian adults who previously had AstraZeneca or Sinopharm COVID-19 shots. But it found half-dose boosting may be less effective in adults primed with the Sputnik V COVID-19 vaccine.
The research is part of an international clinical trial, which also includes Australia and Indonesia, that’s investigating the different COVID-19 booster shot approaches to help guide future vaccination strategies. The Coalition for Epidemic Preparedness Innovations (CEPI) is funding the trial that is being overseen by MCRI.
The first batch of findings, published in The Lancet Regional Health - Western Pacific, and involving 601 participants over 18 years old from Mongolia, reports on the initial responses seen 28-days after vaccination. The study is the first of its kind to assess and compare COVID-19 vaccines widely used in low- and middle-income countries.
MCRI Professor Kim Mulholland, who also sits on the WHO SAGE committee, said the study found that fractional doses elicited an immune response that was non-inferior to a full dose with fewer side effects and was less costly.
“Fractional dosing may improve COVID-19 booster acceptability and uptake and reduce the per-dose cost of COVID-19 booster programs,” he said. Policymakers and immunisation advisory committees can draw upon this data to make flexible boosting schedules decisions.”
The study found half-dose boosted participants reported fewer local reactions than those receiving full doses (60 per cent versus 72 per cent) including less pain and tenderness. They also reported fewer systemic reactions (25 per cent versus 32 per cent) including less fevers, vomiting, diarrhoea and headaches.
The cohort will be followed up at six and 12 months with the data to answer key questions on other aspects of the immune response including the rate of waning and breakthrough infections.
Dr Melanie Saville, Executive Director of R&D at CEPI said; “This CEPI-funded study has generated valuable data about combinations of vaccines that have been widely distributed through COVAX, which will help to inform future booster strategies in countries in the global south. Fractional dosing can contribute to equitable access by making vaccination more acceptable and less costly.”
Researchers from Onoshmed Laboratory, Sukhbaatar District Health Centre, General Laboratory of Clinical Pathology, the University of Melbourne, Mongolian National University of Medical Sciences, Bayangol District Health Centre, Mongolia Ministry of Health and the National Centre for Public Health in Mongolia also contributed to the findings.
Publication: Tsetsegsaikhan Batmunkh, Kerryn A Moore, Helen Thomson, Bolor Altangerel, Otgonjargal Amraa, Naranbaatar Avaa , Lkhagvagaram Batbayar, Khishigjargal Batsukh, Kathryn Bright, Tsogjargal Burentogtokh, Lien Anh Ha Do, Gantuya Dorj, John D Hart, Khulan Javkhlantugs, Sarantsetseg Jigjidsuren, Frances Justice, Shuo Li, Paul V Licciardi, Khaliunaa Mashbaatar, Nadia Mazarakis, Eleanor F G Neal, Cattram Duong Nguyen, Batbayar Ochirbat, Bilegtsaikhan Tsolmon, Alimaa Tuya, Unursaikhan Surenjav, Claire von Mollendorf and Kim Mulholland. ‘Immunogenicity, safety, and reactogenicity of a half-versus full-dose BNT162b2 (Pfizer-BioNTech) booster following a two-dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac priming schedule in Mongolia: a randomised, controlled, non-inferiority trial,’ The Lancet Regional Health - Western Pacific. DOI: 10.1016/j.lanwpc.2023.100953
*The content of this communication is the sole responsibility of the MCRI and does not reflect the views of the NHMRC.
Available for interview:
Professor Kim Mulholland, MCRI Group Leader, New Vaccines
JOURNAL
The Lancet Regional Health - Western Pacific
METHOD OF RESEARCH
Randomized controlled/clinical trial
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Immunogenicity, safety, and reactogenicity of a half-versus full-dose BNT162b2 (Pfizer-BioNTech) booster following a two-dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac priming schedule in Mongolia: a randomised, controlled, non-inferiority trial
