COVID-19 Vaccine Effects on Newborns: Mothers' Origin Matter?
JAMA recently published a study on the consequences of COVID-19 vaccination in pregnancy for newborns.
The results not only indicate the lack of adverse effects but even benefits, so much so that the authors themselves say they are surprised. We believed we had identified one factor that could explain these observations and sent a letter to the journal. Unfortunately the letter was rejected with this reason:
Thank you for your recent letter to the editor. Unfortunately, because of the many submissions we receive and our space limitations in the Letters section, we are unable to publish your letter in JAMA.
After considering the opinions of our editorial staff, we determined your letter did not receive a high enough priority rating for publication in JAMA. We are able to publish only a small fraction of the letters submitted to us each year, which means that published letters must have an extremely high rating.
We are therefore publishing the text of our letter below, which we will also send to the authors of the study should they wish to reply with their own comment.
To the Editor
Norman and coworkers performed a large population-based cohort study including infants born in Sweden and Norway from June 2021 to January 2023, to evaluate any adverse events after exposure to COVID-19 vaccination during pregnancy.1 Results show that COVID-19 vaccination is associated with no increased adverse outcomes, and even with reduced neonatal nontraumatic intracranial hemorrhage (event rates: 1.7 vs 3.2/1000), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000), and mortality (0.9 vs 1.8/1000). Such results are surprising and the authors themselves admit that “It is unlikely that mRNA COVID-19 vaccination during pregnancy directly reduces neonatal mortality”.1
We agree with the authors. Indeed, lower morbidity and mortality is unlikely to result from any protection from COVID-19 since COVID-19 in pregnancy occurs to a similar extent in vaccinated and unvaccinated mothers (16.9% vs 16.7% in Sweden and 16.8% vs 22.8% in Norway) (Table 1). Moreover, neonatal mortality is the same in vaccinated mothers with and without COVID-19 during pregnancy (adjusted odds ratio: 0.68 vs 0.68) (eTable 5).
We would like to propose an explanation for this conundrum. According to data in Table 1, vaccinated mothers are born preferentially in Nordic countries (78.2% vs 52% unvaccinated in Sweden and 84.1% vs 67.3% in Norway), while unvaccinated mothers are born preferentially in Middle East/Africa (22.5% vs 7.4% vaccinated in Sweden and 10.1% vs 3.2% in Norway). Extensive evidence shows that immigrant mothers, when compared to Swedish or Norwegian mothers, suffer from higher risk of newborn death and even of maternal mortality,23 the fertility rate of foreign-born women is higher than that of native-born women in both Sweden and Norway,4 and at least in Norway even paternal country of origin may negatively affect outcomes in newborns to foreign-born women.5 All these factors should be taken into account when assessing neonatal outcomes. For clarity, authors should include the countries of origin of mothers at least for the 88 + 188 died neonates.
Moreover, in the Methods section the authors state that “Infants could only be at risk of neonatal outcomes after they were born (time zero).” Does this imply that miscarriages and stillbirths were not included in the analysis? Finally, neonatal mortality and nearly all the other adverse neonatal outcomes are more frequent in newborns from mothers vaccinated in the first trimester in comparison to those vaccinated in the third trimester (Table 3). Although possibly not statistically significant, such differences should be considered as a signal worthy of further investigation.
Alessandro Soranzo, BSc
Department of Mathematics, Informatics and Geosciences, University of Trieste, Trieste, Italy
Franca Marino, BSc, PhD
Marco Cosentino, MD, PhD
Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy
Author Contributions: all the authors contributed equally and have read and agreed to the published version of the manuscript.
Conflict of Interest Disclosures: none.
Funding/Support: none.
Norman M, Magnus MC, Söderling J, Juliusson PB, Navér L, Örtqvist AK, Håberg S, Stephansson O. Neonatal Outcomes After COVID-19 Vaccination in Pregnancy. JAMA. 2024;331(5):396-407. doi:10.1001/jama.2023.26945
Wallace M, Hiam L, Aldridge R. Elevated mortality among the second-generation (children of migrants) in Europe: what is going wrong? A review. Br Med Bull. 2023;148(1):5-21. doi: 10.1093/bmb/ldad027
Vik ES, Nilsen RM, Aasheim V, Small R, Moster D, Schytt E. Country of first birth and neonatal outcomes in migrant and Norwegian-born parous women in Norway: a population-based study. BMC Health Serv Res. 2020;20(1):540. doi: 10.1186/s12913-020-05415-y
Adsera A, Valdivia M. Migrant family building: Recent evidence and implications. In: OECD. International Migration Outlook 2023. doi: 10.1787/b0f40584-en. Accessed February 18, 2024. https://www.oecd-ilibrary.org/sites/4f8b1ffb-en/index.html?itemId=/content/component/4f8b1ffb-en
Vik ES, Aasheim V, Nilsen RM, Small R, Moster D, Schytt E. Paternal country of origin and adverse neonatal outcomes in births to foreign-born women in Norway: A population-based cohort study. PLoS Med. 2020;17(11):e1003395. doi: 10.1371/journal.pmed.1003395