In a recent study published in the journal PNAS, The researchers investigated the pregnancy outcomes of COVID-19 and the effects of vaccination on these outcomes. They used linked population-level data from birthing facilities between 2014 and 2023 and found that COVID-19 caused infected pregnant women to give birth prematurely. Preterm births are associated with significant lifelong health and socioeconomic consequences. In contrast, early vaccine adopters were protected from these effects and administered as normal. These findings revealed that vaccine availability and vaccination choice may have drastically changed the health landscape for the next generation, especially in the US, where this study was conducted.
Study: Vaccination, immunity and the changing impact of COVID-19 on infant health. Image credit: Unai Huizi Photography / Shutterstock
COVID-19 and pregnancy risks
The 2019 coronavirus disease (COVID-19) remains one of the worst pandemics in human history, with the World Health Organization reporting over 772 million cases and nearly 7 million deaths since the outbreak began in late 2019. Its impact disease extend beyond just morbidity and mortality, however, with outcomes that include widespread socioeconomic loss and severe, population-level declines in mental health.
Survivors of the disease are left with potentially lifelong cardiovascular and neurological comorbidities, with recent research suggesting the increasing prevalence of “long-lasting COVID,” a condition characterized by persistence of COVID-19 symptoms (and, in some cases, appearance of new symptoms ) months or even years after recovery from the initial infection. While most efforts to deal with COVID-19 have targeted older adults because of their higher risk of mortality, emerging evidence shows that children and infants have been significantly affected by the condition.
Studies in younger subjects have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with adverse cardiovascular, cognitive, reproductive, and physical outcomes. In the fall of 2020, researchers identified negative links between COVID-19 and pregnancy, with the former leading to premature births and a greater likelihood of newborns needing hospitalization in the neonatal intensive care unit (NICU). This is particularly worrying given that they suggest that COVID-19 affects generational boundaries and is thought to be the pandemic’s most enduring legacy.
Building a holistic picture of the long-term health effects of COVID-19 in pregnancies faces three major obstacles – 1. The risk of infection is selective, with socioeconomically disadvantaged individuals at higher risk than their more affluent counterparts, 2. The measures and diagnosis of infection vary over time, and 3. SARS-CoV-2 is a rapidly evolving virus. These barriers, especially 2. and 3., are temporal and require long-term follow-up data to draw sufficiently actionable conclusions. Unfortunately, research of this kind is still lacking.
About the study
In the present study, researchers used nine years of data comparing the newborn health outcomes of siblings before and during the pandemic to explore the effects of mothers’ COVID-19 infections on the health of their infants. They used linked administrative vaccination and birth data to overcome the three obstacles mentioned above: the selective risk of infection, irregular screening, and the consequences of an ever-evolving pathogen.
The dataset included restricted birth data from all births in the state of California between January 2014 and February 2023. Data collected included date of birth, infant anthropometrics (height, weight, gestational age), and demographic and anthropometric data mother’s (age, race/ethnicity, zip code of residence, education level, financial status). In order to avoid confounds associated with multiple pregnancies, analyzes were restricted to singleton births.
California presents an ideal source of data due to a government mandate requiring all pregnancies during and after June 2020 to be mandated to be screened for COVID-19. Consequently, data from January 2020 to June 2020 were dropped from the dataset unless the COVID-19 status was reported on the birth certificate due to a voluntary or clinically necessary diagnosis. Additionally, if the COVID-19 status was not reported on the birth certificate, the corresponding data point was removed from the analyses, unless hospital records contained the information.
Statistical analyzes used regression models adjusted for maternal and infant anthropometric and demographic variables.
“Model 1 captures the association between maternal COVID-19 infection and preterm birth using a linear probability model that adjusts only for birth facility fixed effects and month fixed effects. Model 2 adds controls for a large set of potential confounders, including maternal sociodemographic characteristics (age, educational attainment, race/ethnicity, SES disadvantage in zip code of residence, and parity) and major risk factors for preterm birth (maternal hypertension, diabetes, previous preterm birth, large fibroid tumors, asthma, and smoking) ).
Finally, an additional Model 3 was used for mothers who had already given birth to an infant between 2014 and 2020, before the onset of COVID-19. This model compared infant characteristics among offspring of a single mother with COVID-19 infection as the only treatment and determinants of infant health as the only outcome.
Corrections for bias included changes in maternal characteristics such as age between pregnancies, economic status, and zip code of residence at the time of each delivery.
Study findings
Model 1 reveals a significant increase in the probability of preterm birth by 1.4 regression percentage points, equivalent to an alarming 29% increased risk. When incorporating the Model 2 adjustments, this value drops to an even more alarming 15% increased likelihood of preterm births for mothers infected with COVID-19.
Model 3 comparisons between siblings yield similar results – the same mother was more than 25% more likely to give birth preterm when infected with COVID-19 than before contracting the disease.
“Estimation based on sibling comparisons provides the strongest evidence currently available that COVID-19 infection during pregnancy adversely affects infant health.”
Demographic analyzes revealed that exposure and negative consequences were higher in areas with high unemployment rates and in areas with high frequencies of fire smoke. In particular, COVID-19 appeared to lead to preterm births of less than 32 weeks’ gestation, a usually rare condition that corresponds to higher mortality, morbidity and developmental risk for newborns.
Encouragingly, early adopters of the SARS-CoV-2 vaccination were observed to be rescued from the downsides of the effects associated with COVID-19 nearly a year earlier than those who did not have access to the vaccines or chose not to receive them.
“The similarity between quintiles in the impact of pre-vaccine COVID-19 infection suggests that the reduction in the harmful impact of COVID-19 infection is due to vaccination uptake rather than alternative health protective behaviors undertaken by pregnant women residing in vaccination sites’.
conclusions
In the first study using long-term pregnancy and birth data combined with within-mother comparisons, researchers clarified the negative effects of COVID-19 infections on pregnancy outcomes. Their findings show that infection with COVID-19 leads to an almost 30% higher risk of preterm birth, which in extreme cases can be as early as 32 weeks’ gestation. These are associated with severe mortality, morbidity and health outcomes for newborns, some of which may be lifelong.
Vaccination significantly reduced the burden of these conditions, resulting in the observed rescue of preterm births. Unfortunately, reports from the United States (US) reveal that uptake of booster vaccinations has stagnated, especially among racial and socioeconomic minorities, which may cause a resurgence of this transgenerational effect in the future.
