COVID-19 Infection During First Trimester Increases Risk of Neonatal Risks

A new large-scale, population-based cohort study conducted sheds light on the specific risks associated with SARS-CoV-2 infection during pregnancy, revealing that although overall impacts on birth outcomes may be limited, infection during the crucial first trimester is linked to heightened neonatal risk. Simultaneously, the research uncovered significant disparities in who received testing and who tested positive across different socioeconomic and ethnic groups.¹

“Our results demonstrate that a SARS-CoV-2 infection during the first trimester is associated with an increased risk for the newborn to have a low 5-min Apgar score and an increased risk of preterm birth,” the study authors said.¹ “No other significant effects on maternal and neonatal health outcomes were observed regardless of the stage of pregnancy at the time of infection.”

The Dutch retrospective study analyzed data from over 322,000 pregnant women who gave birth in the Netherlands during 2020 and 2021. When considering the entirety of pregnancy, regardless of the trimester, the researchers found no significant effects of SARS-CoV-2 infection on most studied neonatal or maternal health outcomes, such as major postpartum hemorrhage, severe ruptures, or congenital anomalies.¹

However, when investigators stratified the results by trimester, they found that infection during the first trimester was associated with an increased risk of preterm birth, showing 25% higher odds at 5.2% compared with 6.4%. First-trimester infection also increased the risk of a low Apgar score measured 5 minutes after birth, with 50% higher odds observed for this outcome. These adverse outcomes—preterm birth and a low 5-minute Apgar score—are associated with increased infectious morbidity and long-term neurological disabilities.¹

These findings about the timing of infection contrast with results from some earlier case and cohort studies, which often indicated an effect on preterm birth primarily when the infection occurred during the third trimester. Given the potential health risks linked to first-trimester infection, the authors suggested actively mitigating these risks during this early phase of pregnancy. Future research should explore whether vaccination prior to pregnancy could provide protective antibodies during the first trimester.¹

While the Dutch study focused on immediate birth outcomes, separate research conducted by investigators at Mass General Brigham points to potential long-term risks. That study, which examined children up to 3 years old, found that children born to mothers who had COVID-19 while pregnant faced an elevated risk of neurodevelopmental disorders, including autism, speech delays, motor disorders, and other developmental delays. In the Mass General Brigham cohort, the neurodevelopmental risk was associated with 29% higher odds overall, and importantly, this risk was found to be greatest when the maternal infection occurred during the third trimester of pregnancy. These findings support the understanding that COVID-19, like many other maternal infections, may disrupt normal fetal brain development.²

Despite these risks, existing clinical evidence suggests that neonatal SARS-CoV-2 infection is relatively uncommon among infants admitted to the hospital, and the pediatric population appears generally less affected by severe acute respiratory syndrome compared to adults. The majority of neonatal COVID-19 cases are asymptomatic or mildly symptomatic, presenting with symptoms such as cough, rhinorrhea, or low-grade fever. While vertical transmission (in utero or intrapartum) has been described, the common source of neonatal infection remains late infection due to horizontal exposure from caregivers, including parents. A rare but severe complication is neonatal multisystem inflammatory syndrome, which results from a hyper-responsiveness to maternal or neonatal SARS-CoV-2 infection.³

Beyond the direct clinical risks, the Dutch study illuminated significant public health challenges regarding access to care. COVID-19 testing behavior and positive test rates varied considerably among distinct groups of pregnant women. Women from specific minority ethnic groups, such as those originating from Morocco, were significantly less likely to be tested than women of Dutch origin. Yet, when these women were tested, they had notably higher odds of receiving a positive result, suggesting that the natural incidence rates may be underestimated in groups where testing willingness or ability is low. Similar patterns were observed among lower socioeconomic groups: women with lower education and income levels were less likely to be tested but had higher odds of testing positive when they did get tested.¹

“Future research should be conducted to explore the effectiveness of COVID-19 vaccination in preventing infection and its effects on neonatal and maternal health outcomes in the Dutch setting,” the study authors said.¹ “This future research should not solely focus on the effectiveness and effects of a COVID-19 vaccination during pregnancy, but especially also on vaccination prior to pregnancy.”

READ MORE: COVID-19 Resource Center

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REFERENCES

1. Klein PPF, Crone L, Struijs JN. SARS-CoV-2 infections among pregnant women-testing behaviour and neonatal and maternal health outcomes: a Dutch retrospective population-based cohort study. BMJ Open. 2025;15(11):e101803. Published 2025 Nov 4. doi:10.1136/bmjopen-2025-101803

2. COVID-19 during pregnancy linked to higher risk of neurodevelopmental disorders in children. News release. Mass General Brigham. October 30, 2025. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/covid-19-during-pregnancy-linked-to-neurodevelopmental-disorders

3. Galderisi A, Lista G, Cavigioli F, Trevisanuto D. Clinical features of neonatal COVID-19. Semin Fetal Neonatal Med. 2023;28(2):101430. doi:10.1016/j.siny.2023.101430