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Six years after the outbreak of the COVID-19 pandemic, the scientific community continues to investigate the long-term effects of the SARS-CoV-2 virus. One of the central questions researchers have been addressing since the start of the pandemic is how exposure to the virus during pregnancy affects fetal development and early childhood development. A large-scale cohort study recently published in the journal Obstetrics & Gynecology presents new and significant data on the subject [1].

The researchers followed about 18,000 births that occurred in 2020–2021, a period during which most pregnant women were not yet vaccinated. They compared children whose mothers were infected with the virus during pregnancy with children who their mothers were not, and tested their speech and motor development, as well as whether they received a diagnoses of autism spectrum disorder (ASD).

The study’s findings indicate an increase in diagnoses of a wide range of developmental delays among children exposed to the virus in utero: roughly 16% of the exposed children received at least one diagnosis of some sort of neurodevelopmental delay, compared with about 10% of the children whose mothers were not infected. After adjusting for confounding factors, such as socioeconomic status, maternal age, and the child’s sex, it was found that exposure to COVID-19 during pregnancy increases the risk of a neurodevelopmental diagnosis by age three by 29%.

The study identifies two additional factors connected to increased risk: the stage of pregnancy at which infection occurred and the fetus’s sex. Data analysis shows a significant association between the timing of infection and the risk of developmental delay. The main risk was observed in infections that occurred during the third trimester of pregnancy. This is a sensitive period, as it is characterized by massive neuronal growth and the formation of connections between nerve cells in the fetal brain. Among children whose mothers were infected in the first or second trimester, no significant difference was found compared with the control group. Fetal sex is also an important factor: males were found to have a higher risk of neurodevelopmental impairment compared with females. This finding aligns with previous studies showing that the male brain is more sensitive to changes in maternal immune activity during pregnancy [2, 3].

It is important to note that the virus does not cross the placenta and does not directly infect the fetus. The current study, together with previous work by the same research group, indicates that the damage is likely caused by an immune response in the placenta. This response alters the fetal environment and indirectly affects brain development.

The study’s findings reinforce the understanding that maternal viral illnesses during pregnancy can affect fetal development, even without direct infection. They join earlier studies showing that infections during pregnancy can influence fetal development and increase the risk of developmental differences [4–6]. The findings underscore the importance of preventing coronavirus infection during pregnancy, as well as the need for rigorous, long-term developmental monitoring of children whose mothers were infected during pregnancy, in order to detect delays as early as possible and provide supportive intervention.

Hebrew editing: Smadar Raban
English editing: Elee Shimshoni

References:

1. Three-year comparative cohort study
2. Sex-dependent effects of immune activity after COVID-19
3. Sex-specific impact on fetal brain development during pregnancy following maternal COVID-19
4. Effects of maternal immune activation during pregnancy on brain development
5. Risk of psychiatric development in fetuses exposed to intrauterine inflammation
6. Influenza during pregnancy and schizophrenia