As Covid swept across California in early 2020, pediatric infectious diseases physician Karin Nielsen grew alarmed by the crisis erupting in maternity wards. Pregnant women were placed on life support, undergoing emergency C-sections as the virus triggered severe complications. Some died.

Nielsen had just finished a research project on how the emerging infectious disease Zika was causing severe birth defects. Concerned the new coronavirus might have a similar impact, she began recruiting expectant mothers who tested positive for a new study. 

Soon after the study’s participants began giving birth, Nielsen’s colleagues at UCLA’s Mattel Children’s Hospital noticed an unusual number of their newborns requiring intensive care. Nielsen recalls another doctor stopping her to ask, “What’s wrong with the babies in your study?” 

Sure enough, when researchers analyzed videos of the children lying on their backs in what’s called the General Movement Assessment, 14% of the infants showed signs of developmental problems. The test evaluates early motor functions and is often used to assess the risk of neurodevelopmental disorders including cerebral palsy.

Later, during in-clinic assessments, the findings proved equally troubling. At 6-8 months old, 13 of 109 infants born to infected mothers — almost 12% — had failed to reach developmental milestones. In stark contrast, all infants in a control group born before the pandemic showed normal development.

As additional participants from LA and Rio were enrolled, more unsettling results emerged. Around 11.6% of toddlers born to mothers with lab-confirmed SARS-CoV-2 infection during pregnancy showed cognitive, motor, or language problems indicative of neurodevelopmental delays. By comparison, only two of 128 unexposed controls — 1.6% — showed such issues. 

When the eldest of the Covid-exposed babies reached 28 months, the study found another concerning pattern: 23 of 211 children — almost 11% — screened positive for autism spectrum disorder. The finding, presented in May at a medical conference in Copenhagen, compared with an expected prevalence of 1-2% at that age, when some children begin showing signs of the condition. Around one in 36 or under 3% of children are eventually diagnosed with autism, according to the Centers for Disease Control and Prevention. 

“There’s something really going on,” Nielsen said. “We don’t want to alarm the world, but that’s what our data are showing.”

The later findings, currently undergoing peer review ahead of publication, are a reminder that Covid’s long-term consequences, including higher risks for dementia and heart disease, continue to unravel almost five years after the pandemic began. While the virus is generally known to cause more severe symptoms in adults than in children, emerging research suggests that babies exposed to Covid in utero face elevated risks for preterm birth, congenital heart abnormalities and rare conditions, such as organs developing on the opposite side of the body.

Greater odds of autism from in utero exposure to Covid would add another piece to the puzzle. The connection between the virus and autism remains inconclusive: some studies align with Nielsen’s findings, while others report little to no increased risk of developmental or behavioral issues. 

A limitation of Nielsen’s study is its relatively small sample size, with fewer than 250 mother-baby pairs. A robust understanding of the virus’ impact would likely require research involving more than 10,000 children, said Andrea Edlow, a maternal-fetal medicine specialist at Boston’s Massachusetts General Hospital. Such large-scale research has been difficult, particularly during the most deadly waves of the pandemic when clinic restrictions and medical emergencies obstructed consistent testing. 

Nielsen herself is wary of raising unnecessary fears. Autism remains something of a mystery, with its exact triggers still unclear. Scientists suspect an intersection of genetic and environmental factors, but the condition comes in many forms: some children have intellectual disabilities, while others don’t but still struggle with significant behavioral problems, complicating diagnoses. Many individuals with autism also experience co-occurring health issues such as attention-deficit/hyperactivity disorder, seizures, or chronic gastrointestinal problems. In much of the world, an awareness of autism is only starting to catch on. Global autism prevalence was estimated at one in 127 as of 2021 in a study published last week, more than double the one-in-271 ratio reported in 2019, and researchers say this is likely driven by increased awareness and better diagnostic practices. The lack of clear explanations has provided fertile ground for myths, including the debunked belief that vaccines cause autism.

Still, scientists say Nielsen’s study warrants serious attention due to the consistency of its findings. It also stands out for its rigour: trained physicians used standardised assessment tools at multiple points in time to evaluate developmental progress rather than relying on electronic health records or parent-completed questionnaires.

Children born during the Covid era are now reaching the average age for autism diagnoses. Identifying developmental issues early can open the door to speech and behavioural therapies, which are proven to support a child’s development. This makes it a critical moment to study the pandemic’s impact. 

Nielsen, born to a Danish father and Brazilian mother in Rio de Janeiro, where she attended medical school, has dedicated much of her career to studying how maternal infections, such as HIV and Zika, affect child health. 

The mosquito-borne Zika virus is known for causing cerebral palsy and microcephaly, a severe congenital brain malformation that often leads to profound intellectual and developmental disabilities. Other maternal infections such as rubella and certain herpesviruses, particularly during the first trimester, are also known to harm the fetus directly, resulting in issues such as hearing loss, cerebral palsy, and autism.

From the pandemic’s onset, Nielsen sensed that Covid, too, would leave its mark. “We saw this as a new pathogen and an opportunity to investigate its impact on these babies,” Nielsen said. 

She soon saw parallels. In 2021, the WHO confirmed that the coronavirus could cross the placental barrier via the maternal bloodstream, placing it in the same category as viruses like rubella and Zika. Some researchers believe the damage stems from inflammation triggered by the virus or viral components crossing the placenta.

But Covid also appeared to affect fetuses in a unique way. One of the earliest signs emerged in early 2021 in County Cork, Ireland, during a surge of the alpha variant. A cluster of stillbirths in the first three months of that year prompted doctors to investigate. They discovered that the placentas linked to the fetal deaths were infected with the coronavirus, describing them as riddled with lesions likely caused by viral transmission through the maternal bloodstream.

Similar cases began to surface in the US and at least 10 other countries, prompting David Schwartz, an Atlanta-based epidemiologist and perinatal pathologist, to lead an investigation. The findings were startling: on average, more than three-quarters of the tissue in infected placentas had been damaged, cutting off oxygen and nutrients essential for fetal survival. Alarmingly, this damage could occur silently, even in mothers without acute Covid symptoms, offering no warning signs.

“We’ve never seen anything like this with an infectious disease,” said Schwartz, a medical anthropologist and pathologist with 45 years of experience studying placentas affected by pathogens such as HIV, Ebola, yellow fever, and Zika. “So far, I feel very confident in saying this is unique to this virus.”

Studies by Schwartz and Nielsen highlighted that vaccination protects mothers against Covid’s obstetric complications, particularly during waves driven by variants more likely to cause severe disease.

One possible clue to explaining the higher risks of neurodevelopmental issues seen in Nielsen’s study is that Covid, particularly in unvaccinated mothers, increases the risk of preterm delivery. 

In the US in 2021, the rate of preterm births rose by 4% to 10.5%, the highest since at least 2007. The likelihood of stillbirths nearly doubled for American mothers with Covid compared to those who avoided infection during the pandemic’s first year and a half. Similarly, a study in England found that mothers infected with SARS-CoV-2 at delivery were more than twice as likely to experience fetal death or preterm birth.

Another explanation is that prolonged fevers triggered by illnesses like the flu can impair neural development indirectly by activating the maternal immune system. This creates an inflammatory environment in the uterus that can disrupt fetal brain development. 

Nielsen suspects that maternal immune activation might explain the high rates of neurodevelopmental delays observed among the infants in her study. Among at least four toddlers with severe delays, blood tests taken at birth revealed biomarkers of activated microglia – the brain’s immune cells – attacking neurons.

“When you see microglial activation and neuronal signaling pathways traditionally associated with autism showing up in this cohort, it suggests there’s something behind it,” she said. 

Scientists say the full consequences of in utero exposure to the coronavirus may take decades to uncover and understand. Even if a link is established, genetics are likely to play a crucial role, according to Mady Hornig, a physician-scientist in New York. She is also an investigator on the Autism Birth Cohort project, a collaboration between the Norwegian Institute of Public Health and Columbia University studying the development of the condition for more than 20 years. Understanding the interplay of genetics with immune activity, inflammation, and stress might help unravel why some infants may face developmental challenges, she said.

Identifying the various risks “requires additional rigorous study,” Hornig said. If Nielsen’s findings do reflect broader population trends the implications could be profound. “Early neurodevelopmental disturbances have potential implications for disability throughout a lifetime,” she said.

Even small increases in risk could substantially add to the global burden of chronic disease, given the sheer number of pregnancies affected.

Nielsen continues to analyse stored blood and other specimens from the babies in her study. “It’s a new pathogen. We don’t know how it behaves,” she said. “Things might appear down the road that we were not expecting.”

  - Bloomberg