A new study published in the journal JAMA offers reassuring evidence that infants born to mothers with coronavirus disease 2019 (COVID-19), or even asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have little increase in respiratory symptoms over babies born to uninfected mothers.
Evidence of the virus has been found in placental and fetal membrane tissue in the form of genetic material (ribonucleic acid or RNA). Though the infection itself does not seem to be transmitted to the infant before birth, it may happen in the post-natal period.
Earlier, some studies suggested that babies of mothers with positive tests for SARS-CoV-2 were more likely to have respiratory or other illnesses, with preterm birth being a significant risk factor.
In one study of 450 babies born to SARS-CoV-2–positive mothers, six died, but none were positive for the virus, leaving the cause of death ambiguous. Other studies have suggested that 0.5% of infants born to infected mothers died, compared to 0.1% in previous years.
However, the small difference, and the failure to meet the criteria for COVID-19 infection in infants, has cast doubt on these findings. Moreover, most of the mothers of the seven fatal cases, out of 427 babies in total, had the infection 18 to 74 days before delivery, and none had severe or critical disease.
The current study, including over 2,300 infants, shows that term infants born to mothers with confirmed infection have a higher rate of admission for neonatal care. The babies were born at a median of 36 days from a positive test result. Less than 30% of the mothers were positive at the time of childbirth, while 3% of babies were delivered to mothers who returned a positive test within a week of their delivery.
Mothers with the infection were more likely to be from a non-Nordic country, overweight, to be treated with steroids for preterm birth, and to give birth at a facility with a fully equipped neonatal intensive care unit (NICU). The term of pregnancy and the birth weight were also lower in infants born to SARS-CoV-2.
What were the findings?
Some outcomes in newborns were more common in babies born to infected mothers. These include the use of assisted ventilation and intubation at birth, admission, respiratory distress syndrome, any respiratory illness, antibiotics, jaundice, persistent hypertension in the pulmonary circulation.
The greatest increase in risk was for mechanical ventilation, three times more common in this group, though the rarity of this outcome makes the difference small in absolute terms. Others showed a small increase in odds by up to 50%.
It is important to realize that all these outcomes already occur at low rates in babies irrespective of the maternal infection status, and the real difference in risk is quite small.
The odds of dying, prolonged stay in neonatal care, successful breastfeeding were similar in both groups of newborns, as were other serious complications like meconium aspiration, sepsis, and pneumonia.
Again, conditions like hypoxic-ischemic encephalopathy (HIE) grade 2 to 3 and convulsions were increased in the babies of SARS-CoV-2-positive mothers, but the study was underpowered to reflect the significance of this finding.
Though these are related to asphyxia, the small differences may indicate that only some babies are vulnerable, perhaps due to poor placental nutrition or the aggravating effects of maternal fever on HIE at the time of delivery.
As temperatures during childbirth were not recorded, this is not currently verifiable. The researchers estimate that over 33,000 exposed babies would have to be followed up, which would require sampling for over 13 years with equal rates of COVID-19 in pregnancy.
What are the implications?
Based on the findings presented herein, the excess admissions in near-term or term infants of SARS-CoV-2–positive women most likely reflect widened indications for observation and isolation in neonatal units,18 maternal illness after delivery, or recommendations in guidelines.”
The chief reason for the increased incidence of respiratory illness in babies would appear to be the higher risk of preterm birth in SARS-CoV-2-positive pregnancies, rather than a direct effect of the virus on the infant. This could explain many other observed associations such as the increased need for respiratory assistance, higher rates of jaundice and antibiotic use.
With the very low rates of transmission in this study, and no evidence that if it occurs, the outcome is worse, the scientists suggest that rooming in and breastfeeding may be safely permitted. Moreover, the presence of the infection in mothers did not increase the duration of hospital stay.
Babies born to infected mothers were routinely tested, up to three times, but those born to controls were tested only if suspected. In tests done at birth, the viral RNA from the mother may have led to false positives. Despite this detection bias, little evidence of significant transmission was found.
This being a Swedish cohort, the findings may not be generalizable. However, they certainly do give rise to hope that in newborns, at least, the impact of the infection may be negligible.
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