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Pregnant women apparently don’t already have enough to worry about.

Since the pandemic began, there have been numerous reports of young infants, even newborns, being diagnosed with COVID-19. While most of these infections have been mild or even asymptomatic, there have been severe cases and even reports of deaths. In newborns who have been tested, either because of the development of concerning symptoms or because of screening in the setting of maternal infection, it has been unclear exactly how these children acquired the infection.

Were they infected during delivery when exposed to maternal body fluids? Could a caregiver or even a hospital staff member have unknowingly been shedding the virus? Or were they infected prior to delivery, with the virus having evaded the placenta’s protective mechanisms? Although it is likely a rare event, we now have increasing evidence that intrauterine transmission does occur.

While I would never claim that the human placenta is not deserving of our utmost respect and admiration, it is far from perfect when it comes to sparing a developing fetus from a harm. There are, in fact, numerous infectious agents that can cross over from mother to fetus. As a newborn hospitalist, I have historically focused on diseases such as syphilis, HIV, HSV, CMV, and Hepatitis B, all of which are capable of causing severe illness with serious long term consequences. Many intrauterine infections cause damage prior to delivery and can result in the loss of the pregnancy or the need for urgent medical intervention at the time of delivery.

Prior to SARS-CoV-2, the Zika virus was the most recent new potential cause of intrauterine infections, quickly changing how we screen mothers and newborns. One potential pathogen, rubella, is still on my checklist of things to worry about every time I admit a new baby, but it is extremely unlikely that I will ever see a case. Rubella is no longer endemic in the United States, thanks to a very successful vaccine (the R in the MMR), and there are only about five cases of congenital rubella syndrome diagnosed each year. Typically these cases occur when mothers have recently emigrated from countries without a rubella immunization program. Part of my job is to make sure that all my patients’ mothers have documented immunity, and if not, are offered a booster to reduce the risk during a potential future pregnancy.

Reports of congenital SARS-CoV-2 emerge

As I mentioned above, there have been plenty of cases of newborns testing positive for SARS-CoV-2. 2-5% of infants born to mothers with COVID-19 near delivery have tested positive within the first 96 hours of life, most of which have likely not gone on to develop symptoms. But again, some have.

Earlier this month, multiple reports were published where intrauterine infection was found to be extremely likely if not definitively to blame. The first case that I came across involved a premature infant born in Dallas and was published in The Pediatric Infectious Disease Journal. Born at 34 weeks, the baby was initially asymptomatic but was tested at 24 hours of life per hospital protocol because her mother was ill (fever and diarrhea) with COVID-19. This initial test was positive. On the second day of life she began to develop fever and respiratory distress, and a repeat SARS-CoV-2 PCR test at 48 hours of life was again positive.

Other potential causes of fever and respiratory distress in a neonate were considered, such as bacterial pneumonia or sepsis, and were even empirically treated. Tests for these conditions were negative. It was also very unlikely that prematurity would have been the culprit considering the onset after 24 hours of initial stability. After a few days of respiratory support, thankfully not requiring mechanical ventilation, her symptoms had resolved and she was stable breathing only room air. She remained SARS-CoV-2 positive on day 14, but was continuing to feed and grow without symptoms. She was discharged home with mother on day 21.

The hospital performed histopathologic examination of the placenta, which showed diffuse inflammation, and antibody studies of the tissue were positive for SARS-CoV-2. They even performed ultrastructural examination by electron microscopy, which revealed structures consistent with viral particles. The authors, one of whom I used to work with back in the day at Texas Children’s Hospital, concluded that this represented confirmation of congenital SARS-CoV-2 infection. What remains unclear in this case is whether or not the placenta became infected because of maternal viremia and subsequent spread via the blood, or there was ascending spread from the GI tract (remember she had diarrhea) to the placenta by way of the vaginal canal.

Another one!

A second case of almost certain transplacental transmission was reported this month in Nature Communications. This case involved a 35-week infant also born to a mother with COVID-19 and who also developed concerning symptoms after an initial period of stability. Instead of respiratory distress, however, he developed neurologic symptoms and was found to have evidence of inflammation in the spinal fluid believed to be caused by COVID-19 after other possible etiologies were ruled out.

Just as in the first case, the baby was found to have evidence of SARS-CoV-2 infection and the placenta was inflamed and practically teeming with the virus. One interesting addition to the work up that wasn’t included in the first case was testing of the amniotic fluid prior to rupture of membranes. It was also found to be positive. The authors concluded that they had demonstrated transplacental transmission and a rare case of cerebral vasculitis in a newborn.

What does this mean for pregnant women?

There is some benefit from confirmation that SARS-CoV-2 can potentially be spread to a fetus via the placenta. There are a lot of people not taking this pandemic as seriously as they should and this may serve as an inspiration for better adherence to physical distancing recommendations and proper use of facemasks. There is still so much we don’t know about the potential future repercussions, even after asymptomatic infections. Multisystem Inflammatory Syndrome in Children (MIS-C) is a prime example of this. Another potential problem, and one which I’m surprised wasn’t mentioned in either of these case reports, is that COVID-19 may result in preterm labor or a need for preterm delivery.

Hot off the presses!

On July 22nd, the AAP issued updated guidance on the management of newborns born to mothers with confirmed and suspected COVID-19. I will likely cover this issue in more depth in a future post, but I wanted to leave readers with one bit of good news. The AAP initially recommended temporary separation of newborns from their mothers in this context, and most hospitals have done this. I hope that it goes without saying that this is problematic for many, many reasons.

As more data has poured in over the past few months, it has become increasingly clear that there is not a significant difference in the likelihood of infant infection between babies who are separated from their mother and babies who room-in as long as caregivers follow the recommended infection prevention measures, such as wearing a mask during breastfeeding and practicing good hand hygiene. This of course also assumes that the mother is well enough to appropriately care for her child during the newborn’s hospital stay.

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Posted by Clay Jones

Clay Jones, M.D. is a pediatrician and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @SBMPediatrics and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey. The comments expressed by Dr. Jones are his own and do not represent the views or opinions of Newton-Wellesley Hospital or its administration.