We discuss potential complications and postnatal management of infants born to mothers with SARS-CoV-2 infection. We are joined by Kikelomo Babata, MD, Assistant Professor of Neonatal-Perinatal Medicine at the University of Texas Southwestern Medical Center.
Dr. Neeta Goli:
Welcome to Newborn News, a podcast where we discuss educational topics for medical professionals who care for newborns. I'm your host, Dr. Neeta Goli, a pediatrician in the UT Southwestern newborn nursery.
Dr. Neeta Goli:
Welcome back to the podcast. Today, we'll begin our discussion on COVID. This episode, we'll review perinatal COVID exposure. In the next episode we'll discuss neonatal manifestations of the SARS-CoV-2 virus. We are recording remotely due to the ongoing pandemic. We are joined today by Dr. Kikelomo Babata, neonatologist and Assistant Professor of Neonatal-Perinatal Medicine here at UT Southwestern. Dr. Babata's work on COVID includes providing talks to the UT Southwestern Division of Neonatal Perinatal Medicine, providing a regional talk to multiple healthcare stakeholders in the state of Texas via the North Central Texas Trauma Regional Advisory Council, writing a review on COVID in the Newborn for the Greater Pediatric Society of Dallas newsletter, and developing and publishing a protocol for Cochrane Database of Systematic Reviews to understand the safety of breastfeeding and other infant feeding strategies during the COVID-19 pandemic.
Dr. Kikelomo Babata:
Hello.
Dr. Neeta Goli:
Hi, Dr. Babata, thanks for joining us today.
Dr. Kikelomo Babata:
Hi Dr. Goli. Thank you. I'm excited to be here.
Dr. Neeta Goli:
I'm excited to talk about this with you today. Given the evolving literature and practice guidelines regarding this disease process, I'll first of all begin by saying that this episode is being recorded in late November of 2020. Guidelines and recommendations discussed today may and probably will change over time. We may use the terminology SARS-CoV-2, COVID-19 or COVID interchangeably to discuss the virus and its disease process.
Dr. Neeta Goli:
The severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2 virus, which causes the coronavirus disease 2019 or COVID-19, has had an incredibly high burden of disease globally and nationally during this pandemic. As of the time of this taping, the World Health Organization, or WHO has reported over 58 million cases and 1.3 million deaths worldwide, with the Centers for Disease Control and Prevention, or CDC, reporting over 12 million cases and over 250,000 deaths in the US alone. The pandemic has permeated all aspects of our lives and upended day-to-day life for many. Today, we will discuss potential neonatal complications due to maternal infection with SARS-CoV-2 virus in pregnancy.
Dr. Neeta Goli:
Dr. Babata, let's begin by briefly discussing pregnant women. If a woman contracts the SARS-CoV-2 virus while pregnant, how does her prognosis differ from that of a non-pregnant individual with the virus?
Dr. Kikelomo Babata:
Thank you, Dr. Goli. That's a very good question. As recently as this month, the CDC has actually published a report which shows that pregnant women actually have worse outcomes than non-pregnant women. Unfortunately, but not surprisingly, minority women are not only over-represented in the number, but they are also overrepresented in the adverse outcomes. Hispanic women, non-Hispanic Black women and American Indian and Alaska natives are the worst affected.
Dr. Kikelomo Babata:
The November CDC report was based on a data bank of about 400,000 SARS-CoV-2 positive symptomatic women. Take note, this is only women who had symptoms of reproductive age. They found that pregnant women were more likely to be admitted into the intensive care unit. They were more likely to need invasive ventilation. They're more likely to receive ECMO and even more concerning, so among women who are 35 to 44 years of age, pregnant women in this group, were actually four times more likely to need invasive ventilation and two times more likely to die. These numbers should be viewed in the fact that the overall incidence of severe illness is low, but we do need to be aware that there are additional risks for pregnant women who are symptomatic.
Dr. Neeta Goli:
And how is maternal COVID expected to affect the developing fetus?
Dr. Kikelomo Babata:
This is interesting. The data on this is actually quite limited. So far, unlike your classic congenital infections: your toxoplasmosis, your rubella, your CMV, your syphilis, where we all learned in medical school, your classic presentations of cataracts, intracranial calcification and things like that, even more recently, Zika virus with microcephaly. Really there has been no constellation of findings that have been described for COVID-19 yet. So far most of the reports we have are for mothers who have the infection in the second and the third trimester. Outcomes of mothers who are infected in the first trimester are yet to be determined just because of the nature of this illness, the fact that this is a new illness. Perinatal transmission has been reported in up to about 3% of infected women, but their babies for the most part have mild symptoms. There has been an increased rate of preterm birth that has been reported. And interestingly, the preterm birth rates does not appear to differ by symptom status.
Dr. Neeta Goli:
And then has the literature shown any difference in either fetal or neonatal outcome if the affected mom was asymptomatic versus symptomatic?
Dr. Kikelomo Babata:
This is another area that is being studied. There was a recent publication in JAMA by the group in Columbia University. They looked at the cohort of about 101 infants who were born to mothers who had COVID-19. And they found that the actual small number of mothers who had either severe or critical illness, did not transmit their illness to the infants. The findings suggested that mothers who were positive for SARS-CoV-2, including those who had clinical symptoms, may not necessarily need to be separated from their babies in the well baby nursery. An interesting thing that they pointed out is one of the babies they had was positive, had actually been rooming in with his mom without any precautions because the mother was initially negative. The mother turned positive during the admission and this baby ended up being positive.
Dr. Kikelomo Babata:
The group in Italy also published something similar. Again, the mom who was initially not positive, so was not using any precautions in caring for her baby, who turned positive later in her hospital course, her baby also ended up being positive. I think an important thing to keep in mind is that there have been reports of adverse outcomes for neonates in the literature but this illness, this most significant illness is actually not related to whether or not the baby is positive, but related to the severity of mother's illness. For instance, if you have a mom who has ARDS, severe hypoxia that her neonate needs to be delivered, you could have perinatal depression or HIE from that - not necessarily because the baby has COVID. And there was actually a report in the literature of a mother who had a stillbirth because she had ARDS. It wasn't necessarily because the baby was positive for COVID, but just because of the severity of the mother's illness.
Dr. Neeta Goli:
Along those lines, if a mom is severely ill enough to need to be treated with therapeutic agents, for example, some of the ones that are being used currently remdesivir or dexamethasone, does the fetus or neonate have any difference in outcome?
Dr. Kikelomo Babata:
This is interesting and the data on this is not well developed yet. This is kind of an ongoing area in the literature. I was be able to find some reports. Remdesivir, for instance, this medication had been used during the Ebola outbreak so that's already shown to be safe in pregnancy. I did find some case reports, one of them had about three pregnant women who were treated with remdesivir, and essentially what they reported was the mother's response to the treatment. I think of these three mothers, two of them improved. One of them had transaminitis. Two of them were 24 and 25 weeks, the other one was at 34 weeks. They reported the outcome for the infant whose mother was sick at 34 weeks and the baby was born at 37 several weeks without any symptoms.
Dr. Kikelomo Babata:
For dexamethasone on the other hand, dexamethasone, corticosteroids have been widely used in neonatology to advance fetal long maturity. Using it seven days before birth. We all know about the improvement in outcomes. For the regimen that is actually recommended for mothers who have COVID-19, is actually more of a prolonged regimen, which we know when these corticosteroids are used for prolonged periods of time, the babies are more exposed to the adverse effects. Fetal growth restriction, hypoglycemia. Actually what I have found for pregnant women is some authors are actually recommending a combination of starting treatment with dexamethasone and then transitioning over to methylprednisolone, because that does not cross the placenta.
Dr. Kikelomo Babata:
In terms of outcomes specifically for babies who are born to these women, I really could not find a lot of detail in the literature about how these babies do, whether or not these medications are associated with better outcomes for babies or not. We have to keep in mind that even of the mothers who are positive or who have severe illness, that severity of illness has not been found to be associated with worse outcomes in the neonate.
Dr. Neeta Goli:
What is the link between maternal infection with COVID and prematurity?
Dr. Kikelomo Babata:
Actually the studies are actually showing, the CDC reports have shown that there's actually higher preterm birth rates in mothers who are positive for SARS-CoV-2 as opposed to mothers who are not. Some authors have suggested that this might be due to changes in the placenta. Some authors are looking into this because of the illness severity in mothers. Are the babies being delivered early because the mothers are ill? The literature is deferring on that. There's not a consistent opinion on that, but definitely the higher preterm birth rates have been reported from the most recent CDC report.
Dr. Neeta Goli:
What is our management of neonates born to women who were infected with SARS-CoV-2?
Dr. Kikelomo Babata:
Essentially what we do, and if you look at the guidelines, the guidelines that are really wide. They range from hospital to hospital, but essentially we make sure that we at least make sure mother is wearing a mask while she's caring for the baby. The baby being kept about six feet apart from the mother. We allowed direct breastfeeding or breastfeeding or feeding pumped breast milk. We do talk to the mothers about this.
Dr. Kikelomo Babata:
And then essentially we do test the babies at 24 and 48 hours of life. For the most part if the 24 hour test is negative, we do another test at 48 hours and then the baby gets the regular newborn care. The hearing screen, the CCHD and things like that. And if the baby tests negative and baby's clinically doing well, we try to discharge the baby home to an asymptomatic caregiver. We do know that a lot of these babies are going to go to a home where other people may be infected. But for the most part, we really have not seen in the literature as well as our practice, we have not seen babies be readmitted for significant COVID-19 infection after being discharged home.
Dr. Neeta Goli:
And then what is the evidence regarding mom and baby rooming in versus being separated?
Dr. Kikelomo Babata:
I kind of touched on this a little bit earlier. There was a recent Nature review communications paper, which is very good. It actually it's a meta-analysis of 176 published cases of neonatal SARS-CoV-2 infection, so essentially babies who have tested positive. And this paper actually suggested that a lack of separation was associated with an incidence of late infection. This is the infection after 72 hours of age. But the thing is this paper, they don't really talk about what they mean by separation. Do they mean the baby has to be physically in a different room from mom? Or does separation mean the fact that mom is using adequate PPE? Wearing a mask? In the paper though, they do suggest that they do a report that adequate PPE, the protective measures that we have been taking have been associated with a reduced risk of infection in the baby. Published work from a series in New York City, Columbia University, they've published it. They have published some of their findings and they actually allowed their mothers to room in with their infants whether or not they have symptoms and they did not show an increased risk for infection.
Dr. Neeta Goli:
What is the current AAP recommendation on rooming in versus being separated?
Dr. Kikelomo Babata:
The AAP actually recommends giving parents advice. Kind of talking to the parents about the risks or the benefits and encouraging the parents to make an informed decision.
Dr. Neeta Goli:
And then what is the evidence on infected mom's breastfeeding?
Dr. Kikelomo Babata:
I'm excited that you asked me this question because my colleagues and I are actually working on a Cochrane (word?) systematic review on this. The Nature review publication I mentioned earlier has suggested that breastfeeding is not associated with an increased risk of infection. So far there are no documented cases of transmission of infectious virus to an infant or neonate through breast milk. Now there have been occasional reports of detection of viral RNA by reverse transcriptase PCR in breast milk, but this actually does not suggest infectivity.
Dr. Kikelomo Babata:
There has been a study which has been done by Christina Chambers and her group from UCSD. And they actually obtained breast milk samples from about 18 women who have SARS-CoV-2 infection. They obtained 64 samples in total. Each person provided about one to two samples and of all the samples, only one sample tested positive. Now they did cultures on this sample that tested positive and there was no replication, both on the sample that was positive and the samples that were not positive, and they did not show any replication-competent viruses.
Dr. Kikelomo Babata:
Alisa Fox in Mount Sinai, New York, actually has worked further on this and she has actually shown that there's presence of antibodies to SARS-CoV-2 in breast milk. And their data indicate that there is strong secretory IgA dominant SARS-CoV-2 immune response in human milk after infection. And they actually intend to continue comprehensive studies on human milk immune response to SARS-CoV-2. They intend to determine the efficacy of convalescent milk. That's really interesting. They're actually talking about the possibility of looking at the efficacy of convalescent milk antibody as a treatment for COVID-19. Really exciting stuff in the pipeline. They also want to understand the utility of these antibodies in either preventing or mitigating SARS-CoV-2 infection. The data they eventually provide will have implications beyond the pandemic as they will serve to bridge a relatively large knowledge gap regarding human milk immunology.
Dr. Neeta Goli:
Very interesting. Do you have any additional advice or counseling that you typically give these moms when taking their babies home?
Dr. Kikelomo Babata:
I think the most important things I will emphasize for mothers who are taking their babies home is, if other members of the family are sick, then you really want to almost quarantine yourself. You want to quarantine the baby from everyone else. You want to make sure that the baby is not sharing the same spaces with other people who may be sick. You want to make sure everybody in the house is wearing a mask at all times. You want to make sure there's adequate ventilation as much as possible. You want to make sure that you're washing your hands. Those are all important things, washing your hands either before feeding your baby or after feeding your baby, or even before handling any bottles or things like that. Those are things that I really would emphasize for any families. And of course, if the baby does develop any symptoms, to make sure that they talk to their pediatrician.
Dr. Neeta Goli:
What is the known incidence of neonatal SARS-CoV-2 infection either via vertical or horizontal transmission? I think you may have mentioned it earlier.
Dr. Kikelomo Babata:
Yeah, so it's anywhere from 2.6-3%. And it's interesting that, that's what the CDC has reported and that is kind of similar to the numbers that have been described in China as well. Now, the Nature Communications study, which I mentioned, of the 176 infants, suggested that the majority of infants who test positive actually acquire the infection postpartum. They suggested up to about 70%, and about 30% of these, they suggested likely acquired the infection vertically. Now, because of the nature of this infection is really, it can be hard to predict, to know for sure how the infection was acquired, but there are a handful where we can say, where there is strong enough evidence to say that these were definitely vertical, especially where you have placental findings.
Dr. Kikelomo Babata:
Also, Julide Sisman who is one of the neonatologists in our group has actually published one of the first confirmed cases of vertical transmission from an institution. And this was published in the Pediatric Infectious Disease Journal. The affected infant in this case, actually tested positive initially at 24 hours of life and then at 48 hours of life and the baby had symptoms of fever and mild respiratory distress.
Dr. Neeta Goli:
And stay tuned for our next episode when Dr. Babata will return to discuss in detail neonatal SARS-CoV-2 infection.
Dr. Neeta Goli:
To end the episode today, do you have any advice for our listeners while they care for newborns?
Dr. Kikelomo Babata:
Well, I will say, if you or any member of your family is sick, make sure you get tested, make sure you wear a mask, make sure you wash your hands, practice social distancing as much as possible. We are in the midst of a surge right now. You want to make sure you are avoiding large gatherings because these are the ways that people get sick. And if you do get sick and develop symptoms, do not delay in seeking help for your medical provider because people have been reported to actually present later to the hospital and sicker. Definitely if you are sick, make sure you reach out to your medical provider.
Dr. Neeta Goli:
Thanks for joining us today, Dr. Babata.
Dr. Kikelomo Babata:
Thank you. Thank you for having me.
Dr. Neeta Goli:
Thanks for listening to Newborn News. We hope you join us next time. If you like what you hear, make sure to subscribe and leave us a review. If you have questions, comments, feedback or suggestions for future episodes, please email me at NewbornNews@utsouthwestern.edu. As a reminder, this content is educational and is not meant to be used as medical advice. Views or opinions expressed in this podcast are those of myself and my guests, and do not necessarily reflect the views of the university.