Short- and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 in utero or during the perinatal period: preliminary findings

Abstract

The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48–72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48–72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth ( P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). Conclusions : Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life. What is Known: • In utero mother-to-child transmission of SARS-CoV-2 has been documented by several independent studies. • Neonatal COVID-19 is a systemic disease that can be severe, although rarely. What is New: • Newborns exposed in utero to SARS-CoV-2 have mostly a normal auxological, audiological, and neurological development during the first months of life. • Fundus fluorescein angiography revealed that up to 5% of newborns exposed in utero to SARS-CoV2 can show retinal and choroidal abnormalities, including peripheral hypofluorescence of the choroid and increased vascular tortuosity. Supplementary Info...

Infants prenatally exposed to SARS-CoV-2 show the absence of fidgety movements and are at higher risk for neurological disorders: A comparative study

“…Our findings suggest alterations in the CNS, consistent with Zeng et al (2021) who pointed out that some newborns prenatally exposed to SARS-CoV-2 have abnormalities on brain magnetic resonance imaging (MRI), such as abnormal white matter signals, delayed myelination, brain dysplasia and abnormal bilateral periventricular signals [ 37 ]. Also, with Buonsenso et al (2022) [ 38 ] who pointed out in a follow-up study that only a small subgroup of children exposed to SARS-CoV-2 in utero presented abnormalities among these, 15% of children had retinal abnormalities, such as bilateral reduced attention at distance in six cases (30%) and reduced contrast sensitivity in three (15%). Furthermore, our findings are, to some extent, similar to those obtained for infants prenatally exposed to ZIKA, where only some infants had a severely reduced total MOS and where, in the context of ZIKA, this occurred only in those who developed microcephalia [ 3 ].…”

SARS‑CoV‑2 infection and children: Insights from the 6th Workshop on Paediatric Virology (Review)

“…A shorter interval between maternal COVID-19 symptoms and delivery is a risk factor for transmission (91). However, there is no increased risk for neonates apart from abnormal ophthalmologic outcomes identified in 15% of cases in a previous study (92). The absence of the co-expression of TMPRSS2 and ACE-2 in the placenta across the second trimester and at term, as well as the absence of ACE2 in the foetal lung help explain the rarity of vertical transmission (93).…”

“…Looking back, 14 months after the '6th Workshop on Paediatric Virology', the volume of literature and data on SARS-CoV-2 and COVID-19 being published daily by the world scientific community is impressive (83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93). Since the workshop, as expected for a RNA virus, multiple variants of SARS-CoV-2 have emerged.…”

Partnerships in the Comprehensive Management of Multisystem Inflammatory Syndrome in Neonates (MIS-N): Translating 2 Years of Pediatric Practice to the Neonatal Wards

“…With the pediatric COVID ISARIC study group we are following up with both the children who suffered from COVID-19 and MIS-C. Theoretically, we cannot exclude similar long-term problems in patients with MIS-N and, therefore, its inclusion in specific follow-up programs with teams that already gained experience with long-term COVID and MIS-C is advisable, and wise. Importantly, in our Institution we succeeded in developing an organized and multidisciplinary outcome for newborns from mothers suffering with COVID-19 during pregnancy, 44 and will hopefully provide better programs for MIS-N as well.…”