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Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant.

ABSTRACT: The risk and potential consequences of mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy are still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Two PCR-confirmed perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded. In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, drug use, or maternal disease during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants.Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as support COVID-19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412. Date of registration: November 18, 2020 What is Known: •Materno-fetal transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) during pregnancy has rarely been reported so far, but was demonstrated in isolated cases. What is New: •In a study of complete households with documented SARS-CoV-2 infection, including a cohort of pregnant women, we observed perinatal coronavirus transmission at a higher frequency than expected. •We also describe a newborn boy with an eye malformation reminiscent of rubella embryopathy but associated with early gestation SARS-CoV-2 infection of his mother. •A coronavirus-related embryopathy, reported here for the first time, is a finding that requires further investigation.

SUBMITTER: Morhart P

PROVIDER: S-EPMC8341836 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear.ObjectiveTo evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy.Design, setting, and participantsNationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants.ExposuresMaternal test positivity for SARS-CoV-2 in pregnancy.Main outcomes and measuresIn-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2.ResultsOf 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia.Conclusions and relevanceIn a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

Project description:BackgroundInfection during pregnancy can increase the risk of neurodevelopmental disorders in offspring. The impact of maternal SARS-CoV-2 infection on infant neurodevelopment is poorly understood. The maternal immune response to infection may be mimicked in rodent models of maternal immune activation which recapitulate altered neurodevelopment and behavioural disturbances in the offspring. In these models, epigenetic mechanisms, in particular DNA methylation, are one pathway through which this risk is conferred in utero to offspring. We hypothesised that in utero exposure to SARS-CoV-2 in humans may alter infant DNA methylation, particularly in genes associated with neurodevelopment. We aimed to test this hypothesis in a pilot sample of children in Victoria, Australia, who were exposed in utero to SARS-CoV-2.MethodsDNA was extracted from buccal swab specimens from (n = 4) SARS-CoV-2 in utero exposed and (n = 4) non-exposed infants and methylation status assessed across 850,000 methylation sites using an Illumina EPIC BeadChip. We also conducted an exploratory enrichment analysis using Gene Ontology annotations.Results1962 hypermethylated CpG sites were identified with an unadjusted p-value of 0.05, where 1133 CpGs mapped to 959 unique protein coding genes, and 716 hypomethylated CpG sites mapped to 559 unique protein coding genes in SARS-CoV-2 exposed infants compared to non-exposed. One differentially methylated position (cg06758191), located in the gene body of AFAP1 that was hypomethylated in the SARS-CoV-2 exposed cohort was significant after correction for multiple testing (FDR-adjusted p-value <0.00083). Two significant differentially methylated regions were identified; a hypomethylated intergenic region located in chromosome 6p proximal to the genes ZP57 and HLA-F (fwer <0.004), and a hypomethylated region in the promoter and body of the gene GAREM2 (fwer <0.036). Gene network enrichment analysis revealed differential methylation in genes corresponding to pathways relevant to neurodevelopment, including the ERBB pathway.ConclusionThese pilot data suggest that exposure to SARS-CoV-2 in utero differentially alters methylation of genes in pathways that play a role in human neurodevelopment.

Project description:BackgroundMultiple reports have described neonatal SARS-CoV-2 infection, including likely in utero transmission and early postnatal infection, but published estimates of neonatal infection range by geography and design type.ObjectivesTo describe maternal, pregnancy and neonatal characteristics among neonates born to people with SARS-CoV-2 infection during pregnancy by neonatal SARS-CoV-2 testing results.MethodsUsing aggregated data from the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) describing infections from 20 January 2020 to 31 December 2020, we identified neonates who were (1) born to people who were SARS-CoV-2 positive by RT-PCR at any time during their pregnancy, and (2) tested for SARS-CoV-2 by RT-PCR during the birth hospitalisation.ResultsAmong 28,771 neonates born to people with SARS-CoV-2 infection during pregnancy, 3816 (13%) underwent PCR testing and 138 neonates (3.6%) were PCR positive. Ninety-four per cent of neonates testing positive were born to people with infection identified ≤14 days of delivery. Neonatal SARS-CoV-2 infection was more frequent among neonates born preterm (5.7%) compared to term (3.4%). Neonates testing positive were born to both symptomatic and asymptomatic pregnant people.ConclusionsJurisdictions reported SARS-CoV-2 RT-PCR results for only 13% of neonates known to be born to people with SARS-CoV-2 infection during pregnancy. These results provide evidence of neonatal infection identified through multi-state systematic surveillance data collection and describe characteristics of neonates with SARS-CoV-2 infection. While perinatal SARS-CoV-2 infection was uncommon among tested neonates born to people with SARS-CoV-2 infection during pregnancy, nearly all cases of tested neonatal infection occurred in pregnant people infected around the time of delivery and was more frequent among neonates born preterm. These findings support the recommendation for neonatal SARS-CoV-2 RT-PCR testing, especially for people with acute infection around the time of delivery.

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Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant.

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