COVID-19 vaccine hesitancy and acceptance among pregnant people contacting a teratogen information service.

Pregnant people are at increased risk of severe illness from SARS-CoV-2 infection and are more likely to be admitted to an intensive care unit, be put on a mechanical ventilator, and die, if infected. Having COVID-19 during pregnancy also increases the risk of preterm delivery. Vaccination is a critical tool for controlling the COVID-19 pandemic; however, to date, just over 30% of pregnant people in the United States have been vaccinated. It is important to identify any barriers to acceptance of the COVID-19 vaccine among the pregnant population so that specific hesitancy concerns can be addressed. Our objective was to identify the proportion of pregnant people who are unsure or not planning to be vaccinated against COVID-19 and collect information about their reasons for hesitancy. A questionnaire examining views on COVID-19 vaccine interest was administered to 299 pregnant people who contacted MotherToBaby 3/1/21-7/23/21. Questions obtained information about the perception of COVID-19 risk in pregnancy, interest in receiving a COVID-19 vaccine while pregnant, and reasons for acceptance or hesitancy. Within the sample, 21% had already been vaccinated against COVID-19, 43% were planning to get vaccinated, 9% were not planning to receive the vaccine, and 27% were undecided. Women who were not planning to get vaccinated and those that were undecided both said their concern was 'not enough safety information for pregnancy'. Individuals aged 18-25, those who made less than $50,000/year, and those who lived in the Northeast were more likely to be hesitant. Based on these data, continued efforts to collect and communicate high-quality and understandable information to pregnant people about vaccine safety should be a key priority in efforts to increase vaccine acceptance among this group.

A homozygous nonsense mutation in SOX9 in the dominant disorder campomelic dysplasia: a case of mitotic gene conversion.

Campomelic dysplasia (CD; MIM 114290), an autosomal dominant skeletal malformation syndrome with XY sex reversal, is caused by heterozygous de novo mutations in and around the SOX9 gene on 17q. We report a patient with typical signs of CD, including sex reversal, who was, surprisingly, homozygous for the nonsense mutation Y440X. Since neither parent carried the Y440X mutation, possible mechanisms explaining the homozygous situation were a de novo mutation followed by uniparental isodisomy, somatic crossing over, or gene conversion. As the patient was heterozygous for six microsatellite markers flanking SOX9, uniparental isodisomy and somatic crossing over were excluded. Analysis of intragenic single-nucleotide polymorphisms suggested that the homozygous mutation arose by a mitotic gene conversion event involving exchange of at least 440 nucleotides and at most 2,208 nucleotides between a de novo mutant maternal allele and a wild-type paternal allele. Analysis of cloned alleles showed that homozygous mutant cells constituted about 80% of the leukocyte cell population of the patient, whereas about 20% were heterozygous mutant cells. Heterozygous Y440X mutations, previously described in three CD cases, have been identified in seven additional cases, thus constituting the most frequent recurrent mutations in SOX9. These patients frequently have a milder phenotype with longer survival, possibly because of the retention of some transactivation activity of the mutant protein on SOX9 target genes, as shown by cell transfection experiments. The fact that the patient survived for 3 months may thus be explained by homozygosity for a hypomorphic rather than a complete loss-of-function allele, in combination with somatic mosaicism. This is, to our knowledge, the first report of mitotic gene conversion of a wild-type allele by a de novo mutant allele in humans.