Study protocol: childhood outcomes of fetal genomic variants: the PrenatAL Microarray (PALM) cohort study

ABSTRACT: BACKGROUND: The implementation of genomic testing in pregnancy means that couples have access to more information about their child’s genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. METHODS: This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old’s), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. DISCUSSION: This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. TRIAL REGISTRATION: ACTRN12620000446965p; Registered on April 6, 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-021-02809-7.