Cancer in Childhood, Adolescence, or Young Adulthood and Risk of Congenital Malformations and Chromosomal Abnormalities in Children: A Matched Cohort Study and Descriptive Pooled Analysis

<h2>ABSTRACT</h2><h3>Background and aims</h3> Chemotherapy and radiotherapy induce DNA damage, which could affect germ cells of cancer survivors and be transmitted to their children. We assessed the risk of congenital malformations and chromosomal abnormalities among children of cancer survivors using a matched cohort study and descriptive pooling of previous studies. <h3>Methods</h3> We identified all children born in Sweden between 2006-2018. Those with a parental cancer diagnosis ≥1 year before delivery were considered exposed (n=8,625). Each child was matched on sex, birth year and birth region to ten unexposed children. The outcome was ≥1 ICD-10 Q-code, indicating a congenital malformation or chromosomal abnormality. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusting for parental Q-code, parental age, in-vitro fertilization, and maternal BMI, diabetes and smoking. Relative risks (RRs) from previous studies were pooled using a random-effects model. <h3>Results</h3> The prevalence of ≥1 Q-code was similar among exposed (11.9%) and comparator children (11.8%), yielding an adjusted OR=1.01 (95% CI 0.95-1.09). No effect modification was observed by parental age at cancer diagnosis, cancer subtype, or whether the exposure was maternal, paternal or both parents. Pooling results from this and previous studies suggested a small increased risk (parental: RR=1.06, 95% CI 1.02-1.09; paternal: RR=1.06, 95% CI 1.01-1.12; maternal: RR=1.05, 95% CI 1.01-1.09; however, most included studies did not adjust for parental Q-diagnoses. <h3>Conclusions</h3> We found no increased risk of congenital malformations or chromosomal abnormalities among children of cancer survivors; pooled estimates are likely confounded by parental congenital anomalies.