Perinatal complications, mode of delivery, and neurological morbidity in children with COL4A1 / A2 variants

COL4A1 and COL4A2 are genes that help provide structure to blood vessel walls. Changes (variants) in these genes can cause a rare condition called Gould syndrome, which may affect the brain, eyes, kidneys, muscles, and other organs. Some babies experience bleeding or stroke before or around the time of birth, but many questions remain about the best way to manage pregnancy and delivery when a COL4A1 or COL4A2 variant is known or suspected. We used information from the international Gould Syndrome Foundation Registry to preliminarily explore pregnancy, birth, and childhood neurological outcomes in 71 children with COL4A1 or COL4A2 variants. Families completed questionnaires describing pregnancy, delivery, and medical history. Many children had neurological complications, including developmental delay (72%), cerebral palsy (54%), stroke (48%), and epilepsy (42%). About one-quarter had a stroke identified before or shortly after birth. Babies with a stroke identified during pregnancy were more likely to be delivered by Cesarean section, suggesting that doctors often choose Cesarean delivery when prenatal brain injury is detected. We did not find evidence that children born by Cesarean section had lower rates of cerebral palsy, epilepsy, developmental delay, or other neurological complications than children born vaginally. However, this study was not designed to determine whether one delivery method is safer than another. Because the registry relied on family-reported information and included a relatively small number of participants, larger studies with standardized medical data are needed.