Association between oral intake of dydrogesterone during early pregnancy and congenital heart disease: a case-control study

Congenital heart disease is the most frequent form of congenital anomaly in newborn infants and accounts for more than a quarter of all serious congenital abnormalities worldwide. A genetic cause is identified in less than 20% of cases of congenital heart disease and in most cases the cause remains unknown. In the context of the health burden of congenital heart disease, the contribution of non-inherited risk factors is important, especially if the disease is caused by a drug that can be avoided during pregnancy. We sought to determine whether maternal dydrogesterone treatment in early pregnancy is associated with congenital heart disease in the infant. A retrospective case-control study of birth defects and associated risk factors was conducted at Al Rantisi Specialist Paediatric Hospital in the Gaza Strip. Data were obtained and compared between 202 children born with congenital heart disease and a control group of 200 childrenwho did not have congenital heart disease and were randomly selected from the same geographical populations during their admission due to different medical reasons. All children were born in the period of 2010–2013. Data were collected from June, 2013, to December, 2013, by interview with mothers. Dydrogesterone exposure was defined as any reported use during the first trimester of pregnancy. Exclusion criteria included stillbirth, chromosomal abnormalities in the child, and maternal chronic medical illnesses such as diabetes. Binary logistic regression analyses were used to identify any association between drug exposure and congenital heart disease. The study was approved by the human research ethics committee, Ministry of Health, Gaza Strip. Verbal informed consent was obtained from the children's parents. Exposure to dydrogesterone during the first trimester of pregnancy was more frequent among mothers of children born with congenital heart disease (75 of 202) than in mothers of children in the control group (36 of 200; adjusted odds ratio 2·71, 95% CI 1·54–4·24, p