Reproductive decision-making and pregnancy in germline <i>CDH1</i> variant carriers.

Abstract

Diagnosis of a hereditary cancer syndrome may impact family planning, particularly in reproductive age individuals. Factors influencing reproductive decision-making are understudied in individuals with germline <i>CDH1</i> pathogenic or likely pathogenic (P/LP) variants. We characterised reproductive decision-making and perinatal outcomes in 121 individuals aged 18-49 with hereditary diffuse gastric and lobular breast cancer syndrome due to a germline <i>CDH1</i> P/LP variant. Half of individuals (50%, 60/121) reported their <i>CDH1</i> diagnosis impacted family planning. Psychosocial and economic barriers to reproduction were encountered by 47% (56/119) of patients. Additionally, 12% (15/121) of individuals delayed pregnancy to prioritise personal cancer risk management with either endoscopic surveillance, prophylactic total gastrectomy (PTG) or mastectomy. Women were more likely to experience guilt about passing their <i>CDH1</i> variant to offspring compared with men. Perinatal and fetal outcomes were investigated in six women who gave birth at a median time of 24 months (IQR 20-44) after PTG. Maternal micronutrient deficiencies were not uncommon in pregnant women after PTG despite compliance with a bariatric, prenatal multivitamin. Majority of women who became pregnant after PTG reported worsening post-gastrectomy syndromes. Most infants (90%, 9/10) born after PTG were full-term and no fetal complications were reported. Reproductive decision-making is complex in individuals with germline <i>CDH1</i> variants, who often encounter psychosocial and physical challenges during family planning and pregnancy. However, successful pregnancy is possible after PTG with the guidance of a multidisciplinary team including maternal fetal medicine specialists and a registered dietitian. NCT03030404.