OBJECTIVE: In a national retrospective cohort study, we aimed to determine the effect of pregnancy on new von Hippel-Lindau (vHL) tumor development during pregnancy and at 1, 3, and 5 years after conception.

METHODS: We included 52 VHL mutation carriers (26 men and 26 women) with 581 manifestations diagnosed throughout their lifetimes. We analyzed age-dependent manifestation rates using Poisson regression. We compared the women's rates in intervals where they had been pregnant with their age-matched nonpregnant intervals. We investigated possible long-term effects using pregnancy intervals of increasing lengths of 1, 3, and 5 years after conception. Furthermore, we compared age-related manifestation rates for women and men.

RESULTS: From birth to the participants' current age, 581 manifestations were diagnosed; mean age was 37.5 years (range 2-64 years). Seventeen women had completed 30 pregnancies. Manifestation rates in women's pregnant intervals were lower compared with their age-matched nonpregnant intervals (1 year: hazard ratio [HR] = 0.439, 95% confidence interval [CI] 0.131-1.474, p = 0.18; 3 years: HR = 0.412, 95% CI 0.214-0.796, p = 0.0083; and 5 years: HR = 0.450, 95% CI 0.136-1.489, p = 0.19). Men and women had similar manifestation rates, both increasing from their 20s.

CONCLUSIONS: Pregnancy does not aggravate vHL tumor development, and we neither discourage pregnancy in VHL mutation carriers nor recommend intensified surveillance during pregnancy. The pregnancy effect is not due to concurrence of a naturally milder tumor development in women's fertile ages, as the rate of new tumor development increases for both men and women from 20 years of age, even more in men than in women.