Isolated fetal omphalocele, Beckwith-Wiedemann syndrome, and assisted reproductive technologies

To assess the frequency of Beckwith-Wiedemann syndrome (BWS) among fetuses with an ultrasound diagnosis of isolated omphalocele and to examine relevant clinical variables, in particular route of conception.

An ultrasound and consultation database (1988-2007) was searched and cases were included that met the following criteria: omphalocele, no additional major structural anomaly or autosomal aneuploidy, and either newborn examination or molecular diagnostic studies for BWS. Medical records were reviewed and a nested case-control analysis matching day of birth assessed the route of conception, given the changing prevalence of assisted reproduction during the study period.

Thirty cases of isolated omphalocele were identified. Beckwith-Wiedemann syndrome was diagnosed in six cases (6/30 [20.0%]); four by newborn examination (4/6) and two on prenatal molecular studies (2/6). Of note, one case of BWS had a karyotype of 47,XXX, the remainder was euploid. Compared with isolated omphaloceles, fetuses with BWS more often were twins (3/6 vs. 1/24; p < 0.001), had polyhydramnios (4/6 vs. 2/24; p < 0.001), were macrosomic at birth (3/6 vs. 4/24 p < 0.001), and had been conceived by assisted reproduction (3/6 vs. 2/22; p = 0.04). When compared with normal controls matched by date of birth, conception by assisted reproductive technique among BWS births was highly significant, (p < 0001).

Beckwith-Wiedemann syndrome is present in a noteworthy portion of fetuses with isolated omphalocele on ultrasound, and prenatal molecular studies are warranted. Even among this small cohort, a recurring theme of conception by assisted reproduction exists.