Impaired cerebral cortex development in human fetuses with posterior brain abnormalities and diagnosed open neural tube defects at 11 – 13 weeks

Objective:

To evaluate fetal cerebral cortex development at 11 – 15 weeks of gestation in human fetuses with posterior brain abnormalities (BS-BSOB-ratio > 95th centile, CM < 5th centile) and confirmed diagnosis of neural tube defects such as open spina bifida during their 11 – 13-week scan, and to compare it with normal development (Fietz et al. 2010, Lachmann et al. 2011, Scheier et al. 2011).

Methods:

Pregnant women were referred to our first trimester clinic for measurement of nuchal translucency and combined risk assessment for pre-eclampsia, premature birth, fetal growth restriction, chromosomal abnormalities and showing posterior brain abnormalities with diagnosis of open neural tube defects. After deciding for termination of pregnany, the women were invited to take part in our study to evaluate if brain development in fetuses with such congenital abnormalities is already impaired at 11 – 15 weeks of gestation. Neural stem and progenitor cell subpopulations in the fetal human neocortex were analyzed by immunofluorescence for established molecular makers (Fietz et al. 2010). Four fetuses with open neural tube defects were examined and compared with normal fetuses at similar gestational age.

Results:

Cerebral cortex development in fetuses with posterior brain abnormalities was found to be impaired already at a gestational age of 11 weeks. Specifically, we found a reduction in the abundance of a distinct neural progenitor subpopulation in the subventricular zone of a fetus with posterior brain abnormalities when compared to control of similar gestational age. This suggests a differential sensitivity of the various neural progenitor subpopulations to the changes induced by posterior brain abnormalities related to open neural tube defects.

Conclusions:

Already at 11 weeks of gestation, fetuses with neural tube defects such as open spina bifida may show an impaired cerebral cortex development. We are currently analyzing later stages of fetal development to corroborate and extend our findings.

References:

[1] Fietz SA, Kelava I, Vogt J, Wilsch-Bräuninger M, Stenzel D, Fish JL, Corbeil D, Riehn A, Distler W, Nitsch R, and Huttner WB. OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nature Neurosci. 13: 690 – 699, 2010.

[2] Lachmann R, Chaoui R, Moratalla J, Picciarelli G, Nicolaides KH. Posterior brain in fetuses with open spina bifida at 11 to 13 weeks. Prenat. Diagn. 31: 103 – 106, 2011.

[3] Scheier M, Lachmann R, Petros M, Nicolaides KH. Three dimensional sonography of the posterior fossa in fetuses with open spina bifida at 11 – 13 weeks of gestation. Ultrasound Obstet. Gynecol. 38: 625 – 629, 2011.