Association between pulmonary hypoplasia and hypoplasia of arcuate nucleus in stillbirth

To investigate lung development and to correlate pulmonary hypoplasia with hypoplasia of the arcuate nucleus in stillbirths.

We examined 26 stillbirths which occurred after 25 complete gestational weeks. The brainstem and the lung were the particular focus of this study. The brainstem was examined according to the protocol routinely followed in our Institute. As regards the lung examination, the development stage was evaluated on the basis of the correlation between lung and body weight (LW/BW), and according to microscopic parameters, that is, the presence of cartilaginous bronchi up to the distal level and the radial alveolar count (RAC). The normal reference values for the last 3 months of gestation correspond to >0.022 for LW/BW and from 2.2 to 4.4 for RAC.

In 17 cases (65%) pulmonary hypoplasia was observed, characterized by a LW/BW value below 0.022 and RAC below 2.2. In nine cases (35%), microscopic examination of brainstem serial sections showed varying degrees of hypoplasia of the arcuate nucleus (ARCn). In eight cases (31%) the pulmonary hypoplasia was associated with hypoplasia/agenesis of the ARCn.

This study demonstrated that in about a third of stillbirths there is a congenital hypodevelopment of both lung and arcuate nucleus. In these cases the ARCn hypoplasia would exert a negative effect on respiratory movements in utero and therefore on lung development. When the pulmonary hypoplasia is not accompanied by hypodevelopment of this nucleus the explanation could be a failure to block the inhibitory action of the Kölliker-Fuse nucleus.