In vitro fertilisation and use of ovulation enhancers may both influence childhood height in very low birthweight infants.

CONTEXT: Term-born children conceived by in vitro fertilisation (IVF) are reportedly taller than naturally conceived (NC) children. High levels of growth promoting hormones and epigenetic imprinting have been suggested as pathogenetic mechanisms. HYPOTHESIS: Tall stature in prematurely born IVF-conceived (IVF-C) children suggests pre- or early implantation imprinting rather than a postnatal effect. METHODS: We studied 334 very low birthweight (VLBW: birth weight <1500 g) children born prematurely during 1995-1999 and obtained their anthropometric measures at 6-10 years of age. Perinatal and neonatal data were obtained from the Israeli VLBW database. We compared IVF-C, ovulating agents conceived (OA-C) and naturally conceived (NC) groups of children with respect to their and their parents' anthropometry and their perinatal/neonatal variables. RESULTS: Childhood height standard deviation scores (SDSs) were greatest in IVF-C (-0.12 (SD 1.25); p<0.022) and insignificantly greater in OA-C (-0.37 (SD 1.02)) as compared to NC (-0.58 (SD 1.36)) children. The IVF-C and NC groups were significantly different regarding 17 parental and perinatal variables; however, multiple regression analysis including these variables showed that, as compared with NC, IVF-C children had significantly older mothers at birth with earlier follow-up during pregnancy and more multi-fetal pregnancies. CONCLUSIONS: IVF-C and to a lesser extent OA-C prematurely born children are taller than otherwise NC children. After ruling out postnatal and parental causes, we speculate that pre- or early implantation factors might have contributed to the taller stature of IVF-C children.

Congenital dysgranulopoietic neutropenia in two siblings: clinical, ultrastructural, and in vitro bone marrow culture studies.

Two siblings with congenital neutropenia are reported. The first patient, female, died after Pseudomonas sepsis. The second patient male, suffered from recurrent pyogenic infections, with a more benign course. Bone Marrow (BM) and Peripheral Blood (PB) analysis in the second patient revealed a reduced number of granules and myelin bodies in the PB neutrophils, suggesting a developmental defect of primary and secondary granules. BM promyelocytes were almost normal, but the myelocytes and metamyelocytes showed defective granulogenesis. The BM in vitro granulocyte-macrophage-colony-forming cell (GM-CFC) growth and the PB white blood cells (WBC) granulocyte-macrophage-colony-stimulating factor (GM-CSF) production, which were analyzed in the second patient, showed normal numbers of GM-CFC, with differentiation mostly toward monocytes and a defect in the GM-CSF production capacity. The second patient's PB mononuclear cells or serum did not inhibit normal GM-CFC when added to control BM cells. We suggest that in this specific form of congenital neutropenia, which is probably an autosomal recessive disorder, the abnormal neutrophil granule production and the defective provision of GM-CSF by PB WBC are unique pathognomonic characteristics, possibly associated with the overt neutropenia.