Development in children born very preterm after intrauterine growth restriction with abnormal fetal blood flow

Abstract: Delivery of fetuses with intrauterine growth restriction (IUGR) with abnormal umbilical artery blood flow in the second trimester represents a clinical dilemma. So far, no evidence based management protocols are available adressing when to deliver these fetuses. The high risk of hypoxia and fetal death has to be balanced against that of extreme preterm birth with associated morbidity. The clinical routine in Lund has been a proactive management, that is to deliver on fetal indication before occurence of more severe hemodynamic changes. The aim of this study was to evaluate short and long-term consequences in very preterm IUGR fetuses (PT-IUGR) with abnormal blood flow in the umbilical artery. Study I: Mortality and neonatal morbidity did not differ between the PT-IUGR group and the very preterm background population, born before 30 gestational weeks (GW) in 1998-2004, with the exception of chronic lung disease (p <0.01). Survival without major neurological handicap at two years was equal between the two groups. Study II: At early school age, cognitive impairment was more prevalent in boys born very preterm with IUGR compared to a matched very preterm group with BW appropriate for gestational age (PT-AGA). Attention deficit disorders were more prevalent in children in both preterm groups compared to term children with birth weight AGA (T-AGA) (p <0.01). There was a trend towards more behavioral problems in the preterm groups. Study III: Lung function, assessed with spirometry in children at 6-10 years, was reduced in the PT-IUGR group compared to the T-AGA group. The PT-IUGR group had worse lung function when born after 26 GW in comparison to the PT-AGA group (p<0.05). Study IV: Cardiovascular measurements were assessed at 5-8 years. Systolic and mean blood pressure, adjusted for height, was higher in both preterm groups compared to the T-AGA group (p<0.05). Findings in the vascular measurements were different between the preterm groups; the PT-IUGR group had lower aortic stiffness (p<0.01) and lower endothelial-dependent vasodilation compared to the PT-AGA group (p<0.05), and thinner intima media thickness in the carotid artery compared to the T-AGA group (p<0.05). Conclusions: IUGR in very preterm birth did not have an impact on overall mortality or major handicaps. Impairment in lung function was only apparent in the preterm IUGR group after 26 GW, a period of gestation when delivery on fetal indication in general is considered acceptable. The adverse impact of IUGR on cognitive function was present at all gestational ages, but cognitive impairment was only significant in IUGR boys compared to preterm controls. The question whether the cognitive impairment in boys is transient or persistent remains unanswered. It is difficult to understand the implication of the outcomes of lower IMT and aortic stiffness seen in the preterm IUGR group on later cardiovascular health. Further studies have to be performed in older ages. The observed outcome would not seem to be sufficiently severe to refrain from delivery in these very preterm IUGR fetuses and we suggest that it is justified to deliver fetuses with IUGR and abnormal blood flow in the umbilical artery at early gestational age in order to prevent intrauterine death.