Definition, management and prognosis in severe early-onset fetal growth restriction

In severe early-onset fetal growth restriction (FGR), the fetus does not reach its genetic growth potential. Utero-placental insufficiency is the most common cause. FGR is associated with higher fetal mortality and long term child disabilities. Using meta-analysis, we found that 12% of pregnancies complicated by FGR result in antenatal death and 7% in neonatal death, but that only a few prospective studies reported the long-term neurodevelopment of the surviving children. We found an overall neurodevelopmental impairment rate of 11%. We added to that data a prospective study of 74 FGR children at five years, and found that 15% of the children had an abnormal IQ score and 38% had an abnormal motor score.
Several issues in FGR management remain. First, heterogeneity exists in the definition of FGR and a uniform definition is necessary. Second, the optimal moment of delivery, usually by Doppler measurements and cardiotocography, is crucial in the balance between fetal and infant risks. We show that short term variation (STV) of the cardiotocography is not statistically significant associated with fetal acidemia, thus needs to be further investigated. Third, pregnant women with FGR have a high co-incidence with hypertensive disorders in pregnancy, but our analyses show that ‘tight’ control of hypertension probably is associated with a lower birthweight.
In the search to find a possible treatment for FGR, the phosphodiesterase 5 inhibitor sildenafil was investigated in a placebo-controlled randomized controlled trial in 216 pregnant women with FGR. Sildenafil did not reduce the chance of neonatal mortality and morbidity. Moreover, an unexpected increase in neonatal pulmonary hypertension was observed, a finding that needs further investigation. Follow-up of the children born in this trial is underway. Sildenafil treatment is not the long hoped treatment to improve FGR pregnancies.