Management of early-onset fetal growth restriction

This thesis aimed to provide an overview of the management of pregnancies complicated by early-onset FGR from diagnosis to birth. First, in Chapter 2, a prediction model was developed that could help physicians in clinical decision-making with regard to determining whether a patient should be monitored in a level III hospital (i.e. with a neonatal intensive care unit) or if a level II hospital would be sufficient. Also, this prediction tool could serve as an aid during parental counseling when a pregnancy is complicated by early-onset FGR. In Chapter 3 the time sequence of changes in maternal and fetal parameters from diagnosis of early-onset FGR to birth is summarized, which could further aid clinical decision-making in terms of transport of patients and timing of antenatal CCS therapy and birth. Chapters 4, 5, 6, and 7 focus on one of the few antenatal treatment strategies that is currently available to improve neonatal outcomes in pregnancies at risk for preterm birth, namely the administration of antenatal CCS. Evidence for beneficial or harmful effects of antenatal CCS is currently lacking in early-onset FGR as these pregnancies were excluded in the majority of studies and in the remaining studies subgroup analyses have not been performed in previously performed randomized controlled trials. Chapter 4 summarizes the effects of antenatal CCS therapy in animal models of FGR by the performance of a systematic review and meta-analysis. Subsequently, in Chapter 5, the study protocol of the OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction (OPTICORE) study is described, which aimed to (1) compare the main timing strategies of antenatal CCS in early-onset FGR in the Netherlands, and; (2) develop a dynamic, predictive tool for the days until indicated birth. Chapter 6 describes the results of the OPTICORE study regarding the comparison of timing strategies of antenatal CCS in the Netherlands. A similar analysis of practice variation was performed using the Dutch data of the Sildenafil TheRapy in dismal prognosis of early-onset fetal growth restriction (STRIDER) trial, of which results are provided in Chapter 7. Chapter 8 places practice variation in a broader, international context and describes a commentary on practice variation in the management of early-onset FGR pregnancies between the Netherlands and the United Kingdom to address research gaps and implications for future research. Finally, Chapter 9, focuses on long-term, cardiac consequences of FGR assessed by echocardiography as summarized by the performance of a systematic review and meta-analysis in offspring of both animal models of FGR and following a human pregnancy complicated by FGR. The results of this thesis are summarized and put into perspective in the general discussion (Chapter 10). This chapter identifies research gaps and therefore provides directives for future research.