Diagnosis and management of late-onset fetal growth restriction

This thesis describes the impact and the complexity of the diagnosis and management of late-onset fetal growth restriction. Fetal growth restriction is a condition in which the fetus is unable to reach its intrinsic growth potential due to reduced placental function. The lack of oxygen and nutrients hampers the fetus from optimal growth and development. Late-onset fetal growth restriction affects a high number of pregnancies and has a large societal impact in terms of adverse outcomes and an increased risk for the development of cardiovascular disease later in life. This thesis emphasizes that the detection of these fetuses at risk is challenging because symptoms may be subtle at term gestation. Small size as stand-alone modality is only moderately predictive and unreliable. The condition affects both small fetuses and fetuses who are within ‘normal’ birth weight ranges. Small- or large fetal size does not necessarily reflect pathology but puts the fetus at a higher risk and an appropriate size is not a guarantee of normal outcomes. The observed large heterogeneity in Dutch hospital protocols underlines the complexity of the condition. To overcome some of the inconsistencies, a consensus definition and core outcome set were developed. Furthermore, two research protocols to investigate the role of Doppler ultrasound as a marker of placental function in the management of late-onset fetal growth restriction are outlined. The challenge for the coming decade is to implement the consensus definitions and to evaluate (new) placental markers to improve identification of the compromised fetuses at (near) term gestation

Practice variation in diagnosis, monitoring and management of fetal growth restriction in the Netherlands

Objectives: Fetal growth restriction (FGR) is a condition characterized by its complexity in diagnosis and management. There is a need for early accurate diagnosis, evidence-based monitoring and management of FGR to improve neonatal outcomes. This study evaluated differences and similarities in protocols of Dutch hospitals in the approach of (suspected) FGR in the context of the national guideline. Study design: FGR protocols were collected from Dutch hospitals between November 2019 and June 2020. Collected data were coded for further analysis and categorized in eight predetermined key domains of definition, preventive measures, testing, referral, monitoring strategies, interventions, mode of delivery and pathologic placenta examination. Results: 55 of 71 approached hospitals (78 %) responded to the request and 54 protocols (76 %) were obtained. Protocols used variable definitions of FGR, and management was mostly based on fetal biometry results in combination with Doppler results (n = 47, 87 %). In pregnancies with an abdominal circumference (AC) or an estimated fetal weight (EFW) 95th percentile, (preterm) labour induction was recommended in the majority of the protocols regardless of fetal size (≥36 weeks: n = 2, 4 %; ≥37 weeks: n = 41, 76 %, not stated: n = 11, 20 %). Conclusion: This study found practice variation in all predetermined domains of FGR protocols of Dutch hospitals, underscoring the complexity of the condition. The differences found in this study feed the research agenda that informs the process of improving obstetric care by better identification of the fetus at risk for consequences of FGR, improving evidence-based monitoring strategies to identify (imminent) fetal hypoxia, and more accurate timing of delivery

Perinatal mortality rate and adverse perinatal outcomes presumably attributable to placental dysfunction in (near) term gestation: A nationwide 5-year cohort study.

IntroductionPlacental dysfunction can lead to perinatal hypoxic events including stillbirth. Unless there is overt severe fetal growth restriction, placental dysfunction is frequently not identified in (near) term pregnancy, particularly because fetal size is not necessarily small. This study aimed to evaluate, among (near) term births, the burden of hypoxia-related adverse perinatal outcomes reflected in an association with birth weight centiles as a proxy for placental function.Material and methodA nationwide 5-year cohort of the Dutch national birth registry (PeriNed) including 684,938 singleton pregnancies between 36+0 and 41+6 weeks of gestation. Diabetes, congenital anomalies, chromosomal abnormalities and non-cephalic presentations at delivery were excluded. The main outcome was antenatal mortality rate according to birthweight centiles and gestational age. Secondary outcomes included perinatal hypoxia-related outcomes, including perinatal death and neonatal morbidity, analyzed according to birthweight centiles.ResultsBetween 2015 and 2019, 1,074 perinatal deaths (0.16%) occurred in the study population (n = 684,938), of which 727 (0.10%) antenatally. Of all antenatal- and perinatal deaths, 29.4% and 27.9% occurred in birthweights below the 10th centile. The incidence of perinatal hypoxia-related outcomes was highest in fetuses with lowest birthweight centiles (18.0%), falling gradually up to the 50th and 90th centile where the lowest rates of hypoxia-related outcomes (5.4%) were observed.ConclusionPerinatal hypoxia-related events have the highest incidence in the lowest birthweight centiles but are identifiable throughout the entire spectrum. In fact, the majority of the adverse outcome burden in absolute numbers occurs in the group with a birthweight above the 10th centile. We hypothesize that in most cases these events are attributable to reduced placental function. Additional diagnostic modalities that indicate placental dysfunction at (near) term gestation throughout all birth weight centiles are eagerly wanted

Consensus definition of fetal growth restriction in intrauterine fetal death a delphi procedure

Context.—Fetal growth restriction is a risk factor for intrauterine fetal death. Currently, definitions of fetal growth restriction in stillborns are heterogeneous. Objectives.—To develop a consensus definition for fetal growth restriction retrospectively diagnosed at fetal autopsy in intrauterine fetal death. Design.—A modified online Delphi survey in an international panel of experts in perinatal pathology, with feedback at group level and exclusion of nonresponders. The survey scoped all possible variables with an open question. Variables suggested by 2 or more experts were scored on a 5-point Likert scale. In subsequent rounds, inclusion of variables and thresholds were determined with a 70% level of agreement. In the final rounds, participants selected the consensus algorithm. Results.—Fifty-two experts participated in the first round; 88% (46 of 52) completed all rounds. The consensus definition included antenatal clinical diagnosis of fetal growth restriction OR a birth weight lower than third percentile OR at least 5 of 10 contributory variables (risk factors in the clinical antenatal history: birth weight lower than 10th percentile, body weight at time of autopsy lower than 10th percentile, brain weight lower than 10th percentile, foot length lower than 10th percentile, liver weight lower than 10th percentile, placental weight lower than 10th percentile, brain weight to liver weight ratio higher than 4, placental weight to birth weight ratio higher than 90th percentile, histologic or gross features of placental insufficiency/ malperfusion). There was no consensus on some aspects, including how to correct for interval between fetal death and delivery. Conclusions.—A consensus-based definition of fetal growth restriction in fetal death was determined with utility to improve management and outcomes of subsequent pregnancies