Intrauterine Fetal Growth Restriction - New Insights into Prenatal Detection, Definition, Surveillance and Delivery

Fetal growth restriction (FGR) is a common complication of pregnancy. Data presented in this thesis, which mainly originate from the national multicentre Prospective Observational Trial to Optimise Paediatric Health in IUGR (PORTO) study, consolidate knowledge in FGR, and contribute new insights into this important clinical problem. For the purpose of this study, FGR was defined as estimated fetal weight (EFW) below the 10th centile for gestation based on population standards. Contemporary practice was initially evaluated through survey and confirmed the inconsistencies in definition and management of pregnancies with FGR among Irish obstetricians. The PORTO study recruited 1,116 non-anomalous fetuses with EFW \u3c10th \u3ecentile; 1 in 20 infants (n=57) was affected by adverse perinatal outcome and 1 in 4 infants (n=312) required admission to neonatal intensive care. The objective of the primary analysis was to optimise the definition of FGR using population and customised standards and by analysing growth trajectories. Pregnancies at increased risk of adverse outcome were those with abnormal umbilical artery (UA) Doppler, EFWpublications, data showed that there was no single predominant pattern of Doppler deterioration occurring in one fetus over time. UA Doppler was found to be the most important vessel to inform perinatal outcome. Additional analyses focused on delivery outcomes and clinical decision making in FGR which showed that clinicians used ultrasound information to indicate delivery in 77% of cases. Evaluation of placental injuries in FGR identified villous developmental abnormalities as the most common lesion in infants with adverse perinatal outcome. Finally, this work was used to formulate an evidence-based care standard for FGR pregnancies in Ireland which resulted in the development of the first national clinical practice guideline on FGR. Together with published studies from the PORTO results, the guideline provides clinicians with evidence to improve and consolidate their current standard of care

Fetal growth restriction and the risk of perinatal mortality–case studies from the multicentre porto study

Background: Intrauterine growth restriction (IUGR) is the single largest contributing factor to perinatal mortality in non-anomalous fetuses. Advances in antenatal and neonatal critical care have resulted in a reduction in neonatal deaths over the past decades, while stillbirth rates have remained unchanged. Antenatal detection rates of fetal growth failure are low, and these pregnancies carry a high risk of perinatal death. Methods: The Prospective Observational Trial to Optimize Paediatric Health in IUGR (PORTO) Study recruited 1,200 ultrasound-dated singleton IUGR pregnancies, defined as EFW <10th centile, between 24(+0) and 36(+6) weeks gestation. All recruited fetuses underwent serial sonographic assessment of fetal weight and multi-vessel Doppler studies until birth. Perinatal outcomes were recorded for all pregnancies. Case records of the perinatal deaths from this prospectively recruited IUGR cohort were reviewed, their pregnancy details and outcome were analysed descriptively and compared to the entire cohort. Results: Of 1,116 non-anomalous singleton infants with EFW <10th centile, 6 resulted in perinatal deaths including 3 stillbirths and 3 early neonatal deaths. Perinatal deaths occurred between 24(+6) and 35(+0) weeks gestation corresponding to birthweights ranging from 460 to 2260 grams. Perinatal deaths occurred more commonly in pregnancies with severe growth restriction (EFW <3rd centile) and associated abnormal Doppler findings resulting in earlier gestational ages at delivery and lower birthweights. All of the described pregnancies were complicated by either significant maternal comorbidities, e. g. hypertension, systemic lupus erythematosus (SLE) or diabetes, or poor obstetric histories, e. g. prior perinatal death, mid-trimester or recurrent pregnancy loss. Five of the 6 mortalities occurred in women of non-Irish ethnic backgrounds. All perinatal deaths showed abnormalities on placental histopathological evaluation. Conclusions: The PNMR in this cohort of prenatally identified IUGR cases was 5.4/1,000 and compares favourably to the overall national rate of 4.1/1,000 births, which can be attributed to increased surveillance and timely delivery. Despite antenatal recognition of IUGR and associated maternal risk factors, not all perinatal deaths can be prevented

Fetal growth restriction and the risk of perinatal mortality–case studies from the multicentre porto study

Background: Intrauterine growth restriction (IUGR) is the single largest contributing factor to perinatal mortality in non-anomalous fetuses. Advances in antenatal and neonatal critical care have resulted in a reduction in neonatal deaths over the past decades, while stillbirth rates have remained unchanged. Antenatal detection rates of fetal growth failure are low, and these pregnancies carry a high risk of perinatal death. Methods: The Prospective Observational Trial to Optimize Paediatric Health in IUGR (PORTO) Study recruited 1,200 ultrasound-dated singleton IUGR pregnancies, defined as EFW <10th centile, between 24(+0) and 36(+6) weeks gestation. All recruited fetuses underwent serial sonographic assessment of fetal weight and multi-vessel Doppler studies until birth. Perinatal outcomes were recorded for all pregnancies. Case records of the perinatal deaths from this prospectively recruited IUGR cohort were reviewed, their pregnancy details and outcome were analysed descriptively and compared to the entire cohort. Results: Of 1,116 non-anomalous singleton infants with EFW <10th centile, 6 resulted in perinatal deaths including 3 stillbirths and 3 early neonatal deaths. Perinatal deaths occurred between 24(+6) and 35(+0) weeks gestation corresponding to birthweights ranging from 460 to 2260 grams. Perinatal deaths occurred more commonly in pregnancies with severe growth restriction (EFW <3rd centile) and associated abnormal Doppler findings resulting in earlier gestational ages at delivery and lower birthweights. All of the described pregnancies were complicated by either significant maternal comorbidities, e. g. hypertension, systemic lupus erythematosus (SLE) or diabetes, or poor obstetric histories, e. g. prior perinatal death, mid-trimester or recurrent pregnancy loss. Five of the 6 mortalities occurred in women of non-Irish ethnic backgrounds. All perinatal deaths showed abnormalities on placental histopathological evaluation. Conclusions: The PNMR in this cohort of prenatally identified IUGR cases was 5.4/1,000 and compares favourably to the overall national rate of 4.1/1,000 births, which can be attributed to increased surveillance and timely delivery. Despite antenatal recognition of IUGR and associated maternal risk factors, not all perinatal deaths can be prevented

An abnormal cerebroplacental ratio (CPR) is predictive of early childhood delayed neurodevelopment in the setting of fetal growth restriction

Background: Fetal growth restriction accounts for a significant proportion of perinatal morbidity and death. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the "at-risk" fetus in both fetal growth restriction and appropriate-for-gestational-age pregnancies. The Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction group has demonstrated previously that the presence of this "brain-sparing" effect is associated significantly with adverse perinatal outcomes in the fetal growth restriction cohort. However, data about neurodevelopment in children from pregnancies that are complicated by fetal growth restriction are sparse and conflicting. Objective: The aim of the Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction NeuroDevelopmental Assessment Study was to determine whether children born after fetal growth-restricted pregnancies are at additional risk of adverse early childhood developmental outcomes compared with children born small for gestational age. The objective of this secondary analysis was to describe the role of cerebroplacental ratio in the prediction of adverse early childhood neurodevelopmental outcome. Study design: Participants were recruited prospectively from the Perinatal Ireland multicenter observational Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction study cohort. Fetal growth restriction was defined as birthweight Results: Assessments were performed on 198 small-for-gestational-age children, 136 fetal growth-restricted children with abnormal umbilical artery Doppler images and normal cerebroplacental ratio, and 41 fetal growth-restricted children with both abnormal umbilical artery Doppler and cerebroplacental ratio. At 3 years of age, although there were no differences in head circumference, children who also had an abnormal cerebroplacental ratio had persistently shorter stature (P=.005) and lower weight (P=.18). Children from fetal growth restriction-affected pregnancies demonstrated poorer neurodevelopmental outcome than their small-for-gestational-age counterparts. Fetal growth-restricted pregnancies with an abnormal cerebroplacental ratio had significantly poorer neurologic outcome at 3 years of age across all measured variables. Conclusion: We have demonstrated that growth-restricted pregnancies with a cerebroplacental ratio <1 have a significantly increased risk of delayed neurodevelopment at 3 years of age when compared with pregnancies with abnormal umbilical artery Doppler evidence alone. This study further substantiates the benefit of routine assessment of cerebroplacental ratio in fetal growth-restricted pregnancies and for counseling parents regarding the long-term outcome of affected infants.</p

Dynamic growth changes in fetal growth restriction using serial ultrasonographic biometry and umbilical artery doppler: The multicenter PORTO study

Objective: To describe the growth dynamics of fetuses with initial fetal growth restriction (FGR) later outgrowing the 10th centile for estimated fetal weight with respect to perinatal outcomes and maternal factors.Methods: A multicenter prospective study recruited 1116 patients for ultrasound surveillance between 2010 and 2012. All pregnancies were growth-restricted singleton gestations between 24 + 0 and 36 + 0 weeks. Biometry and Doppler analysis were carried out, and delivery and adverse perinatal outcomes were recorded.Results: A total of 193 (17%) fetuses outgrew their diagnosis of initial FGR (surpassed the 10th centile) on their last sonogram before delivery. These fetuses were termed “growers,” to compare with the true FGR group. The mothers of “growers” were less likely to be smokers (14% vs 25%, P = 0.0001) or affected by hypertensive pregnancy complications (5.2% vs 15%, P = 0.001). Of the growers, 49 (25%) had an abnormal umbilical artery Doppler; however, in most cases (33/49, 67%), this was a single epi?sode of raised umbilical artery pulsatility index, which subsequently normalized.Conclusion: There were dynamic growth changes in FGR fetuses, with 17% out?growing their original diagnosis. Positive growth spurts more commonly occurred in healthy mothers. Once a fetus had outgrown the 10th centile, antenatal surveillance could be decreased.</p