Dataset Information

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

ABSTRACT:

Background

Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term.

Objective

The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes.

Methods

This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs.

Results

Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023.

Conclusions

The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities.

Trial registration

ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823.

International registered report identifier (irrid)

DERR1-10.2196/37452.

SUBMITTER: Garcia-Manau P

PROVIDER: S-EPMC9597418 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

Garcia-Manau Pablo P Mendoza Manel M Bonacina Erika E Martin-Alonso Raquel R Martin Lourdes L Palacios Ana A Sanchez Maria Luisa ML Lesmes Cristina C Hurtado Ivan I Perez Esther E Tubau Albert A Ibañez Patricia P Alcoz Marina M Valiño Nuria N Moreno Elena E Borrero Carlota C Garcia Esperanza E Lopez-Quesada Eva E Diaz Sonia S Broullon Jose Roman JR Teixidor Mireia M Chulilla Carolina C Gil Maria M MM Lopez Monica M Candela-Hidalgo Amparo A Salinas-Amoros Andrea A Moreno Anna A Morra Francesca F Vaquerizo Oscar O Soriano Beatriz B Fabre Marta M Gomez-Valencia Elena E Cuiña Ana A Alayon Nicolas N Sainz Jose Antonio JA Vives Angels A Esteve Esther E Ocaña Vanesa V López Miguel Ángel MÁ Maroto Anna A Carreras Elena E

JMIR research protocols 20221011 10

<h4>Background</h4>Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angi ...[more]

PMID: 36222789

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Project description:ObjectiveTo estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation.MethodsThis was a retrospective cohort study of all singleton, nonanomalous pregnancies undergoing ultrasonography to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infectious etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight less than the 10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birth weight less than the 10th percentile. Secondary outcomes included preterm delivery at less than 37 and less than 28 weeks of gestation, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis.ResultsOf 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with a more than fivefold increase in risk of SGA at birth (36.9% compared with 9.1%, adjusted odds ratio [OR] 5.5, 95% CI 4.3-7.0), stillbirth (2.5% compared with 0.4%, OR 6.2, 95% CI 2.7-12.8), and neonatal death (1.4% compared with 0.3%, OR 5.2, 95% CI 1.6-13.5). Rates of indicated preterm birth at less than 37 weeks of gestation (7.3% compared with 3.3%, OR 2.3, 95% CI 1.5-3.5) and less than 28 weeks of gestation (2.5% compared with 0.2%, OR 10.8, 95% CI 4.5-23.4), neonatal need for respiratory support (16.9% compared with 7.8%, adjusted OR 1.6, 95% CI 1.1-2.2), and necrotizing enterocolitis (1.4% compared with 0.2%, OR 7.7, 95% CI 2.3-20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different.ConclusionAlthough fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.

Project description:IntroductionEarly-onset fetal growth restriction is a pregnancy complication often coinciding with abnormal Doppler flow in the umbilical artery. Absent or reversed end-diastolic flow in the umbilical artery is associated with adverse perinatal outcome. As the optimal management of this condition is unclear, the objective of this study was to analyze the time interval from admission to delivery of pregnancies with early-onset fetal growth restriction, while pursuing a policy of postponing delivery unless active management of labor would be required because of fetal distress or maternal condition. We also assessed short- and long-term perinatal outcome.Material and methodsIn this historical cohort study, all pregnant women with singleton pregnancies, admitted during 2004-2015 with early-onset fetal growth restriction were included. Pregnancies with absent or reversed end-diastolic flow (AREDF) were compared with pregnancies with a positive end-diastolic Doppler flow (PEDF). Time until delivery was determined and perinatal outcome was assessed for both groups.ResultsIn our study, 111 women were allocated to the PEDF group and 109 to the AREDF group. In the AREDF group, fetal distress was more often an indication for delivery, in comparison with the PEDF group (p = .004). Median time until delivery in patients admitted between 26 and 28 weeks' gestation was 6+5 weeks in the PEDF group and 1+4 weeks in the AREDF group (p = .001). No statistically significant difference was found between the Doppler groups in the composite adverse neonatal outcome, which includes at least one of the following outcomes: infant respiratory distress syndrome, sepsis, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage >grade 2, periventricular leukomalacia and perinatal death (p = .63).ConclusionsIn this study, comprising pregnancies with early-onset fetal growth restriction, fetal distress was observed more frequently in the AREDF group with the consequence of delivery at an earlier stage of gestation, compared with the PEDF group. AREDF was not associated with increased perinatal morbidity and mortality compared with PEDF.

Project description:Fetal growth restriction (FGR) is associated with short- and long-term morbidity, often with fetal compromise in utero, evidenced by abnormal Doppler velocimetry of fetal vessels. Lipids are vital for growth and development, but metabolism in FGR pregnancy, where fetuses do not grow to full genetic potential, is poorly understood. We hypothesize that triglyceride concentrations are increased in placentas and that important complex lipids are reduced in cord plasma from pregnancies producing the smallest babies (birth weight < 5%) and correlate with ultrasound Dopplers. Dopplers (umbilical artery, UA; middle cerebral artery, MCA) were assessed longitudinally in pregnancies diagnosed with estimated fetal weight (EFW) < 10% at ≥29 weeks gestation. For a subset of enrolled women, placentas and cord blood were collected at delivery, fatty acids were extracted and targeted lipid class analysis (triglyceride, TG; phosphatidylcholine, PC; lysophosphatidylcholine, LPC; eicosanoid) performed by LCMS. For this sub-analysis, participants were categorized as FGR (Fenton birth weight, BW ≤ 5%) or SGA "controls" (Fenton BW > 5%). FGRs (n = 8) delivered 1 week earlier (p = 0.04), were 29% smaller (p = 0.002), and had 133% higher UA pulsatility index (PI, p = 0.02) than SGAs (n = 12). FGR plasma TG, free arachidonic acid (AA), and several eicosanoids were increased (p < 0.05); docosahexaenoic acid (DHA)-LPC was decreased (p < 0.01). Plasma TG correlated inversely with BW (p < 0.05). Plasma EET, non-esterified AA, and DHA correlated inversely with BW and directly with UA PI (p < 0.05). Placental DHA-PC and AA-PC correlated directly with MCA PI (p < 0.05). In fetuses initially referred for inadequate fetal growth (EFW < 10%), those with BW ≤ 5% demonstrated distinctly different cord plasma lipid profiles than those with BW > 5%, which correlated with Doppler PIs. This provides new insights into fetal lipidomic response to the FGR in utero environment. The impact of these changes on specific processes of growth and development (particularly fetal brain) have not been elucidated, but the relationship with Doppler PI may provide additional context for FGR surveillance, and a more targeted approach to nutritional management of these infants.

Project description:ObjectiveTo evaluate the relationship between Doppler and biometric ultrasound parameters measured at diagnosis and perinatal adverse outcome in a cohort of late-onset growth-restricted (FGR) fetuses.MethodsThis was a multicenter retrospective study of data obtained between 2014 and 2019 including non-anomalous singleton pregnancies complicated by late-onset FGR (≥ 32 weeks), which was defined either as abdominal circumference (AC) or estimated fetal weight (EFW) < 10th percentile for gestational age or as reduction of the longitudinal growth of AC by over 50 percentiles compared to ultrasound scan performed between 18 and 32 weeks of gestation. We evaluated the association between sonographic findings at diagnosis of FGR and composite adverse perinatal outcome (CAPO), defined as stillbirth or at least two of the following: obstetric intervention due to intrapartum fetal distress, neonatal acidemia, birth weight < 3rd percentile and transfer to the neonatal intensive care unit (NICU).ResultsOverall, 468 cases with complete biometric and umbilical, fetal middle cerebral and uterine artery (UtA) Doppler data were included, of which 53 (11.3%) had CAPO. On logistic regression analysis, only EFW percentile was associated independently with CAPO (P = 0.01) and NICU admission (P < 0.01), while the mean UtA pulsatility index (PI) multiples of the median (MoM) > 95th percentile at diagnosis was associated independently with obstetric intervention due to intrapartum fetal distress (P = 0.01). The model including baseline pregnancy characteristics and the EFW percentile was associated with an area under the receiver-operating-characteristics curve of 0.889 (95% CI, 0.813-0.966) for CAPO (P < 0.001). A cut-off value for EFW corresponding to the 3.95th percentile was found to discriminate between cases with and those without CAPO, yielding a sensitivity of 58.5% (95% CI, 44.1-71.9%), specificity of 69.6% (95% CI, 65.0-74.0%), positive predictive value of 19.8% (95% CI, 13.8-26.8%) and negative predictive value of 92.9% (95% CI, 89.5-95.5%).ConclusionsRetrospective data from a large cohort of late-onset FGR fetuses showed that EFW at diagnosis is the only sonographic parameter associated independently with the occurrence of CAPO, while mean UtA-PI MoM > 95th percentile at diagnosis is associated independently with intrapartum distress leading to obstetric intervention. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Project description:ObjectiveTo evaluate the role of antenatal administration of corticosteroids for fetal lung maturation on the short-term perinatal outcome of pregnancy complicated by late fetal growth restriction (FGR).MethodsThis cohort study was a secondary analysis of a multicenter prospective observational study, the TRUFFLE-2 feasibility study, conducted between 2017 and 2018 in 33 European perinatal centers. The study included women with a singleton pregnancy from 32 + 0 to 36 + 6 weeks of gestation with a fetus considered at risk for FGR, defined as estimated fetal weight (EFW) and/or fetal abdominal circumference < 10th percentile, or umbilicocerebral ratio (UCR) ≥ 95th percentile or a drop of more than 40 percentile points in abdominal circumference measurement from the 20-week scan. For the purposes of the current study, we identified women who received a single course of steroids to improve fetal lung maturation before delivery. Each exposed pregnancy was matched with one that did not receive antenatal corticosteroids (ACS) (control), based on gestational age at delivery and birth weight. The primary adverse outcome was a composite of abnormal condition at birth, major neonatal morbidity or perinatal death.ResultsA total of 86 pregnancies that received ACS were matched to 86 controls. The two groups were similar with respect to gestational age (33.1 vs 33.3 weeks), EFW (1673 vs 1634 g) and UCR (0.68 vs 0.62) at inclusion, and gestational age at delivery (35.5 vs 35.9 weeks) and birth weight (1925 vs 1948 g). No significant differences were observed between the exposed and non-exposed groups in the incidence of composite adverse outcome (28% vs 24%; P = 0.73) or any of its elements.ConclusionThe present data do not show a beneficial effect of steroids on short-term outcome of fetuses with late FGR. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dataset Information

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

Background

Objective

Methods

Results

Conclusions

Trial registration

International registered report identifier (irrid)

Publications

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

Similar Datasets

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