OPtimal TIming of COrticosteroids in Early-onset Fetal Growth REstriction: the OPTICORE Study (OPTICORE)

The aim of this observational study is to optimize the timing of antenatal corticosteroids administered to patients with pregnancies complicated by early-onset fetal growth restriction in order to reduce neonatal morbidity and mortality. In the Netherlands two main timing strategies of antenatal corticosteroids are commonly practiced. In this study the investigators will compare these two timing strategies regarding CCS administration in early-onset FGR on the combined endpoint of perinatal, neonatal and in-hospital mortality. In addition, the investigators aim to develop a dynamic, prediction tool, a novel technique in prediction research to predict the time-interval in days until delivery within this population. With that, the investigators aim to reduce neonatal morbidity and mortality for future FGR pregnancies.

Study Overview

• Status: Recruiting
• Conditions: Fetal Growth Retardation
• Intervention / Treatment: Drug: Corticosteroid

• Study Type: Observational
• Enrollment (Anticipated): 1800

Contacts and Locations

• Study Contact: Name: J. Kooiman, MD, PhD; Phone Number: 0031653942664; Email: j.kooiman@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 EA
    • Recruiting
    • UMC Utrecht, Wilhelmina Children's Hospital
    • Contact: M. van de Meent, MD, PhD Candidate; Phone Number: 0031611714404; Email: m.vandemeent@umcutrecht.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Singleton pregnancies complicated by early-onset FGR will be included in the study if they opt for active, neonatal management after counselling and are at least 18 years old.

Description

Inclusion Criteria:

• Early-onset FGR in accordance with the consensus-based definition of Gordijn et al. (19);
• Singleton pregnancy;
• Age ≥ 18 years;
• Installed active, neonatal management after counselling (thus having an indication for CCS administration in case of birth < 34 weeks of gestational age).

Exclusion Criteria:

• Multiple pregnancies;
• Fetal congenital abnormalities or antenatal diagnosed genetic disorders;
• Patients who stated that their patient or offspring data may not be used for scientific research.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Early-onset FGR	Drug: Corticosteroid; Antenatal corticosteroids are administered to pregnancies at risk for preterm birth in order to reduce risks of neonatal morbidity and mortality following preterm birth.; Other Names: Dexamethasone; Betamethasone; Antenatal corticosteroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome for the comparison of timing strategies will be the number of perinatal, neonatal and in-hospital deaths in the offspring, assessed by scrutinizing medical records	This data will be validated by use of the Dutch perinatal registration data (Perined)	From date of diagnosis of early-onset FGR up to hospital-discharge of the offspring, date of death of the offspring will be documented.
The primary outcome measure for the dynamic predictive tool will be defined as 'days until delivery'.	Candidate predictors for the dynamic, predictive tool will be: estimated fetal weight, pulsatility index of the umbilical artery, pulsatility index of the cerebral middle artery, cerebroplacental ratio, pulsatility index of veins ductus venosus, absence of interval growth, repetitive decelerations on CTG, short-term variability, subjective fetal movements, presence of hypertensive disorders of pregnancy, use of anti-hypertensive drugs, use of magnesium sulphate, number of hypertensive crises, presence of lung edema, progression of organ dysfunction.	From date of diagnosis of early-onset FGR up to delivery data regarding the candidate predictors, summarized under 'Description', will be documented on every day an ultrasound examination is performed.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mode of birth, assessed by scrutinizing medical records.	Mode of birth defined as vaginal or caesarian section.	This outcome measure will be documented by use of data from the day of birth.
Number of stillbirths, assessed by scrutinizing medical records.	Stillbirth is defined as death of fetus ante- or intrapartum	From diagnosis of early-onset FGR up to delivery this outcome measure will be documented.
Gestational age at birth (in days), assessed by scrutinizing medical records.	Gestational age will be recorded in weeks as well.	This outcome measure will be documented by use of data from the day of birth.
Number of preterm births, assessed by scrutinizing medical records.	Preterm birth defined as delivery before 37.0 weeks of gestational age.	This outcome measure will be documented by use of data from the day of birth.
Number of extremely preterm births, assessed by scrutinizing medical records.	Extremely preterm birth is defined as delivery before 28 weeks of gestational age.	This outcome measure will be documented by use of data from the day of birth.
Birthweight (in grams), assessed by scrutinizing medical records.	Birthweight defined as weight at time of birth (in grams)	This outcome measure will be documented by use of data from the day of birth.
Number of neonates with birthweight < 10th percentile (according to Hoftiezer percentiles), assessed by scrutinizing medical records.		This outcome measure will be documented by use of data from the day of birth.
Number of neonates with birthweight < 3rd percentile (according to Hoftiezer percentiles), assessed by scrutinizing medical records.		This outcome measure will be documented by use of data from the day of birth.
Number of neonates with need for mechanical ventilation, assessed by scrutinizing medical records.	Mechanical ventilation defined as need for intubation and mechanical ventilation to support gas exchange	From delivery up to hopsital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with bronchopulmonary dyspasia, assessed by scrutinizing medical records.	Bronchopulmonary dysplasia is diagnosed if gestational age <32 weeks: at a postmenstrual age of 36 weeks, >21% oxygen has been administered cumulatively for 28 or more days	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with necrotizing enterocolitis ≥ 2 according to the Bell's stages, assessed by scrutinizing medical records.		From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with neonatal seizures, assessed by scrutinizing medical records.	Neonatal seizures defined as transient electrographic change in the brain due to an abnormal, excessive or synchronous neuronal activity either with the occurrence of clinical signs (electro-clinical) or without them (electrographic only) in preterm infants	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with hypoxic-ischemic encephalopathy, assessed by scrutinizing medical records.	Hypoxic-ischemic encephalopathy defined as a clinical syndrome that results from a severe or prolonged hypoxic-ischemic episode before or during birth	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonatal deaths, assessed by scrutinizing medical records.	Death of the neonate within 28 days after birth	From delivery up to 28 days after birth of the offspring this outcome measure will be documented.
Number of in-hospital deaths, assessed by scrutinizing medical records.	Death of the neonate until hospital-discharge	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with respiratory distress syndrome, assessed by scrutinizing medical records.	Neonatal respiratory distress syndrome, characterized by extensive lung inflammation and surfactant catabolism leading to lung dysfunction, with need for surfactant	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with intraventricular hemorrhage, assessed by scrutinizing medical records.	Intraventricular hemorrhage grade 3 according to Papile et al., venous infarction, posthemorrhagic ventricular dilatation needing treatment	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with cystic periventricular leukomalacia, assessed by scrutinizing medical records.	Cystic periventricular leukomalacia is characterized by diffuse injury of the white matter, which possibly leads to cerebral palsy	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with retinopathy of prematurity, assessed by scrutinizing medical records.	Retinopathy of prematurity with plus disease for which treatment is needed	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with neonatal sepsis, assessed by scrutinizing medical records.	Distinction will be made in early-onset vs late-onset and clinical vs culture-proven	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates diagnosed with persistent pulmonary hypertension of the newborn, assessed by scrutinizing medical records.	Persistent pulmonary hypertension of the newborn occurs in case of persistent abnormally, elevated pulmonary vascular resistance after birth, leading to severe hypoxemia	From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Duration of supplemental oxygen therapy during admission of the offspring (in days), assessed by scrutinizing medical records.		From delivery up to hospital-discharge of the offspring this outcome measure will be documented.
Number of neonates with need for mechanical ventilation < 72 hours post-partum, assessed by scrutinizing medical records.	This is defined as need for intubation and mechanical strategies to support gas exchange within 72 hours after birth	From delivery up to 72 hours after birth this outcome measure will be documented.
Number of childs with cognitive impairment, assessed by scrutinizing medical records.	A decreased ability of cognitive function using Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at a corrected age of 24 months,. Severe disability will be defined as a Bayley Mental Development Index score more than 2SD below the mean score (i.e. ≤70). Moderate disability will be defined as a Bayley Mental Development Index score 1 to 2 SD below the mean score (i.e. 71-85)	From delivery up to 24 months corrected age of the offspring this outcome measure will be documented.
Number of childs with motor impairment, assessed by scrutinizing medical records.	A decreased ability of fine and gross motor function using part of the Bayley Scales and Infant and Toddler Development, Third Edition (BSID-III) at corrected age of 24 months. Severe disability will be defined as a score of more than 2 SD below the mean score (i.e. ≤70). Moderate disability will be defined as a score 1 to 2SD below the mean score (i.e. 71-85)	From delivery up to 24 months corrected age of the offspring this outcome measure will be documented.
Number of childs diagnosed with cerebral palsy, assessed by scrutinizing medical records.	Cerebral palsy is a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain	From delivery up to 24 months corrected age of the offspring this outcome measure will be documented.
Number of childs with hearing impairment, assessed by scrutinizing medical records.	A decreased ability of the auditory system requiring hearing aids or deafness	From delivery up to 24 months corrected age of the offspring this outcome measure will be documented.
Number of childs with visual impairment, assessed by scrutinizing medical records.	A decreased ability of the visual system requiring aids or blindness	From delivery up to 24 months corrected age of the offspring this outcome measure will be documented.
Number of maternal deaths, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of patients diagnosed with (pre-)eclampsia, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with a Glasgow Coma Score < 13, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with a stroke or reversible ischaemic neurological deficit, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with a transient ischaemic attack, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with cortical blindness or retinal detachment, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with posterior reversible encephalopathy, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with need for positive inotropic support, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with need for infusion of a third parenteral antihypertensive drug, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with myocardial ischaemia or infarction, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with oxygen saturation below 90%, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with ≥ 50% fraction of inspired oxygen for more than one hour, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with need for intubation, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with pulmonary oedema, assessed by scrutinizing medical records.	Determined by pulmonary auscultation.	From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with need for transfusion of any blood product, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with a platelet count < 50x10^9 per liter with no transfusion, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with hepatic dysfunction, assessed by scrutinizing medical records.	Hepatic dysfunction defined as asparate aminotransferase and alanine aminotransferase elevated more than twice the upper limit of normal.	From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with hepatic haematoma or rupture, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with acute renal insufficiency, assessed by scrutinizing medical records.	Acute renal insufficiency defined as creatinine >150 μmol/L with no pre-existing renal disease.	From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with acute renal failure, assessed by scrutinizing medical records.	Acute renal failure defined as creatinine >200 μmol/L in patients with pre-existing renal disease.	From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers with need for renal dialysis, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with placental abruption, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with severe ascites, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.
Number of mothers diagnosed with Bell's palsy, assessed by scrutinizing medical records.		From diagnosis of early-onset FGR up to six weeks post-partum this outcome measure will be documented.

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Stichting Achmea Gezondheidszor
• Investigators: Principal Investigator: J. Kooiman, MD, PhD, Epidemiologist, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: October 24, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: fetal growth restriction; antenatal corticosteroids; retrospective cohort study; dynamic predictive tool
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Fetal Growth Retardation; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Asthmatic Agents; Respiratory System Agents; Dexamethasone; Betamethasone
• Other Study ID Numbers: 22/613

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No