Clinical trial NCT02583763: Cardiac Displacement From Third Trimester to Early Childhood
Official title: Cardiac Displacement From Third Trimester to Early Childhood
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: IUGR
Fetal Growth Retardation
Intrauterine Growth Restriction
Keywords: pro-brain natriuretic peptide (1-76)
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor I
Echocardiography
Velocity Vector Imaging
Heart Function Tests
Lead sponsor: University Hospital, Linkoeping
Sponsor class: OTHER
Collaborators: name: Ostergotland County Council, Sweden
name: Stiftelsen Samariten
First posted: 2015-10-22
Enrollment: 61
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This is a prospective case-control study in which fetuses from normal pregnancies will be compared with fetuses with IUGR. Parents will be asked to participate in the study in connection with the routine ultrasound examinations at the department of obstetrics to where they have been referred because of suspected IUGR. The control group will be randomly selected among pregnant women who come for routine ultrasound during pregnancy at gestational week 18-20.

Brief summary: The aim is to increase awareness of the relationship between (IUGR) and cardiac function in the foetus, the development of cardiac function over time after delivery and what significance a possible early disturbed myocardial function have for the neonate and the child during the first years of life.

Detailed description: This is a prospective case-control study in which fetuses from normal pregnancies will be compared with fetuses with IUGR. Parents will be asked to participate in the study in connection with the routine ultrasound examinations at the department of obstetrics to where they have been referred because of suspected IUGR. The control group will be randomly selected among pregnant women who come for routine ultrasound during pregnancy at gestational week 18-20.

Surveys will be performed in the third trimester and after delivery. During the ultrasound examinations standardized, moving sequences of the heart will be saved. Analyses will be performed off-line and analysed by vector velocity imaging software. With this technique, the investigator can quantify the chamber wall and myocardial movements. Speed (velocity), movement (displacement) and thickening/deformation (strain and strain rate) will be recorded in a structured and standardized manner.

When performing the analysis the heart's walls are outlined and the software extracts the movement in different directions.

Data will be obtained concerning the participating mothers previous illness, mothers' age, maternal smoking, BMI, any abnormalities during pregnancy, number of previous pregnancies. Other data that will be recorded are means of delivery and any abnormalities during previous pregnancies, such as hypertension, preeclampsia and pre-natal steroid treatment.

Additional data to be collected from the participating fetuses are flow profiles in the umbilical artery, ductus venosus and middle cerebral artery. Abdominal circumference and estimated weight will be registered.

Following delivery, the participating child's height, weight, head circumference and gestational age at birth are registered. Additional data that will be collected after delivery are umbilical vein and umbilical artery acid base values, Apgar score. If admitted to the pediatric ward the investigators will register the number of days hospitalized in the ward for post-natal care and diagnosis. The investigators plan to examine the participating baby with cardiac ultrasound between 12 and 72 hours after delivery and again when the participating child is 3-4 months old and at 7-9 years of age.

The investigators will take a blood sample from the umbilical cord at birth and again at 7-9 years of age. The investigators will analyse the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the participating children's DNA.

Based on power calculation the investigators plan to examine between 20-30 fetuses with IUGR and 40-60 healthy fetuses in the control group.

Eligibility criteria: Inclusion Criteria:

* Inclusion of research subjects: Growth restriction in routine pregnancy ultrasound, verified by specialist control. Gestational age based on Crown Rump Length measurements during the first trimester. Growth restriction defined by a deviation more than 22% from the normal curve at a given gestational age or growth rate deviates more than 10% compared to the previous measurement in relation to the expected weight.
* Inclusion of controls: Control individuals recruited among mothers who come to routine pregnancy ultrasound control at gestational week 18. These are randomly selected and then asked to participate.

Exclusion Criteria:

* Exclusion of both the cases with IUGR and the control cases are major malformations, twin pregnancy, signs of intrauterine infection during pregnancy, significant illness or significant medical treatment of the mother.

Primary outcomes:
measure: Velocity of the Cardiac Walls cm/s Divided With Chamber Length in mm = Quota cm/s / mm
timeFrame: After delivery echocardiography were performed. This is one time point. Due to the known dramatic hemodynamic changes for all children right after birth we defined this time point to somewhere between 12 and 72 hours of age.
Secondary outcomes:
measure: Left Chamber Longitudinal Displacement in the Septal Wall at the AV Valve Level Corrected for Ventricular Length Expressed as a Ratio.
timeFrame: After delivery echocardiography were performed. This is one time point. Due to the known dramatic hemodynamic changes for all children right after birth we defined this time point to somewhere between 12 and 72 hours of age.
measure: Average Longitudinal 4 Segmental Strain in the Cardiac Wall. Shortening of the Myocardium in Systole.
timeFrame: At 3 months
measure: Cardiac Marker Troponin T
timeFrame: At birth and at 9 years of age
measure: Cardiac Marker N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)
timeFrame: At birth and at 9 years of age
measure: Insulin-like Growth Factor-1 (IGF-1)
timeFrame: At birth and at 9 years of age
measure: Insulin-like Growth Factor Binding Protein (IGFBP)
timeFrame: At birth and at 9years of age
measure: DNA Methylation and Gene Expression in Blood Monocytes and Lymphocytes
timeFrame: At birth and at 9 years of age
Other outcomes:
Locations:
city: Linköping
country: Sweden
facility: Dept of Obstetrics and Gynecology
city: Linköping
country: Sweden
facility: Paediatric Department University Hospital
Study officials:
affiliation: Dept of Paediatric, Linköping
name: Olov Änghagen, PhD student
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska University Hospital, Stockholm
name: Nina Nelson, Professor
role: STUDY_CHAIR
affiliation: Dept of Paediatric, Linköping
name: Peter Bang, Professor
role: STUDY_CHAIR
affiliation: Dept of Clinical Physiology, Linköping
name: Jan Engvall, Professor
role: STUDY_CHAIR
affiliation: Dept of Clinical Physiology, Linköping
name: Eva Nylander, Professor
role: STUDY_CHAIR
References:
citation: Anghagen O, Engvall J, Gottvall T, Nelson N, Nylander E, Bang P. Developmental Differences in Left Ventricular Strain in IUGR vs. Control Children the First Three Months of Life. Pediatr Cardiol. 2022 Aug;43(6):1286-1297. doi: 10.1007/s00246-022-02850-y. Epub 2022 Mar 25.