Cardiac Displacement From Third Trimester to Early Childhood

Active, not recruiting

Conditions: Fetal Growth Retardation
Intrauterine Growth Restriction
IUGR

Interventions: Other: Echocardiography
Procedure: Blood sample

Registration Number: NCT02583763

Lead Sponsor: University Hospital, Linkoeping

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 61

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.

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Controls	Blood sample	The moving sequences of the heart movement are collected at two occasions approximately 4 weeks apart. This takes place during gestational weeks 28-36. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 7 years of age. Blood sample will be taken from the umbilical cord at birth and again at 7 years of age. The investigators will analyze the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the children's DNA.
Fetuses/Children with IUGR	Echocardiography	The moving sequences of the heart movement are collected at the regular ultrasound examinations during pregnancy. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 7 years of age. Blood sample will be taken from the umbilical cord at birth and again at 7 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 children's DNA.
Fetuses/Children with IUGR	Blood sample	The moving sequences of the heart movement are collected at the regular ultrasound examinations during pregnancy. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 7 years of age. Blood sample will be taken from the umbilical cord at birth and again at 7 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 children's DNA.
Healthy Controls	Echocardiography	The moving sequences of the heart movement are collected at two occasions approximately 4 weeks apart. This takes place during gestational weeks 28-36. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 7 years of age. Blood sample will be taken from the umbilical cord at birth and again at 7 years of age. The investigators will analyze the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the children's DNA.

Primary Outcome Measures

Name	Time	Method
Velocity of the Cardiac Walls cm/s Divided With Chamber Length in mm = Quota cm/s / mm	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.	Echocardiography images of the heart's walls are outlined and the software extracts the movement in different directions. At each timepoint offline calculation were performed three times on each image and an averaged was calculated. The length of the heart from the level of the AV valve to the apex in left ventricle is used as a measurement for the size of the heart. As the velocity increases when the size of the heart increases a quota is used dividing the velocity by the length of the heart to be able to compare the velocity at different timepoints whe the child is growing. Quota=Left chamber velocity at septum stated in cm/s divided by ventricular length in mm.

Secondary Outcome Measures

Name	Time	Method
Cardiac Marker Troponin T	At birth and at 9 years of age	Comparing cardiac marker troponin T between the two groups
Insulin-like Growth Factor Binding Protein (IGFBP)	At birth and at 9years of age	Comparing Insulin-like growth factor binding protein (IGFBP) between the two groups
DNA Methylation and Gene Expression in Blood Monocytes and Lymphocytes	At birth and at 9 years of age	Changes in DNA methylation and gene expression will be compared between the two groups
Left Chamber Longitudinal Displacement in the Septal Wall at the AV Valve Level Corrected for Ventricular Length Expressed as a Ratio.	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.	Echocardiography images of the heart's walls are outlined and the software extracts the movement in mm in the myocardial wall from end diastole to end systole. The movement of the myocardium from end diastole to end systole at the AV valve level of the septal wall is measured in mm and expressed as a ratio compared to the ventricular length in mm at the end of diastole.
Cardiac Marker N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)	At birth and at 9 years of age	Comparing N-terminal prohormone of brain natriuretic peptide marker NT-ProBNP between the two groups
Insulin-like Growth Factor-1 (IGF-1)	At birth and at 9 years of age	Comparing IGF-1 between the two groups
Average Longitudinal 4 Segmental Strain in the Cardiac Wall. Shortening of the Myocardium in Systole.	At 3 months	Echocardiography images of the heart's walls are outlined and the software extracts the movement in different directions. A 4 chamber view of the hartt is used and calculation of 6 segments (2 basal, 2 mid and 2 apical segments) were performed three times on each image and an averaged was calculated. The 2 basal segments closeset to the AV valve and the two 2 mid segments were summed and averaged into average longitudinal 4 segmental strain. Strain in % is the averege shortening of the myocardium in systole.