Selective intrauterine growth restriction (sIUGR)
Conditions
Interventions
None listed
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
No minimum to 11 Years
Inclusion criteria
Inclusion criteria: - MC twin pregnancies. - Parents aged >=18 years, who are able to consent. - Written informed consent from both parents to participate in this longitudinal study, form being approved by the Ethic Committee.
Exclusion criteria
Exclusion criteria: - The presence of major anatomical abnormalities. - Genetic disorders - Triplet pregnancies or higher order multiple pregnancies. - Twin reversed arterial perfusion (TRAP) - MC twins with single or double fetal demise
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Change in percentage DNA methylation in MSCs at birth within MC twin pairs in relation to measures of intra-uterine discordance: percentage of birthweight difference and percentage of placenta share difference. 2. Within twin pair differences at follow-up in childhood (2, 5, 8 years) with respect to risk of CVD and NDI as explained by the DNA methylation differences at birth. Study parameters of CVD at follow-up: cardiac load reflected by left-ventricular mass, vascular stiffness reflected by aortic pulse-wave velocity (aPWV) and remodelling of the arterial wall (carotid intima-media thickness (cIMT). Study parameters of neurodevelopment: cognitive, language and motor developmental test scores (with a normed mean of 100 and a standard deviation of 15). | — |
Secondary
| Measure | Time frame |
|---|---|
| Prenatal Within twin-pair differences in fetal growth and cardiovascular parameters (ultrasound scans every 2 weeks) • Head- and abdominal circumference, femur length • Cardiac measurements: Tricuspid/mitral regurgitation, cardiothoracic ratio, subjective assessment of (bi-) ventricular hypertrophy • Pulsed wave Doppler measurements: ductus venosus (DV), umbilical vein (VU), umbilical artery (AU), middle cerebral artery (ACM), tricuspid valve (TV), mitral valve (MV), aortic valve (AoV) and pulmonary valve (PV) • Myocardial perfusion imaging (MPI) • Speckle tracking strain analysis of the left and right ventricle • Color Tissue Doppler Imaging (cTDI) of the myocardium Birth Functional read-outs of epigenetic differences in MSCs • Gene expression (gene-specific (qPCR) and whole-transcriptome (RNA-seq). • Cellular metabolism (e.g. using Seahorse Biosciences XF96 Analyzer). Neonatal evaluation (for each twin) • Gestational age at birth • Gender • Apgar score at 1, 5 and 10 minutes • Birth order of twins • Status of the twins: donor versus recipient in TTTS or TAPS; growth restricted versus normal grown co-twin in sIUGR • Differences in brain maturation, myelination, global brain abnormality score and specific types of brain lesions (using the Kidokoro score), cortical thickness and folding and quantitative measures of brain connectivity, and volumetric brain growth • Within-twin pair differences in placental cortisol and scalp hair cortisol • Neonatal mortality: up to 28 days of life • Neonatal morbidity including • Respiratory distress syndrome • Proven early onset neonatal sepsis • Retinopathy of prematurity • Necrotizing enterocolitis[8] • Patent ductus arteriosus • Severe cerebral injury, including at least one of the following • intraventricular hemorrhage >=grade 3[9] • cystic periventricular leukomalacia >=grade 2[10] • ventricular dilatation >p97[11] • porencephalic or parenchymal cysts • severe cerebral lesions associated | — |
Countries
Netherlands
Outcome results
None listed