Growth trajectories of the human fetal brain in healthy and complicated pregnancies and associations with neurodevelopmental outcome in the early life course.


Journal

Early human development
ISSN: 1872-6232
Titre abrégé: Early Hum Dev
Pays: Ireland
ID NLM: 7708381

Informations de publication

Date de publication:
12 2020
Historique:
received: 26 03 2020
revised: 03 09 2020
accepted: 03 10 2020
pubmed: 23 10 2020
medline: 1 10 2021
entrez: 22 10 2020
Statut: ppublish

Résumé

There is a need for non-invasive prenatal markers of the brain to assess fetuses at risk for poor postnatal neurodevelopmental outcome. Periconceptional maternal conditions and pregnancy complications impact prenatal brain development. To investigate associations between growth trajectories of fetal brain structures and neurodevelopmental outcome in children in the early life course. Periconceptional prospective observational cohort. Singleton pregnancies were included in the Rotterdam periconception cohort. Two- and three-dimensional ultrasound scans at 22, 26 and 32 weeks gestational age were analysed. Head circumference (HC), cerebellum, corpus callosum (CC), Sylvian fissure, insula and parieto-occipital fissure (POF) were measured. Neurodevelopment was evaluated using the Age-and-Stages-questionnaire-3 (ASQ-3) and the Child-Behaviour-Checklist (CBCL) at 2 years of age. Linear mixed models, used to estimate the prenatal brain growth trajectories, and linear regression models, used to evaluate the associations between prenatal brain structures and neurodevelopmental outcomes, were applied in the total study population, and in subgroups: fetal growth restriction (FGR), preterm birth (PTB), fetal congenital heart disease (CHD), and uncomplicated controls. Consent for participation was received from parents on behalf of their child 138/203 (68%). ASQ-3 was completed in 128/203 children (63%) and CBCL in 93/203 children (46%). Significant smaller subject-specific growth trajectories (growth rate of CC, HC, left insula, left POF and right POF and the baseline size of CC, HC, left POF and right POF) were found in the FGR subgroup, compared to the other subgroups (all p-values <0.05). In the total group (n = 138), the growth rate of the left insula was associated with poorer ASQ-3 score (β = -869.51; p < 0.05). Healthy controls (n = 106) showed a comparable association (β = -1209.87; p < 0.01). FGR (n = 10) showed a larger baseline size of the right Sylvian fissure in association with poorer CBCL-score (β = 4.13; p < 0.01). In CHD (n = 12) the baseline size of the left Sylvian fissure and its growth rate were associated with respectively poorer and better CBCL-scores (β = 3.11; p < 0.01); (β = -171.99; p < 0.01). In PTB (n = 10) no associations were found. This explorative study suggests associations between ultrasound measurements of fetal brain growth and neurodevelopmental outcome at 2 years of age. In future, this non-invasive technique may improve early identification of fetuses at risk for neurodevelopmental outcome and follow-up postnatal clinical care.

Sections du résumé

BACKGROUND
There is a need for non-invasive prenatal markers of the brain to assess fetuses at risk for poor postnatal neurodevelopmental outcome. Periconceptional maternal conditions and pregnancy complications impact prenatal brain development.
AIMS
To investigate associations between growth trajectories of fetal brain structures and neurodevelopmental outcome in children in the early life course.
STUDY DESIGN
Periconceptional prospective observational cohort.
SUBJECTS
Singleton pregnancies were included in the Rotterdam periconception cohort. Two- and three-dimensional ultrasound scans at 22, 26 and 32 weeks gestational age were analysed.
OUTCOME MEASURES
Head circumference (HC), cerebellum, corpus callosum (CC), Sylvian fissure, insula and parieto-occipital fissure (POF) were measured. Neurodevelopment was evaluated using the Age-and-Stages-questionnaire-3 (ASQ-3) and the Child-Behaviour-Checklist (CBCL) at 2 years of age. Linear mixed models, used to estimate the prenatal brain growth trajectories, and linear regression models, used to evaluate the associations between prenatal brain structures and neurodevelopmental outcomes, were applied in the total study population, and in subgroups: fetal growth restriction (FGR), preterm birth (PTB), fetal congenital heart disease (CHD), and uncomplicated controls.
RESULTS
Consent for participation was received from parents on behalf of their child 138/203 (68%). ASQ-3 was completed in 128/203 children (63%) and CBCL in 93/203 children (46%). Significant smaller subject-specific growth trajectories (growth rate of CC, HC, left insula, left POF and right POF and the baseline size of CC, HC, left POF and right POF) were found in the FGR subgroup, compared to the other subgroups (all p-values <0.05). In the total group (n = 138), the growth rate of the left insula was associated with poorer ASQ-3 score (β = -869.51; p < 0.05). Healthy controls (n = 106) showed a comparable association (β = -1209.87; p < 0.01). FGR (n = 10) showed a larger baseline size of the right Sylvian fissure in association with poorer CBCL-score (β = 4.13; p < 0.01). In CHD (n = 12) the baseline size of the left Sylvian fissure and its growth rate were associated with respectively poorer and better CBCL-scores (β = 3.11; p < 0.01); (β = -171.99; p < 0.01). In PTB (n = 10) no associations were found.
CONCLUSIONS
This explorative study suggests associations between ultrasound measurements of fetal brain growth and neurodevelopmental outcome at 2 years of age. In future, this non-invasive technique may improve early identification of fetuses at risk for neurodevelopmental outcome and follow-up postnatal clinical care.

Identifiants

pubmed: 33091852
pii: S0378-3782(20)30208-5
doi: 10.1016/j.earlhumdev.2020.105224
pii:
doi:

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

105224

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Mila S Welling (MS)

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands.

Sofie C Husen (SC)

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands.

Attie T J I Go (ATJI)

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands.

Irene A L Groenenberg (IAL)

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands.

Sten P Willemsen (SP)

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands; Department of Biostatistics, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands.

Hilmar H Bijma (HH)

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands.

Régine P M Steegers-Theunissen (RPM)

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, 3000, CA, Rotterdam, the Netherlands; Department of Pediatrics, Division of Neonatology, Sophia Children's Hospital, 3000, CA, Rotterdam, the Netherlands. Electronic address: r.steegers@erasmusmc.nl.

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