Changes in structural brain development after selective fetal growth restriction in monochorionic twins

Ultrasound in Obstetrics and Gynecology, vol. 59, pp. 747–755

Abstract

Abstract Objectives Fetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question, FGR singletons have been compared primarily to matched appropriately grown singletons, a design which is inherently biased by differences in genetic and maternal factors. To overcome these limitations, we conducted a within‐pair comparison of neonatal structural cerebral ultrasound measurements in monochorionic twin pairs with selective FGR (sFGR). Methods Structural cerebral measurements on neonatal cerebral ultrasound were compared between the smaller and larger twins of monochorionic twin pairs with sFGR, defined as a birth‐weight discordance (BWD) ≥ 20%, born in our center between 2010 and 2020. Measurements from each twin pair were also compared with those of an appropriately grown singleton, matched according to sex and gestational age at birth. Results Included were 58 twin pairs with sFGR, with a median gestational age at birth of 31.7 (interquartile range, 29.9–33.8) weeks and a median birth weight of 1155 g for the smaller twin and 1725 g for the larger twin (median BWD, 32%). Compared with both the larger twin and the singleton, the smaller twin had significantly smaller cerebral structures (corpus callosum, vermis, cerebellum), less white/deep gray matter and smaller intracranial surface area and volume. Intracranial‐volume discordance and BWD correlated significantly (R2 = 0.228, P < 0.0001). The median intracranial‐volume discordance was smaller than the median BWD (19% vs 32%, P < 0.0001). After correction for intracranial volume, only one of the observed differences (biparietal diameter) remained significant for the smaller twin vs both the larger twin and the singleton. Conclusions In monochorionic twins with sFGR, neonatal cerebral ultrasound reveals an overall, proportional restriction in brain growth, with smaller cerebral structures, less white/deep gray matter and smaller overall brain‐size parameters in the smaller twin. There was a positive linear relationship between BWD and intracranial‐volume discordance, with intracranial‐volume discordance being smaller than BWD. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Authors 9

1. Sophie G. Groene corresponding Aachen Molecular Epidemiology Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands Neonatology Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center · Willem-Alexander Kinderziekenhuis

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

   Neonatology, Willem‐Alexander Children's Hospital, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

   Neonatology, Willem‐Alexander Children's Hospital, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

2. Linda S. de Vries Aachen Neonatology Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center · Willem-Alexander Kinderziekenhuis

   Affiliation as printed

   Neonatology, Willem‐Alexander Children's Hospital, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

3. Femke Slaghekke Aachen Fetal Therapy Department of Obstetrics Leiden University Medical Center Leiden The Netherlands Division of Fetal Therapy Department of Obstetrics, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Fetal Therapy, Department of Obstetrics Leiden University Medical Center Leiden The Netherlands

   Division of Fetal Therapy, Dept. of Obstetrics, Leiden University Medical Center, Leiden, the Netherlands

4. Monique C. Haak Aachen Fetal Therapy Department of Obstetrics Leiden University Medical Center Leiden The Netherlands Division of Fetal Therapy Department of Obstetrics, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Fetal Therapy, Department of Obstetrics Leiden University Medical Center Leiden The Netherlands

   Division of Fetal Therapy, Dept. of Obstetrics, Leiden University Medical Center, Leiden, the Netherlands

5. Bastiaan T. Heijmans Aachen Molecular Epidemiology Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands Division of Molecular Epidemiology Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

   Division of Molecular Epidemiology, Dept. of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands

6. Arno A.W. Roest Aachen Pediatric Cardiology Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center · Willem-Alexander Kinderziekenhuis

   Affiliation as printed

   Pediatric Cardiology, Willem‐Alexander Children's Hospital, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

7. Enrico Lopriore Aachen Neonatology Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center · Willem-Alexander Kinderziekenhuis

   Affiliation as printed

   Neonatology, Willem‐Alexander Children's Hospital, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

8. Jeanine M.M. van Klink Aachen Neonatology Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center · Willem-Alexander Kinderziekenhuis

   Affiliation as printed

   Neonatology, Willem‐Alexander Children's Hospital, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

9. Sylke Jeanne Steggerda Aachen Neonatology Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center · Willem-Alexander Kinderziekenhuis

   Affiliation as printed

   Neonatology, Willem‐Alexander Children's Hospital, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands