title: First trimester size charts of embryonic brain structures.
abstract: OBJECTIVE
  Can reliable size charts of human embryonic brain structures be created from three-dimensional ultrasound (3D-US) visualizations?
  
  
  CONCLUSIONS
  Reliable size charts of human embryonic brain structures can be created from high-quality images.
  
  
  BACKGROUND
  Previous studies on the visualization of both the cavities and the walls of the brain compartments were performed using 2D-US, 3D-US or invasive intrauterine sonography. However, the walls of the diencephalon, mesencephalon and telencephalon have not been measured non-invasively before. Last-decade improvements in transvaginal ultrasound techniques allow a better visualization and offer the tools to measure these human embryonic brain structures with precision.
  
  
  METHODS
  This study is embedded in a prospective periconceptional cohort study. A total of 141 pregnancies were included before the sixth week of gestation and were monitored until delivery to assess complications and adverse outcomes.
  
  
  METHODS
  For the analysis of embryonic growth, 596 3D-US scans encompassing the entire embryo were obtained from 106 singleton non-malformed live birth pregnancies between 7(+0) and 12(+6) weeks' gestational age (GA). Using 4D View (3D software) the measured embryonic brain structures comprised thickness of the diencephalon, mesencephalon and telencephalon, and the total diameter of the diencephalon and mesencephalon.
  
  
  RESULTS
  Of 596 3D scans, 161 (27%) high-quality scans of 79 pregnancies were eligible for analysis. The reliability of all embryonic brain structure measurements, based on the intra-class correlation coefficients (ICCs) (all above 0.98), was excellent. Bland-Altman plots showed moderate agreement for measurements of the telencephalon, but for all other measurements the agreement was good. Size charts were constructed according to crown-rump length (CRL).
  
  
  CONCLUSIONS
  The percentage of high-quality scans suitable for analysis of these brain structures was low (27%).
  
  
  CONCLUSIONS
  The size charts of human embryonic brain structures can be used to study normal and abnormal development of brain development in future. Also, the effects of periconceptional maternal exposures, such as folic acid supplement use and smoking, on human embryonic brain development can be a topic of future research.
  
  
  BACKGROUND
  This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus University Medical Center. M.G. was supported by an additional grant from the Sophia Foundation for Medical Research (SSWO grant number 644). No competing interests are declared.
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Center, Rotterdam, PO Box 2040, 3000 CA, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Gijtenbeek
authors.forename: H
authors.initials: H
authors.lastname: Bogers
authors.forename: I A L
authors.initials: IA
authors.lastname: Groenenberg
authors.forename: N
authors.initials: N
authors.lastname: Exalto
authors.forename: S P
authors.initials: SP
authors.lastname: Willemsen
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: P H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D001921:Brain / Q000196:embryology* / Q000473:pathology; D018568:Crown-Rump Length; D005260:Female; D005865:Gestational Age; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D015999:Multivariate Analysis; D009929:Organ Size; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D012016:Reference Values; D015203:Reproducibility of Results; D016216:Ultrasonography, Prenatal
keywords: embryo development; embryology; pregnancy; prenatal diagnosis; ultrasound