title: Growth trajectories of the human embryonic head and periconceptional maternal conditions.
abstract: OBJECTIVE
  Can growth trajectories of the human embryonic head be created using 3D ultrasound (3D-US) and virtual reality (VR) technology, and be associated with second trimester fetal head size and periconceptional maternal conditions?
  
  
  CONCLUSIONS
  Serial first trimester head circumference (HC) and head volume (HV) measurements were used to create reliable growth trajectories of the embryonic head, which were significantly associated with fetal head size and periconceptional maternal smoking, age and ITALIC! in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment.
  
  
  BACKGROUND
  Fetal growth is influenced by periconceptional maternal conditions.
  
  
  METHODS
  We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort.
  
  
  METHODS
  Bi-parietal diameter and occipital frontal diameter to calculate HC, HV and crown-rump length (CRL) were measured weekly between 9 + 0 and 12 + 6 weeks gestational age (GA) using 3D-US and VR. Fetal HC was obtained from second trimester structural anomaly scans. Growth trajectories of the embryonic head were created with general additive models and linear mixed models were used to estimate associations with maternal periconceptional conditions as a function of GA and CRL, respectively.
  
  
  RESULTS
  A total of 303 3D-US images of 149 pregnancies were eligible for embryonic head measurements (intra-class correlation coefficients >0.99). Associations were found between embryonic HC and fetal HC ( ITALIC! ρ = 0.617, ITALIC! P < 0.001) and between embryonic HV and fetal HC ( ITALIC! ρ = 0.660, ITALIC! P < 0.001) in ITALIC! Z-scores. Maternal periconceptional smoking was associated with decreased, and maternal age and IVF/ICSI treatment with increased growth trajectories of the embryonic head measured by HC and HV (All ITALIC! P < 0.05).
  
  
  CONCLUSIONS
  The consequences of the small effect sizes for neurodevelopmental outcome need further investigation. As the study population consists largely of tertiary hospital patients, external validity should be studied in the general population.
  
  
  CONCLUSIONS
  Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care.
  
  
  BACKGROUND
  This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands Department of Pediatrics, Division of Neonatology, Sophia Children's Hospital, Rotterdam 3000 CA, The Netherlands.
authors.forename: I V
authors.initials: IV
authors.lastname: Koning
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Baken
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
authors.forename: I A L
authors.initials: IA
authors.lastname: Groenenberg
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Husen
authors.affiliation: Department of Pediatrics, Division of Neonatology, Sophia Children's Hospital, Rotterdam 3000 CA, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Dudink
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: S P
authors.initials: SP
authors.lastname: Willemsen
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Gijtenbeek
authors.affiliation: Department of Bioinformatics, Erasmus MC University Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: A H J
authors.initials: AH
authors.lastname: Koning
authors.affiliation: Department of Pediatrics, Division of Neonatology, Sophia Children's Hospital, Rotterdam 3000 CA, The Netherlands.
authors.forename: I K M
authors.initials: IK
authors.lastname: Reiss
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands Department of Pediatrics, Division of Neonatology, Sophia Children's Hospital, Rotterdam 3000 CA, The Netherlands r.steegers@erasmusmc.nl.
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D018568:Crown-Rump Length; D005260:Female; D005307:Fertilization in Vitro; D047109:Fetal Development; D005333:Fetus / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D006257:Head / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000196:embryology*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D016014:Linear Models; D008423:Maternal Age; D009426:Netherlands; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D012907:Smoking; D016216:Ultrasonography, Prenatal / Q000379:methods
keywords: 3D ultrasound; embryo; head circumference; head volume; pregnancy