STUDY QUESTION: 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? SUMMARY ANSWER: 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 in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment. WHAT IS KNOWN ALREADY: Fetal growth is influenced by periconceptional maternal conditions. STUDY DESIGN, SIZE, DURATION: We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort. PARTICIPANTS/MATERIALS, SETTING, 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. MAIN 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 (ρ = 0.617, P < 0.001) and between embryonic HV and fetal HC (ρ = 0.660, P < 0.001) in 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 P < 0.05). LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care. STUDY FUNDING/COMPETING INTERESTS: 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.

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Keywords 3D ultrasound, embryo, head circumference, head volume, pregnancy
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Journal Human Reproduction
Koning, I.V, Baken, L, Groenenberg, I.A.L, Husen, S.C, Dudink, J, Willemsen, S.P, … Steegers-Theunissen, R.P.M. (2016). Growth trajectories of the human embryonic head and periconceptional maternal conditions. Human Reproduction, 31(5), 968–976. doi:10.1093/humrep/dew043