One of the main aims of preterm infant care is to mitigate the impact of preterm birth on the crucial steps of brain development otherwise taking place in utero. Tracking head growth, particularly from birth to term, has been associated with attaining this goal (1). While there are more precise methods of determining head volume (2–6), the tape measure is superior to all of them in effortlessness, availability and safety. However, occipitofrontal head circumference (OFC) is a two-dimensional measure, disregarding vertical head growth. Some of the discrepancies between OFC and brain volume have been shown to be reduced by taking additional measurements into account (5). Ear-to-ear distances (EED) can be measured as easily as OFC and account for the third dimension of head growth. However, the lack of reference values limits the clinical use of additional head measurements. Herein, we set out to close this gap and calculate percentile curves of EED measurements.

To the best of our knowledge these are the first charts of intrauterine EED growth for gestational ages. Since preterm infant growth is frequently assessed by comparing it to intrauterine growth, these charts provide a new tool for assessing head growth in all three dimensions.

We plotted OFC, CHL and BW from our sample in the same manner as EED and contrasted the resulting centiles with those by Fenton and Kim (13) and Voigt et al. (17) (see Figures 5–7). Compared to Voigt et al. (17) these relative differences were always positive, which means that Voigt et al. had larger values, with OFC values mostly within a 5% interval. This is most likely because they excluded multiple gestations while we kept them in our set. Interquartile ranges of relative differences to Fenton and Kim (13). OFCs and CHLs are crossing 0 and mostly fall within a 1% interval (see Supplementary Figure 4). Our centiles of OFC, weight and CHL closely resemble those by Fenton and Kim (13): The differences between 50th percentiles are minute and do not follow the same direction (i.e. one being consistently smaller than the other). Only the extreme percentiles show larger differences, especially for the term gestations. This may indicate that our infants have similar anthropometrics and allow using our new EED charts as an addition to the charts by Fenton and Kim (13).

While we relied on the exact gestational age as reported by the obstetrician, Fenton and Kim (13) rounded gestational ages down to completed weeks and compensated this by shifting the age forward by half a week. The latter has been suggested for low resource settings where one is less certain of gestational ages (18) which seems to work well since the resulting growth curves closely resemble each other with no relevant differences.

Fenton and Kim (13) combined various samples ranging from 623 to 14,146 infants with gestational ages below 30 weeks; our sample contains 786 considering the exact gestational ages reported by the obstetricians. The WHO growth charts for OFC were designed from data of 6,697 term neonates (19). While our sample is smaller since it comes from only one site, its size is well within the range of these studies. Our data are also far more recent at the time of submission than those used by Fenton and Kim (13). Longitudinal growth charts like the one by Ehrenkranz et al., who worked in settings very similar to ours, had some 1,700 patients (20). Earlier charts for small preterms were based on only 205 patients (21).

In spite of advances in optical (5, 6) and radiological (2, 3) three dimensional modeling cranial development is to date almost exclusively described by the planar OFC alone. This is likely due to the fact that it can be determined at minimal costs and with no safety concerns. In comparison with weight and CHL it has low levels of technical and observer bias (22). Due to the technical similarities we feel EEDs may be worth of these attributes as well. Such additional measurements may make help in estimating cranial volumes more precisely and allow for better assessments of multidirectional head growth. This could be particularly useful in the care of preterm infants. Absent OFC growth has been linked to neurodevelopmental impairment (23, 24), but the obviously deleterious disruption of important steps of brain development by preterm birth is not reflected in OFC growth (25).

Since only birth data were used, our charts were not biased by postnatal influences on head growth and shape. Deciding for a uniform approach, we did not consider the differences caused by perinatal factors such as vacuum extraction, breech birth, or caesarian section in our analyses.

The widespread use of CPAP prongs fixed to caps may constitute a factor which influences and possibly reduces OFC growth making a three-dimensional head growth assessment even more important. EED measurements may overcome this issue by providing an additional measurement of head growth in the third dimension, which is not as much influenced by caps. Which of the two EEDs presented here is more useful in following preterm infant head growth cannot yet be determined. Both versions are potentially useful, so correlation of longitudinal growth on the basis of the centiles presented here seem to be in order.

To better follow head growth we suggest using a head volume index (HVI) that combines OFC and vEED to one number that can be calculated easily. For this purpose, we have included percentile curves of HVI. The suitability of HVI as a surrogate of cranial volume to follow cranial growth during preterm infant care needs to be evaluated in future studies. Since we have not measured reference head volumes it is also not clear how HVI may be converted into an estimate of cranial volume.

We herein suggest measuring transfontanellar and transvertical EEDs as additional parameters for following head growth and HVI to assess three-dimensional growth with a single number. We provide percentile graphs and LMS tables to improve understanding of head volume growth in preterm infants. The presented growth charts and LMS tables of transfontanellar and transvertical ear-to-ear distance as well as head volume index may become useful in clinical assessments. Further evaluations, including longitudinal analyses, are needed.

The datasets presented in this article are not readily available because release of the data has not been cleared by neither our institutional review board nor our data protection bureau. Requests to access the datasets should be directed to ascherl@medizin.uni-leipzig.de.

The studies involving human participants were reviewed and approved by Institutional Review Board of the Medical Faculty at the University of Leipzig. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.

UT and NA devised the study protocol and applied for the ethics commission vote. NA measured tEED and vEED of the healthy newborns. RA and NA gathered the charted data, performed all data analyses, and drafted the manuscript. All authors edited and approved the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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