Modeling fetal weight for gestational age: a comparison of a flexible multi-level spline-based model with other approaches

Abstract

We present a model for longitudinal measures of fetal weight as a function of gestational age. We use a linear mixed model, with a Box-Cox transformation of fetal weight values, and restricted cubic splines, in order to flexibly but parsimoniously model median fetal weight. We systematically compare our model to other proposed approaches. All proposed methods are shown to yield similar median estimates, as evidenced by overlapping pointwise confidence bands, except after 40 completed weeks, where our method seems to produce estimates more consistent with observed data. Sex-based stratification affects the estimates of the random effects variance-covariance structure, without significantly changing sex-specific fitted median values. We illustrate the benefits of including sex-gestational age interaction terms in the model over stratification. The comparison leads to the conclusion that the selection of a model for fetal weight for gestational age can be based on the specific goals and configuration of a given study without affecting the precision or value of median estimates for most gestational ages of interest.

Keywords: fetal growth; multi-level models; small for gestational age.

Figure 6:

Simulated individual weight-for-gestational-age trajectories. The curves have been simulated based on a model stratified on the sex variable.

Figure 7:

Simulated individual weight-for-gestational-age trajectories. The curves have been simulated based on a model with sex-gestational age interaction.

Figure 1:

Pregnancies from the Scandinavian dataset: Circles represent weight/gestational age pairs at birth and triangles represent estimated weight/gestational age pairs in utero.

Figure 2:

Individual weight-for-gestational-age paths for males sampled from the Scandinavian dataset. Circles represent weight/gestational age pairs at birth and triangles represent estimated weight/gestational age pairs in utero.

Figure 3:

Individual weight-for-gestational-age paths for females sampled from the Scandinavian dataset. Circles represent weight/gestational age pairs at birth and triangles represent estimated weight/gestational age pairs in utero.

Figure 4:

Weight-for-gestational-age medians. The shaded region represents the proposed model’s 95 % pointwise confidence band.

Figure 5:

Weight-for-gestational-age median trajectories. The shaded region represents the proposed model’s 95% pointwise confidence band.