Samer Mouksassi(1) and Shasha Jumbe(2)
(1) Certara Strategic Consulting, (2) Bill and Melinda Gates Foundation
Objectives: Symmetric intrauterine growth restriction (IUGR) has been used to describe a growth pattern when all biometric measurements appear affected to the same degree, whereas asymmetric IUGR has been used to characterize a small abdominal circumference (AC) compared to other growth parameters. Asymmetric IUGR would then show abnormal ratios such as head circumference (HC)/AC or femur length (FL)/AC ratio. The objectives of this analysis were: i) to determine the joint probability distributions of growth parameters describing Weight/Length and Head circumference (WT/LEN/HC) from 0 to 24 months of age and ii) to study symmetry across the three growth measures parameters in order to provide useful quantitative guidance to Zika clinicians and researchers on measurements of an individuals with a normal/mild-to-moderate/small head relative to other anthropometric measures.
Methods: A joint parametric nonlinear mixed effects model was built using the QRPEM fitting engine. Several parametric models were tested such as an exponential growth with and without decelerating growth rate. Limited covariate testing was done including covariate such as country site, sex, and socioeconomic factors. The model goodness of fit was assessed using graphical tools and simulation based diagnostics (VPC). Parameter uncertainty was obtained from bootstrap resampling.
Results: A joint nonlinear deceleration model for WT/LEN/HC best fitted the data (115060 observations from 1568 subjects) with a full random effects variance covariance matrix. The between subject variability ranged from 50 % (Weight rate of growth) to 10 % (Length at zero month). Overall, there was a good agreement between the observed and simulated data 1 to 97 percentiles. Country and sex were kept in the model. Parameters uncertainty was < 30%. The model could accurately simulate correlated longitudinal data of WT/LEN/HC from 0-24 months and predict probability of stunting as well as the trajectories of HC growth including microcephaly conditional on WT and LEN. WT/HC, LEN/HC and WT/LEN standards were generated.
Conclusions: These results address a key aspect of characterizing WT/LEN/HC relationships and predicting their evolution over time for a specific child not just the population. Potential application of this model includes individualized trivariate growth trajectories for early detection of serious conditions such as stunting and microcephaly.
References:
[1] Peleg et al. Intrauterine Growth Restriction: Identification and Management. Am Fam Physician. 1998 Aug 1;58(2):453-460
This work is presented on behalf of the Healthy Birth, Growth and Development knowledge integration (HBGDki) community and sponsored by the Bill & Melinda Gates Foundation.
Reference: PAGE 25 () Abstr 5819 [www.page-meeting.org/?abstract=5819]
Poster: Drug/Disease modeling - Paediatrics