Jayson D. Wilbur (1,6), Eric Ohuma (2,6), Luo Xiao (3,6), Samer Mouksassi (4,6) and Ryan Hafen (5,6)
: (1) Metrum Research Group, Tariffville CT, (2) University of Oxford, Oxford UK, (3) North Carolina State University, Raleigh NC, (4) Certara, Montreal QC, (5) Hafen Consulting, Seattle WA, (6) Representing the Healthy Birth, Growth and Development knowledge integration (HBGDki) community, Sponsored by the Bill & Melinda Gates Foundation, Healthy birth, growth and development initiative
Objectives: An observed increase in the number of cases of microcephaly in Brazil has been associated with exposure to the Zika virus. In response, a number of organizations have published screening thresholds for microcephaly in terms of measured newborn head circumference [1]. This work evaluates these criteria based on modeling of data on longitudinal fetal growth trajectories and newborn size.
Methods: Functional Principal Components Analysis (fPCA) was employed to model head circumference growth trajectories using non-parametric functions to characterize both the mean trajectory and subject-level random effects.
Results: As expected, microcephaly thresholds that do not account for gestational age ignore an important source of biological variation. However, factors associated with maternal health also contributed to population and subject level deviations from international standards, which do account for gestational age [2].
Conclusions: Establishing fixed cutoffs for microcephaly in terms of newborn head circumference size ignores important sources of variation which can be accounted for using a model-based approach.
References:
[1] Victora, Cesar Gomes, et al. “Microcephaly in Brazil: how to interpret reported numbers?” Lancet (London, England) 387.10019 (2016): 621-624.
[2] Villar, José, et al. “International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.” The Lancet 384.9946 (2014): 857-868.
Reference: PAGE 25 (2016) Abstr 5902 [www.page-meeting.org/?abstract=5902]
Poster: Drug/Disease modeling - Paediatrics