Fetal movements are known to play a key role in prenatal skeletal development. We know this from a number of conditions in which reduced or restricted fetal movements are linked to abnormal affecting newborn babies in which the bones or joints are not properly formed. The most common example is developmental dysplasia of the hip (DDH), where the hip joint is unstable or even dislocated. Another example is arthrogryposis, where multiple joints are abnormally shaped and oriented.
We have investigated a number of different aspects relating to the importance of and impact of fetal movements for prenatal skeletal development, as summarised below.
Stresses and Strains Induced by Human Fetal Movements
We characterised- for the first time- the stresses and strains induced by fetal movements in the bones and joints, and how these stimuli are altered in conditions that predispose a baby to hip dysplasia. We created computational models of babies kicking in utero and calculated the stresses and strains induced in the bones and joints by these kicks.
Dr Stefaan Verbruggen was the postdoctoral researcher leading the research, and the project was funded by Arthritis Research UK (now Versus Arthritis). Fetal movements were automatically tracked from cine MRI scans (obtained from our collaborators at King’s College London) as shown below.
Those movements were modelled using finite element and musculoskeletal models to calculate the force generated by the kick, and the muscle forces acting. Next, the muscle forces were applied to fetal skeletal geometries, obtained from collaborators in Great Ormond Street Hospital. The methodological pipeline is shown below.
Verbruggen SW, Kainz B, Shelmerdine SC, Arthurs OJ, Hajnal JV, Rutherford MA, Phillips AT, Nowlan NC. “Altered biomechanical stimulation of the developing hip joint in presence of hip dysplasia risk factors”. Journal of Biomechanics, in press. Winner of European Society of Biomechanics Perren Award for best scientific paper. (link) (pdf)
Verbruggen SW, Loo JHW, Hayat TTA, Hajnal JV, Rutherford MA, Phillips ATM, Nowlan NC, “Modelling the biomechanics of fetal movements”, 2016. Biomechanics and Modelling in Mechanobiology: 15(4), pp. 995-1004. (link) (pdf)
Role of mechanical forces in joint morphogenesis
The shape of our joints is critical to their function and control, but there are significant gaps in our understanding of how joint shapes develop and form. Through a range of different projects, we have investigated how mechanical forces due to fetal movement mould synovial joints to gain a better understanding of musculoskeletal conditions affecting newborns and children.
Fetal movements, spine development and congenital scoliosis
Congenital scoliosis is a condition in which the newborn spine is curved abnormally, with fused or abnormally shaped vertebrae. It is commonly associated with rib abnormalities. While the causes of congenital scoliosis are currently unknown, there is evidence from some clinical conditions that fetal movements may play a key role in development of the spine. Spine abnormalities have been reported in cases of fetal akinesia deformation sequence (FADS), where the fetus doesn’t move at all, and congenital scoliosis is much more common in babies with arthrogryposis (multiple joint shape abnormalities), a syndrome which is strongly linked to abnormal fetal movements.
We showed that:
- Prolonged rigid paralysis induces severe defects in the developing chick spine, including curvature abnormalities, posterior and anterior vertebral fusions, and altered vertebral shape
- The earlier in development paralysis is started, the more severe the abnormalities
- Flaccid paralysis does not affect spinal curvature or vertebral segmentation.
- Just one day of paralysis in the chick embryo is enough to induce severe abnormalities in spine and rib development
- Single-day immobilisation at embryonic day 3 or 4 resulted in the most pronounced spinal curvature abnormalities, multiple wedged vertebrae and segmentation defects, while single-day immobilisation at E5 led to the most severe rib abnormalities.
- Vertebral segmentation defects were subsequent to earlier vertebral body shape and spinal curvature abnormalities, while rib formation (although delayed) was independent from thoracic vertebral shape or curvature changes.
- In mouse embryos, notochord involution happens normally when skeletal muscle is non functional. However, vertebral segmentation and disc structure depend upon embryonic muscle forces.