Strengths and Limitations
The major strength of this study is its longitudinal design. The current
study is possibly the first study to describe the physiological changes
in sHLA-G levels during pregnancy to post delivery in the North Indian
females. This is a case-control study nested within a unique pregnancy
cohort Garbh-ini. The biospecimen from enrolled participants are being
collected in a longitudinal manner and well curated data on multiple
clinical variables is being documented. We were able to study
associations in a homogenous population with a well-defined phenotype of
SGA. The clinical data available on multiple variables allowed us to
exclude potential confounders in our study. Instead of using traditional
generalized linear models, we used linear mixed model to explore and
compare the trajectories of sHLA-G in mothers delivering SGA vs AGA
infants. The traditional methods can handle only balanced repeated
measure designs. A linear mixed model can handle missingness in the data
(unbalanced repeated measure designs), which our study had because of
unavailability of the sera sample at postpartum (42 days to 6 months) or
because sHLA-G levels were undetectable in some mothers at certain
time-points (26 to 28 weeks) of pregnancy and at delivery. This model
was robust enough to handle the subject-specific variability which was
generated in our study because all the mothers were not sampled at
exactly the same day of pregnancy. Inclusion of a post-partum time point
in this study reflects the levels of sHLA-G at pre-pregnancy or
non-pregnant state. The main limitation of the study is its small sample
size and hence the results should be cautiously interpreted.