Methodological challenges in studying the causal determinants of child growth.
Previous studies of early life influences on later growth in childhood have varied in their analytical approaches, particularly with respect to 'adjustment' for differences in size at the beginning of the growth period examined.



We compared three commonly used statistical models to assess the effect of maternal body mass index (BMI) on growth between 6.5 and 11.5 years in a large cohort of Belarusian children, as follows: (Model 1) analysis of the difference in anthropometric measurements between the two ages; (Model 2) analysis of the measurement at 11.5 years after adjustment for the same measurement at 6.5 years; and (Model 3) analysis of the difference in measurements after adjustment for the measurement at 6.5 years (mathematically identical to Model 2).



Among PROBIT children of obese mothers (BMI ≥ 30 kg/m 2 ) vs those of mothers with normal BMI (18.5 to < 25 kg/m 2 ), Model 1 yielded larger increases in most weight and adiposity outcomes than did Model 2. We show that these larger effects arise because Model 2 parameterizes the effect of maternal BMI twice in same model: once for its effect on size at 6.5 years, and a second time for its effect on growth over the 5-year period between 6.5 and 11.5 years. Similar results were obtained in analogous analyses from cohorts in Boston, MA, and Singapore.



Analysing the effect of exposure on change in outcome between two ages (Model 1) is clearly preferable to 'adjustment' for the outcome at the earlier age whenever the exposure under study affects the outcome at the earlier age.
Department of Pediatrics.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University Faculty of Medicine, Montreal, QC, Canada.
Michael S
MS
Kramer
Department of Pediatrics.
Xun
X
Zhang
Department of Pediatrics, National University of Singapore, and Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore.
Izzuddin
I
Bin Aris
Department of Pediatrics.
Mourad
M
Dahhou
Department of Obstetrics and Gynecology.
Ashley
A
Naimi
Department of Epidemiology, Biostatistics and Occupational Health, McGill University Faculty of Medicine, Montreal, QC, Canada.
Seungmi
S
Yang
School of Social and Community Medicine, University of Bristol, Bristol, UK.|National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, UK.
Richard M
RM
Martin
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Emily
E
Oken
Department of Pediatrics.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University Faculty of Medicine, Montreal, QC, Canada.
Robert W
RW
Platt
D050154:Adiposity; D000886:Anthropometry; D015992:Body Mass Index; D001900:Boston; D015984:Causality; D002648:Child; D002657:Child Development; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009035:Mothers; D009765:Obesity / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D012846:Singapore
cohort studies, life-course epidemiology; developmental origins of health and disease; growth; over-adjustment; regression to the mean