PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of wtpaEurope PMCEurope PMC Funders GroupSubmit a Manuscript
 
Osteoporos Int. Author manuscript; available in PMC Jun 18, 2013.
Published in final edited form as:
PMCID: PMC3685134
EMSID: EMS53623
Similar maternal and paternal relationships with offspring bone mass do not exclude an intrauterine mechanism: Evidence from Southampton Women’s Survey
Nicholas C Harvey, Hazel M Inskip, Keith M Godfrey, and Cyrus Cooper
MRC Lifecourse Epidemiology Unit, (University of Southampton), Southampton General Hospital, Southampton. SO16 6YD, UK
Correspondence and reprint requests to: Professor Cyrus Cooper, MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton SO16 6YD, UK. Tel: +44 (0) 23 8077 7624, Fax: +44 (0) 23 8070 4021, cc/at/mrc.soton.ac.uk
Authors’ emails: NC Harvey (nch/at/mrc.soton.ac.uk); HM Inskip (hmi/at/mrc.soton.ac.uk); KM Godfrey (kmg/at/mrc.soton.ac.uk); C Cooper (cc/at/mrc.soton.ac.uk)
In their recent paper, McDonald-Wallis et al.(1) found that maternal and paternal smoking before pregnancy were related similarly to offspring bone mass at age 10 years. The authors concluded, as in their earlier paper with parental BMI as the predictor(2), that their findings did not support an intra-uterine mechanism, but were mediated by genetic and postnatal environmental factors. We would like to offer an alternative view.
We examined the associations between parental smoking and offspring bone indices, assessed by DXA at birth in the Southampton Women’s Survey(3), an ongoing prospective mother-offspring cohort including detailed characterisation of the women before and during pregnancy. The mean whole body bone mineral content (BMC) at birth of babies born to mothers who smoked in pregnancy was 4.1g lower than that of babies of non-smokers(p=0.002); in contrast the difference by paternal smoking was small and not statistically significant(−0.05g,p=0.98). Additionally, maternal pre-pregnancy BMI was positively associated with offspring whole body BMC at birth(beta=11.9g per kg/m2,p<0.001) but no relationship was observed for paternal BMI(beta=1.2g per kg/m2,p=0.81). These results clearly demonstrate a specific maternal, intrauterine effect on BMC at birth. Indeed, in the papers by MacDonald-Wallis et al., the associations by parent were similar when the imputed dataset was used, but stronger maternal than paternal-child relationships were observed when the un-imputed dataset was analysed. The authors provide a rationale for why the imputed dataset might be preferred, but clearly the use of imputation lends a degree of uncertainty as to the conclusions drawn.
There is likely to be co-linearity between environmental factors present before, during and after pregnancy, influencing mother, father and child, and complicating assessment of the time point(s) at which the biological effect is most important. We found that the lifestyle and health behaviour of women planning a pregnancy is very similar to that of women not aiming to conceive(4). Additionally we have observed strong correlations between maternal triceps skinfold thickness before and during pregnancy (5;6); although women may give up smoking whilst pregnant(7), this abstinence may not continue postnatally, and women who smoke during pregnancy are likely to be those with a long-term commitment to the habit. We therefore suggest that, because some environmental influences are likely to be similar before, during and after pregnancy, the statistical and experimental designs employed by cohort studies without detailed perinatal body composition data do not allow us to be sure that the biological effect is in post-natal and not intra-uterine life. The positive relationship between birthweight and adult BMC, confirmed by a recent meta-analysis(8), does suggest that there is at least some scope for long term modulation of bone mineral accrual originating in the intra-uterine period.
Finally it is clear that environmental factors are an important influence on bone development, whether acting before, during, or soon after pregnancy. Given the small proportion of the variance in bone mineral density explained by genotype in several genome-wide association studies(9;10), results from ALSPAC, SWS and other cohorts emphasize the need to address optimisation of bone mass throughout the lifecourse.
Footnotes
Author disclosure:
No conflicts.
1. Macdonald-Wallis C, Tobias JH, Davey SG, Lawlor DA. Parental smoking during pregnancy and offspring bone mass at age 10 years: findings from a prospective birth cohort. Osteoporos Int. 2010 Oct 22; [PMC free article] [PubMed]
2. Macdonald-Wallis C, Tobias JH, Smith GD, Lawlor DA. Relation of maternal prepregnancy body mass index with offspring bone mass in childhood: is there evidence for an intrauterine effect? Am J Clin Nutr. 2010 Oct;92:872–880. [PMC free article] [PubMed]
3. Inskip HM, Godfrey KM, Robinson SM, Law CM, Barker DJ, Cooper C. Cohort profile: The Southampton Women’s Survey. Int J Epidemiol. 2005 Sep 29;
4. Inskip HM, Crozier SR, Godfrey KM, Borland SE, Cooper C, Robinson SM. Women’s compliance with nutrition and lifestyle recommendations before pregnancy: general population cohort study. BMJ. 2009;338:b481. [PMC free article] [PubMed]
5. Harvey NC, Poole JR, Javaid MK, Dennison EM, Robinson S, Inskip HM, Godfrey KM, Cooper C, Sayer AA. Parental determinants of neonatal body composition. Journal of Clinical Endocrinology and Metabolism. 2007;92:523–526. [PMC free article] [PubMed]
6. Harvey NC, Javaid MK, Arden NK, Poole JR, Crozier SR, Robinson SM, Inskip HM, Godfrey KM, Dennison EM, Cooper C. Maternal predictors of neonatal bone size and geometry: the Southampton Women’s Survey. Journal of Developmental Origins of Health and Disease. 2010 Feb;1:35–41. [PMC free article] [PubMed]
7. Crozier SR, Robinson SM, Borland SE, Godfrey KM, Cooper C, Inskip HM. Do women change their health behaviours in pregnancy? Findings from the Southampton Women’s Survey. Paediatr Perinat Epidemiol. 2009 Sep;23:446–453. [PMC free article] [PubMed]
8. Baird J, Kurshid MA, Kim M, Harvey N, Dennison E, Cooper C. Does birthweight predict bone mass in adulthood? A systematic review and meta-analysis. Osteoporos Int. 2010 Aug 4; [PubMed]
9. Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Richards JB, Zillikens MC, Kavvoura FK, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Grundberg E, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra B, Pastinen T, Pols HA, Sigurdsson G, Soranzo N, Thorleifsson G, Thorsteinsdottir U, Williams FM, Wilson SG, Zhou Y, Ralston SH, van Duijn CM, Spector T, Kiel DP, Stefansson K, Ioannidis JP, Uitterlinden AG. Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet. 2009 Nov;41:1199–1206. [PMC free article] [PubMed]
10. Richards JB, Kavvoura FK, Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Zillikens MC, Wilson SG, Mullin BH, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra BA, Pols HA, Sigurdsson G, Thorsteinsdottir U, Soranzo N, Williams FM, Zhou Y, Ralston SH, Thorleifsson G, van Duijn CM, Kiel DP, Stefansson K, Uitterlinden AG, Ioannidis JP, Spector TD. Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med. 2009 Oct 20;151:528–537. [PMC free article] [PubMed]