title: Maternal age at birth: does it dictate the epigenotypic expression of the trunkal asymmetry of a child?
abstract: BACKGROUND
  Trunkal back asymmetry is considered very important for the selection of children at risk of developing scoliosis. Traditionally, this asymmetry as thoracic or lumbar hump is the main indicator for referral of subjects with idiopathic scoliosis (IS) to clinics from school-screening programs. This asymmetry is also used as the most important sign for further assessment at scoliosis clinics. There are reports suggesting that an epigenetic risk factor for IS is maternal age at birth. However, the influence of maternal age on the development of trunkal asymmetry during growth has not been reported. This report aims to assess if maternal age at birth impacts trunkal asymmetry, and how this parameter may dictate the epigenotypic expression of the trunkal asymmetry of a child.
  
  
  METHODS
  The sample examined: 11832 (5855 males and 5977 females) children and adolescents (5-17 years old, mean age: 11.34±2.79) were screened at their school for back trunkal asymmetry and/or scoliosis. The measurements: The Prujis scoliometer was used to examine the students in standing and sitting forward bending positions. If at least one of child's measured angles was equal to or exceeded 6 or 7 degrees of scoliometer reading, it was labelled as "Asymmetry-6" and "Asymmetry-7" respectively. The age, standing height and body weight of children and maternal age were also documented, among other parameters. The maternal age at birth and children's BMI were subsequently calculated. The statistical analysis: Asymmetries were tested for correlation with maternal age at birth which was transformed to a categorical variable using 5-year intervals. Pearson's χ2 test was used for the univariate analysis, while logistic regression was used for quantitative univariate and multivariate analysis. Statistical significance level was set to p<.05. SPSS and STATA TM v. 11.0 statistical packages were used for the analysis.
  
  
  RESULTS
  Univariate analysis: Univariate analysis showed that the prevalence of asymmetry-6 in boys tended to significantly decrease as mother's age at birth increased (mother's age at birth: <19, 20-24, 25-29, 30-34, 35-39, >40 years, % of asymmetry-6: 11.5%, 9.5%, 8.5%, 7.6%, 5.2%, 5.3%, respectively, (p=0.026). This trend, although present, was not significant in girls. The prevalence of asymmetry-7 also showed a decreasing trend, which was only significant in boys (mother's age at birth: <19, 20-24, 25-29, 30-34, 35-39, >40 years, % of asymmetry-7: 8.7%, 5.9%, 5.9%, 4.6%, 2.6%, 3.5%, respectively, p=0.010). Maternal age at birth, as a continuous variable, was inversely associated with the appearance of asymmetry-6 in both boys and girl s (OR: 0.966, 0.982, 95%CIs: 0.947-0.985, 0.965-0.999, p: 0.001, 0.040, respectively). This was also the case for asymmetry-7 only in boys: (OR: 0.961, 0.982, 95%CIs: 0.938-0.985, 0.962-1.003, p: 0.001, 0.088, respectively). Multivariate analysis: The significant and inverse effect of maternal age at birth on the appearance of asymmetry in boys remained even after adjusting for child's BMI and age. For one year increase of maternal age at birth, the odds of the boys being asymmetrical6 were reduced by 2.8% (OR:0.972, 95% CIs: 0.953-0.992, p: 0.005), adjusting for child's age and BMI. For one year increase of maternal age at birth, the odds of the boys being asymmetrical7 were reduced by 3.2% (OR:0.968, 95% CIs: 0.945-0.992, p: 0.010), adjusting for child's age and BMI. However, the aforementioned correlations were not significant for girls in both cases.
  
  
  CONCLUSIONS
  The influence of maternal age at birth on the development of trunkal asymmetry during growth has not been previously assessed, as evidenced from literature review. The findings of this report indicate that maternal age as an environmental factor in the general population, may possibly influence epigenetically, the occurrence of the initial presentation of trunkal asymmetry in males more than females, as well as IS during growth. Consistent findings reported from the USA, Edinburgh and Sweden reveal increased maternal age as a risk factor for AIS, suggesting maternal factors can predispose to it. It seems that males are more affected by this factor but, unexpectedly in this study, by younger and not older mothers, as reported for AIS in the literature. Low-birth weight associated with younger parental age may also be associated with increased trunkal asymmetry particularly of boys, an hypothesis that need testing. The importance our findings is based on the belief that the intra-uterine environment is crucial in programming the fetus for various health and disease outcomes throughout life.
authors: Department of Trauma and Orthopaedics, Tzanio General Hospital of Piraeus, Piraeus, Greece.
authors: Theodoros B
authors: TB
authors: Grivas
authors: Constantinos
authors: C
authors: Mihas
authors: Christina
authors: C
authors: Mazioti
authors: Nikolaos
authors: N
authors: Zisis
authors: Samantha
authors: S
authors: Sakellaropoulou
authors: Antonios
authors: A
authors: Akriotis
authors: R Geoffrey
authors: RG
authors: Burwell
mesh_terms: D000328:Adult; D017677:Age Distribution; D002648:Child; D002675:Child, Preschool; D044127:Epigenesis, Genetic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D012600:Scoliosis / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult