IGF1 Promoter Polymorphism and Cranial Growth in Individuals Born Very Preterm

Abstract

Background: Major defects in the IGF1 gene are associated with severely reduced cranial and linear growth. The association between IGF1 promoter polymorphisms and growth is uncertain. Aims: To test the effect of the IGF1 192-bp allele on cranial and linear growth and body mass index (BMI) from birth until age 5 years, and on IQ and serum IGF-1 at age 19 years. Methods: In a birth cohort, including 285 individuals born at a gestational age <32 weeks from the Project On Preterm and Small-for-gestational age infants (POPS), cohort anthropometric measurements were analyzed. At age 19 years IGF1 genotype, serum IGF-1 level and IQ were determined. Regression analyses were performed with mixed models. Results: Homozygotes for the 192-bp allele had a slower cranial growth from birth until age 5 years, and a tendency towards less brain sparing and a slower linear growth compared to the other 2 genotype groups. IGF1 genotype was not associated with IQ or BMI development. Head circumference SDS at age 5 years was positively associated with IQ at age 19 years. Conclusion: Homozygosity for the IGF1 192-bp allele is associated with a slower cranial growth from birth until age 5 years in individuals born very preterm.

Head size and growth in the very preterm infant: a literature review

“…7,8,18,19,[21][22][23]27,33 Neurodevelopmental outcome at $2 years was reported in eleven studies (3,817 subjects). 7,9,10,12,14,18,19,21,27,28,36 Nine studies (2,363 subjects) included neuroimaging data, four of which report magnetic resonance imaging (MRI) data. 7,30,32,35 Infants born at #28 weeks gestation (Table S1) were examined in 12 studies, while 22 studies focused on infants of .28 weeks completed gestation (Table S2).…”

“…Eight studies 6,11,21,25,28,29,36,38 accounted for size differences between different ethnic and racial groups, while social factors were considered in 15 studies. 7,8,10,[12][13][14]17,18,21,25,27,28,30,34,36 WHO standards suggest one set of growth curves is appropriate for children throughout the globe; however, this may underestimate the rate of microcephaly and overestimate the rate of large head size in Western European countries. 40 Many studies did not comment on the growth reference charts utilized, and the diversity of growth references chosen is illustrated in Tables S1 and S2.…”

“…Eighteen 6,[9][10][11][12][13][17][18][19][21][22][23]25,28,29,34,38,41 of the 34 studies included were multicentered in nature, improving the generalizability of results. More than half of the 34 papers meeting inclusion criteria were prospective observational studies 7,8,[10][11][12][13]15,17,[19][20][21][22][23]27,28,32,33,35,41,42 and were therefore subject to a number of confounding factors.…”

“…More than half of the 34 papers meeting inclusion criteria were prospective observational studies 7,8,[10][11][12][13]15,17,[19][20][21][22][23]27,28,32,33,35,41,42 and were therefore subject to a number of confounding factors. Only five studies 25,26,30,31,34 were randomized controlled trials.…”

Dietary proteins and IGF I levels in preterm infants: determinants of growth, body composition, and neurodevelopment

“…A polymorphism in the IGF I promotor gene, which is known to regulate serum IGF I levels, has been related with slower cranial growth from birth until 5 y of age (40). Moreover, Hansen-Pupp et al found IGF I levels to correlate with brain volumes while there was no association with cerebral spinal fluid volume.…”