Am J Mens Health. 2012 May 7. [Epub ahead of print]

The Effect of Paternal Age on Fetal Birth Outcomes.

Alio AP, Salihu HM, McIntosh C, August EM, Weldeselasse H, Sanchez E, Mbah AK.

Abstract

Research investigating the role of paternal age in adverse birth outcomes is limited. This population-based retrospective cohort study used the Missouri maternally linked data set from 1989 to 2005 to assess whether paternal age affects fetal birth outcomes: low birth weight (LBW), preterm birth (PTB), stillbirth, and small size for gestational age (SGA). We examined these outcomes among infants across seven paternal age-groups (<20, 20-24, 25-29, 30-34, 35-39, 40-45, and >45 years) using the generalized estimating equation framework. Compared with infants born to younger fathers (25-29 years), infants born to fathers aged 40 to 45 years had a 24% increased risk of stillbirth but a reduced risk of SGA. A 48% increased risk of late stillbirth was observed in infants born to advanced paternal age (>45 years). Moreover, advanced paternal age (>45 years) was observed to result in a 19%, 13%, and 29% greater risk for LBW, PTB, and VPTB (very preterm birth) infants, respectively. Infants born to fathers aged 30 to 39 years had a lower risk of LBW, PTB, and SGA, whereas those born to fathers aged 24 years or younger had an elevated likelihood of experiencing these same adverse outcomes. These findings demonstrate that paternal age influences birth outcomes and warrants further investigation.

PMID:

22564913

[PubMed - as supplied by publisher] 

Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner

Neuron. 2012 Apr 26;74(2):285-99.

De novo gene disruptions in children on the autistic spectrum.

Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee YH, Narzisi G, Leotta A, Kendall J, Grabowska E, Ma B, Marks S, Rodgers L, Stepansky A, Troge J, Andrews P, Bekritsky M, Pradhan K, Ghiban E, Kramer M, Parla J, Demeter R, Fulton LL, Fulton RS, Magrini VJ, Ye K, Darnell JC, Darnell RB, Mardis ER, Wilson RK, Schatz MC, McCombie WR, Wigler M.

Source

Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.

Abstract

Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.
Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:

22542183

[PubMed - in process]