Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood
Background:
Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood.
Methods and Findings:
A sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures.
Conclusions:
The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.
Vyšlo v časopise:
Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood. PLoS Med 6(3): e32767. doi:10.1371/journal.pmed.1000040
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1000040
Souhrn
Background:
Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood.
Methods and Findings:
A sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures.
Conclusions:
The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.
Zdroje
1. TorielloHVMeckJM
2008
Statement on guidance for genetic counseling in advanced paternal age.
Genet Med
10
457
460
2. CrowJF
2000
The origins, patterns and implications of human spontaneous mutation.
Nat Rev Genet
1
40
47
3. Nybo AndersenAMHansenKDAndersenPKDavey SmithG
2004
Advanced paternal age and risk of fetal death: a cohort study.
Am J Epidemiol
160
1214
1222
4. KleinhausKPerrinMFriedlanderYPaltielOMalaspinaD
2006
Paternal age and spontaneous abortion.
Obstet Gynecol
108
369
377
5. RousseauFBonaventureJLegeai-MalletLPeletARozetJM
1994
Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.
Nature
371
252
254
6. BertramLBuschRSpieglMLautenschlagerNTMullerU
1998
Paternal age is a risk factor for Alzheimer disease in the absence of a major gene.
Neurogenetics
1
277
280
7. WhalleyLJThomasBMStarrJM
1995
Epidemiology of presenile Alzheimer's disease in Scotland (1974–88) II. Exposures to possible risk factors.
Br J Psychiatry
167
732
738
8. FransEMSandinSReichenbergALichtensteinPLangstromN
2008
Advancing paternal age and bipolar disorder.
Arch Gen Psychiatry
65
1034
1040
9. JayasekaraRStreetJ
1978
Parental age and parity in dyslexic boys.
J Biosoc Sci
10
255
261
10. McIntoshGCOlshanAFBairdPA
1995
Paternal age and the risk of birth defects in offspring.
Epidemiology
6
282
288
11. VestergaardMMorkAMadsenKMOlsenJ
2005
Paternal age and epilepsy in the offspring.
Eur J Epidemiol
20
1003
1005
12. BrownASSchaeferCAWyattRJBeggMDGoetzR
2002
Paternal age and risk of schizophrenia in adult offspring.
Am J Psychiatry
159
1528
1533
13. ByrneMAgerboEEwaldHEatonWWMortensenPB
2003
Parental age and risk of schizophrenia: a case-control study.
Arch Gen Psychiatry
60
673
678
14. DalmanCAllebeckP
2002
Paternal age and schizophrenia: further support for an association.
Am J Psychiatry
159
1591
1592
15. El-SaadiOPedersenCBMcNeilTFSahaSWelhamJ
2004
Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia.
Schizophr Res
67
227
236
16. MalaspinaDHarlapSFennigSHeimanDNahonD
2001
Advancing paternal age and the risk of schizophrenia.
Arch Gen Psychiatry
58
361
367
17. SiposARasmussenFHarrisonGTyneliusPLewisG
2004
Paternal age and schizophrenia: a population based cohort study.
Bmj
329
1070
18. ZammitSAllebeckPDalmanCLundbergIHemmingsonT
2003
Paternal age and risk for schizophrenia.
Br J Psychiatry
183
405
408
19. WohlMGorwoodP
2007
Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring.
Eur Psychiatry
22
22
26
20. LauritsenMBPedersenCBMortensenPB
2005
Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study.
J Child Psychol Psychiatry
46
963
971
21. GillbergC
1980
Maternal age and infantile autism.
J Autism Dev Disord
10
293
297
22. ReichenbergAGrossRWeiserMBresnahanMSilvermanJ
2006
Advancing paternal age and autism.
Arch Gen Psychiatry
63
1026
1032
23. CantorRMYoonJLFurrJLajonchereCM
2007
Paternal age and autism are associated in a family-based sample.
Mol Psychiatry
12
419
421
24. CroenLANajjarDVFiremanBGretherJK
2007
Maternal and paternal age and risk of autism spectrum disorders.
Arch Pediatr Adolesc Med
161
334
340
25. BergJSBrunetti-PierriNPetersSUKangSHFongCT
2007
Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region.
Genet Med
9
427
441
26. SebatJLakshmiBMalhotraDTrogeJLese-MartinC
2007
Strong association of de novo copy number mutations with autism.
Science
316
445
449
27. WeissLAShenYKornJMArkingDE
2008
Association between microdeletion and microduplication at 16p11.2 and autism.
N Engl J Med
358
667
675
28. StefanssonHRujescuDCichonSPietilainenOPIngasonA
2008
Large recurrent microdeletions associated with schizophrenia.
Nature
455
232
236
29. StoneJLO'DonovanMCGurlingHKirovGKBlackwoodDH
2008
Rare chromosomal deletions and duplications increase risk of schizophrenia.
Nature
455
237
241
30. XuBRoosJLLevySvan RensburgEJGogosJA
2008
Strong association of de novo copy number mutations with sporadic schizophrenia.
Nat Genet
40
880
885
31. AurouxMRMayauxMJGuihard-MoscatoMLFromantinMBartheJ
1989
Paternal age and mental functions of progeny in man.
Hum Reprod
4
794
797
32. Dietz-HelmersA
1974
On correlation between the generation age of the fathers and grandfathers and the intelligence of the descendants.
Experientia
30
567
570
33. NewcombeHBTavendaleOG
1965
Effects of father's age on the risk of child handicap or death.
Am J Hum Genet
17
163
178
34. RobertsJEngelA
1974
Family background, early development and intelligence of children 6–11 years.
Vital Health Statistics
11/142
42
35. MalaspinaDReichenbergAWeiserMFennigSDavidsonM
2005
Paternal age and intelligence: implications for age-related genomic changes in male germ cells.
Psychiatr Genet
15
117
125
36. BromanSHNicholsPLKennedyWA
1975
Preschool IQ. Prenatal and early developmental correlates
Hillsdale, New Jersey
Lawrence Erlbaum Associates
37. LoblMWelcherDWMellitsED
1971
Maternal age and intellectual functioning of offspring.
Johns Hopkins Med J
128
347
361
38. FergussonDMLynskeyMT
1993
Maternal age and cognitive and behavioural outcomes in middle childhood.
Paediatr Perinat Epidemiol
7
77
91
39. ZybertPSteinZBelmontL
1978
Maternal age and children's ability.
Percept Mot Skills
47
815
818
40. NiswanderKRGordonM
1972
The women and their pregnancies
Philadephia
Saunders
41. HardyJB
2003
The Collaborative Perinatal Project: lessons and legacy.
Ann Epidemiol
13
303
311
42. BromanSBienEShaughnessyP
1985
Low achieving children: the first seven years
Hillsdale, New Jersey
Lawrence Erlbaum Associates
43. BayleyN
1969
Bayley scales of infant development
San Antonio, Texas
Psychological Corporation
44. BayleyN
1969
Manual for the Bayley Scales of Infant Development
New York
The Psychological Corporation
45. BeckerKA
2003
History of the Stanford-Binet intelligence scales: content and psychometrics. Stanford-Binet Intelligence Scales, Fifth Edition Assessment Service Bulletin No 1
Itasca, Illinois
RIverside Publishing
46. TermanLMMerrillMA
1960
Stanford-Binet Intelligence Scale
Boston
Houghton Mifflin
47. GrahamFKErnhartCBBermanPW
1963
Brain injury in the preschool child: some developmental considerations: 1. Performance of normal children.
Psychol Monogr
77
1
16
48. WechslerD
1949
Manual for the Wechsler Intelligence Scale for Children
New York
The Psychological Corporation
49. JastakSWilkinsonGSJastakJ
1936
Wide Range Achievement Test. 6th ed
Jastak Associates Inc
50. RuppertDWandMPCarrollRJ
2003
Semiparametric Regression
New York
Cambridge University Press
51. MyrianthopoulosNCFrenchKS
1968
An application of the U.S. Bureau of the Census socioeconomic index to a large, diversified patient population.
Soc Sci Med
2
283
299
52. NeterJKunterMHWassermanWNachtsheimCJ
2004
Applied Linear Statistical Models
Homewood
McGraw-Hill/Irwin
53. WoodSN
2006
Generalized Additive Models: An introduction with R
Boca Raton, Florida
Chapman and Hall/CRC
54. SAS Institute
2001
SAS 9.1.3
Cary, NC
SAS Institute
55. O'BrienGPearsonJ
2004
Autism and learning disability.
Autism
8
125
140
56. AylwardEWalkerEBettesB
1984
Intelligence in schizophrenia: meta-analysis of the research.
Schizophr Bull
10
430
459
57. WoodberryKAGiulianoAJSeidmanLJ
2008
Premorbid IQ in schizophrenia: a meta-analytic review.
Am J Psychiatry
165
579
587
58. WelhamJIsohanniMJonesPMcGrathJ
2008
The Antecedents of Schizophrenia: A Review of Birth Cohort Studies.
Schizophr Bull
E-pub ahead of print. doi:10.1093/schbul/sbn084
59. JonesPRodgersBMurrayRMarmotM
1994
Child development risk factors for adult schizophrenia in the British 1946 birth cohort.
Lancet
344
1398
1402
60. KremenWSBukaSLSeidmanLJGoldsteinJMKorenD
1998
IQ decline during childhood and adult psychotic symptoms in a community sample: a 19-year longitudinal study.
Am J Psychiatry
155
672
677
61. CannonTDBeardenCEHollisterJMRossoIMSanchezLE
2000
Childhood cognitive functioning in schizophrenia patients and their unaffected siblings: a prospective cohort study.
Schizophr Bull
26
379
393
62. BarnettJHSalmondCHJonesPBSahakianBJ
2006
Cognitive reserve in neuropsychiatry.
Psychol Med
36
1053
1064
63. O'DonovanMCKirovGOwenMJ
2008
Phenotypic variations on the theme of CNVs.
Nat Genet
40
1392
1393
64. ValenzuelaMJSachdevP
2006
Brain reserve and cognitive decline: a non-parametric systematic review.
Psychol Med
36
1065
1073
65. SternY
2006
Cognitive reserve and Alzheimer disease.
Alzheimer Dis Assoc Disord
20
112
117
66. Hulshoff PolHESchnackHGPosthumaDMandlRCBaareWF
2006
Genetic contributions to human brain morphology and intelligence.
J Neurosci
26
10235
10242
67. PosthumaDDe GeusEJBaareWFHulshoff PolHEKahnRS
2002
The association between brain volume and intelligence is of genetic origin.
Nat Neurosci
5
83
84
68. TurkheimerEHaleyAWaldronMD'OnofrioBGottesmanII
2003
Socioeconomic status modifies heritability of IQ in young children.
Psychol Sci
14
623
628
69. SteinZSusserM
2000
The risks of having children in later life. Social advantage may make up for biological disadvantage.
BMJ
320
1681
1682
70. PearsonCENichol EdamuraKClearyJD
2005
Repeat instability: mechanisms of dynamic mutations.
Nat Rev Genet
6
729
742
71. BoschMRajmilOEgozcueJTempladoC
2003
Linear increase of structural and numerical chromosome 9 abnormalities in human sperm regarding age.
Eur J Hum Genet
11
754
759
72. GlaserRLBromanKWSchulmanRLEskenaziBWyrobekAJ
2003
The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm.
Am J Hum Genet
73
939
947
73. WyrobekAJEskenaziBYoungSArnheimNTiemann-BoegeI
2006
Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.
Proc Natl Acad Sci U S A
103
9601
9606
74. PerrinMCBrownASMalaspinaD
2007
Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia.
Schizophr Bull
33
1270
1273
75. OakesCCLa SalleSSmiragliaDJRobaireBTraslerJM
2007
Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells.
Dev Biol
307
368
379
76. OakesCCSmiragliaDJPlassCTraslerJMRobaireB
2003
Aging results in hypermethylation of ribosomal DNA in sperm and liver of male rats.
Proc Natl Acad Sci U S A
100
1775
1780
77. KileBTHiltonDJ
2005
The art and design of genetic screens: mouse.
Nat Rev Genet
6
557
567
78. CasparyTAndersonKV
2006
Uncovering the uncharacterized and unexpected: unbiased phenotype-driven screens in the mouse.
Dev Dyn
235
2412
2423
79. McGrathJJ
2007
The surprisingly rich contours of schizophrenia epidemiology.
Arch Gen Psychiatry
64
14
16
80. McGrathJJHearleJJennerLPlantKDrummondA
1999
The fertility and fecundity of patients with psychosis.
Acta Psychiatrica Scandinavica
99
441
446
81. KellerMCMillerG
2006
Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best.
Behav Brain Sci
29
385
404
82. McGrathJJ
2006
The romance of balancing selection versus the sober alternatives: let the data rule (Commentary on Keller and Miller).
Behav Brain Sci
29
417
418
83. BrayIGunnellDDavey SmithG
2006
Advanced paternal age: how old is too old.
J Epidemiol Community Health
60
851
853
84. RoseG
1992
The strategy of preventive medicine
Oxford
Oxford University Press
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2009 Číslo 3
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Pleiotropní účinky statinů na kardiovaskulární systém
- Statiny indukovaná myopatie: Jak na diferenciální diagnostiku?
- Význam hydratace při hojení ran
- DESATORO PRE PRAX: Aktuálne odporúčanie ESPEN pre nutričný manažment u pacientov s COVID-19
Najčítanejšie v tomto čísle
- Setting Research Priorities To Reduce Global Mortality from Childhood Diarrhoea by 2015
- Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood
- Suicide after Leaving the UK Armed Forces —A Cohort Study
- Contrasting Effects of Maternal and Paternal Age on Offspring Intelligence