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 lekárstvo
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa