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    Chen, Wen-Yi 2016. On the relationship between economic conditions around the time of birth and late life cognitive abilities: Evidence from Taiwan. Economics & Human Biology, Vol. 22, p. 126.

    Susser, E. Buka, S. Schaefer, C. A. Andrews, H. Cirillo, P. M. Factor-Litvak, P. Gillman, M. Goldstein, J. M. Ivey Henry, P. Lumey, L. H. McKeague, I. W. Michels, K. B. Terry, M. B. and Cohn, B. A. 2011. The Early Determinants of Adult Health Study. Journal of Developmental Origins of Health and Disease, Vol. 2, Issue. 06, p. 311.


Associations between birth weight, preeclampsia and cognitive functions in middle-aged adults

  • P. Factor-Litvak (a1), N. Straka (a1), S. Cherkerzian (a2) (a3), M. Richards (a4) (a5), X. Liu (a6), A. Sher (a7), G. Neils (a8) and J. Goldstein (a2) (a3) (a9)
  • DOI:
  • Published online: 14 October 2011

Both reductions in birth weight and preeclampsia (PE) have been associated with decrements in scores on tests of intelligence in children and adolescents. We examined whether these decrements persist into middle adulthood and expand into other domains of cognitive functioning. Using data from the Early Determinants of Adult Health project and from the ancillary project, Fetal Antecedents of Major Depression and Cardiovascular Disease, we selected term same-sex sibling sets or singletons from these sets, from the New England Family Study (NEFS) and the Child Health and Development Studies (CHDS), discordant on either fetal growth or PE, to test the hypotheses that prenatal exposure to inflammation was associated with decrements in attention, learning and executive function 40 years later. Exposure was defined as a continuous measure of percentile birth weight for gestational age, reduced fetal growth (<20th percentile of birth weight for gestational age) or maternal PE. Given that the sample was comprised, in part, of sibling sets, the analyses were performed using mixed models to account for the inter-sibling correlations. Analyses were performed separately by study site (i.e. NEFS and CHDS). We found few statistically significant associations (suggesting a possible type II error) consistent with previous literature, suggesting that the associations with low birth weight do not persist into midlife. We discuss the possible reasons for the lack of associations, which include the possible mediating effects of the postnatal environment.

Corresponding author
*Address for correspondence: Dr P. Factor-Litvak, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. (Email
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

2.RO Rieder , SH Broman , D Rosenthal . The offspring of schizophrenics: II. Perinatal factors and IQ. Arch Gen Psychiatry. 1977; 34, 789799.

3.A Many , A Fattal , Y Leitner , MJ Kupfermine , S Harel , A Jaffa . Neurodevelopmental and cognitive assessment of children born growth restricted to mothers with and without preeclampsia. Hypertens Pregnancy. 2003; 22, 2529.

4.A Many , A Fattal-Valevski , Y Leitner . Neurodevelopmental and cognitive assessment of 6-year old children born growth restricted. Int J Gynecol Obstet. 2005; 89, 5556.

5.V Ehrenstein , KJ Rothman , L Pedersen , EE Hatch , HT Sorensen . Pregnancy-associated hypertensive disorders and adult cognitive function among Danish conscripts. Amer J Epidemiol. 2009; 170, 10251031.

6.MK Ounsted , VA Moar , FJ Good , CWG Redman . Hypertension during pregnancy with and without specific treatment; the development of children at the age of four years. Brit J Obstet Gynecol. 1980; 87, 1924.

7.M Ounsted , J Cockburn , VA Moar , CWG Redman . Maternal hypertension with superimposed pre-eclampsia: effects on child development at 7.5 years. Brit J Obstet Gynecol. 1983; 90, 644649.

8.DS Seidman , A Laor , R Gale , . Pre-eclampsia and offspring's blood pressure, cognitive ability and physical development at 17-years-of-age. Brit J Obstet Gynecol. 1991; 98, 10091014.

9.NK Klein , M Hack , N Breslau . Children who were very low birth weight: development and academic achievement at nine years of age. J Dev Behav Pediatr. 1989; 10, 3237.

10.N Breslau , J Delrotto , GG Brown , . A gradient relationship between low birth weight and IQ at age 6 years. Arch Pediatr Adolesc Med. 1994; 148, 377383.

11.N Breslau , H Chilcoat , J DelDotto , P Andreski , G Brown . Low birth weight and neurocognitive status at six years of age. Biol Psychiatry. 1996; 40, 389397.

12.M Petersen , G Greisen , R Kovacs , H Munck , B Friis-Hansen . Status at four years of age in 280 children weighing 2300 g or less at birth. Dan Med Bull. 1990; 37, 546552.

13.L Mutch , A Leyland , A McGee . Patterns of neuropsychological function in a low-birthweight population. Dev Med Child Neurol. 1993; 35, 943956.

14.AL Rikards , WH Kitchen , LW Doyle , . Cognition, school performance and behavior in very low birth weight and normal birth weight children at 8 years of age: a longitudinal study. J Dev Behav Pediatr. 1993; 14, 363368.

15.SC Roth , J Baudin , DC McCormick , . Relation between ultrasound appearance of the brain of very preterm infants and neurodevelopmental impairment at eight years. Dev Med Child Neurol. 1993; 35, 755768.

16.TD Matte , M Bresnahan , M Begg , E Susser . Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study. Br Med J. 2001; 323, 310314.

18.HT Sorensen , S Sabroe , J Olsen , . Birth weight and cognitive function in young adult life: historical cohort study. Br Med J. 1997; 315, 401403.

19.M Richards , R Hardy , D Kuh , ME Wadsworth . Birth weight and cognitive function in the British 1946 birth cohort: longitudinal population based study. Br Med J. 2001; 322, 199202.

20.ML Collaer , M Hines . Human behavioral sex differences: a role for gonadal hormones during early development? Psychol Bull. 1995; 118, 55107.

21.JM Goldstein , LJ Seidman , JM Goodman , . Are there sex differences in neuropsychological functions among patients with schizophrenia? Amer J Psychiatry. 1998; 155, 13581364.

22.JM Goldstein , LJ Seidman , S Santangelo , P Knapp , MT Tsuang . Are schizophrenic men at higher risk for developmental deficits than schizophrenic women? Implications for adult neuropsychological function. J Psychiatr Res. 1994; 28, 483489.

24.JM Goldstein , LJ Seidman , NJ Horton , . Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb Cortex. 2001; 11, 490497.

25.JL Nunez , MM McCarthy . Sex differences and hormonal effects in a model of preterm infant brain injury. Ann NY Acad Sci. 2003; 1008, 281284.

26.MD Lauterbach , S Raz , CJ Sander . Neonatal hypoxic risk in preterm birth infants: the influence of sex and severity of respiratory distress on cognitive recovery. Neuropsychology. 2001; 15, 411420.

27.AS Clark , PS Goldman-Rakic . Gonadal hormones influence the emergence of cortical function in nonhuman primates. Behav Neurosci. 1989; 103, 12871295.

28.E Oken , KP Kleinman , J Rich-Edwards , MW Gillman . A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr. 2003; 3, 6.

29.National High Blood Pressure Education Program Working Group. Report on high blood pressure in pregnancy. Am J Obstet Gynecol. 1990; 163, 16911712.

30.LJ Seidman , HC Breiter , JM Goodman , . A functional magnetic resonance imaging study of auditory vigilance with low and high information processing demands. Neuropsychology. 1998; 12, 505518.

32.KI Bolla , KN Lindgren , C Bonaccorsy , ML Bleecker . Predictors of verbal fluency (FAS) in the healthy elderly. J Clin Psychol. 1990; 45, 623628.

34.N Usui , T Haji , M Maruyama , . Cortical areas related to performance of WAIS digit symbol test: a functional imaging study. Neurosci Lett. 2009; 463, 15.

36.NC Myrianthopoulos , KS French . An application of the US bureau of the census socioeconomic index to a large diversified patient population. Soc Sci Med. 1968; 2, 283299.

38.JA Hutcheon , RW Platt . The missing data problem in birth weight percentiles and thresholds for “small-for-gestational-age”. Amer J Epidemiol. 2008; 167, 786792.

39.SD Shenkin , JM Starr , IJ Deary . Birth weight and cognitive ability in childhood: a systematic review. Psychol Bull. 2004; 130, 9891013.

40.BJ Jefferis , C Power , C Hertzman . Birth weight, childhood socioeconomic environment and cognitive development in the 1958 British birth cohort study. Br Med J. 2002; 325, 305310.

41.W Eriksen , JM Sundet , K Tambs . Birth weight standardized to gestational age and intelligence in young adulthood: a register-based birth cohort study of male siblings. Amer J Epidemiol. 2010; 172, 530536.

42.MG Eide , N Oyen , R Skjaerven , T Bjerkedal . Associations of birth size, gestational age, and adult size with intellectual performance: evidence from a cohort of Norwegian men. Pediatr Res. 2007; 62, 636642.

43.CN Martyn , CR Gale , AA Sayer , C Fall . Growth in utero and cognitive function in adult life: follow up study of people born between 1920 and 1943. Br Med J. 1996; 312, 13931396.

44.GA Kaplan , G Turrell , JW Lynch , . Childhood socioeconomic position and cognitive function in adulthood. Int J Epidemiol. 2001; 30, 256263.

45.E Susser , MG Eide , M Begg . Invited commentary: the use of sibship studies to detect familial confounding. Amer J Epidemiol. 2010; 172, 530536.

46.D Schendel , C Rice , C Cunniff . The contribution of rare diseases to understanding the epidemiology of neurodevelopmental disabilities. Adv Exp Med Biol. 2010; 686, 433453.

47.JM Goldstein , RRJ Lewine . Overview of sex differences in schizophrenia: where have we been and where do we go from here? In Women and Schizophrenia (eds. Castle DJ, McGrath, Kulkarni J), 2000, pp. 111143. Cambridge University Press: Cambridge.

48.JM Goldstein , LJ Seidman , L O'Brien , . Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging. Arch Gen Psychiatry. 2002; 59, 154164.

50.GM De Courten-Myers . The human cerebral cortex: gender differences in structure and function. J Neuropath Exp Neurol. 1999; 58, 217226.

51.SM Resnick , SA Berenbaum , II Gottesman , TJ Bouchard Jr. Early hormonal influences on cognitive functioning in congenital adrenal hyperplasia. Dev Psychol. 1986; 22, 191198.

52.DGM Murphy , G Allen , JV Haxby , . The effects of sex steroids, and the X chromosome on female brain function: a study of the neuropsychology of Turner syndrome. Neuropsychologia. 1994; 32, 13091323.

53.M Schumacher , JJ Legros , J Balthazart . Steroid hormones, behavior and sexual dimorphism in animals and men: the nature–nuture controversy. Exp Clin Endocrinol. 1987; 90, 129156.

54.S Raz , MD Lauterbach , TL Hopkins , . A female advantage in cognitive recovery from early cerebral insult. Dev Psychol. 1995; 31, 958966.

56.JM Zhang , AT Konkle , SL Zup , MM McCarthy . Impact of sex and hormones on new cells in the developing rat hippocampus: a novel source of sex dimorphism? Eur J Neurosci. 2008; 27, 791800.

57.FM Benes , M Turtle , Y Khan , P Farol . Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. Arch Gen Psychiatry. 1994; 51, 477484.

58.TL Jernigan , DA Trauner , JR Hesselink , PA Tallal . Maturation of human cerebrum observed in vivo during adolescence. Brain. 1991; 114, 20372049.

59.JN Giedd , JW Snell , N Lange , . Quantitative magnetic resonance imaging of human brain development: ages 4–18. Cereb Cortex. 1996; 6, 551560.

60.SF Witelson . Neural sexual mosaicism: sexual differentiation of the human temporo-parietal region for functional asymmetry. Psychoneuroendocrinology. 1991; 16, 131153.

61.AJ Saykin , RC Gur , RE Gur , . Normative neuropsychological test performance: effects of age, education, gender and ethnicity. Appl Neuropsychol. 1995; 2, 7985.

62.RC Gur , BI Turetsky , M Matsui , . Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance. J Neurosci. 1999; 19, 40654072.

63.J Harasty , KL Double , GM Halliday , JJ Kril , DA McRitchie . Language-associated cortical regions are proportionally larger in the female brain. Arch Neurol. 1997; 54, 171176.

64.A Singh-Manoux , M Richards , M Marmot . Socioeconomic position across the lifescourse: how does it relate to cognitive function in mid-life? Ann Epidemiol. 2005; 15, 572578.

65.RE Grunau , MF Whitfield , TB Fay . Psychosocial and academic characteristics of extremely low birth weight (⩽800 g) adolescents who are free of major impairment compared with term-born control subjects. Pediatrics. 2004; 114, e725e732.

66.HG Taylor , M Hack , NK Klein . Attention deficits in children with <750 gm birth weight. Child Neuropsychol. 1998; 4, 2134.

67.I Elgren , AJ Lundervold , K Sommerfelt . Aspects of inattention in low birth weight children. Ped Neurol. 2004; 30, 9298.

68.MM Martel , VC Lucia , JT Nigg , N Breslau . Sex differences in the pathway from low birth weight to inattention/hyperactivity. J Abnorm Child Psychol. 2007; 35, 8796.

69.P Factor-Litvak , A Sher . Invited commentary: coming out of the box. Amer J Epidemiol. 2009; 169, 11791181.

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