Obstetric Complications and Schizophrenia: Historical and Meta-Analytic Review

The much-investigated association between obstetric complications and schizophrenia has provided crucial support for developmental and nongenetic etiological models of the disorder. But does such an association really exist? This review outlines the history of the substantial literature examining this association and provides a quantitative synthesis of selected population-based studies. The limitations of the research methods that are currently used are discussed, and possible new lines of inquiry are suggested.

The first mention of an association between birth complications and schizophrenia occurred in the American Journal of Psychiatry in 1934. Rosanoff and colleagues published “The Etiology of So-Called Schizophrenic Psychoses,” based on detailed case reports of 142 pairs of twins concordant and discordant for schizophrenia. The authors concluded that schizophrenia could be regarded (at least in part) as a “decerebration syndrome which may result from birth trauma.” Somewhat surprisingly, nothing further was published on this topic until 1956 when Pasamanick and colleagues proposed their now-classic thesis of a “continuum of reproductive casualty,” whereby pregnancy and birth complications can lead to a gradient of injury extending from fetal and neonatal death through cerebral palsy, epilepsy, mental deficiency, and behavior disorder. The paper by Pasamanick and colleagues initially had its greatest impact on the field of child psychiatry. In the early 1960s, there were reports of significant associations between pregnancy complications (particularly toxemia, bleeding, and severe maternal illness) and childhood psychosis. However, diagnostic uncertainty about the classification of childhood psychosis seems to have halted research in this area. Even though a review in 1966 concluded that “the need for further research…is strongly indicated by these findings” , there was a gap of 10 years before a study by Torrey and colleagues reported an association between bleeding in pregnancy and childhood psychosis.

Research on Low Birth Weight (1966–1970)
In 1966 attention shifted to adult schizophrenia when Lane and Albee reported that the birth weights of 52 hospitalized schizophrenic adults were significantly lower than that of their siblings. Although the difference between the mean birth weights of the patients and their siblings was significant, it was quite small (in the region of 175 g), and few of the patients actually met the criteria for the “low birth weight” category (< 2500 g). Rather, there appeared to be a “shift in distribution” of birth weight within a population of cases compared with noncases. In 1967 Stabenau and Pollin published an analysis of birth histories of 100 pairs of monozygotic twins discordant for schizophrenia and reported that significantly more of the schizophrenic (index) twins had been the lighter of the two at birth and had experienced birth complications, particularly asphyxia. However, other investigators subsequently failed to find significant differences in birth weight between schizophrenic subjects and siblings or comparison subjects. It is likely that these studies were underpowered to find an effect, as the mean difference in birth weights between groups was actually very similar to that originally reported by Lane and Albee. The epidemiological concept of a “population shift” did not come to attention again until recent years.

Studies of High-Risk Groups (1970–1980)
The next phase of the literature was prompted by an analysis of obstetric complication data from the Copenhagen High-Risk Study. The “high-risk” design examined the characteristics of a group of offspring of schizophrenic parents who were at 10–15 times higher risk of developing schizophrenia than individuals from the general population. Mednick found that 70% of the “high-risk” children who were psychiatrically ill by their early 20s had suffered one or more serious pregnancy or birth complications, compared with 15% of the high-risk group who remained well and 33% of the comparison group (i.e., offspring of parents who did not suffer with schizophrenia). Mednick speculated that, given a subject’s genetic predisposition, schizophrenia would appear only if the hippocampus was selectively injured by anoxia at birth. Analyses of other high-risk study groups revealed an excess of unexplained fetal and neonatal deaths, bleeding and swelling during pregnancy, and neonatal problems. However the research strategy focusing on high-risk children was dealt a severe blow by a series a negative findings and, in particular, by two reports that failed to find any differences between the birth histories of schizophrenic women and those of women with other psychiatric disorders. A review concluded that there was little evidence for an excess of obstetric complications in births to parents with schizophrenia. Although this conclusion was later challenged, the era of research focused on high-risk offspring was effectively over by 1980. Indeed, only a handful of papers on the topic of obstetric complications and schizophrenia were published over the next few years, and interest in the topic seemed to have waned. The development of new brain imaging techniques provided the impetus for the next phase of the literature.

Population-Based Studies (1997–present)
This phase of the literature on obstetric complications and schizophrenia began in earnest in 1997 and continues to date. Studies are characterized by large samples drawn from population-based hospital or case registers, with comparison subjects drawn from the same population, and use of standardized, prospective obstetric data from birth records or registers. Investigators usually report odds ratios for individual obstetric complications and control for demographic confounders by matching or statistical adjustment.

It was hoped (indeed expected!) that these large, methodologically robust studies would provide clear, consistent answers about the relationship between individual obstetric complications and schizophrenia, but this has not proved to be the case. As Table 1 shows, the findings from the population-based studies were mostly negative and surprisingly contradictory. Rather than dealing with each of these studies separately, we have elected to carry out a meta-analytic synthesis of the results. Possible reasons for the discrepancies between studies will be discussed after presentation of the findings from the meta-analysis. The standardized fashion of reporting results and the similarities in the methods of the population-based studies lend themselves to a meta-analytic approach. Meta-analysis provides a method for integrating quantitative data from multiple studies by using a weighted average of the results in which larger studies have more influence than smaller studies. It improves the estimates of effect size, increases the statistical power, and helps to make sense out of studies with conflicting conclusions.

The limitations of using a meta-analytic approach for observational studies should be mentioned. Observational studies may yield estimates of association that are influenced to a greater or lesser degree by confounding or bias, and meta-analysis in itself is no defense against such factors (“bias in equals bias out”). The population-based studies in this analysis were relatively free from bias, and the odds ratios were adjusted for confounders such as sex, hospital where the birth took place, and social class. However the samples were drawn from different populations, in terms of geography, age at illness onset, and cohort and period effects, and all these differences could provide sources of confounding factors. Obstetric practices and methods for recording information about different complications vary between countries and over time.

Complications of pregnancy
Bleeding and preeclampsia in pregnancy have been associated with psychosis since the earliest days of such research. Pasamanick and colleagues singled out the “anoxia-producing complications of pregnancy such as toxemia and bleeding” as most likely to be associated with behavior problems.

Preeclampsia came to particular attention in 1996 when Kendell and colleagues reported a very strong association between preeclampsia and later schizophrenia, but, in their attempt to extend the study group and replicate this finding, a flaw in the original study design was uncovered, and a retraction was published. The revised analysis found no significant effect for preeclampsia. However, in the largest single population-based study to date, preeclampsia was the only obstetric risk factor that remained significant after the analysis controlled for all potentially confounding factors . What could be the mechanism of action of this association? The most popular theory at present involves the mechanism of abnormal fetal blood flow resulting in chronic fetal hypoxia or malnutrition.

Bleeding during pregnancy has many causes. Implantation bleeding and abbreviated menses are common in the first month, and placenta praevia and premature separation of the placenta are frequent causes in the last month. The causes of mid-pregnancy bleeding are less well understood. In one study, two-thirds of the cases were found to be due to premature separation, placenta praevia, hydatiform moles, incompetent cervices, and other identifiable causes, while in one-third of the cases, the cause could not be determined. In severe cases of bleeding, the pathogenic effect on the fetus is thought to be anoxia, but, in many cases, the amount of bleeding may be slight, and anoxic brain damage is unlikely. Another explanation is that bleeding can represent a threatened spontaneous abortion. This is consistent with the striking and as yet unexplained findings of an excess of stillbirths and neonatal deaths among schizophrenic women . Rieder and colleagues hypothesized that bleeding was “the result of rather than the cause of injury. In other words the process of uterine rejection could have begun but been interrupted.” Genetic or autoimmune factors may play a part in such a process.

The association between diabetes in pregnancy and later schizophrenia, although strong, is based on only two studies in this analysis, neither of which provided information on the type of diabetes. Indirect support for the association comes from one report that high prepregnancy body mass increases the risk of schizophrenia in the offspring, since high maternal body mass index is associated with non-insulin-dependent diabetes and gestational diabetes. The effects on the developing brain of altered glucose metabolism are not well understood. Poorly controlled maternal diabetes is associated with an increased risk of congenital anomalies and impaired intellectual and psychomotor development in offspring. Insulin-dependent diabetes mellitus has been found to be more common among the first-degree relatives of patients with schizophrenia than among comparison subjects, indicating that an autoimmune process might be involved. Autoimmune mechanisms could also be implicated in the association between rhesus incompatibility and later schizophrenia. Rhesus hemolytic disease of the newborn is an illness with neurological consequences secondary to effects of a maternal antibody. Hemolytic disease can lead to early spontaneous abortion, chronic fetal hypoxia, neonatal asphyxia and pulmonary edema, and neonatal hyperbilirubinemia and kernicterus. The association has independent support from a cohort study that found a twofold increase in relative risk of schizophrenia among men from rhesus-incompatible pregnancies and a report that neonatal hyperbilirubinemia is a risk factor for later mental illness.

Mary Cannon, M.D., Ph.D., M.R.C.Psych., Peter B. Jones, M.D., Ph.D., M.R.C. Psych., and Robin M. Murray, M.D., D.Sc., F.R.C.Psych.


  1. Rosanoff AJ, Handy LM, Plesset IR, Brush S: The etiology of so-called schizophrenic psychoses: with special reference to their occurrence in twins. Am J Psychiatry 1934; 91:247-286
  2. Pasamanick B, Rogers ME, Lilienfield AM: Pregnancy experience and the development of behavior disorder in children. Am J Psychiatry 1956; 112:613-618
  3. Hinton GG: Childhood psychosis or mental retardation: a diagnostic dilemma, II: paediatric and neurologic aspects. Can Med Assoc J 1963; 89:1020-1024
  4. Taft L, Goldfarb W: Prenatal and perinatal factors in childhood schizophrenia. Dev Med Child Neurol 1964; 6:32-43
  5. Terris M, Lapouse R, Monk MA: The relation of prematurity and previous fetal loss to childhood schizophrenia. Am J Psychiatry 1964; 121:476-481
  6. Voster D: An investigation of the part played by organic factors in childhood schizophrenia. J Ment Sci 1960; 106:494-522
  7. Pollack M, Woerner MG: Pre- and perinatal complications and "childhood schizophrenia": a comparison of five controlled studies. J Child Psychol Psychiatry 1966, 7:235-242
  8. Torrey EF, Hersch SP, McCabe KD: Early childhood psychosis and bleeding during pregnancy. J Autism Child Schizophr 1975; 5:287-297
  9. Lane EA, Albee GW: Comparative birth weights of schizophrenics and their siblings. J Psychol 1966; 64:227-231
  10. Stabenau JR, Pollin W: Early characteristics of monozygotic twins discordant for schizophrenia. Arch Gen Psychiatry 1967; 17:723-734
  11. Pollack M, Woerner MG, Goodman W, Greenberg I: Childhood developmental patterns of hospitalized adult schizophrenic patients and non-schizophrenic patients and their siblings. Am J Orthopsychiatry 1966; 36:510-517
  12. Woerner MG, Pollack M, Klein DF: Birth weight and length in schizophrenics, personality disorders and their siblings. Br J Psychiatry 1971; 118:461-464
  13. Woerner MG, Pollack M, Klein DF: Pregnancy and birth complications in psychiatric patients: a comparison of schizophrenic and personality disorder patients with their siblings. Acta Psychiatr Scand 1971; 49:712-721
  14. Jones PB: Longitudinal approaches to the search for the causes of schizophrenia: past, present and future, in Search for the Causes of Schizophrenia, vol IV: Balance of the Century. Edited by Gattaz WF, Hafner H. New York, Springer-Verlag, 1999, pp 91-119
  15. Mednick SA, Schulsinger F: Some premorbid characteristics related to breakdown in children with schizophrenic mothers. J Psychiatr Res 1968; 6(suppl):267
  16. Mednick SA: Breakdown in individuals at high risk for schizophrenia: possible predispositional perinatal factors. Ment Hyg 1970; 54:51-63
  17. Sobel D: Infant malformations and mortality in children of schizophrenic parents. Psychiatr Q 1961; 35:60-64
  18. Rieder RO, Rosenthal D, Wender P, Blumenthal H: The offspring of schizophrenics, I: fetal and neonatal deaths. Arch Gen Psychiatry 1975; 32:200-211
  19. Modrzewska K: The offspring of schizophrenic parents in a North Swedish isolate. Clin Genet 1980; 17:191-201
  20. Rieder RO, Broman SH, Rosenthal D: The offspring of schizophrenics, II: perinatal factors and IQ. Arch Gen Psychiatry 1977; 34:789-799
  21. Wrede G, Mednick SA, Huttunen MO, Nilsson CG: Pregnancy and delivery complications in the births of an unselected series of Finnish children with schizophrenic mothers. Acta Psychiatr Scand 1980; 62:369-381
  22. McNeil TF, Kaij L: Obstetric complications and physical size of offspring of schizophrenic, schizophrenic-like and control mothers. Br J Psychiatry 1973; 123:341-381
  23. Mirdal GKM, Mednick SA, Schulsinger F, Fuchs F: Perinatal complications in children of schizophrenic mothers. Acta Psychiatr Scand 1974; 50:553-568
  24. Cohler BJ, Gallant DH, Grunebaum HU, Weiss JL, Gamer E: Pregnancy and birth complications among mentally ill and well mothers and their children. Soc Biol 1975; 22:269-278
  25. Hanson DR, Gottesman II, Heston LC: Some possible indicators of adult schizophrenia inferred from children of schizophrenics. Br J Psychiatry 1976; 129:142-154
  26. Sameroff AJ, Zax M: Perinatal characteristics of the offspring of schizophrenic women. J Nerv Ment Dis 1973; 157:191-199
  27. Zax M, Sameroff AJ, Babigian HM: Birth outcomes in the offspring of mentally disordered women. Am J Orthopsychiatry 1977; 47:218-230
  28. McNeil TF, Kaij L: Obstetric factors in the development of schizophrenia: complications in the births of preschizophrenics and in reproduction by schizophrenic parents, in The Nature of Schizophrenia: New Approaches to Research and Treatment. Edited by Wynne LC, Cromwell RL, Mathysse S. New York, John Wiley & Sons, 1978, pp 401-429
  29. . Sacker A, Done DJ, Crow TJ: Obstetric complications in children born to parents with schizophrenia: a meta-analysis of case-control studies. Psychol Med 1996; 26:279-287
  30. Jacobsen B, Kinney DK: Perinatal complications in adopted and non-adopted schizophrenics and their controls: preliminary results. Acta Psychiatr Scand Suppl 1980; 285:337-346
  31. Parnas J, Schulsinger F, Teasdale TW, Schulsinger H, Feldman PM, Mednick SA: Perinatal complications and clinical outcome within the schizophrenia spectrum. Br J Psychiatry 1982; 140:416-420
  32. DeLisi LE, Goldin LR, Maxwell E, Karuba DM, Gershon ES: Clinical features of illness in siblings with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 1987; 44:891-896
  33. Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L: Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 1976; 2:924-926
  34. Weinberger DR, DeLisi LE, Perman G, Targum S, Wyatt RJ: Computed tomography scans in schizophreniform disorder and other acute psychiatric disorders. Arch Gen Psychiatry 1982; 39:778-783
  35. Schulsinger F, Parnas J, Petersen ET, Schulsinger H, Teasdale TW, Mednick SA, Moller L, Silverton L: Cerebral ventricular size in the offspring of schizophrenic mothers "a preliminary study. Arch Gen Psychiatry 1984; 41:602-606
  36. Reveley AM, Reveley MA, Murray RM: Cerebral ventricular enlargement in non-genetic schizophrenia: a controlled twin study. Br J Psychiatry 1984; 144:89-93
  37. Murray RM, Lewis SW, Reveley AM: Towards an aetiological classification of schizophrenia. Lancet 1985; 1:1023-1026
  38. Andreasen N, Nasrallah HA, Dunn V, Olson SC, Grove WM, Ehrhardt JC, Coffman JA, Crossett JHW: Structural abnormalities in the frontal system in schizophrenia. Arch Gen Psychiatry 1986; 43:136-144
  39. Weinberger DR: The pathogenesis of schizophrenia: a neurodevelopmental theory, in The Neurology of Schizophrenia. Edited by Nasrallah HA, Weinberger DR. Amsterdam, Elsevier, 1986, pp 397-406
  40. Murray RM, Lewis SW: Is schizophrenia a neurodevelopmental disorder? (editorial) Br Med J 1987; 295:681-682
  41. Weinberger DR: Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44:660-669
  42. Lewis SW, Murray RM: Obstetric complications, neurodevelopmental deviance and risk of schizophrenia. J Psychiatr Res 1987; 21:413-421
  43. Lewis SW, Owen MJ, Murray RM: Obstetric complications and schizophrenia: methodology and mechanisms, in Schizophrenia: Scientific Progress. Edited by Schultz SC, Tamminga CA. New York, Oxford University Press, 1989, pp 56-68
  44. Eagles JM, Gibson I, Bremner MH, Clunie F, Ebmeier KP, Smith NC: Obstetric complications in DSM-III schizophrenics and their siblings. Lancet 1990; 335:1139-1141
  45. O'Callaghan E, Gibson T, Colohan HA, Buckley P, Walshe DG, Larkin C, Waddington JL: Risk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study. Br Med J 1992; 305:1256-1259
  46. Verdoux H, Bourgeois M: A comparative study of obstetric history in schizophrenics, bipolar patients, and normal subjects. Schizophr Res 1993; 9:67-69
  47. Gunther-Genta F, Bovet P, Hohlfield P: Obstetric complications and schizophrenia: a case-control study. Br J Psychiatry 1994; 164:165-170
  48. Hultman CM, O"hman A, Cnattingius S, Wieselgren I-M, Lindstro"m LH: Prenatal and neonatal risk factors for schizophrenia. Br J Psychiatry 1997; 170:128-133
  49. McCreadie RG, Hall DJ, Berry IJ, Robertson LJ, Ewing JI, Geals MF: The Nithsdale schizophrenia surveys, X: obstetric complications, family history and abnormal movements. Br J Psychiatry 1992; 160:799-805
  50. Heun R, Maier W: The role of obstetric complications in schizophrenia. J Nerv Ment Dis 1993; 181:220-226
  51. Foerster A, Lewis SW, Owen MJ, Murray R: Low birth weight and a family history of psychosis predict poor premorbid functioning in psychosis. Schizophr Res 1991; 5:13-20
  52. Rifkin L, Lewis S, Jones P, Toone B, Murray R: Low birth weight and schizophrenia. Br J Psychiatry 1994; 165:357-362
  53. Smith GN, Kopala LC, Lapointe JS, MacEwan GW, Altman S, Flynn SW, Schnieder T, Falkai P, Honer WG: Obstetric complications, treatment response and brain morphology in adult onset and early-onset males with schizophrenia. Psychol Med 1998; 28:645-653
  54. Willinger U, Heiden A, Mesaros K: Obstetric complications, premorbid and current cognitive functioning in schizophrenics and their same sex healthy siblings (abstract). Schizophr Res 1996; 18:100
  55. O'Callaghan E, Larkin C, Kinsella A, Waddington JL: Obstetric complications, the putative familial-sporadic distinction and tardive dyskinesia in schizophrenia. Br J Psychiatry 1990; 157:578-584
  56. McNeil TF, Cantor-Graae E, Nordstrom LG, Rosenlund T: Head circumference in "preschizophrenic" and control neonates. Br J Psychiatry 1993; 162:517-523
  57. Kunugi H, Takei N, Murray RM, Saito K, Nanko S: Small head circumference at birth in schizophrenia. Schizophr Res 1996; 20:165-170
  58. Owen MJ, Lewis SW, Murray RM: Obstetric complications and schizophrenia: a computed tomographic study. Psychol Med 1998; 18:331-339
  59. Kirov G, Jones PB, Harvey I, Lewis SW, Toone BK, Rifkin L, Sham P, Murray RM: Do obstetric complications cause the earlier age at onset in male than female schizophrenics? Schizophr Res 1996; 20:117-124
  60. Nicolson R, Malaspina D, Giedd JN, Hamburger S, Lenane M, Bedwell J, Fernandez T, Berman A, Susser E, Rapoport JL: Obstetrical complications and childhood-onset schizophrenia. Am J Psychiatry 1999; 156:1650-1652
  61. Hutchinson G, Takei N, Bhugra D, Fahy TA, Gilvarry C, Mallett R, Moran P, Leff J, Murray RM: Increased rate of psychosis among African-Caribbeans in Britain is not due to an excess of pregnancy and birth complications. Br J Psychiatry 1997; 171:145-147
  62. Kuller LH: Circular epidemiology. Am J Epidemiol 1999; 150:897-903
  63. Geddes JR, Lawrie SM: Obstetric complications and schizophrenia: a meta-analysis. Br J Psychiatry 1995; 167:786-793
  64. Geddes JR, Verdoux H, Takei N, Lawrie SM, Bovet P, Eagles JM, Heun R, McCreadie RG, McNeil TF, O'Callaghan E, Sto"ber G, Willinger U, Murray RM: Schizophrenia and complications of pregnancy and labor: an individual-patient data meta-analysis. Schizophr Bull 1999; 25:413-423
  65. Fleiss JL: The statistical basis of meta-analysis. Stat Methods Med Res 1993; 2:121-145
  66. Egger M, Smith GD, Phillips AN: Meta-analysis: principles and procedures. Br Med J 1997; 315:1533-1537
  67. Sacker A, Done DJ, Crow TJ, Golding J: Antecedents of schizophrenia and affective illness: obstetric complications. Br J Psychiatry 1995; 166:734-741
  68. Jones PB, Rantakallio P, Hartikainen A-L, Isohanni M, Sipila P: Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 North Finland general population birth cohort. Am J Psychiatry 1998; 155:355-364
  69. Hultman CM, Sparen P, Takei N, Murray RM, Cnattingius S: Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study. Br Med J 1999; 318:421-426
  70. Dalman C, Allebeck P, Cullberg J, Grunewald C, Ko"ster M: Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort. Arch Gen Psychiatry 1999; 56:234-240
  71. Kendell RE, McInneny K, Jusczak E, Bain M: Obstetric complications and schizophrenia: two case-control studies based on structured obstetric records. Br J Psychiatry 2000; 174:516-522
  72. Byrne M, Browne R, Mulryan N, Scully A, Morris M, Kinsella A, Takei N, McNeil T, Walsh D, O'Callaghan E: Labour and delivery complications and schizophrenia: case-control study using contemporaneous labour ward records. Br J Psychiatry 2000; 176:531-536
  73. Dalman C, Thomas HV, David AS, Gentz J, Lewis G, Allebeck P: Signs of asphyxia at birth and risk of schizophrenia: population-based case-control study. Br J Psychiatry 2001; 179:415-416
  74. Done DJ, Johnstone EC, Frith CD, Golding J, Shepherd PM, Crow TJ: Complications of pregnancy and delivery in relation to psychosis in adult life: data from the British Perinatal Mortality Survey sample. Br Med J 1991; 302:1576-1580
  75. Buka SL, Tsuang MT, Lipsitt LP: Pregnancy/delivery complications and psychiatric diagnosis: a prospective study. Arch Gen Psychiatry 1993; 50:151-156
  76. Cannon TD, Rosso IM, Hollister JM, Bearden CE, Sanchez, Hadley T: A prospective cohort study of genetic and perinatal influences in the etiology of schizophrenia. Schizophr Bull 2000; 26:249-256
  77. Rosso IM, Cannon TD, Huttunen T, Huttunen MO, Lo"nnqvist J, Gasperoni TL: Obstetric risk factors for early-onset schizophrenia in a Finnish birth cohort. Am J Psychiatry 2000; 157:801-807
  78. Zornberg GL, Buka SL, Tsuang MT: Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study. Am J Psychiatry 2000; 157:196-202
  79. DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986; 7:177-188
  80. Kendell RE, Juszczack E, Cole SK: Obstetric complications and schizophrenia: a case-control study based on standardised obstetric records. Br J Psychiatry 1996; 168:556-561
  81. Scott JR: Vaginal bleeding in the midtrimester of pregnancy. Am J Obstet Gynecol 1972; 113:329-334
  82. Schaefer C, Brown AS, Wyatt RJ, Kline J, Begg MD, Bresnahan MA, Susser ES: Maternal prepregnant body mass and risk of schizophrenia in the offspring. Schizophr Bull 2000; 26:275-286
  83. Eriksson UJ: The pathogenesis of congenital malformations in diabetic pregnancy. Diabetes Metab Rev 1995; 11:63-82
  84. Wright P, Sham PC, Gilvarry CM, Jones PB, Cannon M, Sharma T, Murray RM: Autoimmune diseases in the pedigrees of schizophrenic and control subjects. Schizophr Res 1996; 20:261-267
  85. Gilvarry CM, Sham PC, Jones PB, Cannon M, Wright P, Lewis SW, Bebbington P, Toone BK, Murray RM: Family history of autoimmune diseases in psychosis. Schizophr Res 1996; 19:33-40
  86. Hollister JM, Brown AS: Rhesus incompatibility and schizophrenia, in Prenatal Exposures in Schizophrenia. Edited by Susser ES, Brown AS, Gorman JM. Washington, DC, American Psychiatric Press, 1999, pp 197-214
  87. Hollister JM, Kohler C: Schizophrenia: a long-term complication of haemolytic disease of the fetus and newborn? Int J Ment Health 2001; 29:38-61
  88. Hollister JM, Laing P, Mednick SA: Rhesus incompatibility as a risk factor for schizophrenia in male adults. Arch Gen Psychiatry 1996; 53:19-24
  89. Dalman C, Cullberg J: Neonatal hyperbilirubinemia "a vulnerability factor for mental disorder? Acta Psychiatr Scand 1999; 100:469-471
  90. Ichiki M, Kunugi H, Takei N, Murray RM, Baba H, Arai H, Oshima I, Okagami K, Sato T, Hirose T, Nanko S: Intra-uterine physical growth in schizophrenia: evidence confirming excess of premature birth. Psychol Med 2000; 30:597-604
  91. Wahlbeck K, Forsen T, Osmond C, Barker DJP, Eriksson JG: Association of schizophrenia with low maternal body mass index, small size at birth and thinness during childhood. Arch Gen Psychiatry 2001; 58:48-52
  92. Bennedsen BE: Adverse pregnancy outcome in schizophrenic women: occurrence and risk factors. Schizophr Res 1998; 33:1-26
  93. Lane A, Kinsella A, Murphy P, Byrne M, Keenan J, Colgan K, Cassidy B, Sheppard N, Horgan R, Waddington JL, Larkin C, O'Callaghan E: The anthropometric assessment of dysmorphic features in schizophrenia as an index of its developmental origins. Psychol Med 1996; 27:1155-1164
  94. McNeil T, Cantor-Graae E, Ishmail B: Obstetric complications and congenital malformations in schizophrenia. Brain Res Brain Res Rev 2000; 31:166-178
  95. Cannon TD, Mednick SA, Parnas J, Schulsinger F, Praestholm J, Vestergaard A: Developmental brain abnormalities in the offspring of schizophrenic mothers, I: contributions of genetic and perinatal factors. Arch Gen Psychiatry 1993; 50:551-564
  96. Cannon TD: On the nature and mechanisms of obstetric influences in schizophrenia: a review and synthesis. Int Rev Psychiatry 1997; 9:387-397
  97. McNeil TF, Cantor-Graae E, Weinberger DR: Relationship of obstetric complications and differences in size of brain structures in monozygotic twin pairs discordant for schizophrenia. Am J Psychiatry 2000; 157:203-212
  98. Goodman R: Are complications of pregnancy and birth causes of schizophrenia? Dev Med Child Neurol 1990; 30:391-406
  99. Nelson KB, Ellenberg JH: Antecedents of cerebral palsy: multivariate analysis of risk. N Engl J Med 1986; 315:81-86
  100. McNeil TF, Cantor-Graae E: Does pre-existing abnormality cause labor-delivery complications in fetuses who will develop schizophrenia? Schizophr Bull 1999; 25:425-435
  101. Wald NJ, Nanachal K, Thompson SG, Cuckle HS: Does breathing other people's tobacco smoke cause lung cancer? Br Med J (Clin Res Ed) 1986; 293:1217-1222
  102. Collaborative Group on Hormonal Factors in Breast Cancer: Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data of 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347:1713-1727
  103. Taubes G: Epidemiology faces its limits. Science 1995; 269:164-169
  104. Cannon M, Jones P, Gilvarry C, Rifkin L, McKenzie K, Foerster A, Murray RM: Premorbid social functioning in schizophrenia and bipolar disorder: similarities and differences. Am J Psychiatry 1997; 154:1544-1550
  105. Zornberg G, Buka SL, Tsuang MT: The problem of obstetrical complications and schizophrenia. Schizophr Bull 2000; 26:249-256
  106. McNeil TF Perinatal risk factors and schizophrenia: selective review and methodological concerns. Epidemiol Rev 1995; 17:107-112
  107. Bagalkote H, Pang D, Jones P: Maternal influenza and schizophrenia in the offspring. Int J Ment Health 2001; 29:3-21
  108. Brown AS: Prenatal infection and adult schizophrenia: a review and synthesis. Int J Ment Health 2001; 29:22-37
  109. Susser E, Lin SP: Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944-1945. Arch Gen Psychiatry 1992; 49:983-988
  110. Huttunen M, Niskanen P: Prenatal loss of father and psychiatric disorders. Arch Gen Psychiatry 1978; 35:427-431
  111. Kinney DK: Prenatal stress and risk for schizophrenia. Int J Ment Health 2001; 29:62-71
  112. Brown AS, Cohen P, Greenwald S, Susser E: Nonaffective psychosis after prenatal exposure to rubella. Am J Psychiatry 2000; 157:438-443
  113. Stewart AL, Rifkin L, Amess PN, Kirkbride V, Townsend JP, Miller DH, Lewis SW, Kingsley DPE, Moseley IF, Foster O, Murray RM: Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm. Lancet 1999; 353:1653-1657
  114. Verdoux H, Geddes JR, Takei N, Lawrie SM, Bovet P, Eagles JM, Heun R, McCreadie RG, McNeil TF, O'Callaghan E, Sto"ber G, Willinger U, Wright P, Murray RM: Obstetric complications and age at onset in schizophrenia: an international collaborative meta-analysis of individual patient data. Am J Psychiatry 1997; 154:1220-1227
  115. Van Os J, Marcelis M: The ecogenetics of schizophrenia: a review. Schizophr Res 1998; 32:127-135
  116. Susser E, Schaefer C, Brown A, Begg M, Wyatt RJ: The design of the Prenatal Determinants of Schizophrenia Study (PDS). Schizophr Bull 2000; 26:257-274
  117. Kandel ER: A new intellectual framework for psychiatry. Am J Psychiatry 1998; 155:457-469
  118. Fearon P, Cannon M, Murray RM: A critique of the idea and science of risk-factor research in schizophrenia. Int J Ment Health 2001; 30:82-90
  119. Benes FM: Emerging principles of altered neural circuitry in schizophrenia. Brain Res Brain Res Rev 2000; 31:251-269
  120. Susser M, Susser E: Choosing a future for epidemiology, II: from black boxes to Chinese boxes and eco-epidemiology. Am J Public Health 1996; 86:674-677
  121. Cotter D, Takei N, Farrell M, Sham PC, Quinn P, Larkin C, O'Callaghan E: Does prenatal exposure to influenza in mice induce pyramidal cell disarray in the dorsal hippocampus? Schizophr Res 1995; 16:233-241
  122. Fatemi SH, Emamian ES, Kist D, Sidwell RW, Nakajima K, Akhter P, Shier A, Sheikh S, Bailey K: Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. Mol Psychiatry 1999; 4:145-154
  123. Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Bernstein D, Yolken RH: Maternal infections and subsequent psychosis among offsrping. Arch Gen Psychiatry 2001; 58:1032-1037
  124. Jones P, Cannon M: The new epidemiology of schizophrenia. Psychiatr Clin North Am 1998; 21:1-26

Source: http://ajp.psychiatryonline.org/cgi/content/full/159/7/1080

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