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Schizophrenia in people with intellectual disability: the role of pregnancy and birth complications
J. M. O'Dwyer
Department of Psychiatry, Northern General Hospital, Sheffield, England

Abstract
The literature suggests that mental illness is more common in people with intellectual disability than in the general population. Having reviewed the literature, Turner (1989) [Psychological hAedidne 19, 301-14] suggested that about 3% of people with intellectual disability also have schizophrenia. As pregnancy and birth complications (PBCs) occur more commonly in people with intellectual disability than in the general population and are also implicated in the aetiology of schizophrenia, it is possible that these conditions share a common aetiology. This study reports on the occurrence of PBCs in those people with intellectual disability who develop schizophrenia. Fifty people with intellectual disability and schizophrenia were matched for age, sex, degree of intellectual disability and presence of epilepsy with a control group who did not suffer from schizophrenia or a schizophreniform psychosis. The obstetric history was obtained and events rated on a scale specifically designed for this study. This PBCs scale consists of six sub-scales covering areas of general maternal health, pregnancy, delivery, medication in labour, total medication score and neonatal score, as well as an overall total score. The study found that people with intellectual disability who develop schizophrenia have significantly higher

rates of PBCs than controls. All of the sub-scales on the PBCs scale were significantly higher in people with schizophrenia, with the exception of the medication scales. Only Tive out of the 50 people with schizophrenia had not had a major obstetric complication, compared to 13 subjects from the control group. A number of abnormalities were specifically higher in people who later developed schizophrenia. These included: abnormally long or short labour; maternal episiotomy; maternal preeclamptic toxaemia; induction of labour; dysmaturity; maternal smoking in pregnancy; and a delay in neonatal crying. The results suggest that PBCs are important in the aetiology of schizophrenia in people with intellectual disability.

Keywords schizophrenia, ititellectual disability, pregnancy and birth complications

Introduction
Schizophrenia and intellectual disability

Correspondence; Dr Jane M. O'Dwyer, Department of Psychiatry, Northern General Hospital, Herries Road, Sheffield S5 7AU, England.

Operational distinctions between idiocy (intellectual disability) and dementia (mental illness) have existed since the seventeenth century. Pinel (1802) suggested that mental illness and intellectual disability were different, but coexisted, a view supported by Esquirol (1845). Descriptions of schizophrenia-like illnesses in people with

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intellectual disability have been reported since the 1870S (Ireland 1877). Out of those with intellectual disability, Tredgold (1903) suggested that, 'considerably more than half had at one time or the other been insane', while Kraepelin (1896, 1902) suggested that about 7% of cases of dementia praecox arose on the basis of idiocy. As the acceptance of the coexistence of various types of mental illness and intellectual disability grew, the prevalence of each was studied. Reports of the prevalence of schizophrenia in people with intellectual disability vary from 1.3% (Lund 1985) to 63% (Hucker et al. 1979). Like other illnesses, the prevalence of schizophrenia greatly depends on the characteristics of the population studied. The prevalence rate tends to be higher in hospitalized populations in comparison with other groups. This is not unexpected and may be the reason for admission. Many earlier studies give falsely high estimates by including people with odd mannerisms and symptoms of what is regarded today as pervasive developmental disorder under the diagnostic category of schizophrenia. In a review of research into this area. Turner (1989) suggested that about 3% of people with intellectual disability also have schizophrenia. He concluded that this is probably an underestimate because of difficulties in making a firm diagnosis.
The aetiology of schizophrenia

prominent. Rosanoff & Inman-Kane (1934) tentatively suggested that schizophrenia, intellectual disability and epilepsy could share a common aetiology; namely, cerebral trauma. However, this idea was not explored further at the time. Even so, a traumatic aetiology in schizophrenia was later supported by Katz (1939) and Anderson (1952), who found higher rates of PBCs in association with the disorder.
Pregnancy and birth complications in schizophrenia

Pathological abnormalities in the brain were described in association with schizophrenia at the beginning of this century (Watson 1910; MacKenzie 1912; Bolton 1913; Rosanoff 1914). Southard (1915) suggested that such abnormalities in people with schizophrenia were 'probably of the nature of an interference with the development of tissues properly laid down embryologically' and tentatively suggested that schizophrenia had a prenatal origin. In an early twin study in schizophrenia, Rosanoff & Inman-Kane (1934) proposed that a large proportion of cases of schizophrenia were results of 'partial decerebration', which was 'mainly of traumatic or infectious origin'. These authors described higher rates of head injury, birth trauma and infection among people with schizophrenia, and concluded that genetic factors would play a minor role where an infectious or traumatic aetiology was

Pregnancy and birth complications (PBCs) include any untoward event of pregnancy and delivery, and can be defined as 'any event in the prenatal or perinatal environment that increases the risk of foetal mortality' (Prechtl 1967). Recent studies investigating the role of PBCs in schizophrenia have reported increased rates of PBCs in people with schizophrenia when compared to: (1) unrelated controls (Pollock & Greenberg 1966; McNeill & Kaij 1978; Jacobsen & Kinney 1980; Wilcox & Nasrallah 1987; Foerster et al. 1991; O'Callaghan et al. 1992; Mednick 1994; Verdoux & Bourgeois 1993; Buka et al. 1993); (2) siblings and/or other family members (Woemer et al. 1973; Pamas et al. 1982; deLisi et al. 1988; Goodman & Emroy 1992; Huen & Maier 1993); (3) co-twins (Stabenau et al. 1967; Bracha et al. 1992; Onstad et al. 1992). The findings of studies investigating the role of PBCs suggest that such complications are important in the aetiology of schizophrenia. Studies suggesting otherwise could be a reflection of small sample size and difficulty in patient recruitment. No previous studies have reported the occurrence of PBCs in people with intellectual disability who develop schizophrenia. The reports of increased PBCs and the theory of an organic aetiology in schizophrenia have been supported by the findings of post-mortem (Bigelow et al. 1983; Jakob & Beckmann 1986; Crow et al. 1989; Bruton et al. 1990) and neuroradiological studies (Weinberger et al. 1979, 1981; Reveley et al. 1982; Andreasen et al. 1986; Cleghorn et al. 1989; Mathew & Wilson 1990; Andreasen et al. 1992; Cannon et al. 1993). Generally, these studies conclude that schizophrenia is associated with abnormalities of the temporal lobe which in turn are

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associated with higher rates of pregnancy and birth complication (Reveley et al. 1984; Silverton et al. 1985; De Lisi et al. 1986; Owen et al. 1988; Cannon et al. 1989; Pearlson 1989; Cannon et al. 1993).
The aetiology of intellectual disability

Birth injuries have been associated with the development of intellectual disability since the last century, when Little (1862) reported a condition of mental deficiency, paralysis, contractures and epilepsy (Little's disease, now cerebral palsy) in which he proposed anoxia was the causative agent. Since then, PBCs have been consistently implicated in the aetiology of intellectual disability. Studies which report the occurrence of obstetric complications in people who develop intellectual disability find consistently higher rates in the latter compared to controls (Lilienfeld et al. 19555 Pasamanick & Lilienfeld 1955; Chefetz 1965J Turner 19755 Nelson & Broman 1977; Rao 1990; Wellesley et al. 1991; Buka et al. 1993). The factors most frequently implicated in the aetiology of intellectual disability are: anoxia and asphyxia in labour (Westgren et al. 1986; Buka et al. 1993)5 malpresentations, most commonly breech (Dale & Stanley 1980; Nilsen & Bergsjo 1985); vaginally delivered breech presentations (Bolte et al. 1986; Luterkort et al. 1987); low birth weight; dysmaturity (Ranntakillo et al. 1985; Dunn 1986); bleeding in pregnancy (Hagberg et al. 1976; Taylor et al. 1985; Nelson & EUenberg 1986); maternal hypertension in pregnancy (Nelson & EUenberg 1986; Szymonowicz & Yu 1987); maternal diabetes (Dekaban & Magee 1958; Robinson 1970); maternal infection with syphilis, rubella, cytomegalovinis, influenza, listeriosis, congenital toxoplasmosis. Varicella zoster and/or Herpes simplex virus (Penrose 1938; Swan & Tostevin 1941; Coffey & Jessop 1959; Manson et al. 1963; Fleck 1973; Hanshaw & Dudgeon 1978; Dudgeon 1984); and drugs or substance use/abuse, most commonly alcohol (Claren & Smith 1978; Olegard et al. 1979; Hagberg et al. 1981; Blomquist etal. 1981). However, the long-term prognosis for people whose births are complicated is influenced by other factors including the underlying cause of the complication and its management. Pregnancy and birth complications are only one of a number of

factors that influence the development of any infant. The occurrence of a disability resulting from obstetric factors depends on the cause, the clinical management and the infant's capacity to overcome adversity. In conclusion, the literature suggests that PBCs are more common in people who develop schizophrenia, and people who develop intellectual disability. Furthermore, people with intellectual disability are more likely to develop schizophrenia. It is possible that the conditions share a common aetiology; namely, that of an anoxic insult to the brain in the pre- or perinatal period.

Materials and methods

Hypothesis

Pregnancy and/or birth complications are more common in people with intellectual disability who develop schizophrenia. Method The present study is a case-controlled investigation to determine whether people with intellectual disability and schizophrenia experience more PBCs than people without schizophrenia.
Subjects

The population was identified by contacting all of the consultant psychiatrists who dealt with people with intellectual disability in Yorkshire, England, and the surrounding areas. They were asked to supply the names of people vsdth a diagnosis of schizophrenia and intellectual disability. Recruitment finished when 50 people with intellectual disability and schizophrenia were included. The psychiatric case notes of each of the potential study patients were examined, and information regarding date and place of birth, gender, number of siblings, birth order, development, past medical and psychiatric history, degree of intellectual disability, family history of mental illness, and intellectual disability (including diagnosis) was recorded, as was the evidence for schizophrenia and the degree of intellectual

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disability. The next of kin was sent a questionnaire regarding the place of birth of their relative and a consent form indicating whether they wished their relative to take part in the study. Information regarding the patient was also obtained from other sources, including obstetric case notes, interviews with subjects, mothers and carers. Each subject was contacted and consent to be interviewed sought. Consent was usually verbal, except in the case of people with literacy skills, from whom written consent was obtained. The next of kin and main carer were contacted, and written consent to interview their relative was obtained. Cases in this study were defined at interview by using the DSM-IV operational criteria for schizophrenia. In those cases in whom symptoms were no longer active, the case notes were examined, and they were included only if the patients met the DSM-IV criteria for schizophrenia as described by the case notes and were receiving treatment for the disorder. The Psychopathology Inventory for Mentally Retarded Adults (Senatore et al. 1985) and the Reiss Screen for Maladaptive Behaviour (Reiss 1988) were completed by the main carer and investigator, and used to corroborate the diagnosis. The investigator traced the maternal obstetric case notes, and a history of the events of the pregnancy and birth were extracted. In cases where the patient's mother was alive, she was asked to recall her obstetric history. The events of the pregnancy and delivery were rated on a scale specifically designed for use in this study. It rates various complications on six sub-scales covering general maternal health, pregnancy, delivery, medication (in labour and total medication scores) and neonatal period, and has a total score for PBCs. The scale is more detailed than previous scales and has a specific medication score. In each case, the degree of intellectual disability was assessed by the investigator and rated using the ICD-IO criteria for mental retardation. The main carer also rated the degree of intellectual disability using the ICD-IO criteria. In cases where there was a difference of opinion, a third rating was obtained from the case notes, another carer or the next of kin: the average of the three ratings was used.

The diagnosis of epilepsy was based on a history of two or more non-febrile seizures before the age of 18 years. Electroencephalogram support was sought, but its absence did not exclude the diagnosis, which was made on clinical descriptions. Each subject met the following inclusion criteria: (1) subjects had intellectual disability; (2) subjects met the DSM-IV criteria for schizophrenia; (3) an obstetric history was available; and (4) consent to interview was available from the subject and their next of kin.

Controls

Each subject with schizophrenia was paired with a control and matched for age, sex, degree of intellectual disability and presence of epilepsy. The procedure for recruitment of the controls was similar to that of people with schizophrenia. Controls imderwent the same assessments and interviews as the subjects, and their obstetric histories were obtained in the same way. Controls met the following inclusion criteria: (1) controls had intellectual disability; (2) controls had no history of schizophrenia or schizophreniform psychosis; (3) obstetric history was available; (4) consent to interview was available from controls and from their next of kin; and (5) each control was a suitable match for one of the subjects in terms of age, sex, degree of intellectual disability and presence of epilepsy. The data were analysed with the SPSS computer programme. Paired sample j-tests, Wilcox signed rank tests and chi-square tests were used as appropriate.

Results Subjects and controls

The initial contact with consultant psychiatrists provided 360 people with intellectual disability and possible schizophrenia. Out of those initially suggested, 310 were excluded, leaving the total study sample of 50 people with schizophrenia as intended. People were excluded for four reasons: (i)

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insufficient evidence of schizophrenia (26%); (2) obstetric history unavailable (57%); and no consent from (3) next of kin (15.5%) or (4) subject (1.5%). Each person with schizophrenia was matched for age, sex, degree of intellectual disability and presence of epilepsy with a control. To establish the control group, 172 people with intellectual disability were contacted. Out of the 122 exclusions, the reasons for exclusion were: obstetric history unavailable (76%), and no consent from next of kin (22%) or control (2%). The group with schizophrenia and the control group were matched for age. The mean age of the group with schizophrenia was 32.2 years (range 19-59 years) and that of the control group was 32.4 years (range 18-61 years); there was no significant difference. The groups were matched for gender (62% male and 38% female). The degree of intellectual disability was also one of the matching variables. Seventy per cent had mild intellectual disability, 28% were moderate and 2% were severely intellectually disabled. There was close agreement between raters when assessing the degree of intellectual disability in controls (Kappa = 0.91), but less in people with schizophrenia (Kappa = 0.58). In each group, there were 15 people with epilepsy (30% of the total sample). All had been diagnosed as having epilepsy before the age of 12 years, and the onset was before the age of one year in 50%. Ethnic origin was the same in both groups: the majority (90%) were Caucasian. The majority either lived with their family or in other community settings. Unexpectedly, the numbers of subjects and controls living in hospital was the same (n = 9) .The frequency of serious head injury (leading to unconsciousness) was the same in both groups
(M = 3).

obsessive compulsive disorder, anxiety disorder, antisocial personality disorder and exhibitionism (8%). Using the Reiss scale for Maladaptive Behaviour, 68% of people with DSM-IV schizophrenia were diagnosed as having a psychosis and 44% as having paranoia. Using the short version of the Reiss scale, subjects with schizophrenia had a mean score of 18.5, which was significantly higher than the controls at 12.5 (z = -3.64; P= 0.0003). The PIMRA revealed that 80% of people with DSM-IV schizophrenia were diagnosed as having schizophrenia, while the mean total PIMRA scores for the group with DSM-IV schizophrenia was 18.2, which was significantly higher than the control group at 12.8 (0 = -3.75; P= 0.0002).

Obstetric history The obstetric history was available from maternal case notes in 10 people with schizophrenia and in 10 controls. The information was available through maternal interviews in 26 people with schizophrenia and 28 controls, while it was attained from both sources in 11 people with schizophrenia and nine controls. As the obstetric history was available from two sources in 20 people, it was possible to compare the two sets of scores on the PBCs scale in these 20 cases. There was little difference in the histories obtained (Kappa = 0.93), and in no case was there disagreement between the history obtained from the mother or case notes regarding the occurrence of major complications. As this PBCs scale had not been used before, another established obstetric complication score (Woemer et al. 1973) was completed for each person. There was a high degree of agreement between the total scores of the two scales (Kappa = 0.91).
Pregnancy and birth complications

Each person was interviewed to determine whether they had a mental illness. By definition, all subjects with schizophrenia met DSM-IV criteria. The majority had paranoid schizophrenia (78%), followed by disorganized (12%) and undifferentiated schizophrenia (10%). An anxiety disorder and an intermittent explosive disorder were present in addition to the diagnosis of schizophrenia in three subjects and one subject, respectively. Out of the controls, 23 (46%) had no mental illness, 16 (32%) an intermittent explosive disorder, seven (14%) an affective disorder, and one person each had

There was no important difference between the groups according to place of birth (x^ = 1.09; d.f. - 2; P= 0.58); the majority of each group (85%) were bom in hospital. The mean age of the mother at the birth of the subjects was 27.4 years (range 17-43 years) for people with schizophrenia and 28.1 years (range 18-43 years) for the control group, which was not statistically significant (paired - 0.64;

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Table I Mean total pregnancy and birth complications scores

Score Number Mean Median Standard deviation Range Schizophrenia Controls 50 7.9 7 Total

Table 2 Pregnancy and birth complications: mean subscale scores*

Scale Schizophrenia Controls Z-value P-value

50
14.9

13
8.6 2-41

6.0 0-27

100 11.4 9 8.1 0-41

(n=50)
Maternal history 0.9(1) Pregnancy 4.54 (4) 3.46(3) Delivery Medication: labour 1.86(2) total 2.92 (2) 4.1 (3) Neonatal Total scores 14.9(13)

(n=50)

0.52(0) 1.9(1) 2.06 (2) 1.5(1) 1.8(2) 1.9(0) 7.9 (7)

-1.81 -4.39 -2.83 -1.30 -2.52 -2.81 -4.34

0.069 O.OOOt 0.005t 0.194 0.01 I t 0.005t O.OOOt

d.f. = 49J P = 0.53). The mean number of siblings for people with schizophrenia was 3.7, which was not significantly different from controls at 3.4 (0 = -0.77; P = 0.44). There was no significant difference regarding order of birth between the groups (x^ = 0.32; d.f. = i; P = 0.57). The scale used to rate PBCs covers maternal health, events during pregnancy, delivery and medication (both in labour and a total medication score which includes medication ingested in the pregnancy), and a neonatal score. It also provides a total score. Higher scores indicate more complicated pregnancies and deliveries. The total difference in PBCs scores between each schizophrenia-control pair are shown in Table i and Figure i. The mean total PBCs score was significantly higher in people with schizophrenia (z = -4.345 P<o.oooi). Therefore, the hypothesis is supported:
40 n

* Figures in brackets represent the median values, t Statistically signiRcant.

subjects with intellectual disability and schizophrenia have an excess of PBCs. However, because this could be the result of higher scores on any sub-scale, the mean and median values of each score are presented (Table 2). Therefore, with the exception of the maternal history and medication used in labour, people with schizophrenia had significantly higher scores on all of the sub-scales as well as on the total PBCs score. The controls were a heterogeneous group with regard to their psychiatric history: less than half did

-30 10 13 16 19 22 25 28 31 34 Casecontrol pair number 37 40 43 46 49

Figure I Total difference in PBCs scores between each schizophrenia-control pair.

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Table 3 Pregnancy and birth complications in the control group: comparisons with various psychiatric disorder?*
Psychiatric disorder Scales Number Maternal history Pregnancy Delivery Medication: labour total Neonatal Affective Explosive Other None 21 0.5 (0.5) 2.33 (2.5) 2(2) 1.3(1) 1.8(1.5) 1.8(1.5) 8.2(8) 0.43 (0) 1.24(1) 1.5(1) 1.4(1) 1.7(1) 1.4(0)

Table 4 Frequency of the most commonly reported pregnancy and birth complications
Complication Long/short labour Air/gas in labour Episiotomy Medication in pregnancy PET/toxaemia Pethedine (in labour) Induction Dysmaturity Mild neonatal illness Smoking in pregnancy Breathing difficulties Crying delay Other neonatal problemst Schizophrenia 33 30 29 24 23 22 22 21 18 19 16 18 13 Controls P-Value

16
0.57(1) 2.29 (3) 1.7(2) 0.86 (0) 1.3(1) 1.86 (0) 0.63 (0) 2.44 (2.5) 2.99 (2) 1.94(2) 2.2 (2) 2.63(1) 10.56(8.5)

Total scores 7.2 (7)

6(5)

17 24 1 9 1 3 12 1 9 9 10 10 9 8 5 4

0.008* 0.240 0.045* 0.160 0.021* 0.690 0.014* 0.017* 0.086 0.026* 0.10 0.002* 0.017*

* Figures in brackets represent the median values.

not have a psychiatric disorder. The mean total PBCs scores between controls with and without a mental illness are summarized in Table 3, and were significantly higher when mental illness or behaviour disorder was present (z = -2.175 P = 0.03). Comparing the controls with no mental illness with people with schizophrenia, the mean PBCs scores are significantly higher in the group with schizophrenia (z = -4.264; P<o.oooi). A further comparison of controls with a diagnosis of mental illness or behaviour disorder, and subjects with schizophrenia revealed that the latter have significantly higher mean scores (0= -3.06; P = 0.002). The differences are maintained when comparing some the individual diagnostic groups (of controls) to the group with schizophrenia. People with affective disorder had significantly lower scores than subjects with schizophrenia (.z = -2.3; P = 0.018). However, although people with schizophrenia had higher scores than those with intermittent explosive disorder, the difference was not statistically significant (0 = -1.78; P = 0.075). There was no significant difference found in the mean total PBCs scores between the controls with intermittent explosive disorder and affective disorder (0 = -0.872; P = 0.38). As the groups were matched for the presence of epilepsy, the degree of intellectual disability and gender, therefore the differences in PBCs scores between subjects with schizophrenia and controls are unlikely to be caused by these factors.

* Statistically significant. t Including neonatal jaundice, somnolence, neonatal surgery, abnormal muscle tone, severe neonatal vomiting, transfusions and septicaemia.

The frequency of different pregnancy or birth complications is shown in Table 4. With the exception of older maternal age at birth, false labour and severe congenital defects in the baby, all complications rated were all more common in the mothers of people who subsequently developed schizophrenia. Out of the group with schizophrenia, onlyfivehad not suffered some major pregnancy or birth complication (including events in pregnancy and delivery). This contrasts with the controls, in whom 13 had not suffered some similar type of event (X^ = 5.26; d.f. = r,P= 0.022). Such events included instrumental delivery, dysmaturity, prolonged labour, bleeding in pregnancy and foetal distress syndrome. At interview, each mother was asked whether the baby had been wanted, and if not, whether any steps had been taken to terminate the pregnancy. This information was also collected from the case notes. Mothers had attempted to terminate the pregnancy in nine people who subsequently developed schizophrenia and in two controls. This was statistically significant (x^ = 5.9; d.f. = r, P= 0.015). Methods of attempted termination included overdoses of medication, insertion of foreign bodies to the vagina, physical trauma, and in one case, the

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child was bom after the failure of an apparently successful therapeutic abortion.

Discussion

The original hypothesis states that PBCs are more common in people with intellectual disability who develop schizophrenia. The results provide strong evidence supporting this theory which has not previously been reported. The total PBCs score was higher in subjects with schizophrenia. The findings reported here generally support the results of the early work of Rosonoff et al. (1934) and Katz (1939) in the 1930s, and the bulk of the research findings since then. As the groups were matched for age, sex, degree of intellectual disability and presence of epilepsy, the differences in scores of the groups are unlikely to be explained by any of these factors. The group with schizophrenia had a higher rate of abnormal pregnancies compared to the control group. Only five (10%) people with schizophrenia had not suffered a major obstetric complication, compared to 13 (26%) controls. However, the frequency of major complications in controls was also unexpectedly high: it is likely that such complications accounted for the intellectual disability. The overall PBCs scores are higher in people with schizophrenia, which was not caused by the occurrence of a few specific complications. Rather, most obstetric complications are commoner in mothers of people who develop schizophrenia compared to the controls. Other complications would probably be significantly higher in people with schizophrenia if the sample size was bigger. The finding of abnormally long labour in subjects who subsequently develop schizophrenia supports previous findings, including those of Reddy et al. (1990). Dysmaturity was commoner in the group who developed schizophrenia, which supports the findings of Gillberg et al. (1986), who found that postmaturity was more common in people who develop teenage psychosis. The finding that pre-eclamptic toxaemia was significantly higher in the mothers of people who subsequently developed schizophrenia supports

the findings of Lewis & Murray (1987). The rate of instrumental deliveries was slightly higher in people with schizophrenia, but the rate of caesarean section delivery was the same in both groups (ra = 3). This is contrary to the findings of Anderson (1952), who suggested that caesarean section delivery was of aetiological significance in the development of schizophrenia. However, there are more events in the group with schizophrenia pre-disposing to anoxic brain damage, including abnormally long or short labour, dysmaturity, and pre-eclamptic toxaemia; the Caesarean section rate of the groups is the same. It is possible that people who develop schizophrenia do so as a result of anoxic brain damage, which could be avoided by the more liberal use of Caesarean section delivery. This needs further investigation. That PBCs are higher in people with schizophrenia does not imply that they are the cause of the disorder. It is possible that there is an underlying common factor relating these complications: these could be indicators of foetal or neonatal asphyxia. The nature of the problems reported (e.g. dysmaturity, pre-eclamptic toxaemia and maternal smoking) tend to be of a chronic nature and could result in foetal hypoxia by a variety of mechanisms. This supports the finding of Buka et al. (1993) that subjects suffering from chronic foetal hypoxia had higher rates of cognitive impairment and psychotic disorder. Some complications which occurred in the group with schizophrenia did not occur in the control group at all, making statistical evaluation impossible. These included unstable lie (n = 5), severe emotional shock (n = 4) and abdominal trauma (n = i). As these complications did not occur in the control group their aetiological significance is unknown, but the non-occurrence may be a result of the small numbers in these groups. Older maternal age at birth, false labour and severe congenital defects are the only complications more common in the control group, and none were significantly so. The older maternal age and severe congenital defects could be accounted for by the higher rate of Down's syndrome in the control group. There are other possible explanations for the increase in PBCs scores. People who develop

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schizophrenia could be neurologically impaired from the time of conception, which could give rise to an increase in PBCs. Given the data here, it is not possible to say that this is not the case. However, as the group of subjects with schizophrenia is heterogeneous, with varying degrees of intellectual disability (some had epilepsy and some had a family history of the disorder), it is unlikely that they share some unidentified common factor which results in an increase in birth injuries and schizophrenia. Furthermore, the controls included people with Down's syndrome, and other genetic and chromosomal abnormalities (i.e. foetuses known to be impaired from the moment of conception), so if this notion were true, one might expect higher rates of PBCs in this group of foetuses rather than in those without an initial identified abnormality who subsequently develop schizophrenia. The higher PBCs scores in people who develop schizophrenia remained when subjects with schizophrenia were compared to the controls with mental illness. Subjects with a diagnosis of intermittent explosive disorder or affective disorder had higher scores than the controls without mental disorder, but had lower scores than those with schizophrenia. The difference in scores between the controls with or without mental illness was significant, and is likely to be accounted for by a higher rate of PBCs in people with intermittent explosive disorder. This suggests that PBCs may be an aetiological factor specific to schizophrenia or intermittent explosive disorder, rather than a general factor predisposing to mental illness. The higher rate of obstetric complications in the group with schizophrenia could, in theory, be accounted for by the higher family history of the disorder. However, even though information regarding a family history of mental illness was recorded, relatives were not interviewed to confirm the diagnosis. The study found that there was a family history of schizophrenia in seven people with schizophrenia compared to only two controls. Theoretically, this could cause an apparent increase in PBCs in cases in which the patient's mother had a schizophrenic illness (which occurred in three out of the seven). Although the actual numbers were small, these three cases were not found to have significantly different total PBCs scores compared to the group with schizophrenia as a whole. The

higher rate of attempted termination also deserves comment. In theory, this could be related to maternal schizophrenia, but the present author found that a history of maternal schizophrenia was present in only one of the cases in which termination of pregnancy had been attempted. The results of the study should be interpreted in the light of some methodological difficulties. The diagnosis of schizophrenia in people with intellectual disability is difficult and was based on the DSM-IV criteria, although the Reiss and PIMRA scales were also used. Using the DSM-IV criteria to diagnose schizophrenia in people with intellectual disability has limitations. The symptoms described in DSM-IV are largely abstract concepts and the ability to describe such experiences may be compromised in people with intellectual disability. Eliciting the symptoms depends on verbal ability: in people with no speech the diagnosis may be invalid and unreliable. In subjects without communication skills, the diagnosis of psychotic phenomena is dependent on the interviewer's interpretation of events. However, although using the DSM-IV criteria may exclude some people with schizophrenia, subjects with intellectual disability who fit the DSM-IV criteria for schizophrenia have the disorder. By using DSM-IV criteria, the sample size may have been reduced or selection bias may have been caused by including subjects with more severe illnesses. However, the DSM-IV criteria must suffice in the absence of more accurate diagnostic systems for use in the diagnosis of schizophrenia in this group. Not all of the subjects diagnosed as DSM-IV schizophrenic met the Reiss and PIMRA criteria for the disorder, but it is recommended that the results should be interpreted in the light of the history and mental state examination when using the scales. Considering this, the present author decided that it was appropriate to include people who met the DSM-IV criteria for schizophrenia even if they did not reach the cut-off scores necessary on the other scales to diagnose schizophrenia. The ICD-IO criteria were used to establish the presence of intellectual disability (mental retardation) which is defined as: 'a condition of arrested or incomplete development of the mind, which is especially characterized by impairment of

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skills manifested during the developmental period, which contribute to the overall level of intelligence.' The description in the ICD-IO adds that there should be a 'reduced level of intellectual functioning resulting in diminished ability to adapt to the daily demands of the normal social environment'. All of the people in the study met these criteria. The degree of cognitive impairment was not psychometrically assessed. However, all had had a significant degree of intellectual disability which had come to the attention of the various services before the onset of their psychotic disorder. It could be argued that people with schizophrenia and marked negative symptoms are clinically indistinguishable from those with intellectual disability, but given that the subjects with schizophrenia were predominantly of the paranoid sub-type, with none having the diagnosis based on negative symptoms alone, this is unlikely. Furthermore, all of those involved had a clear history of developmental delay prior to the onset of the psychiatric disorder. The sample of people studied may be subject to selection bias. In some of the areas in which the investigation was undertaken, there was no psychiatrist for subjects with intellectual disability, and people with intellectual disability requiring psychiatric services were cared for by either general psychiatrists, or child and family psychiatrists. This could have affected the initial group suggested for inclusion by including people with a borderline intellectual disability or excluding some subjects with mild intellectual disability. People with poor prognostic features are more likely to be in receipt of services and may be more likely to be suggested for inclusion initially. The obstetric complications were rated on a scale specifically designed for this study and correlate highly with scores on Woerner et al.'s (1973) scale. This scale is more detailed and includes issues such as medication, which have not been previously considered. As the scale has only been used in this study, investigations of validity and reliability are necessary. The obstetric history was obtained from obstetric case notes, the mothers recall of the events of the pregnancy and delivery, or both sources. In theory, this could be inaccurate since the history from the mother could be subject to

considerable retrospective falsification in an attempt to explain her offspring's handicap. However, this is unlikely to be limited to the mothers of people with schizophrenia, and would probably be as likely to occur in the control group because PBCs are known to be associated with both schizophrenia and intellectual disability. Furthermore, people are generally more aware of the association between PBCs and intellectual disability, and are unaware of the association between similar events and schizophrenia. The correlation between the obstetric history obtained from the mother and the obstetric case notes was very high, so the present author concluded that the two sources of information were probably equally accurate. There were no cases in which the histories differed with regard to the occurrence of major obstetric complications. The number of subjects excluded because of a lack of data or consent could result in selection bias. A total of 360 people who possibly had schizophrenia were contacted, resulting in only 50 people with schizophrenia with sufficient obstetric information to be included in the study. It is possible that these 50 people represent a small sub-group of those with schizophrenia who have suffered birth injury. This effect is unlikely to be present in the controls, who were a heterogeneous group with regard to mental health. The lack of obstetric data was one of the major reasons that people were excluded from the study, and inevitably, this will have caused some sampling error. It is possible that the obstetric case notes of people known to have suffered some type of birth trauma are kept, which would increase the PBCs scores. However, there is no reason to suppose that this problem is limited to people with schizophrenia and it may have been as likely to occur in the control group. Hospital closures almost always result in mass destruction of case notes, and apart from the practical considerations of having accurate medical records for clinical practice, the current policy of case note destruction compromises researchers investigating the long-term outcome of pre- and perinatal events. Finally, very few people with intellectual disability refused to take part in the study (n = 7,

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1.3%). There could be some under-representation of those refusing as some of the next of kin may have refused because of unwillingness on the part of their relative with intellectual disability to take part. It is also possible that those who agreed to be included are a small sub-group with severe psychotic illness who are more likely to have suffered obstetric complications.

operativen Geburten. Archiv fiir Gynaekoligie 205, 110-15. Bolton G. C. (1913) Pathogenese und Therapie der
genuinen Bpilepsie. Monatschrift fiir Psychiatrie und Neurologie xxxiii, 119-59.

Bracha H. S., Curry E. F., Gottesman I. I., Bigelow L. B. & Cunniff C. (1992) Second trimester markers of foetal size in schizophrenia: a study of mono-zygotic
twins. American Journal of Psychiatry 149, 1355-61.

Conclusion In conclusion, the present study found that those people with intellectual disability who develop schizophrenia have an excess of PBCs. Although diverse, the complications reported are likely to result in increased risks of hypoxia, which seems the most likely common factor. The study also suggests that PBCs interact with an inherited predisposition, resulting in the development of a schizophrenic illness. However, as this is the first study which investigates the pre- and perinatal factors in the development of schizophrenia in people with intellectual disability, there is a need for further research in this area.

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