Cluain Mhuire Community Psychiatric Service, Dublin, Ireland
St Loman's Hospital, Dublin, Ireland
Dublin Institute of Technology, Dublin, Ireland
Hamamatsu University School of Medicine, Hamamatsu, Japan
Department of Public Health, Lund University, Sweden
St Loman's Hospital, Dublin, Ireland, and Department of Public Health, Lund University, Sweden
Cluain Mhuire Community Psychiatric Service, Dublin, Ireland
Correspondence: Dr E. O'Callaghan, Cluain Mhuire Community Psychiatric Service, Newtownpark Avenue, Blackrock, Co. Dublin, Ireland. Tel: +353-1-283 3766; fax: +353-1-283 3886; e-mail: eadbhard{at}indigo.ie
Declaration of interest This study was funded by the Health Research Board of Ireland and the Stanley Foundation.
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ABSTRACT |
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Aims To compare the rate of labour and delivery complications among persons who developed schizophrenia with controls; to establish whether any complication is associated with later schizophrenia.
Method We located the labour ward records of 431 individuals with schizophrenia and of same-gender controls from the same hospital birth series. Mothers were matched by age, socio-economic group and parity. Individual complications were evaluated blindly using two obstetric complication scales.
Results Overall, the rate of labour and delivery complications for those who developed schizophrenia did not differ from that of controls. Males who had presented to psychiatric services before the age of 30 had a greater frequency of and more severe labour/delivery complications than their matched controls.
Conclusions Other than among young-onset males we found no increase in labour and delivery complications among cases.
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INTRODUCTION |
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METHOD |
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Birth records
The maternity hospital labour ward diary detailed the following: parental
names; age of mother; parity, number of pregnancies, length of gestation;
paternal occupation; gender of child; date of birth; mode of delivery;
presentation; whether twin or singleton; birth weight; premature rupture of
membranes; nature of labour; hours in labour; child's and mother's health
immediately after delivery; transfer to baby unit; immediate baptism. The
diary, including a free-text record of the birth and delivery, was recorded
verbatim. Similar data relating to home births, including a 9-day follow-up
record of the baby's health, were also recorded.
Controls
The previous same-gender singleton live birth recorded in the labour ward
diary, matched for maternal age, parity, social class and home/hospital birth,
was selected as a control. The maternal age of the index case ±2 years
was chosen as the age cut-off point for the maternal control. Parity status
was classified as follows: prima gravida (first delivery), multi gravida (2-4
deliveries) or grand multi gravida (more than four deliveries). Social class,
based on paternal occupation, was matched according to the classification
system of O'Hare et al
(1991), which is also used by
the Irish Central Statistics Office. One of the hospitals did not record
paternal occupation, so where possible we obtained this information from the
General Register Office birth register. Because we were unable to establish
whether controls lived to the age at which the risk of developing
schizophrenia occurs, we identified 22 deaths in the first year of life in the
General Register Office death register and replaced them with appropriate
controls. All birth records were rated blindly according to two obstetric
complication scales, scale 1 (Lewis et
al, 1989) and scale 2
(Parnas et al,
1982).
Analyses
Individual items from the obstetric complication scales were analysed
separately using matched pairwise techniques. Odds ratios (ORs) and confidence
intervals (CIs) were calculated for binary variables. Conditional logistic
regression was used to compute for the development of the disorder after
allowing for case-control matching. This procedure was repeated for each of
the items in the separate scales.
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RESULTS |
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Scales
Cases did not differ from controls on scale 1 in terms of either definite
(OR 1.05, 95% CI 0.72-1.54, P=0.85) or equivocal (OR 0.92, 95% CI
0.61-1.40, P=0.76) complications. Because we were evaluating
contemporaneous labour ward records rather than depending on maternal recall,
we also combined the definite and equivocal complications categories and found
no difference between patients and controls. Similarly, scale 2 did not
distinguish between cases and controls in terms of frequency, severity or
total complications score.
In the light of previous findings (O'Callaghan et al, 1992; Kirov et al, 1996; Verdoux et al, 1997; Smith et al, 1998) we split the study groups by age at first diagnosis and gender and found that only males diagnosed with schizophrenia before the age of 30 (Table 3) had a greater number of definite complications than controls on scale 1. Similarly, using scale 2, male patients had a higher frequency of and more severe complications than their matched controls (Table 4).
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Individual complications
The specific complications of Caesarean section (OR 4.00, 95% CI 1.08-22.1,
P=0.04) and narrow pelvis (OR 7.00, 95% CI 0.90-320, P=0.07)
distinguished patients from controls. The individual complications, classified
by gender and age of presentation, for each scale are shown in Tables
5 and
6. We found that Caesarean
section (both emergency and not otherwise specified (NOS)) distinguished
between cases and controls (OR 7.82 x 1014, 95% CI 0-0,
P=0.004) and was specific to males. Those born by Caesarean section
presented to the psychiatric services at a significantly younger age (mean
24.01 years, s.d.=6.3; T=3.76, P=0.003) than those born by
normal delivery (mean 31.4 years, s.d.=10.6). Conditional logistic regression
analysis of the males confirmed that only Caesarean section was significant
(log likelihood removal = 354.9, d.f.=1, P0.001) in
differentiating between cases and controls. For females, only low birth weight
(log likelihood removal = 242.6, d.f.=1, P=0.002) distinguished
between the two groups.
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DISCUSSION |
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Scales and individual labour and delivery complications
Despite applying two frequently used obstetric complication scales we
failed to find differences between cases and controls in terms of overall
complication scores. There is an apparent difference between these overall
results and other large studies in this field
(Kendell et al, 1996;
Hultman et al, 1997).
One potential explanation for the contradictory results may lie in the patient
selection procedures. Many case-control and cohort studies
(Done et al, 1991;
McCreadie et al,
1992; Verdoux & Bourgeois,
1993; Kendell et al,
1996) have relied on information from patients born in recent
years when either their mothers were alive or birth records, particularly
computerised information, were available. Such patients are more likely to
have had a young age at onset. While this study indicates that young male
patients do have an excess of obstetric complications we failed to find any
general effect of obstetric adversity among persons developing the
disorder.
Persons who later developed schizophrenia were more likely to have been born by Caesarean section. This finding complements those of the recent meta-analysis by Verdoux et al (1997) and a National Register study in Denmark (Bennedsen et al, 1998), although in the present study the effect was confined to males. We confirm, using a case register study, the meta-analysis result (Verdoux et al, 1997) that Caesarean section is related to a younger age at first presentation with schizophrenia.
Although this association is interesting, the complication itself is non-specific. Caesarean section is the result of the obstetrician's judgement to intervene in response to a variety of potential risks. Most of the patients in this study were born when the rate of Caesarean section was less than 3% and was rarely an elective procedure. The commonest recorded reasons for section were major antepartum haemorrhage, deep transverse arrest or failure of labour to progress where foetal distress was apparent. Cephalopelvic disproportion was noted in 25% of cases born by Caesarean section, and a clinical note recording narrow pelvis was found more frequently among cases than among controls.
One of the commonest reasons for a narrow maternal pelvis is poor nutrition during adolescence. Mothers born and raised in Third World countries who migrated to the USA are on average shorter and have narrower pelvic dimensions than mothers born in the USA. Those immigrant women who eat a high-protein diet and receive adequate prenatal care give birth to relatively large infants, which results in cephalopelvic disproportion and severe dystocia (Abitbol et al, 1997). In addition to the direct effects of malnutrition (Susser & Lin, 1992), cephalopelvic disproportion merits consideration as a nutritionally related risk factor, particularly for groups previously described as having increased risk of schizophrenia (Warner, 1995; Harrison et al, 1997).
The reported palatal (O'Callaghan et al, 1991; Cantor-Graae et al, 1994; Lane et al, 1997) and craniofacial abnormalities among patients with schizophrenia may not entirely result from genetic factors, as we considered previously but may be related to a moulding process in a narrow pelvis (de la Fuente, 1991). However, a narrow pelvis in itself does not necessarily result in damage to the foetus, since when identified it commonly results in operative delivery.
Among patients, a gestational age of less than 37 weeks occurred more frequently among males whose first diagnosis was before the age of 30. While this result has been reported previously (Jones et al, 1998), such cases, as with Caesarean section and cephalopelvic disproportion, accounted for a modest proportion of our study group. Indeed, despite several individual complications being associated with the later development of schizophrenia, the proportion of cases affected was extremely small, indicating that obstetric adversity is not associated with the majority of cases of schizophrenia, especially when the age at onset is over 30 years.
Although this paper describes a large case-control study which used contemporaneous records, the fact that many individual labour and delivery complications occur at a frequency of less than 10% in the general population suggests that the cross-referencing of population-based obstetric databases with psychiatric case registers is necessary in order to address definitively the contribution of individual complications to the risk of schizophrenia.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication April 12, 1999. Revision received August 23, 1999. Accepted for publication August 26, 1999.