The psychosocial outcome of pregnancy in women with psychotic disorders

Schizophrenia Research 71 (2004) 49 – 60 www.elsevier.com/locate/schres

The psychosocial outcome of pregnancy in women with psychotic disorders Louise Michele Howard a,*, Claudia Goss b, Morven Leese a, Louis Appleby c, Graham Thornicroft a a

PO29, Section of Community Psychiatry, Health Services Research Department, Institute of Psychiatry, London SE5 8AF, UK b Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Verona, Italy c Centre for Women’s Mental Health Research, The University of Manchester, Williamson Building, Oxford Road, Manchester M13 9PL, UK Received 25 August 2003; accepted 21 January 2004 Available online 8 March 2004

Abstract Objective: To investigate the psychosocial outcome of pregnancies in women with a history of psychotic disorder in an epidemiologically representative sample and to determine the predictors of having a baby looked after by social services in the first year of life. Method: Historical matched controlled cohort study and nested case control study using the General Practice Research Database (GPRD), an anonymised primary care database, in women with a history of psychotic disorders who gave birth in 1996 – 1998 (199 cases and 787 controls). Results: Twenty-seven percent of cases had a psychotic episode and a further 38% had nonpsychotic depression in the first year after birth. Women with nonaffective psychoses were at a significantly higher risk of postnatal depression compared with controls (adjusted rate ratio 2.07, 95% CI 1.45 – 2.96, p < 0.001). Cases were well supported with 72% in a cohabiting relationship and only 38% on benefits. The only significant predictor of parenting difficulties was recent contact with psychiatric services. Conclusions: Women with a history of psychotic disorder are at high risk of psychiatric illness postpartum, particularly a twofold risk of postnatal depression, even if they have not been in contact with psychiatric services during pregnancy. However, this epidemiologically representative sample has better parenting outcomes than has been previously reported for specialist treated cases. Liaison between all professionals involved in the care of mothers with psychotic disorders during and after pregnancy is essential to optimise care for them and their families. D 2004 Elsevier B.V. All rights reserved. Keywords: Schizophrenia; Parenting; Postnatal depression; Primary health care

1. Introduction Recent reports have indicated that the majority of women with psychotic disorders bear children * Corresponding author. Tel.: +44-20-7848 0735; fax: +44-207277-1462. E-mail address: [email protected] (L.M. Howard). 0920-9964/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2004.01.003

(McGrath et al., 1999; Howard et al., 2001) and that a significant proportion remain involved in the care of their children (Gopfert et al., 1996; White et al., 1995), though the fertility rate of women with psychotic disorders, notably schizophrenia, is lower than in matched controls (Howard et al., 2002). It is not clear whether pregnancy makes psychotic disorders better or worse. Women with pre-existing schizophrenia may be

50

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

less likely to decompensate during pregnancy than postpartum (Trixler et al., 1995) but women with pre-existing mental illness may avoid services during pregnancy for fear of losing their children. Postpartum, women with narrowly defined schizophrenia appear to have an illness that takes its usual course, with no increase in risk immediately postpartum (McNeil, 1986; Davies et al., 1995), though women with schizophrenia with an affective component are at higher risk of relapse (Davies et al., 1995). Women with a history of bipolar disorder (BPD) or puerperal psychosis are at particularly high-risk postpartum (Kendell et al., 1987; Marks et al., 1992). Rates of suicide during pregnancy and postpartum are low other than immediately after childbirth (Appleby, 1991) and, as the periods of maximum risk of suicide and postpartum psychosis coincide, this suggests that those women who do kill themselves soon after childbirth are psychotic. Rates of deliberate self harm have also been reported to be lower in women in the first postnatal year compared with other women (Appleby and Turnbull, 1995) but this study was too small to detect the effect of the presence of a child on the risk of deliberate self harm on women with psychoses. Platz and Kendell (1988) have reported that women admitted with puerperal psychotic episodes had fewer subsequent suicides compared with women admitted with non puerperal psychotic episodes. Women with psychoses therefore may be at less risk of suicide and deliberate self harm during pregnancy and postpartum than at other times as the presence of a child appears to be protective but no studies have examined suicide and deliberate self harm in a primary care cohort of pregnant women with psychoses at these times and they are likely to remain at higher risk of suicide than other women during pregnancy and postpartum. The rate of postnatal depression—which affects 10% to 12% of childbearing women (O’Hara and Swain, 1996)—in women with psychoses is also unclear even though postnatal depression is a cause of significant morbidity for the mother and is associated with deficits in maternal – infant interactions (Field et al., 1985), reduced likelihood of secure attachment (Martins and Gaffan, 2000) and deficits in child cognitive and emotional development, particularly in boys living in areas of socioeconomic deprivation (Murray and Cooper, 1996; Carter et al.,

2001; Hay et al., 2001). These problems could compound the parenting difficulties already present in women with enduring psychosis. Mothers with schizophrenia are often considered to be unable to care for their children—rates of babies in care have been reported in up to 50% of women with schizophrenia compared with 10% in women with BPD admitted to a psychiatric mother and baby unit in the UK (Kumar et al., 1995). Social support to a mentally ill parent has been shown to protect children from disturbance (Rutter and Quinton, 1984), but others have suggested that the most important single predictor of parenting outcome is a diagnosis of schizophrenia (Hipwell and Kumar, 1996). Howard et al. (2003a) found risk factors for social services supervision of the baby after discharge from psychiatric mother and baby units in the UK included a diagnosis of schizophrenia or personality disorder, behavioural disturbance, lower social class, no cohabitee, and psychiatric illness in the partner. However, studies of hospitalised women are unlikely to be representative of women with mental disorders in the community. 1.1. Aims The aims of this study were firstly to investigate the psychosocial status, contacts with psychiatric services, and psychiatric outcome of pregnancies in women with psychotic disorders in an epidemiologically representative sample, and secondly to determine the proportion of babies looked after by social services in the first year postpartum and to investigate predictors of parenting difficulties. We hypothesised that women with psychotic disorders would be at a significantly increased risk of postnatal depression compared with matched controls. Our secondary hypothesis was that women with schizophrenia, poor social support and younger age would be more likely to have parenting difficulties than women with affective psychosis.

2. Methods 2.1. Study population and study design This study uses the data from General Practice Research Database (GPRD) which was set up in 1987

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

and contains the computerised medical records of over 8 million patients in primary care in the UK. In April 1996, 480 practices were participating in the GPRD but the number of participating practices decreased subsequently (to 376 by 1.1.97) due to practices switching to newer software systems which have only recently been incorporated into the GPRD. Data recorded include prescription details, clinical events, preventive care provided, specialist referrals, hospital admissions and their major outcomes. Clinical data are stored and retrieved by means of Oxford Medical Information System (OXMIS) codes (Perry, 1978) and, more recently, Read codes for diseases, which are cross-referenced to the International Classification of Diseases (ICD9 and ICD10) by the UK National Health Service Information Authority. The data collected are audited regularly and the participating general practices subjected to a number of quality checks by the Office for National Statistics (ONS), including internal validation by cross-checking within practices and by comparisons with national statistics (Lis and Mann, 1995; ONS, 1996; Walley and Mantgani, 1997). Only practices that comply with this quality control [i.e. are ‘‘up-to-research standard’’ (UTS)] are retained in the database. Data are stored in four tables linked by a unique patient identifier. The data are representative of the general population— comparisons of the population by age and sex with data from the 1991 census shows that these age distributions are broadly similar (ONS, 1996), though there is a bias towards larger group practices. 2.1.1. Study design Historical matched controlled cohort using the General Practice Research Database (GPRD) and nested case control study of a sample of cases. 2.1.2. Study population Cases: All women aged 15– 44 with a diagnosis of psychotic disorder at any time on the GPRD up to the index birth (all relevant codes) or a prescription for a neuroleptic depot, an atypical antipsychotic or lithium (used as markers for psychotic disorders), who have had a child in 1996/1997/1998 identified in a previous study (Howard et al., 2002). Control cohort: Women, with no history of psychosis (or prescriptions of marker drugs listed above), who have had children in the same years, matched for

51

age ( F 2 years) and general practice. Four controls were searched for on the database to optimise the statistical power of the study. Where a mother had more than one delivery in the study period the first was used as the index delivery. Maternal records are linked to their baby’s records on the GPRD through a household number. This household number was used with the date of delivery from the maternal record and matched with the baby’s birthday (which is given as the first day of the month of birth on the GPRD to maintain confidentiality) to identify the babies born to the subjects during the study period. Where there was no baby recorded in the household and no record of stillbirth or neonatal death, babies were traced using GP questionnaires to check whether babies had died or had been removed from the mother at or soon after birth. Data on babies were extracted from maternal and/or infant records where available. 2.2. Measures Potential predictors of parenting outcome were taken from records up to 2 years before the index delivery where available and included demographic details, medical and psychiatric history (i.e. details of any history of any medical or psychiatric diagnosis, hospital referrals, letters or admissions), illicit drug use, oral or parenteral prescribed medication, smoking and alcohol recorded during pregnancy. Outcomes for the mother examined for the pregnancy and the year after delivery were: date of booking, psychiatric episodes and admissions post partum. Psychiatric episodes were defined as any psychiatric admission or new psychiatric problems as detailed in GP records or leading to psychiatric referral. Postnatal depression was defined as a new prescription of antidepressants or a new depressive episode recorded in the first 6 months postpartum. In addition, questionnaires were sent to the GPs of cases who belonged to practices on the GPRD which participate in questionnaire research. The questionnaires consisted of questions asking for details on mothers’ ethnicity (Office for National Statistics categories of ethnicity were included in the questionnaire), marital status at the time of birth, and social factors in the first year post partum, including living situation and social services interventions. The outcome of interest

52

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

was whether the baby had been looked after by social services, or considered ‘‘at risk’’ (placed on an at risk register or a care or protection order or were the subject of a case conference). A case control study was carried out where cases were defined as mothers with psychosis with babies ‘‘at risk’’, and controls were mothers with psychosis whose babies were not considered at risk. An abbreviated level of functioning based on the Global Assessment of Functioning (GAF) was included in the questionnaire (Endicott et al., 1976) (see Appendix A), as a possible predictor of having the baby at risk. In addition to the postal questionnaires, practices were telephoned three times in order to obtain a high response rate. 2.3. Statistical analysis All data were analysed using Stata version 6. An initial descriptive analysis examined the demographic details of the cohorts, the proportion of substance misusers and smokers, medical and psychiatric histories, and prescribed drugs during pregnancy. Associations between possible predictors and outcomes were examined. Logistic regression was used to allow for confounding variables for dichotomous outcomes, Poisson regression for rates (single event per patient) and negative binomial regression for multiple event data. The ‘‘cluster’’ option in Stata was used to allow for the effect of correlations within matchgroups on estimates of standard errors and significance levels. Ninety-five percent confidence intervals are reported. When a test was positive in the context of multiple testing, a Simes’ correction (Simes, 1986) was made. Where comparisons between patients with affective psychosis and nonaffective psychosis were made, the affective psychosis patient group consisted of women with depressive psychosis or bipolar disorder, and the nonaffective psychosis patient group consisted of schizophrenia, paranoid psychosis and psychosis Not Otherwise Specified (NOS).

3. Results 3.1. Descriptive data All cases with deliveries in 1996 – 1998 were matched with women for age and practice and deliv-

ery where possible. Controls could not be found for two cases (one aged 38 and the other 45); these cases were therefore not used. There were 199 cases and 787 control mothers. One hundred and fifty-five cases had diagnoses recorded on the GPRD. The other 44 cases were included because they had been prescribed a depot, an atypical antipsychotic or lithium. The 155 cases with OXMIS or Read diagnoses recorded were given cross-referenced ICD diagnoses as follows: 34 (22%) schizophrenia, 20(13%) paranoid psychosis, 26 (17%) psychosis not otherwise specified (NOS), 33 (21%) bipolar disorder, 12 (8%) depressive psychosis, 22 (14%) puerperal psychosis, 6 (4%) schizo-affective psychosis, 2 (1%) drug induced psychosis. Nineteen percent (146/787) controls had had a psychiatric episode; most of these had neurotic depression (92%), 3% had anxiety disorder, 1% had drug dependence and 5% had an unclear diagnosis. One hundred and seventy-two case babies were identified including three sets of twins. Six did not have UTS data leaving 163 mother –infant dyads (166 babies). Of the 30 cases without linked-baby data, 5 had a stillbirth and 4 had a neonatal death (for further details, see Howard et al., 2003a,b). There was a higher probability of having an unidentified baby in cases (21/193) than controls (39/ 752) [v2(1) = 8.38, p = 0.004, OR = 2.23 CI 1.29– 3.87]. This was not because there was any difference in the proportion of cases (13%) leaving a practice compared with controls (13%). Of the 21 cases with unidentified babies, 7 had a diagnosis of schizophrenia, 3 manic depression, 3 paranoid psychosis, 1 schizo-affective disorder, 1 with puerperal psychosis, 6 with diagnosis not known. Of the 39 controls with unidentified babies, 33 had no psychiatric diagnosis, 1 had drug dependence, and 5 had neurotic depression. There were no significant differences in follow-up times between cases and controls [range = 382– 3534 days, mean = 2176, S.D. = 863 for cases; range =379 – 4255, mean = 2128, S.D. = 936 for the controls (t = 0.67, p = 0.51)]. There were also no significant differences for follow-up times before birth ( p = 0.43) and after birth ( p = 0.14). The age range of the cases was 17– 42 (mean = 29.60, S.D. = 5.91), and for the controls was 18 –43 (mean = 29.60, S.D. = 5.79).

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

3.1.1. Medical history Fifteen (7.5%) cases and 87 (11%) controls [v2(1) = 2.12, p = 0.12] had 1 or more medical problems in the 2 years before the index delivery. There were no significant differences between cases and controls for any medical condition other than a trend for cases to have a higher risk of epilepsy [3 (1.5%) cases—2 affective psychosis and 1 schizophrenia— compared with 2 (0.3%) controls; Fisher’s exact test p = 0.06]. 3.1.2. Substance misuse history Cases were more likely to use illicit drugs before pregnancy [5 (2.5%) cases and 4 (0.5%) controls; Fisher’s exact test p = 0.02], although when cases without diagnoses were excluded (two had a history of illicit drug abuse) the results indicated only a trend in this direction (Fisher’s exact test p = 0.09). 3.1.3. Pregnancy The alcohol, smoking and substance misuse histories of this sample has been described previously (Howard et al., 2003b) so only details relevant to this study are given. Of those women with alcohol intake recorded, more cases [5 (29%)] than controls [25 (12%)] were noted to be drinking 1 unit or more per week [v2(1) = 4.16, p = 0.04]. This did not appear to reflect a bias of GPs’ concern for cases; in fact the alcohol data for cases was less likely to be recorded in cases [missing in 182 (92%) cases and 578 (73%) controls] [v2(1) = 29.17, p < 0.001]. Of those women with smoking data recorded, 12 (23.6%) of the 51 cases and 37 (12.4%) of the 298 controls were smoking [v2(1) = 4.46, p = 0.04]. There was no difference in illicit drug use during pregnancy [2 (1%) cases and 1 (0.1%) control; Fisher’s exact test p = 0.11]. During pregnancy 51 (26%) cases and 40 (5%) controls were prescribed psychotropic drugs. Fortyone percent of women with schizophrenia had a record of at least one antipsychotic drug prescription during pregnancy. Two percent (n = 4) cases were prescribed anti-epileptics, 12% (n = 24) antidepressants, 14% (n = 28) antipsychotics (including those prescribed for hyperemesis, and atypicals), 4% (n = 7) lithium and 3% (n = 6) benzodiazepines. Seventy-two (36%) cases and 20 (3%) controls had at least 1 psychiatric out-patient appointment in the 2 years before, or during, the pregnancy. Sixteen (8%)

53

cases had a psychiatric admission during pregnancy; no control had an admission. Eight (4%) cases [with diagnoses psychosis NOS (n = 3), bipolar disorder (n = 1), schizophrenia (n = 1), diagnosis not known (n = 3)], but no controls, took an overdose during pregnancy. 3.2. Psychiatric morbidity in the postpartum period (for women with live deliveries) Cases were at high risk of relapse, even if there was no evidence of active illness in the 2 years previous to the index delivery, i.e. no contact with psychiatric services and no episodes recorded in primary care. In the first year postpartum, of the 194 cases with live deliveries most had a psychiatric episode—73 (38%) had nonpsychotic depression/anxiety, 19 (10%) had affective psychosis, 17 (9%) had puerperal psychosis, 9 (5%) had schizophrenia, 2 (1%) had schizo-affective psychosis, 4 (2%) had psychosis NOS and 5 (3%) had unclear diagnosis. Of the 782 controls with live deliveries, 667 (85%) did not have a psychiatric episode postpartum, 114 (15%) had depression and 1 (0.1%) had an episode with an unclear diagnosis. The pattern of relapse over the first year was similar for most diagnostic categories with 20 –40% having a nonpsychotic depressive or anxiety disorder and significant proportions having psychotic episodes. For example, of the 33 cases with schizophrenia and a live delivery, 55% had a psychiatric episode in the first year postpartum: 6 (18%) had nonpsychotic depression/anxiety, 9 (27%) had a schizophrenic episode, 1 (3%) had a diagnosed affective psychosis, 1(3%) schizo-affective psychosis, and 1 (3%) an episode with no clear diagnosis on the database. Of the 45 cases with affective psychosis with a live delivery, 25 (56%) had an episode postpartum: 13 (29%) had nonpsychotic depression/anxiety, 2 (4%) had a recorded diagnosis of puerperal psychosis and 9 (20%) had affective psychosis, with other episodes having diagnoses not recorded. There was no significant difference between the rate of women having a depressive episode or psychotic episode in women with affective disorder (n = 45) compared with schizophrenia (n = 33): rate ratio (RR) = 1.78, 95% CI 0.68 – 4.70, z = 1.17, p = 0.24 for depressive episodes, and RR = 0.82, 95% CI 0.37 – 1.83, z = 0.48, p = 0.64 for psychotic

54

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

episodes. There was also no difference between the rate of women having a depressive episode comparing women with affective disorder (n = 45) and nonaffective psychosis (n = 78) (RR = 1.01, 95% CI 0.52 – 1.98, z = 0.04, p = 0.97) or for psychotic episodes (RR = 1.06, 95% CI 0.53 – 2.15, z = 0.17, p = 0.86). In addition to the increased rate of women with a history of affective psychoses having depression compared with controls (RR = 2.10, 95% CI 1.28 –3.43, z = 2.96, p = 0.003), there was also a noteworthy increased rate of women having depression in women with nonaffective psychotic disorders compared with controls (RR = 2.07, 95% CI 1.45 – 2.96, z = 4.02, p < 0.001). The first 3-month postpartum was a time of particularly high risk for psychosis and depression in women with affective and nonaffective psychotic disorders. Fifty-one of the 194 cases (26%) had an episode of depression/anxiety, 15 (8%) had puerperal psychosis, 6 (3%) had schizophrenia, 15 (8%) had affective psychosis, 2 (1%) had schizo-affective psychosis, 3 (2%) had psychosis NOS, and 2 (1%) had an unclear episode in the first 3 months. By comparison, of the 781 controls, 49 (6%) had an episode of depression/anxiety. The rate ratios for depressive episodes and any episodes for cases versus controls in the first 3 months and for the first year are given in Table 1.

Table 1 Rate ratios of psychiatric episodes postpartum in cases (n = 194) versus controls (n = 781) (95% CI) Crude rate ratio

Adjusted rate ratioa

p-value

In first 3 months Any psychiatric episode Nonpsychotic depressive episode

7.72 (5.65, 10.53) 2.54 (1.98, 3.26)

6.65 (4.64, 9.54) 2.14 (1.52, 3.03)

< 0.001

In first year Any psychiatric episode Nonpsychotic depressive episode

4.32 (3.55, 5.24) 2.45 (1.91, 3.15)

3.71 (2.91, 4.72) 2.04 (1.45, 2.88)

< 0.001

< 0.001

< 0.001

a Adjusted for active illness (i.e. contact with psychiatric services in the 2 years before the index delivery).

Women with affective disorders (n = 45) who relapsed with a psychotic episode (24%) all did so in these first 3 months, rather than later in the first year postpartum. A further 11 of this group (24%) had nonpsychotic depression/anxiety in this early period, and 2 women had such episodes later in the year. Twenty-one percent of the women with schizophrenia (n = 33) also had a psychotic episode in the first 3 months and 4 (12%) had depression/ anxiety. Using follow-up data the rate ratio comparing depressive episodes in affective disorder patients (n = 45) with controls was 2.0 (95% CI 1.23– 3.23, z = 4.74, p = 0.005) and comparing the nonaffective group (n = 78) with controls the RR was 2.19 (95% CI 1.53– 3.13, z = 4.28, p < 0.001), i.e. the increased risk of nonpsychotic depression in first 3 months postpartum was present for different diagnostic categories of psychosis and was not explained purely by those with diagnosed affective components. There was no significant difference between women with affective or nonaffective psychoses for depressive episodes (RR = 0.91, 95% CI 0.47– 1.78, z = 0.27, p = 0.79) or psychotic episodes (RR = 0.92, 95% CI 0.44, 1.91, z = 0.23, p = 0.82). The rate of admissions in the first year postpartum for cases with live deliveries (using the negative binomial distribution) was 0.4 admission/year (95% CI 0.31 – 0.52) in the cases. There were three admissions in the controls (0.005 admission/year). There was no difference in the rate of admissions for women with affective psychosis (0.54 admission/year, 95% CI 0.32– 0.91, n = 45) and schizophrenia (0.57 admissions/year, 95% CI 0.33 – 0.97, n = 33) (RR = 0.95, 95% CI 0.45 –2.02, z = 0.13, p = 0.9). Using the Poisson distribution, there was also no difference between these two diagnoses in the rate of admissions in the first 3 months after the delivery with 0.36 admissions/year (95% CI 0.21– 0.53) in women with affective psychosis and 0.27 admission/year (95% CI 0.13 – 0.53 ) in the cases with schizophrenia (RR = 1.34, 95% CI 0.55 –3.23). No suicides were recorded in the GPRD. One hundred and forty (70%) cases and 108 (14%) controls were prescribed psychotropic medication after pregnancy. Fewer cases than controls (127 (64%) cases and 605 (77%) controls) received advice on contraception (v2(1) = 14.16, p < 0.01).

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

3.3. Parenting difficulties from questionnaire data in nested case control study One hundred and ten (out of 124) questionnaires were returned, but nine did not contain any information because the patients had transferred out of the practice; in addition, one patient did not give consent. The patients (n = 100) in the participating practices were representative of the other cases identified on the GPRD (n = 99) in terms of age ( p = 0.92) and diagnosis ( p = 0.22). Eighty-four percent of the 100 women were white British, 2 white Irish, 3 white others, 1 black Caribbean, 1 black African, 1 Asian British, 1 Asian Indian, 3 Asian Pakistani, 1 mixed parentage white/black Africans and no ethnicity given for three women. Seventy-two were married or cohabiting, 6 women were living alone at the time of birth, 5 were living with mother and 1 was living in a psychiatric institution, with no data in 15. In 7 cases, the baby’s father had a psychiatric history, but information was not known in 42% of families. Forty seven percent of the mothers had one or more children (one child in 26, 2 in 13 cases, 3 in 4 cases, 4 in 3, 5 in 1 case and information was not known in 5). Ninety-six women lived in their own home for most of the first year postpartum, but three women lived in a hostel or other institutions. The GPs indicated on the abbreviated Global Assessment of Functioning (GAF) that 16 mothers had a low level of functioning during the first year post partum, 39 had an intermediate level and 35 a high level of functioning. Most mothers (84%) were the main carer of their child in the first year of life, but in four cases the father was the main carer and in two cases the grandmother. Eight percent (7/87) babies were put on an at risk register and two on a protection or care order (information was not known in 15). Six per cent (5/91) babies were in the care of social services in the first year of life (range 11– 12 months); four of these babies had mothers with a diagnosis of schizophrenia (i.e. 25% of the 16 mothers with schizophrenia were in care) and the other baby’s mother had a diagnosis of psychosis NOS although she also had a history of amphetamine abuse; these cases were not clustered in any one region. There were nine babies considered by social services to be ‘‘at risk’’ (i.e. there was a history of a case conference, or placement on an at risk register, or the

55

baby had been looked after by social services). There was no difference between the age of the mothers of babies ‘‘at risk’’ and other mothers (K-Wallis p = 0.32) or proportion of babies ‘‘at risk’’ in mothers with BPD compared with schizophrenia [v2(1) = 0.09, p = 0.76]. Other comparisons between mothers who had a baby at risk and mothers with psychosis with a baby not at risk are given in Table 2. Data were not recorded by Table 2 Characteristics of mothers with babies at risk

Ethnicity White Non-white Living Alone Not alone Benefits On benefits Not on benefits Father’s psychiatric illness Yes No Other children Yes No Level of functioning Low Moderate High Contact with psychiatric servicesa Yes No Psychotropic drugs during pregnancy Yes No Substance misuse Yes No Booking Before 13 weeks After 13 weeks

Babies at risk

Babies not considered at risk

Total

Fisher’s exact p

7 (88%) 1 (12%)

82 (92%) 7 (8%)

89 (92%) 8 (8%)

0.51

1 (17%) 5 (83%)

5 (7%) 72 (93%)

6 (7%) 77 (93%)

0.37

4 (67%) 2 (33%)

22 (36%) 40 (64%)

26 (38%) 42 (62%)

0.19

1 (33%) 2 (67%)

6 (11%) 48 (89%)

7 (12%) 50 (88%)

0.33

2 (22%) 7 (78%)

45 (52%) 41 (48%)

47 (49%) 48 (51%)

0.16

2 (29%) 5 (71%) 0

14 (17%) 34 (41%) 35 (42%)

16 (18%) 39 (43%) 35 (39%)

0.06

9 0

36 (40%) 55 (60%)

45 (45%) 55 (55%)

< 0.001

4 (44%) 5 (56%)

21 (23%) 70 (77%)

25 (25%) 75 (75%)

0.22

0 9

7 (9%) 76 (91%)

7 (8%) 85 (92%)

1.0

7 (78%) 2 (22%)

81 (94%) 5 (6%)

88 (93%) 7 (7%)

0.13

a Any psychiatric contacts during or in the 2 years before pregnancy.

56

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

GPs for some of the variables examined. The only significant difference was that mothers of babies at risk were more likely to be in contact with psychiatric services—this remained significant after correcting for multiple testing with Simes’ test (Simes, 1986).

4. Discussion Cases were at very high risk of psychiatric illness postpartum, even if they had no psychiatric contact during or before pregnancy. This increased risk was particularly high in the first three months. This increased risk has been reported in the literature, particularly for cases with a history of bipolar disorder (Marks et al., 1992). However, cases were not only at risk of relapse of their psychotic illness. Even if they did not have a psychotic relapse they were also at an increased risk of nonpsychotic depression. This increased risk was found in women with a diagnosis of nonaffective psychosis in addition to the women with affective disorder, though it is possible that some of these episodes were prodromes of an acute psychotic episode or that some of these cases of nonaffective psychosis were misdiagnosed and had an affective component to their illness. An increased risk of postnatal depression has not been previously investigated in patients with schizophrenia to our knowledge and therefore may be relatively neglected by health professionals who will be monitoring their patients for psychotic relapses. Depression is increasingly recognised to be part of psychotic disorders such as schizophrenia but there is little consensus on how to treat depression in the context of schizophrenia and related disorders (Addington et al., 2002), particularly in the postpartum situation. Postnatal depression in women with psychotic disorders may be due to the stress of looking after a baby while also trying to cope with consequences of chronic severe mental illness and the fear that the baby will be taken away into the care of social services (Apfel and Handel, 1993). Cases also had a high risk of psychiatric admission. The risk of admission after childbirth is well documented, particularly for women with bipolar disorder (Kendell et al., 1987); among women with functional psychoses women diagnosed with schizophrenia had the lowest risk of admission after delivery (McNeil, 1986; Terp and Mortensen, 1998). The lack of a

significant difference in rates of admission between women with affective psychoses and schizophrenia may reflect a lack of statistical power. Alternatively, more women with schizophrenia may have cared for their babies postpartum in the 1990s than previously and this may have led to an increased risk of relapse and an increased likelihood of admission for parenting assessments in addition to treatment for a psychotic episode. Parenting assessments take place on psychiatric mother and baby units in the UK and this may explain the higher rates of admission in women with schizophrenia that appear in this study compared with previous work. Community care and home treatment by perinatal services may lead to decreases in admissions for psychotic disorders in the postpartum period in the future—a recent study found only a slightly increased risk (1.09) of admission postpartum for functional psychosis (Terp and Mortensen, 1998). Only a small proportion of cases took overdoses (4%) or were admitted to a psychiatric hospital (8%) during pregnancy, but overdose during pregnancy could be potentially very serious for the developing foetus. Little is known on the prevalence of deliberate self harm during pregnancy but this study suggests that a significant minority of women with a history of psychotic disorders take overdoses during pregnancy and this proportion is probably an under-estimate as not all will be known to the general practitioner. Previous reports suggest pregnant women are most likely to overdose using paracetamol or iron (Rayburn et al., 1984; Tran et al., 1998) though the drugs used by the women in this study may have been other prescribed drugs, particularly psychotropics; unfortunately, this level of detail was not recorded on the GPRD. Health professionals may be aware of the psychiatric vulnerability of women with psychosis during pregnancy and postpartum but other aspects of antenatal and postnatal care did not appear to be met, e.g. counselling on ante-natal smoking and alcohol and contraception (see also Howard et al., 2003b). Twenty-five percent of cases, with 41% of women with schizophrenia, were prescribed psychotropic drugs during pregnancy. There is a balance between the risk to the foetus and the risk of relapse during pregnancy and postpartum (Yonkers and Little, 2001) and we do not know whether the proportion of women prescribed medication during pregnancy in this study is optimal: this needs investigation using prospective

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

cohort studies with a longer duration of follow up of neurobehavioural outcomes in the children. This study was also unable to elucidate other health and social care needs of these patients and these need urgent future investigation. Five babies of 91 cases on whom there was questionnaire data were looked after by social services in the first year postpartum. This is perhaps inevitably more frequent than found in national statistics: 2.9 children under 1 year of age per 1000 live births were in local authority care in 1998 in England (Macfarlane et al., 2000). However, the proportion of looked after babies found in this study is smaller than in previous reports (e.g. Kumar et al., 1995) and may reflect the high levels of support available to women in the community with less severe psychotic illnesses compared with women seen in secondary care. GPs reported that 72% of women with psychosis in a sample of this epidemiologically representative population were in a cohabiting relationship (although we do not have information about the quality of these relationships) and only 38% were known to be on benefits. By comparison, 81% of mothers in a south London sample were on benefits (Howard et al., 2001), reflecting differences between research carried out in deprived inner city areas and the more nationally representative nature of this study. There were no significant differences between mothers whose babies were considered by social services to be at risk, and the other mothers, on a number of social factors including marital status, financial status as measured by benefits, and number of children. This may reflect the small number of babies at risk which makes it difficult to detect predictors in this study. However they were significantly more likely to have had recent contact with psychiatric services and had a lower level of functioning, possibly reflecting more active illness which is seen to necessitate supervision by social services. Our measure of functioning has not been validated; though only limited conclusions can therefore be made. Psychiatrists in contact with pregnant patients may be more likely than GPs to refer them to social services. In addition, some mothers in some parts of the UK needing psychiatric admission for postpartum relapse would not have access to a mother and baby unit in some parts of the UK and may therefore need to have their baby under social services supervision

57

for this reason. We could not examine the quality of parenting in families. However, those babies who remained with their biological families had no differences in hospital contacts or patterns of consultations in primary care compared with matched controls which suggests that they are adequately cared for physically (Howard et al., 2002). Women with psychoses may have difficulties parenting because psychotic symptoms may affect the mother– infant relationship through involvement of the child in delusions, hallucinations or passivity experiences, by making the mother unavailable because of her experiences, or through neglect or absence of desirable behaviours resulting in an impoverished environment for the child. A recent study using standardised methods to assess interaction found that women with schizophrenia were more remote, insensitive, intrusive and self absorbed than women with affective disorders, while the 4-monthold infants of the mothers with schizophrenia were more avoidant (Riordan et al., 1999). Our finding of an increased risk of postnatal depression suggests that parenting difficulties may also arise as a result of depressive symptoms which are known to lead to difficulties in mother – infant interactions (e.g. Field et al., 1985; Murray and Cooper, 1996). However, there are potential sources of bias to this study including loss to follow up and misclassification. Loss to follow up should be minimal as registrations with primary care and exits from the database are carefully recorded. Misclassification of diagnosis is possible but a previous study of the validity of psychosis diagnoses using this database has demonstrated high predictive values (Nazareth et al., 1993). In addition, the proportions of diagnostic categories of psychosis found in all childbearing aged women on the GPRD, from which these pregnant cases have been identified (Howard et al., 2002) were similar to those in an epidemiologically representative population of patients with psychosis identified in South London (Thornicroft et al., 1998). Analysis of the GPRD has found a prevalence of 29.2 per 10,000 for schizophrenia in 1996 and 30 per 10,000 in 1997 which is similar to previous estimates of incidence and prevalence in the UK (Thornicroft et al., 1998; Meltzer et al., 1995). It is however possible that controls may have had a history of psychosis which was not recorded on the GPRD with no documenta-

58

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

tion of markers of psychosis i.e. prescriptions of a depot, atypical antipsychotics or lithium. If this was the case, differences between cases and controls would be attenuated rather than increased and the direction of our findings would be unchanged. There have been no specific validation studies of depression on the GPRD and misclassification of depression is possible; however, our finding of a 6% prevalence of depression in controls is similar to previous studies (O’Hara and Swain, 1996) as GPs underdiagnose postnatal depression, only detecting 50% of the depressive episodes in the community (Briscoe, 1986). Depression in psychotic patients may be particularly difficult to diagnose, but it is unlikely that GPs would over diagnose depression in patients known to them as patients with psychosis. Substance misuse is under recorded when compared with national data and data from other surveys (Howard et al., 2002). The validity and reliability of other variables recorded on the GPRD is discussed elsewhere (Howard et al., 2002). Social class is an important confounder of many of the outcomes measured in this study. The use of health services differs between social classes. For example, people in the lowest social classes are least likely to seek early antenatal care and working-class adults are likely to be more ill than middle-class adults before seeking help (DHSS, 1980). Matching for general practice was an attempt to control for neighbourhood as a proxy for social class though this has its limitations. There is some debate as to how accurately neighborhood can act as a proxy for socio-economic status (Danesh et al., 1999; McLoone and Ellaway, 1999) and use of an area measure rather than an individual measure could result in an underestimation of potential effects associated with socioeconomic position (Ben-Shlomo and Davey Smith, 1999), particularly as other risk factors measured in this study were at the individual level. Individual socioeconomic status could not be measured in this study and some residual confounding is therefore possible. Other variables relevant to this study not recorded on the GPRD include marital status, parity, and employment. Mental health professionals therefore need to be aware of pregnancy in women with schizophrenia to enable a discussion of the risks and benefits of medication during pregnancy, ensure optimal antenatal and postnatal care and monitor the mental state to

detect and treat psychotic relapse and/or postnatal depression in women with a history of psychosis. Future research should evaluate the needs of women with psychosis during pregnancy and postpartum and develop appropriate interventions to prevent relapse in these vulnerable mothers. A small but significant proportion of babies of mothers with psychotic disorders are looked after by social services. More research is needed to identify predictors of poor parenting in these vulnerable families. Liaison between all professionals involved in the care of mothers with psychotic disorders is essential to optimise care for them and their families.

Acknowledgements LH was supported by a Wellcome Trust Health Services Research training fellowship.

Appendix A . Abbreviated Global Assessment of Functioning (Endicott et al., 1976) Please circle the patient’s average level of functioning in the baby’s first year of life: High—no or mild symptoms or some difficulty in social functioning but generally functioning pretty well. Moderate—moderate symptoms (e.g. flat affect) or moderate difficulty in functioning (e.g. few friends, conflict with family). Low—serious symptoms (e.g. suicidal ideation, illogical speech) or serious impairment in functioning (e.g. self-neglect).

References Addington, D.D., Azorin, J.M., Falloon, I.R., Gerlach, J., Hirsch, S.R., Siris, S.G., 2002. Clinical issues related to depression in schizophrenia: an international survey of psychiatrists. Acta Psychiatr. Scand. 105 (3), 189 – 195. Apfel, R.J., Handel, M.H., 1993. Madness and Loss of Motherhood: Sexuality, Reproduction and Long-Term Mental Illness American Psychiatric Press, Washington DC. Appleby, L., 1991. Suicide during pregnancy and in the first postnatal year. BMJ 302, 137 – 140.

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60 Appleby, L., Turnbull, G., 1995. Parasuicide in the first postnatal year. Psychol. Med. 25, 1087 – 1090. Ben-Shlomo, Y., Davey Smith, G., 1999. Commentary: socio-economic position should be measured accurately. BMJ 318, 844 – 845. Briscoe, M., 1986. Identification of emotional problems in postpartum women by health visitors. BMJ 292, 1245 – 1247. Carter, A.S., Garrity-Rokous, E.F., Chazan-Cohen, R., Little, C., Briggs-Gowan, M.J., 2001. Maternal depression and comorbidity: predicting early parenting, attachment security, and toddler social – emotional problems and competencies. J. Am. Acad. Child Adolesc. Psych. 40 (1), 18 – 26. Danesh, J., Gault, S., Semmence, J., Appleby, P., Peto, R., 1999. Postcodes as useful markers of social class: population based study in 26,000 British households. BMJ 318 (7187), 843 – 844. Davies, A., Mclovor, R.J., Kumar, R.C., 1995. Impact of childbirth on a series of schizophrenic mothers: a comment on the possible influence of oestrogen on schizophrenia. Schizophr. Res. 16, 25 – 31. Department of Health and Social Security, 1980. Inequalities in Health: Report of a Research Working Group DHSS, London. Endicott, J., Spitzer, R.L., Fleiss, J.L., Cohen, J., 1976. The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Arch. Gen. Psychiatry 33, 766 – 771. Field, T., Sandberg, D., Garcia, M., Vega-Lahr, N., Goldstein, S., Guy, L., 1985. Pregnancy problems, postpartum depression and early mother – infant interactions. Dev. Psychol. 21, 1152 – 1156. Gopfert, M., Webster, J., Seeman, M.V., 1996. Parental Psychiatric Disorder. Cambridge Univ. Press, Cambridge. Hay, D.F., Pawlby, S., Sharp, D., Asten, P., Mills, A., Kumar, R., 2001. Intellectual problems shown by 11-year-old children whose mothers had postnatal depression. J. Child Psychol. Psychiatry 42 (7), 871 – 889. Hipwell, A.E., Kumar, C., 1996. Maternal psychopathology and prediction of outcome based on mother – infant interaction ratings (BMIS). Br. J. Psychiatry 169, 655 – 661. Howard, L.M., Kumar, C., Thornicroft, G., 2001. The psychosocial characteristics of mothers with psychotic disorders. Br. J. Psychiatry 178, 427 – 432. Howard, L.M., Kumar, C., Leese, M., Thornicroft, G., 2002. The general fertility rate in women with psychotic disorders. Am. J. Psychiatry 159, 991 – 997. Howard, L.M., Shah, N., Salmon, M., Appleby, L., 2003a. Predictors of social services supervision of babies of mothers with mental illness after admission to a psychiatric mother and baby unit. Soc. Psychiatry Psychiatr. Epidemiol. 38 (8), 450 – 455. Howard, L.M., Goss, C., Thornicroft, G., 2003b. The medical outcome of pregnancy in women with psychotic disorders and their infants in the first year post partum. Br. J. Psychiatry 182, 63. Kendell, R.E., Chalmers, J.C., Platz, C., 1987. Epidemiology of puerperal psychos. Br. J. Psychiatry 150, 662 – 673. Kumar, R., Marks, M., Platz, C., Yoshida, K., 1995. Clinical survey of a psychiatric mother and baby unit: characteristics of 100 consecutive admissions. J. Affect. Disord. 33, 11 – 22.

59

Lis, Y., Mann, R.D., 1995. The Vamp research multi-purpose database in the UK. J. Clin. Epidemiol. 48, 41 – 43. Macfarlane, A., Mugford, M., Henderson, J., Furtado, A., Stevens, J., Dunn, A., 2000. Birth counts. Statistics of Pregnancy and Childbirth. The Stationary Office, London, p. 563. Marks, M.N., Wieck, A., Checkley, S.A., Kumar, R., 1992. Contribution of psychological and social factors to psychotic and non psychotics relapse after childbirth in women with previous history of affective disorder. J. Affect. Disord. 24, 253 – 263. Martins, C., Gaffan, E.A., 2000. Effects of early maternal depression on patterns of infant – mother attachment: a meta-analytic investigation. J. Child Psychol. Psychiatry 41 (6), 737 – 746. McGrath, J.J., Hearle, J., Jenner, L., Plant, K., Drummond, A., Barkla, J.M., 1999. The fertility and fecundity of patients with psychoses. Acta Psychiatr. Scand. 99, 441 – 446. McLoone, P., Ellaway, A., 1999. Postcodes don’t indicate individuals’ social class. BMJ 319 (7215), 1003 – 1004. McNeil, T.F., 1986. A prospective study of postpartum psychoses in a high-risk group. Acta Psychiatr. Scand. 74, 205 – 216. Meltzer, H., Gill, B., Petticrew, M., Hinds, K., 1995. The prevalence of psychiatric morbidity among adults living in private households. OPCS Surveys of Psychiatric Morbidity in Great Britain. Report 1, HMSO, London. Murray, L., Cooper, P.J., 1996. The impact of postpartum depression on child development. Int. Rev. Psychiatry 8, 55 – 63. Nazareth, I., King, M., Haines, A., Rangel, L., Myers, S., 1993. Accuracy of diagnosis of psychosis on general practice computer system. BMJ 307, 32 – 44. Office of National Statistics (ONS), 1996. The General Practice Research Database. Information for Researchers. O’Hara, M.W., Swain, A.M., 1996. Rates and risks of postpartum depression: a meta-analysis. Int. Rev. Psychiatry 8, 37 – 54. Perry, J. (Ed.), 1978. OXMIS Problem Codes for Primary Medical Care. OXMIS Publications, Oxford. Platz, C., Kendell, R.E., 1988. A matched-control follow-up and family study of ‘puerperal psychoses’. Br. J. Psychiatry 153, 90 – 94. Rayburn, W., Aronow, R., DeLancey, B., Hogan, M.J., 1984. Drug overdose during pregnancy: an overview from a metropolitan poison control centre. Obstet. Gynecol. 64 (5), 611 – 614. Riordan, D., Appleby, L., Faragher, B., 1999. Mother – infant interaction in post-partum women with schizophrenia and affective disorders. Psychol. Med. 29, 991 – 995. Rutter, M., Quinton, D., 1984. Parental psychiatric disorder: effects on children. Psychol. Med. 14, 853 – 880. Simes, R.J., 1986. An improved Bonferroni procedure for multiple tests of significance. Biometrika 73, 751 – 754. Terp, I.M., Mortensen, P.B., 1998. Post-partum psychoses. Clinical diagnosis and relative risk of admission after parturition. Br. J. Psychiatry 172, 521 – 526. Thornicroft, G., Strathdee, G., Phelan, M., Holloway, F., Wykes, T., Dunn, G., McCrone, P., Leese, M., Johnson, S., Szmukler, G., 1998. Rationale and design: PRiSM psychosis study 1. Br. J. Psychiatry 173, 363 – 370. Tran, T., Wax, J.R., Steinfeld, J.D., Ingardia, C.J., 1998. Acute intentional iron overdose in pregnancy. Obstet. Gynecol. 92 (4 Pt. 2), 678 – 680.

60

L.M. Howard et al. / Schizophrenia Research 71 (2004) 49–60

Trixler, M., Gati, A., Tenyi, T., 1995. Risks associated with childbearing in schizophrenia. Acta Psychiatr. Belg. 95 (3), 159 – 162. Walley, T., Mantgani, A., 1997. The UK general practice research database. Lancet 350, 1097 – 1099. White, C.L., Nicholson, J., Fisher, W.H., Geller, J.L., 1995. Moth-

ers with severe mental illness caring for children. J. of Nerv. Ment. Dis. 183, 398 – 403. Yonkers, K.A., Little, B.B., 2001. Management of Psychiatric Disorders in Pregnancy. Arnold, London, p. 195.