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Reproductive patterns in psychotic patients
Schizophrenia Research 121 (2010) 234–240
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Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s
Reproductive patterns in psychotic patients☆,☆☆ T.M. Laursen ⁎, T. Munk-Olsen National Centre for Register-Based Research, Aarhus University, Taasingegade 1, 8000 Aarhus C, Denmark
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Article history: Received 8 March 2010 Received in revised form 10 May 2010 Accepted 16 May 2010 Available online 8 June 2010 Keywords: Epidemiology Fertility Abortion Psychotic disorder Population-based
a b s t r a c t Context: Longitudinal epidemiological studies have shown worse outcomes in patients with psychotic disorder than in the general population. The reproductive pattern may be seen as a measure of outcome following psychotic disorder onset, and it may be measured as the rate of child births where the rate is a proxy measure of well-being. Objective: To examine reproductive patterns following psychotic disorder onset by comparing the fertility rates of patients with schizophrenia and bipolar disorder with those of other psychiatric patients and the general population, taking into account parental status at diseaseonset, time since onset, and the possible effect of abortions-rates. Methods: A prospective register-based cohort study drawing on the entire Danish population born after 1950. Incidence Rate Ratios (IRRs) of fertility were analysed using survival analysis. Results: Compared with the general population, the lowest first-child fertility rate was found among men (IRR = 0.10) and women (IRR = 0.18) with schizophrenia. In comparison, bipolar male patients had an IRR = 0.32 and female patients an IRR = 0.36, while male unipolar patients had an IRR = 0.46 and female patients an IRR = 0.57. In the group with other psychiatric disorders men had an IRR = 0.51 and women an IRR = 0.70. Conclusions: The results of the present study show a selection process where persons with more severe disorders are less likely to become parents. The reduced fertility was strongly influenced by the time since psychiatric disorder onset; thus, the longer the time since onset, the higher the fertility. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Longitudinal epidemiological studies have shown worse outcomes in patients with schizophrenia and bipolar disorder (psychotic disorders) than in patients with other psychiatric disorders and in the general population. These outcomes include markedly elevated mortality rates from all causes of death (Harris and Barraclough, 1998; Laursen et al., 2007b), suicide (Hiroeh et al., 2001), increased somatic and medical comorbidity (Laursen et al., 2009; Jeste et al., 1996), more
☆ Dr. TM Laursen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. ☆☆ This study was approved by the Danish Data Protection Agency. ⁎ Corresponding author. E-mail address: [email protected] (T.M. Laursen). 0920-9964/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2010.05.018
unhealthy diets (Brown et al., 1999), higher rates of cigarette smoking (Itkin et al., 2001; Dalack et al., 1998; Jeste et al., 1996), and negative social consequences (Agerbo et al., 2004). The reproductive pattern of a patient after psychotic disorder onset may also be considered an outcome measure. Men and women becoming parents have been shown to form a population segment that, among others, has a lower risk of cancer (Dalton et al., 2004) and psychiatric disorders (MunkOlsen et al., 2006). Several studies have found reduced fertility rates among persons with schizophrenia or a combined measure of psychosis (McGrath et al., 1999; Haukka et al., 2003; Howard et al., 2002; Svensson et al., 2007; Bhatia et al., 2004), with only one recent study showing an opposite result (Nimgaonkar et al., 1997). A study detected no reduced fertility rates in patients with bipolar disorder (affective psychosis) (MacCabe et al., 2009). However, many of these studies are flawed because they have not duly considered the dimensions
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of ‘how’ and ‘when’ to measure reproduction. The average age at which schizophrenia sets in is in the early 20s, while bipolar disorders set in later (Laursen et al., 2007a). Common for the two disorders, and for many other psychiatric disorders, is that disease strikes during the primary reproductive period of both men's and women's lives. It should therefore be taken into account how many (if any) children the person has before disorder onset. Furthermore, women with psychotic disorders are often advised not to have children (Viguera et al., 2002a) and they may choose to have an induced abortion. The rates of induced abortion in women with psychotic disorders should therefore also be taken into account as a possible explanation for their reduced fertility. The aim of the present study was to examine reproductive patterns following psychotic disorder onset by comparing the rates of childbirths in patients with schizophrenia and bipolar disorder with those of other psychiatric patients and members of the general population who had not been admitted to a psychiatric hospital, taking into account parental status at the time of onset of the disorder, time since onset of the disorder, and the possible effect of abortions. 2. Methods We established a cohort study and obtained data on the vital status of the cohortees and their children. Information was drawn from the Danish Civil Registration System (Pedersen et al., 2006). We linked this information to the Danish Psychiatric Central Register (Munk-Jorgensen and Mortensen, 1997) from where we obtained information on inpatient psychiatric treatment, and to the The Danish National Hospital Register (Andersen et al., 1999) from where we obtained information about induced abortion. We used the unique personal identification number assigned to all people living in Denmark to link data drawn from the registers (Pedersen et al., 2006). 2.1. Study population and follow-up period The population-based cohort comprised all individuals born in Denmark between 1 January 1950 and 1 January 1991. The overall follow-up began on 1 January 1970 and ended on 31 December 2006. Cohortees were followed individually from their 15-year birthday until date of death, emigration, or end of the follow-up period, whichever came first. 2.2. Assessment of psychiatric disorder, childbirth, and induced abortion Cohort members were categorized as suffering from a psychiatric disorder if they were admitted to a psychiatric hospital. The diagnostic system used until 31 December 1993 was the ICD8 (World Health Organization, 1971), and from 1 January 1994, the ICD10 (World Health Organization, 1994) classification was used. Diagnoses were categorised as follows: psychotic disorder covering bipolar disorder (ICD8: 296.19 or 296.39, ICD10: F30 or F31) and schizophrenia (ICD8: 295 (excluding 295.79), ICD10: F20); a comparison group of all cohortees with unipolar disorder (ICD8: 296.09, 296.29, 296.99, 298.09, 300.49, or 300.19, ICD10: F32 or F33); and, finally, a category of the remaining psychiatric disorders
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consisting of all admissions to psychiatric hospital not included in the above categories (including personality disorders, ICD8 301[minus 301.83], ICD10 F60,F61). Psychiatric status was treated as a time-depended covariate. All childbirths were identified from the Danish Civil Registration System (Pedersen et al., 2006). All births including twin birth were examined; however, the second twin was not counted as an outcome when we examined having the next child. We did not distinguish between adopted or biological children. In Denmark (2006), there are approximately 1000 adoptions (half of them stepchildren adoptions) and 60,000 births per year. Induced abortion became legal in Denmark in 1973 and all women aged 18 years or more can have a pregnancy terminated within the first 12 weeks of gestation. Around 5% of all induced abortions are performed after the 12th week of gestation and are granted mainly on medical or social indications after a request has been made to the regional health and social authorities. Through the Danish National Hospital Register (Andersen et al., 1999) we obtained information on dates of 1st or 2nd trimester induced abortions (ICD8 codes: 640, 641 or 642, ICD10 codes: O04, O05, or O06) since 1977. For all analyses, including the variable abortions, followup began in 1977. Up to 1993, we had only records of abortions made during inpatient stays; thus, we included approximately 90% of all induced abortions relative to the official number of induced abortions in the period. We constructed a new measure from the variables first induced abortion and first live born child. This measure, which was the first (if any) of the two events, was named first reproductive event. 2.3. Statistical analyses We analysed data as a cohort study with survival analysis techniques, using Poisson regression with the logarithm of the person years as an offset. This method approximates a Cox regression (Andersen et al., 1993; Laird and Olivier, 1981). Using a Poisson regression and person years takes into account the different lengths of follow-up in the cohortees. The GENMOD procedure in SAS version 9.1 (SAS Institute Inc, Cary, NC) was used. Outcome measures comparing fertility incidence rates of two groups were denoted incidence rate ratios (IRRs). IRRs compare the incidence rate (number of new cases per time unit) in one group with the incidence rate in a comparison group (named reference group), and can be interpreted as relative risks. All IRRs were adjusted for or stratified by gender, calendar time, and age and were calculated by log-likelihood estimation. Wald's 95% confidence intervals were used. 3. Results In the follow-up period from 1970 to 2006, a total of 2,819,941 cohort members were followed for 34,898,001 person-years during which 1,587,709 persons had at least one child. Firstly, we examined the IRRs of having the first child among cohort members with no children and found that men (IRR = 0.10; 95% CI (0.09, 0.11)) and women (IRR = 0.18; 95% CI (0.17, 0.20)) with schizophrenia had the lowest observed fertility compared with their respective counterparts with no
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psychiatric admission (Table 1). Among cohortees with a psychiatric disorder, cohort members with bipolar disorder had higher fertility (men IRR = 0.32; 95% CI (0.29, 0.36), women IRR = 0.36; 95% CI (0.33, 0.40)), members with unipolar polar disorder even higher (men IRR = 0.46; 95% CI (0.43, 0.48), women IRR = 0.57; 95% CI (0.55, 0.60)), while the group of patients with remaining disorders had the highest fertility (men IRR = 0.51; 95% CI (0.50, 0.52), women IRR = 0.70; 95% CI (0.69, 0.72)), Table 1. Secondly, we compared the fertility among cohortees with one child by comparing incidence rates of having the second child. The same pattern with low rates among cohortees with schizophrenia and bipolar disorder emerged; however, the fertility IRR was higher, especially among men, Table 1. Thirdly, fertility among cohortees with two children was measured with the third child as the outcome. Cohortees with schizophrenia and bipolar disorder had higher fertility IRRs than when rates from one to two children were examined; and it was now at the same level as the IRRs of those with a unipolar disorder. Interestingly, the group of patients with remaining disorders had higher fertility rate ratios than healthy cohortees (men and women with no records of psychiatric admission). Finally, the fertility among cohort members with three children was examined, and all psychiatric subgroups had fertility rates similar to that of the comparison group (no psychiatric admission), with the group of patients with the remaining disorders having a significantly higher fertility. The excess rate of fertility among persons in the rest group was not driven by personality disorders as we found fertility rates in the personality disorders subgroup equaling 1.18; 95% CI (1.07, 1.31) for women and 1.34; 95% CI (1.21, 1.49) for men, which was very similar to the entire group with remaining psychiatric disorders (results not shown in tables).
Among women with psychiatric disorders, the overall rates of childbirth were reduced compared with those of healthy women. We also examined if a reduction in fertility rates was explained by an increased abortion rate in this group of women. In a separate analysis of women's fertility among cohortees without children, we compared rates of induced abortion in women with psychiatric disorders with those of their counterparts without previous psychiatric admissions. We found an increased IRR of abortions in all psychiatric subgroups, except a slightly decreased IRR in women with schizophrenia, Table 2. The IRR for women with a psychiatric disorder was slightly higher for the first reproductive event (either childbirth or abortion) than for the first child, Table 2. 3.1. Additional analyses Additional analyses on cohortees without children showed that time measured as number of days since first psychiatric admission was an important effect modifier, as the rates of having the first child were much influenced by proximity to the date of admission with a psychiatric disorder. This was apparent especially in women, as the IRR of having first child rose with time since admission (Table 3). The only exception was men being diagnosed with bipolar affective disorder who had a high IRR of a first child around the time of disorder onset. Further analyses demonstrated that age in general influenced reproductive patterns in patients with psychiatric disorders: compared with their respective counterparts, younger cohortees with a psychiatric disorder had higher fertility rates than older cohortees. Thus, an effect modification of the IRR by cohortee age (in both genders) was present, with especially cohortees younger than 26 years having higher IRRs, Figs. 1 and 2.
Table 1 Incidence rate ratio of becoming a parent among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions.
Women 0 → 1 Child
a
1 → 2 Children
a
2 → 3 Children
a
3 → 4 Children
a
Men 0 → 1 Child
a
1 → 2 Children
a
2 → 3 Children
a
3 → 4 Children
a
N of IRR N of IRR N of IRR N of IRR
births
N of IRR N of IRR N of IRR N of IRR
births
births births births
births births births
Schizophrenia
Bipolar disorder
Unipolar disorder
Rest group
Never admitted
572 0.18 327 0.30 117 0.78 35 1.10
376 0.36 262 0.42 91 0.72 34 1.25
1959 0.57 (0.55, 1684 0.52 (0.50, 682 0.76 (0.71, 224 1.05 (0.92,
9833 0.70 (0.69, 0.72) 7610 0.58(0.57, 0.60) 3501 1.11 (1.07, 1.15) 1123 1.23 (1.16, 1.30)
827,141 1.00 (Ref.) 614,331 1.00 (Ref.) 189,408 1.00 (Ref.) 37,858 1.00 (Ref.)
9909 0.51 (0.50, 7296 0.54 (0.53, 3373 1.06 (1.02, 1164 1.27 (1.19,
736,252 1.00 (Ref.) 520,312 1.00 (Ref.) 164,759 1.00 (Ref.) 35,804 1.00 (Ref.)
661 0.10 360 0.31 131 0.76 32 0.87
(0.17, 0.20) (0.27, 0.34) (0.65, 0.94) (0.79, 1.53)
(0.09, 0.11) (0.28, 0.35) (0.64, 0.90) ( 0.62, 1.23)
296 0.32 232 0.59 86 0.86 22 0.83
(0.33, 0.40) (0.37, 0.47) (0.59, 0.89) (0.89, 1.75)
(0.29, 0.36) (0.52, 0.67) (0.70, 1.07) (0.55, 1.27)
1102 0.46 (0.43, 903 0.57 (0.54, 416 0.88 (0.80, 155 1.08 (0.93,
0.60) 0.55) 0.82) 1.20)
0.48) 0.61) 0.97) 1.27)
0.52) 0.55) 1.09) 1.34)
Reference: cohort members never admitted to a psychiatric hospital. Stratified by being a parent for the 1st, 2nd, 3rd, and 4th time. Follow-up period from 1 January 1970 to 31 December 2006. Adjusted for age and calendar time. a “0 → 1 child” is the incidence rate ratio (IRR) of having the first child; comparison between persons having one of the four psychiatric disorders with the part of the populations never admitted to a psychiatric hospital as the reference group. In the same way, “1 → 2 Children” is the IRR for having the second child, only among parents with one child. “2 → 3 Children” is the IRR for having the third child among parents with two children. “3 → 4 Children” the IRR of having the fourth child among parents with three children.
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Table 2 Incidence rate ratio of becoming a parent for the first time, having the first abortion, or experiencing the first reproductive event among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions. Women First child a First abortion First reproductive event b
N of births IRR N of abortions IRR N of rep. eve. IRR
Schizophrenia
Bipolar disorder
Unipolar disorder
Miscellaneous ‘Other disorders’
Never admitted
538 0.18 ( 0.16, 0.19) 399 0.90 ( 0.81, 0.99) 683 0.25 ( 0.23, 0.27)
358 0.36 (0.33, 0.40) 255 1.18 ( 1.03, 1.34) 402 0.46 ( 0.42, 0.51)
1718 0.54 ( 0.52, 0.57) 1136 1.34 ( 1.26, 1.42) 1,768 0.62 ( 0.59, 0.65)
8845 0.69 ( 0.66, 0.69) 5792 1.71 ( 1.66, 1.75) 9146 0.77 ( 0.75, 0.79)
728,063 1.00 ref. 260,365 1.00 ref. 775,645 1.00 ref.
Reference: cohort members never admitted to a psychiatric hospital. Follow-up period from 1 January 1977 to 31 December 2006. Adjusted for age and calendar time. a Numbers differ from the first line in Table 1, as the follow-up starts in 1970 in Table 1 and in 1977 in this table. Note that there is an extensive overlap between women who have an induced abortion and those having a child. b First reproductive event defined as the first childbirth or the first abortion, whichever came first.
4. Discussion 4.1. Key findings We found a reduced fertility among both women and men with psychiatric disorders. Persons with schizophrenia had the lowest fertility followed by bipolar disorder, unipolar disorder, and the remaining disorders. The reduced fertility was most pronounced among cohortees with a psychiatric disorder when having the first child was used as the outcome. Furthermore, reproductive rates rose with time since the first psychiatric admission, and men with a psychiatric disorder had a lower fertility than women with a psychiatric disorder, and higher induced abortion rates in women with a psychiatric disorder explained only a small proportion of their lower fertility. 4.2. Timing, measurement and magnitude of reduced fertility Several papers have showed reduced fertility among persons with a psychotic disorder (McGrath et al., 1999; Haukka et al., 2003; Howard et al., 2002; Svensson et al., 2007; Bhatia et al., 2004; MacCabe et al., 2009), but separate analysis of bipolar affective disorder (or affective psychosis) has yielded less uniform results (MacCabe et al., 2009). In the present study, fertility was modified by the number of previous children. Both men and women with schizophrenia who had a least two children had the same incidence rate of having the next child as those with bipolar disorder, and
almost the same rate as the general population. This may be ascribed to a selection mechanism where those among persons with schizophrenia/bipolar disorder with the mildest symptoms choose to have children and therefore obtain almost the same fertility rates as the general population. The low rates of having the first child among men with schizophrenia may be ascribed to a very strong negative selection, and schizophrenic men had an average IRR that was only 0.10 of the comparison group without psychiatric admissions. For the age group 30–31 years, which was the average age at which Danish men had their first child in 2006, the IRR was only 0.08 (Fig. 2). Schizophrenic women had higher fertility rates with an IRR equaling 0.14 of that of the comparison group at the average age of their first child (Fig. 1). Other studies have not shown a similarly large reduction in the rates of having children. Howard et al found an IRR of approximately 0.50 in women with psychotic disorders, but found the same pattern as in our study: women with non-affective psychosis (including schizophrenia) had a lower IRR than those with affective psychosis (including bipolar disorder) (Howard et al., 2002). McGrath et al. also found reduced fertility; especially among men with nonaffective psychosis (schizophrenia) (McGrath et al., 1999). In comparison, MacCabe et al. detected no reduced IRR of fertility in persons with affective psychosis (bipolar disorder), but found a reduced IRR of fertility among persons with schizophrenia (MacCabe et al., 2009), although fertility was not as reduced as in the present paper. Similarly, Haukka et al.
Table 3 Incidence rate ratio (IRR) for having the first child according to time since first psychiatric admission. Time since admission (months) Women 0–9 10–18 19–24 25–36 37–48 Men 0–9 10–18 19–24 25–36 37–48 a
Schizophrenia IRR a (95% CI)
Bipolar disorder IRR a (95% CI)
Unipolar disorder IRR a (95% CI)
0.07 0.15 0.21 0.22 0.27
(0.04–0.11) (0.11–0.22) (0.15–0.30) (0.17–0.28) (0.21–0.34)
0.12 0.20 0.33 0.35 0.32
(0.06–0.23) (0.12–0.34) (0.20–0.54) (0.25–0.49) (0.23–0.46)
0.32 0.58 0.69 0.79 0.64
(0.26–0.40) (0.50–0.68) (0.58–0.82) (0.70–0.89) (0.56–0.74)
0.07 0.09 0.10 0.13 0.13
(0.05–0.11) (0.07–0.13) (0.07–0.15) (0.10–0.16) (0.10–0.16)
0.29 0.14 0.30 0.23 0.31
(0.18–0.47) (0.07–0.29) (0.17–0.54) (0.15–0.38) (0.20–0.47)
0.32 0.43 0.52 0.54 0.65
(0.25–0.41) (0.35–0.54) (0.41–0.67) (0.46–0.65) (0.55–0.77)
IRR adjusted for age and calendar time. Reference group: Women, respectively men, never admitted to a psychiatric hospital.
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4.3. Gender differences
Fig. 1. Incidence rate ratio of a women becoming a mother for the first time among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions. Stratified by age of the cohort members. Adjusted for calendar period. Follow-up period from 1 January 1970 to 31 December 2006. Reference: cohort members never admitted to a psychiatric hospital.
Women with schizophrenia in the age group 28–29 had a fertility rate of 0.14 of that of the reference population (Fig. 1), which was very low, but yet higher than that seen among men. In general, the IRR was strongly influenced by the cohortee's gender. Women with a psychiatric disorder, especially schizophrenia, did not have as strongly reduced fertility rates as men with schizophrenia, and fertility rose more quickly after their first admission. This observation is in line with those made in previous studies (McGrath et al., 1999). The higher fertility rates among schizophrenic women (compared with schizophrenic men) may be explained partly by women having milder symptoms than men during the reproductive age range (Kohler et al., 2009). Men with schizophrenia appear to have more negative symptoms, fewer social networks, and to be more exposed to social problems and isolation (Thorup et al., 2007), which could all explain the observed lower fertility rates. 4.4. Influence of induced abortion
(Haukka et al., 2003) found a reduced number of children among persons with schizophrenia; however, the reported reduction was less pronounced than in the present study. Importantly, some studies did not stratify by gender, which should be done as gender combined with diagnosis significantly influences the number of children as demonstrated in the present study. Proximity to the onset of psychiatric disorder measured as the date of first-time psychiatric admission predicts the IRR of having the first child (Table 3). This could support the idea of a selection among persons with less severe symptoms as their fertility rate rose with time since onset. It seems very likely that symptoms are most severe at the time of the first episode entailing admission, and that they then gradually become less severe, thereby “allowing” the persons to consider having a child. However, this pattern did not hold for men with a bipolar disorder who had no reduced fertility in the period shortly following disorder onset. On the contrary, they had a higher fertility during the first nine months after the date of first admission, which could be explained by more promiscuous behavior during manic periods (Robinson et al., 2009).
Fig. 2. Incidence rate ratio of a man becoming a father for the first time among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions. Stratified by age of the cohort members. Adjusted for calendar period. Follow-up period from 1 January 1970 to 31 December 2006. Reference: cohort members never admitted to a psychiatric hospital.
Women's mental health influences their reproductive decisions (Major et al., 2008), and fertility rates could be influenced by the fact that some women with psychotic disorders may have been advised not to become pregnant (Viguera et al., 2002b). Although women with a psychiatric disorder had higher rates of abortion in the current study than the comparison group, their IRR of first reproductive event (the first birth or abortion, if any) was only slightly higher than their IRR of first birth. The higher abortion rates could therefore not explain the lower fertility rates. 4.5. Comparison with outcome studies A worse outcome in schizophrenic than in bipolar patients was first mentioned in the original definition of schizophrenia (Dementia Praecox) by Emil Kraepelin (Angst, 2002). If we assume that having a child is a proxy measure for a person's physical and mental well-being, the present study confirms this early definition by demonstrating a lower rate of childbirths among schizophrenic patients than among patients with bipolar disorder. This observation is in line with those made in other studies of outcomes following bipolar and schizophrenia which show, e.g., a higher mortality (Harris and Barraclough, 1998; Laursen et al., 2007b) and higher somatic and medical comorbidity (Laursen et al., 2009; Jeste et al., 1996) in persons with schizophrenia than in persons with other psychotic disorders. We compared reproductive patterns in patients with psychotic disorders with patterns among patients admitted with unipolar affective disorder, which also includes disorders with no psychotic symptoms. This comparison produced higher fertility rates in both men and women with unipolar disorders. A better outcome in unipolar disorder has also been shown in other outcome studies (Laursen et al., 2007b). 4.6. Strengths and limitations Register-studies offer both advantages and limitations. The present study made full use of population registers and, to our knowledge, it is the first study to fully describe
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reproductive patterns (up to four children) in patients with psychiatric disorders. The study furthermore, benefits from available, precise information on the number of children, the timing of the first psychiatric contacts, including information on diagnoses, and on induced abortion. Many psychotropic drugs have been shown to influence patients' behavior and thus their fertility rates. Anti psychotic medication and the shifting from one drug to another could have a strong influence on the pateints' well-being , especially shortly after onset of the disorder. Unfortunately, we did not have information on medication usages and prescriptions in our cohort and thus we could not examine this issue further. In the present study, we assumed that disorder onset was the day of first admission. However, there is no available information on the duration and severity of symptoms leading up to the time of admission, which would have allowed us to more fully describe the influence psychiatric disorders have on reproduction patterns. It is likely that the prodromal phase can last for years, and that the first admission does not occur immediately after psychosis onset. In the ICD8 period (up to 1993), we had information only on 90% of the induced abortions, but we have no reason to believe that this information differed between cohortees with a psychiatric disorder and those without a diagnosis, and the IRR was thus only affected to a lesser degree. Moreover, we have no information on spontaneous abortions, and therefore cannot rule out that differences in spontaneous abortion rates can explain (some of) the differences in fertility. However, the number of spontaneous abortions among women with a psychiatric disorder should be much increased to counteract the observed decreased fertility in the group of women with psychiatric disorders. In this study, we had access to clinical diagnoses. However, other studies have validated the clinical diagnoses of bipolar disorder and schizophrenia in the Danish Psychiatric Central Register against diagnoses established according to research criteria, and they found a high level of agreement between the diagnoses (Munk-Jorgensen and Mortensen, 1997; Kessing, 1998; Jakobsen et al., 2005). 5. Conclusion Drawing on the entire Danish population, we were able to describe reproductive patterns in patients with psychotic disorders. Fertility rates among persons with a psychiatric disorder are highly dependent on diagnosis. Compared with the part of the population with no psychiatric hospitalization, persons with schizophrenia had the lowest rates of childbirths. Persons with bipolar disorder had lower rates than persons with unipolar disorder and persons in the group consisting of the remaining disorders. Men with a psychiatric disorder had lower fertility rates than women with a psychiatric disorder in all diagnostic groups examined. Women with a psychiatric disorder had higher rates of induced abortion in general, but this does not explain their decreased fertility rate compared with the general population. Persons with a psychiatric disorder who were already a parent had a less reduced fertility rate for having the next child. The reduced fertility was strongly influenced by the time since psychiatric disorder onset; thus, the longer the time since onset, the higher the fertility.
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Measuring fertility as overall rates of number of children conceals the facts that a certain group of persons with psychotic disorders have very low fertility rates. Importantly, gender, diagnosis, number of children, and time since diagnosis must be taken into account before a real description of fertility can be made. Assuming that fertility rates are a proxy measure of physical and mental well-being, the results of the present study suggest a selection process where persons with more severe disorders are less likely to become parents. Role of funding source The Stanley Medical Research Institute and The Danish Medical Research Council had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Contributors Dr. Thomas Munk Laursen (TML) designed the study and wrote the protocol. Authors TML and Trine Munk-Olsen managed the literature searches and analyses. Author TML undertook the statistical analysis, and author TML wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript. Conflict of interest None. Acknowledgments This study was supported by The Stanley Medical Research Institute. Dr. T Munk-Olsen has received financial support from The Danish Medical Research Council (Reference number: 09-063642/FSS).
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Kohler, S., van der Werf, M., Hart, B., Morrison, G., McCreadie, R., Kirkpatrick, B., Verkaaik, M., Krabbendam, L., Verhey, F., van, O.J., Allardyce, J., 2009. Evidence that better outcome of psychosis in women is reversed with increasing age of onset: a population-based 5-year follow-up study. Schizophr. Res. 113, 226–232. Laird, N., Olivier, D., 1981. Covariance analysis of censored survival data using log-linear analysis techniques. J. Am. Stat. Assoc. 76, 231–240. Laursen, T.M., Munk-Olsen, T., Nordentoft, M., Mortensen, P.B., 2007a. A comparison of selected risk factors for unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia from a Danish population-based cohort. J. Clin. Psychiatry 68, 1673–1681. Laursen, T.M., Munk-Olsen, T., Nordentoft, M., Mortensen, P.B., 2007b. Increased mortality among patients admitted with major psychiatric disorders: a register-based study comparing mortality in unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia. J. Clin. Psychiatry 68, 899–907. Laursen, T.M., Munk-Olsen, T., Agerbo, E., Gasse, C., Mortensen, P.B., 2009. Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder. Arch. Gen. Psychiatry 66, 713–720. MacCabe, J.H., Koupil, I., Leon, D.A., 2009. Lifetime reproductive output over two generations in patients with psychosis and their unaffected siblings: the Uppsala 1915–1929 Birth Cohort Multigenerational Study. Psychol. Med. 39, 1667–1676. Major, B., Applebaum, M., Beckman, L., Dutton, M., Russo, N., West, C., 2008. APA task Force on Mental Health and Abortion, pp. 1–91. 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. Munk-Jorgensen, P., Mortensen, P.B., 1997. The Danish Psychiatric Central Register. Dan. Med. Bull. 44, 82–84. Munk-Olsen, T., Laursen, T.M., Pedersen, C.B., Mors, O., Mortensen, P.B., 2006. New parents and mental disorders: a population-based register study. JAMA. 296, 2582–2589.
Nimgaonkar, V.L., Ward, S.E., Agarde, H., Weston, N., Ganguli, R., 1997. Fertility in schizophrenia: results from a contemporary US cohort. Acta Psychiatr. Scand. 95, 364–369. Pedersen, C.B., Gotzsche, H., Moller, J.O., Mortensen, P.B., 2006. The Danish Civil Registration System. A cohort of eight million persons. Dan. Med. Bull. 53, 441–449. Robinson, G.E., Stotland, N.L., Russo, N.F., Lang, J.A., Occhiogrosso, M., 2009. Is there an “abortion trauma syndrome”? Critiquing the evidence. Harv. Rev. Psychiatry 17, 268–290. Svensson, A.C., Lichtenstein, P., Sandin, S., Hultman, C.M., 2007. Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective. Schizophr. Res. 91, 238–245. Thorup, A., Petersen, L., Jeppesen, P., Ohlenschlaeger, J., Christensen, T., Krarup, G., Jorgensen, P., Nordentoft, M., 2007. Gender differences in young adults with first-episode schizophrenia spectrum disorders at baseline in the Danish OPUS study. J. Nerv. Ment. Dis. 195, 396–405. Viguera, A.C., Cohen, L.S., Bouffard, S., Whitfield, T.H., Baldessarini, R.J., 2002a. Reproductive decisions by women with bipolar disorder after prepregnancy psychiatric consultation. Am. J. Psychiatry 159, 2102–2104. Viguera, A.C., Cohen, L.S., Bouffard, S., Whitfield, T.H., Baldessarini, R.J., 2002b. Reproductive decisions by women with bipolar disorder after prepregnancy psychiatric consultation. Am. J. Psychiatry 159, 2102–2104. World Health Organization, 1971. Klassifikation af sygdomme; Udvidet dansk-latinsk udgave af verdenssundhedsorganisationens internationale klassifikation af sygdomme. 8 revision, 1965 [Classification of diseases: Extended Danish-Latin version of the World Health Organization International Classification of Diseases, 8th revision, 1965], 1 edn. Danish National Board of Health, Copenhagen. World Health Organization, 1994. WHO ICD-10: Psykiske lidelser og adfærdsmæssige forstyrrelser. Klassifikation og diagnosekriterier [WHO ICD-10: Mental and Behavioural Disorders. Classification and Diagnostic Criteria]. Munksgaard Danmark, Copenhagen.
Contents lists available at ScienceDirect
Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s
Reproductive patterns in psychotic patients☆,☆☆ T.M. Laursen ⁎, T. Munk-Olsen National Centre for Register-Based Research, Aarhus University, Taasingegade 1, 8000 Aarhus C, Denmark
a r t i c l e
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Article history: Received 8 March 2010 Received in revised form 10 May 2010 Accepted 16 May 2010 Available online 8 June 2010 Keywords: Epidemiology Fertility Abortion Psychotic disorder Population-based
a b s t r a c t Context: Longitudinal epidemiological studies have shown worse outcomes in patients with psychotic disorder than in the general population. The reproductive pattern may be seen as a measure of outcome following psychotic disorder onset, and it may be measured as the rate of child births where the rate is a proxy measure of well-being. Objective: To examine reproductive patterns following psychotic disorder onset by comparing the fertility rates of patients with schizophrenia and bipolar disorder with those of other psychiatric patients and the general population, taking into account parental status at diseaseonset, time since onset, and the possible effect of abortions-rates. Methods: A prospective register-based cohort study drawing on the entire Danish population born after 1950. Incidence Rate Ratios (IRRs) of fertility were analysed using survival analysis. Results: Compared with the general population, the lowest first-child fertility rate was found among men (IRR = 0.10) and women (IRR = 0.18) with schizophrenia. In comparison, bipolar male patients had an IRR = 0.32 and female patients an IRR = 0.36, while male unipolar patients had an IRR = 0.46 and female patients an IRR = 0.57. In the group with other psychiatric disorders men had an IRR = 0.51 and women an IRR = 0.70. Conclusions: The results of the present study show a selection process where persons with more severe disorders are less likely to become parents. The reduced fertility was strongly influenced by the time since psychiatric disorder onset; thus, the longer the time since onset, the higher the fertility. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Longitudinal epidemiological studies have shown worse outcomes in patients with schizophrenia and bipolar disorder (psychotic disorders) than in patients with other psychiatric disorders and in the general population. These outcomes include markedly elevated mortality rates from all causes of death (Harris and Barraclough, 1998; Laursen et al., 2007b), suicide (Hiroeh et al., 2001), increased somatic and medical comorbidity (Laursen et al., 2009; Jeste et al., 1996), more
☆ Dr. TM Laursen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. ☆☆ This study was approved by the Danish Data Protection Agency. ⁎ Corresponding author. E-mail address: [email protected] (T.M. Laursen). 0920-9964/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2010.05.018
unhealthy diets (Brown et al., 1999), higher rates of cigarette smoking (Itkin et al., 2001; Dalack et al., 1998; Jeste et al., 1996), and negative social consequences (Agerbo et al., 2004). The reproductive pattern of a patient after psychotic disorder onset may also be considered an outcome measure. Men and women becoming parents have been shown to form a population segment that, among others, has a lower risk of cancer (Dalton et al., 2004) and psychiatric disorders (MunkOlsen et al., 2006). Several studies have found reduced fertility rates among persons with schizophrenia or a combined measure of psychosis (McGrath et al., 1999; Haukka et al., 2003; Howard et al., 2002; Svensson et al., 2007; Bhatia et al., 2004), with only one recent study showing an opposite result (Nimgaonkar et al., 1997). A study detected no reduced fertility rates in patients with bipolar disorder (affective psychosis) (MacCabe et al., 2009). However, many of these studies are flawed because they have not duly considered the dimensions
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of ‘how’ and ‘when’ to measure reproduction. The average age at which schizophrenia sets in is in the early 20s, while bipolar disorders set in later (Laursen et al., 2007a). Common for the two disorders, and for many other psychiatric disorders, is that disease strikes during the primary reproductive period of both men's and women's lives. It should therefore be taken into account how many (if any) children the person has before disorder onset. Furthermore, women with psychotic disorders are often advised not to have children (Viguera et al., 2002a) and they may choose to have an induced abortion. The rates of induced abortion in women with psychotic disorders should therefore also be taken into account as a possible explanation for their reduced fertility. The aim of the present study was to examine reproductive patterns following psychotic disorder onset by comparing the rates of childbirths in patients with schizophrenia and bipolar disorder with those of other psychiatric patients and members of the general population who had not been admitted to a psychiatric hospital, taking into account parental status at the time of onset of the disorder, time since onset of the disorder, and the possible effect of abortions. 2. Methods We established a cohort study and obtained data on the vital status of the cohortees and their children. Information was drawn from the Danish Civil Registration System (Pedersen et al., 2006). We linked this information to the Danish Psychiatric Central Register (Munk-Jorgensen and Mortensen, 1997) from where we obtained information on inpatient psychiatric treatment, and to the The Danish National Hospital Register (Andersen et al., 1999) from where we obtained information about induced abortion. We used the unique personal identification number assigned to all people living in Denmark to link data drawn from the registers (Pedersen et al., 2006). 2.1. Study population and follow-up period The population-based cohort comprised all individuals born in Denmark between 1 January 1950 and 1 January 1991. The overall follow-up began on 1 January 1970 and ended on 31 December 2006. Cohortees were followed individually from their 15-year birthday until date of death, emigration, or end of the follow-up period, whichever came first. 2.2. Assessment of psychiatric disorder, childbirth, and induced abortion Cohort members were categorized as suffering from a psychiatric disorder if they were admitted to a psychiatric hospital. The diagnostic system used until 31 December 1993 was the ICD8 (World Health Organization, 1971), and from 1 January 1994, the ICD10 (World Health Organization, 1994) classification was used. Diagnoses were categorised as follows: psychotic disorder covering bipolar disorder (ICD8: 296.19 or 296.39, ICD10: F30 or F31) and schizophrenia (ICD8: 295 (excluding 295.79), ICD10: F20); a comparison group of all cohortees with unipolar disorder (ICD8: 296.09, 296.29, 296.99, 298.09, 300.49, or 300.19, ICD10: F32 or F33); and, finally, a category of the remaining psychiatric disorders
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consisting of all admissions to psychiatric hospital not included in the above categories (including personality disorders, ICD8 301[minus 301.83], ICD10 F60,F61). Psychiatric status was treated as a time-depended covariate. All childbirths were identified from the Danish Civil Registration System (Pedersen et al., 2006). All births including twin birth were examined; however, the second twin was not counted as an outcome when we examined having the next child. We did not distinguish between adopted or biological children. In Denmark (2006), there are approximately 1000 adoptions (half of them stepchildren adoptions) and 60,000 births per year. Induced abortion became legal in Denmark in 1973 and all women aged 18 years or more can have a pregnancy terminated within the first 12 weeks of gestation. Around 5% of all induced abortions are performed after the 12th week of gestation and are granted mainly on medical or social indications after a request has been made to the regional health and social authorities. Through the Danish National Hospital Register (Andersen et al., 1999) we obtained information on dates of 1st or 2nd trimester induced abortions (ICD8 codes: 640, 641 or 642, ICD10 codes: O04, O05, or O06) since 1977. For all analyses, including the variable abortions, followup began in 1977. Up to 1993, we had only records of abortions made during inpatient stays; thus, we included approximately 90% of all induced abortions relative to the official number of induced abortions in the period. We constructed a new measure from the variables first induced abortion and first live born child. This measure, which was the first (if any) of the two events, was named first reproductive event. 2.3. Statistical analyses We analysed data as a cohort study with survival analysis techniques, using Poisson regression with the logarithm of the person years as an offset. This method approximates a Cox regression (Andersen et al., 1993; Laird and Olivier, 1981). Using a Poisson regression and person years takes into account the different lengths of follow-up in the cohortees. The GENMOD procedure in SAS version 9.1 (SAS Institute Inc, Cary, NC) was used. Outcome measures comparing fertility incidence rates of two groups were denoted incidence rate ratios (IRRs). IRRs compare the incidence rate (number of new cases per time unit) in one group with the incidence rate in a comparison group (named reference group), and can be interpreted as relative risks. All IRRs were adjusted for or stratified by gender, calendar time, and age and were calculated by log-likelihood estimation. Wald's 95% confidence intervals were used. 3. Results In the follow-up period from 1970 to 2006, a total of 2,819,941 cohort members were followed for 34,898,001 person-years during which 1,587,709 persons had at least one child. Firstly, we examined the IRRs of having the first child among cohort members with no children and found that men (IRR = 0.10; 95% CI (0.09, 0.11)) and women (IRR = 0.18; 95% CI (0.17, 0.20)) with schizophrenia had the lowest observed fertility compared with their respective counterparts with no
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psychiatric admission (Table 1). Among cohortees with a psychiatric disorder, cohort members with bipolar disorder had higher fertility (men IRR = 0.32; 95% CI (0.29, 0.36), women IRR = 0.36; 95% CI (0.33, 0.40)), members with unipolar polar disorder even higher (men IRR = 0.46; 95% CI (0.43, 0.48), women IRR = 0.57; 95% CI (0.55, 0.60)), while the group of patients with remaining disorders had the highest fertility (men IRR = 0.51; 95% CI (0.50, 0.52), women IRR = 0.70; 95% CI (0.69, 0.72)), Table 1. Secondly, we compared the fertility among cohortees with one child by comparing incidence rates of having the second child. The same pattern with low rates among cohortees with schizophrenia and bipolar disorder emerged; however, the fertility IRR was higher, especially among men, Table 1. Thirdly, fertility among cohortees with two children was measured with the third child as the outcome. Cohortees with schizophrenia and bipolar disorder had higher fertility IRRs than when rates from one to two children were examined; and it was now at the same level as the IRRs of those with a unipolar disorder. Interestingly, the group of patients with remaining disorders had higher fertility rate ratios than healthy cohortees (men and women with no records of psychiatric admission). Finally, the fertility among cohort members with three children was examined, and all psychiatric subgroups had fertility rates similar to that of the comparison group (no psychiatric admission), with the group of patients with the remaining disorders having a significantly higher fertility. The excess rate of fertility among persons in the rest group was not driven by personality disorders as we found fertility rates in the personality disorders subgroup equaling 1.18; 95% CI (1.07, 1.31) for women and 1.34; 95% CI (1.21, 1.49) for men, which was very similar to the entire group with remaining psychiatric disorders (results not shown in tables).
Among women with psychiatric disorders, the overall rates of childbirth were reduced compared with those of healthy women. We also examined if a reduction in fertility rates was explained by an increased abortion rate in this group of women. In a separate analysis of women's fertility among cohortees without children, we compared rates of induced abortion in women with psychiatric disorders with those of their counterparts without previous psychiatric admissions. We found an increased IRR of abortions in all psychiatric subgroups, except a slightly decreased IRR in women with schizophrenia, Table 2. The IRR for women with a psychiatric disorder was slightly higher for the first reproductive event (either childbirth or abortion) than for the first child, Table 2. 3.1. Additional analyses Additional analyses on cohortees without children showed that time measured as number of days since first psychiatric admission was an important effect modifier, as the rates of having the first child were much influenced by proximity to the date of admission with a psychiatric disorder. This was apparent especially in women, as the IRR of having first child rose with time since admission (Table 3). The only exception was men being diagnosed with bipolar affective disorder who had a high IRR of a first child around the time of disorder onset. Further analyses demonstrated that age in general influenced reproductive patterns in patients with psychiatric disorders: compared with their respective counterparts, younger cohortees with a psychiatric disorder had higher fertility rates than older cohortees. Thus, an effect modification of the IRR by cohortee age (in both genders) was present, with especially cohortees younger than 26 years having higher IRRs, Figs. 1 and 2.
Table 1 Incidence rate ratio of becoming a parent among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions.
Women 0 → 1 Child
a
1 → 2 Children
a
2 → 3 Children
a
3 → 4 Children
a
Men 0 → 1 Child
a
1 → 2 Children
a
2 → 3 Children
a
3 → 4 Children
a
N of IRR N of IRR N of IRR N of IRR
births
N of IRR N of IRR N of IRR N of IRR
births
births births births
births births births
Schizophrenia
Bipolar disorder
Unipolar disorder
Rest group
Never admitted
572 0.18 327 0.30 117 0.78 35 1.10
376 0.36 262 0.42 91 0.72 34 1.25
1959 0.57 (0.55, 1684 0.52 (0.50, 682 0.76 (0.71, 224 1.05 (0.92,
9833 0.70 (0.69, 0.72) 7610 0.58(0.57, 0.60) 3501 1.11 (1.07, 1.15) 1123 1.23 (1.16, 1.30)
827,141 1.00 (Ref.) 614,331 1.00 (Ref.) 189,408 1.00 (Ref.) 37,858 1.00 (Ref.)
9909 0.51 (0.50, 7296 0.54 (0.53, 3373 1.06 (1.02, 1164 1.27 (1.19,
736,252 1.00 (Ref.) 520,312 1.00 (Ref.) 164,759 1.00 (Ref.) 35,804 1.00 (Ref.)
661 0.10 360 0.31 131 0.76 32 0.87
(0.17, 0.20) (0.27, 0.34) (0.65, 0.94) (0.79, 1.53)
(0.09, 0.11) (0.28, 0.35) (0.64, 0.90) ( 0.62, 1.23)
296 0.32 232 0.59 86 0.86 22 0.83
(0.33, 0.40) (0.37, 0.47) (0.59, 0.89) (0.89, 1.75)
(0.29, 0.36) (0.52, 0.67) (0.70, 1.07) (0.55, 1.27)
1102 0.46 (0.43, 903 0.57 (0.54, 416 0.88 (0.80, 155 1.08 (0.93,
0.60) 0.55) 0.82) 1.20)
0.48) 0.61) 0.97) 1.27)
0.52) 0.55) 1.09) 1.34)
Reference: cohort members never admitted to a psychiatric hospital. Stratified by being a parent for the 1st, 2nd, 3rd, and 4th time. Follow-up period from 1 January 1970 to 31 December 2006. Adjusted for age and calendar time. a “0 → 1 child” is the incidence rate ratio (IRR) of having the first child; comparison between persons having one of the four psychiatric disorders with the part of the populations never admitted to a psychiatric hospital as the reference group. In the same way, “1 → 2 Children” is the IRR for having the second child, only among parents with one child. “2 → 3 Children” is the IRR for having the third child among parents with two children. “3 → 4 Children” the IRR of having the fourth child among parents with three children.
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Table 2 Incidence rate ratio of becoming a parent for the first time, having the first abortion, or experiencing the first reproductive event among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions. Women First child a First abortion First reproductive event b
N of births IRR N of abortions IRR N of rep. eve. IRR
Schizophrenia
Bipolar disorder
Unipolar disorder
Miscellaneous ‘Other disorders’
Never admitted
538 0.18 ( 0.16, 0.19) 399 0.90 ( 0.81, 0.99) 683 0.25 ( 0.23, 0.27)
358 0.36 (0.33, 0.40) 255 1.18 ( 1.03, 1.34) 402 0.46 ( 0.42, 0.51)
1718 0.54 ( 0.52, 0.57) 1136 1.34 ( 1.26, 1.42) 1,768 0.62 ( 0.59, 0.65)
8845 0.69 ( 0.66, 0.69) 5792 1.71 ( 1.66, 1.75) 9146 0.77 ( 0.75, 0.79)
728,063 1.00 ref. 260,365 1.00 ref. 775,645 1.00 ref.
Reference: cohort members never admitted to a psychiatric hospital. Follow-up period from 1 January 1977 to 31 December 2006. Adjusted for age and calendar time. a Numbers differ from the first line in Table 1, as the follow-up starts in 1970 in Table 1 and in 1977 in this table. Note that there is an extensive overlap between women who have an induced abortion and those having a child. b First reproductive event defined as the first childbirth or the first abortion, whichever came first.
4. Discussion 4.1. Key findings We found a reduced fertility among both women and men with psychiatric disorders. Persons with schizophrenia had the lowest fertility followed by bipolar disorder, unipolar disorder, and the remaining disorders. The reduced fertility was most pronounced among cohortees with a psychiatric disorder when having the first child was used as the outcome. Furthermore, reproductive rates rose with time since the first psychiatric admission, and men with a psychiatric disorder had a lower fertility than women with a psychiatric disorder, and higher induced abortion rates in women with a psychiatric disorder explained only a small proportion of their lower fertility. 4.2. Timing, measurement and magnitude of reduced fertility Several papers have showed reduced fertility among persons with a psychotic disorder (McGrath et al., 1999; Haukka et al., 2003; Howard et al., 2002; Svensson et al., 2007; Bhatia et al., 2004; MacCabe et al., 2009), but separate analysis of bipolar affective disorder (or affective psychosis) has yielded less uniform results (MacCabe et al., 2009). In the present study, fertility was modified by the number of previous children. Both men and women with schizophrenia who had a least two children had the same incidence rate of having the next child as those with bipolar disorder, and
almost the same rate as the general population. This may be ascribed to a selection mechanism where those among persons with schizophrenia/bipolar disorder with the mildest symptoms choose to have children and therefore obtain almost the same fertility rates as the general population. The low rates of having the first child among men with schizophrenia may be ascribed to a very strong negative selection, and schizophrenic men had an average IRR that was only 0.10 of the comparison group without psychiatric admissions. For the age group 30–31 years, which was the average age at which Danish men had their first child in 2006, the IRR was only 0.08 (Fig. 2). Schizophrenic women had higher fertility rates with an IRR equaling 0.14 of that of the comparison group at the average age of their first child (Fig. 1). Other studies have not shown a similarly large reduction in the rates of having children. Howard et al found an IRR of approximately 0.50 in women with psychotic disorders, but found the same pattern as in our study: women with non-affective psychosis (including schizophrenia) had a lower IRR than those with affective psychosis (including bipolar disorder) (Howard et al., 2002). McGrath et al. also found reduced fertility; especially among men with nonaffective psychosis (schizophrenia) (McGrath et al., 1999). In comparison, MacCabe et al. detected no reduced IRR of fertility in persons with affective psychosis (bipolar disorder), but found a reduced IRR of fertility among persons with schizophrenia (MacCabe et al., 2009), although fertility was not as reduced as in the present paper. Similarly, Haukka et al.
Table 3 Incidence rate ratio (IRR) for having the first child according to time since first psychiatric admission. Time since admission (months) Women 0–9 10–18 19–24 25–36 37–48 Men 0–9 10–18 19–24 25–36 37–48 a
Schizophrenia IRR a (95% CI)
Bipolar disorder IRR a (95% CI)
Unipolar disorder IRR a (95% CI)
0.07 0.15 0.21 0.22 0.27
(0.04–0.11) (0.11–0.22) (0.15–0.30) (0.17–0.28) (0.21–0.34)
0.12 0.20 0.33 0.35 0.32
(0.06–0.23) (0.12–0.34) (0.20–0.54) (0.25–0.49) (0.23–0.46)
0.32 0.58 0.69 0.79 0.64
(0.26–0.40) (0.50–0.68) (0.58–0.82) (0.70–0.89) (0.56–0.74)
0.07 0.09 0.10 0.13 0.13
(0.05–0.11) (0.07–0.13) (0.07–0.15) (0.10–0.16) (0.10–0.16)
0.29 0.14 0.30 0.23 0.31
(0.18–0.47) (0.07–0.29) (0.17–0.54) (0.15–0.38) (0.20–0.47)
0.32 0.43 0.52 0.54 0.65
(0.25–0.41) (0.35–0.54) (0.41–0.67) (0.46–0.65) (0.55–0.77)
IRR adjusted for age and calendar time. Reference group: Women, respectively men, never admitted to a psychiatric hospital.
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4.3. Gender differences
Fig. 1. Incidence rate ratio of a women becoming a mother for the first time among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions. Stratified by age of the cohort members. Adjusted for calendar period. Follow-up period from 1 January 1970 to 31 December 2006. Reference: cohort members never admitted to a psychiatric hospital.
Women with schizophrenia in the age group 28–29 had a fertility rate of 0.14 of that of the reference population (Fig. 1), which was very low, but yet higher than that seen among men. In general, the IRR was strongly influenced by the cohortee's gender. Women with a psychiatric disorder, especially schizophrenia, did not have as strongly reduced fertility rates as men with schizophrenia, and fertility rose more quickly after their first admission. This observation is in line with those made in previous studies (McGrath et al., 1999). The higher fertility rates among schizophrenic women (compared with schizophrenic men) may be explained partly by women having milder symptoms than men during the reproductive age range (Kohler et al., 2009). Men with schizophrenia appear to have more negative symptoms, fewer social networks, and to be more exposed to social problems and isolation (Thorup et al., 2007), which could all explain the observed lower fertility rates. 4.4. Influence of induced abortion
(Haukka et al., 2003) found a reduced number of children among persons with schizophrenia; however, the reported reduction was less pronounced than in the present study. Importantly, some studies did not stratify by gender, which should be done as gender combined with diagnosis significantly influences the number of children as demonstrated in the present study. Proximity to the onset of psychiatric disorder measured as the date of first-time psychiatric admission predicts the IRR of having the first child (Table 3). This could support the idea of a selection among persons with less severe symptoms as their fertility rate rose with time since onset. It seems very likely that symptoms are most severe at the time of the first episode entailing admission, and that they then gradually become less severe, thereby “allowing” the persons to consider having a child. However, this pattern did not hold for men with a bipolar disorder who had no reduced fertility in the period shortly following disorder onset. On the contrary, they had a higher fertility during the first nine months after the date of first admission, which could be explained by more promiscuous behavior during manic periods (Robinson et al., 2009).
Fig. 2. Incidence rate ratio of a man becoming a father for the first time among cohort members previously admitted with schizophrenia, bipolar disorder, unipolar disorder, or other psychiatric admissions. Stratified by age of the cohort members. Adjusted for calendar period. Follow-up period from 1 January 1970 to 31 December 2006. Reference: cohort members never admitted to a psychiatric hospital.
Women's mental health influences their reproductive decisions (Major et al., 2008), and fertility rates could be influenced by the fact that some women with psychotic disorders may have been advised not to become pregnant (Viguera et al., 2002b). Although women with a psychiatric disorder had higher rates of abortion in the current study than the comparison group, their IRR of first reproductive event (the first birth or abortion, if any) was only slightly higher than their IRR of first birth. The higher abortion rates could therefore not explain the lower fertility rates. 4.5. Comparison with outcome studies A worse outcome in schizophrenic than in bipolar patients was first mentioned in the original definition of schizophrenia (Dementia Praecox) by Emil Kraepelin (Angst, 2002). If we assume that having a child is a proxy measure for a person's physical and mental well-being, the present study confirms this early definition by demonstrating a lower rate of childbirths among schizophrenic patients than among patients with bipolar disorder. This observation is in line with those made in other studies of outcomes following bipolar and schizophrenia which show, e.g., a higher mortality (Harris and Barraclough, 1998; Laursen et al., 2007b) and higher somatic and medical comorbidity (Laursen et al., 2009; Jeste et al., 1996) in persons with schizophrenia than in persons with other psychotic disorders. We compared reproductive patterns in patients with psychotic disorders with patterns among patients admitted with unipolar affective disorder, which also includes disorders with no psychotic symptoms. This comparison produced higher fertility rates in both men and women with unipolar disorders. A better outcome in unipolar disorder has also been shown in other outcome studies (Laursen et al., 2007b). 4.6. Strengths and limitations Register-studies offer both advantages and limitations. The present study made full use of population registers and, to our knowledge, it is the first study to fully describe
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reproductive patterns (up to four children) in patients with psychiatric disorders. The study furthermore, benefits from available, precise information on the number of children, the timing of the first psychiatric contacts, including information on diagnoses, and on induced abortion. Many psychotropic drugs have been shown to influence patients' behavior and thus their fertility rates. Anti psychotic medication and the shifting from one drug to another could have a strong influence on the pateints' well-being , especially shortly after onset of the disorder. Unfortunately, we did not have information on medication usages and prescriptions in our cohort and thus we could not examine this issue further. In the present study, we assumed that disorder onset was the day of first admission. However, there is no available information on the duration and severity of symptoms leading up to the time of admission, which would have allowed us to more fully describe the influence psychiatric disorders have on reproduction patterns. It is likely that the prodromal phase can last for years, and that the first admission does not occur immediately after psychosis onset. In the ICD8 period (up to 1993), we had information only on 90% of the induced abortions, but we have no reason to believe that this information differed between cohortees with a psychiatric disorder and those without a diagnosis, and the IRR was thus only affected to a lesser degree. Moreover, we have no information on spontaneous abortions, and therefore cannot rule out that differences in spontaneous abortion rates can explain (some of) the differences in fertility. However, the number of spontaneous abortions among women with a psychiatric disorder should be much increased to counteract the observed decreased fertility in the group of women with psychiatric disorders. In this study, we had access to clinical diagnoses. However, other studies have validated the clinical diagnoses of bipolar disorder and schizophrenia in the Danish Psychiatric Central Register against diagnoses established according to research criteria, and they found a high level of agreement between the diagnoses (Munk-Jorgensen and Mortensen, 1997; Kessing, 1998; Jakobsen et al., 2005). 5. Conclusion Drawing on the entire Danish population, we were able to describe reproductive patterns in patients with psychotic disorders. Fertility rates among persons with a psychiatric disorder are highly dependent on diagnosis. Compared with the part of the population with no psychiatric hospitalization, persons with schizophrenia had the lowest rates of childbirths. Persons with bipolar disorder had lower rates than persons with unipolar disorder and persons in the group consisting of the remaining disorders. Men with a psychiatric disorder had lower fertility rates than women with a psychiatric disorder in all diagnostic groups examined. Women with a psychiatric disorder had higher rates of induced abortion in general, but this does not explain their decreased fertility rate compared with the general population. Persons with a psychiatric disorder who were already a parent had a less reduced fertility rate for having the next child. The reduced fertility was strongly influenced by the time since psychiatric disorder onset; thus, the longer the time since onset, the higher the fertility.
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Measuring fertility as overall rates of number of children conceals the facts that a certain group of persons with psychotic disorders have very low fertility rates. Importantly, gender, diagnosis, number of children, and time since diagnosis must be taken into account before a real description of fertility can be made. Assuming that fertility rates are a proxy measure of physical and mental well-being, the results of the present study suggest a selection process where persons with more severe disorders are less likely to become parents. Role of funding source The Stanley Medical Research Institute and The Danish Medical Research Council had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Contributors Dr. Thomas Munk Laursen (TML) designed the study and wrote the protocol. Authors TML and Trine Munk-Olsen managed the literature searches and analyses. Author TML undertook the statistical analysis, and author TML wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript. Conflict of interest None. Acknowledgments This study was supported by The Stanley Medical Research Institute. Dr. T Munk-Olsen has received financial support from The Danish Medical Research Council (Reference number: 09-063642/FSS).
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