Effectiveness of comprehensive supports for schizophrenic women during pregnancy and puerperium: Preliminary study

Authors


Osamu Nishizawa, MD, Department of Neuropsychiatry, University of the Ryukyus Faculty of Medicine, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. Email: o.zawanishi@nifty.ne.jp

Abstract

Abstract  The risks of deteriorated psychiatric symptoms/daily life functioning should be warned of in schizophrenic women during pregnancy and puerperium. The purpose of the present paper was to prospectively monitor mental status and functioning of pregnant women with schizophrenia, and investigate the effects of various supports. Subjects were 20 schizophrenic women who visited a clinic providing care and support for pregnant women with psychiatric diseases, consisting of 12 patients with psychotic deterioration (deterioration group) and eight remitted stable patients (stable group). Psychiatric assessments were performed using Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) at three time-points: at the first examination, after fixed prescription during pregnancy, and after delivery. The types/doses of drugs and other non-drug-related supports (13 items) were recorded during the study period. Although a higher total PANSS score at the first examination (P = 0.004) and lower GAF scores at the first examination and even after fixed prescription (P = 0.0003) were observed in the deterioration group, those after delivery finally caught up with the levels in the stable group. Doses of antipsychotic drugs were gradually increased in the deterioration group although no significant differences in chlorpromazine equivalent doses were found between the two groups after fixed prescription. There was a positive correlation between the number of non-drug-related supports and amelioration score in PANSS (rs = 0.553, P = 0.012). These findings suggest that comprehensive intervention is a requisite in pregnant schizophrenic women, especially with psychotic deterioration, and that non-drug-related supports may also contribute to maintenance of good and stable mental status in these patients.

INTRODUCTION

Recent advances in diagnosis and therapy including psychiatric rehabilitation are able to improve the quality of life of schizophrenia patients. In particular it is now expected that women suffering from schizophrenia can marry and have children.1 However, it has been reported that schizophrenic women have a higher risk of psychotic deterioration during pregnancy, puerperium and child-care periods2,3 because these hazardous periods are often accompanied by high stress, increased concern and biological changes, for example new adaptation to maternal role and the burden of child care as well as endocrinological changes, all of which can cause deteriorated mental condition in vulnerable patients.

One problem is psychotic relapse due to non-adherence to neuroleptic medication during these periods, which may possibly lead to such poor outcome as termination of pregnancy, obliged cesarean section and institutionalization of their offspring due to poor child-care capability.4,5 Although some drugs can adversely affect fetal growth especially during the first trimester of pregnancy,6,7 discontinuation of medication does not seem to be a realistic strategy for pregnant women with schizophrenia. In addition, teratogenic effects of psychotropic drugs have not been fully clarified, even though some ranked evaluation of safety for embryo/fetus has been provided by Food and Drug Administration (FDA)8 and American Academy of Pediatrics (AAP).9 Therefore, in principle, individualized drug regimens at minimal effective dosages are carefully selected to maintain stable psychiatric status throughout pregnancy and the post-partum period.

Apart from pharmacotherapy, more attention should be paid to other medical monitoring and care to maintain good physical condition and stable pregnancy/delivery process in schizophrenic women because these patients are usually at higher risk of obstetric complications,10–12 and have insufficient self-control and self-care capability, for example when strict diet control is required for the treatments of toxemia and diabetes. Thus, close collaboration between psychiatrists and obstetricians is required during pregnancy. Even after delivery, comprehensive support should be provided to post-partum patients from various psychosocial aspects using regional supporting network.13,14

Despite the aforementioned importance of support and care for pregnant women with schizophrenia, very few studies have systematically focused on continuous monitoring of psychiatric symptoms and functioning during pregnancy/puerperium and protective/supportive effects of drug- or non-drug-related factors on the outcome of these patients. We have opened a special clinic for pregnant women with psychiatric disorders, providing comprehensive support and care for psychiatric relapse prevention with stable pregnancy/delivery process in cooperation with obstetricians and various comedical workers since 2000. Therefore, we prospectively monitored mental status and functioning of pregnant women with schizophrenia, and investigated the effects of drug factors and various non-drug-related supports in the present study.

METHODS

Subjects were 20 schizophrenic women who visited the special clinic providing support/care during pregnancy/puerperium periods at University of the Ryukyus Faculty of Medicine. All the subjects met diagnostic criteria for schizophrenia according to ICD-10.15 Diagnosis and types of schizophrenia were determined by two well-trained psychiatrists. These subjects were divided into two groups, consisting of 12 patients with psychotic deterioration (deterioration group) and eight remitted stable patients (stable group) after psychiatric assessments at the first examination. In the former group the reasons for deterioration symptoms were discontinuation of medication (n = 7), drug-naïve condition (n = 3) and spontaneous relapse despite medication (n = 2). The backgrounds of these two groups are summarized in Table 1.

Table 1.  Subject characteristics
 Deterioration group (n = 12)Stable group (n = 8)P
  1. Wilcoxon rank-sum test, Fischer's exact test and Kruskal-Wallis test were used for comparisons.

  2. NS, Not significant (P ≥ 0.05).

Age (years)
 Onset of disease24.8 ± 6.230.6 ± 5.30.031
 Marriage27.9 ± 5.130.9 ± 7.0NS
 At first examination33.0 ± 5.539.0 ± 2.60.010
Type of schizophrenia
 Paranoid54NS
 Undifferentiated31 
 Hebephrenic30 
 Catatonic13 
Pregnancy
 Primipara/Multipara5/75/3NS
 Trimester at first examination
  First44NS
  Second13 
  Third71 
 Week at delivery39.0 ± 1.739.5 ± 1.5NS
Assessment (week of pregnancy/puerperium)
 At first examination 23.8 ± 11.816.8 ± 11.3NS
 At fixed prescription34.2 ± 6.129.3 ± 9.5 NS
 After delivery 8.4 ± 1.87.3 ± 3.2NS

Psychiatric assessments were performed using Positive and Negative Syndrome Scale (PANSS)16 and Global Assessment of Functioning (GAF)17 at three time-points: at the first examination immediately after being referred to the clinic at University of the Ryukyus Faculty of Medicine, after fixed prescription during pregnancy defined as the week of pregnancy when drug regimen was fixed to exactly the same as those at delivery, and finally after delivery. The number of weeks of pregnancy/puerperium at three time-points did not differ between the deterioration and stable groups (Table 1).

Psychotropic drugs during pregnancy/puerperium were prescribed based on a flexible-dose design according to the results of psychiatric assessments, although these were in principle set at the minimum for each individual unless psychiatric symptoms worsened. The drug doses were expressed as chlorpromazine-equivalence for antipsychotic drugs, diazepam-equivalence for anxiolytic/hypnotic drugs and biperiden-equivalence for antiparkinsonian drugs, using equivalent conversion of psychotropic drugs reported by Inagaki and Inada.18

Other non-drug-related supports (13 items)19 were listed as follows: (i) consent to child-care support by husband; (ii) consent to other family support for child care; (iii) consultation with regional public health nurses; (iv) regular meeting between psychiatrists and obstetricians; (v) group conference among the midwives, public health nurses and psychiatrists; (vi) admission to the psychiatric ward during pregnancy (relapse intervention); (vii) admission to the psychiatric ward after delivery (post-partum mental care); (viii) education and skill training of child care for patients (mother–baby unit); (ix) education and skill training of child care for other family caregivers; (x) visiting child-care support from regional resources (public health nurses, care-helpers and volunteers); (xi) consultation with child welfare center; (xii) short-term use of nursery institutes; and (xiii) follow-up consultation for child care with psychiatrists and obstetricians. The numbers of aforementioned supports provided were recorded during the study period. The commencement times of each support is summarized in Table 2.

Table 2.  Non-drug-related support
Non-drug-related supportDuring pregnancyAfter delivery
1st−2nd trimester3rd trimester
Consent to child-care support by husband940
Consent to other family support for child care572
Consultation with regional public health nurses297
Regular meeting with obstetricians4122
Conference with midwives and public health nurses084
Admission to the psychiatric ward
 During pregnancy160
 After delivery005
Education and skill training of child care
 Patients (use of mother-baby unit)0012
 Other family caregivers009
Visiting child-care support from regional resources003
Consultation with child welfare center004
Short-term use of nursery institutes006
Follow-up consultation for child care0016

This intervention study was done in clinical situations, designed to promote a stable psychiatric state and good child-care capability in schizophrenic mothers. Therefore, all of the supports including modification of pharmacotherapy and non-drug-related supports were uncontrolled and purely individualized. Although psychiatrists informed each patient and her family of the necessity for various supports, the final decision to receive these supports was made by patients and their family. Regarding data processing, written informed consent was obtained from each subject and her family (husband and parents). All of the results were recorded as anonymous and grouped after being encoded or numbered, adhering to the privacy policy to protect personal information. This study was approved by the Ethics Committee of the University of the Ryukyus Faculty of Medicine.

Wilcoxon rank–sum test, Fisher's exact test and Kruskal–Wallis test were used for comparison of subjects' backgrounds and the number of supports between the deterioration and stable groups. The Friedman rank test followed by Wilcoxon signed-rank test with Bonferroni's correction was applied for intragroup comparison of drug dosages and the scores of clinical assessments (PANSS and GAF) among the aforementioned three phases. Two-way repeated measures anova followed by Scheffe test as a post-hoc analysis was used for comparisons of scores of PANSS and GAF between the deterioration and stable groups at each time-point. The Spearman rank test was applied to analyze the correlations between the number of non-drug-related supports and amelioration scores of PANSS and GAF. P ≤ 0.05 was regarded as significant. SPSS 11.0 for Windows (SPSS Japan, Tokyo, Japan) and StatView 5 for Windows (SAS Japan, Tokyo, Japan) were used for statistical analysis.

RESULTS

Regarding the subjects' backgrounds, the mean age at disease onset (P = 0.031) and the first examination (P = 0.010) were significantly younger in the deterioration group than in the stable group, although there were no significant differences in types of schizophrenia, proportion of primipara/multipara, trimester at the first examination and week at delivery between the two groups (Table 1).

Dosages of antipsychotic drugs were gradually increased in the deterioration group. Although the deterioration group received lower chlorpromazine-equivalent neuroleptic doses than the stable group at the first examination (66.7 ± 107.8 mg/day vs 456.9 ±499.9 mg/day; P = 0.016), thereafter the average dosages became almost identical with those in the stable group (216.2 ± 195.0 mg/day vs 185.7 ± 167.8 mg/day after fixed prescription; 395.5 ± 455.4 mg/day vs 405.5 ± 516.2 mg/day after delivery). Similarly, no significant differences in dosages of anxiolytics/hypnotics (diazepam equivalent) and antiparkinsonian drugs (biperiden equivalent) were observed between these two groups at any time-points.

Out of the 20 patients, five (25%) underwent cesarean section due to obstetric complications (placenta previa, breech presentation, cephalopelvic disproportion, severe toxemia, post-term pregnancy), and three patients (15%) needed induction of labor due to hypotonic uterine dysfunction. Five neonates had transient abnormalities, that is, difficulty in feeding, respiratory acidosis, cyanosis with hypoxemia, polycythemia and low birthweight. Severity of symptoms (PANSS)/functioning (GAF) and dosages of antipsychotic drugs (chlorpromazine equivalent) did not affect the outcome of maternal condition at delivery or neonatal complications. Among 12 deterioration patients, seven (58.3%) during pregnancy and three (25%) after delivery needed to be admitted to psychiatric ward due to unstable mental status, while two (25%) out of eight remitted stable patients had mild psychotic relapse within 1 week after delivery and needed admission to the psychiatric ward.

In the deterioration group, PANSS score was significantly reduced (P = 0.002) while GAF score was significantly elevated (P = 0.003) after delivery compared with those at the first examination during pregnancy. Although a higher total PANSS score was observed at the first examination (P = 0.004), and lower GAF score was observed at the first examination (P = 0.0003) and also after fixed prescription (P = 0.004) in the deterioration group, those after delivery caught up with the levels in the stable group (Fig. 1).

Figure 1.

Comparison of (a) Positive and Negative Syndrome Scale (PANSS) and (b) Global Assessment of Functioning (GAF) scores between the (▴) deterioration and (●) stable groups at first examination, fixed prescription and after delivery. Significant differences were found between the two groups on two-way repeated measures anova followed by Scheffe test (a, P = 0.004; b, P = 0.0003; c, P = 0.0004).

Regarding non-drug-related supports, preparation for future child-care support in collaboration with family and regional resources was started during pregnancy, while actual child-care support was offered by various specialists after delivery (Table 2). No significant difference was found in the average number of supports between the deterioration and stable groups (7.9 ± 1.3 vs 5.5 ± 2.6). However, deterioration patients more frequently received consultation with regional public health nurses (P = 0.049), conference with midwives and public health nurse (P = 0.019) and admission to the psychiatric ward during pregnancy (P = 0.015). Similarly, the most necessary key supports in more severe cases (PANSS ≥ 100) were consultation with regional public health nurses (90%), conference with the midwives and public health nurses (90%) and admission to the psychiatric ward during pregnancy (70%). There was a positive correlation between the number of non-drug-related supports and amelioration score in PANSS (rs = 0.553, P = 0.012), while no significant correlation was found between the number of supports and amelioration score in GAF (Fig. 2).

Figure 2.

Correlations between the number of non-drug-related supports and amelioration scores (subtraction of post-partum scores from baseline at the first examination) of (a) Positive and Negative Syndrome Scale (PANSS) and (b) Global Assessment of Functioning (GAF) in 20 schizophrenic women consisting of (▴) deterioration and (●) stable cases. (a) A positive correlation was found between the number of non-drug-related supports and amelioration scores of PANSS on Spearman rank test (rs = 0.553, P = 0.012). (b) rs = 0.240, NS.

DISCUSSION

Problems associated with pregnancy in schizophrenic women have been discussed in several meta-analyses of case–control studies20,21 and population-based investigations,10,22,23 mainly focusing on obstetric complications in a retrospective manner. Although prevention of psychotic relapse during pregnancy and puerperium appears to be an important issue,5,6 there have been few prospective studies assessing mental conditions of schizophrenic women during these periods and examining protective effects of comprehensive supports. The present study is the first study to monitor intra-individual changes in psychiatric symptoms/daily life functioning throughout pregnancy and puerperium periods and to examine the effectiveness of modified pharmacotherapy and non-drug-related supports. Because the present study was limited in the uncontrolled study design and small number of subjects (20 in total), the present results are still preliminary and should be interpreted cautiously.

Despite the small study size, the present results indicated high risk of psychotic relapse due to discontinuation of medication in pregnant schizophrenic women for fear of adverse effects of drugs on embryo/fetus and deteriorated psychiatric symptoms after delivery even in remitted patients. Although earlier onset has been generally regarded as a risk factor of poor prognosis, it did not directly disturb the final treatment outcome in the deterioration group at the end of the present study. However, these subjects with earlier onset tend to have a higher risk of psychotic relapse due to poor adherence to medication. The exacerbations of schizophrenia are possibly associated with poorer outcome of pregnancy and more difficulties in parenting, which may lead to unwilling termination of pregnancy by surrogate decision making24 and disturbing consequences for early mother–infant relationship,5 respectively. To promote successful pregnancy with a stable mental status, schizophrenic women of childbearing age should be made aware that maintenance treatment at minimal effective neuroleptic doses during pregnancy would be more beneficial than avoiding small teratogenic risks by withholding pharmacotherapy.5 In order to guarantee quality of child care, more sensitive attention should be paid to post-partum psychological changes, because the majority of psychotic breakdowns are observed during this period.6

Earlier intervention by psychiatrists appears to be effective for pregnant schizophrenic women, especially those with psychotic deterioration, because the present study shows that most of the deterioration subjects recovered from deteriorated psychiatric symptoms and worsened daily life functioning before delivery (Fig. 1) by successful modification of pharmacotherapy and psychiatric admission for relapse intervention. In eight remitted pregnant women, neuroleptic dosages were reduced during late pregnancy to assure safer delivery for both mothers and neonates. However, two patients had mild psychotic relapse and needed short-term admission. This implies that there may be difficulty in balancing the minimal effective policy during pregnancy and prevention of post-partum relapse.

Not only regular medication but also non-drug-related supports were at least partly attributable to favorable outcome for schizophrenic mothers and their offspring. With regard to post-partum mental care, these supports may reduce the burden of new adaptation to the maternal role and help to access social support networks to increase parenting capability.5,13 These protective effects are reflected by a positive relationship between the number of various supports and reduction in psychiatric symptoms (Fig. 2), although the possibility that patients with severe cases but who are potential treatment responders have more chance to receive various services cannot be entirely neglected. In addition, the present study also implies that more use of supportive collaboration with midwives and regional resources should be taken into consideration from an early stage of pregnancy especially in deterioration patients with severe parenting difficulties. These findings suggest that comprehensive monitoring and intervention are required in schizophrenic women throughout pregnancy and the post-partum period to support their new life stage and improve their quality of life.

Meanwhile, the present study found a relatively high frequency of obstetric complications for both mothers and neonates, similar to that reported in previous epidemiological studies.10,22,23 Larger-sized studies have demonstrated that schizophrenic women are more likely to have risks of placental abruption, preterm delivery, low birthweight, stillbirth and neonatal death.10–12 These obstetric complications are not only discouraging for schizophrenic mothers, they are also disturbing with regard to the future of the offspring because a history of obstetric complications, for example fetal hypoxia, low birthweight and minor physical anomalies, is regarded as a plausible risk factor for future onset of schizophrenia at younger age.25–27 Although obstetric complications were appropriately treated by early intervention, and abnormalities seen in neonates were mild and transient in the present study, aforementioned previous reports together with the present findings justify the necessity of close collaboration between psychiatrists and obstetricians when treating pregnant women with schizophrenia.

The present study did not directly focus on assessments of child-care capability of schizophrenic mothers and their family caregivers or long-term observation of physical and mental growth in their offspring. To investigate these clinically important issues, future controlled studies with a larger number of subjects in a longer follow-up period is necessary.

CONCLUSION

The present study suggests that follow-up monitoring of symptoms/functioning and earlier intervention for psychotic deterioration are effective in schizophrenic women during pregnancy and puerperium periods, and that it may lead to improved parenting capability and established mother–infant relationship. Not only regular medication but also non-drug-related supports during pregnancy are at least partly attributable to reduction in psychiatric symptoms. In particular, patients with severe cases should receive early intervention, that is, not only admission during pregnancy but also use of the network of midwives and regional resources for future child-care support. The relatively high frequency of obstetric complications in these subjects justifies the necessity of close collaboration between psychiatrists and obstetricians. These comprehensive supports should be routinely provided to pregnant schizophrenic women for their new life stage and better quality of life.

Ancillary