Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT00686946 |
| Other study ID # |
114/04 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2005 |
| Est. completion date |
December 2025 |
Study information
| Verified date |
November 2023 |
| Source |
The Alfred |
| Contact |
Prof Jayashri Kulkarni, MBBS,FRANZCP |
| Phone |
61-3-9076-6564 |
| Email |
jayashri.kulkarni[@]med.monash.edu.au |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The National Register of Antipsychotic Medication in Pregnancy (NRAMP)is an observational,
nationwide study involving women of child-bearing age who take antipsychotic medication
during pregnancy. It follows the pathway of mother and baby during pregnancy and for the
first 12 months of the baby's life, in order to develop evidence-based guidelines for the
best use and effect of antipsychotic medication during pregnancy, thereby informing clinical
treating teams with regard to the management of their patients in this vulnerable population
group.
The investigators hypothesize that the provision of such evidence-based guidelines will
improve the management and outcomes for mother and baby during pregnancy, birth and the
postnatal phase, providing a positive impact on maternal and child health and wellbeing for
present and future generations.
Description:
The desire to reproduce is both a powerful urge and a basic human right for women regardless
of mental health status. Deinstitutionalised treatment for mental illness, better
pharmacotherapies, and generally higher expectations for a normal quality of life have the
potential to raise the incidence of pregnancy in women with psychosis (Miller, Bloom &
Resnick, 1992). The right of women with mental illness to become parents places
responsibility upon health care professionals to ensure sound antenatal and ongoing care is
available.
Ethical duty of care aside, good antenatal treatment appears prudent given the greater risk
of obstetric complications in women with schizophrenia (Sacker et al, 1996). In a meta
analysis of studies examining outcomes for pregnant women with and without schizophrenia,
evidence exists of a small but statistically significant increase in the risk of low birth
weight and inferior neonatal condition in infants of the schizophrenia cohort (Sacker et al,
1996). A recent meta analysis (Webb, et al, 2005) summarized that exposure to maternal
psychotic illness is associated with a "higher than expected" risk of perinatal and infant
mortality, including an almost twofold chance of fetal death or stillbirth (p.1052).
Jablensky and colleagues (2005) further discovered that women whose psychiatric illness
commenced before the birth of their child were significantly more likely to experience
obstetric complications than women whose first admission for mental illness was after the
delivery. Moreover, the offspring of women with schizophrenia carry with them an increased
risk for developing psychosis (Mednick, Parnas & Schulsinger, 1987). This observation has
driven the neurodevelopmental hypothesis about the aetiology of schizophrenia, which posits
that alterations to early fetal brain development in utero might lead to a predisposition to
the formation of schizophrenia later in life (Lewis & Murray, 1987). Such perinatal
contributions to adult mental health outcomes points to the necessity to provide pregnant
women who have psychosis, with proper and specialized treatment.
Despite these clear arguments for a thorough understanding of the needs of pregnant women
with schizophrenia, current research is limited. In particular, there is currently very
little evidence regarding the use of antipsychotic medication in pregnancy upon fetal
development and maternal health. Over the last four decades, intermittent studies have sought
to investigate the teratogenicity of the older or typical antipsychotics upon fetal
development. Earlier reports were generated from pregnancy outcomes of women treated with
these medications for hyperemesis gravidarum, not from women with schizophrenia (Kerns,
1989); as such, it is difficult to extrapolate initial findings across these two cohorts with
confidence. Limb defects in children born to women who were given large doses of haloperidol
in early pregnancy are outlined in case reports (Goldberg & Nissam, 1994). Patton and
colleagues (2002) also reviewed three other larger studies and concluded that a significant
increased chance exists for babies exposed to phenothiazines to develop congenital
malformations, compared with the incidence within the general population.
The newer or second generation antipsychotics (SGAs) have not been studied in any great
detail; to date, to our knowledge, there have been no blinded or randomized studies examining
birth outcomes in women taking SGAs, and these are unlikely given ethical considerations.
Prescribing guidelines laid out in MIMS (2003) for all current SGAs include pregnancy as a
"special precaution" and despite the gravity of associated risks of teratogenesis, there are
few publications examining atypical antipsychotic medication use in pregnant women. In their
review, Patton and colleagues (2002) cite four studies on the outcome of clozapine use,
noting that for a total five cases no congenital abnormalities were reported, although one
infant experienced low grade fever and seizure, with gastroesophageal reflux. Grigoriadis and
Seeman (2002) suggest that the increased risk of agranulocytosis and seizures in babies,
coupled with the identification of both pregnancy and clozapine as potentially increasing the
likelihood of thromboembolisms, render this a medication to be avoided during pregnancy.
Twenty-three Olanzapine-exposed pregnancies were observed by Goldstein and colleagues (2000),
who found there was no increased risk of spontaneous abortion, stillbirth, prematurity or
major malformation. The authors were, however, swift to assert that studies of greater sample
sizes and over a protracted time period are necessary before olanzapine can be declared
"safe" with confidence.
Thus, clinicians remain in a conundrum; although in general today's antipsychotic drugs
produce fewer side effects, are better tolerated by the patient, and more effectively target
the symptoms of psychosis, little evidence has been presented to reassure prescribers that
their impact upon fetal development is minimal. A proven, evidence based method for achieving
a balance between maternal mental health with minimal risk to the fetus must be researched
and evidenced. Therefore, we have established The National Register of Antipsychotic
Medication in Pregnancy (NRAMP) as a non-interventional means of providing information about
pregnancies and outcomes for women with psychosis, and their babies. Not only is NRAMP
seeking to record large scale obstetric information in a prospective fashion, including
pharmacotherapy during pregnancy and beyond, it is also capitalizing on the opportunity to
track alterations to mental health symptoms of women during pregnancy and in the post partum
period, and to gather valuable insights into the attitudes of this cohort as they make the
transition into parenthood.
The combination of poor psychosocial history, existing involvement with child protection
agencies, psychiatric diagnoses and admissions, medications and substance abuse, present many
issues affecting outcomes for both mother and child during the perinatal period. Our study
involves extensive collaboration between many different clinical groups, and will culminate
in an important best-practice resource to improve the quality of life for both present and
future generations. The identification of a history of serious mental illness and a planned
management strategy are therefore essential if we are to improve outcomes for mother and
baby.
This then, is the driving force behind the establishment of The National Register of
Antipsychotic Medication in Pregnancy (NRAMP), and is a much-needed strategy to improve the
management of serious mental illness for women who become pregnant.
This investigator initiated study has been funded by Janssen-Cilag, AstraZeneca, Hospira,
Lilly and the Australian Rotary Health Research Fund. NB: AstraZeneca provided funding up to
and including 250 consented participants. The study continues to recruit.
