Medications are often needed to support the mental health of people who might become pregnant. Among patients with one specific mental health condition called bipolar disorder that includes episodes of disabling depression and periods of uncontrollable energy, stopping treatment because of pregnancy may result in the worsening of symptoms, which may be harmful to the patient and their child. However, information on the effects of these treatments during pregnancy is limited. Since studies rarely include pregnant patients, further research is needed to evaluate the safety of these medications when taken during pregnancy.
This study will compare the risks of multiple outcomes in the children of people with bipolar disorder who used bipolar medications during pregnancy to the outcomes in those who did not receive these medications during pregnancy. The outcomes in the children will include stillbirth, premature birth, major birth defects, and developmental delay. The results of these studies will provide information to pregnant patients and clinicians to guide decisions about use of bipolar disorder medications during pregnancy.
Our objective is to study which medications to treat bipolar disorder, and what doses, pose the highest risks of major congenital anomalies and developmental delays to help clinicians and patients make decisions regarding treatment during pregnancy. This information has the potential to improve the lives of all children whose birthing parent needs treatment for bipolar disorder during pregnancy, while continuing to support the parents’ health.
The study population will be patients in CPRD Aurum and CPRD GOLD with at least one diagnosis of bipolar disorder and at least one prescription for a medication to treat bipolar disorder (aripiprazole, asenapine, carbamazepine, haloperidol, lamotrigine, lithium, lurasodone, olanzapine, quetiapine, risperidone, topiramate, valproate products, and ziprasidone), at any time. The population will be restricted to patients with at least one eligible pregnancy defined as an estimated start of pregnancy on or after January 1, 2000, patients aged 14-45 years, and at least one year of recorded medical data to assess prescriptions and covariates of interest before pregnancy.
We propose two studies using this cohort, with the following outcomes in offspring: 1) major congenital anomalies, with a particular focus on cardiac anomalies, diagnosed in pregnancy or within the first year after birth, and 2) developmental delay, including autism spectrum disorder, speech and language delay, and motor delay, diagnosed in early childhood. HES APC will be used to provide supporting evidence for congenital anomalies, where available. For each study we will evaluate outcomes of interest in offspring, by exposure to drug class (atypical antipsychotic, mood stabilizer, other) and individual drug type received during pregnancy. We will evaluate dosage, concomitant use of multiple study drugs, and switching of drugs. We will provide descriptive statistics for the patient population including covariates of interest. Logistic regression and general linear models will be used to calculate relative risks.
Study 1
Primary: major congenital anomalies.
Secondary: nervous system anomalies; eye ear face neck anomalies; circulatory system anomalies; respiratory system anomalies; cleft lip and palate; digestive system anomalies; genital anomalies; urinary anomalies; musculoskeletal anomalies; general anomalies.
Study 2
Primary: developmental delay.
Secondary: autism spectrum disorder; speech and language delay; motor delay.
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Catherine Vasilakis-Scaramozza - Corresponding Applicant - BCDSP - Boston Collaborative Drug Surveillance Program
Katrina Hagberg - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Rebecca Persson - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Mother-Baby Link;CPRD GOLD Mother-Baby Link