Exposure to selective serotonin reuptake inhibitors in early pregnancy and the risk of miscarriage.

OBJECTIVE: To investigate whether exposure to selective serotonin reuptake inhibitors (SSRIs) in early pregnancy is associated with miscarriage. METHODS: This was a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2010. All births were identified using the Medical Birth Registry, and all records of induced abortion or miscarriage were gathered from the National Hospital Register. Data on SSRI use were gathered from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women exposed to an SSRI in early pregnancy and the hazard of miscarriage in women discontinuing treatment before pregnancy. RESULTS: We identified 1,279,840 pregnancies (911,569 births, 142,093 miscarriages, 226,178 induced abortions). Of the 22,884 exposed to an SSRI during the first 35 days of pregnancy, 12.6% (2,883) ended in miscarriage compared with 11.1% among unexposed. The adjusted hazard ratio of having a miscarriage after exposure to an SSRI was 1.27 (95% confidence interval [CI] 1.22-1.33) compared with unexposed. Women discontinuing SSRI treatment 3-12 months before pregnancy also had an increased hazard ratio of having a miscarriage compared to unexposed (1.24, 95% CI 1.18-1.30). CONCLUSION: Women exposed to SSRIs during early pregnancy were at increased risk of miscarriage as were women discontinuing SSRI treatment before pregnancy, and these risks were similar. Therefore, treatment with SSRIs during pregnancy should not be discontinued as a result of fear of miscarriage. LEVEL OF EVIEDENCE:: II.

Prevalence of antidepressant use during pregnancy in Denmark, a nation-wide cohort study.

AIM: The aim of this study was to assess the prevalence and patterns of exposure to antidepressants before, during and after pregnancy in a cohort including all pregnant women in Denmark between 1997 and 2010. METHODS: We performed a retrospective cohort study including 912 322 pregnancies. Information was retrieved from the Danish Birth Registry and The Register of Medicinal Product Statistics to identify women redeeming an antidepressant prescription during pregnancy. Exposure periods were based on standard treatment doses and dispensed pack sizes. RESULTS: We identified 19 740 pregnancies exposed to an antidepressant at some point during pregnancy. The rate of exposure increased from 0.2% in 1997 to 3.2% in 2010. We found that the rate of exposure was halved during the first 3 months of pregnancy. In contrast, we describe a clear increase in exposure after pregnancy among pre-delivery treatment-naïve women. CONCLUSIONS: In spite of uncertainty concerning antidepressants' safety during pregnancy we find a 16-fold increase in exposure rates between 1997 and 2010. The rates describe a sharp decrease in exposure during pregnancy that is probably caused by physicians' hesitation to prescribe antidepressants and women's fear of unwanted effects on the unborn child. More studies are needed to clarify the consequences of antidepressant discontinuation during pregnancy.

Trimethoprim Use prior to Pregnancy and the Risk of Congenital Malformation: A Register-Based Nationwide Cohort Study.

Objectives. The aim of the study was to investigate whether the use of the antifolate antibiotic trimethoprim during the 12 weeks before conception was associated with congenital malformations. Methods. We conducted a nationwide register-based cohort study including all Danish women giving birth from 1997 to 2004. All women with at least one prescription of trimethoprim dispensed during the 12 weeks before conception were identified. Results. There was a doubling of congenital malformations in offspring to women exposed to trimethoprim in the 12 weeks before conception. The adjusted odds ratio (OR) of major congenital malformation was 1.87, 95% confidence interval (CI) 1.25-2.81. There was a significant increase in major malformations of the heart (OR = 2.49; 1.18-5.26) and limbs (OR = 2.18; 1.13-4.23). Conclusions. In this study, we found an association between exposure to trimethoprim during the 12 weeks before conception and an increased risk of heart and limb defects.

Clarithromycin in early pregnancy and the risk of miscarriage and malformation: a register based nationwide cohort study.

BACKGROUND: The antibiotic clarithromycin has been associated with fetal loss in animals and a study has found a doubling in the frequency of miscarriages among women using clarithromycin in pregnancy. The aim of the study was to investigate whether clarithromycin use in early pregnancy was associated with an increased risk for miscarriages and major malformations. METHODS: We conducted a nationwide cohort study including all women in Denmark with a known conception between 1997 and 2007. The Fertility Database was used to identify all women giving birth and the National Hospital Register was used to identify all women with a record of miscarriage or induced abortion. Prescription data was obtained from the National Prescription Register. The primary outcome was the number of miscarriages and offspring with major congenital malformations among users of clarithromycin compared to non-users. RESULTS: We identified 931 504 pregnancies (705 837 live births, 77 553 miscarriages, and 148 114 induced abortions). 401 women redeemed a prescription of clarithromycin in the first trimester of which 40 (10.0%) experienced a miscarriage and among the live born nine (3.6%) had offspring with malformations. The hazard ratio (HR) of having a miscarriage after exposure to clarithromycin was 1.56 (CI95% 1.14-2.13). There was no increased hazard of having a miscarriage when being exposed to penicillin or erythromycin. There was no increased prevalence (OR = 1.03 (CI95% 0.52-2.00)) of having offspring with malformations after exposure to clarithromycin. CONCLUSIONS: We found an increased hazard of miscarriage but no increased prevalance of having offspring with malformations among women redeeming a prescription of clarithromycin in early pregnancy. This is supported by previous studies in animals and humans. However, further research is required to explore the possible effect of treatment indication on the associations found.

Health care use by patients with somatoform disorders: a register-based follow-up study.

OBJECTIVE: Studies have shown a greater use of medical than mental health services in patients with somatoform disorders. However, not many studies are based on structured interviews and include the entire somatoform spectrum of diagnoses. We conducted a register-based case-control study to investigate medical care use prior to and three years after diagnosis in patients with somatoform disorders. METHODS: We included 380 patients with somatoform diagnoses (SCID-NP for DSM-IIIR) in a case-control study and compared them with 174 patients with anxiety disorders and 5540 controls from the background population. Data from the Danish National Registers were used to assess health care use in both primary and secondary care. RESULTS: Somatoform patients incurred 2.11 (2.09-2.12) times the primary care visits of controls. They had 3.12 (3.08-3.16) times as many somatic bed-days than controls and 3.94 (3.91-3.97) as many psychiatric bed-days. Primary care use remained stable 3 years after diagnosis (p = 0.14) and the award of disability pension (p = 0.82). However, the number of somatic admissions decreased from 5.64 to 2.76 (p = 0.0004) 3 years after diagnosis. Somatization had an independent effect on health care use when controlling for psychiatric comorbidity. CONCLUSIONS: Patients with somatoform disorders make significantly greater use of health care services than do controls and patients with anxiety. Somatoform patients made more use of psychiatric services than expected. The use of somatic health care was independent of psychiatric comorbidity. Primary care use and disability pension award were not influenced by proper diagnosing of somatoform disorders whereas number of somatic admissions were halved.

Effects of escitalopram in prevention of depression in patients with acute coronary syndrome (DECARD).

OBJECTIVE: Depression is a major problem in patients after acute coronary syndrome (ACS) with negative impact on survival and quality of life. No studies have examined prevention of post-ACS depression. We examined whether treatment with escitalopram can prevent post-ACS depression. METHODS: We have conducted a randomised controlled trial. Between November 2004 and December 2007, 240 patients in 2 university hospitals in Copenhagen, Denmark, with ACS were randomised. Patients were randomised to a double-blind treatment with escitalopram or matching placebo for 1 year. Main outcome measure was the incidence of ICD-10 depressive episode. RESULTS: Of 120 patients treated with escitalopram 2 developed depression versus 10 in placebo treated group (log rank, p=0.022). In multivariate analysis treatment with placebo and high Hamilton Depression Scale score at baseline were associated with development of depression. Patients were well matched at baseline. CONCLUSION: Twelve months treatment with escitalopram prevented depression in post-ACS patients.