Search tips
Search criteria

Results 1-6 (6)

Clipboard (0)
more »
Year of Publication
Document Types
1.  Adverse pregnancy outcomes after exposure to methylphenidate or atomoxetine during pregnancy 
Clinical Epidemiology  2015;7:139-147.
To determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD).
Materials and methods
This was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers.
We identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03–2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11–2.20). The aRR of Apgar scores <10 was increased among exposed women (aRR 2.06, 95% CI 1.11–3.82) but not among unexposed women with ADHD (aRR 0.99, 95% CI 0.48–2.05).
MPH/ATX was associated with a higher risk of SA, but our study indicated that it may at least partly be explained by confounding by indication. Treatment with MPH/ATX was however associated with low Apgar scores <10, an association not found among women with ADHD who did not use MPH/ATX.
PMCID: PMC4317061  PMID: 25657597
attention deficit/hyperactivity disorder; ADHD; methylphenidate; atomoxetine; pregnancy outcomes
2.  Antidepressant exposure in pregnancy and risk of autism spectrum disorders 
Clinical Epidemiology  2013;5:449-459.
Both the use of antidepressant medication during pregnancy and the prevalence of autism spectrum disorder have increased during recent years. A causal link has recently been suggested, but the association may be confounded by the underlying indication for antidepressant use. We investigated the association between maternal use of antidepressant medication in pregnancy and autism, controlling for potential confounding factors.
We identified all children born alive in Denmark 1996–2006 (n=668,468) and their parents in the Danish Civil Registration System. We obtained information on the mother’s prescriptions filled during pregnancy from the Danish National Prescription Registry, and on diagnoses of autism spectrum disorders in the children and diagnoses of psychiatric disorders in the parents from the Danish Psychiatric Central Register. In a cohort analysis, we estimated hazard ratios of autism spectrum disorders in children exposed to antidepressant medication during pregnancy compared with children who were not exposed, using Cox proportional hazards regression analysis. Furthermore, we estimated the risk for autism spectrum disorder in a sibling design.
Children exposed prenatally to antidepressants had an adjusted hazard ratio of 1.5 (95% confidence interval [CI] 1.2–1.9) for autism spectrum disorder compared with unexposed children. Restricting the analysis to children of women with a diagnosis of affective disorder, the adjusted hazard ratio was 1.2 (95% CI 0.7–2.1), and the risk was further reduced when exposed children were compared with their unexposed siblings (adjusted hazard ratio 1.1; 95% CI 0.5–2.3).
After controlling for important confounding factors, there was no significant association between prenatal exposure to antidepressant medication and autism spectrum disorders in the offspring.
PMCID: PMC3832387  PMID: 24255601
antidepressants; depression; autism; autism spectrum disorder; childhood autism; pregnancy
3.  Prenatal Antidepressant Exposure and Risk of Spontaneous Abortion – A Population-Based Study 
PLoS ONE  2013;8(8):e72095.
To estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy.
From the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who were diagnosed with depression from the Danish Psychiatric Central Registry. Adjusted relative risks (aRR) of spontaneous abortion were estimated according to exposure to antidepressants or maternal depression using binomial regression.
Of the 1,005,319 pregnancies (547,300 women) identified, 114,721 (11.4%) ended in a spontaneous abortion. We identified 22,061 pregnancies exposed to antidepressants and 1,843 with a diagnosis of depression with no antidepressant use, of which 2,637 (12.0%) and 205 (11.1%) ended in a spontaneous abortion, respectively. Antidepressant exposure was associated with an aRR of 1.14 (95% confidence interval (CI) 1.10–1.18) for spontaneous abortion compared with no exposure to antidepressants. Among women with a diagnosis of depression, the aRR for spontaneous abortion after any antidepressant exposure was 1.00 (95% CI 0.80–1.24). No individual selective serotonin reuptake inhibitor (SSRI) was associated with spontaneous abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and duloxetine were associated with spontaneous abortions among women with depression but we had no information on potential differences in disease severity and only few pregnancies were exposed in the population.
We identified a slightly increased risk of spontaneous abortion associated with the use of antidepressants during pregnancy. However, among women with a diagnosis of depression, antidepressants in general or individual SSRI in particular were not associated with spontaneous abortions. Further studies are warranted on the newer non-SSRI antidepressants, as we had insufficient data to adjust for important confounding factors.
PMCID: PMC3756033  PMID: 24015208
4.  Maternal Use of Antibiotics and the Risk of Childhood Febrile Seizures: A Danish Population-Based Cohort 
PLoS ONE  2013;8(4):e61148.
In a large population-based cohort in Denmark to examine if maternal use of antibiotics during pregnancy, as a marker of infection, increases the risk of febrile seizures in childhood in a large population-based cohort in Denmark.
All live-born singletons born in Denmark between January 1, 1996 and September 25, 2004 and who were alive on the 90th day of life were identified from the Danish National Birth Registry. Diagnoses of febrile seizures were obtained from the Danish National Hospital Register and maternal use of antibiotics was obtained from the National Register of Medicinal Product Statistics. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazard regression models.
We followed 551,518 singletons for up to 5 years and identified a total of 21,779 children with a diagnosis of febrile seizures. Slightly increased hazard ratios were observed among most exposure groups when compared to the unexposed group, ex. HR 1.08 95% CI: 1.05–1.11 for use of any systemic antibiotic during pregnancy.
We found weak associations between the use of pharmacologically different antibiotics during pregnancy and febrile seizures in early childhood which may indicate that some infections, or causes or effects of infections, during pregnancy could affect the fetal brain and induce susceptibility to febrile seizures.
PMCID: PMC3627381  PMID: 23613800
5.  Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study 
Objective To investigate any association between selective serotonin reuptake inhibitors (SSRIs) taken during pregnancy and congenital major malformations.
Design Population based cohort study.
Participants 493 113 children born in Denmark, 1996-2003.
Main outcome measure Major malformations categorised according to Eurocat (European Surveillance of Congenital Anomalies) with additional diagnostic grouping of heart defects. Nationwide registers on medical redemptions (filled prescriptions), delivery, and hospital diagnosis provided information on mothers and newborns. Follow-up data available to December 2005.
Results Redemptions for SSRIs were not associated with major malformations overall but were associated with septal heart defects (odds ratio 1.99, 95% confidence interval 1.13 to 3.53). For individual SSRIs, the odds ratio for septal heart defects was 3.25 (1.21 to 8.75) for sertraline, 2.52 (1.04 to 6.10) for citalopram, and 1.34 (0.33 to 5.41) for fluoxetine. Redemptions for more than one type of SSRI were associated with septal heart defects (4.70, 1.74 to 12.7)). The absolute increase in the prevalence of malformations was low—for example, the prevalence of septal heart defects was 0.5% (2315/493 113) among unexposed children, 0.9% (12/1370) among children whose mothers were prescribed any SSRI, and 2.1% (4/193) among children whose mothers were prescribed more than one type of SSRI.
Conclusion There is an increased prevalence of septal heart defects among children whose mothers were prescribed an SSRI in early pregnancy, particularly sertraline and citalopram. The largest association was found for children of women who redeemed prescriptions for more than one type of SSRI.
PMCID: PMC2749925  PMID: 19776103
6.  Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study 
Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth.
Design Population based cohort study.
Setting Register based study in Denmark, 1997-2008.
Participants 983 305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1 February 1997 to 31 December 2008 were linked to the Danish Register of Medicinal Product Statistics to obtain information on use of antiepileptic drugs.
Main outcome measures Risk ratio of spontaneous abortion and stillbirth after use of antiepileptic drugs during pregnancy, estimated by using binomial regression adjusting for potential confounders of maternal age, cohabitation, income, education, history of severe mental disorder, and history of drug misuse.
Results Antiepileptic drugs were used in a total of 4700 (0.5%) pregnancies. 16 out of 100 pregnant women using antiepileptics and 13 out of 100 pregnant women not using antiepileptics experienced a spontaneous abortion. After adjusting for potential confounders pregnant women using antiepileptics had a 13% higher risk of spontaneous abortions than pregnant women not using antiepileptics (adjusted risk ratio 1.13, 95% confidence interval 1.04 to 1.24). However, the risk of spontaneous abortion was not increased in women with an epilepsy diagnosis (0.98, 0.87 to 1.09), only in women without a diagnosis of epilepsy (1.30, 1.14 to 1.49). In an analysis including women with at least two pregnancies with discordant antiepileptic drug use (for example, use in the first pregnancy but not in the second), the adjusted hazard ratio for spontaneous abortion was 0.83 (0.69 to 1.00) for exposed pregnancies compared with unexposed pregnancies. Stillbirth was identified in 18 women who used antiepileptic drugs (unadjusted risk ratio 1.29, 0.80 to 2.10).
Conclusion Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies in the same woman, we found no overall association between the use of antiepileptic drugs during pregnancy and spontaneous abortions. Therefore unmeasured confounding may explain the slight increased risk for spontaneous abortion with any antiepileptic drug use (among women both with and without epilepsy). We found no association between antiepileptic drug use during pregnancy and stillbirth, but the statistical precision was low.
PMCID: PMC4141333  PMID: 25150301

Results 1-6 (6)