Maternal disease and medication use in pregnancy
Medication use during pregnancy is common. Pregnant women may take medications for chronic conditions (such as asthma or epilepsy), as well as for acute conditions (such as an infection).
The safety of many medications for use in pregnancy is often not known at the moment that the medication is licensed because animal studies are seriously limited in their ability to predict human teratogenic effects, and pregnant women are excluded from pre-marketing clinical trials. In addition, teratogenic effects in humans cannot be predicted reliably from the class of a drug or from what is known about its pharmacology and toxicology.
Many medications are contraindicated in pregnancy or contain special warnings because they have not been sufficiently studied during pregnancy to know the possible risks. For women with chronic diseases where medication use is essential to their health and to the health of their fetus, uncertainty about medication safety particularly needs to be addressed.
Some maternal diseases increase the risk of congenital anomalies. It can often be difficult to differentiate the risk of a medication and the risk of the disease the medication is prescribed for.
EUROCAT and EUROmediCAT
EUROmediCAT is a European research consortium dedicated to improving medication safety in pregnancy. The EUROmediCAT consortium was established in 2011 as a daughter project of EUROCAT, with the aim of building a system for systematic identification of teratogenic effects of medication use in pregnancy. The EUROmediCAT Central Database consists of the 19 EUROCAT member registries who can provide data on medication use in pregnancy. In addition, EUROmediCAT performs analyses using their distributed databases including disease cohorts, population linked cohorts and electronic healthcare databases. To see information on the EUROmediCAT network access the EUROmediCAT website.
EUROCAT and ENCePP
The EUROCAT Central Registry with the University of Groningen were involved in the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) of the European Medicines Agency (EMA), an important forum for pharmacovigilance, to develop a code of conduct for scientific independence and transparency, particularly for industry funded pharmacovigilance studies.
EUROCAT and EUROmediCAT seeks to maintain the highest standards of scientific independence and transparency, in accordance with the ENCePP Code of Conduct
.What do EUROCAT and EUROmediCAT data tell us about disease and medication use during pregnancy?
Studies using EUROCAT and EUROmediCAT data have helped contribute to the scientific literature on risks and safety of maternal disease and medication use during pregnancy.
Diabetes in Pregnancy
Children of diabetic mothers have an increased incidence of congenital anomalies. EUROCAT studies have investigated the types of anomalies that are more likely to arise in pregnancies of mothers with pre-existing and gestational diabetes, such as congenital heart defects, laterality anomalies, neural tube defects, omphalocele, and renal anomalies1-3. EUROCAT data showed no increased risk of anomalies with the use of insulin analogues compared to human insulin4, and no increased risk with the use of metformin5.
Underweight and Overweight
Data from EUROCAT registries have added to the evidence that both obesity and underweight (as measured by body mass index (BMI) is associated with increased risk of congenital anomalies. EUROCAT data from Northern England and Italian registries found maternal underweight was associated with atrial septal defect, genital anomalies, urinary anomalies, and orofacial clefts while maternal overweight was associated with heart, eye, neural tube and nervous system anomalies 6,7. Data from the Northern Netherlands suggests the risk associated with maternal overweight is further increased when the mother also smokes during pregnancy8.
Zika
Zika is a virus transmitted by mosquitoes. Most people infected with Zika do not have any symptoms, but in those that do the infection is usually mild. However, Zika virus infection during pregnancy can cause microcephaly and other congenital anomalies, collectively referred to a Zika syndrome. In February 2016, the World Health Organization declared a public health emergency in relation to Zika-related microcephaly. By September 2016 EUROCAT had confirmed that it would be able to detect an outbreak of Zika in Europe resulting in similar increases in microcephaly to the magnitude observed in Brazil. The research also highlighted the need for consistent diagnostic criteria for microcephaly across Europe9.
Anti-epileptics
EUROCAT studies have added to the literature on the types of anomalies that are more likely to arise in pregnancies exposed to specific types of antiepileptics. For example, as well as the known increased risk of spina bifida with the use of Valproic acid, EUROCAT data has also found increased risks of atrial septal defect, cleft palate, hypospadias, and craniosynostosis10. Other than spina bifida, EUROCAT studies have found no additional anomalies associated with carbamazepine exposure11. No increased risk was found with the use of Lamotrigine12.
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are a type of commonly used antidepressant. Examples include citalopram, fluoxetine, paroxetine, and sertraline. Several EUROCAT studies have reported associations between the use of SSRIs in the first trimester of pregnancy and an increased risk of congenital heart defects, including a dose-response relationship13-15.
Other Medications and Diseases
EUROCAT data has also contributed to the literature on several other medications and diseases including asthma medications16,17, methadone18, beta-blockers19, and more20-23. EUROCAT also frequently contributes to the literature on medication safety in pregnancy through the use of its classification system for congenital anomalies and prevalence statistics, by other international research groups.
European Signal Detection
Signal detection is the processes of identifying possible associations between medications and adverse outcomes, such as congenital anomalies. Identified signals are not evidence that the medication causes the congenital anomaly but indicate that any association should be investigated further to confirm or refute. Signal detection work may help identify possible harmful effects of medications earlier.
EUROmediCAT is continuing to work towards routine signal detection and has been investigating the best way to undertake signal detection within its datasets. Several studies using EUROmediCAT data have found signals that now require further investigation24-27.
References