Teratogen Information Systems

The use of drugs in pregnancy is a debated and extremely interesting topic for a series of reasons. Since the Sixties, when the thalidomide tragedy occurred, healthcare professionals have been more and more careful in prescribing drugs during pregnancy. On the other hand, however, the increased availability of over-the-counter products, self-prescription, the availability of new molecules on the market and the increase of pregnant women with chronic diseases has determined a wide exposure to drugs during pregnancy.¹
A survey carried out between 2008 and 2012 by the Italian Health Institute in the Lazio Region over 3 hospitals showed that 80.6% of the pregnant women received at least a prescription for one drug, excluding vitamins and minerals: among these, 4.3% took a potentially teratogen drug.² Studies carried out at international level confirm this situation.^3,4
The use of drugs in pregnancy has often generated doubts and uncertainties in the prescriber, with consequent disorientation in the users. From a clinical point of view, questions without certain answers could lead the women to impulsive decisions, such as discontinuing a therapy necessary for their health, terminating the pregnancy for the fear of having damaged the embryo, or unaware or incautious exposure to teratogen substances.

The benefits of counselling services

As a consequence of the limited available knowledge and in order to provide updated and punctual answers to the request of information, several countries have set up Teratology Information Services (TIS), where multidisciplinary teams have access to relevant data source. These centres, mostly operating by the model "telephone enquire/response", are open to both health professionals and women.
TIS offer counselling about exposure, or risk of exposure, to chemical substances, infective agents or radiations to health professionals and women before and in pregnancy and in breastfeeding.
The clinical relevance of these Services is clearly stated by their volume of activity: for example, the Poison Information Centre in Bergamo - one of the most active from this point of view - in 2016 received 34,558 calls for the use of drugs in pregnancy and /or breastfeeding.⁵ The biggest part of the enquires regarded drugs and in particular antidepressants, anxiolytics and antipsychotics. Only a small amount regarded exposure to known teratogen. In the clinical practice, the counselling might interest exposure to infective agents, recreational drugs, environmental toxic substances or radiations.

Before and after counselling

From a methodological point of view, the counselling could be prospective or retrospective:⁶ in the first case the exposure has not been verified yet, in the second case, on the contrary, the counselling regards exposures that have already taken place.
In the prospective counselling, it is fundamental to evaluate firstly the indication of the therapy, considering if the drug is necessary for the maternal pathology and if it is of proved effectiveness. For example, a woman with epilepsy needs a treatment to preserve her health and the foetus' one. In this case, it would be a needed and effective therapy that will have to be, nevertheless, managed by a multidisciplinary team in charge of evaluating the type of molecule with the least teratogen risk, the doses and the intake modalities. On the contrary, products like, for example, symptomatic drugs for cough, are not essential and therefore from a general point of view should not be recommended in pregnancy.
The retrospective counselling, on the other hand, concerns an exposure that has already taken place. In this case, all the available studies will be evaluated in order to assess the possible risks related to the drug, defining the risk type and level and the possible diagnostic test or, on the contrary, to reassure the women.
If the counselling request comes from a woman in preconception phase (preconception prospective consultation) it will be possible to accurately evaluate the potential exposure risks, the effectiveness of the treatment and the potential change in therapy with another drug clinically effective and safe for the foetus. The prospective counselling allows, therefore, the putting in place of strategies of primary prevention able to significantly modify the maternal and foetal outcomes and it is then always beneficial, especially in women with chronic diseases.
The prospective counselling in pregnancy or breastfeeding allows to suggest strategies to reduce the absorption of the active substance by the foetus or newborn: for example, administering the daily dose of some drugs in a more fractioned way can reduce the plasmatic levels of the active substance; in breastfeeding, administering the therapy after feeding the newborn can diminish the neonatal exposure. In regard to breastfeeding and evaluating of the risks related to medical treatments, the Italian Ministry of Health has recently published a "Position statement on the use of medicines in breastfeeding" in order to offer guidance for the correct management of the information about drug safety during breastfeeding.⁷
In regard to the TIS activity, collecting exposure data, both prospective and retrospective, is also essential for the post marketing research on drugs in pregnancy and breastfeeding, for whom the available data before marketing is limited, for obvious ethical reasons.
The European Network of TIS, the ENTIS,⁸ was founded in 1990 in Milan, with the aim of coordinating the activities of the several European TIS and promoting the prevention of congenital defects. OTIS (Organization of Teratology Information Specialists) is the analogous US association that provides teratology counselling through the service accessible from the website www.motherisk.org.
Coordinating more TIS, by ENTIS and OTIS, allows a wider collection of case reports of women taking a certain drug, allowing to carry out collaborative studies;⁹ in fact it is essential to produce new knowledge¹⁰ and to publish online information and databases in order to share all the available information.
In the clinical practice, the physician who has in care women in fertile age will see women at low risks, i.e. women in good health, and women at high risk, i.e. with chronic diseases and undergoing treatments or with a complicated obstetric history: in the first case, the majority of the population, adequate counselling is necessary for promoting correct and healthy life styles, supporting with the common problems linked to pregnancy and recommending a judicious use of drugs, avoiding exposure to over-the-counter products or drug when unnecessary.^11,12
In the high-risk group, on the other hand, it is very often required the use of multidisciplinary diagnostic and therapeutic measures, in order to safeguard the maternal and foetal health. In this case, the health professional involved in the clinic management of the complex pathologies can receive important support from TIS, that provide highly specialised information on clinic counselling and allow to prevent and/or reduce the reproductive damage.