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Drugs and Birth Defects: a knowledge database providing risk assessments based on national health registers

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To present concept, methods and use of a knowledge database providing assessments of potential fetal risks for all drugs on the Swedish market.

Methods

Assessments of fetal risks are made primarily by analyzing prospective epidemiological data from the Swedish Medical Birth Register on drug intake in relation to birth outcome. This is complemented by evaluation of the scientific literature. Following standardized working procedures, a statement is compiled for each substance, which is also classified into one of three categories depending on the estimated risk level. The final documents include drug product names on the market, via linkage to a medicinal products register. The information is free and published on the website www.janusinfo.se. It can also be used as an integrated part of electronic health records.

Results

The database covers assessments of fetal risks for close to 1,250 medicinal drug substances on the Swedish market. Each year, 96,000 searches are made, which might be compared to the around 100,000 children born in Sweden yearly. Apart from the Swedish Physicians’ Desk Reference (Fass), the database is the most commonly used resource among specialists within gynaecology and perinatal medicine for information on drugs during pregnancy.

Conclusions

A non-commercial knowledge base with assessments of fetal risk of different drugs is valued by health care professionals and is used extensively in Sweden. Based on analyses of national health registers, the database provides unique information on teratogenic drug risks.

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Notes

  1. The data comprise users searching for information on drugs in connection with pregnancy or breast feeding.

Abbreviations

MBR:

Swedish Medical Birth Register

MPR:

Medicinal Products Register

SOP:

Standard Operating Procedure

ATC code:

Anatomic Therapeutic Chemical classification code

SPC:

Summaries of Product Characteristics

PDR:

Physicians’ Desk Reference

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Acknowledgements

This work was in part supported by grants from the Swedish Research Council (VR 2011-3440 and VR 2011-7381) and Karolinska Institutet. The authors would like to express their gratitude to:

• The scientific advisory board: Olle Eriksson, Stellan Håkansson, Ann-Marie K Molin, Birgitta Norstedt Wikner, Katarina Wide, Inga Wihman Fröding and Inger Öhman, for improving the contents and functions of the database.

• Colleagues at Stockholm County Council: Britt Wessel, Elisabeth Törnqvist, Emma Hultén, Tero Shemeikka, Margaretha Julander and Anette Rickebjer, for quality assurance of the database and for sharing ideas and experience from working with similar databases; Pierre Arthuis and Fadi Jazzar for technical maintenance and David Finer for English language editing.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Ulrika Nörby.

Appendix A

Appendix A

For each substance, the lowest detectable risk ratio \( \left( {\widehat{{RR}}} \right) \) for any weeded malformation was calculated through the following equation [26]:

Let c denote the number of cases per control, n the number of cases, p0 the estimated exposure rate among controls, α the desired value for the significance level, and β the desired value for 1-power. Then \( {{{\left( {\widehat{{RR}}} \right) = 1 + \surd {\mathrm { A}}\left\{ {{\mathrm{B}}\surd {\mathrm{A}}\pm {{\left[ {{\mathrm{A}}{{\mathrm{B}}^2} + 4{\mathrm{C}}} \right]}^{{ \frac{1}{2} }}}} \right\}}} \left/ {C} \right.} \)

where

$$ {\text{A}} = {\left( {{{\mathrm{Z}}_{\alpha }} + {{\mathrm{Z}}_{\beta }}} \right)^2} $$
$$ {\text{B}} = 1 + 2{{\mathrm{p}}_0} $$
$$ {\text{C}} = 2{{\mathrm{p}}_0}\left[ {{\mathrm{cn}}\left( {1 - {{\mathrm{p}}_0}} \right) - {\mathrm{A}}{{\mathrm{p}}_0}} \right] $$

As specified in the Methods section, we used α = 0.05 (two-sided) and β = 0.2 for our calculations of lowest detectable risk ratio.

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Nörby, U., Källén, K., Eiermann, B. et al. Drugs and Birth Defects: a knowledge database providing risk assessments based on national health registers. Eur J Clin Pharmacol 69, 889–899 (2013). https://doi.org/10.1007/s00228-012-1399-y

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