Sodium Valproate Review : Who knew What and When ?

Cumulative meta-analysis gives extra insights

2018 Abstract

Sodium valproate is licensed in the EU for treating generalised, partial or other forms of epilepsy. It has also been used to treat bipolar disorder and to prevent migraine. In February of this year, the European Medicines Agency recommended that sodium valproate should not be used during pregnancy unless no other effective treatment is available, and that it must not be used in women able to have children, unless the conditions of a pregnancy prevention programme are met. These measures to protect women and their children are welcome, but we argue that they should have been instituted several years ago, as the evidence was clear as far back as 1990 that there were risks of congenital malformations in women exposed to valproate.

Our analysis shows the value of cumulative meta-analysis, which, in our view, should be performed as standard in systematic reviews when any concerns about harms arise during the use of medications. …

…, we consider that drug companies, journal editors, prescribers and systematic reviewers have all acted too late. We, therefore, consider that from 1990 individuals should have been offered the opportunity to switch to treatments with lower risks, where they existed, and given minimum effective doses of valproate if alternative treatments were not available or advisable. In the intervening years, many women’s children will have been harmed. Manufacturers and regulators should be responsible for ensuring that cumulative analyses are carried out as part of postmarketing risk management plans.

Oral hormone pregnancy tests and the risks of congenital malformations

A systematic review and meta-analysis, October 2018.
Includes Primodos drug victims testimonials.

Overview

  • Sources :
    • read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
    • read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • Testimonials : read some real stories told by the Primodos victims, see the post comment section.
  • Commenting : scroll down this page until you reach the header “Have your say! Share your views” and the box “Enter your comment here…“.

Abstract

Background
Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations.

Methods

I am fully supportive of this article on the effects of hormone pregnancy tests as it stands. I have no substantive criticism of the content or methods.

Dr David Healy, professor of psychiatry, psychopharmacologist, scientist and author.

We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies.

Results
We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs.

Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I2 = 0%).

Exposure to HPTs was associated with an increased risk of

  • congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I2=0%);
  • nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I2 = 78%);
  • gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I2 = 54%);
  • musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I2 = 0%);
  • the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I2 = 0%).

Conclusions
This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.

Reactions

Prof. Henegan’s systematic analyses of epidemiological studies, is a scientific review which members of the Association for children damaged by HPT’s have waited over 45 years for. The findings are incredible and mirror the congenital abnormalities suffered by our members. It is a scandal that this epidemiological study was not commissioned by the Government Health Authorities and we cannot thank Prof. Heneghan and his colleagues enough, for the comprehensive and utterly compelling review.

Marie Lyon,
Assocation for Children Damaged by Hormone Pregnancy Tests, UK

Important Note

Are you a Primodos-victim ?
Send a request to join the group Primodos (The Forgotten Thalidomide) ACDHPT on Facebook.

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