Primodos and Birth Defects : What was the Risk?

Sky News investigation exposes Primodos pregnancy drug cover-up

Around 1.5 million women in Britain in the 1960s and 1970s took Primodos in the early stages of pregnancy. Some say their pregnancies resulted in miscarriage or birth defects.

Sky News’ hour-long documentary Primodos: The Secret Drug Scandal is presented by senior political correspondent Jason Farrell, who has been investigating it for six years.

Sky News revealed how documents were destroyed and information withheld about a drug that may have deformed and killed babies in the womb.

More Information

Primodos : The Secret Drug Scandal

Sky News investigation exposes Primodos pregnancy drug cover-up

Sky News’ hour-long documentary Primodos: The Secret Drug Scandal is presented by senior political correspondent Jason Farrell, who has been investigating it for six years.

Sky News reveals how documents were destroyed and information withheld about a drug that may have deformed and killed babies in the womb.

More Information

Primodos Duogynon used for Abortions

Sky News investigation exposes Primodos pregnancy drug cover-up

Sky News’ hour-long documentary Primodos: The Secret Drug Scandal is presented by senior political correspondent Jason Farrell, who has been investigating it for six years.

Sky News reveals how documents were destroyed and information withheld about a drug that may have deformed and killed babies in the womb.

More Information

  • Sky News March 2017 press releases:
    • Calls for public inquiry over Primodos pregnancy drug after Sky News documentary, Sky News, March 2017.
    • Primodos: Sky News exposes pregnancy drug cover-up on Sky News, March 2017.
    • ‘Taking Primodos caused me lifetime of regret‘: The story of mother Marie Lyon, Sky News, March 2017.
    • UK pregnancy test drug Primodos used for abortions in Germany, Sky News, March 2017.
  • Sign the petition : Expose cover up of Hormone Pregnancy Tests on 38degrees.
  • Our blog posts about the primodos pregnancy test drug.
  • Watch more videos about prescription drugs side-effects on YouTube.

Primodos Pregnancy Drug Cover-Up

Sky News investigation exposes Primodos pregnancy drug cover-up

Sky News’ hour-long documentary Primodos: The Secret Drug Scandal is presented by senior political correspondent Jason Farrell, who has been investigating it for six years.

Sky News reveals how documents were destroyed and information withheld about a drug that may have deformed and killed babies in the womb.

More Information

  • Sky News March 2017 press releases:
    • Calls for public inquiry over Primodos pregnancy drug after Sky News documentary, Sky News, March 2017.
    • Primodos: Sky News exposes pregnancy drug cover-up on Sky News, March 2017.
    • ‘Taking Primodos caused me lifetime of regret‘: The story of mother Marie Lyon, Sky News, March 2017.
    • UK pregnancy test drug Primodos used for abortions in Germany, Sky News, March 2017.
  • Sign the petition : Expose cover up of Hormone Pregnancy Tests on 38degrees.
  • Our blog posts about the primodos pregnancy test drug.
  • Watch more videos about prescription drugs side-effects on YouTube.

Primodos Pregnancy Test Linked to Child’s Death

Sky News investigation exposes Primodos pregnancy drug cover-up

Sky News’ hour-long documentary Primodos: The Secret Drug Scandal is presented by senior political correspondent Jason Farrell, who has been investigating it for six years.

Sky News reveals how documents were destroyed and information withheld about a drug that may have deformed and killed babies in the womb.

More Information

  • Sky News March 2017 press releases:
    • Calls for public inquiry over Primodos pregnancy drug after Sky News documentary, Sky News, March 2017.
    • Primodos: Sky News exposes pregnancy drug cover-up on Sky News, March 2017.
    • ‘Taking Primodos caused me lifetime of regret‘: The story of mother Marie Lyon, Sky News, March 2017.
    • UK pregnancy test drug Primodos used for abortions in Germany, Sky News, March 2017.
  • Sign the petition : Expose cover up of Hormone Pregnancy Tests on 38degrees.
  • Our blog posts about the primodos pregnancy test drug.
  • Watch more videos about prescription drugs side-effects on YouTube.

Primodos and Gestest Drugs Use Linked to Horrific Birth Defects

Sky News investigation exposes Primodos pregnancy drug cover-up

Sky News’ hour-long documentary Primodos: The Secret Drug Scandal is presented by senior political correspondent Jason Farrell, who has been investigating it for six years.

Sky News reveals how documents were destroyed and information withheld about a drug that may have deformed and killed babies in the womb.

More Information

  • Sky News March 2017 press releases:
    • Calls for public inquiry over Primodos pregnancy drug after Sky News documentary, Sky News, March 2017.
    • Primodos: Sky News exposes pregnancy drug cover-up on Sky News, March 2017.
    • ‘Taking Primodos caused me lifetime of regret‘: The story of mother Marie Lyon, Sky News, March 2017.
    • UK pregnancy test drug Primodos used for abortions in Germany, Sky News, March 2017.
  • Sign the petition : Expose cover up of Hormone Pregnancy Tests on 38degrees.
  • Our blog posts about the primodos pregnancy test drug.
  • Watch more videos about prescription drugs side-effects on YouTube.

The Diethylstilbestrol Legacy

A Powerful Case Against Intervention in Uncomplicated Pregnancy

2016 Report Abstract

Although the basic tenet of medicine is “First, do no harm,” history is filled with good intentions that were at best unhelpful and at worst harmful. Because medicine seeks to cure afflictions, there is an overwhelming desire on the part of health providers and patients to administer treatment. In certain settings, treatment can be reasonable despite a risk of adverse consequences: for example, if the disease is cured or its morbidity abated and the treatment consequences are less disabling than the disease itself.

In the absence of overt disease, the question of whether to apply an intervention is far more challenging. The safety of interventions must be weighed against the population’s level of risk, the morbidity and/or mortality associated with the disease, and the intervention’s efficacy (eg, BRCA1 mutation, mastectomy, reduced breast cancer risk). Interventions must meet an especially high standard of safety and efficacy when administered in low-risk populations or in settings in which the morbidity associated with the disease is minor. In the worst-case scenario, an intervention may be both ineffective for its primary purpose and cause iatrogenic illness.

The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy,
Pediatrics, November 2016, VOLUME 138 / ISSUE Supplement 1, Supplement_1/S42.abstract, November 2016.

Interventions in pregnancy are especially problematic because of the complex physiology of the condition and the possibility of causing short- and long-term adverse consequences in both the mother and her offspring. The continuing story of diethylstilbestrol (DES), a synthetic estrogen, shows the importance of caution when evaluating the merits of interventions involving pregnant women. With regard to DES, investigators believed that pregnancy loss was caused in part by a decrease in estrogen and that administering DES to pregnant women would help maintain a healthy pregnancy. Moreover, because endogenous estrogen concentrations increase dramatically during a healthy pregnancy, supplementation with DES was deemed harmless. During its early years of use, DES was administered to women with threatened pregnancy loss or a history of pregnancy loss. Eventually, DES was advertised to the medical community for “routine prophylaxis in ALL pregnancies” and administered to women with otherwise healthy pregnancies.

By the time DES was formally evaluated, it was standard of care in high-risk obstetrics practices. The first clinical trial to determine the efficacy of DES, reported in 1953, showed that DES did not improve pregnancy outcome. (Indeed, a subsequent reanalysis of the data revealed that DES increased the risk of spontaneous abortion, preterm birth, and neonatal death) Despite lack of evidence supporting a benefit, DES continued to be prescribed during pregnancy until 1971, when a small study showed a stunning 40-fold increase in the risk of clear cell adenocarcinoma (CCA) of the vagina and cervix in girls and young women who were prenatally exposed to DES. Several months later, the Food and Drug Administration issued a bulletin indicating that the use of DES was contraindicated in pregnancy. By then, however, millions of women, along with their sons and daughters, had been needlessly exposed.

In addition to the increased risk of CCA of the vagina and cervix, daughters exposed in utero to DES also suffered from an increased occurrence of reproductive tract abnormalities, infertility, and pregnancy complications; earlier menopause; twice the incidence of cervical dysplasia; and a possible elevated risk of breast cancer and continued increased risk of CCA in middle age. Recent preliminary data indicate the possibility of an increased risk of cardiovascular disease and diabetes in the prenatally exposed women. Mothers administered DES during pregnancy have an increased risk of breast cancer incidence and mortality. Sons who were exposed in utero have an increased risk of genitourinary defects and a possible increase in testicular cancer. The possibility of epigenetic transmission with consequent adverse outcomes in the offspring of prenatally exposed women is under investigation. Preliminary findings showed increased menstrual irregularity and a possible excess of ovarian cancer in very young women.

The link between prenatal DES exposure and subsequent adverse health outcomes, most of which are fairly common, may easily have escaped detection. The investigation of DES outcomes was initiated solely because a rare tumor occurred in a cluster of cases at an unusually young age, decades before the usual age of presentation. This historical example underscores the necessity of carefully weighing the risks and benefits of interventions in pregnancy and long-term monitoring of the health outcomes in mothers and offspring.

Whether and/or when to use pharmaceutical intervention in pregnancy continues to pose special challenges. At the present time, progesterone used to prevent pregnancy loss appears to be effective, although more data are needed. Thus far, there is little evidence of short-term adverse consequences for the offspring, but continued monitoring of mothers and offspring is warranted to identify any short- or long-term adverse effects. The use of progestins for luteal phase and early pregnancy support after in vitro fertilization is routine, and there are even fewer data on potential short- and long-term risks of this therapy. The tragic legacy of DES supports a cautious approach to the use of pregnancy interventions and assiduous appraisal of their effects.

Rebecca Troisi, Elizabeth E. Hatch, Linda Titus,
Reviewed by Dr Robert Hoover,

Click to download the full paper.

More DES DiEthylStilbestrol Resources

Evidence that bisphenol S crosses the human placenta

Common BPA alternative, BPS, crosses into placenta

Bisphenol S (BPS), found in baby bottles, personal care products and thermal receipts, is a replacement chemical for BPA and was introduced when concern was raised about possible health effects of that plastic compound.

As with BPA, there is evidence that BPS is an endocrine disruptor. Canadian and Chinese scientists have found the “first evidence” that BPS can cross the human placenta.

2017 Study Abstract

Human studies show associations between maternal bisphenol A (BPA) exposure and developmental effects in children, yet biomonitoring of BPA metabolites in maternal and fetal serum remains limited, and less is known for BPA alternatives. BPA-glucuronide, BPA-sulfate, and bisphenol S (BPS) were quantified in 61 pairs of maternal and cord sera from Chinese participants.

Bisphenol A Metabolites and Bisphenol S in Paired Maternal and Cord Serum, Environmental Science & Technology, DOI: 10.1021/acs.est.6b05718, January 22, 2017.

Total BPS was only detectable in four maternal (<0.03–0.07 ng/mL) and seven cord sera (<0.03–0.12 ng/mL), indicating low exposure but providing the first evidence that BPS crosses the human placenta. Total BPA metabolites in cord serum were significantly higher than in maternal serum (p < 0.05), suggesting that these may be formed in the fetus or cleared more slowly from the fetoplacental compartment. Unlike the pharmacokinetic results from controlled oral exposure studies in which BPA-glucuronide is the major BPA metabolite, here, BPA-sulfate was the dominant metabolite (GM: 0.06 and 0.08 ng/mL), significantly higher than BPA-glucuronide (GM: 0.02 and 0.04 ng/mL) (p < 0.01) in both maternal and cord sera. Moreover, the proportion of BPA-sulfate increased with total BPA.

These are the first human data for BPA metabolites in paired maternal and cord serum, and results suggest that the human fetus and pregnant mother have unique exposure to BPA metabolites. Direct analysis of BPA metabolites in serum provides complementary information for evaluating early life-stage exposure and risks of BPA.

Mother’s diet in pregnancy may have lasting effects for offspring

Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults

A poor diet during pregnancy can cause biological changes that last throughout life, according to research from Imperial College London.

The study Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults, published this week in the journal Cell Reports, showed that when pregnant mice were fed a diet deficient in protein this interfered with the expression of genes within the embryo that are known to be important for healthy growth.

The impact of adversity, such as a poor diet in early life, and whether this might cause lasting effects has long intrigued scientists. There have been suggestions that the children of women pregnant during famines, for example, may suffer harmful effects later in life. This new study offers a new way to visualise such effects and possible ways to counter these.

The researchers, at the Medical Research Council London Institute of Medical Sciences (MRC LMS), developed novel imaging techniques that enabled them to visualise genes as they were switched “on” or “off” in mouse embryos as they grew. This enabled the team to see exactly where alterations in response to maternal diet were happening and, crucially when during pregnancy key changes took place.

Understanding how genes are controlled and kept “on” or “off” is a relatively new field of science known as “epigenetics”. This is the first time such epigenetic effects have been visualised during development in this way, using a simple but powerful bioluminescent imaging approach.

The team attached enzymes from fireflies (luciferase) or bacteria (beta-galactosidase) onto the gene they were studying, and watched how this produced a glow as the gene was turned “on” in mice.

The research focused on a group of genes called “imprinted” genes, and on one in particular known as Cdkn1c. Imprinted genes are intriguing because although a copy of the gene is inherited from each parent, as usual, only one of these copies is active. The other copy is kept idle, or “silenced”. In the case of Cdkn1c, only the copy inherited from the mother is active.

Using their new visualising technique, the team showed that if a mouse carried the copy of the gene from the father, which is “silenced”, then it could not be seen. If they used either diet or drugs to re-activate it, they were able to see the gene glow. The researchers expect that this new way to “see” when imprinted genes are active or silent will prove valuable for many other scientists who are investigating epigenetic effects in our bodies.

Imprinted genes

Dr Mathew Van de Pette, a lead author based at the MRC LMS, said:

“There are around 100 imprinted genes, about 0.4% of the total in the genome, and most appear to have their greatest impact during pregnancy.
The pattern by which imprinted genes are ‘set’ in early life plays an important part in the development of healthy offspring. If a gene is ‘miss-set’ then problems may occur later.
We found that mice fed a low protein diet in pregnancy produced offspring in which the father’s copy of the gene became active and stayed that way. This demonstrates a clear link between early life adversity and later life outcomes.”

Professor Amanda Fisher, who led the study and is director of the MRC LMS, said:

“We were surprised that this change in diet permanently affected the expression of this imprinted gene.
Our work suggests there may be a window of vulnerability when diet can indeed have an effect, and that once these genes are set, they’re set for life.
The good news is that we’ve also shown that it’s possible to avoid this with a normal diet.”

Kate Wighton, Imperial College London newssummary, 03 February 2017.

High body mass index during pregnancy not associated with a long term risk of obesity in offspring

High Pregnancy BMI Not Linked to Offspring BMI

This new study looked at whether increased body mass index (BMI) in mothers while pregnant was causally associated with excess weight in offspring during childhood and adolescence. It also examined whether this effect was over and above the expected contribution of genes to being overweight.

2017 Study Abstract

Background

It has been suggested that greater maternal adiposity during pregnancy affects lifelong risk of offspring fatness via intrauterine mechanisms. Our aim was to use Mendelian randomisation (MR) to investigate the causal effect of intrauterine exposure to greater maternal body mass index (BMI) on offspring BMI and fat mass from childhood to early adulthood.

Methods and Findings

Using Genetic Variation to Explore the Causal Effect of Maternal Pregnancy Adiposity on Future Offspring Adiposity: A Mendelian Randomisation Study, PLOS one, dx.doi.org/10.1371/journal.pmed.1002221, January 24, 2017.

Image credit remon rijper.

We used maternal genetic variants as instrumental variables (IVs) to test the causal effect of maternal BMI in pregnancy on offspring fatness (BMI and dual-energy X-ray absorptiometry [DXA] determined fat mass index [FMI]) in a MR approach. This was investigated, with repeat measurements, from ages 7 to 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 2,521 to 3,720 for different ages). We then sought to replicate findings with results for BMI at age 6 in Generation R (n = 2,337 for replication sample; n = 6,057 for total pooled sample).

In confounder-adjusted multivariable regression in ALSPAC, a 1 standard deviation (SD, equivalent of 3.7 kg/m2) increase in maternal BMI was associated with a 0.25 SD (95% CI 0.21–0.29) increase in offspring BMI at age 7, with similar results at later ages and when FMI was used as the outcome.

A weighted genetic risk score was generated from 32 genetic variants robustly associated with BMI (minimum F-statistic = 45 in ALSPAC). The MR results using this genetic risk score as an IV in ALSPAC were close to the null at all ages (e.g., 0.04 SD (95% CI -0.21–0.30) at age 7 and 0.03 SD (95% CI -0.26–0.32) at age 18 per SD increase in maternal BMI), which was similar when a 97 variant generic risk score was used in ALSPAC.

When findings from age 7 in ALSPAC were meta-analysed with those from age 6 in Generation R, the pooled confounder-adjusted multivariable regression association was 0.22 SD (95% CI 0.19–0.25) per SD increase in maternal BMI and the pooled MR effect (pooling the 97 variant score results from ALSPAC with the 32 variant score results from Generation R) was 0.05 SD (95%CI -0.11–0.21) per SD increase in maternal BMI (p-value for difference between the two results = 0.05). A number of sensitivity analyses exploring violation of the MR results supported our main findings. However, power was limited for some of the sensitivity tests and further studies with relevant data on maternal, offspring, and paternal genotype are required to obtain more precise (and unbiased) causal estimates.

Conclusions

Our findings provide little evidence to support a strong causal intrauterine effect of incrementally greater maternal BMI resulting in greater offspring adiposity.