Preterm Birth, Fetal Growth, Age at Menarche among Women exposed prenatally to DiEthylStilbestrol

DES exposed daughters more likely to have begun menstruating at younger age

DES Follow-up Study Summary

National Cancer Inst logo image
DES exposed daughters appeared to weigh slightly less and have a higher risk of being born prematurely than unexposed daughters. They also were somewhat more likely to have begun menstruating at age 10 or younger.

Research has suggested that early life characteristics, such as size at birth and age at menarche, may be associated with health conditions later in life. For example, some studies have suggested that low birth weight babies tend to have a higher risk of cardiovascular disease later in life. Other studies have shown that women who begin having periods at a young age have a slightly higher risk of breast cancer than those who begin menstruation later.

Although there has been a great deal of research on health of the 2nd generation (DES daughters) later in life, little attention has been paid to whether they were similar in terms of birth weight and other early life factors. Results from one of the early clinical trials of DES suggested that it might be related to lower birth weight and a higher risk of preterm birth. We conducted a systematic evaluation of DES daughters participating in the NCI DES Follow-up Study to determine whether there were any differences in birth weight, length of gestation, and the average age of first menstruation in the DES-exposed compared to unexposed daughters.

We found that there was a 2 to 3 fold increase in risk of having been born prematurely (before 37 weeks gestational age) among the DES-exposed compared to unexposed daughters. On average, DES daughters tended to weigh slightly less at birth, and there was also a 60% higher risk of being born too small, or small for gestational age (SGA), defined as less than the 10th percentile of birth weight at each gestational age. We found stronger effects for birth weight, SGA, and preterm birth among women who were participants in the original DESAD study, as compared to those who were in the Dieckmann clinical trial, suggesting that part of the effect may have been due to the higher risk pregnancies among the exposed women and not solely to DES exposure.

When we evaluated the risk of having started menstruation before age 11, we found no difference between the DES exposed and unexposed daughters. However, DES daughters did have a small increased risk (40%) of starting menarche very young-at age 10 or less-but this was based on very small numbers of participants who had very early menstruation.

In summary, DES exposed daughters appeared to weigh slightly less and have a higher risk of being born prematurely than unexposed daughters. They also were somewhat more likely to have begun menstruating at age 10 or younger. These effects may have a small impact on the risk of some diseases occurring later in life.

2011 Study Abstract:

Diethylstilbestrol (DES), a synthetic estrogen used in pregnancy during the 1950s and 1960s, provides a model for potential health effects of endocrine disrupting compounds in the environment. We evaluated prenatal exposure to DES, based on medical record review, in relation to gestational length, fetal growth, and age at menarche in 4429 exposed and 1427 unexposed daughters. DES exposure was associated with an increase in preterm birth (odds ratio (OR)=2.97; 95% CI=2.27, 3.87), and a higher risk of small for gestational age (SGA) (OR=1.61; 95% CI=1.31, 1.98). The association between DES exposure and early menarche was borderline, with stronger effects when early menarche was defined as ≤ 10 years (OR=1.41 95% CI=0.97, 2.03) than defined as ≤ 11 years (OR=1.16; 95% CI=0.97, 1.39). This study provides evidence that prenatal DES exposure was associated with fetal growth and gestational length, which may mediate associations between DES and health outcomes in later life.

Sources:

  • Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES),NCBI, PMID: 21130156, 2011 Feb;31(2):151-7. doi: 10.1016/j.reprotox.2010.11.006. Epub 2010 Dec 2. Full text link.
  • NCI, DES Follow-up Study Published Papers.
More DES DiEthylStilbestrol Resources

For clinical Trials to succeed, they need more diverse Cohorts of Volunteers

Could Increasing Diversity in Clinical Trials Save Lives?

Increasing Diversity in Clinical Trials Can Save Lives
We need clinical-trial data that more accurately reflects real-world diversity

It is important to increase the diversity of clinical-trial participants because there is growing evidence that gender and ethnicity play important roles in health care outcomes. Not only are certain groups at higher risk for specific diseases, but race and ethnicity play a role in how patients respond to drugs.

Read Increasing Diversity in Clinical Trials Can Save Lives (Op-Ed)
by Dr. Bruce Moskowitz, LiveScience, 01 July 2013.

Our posts tagged All TrialsPharmaceutical industry.

Warnings of Three-Person IVF Risks

The Move Crosses a Crucial Ethical Line

Warning of three-person IVF 'risks'
The move crosses a “crucial ethical line”

Concerns about the safety of a pioneering therapy to create babies with DNA from three people are raised by researchers in the UK and Australia.

The idea has also raised ethical concerns from groups concerned about the impact of altering human genetic inheritance.

Read Warning of three-person IVF ‘risks’
by James Gallagher, BBC News, 19 Sept 2013.

Related post: The UK Government considering #IVF Babies Creation with Three Genetic Parents.

Understanding why some Women have repeated Miscarriages

“Crucial” new recurrent miscarriage insight

'Crucial' new recurrent miscarriage insight
Losing several pregnancies in a row causes incredible psychological distress and anguish

Fertility scientists say they have made a “crucial breakthrough” – that “steroids shouldn’t be given to all” – in understanding why some women have repeated miscarriages.

Read Crucial’ new recurrent miscarriage insight
by James Gallagher, BBC News Health and Science, 12 Sept 2013.

DES daughters have a higher risk of recurrent miscarriages.
If you know or think you may have been exposed to DES it’s important to inform your doctor and gynaecologist.

More about DES pregnancy risks – read DES studies on fertility and pregnancy.

Incidence of Squamous Neoplasia of the Cervix and Vagina in Women exposed prenatally to DES

The 2001 stuy findings support an association between in-utero DES exposure and high-grade squamous neoplasia.

DES Follow-up Study Summary

National Cancer Inst logo image
The 2001 stuy findings support an association between in-utero DES exposure and high-grade squamous neoplasia.

Women exposed to Diethylstilbestrol (DES) before birth (in the womb), known as DES Daughters, are at increased risk for clear cell adenocarcinoma of the vagina and cervix, but the effect of in utero DES exposure on later development of squamous neoplasia in the cervix and vagina is uncertain. This combined follow-up study of 3,899 DES Daughters (median age 38) and 1,374 unexposed daughters (median age 39) was followed 1982-1995. Subjects were drawn from three previously studied cohorts (DESAD, Dieckmann, and Horne). The purpose was to examine the long-term risk of developing high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract in DES Daughters compared with unexposed daughters.

The study found a small but significant increase in HSIL among DES Daughters in all age groups, including those over age 40. A total of 111 pathology-confirmed HSIL cases occurred, including five of the vagina, one of the vulva and two cases of invasive cervical cancer. The overall relative risk was 2.1 among DES-exposed versus unexposed. The relative risk among those whose mothers were prescribed DES within 7 weeks of the last menstrual period was 2.8 compared with 1.35 among women exposed for the first time at 15 weeks or later. Women with documented high-grade neoplasia before 1982 were excluded because prior treatment of the cervix may lower the subsequent finding of intraepithelial neoplasia. Researchers could not rule out that more frequent and intensive screening among DES-exposed women played a role in these findings.

Neoplasia is abnormal and uncontrolled cell growth; a neoplasm is new growth of benign or malignant tissue. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. These flat cells look like fish scales under a microscope. Squamous intraepithelial lesion (SIL) is a general term for the abnormal growth of squamous cells on the surface of the cervix. The changes in the cells are described as low grade or high grade, depending on how much of the cervix is affected and how abnormal the cells appear. Cervical intraepithelial neoplasia (CIN) is a general term for the growth of abnormal cells on the surface of the cervix. Numbers from 1 to 3 may be used to describe how much of the cervix contains abnormal cells. High-grade squamous intraepithelial lesion (HSIL) is a precancerous condition in which the cells of the uterine cervix are moderately or severely abnormal. In this study, grades 2 and 3 were considered high.

2001 Study Abstract

OBJECTIVES:
Women exposed prenatally to Diethylstilbestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES.

METHODS:
A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates.

RESULTS:
The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis.

CONCLUSIONS:
The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

Sources

  • Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States),NCBI, PMID: 11714112, 2001 Nov;12(9):837-45.
  • NCI, DES Follow-up Study Published Papers.
More DES DiEthylStilbestrol Resources

Valproate Anti-Seizure Products contraindicated in Pregnant Women

Reducing Epilepsy Drug Doses Key to Cutting Birth Defects

The FDA is advising health care professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women.

” The U.S. Food and Drug Administration (FDA) is advising health care professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches. Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant.1 Stronger warnings about use during pregnancy will be added to the drug labels, and valproate’s pregnancy category for migraine use will be changed from “D” (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to “X” (the risk of use in pregnant women clearly outweighs any possible benefit of the drug).
With regard to valproate use in pregnant women with epilepsy or bipolar disorder, valproate products should only be prescribed if other medications are not effective in treating the condition or are otherwise unacceptable. Valproate products will remain in pregnancy category D for treating epilepsy and manic episodes associated with bipolar disorder.
With regard to women of childbearing age who are not pregnant, valproate should not be taken for any condition unless the drug is essential to the management of the woman’s medical condition. All non-pregnant women of childbearing age taking valproate products should use effective birth control.
Valproate products include: valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics.
This alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study showing that children exposed to valproate products while their mothers were pregnant had decreased IQs at age 6 compared to children exposed to other anti-epileptic drugs (see Data Summary).1 The difference in average IQ between the children who had been exposed to valproate and the children who had been exposed to other antiepileptic drugs varied between 8 and 11 points depending on the drug to which valproate was compared.
FDA previously communicated initial findings about this risk in a June 2011 Drug Safety Communication. At that time, FDA also worked with valproate manufacturers to revise the drug labels after interim results from the NEAD study showed lower cognitive test scores at age 3 in children exposed to valproate compared to children exposed to other antiepileptic drugs.
Women who are pregnant and taking a valproate medication should not stop their medication but should talk to their health care professionals immediately. Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby.
It is not known whether there is a specific time period during pregnancy when valproate exposure can result in negative cognitive effects. Similarly, there is no known time during pregnancy in which exposure may be considered to have less risk for decreased IQ in children. Because the women in the NEAD study were exposed to antiepileptic drugs throughout pregnancy, whether the risk for decreased IQ was related to a particular time period during pregnancy could not be assessed.
FDA is working with manufacturers to change the drug labels for valproate products with this updated risk information. FDA continues to evaluate information about the potential risks of valproate use during pregnancy and will update the public as more information becomes available.
Pregnancy Category X means that studies in animals or humans have shown positive evidence of fetal risk, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefits. Category D means there is positive evidence of risk to a baby based on data from studies or other experience in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. ”

Sources: FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children
Last Updated 13/05/2013 – PDF

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Perturbateurs Endocriniens et Phtalates, effets sur la santé et focus fertilité

Vidéo extraite du colloque organisé à l’Assemblée nationale le 10 avril 2012 : Phtalates – Hold up sur la fertilité !

  • Video by RESenvsante, avec Shanna Swan
  • Les perturbateurs endocriniens : qu’est ce que c’est ?
  • Les phtalates : où les trouve-t-on ?
  • Les perturbateurs endocriniens : quel impact sur notre santé ?
  • Quelle législation souhaitable ?

Omniprésents dans notre quotidien les phtalates soulèvent depuis longtemps de nombreuses préoccupations et sont devenus emblématiques du débat autour de Reach, la nouvelle réglementation chimique communautaire. C’est aujourd’hui pour leur caractère de perturbateurs endocriniens, et au vu des données nouvelles, que l’action réglementaire est plus que jamais nécessaire sur l’ensemble de cette famille de substances.

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How healthy are IVF Babies?

Slightly higher Rate of Mental Retardation, study says

How Healthy Are IVF Babies?
One way that egg cells may be fertilized with sperm cells in an IVF lab

Does IVF make children more vulnerable to certain cognitive or other developmental issues? In the largest study to date looking at the connection between IVF procedures and neurological disorders, scientists found a small but significant risk of intellectual disabilities among twins and triplets, though not among singleton births.

Prenatal DiEthylStilbestrol Exposure and Risk of Breast Cancer

Women with prenatal exposure to DES have an increased risk of breast cancer after age 40 years

DES Follow-up Study Summary

National Cancer Inst logo image
This 2006 study results, from the first prospective study on the subject, suggest that women with prenatal exposure to DES have an increased risk of breast cancer after age 40 years.

One of the main purposes of our study is to examine whether prenatal Diethylstilbestrol (DES) exposure influences risk of breast cancer or other cancers in addition to cancers of the vagina and cervix. Results from our most recent analysis of prenatal DES exposure and breast cancer were published in the scientific journal Cancer Epidemiology Biomarkers and Prevention.

Questionnaire data collected in 2001, 1997, and 1994 were used to examine this issue among daughters participating in the study. 4,817 study participants whose mothers took DES while pregnant with them were compared with 2,073 participants who were unexposed. Medical records were obtained to confirm cancer diagnoses. A total of 102 participants were diagnosed with invasive breast cancer. Comparisons of exposed and unexposed women took into account differences in age and other factors such as number of births, age at first birth, and age at first menstruation that are related to breast cancer risk.

Before age 40, women exposed to DES prenatally were not at higher breast cancer risk compared to unexposed women. However, at ages 40 and older, DES-exposed women had two times the breast cancer risk of unexposed women. It appeared that the increase for exposed relative to unexposed women continued to rise with increasing age, but most study participants were still under 50 when the last questionnaire was completed and it is too early for definitive results. Data from the 2006 follow-up questionnaire will provide better information on this question. The association of DES exposure with breast cancer risk was present regardless of whether a participant had a family history of breast cancer or had used female hormone supplements.

Although breast cancer is the most common cancer in U.S. women, most women will never develop breast cancer. That is still the case for women exposed to DES prenatally – most will never develop breast cancer. Based on U.S. cancer registry data, for every 1,000 DES-exposed women aged 45-49, we would expect 4 new cases of breast cancer each year, compared to 2 new cases per year in 1,000 unexposed women.

Under American Cancer Society recommendations, all women who are 40 years or older are advised to undergo yearly mammograms to screen for early breast cancers. Women who were exposed to DES should follow this screening guideline if they are not already doing so.

2006 Study Abstract

It has been hypothesized that breast cancer risk is influenced by prenatal hormone levels. Diethylstilbestrol (DES), a synthetic estrogen, was widely used by pregnant women in the 1950s and 1960s. Women who took the drug have an increased risk of breast cancer, but whether risk is also increased in the daughters who were exposed in utero is less clear. We assessed the relation of prenatal DES exposure to risk of breast cancer in a cohort of DES-exposed and unexposed women followed since the 1970s by mailed questionnaires. Eighty percent of both exposed and unexposed women completed the most recent questionnaire. Self-reports of breast cancer were confirmed by pathology reports. Cox proportional hazards regression was used to compute incidence rate ratios (IRR) for prenatal DES exposure relative to no exposure. During follow-up, 102 incident cases of invasive breast cancer occurred, with 76 among DES-exposed women (98,591 person-years) and 26 among unexposed women (35,046 person-years). The overall age-adjusted IRR was 1.40 [95% confidence interval (95% CI), 0.89-2.22]. For breast cancer occurring at ages >or=40 years, the IRR was 1.91 (95% CI, 1.09-3.33) and for cancers occurring at ages >or=50 years, it was 3.00 (95% CI, 1.01-8.98). Control for calendar year, parity, age at first birth, and other factors did not alter the results. These results, from the first prospective study on the subject, suggest that women with prenatal exposure to DES have an increased risk of breast cancer after age 40 years. The findings support the hypothesis that prenatal hormone levels influence breast cancer risk.

Sources

  • Prenatal diethylstilbestrol exposure and risk of breast cancer,NCBI, PMID: 16896041, 2006 Aug;15(8):1509-14. Full text: Cancer Epidemiol Biomarkers Prevention link.
  • NCI, DES Follow-up Study Published Papers.
More DES DiEthylStilbestrol Resources

Chemical Brain Drain: One out of Six Children suffers from Neurodevelopmental Abnormality

Environmental Pollution impairs Children’s Brain Development

Only One Chance – to develop a brain, but it is at risk due to environmental chemicals.