Jill Escher
Escher Fund for Autism
Jeanne Conry, MD
American Congress of Obstetricians and Gynecologists
PO Box 70620
Washington, DC 20024-9998
October 14, 2013
Re: Urgent request to revise clinical practices to protect fetal germ cells from pharmaceutical exposure
Dear Dr. Conry:
I am writing with a most unusual request, as I realize it is not altogether common for a mother to advance a wholesale paradigm shift in the practice of obstetrics and gynecology, maternal-fetal medicine, and reproductive endocrinology. But in this case, the stakes are so high, the consequences so catastrophic, and the blind spot so glaring, I feel I have no choice but to speak up, and loudly.
My appeal is both common-sense and grounded in science: that clinicians working with pregnant women take into consideration risks of pharmaceutical exposures to fetal germ cells, the delicate precursor cells to egg and sperm, before administering or recommending any drug before or during pregnancy. These all-important cells will confer the genetic and epigenetic material from which the following generation (the patients’ grandchildren) will spring. But if these cells, which undergo rapid and environmentally vulnerable synthesis in utero, are genetically or epigenetically(fn) adulterated by exogenous exposures, abnormal development of the grandoffspring may result.
It goes without saying that pregnancy exposure affects three generations simultaneously: the mother, her baby, and the baby’s germ cells. The medical profession has a laudable recent history of concern for the myriad proximal fetal effects of in utero chemical and drug exposure, but for reasons that are difficult to comprehend, thus far such concern has not extended to the fetal proto-gametes, which are arguably the most critical cells within the fetal body.
Perhaps these third-generation tissues have not garnered the profession’s attention due to a faulty assumption that, short of outright mutagenesis of protein-coding sections of the genome, human germ cells, and the process of early oogenesis and spermatogenesis, are somehow immune to environmental influence. But we know this is not true: during certain windows of susceptibility, particularly the period of epigenetic germline reprogramming that occurs in weeks 6-18, abnormal exposures can exert strong influence on the molecular integrity of the germline. Aside from epimutagenesis, exposures can destabilize protein-coding or non-protein coding regions of the genome, damage DNA repair mechanisms, or provoke atypical transposon activity. Of particular relevance is research demonstrating marked germline effects of endocrine-disrupting substances that disrupt or augment hormone actions, which is not surprising in light of the density of hormone receptors populating the membranes of these precious cells.
Germline development is a highly conserved, but dynamic and environmentally responsive process chaperoned by hormones, and choreographed with tremendous molecular precision over billions of years of evolution. Small perturbations in epigenetic marking can, for example, lead to imprinting disorders such as Prader-Willi or Angelman’s syndromes. Defects in epigenetic mechanisms are also implicated in Rett Syndrome, for example. Studies in animal models demonstrate that gestational chemicals can wreak multigenerational havoc, resulting in numerous pathologies, including behavioral abnormalities, defects in sexual development and fertility, metabolic disruptions, and cancer. In human epidemiology, we have observed third-generation effects of diethystilbestrol and nutritional stress.
My interest in this area stems from personal experience. I was born in 1965 after having been exposed in utero to a cocktail of ob/gyn-administered chemicals, including ovulation-inducing drugs and seven months of various synthetic steroid hormones (progestins, glucocorticoids, and estrogens) that were fairly commonly used in the 1960s and intended at the time for the prevention of miscarriage. I know of my drug exposures in detail owing to the miracle of having recently obtained my prenatal medical records from a Los Angeles ob/gyn office where my mother had been a patient. Almost all such records have been destroyed; few of my generation know of their prenatal drug exposures in any detail.
Ordinarily, such old records would be of little interest, but the concern runs not so much to my somatic cells, though my body and brain were certainly permanently altered by those early exposures. The concern runs to my ova, as my children, who are genetically normal and came from normal, healthy pregnancies with no risk factors, are idiopathically autistic.
After connecting the dots between my endocrine-disrupting prenatal exposures, likely epigenetic perturbations during early oogenesis, studies showing autism risk genes “hotspots,” abnormal methylation in post-mortem autism brains, and my children’s mysteriously impaired neurodevelopment, I found family after family after family with the same story. In the course of my surveys of autism families, I found that about 30 percent of autistic children were born of parents who suffered substantial prenatal pharmaceutical drug exposures during the heyday of the prenatal pharmaceutical craze of the 1950s, 60s, and 70s.
Those drug exposures include progestins, synthetic estrogens, glucocorticoids, sedatives (such as phenobarbital), anti-nausea medications, and psychoactive medications. The prevailing false belief in those decades regarding the protective “placental barrier,” combined with the explosion of new and heavily marketed synthetic drugs, led to the unprecedented mass medicating of pregnant women in that era. This meant, of course, that three generations were medicated at once.
Only the most vulnerable of those generations was not the mother or the fetus, but the relatively unadorned and unprotected germline; and the molecular-level birth defects to that generation would lay dormant for several decades. It is not a coincidence that the autism epidemic began in the 1980s, or that autism has been shown to be highly “heritable” among siblings, even without any autism in the family ancestry, or that a significant subset of autism appears to involve de novo changes in gene function involving hypermutable long genes on the genome.
Distressingly, women’s use of medications before and during pregnancy seems to have abated little. Hormone drugs remain widely and intensively used in fertility practice, maternal antidepressant and ADHD drug use is rampant, anti-nausea drugs have drifted back into fashion, and, given the growing incidence of diabetes, PCOS, digestive problems, thyroid disease and hypertension, the use of many other drugs, many of them endocrine disruptors, has also climbed.
In light of widespread gestational pharmaceutical use and the risks of perpetuating the horror of chemically induced fetal germline disruption, combined with your organization’s mission to promote patients’ and the public health, I ask your organization to please consider the following:
Publish this letter in the ACOG Newsletter and other publications, both paper and online.
Support my petition to the FDA. The Escher Fund for Autism has petitioned the FDA to consider potential impacts of prenatal pharmaceuticals on fetal germ cells, and to advise consumers of potential germline risks. In an unfathomable lapse in judgment, scientific understanding, and diligence, the FDA has never before considered fetal germline impacts of pharmaceutical drugs. Please find my petition, and submit comments online, by searching “Escher Fund for Autism FDA Petition.”
Warn all pregnant and pre-pregnant patients of potential dangers to fetal germline. Systematically inform women who are pregnant or considering having a child of exposure risks to fetal germline posed by not just prescription pharmaceuticals, but also OTC drugs, smoking, drinking, recreational drugs, pesticides, endocrine disruptors, and poor nutrition. Of greatest concern, however, are the acute drug and pharmaceutical exposures.
Support full disclosure to exposed individuals. Support a national policy requiring that all children born of medicated pregnancies, including all children resulting from fertility treatments, be advised in writing of their specific exposures, including timing, doses and identity of all drugs and manipulations used, and that these F1 offspring be counseled regarding the heightened risk of bearing F2 children with developmental impairments.
Support a policy requiring retention of all prenatal medical records indefinitely. Because prenatal exposures can have lifelong health consequences, in addition to germline consequences, we must ensure that all prenatal medical records are kept in electronic media that can be accessed by all three generations directly exposed to the drugs.
Advocate for biologically conservative, and evolutionarily compatible, clinical practice. Support clinical practice that refrains from prescribing any drug, particularly any drug with hormonal or endocrine-disrupting properties, unless absolutely necessary. For example, advocate for cessation of use of discretionary glucocorticoids, which have already been demonstrated to have adverse germ cell impacts, and minimize use of progesterone and progestins, particularly during weeks 6-18 of gestation when germline synthesis is at its height. Minimize, and attempt to eliminate, use of antidepressant drugs, which have endocrine-disrupting properties. And take extreme care to minimize periconceptional exposures, as that period presents another window of susceptibility to epigenetic derangement.
Advocate for clinical practice that emphasizes restoration of natural fertility and endogenous hormonal normalcy. School your professionals in the principles of evolutionary medicine and ancestral health so they can expand their clinical toolbox to include reproduction-compatible interventions well beyond genotoxic approaches pharmaceutical companies are pitching. For example, focus on supporting women’s transitions to highly nutritious, low-inflammation diets free of sugar, grains, or processed food, but rich in healthy fats and dietary cholesterol, and dense with micronutrients and natural (not synthetic) folate and other methyl donors. Reduction of endocrine-disrupting compounds, whether natural or synthetic, is also essential.
While we may be many decades away from fully understanding every mechanism of molecular genetics and epigenetics affected by every prenatal drug and chemical exposure, is beyond debate that xenobiotic in utero exposures can cause errors in germ cells. When in 1961 we perceived that thalidomide was causing horrific birth defects, no one said, “Let’s first ascertain the physiological mechanism before we issue a prudent warning.” Synthetic adulteration of germline, however inadvertent it may have been, represents the greatest medical disaster in history, having spawned a torrent of incapacitating disability among those born within the last three decades, and its catastrophic multigenerational effects will echo through the centuries. We can, however, stem further damage.
Thank you for your prompt attention to this matter. Please feel free to contact me any time, I am at your disposal.
Very truly yours,
/s/
Jill Escher
cc:
ACOG board members
With similar letters to:
Fertility and Sterility, editorial board members
American Society for Reproductive Medicine, board members
Society for Maternal-Fetal Medicine, board members
Society for Reproductive Endocrinology, board members
American Medical Association
Rachel Turow, JD, Food and Drug Administration
Margaret Hamburg, MD, Commissioner of the Food and Drug Administration
(fn) In the event of unfamiliarity with epigenomics, epigenetic mechanisms refer to the many layers of molecular mechanisms that affect gene expression and regulate genome dynamics. Two of the major categories of epigenetic marks are DNA methylation and histone modifications.
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