birth defects Archives - Hormones Matter

Pollution, Disease and Birth Defects

Published on January 8, 2014

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My mother was diagnosed with cancer when I was in high school, and her prognosis did not look good. Though there were many factors that attributed to the disease, from genetics to stress, she was the first one to point out to me the potential impact the environment may have had on her health.

After all these years, one particular conversation I had with her stands out in my mind: We were walking around our neighborhood when she stopped and asked, “Do you see that?” She was pointing at the roofs of the houses. “The sides of the roofs facing the freeway are covered in soot and are much darker than those facing away from the freeway.” She paused in thought for a moment and continued, “If the exhaust from the freeway is doing that to our roofs, imagine what it’s doing to our bodies.” She then began naming all the neighbors that had been diagnosed with cancer – my mother was certain there was a correlation between our neighborhood’s health and our proximity to the freeway. She was onto something.

The 2010 Global Study of Disease recently ranked air pollution, referred to as “ambient particulate matter pollution,” as the seventh leading risk factor for disease worldwide. Air pollution is now ranked much higher as a risk factor than in previous years, which may be a result of advances in science: rather than presuming air pollution just affects big cities, high-resolution satellite data and chemical transport models allow researchers to determine air pollution levels in both urban and rural areas alike.

Now researchers realize that air pollution accounts for a large burden of disease, contributing to 3.2 million deaths in 2010. It’s no wonder that the authors of the study felt it emphasized the need to “implement more stringent regulation on vehicle and industrial emissions, reduce agricultural burning or land clearing by fire, and curb and reverse deforestation and desertification to reduce ambient particulate matter from dust.” Reducing air pollution would decrease disease and reduce the incidences of death.

Though a large majority of those impacted by air pollution lived in densely populated cities, such as China, residents of the United States are by no means in the clear air.

A study published in the American Journal of Epidemiology conducted research a little closer to home – in the San Joaquin Valley in California. In this study, researchers sought to determine whether air pollution and traffic exposure increased the risk of birth defects. Unfortunately, signs point to yes.

Mothers exposed to higher levels of carbon monoxide and nitrogen oxide (traffic-related air pollutants) during the first 2 months of pregnancy were almost twice as likely to give birth to children with neural tube defects, or defects of the brain and spinal cord. The San Joaquin Valley is just one of many highly polluted regions in the United States, and the study clearly demonstrates an association between traffic pollutants and birth defects.

Recognizing that air pollution greatly affects our health and well-being is the first step. Pushing for a cleaner environment is the second. Veerabhadran Ramanathan, Director of the Center for Atmospheric Sciences at the Scripps Institution of Oceanography, recently spoke at the Climate Justice Forum on April 11th, recognizing the relation between small particulate pollution and pulmonary and heart disease, effects that are exacerbated in infants and the elderly. But he also pointed out that such pollutants can be reduced. Black carbon, a powerful pollutant, has been reduced by 50% in California, just from stricter diesel regulation.

Environmental regulation can significantly reduce pollutants and improve public health, which doesn’t just affect far away nations – it affects us all. My mother intended to relocate but was never able to; she died the summer before my first year of college. Most of us aren’t in a position to move from polluted areas, so we need to vocalize our concerns, vote for those who are looking out for our best interests and public health interests, and ensure we can all breathe in the clean air.

Assisted Reproductive Technologies, Birth Defects and Epigenetics

by Chandler Marrs, PhD

Published on October 30, 2013

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Assisted reproductive technologies (ART) have grown in popularity and success over the recent decade. According to the CDC, in 2011 there were 61,610 babies born via ART, representing 1% of the US newborn population, nearly doubling ART use in just one decade. ART can be a blessing for the nearly 6% of US couples struggling with fertility issues. In the 30 years since ART began, there have been over 3.5 million children conceived using ART, many of whom are now adults of reproductive age. One wonders, what long-term, transgenerational effects might exist from ART; will those conceived via an assisted reproductive technology, also require reproductive assistance? Are the rates of cancer, especially reproductive cancers and hormone dependent cancers known to be epigenetic in nature, increased? Each of these questions remains to be addressed fully, but here is what is known so far.

The Basics – What is ART?

Assisted reproductive technologies refer to the techniques used to bring sperm and egg together in order to achieve pregnancy. The methods of assisted reproductive technologies include: in vitro fertilization – embryo transfer (IVF-ET), gamete intrafallopian transfer (GIFT), zygote intra-fallopian transfer (ZIFT), and frozen embryo transfer (FET). By far the most common is IVF- ET with fully 99% of couples using this method of assisted reproductive technology. IVF begins with intense hormone treatment to stimulate maternal oocyte production. Those eggs are removed and fertilized with the donor or partner’s sperm. In most cases, eggs and sperm are placed in a petri dish and allowed to mix freely. In some cases, additional manipulation is required and the sperm is injected into the egg. This is called intracytoplasmic sperm injection or ICSI. IVF plus ICSI appears to account for a large subset of the birth defects associated with IVF.

Early Indicators of Birth Defects with Assisted Reproductive Technologies

A 2007 study of California couples found that children conceived using ART, especially those conceived with ICSI, had a 35% increase in risk for birth defects compared to those conceived naturally. Most common among them were eye abnormalities, heart defects and malformations of the genitourinary tract. Other studies have linked ART to an increased risk major structural malformations of the heart, cleft lip and palate, esophogeal atresia (the esophogus dead-ends in a pouch rather than into the stomach where it should be) and anorecto atresia – (a malformed anal opening).

Among the few studies addressing birth defects and developmental anomalies post infancy, a Chinese study found an increase in observed birth defects in ART males as time progressed, compared to females and compared to those observed at birth. In fact the rate of observed birth defects doubled over the course of the 3 years. Similarly, a study looking at one year olds conceived via ART found a doubling of the rate of multiple major birth defects including chromosomal and musculoskeletal defects.

Long Term Consequences of ART

Studies looking at longer-term difficulties, whether health or developmentally related are few and have had mixed results, always ending with the caveat that it is unclear whether the assisted reproductive technology or the original infertility itself was to blame for the defect. There does seem to be a near doubling of the risk of some rare cancers children conceived via ART, but again the data sets are small and the risk of theses cancers in general is low.

A more recent study compared cardiac function between children and young adults conceived naturally versus those conceived with ART. What they found was striking. The apparently healthy individuals with no visible malformations who were conceived by ART had significant decreases in cardiac and pulmonary functioning by a number of parameters. There was marked vascular dysfunction of the systemic and pulmonary circulation, to which the authors of the study suggest may lead to premature cardiac morbidity at a rate similar to rates seen in type 1 diabetes.

ART and Imprinting Errors

A number of ART epigenetic studies published have assessed the risk or rate of what are called imprinting errors. Imprinting errors occur when genes are incorrectly silenced. A individual normally gets one active imprinted gene, either from mom or dad. When errors occur, they may get two active or two inactive copies. Children born from assisted reproductive technologies have an increased risk of imprinting errors compared to the rest of the population. The common conditions that arise include:

Beckwith – Wiedmann Syndrome – an overgrowth syndrome where children are larger than normal
Angelman Syndrome – characterized by severe developmental disability and seizures
Prader -Willi – a syndrome characterized by short stature, developmental delay, and compulsive eating

As with the some of the other birth defects observed with ART, those using ICSI – the forcible injection of the sperm into the egg, seem to proffer higher risks and seem to affect males more than females (or perhaps, as is the case with most research, it is the male offspring that are studied more frequently). Of note, the combination of ICSI and environmental endocrine disrupting chemical exposures is linked to trends in demasculization and potential sterility.

Epigenetics and Assisted Reproductive Technologies

Thus far the notion of epigenetic changes in children conceived via assisted reproductive technologies has been limited to research on the aforementioned imprinting errors, also called epimutations. Research on the broader consequences ART, particularly in general health and reproductive health is lacking. The exposure to hyper hormonal states common in many assisted reproductive technologies has the possibility of disrupting critical hormone pathways across the lifespan of the offspring and may impact his/her reproductive health in subtle, and not so subtle, ways. Some effects may not appear until much later in life and certainly there is the possibility of transgenerational changes as those observed with DES, dexamethasone and other hormone exposures during embryonic and fetal development. Additionally, as evidenced by the study on cardiac-pulmonary function, it is conceivable that many of the epigenetic effects will be functional in nature versus more obvious structural malformations. However, because ART bypasses the natural buffers in human reproduction that might have otherwise selected out for specific traits, it is difficult to disentangle native ‘deficits’ – those of the mom and dad – versus those directly linked to the procedure itself. Only time will tell what the effects of ART are on the health and functioning of subsequent generations.

Thalidomide: an Apology 50 Years too Late?

by Lisbeth Prifogle, MFA

Published on September 6, 2012

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Fifty years ago, if you were pregnant you might have been prescribed or bought thalidomide over the counter for morning sickness. While the drug was labeled “harmless,” if a woman took this drug while pregnant, there was a good chance that she would have a child with phocomelia, or seal limbs. One of the many dangerous side effects was a birth defect where the bones of the arms and legs fail to develop properly and literally look like seal flippers.

Origins and Side Effects

Thalidomide was developed in Germany in 1957 and was considered safe enough to be sold over the counter in some countries. It was sold in 45 countries. The FDA in the US never approved it, but there were victims who were part of a clinical trial where 20,000 patients received the drug, as well as patients who obtained the drug abroad.

In 1967, the drug was pulled from the market. It is now reported that 10,000 – 20,000 babies were born with severe birth defects during the 5 years that it was on the market.

Martin W. Johnson, director of the Thalidomide Trust of Great Britain, stated that about 40 percent of babies with thalidomide-induced defects died before their first birthday, and approximately 50 percent of those living today live with chronic pain. Of course, phocomelia isn’t the only birth defect; many other babies suffered heart problems, damaged hearing or eyesight, and even brain damage.

Apology – Too Little Too Late?

It’s been over fifty years since this tragic drug mishap and the CEO of Gruenenthal, Harald Stock, is finally apologizing to the victims. Is it enough?

Geoff Adams-Spink, born in 1962 with multiple impairments caused by thalidomide and a BBC journalist for 22 years, wrote an Op-Ed piece about this apology stating:

“The Wirtz family [predecessors to Harald Stock] has grown fat on the backs of thousands of families whose lives have been torn apart by a medicine originally marketed as “totally without harm.” If they really want to make amends, they should put their entire wealth at the disposal of the world’s thalidomide survivors before it’s too late.”

He’s not alone; many of the victims feel more insulted than compensated by this financially absent, PR stunt of an apology. This includes an Australian woman, Lynette Rowe, who recently won a multi-million dollar settlement in July against Diageo Plc, the legal successor to thalidomide’s Australian distributor. Wendy Rowe, Lynette’s mother who took the drug while pregnant, told journalists, “Our family couldn’t have gone into silent shock. We had to get up and face each day and every day and cope with the incredible damage that Gruenenthal drug did to Lyn and our family.”

Today’s Uses and the Future of Thalidomide

In 1964, Israeli scientist, Jacob Sheskin, discovered thalidomide could control leprosy by reducing the inflammation caused by the disease. In 1998, the FDA approved it for multiple myeloma, a cancer of plasma cells in the blood. Because leprosy is still a serious problem for populations in Africa and South America, there are women taking thalidomide as treatment and giving birth to babies with phocomelia and other birth defects. Due to this ongoing use and therefore side effects, scientists have continued to study why thalidomide is so dangerous. They recently discovered that the protein cereblon latches on to the thalidomide and is a major reason for the tissue damage in the fetus.

In the US, thalidomide is used, but under extreme restrictions for both men and women. The FDA has put in place the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.^®) to make sure that pregnant women do not take thalidomide and that women do not become pregnant while taking thalidomide. According to PubMed Health: “All people who are prescribed thalidomide, including men and women who cannot become pregnant, must be registered with S.T.E.P.S.^®, have a thalidomide prescription from a doctor who is registered with S.T.E.P.S.^®, and have the prescription filled at a pharmacy that is registered with S.T.E.P.S.^® in order to receive this medication.” Furthermore, it is only prescribed one month at a time and a doctor’s visit is required for additional prescription. Women must use two acceptable forms of birth control for four weeks prior to taking the drug. A weekly pregnancy test is also required every week for the first month and monthly thereafter if you have regular menstrual cycles (every two weeks if you have irregular cycles). And for the men, you are instructed to use a condom because thalidomide can be transferred through the sperm causing birth defects as well.

What about Other Victims of Other Drugs

Fifty years and a verbal apology is all the victims of thalidomide have received. The apology stated:

“We also ask for forgiveness for not reaching out to you from human to human for almost 50 years … We ask that you see our long speechlessness as a sign of the silent shock that your fate has caused us.”

This is what happens when we do not hold the pharmaceutical or medical device industries responsible for their products. It makes me wonder how long it will take before Gardasil and Cervarix are taken off the market? How long will it take for the victims, like Alexis in A Life Ruined by Gardasil, who suffer from mild to severe side effects, including death, to receive any sort of compensation, if ever? What about other drugs with more side-effects? To the victims of thalidomide the apology might not seem like enough, but I see it as an admittance of guilt that the company, and those who approved the drug, put profits above safety. This apology is a start and maybe someday soon we’ll see more pharmaceutical companies taking responsibility for the damages they leave on their patients.

The photo is a work of the National Institutes of Health, part of the United States Department of Health and Human Services. As a work of the U.S. federal government, the image is in the public domain.