Of Plagues and Vampires: Believable Myths and Unbelievable Facts from Medical Practice

by Michael Hefferon

  And lately, pregnancies in women into the sixth and even seventh decade of their lives are no longer making headlines. But are we covering up uncomfortable facts about childbearing in later life?

  The era of modern reproductive choices began in the 1960s with contraception and legalized abortion. Women could postpone pregnancy while they embarked upon careers. As a result, despite the falling birth rate over the past three decades, the birth rate among women aged between 35 and 55 has risen.

  This rise is associated with upbeat media reporting of older women having babies, often through the use of reproductive technology (fertility treatment/donor sperm/donor eggs/ freezing eggs/IVF). These favourable reports have been based on small numbers and early results.

  The media’s positive portrayal of youthful-looking women balancing home life and career is well accepted. But as we age, we acquire medical conditions that can complicate pregnancy: for example, diabetes, hypertension, and risk of premature birth. So even with much popular support promoting motherhood and encouraging a level playing field for women, is 40 the new 20, reproductively speaking?

  I recall when I was a resident in obstetrics that 29 was considered the peak age for childbearing — in other words, things were going downhill after age 29. Pregnant women were considered “elderly” at 35. We seldom saw pregnancies in women after 40, and if we did, it was seldom a primagravid (first pregnancy) and rarely a multiple pregnancy. Today the definition of Advanced Maternal Age has crept up to 40, and now the term “Very Advanced Maternal Age” is used for women over 45.

  The choice to delay may also be a product of many young fertile women hearing their mothers or grandmothers describe how their aspirations in life were diverted by the arrival of a baby. Or many may feel that their partners are not ready to settle, despite the fact that women are most fertile between the ages of 15 and 30.

  This is where the science kicks in. A woman’s eggs are as old as she is. Whereas men make sperm every month or two, women are born with a full quota of eggs. Over time, then, as these eggs age, their chromosomes are less likely to divide properly (a condition called aneuploidy). The rate of aneuploidy by age 40 is 75 percent. The majority of fetuses with aneuploidy will abort spontaneously. But the incidence of Down Syndrome rises from to 1 in 400 with a mother in her early twenties to 1 in 60 at age 40. Incidence of other aneuploidies — Patau Syndrome and Edwards Syndrome, chromosome abnormalities not unlike Downs — increase twentyfold.

  Yes, these concerns are reduced by the use of donor eggs, but such interventions do not guarantee a receptive uterus.

  Although there is no current definition of advanced paternal age, studies are showing decreases of sperm quality and motility after age 35. As well, recent studies have indicated an association between autism and advanced paternal age.

  Unfortunately, when sex-education classes discuss the deferral of pregnancy, childlessness and birth defects are seldom mentioned. But they should be. Older women can give birth to healthy children, but the chances get slimmer with time. So while the key to informed choice is education, we need to recognize that, as far as having babies is concerned, 40 is not the new 20 — despite what we may be led to believe.

  REFERENCES

  Dietl, A., S. Cupisti, and U. Zollner. Pregnancy and obstetric outcomes in women over 40 years of age. Gebertshilfe Frauenheild, vol. 78, no. 8, August 2015, pp. 827–832.

  Delpisheh, A., L. Brabin, and B.J. Brabin. Pregnancy in late life: A hospital-based study of outcomes. J Womens Health, vol. 17, no. 6, July 2008, pp. 965–970.

  11 GOUTY OLD MEN?

  SO WHAT DID Henry VIII, Phillip II of Spain, and Luciano Pavarotti have in common? Beethoven and Leonardo da Vinci? Pitt the elder and Pitt the younger? You guessed right if you said they all had gout.

  Although we have known about gout for at least 4,000 years, the stereotypic image of a Pickwickian older gentleman bingeing on port and Stilton has dominated society’s image of gout. But what is true, and what is myth?

  Gout has often been referred to as the “disease of kings” — Charles IV, V, and VII were all sufferers. But gout also afflicted Queen Anne of Denmark and Queen Anne Stuart of Scotland.

  To get beyond the popular stereotype of persons with gout, it’s important to know that gout is not a lifestyle disease but an inherited disorder of uric acid metabolism. Gout is in fact caused by uric crystals collecting around a joint, such as the big toe, and causing severe arthritic pain. Although the uric acid crystals were first identified as a cause of gout in 1859, it was not until 1988 that a Nobel Prize was awarded for the discovery of a medication (allopurinol) that would reduce the production of uric acid crystals.

  Gout is the commonest cause of arthritis in men over 40, and as people are living longer, it’s on the increase. By the age of 60, the incidence of gout in men and women is equal.

  Most of us can eat, drink, and be merry without fear of developing gouty arthritis, but many people with gout are quite abstemious. It’s not a complete myth that rich diet can be associated with gout, however. Beer, liver, and sardines are all very high in purines (a form of animal protein) and are hard to metabolize if you have a genetic deficiency of the enzymes that break down purines.

  So people with gout do need to watch their diet — just like the rest of us.

  REFERENCES

  Rider, T., and K. Jordan. The modern management of gout. Rheumatology, vol. 49, no. 1, 2010, pp. 5–14.

  Roddy, E., and H. Choi. Epidemiology of gout. Rheumatic Disease Clinics of North America, vol. 40, no. 2, 2014., pp. 155–175.

  12 THE RIB MYTH: DO WOMEN HAVE ONE MORE THAN MEN?

  HERE’S A PRE-MED exam question:

  Is it a myth that women have an extra rib compared to men?

  Yes

  No

  Maybe

  Men have the extra rib

  None of the above

  When this question is posed to medical trainees or even medical professionals, the instant reaction is hesitation. Somehow, our brains will jumble what we learn in the medical training with what we’ve heard early in life. This is more particular to those of us over the age of 40, and most of us who are from Judeo-Christian backgrounds. Younger folks, who are not as likely to be influenced by the Bible, are less likely to be confused on the topic. In Genesis 2:22, God takes a rib from Adam and makes a woman (Eve). This is the ancient story of creation in the Old Testament.

  Darwin long ago provided us with a scientific alternative to creationism, and most people no longer adhere to the Adam and Eve story. But is there more to it than Genesis?

  One day as I was spinning the rib myth for trainees in the paediatric common room, a young woman spoke up. “My mother has one more rib than my father. My sister also has an extra rib. Both have had surgery to remove it, and I’m being investigated myself for having an extra rib!”

  Could this be? Three women in one family with an extra rib not found in male family members?

  This young woman, a dietary intern who was rotating through Paediatrics that week, was describing a condition called Thoracic Outlet Syndrome caused by a cervical rib — indeed, an extra rib — in the neck area. The result is often compression of nerves and blood vessels coming through the neck into the arm. The condition affects 0.6 percent of the population, but females are affected three times more often than men. This would translate to 30 million females worldwide having an extra rib, and only 15 million males. And so, technically, it is indeed more common for a woman to have this condition, but it has very little to do with myth!

  REFERENCES

  Genesis 2: 22: “Then the Lord made a woman from the rib he had taken out of man.”

  Dolansky, S. The immortal myth of Adam and Eve. https:// thetorah.com/the-immortal-myth-of-adam-and-eve/.

  13 EQUAL SEX RATIO AT BIRTH?

  ULTRASOUND NOW ALLOWS us to know the gender of a foetus after about 18 weeks of gestation. Boy or girl? The odds are 50:50 — right?

  The answer may not be as o
bvious as the question. It’s a myth that the actual sex ratio is 50:50. In developed countries, 105 boys are born for every 100 girls. In China, and in the East in general, the figure runs from 110 to 118 boys per 100 girls. (Chinese figures are affected by the preferential abortion of females and by the one-child law, but other eastern countries have higher ratios without these laws.)

  Parental age (maternal and paternal) can cause a change in this ratio, with older parents being less likely to have a boy.

  So why might all this be? Theories abound, but the following factors may be relevant:

  1. A male foetus is less likely to make it to term. Intrauterine deaths are more commonly male, and survival in the pre-term infant is biased towards females. Therefore we could surmise that nature starts with an excess of boys for this reason. (Remind me again, which is the weaker sex?) However, advances in antenatal care in the past 70 years may have benefited male foetuses more than females.

  We suspect that gender ratios at birth may have been 50:50 in the nineteenth century, when many of these male offspring were not salvageable.

  2. Male offspring were more likely to be killed in war or in accidents, ending up with women outliving them in later life.

  3. In pediatric practice, in the 1970s and 1980s, I recall many families with multiple children — indeed, it seems that fewer people had children, but those who did had more children. Also conspicuous was the observation that some large families had five girls, while other families might have six boys. The question arises: once you have a boy, are you destined to have more boys? Once you have a girl, are you more likely to have girls?

  The situation is not so simple, but there are patterns that suggest that this may be more the case with boy babies. Allowing that your chance of conceiving and giving birth to a girl on the first try is 49.5 percent, if you go ahead and try for a girl after having one male child, your chances are 50:50, and after having two boys, this goes down to 47.7 percent. After three boys, that chance of having a girl falls to 43 percent. Not massive ratio changes, but significant in a world of over seven billion people.

  4. The percentage of boys born increases during and after wartime. Why would that be? Did heaven replace the losses at the Somme with a male ratio imbalance? It’s a fact that male births (and all births) spiked in 1857 (the Crimean War), 1919, and 1946.

  The age of the mother at conception does not affect the gender of the child, but the age of the father does. Younger men are more likely to conceive boys.

  Other theories suggest that tall men are more likely to produce boys. It’s also true that taller men are more likely to survive war.

  Put all this together, and consider that taller, younger men, returning from combat with burning passion, eager to be intimate more often, might do so at times in the cycle that would favour male embryo creation — mid-cycle — and these ratios are not hard to believe.

  In conclusion, then, whether in war or peace, it’s a myth to believe that the sex ratio of our babies is 50:50.

  REFERENCES

  Catalano, R., and T. Bruckner . Secondary sex ratios and male lifespan: Damaged or culled cohorts. School of Public Health, University of California. 2006.

  Graffelman, J., and R.F. Hoekstra. A statistical analysis of the effect of warfare on the human secondary sex ratio. Human Biology, vol. 72, no. 3, 2000, pp. 433–444.

  Bernstein, M.E. A genetic explanation of wartime secondary sex ratios. American Journal of Human Genetics, vol. 10, no. 1, 1958, pp. 68–70. PMID-13520702.

  TERMINATING THE CANCER MYTH

  14 A VITAMIN CURE FOR CANCER?

  THE BENEFITS OF VITAMINS have led to a multi-million dollar industry that has far exceeded the original intent of these products.

  Vitamin deficiencies, particularly deficiencies in vitamin C such as scurvy and vitamin D such as rickets, were landmark discoveries in the progress of nutritional medicine. For instance, deficiencies in Vitamin B, which has 12 components including thiamine (B1), folic acid (B9), and cobalmin (B12), can contribute to problems from mood disorders to heart disease.

  In the 1940s, there were popular theories regarding the benefit of vitamins for just about everything. In Boston, Dr. Sidney Farber was interested in blood disorders. He had seen the benefit of some B vitamins in treating pernicious anemia. Thus he set out to treat patients with childhood leukemia with Vitamin B9, or folic acid. These unfortunate children rapidly declined and died within weeks instead of months. The cause was that vitamin B9 was feeding the leukemia cells and actually helping the cancer (leukemia) cells to grow.

  Dr. Farber set about finding an agent that would do the opposite — choke off the cancer cells. He teamed up with his laboratory to synthesize an “anti-folic acid agent” called Methotrexate. Methotrexate prolonged the children's lives, but it was 20 more years before the arrival of “combination chemotherapy,” which resulted in significant survival of children with acute leukemia. Dr. Farber became known as the father of chemotherapy and has been honoured by the great Dana-Farber Cancer Institute in Boston, named for him with support from the Charles Dana foundation.

  When I was a student in the 1970s, survival in acute leukemia in children was about 20 percent. Many of these children sustained life-long complications from chemotherapy and radiation. By the time I was a resident, this survival figure had risen to 40 percent. Still, many patients succumbed to complications and infections. In 2017, the long-term survival rate among girls with standard-risk acute lymphoblastic leukemia was 94 percent, with complications being rare.

  So it was the discovery of an agent that would block a vitamin that resulted in the discovery of chemotherapy. And, in its time, this discovery almost did not happen. Sidney Farber was born in Buffalo in 1903 into a Jewish family. He was one of 14 children. In the 1920s, many Jewish students were refused entry to US medical schools on the basis of quotas. The Farbers spoke German, and Sidney found a place at the University of Heidelberg. Such was his success in that first year that he was admitted to Harvard as a second-year student.

  REFERENCES

  Simone, J.V. Fifty years in hematology: Research that revolutionized patient care. American Society of Hematology; 50th Anniversary Meeting, 2008.

  Foley, G.E. Obituary for Sidney Farber. American Association for Cancer Research, vol. 34, 1974, pp. 658–661.

  15 IS CHILDHOOD CANCER INCURABLE?

  PERHAPS NO VISION in our media is more potent than that of a small child, left without hair as a result of cancer treatment. It’s barely believable that life, or circumstance, or God, could be cruel enough to allow a young child to be diagnosed with cancer.

  Many of these images are used to increase awareness of the terrible plight of these children, and their families. They are basically our neighbours.

  And make no mistake, these images do raise awareness. Better still, they raise money. And that may be considered money well spent. Advances in care have benefited from research funding. Thankfully, expectations may now increase along with it.

  So, how rare is cancer in children today? While we can hardly say that childhood cancer is common, it is the leading cause of death by disease in the developed world, in children aged two through 18.

  This year, in Canada, there will be 2,000 cancer diagnoses in persons aged 18 and under. Approximately 80 percent of these children will survive their ordeal.

  Thus comes a new cohort of survivors of childhood cancer, who need to be followed medically for the remainder of their lives. Many and most will lead normal, healthy, productive lives that would not have been possible a generation ago.

  However, the medical follow-up is life-long. Although many people will encounter little or no long-term medical complications, some will have lasting effects from their disease and/or its treatment.

  These late effects can depend on the type and location of cancer, the type and dose of chemotherapy, the child’s age when treated, and any other health problems that may have existed before diagnosis.

  Late adverse effec
ts can include growth suppression, hormone and fertility problems, radiation toxicity, secondary (later) cancers, steroid toxicity, learning difficulties, and emotional problems. Complications, and after-effects from bone marrow transplantation, can also be significant.

  In brief, there are three main types of childhood cancer (and many more types that are less common). These are acute leukemias, brain tumours, and lymphoma.

  These three diagnoses account for the majority of cancers in children. (Others such as Wilms Tumour, a kidney malignancy, and neuroblastoma, a nervous-system tumour, are unique to pediatrics but are not as common as the first three mentioned.

  So it comes as no surprise that the leukemias (cancer of the bone marrow, the spongy centre of bones that makes blood cells) represent over 30 percent of all childhood cancers. There are clearly high risk and low risk groups. The good news is that in the lowest risk group, a survival rate of 94 percent is now possible.

  Through history, a survival of five years past diagnosis has been judged to be a cure. (This definition is not universally adhered to). More importantly, the disease-free, intact survival has massively increased. In children, this is important, as in the past the use of radiation was associated with disfigurement, particularly after spinal radiation.

  The discovery that spinal radiation was not needed in milder cases of leukemia, and the more selective use of radiation with other tumours, has led to better outcomes with less or no disfigurement. How was this achieved? We need more than money, and goodwill to turn around such a plague. The answer is collaboration.

  The Children’s Oncology Group (COG) is a clinical trials group with more than 200 member institutions in United States, Canada, Australia, and New Zealand. The COG has enabled data from all regions of these countries to be assessed and outcomes to be compared, looking at the factors that may have affected outcomes in these children.