The More You Know: The Ethics of Prenatal Testing

November 19, 2014

Denise Balkissoon

Today's Parent

Expectant parents can spend hours pondering what their unborn baby will look like. Will he or she inherit typically desirable traits—like height, athletic ability or a cute dimple—or less coveted ones, like problem skin or crooked teeth? From the time my baby was a sexless embryo, I figured he or she would have brown eyes like both my husband and me (brown is a dominant gene for eye colour). My husband, Steve, optimistically hoped that our baby would end up with my hair, which is thicker and more abundant than his.

Early in my pregnancy, I asked my doctor if I should worry that one of my aunts was born with a congenital heart condition. I knew that the baby could grow up to have moles that develop into melanomas, since that has been an issue for Steve’s relatives, but I was glad that neither of our families have a history of Alzheimer’s or Parkinson’s.

As medicine advances, we don’t have to wonder as much about these “what if” questions if we don’t want to. Thanks to prenatal testing, your baby’s genetic future is becoming less of an unknowable mystery. While parents may not be testing for the adorable-dimple or long-eyelashes genes yet, it is indeed possible, scientifically. No longer satisfied with affecting the “nurture” part of the baby equation through careful diet, exercise and various overachiever parenting philosophies, we are digging into the “nature” side, too.

In my circle of friends, it’s now almost assumed that parents will find out a fetus’s sex at the 20-week ultrasound, and those who choose not to find out are considered cute hippies. The majority of pregnant women also opt for prenatal screening tests. Parents whose ethnic background or family medical history mark them as high-risk for certain conditions regularly undergo specific prenatal tests, often funded by provincial governments. (Ashkenazi Jews in Ontario, for example, are offered seven tests for conditions common in that population,including one for Tay-Sachs, a neurodegenerative disease.)

Those who are willing and able to spend their own money can find out a lot more, with a lot more certainty. Before performing in vitro fertilization (IVF), private fee-for-service clinics can test an embryo to rule out specific conditions, or exhaustively screen all of its 23 chromosomes for a whole list of diseases.

Then there’s microarray analysis, offered by some Canadian clinics and hospitals already, which examines all chromosomes at a higher resolution (above what’s checked by chromosome analysis). Microarray can detect submicroscopic unbalanced chromosome abnormalities, including identifiers for autism and other mild intellectual disabilities. American researchers have successfully incubated a baby made of a father’s sperm and eggs combined from two different women, eliminating certain diseases but raising the question of what other ethical issues—or risk factors—might have been introduced. There are no guidelines about what percentage of risk, for which diseases, should be cause for worry (or action—often there is nothing a parent can do but wait and see). And yet, there’s a race on to find the fastest way to map the entire gene sequence of a newborn.

Early in my second trimester, an ultrasound informed us that I was having a boy. (I didn’t need to know, but my husband insisted he couldn’t focus his naming efforts otherwise.) The same ultrasound was analyzed along with a blood sample to determine that I had a lower-than-average chance of giving birth to a baby with Down syndrome or with spina bifida. At the time, I was unaware that I could have sought much more specific information. But as my pregnancy continued, I realized I had barely nudged the emerging genetic frontier.

The more you know

The ultrasound-plus-blood-sample test that I opted for is called the IPS, for Integrated Prenatal Screening. It’s a Canadian standard, but at around 10 years old, it’s no longer considered cutting edge. The Non-Invasive Prenatal Test (NIPT), a highly accurate DNA test, is the new kid on the block, introduced in Ontario and British Columbia in mid-2013. I wasn’t surprised when my long-time friend Mark Bolusmjak told me that he and his wife, Hanna Faghfoury, were some of Canada’s first expectant parents to choose to screen their unborn child for genetic conditions using the NIPT. Bolusmjak has always been a data-hungry kind of guy (in high school, he read The Joy of Math for fun), and Faghfoury is equally science-minded—she learned about the test during her work as a geneticist at Toronto’s Mount Sinai Hospital. The test is now free for certain high-risk expectant parents, but last fall, Bolusmjak and Faghfoury decided to pay $800 for it out of pocket.

“It’s a better test, done earlier,” says Faghfoury, comparing the NIPT to the test that I had, the IPS. “It’s highly specific and sensitive.”

Both tests screen for three chromosomal conditions: Down syndrome (Trisomy 21), neural tube defects like spina bifida, and Trisomy 18 (also known as Edwards syndrome). The IPS is done in two parts: a blood test and nuchal translucency scan (measuring fluid behind the baby’s neck via ultrasound) at between nine and 13 weeks, and another blood test between 15 and 21 weeks. But the NIPT can be done as early as nine weeks into a pregnancy, before many expectant couples have passed the first trimester mark or started sharing their news. The NIPT also searches for certain abnormalities in a fetus’s sex chromosomes, in addition to the three conditions IPS can identify. For couples itching to know as much information, as soon as possible, this is a good thing.

“In the first trimester, I was still in the mindset that things might go wrong, and I wasn’t as emotionally invested or stressed out about the test results,” says Faghfoury. She appreciated the chance to learn about any complications as soon as possible.

They also liked that the NIPT gives definite positive or negative results—yes, the fetus has a condition, or no, it does not—and is completely safe for both the mom and fetus, requiring only a blood sample from the mother (and, sometimes, a cheek swab from the dad). With IPS, results are expressed as a risk factor: A favourable result for an average 30-year-old woman still means that she has a one in 1,000 chance of giving birth to a baby with Down syndrome, while a 40-year-old woman who gets a probability of one in 12 still doesn’t know for sure.

There’s also a chance of getting a “false positive” (when tests indicate the baby has a condition, but it doesn’t) or a “false negative” (when the baby has the condition but it doesn’t show up on the tests). Parents who want a more definitive result after IPS must choose between an amniocentesis, which involves inserting a needle through the abdomen and uterus to retrieve a fluid sample from inside the amniotic sac, or chorionic villus sampling (CVS), which tests a piece of placenta. Both give a clear, 100 percent reliable result, but carry a number of risks, including a small, but still worrisome, increase in the chance of miscarriage.

Despite the couple’s affinity for data, they didn’t know for sure what it would mean for them if they found out their child had any of the conditions. “I’m big on informed choice, but I wasn’t entirely clear what I would do with the information,” says Faghfoury. Still, they felt like more solid results, earlier on, would be better.

Read more: Anxiety during pregnancy>

When Faghfoury and Bolusmjak told me about their choice to get and pay for NIPT, I was six months pregnant, and 36 years old. I knew the risk of having a baby with chromosomal conditions increases with a woman’s age. But the IPS found our baby’s risk factors to be the same as if I were 31, so we figured that was good news and skipped further amnio or CVS. As my pregnancy progressed, however, I succumbed to the perils of googling rare medical conditions, and began to get anxious.

Take the blood condition thalassemia. I had never heard of it until I was seven months along, but it’s apparently common among those with Asian, South Asian, Middle Eastern or African heritage. Faghfoury, whose parents are from Iran, had her fetus tested, so I started to fret about my Indian great-grandparents. I also started to dread the heel-prick test given to every Ontario newborn, where a blood sample is taken from an infant’s teeny-tiny foot to test for 28 genetic conditions. (All provinces do some form of genetic screening, but the processes and policies vary.) Less than one percent of babies end up with any of these conditions, and yet, I worried.

In the abstract, this kind of science is mind-blowingly amazing to me. We’ve come so far in a short amount of time. (Consider that obstetric ultrasounds, first used in Scotland in the late 1950s, weren’t available to most pregnant women in North America until the 1970s.) But when it came to a real live baby, I couldn’t figure out how much information I wanted—and at what stage in my pregnancy. Advocates believe genetic screening could revolutionize medicine, allowing doctors to treat a patient or a population’s most pressing issues, and research funds could go to where they’re most needed. Users appreciate the chance to make decisions based on real risk factors, and have enthusiastically embraced the chance to learn about their genomes. And if a parent or grandparent has been adopted and doesn’t know his or her family medical history, science can help fill in some of the missing branches in the family tree.

Mail-order testing

For the past seven years, the California-based lab 23andMe has been selling home genetics kits, now newly available in Canada for $199. Customers collect saliva (their own or their children’s) in a test tube, then send it in for an analysis of their ancestry, carrier status and risk factors for more than 100 conditions, including Alzheimer’s and Parkinson’s. The company reports more than 750,000 clients around the world. Founder Anne Wojcicki, a biologist and ex-wife of Google founder Sergey Brin (who has been public about his family history of Parkinson’s), has stated that her ultimate goal is to sign up 25 million people.

In the US, the Food and Drug Administration (FDA) has thrown a wrench in the gears, characterizing 23andMe as a DNA-gathering free-for-all by a private company. The FDA has also objected to the company’s splashy marketing campaign (“Know more about your health!”) and said that it was “concerned about the public health consequences of inaccurate results,” then ordered the company to stop selling its tests as a “medical device.”

Bioethicists worry that 23andMe and its inevitable competitors will concentrate on making a mint off newfound screening capabilities and storing private health data, leaving everyone else to figure out the ethics afterward. Should parents inform their children they have a one in 400 chance of developing Alzheimer’s later, or keep it a secret? If they’re going to tell them, what’s the right age? How would that knowledge change the way they parent that child, or affect the goals a young person sets for himself as he envisions his future?

Skeptics of commercial tests counter that most genetic information is too new and vague to be reliably interpreted by non-scientists, and might lead to unethical behaviour. Carriers of Huntington’s disease, for instance, have already been denied insurance or charged higher premiums in British Columbia, and both the federal and Ontario parliaments are currently considering human-rights-code amendments to prevent “genetic discrimination.”

Today, as 23andMe’s legal appeal churns through the US court system, the company continues to sell its tests with a modified approach: After buyers send in their saliva samples, they no longer receive a medical report, just raw genetic data that they must pay another scientist to interpret.

Personal choice

While my husband and I were fortunate enough not to encounter any of the truly difficult prenatal decisions other couples face, I soon realized that choices about genetic testing have been made by my family, friends and just about every parent I know. Omniya Hussein, my sister-in-law’s sister-in-law, knows about the joys and sacrifices involved in special-needs caregiving: Her husband’s sister has Down syndrome. They’re also devout Muslims. She explained to me that her faith would never allow for a termination, so she and her husband decided against IPS for each of her three pregnancies.

“Any child is a gift from God,” she says. “Children born with a condition like cerebral palsy or Down syndrome are like angels on Earth, a hidden blessing. And we wouldn’t have done anything differently anyway,” she says. They also chose not to learn the sexes in advance.

Another distant relative of mine is Susan Hagerman (her stepdaughter is married to my brother). When she was pregnant 10 years ago, Susan chose amniocentesis because she herself has myotonic dystrophy. It’s the most common form of muscular dystrophy, which is characterized by progressive muscle weakness and degeneration, as well as occasional heart problems and intellectual disabilities. Susan’s health issues are moderate—she’s had cataracts and weakness in her hands and legs—but one of her nephews needs a ventilator at night to breathe and is severely physically disabled.

Susan and her husband began trying to have a baby when she was 30. It took nine years and three cycles of IVF before she successfully became pregnant. Still, she planned on terminating if the fetus tested positive.

“I made a decision, before I got pregnant, about what I would do if I had a baby with myotonic dystrophy,” says Hagerman, whose son is now nine years old. “I would not have kept the baby.”

There are no cures for genetic conditions, so these tests are purely diagnostic. All of them happen early enough that parents could either choose an abortion or begin to prepare for a child’s special needs.

Risky business

Geneticist David Chitayat, head of the prenatal diagnosis and medical genetics program at Mount Sinai Hospital in Toronto, says that when the technology exists, it’s unethical not to let a parent know that they might have a particularly difficult job ahead of them.

“We’re here to support and help the parents,” says Chitayat. “If somebody thinks they cannot raise a child with Down syndrome, you don’t force them to do that.”

He wishes more tests were currently available for free—specifically, he believes that the Ontario Ministry of Health, under which he works, should already be paying for prenatal tests for spinal muscular atrophy, fragile X syndrome and cystic fibrosis.

“Fragile X is the second-most common intellectual disability after Down syndrome,” he says. (About 25 in 100,000 boys are born with this condition.) He points out that Caucasian couples also have a one in 25 chance of having a baby who’s a carrier for cystic fibrosis, but unless there is a family history of the condition, they won’t learn more about their baby’s status until the newborn heel-prick test. (And even then, false positives are common.)

Chitayat also believes that the results of prenatal tests belong to the parents. Legally, in some provinces, the government agrees: In 2012, the BC government banned doctors from withholding ultrasound results from parents they suspected might get a sex-selective abortion.

One group that sees a downside to advancements in genetic testing is the Canadian Down Syndrome Society.

“The primary goal of genetic research should not be to reduce Down syndrome births, but to improve healthcare,” says Kirk Crowther, the group’s executive director.

One in 781 babies are born with the syndrome, and between 85 and 90 percent of parents who receive a prenatal determination of Down syndrome choose to terminate. His organization asks doctors and genetic counsellors to be “neutral” in discussions with parents: using the word “determination” instead of “diagnosis” when giving results, for example. Children with Down are a crucial part of many loving families, and many grow up to attend post-secondary school, get married and become financially independent.

Crowther, who lives in Calgary, says it’s hurtful to people with Down to think that there are those who want to see them “eliminated,” and fears that the earliness of an NIPT diagnosis (nine or 10 weeks) will lead to more terminations.

“Down is more easily identified than other risks,” he says. “What’s next on the list? Other diseases? Blondes or brunettes? I worry about the future.”

If Hagerman were having a baby now instead of 10 years ago, she could opt for pre-implantation genetic diagnosis, or PGD, which screens embryos for single gene abnormalities before they’re implanted in the uterus via IVF. At Olive Fertility Centre in Vancouver, this can cost up to $18,000. The private clinic was co-founded by reproductive endocrinologist Al Yuzpe, who also set up the country’s first IVF clinic in 1995. Most of his PGD clients already know they have specific risks from hereditary conditions, which include myotonic dystrophy like Hagerman’s, as well as Huntington’s disease and the strain of breast cancer caused by the BRCA genes that Angelina Jolie made famous. (If you have a BRCA1 or BRCA2 mutation, you have a 40 to 80 percent chance of developing breast cancer. If you’re a carrier of the gene, your baby has a 50 percent chance of inheriting it.)

Olive also offers pre-implantation genetic screening, or PGS, a broader scan of all 23 pairs of chromosomes for too much or too little genetic material. (In cases where there is too much or too little genetic material, an embryo may not implant, or will implant but result in miscarriage.) It’s usually chosen by couples undergoing IVF who are older and have elevated risk levels, or those who’ve had recurrent miscarriages.

Rolling the dice

Yuzpe is very clear that he isn’t promising clients a perfectly healthy child. If prospective parents ask him to eliminate risk entirely, he informs them that three to five percent of all babies are diagnosed with an abnormality in their first year of life, and often the cause isn’t genetic and can’t be screened for. He says carriers of unwanted genes have four options: conceive naturally and then undergo the standard prenatal tests before choosing whether to continue with a pregnancy; opt for embryo-screening PGD; or choose donor eggs or donor sperm instead. The fourth choice is to adopt. If none of those options are reassuring enough, Yuzpe advises that perhaps parenthood isn’t the best lifestyle decision for them.

“Maybe it’s time to consider child-free living,” he says. “Pregnancy is a risk.”

As is the rest of parenthood—something I realized on day one. There are so many unknowns. My son, Lennox, now 10 months old, was born during an ice storm, in an unplanned, lightning-fast, somewhat terrifying home birth. It wasn’t at all what we’d expected, but he arrived robust and healthy.

Bolusmjak and Faghfoury’s daughter, now six months old, is also thriving.Though both Faghfoury and I had envisioned how our labours would go, in the end it was completely out of our control—and that’s how our children’s futures will be, too: what foods they’ll grow to love and hate, whether they’ll be late walkers or early talkers, whether they’ll be outgoing or shy, and which unforeseen health problems they might encounter as they get older.

My guess is that their daughter will be particular and science-minded, like her parents, while our son will be prone to messiness and winging it, like Steve and me. But we’ll have to wait to find out. What I hope for, most of all, is that they’ll both be safe and well.

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