At first, the infant, mewling and puking in the nurse’s arms
Fussing babies were the least worry of mothers and nurses in Shakespeare’s day. Infant mortality was high – indeed, in an age that was ignorant of the need for good hygiene, weaning was risky, especially in hot weather, when foods might be tainted. In a vast number of cases, it led to death.
Today, the overwhelming majority of infants in Canada are healthy. Infant mortality rates have dropped significantly over the past century; the rate is currently six per 1,000 births, according to the Canadian Institute of Child Health, compared with the late 1800s, when one in 10 children died in their first year of life. The decrease is due to major strides in medical care, including advances in care for premature babies, sound nutrition, immunization, cleaner water, and improved plumbing and sewage control, says Dr. Hugh O’Brodovich, chair of the department of paediatrics.
Modern public health policies have resulted in thriving infants who would have been miracle babies in Elizabethan times. Similarly, recent developments in maternal-fetal medicine have created what to the modern onlooker may seem like “sci-fi babies.” For example, a small number of fetuses are being operated on inside the uterus for such disorders as heart defects, spina bifida and diaphragm malformations. “These are highly experimental procedures, and they’re not being done in any Toronto hospitals, because of questionable outcomes,” says Dr. Knox Ritchie, chair of the department of obstetrics and gynaecology. Operations that are performed in Toronto include interventions to repair lung and urinary tract malformations.
High-tech interventions are highly dramatic – and extremely expensive. Do the results justify the costs, especially when funds for cancer treatment and home care for the elderly are limited? When it comes to resource allocation, “the more relevant debate is over the resources directed toward very premature babies,” says Dr. Ritchie. For example, he says the leading centre dealing with premature births in the Netherlands has decided to stop the active intensive treatment of babies born before 25 weeks’ gestation. The decision was based on research showing that many infants born at 23 and 24 weeks didn’t survive, and of those who did, half had severe physical or mental handicaps by the age of two.
While fetal screenings may not be as dramatic as fetal surgery, they are imperative tools: Sharon Vanderwerff (BA 1991 New College) was 36 weeks pregnant with her first child when her doctor noticed she had extremely high blood pressure and all the signs of early labour. She immediately sent Vanderwerff to Mount Sinai Hospital’s high-risk pregnancy clinic for an ultrasound. When the technician took a long time examining her, then left to fetch a doctor, Vanderwerff thought, “Something’s wrong.” Her instincts were right. The scan showed that the baby’s brain lacked a corpus callosum – the tissue that connects the brain’s two hemispheres, allowing it to develop and grow.
Later, tests at Mount Sinai and the Hospital for Sick Children revealed that baby Alexis, born in March of 1997, was afflicted with a rare disorder – she had a gene mutation that hampered the production of energy in her cells and prevented her from developing properly.
Given the severity of the baby’s condition, Vanderwerff and her husband, Blake Melnick (BEd 1992), decided against experimental genetic treatments. Instead, they took their baby home, where she died eight months later. “Our decision was to make sure our daughter had a very good quality of life as opposed to a quantity of life,” says Vanderwerff. “It wasn’t life at all costs.”
Dr. David Chitayat, head of Mount Sinai’s prenatal diagnosis and medical genetics program and medical director of U of T’s master’s program in genetic counselling, helped rule out some genetic conditions in Alexis. He explains the challenges of examining a baby prenatally: “We are just peeking from a keyhole into the pregnancy through certain devices, trying to tell the parents if the baby is fine or not.” Some of the tools he uses to peek through that keyhole are nuchal translucency screening, which provides risk figures for Down syndrome and other chromosomal abnormalities; maternal serum screening, which screens for the risk of Down syndrome and spina bifida; and ultrasounds, which, at 19 weeks gestation, can detect about 80 per cent of structural abnormalities.
Chitayat is also trying to track the outcome of different chromosome abnormalities – especially sex-chromosome abnormalities – that are detected prenatally, through long-term follow-up of patients. Ultimately, all of his work aspires to answer a couple’s two biggest questions after the birth of a baby with an abnormality: What lies ahead for our baby? And are we at risk in future of passing along a genetic condition?
There is a second chapter to Vanderwerff and Melnick’s story. Alexis’s skin biopsy results allowed doctors to pinpoint the gene mutation associated with the enzyme deficiency. That meant when Sharon became pregnant just before Alexis died, the fetus could be checked for Alexis’s condition. “If the tools were there to help us to know if we would have another child born with a terminal illness, we were going to use them,” says Vanderwerff. “We would not knowingly go through what we went through again.”
But there was one catch: because Alexis’s condition was so rare, a medical screening test wasn’t available. Instead, a scientist at Sick Kids worked from ground zero, running DNA sequences to determine if the gene mutation was present. The tests came back negative: the fetus had only a three per cent chance of having the syndrome.
In November 1998, Vanderwerff gave birth to a healthy baby girl named Parker Grace. In May, the couple had their third daughter, Rowan Alexis. Each girl carries part of Alexis Parker’s name – a legacy from a sister who helped forecast their own health.
Finding another piece of the cystic fibrosis puzzle
U of T researchers have discovered yet another piece in the puzzle of cystic fibrosis (CF), a chronic inherited disease that typically reveals itself in childhood. The condition causes abnormal secretion of mucus and can lead to severe respiratory problems as well as other health concerns. The newest finding is a defective protein that appears to cause a milder form of the disease (pancreatic-sufficient CF), which affects 10 to 15 per cent of CF patients.
According to lead researcher Dr. Charles Deber, a professor of biochemistry and senior scientist at the Hospital for Sick Children, the protein, called CFTR, regulates the balance of salt (sodium chloride) moving across cell membranes in the lungs and pancreas. In the milder form of CF, segments of this protein stick together, interfering with the flow of chloride in and out of the cell.
The finding, which was published recently in the scientific journal Nature Structural Biology, means scientists can now begin research that could lead to new drug treatments. “We will look for molecules that could possibly break up the abnormal bond that is causing the protein strands to stick together,” says Dr. Deber.
This latest discovery builds on years of cystic fibrosis research by scientists at the Hospital for Sick Children, including the discovery of the CF gene in 1989 by Dr. Lap-Chee Tsui, professor of molecular and medical genetics at U of T.
Understanding pre-term labour
It is estimated that between five and 10 per cent of babies born in Canada come into the world prematurely. These fragile, medically compromised infants account for 70 per cent of neonatal deaths.
Those born before 28 weeks have a 40 times greater chance than full-term babies of having such problems as cerebral palsy, motor or mental disabilities, blindness or lung disease, according to Stephen Lye, co-head of the development and fetal health program at Mount Sinai’s Samuel Lunenfeld Research Institute, and a professor of obstetrics, gynaecology and physiology. There are not only short-term medical costs (keeping a baby alive in a neonatal intensive-care unit can cost $3,000 a day), but also long-term expenses to the health-care system if a baby has a chronic disability, he says.
Why are some babies in such a hurry to be born? One reason for the rise in pre-term labour is the increase in multi-fetal pregnancies. This is due not only to assisted reproduction, but also to advanced maternal age – women are tending to have babies later in life, and older women have a greater chance of ovulating more than one egg at a time, says Lye.
Lye, who also holds a Canada Research Chair in fetal, neonatal and maternal health, is looking into genetic factors that may cause premature births. When a woman goes into labour, the muscle of her uterus moves from a dormant state to a highly active one, and Lye suspects that certain genes must be expressed or “turned on” before this happens. He is trying to identify those genes and understand how they are regulated. “If we know why they’re turned on in labour, then we may be able to turn them off and allow the uterus to stay quiet till full term,” he says.