New Zealand research could pave the way for a new, safe treatment for babies whose growth in the womb is stunted by problems with the placenta. The research team have also discovered a possible basis for a blood test for mothers that could identify at-risk babies in utero.
Fetal growth restriction is usually linked to problems with the placenta that mean the fetus does not get enough nutrients and oxygen. It affects 5-10 percent of babies, or 25 million per annum globally (3,000-6,000 in New Zealand).
Currently, there is no treatment except to induce birth early, but babies born premature carry a greater risk of problems with growth, learning, and adult diseases such as obesity and diabetes than babies born at term. Babies who did not grow properly in utero are also more at risk of being stillborn or dying shortly after birth.
Researchers at the University of Auckland-based Liggins Institute and the University of Otago injected a growth factor called insulin-like growth factor-1, or IGF1, into the amniotic fluid surrounding growth-restricted sheep fetuses. Their findings, published today in the Journal of Physiology, are the first to show that not only does IGFI boost growth in late pregnancy, it has no negative effects on survival rates or health and development in the two weeks following birth.
“There was a risk that the placenta would be unable to meet the increased demands of the larger fetus during periods of stress, such as labour, so our findings are reassuring,” says study lead Professor Frank Bloomfield, director of the Liggins Institute.
IGF1, a naturally occurring growth-promoting hormone, has previously been shown to improve fetal growth in mammals, but this was the first study to look at its long-term effects. The team tracked the lambs’ growth and hormonal functioning into adulthood, and those yet-to-be published findings will fill in the picture.
“Then the next step would be to test this potential treatment in at-risk pregnant women,” says Professor Bloomfield.
“A treatment that improved growth, presumably through improving placental function as the animals do not show any signs of getting more compromised, would mean that growth-restricted babies may be able to stay in the womb longer. This could be a very important factor for improving long-term outcome, as it is preterm delivery that is the major problem for these babies.”
The researchers also discovered that a placental hormone in the mother’s blood (called NTproCNP) is linked with levels of oxygen the fetus receives – a key indicator of fetal wellbeing – and with size at birth.
Currently, oxygen levels can be measured only by methods that put the fetus at risk and, at most, only half of the cases of fetal growth restriction are picked up in utero. Health professionals generally rely on routine measurements of the mother’s belly to identify growth issues and then use ultrasound to get a measure of the fetal wellbeing.
“A blood test that could detect a biomarker for fetal wellbeing would be a huge benefit – simple, non-invasive, quick and inexpensive,” says Professor Bloomfield, who is also a neonatologist at National Women’s Health, Auckland City Hospital.
The researchers also found that growth factor treatment affected males and females differently following birth. For example, treated male lambs were smaller at birth than a control group of lamb newborns who did not have restricted growth, but treated female lambs were in the same size range as controls.
Professor Bloomfield says the differences are in keeping with an emerging picture of sex differences in early development, and may mean that potential treatments need to be finessed according to the baby’s sex.
The other researchers were Ana-Mishel Spiroski, Dr Mark Oliver, Dr Anne Jaquiery and Professor Jane Harding from the Liggins Institute, and Dr Tim Prickett and Professor Eric Espiner from the University of Otago Department of Medicine.
The study was funded by the Health Research Council.