As every expecting parent learns to their dismay, modern medicine cannot accurately predict when your baby will arrive. The optimistically named “due date” is, from a predictive standpoint, fiction. Only 5% of births occur on the actual due date, and about two-thirds fall within a week before or after the due date.
Not knowing when baby will arrive can be intensely frustrating, and not just because all your friends and family keep calling asking for status updates. Having a baby is a major life event, and it might occur at any moment. Or not. This uncertainty makes securing a care for older children, planning your social calendar, and deciding when to start maternity leave a nightmare.
And those are just the usual hassles. For the 1 in 10 women in the U.S. who deliver prematurely (before 37 completed weeks of pregnancy), medicine’s inability to predict labor’s onset is a far more serious problem. One that is tremendously costly and can lead to lifelong disabilities.
The high costs of premature birth
Preterm birth costs the U.S. healthcare system an estimated $31 billion a year. And despite major medical advances in preemie care over the last 40 years, early birth remains the leading cause of death in newborns, and the second leading cause of death in children under age 5.
More preemies survive today than just a few decades ago. But many survivors suffer long-term complications.
The earlier the birth, the higher the risk. Roughly a third to a half of preemies born before 28 weeks suffer from long-term disabilities, such as blindness, deafness, cerebral palsy, chronic lung disease, and developmental delays. These complications are common enough that preterm birth is the leading cause of childhood disability in the U.S.
For prevention, we need prediction
Roughly two-thirds of preterm births begin with spontaneous early labor or early rupture of the amniotic sac surrounding the baby (commonly known as water breaking or leaking).
(The remainder are medically induced because of pregnancy or fetal complications.)
Here’s the rub: If we could just identify who would give birth early, we could intervene early in pregnancy to lower their risk. Giving progesterone to at-risk women may cut their risk of early delivery in half. The use of cervical pessary, a medical device used to close the cervix, may also lower women’s risk.
(Note to pregnant women: Research has not shown bed rest as effective at preventing preterm labor, according to a recent Cochrane meta-analysis).
Our current prediction tools are not good enough
Right now, the two tests that are sometimes used to predict risk for preterm delivery—ultrasound measurements of the length of the cervix and detection of fetal fibronectin (a protein) in cervical fluid—miss the critical window for intervention. These tools are helpful for diagnostics after a woman presents with signs of preterm labor. But they are not accurate enough to serve as screening tools before labor starts.
The so-called risk factors approach is also inadequate. For starters, the list of potential risks factors is long—extreme chronic stress, experiencing domestic abuse, poverty, a lack of education, infections, gum disease, infections, smoking, and drug use—and many women with these risk factors have healthy, full term pregnancy.
A few women have an identifiable high risk of preterm birth. Women carrying twins have a roughly 50% chance of delivering early; those carrying triplets have an over 90% chance. And women with a prior preterm birth have a 14-15% chance of delivering early again.
Unfortunately, these women with an easily identifiable risk represent only a fraction of the women who deliver early: 30 and 40% of women who deliver early are first-time mothers; and 80% carry only a single baby.
So how do we catch all the women who have no idea they are at risk of preterm delivery until the day their water breaks or labor starts? This question is finally getting some of the attention it deserves.
Researchers are hunting for hormones and scraps of DNA in women’s blood that might augur early birth. The furthest of along of these efforts, the PreTRM® test developed by Sera Prognostics, recently received approval from New York State. The PreTRM® test uses blood-based proteins to identify women at high risk for preterm birth. In their a study of over 5,000 low risk women carrying singletons, their test accurately identified 75% of the women who experienced a spontaneous preterm birth.
Researchers at Stanford, led by Stephen Quake, PhD, professor of bioengineering and of applied physics at Stanford and Mads Melbye, MD, visiting professor of medicine, are also hot on the trail of a preterm birth risk assessment based on the cell-free DNA found in pregnant women’s blood.
We applaud these efforts, but alone they are insufficient
Knowing who is likely to give birth early is certainly key, but so is determining when early labor will occur.
I learned this when a close friend’s water began leaking, at the end of her second trimester. She was not yet in labor, and no one could tell her when it might begin. It could be within hours or take a month or longer, the doctors told her. The uncertainty was terrible. She had no idea what kind of complications to prepare for, or whether her baby would face a several months long stay in the NICU and was likely to survive without serious disabilities.
The strain on expecting parents is terrible. But knowing when labor will begin is also critical medically. Two interventions need to be timed to in the days before preterm birth: corticosteroid shots and, for preemies born at less than 32 weeks, magnesium sulfate.
Since the 1990s, we have known that babies whose mothers received corticosteroids for at least 24 hours before birth have better fetal lung development, fewer long-term complications, and a dramatically improved chance of survival. But if more than a week elapses between the steroids and birth, the benefits fade. Since repeatedly giving steroids may worsen long-term neurocognitive outcomes, ideally steroids are a one-shot deal.
The timing of magnesium sulfate is similarly critical. Magnesium sulfate, sometimes known simply as “The Mag”, is notoriously unpleasant. It is given for a variety of indications, including to slow down labor and to prevent seizures in women with preeclampsia. And it seems to help protect preemies’ fragile brains. Receiving infusions shortly before birth lowers babies’ risk of cerebral palsy and neurocognitive delays.
Unlike corticosteroids, magnesium sulfate can be repeatedly administered, but, because magnesium competes with calcium in the fetus’s rapidly forming bones, giving The Mag for more than 5-7 days raises a baby’s risk for weak bones.
In short, when it comes to intervention, timing is critical. Knowing who will go into preterm labor is incredible valuable. Knowing when is another equally important piece of the puzzle.
The Bloomlife Research team is tackling this final piece of the puzzle. We are working to turn labor contraction data into clinical diagnostic tools that detect preterm labor. The work is still in early days, but we are excited to contribute to the fight against premature birth. Read more about our ongoing research initiatives HERE.
