Could a new drug prevent premature births?

About 50,000 babies are born prematurely every year in the UK and although survival rates have improved in recent years, modern medicine has still not found a way to prevent babies from being born too early. But this long-running quest may be a step closer to its goal with the discovery of a pathway that links premature labour to infection.

The normal human gestation period is 40 weeks from the first day of the woman’s last period (38 weeks from the moment that sperm and egg meet), and a premature birth is defined as one that occurs before the 37th week, ie, at least three weeks early.

The earlier a child is born, the smaller and less developed they will be and the greater the dangers they face. Human babies are designed to be ready to meet the outside world after spending somewhere between 38 and 42 weeks in the protective environment of the womb and those born earlier will struggle to deal with challenges such as keeping warm, breathing and fighting infection.

Thanks to recent advances in neonatal medicine, the outlook for premature babies has never been better — but 1,500 still die every year in the UK. Many more have to spend weeks, sometimes months, in intensive care and risk being left with long-term disabilities such as cerebral palsy, learning difficulties, blindness and deafness.

The earlier a baby is born, the greater the dangers. At one end of the spectrum, those born after 32 weeks rarely develop serious problems, while at the other, about half of all babies born between 23 and 25 weeks will be left with some form of long-term disability. The youngest surviving premature baby so far, Amillia Taylor, was born in America in 2007 after 21 weeks, six days and weighed less than 10oz (280g).

There are numerous risk factors associated with premature labour, ranging from abnormalities of the cervix that make it difficult for the womb to hold a pregnancy, to trauma and strenuous physical exertion. Smokers, people who abuse drugs and women with a high caffeine intake are also more likely to have their baby early, as are those carrying twins and anyone who has had a previous pre-term labour.

Maternal wellbeing is important during pregnancy and women with conditions such as kidney disease, diabetes and pre-eclampsia are at higher risk, too — although doctors may induce labour in many of these women, or perform a Caesarean section, because the risks to mother and baby of continuing the pregnancy outweigh the risks of being born early.

The link with infection is well established and the likes of malaria, HIV and the bacterium mycoplasma account for the lion’s share of premature births across the globe. But in developed countries the causative infections are often more subtle, ranging from urinary tract infections (“cystitis”) and common sexually transmitted diseases (STDs) to low-grade infections of the cervix and womb that don’t even cause symptoms.

There has been a lot of interest in recent years in the link between symptom-less infections and the risk of premature labour. Bacteria in and around the womb (most pregnant women have some bacteria in the womb) can trigger an inflammatory cascade that leads to a build-up of chemicals that trigger labour. These chemicals include prostaglandins — the very hormones contained in the pessaries that doctors use to induce labour artificially.

Recent research has centred on the use of antibiotics to treat underlying symptom-less infections, but the results are mixed. There is now a consensus that, while antibiotics should be used to treat obvious problems such as urinary tract infections and STDs, and may be helpful in women whose waters have broken early, they are of no benefit in delaying labour in women whose waters are intact. Indeed, there is some evidence that they may actually be harmful.

So if killing the bacteria responsible for low-grade infections is not the solution, what about trying to block the inflammatory process that leads to the production of labour- inducing chemicals? This is the approach taken by a team of researchers from Imperial College London, who announced this month that they have found a means to block the pathway that leads to the production of inflammatory proteins.

Research is continuing but the findings could lead to the development of a drug to delay the onset of premature labour — something that has so far proved remarkably elusive. We already have drugs (tocolytics) that can delay the inevitable but their effects tend to be short-lived and they generally buy only enough time to facilitate the transfer of a woman to a hospital with a special care baby unit, and for doctors to give her drugs (steroids) to help to mature her baby’s lungs. The extra time gained may be small but in very pre-term labours a delay of 24 to 48 hours can improve a baby’s chance of survival.

Bed rest used to be standard advice but is now thought to do more harm than good. Although physical overexertion can bring on labour, there is no evidence that bed rest makes any difference to the outcome in women who are showing signs of early labour; on the other hand it does increase the risk of complications such as blood clots.

In fact, there is not much that a woman can do except avoid “lifestyle triggers” such as smoking and report worrying symptoms to her midwife — the most obvious being that her waters have broken, or that she has started contractions.

Fortunately, most women who think that they are starting premature labour are actually having Braxton-Hicks contractions. Unlike real contractions, these tend not to be painful, should not last for more than an hour at a time and are just a sign that your womb is practising for the big day, which hopefully should still be some way off.

The Imperial College study was funded by the children’s charity Action Medical Research and you can find more details at www.action.org.uk.

by : Dr Mark Porter
Source : www.timesonline.co.uk