Placenta’s alarm clock signals when it’s time for birth to begin

Time to push? The moment when pregnancy ends and giving birth begins appears to be controlled by the set of membranes surrounding the fetus, which act like a clock. Drugs that slow down or speed up the clock could help ensure more babies are born close to the standard 40 weeks, giving more infants a fighting chance at life.

Every year, about 15 million babies around the world are born prematurely, before 37 weeks of gestation. The underdeveloped organs of these babies put them at risk of a range of disorders, and a million die before their first birthday. Premature births account for 8 per cent of infant deaths in the UK and 11 per cent in the US, making it the single biggest cause of infant mortality.

On the other hand, an overly long pregnancy comes with its own risks. Deliveries after 42 weeks are more likely to be stillbirths – probably because the placenta doesn’t survive long enough to support the developing fetus at that point. “Timing is extremely important,” says Ramkumar Menon of the University of Texas in Galveston.

Menon and his colleagues are working on a way to ensure babies are born at the right moment, by understanding how normal, full-term births take place. Some theories have already been put forward. Levels of a hormone called CRH increase closer to the time of birth. This hormone controls others, such as oestrogen and progesterone, which also play important roles in birth: they trigger contractions and widen the cervix.

But there must be more to it, says Menon. “It is highly unlikely that one hormone can trigger such a complex process,” he says.

Internal clock

His team thinks the membranes surrounding the fetus act as an alarm clock, ringing off the end of pregnancy and the start of labour. This sac ages as the fetus grows, says the team. By the time the baby is ready for birth, the sac has become so aged that it starts to become inflamed, setting off a chain reaction. As inflammation spreads from the fetal sac to a woman’s uterus, the inflammatory chemicals start wreaking havoc – changing the way hormones act to halt the maintenance of pregnancy and start contractions.

The idea is supported by various threads of evidence. Fetal sac tissue taken from a woman who has given birth naturally shows plenty of signs of ageing under a microscope. But tissue taken from a woman who has just had a caesarean birth, performed before the 40 weeks of pregnancy is up, looks younger. Research in mice also suggests that inflammation builds up as the pregnancy draws to an end.

“The model is very logical and compelling,” says Rebecca Jones at the University of Manchester, UK.

A better way?

Menon’s team has identified a potential cause of the ageing – a protein called p38 MAP kinase, which acts as a “stress signaller”. Ageing tissue activates the protein, which then causes more ageing in a vicious circle. Drugs that act to block the protein might be useful in preventing preterm births, says Menon.

Andres Lopez Bernal at the University of Bristol in the UK cautions that using drugs like this could have unintended side effects. “These proteins are notably promiscuous,” he says. P38 alone interacts with 600 other chemicals and receptors, he says. “You would definitely need selective drugs that act on the uterus or cervix.”

But Jones thinks that, if treatment could be targeted to the right organs, p38 inhibitors could be a good idea. Drugs that activate the protein, on the other hand, might be useful in initiating labour. “At the moment, women who don’t go into labour will be induced at 42 weeks, sometimes using a little hook to rupture the membranes,” says Jones. “There might be a better way. This is an exciting new direction.”

Read more: Premature birth: How its effects can stay with you for life; Being born early is now the chief cause of infant death; World’s most premature baby set to leave hospital