The prevention and treatment of pre-term labour is important to reduce adverse events for the baby.

PRE-TERM is the leading cause of death in the first week of life (neonatal mortality) in most developed and middle-income countries. Pre-term labour precedes 40 to 50% of pre-term births. It is important to recognise that pre-term labour is not the only way that results in pre-term birth; many pre-term births are preceded by either medical or obstetric problems.

Although pre-term labour is defined as regular contractions that occur before 37 completed weeks of pregnancy, associated with changes in the cervix, babies born before 34 weeks experience most mortality and handicap, if they survive. Babies born pre-term are more likely to have problems breathing, feeding, and regulating temperature as well as other problems. The likelihood of these problems arising is greater, the more pre-term a baby is.

Happy mums-to-be: Expecting mothers bumping bellies as they joke around during a baby shower in Las Vegas, Nevada. Many pre-term births are preceded by either medical or obstetric problems.

Risk factors

There are several factors that increase the risk of pre-term birth. They include:

> Maternal age – the risk is highest among the youngest and oldest mothers (below 15 and above 45 years). Mothers aged 25 to 29 years are at lowest risk.

> Socio-economic status – there is a significant association between decreasing affluence and the risk of pre-term delivery.

> Previous pre-term delivery increases the risk of a subsequent delivery also being pre-term by three times.

> Inter-pregnancy interval – an interval of six months or less between the first delivery and the second conception increases the risk of having a pre-term second delivery by two times.

> Multiple pregnancy – compared to single babies, babies of multiple births are eight times more likely to be born pre-term.

> Smoking – the rate of low birth weight delivery is twice among current smokers than in former or non-smokers.

> Pregnancy hypertension increases the risk of pre-term delivery by four times.

Diagnosis

The diagnosis of pre-term labour is difficult. The progressive opening up (dilatation) of the cervix is probably the only conclusive proof of labour. Even the demonstration of amniotic fluid draining from the vagina is associated with progressive labour in about 20% of cases.

Many tests to identify women at risk of pre-term labour have been proposed and evaluated. Only ultrasound and foetal fibronectin have been shown to have benefit. Ultrasound to determine cervical length, foetal fibronectin testing or a combination of both may be useful in determining which women are at high risk of pre-term delivery. The usefulness of ultrasound and foetal fibronectin may rest mainly with their ability to identify women who are least likely to deliver. Foetal fibronectin testing may be useful, when there are symptoms of pre-term labour, to identify those with negative values and a reduced risk of pre-term birth, thus avoiding unnecessary intervention.

Management

In about 80% of women with presumptive pre-term labour, pre-term delivery will not occur. Many factors influence the decision to intervene when there are symptoms of pre-term labour. They include the probability of progressive labour, duration of pregnancy and the risks of treatment. Historically, the criteria for determining when intervention is needed included regular contractions that do not diminish with bed rest or hydration, changes in the cervix during an observation period, or a cervix that is dilated on admission. However, all these criteria are inaccurate predictors of pre-term delivery.

It is reasonable not to use medicines to stop pre-term labour (tocolytic), as there is no clear evidence that they improve mortality or serious morbidity. However, tocolysis should be considered if the few days gained would be put to good use, such as completing a course of corticosteroids or transfer of the mother with the baby in utero to a hospital with facilities for premature babies.

The use of antenatal corticosteroids reduces the incidence of respiratory distress in pre-term babies. There is also an associated reduction of the risk of neonatal death and brain haemorrhage. The effect of corticosteroids is optimal if the baby is delivered more than 48 hours and less than seven days after the start of treatment.

Tocolytics that are used to inhibit labour between 24 and 33 weeks of pregnancy may permit a delay in delivery of at least 48 hours. The greatest benefit is gained by using the delay to administer measures that will benefit the baby.

> Beta-agonists like salbutamol, terbutaline and ritodrine have proven efficacy in delaying delivery for 24 hours, 48 hours and seven days. However, they are associated with a large number of maternal side effects like palpitations, tremors, nausea, vomiting, headache and chest pain. Rare but potentially life threatening adverse effects has been reported with beta-agonists. Caution is needed when beta-agonists are used in those who have medical or obstetric conditions like suspected heart conditions, diabetes mellitus, thyrotoxicosis and pregnancy hypertension.

> Atosiban, an oxytocin receptor antagonist, is effective in delaying delivery for 48 hours and seven days. Atosiban and beta-agonists have comparable effectiveness. However, atosiban has substantially fewer maternal side effects especially cardiovascular side effects.

> Indomethacin, a cyclo-oxygenase inhibitor, when compared with tablets that do not contain any medicine (placebo) appears to significantly delay delivery for 48 hours and seven days. Although there are fewer side effects than beta-agonists, concerns have been raised about its safety with observational studies suggesting possible increased rates of brain haemorrhage, enterocolitis, transient impairment of kidney function and premature closure of ductus arteriosus. Recently, interest has focused on cyclo-oxygenase type 2 inhibitors as potential tocolytics. Their efficacy is unproven and at present, their use is confined to clinical trials.

> Calcium channel blockers like nifedipine appear effective in delaying delivery for more than 48 hours. A theoretical risk of adverse effects on foetal or placental circulation following nifedipine exposure has been suggested but this has not been confirmed with clinical data. Further information about its safety is required.

> Nitric oxide is a potential tocolytic and has been compared with ritodrine in a clinical trial. Further evaluation is needed before it can be recommended for routine clinical use.

Antibiotics are not recommended if it is prescribed for the sole purpose of preventing pre-term delivery. Currently, it seems prudent to follow protocols for antibiotic prophylaxis against early onset group B streptococcal infection, but there is little evidence that this approach will prolong pregnancy.

Conclusions

Pre-term labour poses a diagnostic and therapeutic dilemma for the doctor. There is still no clear evidence that tocolytics improve outcome following pre-term labour and so it is reasonable not to use them. The main effect of tocolytics when used in pre-term labour is to reduce the numbers who deliver within seven days of starting the medicines. There is insufficient evidence for reliable conclusions about substantive effects on mortality or serious morbidity.

If a tocolytic medicine is required, atosiban or nifedipine appear preferable as they have fewer side effects and comparable effectiveness. Atosiban is licensed for this usage but nifedipine is not. Further evidence is required about the relative effects of these two medicines on substantive outcomes like neonatal mortality and morbidity, and on safety and long-term outcome for the baby.

The doctor will discuss with the patient the current situation in knowledge about pre-term labour and its management. The patient’s preferences and that of her spouse will be taken into account in determining the management of pre-term labour.

Source: Dr Milton Lum