Pre-Term Birth

Introduction

Pre-term birth is defined as birth before 37 weeks’ completed gestation. It occurs in around 10% of births and affects 15 million pregnancies worldwide annually. Almost one-third of pre-term births in the United Kingdom are iatrogenic (following deliberate medical intervention) when the risks of continuing the pregnancy, for either the mother or the baby, outweigh the risks of prematurity.

Prematurity is the leading cause of perinatal morbidity and mortality; pre-term birth is responsible for over a quarter of all neonatal deaths. Prematurity is associated with significant early neonatal morbidity, including ischaemic brain injuries, necrotising enterocolitis, retinopathy and respiratory distress syndrome. Later pre-term births are associated with neurodevelopmental delay in the infant and in adulthood with metabolic conditions, including diabetes and hypertension. The resultant short- and longer-term medical needs of these individuals have huge economic implications for health systems worldwide. While there is substantial morbidity with early pre-term births, there are far greater numbers of moderate to late pre-term births, which contribute a greater overall burden to health care systems. Prematurity is a global issue. However, there is stark contrast in mortality between countries, with 90% of extremely pre-term infants dying in low-resource settings versus 90% survival in high-resource settings, where advanced neonatal care is available.

Research into the definitive mechanisms involved in pre-term labour and its prevention has proven to be a difficult task. As a result, prematurity is one of the most challenging problems facing obstetricians and neonatologists.

Definitions

• Pre-term : Birth at gestation of less than 37 completed weeks

• Late pre-term : Birth at gestation between 34 ⁺⁰ and 36 ⁺⁶ completed weeks

• Moderately pre-term : Birth at gestation between 32 ⁺⁰ and 33 ⁺⁶ completed weeks

• Very pre-term : Birth at gestation between 28 ⁺⁰ and 31+6 completed weeks

• Extremely pre-term : Birth at gestation of less than 28 completed weeks

• Pre-term labour : Regular uterine contractions accompanied by effacement and dilatation of the cervix before 37 completed weeks’ gestation

• Pre-term pre-labour rupture of the membranes (PPROM) : Rupture of the fetal membranes before 37 completed weeks’ gestation, at least 1 hour before the onset of labour

Aetiology and Predisposing Factors

Around two-thirds of pre-term births are following spontaneous pre-term labour, with the remainder physician indicated. However, many of the conditions triggering decision to perform iatrogenic pre-term birth overlap with those causing spontaneous pre-term labour. The observed precursors to pre-term birth are heterogenous, as listed in Box 29.1 , and are likely multifactorial.

Inflammation has emerged as a potential unifying feature, with localised release of cytokines and proteases potentially triggering cervical ripening, rupture of amniotic membranes, and initiation of uterine activity. Progesterone acts as an endogenous tocolytic and is functionally suppressed by cytokines. Bacterial infection – and, thus, inflammation, both intra- and extrauterine – carries a significant risk of pre-term birth, whilst non-infective inflammatory conditions such as uterine stretch (polyhydramnios, multiple pregnancy) and antepartum haemorrhage are also associated with pre-term birth. Fetal and maternal stressors, including fetal growth restriction and maternal depression, are known to be associated with pre-term birth.

Identifying Women at Increased Risk of Pre-Term Birth

A number of strategies have been proposed to identify women who have an increased risk of pre-term birth. These include clinical risk scoring, cervical assessment and the measurement of fetal fibronectin (fFN). The available strategies, as outlined later, are moderately useful in identifying at-risk women and targeting interventions but better at helping to avoid unnecessary intervention in low-risk women.

Whilst a number of risk-scoring systems have been devised based on the recognised risk factors, none has been shown to be reliably effective in the prediction of pre-term birth. The strongest association is a history of previous pre-term birth, increasing this risk of recurrent pre-term birth by up to 5 times. Across the United Kingdom, there has been an increase in the provision of specialist antenatal care for women with risks for pre-term birth, which can help provide tailored antenatal care and surveillance.

Cervical insufficiency affects around 1% of pregnancies, and is associated with almost 10% of mid-­trimester losses. Cervical length measurement is a ­useful tool in risk stratification. A normal cervical length in pregnancy, when measured by transvaginal ultrasound, is between 34 and 40 mm and with no funnelling at the internal os ( Fig. 29.1 ). Women with a cervix less than 25 mm in length can be considered at risk. The predictive value is best when applied to an already at-risk population rather than a mixed population; therefore, screening is advocated only in women with other significant risk factors for pre-term birth. Up to half of women with a cervical length under 25  m will remain pregnant beyond 34 weeks. fFN is an adhesion molecule involved in maintaining the integrity of the choriodecidual extracellular matrix. It is usually not detectable on a high vaginal swab of cervicovaginal secretions after 20 weeks until term or membrane rupture; thus, if it is found to be present, it implies disruption of the matrix. Whilst most useful in stratifying women with symptoms of threatened pre-term labour, fFN has potential to be useful in asymptomatic women. A positive fFN in an asymptomatic woman confers a 14 times relative risk of birth before 32 weeks’ gestation. The sensitivity is optimal when used in a high-risk population (e.g., women with previous pre-term birth). However, good-quality data on effectiveness in clinical practice are lacking. Other biomarkers are also available; however, fFN is the best characterised and most widely used in the United Kingdom.

Screening for vaginal infection has been considered to be a method to identify those at high risk of pre-term labour but is not routinely done in the low-risk, asymptomatic population. Bacterial vaginosis, which is present in 10% to 20% of pregnant women, is associated with a doubling of the odds of pre-term birth if identified in the third trimester. Unfortunately, clinical trials have demonstrated that the risk of pre-term labour is unchanged after treating bacterial vaginosis. In those considered to have other risk factors for pre-term labour, it is reasonable to treat bacterial vaginosis if identified, rather than screen asymptomatic women.

Prevention of Pre-Term Labour

The aim of the following interventions is to improve the perinatal morbidity and mortality associated with pre-term birth. Research is ongoing to see whether women treated with these interventions to prolong gestation have corresponding improvements in long-term outcomes for their children.