Preterm Labour and Delivery

Introduction

Although preterm deliveries constitute a small proportion of all births, their contribution to serious complications, especially those leading to perinatal death and morbidity, is hugely disproportionate. In 2010 it was estimated that 14.9 million babies worldwide (around 11.1% of all births) were premature. Globally, preterm birth is the single biggest cause of neonatal death. Babies born at ‘term’ (conventionally considered to be 37−42 weeks of gestation) have consistently better outcomes than those born ‘preterm’, with the risk of neonatal mortality and morbidity rising exponentially as the gestation of delivery decreases. Preterm labour is the single biggest cause of preterm birth, so that effective ‘treatment’ of preterm labour could have a major impact on global perinatal health. Such treatments include those aimed at preventing or halting preterm labour and those that improve outcomes for babies of women in preterm labour. After decades in which there were few effective therapies, some promising strategies are emerging, which improve outcomes in a subset of women and babies. Despite this, the global toll of the adverse effects of preterm birth continues to rise, with preterm labour remaining the single biggest cause of neonatal mortality and morbidity in resource-rich countries.

Definition

The definition of preterm birth is not without controversy. The ICD10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision) definition of preterm labour is the onset (spontaneous) of labour before 37 weeks of gestation ( http://apps.who.int/classifications/icd10/browse/2010/en#/O60 ),thus preterm birth under this definition is considered to be birth before 37 completed weeks of gestation. This definition remains unchanged in ICD11, due to be published in 2019. The lower gestational limit is not defined under this system, although the WHO recommends that all babies born with any signs of life should be considered live births (and hence would be included). The lack of a consensus about the lower limit of preterm birth causes problems in comparing data among countries, with many countries (including Scotland, the USA and Brazil) not defining their lower gestational limit, some (such as Switzerland and Denmark) using a lower limit of 22 weeks and others (including Australia and Canada) using 20 weeks as the lower gestational limit of preterm birth. Thus a woman who delivers a baby at 21 weeks with no signs of life would be likely to be considered to have had a miscarriage in Switzerland and Denmark, and probably in the majority of countries with no defined lower limit, but would be considered to have had a stillbirth in Australia and Canada. The birth would be defined as a preterm birth in the latter two countries but not the former two. Comparisons are further complicated by the use in some countries of low birth weight as a surrogate for preterm birth: this is inappropriate because not all small babies are preterm, and not all preterm babies are small. Lastly, due to the phenomenon of delayed ovulation, where ultrasound is used to estimate gestational age (as is common in many resource-rich countries), the calculated mean duration of pregnancy is consistently shorter, and the rate of prematurity is around 20% higher, than when gestation is calculated from the date of the last menstrual period.

A recent report by the Global Alliance to Prevent Prematurity and Stillbirth has highlighted that similar aetiologies (albeit in different proportions) are involved in a pregnancy loss in the second trimester and in the mid third trimester, and that the risk of adverse outcome for the neonate decreases progressively as gestation advances, even beyond 37 weeks’ gestation. They propose a new definition and classification system whereby preterm birth would be ‘any birth (which includes stillbirths and pregnancy terminations) that occurs after 16 weeks’ gestation and before term (i.e. 39 weeks’ gestation). The complete population of preterm deliveries within the gestational range as described earlier includes live births, stillbirths, multiple pregnancies, pregnancy terminations, and newborn infants with congenital malformations. The recommendation from this group is that ‘gestational age estimation should, whenever possible, be corroborated by an early, high quality ultrasound and the best obstetric estimate be used for all gestational age determinations’.

Preterm Labour Versus Preterm Birth

The focus of this chapter is preterm labour, although this is not the only pathway to preterm birth. A categorization of (spontaneous) preterm labour, preterm prelabour rupture of membranes and elective (induced) preterm birth has been widely used, with Scottish data suggesting that the proportions of each (amongst all singletons delivering preterm) are 62%, 15% and 23% respectively. Villar proposes that preterm birth is defined by pathway to delivery (spontaneous or care giver initiated) AND signs of initiation of parturition (evidence of initiation of parturition (including preterm prelabour rupture of membranes) or no evidence of initiation of parturition) AND the presence of significant fetal, maternal or placental pathological conditions. Under this classification, both preterm labour and preterm prelabour rupture of membranes would be considered to have evidence of initiation of parturition, whereas elective (induced) preterm birth would not. The pathway to delivery would be spontaneous in women presenting in preterm labour and those with preterm prelabour membrane rupture (because oxytocin augmentation of contractions is also considered in the spontaneous category) but would be care-giver initiated in women undergoing elective (induced) preterm birth.

Incidence of Preterm Birth

Despite much effort, there has been little fall in preterm birth rates globally over the last 20 years. In Scotland in 2017, 6.4% of singleton babies were born before 37 completed weeks’ gestation; these rates have been fairly constant for the last 20 years ( Fig. 2.1 ). Rates in the USA for 2017 were higher, at 9.8%. Globally, preterm birth complications account for an increasing proportion of under-5 deaths, with a population-attributable fraction [95% confidence intervals] of 25.3% ([21.7–28.7], 0.478 million [0.394–0.552]) in 2015.

Aetiology and Mechanisms

The ‘cause’ of preterm labour is incompletely understood. Preterm labour is often accompanied by one or more of the following pathologies: intrauterine infection, intrauterine inflammation, utero-placental ischaemia, utero-placental haemorrhage, uterine stretch and maternal stress. It is not possible to determine whether these events ‘cause’ preterm labour, although there is strong circumstantial evidence of the role of intrauterine infection and inflammation. This is firstly because, even using relatively insensitive culture techniques, around 25–40% of women in preterm labour have demonstrable intrauterine infection. The proportion rises progressively as gestational age of labour onset declines. Secondly, intrauterine infection/inflammation stimulates an inflammatory response, including production of prostaglandins, implicated in increasing cervical ripening and myometrial contractility. Lastly, in animal models, intrauterine injection of microorganisms or proinflammatory agents (such as lipopolysaccharide) is effective in stimulating preterm labour.

Risk Factors

The risk factors associated with preterm labour are listed in Table 2.1 .

Outcomes

There is a clear inverse dose−response relationship between gestation of preterm birth and risk of perinatal death, with outcomes being worst in babies born at earlier gestational ages, and the nadir not being reached until 40 weeks’ gestation. For example, UK data show 40% of babies who are live born at 24 weeks’ gestation survive to discharge from hospital, rising through 66% at 25 weeks to 77% at 26 weeks. Babies who survive preterm birth also have a greater incidence of morbidity, and again this is inversely proportional to gestational age at delivery. For example, in the EPICure study (a prospective cohort of around 300 children who were born before 25 weeks’ gestation in 1995, and who survived to reach the neonatal unit), 49% had neuromotor or sensory (sight or hearing) disability (with 23% of the total having severe disability) when assessed at 30 months of age, and the remainder had no disability according to the study criteria. Subsequent studies have confirmed a ‘dose dependent’ effect of prematurity on long-term adverse health outcomes, which is inversely proportional to gestational age at delivery. As with death, the nadir of ‘prematurity’ on educational attainment at school is not reached until birth at 40 weeks of gestation, suggesting that even those who apparently have ‘no disability’ suffer long-term adverse consequences of prematurity. Although there was no change in disability rates amongst survivors between 1995 and 2006, babies born extremely preterm were more likely to survive, suggesting improvements in perinatal care.

Prediction

A major goal of obstetric research is to be able to identify predictive factors for preterm birth by evaluating asymptomatic women in the first half of pregnancy. Although clinical risk factors for preterm labour have been identified, and predictive tests proposed, no strategy is sufficiently effective to be in widespread use in clinical practice. One of the most widely used clinical indicators, history of spontaneous preterm birth in a previous pregnancy, is associated with likelihood ratios of 4.62 (95% confidence interval [CI] 3.28–6.52) and 2.26 (95% CI 1.86–2.74) respectively for birth before 34 and 37 weeks’ gestation in a subsequent pregnancy. The most widely used and the most effective tests for preterm labour prediction in asymptomatic women are detection of fetal fibronectin (fFN) in vaginal fluid and cervical length measurement. The predictive ability of these strategies varies with the gestation of testing, the definition of a positive test (e.g. the length of the cervix or the quantitation of the fFN) and the gestation of delivery being predicted. Typical summary likelihood ratios from meta-analyses of a range of studies are shown in Table 2.2 . There is some evidence that fFN testing reduces the risk of preterm birth, with odds ratios of 0.54 (95% CI 0.34–0.87), although no benefit in terms of reduction in adverse outcomes was seen. Newer tests are continually being proposed and evaluated – each of cervicovaginal fluid prolactin and proteome profile and matrix metalloproteinase-8 in amniotic fluid shows promise, but they require further studies to define their efficacy.