Epidemiology of stillbirth

Stillbirth is defined as delivery of a baby in the perinatal period, which fails to show any signs of life. The definition of the start of the perinatal period varies between countries. In the USA, it is 20 weeks of gestational age (wkGA) and in the UK, it is 24 wkGA . The rate of stillbirth in high-income countries varies from 1.3 per 1000 to 8.8 per 1000 with an average of 3.5 per 1000 . The clear majority of stillbirths in high-income countries is the result of intra-uterine foetal death before the onset of labour (antepartum stillbirth) . Deaths occurring during labour (intrapartum stillbirths) account for 5–10% of all stillbirths in high-income countries, but account for a much larger proportion of losses in low- and middle-income countries (LMICs) . A range of maternal characteristics has been associated with the risk of stillbirth. One of the most systematic and methodologically sound analyses of such risk factors was performed by the NICHD’s Stillbirth Collaborative Research Network . Their analysis of risk factors identifiable at the start of pregnancy is tabulated ( Table 2 ).

Causes and classification of stillbirth

Aside from the sub-division of stillbirths into intrapartum and antepartum, losses can also be classified according to the presumed cause. However, this process is complicated by the fact that relatively few losses have a completely understood cause of death. The remainder have varying degrees of uncertainty in the mechanism(s) leading to death. This is illustrated in Figure 1 in relation to ascribing cause of death in the presence of a range of maternal medical conditions.

Representation of the continuum of uncertainty in ascribing cause for stillbirth, using the example of losses associated with maternal medical conditions. ALT denotes alanine transaminase; GA denotes gestational age. Reproduced with permission from a report of an NICHD workshop (Reddy et al., Obstet Gynecol 2009;114:901–914).

A diverse – if not bewildering – array of classification systems have been developed . One of the main characteristics which determines variation between the systems is the extent to which they will attribute a given associated condition or finding as being the cause of death. For example, an unexpected and unexplained stillbirth of an infant at 39 weeks where the baby’s birth weight was on the second percentile for sex and GA might be defined as unexplained in one classification system and as being due to foetal growth restriction (FGR) in another. In a sense, both classifications are correct. The actual cause of death is unknown; hence, the loss is strictly unexplained. However, it is known that birth weight <3rd percentile is associated with a 10-fold risk of stillbirth at term . Hence, it is very likely that the baby’s death was related to its size. The subject of classification of stillbirth is reviewed in detail elsewhere .

In the context of screening, one of the key associations for stillbirth is poor foetal growth. It is estimated that ∼30–50% of stillbirths are associated with low birth-weight percentile, and this is assumed to reflect FGR, which in turn presumed to be related, in a large proportion of cases, to placental dysfunction . This association is important in the context of screening, as a number of tools exist to quantify both foetal growth and placental function.

Clinical factors associated with stillbirth risk

Reduced foetal movements (RFMs) are one of the key symptoms associated with the risk of stillbirth. This subject has been reviewed in detail elsewhere . Failure of medical and midwifery staff to respond appropriately to RFMs was one of the other major potentially preventable causes of stillbirth in the MBRRACE-UK review described above . The RCOG (Royal College of Obstetricians and Gynaecologists) in the UK has issued a guideline for the management of women who present with reduced movements . Another major symptom associated with stillbirth risk is antepartum haemorrhage. In the absence of placenta praevia or cervical pathology, this is likely to represent bleeding from the placenta and may be a harbinger of later abruption. Finally, acquired disorders of pregnancy (such as GDM or pre-eclampsia) could be associated with maternal symptoms. Management is based on specific testing for the condition in question.

Response to women with symptoms associated with stillbirth risk

At preterm GAs, foetal monitoring is indicated. Generally, the first line of assessment is cardiotocography (CTG, also called a non-stress test in the USA). Interestingly, the RCOG guideline on RFMs does not recommend computerised CTG , which uses objective analysis of the trace, including computerised assessment of beat-to-beat variability. However, the Cochrane reviews do not indicate any benefits of using non-computerised CTG (and a trend towards harm) compared with using nothing, and a reduced risk of perinatal death using computerised CTG analysis compared with non-computerised CTG (for review, see Smith 2015) . Hence, computerised CTG is a reasonable first step. The next level of assessment is an ultrasound scan. The ultrasound scan is performed if other risk factors are present, and can also be performed in low-risk women who are presenting with their second (or greater) episode of RFMs. The key evidence-based measurement in high-risk pregnancies is Doppler flow velocimetry of the umbilical artery. However, generally, foetal biometry and amniotic fluid measurement would also be performed, sometimes with additional Doppler measurements (middle cerebral artery). The evidence base supporting these supplementary measurements is poor: this is a key area for further research and multiple recommendations of the prioritisation exercise for stillbirth research touched on this area.

At term, induction of labour should be considered for women presenting with RFMs. At 37–38 weeks, induction is still associated with increased risks of perinatal morbidity and should only be offered if foetal assessment is non-reassuring, there are other risk factors or if there have been multiple episodes of RFMs. However, perinatal outcome is optimal at 39–41 weeks and induction should be considered for any women presenting with RFMs at ≥39 weeks. Epidemiological evidence showed that universal induction at 39 weeks would reduce overall rates of stillbirth . However, for women with a single episode of RFMs, who have no other risk factors, and who want to avoid intervention, it is reasonable not to induce labour, as the absolute risk of stillbirth is likely to be <1%. The basis for this statement is that the background risk of stillbirth at term is one to two per 1000, and it is unlikely that a single episode of RFMs in an otherwise low-risk woman is associated with a >5-fold risk of stillbirth.