Stillbirth rates

The UK rate of stillbirth is 4.16 per 1000 total births [6]. This mortality rate is higher than that reported by other high‐income countries, where worldwide estimates show an average stillbirth rate (at 28 weeks’ gestation) of 3.5 per 1000 births (Fig. 29.1). There are 2.6 million stillbirths globally, with more than 7178 deaths daily [2]. The majority of deaths occur in developing countries, with 98% occurring in low‐ and middle‐income countries.

Significant regional differences in the stillbirth rate have been noted [7]. The variation in stillbirth rates may primarily reflect multicultural differences, with women in lower socioeconomic groups having twice the stillbirth risk compared with women from higher socioeconomic groups. Unfortunately, there are significant variations in data collection, definitions (especially gestational age cut‐offs) and research methodology that make direct comparisons between countries difficult. Furthermore, variations in access to termination of pregnancy services impact on stillbirth rates that is difficult to account for. Regions with the highest stillbirth rates have some of the most significant limitations in data quality [8]. The number of stillbirths has reduced more slowly than has maternal mortality or mortality in children younger than 5 years, which were explicitly targeted in the Millennium Development Goals [9, 10].

The fact that regional and national differences in stillbirth rate exist and appear to be related to wider factors impacting on women’s health suggests that reduction in the rate of stillbirth is possible and potentially a useful indicator of improving socioeconomic and healthcare systems. This is published as the annual rate of reduction, and allows comparison over time of the stillbirth rate within one region or country.

Classification of stillbirth

Broadly, stillbirths may be divided into those associated with intrapartum or antepartum death, with further stratification by gestational age. Globally, about half of all stillbirths occur in the intrapartum period, representing the greatest time of risk. The estimated proportion of stillbirths that are intrapartum varies from 10% in developed regions to 59% in South Asia [2,11].

The aetiology of stillbirth is multifactorial and despite intensive investigation of potential causes, many cases remain unexplained. Another complicating factor is that often more than one condition may contribute to stillbirth in an individual case (e.g. preterm rupture of membranes with infection in a fetus with polyhydramnios secondary to gastrointestinal obstruction). Additionally, conditions may be associated with stillbirth without directly causing them (well‐controlled gestational diabetes and a cord event).

Several classification systems for causes of stillbirth have been developed. No single classification system is universally accepted as each has its own strengths and weaknesses. There are additional sources of confusion when considering the challenge of classification. First, the definition of stillbirth varies among investigators, countries, health organizations and classification schemes. Second, many systems are designed to classify perinatal mortality and therefore by definition include both stillbirths and neonatal deaths. It is likely that stillbirth and neonatal death have many similar, overlapping but distinct sets of disease states. However, aetiologies for neonatal death may not be relevant to intrauterine fetal demise, for example at 20 weeks of gestation. Additionally, classification systems can include a single aetiology, which is problematic given the complexity of stillbirth, and means that a single distinct cause cannot be attributed to the majority of cases.

A recent systematic review identified 81 systems for classification of causes of stillbirth [12]. Many of these different systems have been developed for different purposes, for example to attribute the most likely cause as part of counselling for grief and future pregnancies, or to assist clinicians in defining best practice, or to develop strategies for the prevention of stillbirth through health service organizational changes. Consequently, the different classification systems prioritize information in different ways, which means they are not directly comparable.

There are national and international drivers to reduce the stillbirth rate. One of the key factors that has been highlighted is the importance for healthcare systems of understanding the changes and measures that need to take place to improve stillbirth rates, by studying attributable causes over time. To facilitate this, a uniform system of classification is required. The perfect system does not exist given the complexity of the aetiology of stillbirth. The UK has recently adopted the Frøen–Codac 2009 classification system [13] for use in national perinatal mortality surveillance. This classification system has been shown to record the primary cause of 46–47% of all stillbirths as ‘unknown’ [14, 15]. This system is designed to be applicable to high and low socioeconomic nations and involves detailed recording and sub‐analysis.

Alternative classification systems include Wigglesworth [16] (66.2% of stillbirths remain unexplained) and relevant condition at death or ReCoDe [17] (Table 29.1). The latter classification mentions the coding of primary and secondary ‘causes’ of stillbirth, the goal being to identify the relevant conditions present at the time of death in utero. It is a hierarchical classification where the hierarchy starts from the conditions directly affecting the fetus and moves ‘outward’ in anatomical groups. These authors emphasize the important contribution of fetal growth restriction, with approximately 50% of stillbirths associated with fetal growth restriction. The ReCoDe classification may be able to assign a cause for 85% of cases of stillbirth.

Aetiology

Stillbirth has multiple associated maternal and fetal risk factors (Table 29.2). In two‐thirds of pregnancies that result in stillbirth, more than one factor is known to be associated with stillbirth and so it is often unclear what the actual cause of death is.

Several risk factors for stillbirth are present prior to pregnancy, including parity, ethnicity, socioeconomic status and mental health problems. Interestingly, the risk for stillbirth and parity is bimodal, with both nulliparity and a parity of three or higher being risk factors for stillbirth. It is likely that the root cause of stillbirth with parity is different in the nulliparous and multiparous woman and that different strategies will be required to address them [18]. In the UK, mothers of African, African‐Caribbean and South Asian ethnic origins have been shown to have a higher risk of stillbirth than women of Caucasian origin. First‐generation migrants, regardless of ethnic origin, also have a higher risk of stillbirth than women born in and brought up in the UK. Maternal age appears to have a bimodal distribution, with pregnancies in women younger than 25 and older than 35 years of age being at greater risk for stillbirth.

One of the main risks for stillbirth is presumed placental dysfunction, which commonly results in impaired fetal growth [3] Very low birthweight (less than 3rd centile) is associated with a 10‐fold increased risk of stillbirth [19]. Although placental dysfunction is not currently modifiable, recognition of the association between fetal growth rates and stillbirth allows risk stratification of pregnancies, with greater surveillance of pregnancies with intrauterine growth retardation and consideration of elective delivery timed to allow an appropriate balance between the risk of stillbirth and infant mortality [20].

Specific population attributable risk (PAR) factors for stillbirth have also been defined. The PAR factor score indicates the relative increase in risk of stillbirth associated with specific risk factors when applied to women in higher income countries. PAR factors are particularly important as many of them are potentially modifiable and the score indicates the increased risk of stillbirth related to the risk factor [10] (Fig. 29.1). Key risks include maternal infection, hypertension, diabetes mellitus, underlying chronic diseases as well as nutrition, obesity and smoking. Cigarette smoking is strongly associated with increased risk of stillbirth, with a PAR factor score of 7%. Smoking is known to result in fetal growth restriction, and although the mechanism is uncertain it may be due to an impact on placental function. Cessation of smoking during early pregnancy has been demonstrated to reduce the incidence of intrauterine growth restriction, premature birth and stillbirth [21]. Early pregnancy smoking cessation programmes are therefore important for the health of both mother and child.

Maternal obesity is a particularly important modifiable risk factor. Obesity is associated with a PAR score of 8–18%. Conversely, maternal age over 35 and maternal smoking both had PAR scores of around 7%. The risk of stillbirth is doubled among women with the highest body mass index (BMI) category (2.19, 2.03–2.36) compared with women with a normal BMI. Several pregnancy complications associated with maternal obesity, notably gestational diabetes and pre‐eclampsia, have been implicated in fetal death and stillbirth [22]. The method by which obesity leads to stillbirth is unclear, although there are a number of potential mechanisms and it is likely that obesity has its effects via multiple pathways simultaneously [23]. It is well described that obesity during pregnancy increases the risk of gestational diabetes mellitus as well as hypertensive disorders, both pre‐existing and gestational. Both gestational diabetes and hypertension are established risk factors for stillbirth [24]. A recent publication from MBRRACE suggests that some cases of stillbirth could have been avoided if gestational diabetes had been diagnosed early at the screening stage and managed appropriately. In some cases of stillbirth, had the pregnancy been screened adequately for gestational diabetes, the stillbirth might have been avoided [15]. Obesity also increases the risk of hyperlipidaemia during pregnancy. Hyperlipidaemia reduces prostacyclin secretion and enhances peroxidase production. This in turn results in vasoconstriction and platelet aggregation and may contribute to pre‐eclampsia through this mechanism [24]. Other conditions such as sleep apnoea are more common in obesity and obese pregnant women have more extended periods of snoring, more apnoea–hypoxia events, and more episodes of oxygen desaturation during sleep than non‐obese pregnant women. It is possible that this greater tendency towards sleep apnoea and its consequent hypoxia reduces oxygen delivery to the fetus, thereby increasing the risk of stillbirth [25]. Women with obesity may be less able to perceive changes in fetal movement than women with a normal BMI and it has been suggested that this may lead to delayed presentation with a fetus at risk of antepartum death. Obese women may also experience more difficulty with labour and delivery, and monitoring during labour can be technically challenging in obese women.

Socioeconomic factors are also important in the aetiology of stillbirth. In the UK, pregnancies in women living in areas with the highest levels of social deprivation are over 50% more likely to end in stillbirth or neonatal death compared with births from the least deprived areas [5]. For women who are first‐generation immigrants living in socially deprived conditions, the risk of stillbirth is more than twice the rate of stillbirth in women born in the UK, even from the same socioeconomic class and ethnic background [26]. The reasons for this difference are likely multifactorial. There is a greater incidence of obesity, poor nutrition and smoking in the population of women from deprived economic backgrounds and women who are socially disadvantaged are less likely to receive adequate antenatal care. A common factor underlying many stillbirths – the absence or low quality of antepartum and intrapartum care – means that referral for increased supervision is less likely to occur [27].

Finally, domestic abuse is an important aetiological factor. The mechanisms by which domestic abuse contributes to increased perinatal mortality are not fully understood. One possible pathway is a direct effect of blunt physical trauma causing disruption to the placenta and fetal death. A second possible mechanism is elevated maternal stress levels and poor nutrition, both of which are associated with low birthweight or preterm delivery and are well‐known risk factors for perinatal and infant mortality. Thirdly, and probably most importantly, a woman who is experiencing domestic abuse may have particular difficulties accessing and using antenatal care services. Ensuring that women who suffer from domestic abuse are able to access antenatal care is a key consideration when designing antenatal care pathways [28].

Diagnosis of intrauterine fetal demise and antepartum stillbirth

Women with intrapartum stillbirth may present with diminished sensation of fetal movements, although it is more common for women to present with a condition associated with intrapartum stillbirth such as pre‐eclampsia, chorioamnionitis and placental abruption. Diagnosis of intrapartum fetal death cannot be made clinically or on the basis of cardiotocography. The diagnosis of intrapartum fetal death should only be made by real‐time ultrasonography. Ultrasound is required to demonstrate absent fetal cardiac activity [29]. Ultrasound may additionally demonstrate Spalding’s sign (collapse of the fetal skull with overlapping bones) or fetal hydrops. Ultrasound is less reliable at detection of occult placental abruption.

Once the diagnosis has been confirmed, the parents can be told prior to delivery, which allows them to be prepared for the stillbirth. It is important to acknowledge emotional responses for all the caregivers following a diagnosis of stillbirth [30]. Telling parents about the diagnosis must be made in a clear and empathic manner. The manner in which the diagnosis is communicated remains with parents and affects the subsequent grief response. One large systematic review demonstrated that responses from parents and staff were often related: the behaviours and actions of staff have a memorable impact on parents while staff described emotional, knowledge and system‐based barriers to providing effective care [31].

Management of antepartum stillbirth

In the absence of issues regarding maternal well‐being, the choice of induced delivery or waiting for spontaneous labour must be given to couples following the diagnosis of intrauterine fetal demise. Waiting for spontaneous labour carries risks, including maternal disseminated intravascular coagulation (DIC) and chorioamnionitis. The risk of DIC is 10% if the intrauterine death occurred within 4 weeks and rises to 30% after 4 weeks. Maternal haematology, including platelet count, fibrinogen and coagulation studies, should be regularly monitored for the development of DIC [32].

Because of the risk of complications, women should be counselled that induction of labour is generally the safest option and that vaginal delivery is likely the best option for those planning subsequent pregnancies. Induction of labour using mifepristone has been shown to reduce the time from the start of induction until delivery for women in the third trimester. For women with a second‐trimester intrauterine fetal death and an unripe cervix, vaginal misoprostol has been shown to be more effective than intravenous oxytocin at inducing labour [33]. However, it is important to note that misoprostol remains unlicensed in the UK for the induction of labour for second‐trimester intrauterine death. For women with a previous caesarean section, or uterine scar from other surgery, there is limited evidence to help guide the management of induction of labour. Although most of the evidence of significant risks of induction of labour in women with previous uterine surgery relate to adverse fetal outcomes rather than adverse maternal outcomes, induction of labour following fetal demise using prostaglandin is considered reasonable [34]. Although misoprostol is associated with increased risk of uterine rupture, using lower doses (25–50 µg) will reduce this [35]. An alternative to pharmacological induction of labour is mechanical cervical ripening. This may reduce the risk of uterine rupture from pharmacological agents but the risk of infection and subsequent maternal morbidity may increase [36,37].

Legal considerations following stillbirth

The current law on stillbirth registration is set out in the Births and Deaths Registration Act 1953, amended by the Still‐Birth (Definition) Act 1992. The legal definition of stillbirth is ‘any child expelled or issued forth from its mother after the 24th week of pregnancy that did not breathe or show any other signs of life’.

A fully registered doctor or midwife must medically certify stillbirth; the doctor or midwife must have been present at the birth or examined the baby after birth. HM Coroner must be contacted if there is doubt about the status of a birth and the police should be contacted if there is suspicion of deliberate action to cause stillbirth. In the UK referrals to the coroner should also occur for an apparently fresh stillbirth not attended by a healthcare professional or should there be any concern regarding potential for criminal act, such as common assault.

Fetal deaths delivered later than 24 weeks that had clearly occurred before the end of the 24th week do not have to be certified or registered. The baby can be registered as indeterminate sex awaiting further tests.

Within the UK, the mother (or father if the couple were married at the time of birth) is responsible for registering the stillbirth, normally within 42 days (21 days in Scotland) but with a final limit of 3 months for exceptional circumstances. Routine birth and parental information is required to register the birth and the birth is entered onto the Stillbirth Register, which is separate from the standard Register of Births. The parents are then issued with a Certificate of Stillbirth and the documentation for burial or cremation. A certificate for cremation cannot be issued before the registration.

Stillbirths are currently not routinely covered by coronial law, except in Northern Ireland. There are examples of parents who have petitioned for the circumstances surrounding the death of their baby to be referred to the coroner (or procurator fiscal in Scotland) when parents have felt that local hospital reviews were inadequate. In some such cases, the coronial reports have highlighted vital gaps in quality of care [38].

Lactation suppression

Suppression of lactation is of psychological importance for some women following the loss of their baby. Simple measures such as a supportive bra, ice packs and analgesics can be used, but up to one‐third of women using these measures will experience severe breast pain [39]. It is important to ascertain the mother’s wishes: many women desire to suppress lactation, while some women wish to make altruistic donations to breast milk banks.

A single dose of cabergoline (1 mg) seems to be as effective as bromocriptine (2.5 mg twice daily) for 14 days [40] for lactation suppression. Dopamine antagonists may cause transient hypertension and therefore may be contraindicated in patients with hypertension [41].

Psychological aspects

The death of a baby is a profound loss [42]. The grief following the death of a baby may be different from other types of bereavement. From the moment that the pregnancy has been confirmed, the parents envision an entire lifetime for themselves and their baby. These expectations develop during the pregnancy and with the death of their baby, parents lose an entire future [43]. It is important to acknowledge the necessary grief of families and offer appropriate individualized support [44, 45].

There is considerable interpersonal variation in grief and mourning. This is true for different family members and issues can arise between partners when they cannot synchronize their grief and this subsequently may be a source of interpersonal and relationship stress. Ultimately, this results in a significantly increased risk of relationship breakdown between the parents following stillbirth [46, 47].

Bereavement is also a significant risk factor for development of psychiatric illness. Among mothers, the relative risk of being hospitalized for any psychiatric disorder is highest during the first year after the death of the child but remains significantly elevated 5 years or more after the death [48].

Multiple pregnancy with loss of one of the babies presents particular emotional challenges for families. Parental attachment to surviving babies is often difficult and approximately one‐third of couples experience difficulties coping at home following the birth [49]. Informal and formal support for bereaved couples should be offered [50].

Follow‐up investigations

Understanding how or why their baby has died can help the parents in their grieving process. Any findings can be used to inform the parents if there is a risk to future pregnancies and the level of this risk and can help identify any additional treatment or surveillance in any future pregnancy. All parents should be offered investigations to help determine the cause of the stillbirth whilst respecting their wishes.

The Royal College of Obstetricians and Gynaecologists (RCOG) has a suggested list of investigations [29].

• Serological investigations include maternal haematological studies and routine biochemistry (may help diagnose and manage pre‐eclampsia and its complications, sepsis and intrahepatic cholestasis of pregnancy and identify diabetes), Kleihauer test (fetal–maternal haemorrhage in addition to dose of anti‐RhD gamma‐globulin), and maternal infection screen (parvovirus B19, rubella, cytomegalovirus, herpes simplex and Toxoplasma gondii and others as indicated). Thrombophilia and antiphospholipid screening is currently recommended, although the association between inherited thrombophilias and intrauterine fetal demise is uncertain.
  
• Antibody screening and anti‐Ro and anti‐La antibodies will be indicated if there is concern regarding fetal anaemia or hydrops. Parental screening for fetal/neonatal alloimmune thrombocytopenia will be indicated if there is evidence of otherwise unexplained fetal bleeding.
  
• Cytogenetic analysis should be offered (especially if there is evidence of dysmorphic features or a congenital anomaly) either from samples taken at the time of post‐mortem or from the placenta or cord at delivery [51].
  
• Histopathological examination of the placenta is recommended in all cases of stillbirth. Although some reports find causal or contributory placental abnormalities in up to 60% of stillbirths, the significance of such findings in many cases remains uncertain [52].

Parents should be offered full post‐mortem examination to help explain the cause of an intrauterine fetal demise as this can provide more information than other (less invasive) tests and can sometimes be crucial to the management of future pregnancies [53]. Post‐mortem may not be acceptable to parents because of individual, cultural or religious beliefs and their decision must be respected. Alternative options to invasive post‐mortem may be considered, including post‐mortem MRI and tissue diagnostics [54,55]. Written consent must be obtained for any invasive procedure on the baby, including tissues taken for genetic analysis. Consent should be sought or directly supervised by an obstetrician or midwife trained in special consent issues and the nature of perinatal post‐mortem.

Large‐scale studies involving health economics are needed to determine which investigations are most appropriate after stillbirth [56].

Management of a future pregnancy and prevention

There is limited evidence to help guide the timing of subsequent pregnancy. Historical data suggested that pregnancies occurring within 6 months of a stillbirth were associated with increased risks of preterm birth, low birthweight and small‐for‐gestational‐age babies and outcome. However, couples should be reassured that the absolute risk remains low [].

Two interventions may assist in reducing stillbirth: firstly, smoking cessation advice should be offered if indicated and, secondly, overweight women (BMI >30 kg/m²) should be advised to lose weight [60, 61]. Further advice on adequate nutrition and a healthy lifestyle may also reduce subsequent stillbirth. Global strategies that have been advocated in addition to the above include screening and treatment of syphilis, presumptive treatment for malaria, insecticide‐treated mosquito nets, birth preparedness, access to emergency obstetric care, caesarean section for breech presentation, and elective induction for post‐term delivery [62].

In a future pregnancy, couples should be offered pregnancy care in a specialist unit with access to obstetrician‐led care. Management of the pregnancy will depend on the history of the loss, for example reducing risk of pre‐eclampsia by low‐dose aspirin, serial growth scans to assess fetal growth in cases of suspected growth restriction and/or pre‐eclampsia, and cervical length assessment and possible cervical cerclage in cases of preterm labour.

Early term induction of labour may be offered especially in cases of previous pre‐eclampsia and where there are placental issues including placental abruption, while acknowledging the limited evidence base for this practice [63].

The management of the subsequent pregnancy is important as there is an increased recurrence risk of pre‐eclampsia and placental abruption following a stillbirth [64,65]. Additional psychological support is often required [50]. There may also be a delayed grief reaction and an effect on mother–baby bonding [66].

Internationally, there is a focus on reducing the stillbirth rate. The Every Newborn Action Plan has the target of 12 or fewer stillbirths per 1000 births in every country by 2030; 94 mainly high‐income countries and upper middle‐income countries have already met this target, although with noticeable disparities [9, 67].

Whilst the social and societal benefits in reduction of stillbirth are obvious, the cost–benefit analysis also shows that there may be a significant return on investment for interventions to reduce the number of stillbirths. Improvements in maternal, newborn and child health services could generate as much as 10‐fold to 25‐fold returns in economic and social benefits [68]. A Lancet series makes the case for a more than triple return on investment for prevention of stillbirths, in reducing maternal deaths, newborn deaths and stillbirths. The economic and social benefits associated with reductions in stillbirths compared with the cost of the interventions to achieve this reduction make a powerful case for healthcare investment into this aspect of maternity care [69].