In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Classification of evidence levels (1++ to 4) and grades of recommendations (A–D) are defined at the end of the "Major Recommendations" field.
What Is the Optimal Method for Diagnosing Late Intrauterine Fetal Death (IUFD)?
D - Auscultation and cardiotocography should not be used to investigate suspected IUFD.
D - Real-time ultrasonography is essential for the accurate diagnosis of IUFD.
What Is the Best Practice for Discussing the Diagnosis and Subsequent Care?
B - Discussions should aim to support maternal/parental choice.
D - Parents should be offered written information to supplement discussions.
Many strategies have been described for discussing bad news. Late IUFD poses particular difficulties as it is often sudden and unexpected. A crucial component is to determine the emotional feelings and needs of the mother and her companions. This empathetic approach seeks to identify and understand women's thoughts and wishes but without trying to shape them. Women with an IUFD and their partners value acceptance and recognition of their emotions highly. [Evidence level 3]
The developers concluded that carers should neither persuade parents nor make assumptions that would limit parental choice. Initial discussions can be used to emphasise choice in decision making. [Evidence level 2]
Investigation of the Cause of Late IUFD
What Are the General Principles of Investigation?
D - Clinical assessment and laboratory tests should be recommended to assess maternal wellbeing (including coagulopathy) and to determine the cause of death, the chance of recurrence and possible means of avoiding further pregnancy complications.
C - Parents should be advised that no specific cause is found in almost half of stillbirths.
B - Systems that use customised weight charts and capture multiple contributing factors should be used to categorise late IUFDs.
An important purpose of investigation is to assess maternal wellbeing and ensure prompt management of any potentially life-threatening maternal disease. This includes a detailed history of events during pregnancy and clinical examination for pre-eclampsia, chorioamnionitis and placental abruption. There is also a moderate risk of maternal disseminated intravascular coagulation (DIC): 10% within 4 weeks after the date of late IUFD, rising to 30% thereafter. This can be tested for by clotting studies, blood platelet count and fibrinogen measurement. [Evidence level 3]
Are There Any Special Recommendations for Women with an IUFD Who Are Rhesus D (RhD)-Negative?
C - Women who are RhD-negative should be advised to have a Kleihauer test undertaken urgently to detect large feto–maternal haemorrhage (FMH) that might have occurred a few days earlier. Anti-RhD gammaglobulin should be administered as soon as possible after presentation.
C - If there has been a large FMH, the dose of anti-RhD gammaglobulin should be adjusted upwards and the Kleihauer test should be repeated at 48 hours to ensure the fetal red cells have cleared.
D - It is important to know the baby's blood group; if no blood sample can be obtained from the baby or cord, RhD typing should be undertaken using free fetal DNA (ffDNA) from maternal blood taken shortly after birth.
What Tests Should Be Recommended to Identify the Cause of Late IUFD?
A - Tests should be directed to identify scientifically proven causes of late IUFD.
Commonly associated antepartum conditions include congenital malformation, congenital fetal infection, antepartum haemorrhage, pre-eclampsia and maternal disease such as diabetes mellitus. The common causes of intrapartum death include placental abruption, maternal and fetal infection, cord prolapse, idiopathic hypoxia–acidosis and uterine rupture. [Evidence level 3]
Transplacental infections associated with IUFD include cytomegalovirus [Evidence level 2+], syphilis [Evidence level 1+] and parvovirus B19 [Evidence level 2++] as well as listeria [Evidence level 2+], rubella [Evidence level 3], toxoplasmosis [Evidence level 2+], herpes simplex [Evidence level 2+], coxsackievirus, leptospira, Q fever, and Lyme disease. Malaria parasitaemia has also been associated with stillbirth (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3–4.1) [Evidence level 2++].
Ascending infection, with or without membrane rupture, with Escherichia coli, Klebsiella, Group B Streptococcus, Enterococcus, mycoplasma/ureaplasma, Haemophilus influenzae and Chlamydia are the more common infectious causes in developed countries. Other infections are either historical causes or common only in developing countries. [Evidence level 2+]
Table 1 in the original guideline document summarises the diagnostic tests available, their indications and value and the evidence to support their use.
What Precautions Should Be Taken When Sexing the Baby?
B - If there is any difficulty or doubt, rapid karyotyping should be offered using quantitative fluorescent polymerase chain reaction (QF-PCR) or fluorescence in situ hybridisation (FISH).
What Is Best Practice Guidance for Cytogenetic Analysis of the Baby?
D - Samples from multiple tissues should be used to increase the chance of culture.
D - More than one cytogenetic technique should be available to maximise the chance of informative results.
D - Culture fluid should be stored in a refrigerator and thawed thoroughly before use.
Karyotyping is important as about 6% of stillborn babies will have a chromosomal abnormality. [Evidence level 3]
Some abnormalities are potentially recurrent and can be tested for in future pregnancies. Culture potentially provides the greatest range of genetic information (trisomies, monosomies, translocations, major deletions and marker chromosomes). Microdeletions have to be requested specifically, usually according to the result of any postmortem examination. If all cultures fail, QF-PCR can be performed on extracted DNA. [Evidence level 2+ extrapolated]
Many laboratories are moving towards DNA-based methods for routine chromosome analysis, avoiding the need for cell culture. It is a reliable (<0.01% failure rate), efficient and cheap technique for detecting common aneuploidies. It provides slightly less detailed limited genetic information and is unreliable for the detection of translocations and marker chromosomes. [Evidence level 2++ extrapolated]
A range of tissue types can be used (see below), but all cell cultures can fail. [Evidence level 3]
Contamination with bacteria is an avoidable reason for failure to obtain results. [Evidence level 2++ extrapolated]
Culture fluid containing antibiotics can reduce this risk. Perinatal specimens suitable for karyotyping include skin, cartilage and placenta. Skin specimens are associated with a higher rate of culture failure (~60%), twice that of other tissues, including placenta. Placenta usually has the advantages of being the most viable tissue and of more rapid cell culture, but the disadvantages of maternal contamination and placental pseudomosaicism. The next best is cartilage, e.g., patella, but cartilage is harder to sample. Amniocentesis can also provide cytogenetic results if the mother chooses expectant management, but patient acceptability and safety (infection) of amniocentesis has not been investigated in this setting. [Evidence level 3]
Placental biopsy (approximately 1 cm diameter) should be taken from the fetal surface close to the cord insertion (to avoid tissue of maternal origin). Skin biopsy should be deep to include underlying muscle (about 1 cm in length from the upper fleshy part of the thigh). The skin can be closed with wound adhesive strips and tissue adhesives, but this is less successful when the baby is severely macerated.
What Is the Guidance on Perinatal Postmortem Examination for Maternity Clinicians?
C - Parents should be offered full postmortem examination to help explain the cause of an IUFD.
C - Parents should be advised that postmortem examination provides more information than other (less invasive) tests and this can sometimes be crucial to the management of future pregnancy.
D - 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 postmortem, including retention of any tissues for clinical investigation, research and teaching.
D - Pathological examination of the cord, membranes and placenta should be recommended whether or not postmortem examination of the baby is requested.
D - The examination should be undertaken by a specialist perinatal pathologist.
D - Less invasive methods such as needle biopsies can be offered, but these are much less informative and reliable than conventional postmortem.
D - Ultrasound and magnetic resonance imaging (MRI) should not yet be offered as a substitute for conventional postmortem.
D - Magnetic resonance imaging can be a useful adjunct to conventional postmortem.
Labour and Birth
What Are the Recommendations for Timing and Mode of Birth?
C - Recommendations about labour and birth should take into account the mother's preferences as well as her medical condition and previous intrapartum history.
D - Women should be strongly advised to take immediate steps towards delivery if there is sepsis, pre-eclampsia, placental abruption or membrane rupture, but a more flexible approach can be discussed if these factors are not present.
D - Well women with intact membranes and no laboratory evidence of disseminated intravascular coagulation (DIC) should be advised that they are unlikely to come to physical harm if they delay labour for a short period, but they may develop severe medical complications and suffer greater anxiety with prolonged intervals. Women who delay labour for periods longer than 48 hours should be advised to have testing for disseminated intravascular coagulation twice weekly (see Table 1 in the original guideline document).
D - Women contemplating prolonged expectant management should be advised that the value of postmortem may be reduced.
How Should Labour Be Induced for a Woman with an Unscarred Uterus?
D - A combination of mifepristone and a prostaglandin preparation should usually be recommended as the first-line intervention for induction of labour.
B - Misoprostol can be used in preference to prostaglandin E2 because of equivalent safety and efficacy with lower cost but at doses not currently marketed in the United Kingdom (UK).
A - Women should be advised that vaginal misoprostol is as effective as oral therapy but associated with fewer adverse effects.
What Is Best Practice for Induction of Labour for a Woman with a History of Lower Segment Caesarean Section (LSCS)?
D - A discussion of the safety and benefits of induction of labour should be undertaken by a consultant obstetrician.
A - Mifepristone can be used alone to increase the chance of labour significantly within 72 hours (avoiding the use of prostaglandin).
A - Mechanical methods for induction of labour in women with an IUFD should be used only in the context of a clinical trial.
C - Women with a single lower segment scar should be advised that, in general, induction of labour with prostaglandin is safe but not without risk.
C - Misoprostol can be safely used for induction of labour in women with a single previous LSCS and an IUFD but with doses not yet marketed in the UK.
C - Women with two previous LSCS should be advised that in general the absolute risk of induction of labour with prostaglandin is only a little higher than for women with a single previous LSCS.
D - Women with more than two LSCS deliveries or atypical scars should be advised that the safety of induction of labour is unknown.
What Are the Recommendations for Intrapartum Antimicrobial Therapy?
C - Women with sepsis should be treated with intravenous broad-spectrum antibiotic therapy (including antichlamydial agents).
Are There Any Special Recommendations for Pain Relief in Labour?
D - Diamorphine should be used in preference to pethidine.
D - Regional anaesthesia should be available for women with an IUFD.
D - Assessment for DIC and sepsis should be undertaken before administering regional anaesthesia.
What Are the Recommendations for Women Labouring with a Scarred Uterus?
D - Women undergoing vaginal birth after caesarean (VBAC) should be closely monitored for features of scar rupture.
B - Oxytocin augmentation can be used for vaginal birth after caesarean, but the decision should be made by a consultant obstetrician.
What Are the Options for Suppression of Lactation?
A - Women should be advised that almost one-third of those that choose nonpharmacological measures are troubled by excessive discomfort.
A - Women should be advised that dopamine agonists successfully suppress lactation in a very high proportion of women and are well tolerated by a very large majority; cabergoline is superior to bromocriptine.
D - Dopamine agonists should not be given to women with hypertension or pre-eclampsia.
D - Estrogens should not be used to suppress lactation.
Psychological and Social Aspects of Care
What Psychological Problems Can Follow Late IUFD?
B - Carers must be alert to the fact that mothers, partners and children are all at risk of prolonged severe psychological reactions including post-traumatic stress disorder but that their reactions might be very different.
What Is Best Practice for Use of Interventions That Might Aid Psychological Recovery?
D - Carers should be aware of and responsive to possible variations in individual and cultural approaches to death.
A - Counselling should be offered to all women and their partners.
D - Other family members, especially existing children and grandparents, should also be considered for counselling.
A - Debriefing services must not care for women with symptoms of psychiatric disease in isolation.
D - Parents should be advised about support groups.
D - Bereavement officers should be appointed to coordinate services.
What Is the Evidence for Seeing, Holding, Naming and Mementos?
C - Carers should avoid persuading parents to have contact with their stillborn baby, but should strongly support such desires when expressed.
C - Parents should be offered, but not persuaded, to retain artefacts of remembrance.
C - Maternity units should have the facilities for producing photographs, palm and foot prints and locks of hair with presentation frames.
What Are the Recommendations for Spiritual Guidance, Burial, Cremation and Remembrance?
C - The legal responsibility for the child's body rests with the parents but can be delegated to hospital services.
C - Parents should be allowed to choose freely about attendance at a funeral service.
What Advice Should Be Given about Fertility?
C - Information about fertility and contraception should be offered to mothers before returning home.
What Are the Recommendations for the Content of the Follow-up Appointment?
C - Women should be offered general prepregnancy advice, including support for smoking cessation.
B - Women should be advised to avoid weight gain if they are already overweight (body mass index over 25) and to consider weight loss.
C - An offer should be made to discuss the potential benefit of delaying conception until severe psychological issues have been resolved.
A - Carers should be aware that while mothers tend to experience greater anxiety when conception occurs soon after a fetal loss, partners are more likely to suffer anxiety if conception is delayed.
B - Parents can be advised that the absolute chance of adverse events with a pregnancy interval less than 6 months remains low and is unlikely to be significantly increased compared with conceiving later.
Women might wish to keep a written log of questions and comments. Some women/couples might wish to use this to help set the agenda themselves at the start of the meeting. As well as an opportunity to ask about the physical and emotional wellbeing of the mother and her partner, the meeting allows parents time to discuss the results of tests and the likely cause of late IUFD. The meeting can also focus on the prognosis and options for future pregnancies. The discussion should cover general preparation for pregnancy: lifestyle, folic acid supplementation and rubella vaccination. Parents often desire an open, honest discussion with an opportunity to make comments and the chance to raise any concerns they might have. If care has been suboptimal, parents might want this to be acknowledged, lessons to be learned and care in the future to be improved.
Pregnancy Following Unexplained Stillbirth
What Recommendations Should Be Made for Pregnancy Following Unexplained Late IUFD?
B - Women with a previous unexplained IUFD should be recommended to have obstetric antenatal care.
What Recommendations Should Be Made for Maternal Care after the Next Birth?
C - Carers should be vigilant for postpartum depression in women with a previous IUFD.
C - Carers should be aware that maternal bonding can be adversely affected.
Grades of Recommendation
A - At least one meta-analysis, systematic review or randomised controlled trial rated as 1++ and directly applicable to the target population; or
A systematic review of randomised controlled trials or a body of evidence consisting principally of studies rated as 1+ directly applicable to the target population and demonstrating overall consistency of results
B - A body of evidence including studies rated as 2++ directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C - A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D - Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Good Practice Point - Recommended best practice based on the clinical experience of the guideline development group.
Classification of Evidence Levels
1++ High-quality meta-analyses, systematic review of randomised controlled trials or randomised controlled trials with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a low risk of bias
1- Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a high risk of bias
2++ High-quality systematic reviews of case–control or cohort studies or high quality case–control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal
2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal
2- Case–control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal
3 Non-analytical studies; e.g., case reports, case series
4 Expert opinion