GTG 55 | Late Intrauterine Fetal Death & Stillbirth

This post highlights the key updates from the November 2024 revision of GTG 55: Late Intrauterine Fetal Death (IUFD) and Stillbirth. These updates bring critical changes that are not only pivotal for clinical practice but also for anyone preparing for the MRCOG exams.

GTGs remain an invaluable resource for MRCOG preparation, and understanding these updates in depth is key to staying ahead. I’ve summarized the main points in this post, making it a concise and accessible guide for busy professionals.

I hope you find this post informative and helpful. Your feedback and suggestions to enhance future posts are always appreciated—feel free to share your thoughts in the comments!

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Definitions

Late Intrauterine Fetal Death

• Babies with no signs of life in utero after 24⁺⁰ completed wks of pregnancy

Stillbirth

• Baby delivered with no signs of life known to have died after 24⁺⁰ completed wks of pregnancy

Background & Epidemiology

• Late IUFD 1 in 250
• Sudden Infant death 1 per 10000 live births
• According to MBRRACE-UK National Perinatal Mortality Surveillance Report
• Extended perinatal mortality reduced by 18% ^{over 6 years} 
• Stillbirth reduced by just over 20%
• Stillbirths in 2021  3.54 per 1000 total births in UK
• Babies of women living in the most deprived areas – twice as likely to be stillborn
• Black & Black British ethnicity - twice stillbirth rates

Diagnosis of IUFD

• Avoid auscultation for fetal heart by Pinard stethoscope or Doppler USG or CTG 

Real-time USG

• Essential for accurate dx – allows direct visualization of fetal heart
• Offer discussion of USG findings with parents – for anticipated appearance of baby at birth & explain time of fetal death
• Sensitivity to diagnose occult placental abruption 15%
• Patient may have passive fetal movements; must counsel & may offer repeat scan 

Communicating the diagnosis 

• Provide written information
• Use clear language
• Avoid jargons
• Use professional interpreter
• Give time to absorb the news
• Support maternal/paternal choices

Labour & Birth

• Informed decision b/w parents & experienced obstetrician
• Consider woman’s choice, medical conditions & previous intrapartum history

Suitable Birth facilities  

• Depend on individual circumstances
• Special labour wards room with special focus on emotional & practical needs
• Care to be given by an experienced midwife + obstetrician

Options for birth   SVD  IOL ^{immediate/delayed}  CS  Expectant

Vaginal birth   

• Recommended for most women
• VD Emotionally distressing in IUFD 47% ^{vs 7% in live births}
• VD can occur within 24 hrs of IOL in ~90%
• ↑ shoulder dystocia, clinical chorioamniotis, PPH & retained placenta
• 4-fold ↑ in severe maternal morbidity

Caesarean Section  

• needed for some 
• ↓ perineal trauma, urinary incontinence & POP 
• ↑ surgical morbidity, ↑ risks for fertility & ↑ risks in future pregnancies

Timing of Birth

• No optimal interval to birth

Physically well + Intact membranes + No lab evidence of DIC

• can delay labour for 48 hours   
• if longer then must have testing for DIC
• 10% risk of DIC within 4 weeks
• Interval b/w dx & delivery can ↑ anxiety & DIC

Prolonged Expectant mx

• may ↓ diagnostic value of postmortem
• ≥24 hrs interval from dx to start of labour associated with ↑ risk of moderately severe anxiety or worse OR 4.8

Pool birth   

• Can be offered Late IUFD not a contraindication

Induction of labour

• First-line intervention   Combination of Mifepristone & Misoprostol

FIGO Misoprostol Dosing Regimen 2023
A single 200 mg Mifepristone followed by:
24+0 – 24+6 wks	400 μg misoprostol every 3 hrs
25+0 – 27+6 wks	200 μg misoprostol every 4 hrs
From 28+0 wks	25–50 μg vaginal misoprostol every 4 hrs or 50–100 μg oral misoprostol every 2 hrs

Mifepristone Use

Mifepristone + Misoprostol  vs misoprostol alone

• Significantly shorter time to birth 6.72 ±3.34 hrs vs 11.81 ±6.33 hrs
• Mean induction-birth interval shorter 9.8 vs 16.3
• Less # of misoprostol doses needed & earlier onset of labour
• Mifepristone prior to misoprostol ↑ chance of vaginal birth from 71% to 92%

Misoprostol  

• off-label in UK for IOL in stillbirth
• Vaginal as effective as oral with fewer side effects
• Both routes up to 100% effective in achieving birth at 48 hrs
• Preferable to prostaglandin E2 with equivalent safety, lower cost & lower doses

IOL with previous CS

• Discuss benefits & harms of IOL
• Undergoing VBAC   must monitor closely for features of scar rupture
• Can use oxytocin augmentation after discussion with consultant
• Misoprostol can be used b/w 13⁺⁰ – 27⁺⁶ wks
• 24⁺⁰ -24⁺⁶ wks   400 μg  buccal/sublingual/vaginal/oral every 3 hrs
• 25⁺⁰ – 27⁺⁶ wks   200 μg buccal/sublingual vaginal/oral every 4 hrs
• >27⁺⁶ wks   Insufficient evidence for specific regimen

With ≥2 CS  

• Safety of IOL Unknown 

Intrapartum antimicrobial therapy

• Chorioamnionitis in up to 26% of late IUFDs 
• Can cause severe sepsis if not treated can cause severe DIC

Pain relief  

• More analgesia needed  Make all usual methods available
• Diamorphine better pain relief vs pethidine BUT duration of labour prolonged & more pain overall
• Parenteral opioids   Provide some pain relief & moderate satisfaction
• Neuraxial labour analgesia   can be given No ↑ risk of perinatal laceration
• Regional   Contraindicated in DIC

Care before returning home

• Discuss lactation, milk donation/suppression
• Advise about expected physical symptoms, bleeding/pain
• Ensure continuity of care   
• Involve specialist/bereavement midwife
• Advice on contraception

Lactation suppression

• 1/3 who choose non-pharmacological measures experience excessive discomfort
• Dopamine agonists   generally well-tolerated
• Balance the risks & benefits if HTN or PET
• Cabergoline ^{single dose 1mg}  better than bromocriptine ^{2.5mg BD for 14 days}

Thromboprophylaxis

• Routinely assess for TPX
• IUFD in current pregnancy is an independent risk factor for VTE 
• 6 times higher risk than a live birth
• If DIC  Discuss heparin TPX with a haematologist

Whom to inform about women?

• All key staff responsible for woman’s care
• Cancel all existing antenatal appointments
• Inform primary care healthcare professionals

Investigations 

Table 2 (please click the image for clarity)

General Principles

• For 95% of parents, it is important to have an explanation of their baby’s death
• Conventional diagnostic systems fail to identify a specific cause in about 50% of IUFD

Detailed history   vital first step

Clinical & Lab tests to  

• assess maternal wellbeing, determine cause of fetal death, chance of recurrence & possible means of avoiding further pregnancy complications

Use systems with fetal birthweight centile & capture multiple contributing factors ^{↓ unclassified late IUFDs}

Recommended to have

• medical history evaluation, postmortem, placental pathological examination, genetic analysis, microbiology of fetal & placental tissues & a Kleihauer test
• With full investigations ^{including postmortem + placental histology} possible or probable cause found in up to ¾ cases
• If a cause is found  can potentially influence care in future pregnancy

Usefulness of each test

• Placental pathology 65%  
• Postmortem 42% 
• Genetic testing 12%  
• Antiphospholipid antibodies 11% 
• FMH 6%
• Glucose screen 1.5%
• Parvovirus 0.4%  
• Syphilis 0.2%

The most useful tests are placental pathology & fetal postmortem followed by genetic testing & testing for antiphospholipid antibodies

Transplacental infections associated with IUFD

• CMV, Syphilis, Parvovirus, Listeria, Rubella, HSV, Toxoplasmosis, Coxsackievirus, Leptospira, Q fever, Lyme disease
• Malaria parasitaemia also associated OR 2.3
• Ascending infection ^{±membrane rupture} with Escherichia coli, Klebsiella pneumoniae, Group B Streptococcus, Enterococcus, Mycoplasma/Ureaplasma, Haemophilius influenzae, and chlamydia more common in developed countries

COVID-19

• ↑ rate of stillbirth in non-vaccinated 
• ↑ rates with delta variant

Rhesus D Negative Blood group

• FMH - A silent cause of late IUFD
• Offer   Keilhauer test Urgently
• Give   Anti RhD as soon as possible
• Anti-RhD within 72 hrs but beneficial up to 10 days
• If large FMH  adjust anti-RhD dose & Repeat Keilhauer test at 48 hrs
• Fetal blood group determined by free fetal DNA testing

Determining fetal sex 

• May be difficult
• 2 experienced health professionals should examine external genitals in extreme preterm, severely macerated or hydrops
• Any doubt  Offer rapid genetic testing ^{on skin or placental tissue}
• Stillborn babies can be registered as indeterminate sex

Cytogenetic Analysis  

• Only if consented
• 6-13% stillborn have cytogenetic anomaly
• Abnormal result   Refer to clinical geneticists

Perinatal Postmortem  

• Offer full PM to all
• Use Consent form with sections on purpose, extent of examination, possible organ/tissue retention
• Must take consent for invasive procedure
• Allow ample time to discuss in a quiet, private place ^{minimum of 1 hr}
• Supplement with written information
• PM can provide crucial information for future pregnancy

Perinatal Postmortem  Full PM declined

• Offer non-invasive, minimally invasive & limited PM
• USG & MRI as substitute for conventional PM
• X-rays ONLY for targeted use such as suspected skeletal anomaly

Aspects of care

Appropriate bereavement counselling for all ^{significantly reduces grief symptoms}

• Women, partners, children & grandparents are all at risk of prolonged severe psychological reactions including PTSD

Parents at ↑ risk of hospital admission ^{d/t postnatal depression & suicide}

• Bereaved parents have markedly ↑ mortality – up to 25 yrs ^{after death of their child}
• Risk of completed suicide – higher in women with late IUFD aOR 5.2

Partners also experience severe grief response even leading to PTSD

• Parental relationships have 40% ↑ risk of dissolving

Support groups like Sands, or Charities like PATELS, Baby loss counselling helpful

Legal requirements for medical certification

• Baby must be registered within 42 days
• Responsibility of parents to register but can delegate task to HCP
• Stillbirth medically certified by a fully registered doctor or midwife who must have been present at birth or examined the baby after birth
• Contact HM Coroner if doubt about the status of a birth
• Parents may name the baby, but once stillbirth registered, names cannot be added or changed
• Babies can be registered as indeterminate sex

Cremation

• Cremation Form 3 (CF3) to be completed application for cremation of remains of a stillborn child
• Together with a copy of Stillbirth Certificate ^{AKA Cremation Form 9,} CF3 submitted to Medical Referee, who issues Cremation Form 10 ^{authorisation to cremate a stillborn child}
• Cremation Form 2 is the equivalent of CF3 for retained body parts of a stillborn child when the body has already been cremated

Follow-up

• Time of appointment  6-12 wks
• Before the visit – ensure all results are available – if delayed offer an interim visit
• Inform parents about review process & keep them engaged
• Give plain English summary of review process & discuss
• Offer general pre-pregnancy advice ^{smoking cessation, healthy weight mx}
• Meeting to be documented

Pregnancy after Stillbirth

Previous IUFD - the single most important risk factor for recurrence 4-8 fold ↑ risk

Subsequent ANC

• Obstetrician-led care  
• Support emotionally
• Low dose aspirin^150mg   for ALL
• Fetal biometry & amniotic fluid measurement ^{with UA doppler flow velocimetry} every 3-4 wks from 26-28 wks – previous IUFD ↑es risk of SGA OR 1.39
• Screen for GDM   44% higher risk of IUFD if not screened
• No routine LMWH   unless other medical considerations, thrombophilia or APS
• IOL or birth by 39⁺⁰ wks reduces perinatal death & other adverse events

All stillbirths should be reported to:

• MBRRACE-UK
• National Maternity and Perinatal Audit
• PMRT database
• Maternity and Newborn Safety Investigations (MNSI) (if intrapartum)

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