ICP: A midwifery perspective

Abstract

Background

ICP is a liver condition specific to pregnancy affecting 0.5–0.6% of pregnancies in Australia.

Aims

to review the SOMANZ guidelines and extrapolate information relevant to midwives proving care for women with ICP.

Findings

Multidisciplinary input is essential in caring for women with ICP and their families. Non-fasting TSBA samples ≥19 µmol/L are diagnostic in the presence of pruritus. Peak TSBA denotes the severity of the disease. Increased risk of stillbirth is small when peak TSBA ≥100 µmol/L.

Conclusion

Midwives play an essential role in supporting women with ICP helping them navigate complex appointments and manage the pruritus and concomitant issues.

Keywords

Intrahepatic cholestasis of pregnancy (ICP)midwives peak total serum bile acids (TBSA)

Background

Intrahepatic cholestasis of pregnancy (ICP) was first described in 1883 by Ahlfield as ‘recurrent jaundice in pregnancy with resolution following birth’, but pruritus was not mentioned. In the 1950s case reports described severe itching in pregnancy, with or without jaundice, resolving following childbirth, with high recurrence rates.¹ Over time the condition, now globally known as ICP, has been described as: jaundice of pregnancy, obstetric hepatosis, hepatosis gestationalis, or obstetric cholestasis.²

There was a paucity of data regarding ICP until the 1980s, when several renowned clinicians and scientists began investigating reports of itching in pregnancy, varying degrees of liver enzyme derangement, maternal jaundice, meconium-stained liquor and unexplained stillbirth. This was reflected in the Royal College of Obstetricians and Gynaecologists Green Top Guidelines, first published in 2006, revised in 2011 and 2022, as research into this heterogeneous condition developed and management changed to improve outcomes for women and their babies.³

The Society of Obstetric Medicine ICP guidelines were developed by a multidisciplinary team to identify and synthesise currently available evidence regarding ICP, leading to effective diagnostic criteria and management, based on the most recent high-quality evidence, and identifying future research areas.⁴

Midwifery perspective

Midwives develop and maintain a unique relationship with women pre-conceptually and throughout the pregnancy continuum. Midwifery is grounded in women-centred care and developing new, and utilising existing, research evidence is fundamental to providing optimal care for mothers, infants and families. High-quality midwifery care is proven to improve sexual, reproductive, maternal, newborn and adolescent health in all resource settings.⁵ Inherent in providing optimal care is midwives cognisance of deviations in maternal, fetal or infant health, research awareness, and appropriate referral. Thus, ensuring timely management to improve outcomes for women, babies and families.

In Australia, maternity care is commonly compounded by geographical location, for those living regionally or remotely, appropriate and timely referral, +/− transfer, is key to maternal physical and psychological well-being.

Midwives are frequently the first health care professional pregnant women engage with and their ongoing relationship means initial signs and symptoms of complications, or maternal report of concerns, are initially reported to midwives.

What is intrahepatic cholestasis of pregnancy?

ICP is a pregnancy-specific liver disease, characterised by pruritus and increased total serum bile acids (TSBA).⁴ The incidence of ICP in Australia is 0.6–0.7%.^6,7 Meaning, of the 311,360 women who birthed in 2021⁸ approximately 2000 experienced ICP. Given this condition is relatively rare, midwives may see women with ICP infrequently. But it is important to maintain awareness of the condition, and be cognisant of contemporaneous research, outcomes and management strategies, to enable them to support women during a challenging time.

The role of bile acids

Bile acids are produced in the liver and stored in the gallbladder, they promote the absorption of lipids in the small intestine and regulate cholesterol homeostasis.⁹ In ICP, the flow of bile is sluggish, leading to excessive bile acids, causing toxicity.

Epidemiology

Wide variation in the incidence of ICP by ethnicity has long been reported. For example, in Chile, ICP in Araucanian Indians is 10-fold higher than in other populations, a large Swedish population study reported an incidence of 1.5%, and in the UK, women from the Indian subcontinent were twice as likely to develop ICP than their Caucasian counterparts.^10–12 Midwives, therefore, need to be mindful of the heritage of women they care for, especially in a multicultural country, like Australia.

Genetic susceptibility

Women with mothers or sisters who had ICP are at increased risk. One study reported a 6% risk of developing ICP in these women, compared to the general antenatal population (0.54%).¹³ Therefore, midwives should ask women about the pregnancy health of their mothers and sisters.

Genetic variants of bile acid transporters have been identified in women with ICP and whole-genome sequencing has detected liver-enriched gene variation and specific liver regulatory elements in those with previous ICP. Thereby proposing potential mechanisms contributing to susceptibility to ICP.¹⁴

Multiple pregnancies

Multi-fetal pregnancies have long been associated with a 5-fold increased risk of developing ICP.¹⁵ More recently, twin pregnancies achieved through in-vitro fertilisation (IVF) have been associated with early-onset ICP (p = 0.015), and increased frequency of symptoms, compared to those spontaneously conceived.¹⁶ Women with positive Hepatitis C serology are at increased risk and develop ICP at earlier gestations, although the mechanisms are currently not understood.⁴

Past or present gallstones (cholelithiasis) are also more common in women with ICP.¹⁷

These risk factors underpin the importance of ensuring a detailed history is taken at booking and reviewed subsequently, including blood results. None of these factors guarantee the woman will develop ICP but being aware enables midwives to provide holistic individualised care for the woman and her family.

ICP usually develops around 30 weeks’ gestation or later, but can occur much earlier, with occurrence in the first trimester reported.¹⁸ Midwives therefore need to be mindful of this condition when seeing a woman complaining of pruritus, regardless of gestation.

Signs and symptoms

Women with ICP often report feeling tired, generally unwell and loss of appetite.¹⁹ They may also report right upper quadrant pain or tenderness. The reasons for this are unclear but any such reports require medical review. The main symptom is pruritus, with no associated rash, although excoriations are common. The itch ranges from mild to severe, and the severity is not dictated by degree of liver enzyme disruption. The itch initially starts on the palms of hands and soles of feet but can become generalised. Figure 1 identifies the distribution of reported itch from one multinational survey.²⁰

Figure 1.

Location of itch, modified from ICP support data.²⁰

For many the itching is worse at night, disturbing sleep and adversely impacting mental health.²⁰

Women commonly report itching in pregnancy, often with an associated rash. It is therefore important that midwives can differentiate between ICP and other skin conditions or lesions. Other skin conditions are not associated with liver enzyme derangement. If unsure, referring for a non-fasting blood test to assess total serum bile acids is required.

Other symptoms of ICP include dark urine, caused by excretion of bile pigments⁴ and pale stools. Rarely the woman may develop jaundice and steatorrhoea. ICP is diagnosed after the exclusion of other differential diagnoses and in the presence of increased concentrations of non-fasting total serum bile acids (TSBA) in women with itch, and no other dermatological or liver active liver pathology.⁴

A non-fasting TSBA ≥ 19 µmol/L has good sensitivity and specificity to reliably diagnose ICP.²¹ If a fasting sample is used TSBA levels ≥10 µmol/L confirms mild ICP. Whilst the sensitivity of fasting samples is high the sensitivity is low (<30%) for mild disease.²² Therefore, a non-fasting sample is optimal.

ICP is further categorised as severe, when the peak TSBA ≥40 µmol/L, and very severe when peak TSBA ≥100 µmol/L. See Table 1 for an overview of the management, depending on the level.

Table 1.

ICP management and midwifery care according to total serum bile acid level.

TSBA level	Diagnosis	Management	Midwifery care
<19 µmol/L	Normal	If itch persists, repeat non-fasting TSBA fortnightly Multidisciplinary team^a input	Reassurance, support Store topical creams in the fridge and use to alleviate itching. Ensure fortnightly repeat testing whilst itching persists.
19–39 µmol/L	Mild ICP	Repeat non-fasting TSBA fortnightly. Follow-up dependent on TSBA. Ursodeoxycholic acid (UDCA) may be considered. Out-patient management if clinically well.	Reassurance, support Store topical creams in the fridge and use them to alleviate itching. Ensure fortnightly repeat testing.
40–99 µmol/L	Severe ICP	Repeat non-fasting TSBA weekly. Check PT/INR and/or APTT and repeat prior to elective birth. INR ≥ 1.4. UDCA may be given. Consider birth plan if ≥38/40.	Reassurance, support, explanation. Ensure awareness of reporting decreased/absent fetal movements urgently. Acknowledgement of maternal anxiety provides empathetic psycho-social support. Discussion of risks and benefits of planned birth prior to 39/40, or 36/40 for very severe ICP.
≥100 µmol/L	Very severe ICP	No further benefit of repeating TSBA. UDCA may be given. Admission for assessment and plans for birth (especially ≥36/40)

Multidisciplinary team input is essential: midwives, GPs, obstetricians, obstetric physicians.

PT/INR: prothrombin time/international normalised ratio; APTT: activated partial thromboplastin time; UDCA: ursodeoxycholic acid.

TSBA assays are not well standardised, ideally, serial tests should be analysed in the same laboratories.²³ Large multinational clinical trials may have failed to account for non-standardisation of TSBA, despite diagnosis depending on these.²³

This inter-laboratory variation must be considered when women are transferred between services, and midwives are well placed to identify this and explain variations to the woman and family.

The severity of ICP is dictated by peak TSBA. There are no reliable data suggesting a fall in peak TSBA confers risk reduction.²⁴ Many women, especially those with mild ICP, experience a progressive decline in TSBA as gestation advances, even without treatment.²⁴

It is important that midwives understand ICP categorisation, so they can provide accurate information to women and their families and refer appropriately. This is especially important when women live in rural and remote areas and may require transfer for tertiary-level care.

Complications associated with ICP

Women with ICP are at increased risk of both pre-eclampsia (10-fold) and gestational diabetes (3-fold)⁶ due to the abnormal metabolic profile women exhibited, in addition to the hepatic features of ICP.^25,26 Midwives caring for women with ICP should remain vigilant for these concurrent complications of pregnancy, which are likely to further compromise maternal and fetal wellbeing.

ICP has been associated with increased rates of spontaneous preterm birth, fetal distress and meconium-stained liquor when the peak TSBA ≥40 µol/L.^11,27 Overall, the risk of stillbirth is small, but in women with peak TSBA ≥100 it is increased (hazard ratio [HR] 30.50 [95% CI 8.83 to 105.30]; p ≤ 0.0001).²⁷

Therefore, midwives can reassure women with mild disease (peak TSBA ≤ 39 µmol/L) that the risks of these adverse outcomes are similar to those of the general population. With women with peak TSBA ≥40 µol/L midwives should explain the importance of monitoring fetal movements, and urgently attending for review should these be diminished or absent.

Management of women with ICP

As shown in Table 1, regular assessments of TSBA are required. These should be repeated fortnightly (or as per local guidelines) for women with itch and normal TSBA or with mild ICP (TSBA 19–39 µmol/L). It should be remembered the degree of itching is not indicative of liver enzyme derangement.

If TSBA ≥40 µmol/L severe ICP is diagnosed.

If TSBA ≥ 100 µmol/L very severe ICP is diagnosed. As the diagnosis relies on the peak TSBA there is no value in repeating the blood test once this level is attained.

Table 1 also identifies the additional coagulation studies required following diagnosis of severe/very severe ICP and repeated prior to planned birth.

Treatments for ICP may be prescribed depending on the severity of the condition and the gestation at onset. Cochrane reviews and meta-analyses have shown inconclusive benefits of currently used treatments.^28,29

In early-onset ICP ursodeoxycholic acid (UDCA) is recommended. As a secondary bile acid, it replaces the toxic bile acids in the overall bile acid pool³⁰ and improves the flow of bile.³¹ UDCA use has only been associated with a small improvement in pruritus.²⁸ In one RCT comparing UDCA with placebo only a small, but potentially, clinically significant improvement in itch was reported, conversely, women considered a 25% reduction in itch as unhelpful.²⁴

Women commencing UDCA require support during the dosing regime, which commences at 500–1500 mg daily, dependent on the severity of the disease, commonly using twice-daily doses, which are increased weekly to a maximum 2000 mg per day. Midwives can support women as they adjust these medications and manage their expectations around the drug's impact on pruritus.

Other potential treatment options include rifampicin, a semisynthetic antibiotic, which reduces serum bile acids in non-pregnant populations and is currently under investigation in the TUFFIFIC trial.³² Other potential treatments have been validated in non-pregnant populations, (e.g., naloxone), but in pregnancy require experienced clinician guidance.

There is insufficient evidence to support the use of other treatments including guar gum, activated charcoal, dexamethasone, cholestyramine and traditional remedies.²⁸

Antihistamines may be prescribed for relief from itching, and sedating varieties may aid sleep, but these are untested in randomised controlled trials.⁴

Midwives should be aware of ongoing research and mindful that the evidence gained may change future management. The limited treatment options currently available further identify the importance of research.

Non-pharmacological interventions, such as topical emollients, are likely to be safe and can provide relief from itching, but have not been tested in clinical trials. Storing these in the fridge can improve relief.

Women with ICP should keep cool, avoiding hot showers, cold compresses can relieve itching. Adequate nutrition, hydration and sleep are important. As are gentle movement, exposure to sunlight, social interaction, and audio-visual distraction.⁴ Women with ICP often experience low mood and anxiety, and the constant itching can be isolating. Encouraging women to maintain interactions with friends and go out as normal will help elevate their mood. Working with family and friends is also important to ensure they can best support the woman.

Fetal monitoring

In singleton pregnancies, with appropriately grown fetuses and no pre-eclampsia or GDM, serial ultrasound scans and CTG monitoring are not required. There have been case reports of fetal deaths following normal cardiotocographs (CTGs) (7 h to 5 days) and documented normal fetal movements associated with ICP. Umbilical artery Doppler studies have similarly failed to identify compromised fetuses or predict adverse outcomes in pregnancies complicated by ICP.³³

Midwives need to ensure women know that any alteration in fetal movements should be reported urgently, and full fetal assessment and CTG should be undertaken.

ICP causes anxiety and everyone supporting these women should acknowledge this and provide empathetic psycho-social support. This is particularly so for midwives who are privileged to develop a strong bond with women in their care, and can often be the key professional to help them navigate complex obstetric/obstetric medicine appointments.

Intrapartum care

Many women will request induction of labour due to the distress caused by the pruritus and increased anxiety. As identified in Table 1 this should be considered at 36 and 38 weeks in women with very severe and severe disease, respectively. For women with mild disease, midwives, and other health professionals, should discuss the risks and benefits of induction prior to term.

Evidence shows the risk of stillbirth for women with peak TSBA 40–99 µmol/L is comparable to the general population (0.28%). When the peak TSBA exceeds 100 µmol/L this risk increases to 3.4% (1:29 cases of severe ICP).²⁷

Many women with severe or very severe diseases will have a planned birth, and midwifery input is essential to ensure women understand the processes, and recommendations to optimise the care they and their infant receive.

Coagulation studies should be undertaken prior to induction or elective caesarean. If the PT/INT or APPT are abnormal, correction of this should be undertaken, including the administration of vitamin K.

Continuous CTG monitoring is recommended for those with severe and very severe ICP regardless of onset of labour.⁴

Early studies indicated an association between postpartum haemorrhage (PPH) and ICP,³⁴ although subsequent studies refute this³⁵ active management of the third stage is recommended for all women with ICP.⁴ All newborns of mothers with ICP should receive parenteral vitamin K, regardless of the severity of the disease.

Routine immediate postnatal care should be provided for these mothers and infants. The pruritus usually resolves within 48 h of birth and any treatment can be discontinued immediately post-birth. There are no implications for neonatal health post-birth.

Midwives caring for women postnatally should inform women that they should have liver function tests, including TSBA and serum transaminases checked at the routine 6 weeks’ postnatal visit and any abnormalities require further investigation.

When advising women about family planning, it is important to note that hormonal contraception is not contraindicated, but if pruritus reoccurs with use, further investigations are required.

Longer-term health implications following ICP

Whilst the scope of practice for midwives only extends briefly into the postnatal period, it is useful to know about the longer-term implications of ICP, to empower women to manage their subsequent health and wellbeing. Understanding the longer-term effects on women and their offspring will also increase professional knowledge and optimise care.

There is no consensus regarding follow-up for women with ICP, although an annual review of liver biochemistry has been identified as appropriate.⁴ Women with severe ICP are at increased risk of chronic liver disease.⁴

Registry data from Sweden has shown that women who experienced ICP are at increased risk of developing certain diseases later in life. These include: liver and biliary tree carcinoma, some immune-mediated diseases such as Type 2 diabetes, thyroid disease, psoriasis, Crohn's disease and a smaller increased risk of cardiovascular disease.³⁶

The offspring of pregnancies complicated by ICP have been shown to have increased risk of food allergy at age 6 months, but as 90% of these children were born by caesarean section, this could be due to microbiome and antibiotic use.³⁷

Research also suggests that at 16 years of age compared to those born following uncomplicated pregnancies, males from ICP-affected pregnancies had increased BMIs and fasting insulin, and females from ICP-complicated pregnancies had increased waist and hip measurements and lower fasting high-density lipoproteins (HDL) cholesterol.³⁸ But more research is required in this area.

Conclusions

For women with ICP midwives are an integral part in the multidisciplinary team, providing midwifery care and support whilst helping them navigate complex medical appointments. This is particularly important when transfer is required, and new relationships need to be established. Continuity of care ensures midwives can detect variations in psychological well-being and support the woman and her family at this difficult time.

Being informed and up-to-date enables midwives to provide the best information to aid informed choices and optimise outcomes for these women and their children. Informing women and colleagues about the UK-based charity ICP Support, which has international reach with a website providing up-to-date information and research in this area, for women and health care professionals and support for women via Facebook, online meetings (ZOOM) and email (https://www.icpsupport.org/).

Footnotes

Contributorship

Annette Briley and Megan Cooper researched the literature and reviewed the current guidelines. All authors reviewed and edited the manuscript and approved the final version of the manuscript.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval

Not applicable.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Guarantor

Annette Briley.

Informed consent

Not applicable.

Patient consent

Not applicable.

Trial registration

Not applicable.

ORCID iD

Annette Briley

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