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ORIGINAL ARTICLE
Year : 2020  |  Volume : 47  |  Issue : 1  |  Page : 28-32

Impact of obstetric cholestasis on fetal outcome – An observational study


Department of Gynecology and Obstetrics, SKIMS, Srinagar, Jammu and Kashmir, India

Date of Submission10-Mar-2020
Date of Acceptance30-Apr-2020
Date of Web Publication23-Jun-2020

Correspondence Address:
Dr. Beenish Jeelani
Department of Gynecology and Obstetrics, SKIMS, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.JSS_18_20

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  Abstract 


Background: Intrahepatic cholestasis of pregnancy (ICP) or obstetric cholestasis (OC), while classified as a pregnancy dermatosis, is in fact the most common liver disease of pregnancy associated with significant fetal mortality and morbidity, as well as lifelong health risks for the offspring. Older studies using biochemical abnormalities to diagnose OC have reported a perinatal mortality rate of 10%–15%. This has been reduced to 3.5% or less in more recent studies using policies of active management. ICP is relatively benign to women, but it has been reported to have important fetal implications with increased risk of respiratory distress, preterm delivery, low birth weight, meconium staining of amniotic fluid, fetal bradycardia, fetal distress, and fetal demise. Objective: The objective was to study the impact of OC on fetal outcome. Materials and Methods: The present study was a comparative study carried out on 55 pregnant patients who presented with OC of pregnancy between 30 weeks and 40 weeks of gestation. It was conducted in the Department of Obstetrics and Gynaecology, SKIMS, Soura, Srinagar, from June 2019 to November 2019. The study participants were classified into Group A: total bile acid level (TBA) <40 μmol/l and Group B: TBA >40 μmol/l. The fetal outcome was studied in terms of respiratory distress, low birth weight, stillbirth, and intrauterine fetal demise (IUFD). Results: Out of 55 patients diagnosed with ICP, 35 patients belonged to Group A with TBA <40 μmol/l and 20 patients belonged to Group B with TBA >40 μmol/l. In Group A, only five (14.2%) cases of fetal complications were reported, among which three (60%) fetuses had respiratory distress and two (40%) had low birth weight. Most of the fetal complications occurred in Group B patients with TBA >40 μmol/l, among which ten (55.5%) fetuses had respiratory distress, five (27.7%) fetuses had low birth weight, and there was one (5.5%) stillbirth and two (11.1%) IUFDs. Conclusion: ICP is a relatively common condition that occurs in pregnancy as a consequence of the cholestatic effect of raised estrogen and progesterone in genetically susceptible women. Most of the fetal complications occur in those with higher bile acid pool. The agents that reduce maternal bile acids may reduce fetal complications, but if the mechanism of fetal death involves bile salt-induced fetal arrhythmias without any placental insufficiency, it may be that such monitoring will not be effective in preventing ICP-associated fetal loss.

Keywords: Intrahepatic cholestasis of pregnancy, intrauterine fetal demise, obstetric cholestasis, respiratory distress, total bile acid level


How to cite this article:
Posh S, Ajaz S, Jeelani B, Khurshid R. Impact of obstetric cholestasis on fetal outcome – An observational study. J Sci Soc 2020;47:28-32

How to cite this URL:
Posh S, Ajaz S, Jeelani B, Khurshid R. Impact of obstetric cholestasis on fetal outcome – An observational study. J Sci Soc [serial online] 2020 [cited 2020 Jul 15];47:28-32. Available from: http://www.jscisociety.com/text.asp?2020/47/1/28/287484




  Introduction Top


Classified as a pregnancy dermatosis with an initial presentation of pruritus, obstetric cholestasis (OC) is in fact a liver disease unique to pregnancy. Intrahepatic cholestasis of pregnancy (ICP) has been described in literature as “complex,” “peculiar,” and “intriguing,” owing to its multifaceted and poorly understood pathophysiology and etiology. The Society for Maternal-Fetal Medicine concurs that OC should be diagnosed when the total bile acids (TBAs) or the serum bile acids are measured at 10 μmol/l. OC differs from the other pregnancy dermatoses in that there is no primary rash or lesions, but there is potential for maternal morbidity, significant risk for fetal morbidity and mortality, and implications for future health of the offspring. ICP has also been known as recurrent idiopathic jaundice of pregnancy, OC, and pruritus gravidarum. Signs and symptoms of the disease include pruritus, jaundice, dysuria, steatorrhea, and excoriations from scratching.[1]

Women with OC are known to have altered immunity, abnormal hormone metabolism, and genetic predisposition, and be subject to environmental influences. The maternal course of ICP is considered to be benign with symptoms such as pruritus resolving and liver enzymes and serum bile acids decreasing within a few weeks after birth.[2] Estrogen and estrogen-containing oral contraceptive pills have been known to cause cholestasis due to inhibition of the hepatocellular bile salt export pump. Fetal complications of ICP are likely to relate to raised fetal serum bile acids namely taurocholic and taurodeoxycholic acid.[3],[4],[5]

Fetal disease

There are consistent reports of adverse fetal outcomes in association with the condition. Many studies have attempted to correlate maternal serum biochemistry with fetal outcomes.

Meconium staining of the amniotic fluid

The incidence of meconium staining of amniotic fluid (MSAF) in normal-term pregnancies is 15% and is considered to be a sign of fetal distress. In ICP, MSAF has been reported in 16%–58% of all cases and up to 100% of cases affected by intrauterine death.[6],[7]

Cardiotocographic abnormalities

Both antepartum and intrapartum cardiotocograpic abnormalities have been reported in association with ICP, including reduced fetal heart rate variability, decelerations, tachycardia, and bradycardia.[8]

Preterm labor

There is an increased risk of spontaneous preterm labor, which has been reported in as many as 60% of deliveries in some studies, but most studies report rates of 30%–40% in ICP cases without active management.[9],[10] The rate of this complication was significantly higher in ICP pregnancies with maternal fasting serum bile acids >40 mmol/l.

Respiratory distress syndrome

There is an increased risk of respiratory distress syndrome with either induction of labor or elective cesarean section at 37 weeks' gestation. It occurs in about 22%–33% patients.[11],[12]

Sudden intrauterine death

Causes for sudden intrauterine fetal demise (IUFD) include fetal arrhythmia,[8] meconium-induced vasoconstriction of the placental chorionic vessels,[13] selenium deficiency,[14] acute fetal asphyxia,[15] and impaired fetal adrenal function.[16]

The perinatal mortality in OC has been reduced to 3.5% or less in more recent studies using policies of active management. The term active management may encompass many different clinical practices, including increased fetal monitoring, frequent biochemical testing, pharmacotherapy with ursodeoxycholic acid (UDCA), or delivery at 37–38 weeks' gestation. These management protocols are based on evidence showing that stillbirths in ICP tend to cluster around 37–39 weeks.[17]

Management

UDCA has been shown to have greater efficacy than other treatment modalities, including the use of S-adenosyl-L-methionine, dexamethasone, cholestyramine and guar gum, regarding maternal pruritus, and improving TBA levels and serum transaminases.[18]


  Materials and Methods Top


It was a prospective observational study done in the Department of Gynecology and Obstetrics, SKIMS Maternity Hospital, from June to November, 2019. On an average, about 2–3 patients of OC were included per week to reach final sample size of 55 patients. The A total of 76 patients with itching were studied, out of which 55 women diagnosed with clinical OC were included in this comparative study. The remaining 21 patients were excluded as some of them had dermatological disease such as scabies; others had chronic liver disease and choledocholithiasis; and some had acute fatty liver of pregnancy (AFLP). The prevalence of OC in our population is 14.6%. Patients were identified as having clinical OC, if they presented between 30 and 40 weeks of gestation with clinical symptoms of pruritus that could not be defined by any other etiology along with elevated liver enzymes. History and examination details of the study patients were noted. All necessary ANC investigations, especially liver function test (LFT), serum bile acid levels, nonstress test, and ultrasound examinations, were done. The biochemical tests such as LFT and serum bile acids were done at the Central laboratory of SKIMS. The criteria that were used for diagnosing OC were raised level of serum bile acids (>10 μmol/l) and/or pruritus coinciding with liver dysfunction. The study patients were classified as:

  • Group A: TBA level <40 μmol/l and
  • Group B: TBA level >40 μmol/l.


Respiratory distress was defined as any neonate that required intubation, continuous positive airway pressure, bag/mask ventilation postpartum, diagnosis of pneumonia, documentation of respiratory distress secondary to meconium aspiration, or documentation by a health-care provider based on physical examination. Babies were defined as low birth weight when their weight was <2500 g at birth.

Inclusion criteria

  1. Primigravida
  2. Gestational age between 30 and 40 weeks
  3. Pruritus with elevated liver enzymes (alanine aminotransferase >41 U/l and/or aspartate aminotransferase >40 U/l)
  4. Singleton pregnancy.


Exclusion criteria

  1. Chronic liver disease (hepatitis B, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, symptomatic cholelithiasis, cholecystitis, Wilson's disease, alpha-1-antitrypsin deficiency, cytomegalovirus, Epstein–Barr virus, or autoimmune hepatitis)
  2. Human immunodeficiency virus infection
  3. Smoking, alcohol, and drug addiction
  4. Dermatological diseases with itching and rash
  5. AFLP
  6. Hemolysis, elevated liver enzymes, and low platelet count syndrome
  7. Multiple pregnancy
  8. Gestational hypertension
  9. Intrauterine growth restriction, oligohydramnios, and anemia.



  Results Top


Out of a total of 55°C patients, fetal complications occurred in 23 (41.8%) patients with no case of fetal complication reported in 32 (58.1%) patients, as shown in [Table 1] [Figure 1].
Table 1: Fetal complications in intrahepatic cholestasis of pregnancy patients

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Figure 1: Percentage of fetal complications in intrahepatic cholestasis of pregnancy patients

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In [Table 2] [Figure 2], out of the 55 patients diagnosed with ICP, 35 (63.6%) patients belonged to Group A with TBA <40 μmol/l and 20 (36.3%) patients belonged to Group B with TBA >40 μmol/l.
Table 2: Fetal complications in intrahepatic cholestasis of pregnancy patients

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Figure 2: Classification of intrahepatic cholestasis of pregnancy patients on the basis of total bile acid levels

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In Group A, only five (14.2%) cases of fetal complications were reported, with the remaining 30% (5.7%) patients having no fetal complication. On the other hand, 18 (90%) fetuses had complications in Group B, with 2 (10%) patients having no fetal complication, as shown in [Table 3] [Figure 3].
Table 3: Frequency of fetal complications between Groups A and B

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Figure 3: Frequency of fetal complications between Groups A and B

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In [Table 4] [Figure 4], in Group A, only five (14.2%) cases of fetal complications were reported, among which three (60%) fetuses had respiratory distress and two (40%) had low birth weight. The average birth weight in Group A was 2.91 kg. There was no stillbirth or IUFD in Group A. Most of the fetal complications occurred in Group B, among which ten (55.5%) fetuses had respiratory distress and five (27.7%) fetuses had low birth weight. The average birth weight in Group B was 2.68 kg. There were one (5.5%) stillbirth and two (11.1%) IUFDs in Group B, as shown in [Table 4] [Figure 4]. There were four preterm deliveries in each group.
Table 4: Comparison of fetal complications between Groups A and B

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Figure 4: Comparison of fetal complications between Groups A and B

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  Discussion Top


Although OC is usually relatively benign to the mother, it is known that the risk of fetal complications is increased in pregnancies affected by OC. These include increased risks of respiratory distress, meconium-stained amniotic fluid, low birth weight, stillbirth, and IUFD.

In our study, out of a total of 55°C patients, fetal complications were reported in 23 (41.8%) cases, while there was no such complication in 32 (58.1%) cases, as shown in [Table 1] [Figure 1]. In our study, 35 (63.6%) patients had lower bile acid levels and only 20 (36.3%) had higher bile acid levels, as shown in [Table 2] [Figure 2].

In our study, we found that most (90%) of the fetal complications occurred in those patients with higher bile acid levels (Group B) in comparison to Group A (14.2%), as shown in [Table 3] [Figure 3]. This suggests that higher serum bile acid levels are associated with higher rate of perinatal morbidity and mortality. This is in agreement with the study conducted by Laatikainen, Ikonen, Glantz et al.,[4],[5] who demonstrated that ICP cases with higher maternal serum bile acid levels (>40 μmol/l) more commonly have pregnancies complicated by meconium-stained liquor, cardiotocograph abnormalities, and fetal asphyxial events. They concluded that pregnancies in women with TBA >40 mmol/l had an increased fetal risk of preterm delivery, asphyxial events, meconium staining of amniotic fluid, and green staining of placenta and membranes, whereas those with TBA between 10 and 39 mmol/l had minimal to no increased risk compared to women with pruritus but normal TBA, and that based on these findings, the latter women could be managed expectantly and possibly reduce the costs of medical care.

In Group A, only five (14.2%) cases of fetal complications were reported, among which three (60%) fetuses had respiratory distress, as shown in [Table 4] [Figure 4]. On the other hand, in Group B, ten (55.5%) fetuses had respiratory distress. It has been reported by Zecca et al.[19],[20] that the incidence of respiratory distress syndrome in neonates born to mothers with ICP is twice that of the normal population. This can be due in part to the earlier gestational age at delivery, but neonatal respiratory distress syndrome has been demonstrated to be associated with ICP, based on an analysis of bronchoalveolar lavage fluid of neonates born to mothers with ICP.[12] Specifically, it has been hypothesized that bile acids can produce surfactant depletion in the alveoli.[19],[20] Animal models have shown microscopic findings of atelectasis, poling of eosinophilic substances in intra-alveolar spaces, and formation of hyaline membranes in rabbits after intratracheal instillation of taurocholic acid. When treated with surfactant, alveoli responded appropriately, and had increased aeration.[21]

In [Table 4] [Figure 4], two (40%) fetuses had low birth weight in Group A, whereas in Group B, five (27.7%) fetuses had low birth weight. Li et al.[22] demonstrated that neonatal birth weight is lower in ICP pregnancies than in normal pregnancies.

In our study, there was no stillbirth or IUFD in Group A, whereas in Group B, there were one (5.5%) stillbirth and two (11.1%) IUFDs, as shown in [Table 4] [Figure 4]. A study by Fisk et al.[23] concluded that meconium staining and IUFD occurred more in those with higher TBA levels. The risk of fetal morbidity and mortality in ICP is higher than that in the general population.[5],[23],[24],[25],[26] In another study conducted by Estiú et al.,[27] it was reported that the probability of meconium staining of amniotic fluid in OC patients was enhanced four times as compared to normal obstetric patients.


  Conclusion Top


Our study suggests that there is a significant risk for fetal morbidity and mortality in OC with evident implications for future health of the offspring. In our study of 55 ICP patients, 23 (41.8%) pregnancies resulted in perinatal complications, with respiratory distress being the most common complication. We also found that most of the fetal complications occur in those with higher bile acid pool. This suggests that the sensitivity of bile acids can be used as a predictive marker of fetal risk in OC. This implies that pregnancies affected by OC fall in the high-risk category and need fetal surveillance. The agents that reduce maternal bile acids may reduce fetal complications, but if the mechanism of fetal death involves bile salt-induced fetal arrhythmias without any placental insufficiency, it may be that such monitoring will not be effective in preventing ICP-associated fetal loss.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
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Glantz A, Marschall HU, Lammert F, Mattsson LA. Intrahepatic cholestasis of pregnancy: A randomized control trial comparing dexamethasone and ursodeoxycholic acid. Hepatology 2005;42:1399-405.  Back to cited text no. 18
    
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23.
Fisk NM, Storey GN. Fetal outcomes in obstetric cholestasis. Br J Obstet Gynaecol 1988;95:1137-43.  Back to cited text no. 23
    
24.
Rioseco AJ, Ivankovic MB, Manzur A, Hamed F, Kato SR. Intrahepatic cholestasis of pregnancy: A retrospective case-control study of perinatal outcome. Am J Obstet Gynecol 1994;170:890-5.  Back to cited text no. 24
    
25.
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26.
Laatikainen T, Tulenheimo A. Maternal serum bile acid levels and fetal distress in cholestasis of pregnancy. Int J Gynaecol 1984;22:91-4.  Back to cited text no. 26
    
27.
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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