European Journal of Cardiovascular Medicine

Intrahepatic cholestasis of pregnancy is most common pregnancy related liver disorder and unique to pregnancy. It is characterised by pruritus with onset in the 2nd or 3rd trimester of pregnancy without skin rash, elevated serum amino transferases and bile acid levels and spontaneous relief of signs and symptoms within 2-3 weeks after delivery[1,2]. The symptoms and biochemical abnormalities resolve rapidly after delivery but may recur in subsequent pregnancies and with the use of hormonal contraception.

The incidence of ICP (Intrahepatic cholestasis of pregnancy) varies widely with geographical location and ethnicity[3]. ICP affects 0.7% of pregnancies in whites in the United Kingdom and approximately double this proportion of women of South Asian in origin[4,5]. In South Asian population, it varies from 0.8 to 1.4 %.

The etiology of ICP is elusive, although current investigations suggest a combination of hormonal, genetic, and inflammatory factors that impair bile secretory function, which increases maternal serum bile acid and elevates the production of liver enzymes6.

Patients with intra hepatic cholestasis of pregnancy have distressing pruritus worsening at night and affect mainly the abdomen and palms and soles[1,5]. According to several studies, although the maternal course is usually benign, except slight increase in risk of postpartum haemorrhage and there is an increased risk of perinatal morbidity and mortality as in increased risk of spontaneous preterm delivery, non- reassuring feta status, fetal compromise, meconium-stained amniotic fluid, and intrauterine fetal demise(IUFD)[6,7,8].

The presenting feature of intrahepatic cholestasis of pregnancy is pruritus in the majority of cases. This typically occurs in the third trimester, with up to 80% of women presenting after 30 weeks of gestation[9,10] and some patients presenting as early as in the seventh gestational week.

To find out the adverse effects of intrahepatic cholestasis of pregnancy on feto- maternal outcomes.

Experimental design: It was a prospective observational study

Place of Study: The study was conducted at department of obstetrics and gynaecology in Chittaranjan Seva Sadan College of Obstetrics & Gynecology and Child Health.

Study period: 1 ½ years (March 2018 to July 2019)

Sample Size: 100 women (112 considered for study, among them 4 developed preeclampsia, 5 cases were lost to follow up and 3 cases refused to be a part of the study)

Inclusion criteria:

All Primigravid and Multigravida mothers attending OPD/ admitted in antenatal ward with complaints

-pruritis (or

-clinical jaundice (or)

-combination of complaints with period of gestation between 28-40 weeks.

Exclusion criteria:

1. Any H/O Hepatic Infection
2. Any H/O Hepatotoxic Drugs
3. Past H/O Liver and Gall Bladder Diseases
4. Pruritus Due to Any Skin Disease
5. Pregnant women with Chronic Hypertension, Pre-Eclampsia, Eclampsia
6. Pregnant women with thyroid disorder
7. Pregnant women with Gestational Diabetes Mellitus
8. Common haematological disorders

Parameters to be studied:

1. Maternal demographic data – Age, weight, height, BMI, Parity, Gestational age.
2. Antepartum fetal surveillance tests: NST (cardiotocography), USG for feto-placental profile, AFI. Same were repeated when indicated.
3. Labor events

• Onset of labour – Spontaneous or induced
• Mode of delivery – normal, instrumental or LSCS
• Indication for Caesarean section
• Partogram
• FHR tracing by CTG or intermittent auscultation by stethoscope or fetal Doppler
• Colour of liquor
• History of labour augmentation
• Induction of labour and indication of induction.
• Postpartum complications (like PPH)

4. Perinatal outcomes:

• Nonreactive NST (abnormal CTG)
• Meconium stained liquor
• Fetal distress/bradycardia
• Rate of caesarean section
• Low Birth weight
• Low Apgar score at 1&5 minutes
• Admission to NICU
• No. of day(s) stay in NICU
• Intrauterine fetal demise
• Perinatal mortality

Statistical Analysis

Data were entered into Excel and analysed using SPSS and Graph Pad Prism. Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests were used to compare independent groups, while paired t-tests accounted for correlations in paired data. Chi-square tests (including Fisher’s exact test for small sample sizes) were used for categorical data comparisons. P-values ≤ 0.05 were considered statistically significant.

Table 1: Table showing age distribution of the patients (N=100)

Table 2: Table showing Indication of LUCS and type of LUCS

Table 3: Distribution of PPROM, Pre-term of Labour, PPH, LBW (<2.5kg)

Table 4: Distribution of APGAR at 1 minute<6, APGAR at 5, NICU Admission

The majority of patients (42%) were in the 21–25 age group, followed by 35% in the 26–30 group, and 14% in the 17–20 group. Only 8% were aged 31–35, and 1% were over 35. The distribution was statistically significant with a P value < 0.00001, indicating a strong association between age and patient frequency.

The mean ± standard deviation of the patients’ age was 24.91 ± 4.23 years. This reflects a predominantly young adult population with moderate age variability.

Among the indications for LUCS, Pathological CTG with OC (15.3%) and IF with OC (15.3%) were the most common overall, predominantly seen in EMLUCS cases. Other frequent indications included MSL with FD (11.9%) and Persistent less FM (10.2%). The distribution of indications between ELCS and EMLUCS was statistically significant (P < 0.0001), highlighting differing clinical scenarios.

Out of 100 patients, 8% had PPROM (Preterm Premature Rupture of Membranes), while 92% did not. This shows that PPROM was relatively uncommon in the study population. The difference was statistically significant with a P value < 0.0001, indicating a non-random distribution.

In the study, 2% of patients experienced preterm labor, while 98% did not. This indicates a low incidence of preterm labor among the participants. The finding was statistically significant with a P value < 0.0001, suggesting a meaningful difference.

Among the patients, 8% experienced postpartum hemorrhage (PPH), whereas 92% did not. Although PPH occurred in a minority, it remains a critical concern. The distribution was statistically significant with a P value < 0.0001, indicating a non-random pattern.

In this study, 29% of newborns had low birth weight (LBW <2.5 kg), while 71% had normal birth weight. This highlights a notable prevalence of LBW among the cases. The association was statistically significant with a P value < 0.0001, indicating a significant deviation from random distribution.

At 1 minute, 20% of newborns had an APGAR score <6, while 80% had scores ≥6, indicating good initial adaptation. The occurrence of low APGAR scores was relatively limited but clinically significant. The result was statistically significant with a P value < 0.0001, suggesting a non-random distribution.

At 5 minutes, 8.5% of newborns had an APGAR score <6, while 91.5% showed improved scores ≥6, indicating better postnatal recovery. Though fewer newborns had low scores at this stage, it remains clinically relevant. The distribution was statistically significant with a P value < 0.0001.

In this study, 18.9% of newborns required NICU admission, while 81.1% did not, reflecting a moderate need for intensive neonatal care. This indicates that a significant minority of infants faced complications. The result was statistically significant with a P value < 0.0001, indicating a strong association.

The predominance of patients aged 21–30 years suggests that this age group is most commonly affected or seeks care, likely reflecting peak reproductive years. The significant P value (<0.00001) confirms a non-random age distribution, emphasizing age as a key factor in patient demographics. This aligns with existing literature highlighting young adults as the primary reproductive population. A similar study, The predominance of patients aged 21–30 years in this study indicates that ICP primarily affects women in their peak reproductive years, consistent with previous research. A similar age distribution was reported by Geenes et al. (2014), who found that ICP commonly presents in young adult women, reflecting physiological and hormonal changes during this period. The significant P value (<0.00001) in our study supports a non-random pattern, underscoring age as a critical demographic factor in ICP incidence and outcomes.[11]

The mean age of 24.91 ± 4.23 years indicates that the study population mainly consisted of young adults within a relatively narrow age range. This moderate variability suggests most patients were in their prime reproductive years. Such age distribution is consistent with typical childbearing demographics in clinical settings.

The study shows that Pathological CTG with OC and IF with OC were leading indications for LUCS, especially in EMLUCS cases, reflecting critical fetal concerns. Other notable indications like MSL with FD and Persistent less FM emphasize varied clinical challenges. The significant P value (<0.0001) highlights distinct patterns between ELCS and EMLUCS groups, underscoring tailored clinical decision-making. The study identifies Pathological CTG with obstetric complications (OC) and induction failure (IF) with OC as primary indications for lower uterine cesarean sections (LUCS), particularly in emergency cases (EMLUCS), highlighting significant fetal distress. Similar findings were reported by Reddy et al. (2017), where fetal monitoring abnormalities and labor complications were leading causes for emergency cesarean deliveries in ICP patients. Other indications such as malpresentation with fetal distress (MSL with FD) and persistent reduced fetal movements further emphasize the complex clinical scenarios faced. The highly significant P value (<0.0001) in this study underscores the need for individualized clinical management between elective and emergency cesarean groups in ICP cases.[12]

In this study, PPROM was observed in 8% of patients, indicating it is a relatively infrequent but important complication. The significant P value (<0.0001) suggests that the occurrence of PPROM is not due to chance and may have clinical relevance. These findings highlight the need for careful monitoring of at-risk pregnancies.

The low incidence of preterm labor at 2% reflects a relatively stable pregnancy outcome within the study population. The highly significant P value (<0.0001) indicates this low rate is unlikely due to chance. This suggests effective management or low risk factors for preterm labor among participants. The low incidence of preterm labor at 2% in this study indicates relatively favorable pregnancy outcomes among women with ICP. Comparable findings were reported by Glantz et al. (2004), who observed that with appropriate monitoring and management, the risk of preterm labor in ICP cases can be minimized. The highly significant P value (<0.0001) in the present study suggests that this low incidence is statistically meaningful, reflecting effective clinical interventions or inherently low risk in the study population.[13]

Postpartum hemorrhage affected 8% of patients, underscoring it as a notable but less frequent complication. Despite the low incidence, its statistical significance (P < 0.0001) highlights the importance of vigilant monitoring and management. These findings reinforce PPH as a critical factor in maternal care.

The study revealed a significant prevalence of low birth weight (29%), indicating considerable neonatal risk within the population. The statistically significant P value (<0.0001) suggests this finding is unlikely due to chance. This emphasizes the need for targeted interventions to improve birth outcomes.

At 1 minute, 20% of newborns had APGAR scores below 6, indicating some initial distress in a notable minority. The majority (80%) showed good adaptation, but the significant P value (<0.0001) highlights that low scores were not due to chance. This underscores the importance of immediate neonatal assessment and care. At 1 minute, 20% of newborns had APGAR scores below 6, indicating initial neonatal distress in a significant minority of cases. Similar results were observed by Reyes et al. (2018), who reported increased rates of low APGAR scores in infants born to mothers with ICP, underscoring the heightened risk of early neonatal compromise. The significant P value (<0.0001) in this study emphasizes the importance of vigilant neonatal assessment and prompt intervention to improve outcomes.[14]

By 5 minutes, the proportion of newborns with APGAR scores <6 decreased to 8.5%, reflecting improved neonatal condition after initial intervention. The majority (91.5%) showed good recovery, yet the significant P value (<0.0001) indicates this decline in low scores is meaningful. This highlights the effectiveness of immediate postnatal care in stabilizing newborns.

NICU admission was required for 18.9% of newborns, indicating a notable proportion faced complications needing specialized care. The majority (81.1%) did not require NICU, reflecting overall favorable neonatal outcomes. The statistically significant P value (<0.0001) emphasizes the importance of identifying and managing at-risk infants promptly. NICU admission was necessary for 18.9% of newborns, highlighting that a significant subset of infants born to mothers with ICP experienced complications requiring specialized care. This finding aligns with the study by Geenes et al. (2014), which reported increased neonatal intensive care admissions among infants of ICP-affected pregnancies due to risks like respiratory distress and prematurity. The statistically significant P value (<0.0001) in our study underscores the critical need for early identification and proactive management of at-risk neonates.[15].

Intrahepatic cholestasis of pregnancy (ICP) significantly impacts feto-maternal outcomes, predominantly affecting women in their prime reproductive age. This study highlights that ICP is associated with increased risks of adverse fetal events, including low birth weight, low APGAR scores, and a higher rate of NICU admissions, emphasizing the need for vigilant fetal monitoring. Though the incidence of preterm labor and postpartum hemorrhage was low, the statistically significant findings underscore the importance of timely clinical interventions to mitigate complications. Emergency lower uterine cesarean sections were often indicated due to fetal distress and pathological CTG findings, reflecting the critical fetal concerns linked to ICP. Overall, effective management protocols and early detection are vital to improving neonatal and maternal outcomes. Close surveillance, individualized care, and prompt decision-making can reduce morbidity, supporting better prognoses in pregnancies complicated by ICP. Future studies are encouraged to further refine management strategies and minimize risks associated with this condition. 

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