European Journal of Cardiovascular Medicine

Pregnancy is a unique medical condition characterized by various typical physiological changes that impact body organs, including the liver. The liver performs crucial metabolic and synthetic functions in the body. Jaundice and pregnancy are rarely linked despite various external and internal factors. Jaundice is a symptom of liver and bile duct dysfunction, not a disease itself.  Abnormal liver function tests can be found in 3-5% of pregnancies due to various factors such as viral hepatitis, gallstones, chronic liver disease, hyperemesis gravidarum, preeclampsia, HELLP syndrome, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy.[1] Liver disease, although rare, can lead to substantial illness and death for both the pregnant woman and the fetus.

Concerning fetal effects include increased rates of intrauterine deaths, stillbirths, meconium staining of amniotic fluid, fetal distress, and the transmission of viral hepatitis from the mother to the fetus, leading to chronic liver disease.[2,3]Complications such as DIC, coagulation disorders, hepatic encephalopathy, APH, and PPH may lead to negative maternal and perinatal outcomes. However, this occurs in women not only with jaundice but also with fever, dehydration, hypoglycemia, and severe malnourishment. The genetic contribution of the fetus may play a role in certain maternal conditions such as AFLP. Several studies have documented negative fetal outcomes such as intrauterine death (1-2%), meconium staining of amniotic fluid (15-50%), prematurity (2-27%), and complications related to iatrogenic prematurity. The UKOSS report states that the perinatal mortality risk for AFLP is 10%, but this rate could be significantly higher in developing countries. Liver rupture can increase the perinatal death rate to 60%. Hyperemesis may lead to fetal growth restriction, while severe cases with Wernicke’s encephalopathy can result in pregnancy loss.[4]

An observational study was carried out in the obstetrics and gynaecology department of a tertiary care hospital in Central India for a duration of 1 year. The sample size was determined in R studio software using the standard formula [pwr. Chisq. test (effect size=0.60, df=1, power=0.80, sig. level = 0.05)] at a 95% significance level. With a power of 80%, the minimum required sample size was calculated to be 43. 50 patients with abnormal liver functions were included in the study. This study included all pregnant patients who had abnormal liver function tests. Patients with normal liver function were not included. All patients provided written informed consent before participating in the study. Demographic information and a thorough clinical history were gathered, which included age, obstetrical history, number of pregnancies, and cause. A thorough laboratory investigation was conducted to examine the complexities related to biochemical parameters. Maternal and foetal results were also documented. The collected data was structured in Microsoft Excel. Analysed the association between biochemical factors and maternal and foetal outcomes using a chi-square test on a freely available online statistical calculator. A P value less than 0.05 was deemed statistically significant.

The study comprised 50 patients, with the majority falling within the age range of 21 to 30 years, constituting 80% of the sample. Specifically, 44% were between 21 to 25 years old, while 36% were within the 26 to 30-year-old bracket. Patients under 20 years old accounted for 12% of the sample, while those older than 31 years comprised only 8%. The mean age of the patients was 25.2 years, with a standard deviation of 3.78, suggesting a relatively homogeneous distribution around this average age.

Table 2 presents the laboratory parameters of 25 patients, showcasing various categories and the corresponding percentages within each category. Hemoglobin (Hb) levels below 7 gm% were predominant, constituting 76% of the sample, while Hb levels above 7 gm% were observed in 24% of patients. In terms of Total Leukocyte Count, the majority fell within the range of 7000-11000 cells/µL (60%), with 12% below 7000 cells/µL and 28% above 11000 cells/µL. Platelet counts varied, with 32% below 50000 cells/µL, 28% between 51000-150000 cells/µL, and 40% above 150000 cells/µL. Total bilirubin levels below 2 mg/dL were noted in 60% of patients, while direct bilirubin levels below 0.2 mg/dL were observed in 20% of cases. SGOT and SGPT levels above 70 U/L were prevalent in 76% of patients, while those below 70 U/L were seen in 24%. Alkaline phosphatase levels above 180 IU/L were recorded in 68% of patients. Lactate dehydrogenase levels above 600 U/L were noted in 84% of cases. In terms of albumin levels, 60% were above 2.5 gm/dL. Total protein levels above 8.5 gm/dL were observed in 52% of patients, with 48% below this threshold. Urea levels above 6.8 mg/dL were found in 60% of patients, while creatinine levels above 1.4 mg/dL were seen in the same proportion.

Table 3 outlines the maternal and fetal outcomes observed in the study. Among neonatal outcomes, 56% of infants were classified as low birth weight, while 44% experienced intrauterine growth restriction (IUGR). Additionally, 40% were born preterm, and 12% sadly resulted in neonatal death. Regarding maternal outcomes, 44% of deliveries were conducted via lower segment cesarean section (LSCS), and 40% of neonates required admission to the intensive care unit (ICU). Furthermore, 36% of mothers received blood transfusions, indicating complications during delivery. However, maternal mortality was relatively low, with only 4% of mothers experiencing fatal outcomes.

Table 4 provides insights into the association between abnormal laboratory parameters and adverse fetal and maternal outcomes. Among the fetal outcomes, elevated levels of total bilirubin (>2mg/dL) were significantly associated (P=0.046) with adverse fetal outcomes, while direct bilirubin levels (>0.3mg/dL) also showed a significant association (P=0.024). Additionally, high levels of SGOT (>70U/Lit) were significantly associated (P=0.010) with adverse maternal outcomes. Alkaline phosphatase levels (>180IU/Lit) also exhibited a significant association (P=0.023) with adverse maternal outcomes. Hemoglobin levels below 7gm% showed a marginal significance (P=0.05) in association with both adverse fetal and maternal outcomes. Other parameters such as SGPT, LDH, albumin, total protein, urea, creatinine, and total leukocyte count did not show statistically significant associations with adverse fetal or maternal outcomes in this study.

HELLP syndrome is characterized by elevated blood pressure along with proteinuria or end-organ dysfunction occurring after 20 weeks of gestation in the absence of proteinuria.[5]In this study, HELLP syndrome was the most prevalent syndrome observed at 44%, followed by acute fatty liver of pregnancy (AFLP) at 32%, preeclampsia at 28%, cholestasis of pregnancy at 28%, and hyperemesis gravidarum (HEG) at 12%. In a study conducted by Reddy et al, HELLP syndrome was the most prevalent, affecting 33.3% of patients, followed by acute fatty liver of pregnancy in 22.2% and intrahepatic cholestasis of pregnancy in 11.1% of patients.[6] In a study by Suresha et al and Allen et al, HELLP syndrome was found to be the second most common cause after eclampsia and preeclampsia, respectively. [7,8] Satia et al. found that viral hepatitis was the most common cause (62%), followed by cholestasis of pregnancy (24%).[9 ]The pathogenesis of HELLP syndrome is still not clearly understood but is believed to be related to pregnancy.[10,11 ]However, in this study, it can also be linked to the presence of HELLP syndrome, which is connected to vascular endothelial abnormalities. [12]

Liver dysfunction was apparent in a significant number of patients due to elevated levels of bilirubin.SGOT, SGPT, and bilirubin levels were elevated in 76%, 76%, and 40% of cases, respectively. In a related study, Ronceglia et al. documented a moderate increase in bilirubin levels ranging from 1 to 10 mg% along with hypoglycemia.[13 ]Shinde et al. also observed higher bilirubin levels in pregnant patients with jaundice compared to non-pregnant patients.[14] During the study, 38.4% of pregnant patients had serum bilirubin levels between 11 - 15 mg/dl, while 19.2% had levels between 16 and 25 mg/dl. Among non-pregnant patients, 36.5% had serum bilirubin levels between 6 and 10 mg/dl.[14]The primary adverse neonatal outcome was low birth weight in 56% of cases, followed by intrauterine growth retardation (IUGR) in 44%.40% of the neonates were preterm, and the neonatal death rate was 12%. The study found that 12% of perinatal deaths were attributed to jaundice. Parveen et al. also identified low birth weight as the most common adverse fetal outcome.[15]Low levels of haemoglobin in mothers can lead to restricted oxygen supply to the fetus, resulting in intrauterine growth restriction and low birth weight.[16] Bora et al. found a significant association between fetal birth weight and anemia (mild and severe).[17]Interestingly, Singh et al. reported a very high perinatal mortality rate of 45.45%. [18]

The most frequent adverse outcomes among mothers were the need for emergency lower segment cesarean section (44%), admission to the intensive care unit (40%), and blood transfusion (36%).One maternal death (4%) was observed in the current study. D'Souza et al. found disseminated intravascular coagulation (DIC) to be the most common adverse maternal outcome.[19]Kamalajayaram et al reported a maternal death rate of 33.3%, while Singh et al reported a rate of 10%. [20,18]HELLP syndrome is linked to weight gain and edema in 60% of cases, with a maternal mortality rate of 20% and a neonatal mortality rate of 31%.[20]During pregnancy, acute fatty liver results in a maternal mortality rate of 18%, increased risk of preterm labor, and a perinatal mortality rate of 23%.[20]

Increased levels of serum total bilirubin (P=0.046) and direct bilirubin (P=0.024), thrombocytopenia (P=0.027), and low hemoglobin levels (P=0.05) were significantly linked to negative outcomes for the fetus. While the median maternal haemoglobin levels were generally within the normal range, females who experienced adverse events had notably lower levels. Several studies have detailed the connection between maternal anemia and negative fetal outcomes.[17,21]Elevated direct bilirubin, SGOT, and alkaline phosphatase levels, low hemoglobin level, and thrombocytopenia were significantly linked to negative maternal outcomes in the patients. Maternal deaths increased in direct correlation with the serum bilirubin levels. Trivedi et al also documented comparable results.[22]Trivedi et al. mentioned that an initial bilirubin level greater than 10 at admission is linked to unfavorable maternal outcomes and increased maternal mortality.[22] Thus, these laboratory parameters may serve as an indicator of negative maternal and fetal results.

Recent studies on this topic are scarce, making this study a significant contribution to understanding the impact of jaundice during pregnancy. Conducting a comparative study between pregnant women with and without jaundice would help in obtaining definitive conclusions.

Pregnant individuals with liver abnormalities constitute a distinct subgroup.The symptoms are typically vague. Hepatic abnormalities during pregnancies have a negative impact on both maternal and neonatal outcomes. Maternal anemia, thrombocytopenia, coagulopathy, and hyperbilirubinemia are also present.Timely identification of these patients is essential and can decrease the negative consequences for both the mother and the newborn.

1. Hay JE. Liver disease in pregnancy. Hepatology. 2008 Mar 1;47(3):1067-76.
2. Joshi D, James A, Quaglia A, Westbrook R, Heneghan M. Liver disease in pregnancy. The Lancet. 2010;375(9714):594–605.
3. Lata I. Hepatobiliary diseases during pregnancy and their management: An update. International journal of critical illness and injury science. 2013 Jul;3(3):175.
4. (High risk pregnancy-management options James, Steer, Weiner, Gonik, Crowther, Robson-4^th ed).

5. SharmaAV,JohnS.LiverDiseaseinPregnancy. InStat Pearls [Internet] 2019 Jul 30. Stat Pearls Publishing. Available from: https://ncbi.nlm.nih. gov/books/ NBK482201/
6. Reddy MG, Prabhakar GC, Sree V. Maternal and fetal outcome in jaundice complicating pregnancy. J NTRUni Health Sci. 2014; 3: 231-33.
7. Suresh I, Vijaykumar TR, Nandeesh HP. Predictors of fetal and maternal outcome in the crucible ofhepatic dysfunction during pregnancy. Gastroentero Res. 2017;10(1): 21.
8. Allen AM, KimWR,LarsonJJ,et al.Theepidemiology of liver diseases unique to pregnancy in a US community: a population-based study. Clin Gastroenterol Hepatol. 2016;14: 287-94.
9. Satia MN, Jandhyala MA. Study of fetomaternal out comes in cases of jaundice a tatertiary care center.IntJRepContraceptObstGynecol2016;5: 2352 - 57.
10. Stephen G, Mgongo M, Hussein Hashim T, Katanga J, Stray-Pedersen B, Msuya SE. Anaemia in pregnancy: Prevalence, risk factors, and adverse perinatal outcomes in Northern Tanzania . Anemia. 2018;ArticleID 1846280; 1-9.
11. Bakrim S, Motiaa Y, Ouarour A, Masrar A. Hematological parameters of the blood count in a healthy population of pregnant women in the Northwest of Morocco(Tetouan-M’diq-Fnideq provinces).Pan Afr Med J. 2018; 29:1-2.
12. Lata I. Hepatobiliary diseases during pregnancy and their management: An update. Int J Crit Illn Inj Sci. 2013; 3:175-82.
13. Ronceglia N, Trio D. Roffi L, et al. Intrahepatic cholestasis in pregnancy: incidence, clinical course, complications. Ann Obst Gynecol Med Perinat. 1991; 112:146-51.
14. ShindeNR,PatilTB,DeshpandeAS,GulhaneRV,Patil MB, Bansod YV. Clinical profile, maternal and fetal outcomes of acute hepatitis E in pregnancy. Ann Med Health Sci Res. 2014; 4:133-39.
15. ParveenT,BegumF,AkhterN.Feto-MaternalOutcome of Jaundice in Pregnancy in a Tertiary Care Hospital. Mymensingh Med J. 2015; 24: 528-36.
16. Stangret A, Wnuk A, Szewczyk G, Pyzlak M, Szukiewicz D. Maternal hemoglobin concentration and hematocrit values may affect fetus development by influencing placental angiogenesis.J Matern Fetal Neonatal Med. 2017; 30:199-204.
17. Bora R, Sable C, WolfsonJ, BoroK, RaoR. Prevalence of anemia in pregnant women and its effect on neonatal outcomes in Northeast India. J Matern Fetal Neonatal Med. 2014; 27: 887-91.
18. SinghS, Chauhan R, Patel RS.Jaundice in pregnancy. J ObstGynecol India. 1991; 41:187-89.
19. D'Souza AS, Gupta G, Sandeep SG, Katumalla FS, GoyalS. Maternalandfetal outcomeinliver diseases of pregnancy: a tertiary hospital experience. International Journal of Scientific and Research Publications. 2015; 5:1-4.
20. Kamalajayaram V, Rama Devi A. A study of maternal mortality in jaundice. J Obst Gynecol India. 1988; 38: 439-41.
21. Manisha N, Manoj KC, Saswati SC, Swapna DK, Umesh CS, Premila W, Marian K. Association between maternal anaemia and pregnancy outcomes: A cohort study in Assam, India. BMJ Global Health. 2016;1:Trivedi SS, Goyal U, Gupta U. A study of maternal mortality due to viral hepatitis. J Obstet Gynecol India. 2003; 53: