Obstetric cholestasis and its impact on the maternal outcome

Obstetric cholestasis and its impact on the maternal outcome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Obstetric cholestasis and its impact on the maternal outcome EKTA TIWARI, Dr.SHAZIA PARVEEN, DR.NASREEN NOOR This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3684427/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract AIM To evaluate the association of GDM and pre-eclampsia in women with obstetric cholestasis MATERIAL AND METHODS Pregnant women with >28weeks gestation attending ANC, OPD and labour room of J.N.M.C.H,AMU, Aligarh U.P (India) from 2020-2022 were included in the study after taking informed consent and ethical approval from the Institute. Women were divided into two groups ie group 1 having 200 women with IHCP and group 2 having 200 healthy pregnant women, both the groups were followed up for the development of GDM and pre-eclampsia. RESULTS A statistically significant association was observed between IHCP and development of GDM (26.5% & Odds ratio 1.64) and pre-eclampsia (17% & Odds ratio 1.95) (p<0.05), also GDM and pre-eclampsia were found to be significantly associated with the severity of cholestasis (p<0.05). Thus on calculating odds ratio, we found higher odds of developing GDM and Pre-eclampsia in IHCP group with raised serum bile acid levels, maximum at 60μmol/L level as compared to 10-40 μmol/L (GDM: OR:8.647 & Pre-eclampsia: OR:6.303). Induction and cesarean rate was significantly higher in IHCP group (p<0.05). CONCLUSION Our study concludes significant association of IHCP with GDM and Pre- eclampsia as all three shares common pathogenetic pathways and greater risk of development was at higher serum bile acid levels. Serum bile acid levels Intrahepatic cholestasis of pregnancy Gestational diabetes mellitus Pre-eclampsia Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Intrahepatic cholestasis of pregnancy (IHCP), usually occurs in the late second or third trimester and is one of the most frequent liver disorders seen in pregnancy. It’s a reversible cholestatic disease as it resolves spontaneously within 4–6 weeks post-delivery 1 , 2 It is diagnosed on the basis of pruritus without rash predominantly of the palms and soles, increased levels of liver enzymes (AST; ALT), and raised serum bile acid levels (≥ 10 µmol/L) 3,4 . The general incidence of IHCP depending on the geographic variation varies from 1.0–27.6%. 5,6 It shows differences based on environmental factors and ethnic groups. , Incidence is 1.24% in the Indian population, while it is 1.46% in the Pakistani population, the white population has a low incidence of 0.62%. 7,8 Pathogenesis of IHCP seems to be multifactorial, but the exact mechanism is not known. Hormonal changes during pregnancy i.e., elevated estrogen and progesterone levels as well as the alteration in the cell membrane configuration of bile ducts and liver cells along with defective transport mechanisms in biliary canaliculi indicate a strong genetic cause. 9 , 10 Studies have demonstrated genetic mutations in several genes e.g., ABCB4 and ABCB11 gene encodes for MDR3 protein and BSEP (bile salt export pump) protein respectively. However, geographic distribution and exogenous factors like higher maternal age and low selenium level also affect the incidence. 11 , 12 . MATERIAL AND METHODS Pregnant women attending ANC, OPD, and labor ward at J.N.M.C.H, AMU, Aligarh, U.P (India) with > 28weeks gestation with complaint of itching over palm and soles, derranged liver enzymes (AST/ALT doublely raised) and raised serum bile acid (more than 10 micromol/L) were included in the study from 2020–2022 after taking informed consent and ethical approval from the Institute. The study was prospective cohort observational type. All the study participants Inclusion Criteria Pregnant women with gestation age of > 28 weeks with Obstetrics cholestasis. Exclusion Criteria Known cases of GDM and pre-eclampsia, pruritus due to other known dermatological causes, infective hepatitis, and other medical disorders like thyroid disorders, DM, CAD, etc. After taking informed consent all participants underwent detailed history, examination and routine investigations like CBC, RFT, LFT, urine routine microscopy, and serum bile acid levels were done. Women were divided into two groups - Group 1 (IHCP) - Two hundred women diagnosed with IHCP Group 2 (Non-IHCP)- Two hundred healthy pregnant women Both the groups were compared for assessing the risk of development of GDM and Pre-eclampsia. After taking informed consent all participants underwent detailed history, examination and routine investigations. IHCP was diagnosed on the basis of complaint of itching, doubly raised liver enzymes and serum bile acid level > 10 µmol/L. Method of estimation of Serum Bile acid: Total serum bile acid levels were estimated by Beckman coulter AU680 Clinical Chemistry Analyser using Enzymatic method with cutoff value 10 µmol/L. GDM was diagnosed on the basis of diabetes in pregnancy study group of india DIPSI criteria i.e., blood sugar recorded 2 hours after giving 75gm oral glucose in 250 ml of water. A value of more than 140mg% was labelled as GDM. Pre-eclampsia was diagnosed with a BP ≥ 140/90mmHg on 2 occasions 4hours apart with proteinuria more than 300mg in a 24-hour urine collection. Sample size: Data were analyzed using SPSS version 23.0 Statistical tests: Chi-square test (p-value) and odds ratio. OBSERVATION & RESULTS In our study, the mean age was 27.32 ± 5.3 years in group 1 (IHCP) and 25.92 ± 4 years in group 2 (Non- IHCP). Both groups were comparable with regard to age. Majority of women in both the groups were literate and were primigravida (65% in group 1 and 70.5%in group 2). The mean gestational age at the time of delivery in group 1 was 37.5 ± 1.7 weeks while in group 2 was 38.1 ± 1.4 weeks . In group 1 majority of the cases had serum bile acid levels between 10–40µmol/L (57.5%) followed by 41–60µmol/L (30.0%) and > 60µmol/L (12.5%) (Fig. 1 ) Mean ALP, AST and ALT were significantly higher in the cases having serum bile acid levels above 60 µmol/ as compared to 10–40 µmol/l i.e., liver enzymes were significantly higher at higher bile acid levels. (p < 0.001) The occurrence of GDM was found in 26.5% of cases in the IHCP group while it was just 18% in non IHCP group and on comparing the groups the difference was found to be statistically significant. (p < 0.05 & OR:1.64) (Table 1 & Fig. 2 ) Table 1 Association of IHCP with development of GDM Maternal outcome Group 1-IHCP (n = 200) Group2-Non IHCP (n = 200) Odd Ratio p-value No. of patients (%) No. of patients (%) GDM Yes 53 26.5 36 18.0 1.64 0.041 No 147 73.5 164 82.0 *odd ratio (OR:1.64: 95% CI :1.02–2.65) Similarly, the development of pre-eclampsia was found in 17% of cases in the IHCP group while it was seen in 9.5% in non IHCP group, and on comparing the groups the difference was found to be statistically significant. (p < 0.05 & OR:1.95) (Table 2 & Fig. 3 ) Table 2 Association of IHCP with development of preeclampsia Maternal outcome Group1-IHCP (n = 200) Group2-Non IHCP (n = 200) Odds Ratio p-value No. of patients (%) No. of patients (%) Pre-eclampsia Yes 34 17.0 19 9.5 1.95 0.028 No 166 83.0 181 90.5 *Odds ratio (OR 1.95, 95% CI:1.07–3.55) The risk of development of GDM and pre-eclampsia was significantly more in IHCP cases with a higher level of serum bile acid i.e., at > 60µmol/L as compared to 10–40 µmol/L (p < 0.05) (GDM: OR:8.647 & Pre-eclampsia: OR:6.303) (Table 3 ) Table 3 Association of Serum bile acid with development of GDM Outcome Serum Bile Acid Levels (µmol/L) Odds Ratio (OR) p-value 10–40 (n = 115) 40–60 (n = 60) > 60 (n = 25) No. of patients (%) No. of patients (%) No. of patients (%) GDM Yes 17 14.8 21 35.0 15 60.0 8.647 < 0.001 No 98 85.2 39 65.0 10 40.0 Pre-eclampsia Yes 11 9.5 13 21.6 10 40.0 6.303 < 0.001 No 104 90.5 47 78.4 15 60.0 *GDM Odds ratio (OR: 8.647; 95% CI: 3.34–22.39) *Pre-eclmapsia Odds ratio (OR: 6.303 ; 95% CI: 2.29–17.36) Significantly higher rates of induction of labor (60.5%) and cesarean delivery (67.5%) were noted in the IHCP group as compared to non-IHCP (p < 0.05). DISCUSSION Pregnancy itself is a cholestatic condition and chronic liver diseases mostly unmask during pregnancy with clinical manifestation of cholestasis. 13 Intrahepatic cholestasis of pregnancy (IHCP) is the most frequent cause of cholestasis of pregnancy and pathogenesis is thought to be multifactorial, mostly depending on genetic configuration, geographical area, environmental changes, and ethnicity 14 Though it is considered to be a milder disease from a mother’s point of view several studies showed that IHCP is associated with a significant risk of developing pre-eclampsia as well as GDM. 15 GDM, pre-eclampsia, and, IHCP, all three shares a common pathway in its pathogenesis, and the Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily of ligand-regulated receptors that function as a bile acid sensor, plays a crucial role in maintaining bile acid, cholesterol, and glucose metabolism. It is supposed that FXR is expressed by pancreatic β-cells and regulates insulin metabolism 16 and a decrease in FXR and TGR5 activities causes aberrant bile acid and blood glucose homeostasis thus explaining the association of GDM and IHCP 17 Similarly higher level of bile acid in IHCP has been found to cause vasoconstriction of the chorionic plate veins which leads to structural damage of the placenta by causing impairment of the placental antioxidant system, resulting in the formation of an increased number of placental syncytial knots, found on histopathological examination and bile acid also cause endothelial injury in kidney and lungs by causing oxidative damage which further promote the formation of reactive oxygen species and a variety of vasoactive mediators, including endoglin-1, soluble fms-like tyrosine kinase receptor (sFlt-1), these findings were also seen in pre-eclampsia pathogenesis, thus explaining the relation between pre-eclampsia and IHCP 18 , 19 The present study showed a significant association of IHCP with increased risk of development of GDM and pre-eclampsia, these results were found to be consistent with the studies done by Liu et al, Marathe et al, Celik et al, Arthuis et al, Yadav et al, Rizvi and Raina et al, Naga et al, Matan et al and Samjhak et al 20 – 28 IHCP was also associated with higher rates of induction of labor and cesarean delivery, similar results were found in studies done by Liu et al, Yadav et al, Rizvi and Raina et al and Naga et al. 20 , 24 – 26 CONCLUSION The present study conducted on 200 women diagnosed with IHCP and 200 healthy pregnant women suggested an overall higher risk of development of GDM and pre-eclampsia in women with IHCP as compared to healthy pregnant women. We also found that there was a significant association between the occurrence of GDM and pre-eclampsia with raised serum bile acid levels. Thus, women with IHCP should be treated as a high-risk pregnancy and followed up in ANC visits with liver enzymes and serum bile acids They should also be kept under close surveillance for follow-up in regular ANC clinics and most importantly for early detection of the development of GDM and pre-eclampsia to prevent maternal and fetal complication and appropriate management. Since our study was done in a single center so its findings cannot be generalized to the whole population and due to the lack of availability of previous pregnancy records, women with a history of IHCP in previous pregnancy were not assessed for increased risk of IHCP in the subsequent pregnancy. Thus, we recommend a multicentric large randomized trial to ascertain the true relationship between IHCP and adverse maternal outcomes. DECLARATIONS Ethical consideration No conflict of interest It was observational study participants were included in the study after informed consent REFERENCES 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. Mikolasevic I, Filipec-Kanizaj T, Jakopcic I, Majurec I, Brncic-Fischer A, Sobocan N, et al. Liver disease during pregnancy: A challenging clinical issue. Med Sci Monit. 2018;24:4080-90. doi: 10.12659/MSM.907723, PMID 29905165. Hassan N, Khurshid R, Muzamil M, Parveen S. Cholestasis of pregnancy: effects on maternal and fetal outcome. Int J Reprod Contraception, Obstet Gynecol. 2020;9(8):3202. doi:10.18203/2320-1770.ijrcog20203296 Lim E, Mouyis M, MacKillop L. Liver diseases in pregnancy. Clin Med (Lond). 2021 Sep;21(5):e441-e445. doi: 10.7861/clinmed.2021-0497. PMID: 34507927; PMCID: PMC8439517. Jurk SM, Kremer AE, Schleussner E. Intrahepatic Cholestasis of Pregnancy. 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Intrahepatic cholestasis of pregnancy (Green top guideline no 43) Published 9; 2022 [cited August 2022]. Available from: https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/intrahepatic-cholestasis-of-pregnancy-green-top-guideline-no-43/. Dixon PH, Sambrotta M, Chambers J, Taylor-Harris P, Syngelaki A, Nicolaides K, et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. Sci Rep. 2017;7(1):11823. doi: 10.1038/s41598-017-11626-x, PMID 28924228. Aydın GA, Özgen G, Görükmez O. The role of genetic mutations in intrahepatic cholestasis of pregnancy. Taiwan J Obstet Gynecol . 2020;59(5):706-710. doi:10.1016/j.tjog.2020.07.014 Renga B, Mencarelli A, Vavassori P, Brancaleone V, Fiorucci S. The bile acid sensor FXR regulates insulin transcription and secretion. Biochim Biophys Acta - Mol Basis Dis . 2010;1802(3):363-372. doi:10.1016/J.BBADIS.2010.01.002 Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 2000;6(3):517-26. doi: 10.1016/S1097-2765(00)00051-4. Liu C, Gao J, Liu J, Wang X, He J, Sun J, et al. Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes and preeclampsia. Ann Transl Med. 2020;8(23):1574. Marathe JA, Lim WH, Metz MP, Scheil W, Dekker AG, Hague WM. A retrospective cohort review of intrahepatic cholestasis of pregnancy in a South Australian population. Eur J Obstet Gyne col Reprod Biol. 2017;218:33-38. Çelik S, Çalışkan CS, Çelik H, Güçlü M, Başbuğ A. Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy. Ginekologia Polska 2019;90(4):217–222 Arthuis C, Diguisto C, Lorphelin H, Dochez V, Simon E, Perrotin F, et al. Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study. PLoS ONE 2020;15(2): e0228213 Yadav R, Rani K and Najam R. Maternal and fetal outcomes in pregnancies complicated with intrahepatic cholestasis of pregnancy. International Journal of Clinical Obstetrics and Gynaecology 2021; 5(5): 152-156 Rizvi SM, Raina R. Fetomaternal outcome in jaundice complicating pregnancy. J Soc Obstet Gynaecol Pak 2018;8(3):176-9. Naga VKM, Joseph B, Kalappa MS. Obstetric Outcome in Women with Intrahepatic Cholestasis: A 3-year Study in a Tertiary Care Hospital in Bengaluru. Journal of South Asian Federation of Obstetrics and Gynaecology. 2019;11(2) Matan Mor M, Shmueli A, Krispin E, et al. Intrahepatic cholestasis of pregnancy as a risk factor for preeclampsia. Arch Gynecol Obstet 2020;301:655–664 Šimják P, Krejčí, H., Hornová, M, Mráz, M, Pařízek, A, Kršek, M et al. Establishing the Optimal Time for Induction of Labor in Women with Diet-Controlled Gestational Diabetes Mellitus: A Single-Center Observational Study. J. Clin. Med. 2022, 11, 6410. https://doi.org/ 10.3390/jcm11216410 Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 19 Feb, 2024 Reviewers invited by journal 28 Dec, 2023 Editor invited by journal 17 Dec, 2023 Editor assigned by journal 15 Dec, 2023 First submitted to journal 14 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3684427","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264017582,"identity":"77695e58-a27a-424f-b736-9e3659fcab1b","order_by":0,"name":"EKTA TIWARI","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYDACHhBhAMTMjI0PPv6xAbIYGw/g18LMwHAArIW52XBmQxpISwMRWsAs9jZp3obDYCZeLfw85w9+/lBwWN68nRGoZcd5u7Xth4G21NhE49Ii2dvMLHHA4LDhnMOMzZZzz9xO3nYmEajlWFpuAw4tBueZGYBabjPOAHr/xhu228lmB4BaGBsO49Rif56Z+QdQiz1QS4MED9u5ZLPzD/FrMeBtZgPZkgjU0iTJ23bAzuwGAVskzhw2szhj8D8ZqKXZcMaZ5ASzG0BbEvD4hb8n8fGNij9ptjP4jz988KHCzt7sfDqQUWODUwsGSASrTCBWOQjYk6J4FIyCUTAKRgYAAAuPZ68CqafWAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-1499-1699","institution":"Jawaharlal Nehru Medical College and Hospital: Jawaharlal Nehru Medical College","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"EKTA","middleName":"","lastName":"TIWARI","suffix":""},{"id":264017583,"identity":"4a07a5a6-8c64-4526-bc54-18d3af1c368e","order_by":1,"name":"Dr.SHAZIA PARVEEN","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"Dr.","firstName":"SHAZIA","middleName":"","lastName":"PARVEEN","suffix":""},{"id":264017584,"identity":"0524f3c8-578f-4cbb-93ea-f28973c1bf47","order_by":2,"name":"DR.NASREEN NOOR","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"DR.","firstName":"NASREEN","middleName":"","lastName":"NOOR","suffix":""}],"badges":[],"createdAt":"2023-11-30 02:16:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3684427/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3684427/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49133499,"identity":"58884437-9acc-404b-a4b1-37ebb57cbb82","added_by":"auto","created_at":"2024-01-03 16:43:53","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56291,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCases distribution on the basis of serum bile acids\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3684427/v1/8eb74f768fa301431c0bcda7.jpeg"},{"id":49133500,"identity":"ed709a30-cc1e-4d30-adbd-0a59280d32a2","added_by":"auto","created_at":"2024-01-03 16:43:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1043041,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssociation of IHCP with development of GDM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*p value \u0026lt;0.05 and Odds ratio:1.64 (95% CI :1.02-2.65)\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3684427/v1/2a931aa4ad49f2caab0885ad.png"},{"id":49133501,"identity":"7c449589-2947-42ab-890f-68ed80af12b4","added_by":"auto","created_at":"2024-01-03 16:43:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1022633,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssociation of IHCP with development of Pre-eclampsia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ep value \u0026lt;0.05 and Odds ratio: 1.95 (95% CI:1.07-3.55)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3684427/v1/d9d1ec8b4c7e15617e68a539.png"},{"id":49134273,"identity":"14404511-5018-4aa9-9972-2bbbc9862a2f","added_by":"auto","created_at":"2024-01-03 16:51:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":378920,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3684427/v1/0cf9841a-5afe-433a-acf8-11328e03e6e3.pdf"}],"financialInterests":"","formattedTitle":"Obstetric cholestasis and its impact on the maternal outcome","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eIntrahepatic cholestasis of pregnancy (IHCP), usually occurs in the late second or third trimester and is one of the most frequent liver disorders seen in pregnancy. It\u0026rsquo;s a reversible cholestatic disease as it resolves spontaneously within 4\u0026ndash;6 weeks post-delivery \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e It is diagnosed on the basis of pruritus without rash predominantly of the palms and soles, increased levels of liver enzymes (AST; ALT), and raised serum bile acid levels (\u0026ge;\u0026thinsp;10 \u0026micro;mol/L)\u003csup\u003e3,4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe general incidence of IHCP depending on the geographic variation varies from 1.0\u0026ndash;27.6%.\u003csup\u003e5,6\u003c/sup\u003e It shows differences based on environmental factors and ethnic groups.\u003csup\u003e,\u003c/sup\u003e Incidence is 1.24% in the Indian population, while it is 1.46% in the Pakistani population, the white population has a low incidence of 0.62%.\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePathogenesis of IHCP seems to be multifactorial, but the exact mechanism is not known. Hormonal changes during pregnancy i.e., elevated estrogen and progesterone levels as well as the alteration in the cell membrane configuration of bile ducts and liver cells along with defective transport mechanisms in biliary canaliculi indicate a strong genetic cause.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Studies have demonstrated genetic mutations in several genes e.g., ABCB4 and ABCB11 gene encodes for MDR3 protein and BSEP (bile salt export pump) protein respectively. However, geographic distribution and exogenous factors like higher maternal age and low selenium level also affect the incidence.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cp\u003ePregnant women attending ANC, OPD, and labor ward at J.N.M.C.H, AMU, Aligarh, U.P (India) with \u0026gt;\u0026thinsp;28weeks gestation with complaint of itching over palm and soles, derranged liver enzymes (AST/ALT doublely raised) and raised serum bile acid (more than 10 micromol/L) were included in the study from 2020\u0026ndash;2022 after taking informed consent and ethical approval from the Institute. The study was prospective cohort observational type. All the study participants\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInclusion Criteria\u003c/strong\u003e \u003cp\u003ePregnant women with gestation age of \u0026gt;\u0026thinsp;28 weeks with Obstetrics cholestasis.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eExclusion Criteria\u003c/strong\u003e \u003cp\u003eKnown cases of GDM and pre-eclampsia, pruritus due to other known dermatological causes, infective hepatitis, and other medical disorders like thyroid disorders, DM, CAD, etc.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e After taking informed consent all participants underwent detailed history, examination and routine investigations like CBC, RFT, LFT, urine routine microscopy, and serum bile acid levels were done.\u003c/p\u003e \u003cp\u003eWomen were divided into two groups - Group 1 (IHCP) - Two hundred women diagnosed with IHCP\u003c/p\u003e \u003cp\u003eGroup 2 (Non-IHCP)- Two hundred healthy pregnant women\u003c/p\u003e \u003cp\u003eBoth the groups were compared for assessing the risk of development of GDM and Pre-eclampsia.\u003c/p\u003e \u003cp\u003eAfter taking informed consent all participants underwent detailed history, examination and routine investigations.\u003c/p\u003e \u003cp\u003eIHCP was diagnosed on the basis of complaint of itching, doubly raised liver enzymes and serum bile acid level\u0026thinsp;\u0026gt;\u0026thinsp;10 \u0026micro;mol/L.\u003c/p\u003e \u003cp\u003eMethod of estimation of Serum Bile acid: Total serum bile acid levels were estimated by Beckman coulter AU680 Clinical Chemistry Analyser using Enzymatic method with cutoff value 10 \u0026micro;mol/L.\u003c/p\u003e \u003cp\u003eGDM was diagnosed on the basis of diabetes in pregnancy study group of india DIPSI criteria i.e., blood sugar recorded 2 hours after giving 75gm oral glucose in 250 ml of water. A value of more than 140mg% was labelled as GDM.\u003c/p\u003e \u003cp\u003ePre-eclampsia was diagnosed with a BP\u0026thinsp;\u0026ge;\u0026thinsp;140/90mmHg on 2 occasions 4hours apart with proteinuria more than 300mg in a 24-hour urine collection.\u003c/p\u003e \u003cp\u003eSample size:\u003c/p\u003e \u003cp\u003eData were analyzed using SPSS version 23.0\u003c/p\u003e \u003cp\u003eStatistical tests: Chi-square test (p-value) and odds ratio.\u003c/p\u003e"},{"header":"OBSERVATION \u0026 RESULTS","content":"\u003cp\u003eIn our study, the mean age was 27.32\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;5.3 years in group 1 (IHCP) and 25.92\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;4 years in group 2 (Non- IHCP). Both groups were comparable with regard to age. Majority of women in both the groups were literate and were primigravida (65% in group 1 and 70.5%in group 2).\u003c/p\u003e \u003cp\u003eThe mean gestational age at the time of delivery in group 1 was 37.5\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1.7 weeks while in group 2 was 38.1\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1.4 weeks .\u003c/p\u003e \u003cp\u003eIn group 1 majority of the cases had serum bile acid levels between 10\u0026ndash;40\u0026micro;mol/L (57.5%) followed by 41\u0026ndash;60\u0026micro;mol/L (30.0%) and \u0026gt;\u0026thinsp;60\u0026micro;mol/L (12.5%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMean ALP, AST and ALT were significantly higher in the cases having serum bile acid levels above 60 \u0026micro;mol/ as compared to 10\u0026ndash;40 \u0026micro;mol/l i.e., liver enzymes were significantly higher at higher bile acid levels. (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/p\u003e \u003cp\u003eThe occurrence of GDM was found in 26.5% of cases in the IHCP group while it was just 18% in non IHCP group and on comparing the groups the difference was found to be statistically significant. (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 \u0026amp; OR:1.64) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u0026amp; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of IHCP with development of GDM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eMaternal outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eGroup 1-IHCP (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eGroup2-Non IHCP (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOdd Ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eNo. of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eNo. of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e1.64\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.041\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e*odd ratio (OR:1.64: 95% CI :1.02\u0026ndash;2.65)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSimilarly, the development of pre-eclampsia was found in 17% of cases in the IHCP group while it was seen in 9.5% in non IHCP group, and on comparing the groups the difference was found to be statistically significant. (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 \u0026amp; OR:1.95) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u0026amp; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of IHCP with development of preeclampsia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eMaternal outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eGroup1-IHCP (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eGroup2-Non IHCP (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOdds\u003c/p\u003e \u003cp\u003eRatio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eNo. of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eNo. of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e1.95\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e*Odds ratio (OR 1.95, 95% CI:1.07\u0026ndash;3.55)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe risk of development of GDM and pre-eclampsia was significantly more in IHCP cases with a higher level of serum bile acid i.e., at \u0026gt;\u0026thinsp;60\u0026micro;mol/L as compared to 10\u0026ndash;40 \u0026micro;mol/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (GDM: OR:8.647 \u0026amp; Pre-eclampsia: OR:6.303) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of Serum bile acid with development of GDM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c8\" namest=\"c3\"\u003e \u003cp\u003eSerum Bile Acid Levels (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003cp\u003e(OR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e\u003cb\u003e10\u0026ndash;40 (n\u0026thinsp;=\u0026thinsp;115)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u003cb\u003e40\u0026ndash;60 (n\u0026thinsp;=\u0026thinsp;60)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026gt;\u0026thinsp;60 (n\u0026thinsp;=\u0026thinsp;25)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eNo. of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eNo. of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eNo. of patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e8.647\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e40.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e40.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e6.303\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e78.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e*GDM Odds ratio (OR: \u003cb\u003e8.647;\u003c/b\u003e 95% CI: 3.34\u0026ndash;22.39)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e*Pre-eclmapsia Odds ratio (OR: \u003cb\u003e6.303 ;\u003c/b\u003e95% CI: 2.29\u0026ndash;17.36)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSignificantly higher rates of induction of labor (60.5%) and cesarean delivery (67.5%) were noted in the IHCP group as compared to non-IHCP (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003ePregnancy itself is a cholestatic condition and chronic liver diseases mostly unmask during pregnancy with clinical manifestation of cholestasis.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Intrahepatic cholestasis of pregnancy (IHCP) is the most frequent cause of cholestasis of pregnancy and pathogenesis is thought to be multifactorial, mostly depending on genetic configuration, geographical area, environmental changes, and ethnicity\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Though it is considered to be a milder disease from a mother\u0026rsquo;s point of view several studies showed that IHCP is associated with a significant risk of developing pre-eclampsia as well as GDM.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGDM, pre-eclampsia, and, IHCP, all three shares a common pathway in its pathogenesis, and the Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily of ligand-regulated receptors that function as a bile acid sensor, plays a crucial role in maintaining bile acid, cholesterol, and glucose metabolism. It is supposed that FXR is expressed by pancreatic β-cells and regulates insulin metabolism\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and a decrease in FXR and TGR5 activities causes aberrant bile acid and blood glucose homeostasis thus explaining the association of GDM and IHCP\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSimilarly higher level of bile acid in IHCP has been found to cause vasoconstriction of the chorionic plate veins which leads to structural damage of the placenta by causing impairment of the placental antioxidant system, resulting in the formation of an increased number of placental syncytial knots, found on histopathological examination and bile acid also cause endothelial injury in kidney and lungs by causing oxidative damage which further promote the formation of reactive oxygen species and a variety of vasoactive mediators, including endoglin-1, soluble fms-like tyrosine kinase receptor (sFlt-1), these findings were also seen in pre-eclampsia pathogenesis, thus explaining the relation between pre-eclampsia and IHCP\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe present study showed a significant association of IHCP with increased risk of development of GDM and pre-eclampsia, these results were found to be consistent with the studies done by Liu et al, Marathe et al, Celik et al, Arthuis et al, Yadav et al, Rizvi and Raina et al, Naga et al, Matan et al and Samjhak et al \u003csup\u003e\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25 CR26 CR27\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e IHCP was also associated with higher rates of induction of labor and cesarean delivery, similar results were found in studies done by Liu et al, Yadav et al, Rizvi and Raina et al and Naga et al. \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe present study conducted on 200 women diagnosed with IHCP and 200 healthy pregnant women suggested an overall higher risk of development of GDM and pre-eclampsia in women with IHCP as compared to healthy pregnant women. We also found that there was a significant association between the occurrence of GDM and pre-eclampsia with raised serum bile acid levels. Thus, women with IHCP should be treated as a high-risk pregnancy and followed up in ANC visits with liver enzymes and serum bile acids They should also be kept under close surveillance for follow-up in regular ANC clinics and most importantly for early detection of the development of GDM and pre-eclampsia to prevent maternal and fetal complication and appropriate management.\u003c/p\u003e \u003cp\u003eSince our study was done in a single center so its findings cannot be generalized to the whole population and due to the lack of availability of previous pregnancy records, women with a history of IHCP in previous pregnancy were not assessed for increased risk of IHCP in the subsequent pregnancy. Thus, we recommend a multicentric large randomized trial to ascertain the true relationship between IHCP and adverse maternal outcomes.\u003c/p\u003e"},{"header":"DECLARATIONS","content":"\u003cp\u003e\u003cstrong\u003eEthical consideration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflict of interest\u003c/p\u003e\n\u003cp\u003eIt was observational study participants were included in the study after informed consent\u003c/p\u003e"},{"header":"REFERENCES","content":"\u003col\u003e\n\u003cli\u003ePosh S, Ajaz S, Jeelani B, Khurshid R. Impact of obstetric cholestasis on fetal outcome \u0026ndash; An observational study. J Sci Soc 2020;47:28-32.\u003c/li\u003e\n\u003cli\u003eMikolasevic I, Filipec-Kanizaj T, Jakopcic I, Majurec I, Brncic-Fischer A, Sobocan N, et al. Liver disease during pregnancy: A challenging clinical issue. Med Sci Monit. 2018;24:4080-90. doi: 10.12659/MSM.907723, PMID 29905165.\u003c/li\u003e\n\u003cli\u003eHassan N, Khurshid R, Muzamil M, Parveen S. Cholestasis of pregnancy: effects on maternal and fetal outcome. Int J Reprod Contraception, Obstet Gynecol. 2020;9(8):3202. doi:10.18203/2320-1770.ijrcog20203296\u003c/li\u003e\n\u003cli\u003eLim E, Mouyis M, MacKillop L. Liver diseases in pregnancy. Clin Med (Lond). 2021 Sep;21(5):e441-e445. doi: 10.7861/clinmed.2021-0497. PMID: 34507927; PMCID: PMC8439517.\u003c/li\u003e\n\u003cli\u003eJurk SM, Kremer AE, Schleussner E. Intrahepatic Cholestasis of Pregnancy. \u003cem\u003eGeburtshilfe Frauenheilkd\u003c/em\u003e. 2021;81(8):940-947. doi:10.1055/a-1522-5178\u003c/li\u003e\n\u003cli\u003eSenocak GNC, Yilmaz EPT. Maternal and Fetal Outcomes in Pregnancies Complicated by Intrahepatic Cholestasis. Eurasian J Med. 2019;51(3):270-272. \u003c/li\u003e\n\u003cli\u003eUzel K, Bilir F, Astepe B. The intrahepatic cholestasis of pregnancy and maternal-fetal results. 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The bile acid sensor FXR regulates insulin transcription and secretion. \u003cem\u003eBiochim Biophys Acta - Mol Basis Dis\u003c/em\u003e. 2010;1802(3):363-372\u003c/li\u003e\n\u003cli\u003eGoodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 2000;6(3):517-26. \u003c/li\u003e\n\u003cli\u003ePegu B, Mehrotra M, Yadav A, Sahoo PSK. Cholestasis of pregnancy: a prospective analysis from a South Andaman teaching hospital. Int J Reprod Contraception, Obstet Gynecol. 2019;8(5):1895. doi:10.18203/2320-1770.ijrcog20191939.\u003c/li\u003e\n\u003cli\u003eMoreira C, Barros T, Braga A, Braga J. 656 Intra-hepatic cholestasis of pregnancy: treatment and obstetric outcomes. Eur J Obstet Gynecol Reprod Biol. 2022;270. doi:10.1016/j.ejogrb.2021.11.398\u003c/li\u003e\n\u003cli\u003eRCOG. Intrahepatic cholestasis of pregnancy (Green top guideline no 43) Published 9; 2022 [cited August 2022]. Available from: https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/intrahepatic-cholestasis-of-pregnancy-green-top-guideline-no-43/.\u003c/li\u003e\n\u003cli\u003eDixon PH, Sambrotta M, Chambers J, Taylor-Harris P, Syngelaki A, Nicolaides K, et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. Sci Rep. 2017;7(1):11823. doi: 10.1038/s41598-017-11626-x, PMID 28924228.\u003c/li\u003e\n\u003cli\u003eAydın GA, \u0026Ouml;zgen G, G\u0026ouml;r\u0026uuml;kmez O. The role of genetic mutations in intrahepatic cholestasis of pregnancy. \u003cem\u003eTaiwan J Obstet Gynecol\u003c/em\u003e. 2020;59(5):706-710. doi:10.1016/j.tjog.2020.07.014\u003c/li\u003e\n\u003cli\u003eRenga B, Mencarelli A, Vavassori P, Brancaleone V, Fiorucci S. The bile acid sensor FXR regulates insulin transcription and secretion. \u003cem\u003eBiochim Biophys Acta - Mol Basis Dis\u003c/em\u003e. 2010;1802(3):363-372. doi:10.1016/J.BBADIS.2010.01.002\u003c/li\u003e\n\u003cli\u003eGoodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 2000;6(3):517-26. doi: 10.1016/S1097-2765(00)00051-4.\u003c/li\u003e\n\u003cli\u003eLiu C, Gao J, Liu J, Wang X, He J, Sun J, et al. Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes and preeclampsia. Ann Transl Med. 2020;8(23):1574. \u003c/li\u003e\n\u003cli\u003eMarathe JA, Lim WH, Metz MP, Scheil W, Dekker AG, Hague WM. A retrospective cohort review of intrahepatic cholestasis of pregnancy in a South Australian population. Eur J Obstet Gyne col Reprod Biol. 2017;218:33-38.\u003c/li\u003e\n\u003cli\u003e\u0026Ccedil;elik S, \u0026Ccedil;alışkan CS, \u0026Ccedil;elik H, G\u0026uuml;\u0026ccedil;l\u0026uuml; M, Başbuğ A. Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy. Ginekologia Polska 2019;90(4):217\u0026ndash;222\u003c/li\u003e\n\u003cli\u003eArthuis C, Diguisto C, Lorphelin H, Dochez V, Simon E, Perrotin F, et al. Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study. PLoS ONE 2020;15(2): e0228213\u003c/li\u003e\n\u003cli\u003eYadav R, Rani K and Najam R. Maternal and fetal outcomes in pregnancies complicated with intrahepatic cholestasis of pregnancy. International Journal of Clinical Obstetrics and Gynaecology 2021; 5(5): 152-156\u003c/li\u003e\n\u003cli\u003eRizvi SM, Raina R. Fetomaternal outcome in jaundice complicating pregnancy. J Soc Obstet Gynaecol Pak 2018;8(3):176-9.\u003c/li\u003e\n\u003cli\u003eNaga VKM, Joseph B, Kalappa MS. Obstetric Outcome in Women with Intrahepatic Cholestasis: A 3-year Study in a Tertiary Care Hospital in Bengaluru. Journal of South Asian Federation of Obstetrics and Gynaecology. 2019;11(2)\u003c/li\u003e\n\u003cli\u003eMatan Mor M, Shmueli A, Krispin E, et al. Intrahepatic cholestasis of pregnancy as a risk factor for preeclampsia. Arch Gynecol Obstet 2020;301:655\u0026ndash;664\u003c/li\u003e\n\u003cli\u003e\u0026Scaron;imj\u0026aacute;k P, Krejč\u0026iacute;, H., Hornov\u0026aacute;, M, Mr\u0026aacute;z, M, Pař\u0026iacute;zek, A, Kr\u0026scaron;ek, M et al. Establishing the Optimal Time for Induction of Labor in Women with Diet-Controlled Gestational Diabetes Mellitus: A Single-Center Observational Study. J. Clin. Med. 2022, 11, 6410. https://doi.org/ 10.3390/jcm11216410\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Serum bile acid levels, Intrahepatic cholestasis of pregnancy, Gestational diabetes mellitus, Pre-eclampsia","lastPublishedDoi":"10.21203/rs.3.rs-3684427/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3684427/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eAIM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the association of GDM and pre-eclampsia in women with obstetric cholestasis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMATERIAL AND METHODS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePregnant women with \u0026gt;28weeks gestation attending ANC, OPD and labour room of J.N.M.C.H,AMU, Aligarh U.P (India) from 2020-2022 were included in the study after taking informed consent and ethical approval from the Institute. Women were divided into two groups ie group 1 having 200 women with IHCP and group 2 having 200 healthy pregnant women, both the groups were followed up for the development of GDM and pre-eclampsia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA statistically significant association was observed between IHCP and development of GDM (26.5% \u0026amp; Odds ratio 1.64) and pre-eclampsia (17% \u0026amp; Odds ratio 1.95) (p\u0026lt;0.05), also GDM and pre-eclampsia were found to be significantly associated with the severity of cholestasis (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eThus on calculating odds ratio, we found higher odds of developing GDM and Pre-eclampsia in IHCP group with raised serum bile acid levels, maximum at 60μmol/L level as compared to 10-40 μmol/L (GDM: OR:8.647 \u0026amp; Pre-eclampsia: OR:6.303). Induction and cesarean rate was significantly higher in IHCP group (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONCLUSION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study concludes significant association of IHCP with GDM and Pre- eclampsia as all three shares common pathogenetic pathways and greater risk of development was at higher serum bile acid levels.\u003c/p\u003e","manuscriptTitle":"Obstetric cholestasis and its impact on the maternal outcome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 16:43:48","doi":"10.21203/rs.3.rs-3684427/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-02-19T18:39:54+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-12-28T08:42:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Archives of Gynecology and Obstetrics","date":"2023-12-17T11:48:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-15T11:20:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2023-12-14T09:34:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4b181209-36fb-4812-98cc-db95c7cb5571","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-06-06T05:45:42+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 16:43:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3684427","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3684427","identity":"rs-3684427","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}