Intrahepatic Cholestasis of Pregnancy and Its Association with Preeclampsia and Gestational Diabetes: A Retrospective Analysis

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It occurs in approximately 1/1000 to 1/10000 of pregnancies and usually resolves during the postpartum period without causing any hepatic sequelae or mortality in the mother. This is a condition complicated by itching in the body, increased liver enzymes and fasting bile acid levels (≥ 10 µmol/L). Although the relationship of intrahepatic cholestasis (ICP) with Gestational Diabetes Mellitus (GDM) and preeclampsia has been evaluated in studies, there are few studies examining the relationship of intrahepatic cholestasis with GDM and preeclampsia. Methods Patients who gave birth in our hospital between January 2018 and March 2022 were retrospectively reviewed from the hospital database and patient file records. Patients who were diagnosed with intrahepatic cholestasis and gave birth during the study period were retrospectively compared with all other patients who gave birth. Results In our study, consistent with previous studies, we demonstrated a higher risk of GDM and pre-eclampsia in women with ICP compared to those without ICP. In our study, we observed a significant correlation between ICP and adverse perinatal outcomes. There was a statistically significant relation between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery, 5th minute Apgar score < 7 and presence of Neonatal Care Unit (NICU). On the other hand, no significant relationship was found between the presence of ICP and the presence of Small Gestational Age (SGA) and meconium. In our study, there was a significant relationship between the presence of ICP and mode of delivery, and the presence of postpartum hemorrhage (PPH) (p < 0.05). Those with ICP were found to have a lower gestational week and birth weight at birth, and a higher rate of caesarean delivery and PPH. Conclusion Our study suggested that patients with ICP had increased risk of development of GDM and preeclampsia. bile acid gestational diabetes mellitus intrahepatic cholestasis of pregnancy preeclampsia Take home message Our study suggested that patients with ICP had increased risk of development of GDM and preeclampsia. Accordingly, we showed that it is associated with preterm birth and adverse perinatal outcomes. Introduction Intrahepatic cholestasis of pregnancy is the most common pregnancy-specific liver disease. It is observed in an average of 1/1000 to 1/10000 of pregnancies and has a benign character that usually resolves in the postpartum period without causing any hepatic sequelae or mortality in the mother [ 1 ]. Intrahepatic cholestasis of pregnancy is a pregnancy-specific condition that frequently occurs in the third trimester or late second trimester. It is a condition complicated by pruritus in the body, increased liver enzymes, and fasting bile acid levels (≥ 10 µmol/L) [ 2 , 3 ]. In contrast to the maternal condition, fetal morbidity and mortality are increased in cases of intrahepatic cholestasis in which severe maternal morbidity and mortality are usually not observed. Intrahepatic cholestasis may cause preterm labor, abnormal intrapartum fetal heart tracing and sudden intrapartum fetal death [ 4 , 5 ]. The most common reason for admission to the hospital in these patients is widespread itching in the extremities and skin lesions as a result of itching [ 6 ] Although clearly not identified some of the following factors including genetic predisposition, environmental and hormonal factors also play a role [ 7 , 8 ]. Ursodeoxycholic acid is the first choice in reducing maternal symptoms [ 9 ]. Along with gestational cholestasis, both preeclampsia and gestational diabetes (GDM) affect the mother and fetus. The first study to systematically describe highly significant associations between intrahepatic cholestasis and GDM and preeclampsia was conducted in 2013 [ 10 ]. Although the relationship of intrahepatic cholestasis (ICP) with Gestational Diabetes Mellitus (GDM) and preeclampsia has been evaluated in studies, there are few studies examining the relationship of intrahepatic cholestasis with GDM and preeclampsia [ 10 – 16 ] A meta-analysis found that the risk of GDM and preeclampsia increased approximately 2-fold in women with cholestasis [ 10 ]. Another study revealed an increased risk of GDM in pregnant women diagnosed with cholestasis [ 11 ]. Another two study revealed an increased risk of preeclampsia in pregnant women diagnosed with cholestasis, and especially in twin pregnant women [ 12 , 13 ]. In a retrospective cohort study, compared to the general population, a greater proportion of pregnant women diagnosed with cholestasis were also affected by gestational diabetes, preeclampsia and/or spontaneous preterm birth [ 14 ]. In a prospective study, ICP was associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. These findings may have implications for the future health of affected offspring [ 15 ]. A significant difference was found between the two groups in terms of the incidence of hypothyroidism, thrombophilia, gestational diabetes, gestational hypertension, postpartum hemorrhage, and preterm birth in ICP patients [ 16 ]. In addition, there is a high degree of heterogeneity and a relatively lack of reliable data in studies of Intrahepatic cholestasis and Gestational diabetes mellitus. In this study, we aimed to review the adverse maternal and perinatal outcomes of intrahepatic cholestasis in our hospital and to investigate the relationship between intrahepatic cholestasis, and the risk of gestational diabetes and preeclampsia. Materials and Methods Patients who delivered in our hospital between January 2018 and March 2022 were retrospectively reviewed from the hospital database and patient file records. In our study, 1686 patients were evaluated, and among these patients, 54 patients were evaluated in the ICP group and 1632 patients were evaluated in the control group. The patients with ICP after 20 weeks of gestation, followed and delivered at our institution were included to the study group. The diagnosis of intrahepatic cholestasis was based on elevated liver enzymes and elevated maternal serum total bile acid levels (≥ 10 µmol/L). Women delivered at our institution during the study period were included to the control group. Ultrasonographic evaluations of all patients were performed by an obstetrician and gynecologist. All pregnancies complicated with severe congenital malformations such as chromosomal abnormalities and/or multiple congenital anomalies, all twin and, higher multiple pregnancies and, cases with missing data were excluded. Data; including maternal demographic and obstetrics characteristics, maternal age, gravida, parity, pre-pregnancy body mass index (BMI), assisted reproductive technique (ART), presence of GDM and preeclampsia. Perinatal outcomes, gestational age at birth, birth weight, induction of labor, delivery method, postpartum hemorrhage, preterm delivery (iatrogenic and spontaneous), small gestational age (SGA), Apgar score, stillbirth, and neonatal death data were evaluated. Preeclampsia was defined according to the American College of Obstetricians and Gynecologist guidelines [ 17 ]. Gestational Diabetes Mellitus was defined according to World Health Organization criteria [ 18 ]. Preterm labor was defined as delivery after 24 weeks and before 37 completed gestational weeks. SGA was defined as a birth weight < 10th percentile and low Apgar score was defined as a score < 7 at 5 minutes after birth. Stillbirth was used to define fetal death at or above 20 weeks of gestation and, neonatal death was defined as the death of an infant between 0 and 28 days after birth. The grading criteria for BMI were based on the recommendations of the Obesity Working Groups. Postpartum hemorrhage (PPH) was defined as blood loss of ≥ 500 mL within 24 hours after vaginal delivery or ≥ 1,000 mL after cesarean delivery. Severe postpartum hemorrhage was defined as blood loss of ≥ 1,000 mL within 24 hours after delivery [ 19 ]. The primary outcome of this study was to determine the incidence of GDM and preeclampsia among women diagnosed with intrahepatic cholestasis. Secondary outcomes were to determine the relationship among intrahepatic cholestasis, stillbirth, gestational age at delivery, birth weight, induction of labor, mode of delivery, presence of postpartum hemorrhage, preterm delivery (iatrogenic and spontaneous), small gestational age (SGA), 5 min Apgar score, Neonatal Care Unit (NICU) hospitalization and neonatal death. The ethics committee approval of this study was obtained by the ethics committee. The study was written in accordance with the Principles of the Declaration of Helsinki. In our study, an Informed Consent form was obtained from the patients and the rules regarding animal rights were followed. Firstly, the data obtained from the participants were summarized with descriptive statistics. Then, independent samples t-test was used for the difference of means between binary categories and chi-square test was used to analyze the relationships between categorical data. Statistical significance was accepted as P value < 0.05. The research data were statistically analyzed using SPSS version 20 (IBM SPSS Statistics, IBM Corporation, Armonk, NY, USA). Results The mean age of the participants was 29.71±5.13 years. ICP was present in 3.2% of the participants. Preeclampsia and GDM was encountered with the rates of 1.7% and 7.2% respectively. Cesarean section was performed in 49.3% of the participants. The mean age and pre-pregnancy BMI of the participants were significantly higher in ICP group compared to control group (respectively p:0.015, p:0.005). On the other hand, the mean gravida and parity were similar between the groups (p:0.126). The presence of ART, GDM were significantly higher in ICP compared to controls (respectively p:0.025, p:0.029). The presence of preeclampsia were significantly higher in ICP compared to controls (p<0.001). However chronic HT was similar between the groups. Mean serum bile acid level was 19.3±3 μmol/L in ICP group. Table 1 showed the comparison of the patients with ICP and controls. ICP increased the risk of preeclampsia (HR 16,4, p:0.005). Furthermore, ICP increased the risk of GDM (HR: 2.42, p:0.033). Age, BMI, gravida, parity, ART was not associated with the risk of preeclampsia and GDM. Table showed risk factors for development of preeclampsia and GDM (Table 1). Table 1. Analysis of risk factors for preeclampsia and GDM Preeclampsia GDM HR (95% CI) p HR (95% CI) p ICP no yes 16.4 (6-44) 0.005 2.42 (1.07-5.46) 0.033 Age 0.96 (0.88-1.0) 0.405 1.01 (0.97-1.04) 0.536 BMI 1.1 (0.98-1.30) 0.0760 0.90 (0.80-1.01) 0.081 Gravida 3.0 (0.70-13.3) 0.133 1.22 (0.48-3.44) 0.614 Parity 0.64 (0.14-2.81) 0.560 0.75 (0.27-2.02) 0.572 ART no yes 0.12 (0-1.01) 0.998 1.14 (0.38-3.39) 0.813 GDM no yes 0.80 (0.17-3.66) 0.781 - - Gestational age 1.01 (0.77-1.31) 0.940 Preeclampsia no yes - - 0.78 (0.17-3.57) 0.758 There was a statistically significant difference between the mean gestational week and birth weight at birth according to the presence or absence of ICP (p<0.001). There was also a significant correlation between the presence of ICP and both mode of delivery and, the presence of postpartum hemorrhage (respectively p<0.001, p:0.044). The mean gestational week and birth weight at delivery were lower, and the rate of cesarean delivery and PPH were higher in those with ICP. There were statistically significant relationships between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery (respectively p:0.012, p<0.001). There were statistically significant relationships between the presence of ICP and 5 th minute Apgar score < 7, presence in NICU (respectively p:0.034, p<0.001). On the other hand, there was no significant relationship between the presence of ICP and SGA and meconium (respectively p:0.055, p:0.151). Spontaneous preterm delivery, iatrogenic preterm delivery, 5 th minute Apgar score <7 and NICU were found to be proportionally higher in those with ICP (Table 2). Table 2. Relationship between İntrahepatic Cholestasis and Neonatal Outcomes ICP p Yes No Gestational week at birth 36,62±1,56 37,69±1,45 <0,001 Birth weight 2847,59±296,08 3127,60±428,50 <0,001 Mode of delivery Caesarean section 39 (%72,2) 792 (%48,5) <0,001 NSVD 15 (%27,8) 840 (%51,5) PPH Yes 2 (%3,7) 15 (%0,9) 0,044 No 52 (%96,3) 1617 (%99,1) Spontaneous preterm labor Yes 2 (%3,7) 11 (%0,7) 0,012 No 52 (%96,3) 1621 (%99,3) Iatrogenic preterm labor Yes 10 (%18,5) 16 (%1) <0,001 No 44 (%81,5) 1616 (%99) SGA Yes 2 (%3,7) 16 (%1) 0,055 No 52 (%96,3) 1616 (%99) Meconium Yes 2 (%3,7) 22 (%1,3) 0,151 No 52 (%96,3) 1610 (%98,7) 5th minute Apgar <7 Yes 2 (%3,7) 14 (%0,9) 0,034 No 52 (%96,3) 1618 (%99,1) NICU Yes 13 (%24,1) 114 (%7) <0,001 No 41 (%75,9) 1518 (%93) Stillbirth Yes 0 (%0) 0 (%0) 0.943 No 54 (%100) 1632 (%100) Discussion This retrospective study had two main findings. ICP showed a strong relationship with GDM and pre-eclampsia. Women diagnosed with ICP had a significantly increased risk for adverse perinatal outcomes. In our study, consistent with previous studies, we demonstrated a higher risk of GDM and preeclampsia in women with ICP compared to those without ICP (10,14). The mechanisms underlying the direct association of ICP with GDM and preeclampsia remain unclear. Martineau et al. reported that ICP was characterized by glucose intolerance and dyslipidemia, consistent with the metabolic syndrome [ 15 ]. Women with ICP exhibited higher triglyceride, total cholesterol, LDL and VLDL levels and these indices were also related with an increased risk of preeclampsia and GDM [ 16 , 17 ]. In our study, cholesterol levels were not evaluated. It has been shown that women with higher BMI and impaired metabolic pathways may also be at increased risk for adverse outcomes of pregnancy [ 18 , 19 ]. Our study also showed that the incidence of GDM and pre-eclampsia was significantly increased in overweight pregnant women with ICP. In our study, we observed a significant relationship between ICP and adverse perinatal outcomes. The relationship between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery, 5th minute Apgar score < 7 and NICU stay showed adverse effects of ICP on perinatal outcomes. On the other hand, there was no significant relationship between the presence of ICP and SGA and meconium. In the study published by Geenes et al. which included a very large population, it was found that the risk of meconium-stained amniotic fluid was higher in severe ICP. However, no neonatal meconium aspiration syndrome was shown in the study, and it was claimed that the need for neonatal intensive care was generally associated with preterm birth and the negative consequences it caused. In addition, in the same study, babies with SGA were found to be less in the cholestasis group than in the control group [ 20 ], which is similar to our study. Williamson et al. previously reported that ICP was associated with an increased risk of stillbirth [ 21 ]. ICP is characterized by fetal death without any clear cause, but since there is currently no specific way to monitor the fetus, the pregnancy is usually terminated beforehand to avoid adverse pregnancy outcomes. With effective management during pregnancy, there was no increased incidence of stillbirth in our study, in agreement with previously published studies. In patients diagnosed with ICP, the mean gestational age and birth weight at birth were found to be low. The Royal College of Obstetrics and Gynecology does not recommend active management, although optimal timing of delivery in ICP is difficult given the paucity of high-quality studies [ 22 ]. A recent meta-analysis showed an increased risk of stillbirth in women with ICP when serum bile acid concentrations were 100 µmol/L or more [ 23 ], but bile acid is not always a reliable monitoring index [ 5 ]. Relatedly, stillbirth may not have been detected since the highest serum acid level in our study group was 29.9 µmol/L. We encourage clinicians to monitor bile acid levels and recommend that they make an individualized decision about whether the risks of preterm birth outweigh the risks of disease. In our study, both spontaneous and iatrogenic preterm birth were found higher in the ICP group. Especially, the high rate of iatrogenic preterm labor may reflect concerns with regard to the risk of fetal death or adverse outcome in pregnancies complicated by high maternal serum bile acids, and therefore the clinicians managing these pregnancies may have preferred a management strategy of induction of labor prior to 37 weeks despite emerging concerns about special education needs [ 24 ] and poorer school performance [ 25 ] in babies born late preterm. Spontaneous preterm labor may be explained by a dose-dependent bile acid effect on myometrial contractility, as has been demonstrated in rodents [ 26 ]. Further-more, myometrial cells from women with ICP are more responsive to oxytocin, and cells from normal women demonstrate an increased response to oxytocin in the presence of bile acids [ 27 , 28 ]. PPH is defined as blood loss of more than 500 mL within 24 hours after delivery. In our study, there was a significant correlation between the presence of ICP and both mode of delivery and, the presence of postpartum hemorrhage (PPH). In the ICP group, the mean gestational week and, birth weight at delivery were found to be lower and, the rate of cesarean delivery and PPH were found to be higher. However, in these patients, postpartum hemorrhage was treated with conservative methods without the need for any surgical or additional procedures such as postpartum hysterectomy, uterine artery ligation, hypogastric artery ligation, balloon tamponade, b-lynch suturing. Additionally, no patient required massive blood product transfusion and no exitus occurred due to postpartum hemorrhage. The low frequency of postpartum hemorrhage in our study may be explained by the different definitions used or underestimation of blood loss. This study was conducted as a single-center, retrospective cohort study with large samples of ICP patients demonstrating the prevalence and characteristics of ICP in our hospital. In our study, cesarean section rates were found to be higher in pregnancies in the ICP group. In a recent study Kong et al. demonstrated that women with severe ICP also had a significantly higher incidence of planned and unplanned CS compared with mild ICP subjects, as the indications for CS showed that fetal intolerance was higher in severe ICP compared with mild ICP [ 29 ] Shemer et al. reported that the risk of emergency cesarean section in ICP with spontaneous onset of labor did not differ from non ICP women with spontaneous onset of labor [ 30 ]. Generally, from studies of Brouwers et al and Stenhiles et al, we have known that intrahepatic cholestasis increases the risk of preterm labor, abnormal intrapartum fetal heart tracing and sudden intrapartum fetal death [ 4 , 5 ]. These known risks are the most likely reasons why the patients with ICP have a higher frequency of cesarean section compared to spontaneous delivery. There are undoubtedly some limitations of our study. This study can be considered as a retrospective study, which may raise some concerns about data quality. These risks are thought to be related to patient selection risks and information bias. Furthermore, we did not evaluate the relationship between ICP and GDM or ICP and pre-eclampsia for time of onset. The relationship between bile acid concentrations and the risk of GDM or pre-eclampsia was not evaluated. Therefore, it is necessary to further analyze the time frame for any relationship between ICP and GDM or pre-eclampsia and to better understand the potential mechanisms of any correlation. In conclusion our study suggested that patients with ICP had increased risk of development of GDM and preeclampsia. Accordingly, we showed that it is associated with preterm birth and adverse perinatal outcomes. The authors declare that they have no conflict of interest. Declarations Author Contribution Ata Can: Data collection or management, Data analysis, Manuscript writing/editing Atlihan Ufuk: Data collection or management, Data analysis, Manuscript writing/editing Avsar Huseyin Aytug: Protocol/project development, Data collection or management, Data analysis, Manuscript writing/editing Erkilinc Selcuk: Protocol/project development, Manuscript writing/editing References Pathak B, Sheibani L, Lee RH (2010) Cholestasis of pregnancy. Obstet Gynecol Clin North Am. ;37(2):269 – 82. doi: 10.1016/j.ogc.2010.02.011. PMID: 20685553 Diken Z, Usta IM, Nassar AH (2014) A clinical approach to intrahepatic cholestasis of pregnancy. Am J Perinatol. ;31(1):1–8. doi: 10.1055/s-0033-1333673. Epub 2013 Jan 28. 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Sex Reprod Healthc. ;4(1):17–22. doi: 10.1016/j.srhc.2012.11.005. Epub 2012 Dec 11. PMID: 23427928 Cite Share Download PDF Status: Published Journal Publication published 16 Apr, 2024 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Reviewers agreed at journal 01 Feb, 2024 Reviewers invited by journal 01 Feb, 2024 Editor invited by journal 17 Dec, 2023 Editor assigned by journal 13 Dec, 2023 First submitted to journal 12 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-3744861","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270663132,"identity":"edb21d9a-b2d1-4669-a448-816d21f0e15e","order_by":0,"name":"Huseyin Aytug Avsar","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Huseyin","middleName":"Aytug","lastName":"Avsar","suffix":""},{"id":270663133,"identity":"fb7fc12c-3b1b-424d-ae59-721e9dbf94b9","order_by":1,"name":"Ufuk Atlihan","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ufuk","middleName":"","lastName":"Atlihan","suffix":""},{"id":270663134,"identity":"50d3cc14-8bc7-4f97-ba4d-b39a48125809","order_by":2,"name":"Can Ata","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYHACxgdAQs4AzDawIEoLswFDAoOxAQMzSIsEUVrYBIBaEjeAtTAQoYW//ewxhp8/7NK3s/cf3fCjQAIo0p2AV4vEmby0hz0Jybk7ew6z3ewBOkzizNkNeLUYMOSYG/AkMOduuJHMdoMHqMVAIpeAFv43ZpJ/EurTDYBabv4hSotEjpk0T8LhBJCW20TZInHjjbGxTNpxww1nDpvdljGQ4CHoF/7+HMOHb2yq5Q2ONz67+eaPjRx/ey9+LRiAhzTlo2AUjIJRMAqwAgD99kQqx9NcqAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-0841-0480","institution":"İzmir Democracy University Buca Seyfi Demirsoy Education and Research Hospital: TC Saglik Bakanligi Buca Seyfi Demirsoy Egitim ve Arastirma Hastanesi","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Can","middleName":"","lastName":"Ata","suffix":""},{"id":270663135,"identity":"53c8d1da-5acc-42fb-8950-735ac42d74a8","order_by":3,"name":"Selcuk Erkilinc","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Selcuk","middleName":"","lastName":"Erkilinc","suffix":""}],"badges":[],"createdAt":"2023-12-12 16:29:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3744861/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3744861/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00404-024-07507-0","type":"published","date":"2024-04-16T11:52:02+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54762786,"identity":"7904bfe8-c418-4a1b-aa49-9d5fe2b9da62","added_by":"auto","created_at":"2024-04-16 11:52:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":202511,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3744861/v1/3910eb1e-a295-43fb-814d-86a21a1905a0.pdf"}],"financialInterests":"","formattedTitle":"Intrahepatic Cholestasis of Pregnancy and Its Association with Preeclampsia and Gestational Diabetes: A Retrospective Analysis","fulltext":[{"header":"Take home message","content":"\u003cp\u003eOur study suggested that patients with ICP had increased risk of development of GDM and preeclampsia. Accordingly, we showed that it is associated with preterm birth and adverse perinatal outcomes.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eIntrahepatic cholestasis of pregnancy is the most common pregnancy-specific liver disease. It is observed in an average of 1/1000 to 1/10000 of pregnancies and has a benign character that usually resolves in the postpartum period without causing any hepatic sequelae or mortality in the mother [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Intrahepatic cholestasis of pregnancy is a pregnancy-specific condition that frequently occurs in the third trimester or late second trimester. It is a condition complicated by pruritus in the body, increased liver enzymes, and fasting bile acid levels (\u0026ge;\u0026thinsp;10 \u0026micro;mol/L) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In contrast to the maternal condition, fetal morbidity and mortality are increased in cases of intrahepatic cholestasis in which severe maternal morbidity and mortality are usually not observed. Intrahepatic cholestasis may cause preterm labor, abnormal intrapartum fetal heart tracing and sudden intrapartum fetal death [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The most common reason for admission to the hospital in these patients is widespread itching in the extremities and skin lesions as a result of itching [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Although clearly not identified some of the following factors including genetic predisposition, environmental and hormonal factors also play a role [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Ursodeoxycholic acid is the first choice in reducing maternal symptoms [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Along with gestational cholestasis, both preeclampsia and gestational diabetes (GDM) affect the mother and fetus. The first study to systematically describe highly significant associations between intrahepatic cholestasis and GDM and preeclampsia was conducted in 2013 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Although the relationship of intrahepatic cholestasis (ICP) with Gestational Diabetes Mellitus (GDM) and preeclampsia has been evaluated in studies, there are few studies examining the relationship of intrahepatic cholestasis with GDM and preeclampsia [\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14 CR15\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] A meta-analysis found that the risk of GDM and preeclampsia increased approximately 2-fold in women with cholestasis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Another study revealed an increased risk of GDM in pregnant women diagnosed with cholestasis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Another two study revealed an increased risk of preeclampsia in pregnant women diagnosed with cholestasis, and especially in twin pregnant women [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In a retrospective cohort study, compared to the general population, a greater proportion of pregnant women diagnosed with cholestasis were also affected by gestational diabetes, preeclampsia and/or spontaneous preterm birth [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In a prospective study, ICP was associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. These findings may have implications for the future health of affected offspring [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A significant difference was found between the two groups in terms of the incidence of hypothyroidism, thrombophilia, gestational diabetes, gestational hypertension, postpartum hemorrhage, and preterm birth in ICP patients [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In addition, there is a high degree of heterogeneity and a relatively lack of reliable data in studies of Intrahepatic cholestasis and Gestational diabetes mellitus. In this study, we aimed to review the adverse maternal and perinatal outcomes of intrahepatic cholestasis in our hospital and to investigate the relationship between intrahepatic cholestasis, and the risk of gestational diabetes and preeclampsia.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003ePatients who delivered in our hospital between January 2018 and March 2022 were retrospectively reviewed from the hospital database and patient file records. In our study, 1686 patients were evaluated, and among these patients, 54 patients were evaluated in the ICP group and 1632 patients were evaluated in the control group. The patients with ICP after 20 weeks of gestation, followed and delivered at our institution were included to the study group. The diagnosis of intrahepatic cholestasis was based on elevated liver enzymes and elevated maternal serum total bile acid levels (\u0026ge;\u0026thinsp;10 \u0026micro;mol/L). Women delivered at our institution during the study period were included to the control group. Ultrasonographic evaluations of all patients were performed by an obstetrician and gynecologist. All pregnancies complicated with severe congenital malformations such as chromosomal abnormalities and/or multiple congenital anomalies, all twin and, higher multiple pregnancies and, cases with missing data were excluded. Data; including maternal demographic and obstetrics characteristics, maternal age, gravida, parity, pre-pregnancy body mass index (BMI), assisted reproductive technique (ART), presence of GDM and preeclampsia. Perinatal outcomes, gestational age at birth, birth weight, induction of labor, delivery method, postpartum hemorrhage, preterm delivery (iatrogenic and spontaneous), small gestational age (SGA), Apgar score, stillbirth, and neonatal death data were evaluated. Preeclampsia was defined according to the American College of Obstetricians and Gynecologist guidelines [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Gestational Diabetes Mellitus was defined according to World Health Organization criteria [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Preterm labor was defined as delivery after 24 weeks and before 37 completed gestational weeks. SGA was defined as a birth weight\u0026thinsp;\u0026lt;\u0026thinsp;10th percentile and low Apgar score was defined as a score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 minutes after birth. Stillbirth was used to define fetal death at or above 20 weeks of gestation and, neonatal death was defined as the death of an infant between 0 and 28 days after birth. The grading criteria for BMI were based on the recommendations of the Obesity Working Groups. Postpartum hemorrhage (PPH) was defined as blood loss of \u0026ge;\u0026thinsp;500 mL within 24 hours after vaginal delivery or \u0026ge;\u0026thinsp;1,000 mL after cesarean delivery. Severe postpartum hemorrhage was defined as blood loss of \u0026ge;\u0026thinsp;1,000 mL within 24 hours after delivery [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The primary outcome of this study was to determine the incidence of GDM and preeclampsia among women diagnosed with intrahepatic cholestasis. Secondary outcomes were to determine the relationship among intrahepatic cholestasis, stillbirth, gestational age at delivery, birth weight, induction of labor, mode of delivery, presence of postpartum hemorrhage, preterm delivery (iatrogenic and spontaneous), small gestational age (SGA), 5 min Apgar score, Neonatal Care Unit (NICU) hospitalization and neonatal death. The ethics committee approval of this study was obtained by the ethics committee. The study was written in accordance with the Principles of the Declaration of Helsinki. In our study, an Informed Consent form was obtained from the patients and the rules regarding animal rights were followed. Firstly, the data obtained from the participants were summarized with descriptive statistics. Then, independent samples t-test was used for the difference of means between binary categories and chi-square test was used to analyze the relationships between categorical data. Statistical significance was accepted as P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The research data were statistically analyzed using SPSS version 20 (IBM SPSS Statistics, IBM Corporation, Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean age of the participants was 29.71\u0026plusmn;5.13 years. ICP was present in 3.2% of the participants. Preeclampsia and GDM was encountered with the rates of 1.7% and 7.2% respectively. Cesarean section was performed in 49.3% of the participants. The mean age and pre-pregnancy BMI of the participants were significantly higher in ICP group compared to control group (respectively p:0.015, p:0.005). On the other hand, the mean gravida and parity were similar between the groups (p:0.126). The presence of ART, GDM were significantly higher in ICP compared to controls (respectively p:0.025, p:0.029). The presence of preeclampsia were significantly higher in ICP compared to controls (p\u0026lt;0.001). However chronic HT was similar between the groups. Mean serum bile acid level was 19.3\u0026plusmn;3 \u0026mu;mol/L in ICP group. Table 1 showed the comparison of the patients with ICP and controls. ICP increased the risk of preeclampsia (HR 16,4, p:0.005). Furthermore, ICP increased the risk of GDM (HR: 2.42, p:0.033). \u0026nbsp;Age, BMI, gravida, parity, ART was not associated with the risk of preeclampsia and GDM. Table showed risk factors for development of preeclampsia and GDM (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1. Analysis of risk factors for preeclampsia and GDM\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.937694704049843%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"40.03115264797508%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePreeclampsia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"40.03115264797508%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGDM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eno\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16.4 (6-44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.42 (1.07-5.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e0.96 (0.88-1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.405\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e1.01 (0.97-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e1.1 (0.98-1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.0760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.90 (0.80-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eGravida\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e3.0 (0.70-13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e1.22 (0.48-3.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.614\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eParity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e0.64 (0.14-2.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.560\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.75 (0.27-2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.572\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eART\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eno\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.12 (0-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.14 (0.38-3.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.813\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eGDM\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eno\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.80 (0.17-3.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.781\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003eGestational age\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e1.01 (0.77-1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e0.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003ePreeclampsia\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eno\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.906687402799378%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.78 (0.17-3.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.06220839813375%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant difference between the mean gestational week and birth weight at birth according to the presence or absence of ICP (p\u0026lt;0.001). There was also a significant correlation between the presence of ICP and both mode of delivery and, the presence of postpartum hemorrhage (respectively p\u0026lt;0.001, p:0.044). The mean gestational week and birth weight at delivery were lower, and the rate of cesarean delivery and PPH were higher in those with ICP. \u0026nbsp;There were statistically significant relationships between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery (respectively p:0.012, p\u0026lt;0.001). \u0026nbsp;There were statistically significant relationships between the presence of ICP and 5\u003csup\u003eth\u003c/sup\u003e minute Apgar score \u0026lt; 7, presence in NICU (respectively p:0.034, p\u0026lt;0.001). On the other hand, there was no significant relationship between the presence of ICP and SGA and meconium (respectively p:0.055, p:0.151). Spontaneous preterm delivery, iatrogenic preterm delivery, 5\u003csup\u003eth\u003c/sup\u003e minute Apgar score \u0026lt;7 and NICU were found to be proportionally higher in those with ICP\u003cins cite=\"mailto:cansu%20bulut\" datetime=\"2023-11-27T19:51\"\u003e\u0026nbsp;\u003c/ins\u003e(Table 2).\u003c/p\u003e\n\u003cp\u003eTable 2.\u0026nbsp;Relationship between İntrahepatic Cholestasis and Neonatal Outcomes\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"98%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"44.44444444444444%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eICP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.444444444444443%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.444444444444443%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" valign=\"top\"\u003e\n \u003cp\u003eGestational week at birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e36,62\u0026plusmn;1,56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e37,69\u0026plusmn;1,45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" valign=\"top\"\u003e\n \u003cp\u003eBirth weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2847,59\u0026plusmn;296,08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e3127,60\u0026plusmn;428,50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" valign=\"top\"\u003e\n \u003cp\u003eMode of delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eCaesarean section\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e39 (%72,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e792 (%48,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003eNSVD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.444444444444443%\" valign=\"top\"\u003e\n \u003cp\u003e15 (%27,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.444444444444443%\" valign=\"top\"\u003e\n \u003cp\u003e840 (%51,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" valign=\"top\"\u003e\n \u003cp\u003ePPH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2 (%3,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e15 (%0,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0,044\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.444444444444443%\" valign=\"top\"\u003e\n \u003cp\u003e52 (%96,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.444444444444443%\" valign=\"top\"\u003e\n \u003cp\u003e1617 (%99,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSpontaneous preterm labor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2 (%3,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e11 (%0,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0,012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e52 (%96,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e1621 (%99,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIatrogenic preterm labor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e10 (%18,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e16 (%1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e44 (%81,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e1616 (%99)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2 (%3,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e16 (%1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0,055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e52 (%96,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e1616 (%99)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMeconium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2 (%3,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e22 (%1,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0,151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e52 (%96,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e1610 (%98,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e5th minute Apgar \u0026lt;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2 (%3,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e14 (%0,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0,034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e52 (%96,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e1618 (%99,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eNICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e13 (%24,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e114 (%7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e41 (%75,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e1518 (%93)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.303030303030305%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eStillbirth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.161616161616163%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0 (%0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0 (%0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.090909090909092%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.943\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e54 (%100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.666666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e1632 (%100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study had two main findings. ICP showed a strong relationship with GDM and pre-eclampsia. Women diagnosed with ICP had a significantly increased risk for adverse perinatal outcomes. In our study, consistent with previous studies, we demonstrated a higher risk of GDM and preeclampsia in women with ICP compared to those without ICP (10,14).\u003c/p\u003e \u003cp\u003eThe mechanisms underlying the direct association of ICP with GDM and preeclampsia remain unclear. Martineau et al. reported that ICP was characterized by glucose intolerance and dyslipidemia, consistent with the metabolic syndrome [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Women with ICP exhibited higher triglyceride, total cholesterol, LDL and VLDL levels and these indices were also related with an increased risk of preeclampsia and GDM [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In our study, cholesterol levels were not evaluated. It has been shown that women with higher BMI and impaired metabolic pathways may also be at increased risk for adverse outcomes of pregnancy [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Our study also showed that the incidence of GDM and pre-eclampsia was significantly increased in overweight pregnant women with ICP.\u003c/p\u003e \u003cp\u003eIn our study, we observed a significant relationship between ICP and adverse perinatal outcomes. The relationship between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery, 5th minute Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 and NICU stay showed adverse effects of ICP on perinatal outcomes. On the other hand, there was no significant relationship between the presence of ICP and SGA and meconium. In the study published by Geenes et al. which included a very large population, it was found that the risk of meconium-stained amniotic fluid was higher in severe ICP. However, no neonatal meconium aspiration syndrome was shown in the study, and it was claimed that the need for neonatal intensive care was generally associated with preterm birth and the negative consequences it caused. In addition, in the same study, babies with SGA were found to be less in the cholestasis group than in the control group [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], which is similar to our study. Williamson et al. previously reported that ICP was associated with an increased risk of stillbirth [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. ICP is characterized by fetal death without any clear cause, but since there is currently no specific way to monitor the fetus, the pregnancy is usually terminated beforehand to avoid adverse pregnancy outcomes. With effective management during pregnancy, there was no increased incidence of stillbirth in our study, in agreement with previously published studies. In patients diagnosed with ICP, the mean gestational age and birth weight at birth were found to be low. The Royal College of Obstetrics and Gynecology does not recommend active management, although optimal timing of delivery in ICP is difficult given the paucity of high-quality studies [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA recent meta-analysis showed an increased risk of stillbirth in women with ICP when serum bile acid concentrations were 100 \u0026micro;mol/L or more [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], but bile acid is not always a reliable monitoring index [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Relatedly, stillbirth may not have been detected since the highest serum acid level in our study group was 29.9 \u0026micro;mol/L. We encourage clinicians to monitor bile acid levels and recommend that they make an individualized decision about whether the risks of preterm birth outweigh the risks of disease.\u003c/p\u003e \u003cp\u003eIn our study, both spontaneous and iatrogenic preterm birth were found higher in the ICP group. Especially, the high rate of iatrogenic preterm labor may reflect concerns with regard to the risk of fetal death or adverse outcome in pregnancies complicated by high maternal serum bile acids, and therefore the clinicians managing these pregnancies may have preferred a management strategy of induction of labor prior to 37 weeks despite emerging concerns about special education needs [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and poorer school performance [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] in babies born late preterm. Spontaneous preterm labor may be explained by a dose-dependent bile acid effect on myometrial contractility, as has been demonstrated in rodents [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Further-more, myometrial cells from women with ICP are more responsive to oxytocin, and cells from normal women demonstrate an increased response to oxytocin in the presence of bile acids [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePPH is defined as blood loss of more than 500 mL within 24 hours after delivery. In our study, there was a significant correlation between the presence of ICP and both mode of delivery and, the presence of postpartum hemorrhage (PPH). In the ICP group, the mean gestational week and, birth weight at delivery were found to be lower and, the rate of cesarean delivery and PPH were found to be higher. However, in these patients, postpartum hemorrhage was treated with conservative methods without the need for any surgical or additional procedures such as postpartum hysterectomy, uterine artery ligation, hypogastric artery ligation, balloon tamponade, b-lynch suturing. Additionally, no patient required massive blood product transfusion and no exitus occurred due to postpartum hemorrhage. The low frequency of postpartum hemorrhage in our study may be explained by the different definitions used or underestimation of blood loss. This study was conducted as a single-center, retrospective cohort study with large samples of ICP patients demonstrating the prevalence and characteristics of ICP in our hospital.\u003c/p\u003e \u003cp\u003eIn our study, cesarean section rates were found to be higher in pregnancies in the ICP group. In a recent study Kong et al. demonstrated that women with severe ICP also had a significantly higher incidence of planned and unplanned CS compared with mild ICP subjects, as the indications for CS showed that fetal intolerance was higher in severe ICP compared with mild ICP [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] Shemer et al. reported that the risk of emergency cesarean section in ICP with spontaneous onset of labor did not differ from non ICP women with spontaneous onset of labor [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Generally, from studies of Brouwers et al and Stenhiles et al, we have known that intrahepatic cholestasis increases the risk of preterm labor, abnormal intrapartum fetal heart tracing and sudden intrapartum fetal death [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These known risks are the most likely reasons why the patients with ICP have a higher frequency of cesarean section compared to spontaneous delivery.\u003c/p\u003e \u003cp\u003eThere are undoubtedly some limitations of our study. This study can be considered as a retrospective study, which may raise some concerns about data quality. These risks are thought to be related to patient selection risks and information bias. Furthermore, we did not evaluate the relationship between ICP and GDM or ICP and pre-eclampsia for time of onset. The relationship between bile acid concentrations and the risk of GDM or pre-eclampsia was not evaluated. Therefore, it is necessary to further analyze the time frame for any relationship between ICP and GDM or pre-eclampsia and to better understand the potential mechanisms of any correlation.\u003c/p\u003e \u003cp\u003eIn conclusion our study suggested that patients with ICP had increased risk of development of GDM and preeclampsia. Accordingly, we showed that it is associated with preterm birth and adverse perinatal outcomes.\u003c/p\u003e \u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAuthor Contribution\u003c/h2\u003e \u003cp\u003eAta Can: Data collection or management, Data analysis, Manuscript writing/editing\u003c/p\u003e \u003cp\u003eAtlihan Ufuk: Data collection or management, Data analysis, Manuscript writing/editing\u003c/p\u003e \u003cp\u003eAvsar Huseyin Aytug: Protocol/project development, Data collection or management, Data analysis, Manuscript writing/editing\u003c/p\u003e \u003cp\u003eErkilinc Selcuk: Protocol/project development, Manuscript writing/editing\u003c/p\u003e "},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePathak B, Sheibani L, Lee RH (2010) Cholestasis of pregnancy. 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PMID: 23427928\u003c/span\u003e\u003c/li\u003e\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":"bile acid, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, preeclampsia","lastPublishedDoi":"10.21203/rs.3.rs-3744861/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3744861/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eIntrahepatic cholestasis of pregnancy is the most common pregnancy-specific liver disease. It occurs in approximately 1/1000 to 1/10000 of pregnancies and usually resolves during the postpartum period without causing any hepatic sequelae or mortality in the mother. This is a condition complicated by itching in the body, increased liver enzymes and fasting bile acid levels (\u0026ge;\u0026thinsp;10 \u0026micro;mol/L). Although the relationship of intrahepatic cholestasis (ICP) with Gestational Diabetes Mellitus (GDM) and preeclampsia has been evaluated in studies, there are few studies examining the relationship of intrahepatic cholestasis with GDM and preeclampsia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients who gave birth in our hospital between January 2018 and March 2022 were retrospectively reviewed from the hospital database and patient file records. Patients who were diagnosed with intrahepatic cholestasis and gave birth during the study period were retrospectively compared with all other patients who gave birth.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn our study, consistent with previous studies, we demonstrated a higher risk of GDM and pre-eclampsia in women with ICP compared to those without ICP. In our study, we observed a significant correlation between ICP and adverse perinatal outcomes. There was a statistically significant relation between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery, 5th minute Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 and presence of Neonatal Care Unit (NICU). On the other hand, no significant relationship was found between the presence of ICP and the presence of Small Gestational Age (SGA) and meconium. In our study, there was a significant relationship between the presence of ICP and mode of delivery, and the presence of postpartum hemorrhage (PPH) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Those with ICP were found to have a lower gestational week and birth weight at birth, and a higher rate of caesarean delivery and PPH.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study suggested that patients with ICP had increased risk of development of GDM and preeclampsia.\u003c/p\u003e","manuscriptTitle":"Intrahepatic Cholestasis of Pregnancy and Its Association with Preeclampsia and Gestational Diabetes: A Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-05 08:12:54","doi":"10.21203/rs.3.rs-3744861/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-02-01T18:29:44+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-01T10:01:07+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Archives of Gynecology and Obstetrics","date":"2023-12-17T11:50:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-13T12:46:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2023-12-12T10:45:34+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":"535ca0e6-0e03-4f36-9d16-a30300cb6393","owner":[],"postedDate":"February 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-04-16T11:52:02+00:00","versionOfRecord":{"articleIdentity":"rs-3744861","link":"https://doi.org/10.1007/s00404-024-07507-0","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2024-04-16 11:52:02","publishedOnDateReadable":"April 16th, 2024"},"versionCreatedAt":"2024-02-05 08:12:54","video":"","vorDoi":"10.1007/s00404-024-07507-0","vorDoiUrl":"https://doi.org/10.1007/s00404-024-07507-0","workflowStages":[]},"version":"v1","identity":"rs-3744861","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3744861","identity":"rs-3744861","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}