Hyperemesis gravidarum,gastrointestinal and liver disease in pregnancy

Women of childbearing age may be affected by diseases of the gastrointestinal tract or liver; some have no effect on obstetric outcome, some are improved in pregnancy and some deteriorate. Gastrointestinal or liver disease may be caused by pregnancy and resolve following delivery e.g. hyperemesis gravidarum, pre-eclampsia, acute fatty liver of pregnancy, HELLP syndrome and obstetric cholestasis, or may present for the first time in pregnancy e.g. inflammatory bowel disease, cholelithiasis and hepatitis. These examples and other common gastrointestinal and liver disorders will be discussed giving details of diagnosis, management and effects on pregnancy outcome and also background information on normal liver physiology in pregnancy.     

Medical disorders in pregnancy, including hypertensive diseases

Medical disorders, including hypertensive diseases, may exist prior to pregnancy (eg, connective tissue diseases, chronic hypertension, thyroid disease) or may manifest themselves for the first time during pregnancy (eg, gestational diabetes, gestational hypertension). The outcome for a particular pregnancy will depend on the nature of the disease, the severity of the disease process at onset of pregnancy, and the quality of obstetric and medical management used. Management of pregnancies with preexisting medical disorders should begin before conception. These women should be evaluated to determine the severity of the disorder and to establish the presence of possible target organ damage. In addition, they should be counseled regarding the potential adverse effects of the disease on pregnancy outcome and the effects of pregnancy on their disease. These women should be instructed regarding the importance of early onset of prenatal care and compliance with frequent prenatal visits.     

Connective tissue and skin disorders in pregnancy

Connective tissue disorders are multisystem diseases which most frequently present in young women. They are therefore relatively common in pregnancy and are a challenge to the treating physician. These disorders may affect both mother and baby. Women should be cared for in specialized clinics with the appropriate expertise.Skin disorders are either preexisting, co-incidental or specific to pregnancy. Some of these disorders may have harmful effects on the fetus and therefore appropriate diagnosis is mandatory.In this article, we aim to review current knowledge and the practical management of connective tissue and skin disorders in pregnant women. The possible adverse fetal and neonatal effects of the diseases and the drugs used during pregnancy and breast-feeding are also considered.     

Pregnancy-specific liver diseases

Liver disease presenting in pregnancy may be due to a pregnancy-specific liver disorder, due to previously unrecognised pre-existing liver disease, or de novo liver disorders coincidentally presenting in a pregnant woman. The pregnancy-specific liver diseases can span from mild disease with limited impact on maternal and foetal health to severe disorders that can result in significant morbidity and mortality for mother and foetus. Swift identification of these disorders is essential to allow timely and appropriate management via a multi-disciplinary approach. The pregnancy-specific conditions, including their presentation, investigations, and management are reviewed in this chapter in detail.     

Pregnancy and inborn errors of metabolism

Increasing number of patients with inborn errors of metabolism (IEM) are now reaching adulthood and are in position to reproduce. Because of the rarity of individual disorders our knowledge of risks factors associated with pregnancy is limited. Obstetrics problems in IEM can be divided into two categories: pregnancy effects on maternal metabolic disorders and relation between mother and fetus related to who of them is affected. Detrimental effects upon the fetus may be directly caused by maternal disease, as it occurs in PKU, or indirectly by maternal supplementation with harmful substrate, as occurs in galactosemia. Less commonly, fetal inborn error of metabolism may affect the mother's health. Pregnancies in which the fetus had long-chain hydroxyacyl-CoA dehydrogenase deficiency have been complicated by life-threatening HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) or AFL (acute fatty liver of pregnancy) during third trimester. The management of labor and the postpartum period (for women and newborns) has to be carefully planned to avoid significant metabolic decompensation.     

Current management of the HELLP syndrome

The HELLP syndrome as part of the microangiopathic syndromes requires special attention in terms of a rapid and accurate diagnostic and differential diagnostic workup because of its possibly rapid clinical deterioration. It is defined by the classical triad of hemolysis,elevated liver enzymes and low platelet counts which may lead to prognostically relevant problems in differentiating it from thrombotic-thrombocytopenic purpura and hemolytic-uremic syndrome and other pregnancy-related and unrelated liver diseases, i.e. mainly clinical and laboratory similarities to other liver diseases such as acute fatty liver or intrahepatic cholestasis in pregnancy or pregnancy-unrelated settings like viral hepatitides. The management in the different phases of pregnancy is described in detail. Therapeutic options to prolong pregnancy are discussed as are the possibilities of prophylaxis in subsequent pregnancies and aspects of the followup.     

Gastrointestinal and liver disease in pregnancy

The gastrointestinal system and the liver undergo several physiological changes during pregnancy, an understanding of which is essential to distinguish pathology from normal pregnancy symptoms. This review includes the physiological changes that occur in the gastrointestinal system and liver in pregnancy, common conditions of the liver and gastrointestinal system which can present in pregnancy, including the appropriate investigations, management options and indications for specialist multidisciplinary input.     

Acute liver failure in pregnancy. A case report

BACKGROUND: Liver disease in pregnancy can be grossly divided into those disorders coincidentally occurring during the pregnant state and hepatic diseases limited to pregnancy. Numerous infectious agents can result in acute hepatitis and include not only the hepatitis viruses--A, B, C and E--but herpesvirus and cytomegalovirus as well. Coxsackie B viruses can cause several clinical presentations, ranging from asymptomatic to mild febrile illness to myocarditis and meningitis. Rarely has coxsackievirus infection been associated with fulminant hepatic failure. CASE: A Coxsackie B virus infection resulted in acute liver failure in a gravid woman. The patient was managed expectantly, with resolution of the liver disease and delivery five weeks after discharge. CONCLUSION: The onset of hepatic disease is insidious, with only vague symptoms or minor complaints often heralding the progression to liver failure. A careful history, physical examination and appropriate diagnostic tests can help determine the etiology of hepatic disease and help decide whether expectant management of the gravid patient or immediate delivery is appropriate.     

Imitators of severe preeclampsia

There are several obstetric, medical, and surgical disorders that share many of the clinical and laboratory findings of patients with severe preeclampsia-hemolysis, elevated liver enzymes, and low platelets syndrome. Imitators of severe preeclampsia-hemolysis, elevated liver enzymes, and low platelets syndrome are life-threatening emergencies that can develop during pregnancy or in the postpartum period. These conditions are associated with high maternal mortality, and survivors may face long-term sequelae. Perinatal mortality and morbidity also remain high in many of these conditions. The pathophysiologic abnormalities in many of these disorders include thrombotic microangiopathy, thrombocytopenia, and hemolytic anemia. Some of these disorders include acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and acute exacerbation of systemic lupus erythematosus. Because of the rarity of these conditions during pregnancy and postpartum, the available literature includes only case reports and case series describing these syndromes. Consequently, there are no systematic reviews or randomized trials on these subjects. Differential diagnosis may be difficult due to the overlap of several clinical and laboratory findings of these syndromes. It is important that the clinician make the accurate diagnosis when possible because the management and complications from these syndromes may be different. For example, severe preeclampsia and acute fatty liver of pregnancy are treated by delivery, whereas it is possible to continue pregnancy in those with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome and exacerbation of systemic lupus erythematosus. This review focuses on diagnosis, management, and counseling of women who develop these syndromes based on results of recent studies.     

Gastrointestinal disorders in pregnancy.

Gastrointestinal disorders constitute one of the most frequent complaints of pregnancy. An understanding of the mode of presentation and the incidence of the various gastrointestinal disorders will optimize care in obstetric patients. Disorders of the esophagus, stomach, duodenum, ilium, jejunum, colon, rectum, and appendix are individually discussed with reference to physiologic changes in pregnancy, infectious diseases, autoimmune disease, and ulcer formation.     

Hormone therapies in pregnancy

Maternal endocrine disorders can have detrimental effects on the fetus and the pregnancy can affect the course of a pre-exisiting endocrinopathy or induce the onset of one of these disorders. Therapies for endocrine disorders are not always safe to administer during pregnancy. Before administering any therapy to the mother, the effects on the fetus, the degree of placental trespassing as well as the potential damaging effects must be assessed. An accurate evaluation of the risks/benefits of any drug to be used on the mother is needed, assessing above all a potential theratogenic effect. In this review, the incidence of the main endocrine disorders, their evolution during pregnancy, their effects on mothers and fetuses and new acquisition on the treatment during pregnancy are discussed.     

Hepatitis B – chronic carrier status and pregnancy outcomes: An obstetric perspective

Antenatal screening for hepatitis B surface antigen (HBsAg) only identifies women with hepatitis B virus (HBV) infection for neonatal immunoprophylaxis. It does not reflect the phase of chronic infection, viral genotype and activity, hepatic inflammation, or other co-existing liver disorders. Coinfection with other viruses and micro-organisms may also be present. These factors in various combinations can impact pregnancy outcomes, and they are probably responsible for the conflicting literature on this issue. Pregnancy complications may interact with maternal HBV infection and hepatitis flares, leading to serious and lethal complications. Hepatitis flares are common especially postpartum, and they are unpredictable and unpreventable with antiviral treatment. Evidence on the association between HBsAg seropositivity with gestational diabetes mellitus, preterm birth, increased foetal growth, and reduced pregnancy hypertensive disorders is stronger than other adverse pregnancy outcomes. Baseline assessment of liver function, and viral markers and activity, can delineate the truly high-risk pregnancies for close monitoring.     

Subfertility and gastrointestinal disease: 'unexplained' is often undiagnosed

Subfertility can be more reliably explained and effectively treated with an improved understanding of the contribution of chronic medical disease to reproductive dysfunction. This review addresses several common gastrointestinal disorders which are increasingly implicated in infertility and early pregnancy loss: celiac disease, inflammatory bowel disease (ulcerative colitis and Crohn's disease), and hemochromatosis. Appreciating the reproductive impact of these comorbidities and their treatments enables clinicians to accurately counsel patients and to modify medical and fertility treatments based on etiology. Because unexplained infertility can represent the initial presentation of undiagnosed medical disease, considering these often-subclinical gastrointestinal disorders in the differential diagnosis of subfertility provides an opportunity not only to increase the probability of conception and uncomplicated pregnancy, but also to improve overall maternal health.     

Liver diseases and pregnancy. I: The liver in normal pregnancy--liver diseases caused by pregnancy

In its introduction, this review deals with the influence of normal pregnancy on the liver. Then, intrahepatic cholestasis of pregnancy and acute fatty liver of pregnancy as diseases peculiar to pregnancy are considered intensively. A second part will be dedicated to liver diseases independent of pregnancy.     

Atypical process of acute disturbance of liver function with severe thrombocytopenia in the third trimester

The authors diagnosed disturbance of liver-function associated with severe thrombopenia in a pregnant woman in the third trimester. Principally, acute fatty liver of pregnancy can be characterized by existing symptoms, e.g. nausea, vomiting, epigastric pain, jaundice, hyperbilirubinemia, moderately elevated SGOT and SGPT levels, thrombopenia, leukocytosis, low fibrinogen level and disseminated intravascular coagulopathy, but hepatomegaly, purpura and petechia on lower and upper extremities, and high ALP and GGT levels during postpartum period do not confirm suspicion of this diagnosis. The present report draws attention to the difficulties of differential diagnosis of pregnancy-induced elevated liver enzymes diseases associated with low platelets, as there are several identical pathophysiological processes. Although causes and exact pathophysiology of disorders are unknown, similar symptoms during the process of diseases leave the question open whether they are different diseases or whether they are different manifestations of the same disease, and what kind of relationship exists between these diseases and preeclampsia. This case suggests careful evaluation of the whole clinical picture, moreover it is emphasized that prompt, aggressive treatment of hemostatic disturbance and the expeditious delivery can save maternal life.     

Complications and late sequelae of contraception including sterilization (proceedings)

Epidemiological studies of the complications and sequelae of oral contraceptives, IUDs, and sterilization are reviewed. The author also assesses the risks associated with each method. Thromboembolism, cerebrovascular disorders, myocardial infarct, breast, liver, and other neoplasms; other liver and gallbladder diseases; hypertension; postcontraceptive amenorrhea, temporary infertility, congenital abnormalities, and a variety of side effects have been reported for oral contraceptives. For IUDs, the chief dangers are those of ascending infection and its long-term effects on fertility, and the danger to the developing fetus and the mother when pregnancy occurs with the IUD in place. Mortality from sterilization is about 7 per 100,000 patients. The author compares pregnancy-associated mortality with rates for the various contraceptive methods, and concludes that, although contraception is not without risk, the risk for all methods is less than that of pregnancy.     

Hyperemesis gravidarum,gastrointestinal and liver disease in pregnancy

Up to 80% of pregnant women experience discomfort due to symptoms originating from the gastrointestinal tract; ∼5% of them have more severe disease that can adversely affect maternal and fetal outcome. This review presents options of symptomatic relief for the common complaints of the gastrointestinal tract. It also discusses the management of the commonest or most serious conditions of the gastrointestinal tract and liver that can coexist or appear for the first time in pregnancy.     

Study of the liver changes by B-ultrasound and histopathology in severe pregnancy induced hypertension

OBJECTIVE: To investigate the liver changes in severe pregnancy induced hypertension (PIH) on B-ultrasound and pathological examination and to detect a possible connection with fatty liver of pregnancy. METHODS: From Jan 1992 to Nov 1997, 90 pregnant women in the third trimester were enrolled for study. They were divided into 3 groups: the pregnant women with liver diseases; mild and moderate PIH; and severe PIH (30 cases each). Ultrasonography of the liver was performed on each patient after admission. 15 percutaneous liver biopsies were performed under the guidance of real-time ultrasound scans on 15 severe PIH patients with or without liver dysfunction. Tissues were stained with specific lipid staining (Sudan) and with hematoxylin-eosin. All specimens were analyzed by light microscopy. RESULTS: Fatty liver was observed by B-ultrasound in 2 and 12 cases of the pregnancy with liver diseases group and the severe PIH group, respectively. 14 of the 15 liver biopsy specimens showed fatty infiltration of varying degrees. however, only 8 of the 14 cases were detected fatty liver by B-ultrasound. CONCLUSIONS: These findings suggest that liver involvement in severe PIH is a pathological change. Severe PIH and acute fatty liver in pregnancy could have related pathogenesis components of the same.     

Inherited long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and a fetal-maternal interaction cause maternal liver disease and other pregnancy complications.

Fetal-maternal interactions are critical determinants of maternal health during pregnancy and perinatal outcome. This review explores the causative relationship of a fetal disorder of mitochondrial fatty acid oxidation, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and the serious maternal liver diseases of pregnancy-preeclampsia, the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts), and acute fatty liver of pregnancy. Features of the metabolic adaptation necessitated during the fetal-neonatal transition; common phenotypes of pediatric fatty acid oxidation disorders, including neonatal hypoketotic, hypoglycemia and hepatic crisis; and clinical abnormalities of HELLP and acute fatty liver of pregnancy are presented. Evidence that a common mutation in the alpha-subunit (LCHAD) of trifunctional protein, E474Q, is always one of the mutant alleles in fetal isolated LCHAD deficiency associated with these disorders of pregnancy that cause high maternal, fetal, and newborn morbidity and mortality is reviewed. Recommendations for molecular testing for LCHAD deficiency in families with life-threatening maternal liver disease are given.     

Neurologic disorders during pregnancy and the puerperium

This article focuses on epilepsies, autoimmune diseases such as multiple sclerosis and myasthenia, serious problems associated with stroke and pseudotumor cerebri, and some common problems such as headaches and the carpal tunnel syndrome, examining the effects of pregnancy and the puerperium on these disorders and the influence of these disorders on pregnancy.