Intrahepatic cholestasis of pregnancy: a critical review

Intrahepatic cholestasis of pregnancy (ICP) is a disease predominantly of the third trimester of pregnancy, characterized primarily by pruritus, biochemical disturbances in liver enzymes, and less frequently jaundice. Although maternal pruritus can be severe, overall maternal morbidity and mortality associated with ICP is low. However, fetal morbidity and mortality are significant with associated risks for meconium-stained amniotic fluid, acute onset of fetal compromise, spontaneous preterm labor, and intrauterine fetal demise. Current literature recommends obstetric management that includes frequent fetal surveillance with delivery when fetal lung maturity has been established.     

Hepatic disorders severely affected by pregnancy: medical and obstetric management

Hepatic disorders severely affected by pregnancy include choledochal cysts that can be compressed by the gravid uterus and potentially rupture; hepatic adenomas that exhibit accelerated growth because of hyperestrogenemia during pregnancy; acute intermittent porphyria that is exacerbated by increased female sex hormones during pregnancy; splenic artery aneurysms that can rupture during pregnancy because of compression by the gravid uterus; Budd-Chiari syndrome that is promoted by hyperestrogenemia; and hepatitis E and herpes simplex hepatitis that are particularly severe during pregnancy. Hepatic disorders unique to pregnancy include intrahepatic cholestasis of pregnancy; acute fatty liver of pregnancy; preeclampsia and eclampsia; and hemolysis, elevated liver function tests, and low platelet count (HELLP) syndrome. Most disorders uniquely related to pregnancy are treated by prompt fetal delivery as soon as the fetus is sufficiently mature.     

Endocarditis during pregnancy

The incidence of infective endocarditis during pregnancy has been reported to be 0.006%. The maternal mortality rate can reach 33%, with most deaths related to heart failure or an embolic event. The rate of fetal mortality can reach 29%. Heart diseases are the most important nonobstetric causes of maternal death during pregnancy, accounting for 10% of maternal deaths. As many as 3% of women have a form of cardiac disease diagnosed during or in the period preceding pregnancy, with 70 to 80% of the cardiac conditions having congenital causes.     

Endoscopic retrograde cholangiopancreatography during pregnancy

Physiologic changes of pregnancy leave women at increased risk for gallstone complications. Endoscopic retrograde cholangiopancreatography (ERCP) during pregnancy was first reported in 1990 for the treatment of complicated gallstone disease. Since then, numerous reports have shown that if certain precautionary measures are taken, therapeutic ERCP can be safely performed during pregnancy. A multidisciplinary approach that involves obstetrics, surgery, and gastroenterology is necessary to help ensure maternal and fetal safety. This article addresses the physiologic changes that increase a women's risk for gallstone complications, the indications for ERCP, the safety of ERCP, and its use within the last 15 years.     

Pharmacologic treatment of hypertensive disorders during pregnancy

Pregnancy complicated by hypertension is a common problem faced by clinicians. It can lead to substantial maternal and/or fetal/neonatal morbidity and mortality. There are a variety of medications that can be used during pregnancy either for treatment of significant chronic hypertension or in cases of acute severe hypertension. Most antihypertensive drugs have been shown to be safe for use in pregnancy. A variety of medications are available to treat more severe hypertension, although the use of pharmacologic therapy to treat mild chronic hypertension during pregnancy has not been supported in the literature. The data are more limited concerning drugs that would be used in the event of hypertensive emergencies or in an intensive care setting; however, in such a situation, maternal health and life become paramount and, despite lack of good studies, appropriate treatment should be rendered.     

Thyroid disease and pregnancy

Thyroid disease is common in younger women and may be a factor in reproductive dysfunction. This probably only applies to severe cases of hyper- or hypothyroidism. Once adequately treated, neither of these disorders significantly impacts on fertility. The key is to recognize and to treat thyroid disorders in the reproductive-age woman before conception. Thyroxine therapy and even antithyroid drug therapy should be continued during pregnancy as necessary. Pregnancy is a euthyroid state that is normally maintained by complex changes in thyroid physiology. The fetal and neonatal hypothalamic-pituitary-thyroid system develops independently, but it may be influenced by thyroid disease in the mother. Early pregnancy is characterized by an increase in maternal T4 secretion stimulated by hCG and an increase in TBG, resulting in the elevated total serum T4 in pregnancy. The debate continues as to whether maternal T4 is important in early or late fetal brain development. If so, the physiologic changes in thyroid hormone secretion and transport in early pregnancy would help to ensure that a sufficient amount of thyroid hormone was available. There is new evidence in human subjects that substantial maternal T4 can cross the placenta during pregnancy, and this may be particularly important when fetal thyroid function is compromised as a result of congenital hypothyroidism. Maternal and fetal/neonatal outcomes in pregnancy are adversely affected if severe hypothyroidism is undiagnosed or inadequately treated. Thyroid function tests should be obtained during gestation in women taking T4 and appropriate dose adjustments should be made for TSH levels outside a normal range. The TSH-receptor blocking antibodies from the mother are a recognized cause of congenital hypothyroidism in the fetus and neonate that can be permanent or transient. If neonatal hypothyroidism is detected through neonatal screening programs, and prompt and adequate T4 replacement therapy is instituted as soon as possible following delivery, subsequent growth and development are usually normal. Paradoxically, pregnancy often has a favorable effect on the course of maternal Hashimoto's disease, although there is the risk of relapse postpartum. Pathophysiologic conditions of hCG secretion such as gestational trophoblastic disease and hyperemesis gravidarum may present as thyrotoxicosis in pregnancy, but the main cause of this syndrome is Graves' disease. The mainstay of treatment is antithyroid drugs and either propylthiouracil or methimazole may be used safely. Subtotal thyroidectomy, after medical control, is the alternative treatment, but radioiodine ablation is contraindicated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hepatitis B mother-to-child transmission

Approximately 350 million people are estimated to be chronically infected with hepatitis B virus, leading to an important public health problem. In highly endemic areas where 8 to 15% of people are chronically infected with hepatitis B virus, the risk for the neonate to be perinatally infected by the chronically infected mother, then to become chronically infected themselves, is very high. In those countries, the World Health Organization recommends hepatitis B vaccination systematically at birth, independent of hepatitis B virus maternal status. This vaccination program has begun to induce a rapid decrease in the number of acute hepatitis B virus infections and has also had a secondary effect of a decrease in related sequels. Lamivudine (Zeffix^®, GlaxoSmithKline), when associated with the immunization of the neonate, was recently demonstrated to dramatically reduce the residual risk of perinatal transmission. In intermediate and low endemicity areas, a systematic hepatitis B surface antigen screening is recommended during pregnancy, allowing, in the case of positivity, a selective hepatitis B virus neonate immunization during the first 12 h of life. Hepatitis B virus vaccination of children born to hepatitis B surface antigen-positive mothers confers long-term immunity.     

Clinical manifestations and outcomes of parvovirus B19 infection during pregnancy in Japan

Parvovirus B19 is a small DNA virus. Infection with parvovirus B19 during pregnancy may cause serious complications in the fetus, including hydrops fetalis and fetal death. The purpose of the present study is to clarify the clinical manifestations and outcomes of parvovirus B19 infection during pregnancy. This prospective study enrolled 478 women with suspected B19 infections during pregnancy between 1999 and 2004. One hundred cases (21%) of B19 infection were detected in 478 pregnant women who had been exposed to B19. Serological infection was confirmed by measurement of B19-specific IgM and IgG in sera. Forty-nine cases reported maternal clinical symptoms and 51 cases were asymptomatic. Facial rash was the most common symptom, with 51% (25/49) of the symptomatic patients complaining of either a facial, body or limb rash. The most common infectious source was children living in the home. Overall, the incidence of adverse fetal effects (including hydrops fetalis and fetal death) related to intrauterine B19 infection was 7% (7/100), and all seven cases were exposed to B19 infection before 20 weeks of gestation. Although half of the cases with parvovirus B19 infections during pregnancy were asymptomatic, patients with adverse fetal effects tended to be symptomatic including rash and fever. These clinical data may supply useful information to produce clinical guidelines for managing B19 infection during pregnancy.     

超声评估妊娠期高血压疾病对晚孕期母胎心功能及胎儿生长发育的影响

目的使用超声参数较为全面、系统的评估妊娠期高血压疾病母胎心功能及胎儿生长发育,为母胎一体化管理提供有价值的信息。方法选取孕周28～41+6周的孕妇150例,妊娠期高血压疾病孕妇60例为疾病组,与其孕龄匹配且血压正常的孕妇90例为对照组。测量的超声参数:(1)孕妇LVDd、LAD、IVSTd、LVPWTd、LVEF、二尖瓣环运动速度的Ea/Aa值。(2)胎儿右心室Tei指数。(3)胎儿BPD、HC、AC、FL。结果疾病组孕妇LVDd、LAD、IVSTd、LVPWTd均较对照组增高(P<0.05),疾病组孕妇舒张功能减低者较对照组增多(P<0.05),疾病组胎儿右心室Tei指数较对照组增高(P<0.05),与孕妇血压呈正相关(P<0.05),疾病组胎儿BDP、HC、AC、FL均较对照组减小(P<0.05)。结论通过对妊娠期高血压疾病孕妇母胎心功能及胎儿生长发育超声参数的研究,可对妊娠期高血压疾病母胎情况进行监测。     

Chronic renal disease and pregnancy

Women who have chronic renal disease are at increased risk for maternal and fetal morbidity and mortality during pregnancy. The severity of the renal disease is correlated with the degree of morbidity and mortality. Chronic renal disease ranges from asymptomatic bacteriuria (ASB) to end stage renal disease requiring hemodialysis and/or renal transplantation. Pregnant women with chronic renal disease require specialized nursing care. Communication between obstetrical nurses and renal nurses is extremely important to ensure holistic care of these patients.     

Hepatitis B mother--to--child transmission

Approximately 350 million people are estimated to be chronically infected with hepatitis B virus, leading to an important public health problem. In highly endemic areas where 8 to 15% of people are chronically infected with hepatitis B virus, the risk for the neonate to be perinatally infected by the chronically infected mother, then to become chronically infected themselves, is very high. In those countries, the World Health Organization recommends hepatitis B vaccination systematically at birth, independent of hepatitis B virus maternal status. This vaccination program has begun to induce a rapid decrease in the number of acute hepatitis B virus infections and has also had a secondary effect of a decrease in related sequels. Lamivudine (Zeffix, GlaxoSmithKline), when associated with the immunization of the neonate, was recently demonstrated to dramatically reduce the residual risk of perinatal transmission. In intermediate and low endemicity areas, a systematic hepatitis B surface antigen screening is recommended during pregnancy, allowing, in the case of positivity, a selective hepatitis B virus neonate immunization during the first 12 h of life. Hepatitis B virus vaccination of children born to hepatitis B surface antigen-positive mothers confers long-term immunity.     

Preventive strategies in chronic liver disease: part I. Alcohol, vaccines, toxic medications and supplements, diet and exercise.

Chronic liver disease is the 10th leading cause of death in the United States. Hepatitis C virus infection is the most frequent cause of chronic liver disease and the most common indication for liver transplantation. Preventive care can significantly reduce the progression of liver disease. Alcohol and hepatitis C virus are synergistic in hastening the development of cirrhosis; therefore, patients with hepatitis C infection should abstain from alcohol use. Because superinfection with hepatitis A or B virus can lead to liver failure, vaccination is recommended. Potentially hepatotoxic medications should be used with caution in patients with chronic liver disease. In general, nonsteroidal anti-inflammatory drugs should be avoided; acetaminophen in a dosage below 2 g per day is the safest choice. Many herbal remedies are potentially hepatotoxic, and only milk thistle can be used safely in patients who have chronic liver disease. Weight reduction and exercise can improve liver function in patients with fatty liver.     

Hepatitis B virus (HBV) in the elderly: an underestimated problem?

Hepatitis B infection in the aged can be underestimated as the clinical and serological pictures can be rather peculiar in these subjects. Institutions for the elderly carry an increased risk of HBV spread as do many other closed communities. People from lower socioeconomic class and from countries with a high HBV prevalence are less susceptible to infection as they are already immunized by previous infections. However, epidemics have been described in homes for the aged, mostly from those for wealthy people or from those in low prevalence countries. When infected the elderly tend to develop a subclinical hepatitis detected only by serum analysis. These infections are frequently followed by asymptomatic chronic carriage of HBsAg. This phenomenon may be due to alterations of the immune system in the aged, which is also suggested by the finding of very poor antibody responses to hepatitis B vaccines in the aged. Overt acute hepatitis is infrequent. It usually have a benign course, even if occasionally cholestatic. Very active type B chronic hepatitis is very rare, while most elderly patients with HBsAg-positive chronic liver disease have cirrhosis as the end stage of chronic hepatitis acquired previously.     

Myocardial infarction in pregnancy

The number of women experiencing myocardial infarction (MI) in pregnancy is relatively negligible. However, the incidence of MI in pregnancy may be on the rise, and maternal and neonatal morbidity and mortality is significant. While diagnosis may be difficult, perinatal nurses must be knowledgeable about the risk factors and various means of treatment for the woman and family experiencing this acute complication of pregnancy. Precis: MI in pregnancy is rare, but can produce significant maternal and fetal morbidity and mortality. Challenges in diagnosis and treatment of MI in pregnancy are discussed.     

The pathophysiology of acute syphilitic funisitis.

There is an increase in the number of cases of syphilis in pregnancy in the United States. Fetal death may occur in syphilis from acute or chronic infections. A case is presented in which an acute fetal infection occurred. The patient presented at 31 weeks' gestation, with a decrease in fetal movements and non-reactive cardiotocography. Ultrasound and Doppler analysis of the fetal heart, cerebral and umbilical arteries, aorta and umbilical vein led to the suspicion of acute cardiac failure. An amniocentesis yielded a white cell count of 1122 white blood cells, with 91% polymorphs, but the Gram stain was negative. The fetus developed a persistent bradycardia and was delivered. The diagnosis of acute severe syphilitic funisitis was suspected from histological sections of the cord. Diagnosis was established from maternal and fetal blood. Modern ultrasound techniques, including imaging, Doppler and cardiotocography, can lead to the analysis of the pathophysiology of disease states. An acute syphilitic infection should be suspected when this constellation of findings is found.     

Cardiac drug use in pregnancy: safety,effectiveness and obstetric implications

Morbidity and mortality due to cardiovascular disease is increasing in pregnancy. The physiologic changes of normal pregnancy serve as a ‘stress test’ on the cardiovascular system. This may lead to the unmasking of a latent underlying cardiac condition or the new onset of maternal cardiovascular disease, with an attendant increase in adverse maternal and fetal outcomes. Some women with pre-existing cardiac conditions may be receiving medications that need to be altered during pregnancy owing to a risk of adverse effects on the developing fetus, but for most cardiac conditions, there are safe and effective treatment options. Women should be educated that abrupt discontinuation of cardiac medications during pregnancy usually poses a greater risk than the medications themselves, and a plan of judicious drug selection should be implemented (ideally prior to conception).     

Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury.     

The effects of rhinitis, asthma, and acute respiratory distress syndrome as acute or chronic pulmonary conditions during pregnancy

Pulmonary complications from both obstetrical and non-obstetrical causes contribute to a mortality rate as high as 80% in the pregnant population. The effect of numerous mechanical and biochemical physiologic alterations during pregnancy can influence the maternal and fetal outcomes in a woman with a pulmonary complication. Progesterone, the primary hormone of pregnancy, is a respiratory stimulant that enhances carbon dioxide release and alters the maternal pH in favor of releasing oxygen to the fetus. During systemic compromise, which may be experienced as an acute asthmatic attack or respiratory distress syndrome, desaturation and carbon dioxide retention ensue. Under these conditions, the fetus is at risk for perinatal hypoxemia. Although prompt recognition and treatment are important to minimize maternal, fetal, and neonatal morbidity and mortality, evidence-based literature regarding critical care techniques that promote optimal obstetrical outcomes is limited. Therefore, a collaborative approach to the care of these women is warranted. In addition to critical care, emergency medicine, and obstetrical nurses, the medical team may include an obstetrician, a perinatologist, a neonatologist, a pulmonologist, an intensivist, and an immunologist.     

Importance of hepatitis vaccination in patients with chronic liver disease

Acute hepatitis A or B infection can be lethal in patients with chronic liver disease. Safe and effective vaccines are currently available to prevent hepatitis A and B. Despite wide availability of vaccines, most patients with chronic liver disease are not immunized, in part due to nonuniform and inconsistent current recommendations for this population. A better understanding of the importance of preventing acute hepatitis A and B in patients with chronic liver disease and a proactive approach to vaccination by primary care physicians can positively influence the outcome of patients with chronic liver disease.