Obstentrics_Williams

Obstentrics_Williams. Also called delta hepatitis, this is a defective RNA virus that is a hybrid particle with an HBsAg coat and a delta core. he virus must co-infect with hepatitis B either simultaneously or secondarily. It cannot persist in serum longer than hepatitis B virus. Transmission is similar to hepatitis B. Chronic coinfection with Brand D hepatitis is more severe and accelerated than with HBV alone, and up to 75 percent of afected patients develop cirrhosis. HDV infection is detected by the presence of anti-HDV and HDV DNA. Neonatal transmission is unusual, as neonatal HBV vaccination usually prevents delta hepatitis.


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Obstentrics_Williams. This is a single-stranded RNA virus, and transmission occurs via blood and body luids, although sexual transmission is ineicient. Up to a third of anti-HCV positive persons have no identifiable risk factors (Dienstag, 2015b). Screening for HCV is recommended for HIV-infected individuals, persons with injection drug use, hemodialysis patients, children born to mothers with HCV, persons exposed to HCV-positive blood or body fluids, persons with unexplained elevations in transaminase values, and recipients of blood or transplants before July 1992. Prenatal screening is recommended for high-risk women, and in the United States, seroprevalence rates reach 1 to 2.4 percent (American College of Obstetricians and Gynecologists, 2016; Arshad, 2011). It is higher in women who are infected with HIV. Santiago-Munoz and associates (2005) found that 6.3 percent of HIV-infected pregnant women at Parkland Hospital were co-infected with hepatitis B or C.


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Obstentrics_Williams. Hepatic, Biliary, and Pancreatic Disorders 1065 Acute HCV infection is usually asymptomatic or yields mild symptoms. Only 10 to 15 percent develop jaundice. he incubation period ranges from 15 to 160 days with a mean of 7 weeks. Transaminase levels are elevated episodically during the acute infection. Hepatitis C RNA testing is now preferred for HCV diagnosis. RNA levels may be found even before elevations of transaminase and anti-HCV levels. Speciically, anti-HCV antibody is not detected for an average of 15 weeks and in some cases up to a year (Dienstag, 20 15a).


Obstentrics_Williams

Obstentrics_Williams. Nearly 80 to 90 percent of patients with acute HCV will be chronically infected. Although most remain asymptomatic, approximately 20 to 30 percent progress to cirrhosis within 20 to 30 years. Transaminase values fluctuate, and HCV RNA levels vary over time. Liver biopsy reveals chronic disease and fibrosis in up to 50 percent, however, these indings are oten mild. Overall, the long-term prognosis for most patients is excellent. As expected, most pregnant women diagnosed with HCV have chronic disease. HCV infection was initially thought to have limited pregnancy efects. However, more recent reports have chronicled modestly increased fetal risks for low birthweight, NICU admission, preterm delivery, and mechanical ventilation (Berkley, 2008; Pergam, 2008; Reddick, 201l). In some women, high-risk behaviors associated with HCV infection.


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Obstentrics_Williams. he primary adverse perinatal outcome is vertical transmission of HCV infection to the fetus-infant. This is higher in mothers with viremia (Indolfi, 2014; Joshi, 2010). Airoldi and Berghella (2006) cited a rate of 1 to 3 percent in HCV-positive, RNA-negative women compared with 4 to 6 percent in those who were RNA-positive. In a report from Dublin, the vertical transmission rate in 545 HCV-infected women was 7. I-percent in RNA-positive women compared with none in those who were RNA-negative (McMenamin, 2008). Some have found an even greater risk when the mother is co-infected with HIV (Snidjewind, 2015; T ovo, 2016). Invasive prenatal diagnostic procedures have not been reported to increase transmission to the fetus. However, Rae and Sheield (2014) note that few studies have addressed this possibility, and they recommend avoiding traversing the placenta during amniocentesis. Approximately two thirds of prenatal transmission cases occur peripartum. HCV genotype, invasive prenatal


Obstentrics_Williams

Obstentrics_Williams. this possibility, and they recommend avoiding traversing the placenta during amniocentesis. Approximately two thirds of prenatal transmission cases occur peripartum. HCV genotype, invasive prenatal procedures, breastfeeding, and delivery mode are not associated with mother-to-child transmission. That said, invasive procedures such as internal electronic fetal heart rate monitoring are avoided. HCV infection is not a contraindication to breastfeeding.


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Obstentrics_Williams. No licensed vaccine is available for HCV prevention. The chronic HCV infection treatment has traditionally included alpha interferon (standard and pegylated), alone or in combination with ribavirin. This regimen is contraindicated in pregnancy because of the teratogenic potential of ribavirin in animals (Joshi, 2010). he initial 5-year review of the Ribavirin Pregnancy Registry found no evidence for human teratogenicity. However, the registry has enrolled fewer than half of the necessary numbers to allow a conclusive statement to be made (Roberts, 2010). The development and study of direct-acting and host-targeted antiviral drugs in the past decade shows great promise for chronic hepatitis C management (Liang, 2013; Lok, 2012; Poordad, 2013). Current interferon-free, ribavirin-free regimens are being evaluated, although no data are available for pregnant women.


Obstentrics_Williams

Obstentrics_Williams. This water-borne RNA virus usually is enterically transmitted by contaminated water supplies. Hepatitis E is probably the most common cause of acute hepatitis (Hoofnagle, 2012). It causes epidemic outbreaks in third-world countries with substantial morbidity and mortality rates. Pregnant women have a higher case-fatality rate than nonpregnant individuals. In a metaanalysis of nearly 4000 subjects from Asia and Africa, Jin and coworkers (2016a) reported maternal and fetal case-fatality rates of 21 and 34 percent, respectively. Fulminant hepatitis, although rare overall, is more common in gravidas and contributes to the increased mortality rates. An altered innate immune response to incipient hepatitis E infection during pregnancy, afecting macrophage function and toll-like receptor signaling, may be a factor in the development of fulminant hepatitis (Sehgal, 2015).


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Obstentrics_Williams. A recombinant HEV vaccine has been developed and licensed in China. It is >95 percent efective for 12 months after vaccination. Long-term eicacy is 87 percent, and protective titers are maintained for up to 4.5 years (Zhang, 2015). Preliminary data from inadvertently vaccinated pregnant women show no adverse maternal or fetal events (Wu, 2012). At this time, it is unclear if this Chinese-licensed vaccine is efective in other areas of the world where other genotypes predominate. Genotype 4 is most common in China, and types 2 and 3 are more common in the Americas. A Food and Drug Administration (FDA) approved vaccine is not available at this time. Hepatitis E is found worldwide, and although the highest prevalence is in east Asia, the CDC (2015) lists Mexico as a highly endemic country. Seroprevalence rates vary by age and geography, but overall seroprevalence rates of 10 percent have been reported. Durango State has the highest rate (37 percent) (Fierro, 2016).


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Obstentrics_Williams. Hepatitis G is the former name of an RNA flavivirus now known as HPvG or human pegivirus. This blood-borne infection of the liver, spleen, bone marrow, and mononuclear cells of the peripheral blood does not actually cause hepatitis (Chivero, 2015). It is thought to infect 750 million people worldwide, with up to two times that many with evidence of past infection. It may modulate the immune response, particularly during coinfection with HIV. Currently, no treatment aside from basic blood and body luid precautions is recommended. Vertical transmission (to the fetus/infant) and horizontal transmission (to peers) has been described (Trinks, 2014).


Obstentrics_Williams

Obstentrics_Williams. his is a generally progressive chronic hepatitis that is important to distinguish from other forms. Autoimmune hepatitis is more common in women and frequently coexists with other types of autoimmune disease, particularly autoimmune thyroid disease and Sjogren syndrome. Symptoms are typical of acute and chronic hepatitis, but one quarter may be asymptomatic. Rates of cirrhosis vary worldwide, but in western countries autoimmune hepatitis is more common and is characterized by multiple autoimmune antibodies such as antinuclear antibodies (ANA) and anti-smooth muscle antibody. Type 2 autoimmune hepatitis has an even higher prevalence in females and typically a more aggressive presentation. he incidence peaks in childhood and adolescence, before peak reproductive years. Treatment employs corticosteroids, alone or combined with azathioprine. Failure to respond to these two agents is more frequent in those with type 2 disease, and nearly all women with type 2 disease require more intensive


Obstentrics_Williams

Obstentrics_Williams. alone or combined with azathioprine. Failure to respond to these two agents is more frequent in those with type 2 disease, and nearly all women with type 2 disease require more intensive therapy that is sustained long term (Vierling, 2015). In some patients with progressive disease and cirrhosis, hepatocellular carcinoma develops. In general, autoimmune hepatitis-especially when severeincreases the risk of adverse pregnancy outcomes.


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Obstentrics_Williams. Westbrook and coworkers (2012) reported the outcomes of 81 pregnancies in 53 women. A third had a flare, and these were more common in those not taking medication and those with active disease in the year before conception. Maternal and fetal complications were higher among women with cirrhosis, particularly with respect to the risks of death or need for liver transplantation during the pregnancy or within 12 months postpartum. From one Swedish national database analysis, frequencies of preterm birth, low birthweight, and diabetes were higher, but not those of preeclampsia or cesarean delivery (Stokkeland, 2016). Danielsson Borssen (2016) reported stable or mild disease in 84 percent of 58 women who delivered 100 newborns. Nearly a fourth of cases were delivered before 38 weeks, and a postpartum flare developed in a third. Cirrhosis was present in 40 percent, and these women experienced more complications during pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Chronic hepatitis and cirrhosis can result from iron and copper overload. Iron overload may stem from a primary cause that is generally inherited, such as hereditary hemochromatosis, or originates secondary to complications of certain hemoglobinopathies. Many of the gene mutations underlying hereditary hemochromatosis involve hepcidin and result in dysregulated iron transport (Chap. 4 p. 58). Some of these mutations are more common in certain populations originating from northern Europe (Pietrangelo, 2016; Salgia, 2015). Cardiomyopathy, diabetes, joint disease, and skin changes can coexist with liver disease. Pregnancy outcomes associated with iron overload in hereditary hemochromatosis are driven by the degree of liver dysfunction, although higher iron levels may afect birthweight (Dorak, 2009).


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Obstentrics_Williams. A form of neonatal hemochromatosis that does not afect the mother is now thought to be alloimmune and is called gestational aloimmune liver disease (Anastasio, 2016). With this, maternal autoantibodies cross to the fetus and mediate dysfunction of iron homeostasis, although the antigenic target of these alloantibodies remains unclear. It is associated with significant neonatal morbidity and mortality, and frequently recurs in subsequent pregnancies. In these cases, antepartum treatment with intravenous immunoglobulin (IVIG) may improve outcomes (Feldman, 2013; Roumiantsev, 2015).


Obstentrics_Williams

Obstentrics_Williams. Copper overload leading to chronic hepatitis and cirrhosis is Wilson disease. This systematic condition can also manifest with cardiomyopathy, renal disease, neuropsychiatric symp toms, and certain endocrine abnormalities. A Kayser-Fleischer ring surrounding the iris is highly speciic, but a suspected diagnosis generally requires genetic analysis. Autosomal reces sive mutations of the A TP7B gene underlie this disorder. his gene codes for the P-type ATPase involved in copper transport to ceruloplasmin and bile (Bandman, 2015). With Wilson disease, infertility may be present, but preg nancy outcomes among afected women who do conceive are inluenced by disease severity. Malik and colleagues (2013) reported four cases in pregnancy, and three had associated ges tational hypertension or preeclampsia. Maternal and neonatal outcomes were good, and the authors review chelation therapy with penicillamine and zinc sulfate in pregnancy. he American


Obstentrics_Williams

Obstentrics_Williams. College of Gastroenterology states that few data guide which of the various chelating agents is best (Tran, 2016). These include penicillamine, zinc, and trientine, and any theoretical risks are outweighed by the risks of discontinuing therapy. he latter include not only hepatic decompensation, but also injury to the placenta and fetal liver. Accordingly, the American College continue their chelation therapy, although a dose reduction of 25 to 50 percent should be considered to promote wound heal ing in the event of a surgical delivery. As a reminder, copper ions regulate the activity of proteins essential to wound repair.


Obstentrics_Williams

Obstentrics_Williams. his condition is frequently comorbid with obesity and is the most common chronic liver disease in the United States (Diehl, 2017). Its most severe form-nonacoholic steatohepatitis (NASH)-is an increasingly recognized condition that may occasionally progress to hepatic cirrhosis. Nonalcoholic fatty liver disease (NAFLD) is a macrovesicular fatty liver condition that resembles alcohol-induced liver injury but is seen without this substance abuse. Obesity, type 2 diabetes, and hyperlipidemiasyndrome X-frequently coexist (Chap. 48 p. 938). The current hypothesis suggests that these conditions may interact with other unknown etiological agents to cause multiple insults or "hits" leading to hepatic injury. For example, half of persons with type 2 diabetes have NAFLD, and insulin resistance has been postulated to act as one possible "hit" (Buzzetti, 2016). Browning and associates (2004) used MR spectroscopy to determine the prevalence ofNAFLD in Dallas County and found that approximately a


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Obstentrics_Williams. been postulated to act as one possible "hit" (Buzzetti, 2016). Browning and associates (2004) used MR spectroscopy to determine the prevalence ofNAFLD in Dallas County and found that approximately a third of adults were afected. This varied by ethnicity, with 45 percent of Hispanics, 33 percent of whites, and 24 percent of blacks being afected. Most people-80 percent-found to have steatosis had normal liver enzymes. In a study of obese adolescents undergoing bariatric surgery, more than a third had fatty liver without hepatitis, whereas an additional 20 percent had borderline or definite NASH (Xanthakos, 2015).


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Obstentrics_Williams. Liver damage follows a progressive continuum from NAFLD to NASH and then to hepatic ibrosis that may progress to cirrhosis (Goh, 2016). Still, in most persons, the disease is usually asymptomatic, and it is a frequent explanation for elevated serum transaminase levels found in blood donors and during Hepatic, Biliary, and Pancreatic Disorders 1067 other routine screening. Indeed, NAFLD is the cause of ele vated asymptomatic transaminase levels in up to 90 percent of cases in which other liver disease is ultimately excluded. It also is the most common cause of abnormal liver tests among adults in this country. Currently, weight loss along with control of diabetes and dyslipidemia is the only recommended treatment.


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Obstentrics_Williams. Fatty liver iniltration is probably much more common than realized in obese and diabetic gravidas. During the past decade, we encountered an increasing number of pregnant women with these disorders. Once severe liver injury, that is, acute fatty liver of pregnancy, is excluded, gravidas with fatty liver iniltra tion have no greater rates of adverse outcomes relative to liver involvement compared with pregnant women of similar weight. That said, some emerging data indicate that this condition may portend adverse pregnancy outcomes. In 110 pregnancies with NAFLD from the Swedish Medical Birth and the National


Obstentrics_Williams

Obstentrics_Williams. That said, some emerging data indicate that this condition may portend adverse pregnancy outcomes. In 110 pregnancies with NAFLD from the Swedish Medical Birth and the National Patient Registries, risks of gestational diabetes, preeclampsia, pre teI'm birth, and low-birthweight newborns were two-to threefold greater than in unafected women (Hagstrom, 2016). Yarrington and associates (2016) reported a high rate of gestational diabetes among nonobese women without liver disease, alcohol use, or diabetes, and who had elevated alanine transaminase levels in the irst trimester. s the obesity endemic worsens, adverse efects of this liver disorder on pregnancy will be clarified.


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Obstentrics_Williams. Irreversible chronic liver injury with extensive fibrosis and regenerative nodules is the inal common pathway for several disorders. Laennec cirrhosis from chronic alcohol exposure is the most frequent cause in the general population. But in young women-including pregnant women-most cases are caused by postnecrotic cirrhosis from chronic hepatitis Brand C. Many cases of cryptogenic cirrhosis are now known to be caused by NAFLD (Goh, 2016). Clinical manifestations of cirrhosis include jaundice, edema, coagulopathy, metabolic abnormalities, and portal hypertension with gastroesophageal varices and with splenomegaly that may cause thrombocytopenia. The incidence of deep-vein thromboembolism is increased (S0gaard, 2009). The prognosis is poor, and 75 percent have progressive disease that leads to death in 1 to 5 years. Women with symptomatic cirrhosis frequently are infertile.


Obstentrics_Williams

Obstentrics_Williams. Women with symptomatic cirrhosis frequently are infertile. hose who become pregnant generally have poor outcomes. Common complications include transient hepatic failure, variceal hemorrhage, preterm delivery, fetal growth restriction, and maternal death (Tan, 2008). Outcomes are generally worse if esophageal varices coexist. Another potentially fatal complication of cirrhosis arises from associated splenic artery aneurysms. Up to 20 percent of ruptures occur during pregnancy, and 70 percent of these rupture in the third trimester (Palatnik, 2017; Tan, 2008). In a review of 32 gravidas with aneurysm rupture, the mean aneurysm diameter was 2.25 cm, and in half of cases, the diameter was <2 cm (Ha, 2009). The 22-percent maternal mortality rate was likely related to the emergent presentation of these events. Parrish and colleagues (2015) described embolization of a 13 X 9 mm aneurysm in the third trimester leading to a splenic abscess and sepsis 3 weeks later.


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Obstentrics_Williams. In pregnant women, approximately half of cases of esophageal varices originate from cirrhosis or extrahepatic portal vein obstruction, which leads to portal system hypertension. Some cases of extrahepatic hypertension develop following portal vein thrombosis associated with one of the thrombophilia syndromes (Chap. 52, p. 1005). Others follow thrombosis from umbilical vein catheterization when the woman was a neonate, especially if she was born preterm.


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Obstentrics_Williams. With either intrahepatic or extrahepatic resistance to low, portal vein pressure rises from its normal range of 5 to 10 mm Hg, and values may exceed 30 mm Hg. Collateral circulation develops that carries portal blood to the systemic circulation. Blood drains into the gastric, intercostal, and other veins to the esophageal system, where varices develop. Bleeding is usually from varices near the gastroesophageal junction, and hemorrhage can be torrential. Bleeding during pregnancy from varices occurs in a third to half of afected women and is the major cause of maternal mortality within thisrgroup (Tan, 2008).


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Obstentrics_Williams. Maternal prognosis with esophageal varices largely depends on whether these rupture. Mortality rates are higher if varices are associated with cirrhosis compared with rates for varices without cirrhosis-18 versus 2 percent, respectively. Perinatal mortality rates are high in women with varices and are worse if cirrhosis caused the varices. Increased rates of neonatal demise, preterm birth, low birthweight, preeclampsia, and postpartum hemorrhage have been reported (Puljic, 2016). Treatment is the same as for nonpregnant patients. Preventatively, all patients with cirrhosis, including pregnant women, should undergo endoscopic screening for identification of variceal dilatation (Bacon, 2015). Beta-blocking drugs such as propranolol are given to reduce portal pressure and hence the bleeding risk (Bissonnette, 2015; Tran, 2016).


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Obstentrics_Williams. For acute bleeding and for prophylaxis, endoscopic band ligation is preferred to sclerotherapy as it avoids any potential risks of injecting sclerotherapeutic chemicals (Bissonnette, 2015; Tan, 2008). Acute medical management for bleeding varices veriied endoscopically includes the intravenous (IV) vasoconstrictors octreotide or somatostatin along with endoscopic banding. Vasopressin is less often used (Bacon, 2015). Baloon tamponade using a triple-lumen tube placed into the esophagus and stomach to compress bleeding varices can be lifesaving if endoscopy is not available. An interventional radiology procedure-tranjugular intrahepatic portosystemic stent shunting (TIPSS)-can also control bleeding from gastric varices that is unresponsive to other measures (Bissonnette, 2015; Tan, 2008). This procedure can be done electively in patients with prior variceal hemorrhage.


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Obstentrics_Williams. This drug is the most common cause of acute liver failure in the United States (Lee, 2013). Acetaminophen is often used during pregnancy, and overdose-either accidentally or by attempted suicide-may lead to hepatocellular necrosis and acute liver failure (Bunchorntavakul, 2013). Massive necrosis causes a cytokine storm and multiorgan dysfunction. Early symptoms of overdose are nausea, vomiting, diaphoresis, malaise, and pallor. With an acute overdose, after a latent period of 24 to 48 hours, liver failure ensues and usually begins to resolve in 5 days. In a prospective Danish study, only 35 percent of patients who were treated for fulminant hepatic failure spontaneously recovered before being listed for liver transplantation (Schmidt, 2007).


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Obstentrics_Williams. The antidote is N-aceycysteine, which must be given promptly. he drug is thought to increase glutathione levels, which aid metabolism of the toxic metabolite, N-acetyl-pbenzoquinoneimine. he need for treatment is based on projections of possible plasma hepatotoxic levels as a function of the time from acute ingestion. For this, many poison control centers use the nomogram established by Rumack and Matthew (1975). A plasma level is measured 4 hours after ingestion, and if the level is > 150 1g/mL, treatment is given (Smilkstein, 1988). If plasma determinations are not available, empirical treatment is given if the ingested amount exceeded 7.5 g. An oral loading dose of 140 mg/kg of N-acetylcysteine is followed by 17 maintenance doses of 70 mg/kg every 4 hours for 72 hours of total treatment time. Both the oral and an equally eicacious IV dosing regimen have been reviewed by Hodgman and Garrard (2012). he drug has been reported to reach therapeutic concentrations in the fetus (Wiest,


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Obstentrics_Williams. time. Both the oral and an equally eicacious IV dosing regimen have been reviewed by Hodgman and Garrard (2012). he drug has been reported to reach therapeutic concentrations in the fetus (Wiest, 2014).


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Obstentrics_Williams. After 14 weeks' gestation, the fetus has some cytochrome P450 activity necessary for metabolism of acetaminophen to the toxic metabolite. Riggs and colleagues (1989) reported follow-up data from the Rocky Mountain Poison and Drug Center in 60 women sufering overdose. he likelihood of maternal and fetal survival was better if the antidote was given soon after overdose. At least one 33-week fetus appears to have died as a direct result of hepatotoxicity 2 days after maternal ingestion. In another case, Crowell and associates (2008) reported a case of acetaminophen overdose at 32 weeks' gestation. The woman had taken 9.75 grams of acetaminophen approximately 1.5 hours prior to arrival. With treatment, the patient survived and went on to deliver a healthy term neonate.


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Obstentrics_Williams. This benign lesion of the liver is characterized in most cases by a well-delineated accumulation of normal but disordered hepatocytes that surround a central stellate scar. hese usually can be diferentiated from hepatic adenomas by magnetic resonance (vIR) or computed tomographic (CT) imaging. Except in the rare situation of unremitting pain, surgery is rarely indicated, and most women remain asymptomatic during pregnancy. In one review of 20 cases in Germany, no woman had related complications during pregnancy (Rifai, 2013). hree women showed 20-percent tumor growth; in 10 patients, the tumor decreased in size; and the remaining seven were unchanged across pregnancy. Ramirez-Fuentes and associates (2013) studied 44 lesions with MR imaging in 30 women. Of the lesions, 80 percent were unchanged in size, and most of the remainder decreased in size. They concluded that size changes were unrelated to pregnancy, combination oral contraceptive (COC) use, or menopause. Notably, this lesion


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Obstentrics_Williams. in size, and most of the remainder decreased in size. They concluded that size changes were unrelated to pregnancy, combination oral contraceptive (COC) use, or menopause. Notably, this lesion is not a contraindication to estrogen-containing contraceptives (Chap. 38, p. 692).


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Obstentrics_Williams. Hepatic, Biliary, and Pancreatic Disorders 1069 -This is an uncommon benign neoplasm but has a 5-percent risk of malignant transformation and a significant risk of rupture-associated hemorrhage, particularly in pregnancy. s just discussed, adenomas can usually be diferentiated from focal nodular hyperplasia by MR or CT imaging. Adenomas have a 9:1 predominance among women and are strongly linked with COC use. The rupture risk progresses with lesion size, and surgery is generally recommended for tumors measuring >5 cm (Agrawal, 2015). T ran and colleagues (2016) recommend sonographic surveillance of hepatic adenomas during pregnancy. In one review of 27 cases in pregnany, 23 became apparent in the third trimester .nd puerperium (Cobey, 2004). Bleeding complicated no tumors measuring <6.5 cm. However, 16 of27 women (60 percent) with an adenoma presented with tumor rupture that resulted in seven maternal deaths and six fetal deaths. Of note, 13 of 27 women presented within 2 months


Obstentrics_Williams

Obstentrics_Williams. cm. However, 16 of27 women (60 percent) with an adenoma presented with tumor rupture that resulted in seven maternal deaths and six fetal deaths. Of note, 13 of 27 women presented within 2 months postpartum, and in hal, hemorrhage heralded rupture. Wilson and coworkers (2011) described two cases of bleeding hepatic adenoma during pregnancy. One was managed by laparoscopic segmental resection, and another, which followed liver biopsy, required open surgery. The authors discourage biopsy during pregnancy for suspected hepatic adenomas, and emphasize the feasibility of resection for problematic lesions.


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Obstentrics_Williams. In 2013 in the United States, 5921 adult liver transplants were performed, and 34 percent of patients were women (Kim, 2015b). Currently, more than 65,000 recipients of liver transplant are living, and one literature review cited 450 pregnancies in 3026 women who had undergone transplantation (Deshpande, 2012). Although their live-birth rate of 80 percent and miscarriage rate compare favorably with those of the general population, risks of preeclampsia, cesarean delivery, and preterm birth are significantly elevated. A fourth of pregnancies were complicated by hypertension, approximately a third resulted in preterm birth, and in 10 percent, there was one or more rejection episodes (Table 55-4). Importantly, 4 percent of mothers had died within a year after delivery, but this rate is comparable to that in nonpregnant liver transplantation patients. Ghazali and associates (2016) analyzed the National Inpatient Sample database and found 2.r1 liver transplants per 100,000 deliveries.


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Obstentrics_Williams. to that in nonpregnant liver transplantation patients. Ghazali and associates (2016) analyzed the National Inpatient Sample database and found 2.r1 liver transplants per 100,000 deliveries. Pregnancies after liver transplant had signiicantly greater risks of maternal and fetal complications, including hypertensive disorders, gestational diabetes, and postpartum hemorrhage. Rates of preterm birth, fetal growth restriction, and congenital anomalies were also increased. Mattila and colleagues (2017) found that half of the women they cared for had maternal complications.


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Obstentrics_Williams. In the United States, 20 percent of women older than 40 years have gallstones. Most stones contain cholesterol, and its overse cretion into bile is thought to be a major factor in stone forma tion. The cumulative risk of all patients with silent gallstones to require surgery for symptoms or complications is 10 percent at 5 years, 15 percent at 1° years, and 18 percent at 15 years (Greenberger, 2015). For these reasons, prophylactic cholecys tectomy is not warranted for asymptomatic stones. For symp tomatic gallstone disease, nonsurgical approaches have been used and include oral bile acid therapy with ursodeoxycholic acid and extracorporeal shock wave lithotripsy. Experience with these during pregnancy is lacking.


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Obstentrics_Williams. Acute cholecystitis usually develops when the cystic duct is obstructed. Bacterial infection plays a role in 50 to 85 percent of cases. In more than half of patients with acute cholecystitis, a history of prior right upper quadrant pain from cholelithiasis is elicited. With acute disease, pain is accompanied by anorexia, nausea and vomiting, low-grade fever, and mild leukocytosis. As shown in Figure 55-3, sonography can help visualize stones, and both false-positive and false-negative rates range from 2 to 4 percent (Greenberger, 2015). In acute cases, medical therapy consists of IV luids, antimicrobials, analgesics, and in some instances, nasogastric suction, before surgical therapy. Laparoscopic cholecystectomy is the preferred treatment for most patients.


Obstentrics_Williams

Obstentrics_Williams. After the irst trimester, the gallbladder fasting volume and the residual volume after postprandial emptying are doubled. Incomplete emptying may result in retention of cholesterol crystals, a prerequisite for cholesterol gallstones. Maringhini and colleagues (1993) showed that the incidence of biliary sludge-which can be a forerunner to gallstones-and gallstones in pregnancy are 31 and 2 percent, respectively. Ko and colleagues (2014), however, cited a combined incidence of <5 percent. Others have identiied asymptomatic gallstones in FIGURE 55-3 This sonogram shows mUltiple hyperechoic gallstones filling an anechoic gallbladder. 2.5 to 10 percent of more than 1500 pregnant or postpartum women (Maringhini, 1993; Valdivieso, 1993).


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Obstentrics_Williams. 2.5 to 10 percent of more than 1500 pregnant or postpartum women (Maringhini, 1993; Valdivieso, 1993). Postpartum, sludge frequently regresses, and occasionally gallstones will resorb. Still, within a year ter delivery, hospitalization for gallbladder disease remains relatively common, particularly for women managed conservatively in pregnancy. Jorge and coworkers (2015) reported that half of 53 women with symptomatic gallstones in pregnancy underwent postpartum cholecystectomy. In 80 percent of these women, recurrent symptoms developed prior to surgery, requiring readmission in half.


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Obstentrics_Williams. Acute cholecystitis during pregnancy or the puerperium is common and usually associated with gallstones or biliary sludge. Symptomatic cholecystitis is initially managed in a manner similar to that for nonpregnant women. In the past, most favored medical therapy. However, the recurrence rate during the same pregnancy is high, and 25 to 50 percent of women ultimately required cholecystectomy for persistent symptoms. Moreover, if cholecystitis recurs later in gestation, preterm labor is more likely and cholecystectomy is technically more diicult.


Obstentrics_Williams

Obstentrics_Williams. For these reasons, operative and endoscopic interventions are increasingly favored over conservative measures. Othman and coworkers (2012) showed that women managed conservatively had more pain, more recurrent visits to the emergency department, more hospitalizations, and a higher rate of cesarean delivery. Dhupar and associates (2010) reported more complications with conservative management of gallbladder disease compared with laparoscopic cholecystectomy in pregnancy. hese included multiple admissions, prolonged total parenteral nutrition, and unplanned labor induction for worsening gallbladder symptoms. Cholecystectomy was performed safely in all trimesters. Only one of 19 patients who underwent laparoscopic cholecystectomy had a complication, which did not require further surgery. A metaanalysis found that cholecystectomy does not increase the risk of preterm labor or of maternal or fetal mortality (Athwal, 2016). Management at Parkland Hospital has evolved to a more aggressive


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Obstentrics_Williams. metaanalysis found that cholecystectomy does not increase the risk of preterm labor or of maternal or fetal mortality (Athwal, 2016). Management at Parkland Hospital has evolved to a more aggressive surgical approach, especially if there is concomitant biliary pancreatitis as subsequently discussed. During the past two decades, laparoscopic cholecystectomy has evolved as the favored surgical approach and is discussed in Chapter 46 (p. 901).


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Obstentrics_Williams. Relief from symptomatic biliary duct gallstones during pregnancy has been greatly aided by use of endoscopic retrograde cholangiopancreatography (ERCP) (Fogel, 2014; Menees, 2006). he procedure is performed if common duct obstruction is suspected or proven. Approximately 10 percent of patients with symptomatic stone disease have common duct stones (Stinton, 2012). ERCP can be modiied in many cases so that radiation exposure from luoroscopy is avoided (Sethi, 2015).


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Obstentrics_Williams. Tang and associates (2009) reported results from 68 ERCP procedures performed in 65 pregnant women at Parkland Hospital. ll but two women had gallstones, and sphincterotomy was performed in all but one woman. Common duct stones were identified in half of these 65 women, and in all but one, the stones were successfully removed. A biliary stent was placed in 22 percent of cases and removed after delivery. Complications were minimal, and post-ERCP pancreatitis developed in 16 percent. Pregnancy outcomes were not diferent than for the general obstetrical population. As a less invasive approach, 1R cholangiopancreatography (MRCP) has been reported to have utility in pregnancy in small, retrospective case series. Wu and colleagues (2014) caution against its use in pregnancy, particularly for seriously ill women. Also, MRCP is not readily available, and this may lead to delayed deinitive management.


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Obstentrics_Williams. Ascending cholangitis can complicate acute biliary obstruction. Nearly 70 percent of afected patients develop Charcot triad-jaundice, abdominal pain, and fever. The diagnosis is aided by sonography, and treatment is broad-spectrum antibiotics and biliary drainage by ERCP (Greenberger, 2015). Acute pancreatic inlammation is triggered by factors that cause activation of pancreatic trypsinogen followed by autodigestion. It is characterized by cell-membrane disruption and proteolysis, edema, hemorrhage, and necrosis (Conwell, 2015; Fogel, 2014). Up to 10 percent of women develop necrotizing pancreatitis, which carries a mortality risk of 15 percent. This rate rises if infection develops (Cain, 2015).


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Obstentrics_Williams. In nonpregnant patients, acute pancreatitis is almost equally associated with gallstones and alcohol abuse. During pregnancy, however, cholelithiasis is almost always the predisposing condition. Other causes are hyperlipidemias, usually hypertriglyceridemia; hyperparathyroidism; congenital ductal anomalies; ERCP; some drugs; and rarely autoimmune pancreatitis (Cain, 2015; Ducarme, 2014). N onbiliary pancreatitis occasionally develops postoperatively, or it is associated with trauma, drugs, or some viral infections. Certain metabolic conditions, including acute fatty liver of pregnancy and familial hypertriglyceridemia, also predispose to pancreatitis (Nelson, 2013). Cases of acute and chronic pancreatitis have been linked to numerous mutations of the cystic fibrosis transmembrane conductance regulator gene (Chang, 2015).


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Obstentrics_Williams. The incidence of pancreatitis varies with the population studied. At Parland Hospital, with a predominant Mexican American population, acute pancreatitis complicated approximately 1 in 3300 pregnancies (Ramin, 1995). At Brigham and Women's Hospital, with a more diversely ethnic population, Hernandez and colleagues (2007) reported an incidence of 1 in 4450. In a multiple-institution :Midwestern three-state review, the incidence of acute pancreatitis was 1 in 3450 (Eddy, 2008). In contrast, from California birth certificate data, the incidence approximated only 1 case in 6000 pregnancies (Hacker, 2015).


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Obstentrics_Williams. Acute pancreatitis is characterized by mild to incapacitating epigastric pain, nausea and vomiting, and abdominal distention. Patients are usually distressed and have low-grade fever, tachycardia, hypotension, and abdominal tenderness. As many as 10 percent have systemic inlammatory response syndrome (SIRS), which causes endothelial activation and can lead to acute respiratory distress syndrome (Chap. 47, p. 921).


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Obstentrics_Williams. Of laboratory tests, serum amylase levels usually measure three times values considered the upper limit of normal. In 173 pregnant women with pancreatitis, the mean amylase value approximated 2000 lUlL, and the mean lipase value approached 3000 lUlL (Table 55-5). Importanty, the degree of enzyme elevation and disease severiy do not reliaby correlate. Indeed, by 48 to 72 hours, amylase levels may return to normal despite other evidence for continuing pancreatitis. Serum lipase activity is also increased and usually remains elevated with continued inlammation. Leukocytosis is usually found, and 25 percent of patients have hypocalcemia. Elevated serum bilirubin and aspartate transaminase levels may signiY gallstone disease. Several prognostic scoring systems have been used to classiY pancreatitis severity, but not all of these are useful in pregnancy. For instance, two of the ive Ranson criteria determined TABLE 55-5. Laboratory Values in 173 Pregnant Women with Acute Pancreatitis


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Obstentrics_Williams. TABLE 55-5. Laboratory Values in 173 Pregnant Women with Acute Pancreatitis Hepatic, Biliary, and Pancreatic Disorders 1071 at admission include variables speciic to nonpregnant patients. Similarly, certain criteria for the Apache II scoring system do not account for the changes in pregnancy physiology. In contrast, the Atlanta Classiication incorporates the degree of organ failure as a measure of severity and may be more applicable in pregnancy (Banks, 2013; Cain, 2015).


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Obstentrics_Williams. Medical treatment mirrors that for nonpregnant patients. This includes analgesics, IV hydration, and measures to decrease pancreatic secretion by interdiction of oral intake. Other than supportive therapy, antibiotics when appropriate, and targeted surgical interventions in the case of gallstone pancreatitis, no particular treatment schemes have improved outcomes. In a series by Ramin and colleagues (1995), all 43 afected pregnant women responded to conservative treatment and were hospitalized for a mean of8.5 days. Nasogastric suction does not improve outcomes of mild to moderate disease, but enteral feeding may be helpul once pain improves and associated ileus resolves. For women with more severe pancreatitis and a prolonged disease course, total enteral nutrition using nasojejunl feeding is superior to total parenteral nutrition (Cain, 2015; Conwell, 2015). If there is bacterial superinfection of necrotizing pancreatitis, sepsis, or cholangitis, then broad-spectrum antimicrobials


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Obstentrics_Williams. is superior to total parenteral nutrition (Cain, 2015; Conwell, 2015). If there is bacterial superinfection of necrotizing pancreatitis, sepsis, or cholangitis, then broad-spectrum antimicrobials are administered. If common duct stones are found, then ERCP is indicated (Fogel, 20 14; Tang, 2010). Cholecystectomy is considered after inflammation subsides because women with galls tonic pancreatitis carry an increased risk of recurrent pancreatitis (Cain, 2015).


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Obstentrics_Williams. Pregnancy outcomes are afected by acute pancreatitis severity. Eddy and associates (2008) reported a 30-percent preterm delivery rate, and 11 percent were delivered before 35 weeks' gestation. There were two pancreatitis-related maternal deaths. Importantly, almost a third of 73 women had recurrent pancreatitis during pregnancy. Of the 342 pregnancies complicated by pancreatitis in the California study, preterm delivery and fetal mortality rates were increased (Hacker, 2015). Also, preeclampsia risk was increased fourfold.


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Obstentrics_Williams. Few reports describe pregnancy following pancreas transplantation. Of 44 pregnancies in 73 women following pancreaskidney transplantation, outcomes are encouraging, and vaginal delivery has been described CMastrobattista, 2008). Although the incidence of hypertension, preeclampsia, preterm delivery, and fetal-growth restriction are high, there was only one perinatal death. Four rejection episodes developed during pregnancy and were treated successfully. Pancreatic islet autotransplanta tion may be performed to prevent diabetes following pancre Serum lipase 3076 36-41,824 atectomy, and at least three successful pregnancies have been 1.7 0.1-8.71 0.2-1.3 reported (J ung, 2007). Leukocytes 10,700 1000-27,200 3900-10,700 Abu-Hayyeh S, Ovadia C, Lieu T, et al: Prognostic and mechanistic potenrial of progesterone sulfates in inrrahepatic cholestasis of pregnancy and pruritus gravidarum. Hepatology ,t2016 Agrawal S, Agarwal S, Arnason T, et al: Management of hepatocellular ade


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Obstentrics_Williams. Agrawal S, Agarwal S, Arnason T, et al: Management of hepatocellular ade From Ramin, 1995; Tang, 201n0; Turhan, 2010. noma: recent advances. Clin Gastroenrerol Hepatol 13: 1221, 2015 iroldi J, Berghella V: Hepatitis C and pregnancy. Obstet Gynecol Surv 61(10):666,s2006 American Academy of Pediatrics and the merican College of Obstetricians and Gynecologists: Guidelines for Perinatal Care, 8th ed. Elk Grove Village, AAP, 2017 American College of Obstetricians and Gynecologists: Upper gastrointestinal tract, biliary, and pancreatic disorders. Clinical Updates in Women's Health Care, Vol. l, No.s4, 2012, Reairmed 2015


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Obstentrics_Williams. American College of Obstetricians and Gynecologists: Upper gastrointestinal tract, biliary, and pancreatic disorders. Clinical Updates in Women's Health Care, Vol. l, No.s4, 2012, Reairmed 2015 American College of Obstetricians and Gynecologists: Viral hepatitis in pregnancy. Practice Bulletin No. 86, October 2007, Reairmed 2016 nastasio HB, Gruncy M, Birsner ML, et al: Gestational alloimmune liver disease. A devastating condition preventable with maternal intravenous immunoglobulin. Obstet GynecoIs128:1092, 2016 nzivino C, Odoardi MR, Meschiari E, et al: ABCB4 and ABCB 11 mutations in intrahepatic cholestasis of pregnancy in an Italian population. Dig Liver Dis 45(3):226, 2013 Arshad M, El-Kamary SS, Jhaveri R: Hepatitis C virus infection during pregnancy and the newborn period-are they opportunities for treatment? J Viral Hepat 18(4):229,2011


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Obstentrics_Williams. Mastrobattista JM, Gomez-Lobo V: Pregnancy after solid organ transplantation. Obstet Gynecol 112:919,s2008 Mattila, M, Kemppainen H, Isoniemi H, et al: Pregnancy outcomes after liver transplantation in Finland. Acta Obstet Gynecol Scand 96: 1106, Clin 28(4):499, 2012 Hoofnagle JH, Nelson E, Purcell RH: Hepatitis E. N Engl J Med 36 : 13, Matos A, Bernardes J, Ayres-de-Campos D, et al: Antepartum fetal cerebral hemorrhage not predicted by current surveillance methods in cholestasis of pregnancy. Obstet Gynecol 89:803, 199 McMenamin MB, Jackson AD, Lambert J, et al: Obstetric management of hepatitis C-positive mothers: analysis of vertical transmission in 559 mother-infant pairs. Am J Obstet Gynecol 199:315.e1, 2008 Menees S, Elta G: Endoscopic retrograde cholangiopancreatography during pregnancy. Gastrointest Endose Clin North Am 16:41,2006 Nagy S, Bush Me, Berkowitz R, et al: Pregnancy outcome in liver transplant recipients. Obstet Gynecol 102(1):121,2003


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Obstentrics_Williams. Nagy S, Bush Me, Berkowitz R, et al: Pregnancy outcome in liver transplant recipients. Obstet Gynecol 102(1):121,2003 Nelson DB, Yost NP, Cunningham FG: Acute fatry liver of pregnancy: clinical outcomes and expected durations of recovery. Am J Obstet Gynecol 209(5):456.el,s2013 Nelson DB, Yost NP, Cunningham FG: Hemostatic dysfunction with acute fa try liver of pregnancy. Obstet Gynecol 124:40, 2014 Othman MO, Stone E, Hashimi M, et al: Conservative management of cholelithiasis and its complications in pregnancy is associated with recurrent symptoms and more emergency department visits. Gastrointest Endosc 76(3): 564,s2012 Palatnik A, Rinella ME: Medical and obstetric complications among pregnant women with liver cirrhosis. Obstet Gynecol 129: 1118,s2017 Parrish J, Maxwell C, Beecroft JR: Splenic artery aneurysm in pregnancy. J Obstet Gynecol Can 37:816, 2015


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Obstentrics_Williams. Parrish J, Maxwell C, Beecroft JR: Splenic artery aneurysm in pregnancy. J Obstet Gynecol Can 37:816, 2015 Pereira SP, O'Donohue J, Wendon J, et al: Maternal and perinatal outcome in severe pregnancy-related liver disease. Hepatology 26: 1258, 1997 Pergam SA, Wang CC, Gardella C\I, et al: Pregnancy complications associated with hepatitis C: data from a 2003-2005 Washington state birth cohort. Am J Obstet Gynecol 199:38.el, 2008 Pietrangelo A: Iron and the liver. Liver Int 36: I 16, 2016 Poordad F, Lawitz E, Kowdley Y, et al: Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med 368(1):45, 2013 Puljic A, Salati J, Doss A, et al: Outcomes of pregnancies complicated by liver cirrhosis, portal hypertension, or esophageal varices. J Matern Fetal Med 29:506,s2016 Rac MW, Sheield JS: Prevention and management of viral hepatitis in pregnancy. Obstet Gynecol Clin North Am 41:5-3,s2014


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Obstentrics_Williams. Rac MW, Sheield JS: Prevention and management of viral hepatitis in pregnancy. Obstet Gynecol Clin North Am 41:5-3,s2014 Ramin KD, Ramin SM, Richey SD, et al: Acute pancreatitis in pregnancy. Am J Obstet Gynecol 173:187, 1995 Ramirez-Fuentes C, Marti-Bonmad L, Torregrosa A, et al: Variations in the size of focal nodular hyperplasia on magnetic resonance imaging. Radiologia 55(6):499,s2013 Reddick KLB, Jhaveri R, Gandhi M, et al: Pregnancy outcomes associated with viral hepatitis. J Viral Hepat 18(7):e394, 2011 Reyes H: What have we learned about intrahepatic cholestasis of pregnancy? Hepatology 63:4,s2016 Rifai K, Mix H, Krusche 5, et al: No evidence of substantial growth progression orcomplications oflarge focal nodular hyperplasia during pregnancy. Scand J GastroenteroIs48(1):88, 2013 Riggs BS, Bronstein AC, Kulig K, et al: Acute acetaminophen overdose during pregnancy. Obstet Gynecol 74:247, 1989


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Obstentrics_Williams. Riggs BS, Bronstein AC, Kulig K, et al: Acute acetaminophen overdose during pregnancy. Obstet Gynecol 74:247, 1989 Roberts 55, Miller RK, Jones JK, et al: The Ribavirin Pregnancy Registry: indings after 5 years of enrollinent, 2003-2009. Birth Defects Res A Clin Mol TeratoIs88(7):551,s2010 Rodriguez M, Moreno J, Marquez R, et al: Increased PR interval in fetuses of patients with intrahepatic cholestasis of pregnancy. Fetal Diagn Ther 40(4):298,s2016 Rook M, Vargas j, Caughey A, et al: Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort. PLoS One 7(3):e28343, 2012 Roumiantsev 5, Shah V, Westra SJ, et al: Case records of the Massachusetts general hospital. Case 20-2015. A newborn girl with hypotension coagulopathy, anemia, and hyperbilirubinemia. N Engl J Med 372:2542, 2015 Rumack BH, Matthew H: Acetaminophen poisoning and toxiciry. Pediatrics 55:871, 1975


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Obstentrics_Williams. Rumack BH, Matthew H: Acetaminophen poisoning and toxiciry. Pediatrics 55:871, 1975 Sadler LC, Lane M, North R: Severe fetal intracranial haemorrhage during treatment with cholestyramine for intrahepatic cholestasis of pregnancy. BJOG 102:169, 1995 Salgia RJ, Brown K: Diagnosis and management of hereditary hemochromatosis. C1in Liver Dis 19:187,2015 Satiago-Munoz P, Roberts 5, Sheield j, et al: Prevalence of hepatitis Bsand C in pregnant women who are infected with human immunodeiciency virus. Am J Obstet Gynecol 193:1270,2005 Santos L, Patterson A, Moreea SM, et al: Acute liver failure in pregnancy associated with maternal MCAD deiciency. J Inherit Metab Dis 30(1): 103,s2007 Schmidt LE, Larsen FS: MELD score as a predictor ofliver failure and death in patients with acetaminophen-induced liver injury. Hepatology 45(3):789, 2007


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Obstentrics_Williams. Schmidt LE, Larsen FS: MELD score as a predictor ofliver failure and death in patients with acetaminophen-induced liver injury. Hepatology 45(3):789, 2007 Sehgal R, Patra 5, David P, et al: Impaired monocyte-macrophage functions and defective Toll-like receptor signaling in hepatitis E virus-infected pregnant women with acute liver failure. Hepatology 62: 1683, 2015 Sethi 5, hosani N, Banerjee 5: Radiation-free ERCP in pregnancy: a "sound" approach to leaving no stone unturned. Dig Dis Sci 60:2604, 2015 Sheield JS, Hickman A, Tang J, et al: Eicacy of an accelerated hepatitis B vaccination program during pregnancy. Obstet Gynecol 117(5): 1130, 2011 Sheiner E, Ohel I,Levy A, et al: Pregnancy outcome in women with pruritus gravidarum. J Reprod Med 51 :394, 2006 Shi Z, Tang Y, Wang H, et al: Breastfeeding of newborns by mothers carrying hepatitis B virus: a meta-analysis and systematic review. Arch Pediatr Adolesc Med 165(9):837,s2011


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Obstentrics_Williams. Shi Z, Tang Y, Wang H, et al: Breastfeeding of newborns by mothers carrying hepatitis B virus: a meta-analysis and systematic review. Arch Pediatr Adolesc Med 165(9):837,s2011 Sibai BM: Imitators of severe preeclampsia. Obstet Gynecol 109:956,s2007 Sims HF, Brackett JC, Powell CK, et al: he molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deiciency associated with maternal acute fatty liver of pregnancy. Proc Nat! Acad Sci V 5 A 92:841, 1995 Smilkstein MJ, Knapp GL, Kulig W, et al: Eicacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 319:1557,s1988 Smith EA, Jacques-Carroll L, Walker TY, et al: he National Perinatal Hepatitis B Prevention Program, 1994-2008. Pediatrics 129(4):609,2012 Snidjewind IJ, Smit C, Schutten M, et al: Low mother-to-child-transmission rate of hepatitis C virus in cART treated HIV-1 infected mothers. J C1in ViroIs68:11,s2015


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Obstentrics_Williams. Snidjewind IJ, Smit C, Schutten M, et al: Low mother-to-child-transmission rate of hepatitis C virus in cART treated HIV-1 infected mothers. J C1in ViroIs68:11,s2015 Society for Maternal-Fetal Medicine (SMFM), Dionne-Odom J, Tita AT, et al: #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol 214:6, 2016 S0gaard KK, Horvath-Puh6 E, Gf0nback H, et al: Risk of venous thromboembolism in patients with liver disease: anationwide population-based casecontrol study. Am J Gastroeterol 104(1):96, 2009 Stewart RD, Sheield JS: Hepatitis B vaccination in pregnancy in the Vnited States. Vaccines 1:167,s2013 Stinton LM, Shafer A: Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver 6: 172, 2012 Stokkeland K, Ludvigsson JF, Hultcrantz R, et al: Increased risk of preterm birth in women with autoimmune hepatitis-a nationwide cohort study. Liver lnt 36:76, 2016


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Obstentrics_Williams. Strehlow SL, Pathak B, Goodwin TM, et al: The mechanical PR interval in fetuses of women with intrahepatic cholestasis of pregnancy. Am ] Obstet GynecoIs203:455.el,s2010 Tan], Surti B, Saab 5: Pregnancy and cirrhosis. Liver T ranspl 14(8): 1 081, 2008 Tang 5, Mayo M], Rodriguez-Frias E, et al: Safety and utility ofERCP during pregnancy. Gastrointest Endosc 69:453, 2009 Tang 5], Rodriguez-Frias E, Singh 5, et al: Acute pancreatitis during pregnancy. Clin Gastroenterol Hepatol 8(1):85, 2010 Tovo PA, Calitri C, Scolfaro C, et al: Vertically acquired hepatitis C virus infection: correlates of transmission and disease progression. World] Gastroenterol 22: 1382, 2016 Towers CV, Asrat T, Rumney P: he presence of hepatitis B surface antigen and deoxyribonucleic acid in amniotic fluid and cord blood. Am ] Obstet Gynecol 184: 1514, 2001 Tran TT, Ahn ], Reau NS: ACG clinical guideline: Liver disease and pregnancy. Am J Gastroenterol 111: 176, 2016


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Obstentrics_Williams. Tran TT, Ahn ], Reau NS: ACG clinical guideline: Liver disease and pregnancy. Am J Gastroenterol 111: 176, 2016 Trinks ], Maestri M, Oliveto F, et al: Human pegivirus molecular epidemiology in Argentina: potential contribution of Latin America migration to genotype 3 circulation. ] Med Virol 86:20 6, 2014 Turhan AN, Gonen: M, Kapan 5, et al: Acute biliary pancreatitis related with pregnancy: a 5-year single center experience. Vlus Travma Acil Cerrahi Derg 16(2):160,s2010 Vrganci N, Arapoglu M, Akyildiz B, et al: Neonatal cholestasis resulting from vertical transmission of hepatitis A infection. Pediatr Infect Dis] 22(4):381, 2003 Vsta 1M, Barton ]R, Amon EA, et al: Acute fatty liver of pregnancy: an experience in the diagnosis and management of fourteen cases. Am ] Obstet GynecoIs171:1342,s1994 Valdivieso V, Covarrubias C, Siegel F, et al: Pregnancy and cholelithiasis: pathogenesis and natural course of gallstones diagnosed in early puerperium. Hepatology 17:1,s1993


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Obstentrics_Williams. Victor ]C, Monto AS, Surdina Y, et al: Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl ] Med 357: 1685, 2007 Vierling ]M: Autoimmune hepatitis and overlap syndromes: diagnosis and management. C1in Gastroenterol HepatoIs13:2088, 2015 Vigil-de Gracia P, Montufar-Rueda C: Acute fatty liver of pregnancy: diagnosis, treatment, and outcome based on 35 consecutive cases. ] Matern Fetal Neonatal Med 24(9):1143, 2011 Wang PH, Yang MJ, Lee L, et al: Acetaminophen poisoning in late pregnancy. A case report.] Reprod Med 42:367, 1997 Webb GJ, Elsharkawy AM, Hirschield G: Editorial: the etiology of intrahepatic cholestasis of pregnancy: towards solving a monkey puzzle. Am J Gastroenterol 109:85,2014 Westbrook RH, Yeoman AD, Kriese 5, et al: Outcomes of pregnancy in women with autoimmune hepatitis. J Autoimmun 38(2-3):J239, 2012


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Obstentrics_Williams. Westbrook RH, Yeoman AD, Kriese 5, et al: Outcomes of pregnancy in women with autoimmune hepatitis. J Autoimmun 38(2-3):J239, 2012 Wiest DB, Chang E, Fanning 0, et al: Antenatal pharmacokinetics and placental transfer of N-acetylcysteine in chorioamnionitis for fetal neuroprotection. J Pediatr 165:672,2014 Wikstrom Shemer E, Marschall HV, Ludvigsson JF, et al: Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study. BJOG 120(6):717,s2013 Wilson CH, Manas OM, French JJ: Laparoscopic liver resection for hepatic adenoma in pregnancy.] Clin Gastroenterol 45:828, 2011 World Health Organization: Hepatitis B vaccines. Weekly Epidemiological Record 84(40):405, 2009 Wu T, Zhu FC, Huang SJ, et al: Safety of the hepatitis E vaccine for pregnant women: a preliminaty analysis. Hepatology 55(6):2038, 2012


Obstentrics_Williams

Obstentrics_Williams. Wu T, Zhu FC, Huang SJ, et al: Safety of the hepatitis E vaccine for pregnant women: a preliminaty analysis. Hepatology 55(6):2038, 2012 Wu W, Faigel DO, Sun G, et al: Non-radiation endoscopic retrograde cholangiopancreatography in the management of choledocholithiasis during pregnancy. Dis Endosc 26:691, 2014 Xanthakos SA, Jenkins TM, Kleiner DE, et al: Teen-LABS consortium. High prevalence of nonalcoholic fatty liver disease in adolescents undergoing bariatric surgety. Gastroenterology 149:623, 2015


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Obstentrics_Williams. Xiong HF, Liu ]Y, Guo LM, et al: Acute fatty liver of pregnancy: over six months follow-up study of twenty-ive patients. World J Gastroenterol 21(6):1927,s2015 Yarrington CD, Cantonwine DE, Seely EW, et al: The associarion of alanine aminotransferase in early pregnancy with gestational diabetes. Metab Syndr Relat Disord 14(5):254,2016 Yi P, Chen R, Huang Y, et al: Management of mother-to-child transmission of hepatitis B virus: propositions and challenges. J Clin Virol 77:32,s2016 Ylitalo K, Vanttinen T, Halmesmaki E, et al: Serious pregnancy complications in a patient with previously undiagnosed carnitine palmitoyltransferase 1 deiciency. Am] Obstet Gynecol 192:2060,2005 Zhang J, Zhang F, Huang 5], et al: Long-term eicacy of a hepatitis E vaccine. N Engl] Med 372:914,s2015 ZhangP, Kong WQ, Zhou SP, et al: Acute fatty liver of pregnancy: a retrospective analysis of 56 cases. Chin Med J (Eng!) 129(10): 1208,2016 IRON-DEFICIENCY ANEMIA.. . . . . . . . . . . . . . . . . . . . .. 1076


Obstentrics_Williams

Obstentrics_Williams. IRON-DEFICIENCY ANEMIA.. . . . . . . . . . . . . . . . . . . . .. 1076 MEGALOBLASTIC ANEMIA . . . . . . . . . . . . . . . . . . . . .. 1077 HEMOLYTIC ANEMIA ......i..........i...i.......i.....i. 1078 .APLASTIC AND HYPOPLASTIC ANEMIA.. . . . . . . . . . .. 1080 POL YCYTHEMIAS ..i......i...........i...i......i...... 1081 HEMOGLOBINOPATHIES ..i....i...i......i...i.....i..... 1081 THALASSEMIA SYNDROMES.. . . . . . . . . . . . . . . . . . . .. 1084 PLATELET DISORDERS.. . . . . . . . . . . . . . . . . . . . . . . . .. 1086 INHERITED COAGULATION DEFECTS ....i......i..... 1089 VON WILLEBRAND DISEASE.. . . . . . . . . . . . . . . . . . . .. 1090 In the later months of pregnancy there is a slight increase in the amount of hemoglobin and red corpuscles and a slight increase in the number of white corpuscles, which become markedy accentuated during the first ew days of the puerperium. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) There is virtually nothing from the irst edition of Williams' 1903 textbook that addresses the common anemias of pregnancy. Only pernicious anemia is devoted two paragraphs to say it occasionally appeared in pregnancy. Today, it is well known that pregnant women are susceptible to hematological abnormalities that may afect any woman of childbearing age. hese include chronic disorders such as hereditary anemias, immunological thrombocytopenia, and malignancies such as leukemias and lymphomas. Other disorders arise during pregnancy because of pregnancy-induced demands. Two examples are iron deiciency and megaloblastic anemias. Pregnancy may also unmask underlying hematological disorders. Finally, any hematological disease may irst arise during pregnancy. Importantly, pregnancy induces physiological changes that often confuse the diagnosis of these hematological disorders and assessment of their treatment (Chap. 4, p. 57).


Obstentrics_Williams

Obstentrics_Williams. Normal values for concentrations of many cellular elements during pregnancy are listed in the Appendix (p. 1255). The Centers for Disease Control and Prevention (1998) deined anemia in iron-supplemented pregnant women using a cutof of the 5th percentile-lrl g/dL in the irst and third trimesters, and 10.5 g/dL in the second trimester (Fig. he modest fall in hemoglobin levels and hematocrit values during pregnancy is caused by a relatively greater expansion of plasma volume compared with the increase in red cell volume. he disproportion between the rates at which plasma and erythrocytes are added to the maternal circulation is greatest during the second trimester. Late in pregnancy, plasma expansion essentially ceases, while hemoglobin mass continues to accrue.


Obstentrics_Williams

Obstentrics_Williams. he causes of more common anemias encountered in pregnancy are listed in Table 56-1r. Their frequency is dependent on multiple factors such as geography, ethniciry, socioeconomic level, nutrition, preexisting iron status, and prenatal iron supplementation (American College of Obstetricians and Gynecologists, 2017 a). In the United States, the prevalence of anemia in pregnancy is 3 to 38 percent (Centers for Disease Control and Prevention, 1989). In Latin America and the Caribbean, anemia prevalence ranges from 5 to 45 percent among women of :J taking iron supplements. (Data from the Centers for Disease Control and Prevention, 1989.) childbearing age (1ujica-Coopman, 2015). Rates are also high in Israel, China, India, South Asia, and Africa (Azulay, 2015; Kumar, 2013, Stevens, 2013). Figure 56-2 highlights the global trends in hemoglobin concentrations and anemia thresholds in pregnant and nonpregnant women.


Obstentrics_Williams

Obstentrics_Williams. Most studies of anemia during pregnancy describe large populations and deal with nutritional anemias. Anemia is associated with several adverse pregnancy outcomes including preterm birth (Kidanto, 2009; Kumar, 2013; Rukuni, 2016). Children born to iron-deicient women and without iron supplementation are reported to have lower mental development scores (Drassinower, 2016; Tran, 2014). A seemingly paradoxical inding is that healthy pregnant women with a higher hemoglobin concentration are also at greater risk for adverse perinatal outcomes (Murphy, 1986; von Tempelhof, 2008). This may result from lower than average plasma volume expansion of pregnancy concurrent with normal red cell mass accrual. Scanlon and associates (2000) studied the relationship between maternal hemoglobin levels and rates of preterm or growth-restricted newborns in 173,031 pregnancies. TABLE 56-1. Causes of Anemia During Pregnancy


Obstentrics_Williams

Obstentrics_Williams. TABLE 56-1. Causes of Anemia During Pregnancy Anemia caused by acute blood loss Anemia of inflammation or malignancy Megaloblastic anemia 0.030 ..••. Anemia cutoff for c 0.025 0 (12.0 g/dL) : ..... Anemia cutoff for 0 0.020 . (1 1.0 g/dL) 0.015 : 0.010 0.005 04.06.0 8.010.0 18.0 FIGURE 56-2 Global trends in hemoglobin concentrations in pregnant and nonpregnant women. (Reproduced with permission from Stevens GA, Finucane MM, De-Regil LM, et al: Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and nonpregnant women for 1995-201o1: a systematic analysis of populationrepresentative data, Lancet Glob Health. 2013 Jul;1(l):e16-25.)


Obstentrics_Williams

Obstentrics_Williams. Women whose hemoglobin concentration was three standard deviations above the mean at 12 or 18 weeks' gestation had a 1.3-to 1.8-fold greater incidence of fetal-growth restriction. Placental weight correlates negatively with maternal hemoglobin concentration (Larsen, 2016). hese indings have led some to the illogical conclusion that withholding iron supplementation to cause iron-deiciency anemia will improve pregnancy outcomes (Ziaei, 2007). The two most common causes of anemia during pregnancy and the puerperium are iron deiciency and acute blood loss. In a study of more than 1300 women, 21 percent had thirdtrimester anemia, and 16 percent had iron-deiciency anemia (Vandevijvere, 2013). In a typical singleton gestation, the maternal need for iron averages nearly 1000 mg. Multifetal gestational requirements are considerably higher (Ru, 2016). hese amounts exceed the iron stores of most women and result in iron-deiciency anemia unless supplementation is given.


Obstentrics_Williams

Obstentrics_Williams. Iron deficiency is often manifested by an appreciable drop in hemoglobin concentration. In the third trimester, additional iron is needed to augment maternal hemoglobin and for transport to the fetus. Because the amount of iron diverted to the fetus is similar in a normal and in an iron-deicient mother, the newborn of a severely anemic mother does not sufer from irondeiciency anemia. Neonatal iron stores are related to maternal iron status and to timing of cord clamping. Classic morphological evidence of iron-deiciency anemia is erythrocyte hypochromia and microcytosis (Fig. 56-3). This may be less prominent in the pregnant woman. Serum ferritin levels are lower. And, levels of hepcidin-the master regulator of iron availability-are decreased normally in pregnancy. With iron deiciency, hepcidin levels follow those of serum ferritin (Camaschella, 2015; Koenig, 2014).


Obstentrics_Williams

Obstentrics_Williams. FIGURE 56-3 This peripheral blood smear from a women with iron-deficiency anemia contains many scattered microcytic and hypochromic red cells with characteristic central pallor. These exhibit moderate anisopoikilocytosis, namely, varying sizes and shapes including occasional elliptocytes, which can be oval or pencil-shaped. (Reproduced with permission from Werner Cl, Richardson Dl, Chang SY, et al (eds): Perioperative Considerations. In Williams Gynecology Study Guide, 3rd ed. New York, McGrawHill Education, 201o6: Photo contributor: Dr. Weina Chen.) he initial evaluation of a pregnant woman with moderate anemia includes measurements of hemoglobin, hematocrit, and red cell indices; careful examination of a peripheral blood smear; a sickle-cell preparation if the woman has African origin; and evaluation of serum iron or ferritin levels, or both (Appendix p. 1255). Serum ferritin levels normally decline during pregnancy, and levels < 10 to 15 mg/L confirm iron-deficiency anemia.


Obstentrics_Williams

Obstentrics_Williams. When pregnant women with moderate iron-deficiency anemia are given adequate iron therapy, a hematological response is detected by an elevated reticulocyte count. The rate of rise of hemoglobin concentration or hematocrit is typically slower than in nonpregnant women due to the increasing and larger blood volumes during pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Routinely in pregnancy, daily oral supplementation with 30 to 60 of iron and 400 �g of folic acid is recommended (World Health Organization, 2012). A Cochrane review found that intermittent oral iron supplementation may also be appropriate (Pena-Rosas, 2015). For iron-deficiency anemia, resolution and restitution of iron stores can be accomplished with simple iron salts that provide approximately 200 mg daily of elemental iron. hese include ferrous sulfate, fumarate, or gluconate. If a woman cannot or will not take oral iron preparations, then parenteral therapy is given. Although both are administered intravenously, ferrous sucrose is safer than iron-dextran (American College of Obstetricians and Gynecologists, 2017a; Camaschella, 2015; Shi, 2015). Hemoglobin and ferritin levels show equivalent rises in women treated with either oral or parenteral iron therapy (Breymann, 2017; Daru, 20r16).


Obstentrics_Williams

Obstentrics_Williams. In early pregnancy, anemia caused by acute blood loss is common with abortion, ectopic pregnancy, and hydatidiform mole. Postpartum, anemia commonly stems from obstetrical hemorrhage. Massive hemorrhage demands immediate treatment as described in Chapter 41 (p. 788). If a moderately anemic woman-defined by a hemoglobin value of approximately 7 g/dL-is hemodynamically stable, is able to ambulate without adverse symptoms, and is not septic, then blood transfusions are not indicated. Instead, oral iron therapy is given for at least 3 months (Kraft, 2005) . • Anemia Associated with Chronic Disease Various disorders, such as chronic renal insuiciency, cancer and chemotherapy, human immunodeficiency virus (HIV) infection, and chronic inflammation result in moderate and sometimes severe anemia, usually with slightly hypochromic and microcytic erythrocytes. It is the second most common form of anemia worldwide (Weiss, 2005).


Obstentrics_Williams

Obstentrics_Williams. During pregnancy, women with chronic disorders may develop anemia for the first time. In those with preexisting anemia, it may be intensified as plasma volume expands. Causes include chronic renal insuiciency, inlammatory bowel disease, and connective-tissue disorders. Others are granulomatous infections, malignant neoplasms, rheumatoid arthritis, and chronic suppurative conditions. Chronic renal insuiciency is the most common disorder that we have encountered as a cause of this type of anemia during pregnancy. Some cases are accompanied by erythropoietin deficiency. As discussed in Chapter 53 (p. 1034), during pregnancy in women with mild chronic renal insuiciency, the degree of red cell mass expansion is inversely related to renal impairment. At the same time, plasma volume expansion usually is normal, and thus anemia is intensified (Cunningham, 1990).


Obstentrics_Williams

Obstentrics_Williams. For treatment, adequate iron stores must be ensured. Recombinant eythropoietin has been used successfully to treat anemia stemming from chronic disease (Weiss, 2005). In pregnancies complicated by chronic renal insuiciency, recombinant erythropoietin is usually considered when the hematocrit approximates 20 percent (Cyganek, 2011; Ramin, 2006). One worrisome side efect of this agent is hypertension, which is already prevalent in women with renal disease. Red cell aplasia and antierythropoietin antibodies have also reported (Casadevall, 2002; McCoy, 2008). These anemias are characterized by blood and bone-marrow abnormalities from impaired DNA synthesis. This leads to large cells with arrested nuclear maturation, whereas the cytoplasm matures more normally. Worldwide, the prevalence of megaloblastic anemia during pregnancy varies considerably. It is rare in the United States.


Obstentrics_Williams

Obstentrics_Williams. Megaloblastic anemia developing during pregnancy almost always results from folic acid deficiency. In the past, this condition was referred to as pernicious anemia of pregnancy. It usually is found in women who do not consume fresh green leay vegetables, legumes, or animal protein. As folate deficiency and anemia worsen, anorexia often becomes intense and further aggravates the dietary deiciency. Drugs and excessive ethanol ingestion either cause or contribute (Hesdorfer, 2015).


Obstentrics_Williams

Obstentrics_Williams. In nonpregnant women, the folic acid requirement is 50 to 1 00 �g/ d. During pregnancy, requirements are increased, and 400 �g/ d is recommended. he earliest biochemical evidence is low plasma folic acid concentrations (Appendix, p. 1255). Early morphological changes usually include neutrophils that are hypersegmented and newly formed erythrocytes that are macrocytic. With preexisting iron deiciency, macrocytic erythrocytes cannot be detected by measurement of the mean corpuscular volume. Careful examination of a peripheral blood smear, however, usually demonstrates some macrocytes. As the anemia becomes more intense, peripheral nucleated erythrocytes appear, and bone marrow examination discloses megaloblastic erythropoiesis. Anemia may then become severe, and thrombocytopenia, leukopenia, or both may develop. he fetus and placenta extract folate from maternal circulation so efectively that the fetus is not anemic despite severe maternal anemia.


Obstentrics_Williams

Obstentrics_Williams. For treatment, folic acid is given along with iron, and a nutritious diet is encouraged. By 4 to 7 days after beginning folic acid treatment, the reticulocyte count is increased, and leukopenia and thrombocytopenia are corrected.


Obstentrics_Williams

Obstentrics_Williams. For prevention of megaloblastic anemia, a diet should contain suicient folic acid. The role of folate deiciency in the genesis of neural-tube defects has been well studied (Chap. 13, p. 270). Since the early 1990s, nutritional experts and the American College of Obstetricians and Gynecologists (2016a) have recommended that all women of childbearing age consume at least 400 �g of folic acid daily. More folic acid is given with multifetal pregnancy, hemolytic anemia, Crohn disease, alcoholism, and inflammatory skin disorders. Women with a family history of congenital heart disease may also benefit from higher doses (Huhta, 2015). Women who previously have had infants with neural-tube defects have a lower recurrence rate if a daily 4-mg folic acid supplement is given.


Obstentrics_Williams

Obstentrics_Williams. During pregnancy, vitamin B12 levels are lower than nonpregnant values because of decreased levels of binding proteins, namely, the transcobalamins. During pregnancy, megaloblastic anemia is rare from deficiency of vitamin B12, that is, cyanocobalamin. Instead, a typical example is Addisonian pernicious anemia, which results from absent intrinsic factor that is requisite for dietary vitamin B12 absorption. his autoimmune disorder usually has its onset after age 40 years (Stabler, 2013).


Obstentrics_Williams

Obstentrics_Williams. In our limited experience, vitamin Bl2 deiciency in pregnancy is more likely encountered following gastric resection. hose who have undergone total gastrectomy require 1 000 �g of vitamin B12 given intramuscularly each month. Those with a partial gastrectomy usually do not need supplementation, but adequate serum vitamin B12 levels should be ensured (Appendix, p. 1258). Other causes of megaloblastic anemia from vitamin B12 deiciency include Crohn disease, ileal resection, some drugs, and bacterial overgrowth in the small bowel (Hesdorfer, 2015; Stabler, 2013).


Obstentrics_Williams

Obstentrics_Williams. Several conditions feature accelerated erythrocyte destruction. Damage may be stimulated by a congenital red-cell abnormality or in other cases by antibodies directed against red-cell membrane proteins. Hemolysis may be the primary disorder, and sickle-cell disease and hereditary spherocytosis are examples. In other cases, hemolysis develops secondary to an underlying condition such as systemic lupus erythematosus or preeclampsia. Microangiopathic hemolytic anemia due to malignancy has been reported in pregnancy (Happe, 2016).


Obstentrics_Williams

Obstentrics_Williams. he cause of aberrant antibody production is unknown. Typically, both the direct and indirect antiglobulin (Coombs) tests are positive. Anemias caused by these factors may be due to warm-active autoantibodies (80 to 90 percent), cold-active antibodies, or a combination. hese syndromes also may be classiied as primary (idiopathic) or secondary due to underlying diseases or other factors. Examples of the latter include lymphomas and leukemias, connective-tissue diseases, infections, chronic inlammatory diseases, and drug-induced antibodies (Provan, 2000). Cold-aglutinin disease may be induced by infectious etiologies such as Mycoplasma pneumoniae or Epstein-Barr viral mononucleosis (Dhingra, 2007). Hemolysis and positive antiglobulin test results may be the consequence of either immunoglobulin M (IgM) or immunoglobulin G (IgG) antierythrocyte antibodies. When thrombocytopenia is comorbid, it is termed Evans syndrome (Wright, 2013).


Obstentrics_Williams

Obstentrics_Williams. In pregnancy, hemolysis can be markedly accelerated. Rituximab, along with prednisone, is first-line treatment (Luzzatto, 2015). Coincidental thrombocytopenia usually corrects with therapy. Transfusion of red cells is complicated by antierythrocyte antibodies, but warming the donor cells to body temperature may decrease their destruction by cold agglutinins.


Obstentrics_Williams

Obstentrics_Williams. These hemolytic anemias must be diferentiated from other causes of autoimmune hemolysis. In most cases, hemolysis is mild, it resolves with drug withdrawal, and recurrence is prevented by avoidance of the drug. One mechanism is hemolysis induced through drug-mediated immunological injury to red cells. he drug may act as a high-ainity hapten when bound to a red-cell protein to which antidrug antibodies attach-for example, IgM anti penicillin or anticephalosporin antibodies. Some other drugs act as low-ainity hap tens and adhere to cell membrane proteins. Examples include probenecid, quinidine, rifampin, and thiopental. A more common mechanism for drug-induced hemolysis is related to a congenital erythrocyte enzymatic defect. An example is glucose-6-phosphate dehydrogenase deiciency, which is common in African-American women and discussed later (p. 1080).


Obstentrics_Williams

Obstentrics_Williams. Drug-induced hemolysis is usually chronic and mild to moderate, but occasionally acute hemolysis is severe. Garratty and coworkers (1999) described seven women with severe Coombs-positive hemolysis stimulated by cefotetan given as prophylaxis for obstetrical procedures. Alpha-methyldopa can cause similar hemolysis (Grigoriadis, 2013). Moreover, maternal hemolysis has been reported after intravenous immune globulin therapy (Rink, 2013). Withdrawal of the ofending drug frequently halts the hemolysis.


Obstentrics_Williams

Obstentrics_Williams. Unexplained severe hemolytic anemia can develop during early pregnancy, and it resolves within months postpartum. A clear immune mechanism or red cell defects are not contributory (Starksen, 1983). Because the fetus-neonate also may demonstrate transient hemolysis, an immunological cause is suspected. Maternal corticosteroid treatment is often-bur not alwaysefective (Kumar, 2001). We have cared for a woman who during each pregnancy developed intense severe hemolysis with anemia that was controlled by prednisone. Her fetuses were not afected, and in all instances, hemolysis abated spontaneously after delivery.


Obstentrics_Williams

Obstentrics_Williams. In some cases, hemolysis is induced by conditions unique to pregnancy. Mild microangiopathic hemolysis with thrombocytopenia is relatively common with severe preeclampsia and eclampsia (Cunningham, 2015; Kenny, 2015). This HELLP (hemoysis) devated fiver enzyme levels) Low .latelet count} syndrome is discussed in Chapter 40 (p. 719). Another is acure fatty liver of pregnancy, which is associated with moderate to severe hemolytic anemia (Nelson, 2013). It is discussed in Chapter 55 (p. 1060).