Obstentrics_Williams

Obstentrics_Williams. INR 2.0-3.0 x Two or more prior VTEs with or without thrombophilia 6 weeks INR 2.0-3.0 x 6 weeks Receiving long-term Therapeutic-dose Adjusted-dose Resumption of long-Resumption of anticoagulation LMWH or UFH LMWH or 75% of term anticoagulation long-term a therapeutic dose anticoagulation No prior.VTE prophylactic or intermed iate-dose a nticoag u lation. dose LMWH or intermediate-dose LMWH warfarin target LMWH or UFH INR 2.0-3.0 x mutation INR 2.0-3.0 x TABLE 52-6. Continued mutation INR 2.0-3.0 x or S deficient, INR 2.0-3.0 History of fE Prophylactic NSS Prophylactic NSS anticoagulation with a nticoag u lationC; UFH or LMWH (?plus referral to specialist9 LMWH or UFH plus low-LMWH, both given pregnancy loss r dose aspirin if prior with 75-100 mg/ stillbirth9 aAmerican College of Obstetricians and Gynecologists, 2017a, c. bAmerican College of Chest PhYSicians (Bates, 201n2). (Postpartum treatment levels should be � antepartum treatment.


Obstentrics_Williams

Obstentrics_Williams. bAmerican College of Chest PhYSicians (Bates, 201n2). (Postpartum treatment levels should be � antepartum treatment. dAntithrombin deficiency; doubly heterozygous or homozygous for prothrombin 2021 OA and factor V Leiden. eHeterozygous factor V Leiden or prothrombin 2021 OA; protein S or C deficiency. fFirst-degree relative with fE at <50 years; other major thrombotic risk factors, e.g., obesity, prolonged immobility. 9Women with antiphospholipid syndrome should not use estrogen-containing contraceptives. hTreatment is recommended if the diagnosis of antiphospholipid syndrome is based on three or more prior pregnancy losses. LMWH = low-molecular-weight heparin; NSS = not specifically stated; UFH = unfractionated heparin; fE = venous thromboembolism. Prophylactic, intermediate-, and adjusted-dose regimens are listed in Table 52-5 (p. 1013).


Obstentrics_Williams

Obstentrics_Williams. Prophylactic, intermediate-, and adjusted-dose regimens are listed in Table 52-5 (p. 1013). of high quality data" described earlier by Bates and colleagues compression devices before cesarean delivery for all women (2016) creates considerable variation in the current recommennot already receiving thromboprophylaxis. his recommendations promulgated by the American College of Obstetricians dation was based primarily on consensus and expert opinion. and Gynecologists, the Royal College of Obstetricians, and the For patients undergoing cesarean delivery with additional risk American College of Chest Physicians (Palmero la, 2016). factors for thromboembolism, both pneumatic compression


Obstentrics_Williams

Obstentrics_Williams. In 2011, the American College of Obstetricians and Gynedevices and UFH or LMH may be recommended. he Colcologists (20 17b) recommended placement of pneumatic lege stipulated that cesarean delivery in an emergency setting should not be delayed because of the time necessary to implement thromboprophylaxis. Implementation of this strategy by the Hospital Corporation of America, the largest for-profit obstetrical health care delivery system in the United States, was associated with a reduction in deaths from pulmonary embolism from 7 of 458,097 cesarean births to 1 of 465,880 cesarean births (Clark, 2011, 2014).


Obstentrics_Williams

Obstentrics_Williams. In 2016, the National Partnership for Maternal Safety published several consensus recommendations for the prevention of maternal TE (D'lton, 2016). These recommendations included expanded use of antenatal prophylaxis for women hospitalized 3 days or longer, expanded use of prophylaxis during and after vaginal delivery, and expanded use of pharmacological prophylaxis to most women after cesarean delivery. In response, Sibai and Rouse (2016) expressed concern that these new recommendations derive from sparse data of questionable applicability to obstetrical patients. They called for better quality evidence to measure the benefits, harms, and costs of increased pharmacological thromboprophylaxis. As aptly expressed by Macones (2017), "an intervention, such as increased postcesarean pharmacologic thromboprophylaxis, where there are legitimate concerns about eicacy and safety, requires a much higher degree of evidence before a national guideline is implemented." We agree with these


Obstentrics_Williams

Obstentrics_Williams. thromboprophylaxis, where there are legitimate concerns about eicacy and safety, requires a much higher degree of evidence before a national guideline is implemented." We agree with these sentiments.


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Obstentrics_Williams. Agnelli G, Becattini C, Kirschstein T: Thrombolysis vs heparin in the treatment of pulmonary embolism. Arch Intern Med 162: 2537, 2002 Ahearn GS, Hadjiliadis 0, Govert JA, et al: Massive pulmonary embolism during pregnancy successfully treated with recombinant tissue plasminogen activator. Arch Intern Med 162: 1221, 2002 Akazawa M, Nishida M: Thrombolysis with intravenous recombinant tissue plasminogen activator during early postpartum period: a review of the literature. Acta Obstet Gynecol Scand 96(5):529, 2017 Almawi Y, AI-Shaikh FS, Melemedjian OK, et al: Protein Z, an anticoagulant protein with expanding role in reproductive biology. Reproduction 3,t2013


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Obstentrics_Williams. Almawi Y, AI-Shaikh FS, Melemedjian OK, et al: Protein Z, an anticoagulant protein with expanding role in reproductive biology. Reproduction 3,t2013 American Academy of Pediatrics, American College of Obstetricians and Gynecologists: Guidelines for Perinatal Care, 8th ed. Elk Grove Village, P, 2017 American College of Obstetricians and Gynecologists: Antiphospholipid syn drome. Practice Bulletin No. 132, December 2012, Reairmed 2017 a American College of Obstetricians and Gynecologists: hromboembolism in pregnancy. Practice Bulletin No. 123, September 2011, Reairmed 2017b American College of Obstetricians and Gynecologists: Inherited thrombophilias in pregnancy. Practice Bulletin No. 138, September 2013, Reairmed 20l7c Andersen AS, Berthelsen JG, Bergholt T: Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin. Acta Obstet Gynecol Scand 89(1):15,t2010


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Obstentrics_Williams. MacCallum P, Bowles L, Keeling 0: Diagnosis and management of heritable thrombophilias. BMJ ,t2014 Magnani HN: n analysis of clinical outcomes of91 pregnancies in 83 women treated with danaparoid (Orgaran). hromb Res 125:297,2010 Marik PE, Plante A: Venous thromboembolic disease and pregnancy. N Engl J Med 359:2025, 2008 McDonnell BP, Glennon K, McTiernan A, et al: Adjustment of therapeutic LMWH to achieve specific target anti-FXa activity does not afect outcomes in pregnant patients with venous thromboembolism. J Thromb Thrombolysis 43(1):105,t2017 Morikawa M, Yamada T, Yamada T, et al: Changes in D-dimer levels after cesarean section in women with singleton and twin pregnancies. hromb Res 128:e33, 2011 Mueller MJ, Lebherz TB: Antepartum thrombophlebitis. Obstet Gynecol 34:867, 1969 Murphy N, Broadhurst 01, Khashan AS, et al: Gestation-speciic n-dimer reference ranges: a cross-sectional study. BJOG 122(3):395,2015


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Obstentrics_Williams. Murphy N, Broadhurst 01, Khashan AS, et al: Gestation-speciic n-dimer reference ranges: a cross-sectional study. BJOG 122(3):395,2015 Nelson-Piercy C, Powrie R, Borg J-Y, et al: Tinzaparin use in pregnancy: an international, retrospective study of the safety and eicacy proile. Eur J Obstet Gynecol Reprod Bioi 159:293, 2011 Okoroh E, Azonobi I, Grosse S, et al: Prevention of venous thromboembolism in pregnancy. J Women Health 21:611, 2012 Overcash RT, Somers AT, LaCoursiere DY: Enoxaparin dosing after cesarean delivery in morbidly obese women. Obstet GynecoI125(6):1371, 2015 Paidas MJ, Triche EW, James AH, et al: Recombinant human antithrombin in pregnant patients with hereditaty antithrombin deficiency: integrated analysis of clinical data. Am J Perinatol 33(4):343, 2016 Palmerola KL.D'Alton ME, Brock CO, et al: A comparison of recommendations for pharmacologic thromboembolism prophylaxis ater caesarean delivety from three major guidelines. BJOG 123:2157,2016


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Obstentrics_Williams. Revel MP, Cohen S, Sanchez 0, et al: Pulmonary embolism during pregnancy: diagnosis with lung scintigraphy or CT angiography? Radiology 258:590, 2011 Rheaume M, Weber F, Durand M, et al: Pregnancy-related venous thromboembolism risk in asymptomatic women with antithrombin deficiency: a systematic review. Obstet GynecoIt127(4):649, 2016 Ridge CA, Mhuircheartaigh IN, Dodd JD, et al: Pulmonary CT angiography protocol adapted to the hemodynamic efects of pregnancy. AJR Am J RoentgenoIt197:1058,t2011 Roach RE, Ufering WM, van Hylckama Vlieg A, et al: he risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors. Blood 122(26):4264,t2013 Robertson L, Wu 0, Langhorne P, et al: hrombophilia in pregnancy: a systematic review. Br J HaematoIt132:171, 2005


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Obstentrics_Williams. Robertson L, Wu 0, Langhorne P, et al: hrombophilia in pregnancy: a systematic review. Br J HaematoIt132:171, 2005 Rodger MA, Hague WM, Kingdom J, et al: Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomized trial. Lancet 84(9955):1673, 2014 Rodger MA, Kahn SR, Cranney A, et al: Long-term dalteparin in pregnancy not associated with a decrease in bone mineral density: substudy of a randomized controlled trial. J hromb Haemost 5:1600, 2007 Rodie VA, Thomson AJ, Stewart FM, et al: Low molecular weight heparin for the treatment of venous thromboembolism in pregnancy: a case series. BJOG 109:1020,t2002 Sabadell J, Casellas M, Alijotas-Reig J, et al: Inherited antithrombin deficiency and pregnancy: maternal and fetal outcomes. Eur J Obstet Gynecol Reprod Bioi 149:47, 2010


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Obstentrics_Williams. Sabadell J, Casellas M, Alijotas-Reig J, et al: Inherited antithrombin deficiency and pregnancy: maternal and fetal outcomes. Eur J Obstet Gynecol Reprod Bioi 149:47, 2010 Saccone G, Berghella V, Maruotti GM, et al: Antiphospholipid antibody profile based obstetric outcomes of primary anti phospholipid syndrome: the PREGNANTS study. Am J Obstet GynecoIt216(5):525.e1, 2017 Saeed G, Moller M, Neuzner J, et al: Emergent surgical pulmonary embolectomy in a pregnant woman: case report and literature review. Tex Heart InstJ 41(2):188,t2014 Said JM, Higgins JR, Moses EK, et al: Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstet Gynecol 115:5, 2010a Said JM, Ignjatovic V, Monagle PT, et al: Altered reference ranges for protein C and protein S during early pregnancy: implications for the diagnosis of protein C and protein S deficiency during pregnancy. Thromb Haemost 103:984,t2010b


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Obstentrics_Williams. Sanson BJ, Lensing A W, Prins MH, et al: Safety oflow-molecular-weight heparin in pregnancy: a systematic review. hromb Haemost 81 :668, 1999 Scarsbrook AF, Evans AL, Owen AR, et al: Diagnosis of suspected venous thromboembolic disease in pregnancy. Clin RadioIt61:1, 2006 Seguin J, Weatherstone K, Nankervis C: Inherited antithrombin III deficiency in the neonate. Arch Pediatr Adolesc Med 148:389, 1994 Seligsohn U, Lubetsky A: Genetic susceptibility to venous thrombosis. N Engl J Med 344:1222,t2001 Shanbhag S, Pai N, Ghosh K, et al: Letters to the editor. Prenatal diagnosis in a family with purpura fulminans. Blood Coagul Fibrinolysis 26:350,t2015 Sharpe CJ, Crowther A, Webert E, et al: Cerebral venous thrombosis during pregnancy in the setting of type I antithrombin deficiency: case report and literature review. TransfMed Rev 25:61,t2011 Sibai BM, Rouse OJ: Pharmacologic thromboprophylaxis in obstetrics: broader use demands better data. Obstet GynecoIt128(4):681, 2016


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Obstentrics_Williams. Sibai BM, Rouse OJ: Pharmacologic thromboprophylaxis in obstetrics: broader use demands better data. Obstet GynecoIt128(4):681, 2016 Silver vI, Saade GR, Thorsten V, et al: Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth: the Stillbirth Collaborative Research Network. Am J Obstet Gynecol 215(4):468.e1,2016 Silver M, Zhao Y, Spong CY, et al: Prothrombin gene G20210A mutation and obstetric complications. Obstet Gynecol 115: 14, 2010 Singhal S, Henderson R, Horsield K, et al: Morphometry of the human pulmonary arterial tree. Circ Res 33: 190, 1973 Smith MP, Norris A, Steer PJ, et al: Tinzaparin sodium for thrombosis treatment and prevention during pregnancy. Am J Obstet GynecoIt190:495, 2004 Stein PO, Athanasoulis C, Alavi A, et al: Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 85:462, 1992


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Obstentrics_Williams. Stephenson ML, Serra E, Neeper JM, et al: A randomized controlled trial of difering doses of postcesarean enoxaparin thromboprophylaxis in obese women. J Perinatol 36(2):95, 2016 Stewart A: Warfarin-induced skin necrosis treated with protein C concentrate (human). Am J Health-Syst Pharm 67:901, 2010 Tanimura K, Ebina Y, Sonoyama A, et al: Argatroban therapy for heparininduced thrombocytopenia during pregnancy in a woman with hereditary antithrombin deficiency. J Obstet Gynaecol Res 38:749, 2012


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Obstentrics_Williams. Tanimura K, Ebina Y, Sonoyama A, et al: Argatroban therapy for heparininduced thrombocytopenia during pregnancy in a woman with hereditary antithrombin deficiency. J Obstet Gynaecol Res 38:749, 2012 Tapson VF: Acute pulmonary embolism. N Engl J Med 358:1037,t2008 Tengborn L, Bergqvist 0, Matzsch T, et al: Recurrent thromboembolism in pregnancy and puerperium: is there a need for thromboprophylaxis? Am J Obstet Gynecol 160:90, 1989 Tromeur C, van der Pol LM, Klok FA, et al: Pitfalls in the diagnostic management of pulmonaty embolism in pregnancy. Thromb Res 151 Suppl 1 :S86, 2017 van Mens TE, Scheres LJ, de Jong PG, et al: Imaging for the exclusion of pulmonary embolism in pregnancy. Cochrane Database Syst Rev 1 :CDO 11 053, 2017 van Wijk FH, WolfH, Piek J11, et al: Administration of low molecular weight heparin within two hours before caesarean section increases the risk of wound haematoma. BJOG 109:955, 2002 Virchow R: Gesammelte Abhandlungen zur wissenschaftlichen Medizin.


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Obstentrics_Williams. Virchow R: Gesammelte Abhandlungen zur wissenschaftlichen Medizin. Frankfurt, Medinger Sohn & Co., 1856 Waksmonski CA: Cardiac imaging and functional assessment I pregnancy. Semin PerinatoIt38(5):240, 2014 Waldman M, Sheiner E, Vardi IS: Can we profile patients at risk for thromboembolic events after delivery: a decade of follow up. Am J Obstet Gynecol 208:S234,t2013 Walker MC, Garner PR, Keely EJ, et al: Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol 177: 162, 1997 Wells PS, Anderson DR, Rodger M, et al: Evaluation ofD-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 349: 1227, 2003 PREGNANCY-INDUCED URINARY TRACT CHANGES.... 1025 URINARY TRACT INFECTIONS.. . . . . . . . . . . . . . . . . . .. 1026 NEPHROLITHIASIS.. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1030 PREGNANCY AFTER RENAL TRANSPLANTATION .... 1030 POLYCYSTIC KIDNEY DISEASE . . . . . . . . . . . . . . . . . .. 1031


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Obstentrics_Williams. GLOMERULAR DISEASES ....i......i....i...0..o...i.0...... 1032 CHRONIC KIDNEY DISEASE.. . . . . . . . . . . . . . . . . . . . .. 1034 ACUTE KIDNEY INJURY.. . . . . . . . . . . . . . . . . . . . . . . .. 1036 LOWER GENITAL TRACT LESIONS .0...0.i.......i......i.. 1037 In rare instances in patients suiringfrom pyelitis, the preg nant uterus may so compress the ureter as to cause a dam ming back of the purulent discharge, and thus give rise to a pyelonephritis. -]. Whitridge Williams (1903)


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Obstentrics_Williams. -]. Whitridge Williams (1903) Renal and urinary tract disorders are frequently encountered in pregnancy. Some precede pregnancy-one example being nephrolithiasis. In some women, pregnancy-induced changes may predispose to development or worsening of urinary tract disorders-an example is the markedly increased risk for pyelonephritis, described above by Williams. Finally, some renal pathology is unique to pregnancy, such as preeclampsia. With good prenatal care, however, most women with these disorders will likely have no long-term sequelae. Significant changes in both structure and function within the urinary tract during normal pregnancy are discussed in Chapter 4 (p. 65). he kidneys become larger, and dilatation of the right renal calyces and ureters can be striking Some dilatation develops before 14 weeks and likely E .


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Obstentrics_Williams. E . FIGURE 53-1 The 50th, 75th, and 90th percentiles for maternal renal caliceal diameters measured using sonography in 1395 pregnant women from 4 to 42 weeks' gestation. (Redrawn from Faundes A, Bricola-Filho M, Pinto e Silva JC: Dilatation of the urinary tract during pregnancy: proposal of a curve of maximal caliceal diameter by gestational age. Am J Obstet Gynecol 178: 1082, 1998.) from progesterone-induced relaxation of the muscularis. More marked dilatation is apparent beginning in midpregnancy because of more distal ureteral compression, especially on the right side (Faundes, 1998). There is also some vesicoureteral relux during pregnancy. Because of these physiological changes, the risk of upper urinary infection rises. Also, imaging studies done to evaluate urinary tract obstruction may occasionally be erroneously interpreted.


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Obstentrics_Williams. Evidence of functional renal hypertrophy becomes apparent very soon ater conception. Glomeruli are larger, although cell numbers do not grow (Strevens, 2003). Pregnancy-induced intrarenal vasodilatation develops, and both aferent and eferent resistances decline. This leads to greater efective renal plasma flow and glomerular filtration (Helal, 2012; Hussein, 2014). By 12 weeks' gestation, the glomerular filtration rate (GFR) is already augmented 20 percent above nonpregnant values (Hladunewich, 2004). Ultimately, plasma low and GFR rise by 40 and 65 percent, respectively. Consequently, serum concentrations of creatinine and urea drop substantively across pregnancy, and values within a nonpregnant normal range may be abnormal for pregnancy (Appendix, p. 1257). Other alterations include those related to maintaining normal acid-base homeostasis, osmoregulation, and fluid and electrolyte retention. • Assessment of Renal Function During


Obstentrics_Williams

Obstentrics_Williams. • Assessment of Renal Function During Urinalysis results are essentially unchanged during pregnancy, except for occasional glucosuria. Although protein excretion normally rises, it seldom reaches levels that are detected by usual screening methods. Higby and colleagues (1a994) reported 24-hour protein excretion in pregnancy to be 11a5 mg/d with a 95-percent confidence level of 260 mg/d. Values did not signiicantly difer by trimester (Fig. 4-14, p. 67). Albumin constitutes only a small part of total protein excretion and ranges from 5 to 30 mg/d. Airoldi and Weinstein (2007) concluded that proteinuria must exceed 300 mg/ d to be considered abnormal. Many consider 500 mg/d to be important with gestational hypertension. Investigators have correlated a urinary proteinto-creatinine ratio of :0.3 in a spot urine sample-ideally from a irst morning void-with a 24-hour protein excretion rate of :300 mg (Kuper, 2016).


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Obstentrics_Williams. In one study, 3 percent of 4589 nulliparas screened before 20 weeks had idiopathicihematuria, deined as 1 + or greater blood on urine dipstick (Stehman-Breen, 2002). These women had a twofold risk of developing preeclampsia. In another study of 1000 women screened during pregnancy, the incidence of dipstick hematuria was 15 percent (Brown, 2005). Most women had only trace levels of hematuria, and the falsepositive rate was 40 percent.


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Obstentrics_Williams. If the serum creatinine level in pregnancy persistently exceeds 0.9 mg/dL (75 LmollL), then intrinsic renal disease is suspected. In these cases, some determine the creatinine clearance as an estimate of the GFR. Of other assessment tools, sonography provides imaging of renal size, relative consistency, and elements of obstruction (see Fig. 53-1). Magnetic resonance (MR) imaging of renal masses provides excellent anatomic information (Putra, 2009). Full-sequence intravenous pyelography is not done routinely, but injection of contrast media with one or two abdominal radiographs may be indicated by the clinical situation. The usual clinical indications for cystoscopy are followed. Ureteroscopy is another available tool when indicated.


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Obstentrics_Williams. Although renal biopsy is relatively safely performed during pregnancy, it usually is postponed unless results may change therapy. From a review of 243 biopsies in pregnant women, the incidence of complications was 7 percent-this compares with 1 percent in postpartum women (Piccoli, 2013). Some consider biopsy for rapid deterioration of renal function with no obvious cause or for symptomatic nephrotic syndrome (Lindheimer, 2007 a). We and others have found biopsy helpful in selected cases to direct management (Chen, 2001; Piccoli, 2013). In one series, renal biopsy in 12 normal pregnant volunteers showed that five had slight to moderate glomerular endotheliosis (Strevens, 2003). Recall this is the histopathological lesion that is putatively typical of preeclampsia and is characterized by ibrin deposition within the glomerular endothelium leading to capillary occlusion. In contrast, all 27 women with protein uric hypertension had endotheliosis, and in all but one, it was moderate to


Obstentrics_Williams

Obstentrics_Williams. ibrin deposition within the glomerular endothelium leading to capillary occlusion. In contrast, all 27 women with protein uric hypertension had endotheliosis, and in all but one, it was moderate to severe.


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Obstentrics_Williams. In these cases, if the remaining kidney is normal, renal function becomes augmented. However, women who have donated a kidney have a higher frequency of gestational hypertension or preeclampsia in subsequent pregnancy-IaI versus 5 percent compared with non-donors (Garg, 2015). Otherwise, women with one normal kidney most often have no diiculty in pregnancy. Moreover, kidney donation does not lead to long-term adverse consequences. That said, thorough functional evaluation of the remaining kidney is essential (Ibrahim, 2009).


Obstentrics_Williams

Obstentrics_Williams. These infections are the most frequent bacterial infections complicating pregnancy. Although asymptomatic bacteriuria is the most common, symptomatic infection includes cystitis, or it may involve the renal calyces, pelvis, and parenchyma to cause pyelonephritis. Organisms that cause urinary infections are those from the normal perineal lora. Approximately 90 percent of Escherichia coli strains that cause nonobstructive pyelonephritis have adhesins such as P-and S-imbriae. These are cell-surface protein structures that enhance bacterial adherence and, thereby, virulence (Foxman, 2010; Hooton, 2012).


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Obstentrics_Williams. Data suggest that pregnant women have more severe sequelae from urosepsis. One possible underlying factor is the T -helper cell-Th1/h2 ratio-reversal of normal pregnancy, which is discussed in Chapter 4 (p. 59). Other perturbations of cytokine or of adhesin expression may be contributory (Chaemsaithong, 2013; Sledzinska, 2011). But even if pregnancy itself does not enhance these virulence factors, urinary stasis, vesicoureteral relux, and diabetes predispose to symptomatic upper urinary infections (Czaja, 2009). In the puerperium, several risk factors predispose to urinary infections. Bladder sensitivity to intravesical fluid tension is often diminished due to labor trauma or epidural analgesia.


Obstentrics_Williams

Obstentrics_Williams. In the puerperium, several risk factors predispose to urinary infections. Bladder sensitivity to intravesical fluid tension is often diminished due to labor trauma or epidural analgesia. Bladder sensations can also be obscured by discomfort from vaginal or perineal injury. Normal postpartum diuresis may worsen bladder overdistention, and catheterization to relieve retention often leads to urinary infection. Postpartum pyelonephritis is treated in the same manner as antepartum renal infections (McDonnold, 2012). This refers to persistent, actively multiplying bacteria within the urinary tract in asymptomatic women. he incidence during pregnancy is similar to that in nonpregnant women. It var ies from 2 to 7 percent, and it is characteristically population dependent. he highest incidence is in African-American mul tiparas with sickle-cell trait, and the lowest is in aluent white women of low parity. Asymptomatic infection is also more common in diabetics (Schneeberger, 2014).


Obstentrics_Williams

Obstentrics_Williams. Bacteriuria is typically present at the first antepartum visit. An initial positive urine culture result done as a part of prenatal care should prompt treatment. After this, fewer than 1 percent of women develop a urinary tract infection (Whalley, 1967). A clean-voided specimen containing more than 100,000 organ isms/mL is diagnostic. It may be prudent to treat when lower concentrations are identified, because pyelonephritis devel ops in some women despite colony counts of only 20,000 to 50,000 organisms/mL (Lucas, 1993).


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Obstentrics_Williams. Most studies indicate that if asymptomatic bacteriuria is not treated, approximately 25 percent of infected women will develop symptomatic infection during pregnancy (Smaill, 2015). In a more recent study, only 2.4 percent of treated women developed pyelonephritis (Kazemier, 2015). Eradication of bacteriuria with antimicrobial agents prevents most of these serious infections. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (2017), as well as the U.S. Preventive Services Task Force (2008), recommend screening for bacteriuria at the first prenatal visit. Standard urine cultures may not be cost efective when the prevalence is low. Less expensive screening tests such as the leukocyte esterase/nitrite dipstick are cost efective when the prevalence is ;2 percent (Rogozinska, 2016; Rouse, 1995). Also, a dipstick culture technique has excellent positive-and negative-predictive values (Mignini, 2009). With this, a special agar-coated dipstick is


Obstentrics_Williams

Obstentrics_Williams. is ;2 percent (Rogozinska, 2016; Rouse, 1995). Also, a dipstick culture technique has excellent positive-and negative-predictive values (Mignini, 2009). With this, a special agar-coated dipstick is first placed into urine and then also serves as the culture plate. Because of a high prevalence-5 to 8 percent-at Parkland Hospital, most women are screened by traditional urine culture. Susceptibility determination is not necessary because initial treatment is empirical (Hooton, 2012).


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Obstentrics_Williams. In some but not all studies, covert bacteriuria has been associated with preterm or low-birthweight infants. It is even more controversial whether eradication of bacteriuria decreases these complications. Evaluating a cohort of 25,746 mother-infant pairs, Schieve and coworkers (1994) reported urinary tract infection to be associated with greater risks for low-birthweight infants, preterm delivery, pregnancy-associated hypertension, and anemia. hese findings vary from those of others (Gilstrap, 1981b; Whalley, 1967). Notably, in most studies, cohorts with asymptomatic infection are not evaluated separately from those with acute renal infection (Banhidy, 2007). One Cochrane database review noted insuicient data to answer this question (Smaill, 2015). Bacteriuria responds to empirical treatment with any of several antimicrobial regimens listed in Table


Obstentrics_Williams

Obstentrics_Williams. Bacteriuria responds to empirical treatment with any of several antimicrobial regimens listed in Table Although selection can be based on in vitro susceptibilities, in our extensive experience, empirical oral treatment for 10 days with nitrofurantoin macrocrystals, 100 mg at bedtime, is usually efective. Satisfactory results are also achieved with a 7-day oral course of nitrofurantoin, 100 mg given twice daily (Lumbiganon, 2009). Single-dose antimicrobial therapy is less successful (Widmer, 2015). The important caveat is that, regardless of regimen given, the recurrence rate is approximatey 30 percent. This may indicate covert upper tract infection and the need for longer therapy. hus, after initial therapy, periodic surveillance is necessary to prevent recurrent urinary infections (Schneeberger, 2015).


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Obstentrics_Williams. For recurrent bacteriuria, we have had success with nitrofurantoin, 100 mg orally at bedtime for 21 days (Lucas, 1994). For women with persistent or frequent bacteriuria recurrences, suppressive therapy for the remainder of pregnancy can be given. We routinely use nitrofurantoin, 100 mg orally at bedtime. This drug may rarely cause an acute pulmonary reaction that dissipates on its withdrawal (Boggess, 1996). TABLE 53-1. Oral Antimicrobial Agents Used for Treatment of Pregnant Women with Asymptomatic Bacteriuria Amoxicillin,n3 9 Ampicillin,n2 9 Cephalosporin, 2 9 Nitrofurantoin, 200 mg Trimethoprim-sulfamethoxazole, 320/1600 mg Amoxicillin, 500 mg three times daily Ampicillin, 250 mg four times daily Cephalosporin, 250 mg four times daily Ciprofloxacin, 250 mg twice daily Levofloxacin, 250 or 500 mg daily Nitrofurantoin, 50 to 100 mg four times daily or 100 mg twice daily Trimethoprim-sulfamethoxazole, 160/800 mg twice daily


Obstentrics_Williams

Obstentrics_Williams. Levofloxacin, 250 or 500 mg daily Nitrofurantoin, 50 to 100 mg four times daily or 100 mg twice daily Trimethoprim-sulfamethoxazole, 160/800 mg twice daily Nitrofurantoin, 100 mg four times daily for 10 days Nitrofurantoin, 100 mg twice daily for 5 to 7 days Nitrofurantoin, 100 mg at bedtime for 10 days Nitrofurantoin, 100 mg four times daily for 21 days Nitrofurantoin, 100 mg at bedtime for pregnancy remainder


Obstentrics_Williams

Obstentrics_Williams. Nitrofurantoin, 100 mg four times daily for 21 days Nitrofurantoin, 100 mg at bedtime for pregnancy remainder Lower urinary infection during pregnancy may develop without antecedent covert bacteriuria (Harris, 1981). Cystitis produces dysuria, urgency, and frequency, but with few associated systemic indings. Pyuria and bacteriuria are usually found. Microscopic hematuria is common, and occasionally there is gross hematuria from hemorrhagic cystitis. Although cystitis is usually uncomplicated, the upper urinary tract may become involved by ascending infection. Almost 40 percent of pregnant women with acute pyelonephritis have preceding symptoms of lower tract infection (Gilstrap, 1981a). Women with cystitis respond readily to any of several regimens. Most of the 3-day regimens listed in Table 53-1 are usually 90-percent efective (Fihn, 2003). Single-dose therapy is less efective, and if it is used, concomitant pyelonephritis must be confidently excluded.


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Obstentrics_Williams. Lower urinary tract symptoms with pyuria accompanied by a sterile urine culture may stem from urethritis caused by Chlamydia trachomatis. Mucopurulent cervicitis usually coexists, and azithromycin therapy is efective (Chap. 65, p. 1240).


Obstentrics_Williams

Obstentrics_Williams. Renal infection is one of the most frequent serious medical complications of pregnancy. Data from the 2006 Nationwide Inpatient Sample showed that nearly 29,000 pregnancy-associated hospitalizations were for acute pyelonephritis Qolley, 2012). In one hospital-system database of nearly 550,000 births, its incidence was 0.5 percent (Wing, 2014). Importantly, pyelonephritis is a leading cause of septic shock during pregnancy (Snyder, 2013). In one Parkland Hospital Obstetrical Intensive Care Unit review, 12 percent of antepartum admissions were for sepsis syndrome caused by renal infections (Zeeman, 2003). Urosepsis may be related to an increased incidence of cerebral palsy in preterm infants Qacobsson, 2002). Fortunately, afected mothers sufer no serious long-term sequelae (Raz, 2003). Renal infection develops more frequently in the second trimester, and nulliparity and young age are risks (Hill, 2005).


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Obstentrics_Williams. Renal infection develops more frequently in the second trimester, and nulliparity and young age are risks (Hill, 2005). Pyelonephritis is unilateral and right-sided in more than half of cases, and it is bilateral in a fourth. Fever and shaking chills usually develop rather abruptly, and patients have aching pain in one or both lumbar regions. Anorexia, nausea, and vomiting may worsen dehydration. Tenderness usually can be elicited by percussion in one or both costovertebral angles. he differential diagnosis includes, among others, labor, chorioamnionitis, adnexal torsion, appendicitis, placental abruption, or infarcted leiomyoma. Evidence of the sepsis syndrome is common (Chap. 47, p. 921).


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Obstentrics_Williams. If this infection is suspected, a urine sample obtained by catheterization may be preferred to avoid obscuring contamination from the lower genital tract. he urinary sediment contains many leukocytes, frequently in clumps, and numerous bacteria. Bacteremia is demonstrated in 15 to 20 percent of these women. E coli is isolated from urine or blood in 70 to 80 percent of infections, Klebsiela pneumoniae in 3 to 5 percent, Enterobacter or Proteus species in 3 to 5 percent, and gram-positive organisms, including group B Streptococcus and Staphylococcus aureus, in up to 10 percent of cases (Hill, 2005; Wing, 2000).


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Obstentrics_Williams. Plasma creatinine is monitored because early studies reported that 20 percent of pregnant women developed acute kidney injury . More recent findings, however, show this to be only 5 percent if aggressive fluid resuscitation is provided (Hill, 2005). Follow-up studies have demonstrated that this endotoxin-induced damage is reversible long term. s shown in Figure 53-2, varying degrees of respiratory distress syndrome from endotoxin-induced alveolar injury are manifest in up to 2 percent of women (Cunningham, 1987; Snyder, 2013; Wing, 2014).


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Obstentrics_Williams. Uterine activity from endotoxin is common and is related to fever severity (Graham, 1993). In one study, women with pyelonephritis averaged five contractions per hour at admission, and this decreased to two per hour within 6 hours of intravenous luid and antimicrobial administration (Millar, 2003). Notably, 3-agonist therapy for tocolysis increases the likelihood of respiratory insuiciency from permeability edema (Lamont, 2000). The incidence of pulmonary edema in women with pyelonephritis who were given 3-agonists was reported to be 8 percent-a fourfold increase over that expected (Towers, 1991) . a second-trimester pregnant woman with severe pyelonephritis. A.An extensive infiltrative process and complete obliteration of the diaphragm (white arrows) is seen. B. Improved aeration of lung fields bilaterally is noted as pleural disease resolves (arrows). c. Markedly improved visualization of the lung fields with residual platelike atelectasis and normal appearance of the diaphragm.


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Obstentrics_Williams. TABLE 53-2. Management of the Pregnant Woman with Acute Pyelonephritis Evaluate hemogram, serum creatinine, and electrolytes Monitor vital signs frequently, including urinary output- Establish urinary output �50 mL/hr with intravenous Obtain chest radiograph if there is dyspnea or tachypnea Change to oral antimicrobials when afebrile Discharge when afebrile 24 hours, consider antimicrobial therapy for 7 to 10 days Repeat urine culture 1 to 2 weeks after antimicrobial Modified from Lucas, 1994; Sheffield, 2005. Endotoxin-induced hemoysis is common, and approximately a third of these women with pyelonephritis develop anemia (Cox, 1991). With recovery, hemoglobin regeneration is normal, and acute infection does not afect erythropoietin production (Cavenee, 1994).


Obstentrics_Williams

Obstentrics_Williams. One scheme for management of acute pyelonephritis is shown in Table 53-2. Urine cultures are taken, but prospective trials show that blood cultures are of limited clinical utility (Gomi, 2015; Wing, 2000). We obtain blood cultures if the temperature is >39°C. Intravenous hydration to ensure adequate urinay ouput is the cornerstone of treatment. Antimicrobials are also begun promptly with the caveat that they may initially worsen endotoxemia from bacterial lysis. Surveillance for worsening sepsis syndrome includes serial monitoring of urinary output, blood pressure, pulse, temperature, and oxygen saturation. High fevers are lowered with a cooling blanket and acetaminophen. his is especially important in early pregnancy because of possible teratogenic efects from hyperthermia.


Obstentrics_Williams

Obstentrics_Williams. Antimicrobial therapy usually is empirical, and ampicillin plus gentamicin; cefazolin or ceftriaxone; or an extended-spectrum antibiotic are all 95-percent efective in randomized trials (Sanchez-Ramos, 1995; Wing, 1998,a2000). Fewer than half of E coli strains are sensitive to ampicillin in vitro, but cephalosporins and gentamicin generally have excellent activity. Serum creatinine levels are monitored if nephrotoxic drugs are given. Initial treatment at Parkland Hospital is ampicillin plus gentamicin. Some recommend suitable substitutes if bacterial studies show in vitro resistance. With any of the regimens discussed, response is usually prompt, and 95 percent of women are afebrile by 72 hours (Hill, 2005; Sheield, 2005). ter discharge, most recommend oral therapy for a total of7 to 14 days (Hooton, 2012).


Obstentrics_Williams

Obstentrics_Williams. Persistent Infection. Generally, intravenous hydration and antimicrobial therapy are followed by stepwise defervescence of approximately 1°F per day. With persistent spiking fever or lack of clinical improvement by 48 to 72 hours, urinary tract obstruction, another complication, or both are considered. In these women, renal sonography is recommended to search for obstruction, which is manifest by abnormal ureteral or pyelo caliceal dilatation (Seidman, 1998). Although most women with continuing infection have no evidence of obstruction, some are found to have calculi. Although renal sonography will detect hydronephrosis, stones are not always seen in preg nancy (Butler, 2000; Maikranz, 1987). If stones are strongly suspected despite a nondiagnostic sonographic examination, a plain abdominal radiograph will identiy nearly 90 percent. Another option is the modified one-shot intravenous pyelo injection-which usually provides adequate imaging (Butler, 2000).


Obstentrics_Williams

Obstentrics_Williams. Another option is the modified one-shot intravenous pyelo injection-which usually provides adequate imaging (Butler, 2000). In some women, MR imaging may disclose the cause of persistent infection (Spencer, 2004). Even without urinary obstruction, persistent infection can be due to an intrarenal or perinephric abscess or phlegmon (Cox, 1988; Rai, 2012). Obstruction relief is important, and one method is cystoscopic placement of a double-J ureteral stent (Rodriguez, 1988). Because these stents are usually left in place until after deliv ery, they frequently become encrusted and require replacement. We have found that percutaneous nephrostomy is preferable because the stents are more easily replaced. Finally, surgical removal of stones may be required in some women (p. 1030).


Obstentrics_Williams

Obstentrics_Williams. We have found that percutaneous nephrostomy is preferable because the stents are more easily replaced. Finally, surgical removal of stones may be required in some women (p. 1030). Outpatient Management. This is sometimes done for non pregnant women with uncomplicated pyelonephritis (Hooton, 2012). Outpatient management was described in 92 pregnant axone, two 1-g doses 24 hours apart (Wing, 1999). After this, only a third of the group was considered suitable for outpatient therapy, and these women were randomly assigned either to discharge home and oral antimicrobials or to continued hospi talization with intravenous therapy. A third of the outpatient management group was unable to adhere to the treatment regi men and required readmission. his suggests that outpatient management is applicable to very few gravidas.


Obstentrics_Williams

Obstentrics_Williams. Recurrent urinary tract infection-either covert or symptomatic-develops in 30 to 40 percent of women following completion of pyelonephritis treatment (Cunningham, 1973). Unless other measures are taken to ensure urine sterility, nitrofurantoin, 100 mg orally at bedtime given for the remainder of the pregnancy, reduces bacteriuria recurrence (Van Dorsten, 1987).


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Obstentrics_Williams. Vesicoureteral reflux in early childhood can cause recurrent urinary tract infections, and subsequent chronic interstitial nephritis is attributed to chronic pyelonephritis. Moreover, high-pressure sterile reflux impairs normal renal growth. Combined, this leads to patchy interstitial scarring, tubular atrophy, and loss of nephron mass and is termed relux nephropathy. In some casesespecially those with staghorn calculi-xanthogranulomatous pyelonephritis causes suppurative destruction of renal tissue. In adults, long-term complications of chronic pyelonephritis include hypertension, which may be severe (Beck, 2015; Diamond,a2012).


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Obstentrics_Williams. Perhaps half of women with reflux nephropathy were treated during childhood for renal infections. Many also had surgical correction of reflux as children, and these women commonly have bacteriuria when pregnant (Mor, 2003). In the other half of women with relux nephropathy, a clear history of recurrent cystitis, acute pyelonephritis, or obstructive disease is lacking. Reports describing 939 pregnancies in 379 women with reflux nephropathy indicate that impaired renal function and bilateral renal scarring were associated with increased maternal complications (EI-Khatib, 1994; Jungers, 1996; Kohler, 2003). Chronic renal disease and pregnancy outcome are discussed on page 1034.


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Obstentrics_Williams. Kidney stones develop in up to 9 percent of women during their lifetime with an average age of onset in the third decade (Curhan, 2015). Calcium salts make up approximately 90 percent of stones, and hyperparathyroidism should be excluded. Although calcium oxalate stones in young nonpregnant women are most common, most stones in pregnancy-65 to 75 percent-are calcium phosphate or hydroxyapatite (Ross, 2008; Tan, 2013). Patients who have a stone typically form another one every 2 to 3 years. One study found pregnancy was a risk factor for stone formation (Reinstatler, 2017). Contrary to past teachings, a low-calcium diet promotes stone formation. Thiazide diuretics diminish stone formation. In general, obstruction, infection, intractable pain, and heavy bleeding are indications for stone removal, discussed later.


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Obstentrics_Williams. he incidence of stone disease complicating pregnancy varies. At the low end, the incidence was 0.3 admissions per 1000 pregnancies at Parkland Hospital (Butler, 2000). In an Israeli study, the incidence in nearly 220,000 pregnancies was 0.8 per 1000 (Rosenberg, 2011). In Washington state, the incidence was 1.7 per 1000 pregnancies (Swartz, 2007). Bladder stones are rare, but recurrent infection and labor obstructed by stones have been reported (Ait Benkaddour, 2006; Ruan, 2011).


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Obstentrics_Williams. Data are conflicting whether women with kidney stones have an increased risk for low-birthweight and preterm newborns. In one study of 2239 women with nephrolithiasis compared with normal controls, stones were associated with a signiicantly elevated preterm delivery rate-l0.6 versus 6.4 percent (Swartz, 2007). The more recent nationwide study from Taiwan also found 20-to 40-percent increases in rates of low birthweight and pre term birth (Chung, 2013). In contrast, a study from Hungary reported that pregnancy outcomes, including preterm delivery, were similar in women with stones and normal controls (Banhidy, 2007). Comparable conclusions were drawn from the Israeli study discussed above (Rosenberg, 2011). Pregnant women may have fewer symptoms with stone passage because of urinary tract dilatation (Hendricks, 1991; Tan, 2013). hat said, more than 90 percent of pregnant women with symptomatic nephrolithiasis present with pain.


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Obstentrics_Williams. Gross hematuria is less common than in afected nonpregnant women. It was a presenting symptom in 23 percent of women described by Butler and associates (2000). In another study, however, only 2 percent had gross hematuria (Lewis, 2003). Sonography is usually selected to visualize stones, but many are not detected because hydronephrosis may obscure indings (Iv1cAleer, 2004). Transabdominal color Doppler sonography to detect presence or absence of ureteral "jets" of urine into the bladder may exclude obstruction (As rat, 1998).


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Obstentrics_Williams. If the ureter is abnormally dilated but no stone is seen, then other imaging studies are indicated. While helical computed tomography (CT) scanning is the preferred imaging method for nonpregnant individuals, the associated x-ray exposure has led some to recommend MR imaging as a second-line test in pregnancy (Masselli, 2015). Thus CT scanning is usually avoided during pregnancy if possible (Curhan, 2015; Masselli, 2015). If it is used, the slices can be tailored as needed. White and colleagues (2007) recommend unenhanced helical CT and cite an average fetal radiation dose to be 7 mGy.


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Obstentrics_Williams. Treatment depends on symptoms and gestational age (Semins, 2014). Intravenous hydration and analgesics are given. In up to half of women with symptomatic stones, infection will be identiied, and this is treated vigorously as described earlier (p. 1029). Although stones infrequently cause symptomatic obstruction during pregnancy, persistent pyelonephritis should prompt a search for obstruction due to nephrolithiasis. Urinary obstruction with concomitant infection is an emergency-"pus under pressure" (Curhan, 2015).


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Obstentrics_Williams. Approximately 65 to 80 percent of symptomatic women will improve with conservative therapy, and the stone usually passes spontaneously (Tan, 2013). Others require an invasive procedure such as ureteral stenting, ureteroscopy, percutaneous nephrostomy, transurethral laser lithotripsy, or basket extraction (Butler, 2000; Johnson, 2012; Semins, 2014). Removal by a flexible basket via cystoscopy, although used less often than in the past, is still a reasonable consideration for pregnant women. In one study, 623 various procedures were performed in 2239 symptomatic pregnant women, but less than 2 percent required surgical exploration (Swartz, 200*). Of other treatments, the need for fluoroscopy limits the utility of percutaneous nephrolithotomy (Toth, 2005). Extracorporeal shock-wave lithotripsy is contraindicated in pregnancy.


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Obstentrics_Williams. Following transplantation, the I-year graft survival rate is 95 percent for grafts from living donors and 89 percent for those from deceased donors. Survival rates approximately doubled between 1988 and 1996, due in large part to the introduction of cyclosporine and muromonab-CD3 (OKT3 monoclonal antibody) to prevent and treat organ rejection. Since then, mycophenolate mofetil and tacrolimus have further reduced acute rejection episodes, however, the former is considered teratogenic (Briggs, 2014). he National Transplant Pregnancy Registry reports that 23 percent of fetuses exposed to mycophenolate had birth defects (Coscia, 2010). Importantly, resumption of renal function after transplantation promptly restores fertility in reproductive-aged women (Hladunewich, 2011; Rao, 2016). But, more than half of transplant recipients in one study reported that they were not counseled regarding contraception (French, 2013).


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Obstentrics_Williams. Women after transplantation do better with pregnancy than those with end-stage renal disease receiving dialysis (Saliem, 2016). In one review of 2000 pregnancies in transplant recipi ents, most were treated with cyclosporine and tacrolimus, and approximately 75 percent of pregnancies resulted in a live birth (Coscia, 2010). Studies from other countries describe similar outcomes (Bramham, 2013; Wyld, 20l3). In a study from Uruguay, 62 percent of liveborns were preterm (Orihuela, 2016). Two other reports also cited a high prevalence of pre term delivery (Erman Akar, 2015; Stoumpos, 2016). Notably, the incidence of fetal malformations was not increased, except in those who took mycophenolate mofetil (Coscia, 2010).


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Obstentrics_Williams. The incidence of preeclampsia is increased in all transplant recipients (Brosens, 20l3). In the UK National Cohort Study, the incidence of preeclampsia was 22 percent (Bramham, 2013). From their review, Josephson and McKay (2011) cite an incidence of a third of pregnancies but question the validity of this frequency. Importantly, in some cases, rejection is difficult to distinguish from preeclampsia. hat said, the incidence of rejection episodes approximates 2 to 5 percent (Bramham, 2013; Orihuela, 2016). Viral infections-especially those by poyomavirus hominis 1, also called BK virus, are frequent. In kidney transplant recipients, this virus can cause nephropathy and graft loss, and afected patients generally have an asymptomatic decline in renal function (Wright, 2016). Gestational diabetes is also found in approximately 5 percent of transplant recipients. Both are likely related to immunosuppression therapy. Similar outcomes are reported by other investigators (Al Duraihimh, 2008;


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Obstentrics_Williams. is also found in approximately 5 percent of transplant recipients. Both are likely related to immunosuppression therapy. Similar outcomes are reported by other investigators (Al Duraihimh, 2008; Cruz Lemini, 2007; Ghafari, 2008).


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Obstentrics_Williams. Several requisites should be satisfied by renal transplantation patients before attempting pregnancy G osephson, 2011; Lopez, 2014). First, women should be in good general health for at least 1 to 2 years after transplantation. Also, renal function should be stable and without severe renal insuiciency. Thus, serum creatinine is <2 mg/dL and preferably < 1.5 mg/ dL, and proteinuria is <500 mg/d. Evidence for graft rejection should be absent for 6 months, and pyelocalyceal distention by urography should not be seen. Moreover, hypertension should be absent or well controlled. And last, women should be taking no teratogenic drugs, and drug therapy should be reduced to maintenance levels.


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Obstentrics_Williams. Cyclosporine, tacrolimus, prednisone, and azathioprine are given routinely to renal transplantation recipients Gain, 2004; Lopez, 2014). Cyclosporine blood levels decline during pregnancy, although this was not reported to be associated with rejection episodes (Akturk, 2015; Kim, 2015). Unfortunately, these agents are nephrotoxic and also may cause renal hypertension. In fact, they likely contribute substantively to chronic renal disease that develops in 10 to 20 percent of patients with nonrenal solid-organ transplantation (Goes, 2007). Concern persists regarding the possible late efects in ofspring subjected to immunosuppressive therapy in utero. hese include malig nancy, germ cell dysfunction, and malformations in the chil dren of the ofspring. In addition, cyclosporine is secreted in breast milk (Moretti, 2003).


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Obstentrics_Williams. Finally, although pregnancy-induced renal hyperiltration theoretically may impair long-term graft survival, Sturgiss and study of 34 allograft recipients followed for a mean of 15 years. Others have reported similar findings (Debska-Slizien, 2014; Stoumpos, 2016). Close surveillance is necessary. Covert bacteriuria is treated, and if it is recurrent, suppressive therapy is given for the remainder of the pregnancy. Serial hepatic enzyme concentrations and blood counts are monitored for toxic efects of azathioprine and cyclosporine. Some recommend measurement of serum cyclo sporine levels. Gestational diabetes is more common if corti costeroids are taken, and overt diabetes must be excluded with tation. Surveillance for opportunistic infections from herpesvi rus, cytomegalovirus, and toxoplasmosis is important because these infections are common. Some recommend surveillance for BK virus, however, treatment is problematic Gosephson, 2011).


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Obstentrics_Williams. Renal function is monitored, and the GFR usually increases 20 to 25 percent. If a signiicant rise in the serum creatinine level is detected, then its cause must be determined. Possibilities include acute rejection, cyclosporine toxicity, preeclampsia, infection, and urinary tract obstruction. Evidence of pyelonephritis or graft rejection should prompt aggressive management. Imaging studies and kidney biopsy may be indicated. The woman is carefully monitored for development or worsening of underlying hypertension, and especially superimposed preeclampsia. Management of hypertension during pregnancy is the same as for patients without a transplant.


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Obstentrics_Williams. Because of increased incidences of fetal-growth restriction and preterm delivery, vigilant fetal surveillance is indicated (Chaps. 42, p. 814 and 44, p. 852). Although cesarean delivery is reserved for obstetrical indications, occasionally the transplanted kidney obstructs labor. In all women with a renal transplant, the cesarean delivery rate exceeds 60 percent (Bramham, 2013; Rocha, 2013). This usually autosomally dominant systemic disease primarily afects the kidneys. The disease is found in 1 in 800 live births and causes approximately 5 to 10 percent of end-stage renal disease in the United States. Although genetically heterogeneous, almost 85 percent of cases are due to PD1 gene mutations on chromosome 16, and the other 15 percent to PD2 mutations on chromosome 4 (Zhou, 2015). Prenatal diagnosis is available if the mutation has been identiied in a family member or if linkage is established in the family.


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Obstentrics_Williams. Renal complications are more common in men than in women, and symptoms usually appear in the third or fourth decade. Flank pain, hematuria, proteinuria, abdominal masses, and associated calculi and infection are common. Hypertension develops in 75 percent, and progression to renal failure is a major problem. Superimposed acute kidney injury may also develop from infection or obstruction from ureteral angulation by cyst displacement. Other organs are frequently involved. Asymptomatic hepatic cysts coexist in a third of patients with polycystic kidneys. Hepatic involvement is more common and more aggressive in women, and massive polycystic liver disease is almost exclusively found in multiparous women (Zhou, 2015). Approximately 10 percent of patients with polycystic kidney disease die from rupture of an associated intracranial bery aneurysm. Up to a fourth of patients have cardiac valvular lesions that involve valve prolapse or incompetence.


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Obstentrics_Williams. Because of its generally late onset, adult polycystic kidney disease is uncommon in pregnancy (Banks, 2015). The prognosis for pregnancy in these women depends on the degree of associated hypertension and renal insuiciency. Urinary tract infections are common. One study compared pregnancy outcomes in 235 afected women who had 605 pregnancies with those of 108 unafected family members who had 244 pregnancies (Chapman, 1994). Composite perinatal complication rates were similar-33 versus 26 percent. However, hypertension, including preeclampsia, was significantly more frequent in women with polycystic kidneys. Pregnancy does not seem to accelerate the natural disease course (Lindheimer, 2007b). he glomerulus and its capillaries are subject to various conditions and stimuli that can lead to acute and chronic diseases. Glomerular damage can be caused by toxins or infections or from systemic diseases that include hypertension, diabetes, or systemic


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Obstentrics_Williams. TABLE 53-3. Patterns of Clinical Glomerulonephritis lupus erythematosus (Lewis, 2015). It may also be idiopathic. When there is capillary inflammation, the process is termed glomerulonephritis, and oten, an autoimmune process is involved. Persistent glomerulonephritis eventually leads to worsening renal function. Progression is variable and often does not manifest until chronic renal insuiciency is diagnosed. Lewis and Neilson (2015) group glomerular injuries into six syndromes based on clinical patterns (Table 53-3). Within each of these categories, there are disorders encountered in young women, and thus, these may antedate or irst appear during pregnancy.


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Obstentrics_Williams. Acute glomerulonephritis may result from any of several causes (see Table 53-3). The clinical presentation usually includes hypertension, hematuria, red-cell casts, pyuria, and proteinuria. Varying degrees of renal insuiciency and salt and water retention result in edema, hypertension, and circulatory congestion (Lewis, 2015). The prognosis and treatment of nephritic syndromes depends on their etiology. Some recede spontaneously or with treatment. However, in some patients, rapidy progressive glomerulonephritis leads to end-stage renal failure, whereas in others, chronic glomerulonephritis develops with slowly progressive renal disease.


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Obstentrics_Williams. Lupus nephritis identified before pregnancy has a 50percent chance of laring during pregnancy (Koh, 2015). IgA nephropathy, also known as Berger disease, is the most common form of acute glomerulonephritis worldwide (Wyatt, 2013). he isolated form occurs sporadically, and it may be related to Henoch-Schonlein purpura as the systemic form (Donadio, 2002). Isolated nephritis may be due to anti-glomerular basement membrane (anti-GBM) antibodies. hese may also involve the lungs to manifest as a pulmonary-renal syndrome with alveolar hemorrhage, which is termed Goodpasture syndrome (Friend, 2015; Huser, 2015). Acute nephritic syndromes during pregnancy can be diicult to diferentiate from severe preeclampsia or eclampsia (Cabiddu, Acute Nephritic Syndromes: poststreptococcal, infective endocarditis, SLE, antiglomerular basement membrane disease, IgA nephropathy (Berger disease), ANCA


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Obstentrics_Williams. Acute Nephritic Syndromes: poststreptococcal, infective endocarditis, SLE, antiglomerular basement membrane disease, IgA nephropathy (Berger disease), ANCA Henoch-Schonlein purpura, cryoglobulinemia, membranoproliferative and mesangioproliferative glomerulonephritis Pulmonary-Renal Syndromes: Goodpasture, ANCA vasculitis, Henoch-Schonlein purpura, cryoglobulinemia Nephrotic Syndromes: minimal change disease, focal segmental glomerulosclerosis, membranous glomerulonephritis, diabetes, amyloidosis, others Basement Membrane Syndromes: anti-GBM disease, others Glomerular Vascular Syndromes: atherosclerosis, chronic hypertension, sickle-cell disease, thrombotic microangiopathies, anti phospholipid antibody syndrome, ANCA vasculitis, others Infectious Disease-Associated Syndromes: poststreptococcal, infective endocarditis, HIV, HBV, HCV, syphilis, others


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Obstentrics_Williams. Infectious Disease-Associated Syndromes: poststreptococcal, infective endocarditis, HIV, HBV, HCV, syphilis, others ANCA = antineutrophilic cytoplasmic antibodies; anti-GBM = anti-glomerular basement membrane; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IgA = immunoglobulin A; SLE = systemic lupus erythematosus. Adapted from Lewis, 2015. 2016). One example is systemic lupus erythematosus with a flare during the second half of pregnancy (Bramham, 2012; Zhao, 2013). In some of these cases, renal biopsy is sometimes needed to determine etiology and direct management (Lind heimer, 2007a; Ramin, 2006). Whatever the underlying etiology, acute glomerulonephritis has profound efects on pregnancy outcome. One older study described 395 pregnancies in 238 women with primay glo merulonephritis diagnosed before pregnancy (Pacham, 1989).


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Obstentrics_Williams. merulonephritis, IgA glomerulonephritis, and difuse mesan gial glomerulonephritis. Although most of these women had normal renal function, half developed hypertension, a fourth were delivered preterm, and the perinatal mortality rate after 28 weeks' gestation was 80 per 1000. As expected, the worst peri natal outcomes were in women with impaired renal function, early or severe hypertension, and nephrotic-range proteinuria. women with IgA nephropathy. From their review of more than 300 such pregnancies, Lindheimer and colleagues (2000) con cluded that pregnancy outcome was related to the degree of renal insuiciency and hypertension. Liu and coworkers (2014) reached similar conclusions. Heavy proteinuria is the hallmark of the nephrotic syndromes.


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Obstentrics_Williams. Heavy proteinuria is the hallmark of the nephrotic syndromes. ders that cause immunological or toxin-mediated injury with glomerular capillary wall breakdown to allow excessive filtra tion of plasma proteins. In addition to heavy urine protein excretion, the syndrome is characterized by hypoalbuminemia, hypercholesterolemia, and edema. There frequently is hyper tension, and along with albumin nephrotoxicity, renal insuf iciency eventually develops.


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Obstentrics_Williams. Some of the more frequent causes of the nephrotic syndrome are minimal change disease (10-15 percent), focal segmental glomerulosclerosis (35 percent), membranous glomerulonephritis (30 percent), and diabetic nephropathy. In most cases, renal biopsy will disclose microscopic abnormalities that may help direct treatment (Chen, 2015; Lo, 2014). Edema is problematic, especially during pregnancy. Normal amounts of dietary protein of high biological value are encouraged. The incidence of thromboembolism is increased and varies with the severity of hypertension, proteinuria, and renal insuiciency (Stratta, 2006). Although both arterial and venous thromboses may develop, renal vein thrombosis is particularly worrisome. he value, if any, of prophylactic anticoagulation is unclear. Some cases of nephrosis from primary glomerular disease respond to glucocorticosteroids and other immunosuppressants or cytotoxic drug therapy. In most of those cases caused by infection or drugs, proteinuria


Obstentrics_Williams

Obstentrics_Williams. of nephrosis from primary glomerular disease respond to glucocorticosteroids and other immunosuppressants or cytotoxic drug therapy. In most of those cases caused by infection or drugs, proteinuria recedes when the underlying cause is corrected.


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Obstentrics_Williams. Maternal and perinatal outcomes in women with the nephrotic syndromes depend on its underlying cause and severity. Whenever possible, these should be ascertained, and renal biopsy may FIGURE 53-3 Massive vulvar edema in a pregnant woman with the nephrotic syndrome due to secondary syphilis. (Used with permission from Dr. George Wendel, Jr.) be indicated to determine if the etiology will respond to treat ment. Half of women with nephrotic-range proteinuria will have a rise in daily protein excretion as pregnancy progresses (Packham, 1989). In women with nephrosis cared for at Park land Hospital, we reported that two thirds had protein excre tion that exceeded 3 g/d (Stettler, 1992). At the same time, however, if these women had only mild degrees of renal dys function, they had normally augmented CFR across pregnancy (Cunningham, 1990).


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Obstentrics_Williams. Management of edema during pregnancy can be particularly challenging as it is intensiied by normally increasing hydrostatic pressure in the lower extremities. In some women, massive vulvar edema may develop. An example of massive vulvar edema associated with the nephrotic syndrome caused by secondary syphilis is shown in Figure 53-3. Another major problem is that up to half of these women have chronic hypertension that may require treatment. In these, as well as in previously normotensive women, preeclampsia is common and often develops early in pregnancy.


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Obstentrics_Williams. Most women with nephrotic syndromes who do not have severe hypertension or renal insuiciency will have successful pregnancy outcomes. Conversely, if there is renal insuiciency, moderate to severe hypertension, or both, the prognosis is much worse. In a group of such women with 65 pregnancies cared for at Parkland Hospital, complications were frequent (Stettler, 1992). Protein excretion during pregnancy averaged 4 gl d, and a third of the women had classic nephrotic syndrome. here was some degree of renal insuiciency in 75 percent, chronic hypertension in 40 percent, and persistent anemia in 25 percent. Importantly, preeclampsia developed in 60 percent, and 45 percent had preterm deliveries. Even so, after excluding abortions, 53 of 57 neonates were born alive. In another series, fetal-growth restriction was noted in a third of pregnancies in afected women (Stratta, 2006).


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Obstentrics_Williams. Serious long-term adverse outcomes are a risk for women identiied to have nephrotic syndromes either before or during pregnancy (Su, 2017). In our series above, at least 20 percent of women followed for 10 years progressed to end-stage renal disease (Stettler, 1992). Similarly, in another group of 15 women, by 2 years postpartum, three had died, three had developed chronic renal failure, and two had progressed to end-stage renal disease (Chen, 2001). Of predictors, serum creatinine levela> 1.4 mg/ dL and 24-hour protein excretiona> 1 g/d are associated with the shortest renal survival times following pregnancy (Imbasciati, 2007).


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Obstentrics_Williams. his describes a pathophysiological process that can progress to end-stage renal disease. he National Kidney Foundation describes six stages of chronic kidney disease defined by decreasing GFR. It progresses from stage O-GFR >90 mLi min/1.73 mato stage 5-GFR < 15 mLimin/1.73 ma. Several diseases can worsen renal function, and many result from one of the glomerular diseases discussed earlier. hose that most frequently lead to end-stage disease requiring dialysis and kidney transplantation and their approximate percentages include: diabetes, 35 percent; hypertension, 25 percent; glomerulonephritis, 20 percent; and polycystic kidney disease, 15 percent (Abboud, 2010; Bargman, 2015).


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Obstentrics_Williams. reproductive-aged women with these diseases have varying degrees of renal insuiciency, proteinuria, or both. To counsel regarding fertility and pregnancy outcome, the degree of renal functional impairment and of associated hypertension are assessed. Successful pregnancy outcome in general may be more related to these two factors than to the speciic underlying renal disorder. A general prognosis can be estimated by considering women with chronic renal disease in arbitrary categories of renal function (Davison, 2011). hese include normal or mild impairment--deined as a serum creatinine < 1.5 mg/ dL; moderate impairment-deined as a serum creatinine 1.5 to 3.0 mg/dL; and severe renal insuiciencydeined as a serum creatinine >3.0 mg/dL. Although some have suggested adopting the classification of the National Kidney Foundation, others recommend using the older categories (Davison, 2011a; Piccoli, 201 Oa, 2011). Thus, the obstetrician is ideally familiar with both.


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Obstentrics_Williams. Most women have relatively mild renal insuiciency, and its severity along with any underlying hypertension is prognostic of pregnancy outcome. Renal disease with comorbidities secondary to a systemic disorder-for example, diabetes or systemic lupus erythematosus-portends a worse prognosis (Davison, 2011; Koh, 2015). For all women with chronic renal disease, the incidences of hypertension and preeclampsia, preterm and growthrestricted newborns, and other problems are high (Kendrick, 2015). Despite these, the National High Blood Pressure Education Program (2000) concluded that the prognosis has substantively improved since the 1980s. his has been verified by several reviews (Hladunewich, 2016a; Nevis, 2011; Ramin, 2006).


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Obstentrics_Williams. Loss of renal tissue is associated with compensatory intrarenal vasodilation and hypertrophy of the surviving nephrons. he resultant hyperperfusion and hyperiltration eventually damage surviving nephrons to cause nephrosclerosis and worsening renal function. With mild renal insuiciency, pregnancy causes 0. ..,c :J,� FIGURE 53-4 Blood volume expansion in 44 normally pregnant women at term compared with 29 who had eclampsia; 10 with moderate chronic renal insufficiency (CRI)-serum creatinine 1.5 to 2.9 mg/dL; and four with severe CRI-serum creatinine �3.0 mg/dL . (Data from Cunningham, 1990; Zeeman, 2009.) greater augmentation of renal plasma low and GFR (Baylis, 2003; Helal, 2012). With progressively declining renal function, there is little, if any, augmented renal plasma low. In one study, only half of women with moderate renal insuiciency demonstrated a pregnancy-augmented GFR, and women with severe disease had no increase (Cunningham, 1990).


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Obstentrics_Williams. Importanty, severe chronic renal insuiciency curtails normal pregnancy-induced hypervolemia. Blood volume expansion during pregnancy is related to disease severity and correlates inversely with serum creatinine concentration. As shown in Figure 53-4, women with mild to moderate renal dysfunction have normal blood volume expansion that averages 55 percent. With severe renal insuiciency, however, volume expansion averages only 25 percent, which is similar to that seen with hemoconcentration from eclampsia. In addition, these women have variable degrees of chronic anemia due to intrinsic renal disease. Renal Disease with Preserved Function


Obstentrics_Williams

Obstentrics_Williams. In some women, although glomerular disease has not yet caused renal dysfunction, incidences of pregnancy complications are still increased. As shown in Table 53-4, these problems are less frequent than in cohorts of women with moderate and severe renal insuiciency. Two earlier studies illustrate this. In one describing 123 pregnancies in women with biopsy-proven glomerular disease, only a few of the women had renal dysfunction, yet 40 percent developed obstetrical or renal complications (Surian, 1984). In another study of 395 pregnancies in women with preexisting glomerulonephritis and minimal renal insuiciency, impaired renal function developed in 15 percent during pregnancy, and 60 percent had worsening proteinuria (Packham, 1989). Only 12 percent had antecedent chronic hypertension, however, more than half of the 395 pregnancies were complicated by hypertension. he perinatal mortality rate was 140 per 1000, but even without early-onset or severe hypertension or nephrotic-range


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Obstentrics_Williams. however, more than half of the 395 pregnancies were complicated by hypertension. he perinatal mortality rate was 140 per 1000, but even without early-onset or severe hypertension or nephrotic-range proteinuria, the perinatal


Obstentrics_Williams

Obstentrics_Williams. TABLE 53-4. Complications (Percent) Associated with 5000 Chronic Renal Disease During Pregnancy 4500 90th .�2500 apreeclampsia only. NS = not stated. Data from Alsuwaida, 2011; Cunningham, 1990; Farwell, 2013; Feng, 2015; Imbasciati, 2007; Maruotti, 2012; Nevis, 2011; Packham, 1989; Piccoli, 201 Oa, 2011; Stettler, 1992; Surian, 1984; Trevisan, 2004. death rate was 50 per 1000. Importantly, in 5 percent of these women, worsening renal function was permanent.


Obstentrics_Williams

Obstentrics_Williams. In women with chronic kidney disease who also have renal insuiciency, adverse outcomes are generally directly related to the degree of renal impairment. Outcomes of women with moderate versus severe renal insuiciency are usually not separated (Table 53-5). hat said, Piccoli and associates (2010a) described 91 pregnancies complicated by stage 1 chronic kidney disease. Primarily because of hypertension, 33 percent were delivered preterm, and 13 percent had fetal-growth restriction. Alsuwaida and colleagues (2011) reported similar observations. Other investigators have described pregnancies complicated by moderate or severe renal insuiciency (Cunningham, 1990; Imbasciati, 2007; Zhang, 2015). Despite a high incidence of chronic hypertension, anemia, preeclampsia, preterm delivery, (red points). (Data from Cunningham, 1990; Stettler, 1992. Growth curves are those reported by Alexander, 1996.) and fetal-growth restriction, perinatal outcomes were generally acceptable. As shown in Figure


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Obstentrics_Williams. (Data from Cunningham, 1990; Stettler, 1992. Growth curves are those reported by Alexander, 1996.) and fetal-growth restriction, perinatal outcomes were generally acceptable. As shown in Figure 53-5, fetal growth is frequently impaired and related to renal dysfunction severity.


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Obstentrics_Williams. Prenatal care is tailored for women with chronic renal disease. Frequent monitoring of blood pressure is paramount, and serum creatinine levels, protein/creatinine ratio, and 24-hour protein excretion are quantiied as indicated. Bacteriuria is treated to decrease the risk of pyelonephritis and urther nephron loss. Protein-rich diets are recommended Gim, 2016; Lindheimer, 2000). In some women with anemia from chronic renal insuiciency, a response is seen with recombinant erythropoietin, however, hypertension is a common side efect. Serial sonography is performed to follow fetal growth. he diferentiation between worsening hypertension and superimposed preeclampsia is problematic. Preliminary data indicate that the angiogenic biomarkers placental growth factor (PIGF) and its soluble antiangiogenic receptor (sFlt-l) may be useful to separate chronic from gestational hypertension. This is described in Chapter 40 (p. 716).


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Obstentrics_Williams. In some women, pregnancy may accelerate chronic renal disease progression by increasing hyperfiltration and glomerular pressure to worsen nephrosclerosis (Baylis, 2003; Helal, 2012). his is more likely in women with severe chronic renal insuficiency (Abe, 1991 ; Jones, 1996). For example, Jungers and associates (1995) reported few long-term pregnancy-related adverse efects in 360 women with chronic glomerulonephritis and antecedent normal renal function. However, at 1 year after pregnancy, Jones and Hayslett (1996) reported that 10 percent of such women with moderate or severe renal insuiciency had developed end-stage renal failure-stage 5 chronic kidney disease. In a study from Parkland Hospital, we found that 20 percent of pregnant women with similar insuiciency had developed end-stage renal failure by a mean of 4 years (Cunningham, 1990). Similar indings in women with a median follow-up of 3 years were described by Imbasciati and coworkers (2007). By this time, end-stage disease


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Obstentrics_Williams. renal failure by a mean of 4 years (Cunningham, 1990). Similar indings in women with a median follow-up of 3 years were described by Imbasciati and coworkers (2007). By this time, end-stage disease was apparent in 30 percent of women whose serum creatinine was ::l.4 mg/dL and who had proteinuriaa> 1 g/d. Chronic proteinuria is also a marker for subsequent development of renal failure. In another report from Parkland Hospital, 20 percent of women with chronic proteinuria discovered during pregnancy progressed to end-stage renal failure within several years (Stettler, 1992).


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Obstentrics_Williams. Signiicantly impaired renal function is accompanied by subfertility that may be corrected with chronic renal replacement therapy-either hemodialysis or peritoneal dialysis (Hladunewich, 2016b; Shahir, 2013). Not unexpectedly, these pregnancies can be complicated. In one review of 131 cases, mean fetal birthweights were higher in women who conceived while undergoing dialysis-1530 g versus 1245 g-than in women who conceived before starting dialysis (Chou, 2008). his was also true for 77 pregnancies described by J esudason and coworkers (2014). Similar outcomes from several reports are shown in Table 53-5.


Obstentrics_Williams

Obstentrics_Williams. Outcomes are similar with either hemodialysis or peritoneal dialysis. hus, for the woman already undergoing either method, it seems reasonable to continue that method with consideration for its increasing frequency. In the woman who has never been dialyzed, the threshold for initiation during pregnancy is unclear. Lindheimer and colleagues (2007a) recommend dialysis when serum creatinine levels are between 5 and 7 mg/ dL. Because it is imperative to avoid abrupt volume changes that cause hypotension, dialysis frequency may be extended to five to six times weekly (Reddy, 2007). Certain protocols emphasize attention to replacement of substances lost through dialysis Qim, 2016). Multivitamin doses are doubled, and calcium and iron salts are provided along with suicient dietary protein and calories. Chronic anemia is treated with erythropoietin. To meet pregnancy changes, extra calcium is added to the dialysate along with less bicarbonate.


Obstentrics_Williams

Obstentrics_Williams. Maternal complications are common and include severe hypertension, placental abruption, heart ailure, and sepsis. In a review of 90 pregnancies in 78 women, as well as those shown in Table 53-5, high incidences of maternal hypertension and anemia, preterm and growth-restricted infants, stillbirths, and hydramnios were reported (Piccoli, 2010b).