Pregnancy in Patients on Chronic Ambulatory Peritoneal Dialysis

Pregnancy in Patients on Chronic Ambulatory Peritoneal Dialysis Merit F. Gadallah, MD, Bashir Ahmad, MD, Frederick Karubian, MD, and Vito M. Campese, MD • Both conception and successful completion of pregnancy are rare occurrences in female patients on chronic renal replacement therapy. Only a handful of successful pregnancies and deliveries have been reported in patients receiving hemodialysis (HD). Even less common are reports of successful pregnancy and delivery in patients receiving chronic ambulatory peritoneal dialysis (CAPD). Among the more common causes of fetal loss are abruptio placentae and other causes of spontaneous miscarriage. We report here three cases of pregnancy in patients on CAPD; two of these pregnancies progressed successfully to spontaneous delivery, while the third terminated during an episode of acute peritonitis. Furthermore, we have reviewed the literature concerning the outcome of pregnancy in the dialysis population on CAPD. © 1992 by the National Kidney Foundation, Inc. INDEX WORDS: End-stage renal failure; continuous ambulatory peritoneal dialysis; pregnancy.

I

T IS WELL KNOWN that fertility is markedly impaired in female patients with end-stage renal disease (ESRD). As a result, pregnancy itself is an uncommon occurrence in this group of patients. I . 3 When pregnancy does occur in this clinical setting, it frequently results in spontaneous abortion. In 1971, Confortini et al described, for the first time, a successful pregnancy in a female patient with ESRD receiving maintenance hemodialysis (HD).4 Since that time, several other cases of successful pregnancy in patients on maintenance HDhave been reported. 5 ,6 In addition, the Registry of the European Dialysis and Transplantation Association (EDT A) reported a cohort of 26 female ESRD patients who between 1979 and 1983 successfully completed pregnancy while undergoing maintenance HD. Of these 26 women, 22 conceived after maintenance HD was begun, while the remaining four conceived before the initiation of HD, All patients were on maintenance HD at the time of delivery,7 In regard to continuous ambulatory peritoneal dialysis (CAPO), only a few reports are available describing women who successfully completed pregnancy when this treatment modality was initiated following conception,8,9 Rarer yet are reports of successful conception and pregnancy while undergoing maintenance CAPO for ESRD. 8 ,IO.12 We present the case histories of three women who became pregnant while undergoing maintenance CAPO. Two of the three women successfully delivered healthy, albeit premature infants, while the third pregnancy resulted in spontaneous abortion. In addition, we have reviewed, and present here, the available literature regarding pregnancy in women on CAPO. Excluded from our report are pregnancies that occurred before

the initiation of CAPO as renal replacement therapy. CASE REPORTS Ca~e

1

A 41-year-old Hispanic woman was diagnosed as having ESRO of undetermined etiology in April 1988, Her creatinine clearance determined from 24-hour urinary collection was measured at 2 mL/min. CAPO was initiated at that time with three 2-L exchanges per day. Four months following the initiation of CAPO, the patient complained of vaginal discharge and was diagnosed as having vaginitis. An intrauterine device that had been in place for several years was removed. At that time, it was determined that the patient was 3 months pregnant. She continued CAPO with three exchanges using 1.5% alternating with 2.5% dialysate solution per day, and refused to increase the number of exchanges as advised by her nephrologist. Throughout the course of her pregnancy, she remained normotensive and her blood urea nitrogen (BUN) ranged from 14,3 to 16 mmoljL (40 to 45 mg/dL). Her serum creatinine was in the range of 690 to 778 MmoljL (7.8 to 8.8 mg/dL). The remainder of her chemistries ranged as follows: serum Na 135 to 140 mmol/L, K 3.0 to 4.5 mmol/L, Cl 98 to 102 mmoljL, HC0 3 23 to 29 mmoljL, Ca 2.0 to 2.25 mmol/L (8.1 to 9.0 mg/dL), and PO. 0.87 to 1.66 mmoljL (2.7 to 3.6 mg/dL). Her serum glucose ranged between 4.66 and 5.72 mmoljL (84 to 103 mg/dL), total protein 5.3 to 6.1 g/dL, and serum albumin 26 to 33 giL (2.6 to 3.3 gldL). Her hemoglobin remained between 60 to 65 gil (6.0 to 6.5 g/dL) despite oral iron supplementation. The patient refused blood transfusions, and erythropoietin was not commercially available at that From the Division 0/ Nephrology, Los Angeles County/ University o/Southern California Medical Center, Los Angeles, CA. Received August 29, 1991; accepted in revised form April 14,1992. Address reprint requests to Vito M. Campese, MD, Professor o/Medicine, Department o/Medicine, University o/Southern California, School 0/ Medicine, 2025 Zonal Ave, Los Angeles, CA 90033. © 1992 by the National Kidney Foundation, Inc. 0272-6386/92/2004-0016$3.00/0

American Journal of Kidney Diseases, Vol XX, No 4 (October), 1992: pp 407-410

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408 time. Her medications consisted of folic acid, multivitamins, calcium carbonate 600 mg three times daily with meals, and ferrous sulfate 325 mg twice daily. At 29 weeks of gestation, the patient developed uterine contractions resulting in spontaneous vaginal delivery. The infant was male, with a birth weight of 1,895 g. The Apgar scores were 7 and 9 at I and 5 minutes, respectively. No fetal anomalies were noted. Currently, the patient continues to do very well on maintenance CAPD. The child is 34 months of age, and in normal health.

Case 2 A 27-year-old white woman manifested acute renal failure in 1983 as a result of toxic shock syndrome. She became dialysis-dependent, and underwent maintenance HD for approximately I year. While undergoing HD, she recovered a sufficient amount of renal function to permit discontinuation of dialysis therapy. Over the following 5 years, her renal dysfunction slowly deteriorated. By August 1989, her serum creatinine had increased to 60 I ILmol/L (6.8 mgjdL) with a BUN of 25 mmoljL (70 mgjdL). Her serum hemoglobin was 10.5 gjdL at that time. In December of the same year, BUN was 30.7 mmoljL (86 mgjdL), serum creatinine had increased to 804 ILmol/L (9.1 mgjdL), serum calcium was 1.8 mmoJjL (7.2 mgjdL), serum phosphorus 2.2 mmol/L (6.8 mgjdL), and alkaline phosphatase 400 IUjdL. Despite our recommendations to reinstitute dialysis therapy immediately, the patient eJected to wait until after the Christmas holidays. In February 1990, therefore, a Tenckhoff catheter was placed and peritoneal dialysis was begun shortly thereafter. By May 1990, the patient began to complain of nausea and vomiting. Evaluation of these complaints prompted a biochemical workup including a pregnancy test, which was found to be positive. She stated that she had not been using any type of contraceptive regimen. CAPD was continued with an increase to five exchanges per day. She remained normotensive throughout the pregnancy. In October 1990, she had a serum hemoglobin of 9.1 gjdL and a hematocrit of26.2% and a serum ferritin of30 U (normal, 5 to 120 U). Erythropoietin, 3,000 U thrice weekly, was started. On December 17, 1990, her serum chemistries showed a serum calcium of 2.4 mmoljL (9.6 mgjdL), serum phosphorus 1.65 mmoJjL (5.1 mgjdL), serum creatinine 663 ILmoJj L (7.5 mgjdL), BUN 17.1 mmoJjL (48 mgjdL), cholesterol 521 mgjdL, total protein 7.0 gjdL, serum albumin 29 gjL (2.9 gjdL), alkaline phosphatase 339 IUjdL, sodium 135 mmol/L, potassium 3.8 mmoljL, chloride 98 mmoljL, and CO2 22 mmoJjL. Hemoglobin was III gjL (11.1 gjdL) and hematocrit was 32.5%. On December 18, 1990 she spontaneously delivered a female infant of 38 weeks' gestation. Birth weight was 2,230 g, length was 18 inches, and the Apgar scores were 7 at I minute and 9 at 5 minutes. Currently, the patient is doing well on CAPD at four exchanges a day, while her II-month-old offspring is healthy and doing well.

Case 3 A 39-year-old black woman with ESRD secondary to focal segmental glomerulosclerosis was begun on maintenance CAPD in June 1988. At that time her BUN was 32.5 mmol/

L (91 mgjdL) with a serum creatinine of 1,008 ILmoJjL (11.4 mgjdL). She proceeded to do well on CAPD. She was married and used no contraceptive measures. In March 1991, it was discovered that she was pregnant. An abdominal ultrasound performed at the time showed a 23-week-old fetus developing normally. Vital signs showed a pulse of 80 bpm, blood pressure 112/78 mm Hg, and a weight of 145 lb. Laboratory analysis showed a serum glucose of 4.33 mmoljL (78 mgjdL), serum sodium 135 mmol/L, serum potassium 3.9 mmol/L, serum chloride 95 mmol/L, serum bicarbonate 22 mmol/L, BUN 17.9 mmol/L (50 mgjdL), and serum creatinine 751 ILmoJjL (8.5 mgjdL). Total protein was 5.9 gjdL, while serum albumin was 29 gjL (2.9 gjdL). Her hematocrit was 21.4%, with a serum hemoglobin of71 gjL (7.1 gjdL). At 24 weeks of gestation, the patient developed fever, abdominal pain, and cloudy peritoneal fluid. She was diagnosed with acute peritonitis and therapy with intraperitoneal Cefadyl (E.R. Squibb & Sons, Inc., Princeton, NJ) was initiated. On the following day she suddenly developed a spontaneous rupture of membranes, and shortly thereafter delivered a stillborn baby. The patient recovered from both the peritonitis and the premature rupture of membranes and stillbirth without further sequelae.

DISCUSSION

Pregnancy is a rare occurrence in the patient with advanced renal failure. I -3,13 Recent data on HO patients indicate an incidence of 3.6%.14 Among women with severe impairment of renal function, pregnancy often ends in stillbirth, abruptio placentae, polyhydramnios, and prematurity, as well as many other complications. 5 .7. 15 Aggressive hemodialysis appears to increase the likelihood of a successful outcome. In fact, dialysis patients who retain some significant degree of renal function have a better probability of enjoying a successful pregnancy. The success rate of pregnancy in hemodialysis patients is approximately 20%.14,15 Once a predialysis patient becomes pregnant, CAPO is seldom the modality selected for renal replacement therapy. This is due to concerns that as the pregnancy progresses, the gravid uterus would result in greater abdominal distention, causing discomfort and leaking around the catheter during the dialysate dwell period. And for those patients already undergoing maintenance CAPO when pregnancy occurs, successful outcome of pregnancy is difficult to establish as seen in the scarce data in the literature (Table I). The available reports indicate a success rate of 67%. However, these data should be interpreted with caution, because case reports tend to address successful outcome rather than failure. Redrow et

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409

Table 1. Pregnancy Outcome in Patients on Maintenance CAPO

Patient No.

1 16 211 2b11 38 4 10 5 12 6 (this study) 7 (this study) 8 (this study)

Gestational Age (wk) at Delivery

34 20 32 34 35 32 29 38 24

Reason for Delivery and Method

Fetal nonreactivity, CIS Spontaneous abortion Fetal nonreactivity, CIS Fetal non reactivity, CIS Elective, CIS Spontaneous delivery Spontaneous delivery Spontaneous delivery Spontaneous abortion

Apgar Scores (1 and 5 min)

Weight of Babies at Birth (g)

9/10

1,340

9/9 1/3 10/10

1,080 1,720 1,900 960 1,895 2,230

stillborn

7/9 7/9

Abbreviation: CIS, cesarean section.

al, 8 in a review of the literature, report three cases of pregnancy with favorable outcomes in patients on maintenance CAPD. In addition, Kioko et alii describe a 26-year-old CAPD patient with advanced diabetic nephropathy who completed a successful pregnancy and delivery. In this report, we have described three cases of pregnancy in women on CAPD, two of whom were able to complete successful, albeit premature, pregnanCIes. Once the ESRD patient does become pregnant it is not clear which of the two dialytic modalities is superior in terms of successful completion of pregnancy and health of the product of gestation. Redrow et al 8 have argued that CAPD may be the preferable modality in pregnant women with ESRD. They cite a higher hematocrit, infrequent episodes of hypotension, and no systemic heparin requirement as features of CAPD that provide a safer and more stable hemodynamic and biochemical milieu for the fetus. Hypotensive episodes during dialysis may be particularly harmful because they may lead to hemoperfusion of the placenta and the fetus and may precipitate premature labor. An additional potential advantage of CAPD is that anemia is less severe in these patients. This problem is ofless concern now that erythropoietin is commercially available for human use. Because of potential fetal hypoxia, anemia during pregnancy should be corrected by the use of erythropoietin to achieve hematocrit levels of30% to 35%. However, it is of interest that case 1 delivered a healthy child despite hematocrit that did not exceed 17% throughout pregnancy. This occurred because the patient refused blood trans-

fusions, and because erythropoietin was not available at that time. An additional advantage of CAPD is that impending premature labor can be prevented by the addition of magnesium sulfate to the dialysate to achieve blood levels of 4 to 5 mg/dL. 8 ,17 In fact, pregnant women on CAPD appear to tolerate the pregnancy quite well. Conversely, patients who become pregnant while on HD frequently develop hypertension. This appears to become more common during the third trimester. Increases in blood pressure do not seem to occur frequently in pregnant CAPD patients. Abruptio placentae has also been reported in at least three cases of pregnant patients on HD,5 and in one patient on CAPD. 8 Bennett-Jones et al lO described a women with progressive deterioration in her renal function who was unable to conceive for 15 years. Once she reached ESRD, CAPD was begun. After 3 months of maintenance CAPD, the patient was found to be pregnant. She had an uneventful pregnancy and delivered a healthy baby. Even with the above reports, there is no strong evidence demonstrating that CAPD is superior to HD in the management of the pregnant women with ESRD. In fact, there are some notable complications associated with the CAPD procedure that could complicate pregnancy. Most common and significant of these problems are peritonitis and mechanical obstruction of the dialysis catheter. As reported above, one of our patients experienced spontaneous abortion during an episode of acute peritonitis. However, it is difficult to clearly establish a cause-effect relationship between the two events.

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Certain problems attributable to the hormonal alterations present in ESRO complicate attempts to deliver competent prenatal care and advice to women on dialysis. Since this patient population so infrequently becomes pregnant, discussions regarding family planning and birth control alternatives are not ordinarily undertaken. In addition, given the common irregularity of the menstrual cycle in this population, pregnancy testing is often delayed when symptoms arise. This is well illustrated in case 1 presented here. In this patient, who became pregnant despite the presence of an intrauterine device, the diagnosis of pregnancy was delayed until the third month of gestation when symptoms of vaginitis prompted gynecologic consultation. Our cases, along with those cases previously reported in the literature, raise serious questions relating to family planning and management of pregnant women on CAPO. Further, the importance of prenatal counseling and presentation of birth control alternatives become apparent. Little information is available on the outcome

of pregnancy in dialysis patients. Fine et al 5 reported 90% fetal survival for pregnant women on HO. However, when all dialysis-related pregnancies, including those who abort before the twentieth week of gestation are included, the overall fetal survival has been estimated to be between 20% and 25%Y Even pregnancies that continue well into the third trimester frequently terminate in stillbirth or preterm labor. All reported cases of successful delivery in CAPO patients, including ours, occurred before the 34th week of gestation, with the babies often being small for gestational age. The incidence of congenital abnormalities in babies born to HO patients is unknown. In the EDT A series, two of 35 babies born to mothers on HO manifested congenital malformations. 18 Barri et al l9 have recently reported three babies born to mothers on hemodialysis; one baby developed congenital hydrocephalus. More detailed informations on fetal surveillance, methods of preventing potential premature labor, and issues that relate to delivery in patients on dialysis were recently reviewed by Hou. 20

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pregnancy in a diabetic patient treated with continuous ambulatory peritoneal dialysis. Diabetes Care 6:298-300, 1983 12. Cattran DC, Benzie RJ: Pregnancy in a continuous ambulatory peritoneal dialysis patient. Perit Dial Bull 3: 1314,1983 13. Hou S: Pregnancy in women requiring dialysis for renal failure. Am J Kidney Dis 9:368-373, 1987 14. Roxe DM, Parker J: Report ofasurvey of reproductive function in female hemodialysis patients. Proceedings of the American Nephrology Nurses Association, National Meeting, New Orleans, LA, 1985 15. Registration Committee of EDTA: Successful pregnancies in women treated by dialysis and kidney transplantation. Br J Obstet Gynecol 87:839-845, 1980 16. Melendez R, Franquero C, Gill P, et al: Successful Pregnancy with CAPD. American Nephrology Nurses Association 15:280-282, 1988 17. Elliott JP, O'Keeffe OF, Schon DA, et al: Dialysis in pregnancy: A critical review. Obstet Gynecol Surv 46:319324, 1991 18. Challah S, Wing AJ, Broyer M, et al: Successful pregnancies in women on regular dialysis and women with a functioning transplant, in Andreucci VE (ed): The Kidney in Pregnancy. Boston, MA, Martinus Nijhoff, 1986, pp 188-194 19. Barri YM, Al-Furayh 0, Qunibi WY, et al: Pregnancy in women on regular hemodialysis. Dial Transplant 20:652656,1991 20. Hou S: Pregnancy in continuous ambulatory peritoneal dialysis (CAPD) patients. Perit Dial Int 10:201-204, 1990