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Pregnancy in patients on dialysis

Pregnancy in patients on dialysis

INTRODUCTION — Patients who are on dialysis are much less likely to become pregnant but more likely to have a complicated pregnancy compared with patients with normal kidney function. This topic reviews the effects of end-stage kidney disease (ESKD) on pregnancy outcomes and provides recommendations for management of pregnant patients who are on dialysis.

Related topics on the management of pregnant patients who have nondialysis-requiring chronic kidney disease (CKD), pregnant patients with specific types of nephropathy, and pregnant patients with kidney transplants are all presented separately:

(See "Pregnancy and contraception in patients with nondialysis chronic kidney disease".)

(See "Pregnancy in women with systemic lupus erythematosus".)

(See "Sexual and reproductive health after kidney transplantation".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

EPIDEMIOLOGY — Fertility is decreased in both males and females who are on dialysis [1]. However, while females on dialysis may have erratic and/or absent menstrual cycles, pregnancy still occurs. The reported frequency of conception among females of childbearing age on dialysis appears to be increasing. While studies from the 1990s reported pregnancy rates of 0.3 to 2.2 percent per year [2-5], the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) reported increasing rates of up to 3.3 per 1000 patient-years (3.3 per 1000 patient-years in 1996 to 2008 compared with 0.54 and 0.67 per 1000 person-years from 1976 to 1985 and from 1986 to 1995, respectively) [6]. A retrospective cohort study of over 47,500 females on dialysis between 2005 and 2013 reported an overall pregnancy rate of 17.8 per 1000 patient-years, with the highest rate in females aged 20 to 24 years (40.9 per 1000 patient-years) [7]. Racial differences were noted; rates were highest among Native American patients, Hispanic American patients, and Black patients as compared with White patients. Furthermore, patients with diabetes had the lowest pregnancy rates.

The reasons underlying this observed increased fertility rate are unknown. Potential factors may reflect improved dialysis-related care, including achievement of higher dialysis dose and improved treatment of anemia because of erythropoiesis-stimulating agents (ESAs) leading to improved libido.

The type and timing of dialysis also appears to impact pregnancy rates. The reasons for the difference in outcomes between modalities is not known:

Nocturnal hemodialysis – Patients receiving nocturnal dialysis appear to have higher pregnancy rates compared with conventional hemodialysis. In a small cohort study including 45 females of childbearing age, five females undergoing nocturnal hemodialysis had seven pregnancies, resulting in six live infants [8]. If this finding is reproduced in future studies, it may be related to the higher dialysis dose provided by nightly therapy. (See "Outcomes associated with nocturnal hemodialysis", section on 'Fertility/pregnancy'.)

Peritoneal dialysis – The pregnancy rate is lower among patients on peritoneal dialysis compared with hemodialysis [4,6,9]. In an analysis of registry data from ANZDATA, 2.54 pregnancies per 2000 patient-years occurred among patients on hemodialysis versus only 1.06 among patients on peritoneal dialysis [6]. Similarly, in the aforementioned retrospective cohort study of females on dialysis between 2005 and 2013, females on peritoneal dialysis had a lower likelihood of pregnancy compared with those on hemodialysis (hazard ratio 0.47, 95% CI 0.41-0.55) [7].

OBSTETRIC OUTCOMES — Patients on dialysis historically have had dismal pregnancy outcomes, but these have improved with better delivery of dialysis care. Small studies have suggested that intensified (ie, high frequency) dialysis improves pregnancy outcomes [10,11].

Maternal hypertensive disorders of pregnancy – Hypertensive disorders of pregnancy, including uncontrolled hypertension, preeclampsia, and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are common adverse obstetric events experienced by pregnant persons receiving dialysis [12]. More contemporary studies have shown improvements in these maternal outcomes, perhaps reflecting benefits associated with more intensive dialysis [11,13]. A 2023 systematic review of 14 observational studies published between 2010 and 2020, including 2364 patients and 2754 pregnancies, reported hypertension in 7.7 percent, preeclampsia in 11.9 percent, and HELLP in 0.7 percent of patients [13]. There were no cases of maternal death. Compared with prepregnancy dialysis schedules, the time burden of more intense or high-frequency dialysis can be difficult for some females, and it is important to provide adequate social and emotional support during pregnancy. These females should be screened for depression both during pregnancy and in the postpartum period given the context of a significant chronic illness.

Fetal – Major fetal issues for pregnant females receiving dialysis include high rates of neonatal death/stillbirth, preterm birth, and low birth weight.

Live birth rate – Since approximately 1990, reported live birth rates for females undergoing dialysis have ranged from 40 to 86 percent [3-5,10,13-20]. Factors contributing to the wide range of outcomes may include relatively small study sizes, variations in dialysis intensity, and improvements in antenatal and neonatal care over time. A study of 77 pregnancies in the Australia and New Zealand Dialysis and Transplantation Registry (ANZDATA) from 2001 to 2011 reported a live birth rate of 73 percent, while a Canadian cohort of 22 pregnancies treated with intensified hemodialysis between 2000 and 2013 reported a live birth rate of 86 percent [10,21]. Longer duration of dialysis (>36 hours/week) was associated with an increased live birth rate. For comparison, a 2011 systematic review of over 3500 females with kidney transplants reported a 73.5 percent live birth rate [22].

Patients on dialysis with residual kidney function may have better live birth outcomes. In ANZDATA, the live birth rate was higher for females who conceived before starting dialysis compared with those who conceived after initiation (91 versus 63 percent, respectively), even though all females remained on long-term kidney replacement therapy [21]. The improved outcome may have been due to higher residual kidney function, which often declines with time on dialysis.

Preterm birth – While preterm birth, defined as less than 37 completed weeks of gestation, has been reported in 50 to 100 percent of births to females on dialysis [9,10,13], a contemporary systematic review found multiple studies published in 2018 or later with mean gestational ages of 34 to 36 weeks [13]. Studies have typically not differentiated spontaneous from medically-indicated preterm birth, which remains high because of the high prevalence of hypertensive disorders of pregnancy.

Low birth weight – While earlier small observational studies reported low birth weight occurred in approximately 45 percent of infants born to patients undergoing hemodialysis, a systematic review of studies published between 2010 and 2020 reported significant improvements (intrauterine growth restriction of 5.9 percent, small for gestational age 18.9 percent) [13].

PRECONCEPTION CARE

Preconception counseling — Preconception counseling should be initiated in any female of child-bearing potential. Patients should be informed that pregnancy in patients on dialysis is considered high risk and will require a multidisciplinary effort that involves both a high-risk obstetrician and nephrologist. The following issues should be discussed with the patient prior to conception:

Contraceptive methods to be used until pregnancy is actively attempted (see 'Contraception' below)

Pregnancy outcomes (both maternal and fetal) in the setting of dialysis (see 'Obstetric outcomes' above)

Maternal risks (see 'Maternal complications' below)

Management of medications before, during, and after pregnancy (see 'Management of medications' below)

Management of dialysis during pregnancy (see 'Dialysis prescription and administration' below)

A discussion of preconception care for the general population is presented in detail separately. (See "The preconception office visit".)

Contraception — As pregnancy in females undergoing dialysis is associated with increased maternal and fetal risks, contraceptive counseling is an active part of preconception care to aid planned timing of pregnancy. We discuss contraception with all females with reproductive potential and advise contraceptive use until pregnancy is actively planned. (See "Pregnancy and contraception in patients with nondialysis chronic kidney disease".)

Options for contraception in females with end-stage kidney disease (ESKD) are the same as in the general population. In general, long-acting reversible contraceptives (LARC) are the preferred methods for females who desire the most effective and/or long-acting contraception options. LARC methods include copper intrauterine devices (IUDs), levonorgestrel-releasing IUDs, and the etonogestrel implant. Estrogen-containing methods, including oral pills, the transdermal patch, and vaginal rings, are less preferred because of the markedly increased cardiovascular risk in chronic kidney disease (CKD) and ESKD patients. Both the World Health Organization and the United States Centers for Disease Control and Prevention provide tables of medical eligibility criteria for contraceptive use in females with various characteristics and medical disorders. (See "Contraception: Counseling and selection", section on 'Document medical history/potential contraindications'.)

Timing of conception — Ideally, pregnancy is planned to ensure the optimal timing of conception. The decision to proceed with or delay conception is highly individualized and is impacted by the baseline health of the female, the female's age, and the anticipated wait time for a donor kidney, if applicable. Comorbidities such as systemic lupus erythematosus and diabetes should be optimally controlled prior to conception. In general, pregnancy outcomes are better early in the course of CKD compared with advanced CKD or ESKD.

(See "Effects of advanced maternal age on pregnancy".)

(See "Pregnancy in women with systemic lupus erythematosus", section on 'Preconception evaluation'.)

(See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

For females with ESKD, it may be advantageous to delay pregnancy among dialysis patients who are anticipating kidney transplantation since transplant recipients have a higher incidence of successful pregnancies, fewer complications, and fewer birth abnormalities [23]. This degree of planning is only possible if the patient has a living donor for kidney transplantation. Females awaiting deceased-donor kidney transplantation may be advised not to delay conception until after transplantation due to the prolonged waiting time for a deceased-donor kidney and the progressive reduction in fertility with increasing age. (See "Sexual and reproductive health after kidney transplantation".)

For females who are unable or choose not to delay conception for transplant, we discuss the need for more frequent dialysis during pregnancy (ie, near daily) and that they may have an increased risk of allosensitization after pregnancy (although the magnitude of risk has not been quantified). (See 'Dialysis prescription and administration' below.)

Baseline evaluation — In all dialysis patients who are considering becoming pregnant, we advise a multidisciplinary evaluation that includes a nephrologist and a maternal-fetal medicine specialist (high-risk obstetrician). We perform the following baseline evaluation prior to planned conception:

Assessment of the patient's medication history for potential teratogenic or fetotoxic medications (discontinue and/or substitute medications that have been identified to be potentially teratogenic or fetotoxic [eg, angiotensin-converting enzyme (ACE) inhibitors]).

Vaccination – Patients should receive standard vaccinations included in obstetric care. (See "Immunizations during pregnancy".)

Assessment of blood pressure. (See 'Hypertension' below.)

Measurement of serum urea, bicarbonate, and electrolytes.

Assessment of solute clearance adequacy (urea reduction ratio [URR], Kt/V).

Liver function tests. (See 'Hypertension' below.)

Complete blood count and iron studies (serum iron, total iron-binding capacity [TIBC], percent transferrin saturation [TSAT], and serum ferritin). (See 'Treatment of anemia' below.)

Measurement of serum calcium, phosphorus, and parathyroid hormone. (See 'Metabolic bone disease' below.)

Measurement of serum albumin and assessment of nutritional status. (See 'Nutrition' below.)

Random plasma glucose and, in patients with known or at risk for pregestational diabetes mellitus, glycated hemoglobin (A1C). (See "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management", section on 'First trimester'.)

In patients with systemic lupus erythematosus (SLE), measurement of antiphospholipid antibodies [lupus anticoagulant (LAC), immunoglobulin G (IgG) and IgM anticardiolipin (aCL) antibodies, and IgG and IgM anti-beta2-glycoprotein (GP) I antibodies] and antibodies that can impact the fetus (anti-Ro/SSA, anti-La/SSB). (See "Pregnancy in women with systemic lupus erythematosus", section on 'Risk assessment' and "Pregnancy in women with systemic lupus erythematosus", section on 'Specific laboratory testing'.)

Management of medications

ACE inhibitors and ARBs — Angiotensin-converting enzyme (ACE) inhibitors should not be used during pregnancy, since they are associated with fetal abnormalities. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)

We discontinue ACE inhibitors and angiotensin receptor blockers (ARBs) in all females who are on dialysis and who are trying to conceive. This is different from our approach to nondialysis CKD patients who have proteinuria, in whom we may continue ACE inhibitors or ARBs up until detection of conception. (See "Pregnancy and contraception in patients with nondialysis chronic kidney disease", section on 'ACE inhibitors and ARBs'.)

Unlike predialysis patients with CKD, ACE inhibitors confer only marginal benefit in dialysis-dependent individuals. The potential benefits of ACE inhibitors or ARBs in patients with ESKD include preservation of residual kidney function, although this does not outweigh the potential teratogenic risk. In addition, there are multiple alternate antihypertensive agents that are safe during pregnancy, and pregnancy diagnosis is often delayed in this patient population, increasing the risk of exposure at a more advanced gestational age.

ACE inhibitors may be resumed after delivery. Captopril, enalapril, and quinapril are not present in breast milk [24,25]. (See "Pregnancy and contraception in patients with nondialysis chronic kidney disease", section on 'Postpartum care'.)

Diuretics — We do not use diuretics. Pregnant patients are dialyzed almost daily, and fluid removal is best achieved by careful ultrafiltration with dialysis.

Diagnosis of pregnancy — Pregnancy is diagnosed using both a serum beta-human chorionic gonadotropin (hCG) and ultrasound. The serum beta-hCG alone is not adequate for diagnosis among patients on dialysis. Beta-hCG is excreted by the kidneys, and serum levels may be increased in females with ESKD in the absence of pregnancy, with one study suggesting the use of a higher cutoff of 25 mlU/mL to exclude pregnancy when fertility status is unclear [26]. Among females suspected of being pregnant because of an elevated serum beta-hCG, the ultrasound confirms the presence of a viable fetus and estimates the gestational age. (See "Clinical manifestations and diagnosis of early pregnancy".)

MANAGEMENT DURING PREGNANCY

Monitoring during pregnancy — Pregnant females with end-stage kidney disease (ESKD) on dialysis should be monitored jointly by a nephrologist and by a maternal-fetal medicine specialist familiar with the management of dialysis in a pregnant female. General principles of management are discussed below.

Maternal – We see patients at least monthly during the early first trimester, every two weeks by the second trimester, and weekly by the third trimester. The clinical condition, though, may necessitate closer follow-up throughout pregnancy.

The following assessments should be performed regularly at the patient's dialysis unit as performed in other nonpregnant patients on dialysis:

Assessment of blood pressure at each visit (in addition to daily monitoring at home as needed) (see 'Hypertension' below and 'Maternal complications' below)

Measurement of serum urea, bicarbonate, electrolytes, and glucose

Assessment of solute clearance adequacy (urea reduction ratio [URR], Kt/V)

Complete blood count and iron studies (serum iron, total iron-binding capacity [TIBC], percent transferrin saturation [TSAT], and serum ferritin) (see 'Treatment of anemia' below)

Measurement of serum calcium, phosphorus, and parathyroid hormone (see 'Metabolic bone disease' below)

Measurement of serum albumin and assessment of nutritional status (see 'Nutrition' below)

Liver function tests

The above laboratory tests are in addition to the tests obtained for prenatal care. For patients without a history of pregestational diabetes and no additional risk factors, oral glucose tolerance testing to screen for gestational diabetes is performed at 24 to 28 weeks of gestation. Females receiving glucocorticoids and/or calcineurin inhibitors, as well as those with traditional risk factors for gestational diabetes, undergo additional early screening.

(See "Prenatal care: Initial assessment", section on 'Laboratory tests'.)

(See "Prenatal care: Second and third trimesters", section on 'Periodic assessments and procedures'.)

(See "Gestational diabetes mellitus: Screening, diagnosis, and prevention", section on 'Screening for GDM at 24 to 28 weeks'.)

Fetal – Obstetrical follow-up in this high-risk population typically includes a first-trimester screen in conjunction with an ultrasound assessment of nuchal translucency or a maternal serum screen in the second trimester to assess for chromosomal abnormalities, including Down syndrome. As serum human chorionic gonadotropin (hCG) is one component of both the first-trimester combined test and the second-trimester quadruple test, false-positive tests can occur in females with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD). For these females, the serum results can be interpreted without hCG. However, more invasive testing including chorionic villous sampling or an amniocentesis may be necessary.

(See "Down syndrome: Overview of prenatal screening".)

(See "First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18".)

(See "Prenatal screening for common aneuploidies using cell-free DNA".)

Obstetric monitoring is performed as indicated by the patient's medical condition. A detailed ultrasound to assess fetal anatomy and cervical length is typically performed between 18 to 20 weeks. Cervical length should be assessed as patients on hemodialysis are more prone to cervical incompetence [10]. Thereafter, fetal growth is assessed every three to four weeks. If intrauterine growth restriction is identified, then twice-weekly antenatal testing (biophysical profile with Doppler evaluation of the umbilical cord and/or nonstress test) is typically begun and continued until delivery.

(See "Short cervix before 24 weeks: Screening and management in singleton pregnancies".)

(See "Overview of antepartum fetal assessment".)

(See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)

(See "Short cervix before 24 weeks: Screening and management in singleton pregnancies".)

Nutrition — Attention to nutritional considerations and proper weight gain are essential for a successful pregnancy [27]. Evaluation and follow-up by a dietician familiar with the requirements of pregnancy and ESKD may be helpful.

The diet should be modified among dialysis patients:

Daily protein intake of 1.5 to 1.8 g/kg per day – This is higher than the recommended amount for nonpregnant CKD patients (0.8 g/kg) and for pregnant patients without CKD (approximately 1.1 g/kg) in order to account for amino acid losses with dialysis.

Double doses of water-soluble vitamins and folic acid supplementation of 5 mg/day – The folic acid requirement is higher than for nondialysis individuals because folic acid is cleared by dialysis.

Liberalization of dietary phosphate – Pregnant patients who are on dialysis should not be on any phosphate restriction and generally do not require phosphate binders due to intensification of hemodialysis. In fact, phosphate supplementation may be necessary during dialysis. (See "Outcomes associated with nocturnal hemodialysis", section on 'Phosphate'.)

Assessment of dry weight – In general, females should gain approximately 2 to 4 pounds during the first three months of pregnancy and 1 pound per week thereafter, necessitating regular adjustments to dry weight. Careful clinical assessment of volume status is advised to determine ultrafiltration goals.

Prevention of preeclampsia — Patients with ESKD on dialysis are considered to be at high risk for preeclampsia. Low-dose aspirin therapy has been shown to decrease the risk of preeclampsia in females at moderate to high risk of the disease, but studies have not included patients with ESKD. However, the safety of low-dose aspirin in the general high-risk obstetric population has been well documented. In pregnant patients with ESKD, we weigh the potential risks and benefits of low-dose aspirin therapy and offer treatment to those without any contraindications to aspirin use. The role of aspirin in the prevention of preeclampsia is discussed in more detail elsewhere. (See "Preeclampsia: Prevention", section on 'Low-dose aspirin'.)

Delivery — Most females undergoing dialysis will be delivered at or just beyond 37 weeks if they have not already been delivered for obstetric or medical indications. There is little benefit in allowing the pregnancy to extend beyond this date, and maternal and/or perinatal risk may increase. Further, delivery needs to be timed as these females receive heparin with hemodialysis. Most females can safely undergo induction of labor and vaginal delivery; cesarean delivery is performed for standard obstetric indications.

Preterm delivery may be necessary in the presence of severe preeclampsia, fetal growth restriction, or nonreassuring fetal testing (eg, fetal distress).

Use of magnesium sulfate — Many females get magnesium sulfate before delivery, either to prevent seizures in preeclampsia or to reduce the risk of cerebral palsy before preterm birth of an infant <32 weeks. Magnesium is renally excreted, and toxicity is potentially life threatening due to respiratory depression, arrhythmias, and central nervous system (CNS) depression.

For females who require magnesium sulfate before delivery, we reduce both the loading dose and the infusion rate by one-half. We closely monitor serum levels and follow the patient clinically for evidence of magnesium toxicity.

(See "Inhibition of acute preterm labor", section on 'Dose'.)

(See "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Magnesium sulfate'.)

(See "Eclampsia", section on 'Dosing and toxicity'.)

Maternal complications — Significant potential complications in pregnant patients on dialysis include preeclampsia, infection, and anemia:

Hypertensive disorders – The diagnosis of hypertensive disorders of pregnancy, including preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, is particularly challenging in this patient population, given the high prevalence of preexisting hypertension. Close monitoring for the development of the non-kidney manifestations of preeclampsia, including dropping platelet counts and increasing liver function tests, is often necessary (table 1) [28]. Fetal manifestations of preeclampsia/hypertension may be present (eg, intrauterine growth restriction, signs of fetal distress, abnormal umbilical artery Doppler).

(See "Preeclampsia: Clinical features and diagnosis".)

(See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)

Infection – Pregnant patients on dialysis are at risk for dialysis access-related infections, such as tunneled hemodialysis catheter-related bacteremia, which can be life threatening. Close surveillance is indicated. (See "Central venous catheters: Overview of complications and prevention in adults", section on 'Catheter-related infection' and "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention" and "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

Females who are still making urine should be screened periodically for asymptomatic bacteria and treated as per recommendations in pregnant patients who are not on dialysis. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)

Anemia – Anemia is a common complication among pregnant patients on dialysis. Several factors may contribute to the development of anemia in this patient population, including relative erythropoietin deficiency due to the high demand for red blood cell (RBC) production to support placental and fetal growth, loss of iron and RBCs with frequent and intensive dialysis, and erythropoietin resistance from inflammatory cytokine production. In up to 25 percent of cases, anemia may be severe enough to require blood transfusion [29], which, next to pregnancy, is another sensitizing event that may impact the patient's chances of future transplantation. (See "Anemia in pregnancy" and 'Treatment of anemia' below.)

Management of ESKD during pregnancy

Dialysis prescription and administration — The dialysis prescription should be adjusted as soon as possible after conception.

Preferred modality — We suggest that females who are trying to conceive and all pregnant patients on dialysis be treated with hemodialysis rather than peritoneal dialysis. As noted above, the pregnancy rate is lower among patients on peritoneal dialysis compared with hemodialysis [4,6,9]. (See 'Epidemiology' above.)

In addition, there appears to be a higher rate of small for gestational age (SGA) pregnancies among peritoneal dialysis compared with patients on hemodialysis. In a systematic review of case reports and case series, the prevalence of SGA was 66.7 percent in patients on peritoneal dialysis versus 31 percent in those on hemodialysis [9].

Hemodialysis

Intensive dialysis – Providing more frequent and/or longer dialysis decreases the risk of polyhydramnios, helps control hypertension, increases birth weight and gestational age, improves maternal nutrition, and increases the chances of live birth [20,30]. Most clinicians would increase the frequency of hemodialysis to five or six times per week. The specific dose varies depending on the residual kidney function. Among patients without residual kidney function, we provide ≥36 hours of dialysis per week. In a comparison of data from an intensely dialyzed cohort in Canada (22 patients, mean of 43 hours weekly) versus a retrospective cohort of patients in the United States (70 patients) who were dialyzed for a mean of 17 hours per week, the live birth rates were 48, 75, and 85 percent for patients dialyzed for <20 (n = 46), 21 to 36 (n = 16), and >36 hours (n = 13) weekly, respectively [10]. Among females with established ESKD, the gestational age at delivery was greater in the Canadian cohort versus the United States cohort (36 versus 27 weeks); however, there was no difference in gestational age among females who started dialysis during pregnancy. Mean birth weight tended to be higher in the Canadian cohort than in the United States cohort (2118 versus 1748 g). Further studies will be necessary to refine dialysis dose and determine if less intensive regimens can be safely prescribed as this study had too few patients that received between 30 and 36 hours of dialysis.

Among patients with residual kidney function, we target a blood urea nitrogen (BUN) under 50 mg/dL (16 mmol/L) [14,18,20,30,31], although some experts suggest a lower BUN target of less than 35 mg/dL (12.5 mmol/L) [32]. However, the BUN may not be an accurate measure of uremia (particularly if nutrition is suboptimal); thus, we also follow other biochemical parameters to assess hemodialysis adequacy and obstetrical parameters such as fetal growth and amniotic fluid index.

(See "Prescribing and assessing adequate hemodialysis".)

(See "Fetal growth restriction: Evaluation".)

Potassium – We advise using a dialysate potassium of ≥3 mEq/L. This lessens the risk of hypokalemia, which should be avoided. Hyperkalemia is uncommon because of intensive dialysis, and dialysate concentrations <3 mEq/L are rarely required.

Calcium – We use a dialysate calcium concentration of 1.5 mmol/L (6 mg/dL) in order to avoid the risk of hypocalcemia.

Bicarbonate – We use a dialysate concentration of 30 mEq/L, which is generally sufficient to avoid metabolic acidosis in patients undergoing intensive dialysis. If metabolic acidosis develops, the dialysate bicarbonate may be increased to 35 mEq/L.

Phosphate – If hypophosphatemia develops despite a liberal dietary phosphorus intake (and no phosphate binders), we add sodium phosphate to the dialysate to aim for a concentration of up to 4.5 mg/dL (1.5 mmol/L). The dialysate phosphate concentration is adjusted to maintain pre- and postdialysis phosphate concentrations within the normal range. (See "Technical aspects of nocturnal hemodialysis", section on 'Dialysate composition'.)

Avoid intradialytic hypotension – Pregnant patients should be monitored more closely during dialysis to avoid intradialytic hypotension. This is particularly important during the last portion of a session. Maternal hemodynamic instability may compromise the uteroplacental circulation and may be associated with the induction of uterine contractions [19].

Weekly assessment of volume status – A clinician should perform a careful, weekly physical examination, including an assessment of patient weight, blood pressure, and edema, to help detect the presence of excess fluid. It is difficult to distinguish excess fluid gained between dialysis sessions from that due to pregnancy-associated weight gain. Dry weight increases throughout the pregnancy and should increase approximately 0.5 kg/week during the second and third trimesters. However, this suggested increase in dry weight during pregnancy should not be considered fixed, and dry weight should be continually reassessed and adjusted as needed based upon the patient's blood pressure, volume status, and nutritional status. (See 'Nutrition' above.)

There is no high-quality evidence to guide the optimal ultrafiltration rate or goal in pregnant patients on dialysis. Fluid removal during hemodialysis should be tailored to the individual patient. Since we perform more frequent hemodialysis (ie, five to six times per week) in pregnant patients, we typically target an ultrafiltration goal of 1 to 2 liters per dialysis session, which is similar to that used in patients undergoing nocturnal hemodialysis. In patients whose predialysis blood pressure is >120/70 mmHg, we adjust the ultrafiltration rates during dialysis to avoid lowering the patient's blood pressure below 120/70 mmHg. In patients whose predialysis blood pressure is <120/70 mmHg, we individualize both blood pressure targets and ultrafiltration goals.

Vascular Access – The most appropriate vascular access for dialysis is based on center-specific experience and complication rates. An international observational study found minimal complications associated with tunneled central venous catheters, while arteriovenous fistulas constructed and used during pregnancy had no impact on maternal or fetal outcomes [33].

Anticoagulation – Heparin is considered safe to use for anticoagulation in pregnancy (table 2). (See "Use of anticoagulants during pregnancy and postpartum".)

Peritoneal dialysis — During early stages of pregnancy, intensive dialysis may be provided by increasing the volume and number of exchanges. In later stages, the number of exchanges must be increased (preferably with the use of a cycler) to provide sufficient dialysis since the volume is limited by the expanding uterus. In one report, dialysis was provided using an overnight cycler with 8 to 12 one-liter exchanges over 12 to 16 hours, with four additional manual exchanges during the day [34]. By 30 weeks, the overnight cycler provided up to 20 exchanges of 750 mL over 18 hours.

As with patients on hemodialysis, hypokalemia, hypocalcemia, metabolic acidosis, hypophosphatemia, and hypotension should be avoided. These complications are uncommon with peritoneal dialysis. We limit the use of hypertonic solutions (either 4.25 percent or icodextrin) as much as possible.

Hypertension — Specific blood pressure targets for pregnant patients on dialysis have not been defined [35]. The postdialysis target for nonpregnant patients on dialysis is <140/90 mmHg. In a 2015 trial (Control of Hypertension in Pregnancy Study [CHIPS]) that randomly assigned pregnant females with normal kidney function and gestational or chronic hypertension to diastolic blood pressure treatment targets of 85 or 100 mmHg, there were no differences in maternal, fetal, or neonatal outcomes for the two blood pressure targets, although fewer females in the lower diastolic blood pressure target group developed severe hypertension [36]. In a subsequent randomized trial (Chronic Hypertension and Pregnancy [CHAP] Study) in females with mild chronic hypertension and normal kidney function, a strategy of targeting a blood pressure of less than 140/90 mmHg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small for gestational age birth weight [37]. Neither study included patients on dialysis. (See "Treatment of hypertension in pregnant and postpartum patients".)

The use of blood pressure medications is common among patients with ESKD. Optimal agents for use during pregnancy are discussed elsewhere. (See "Treatment of hypertension in pregnant and postpartum patients".)

Metabolic bone disease — We generally do not need to use phosphate binders during pregnancy, although they are not contraindicated. Hyperphosphatemia is rarely observed because patients are dialyzed almost daily. If phosphate binders are required, then calcium carbonate is preferred as there are limited pregnancy data with respect to other phosphate binders (eg, sevelamer, lanthanum carbonate, calcium acetate). Phosphate binders may reduce the absorption of fat-soluble vitamins and folic acid.

Calcitriol may be used before and during pregnancy, and the indications are the same as for the nonpregnant patient with CKD. (See "Management of secondary hyperparathyroidism in adult nondialysis patients with chronic kidney disease", section on 'Treat persistent and progressive hyperparathyroidism'.)

We generally do not use cinacalcet during pregnancy, because there are limited data regarding safety.

Treatment of anemia — The treatment of anemia among pregnant patients on dialysis is the same as for nonpregnant patients and generally consists of maintaining adequate iron stores and treating with erythropoiesis-stimulating agents (ESAs). ESAs do not cross the placenta because of their large molecular weight.

Pregnant females often require higher doses of ESAs to maintain an adequate red cell mass since the physiologic changes and demands of pregnancy may result in worsening of anemia. The indications and treatment targets for iron and ESAs are the same as for nonpregnant patients on dialysis. (See "Treatment of iron deficiency in patients on dialysis", section on 'Indications' and "Treatment of anemia in patients on dialysis", section on 'Target Hb levels'.)

We give intravenous iron preparations as necessary to maintain adequate iron stores. We and most dialysis centers in the United States use iron sucrose given its favorable safety profile compared with alternate preparations. Preparations other than iron sucrose, such as iron gluconate, may contain benzyl alcohol, which can pass into breast milk. (See "Treatment of iron deficiency in patients on dialysis", section on 'Indications'.)

POSTPARTUM CARE — Routine postpartum care is similar for females on dialysis compared with those with normal kidney function. One exception is that ibuprofen and related nonsteroidal antiinflammatory drugs (NSAIDs) are generally avoided, particularly for females who have some residual kidney function. We continue erythropoiesis-stimulating agents (ESAs) and intravenous iron as needed. There are no contraindications to breastfeeding among patients on dialysis. It is important to avoid aggressive ultrafiltration with dialysis as volume depletion may interfere with breastfeeding. (See "Overview of the postpartum period: Normal physiology and routine maternal care".)

Hypertension should be treated with medications that are considered safe for breastfeeding, such as labetalol, nifedipine, and angiotensin-converting enzyme (ACE) inhibitors that do not get into breast milk (eg, captopril, enalapril, or quinapril) [24,25]. We do not use angiotensin receptor blockers (ARBs), as they have not been adequately studied.

Postpartum, many females will resume their prepregnancy, three-times-weekly dialysis schedules as the intensive schedules recommended during pregnancy are difficult to maintain.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults" and "Society guideline links: Dialysis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topic (see "Patient education: Systemic lupus erythematosus and pregnancy (Beyond the Basics)").

SUMMARY AND RECOMMENDATIONS

Epidemiology – While females on dialysis may have erratic and/or absent menstrual cycles, pregnancy still occurs. The reported frequency of conception among females of childbearing age on dialysis ranges from 0.3 to 2.2 percent per year. (See 'Epidemiology' above.)

Obstetric outcomes – Patients on dialysis historically have had dismal pregnancy outcomes, but these have improved with better delivery of dialysis and neonatal care. Adverse maternal outcomes include higher rates of preeclampsia, induction of labor, and cesarean delivery. Adverse fetal outcomes include stillbirth, preterm birth, and low birth weight. (See 'Obstetric outcomes' above.)

Preconception care

Contraception – As pregnancy in females undergoing dialysis is associated with increased maternal and fetal risks, contraceptive counseling is an active part of preconception care. We discuss contraception with all females with reproductive potential and advise contraceptive use until pregnancy is actively planned. Options for contraception in females with end-stage kidney disease (ESKD) are the same as in the general population, although some contraceptive methods are less preferred because of the markedly increased cardiovascular risk in patients with ESKD. (See 'Contraception' above.)

Timing of conception and baseline evaluation – The decision to proceed with or delay conception is highly individualized and is impacted by the baseline health of the woman, the woman's age, and the anticipated wait time for a donor kidney, if applicable. The possibility of pregnancy should be discussed with all females who are on dialysis and are in childbearing years. Among females who wish to conceive, we discuss the optimal timing of conception, perform a baseline evaluation, and assess the compatibility of their medications with pregnancy. (See 'Timing of conception' above and 'Baseline evaluation' above and 'Management of medications' above.)

Management during pregnancy

Monitoring – Pregnant females with ESKD on dialysis should be monitored jointly by a nephrologist and by a maternal-fetal medicine specialist familiar with the management of dialysis in a pregnant woman. Our approach is defined above. (See 'Monitoring during pregnancy' above.)

Prevention of preeclampsia – Patients with ESKD on dialysis are considered to be at high risk for preeclampsia. Low-dose aspirin therapy has been shown to decrease the risk of preeclampsia in females at moderate to high risk of the disease, but studies have not included patients with ESKD. In pregnant patients with ESKD, we weigh the potential risks and benefits of low-dose aspirin therapy and offer treatment to those without any contraindications to aspirin use. (See 'Prevention of preeclampsia' above.)

Preferred dialysis modality – We suggest hemodialysis rather than peritoneal dialysis for females who wish to become, or are, pregnant (Grade 2B). The pregnancy rate is lower among patients on peritoneal dialysis compared with hemodialysis, and there appears to be a higher rate of small for gestational age (SGA) pregnancies among patients on peritoneal dialysis compared with hemodialysis. (See 'Preferred modality' above.)

Dialysis prescription – The dialysis prescription is adjusted as soon as possible after conception. For all patients on dialysis, we recommend intensification of the dialysis regimen rather than continuing standard dialysis dosing (Grade 1C). Providing more dialysis increases the chances of live birth. For patients on hemodialysis who do not have residual kidney function, we target ≥36 hours dialysis per week. This may be modified for patients with residual kidney function. Our approach is defined above. (See 'Hemodialysis' above.)

For patients who choose to remain on peritoneal dialysis, intensive dialysis may be provided by increasing the volume and number of exchanges. In later stages of pregnancy, the number of exchanges must be increased (preferably with the use of a cycler) to provide sufficient dialysis since the volume is limited by the expanding uterus. (See 'Peritoneal dialysis' above.)

Postpartum care – Routine postpartum care is similar for females on dialysis compared with those with normal kidney function. There are no contraindications to breastfeeding among patients on dialysis. (See 'Postpartum care' above.)

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References

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