In utero growth restriction environment among end-stage kidney disease: Pre-term low-weight baby

INTRODUCTION

Women with end-stage kidney disease (ESKD) rarely become pregnant.^[1] The incidence of pregnancy among women on dialysis is between 0.3% and 2.2%/year with higher rates observed in those who have preserved residual kidney function and have undergone shorter durations of long-term dialysis.^[2]

Pregnancy in women with ESKD carries a higher risk of morbidity for both the mother and fetus, along with an elevated death rate compared to women with normal renal function.^[1] Although pregnancy in women with ESKD has dismal outcomes and significantly considered a high risk, a successful pregnancy is not impossible.^[2]

Chronic kidney disease (CKD) is increasingly rising in Oman. About 1% of the people have severe renal failure with a glomerular filtration rate (GFR) of <30 mL/min/1.73 m².^[3,4] Furthermore, almost 10% of the people have moderate kidney failure between 30 and 60 mL/min/1.73 m².

In addition, almost 30% of the population has mild kidney dysfunction with GFR between 60 and <90 mL/min/1.73 m². Furthermore, there are almost four thousand of the population on dialysis and almost three thousand functioning grafts.^[3,4] The dialysis population in our region, specifically in Oman, is quite young compared to Europe, Japan, and North America.^[5-8] A good percentage of this specific population is eager to have children and make up their families within their community and the country at large.

The present paper reports the case of a 36-year-old woman who got pregnant while on peritoneal dialysis (PD) and delivered successfully, despite being anuric and of advanced age for pregnancy.

CASE REPORT

Our patient is a 36-year-old with ESKD and has three healthy children. She has been on continuous ambulatory PD (CAPD) since October 2015. Her gestational history includes three prior spontaneous vaginal deliveries and one missed abortion at 11 weeks.

CKD was diagnosed incidentally in March 2007 with an unknown etiology, persistent high blood pressure, and proteinuria. She started to follow up with a nephrologist. A kidney biopsy was not performed as her kidney failure was discovered late, with findings of small kidneys and decreased cortico-medullary differentiation.

Her laboratory parameters at the time of initial discovery were as follows: Creatinine (160 μmol/L), urea (11.2 mmol/L), Na (132 mmol/L), K (3.9 mmol/L), CO₂ (19 mmol/L), hemoglobin (Hb) (10.1 g/dL), calcium (2.1 mmol/L), phosphorus (1.5 mmol/L), and albumin (32 g/L). Furthermore, her autoimmune and viral serology were as follows: Antinuclear antibody negative, anti-dsDNA negative, complement normal, and viral serology (including hepatitis and human immunodeficiency virus) was negative.

The kidney ultrasound at the time of initial diagnosis was reported as follows: Both kidneys were normal in shape and position, but small (right kidney 8.6 × 3.1 cm, left kidney 9.3 × 4 cm), and increased cortical echogenicity was seen in both kidneys. There were no focal lesions, and there were no calculi or hydronephrosis changes.

Unfortunately, she gradually progressed to ESKD and started on hemodialysis (HD) in October 2011, attending dialysis sessions regularly 3 times weekly. Dialysis was initially done through a right tunneled internal jugular vein catheter. In February 2012, a left arteriovenous fistula (AVF) was created and later used as permanent vascular access upon maturation.

She underwent a non-related kidney transplantation in April 2013. Unfortunately, 2 years later, she lost graft function due to chronic rejection. As a result, she resumed kidney replacement therapy (KRT) with regular HD through AVF in May 2015. However, she chose to switch to PD, as the modality of KRT. A PD catheter was inserted in September 2015, and PD was initiated in October 2015. Her medications were carvedilol 25 mg twice a day (BID), a ß-adrenergic receptor antagonist (blocks ß1 and ß2 receptors), alfacalcidol 4 μg twice per week, a vitamin D analog, ranitidine 150 mg BID, a histamine-2 blocker, erythrocyte stimulating agent- erythropoiesis-stimulating agents (ESA) (darbepoetin) 40 μg s.c (subcutaneously) every week, an erythropoietin analog, and cinacalcet 30 mg once daily, acts as a calcimimetic by allosteric activation of the calcium-sensing receptor.

She was doing well on CAPD, with a PD prescription of three 2 L exchanges/day, using 1 bag of 1.36%, 1 bag of 2.27%, and 1 bag of icodextrin as exchanges with daily: Total ultrafiltration per day (TUF) 1.2–1.5 L. This PD prescription maintained a Kt/V of >1.7.

At the time she started PD, she was anuric, weighed 46.5 kg, and had regular menstrual cycles. However, almost 2 years later, on August 15, 2017, the patient reported having amenorrhea. Subsequently, an ultrasound confirmed that she was in the 9^th week of gestation.

After providing enough counseling to the patient and her husband concerning the potential adverse outcomes linked to ESKD and pregnancy with advanced age for the mother, they decided to continue with her fifth pregnancy. Intensive HD was offered, but the patient expressed her preference to remain on PD therapy.

A multidisciplinary team approach was instituted to improve the pregnancy environment and minimize the complications of pregnancy. A good counseling regarding the PD complications was explained to the patient, like the risk of peritonitis and the possibility of abdominal discomfort, especially in the last trimester of the pregnancy. The following strategies were taken along with the patient and her partner:

• Intensify PD dose

• Improving Hb using ESA in the form of darbepoetin and IV iron with a proper dose.

• Control blood pressure and volume status

• Diet (adequate supply of calories and protein), by keeping a calorie intake of 30–35 kcal/day and a protein intake of 1.8 g/kg/day

• Decrease intra-abdominal pressure.

She was attending weekly antenatal and PD clinic reviews during her pregnancy. Furthermore, fetal surveillance was done regularly through ultrasound assessment for fetal anatomy and cervical length. A few adjustments were made to the medicines that she was already taking to make sure that there was no contraindication with pregnancy. Cinacalcet was stopped, and we increased the dose of alfacalcidol for better control of secondary hyperparathyroidism.

She remained on her initial PD prescription until the 9^th week of gestation, when her pregnancy was discovered. At that point, her prescription was changed to CAPD four cycles with 2 L fill volume (2 low concentration, 1 medium concentration, and 1 icodextrin concentration). She tolerated this regimen until the 13^th week of gestation, when the patient could not handle the fill volume, so she was converted to continuous cycler PD for the remainder of the pregnancy, with the fill volume adjusted based on her tolerance.

Her total Kt/v during pregnancy ranged between 2.3 and 3.4, with daily TUF ranging from 1.0 to 1.5 L/day, as shown in Table 1.

Figure 1 shows that her blood pressure remained well controlled, and the values ranged between 120 and 140 systolic and diastolic of 80–90 mmHg with antihypertensive medication including labetalol 100 mg twice/day, a combined alpha- and beta-adrenoceptor blocking agent, and nifedipine 20 mg twice/day, a calcium channel blocker. Figure 1 shows the progress of her body weight over the course of her pregnancy. Figure 2 shows that her Hb was also well maintained between 10 and 12 g/dL on ESA (darbepoetin) with correction of iron deficiency. Furthermore, her creatinine, potassium, calcium, and phosphate levels were steady throughout her pregnancy, as shown in Figures 2 and 3. In addition, her serum albumin levels stayed between 20 and 30 g/L, as shown in Figure 2 and Table 2.

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Figure 1:

Blood pressure profile and body weight profile during pregnancy period.

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Figure 2:

Hemoglobulin levels, serum albumin levels and serum creatinine levels during pregnancy period.

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Figure 3:

Serum calcium levels, phosphate levels and potassium levels during pregnancy period.

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Her obstetric follow-up remained uneventful. The in utero growth assessment was done at 33 weeks of gestation with a scan type called trans-abdominal sonography and reported as follows: Gestational age of 33 weeks, heartbeat was present (yes), the presentation was cephalic, and fetal weight was 1949 g. Amniotic fluid was reported as normal, and the placenta was stated as high anterior. The fetal activity was assessed as follows: Breath movement was present (yes), limb movement was present (yes), body movement was present (yes), and the amniotic fluid index (AFI) was 16 mm.

During her weekly antenatal follow-up, an antenatal scan revealed abnormal findings suggesting a high risk for intrauterine fetal demise. It showed a single viable fetus, of cephalic presentation, a normal AFI of 15 cm, a high placenta position, with an estimated fetal weight of 2.1 kg. Furthermore, it showed dilated bowel loops. In addition, an abnormal Doppler showed an umbilical artery with an absence of reverse-end diastolic flow. However, the carotid artery doppler showed a low resistance indicating a brain-sparing effect; in addition, her laboratory tests showed high urea (20 mmol/L), which reflects a negative impact on the fetus.

After discussion with the patient and her partner, the multidisciplinary team decided to proceed with a lower-segment cesarean section. The PD catheter was not removed.

She delivered a baby girl with a weight of 1.5 kg with an Apgar score of 8–9 at the time of delivery. The premature baby of very low birth weight was escorted to the special care baby unit, but she did not require active resuscitation, apart from nasal continuous positive airway pressure (CPAP) for a short time, with a positive end-expiratory pressure (PEEP) of 6, (fraction of inspired oxygen) FIO2 of 30%. The baby was discharged home after 2 weeks in good health.

The mother and her baby were both well, and the mother resumed her usual CAPD regimen without complications.

DISCUSSION

The present case illustrates the possibility of conception, maintenance of gestation, and delivery of a healthy baby in a unique group of the community that wishes to contribute to the development of their family. The success of such a pregnancy requires close follow-up by a multidisciplinary team and improvement of the prenatal environment to sustain the baby’s life in utero. “Potential factors for a successful pregnancy may include enhancing dialysis-related care, such as achieving an adequate dialysis dose, advancements in the treatment of anemia through the use of ESAs, early pregnancy diagnosis, and, finally, a suitable multidisciplinary approach involving gynecologists, nephrologists, nurses, and dietitians.”^[2,9,10]

Reduced fertility is frequent in females with ESKD, and sterility may reach over 90% of all cases.^[1,11,12] Many causes of infertility are mentioned in ESKD women, like anovulation and endocrine complications.^[10,13] Moreover, even in cases of a successful pregnancy in women who have ESKD, there is a high risk of deleterious complications for both the mother and fetus.^[12] This is why we closely monitor those mothers during pregnancies, yet the reported frequency of conception and successful delivery among women of reproductive age on dialysis seems to be rising.^[2,12,14] Pregnancy during dialysis is a challenging case, and to reach a successful pregnancy and delivery, it is essential to maintain adequate dialysis, proper hemodynamic stability, well follow-up, and management of obstetric complications, as well as maintain a target Hb range and correction of malnutrition.^[10,14,15] Hence, pregnant women who have ESKD on dialysis should be observed closely by a nephrologist and by a multidisciplinary team aware of the dialysis approach in this group of patients.^[9,12,16]

Both modalities of dialysis, PD and HD, can be used during pregnancy in dialysis patients.^[17,18] While HD allows for accurate control of fluids, it can potentially result in substantial hemodynamic instability and changes in blood pressure, which can affect the placental circulation. PD can result in a smoother dialysis, with a little change in the mother’s blood volume. Moreover, no requirement for anticoagulation in the PD modality, and PD enables a more unrestricted diet to maintain the nutrition of the mother Table 3.

Researchers suggest that women who want to become or are currently pregnant should be put on HD instead of PD (Grade 2B).^[9,10,19] The rate of conception is reduced in women who are on PD in comparison to those who are on HD.^[12,17,20] Babies born to patients on dialysis may end up having very low birth weight.^[20-22]

Women who prefer to continue PD intensify dialysis are required to reach an adequate Kt/V by increasing the volume and number of exchanges. During the last period of pregnancy, it is reasonable to increase the number of exchanges rather than volume increasing due to uterus enlargement (with use of a cycler) to achieve dialysis adequacy, which should be >1.7/week.^[20,23,24]

During dialysis, maternal pre-dialysis blood urea nitrogen (BUN) levels must be kept below 16 mmol/L, as higher levels are associated with dangerous maternal and fetal complications.^[9,10,14,25] Our patient reached 33 weeks with urea 20 mmol/L, which reflects a negative outcome for the fetus. Blood pressure should be controlled to avoid more complications such as pre-eclampsia using safe and adequate antihypertension medications,^[12,17,26] some of these medications are contraindications in pregnancy, like angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.^[27] Anemia should be managed using erythropoietin and iron to reach a desired Hb level, which is between 10 and 11g/dL, and transferrin saturation above 30%.^[28,29] To avoid malnutrition, it is recommended to keep a calorie intake of 30–35 kcal/day and a protein intake of 1.8 g/kg/day.^[31,32] As we mentioned above, the follow-up should be closed and intensified by nephrologist and obstetrician for both the mother and fetus.^{[10,17,32,33]} Our patient’s pregnancy diagnosis was made early in the 9^th week. During pregnancy, the patient, unfortunately, was anuric, but BUN levels were 16 mmol/L, blood pressure was controlled, and Hb was within target.

An emergency C-section was done for our patient due to abnormal antenatal scan findings. Fortunately, the cesarean section had no complications, but a premature, low-weight female baby was delivered (1.5 kg).

ESKD is one of the many causes of infertility in women in the childbearing age,^[34-36] but with the improvement of dialysis adequacy and the development of pregnant patients’ care, the rate of conception rises in women on dialysis.^[10-12] The risk of mortality and morbidity in pregnant women undergoing PD is still high.^[20,34,37] Therefore, pregnancy needs to be diagnosed early, with intensive dialysis, adequate calorie and protein intake, and regular fetal monitoring during pregnancy to ensure successful delivery with the lowest complications while maintaining PD.^[10,34,38]

CONCLUSION

Both modalities of dialysis, PD and HD, can be used during pregnancy in dialysis patients.^[17,18] The rate of conception is reduced in women who are on PD in comparison to those who are on HD. Suitable cooperation and support between the patient’s family and the healthcare team is very important in guaranteeing an uneventful pregnancy while on PD. Thus, these types of patients should not be put down if they wish to get pregnant, even if they are already on dialysis and fall in the group of advanced age for pregnancy.