The medically complex pregnant patient

Abstract

In our contemporary society, where medical advancements occur daily, many women with complex medical conditions are becoming pregnant and successfully carrying pregnancies to term. We report a case of a complicated, unplanned pregnancy in a newly initiated haemodialysis patient. The patient presented with breathlessness and was discovered to be 13 weeks pregnant while also being diagnosed with bilateral pulmonary embolisms. Unfortunately, she later developed pregnancy-induced complications that required her to remain hospitalised throughout her entire pregnancy. This case illustrates the complex care needed to manage a pregnant woman with multiple co-morbidities. It emphasises the importance of pre-pregnancy counselling and optimizing care among women of childbearing age who have complex medical backgrounds. Such awareness is crucial for both physicians and obstetricians.

Introduction

The prevalence of chronic diseases is increasing among young adults aged 18–34, with obesity and hypertension among the most common conditions. ¹ As more women delay pregnancy, the incidence of medical disorders during pregnancy rises, often due to pre-existing conditions.

We present the inpatient journey of a pregnant woman in her 30s with end-stage renal disease (ESRD) secondary to diabetic kidney disease (DKD).

Case report

A 34-year-old woman presented to the hospital with worsening dyspnea over the past 3 days. She was found to be 13 weeks pregnant and diagnosed with bilateral, large pulmonary embolisms. Her medical history is significant for ESRD, with an estimated glomerular filtration rate of less than 15 mL/min (eGFR), secondary to DKD. She was initiated on haemodialysis (HD) via a right internal jugular vein (IJV) permcath 8 months prior. She also suffers from poorly controlled type II diabetes mellitus (DM), with a hemoglobin A1c (HbA1C) of 8%, hypertension (HTN), and obesity, with a body mass index (BMI) of 34 kg/m². Additionally, she has mixed anaemia due to chronic disease and iron deficiency.

Obstetric history was notable for three non-consecutive first-trimester miscarriages with negative results for anti-phospholipid antibodies, one termination of pregnancy, and one intrauterine death at 39 weeks gestation which was attributed to poorly controlled type II DM.

She was admitted under the care of a maternal medicine internist in the high-dependency unit (HDU) and was managed by a multidisciplinary team that included obstetrics, nephrology, and haematology specialists. Upon examination, she was tachypnoeic, with a respiratory rate of 22 breaths per minute. Her pulse rate ranged from 90 to 115 beats per minute (bpm), her blood pressure (BP) was between 160 and 180 mmHg systolic and in the 90 s diastolic, and her oxygen saturation was 100% on 2 L of supplemental oxygen.

She was initially placed on intravenous (IV) unfractionated heparin (UFH) for two reasons: its shorter half-life, which provided flexibility in case surgical intervention was required after further investigations, and its slight advantage over low molecular weight heparin (LMWH) in patients with ESRD, as UFH is cleared by both the kidneys and liver.

A transthoracic echocardiogram revealed a 5 cm thrombus adherent to the right atrium, extending to the interatrial septum. Her pulmonary artery systolic pressure (PASP) was 43 mmHg, suggesting an intermediate probability of pulmonary hypertension. Given the location and size of the thrombus, the medical team concluded that disrupting anticoagulation to remove the permcath was high risk, as it could lead to further thrombus progression or fragmentation, potentially causing sudden maternal collapse. There was no immediate indication for thrombectomy, as she was haemodynamically stable.

She remained on IV UFH for 2 weeks, after which she was switched to subcutaneous LMWH following confirmation that no surgical intervention was required and after thoroughly discussing the pros and cons of both options with the patient. Her heart rate improved to 80–100 bpm, and she was able to wean off supplemental oxygen.

Her HD sessions were increased to six weekly sessions of 240 min each, which she tolerated well. This adjustment led to a reduction in her urea levels from a baseline of 13–15 mmol/L to 8–10 mmol/L. She received IV iron injections during her HD sessions and underwent a blood transfusion when her haemoglobin (Hb) dropped below 8.0 g/L. Her blood glucose levels were well managed with insulin.

The patient’s BP was challenging to control and was managed with IV Labetalol and oral Nifedipine LA while in the HDU. She then required a combination of four oral BP medications—Labetalol, Nifedipine LA, Methyldopa, and Hydralazine—to maintain her BP below 140/90 mmHg. Despite these challenges, she remained asymptomatic and underwent monthly foetal ultrasounds (US) with Doppler studies, which initially showed normal growth of the baby.

From week 26 onward, her systolic BP surpassed 200 mmHg despite four BP medications. At 27 weeks and 5 days of gestation, a repeat foetal Doppler US revealed intrauterine growth restriction (IUGR) with increased placental resistance, and central redistribution. Pre-eclampsia (PE) biomarkers, specifically placental growth factor (PlGF), were measured and returned low for her gestational age, suggesting a higher likelihood of developing PE and a potential cause of the IUGR. There was no evidence of haemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.

Due to the rising systolic BP, abnormal Doppler results, and low PlGF, the patient was diagnosed with early-onset PE and prepared for delivery. She was transitioned back to IV UFH and underwent a caesarean section at 28 weeks and 5 days, delivering a healthy male infant.

She was discharged on the eighth postoperative day with three antihypertensive medications and resumed her usual three weekly hemodialysis sessions.

Discussion

Pregnancy in women with ESRD is uncommon, primarily due to declining fertility as the eGFR falls below 15 mL/min. Infertility results from several factors, including sexual dysfunction stemming from a negative body image, low libido, anovulation, and altered hormonal patterns. The hypothalamic-pituitary-gonadal axis is disrupted, leading to elevated luteinizing hormone levels and a lack of cyclical release needed for ovulation. Additionally, uterine atrophy occurs due to lower estradiol and progesterone levels caused by uraemia, and the decreased clearance of prolactin by the kidneys further inhibits ovulation.^2,3

However, studies have shown that since the introduction of dialysis, more women with ESRD have experienced successful pregnancies with live births. In recent years, the success rates have increased to as high as 80%, with longer gestational periods, due to intensified dialysis regimens and the widespread use of erythropoietin-stimulating agents (ESA).^2,4 In contrast, data on women undergoing peritoneal dialysis (PD) are less promising. Studies indicate a significantly lower conception rate on PD, potentially due to the hypothesized impact of hypertonic dialysate on normal ovulation. ⁵

Diagnosing pregnancy in women with ESRD can be challenging due to irregular menstrual cycles and amenorrhoea. About 30% of beta-human chorionic gonadotropin (β-hCG) is cleared by the kidneys and inversely correlates with creatinine levels, which can lead to false positive serum pregnancy tests. Thus, confirming pregnancy through US is advisable in women with ESRD.^2,5–7

Managing pregnancy in women with ESRD requires a detailed strategy. First, potential teratogenic medications like angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), cinacalcet, and statins should be discontinued. Folic acid intake should be increased to 5 mg, and water-soluble vitamin dosages should be doubled due to their clearance through intensified hemodialysis regimens.^2,6

Post-dialysis BP targets should be below 140/90 mmHg, with minimal shifts in maternal intravascular volumes to ensure consistent foetaplacental blood flow. ⁵ BP medications commonly used in pregnancy include Nifedipine, Labetalol, Hydralazine, Doxazosin, and Methyldopa.^3,5,6,8

Erythropoietin-stimulating agents should be continued to maintain Hb levels between 100 and 110 g/L.^9,10 Iron deficiency is common in pregnancy, and IV formulations like sucrose and ferric carboxymaltose are used when necessary.^11,12 Phosphate binders should be discontinued and replaced with calcium-based alternatives.^2–6

Current evidence indicates that an intensified HD regimen (>36 h/week) allows for gentler fluid removal, leading to improved BP control and foetal outcomes.^2,9 This regimen also enhances urea clearance. Luders et al. studied 93 pregnancies in women on HD and recommended a mid-week pre-dialysis urea target of <12.5 mmol/L to help adjust dialysis regimens, which led to distinguishing adverse composite foetal outcomes.^9,13 Better volume management and solute clearance could potentially reduce the rates of polyhydramnios, premature membrane rupture, and preterm labor resulting in more successful live births. ⁵

In women with ESRD, the risk of PE increases approximately tenfold. ⁹ Although low-dose aspirin is well established for preterm PE prophylaxis in the general population, its effectiveness in women undergoing dialysis lacks strong data. Moreover, the concurrent use of heparin during hemodialysis and potential underlying platelet dysfunction can raise the risk of bleeding. Therefore, initiating aspirin should be carefully considered on an individual basis.^2,5

The standard definition of PE cannot be applied to pregnant women with ESRD due to the prevalence of chronic HTN, pre-existing proteinuria, or anuria. Therefore, heightened surveillance of symptoms like headaches, blurred vision, and right upper quadrant pain, coupled with IUGR on foetal US and impaired uterine artery flow on Doppler pulsatility, is crucial for early detection of PE in this population.^3,6

Emerging novel biomarkers in the field of PE have proven to be useful tools in diagnosing superimposed PE. High serum concentrations of soluble fms-like tyrosine kinase (sFlt-1) and low levels of placental growth factor (PlGF) can predict PE before clinical symptoms appear in the general population.^8,14 A longitudinal cohort study by Bramham et al. found that PlGF levels below the fifth percentile have strong diagnostic accuracy for superimposed PE requiring delivery within 14 days in women with established hypertension and CKD. Sensitivity is highest between 25 + 0 and 28 + 6 weeks of gestation. ¹⁵

Conclusion

In conclusion, this case highlights the complex medical journey of a pregnant woman with ESRD secondary to DKD. Her experience underscores the importance of vigilant surveillance and comprehensive multidisciplinary care. It also emphasizes the need for comprehensive pre-pregnancy care in women with ESRD, including better management of type II DM, HTN, and weight, as well as counselling on renal transplantation before conception to minimize potential complications.

As healthcare evolves and high-risk pregnancies become more prevalent, managing these cases requires an approach beyond traditional obstetrics. The expanding field of maternal medicine demands that physicians rise to the challenge, providing holistic, multidisciplinary care that ensures the best possible outcomes. Every woman of childbearing age with a pre-existing medical condition should receive individualised, detailed pre-pregnancy counselling to understand the full implications of pregnancy for herself and her foetus.