What is bartter syndrome? 

Bartter syndrome is a rare, genetically inherited kidney disorder that affects around 1 in 1,000,000 individuals in the UK.¹ Bartter syndrome, also known as salt-wasting nephropathy, causes the kidneys to be unable to reabsorb enough salt, leading to its loss in urine. Thus resulting in an imbalance of fundamental electrolytes, including sodium, chloride and potassium, and fluid levels in the body.²

Pregnancy 

During pregnancy, the body experiences a significant rise in hormones and a 50% increase in body fluids.³ The increase in fluid provides the nutrients needed to support the growth and development of the baby and placenta. Fluid retention occurs in pregnancy due to hormonal changes, resulting in a greater demand on the kidneys and electrolytes to support increased body fluid volume and the baby’s growth. 

Why does awareness of bartter syndrome matter?

In some instances, Bartter Syndrome may become apparent during pregnancy and manifest as polyhydramnios- a pregnancy complication characterised by an increased volume of amniotic fluid. Although rare, the condition requires prompt recognition and thorough management due to the complications it can cause to both mother and baby, such as increasing the risk of premature birth.⁴ Thus highlighting the importance of awareness of the condition. 

Due to the rarity of the disorder, there is limited research, as fewer patients are available to conduct large-scale studies to collect long-term prognosis and management data.  

This article aims to increase awareness of Bartter Syndrome regarding pregnancy and discuss the challenges and management associated with the condition. 

Types and causes of bartter syndrome 

There are two primary forms of Bartter syndrome - classic Bartter syndrome and antenatal Bartter syndrome - classified by the age of onset and severity of the condition. Bartter syndrome is classified by the location of the genetic mutations¹ and these are referred to as Types I, II, III, IV and V.  

Classic bartter syndrome

Also referred to as type III Bartter syndrome, classic Bartter syndrome is caused by a genetic mutation in the CLCNKB gene, which encodes proteins crucial for salt reabsorption and blood pressure regulation.⁵ Classic Bartter syndrome usually presents in early childhood with symptoms of dehydration, polyuria (frequent urination), constipation, and low muscle tone (muscular hypotonia).⁶ Classic Bartter syndrome is less severe and has a later onset than antenatal (neonatal) Bartter syndrome, but it can still affect growth and development. 

Antenatal bartter syndrome

Antenatal Bartter syndrome is associated with multiple genetic mutations and is classified into types I, II, and IV. Antenatal Bartter syndrome is more severe than classic Bartter syndrome, as it begins before birth and can be life-threatening. In mothers, symptoms typically present with unexplained excess amniotic fluid (polyhydramnios) that can lead to premature delivery, where fetal symptoms involve polyuria, premature birth, restricted growth and dehydration.⁷

Bartter syndrome and gitelman syndrome 

Both Bartter syndrome and Gitelman syndrome are similar, rare inherited kidney disorders that present with similar symptoms. The location of the genes affected distinguishes the conditions. Bartter syndrome arises from mutations affecting the thick ascending loop of Henle (a part of the kidney's filtering system that transports salt out of the filtrate, diluting it and increasing the salt concentration in the kidneys to allow for the reabsorption of water and the production of concentrated urine). 

Alternatively, Gitelman syndrome arises due to mutations in the distal convoluted tubule, which plays an essential role in the kidney's filtering system and regulates electrolyte balance and fluid volume via selective absorption of sodium, chloride, calcium, and water.⁸

Pathophysiology of bartter syndrome in relation to pregnancy

The molecular defect in all types of Bartter syndrome impairs salt (sodium chloride) reabsorption in the kidneys. Thus resulting in salt wasting and, consequently, hypokalemic (low potassium) and hypochloremic alkalosis (extreme loss of chloride, causing too much bicarbonate to be present in the blood), and dehydration.⁹ During pregnancy, there is an increase in renal workload, and with the addition of Bartter syndrome, impaired salt reabsorption function can increase the risk of dehydration, electrolyte imbalances and potentially premature birth. Additionally, hormonal changes during pregnancy can exacerbate the challenge of managing increased potassium and magnesium loss through the kidneys.

Challenges during pregnancy

Maternal challenges 

During pregnancy, there is an increased need for potassium in the body to allow for the expansion of blood volume and bodily fluids and to maintain adequate nerve and muscle function; however, Bartter syndrome causes a loss of potassium, leading to hypokalemia. This is challenging for the mother as this can lead to symptoms of muscle weakness, cardiac arrhythmias, and in some cases paralysis.¹⁰ Similarly, Bartter syndrome causes imbalances in other electrolytes, including excessive loss of sodium and chloride, and this increased salt and water loss and subsequent reduced water reabsorption can cause severe dehydration and excessive thirst in the mother. Simultaneously, reduced blood and bodily fluid volume can directly affect blood pressure and increase the risk of hypotension.¹

Fetal challenges

In addition, the fetus faces several challenges because the body does not reabsorb crucial electrolytes. These challenges include intrauterine growth restriction (IUGR) and an increased risk of preterm labour due to increased water and salt loss, which consequently leads to increased urination (polyuria). The polyuria creates extra amniotic fluid, which then puts pressure on the uterus and therefore increases the risk of preterm labour.¹¹

Diagnosis in pregnancy 

Diagnosis of Bartter syndrome is made through a combination of detailed clinical history, laboratory testing, and physical examination. A thorough review of medical history includes identifying growth delays, muscle weakness, polyuria, and vomiting. 

Laboratory investigations to diagnose the condition involve analysing amniotic fluid for high chloride levels and normal potassium levels. Other lab tests may involve maternal blood and urine tests to measure electrolyte levels and kidney function.¹²

Differential diagnosis for Bartter syndrome includes other causes of hypokalemic, hypochloremic metabolic alkalosis that could be related to Gitelman syndrome.¹³ Similarly, symptoms of pre-eclampsia also manifest as polyhydramnios and restricted fetal growth.

Management strategies 

Multidisciplinary team

Multidisciplinary teams are an essential part of managing Bartter syndrome in pregnancy due to the rare and complex nature of the condition and its range of effects on both mother and fetus. This team may involve obstetricians, nephrologists and endocrinologists to provide specialised care for both individuals. 

Electrolyte replacement

Additional management of Bartter syndrome includes close monitoring of electrolytes and subsequent electrolyte replacement to supplement losses of sodium, magnesium, and potassium, either through oral supplements or, in more severe cases, intravenous fluids.¹⁴

Drug-based treatment

Other management of Bartter syndrome involves symptom-targeted treatment such as nonsteroidal anti-inflammatory drugs (NSAIDs) that reduce the excretion of electrolytes and decrease the urine output, although with NSAIDs there are associated side effects of perforated intestinal tract, so a combination of other drugs, such as stomach acid blockers, is recommended.¹² Additional drugs called potassium-sparing diuretics may be given, as they increase the excretion of sodium whilst retaining potassium and acid, thus regulating potassium levels and preventing alkalosis. A supplement of sodium chloride may be needed to balance and compensate for the sodium chloride excreted.

Hydration and diet

Adequate salt and water intake is crucial for managing Bartter syndrome, helping compensate for excessive water loss and preventing dehydration. Individuals with Bartter syndrome commonly have an increased craving for a high salt diet, and in some cases, are recommended to indulge in this to increase the levels in the body.¹⁵

Monitoring fetal health

Monitoring fetal health is crucial for detecting and managing polyhydramnios as well as for monitoring and regulating treatment. Monitoring the health of the fetus efficiently prevents further complications of preterm labour, which is a common associated risk of Bartter syndrome. Monitoring may involve regular ultrasounds, non-stress tests and growth scans. 

Delivery and postpartum considerations 

Timing of delivery

Timing of delivery should be carefully considered and monitored based on both maternal and fetal health, due to the associated risks of polyhydramnios arising during pregnancy and the subsequent risk of preterm labour from the pressure on the maternal uterus. 

Labour management

Electrolyte levels should be monitored during labour, as low levels of sodium increase oxytocin levels and excessive fluid intake during labour can lead to hyponatraemia. Hypothermia causes confusion and seizures in both mother and baby, and in severe cases, maternal death.¹⁶

Potassium-sparing diuretics should be avoided during labour as these are usually accompanied by low blood pressure, which can negatively impact the defective kidney and heart function. 

Postpartum care

Continuous electrolyte management should be considered during postpartum care, as the mother's body will need to readjust to normal body fluid levels to prevent further complications such as hypokalemia (low potassium), which results in fatigue, muscle weakness, and cramping. Similarly, the baby should also be monitored for electrolyte disturbances following birth as the imbalance can result in a cascade of high-risk complications, such as cardiac arrhythmias, dehydration and neurological issues.¹⁷

Prognosis and counselling

Individuals with Bartter syndrome generally have a favourable maternal prognosis when the condition is managed efficiently, via electrolyte and renal function monitoring. The baby has increased risks of complications as a consequence of premature birth and a lower birth weight, highlighting the importance of obstetric surveillance. 

Genetic counselling may be beneficial to discuss the autosomal recessive mode of inheritance of the condition, as this means there is a 25% recurrence risk if both parents are carriers. This is also beneficial for providing guidance and support in future pregnancy planning, thereby improving both maternal and fetal outcomes. 

Summary 

Bartter syndrome and pregnancy present high-risk complications; however, they can be managed with appropriate care. The kidney disorder directly impacts electrolyte and fluid balance, which gives rise to challenges that affect both maternal and fetal health, including the risk of dehydration, premature labour, and restricted growth. Early diagnosis, regular monitoring, and a tailored care plan are essential for reducing the risks posed by these challenges. The successful management of Bartter syndrome relies on the efficacy of a multidisciplinary team approach to allow support and achieve the best outcomes for mother and fetus, both antenatally and postnatally. Ultimately, teamwork and timely intervention are crucial for the health outcome of mother and baby.