The patient is an Asian woman in her 30s with no significant medical history and not on regular medication; gravida 2, para 1, was referred to the antenatal diabetic clinic at 9 weeks gestation due to previous gestational diabetes. This article will explore the case of a woman with hyponatraemia and severe gestational hypertriglyceridemia.
Case Presentation
She was not known to have any lipid abnormalities in her previous pregnancy and only has a family history of type 2 diabetes. It was noted she had impaired fasting blood glucose and HbA1c of 41 mmol/mol, which is indicative of gestational diabetes [2].
Metformin 500 mg once daily was commenced together with dietary management to optimise gestational glycaemic control. Dietary management was poorly tolerated due to hyperemesis gravidarum. Basal insulin was introduced at 12 weeks gestation due to persistently elevated blood glucose and this was subsequently optimised to a basal-bolus insulin regimen, with insulin requirements peaking at 40 units daily by 29 weeks gestation. Despite this, foetal growth was normal on ultrasound at 28, 32 and 36 weeks.
The patient was planning a vaginal birth and was due to be induced at 38 weeks gestation. However, at 36+1 weeks’ gestation, the patient presented with reduced foetal movements and a reduction in her insulin requirement, such that she had no insulin requirement for 48 hours prior to the aforementioned presentation. She was then admitted to the labour ward for induction. Her bedside observations and clinical examinations were unremarkable, foetal well-being was satisfactory with the cardiotocograph.
Laboratory Investigations
Unexpectedly during labour, electrolytes revealed severe hyponatraemia of 120 mmol/L, though the patient remained asymptomatic. Inconsistently, venous blood gas revealed normal sodium. A referral to the endocrinology and metabolic medicine teams and advised carrying out detailed biochemical investigations into the cause of hyponatraemia, paying particular interest to the lipid profile.
The patient’s serum cholesterol came back markedly elevated at 34.6 mmol/L (reference range (RR) 0.30–1.80 mmol/L) and triglycerides (TG) were>50 mmol/L (RR 0.3–1.8 mmol/L).
A diagnosis of severe gestational hypertriglyceridemia and pseudo hyponatraemia secondary to severe dyslipidaemia was made. An ultrasound of the abdomen was carried out which showed fatty liver infiltration but no signs of acute pancreatitis.
Treatment Decision and Outcome
After 48 hours of fasting, serum cholesterol and TG levels fell to 24.8 mmol/L and 36.6 mmol/L, respectively. A fat-free diet was commenced as per the recommendation from the diabetic team and dietitian. With continued aggressive dietary modification, by day 12 post-partum, serum cholesterol was 12.6 mmol/L and fasting TG 5.74 mmol/L. Fenofibrate was not initiated as the patient wanted to breastfeed.
At 6 weeks post-discharge, the patient had a normal serum lipid profile and blood glucose levels. With this, the patient reintroduced a normal diet into her lifestyle and both her lipid profile and blood glucose levels remained normal at 6 monthly follow up. She was discharged from follow-up without any further treatment required. The patient was counselled on the high risk of severe hypertriglyceridemia recurring in subsequent pregnancies and that she should inform a health professional before attempting to conceive. However, the patient was not planning any more pregnancies.
Hypertriglyceridemia in pregnancy
Hormonal changes physiologically increase plasma TG levels in pregnancy, particularly in the second and third trimesters [3]. During the second and third trimesters, oestrogen and human placental lactogen levels increase resulting in insulin resistance, increased lipogenesis and increased TG-rich lipoprotein secretion. These metabolic changes usually do not result in adverse clinical outcomes [4].
Severe gestational hypertriglyceridemia is defined as a plasma TG exceeding 11.4 mmol/L, which is associated with an increased risk of pancreatitis [5]. Patients who develop severe gestational hypertriglyceridemia often have predisposing genetic susceptibilities in the TG metabolism pathways. This is either through increased TG production, ineffective lipolysis or decreased hepatic clearance of remnants [6].
Secondary risk factors contributing to severe hypertriglyceridemia include diabetes mellitus (particularly with suboptimal control), hypothyroidism, nephrotic syndrome, alcohol intake and the use of medications such as glucocorticoids, beta-blockers and protease inhibitors [5].
It was deduced that the reduction in insulin requirement was due to a falsely low capillary blood glucose reading caused by hypertriglyceridemia. High TG levels take up volume, decreasing the amount of glucose in the capillary volume [7]. The low serum sodium levels were due to lipemic blood specimens resulting in pseudo hyponatraemia.
Treatment of severe gestational hypertriglyceridemia
There are no published guidelines in the management of severe gestational hypertriglyceridemia and collaboration from obstetrics, endocrinology, metabolic medicine and dietetics is necessary [5, 8]. The goal of treatment is to safely lower plasma TG levels while avoiding maternal and foetal complications, without compromising their nutritional demands. Maternal complications include hypertriglyceridemia-induced pancreatitis, hyperviscosity syndrome, pre-eclampsia and increased risk of hyperlipoproteinaemia in subsequent pregnancies [8]. Fetal complications include macrosomia, preterm labour, prematurity and in-utero death [5]. These can be avoided with prompt recognition and aggressive treatment.
Strict diabetic control is essential to prevent the above-mentioned complications [9]. Women should be counselled to restrict their consumption of high glycaemic index foods including refined sugar and high-fructose beverages. Total daily fat should be less than 20% of total caloric intake but these restrictions may vary depending on TG levels. Dietary restriction is very effective in lowering plasma TG by reducing the substrate for TG synthesis. Adequate essential fatty acid intake is required for both maternal and fetal well-being, as deficiencies may increase the risk of preterm labour, fetal growth restriction and impaired neural and retinal development [5]. This can be addressed by the prescription of omega-3-esters, serving also to lower TG levels.
Pharmacological agents such as fibrates and niacin offer a gradual reduction in plasma TG levels. However, in the acute setting, a more rapid reduction may be desired. To note, therapeutic doses of niacin required to lower TG levels significantly in pregnant patients has yet to be studied. Fibrates may be considered in women after the first trimester, if unresponsive to dietary change and omega-3 fatty acids. Niacin is known to be excreted in breastmilk and it is unclear if fibrates are excreted in breastmilk [5].
Women who remain refractory to treatment may require admission for a supervised fast together with intravenous 5% dextrose or parenteral nutrition. It has been hypothesised that intravenous feeding may have an attenuated TG-raising effect compared with enteral carbohydrate intake [10]. Apheresis [11], whereby triglycerides is specifically removed from the plasma by passing blood through a separation apparatus, may be considered in severe gestational hypertriglyceridemia complicated by pancreatitis or as a bridge to imminent delivery. However, complications such as rebound hypertriglyceridemia, catheter line infection and thrombosis, and foetal deaths have been reported [12].
Intravenous insulin is useful in patients with hyperglycaemia as improved glycaemic control increases LPL activity through increased LPL activation and reduction of LPL inhibition which occurs in the hyperglycaemic state [5].
Learning points
Universal screening for gestation hypertriglyceridemia is not undertaken at present. As this condition is rare, the recommendation would be to monitor for pregnancy-related hypertriglyceridemia in those with pre-pregnancy fasting TG levels greater than 4 mmol/L. In women for whom the fasting lipid profile is previously unknown, triggers for a lipid profile would include; a family history of high TG, features of metabolic syndrome and a history of non-gallstone pancreatitis [9]. This would allow prompt monitoring and early intervention to avoid maternal and fetal complications.
References:
- Barclay K, Koysombat K, Padmagirison R, Kaplan F. Hypertriglyceridaemia in pregnancy: an unexpected diagnosis and its management. BMJ Case Rep. 2022 Aug 29;15(8):e249000. doi: 10.1136/bcr-2022-249000.
- Guidance for maternal medicine services in the coronavirus (COVID-19) pandemic [Internet], 2020. Available: https://www.rcog.org.uk/guidance/coronavirus-covid-19-pregnancy-and-women-s-health/optimising-maternity-services-in-coronavirus-covid-19-pandemic/ [Accessed cited 8 May 2023]
- Herrera E. Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine 2002;19.
- Basaran A. Pregnancy-Induced hyperlipoproteinemia: review of the literature. Reprod Sci 2009;16:431–7. 10.1177/1933719108330569
- Wong B, Ooi T, Keely E. Severe gestational hypertriglyceridemia: a practical approach for clinicians. Obstetric Medicine2015;8:158–67
- Kleess LE, Janicic N. Severe hypertriglyceridemia in pregnancy: a case report and review of the literature. AACE Clin Case Rep 2019;5:e99–103. 10.4158/ACCR-2018-0168
- Ginsberg BH. Factors affecting blood glucose monitoring: sources of errors in measurement. J Diabetes Sci Technol2009;3:903–13. 10.1177/193229680900300438
