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10 April 2023: Articles  Bahrain

Lactic Acidosis Due to Thiamine Deficiency in a Preterm Infant Associated with Inadequate Parenteral Nutrition

Unusual clinical course, Challenging differential diagnosis

Sara Abdulla Hasan1ADEF*, Eman Saleh Shajira1EF

DOI: 10.12659/AJCR.939008

Am J Case Rep 2023; 24:e939008



BACKGROUND: Premature low birth weight infants may require prolonged parenteral feeding, which can be associated with deficiencies of vitamins and micronutrients. Deficiency in thiamine (vitamin B1) can result in metabolic crisis and lactic acidosis. This report describes a premature male infant born at 30 weeks of gestation with thiamine deficiency and lactic acidosis associated with inadequate parenteral nutrition.

CASE REPORT: A preterm boy was born at 30 weeks+5 days, with a weight of 0.830 kilograms and Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Total parenteral nutrition started on day 1 of life. On day 21 of life, while he was on total parenteral nutrition, severe lactic acidosis with a high anion gap was noted. Sepsis work-up along with radiological studies were immediately done, and antibiotics were initiated to cover common suspected organisms. Repeated blood gas analysis showed further increases in lactate levels. A fluid bolus was administered, with no improvement, so sodium bicarbonate was started. Despite all interventions, the lactate level continued to increase up to 13.78 mmol/l. Thiamine deficiency was suspected next, and a dose of vitamin B1 was given intravenously. There was an immediate drop in lactate level, and the patient proceeded to a full recovery.

CONCLUSIONS: This report shows that lactic acidosis is a potentially life-threatening condition that can result from thiamine deficiency. When standard parenteral nutrition preparations are used for prolonged periods in premature neonates, continuous monitoring of vitamin levels, micronutrient levels, and biochemical parameters is required.

Keywords: Aging, Premature, Lactic Acid, thiamine, Parenteral Nutrition


Thiamin (vitamin B1) is a water-soluble nutrient that acts as a coenzyme in biochemical reactions for energy formation, including carbohydrate metabolism, decarboxylation of α-keto acids, pyruvate and branched-chain amino acids, and transketolase reactions of the pentose pathway [1].

Parenteral nutrition is a lifesaving intervention that has been widely used in neonatal intensive care units (NICU). Parenteral nutrition is crucial in enhancing neonate growth, especially if administered in the first 48 hours of life, as it can result in early achievement of normal birth weight and enhance the weight at discharge by providing preterm neonate with nutrients and calories [2].

Moyses et al showed that there is significant benefit in the growth outcome with early administration of parenteral nutrition [3]. Adequate nutrition and calorie administration to the neonate can be ensured by following the guidelines of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) or NICE guidelines while on parenteral nutrition. However, thiamine deficiency can be a fatal adverse effect of parenteral nutrition if it was not included or is inadequate. Therefore, a thiamine dose of 0.35–0.50 mg per kilogram per day should be added to the total parenteral nutrition [4]. According to the World Health Organization, cases of infantile thiamine deficiency should receive a vitamin B1 dose of (25–50 mg intravenously), slowly followed by 10 mg intramuscularly for 1 week, and then to continue a dose of 3–5 mg orally for 6 weeks [5].

Thiamine deficiency has been reported in critically ill patients in intensive care units because thiamine demand increases along with increased metabolic requirements [6]. This happens in preterm neonates in particular because they have rapid growth and poor vitamin stores [6]. Thiamine deficiency is seen in breastfed infants whose mothers have thiamine deficiency as well as in neonates receiving total parenteral nutrition without water-soluble vitamins formulation containing thiamine supplementation or inadequate dosing [6,7]. It is difficult to identify thiamine deficiency early because it starts with nonspecific symptoms, especially in preterm neonates.

Oguz et al and Salvatori et al reported similar cases of thia-mine deficiency in preterm neonates who were on total parenteral nutrition without water-soluble vitamins and developed severe lactic acidosis [8,9[. Severe lactic acidosis might be a sign of thiamine deficiency, which is defined as a lactate blood level greater than 4 mmol/L with pH less than 7.2, serum bicarbonate level below 12 mmol/L, and partial pressure of PaCO2 less than or equal to 42 mmHg [10,11[.

Thiamine blood levels are not routinely measured because reports in the literature do not agree on a specific reference range, thus making the response to a thiamine dose of 50–100 mg intravenously the criterion standard for diagnosis [12,13]. This report describes a preterm male infant born at 30 weeks of gestation with thiamine deficiency and lactic acidosis associated with inadequate parenteral nutrition.

Case Report

A preterm boy (30 weeks+5 days) was born with a weight of 0.830 kilograms through lower segment cesarian section due to intrauterine growth restriction and fetal distress with Apgar score of 8 and 9 at 1 and 5 minutes, respectively. The mother was known to have rheumatoid arthritis, and was on methotrexate, prednisolone, and golimumab, which is an anti-tumor necrosis factor (TNF). She stopped taking methotrexate 3 months prior to this pregnancy in accordance with the instructions of her treating physician.

Immediately after birth, the patient had respiratory distress syndrome and was kept on ventilatory support. Empiric antibiotics were started due to feeding intolerance in the first week of life. Total parenteral nutrition was initiated from day 1 of life, including amino acids, trace elements, Addiphos© (potassium hydroxide, potassium phosphate, disodium phosphate), and SMOFlipid© (soya-bean oil, medium chain triglycerides, olive oil, fish oil). Fat-soluble vitamins were used but without water-soluble vitamins because they were unavailable. Trophic feeding was started according to our unit feeding protocol.

On day 17 of life, the patient demonstrated feeding intolerance in the form of increased abdominal girth, so feeding was stopped. Necrotizing enterocolitis was suspected, and empiric antibiotics were started. The investigations were unremarkable, and his blood culture was negative.

On day 21, we incidentally found severe lactic acidosis with a high anion gap of 24.6 mmol/l, pH 7.2, HCO3 of 13.3 mmol/l and lactate 13.78 mmol/l. Nevertheless, he was vitally and hemodynamically stable with no respiratory, cardiac, central nervous or gastrointestinal symptoms. Blood was collected for ammonia, lactate, electrolytes, and inflammatory markers along with blood culture and radiological investigations including chest and abdominal X-rays. Antibiotics were started as sepsis was suspected.

The laboratory results revealed high levels of lactate (13.73 mmol/L), but other laboratory and radiological investigations were unremarkable, and his blood culture continued to be negative. Subsequent deterioration was noted in blood gas, so a fluid bolus of 10 ml/kg was administered. Workup for metabolic diseases was done with tandem mass spectrometry, but the results were unremarkable. Repeated blood gas showed no improvement, pH was 7.2, HCO3 of 12.6 mmol/l, and he had an elevated anion gap of 29.2 mmol/l and a lactate level of 13.15 mmol/l. The decision to start a bolus of sodium bicarbonate was made, followed by infusion at a rate of 1 mmol/kg/hour, but the persistent acidosis did not improve. The subsequent blood gas results were: pH 7.176, HCO3 level of 12.4 mmol/L, lactate level of 14.11 mmol/L, and anion gap of 27.9 mmol/L. Thiamine deficiency was suspected in view of non-improving lactic acidosis despite bicarbonate infusion with normal other blood investigations and lack of water-soluble vitamins in the patient’s total parenteral nutrition. Thus, 1 dose of vitamin B1 (50 mg) was given intravenously.

Dramatic improvements were noticed within 6 hours, with a normalized pH of 7.342 and HCO3 of 26.6 mmol/L, along with a significant drop in lactate level to 9 mmol/L, followed by 2.7 mmol/L at 24 hours and below 2 mmol/L at 48 hours. Hence, vitamin B1 (50 mg intravenously) was continued daily for 2 weeks. Sodium bicarbonate infusion was gradually stopped after 6 hours of administration of vitamin B1, and blood gas readings were consistently normal. Oral multivitamins (Vitane drops) that contain vitamin A, vitamin D, vitamin B1, vitamin B2, vitamin B6, vitamin B12, ferrous, and zinc were initiated once the patient started to tolerate full feeds. He was subsequently discharged from the Neonatal Intensive Care Unit with corrected gestational age of 41 weeks+4 days and a weight of 1.910 kilograms.


Thiamine deficiency must be considered in preterm neonates who are on total parenteral nutrition with no or inadequate vitamin B1 supplementation, and presenting with lactic acidosis refractory to bicarbonate infusion. Prompt diagnosis and administration of thiamine infusion results in a rapid drop in lactate level. Late or inaccurate diagnosis can result in unfavourable and even fatal outcomes.

Lactic acidosis happens through the activation of anaerobic glycolysis in cases of thiamine deficiency, which in turn converts pyruvate into lactate [14[. Lactic acidosis is classified as type a and type b. The most prevalent type is type a, which results from tissue hypoxia [7[. Hence, improvement can be obtained by enhancing tissue oxygenation through administration of fluids, inotropes to increase the cardiac output, and starting antibiotics for suspected sepsis [7[. Type b is not correlated with tissue hypoxia and have numerous causes, such as malignancies, drug side effects, and metabolic abnormalities, including thiamine deficiency]15[. In a proper therapeutic setting, type a and type b must be distinguished from each other because their courses of therapy differ greatly [7,15.[

Thiamine deficiency in infants is often misdiagnosed because it can present in many forms and can mimic many diseases, especially sepsis, which makes it less suspected by clinicians. This can lead to neonatal death before diagnosis is established [16,17[. Sepsis is usually considered when treating a neonate with high lactate levels, as in our case, sepsis was highly suspected since the mother was on golimumab which is an anti-TNF medication that can cross the placenta and alter the immune status of the infant for up to 1 year [18[. However, all the blood cultures were sterile, and the inflammatory markers were all within normal ranges.

The global awareness of thiamine deficiency and it is prevalence is poorly documented, along with nonavailability of the diagnostic markers [13,17[. Thus, the cause of neonatal death could inadvertently be recorded as clinical sepsis rather than thiamine deficiency, which has a clear impact on accurate reporting and the prevalence of thiamine deficiency. Thauvin et al reported 11 cases of thiamine deficiency in neonates, of which 7 cases died because thiamine deficiency was not initially suspected [19[.

Thiamine deficiency in preterm neonates has no specific symptomatic criteria, and they can sometimes present with acidosis only, which can make the diagnosis harder, as in our case. Oguz et al reported a preterm infant that developed acidosis after 24 days on total parenteral nutrition without thiamine, but no other complications were documented besides the acidosis [8[.

Beriberi is the most common form of thiamine deficiency and has 2 subtypes. Dry beriberi shows neurological symptoms, including Wernicke’s encephalopathy, and wet beriberi shows cardiac symptoms [12[. The symptoms overlap in pediatric age groups, so the term beriberi is used without specification, but infantile beriberi usually presents with clinical features of congestive heart failure [10[. Cardiac arrest due to thiamine deficiency is not documented, but lactic acidosis severity and duration can result in acute cardiac decompensation and thus lead to cardiac arrest [20[. Salvatori et al reported 2 cases of preterm infants on total parenteral nutrition for 40 and 45 days without thiamine and they developed tachycardia with changes in the electrocardiography (ECG) and hypotension along with lactic acidosis, but in both cases, significant improvement was noticed after thiamine supplementation [9[.

Early recognition and treatment of thiamine deficiency are critical because they can prevent long-term consequences and protect the neurons from apoptosis, which in turn prevents the disease from progressing into chronic disability and eventually death if not treated [21[. If thiamine deficiency is suspected early, significant improvements can be noticed immediately after the first dose of thiamine as in our case. The lactic acidosis resolved within hours. Alicia et al reported a case of severe lactic acidosis that improved significantly after the initiation of 50 mg of intravenous thiamine along with a dramatic drop in lactate level to less than 1 mmol/l after 60 hours of therapy. Hence, 50 mg of intravenous thiamine was continued for 2 weeks [7[.


This report has shown that lactic acidosis is a potentially life-threatening condition that can result from thiamine deficiency.

When standard parenteral nutrition preparations are used for prolonged periods in premature neonates, continuous monitoring of vitamin and micronutrient levels and biochemical parameters is required. Future research opportunities include determining a standard definition for thiamine deficiency, identifying point-of-care diagnostics for rapid assessment of thiamine status, and determining the necessary dose and duration of thiamine supplementation in neonatal and pediatric populations presenting with severe lactic acidosis.


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3.. Moyses HE, Johnson MJ, Leaf AA, Cornelius VR, Early parenteral nutrition and growth outcomes in preterm infants: A systematic review and meta-analysis: Am J Clin Nutr, 2013; 97(4); 816-26

4.. Bronsky J, Campoy C, Braegger C, ESPGHAN/ESPEN/ESPR/CSPEN working group on pediatric parenteral nutrition. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Vitamins: Clin Nutr, 2018; 37(6 Pt B); 2366-78

5.. : Thiamine deficiency and its prevention and control in major emergencies, 1999 Available at: https://www.who.int/publications/i/item/WHO-NHD-99.13

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9.. Salvatori G, Mondì V, Piersigilli F, Thiamine deficiency in a developed country: Acute lactic acidosis in two neonates due to unsupplemented parenteral nutrition: JPEN J Parenter Enteral Nutr, 2016; 40(6); 886-89

10.. Smith T, Johnson C, Koshy R, Thiamine deficiency disorders: A clinical perspective: Ann N Y Acad Sci, 2021; 1498(1); 9-28

11.. Foucher CD, Tubben RE, Lactic acidosis: StatPearls [Internet], 2022, Treasure Island (FL), StatPearls Publishing [Updated 2022 Jul 18]

12.. Didisheim C, Ballhausen D, Choucair M, Severe lactic acidosis in a critically ill child: Think about thiamine: J Pediatr Intensive Care, 2021; 10; 307-10

13.. Samprathi M, Mohammad F, Sridhar M, A report of six cases: Am J Trop Med Hyg, 2021; 104(6); 2238-40

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923