Abstract
Background
Thiamine deficiency disorders (TDD) remain a preventable yet underrecognized contributor to maternal and infant morbidity, particularly in low- and middle-income countries. During pregnancy, thiamine deficiency may go undetected despite routine antenatal care and can lead to serious neurological and cardiac complications in breastfed infants. However, data on thiamine status in urban populations receiving standard antenatal supplementation are limited. This study aimed to determine the prevalence of thiamine deficiency in third-trimester pregnant women and to identify associated factors and clinical manifestations in an urban setting of Thailand.
Methods
This cross-sectional study enrolled pregnant women in the third-trimester (≥ 28 weeks of gestation) attending antenatal care in Bangkok, Thailand. Demographic characteristics, obstetric history, dietary habits, medication and supplement use, and TDD-related symptoms were collected using a structured questionnaire. Functional thiamine status was assessed using the erythrocyte transketolase activity coefficient (ETKAC), with abnormal thiamine status defined as ETKAC > 1.25. Penalized logistic regression with Firth’s correction was used to identify factors associated with abnormal ETKAC.
Results
A total of 328 participants (mean age 28.9 years; mean gestational age 31.1 weeks) were included. Although 97.9% reported receiving at least one antenatal supplement, only 53.1% received formulations containing thiamine. Based on ETKAC, 17.7% demonstrated biochemical thiamine deficiency (ETKAC > 1.25). Consumption of refined carbohydrates without thiamine containing supplement was independently associated with deficiency (aOR 4.20, 95% CI 1.30–17.87). Clinical symptoms were nonspecific and largely similar between groups, except for reduced concentration or memory problems, which was more common among participants with thiamine deficiency (p = 0.007).
Conclusion
These findings suggest that despite high antenatal supplementation coverage, nearly one-fifth of third-trimester pregnant women demonstrated biochemical evidence of subclinical thiamine deficiency. Routine clinical assessment was insufficient to identify affected individuals. These findings suggest that current antenatal supplementation strategies may be inadequate to ensure optimal thiamine status during late pregnancy and highlight the need to re-evaluate micronutrient policies in similar urban settings.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12884-026-09653-6.
Keywords: Pregnancy, Thiamine deficiency, Erythrocyte transketolase activity coefficient, Prenatal care, Maternal nutrition
Background
Globally, it is estimated that 20–30% of pregnant women suffer from some vitamin deficiency, highlighting the critical importance of adequate nutrition during pregnancy [1]. The nutritional requirements for both macronutrients and micronutrients increase substantially throughout gestation and lactation [2]. In Thailand, the average caloric intake for working women is approximately 1630 kcal/day [3], increasing to 1806 ± 482 kcal/day during pregnancy [4], particularly in the later trimester when fetal growth accelerates [5].
Among essential micronutrients, vitamin B1 (thiamine) plays a vital role in cellular energy metabolism and neurological function. The recommended daily intake of thiamine for women of reproductive age is 0.9 mg/day, which increases to 1.2 mg/day during pregnancy and lactation [6]. This increased physiological requirement heightens the risk of deficiency and may lead to significant health consequences for both mothers and infants [1, 2, 7–9].
Thiamine is a water-soluble vitamin obtained primarily through dietary intake, particularly from whole grains, grain husks, red meat, and dairy products. However, thiamine is heat-labile, light-sensitive, and its absorption can be influenced by gastrointestinal pH [10]. Several dietary factors may also impair thiamine availability. For example, certain foods and substances containing tannic and caffeic acid such as betel nut, tea, and beetroot may interfere with absorption [11, 12]. In addition, fermented fish products, which are cultural foods commonly consumed in Thailand and other Southeast Asian countries, also contain thiaminase enzyme that degrades the thiamine in the diet [11]. The biological half-life of thiamine in the human body is relatively short, approximately 1–3 weeks, requiring regular dietary replenishment [10, 13]. Furthermore, the absorption and utilization of water-soluble vitamins may vary across individuals, particularly when thiamine is consumed as part of multivitamin preparations [14], which are commonly prescribed during pregnancy.
Thiamine deficiency leads to a spectrum of clinical conditions known as Thiamine Deficiency Disorders (TDDs), which often present with nonspecific symptoms [6, 15, 16]. The most severe manifestation is cardiac beriberi, a potentially fatal condition characterized by heart failure and circulatory collapse [17, 18]. In infants, cardiac beriberi may present with right-sided heart failure and pulmonary hypertension, conditions that are often difficult to diagnose until its late stage [19]. Neurological manifestations, known as dry beriberi, may also occur and can mimic central nervous system infections [13].
In pediatric populations, cardiac beriberi is most frequently reported in breastfed infants younger than three months, particularly in remote settings where maternal nutritional status is inadequate [20]. Breast milk thiamine concentration is strongly correlated with maternal thiamine status [2, 21–23]. In addition, emerging evidence suggests that even mild maternal thiamine deficiency during pregnancy may negatively affect the neurocognitive development of offspring [7, 8, 24].
In the human body, thiamine exists mainly in phosphorylated forms, with approximately 80% present as thiamine diphosphate (ThDP), an essential cofactor for several metabolic enzymes, including erythrocyte transketolase. The erythrocyte transketolase activity coefficient (ETKAC) is widely used as an indirect biomarker of functional thiamine status [25]. However, in many clinical settings, empirical treatment or therapeutic diagnosis is more commonly used due to the limited availability and accessibility of specialized laboratory testing. Thiamine deficiency is well recognized in certain clinical conditions, including chronic alcoholism [26], and is incorporated into treatment guidelines for sepsis [27] and refeeding syndrome associated with severe acute malnutrition [28].
In Thailand, as well as other countries with a white rice-based dietary pattern without further fortification, national food supply analysis is reported to be below recommended levels [6]. When combined with the increased nutritional needs during pregnancy, this may place Thai pregnant women at a higher risk of thiamine deficiency. Furthermore, thiamine supplementation is not routinely included in the national antenatal care program, which may further contribute to this risk.
Given the potential health implications for both mothers and infants, improvement of maternal thiamine status is essential. Therefore, this study aimed to determine the prevalence of subclinical thiamine deficiency among pregnant women in an urban setting in Thailand and to identify associated demographic, supplementation, and dietary factors. By integrating clinical assessment with functional biomarker analysis, this research aims to provide evidence to inform nutritional interventions and antenatal care strategies that improve maternal and infant health outcomes.
Methods
Study design
This cross-sectional study was conducted at Rajavithi Hospital, a large public tertiary hospital with a capacity of 1,200 beds located in Bangkok, Thailand. This represents the urban setting and is easily accessible. The antenatal care outpatient department provides services to patients covered under all the universal health coverage schemes, as well as other healthcare plans, including social security and government employee benefits.
This study was done in collaboration with the Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, and the Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University.
Study population
The participant recruitment process took place from May to December 2025. Eligible participants were pregnant women aged 18 or older with a gestational age of at least 28 weeks who could communicate in Thai. Exclusion criteria included pregnancy complicated by medical conditions requiring regular oral medication, history of gastric bypass surgery or intestinal resection, and specific dietary practices such as vegetarian or ketogenic diets that might substantially alter nutrient intake. Participants were randomly sampled from antenatal care outpatient visits scheduled for routine blood collection.
Outcome measures
The primary outcome of this study was biochemical thiamine deficiency, assessed using the ETKAC. Secondary outcomes included demographic characteristics, obstetric history, dietary habits, medication, supplement use and TDD-related symptoms associated with abnormal thiamine status among third-trimester pregnant women in Bangkok, Thailand.
Demographic and obstetric data
Demographic information collected included age, height, pre-pregnancy body weight, and body weight at enrollment. Obstetric history included gravidity, gestational age, medication use, and supplement intake.
According to Thailand’s national antenatal care guidelines, folic acid supplementation is recommended three months before conception, and folic acid and calcium supplements are routinely provided starting from the first antenatal visit. Iron supplementation and thalassemia screening are recommended for women with anemia, and additional monitoring is recommended for advanced maternal age (≥ 35 years). However, multivitamin supplementation is not routinely included in the standard antenatal care package. Vitamin B complex supplementation is recommended primarily for the prevention of Wernicke encephalopathy in patients with hyperemesis gravidarum [29].
In this study, all medications and supplements received during the two weeks preceding enrollment were recorded. Two thiamine-containing multivitamin supplements were identified and labeled in this study as multivitamin A and multivitamin B. Each tablet contained two milligrams of thiamine and was prescribed for once-daily use.
Dietary assessment
Dietary practices during the preceding week were assessed through structured interviews conducted by trained study staff. The details of carbohydrate and protein types consumed at least 4 days per week were recorded. The frequency of innards consumption, caffeine-containing beverage use, alcohol use, fermented food intake, and betel nut or herb product use was also collected.
Clinical manifestation and physical examination
Because the clinical manifestations of thiamine deficiency are non-specific, participants were asked about the presence and frequency of symptoms potentially related to thiamine deficiency, including reduced concentration/memory problems, irritability, chest pain, fatigue, palpitations, muscle pain, numbness, cramps, weakness, and gastrointestinal manifestations (constipation, loss of appetite, nausea, or vomiting). All enrolled participants also underwent a physical examination by trained medical personnel. The examination included assessment of vital signs, deep tendon reflexes, and the presence of nystagmus to identify clinical signs of thiamine deficiency, such as tachycardia, hyporeflexia and nystagmus during pregnancy [2].
Specimen collection and laboratory assessment
According to the Thai national antenatal care policy, routine blood tests for anemia screening and infectious diseases, including HIV, hepatitis B, and syphilis, are performed during the first antenatal visit and repeated later in pregnancy (at least 28 weeks of gestation or at least 12 weeks after the first test). To minimize additional blood collection, this study collected an additional six milliliters of blood for thiamine analysis at the time of the second routine antenatal blood draw. Blood samples were collected on the same day as recruitment to prevent potential changes in dietary behavior following study enrollment.
Because thiamine is light-sensitive, blood samples were collected in light-protected EDTA tubes, stored at 4–8 °C, and transported to the Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, for laboratory analysis. Erythrocyte transketolase activity was measured using ultraviolet spectrophotometry in washed red blood cells. This enzyme requires ThDP as an essential cofactor. The ETKAC was calculated as the ratio between enzyme activity following stimulation with exogenous thiamine and basal (unstimulated) enzyme activity. This ratio reflects the availability of intracellular thiamine diphosphate.
There is no international consensus on the cutoff of ETKAC. Commonly used thresholds are: ETKAC < 1.15 indicates adequate thiamine status, ETKAC between 1.15 and 1.25 suggests low risk of clinical deficiency, and ETKAC > 1.25 indicates deficiency [25].
Statistical analysis
Previous studies conducted among Karen pregnant women in the area of Thailand-Myanmar border reported a prevalence of thiamine deficiency of 26.9% [24]. However, no prevalence studies have been conducted among pregnant women in urban Thai populations. Sample size calculation using STATCALC (epiinfo) with confidence interval (CI) of 0.95 and a margin of error of 0.05 was established. To account for potential missing data, an additional 10% was added, resulting in a final target sample size of 335 participants.
The data were analyzed using RStudio (version 2025.09.0 + 387; R Foundation for Statistical Computing, Vienna, Austria). Baseline characteristics and dietary practices were summarized descriptively. The distribution of ETKAC was examined using a histogram with a Kernel density overlay. Thiamine status was classified according to ETKAC thresholds as follows: <1.15 indicated adequate status, 1.15–1.25 marginal deficiency, and > 1.25 thiamine deficiency.
For association analyses, thiamine deficiency was analyzed as a binary outcome by combining adequate and marginal status into a single reference category and comparing it with thiamine deficiency (> 1.25), which served as the outcome of interest. Crude odds ratios (cORs) were estimated from univariable models. Multivariable analysis was performed using penalized logistic regression with Firth’s correction to reduce small-sample bias and mitigate potential separation due to sparse exposure categories. All covariates were included in the multivariable model a priori based on biological plausibility and prior evidence, irrespective of their statistical significance in univariable analyses. Associations are reported as odds ratios with 95% CIs.
Self-reported symptoms during the preceding week were summarized by thiamine status using frequencies and percentages. Differences between groups were assessed using the Pearson chi-square test or Fisher’s exact test, as appropriate. Vital signs at the time of assessment, including body temperature, systolic and diastolic blood pressure, and heart rate, were summarized using box-and-whisker plots with overlaid individual observations to illustrate distributions across thiamine status groups. Continuous variables were compared between groups using the Wilcoxon rank-sum test. Deep tendon reflexes and nystagmus were presented descriptively and compared graphically between groups.
Results
Participant characteristics and dietary practices
Of the 335 pregnant women recruited, 328 were included in the final analysis after seven participants withdrew consent because of changes to their scheduled blood collection appointments. The mean age was 28.9 ± 5.7 years, and 56.1% were aged 26–35 years. The mean pre-pregnancy body mass index (BMI) was 23.2 ± 4.7 kg/m²; 42.4% had normal BMI, 30.2% were overweight, and 14.9% were obese. Gestational age ranged from 28 to 39 weeks, with a mean gestational age of 31.14 weeks, with 75.0% between 28 and 32 weeks. Diabetes mellitus and/or hypertension were reported by 13.1% of participants. Frequent consumption (≥ 4 times per week) of refined carbohydrates was reported by 79.9% of women, whereas 20.1% reported frequent consumption of brown or unpolished rice. Innards were consumed at least once weekly by 58.8% of participants, although only 7.0% reported intake ≥ 4 times per week. Caffeine-containing beverages were consumed by 55.2% of women. Alcohol use (1.2%), high-frequency innards intake (7.0%), and betel nut or herb use (1.5%) were infrequent and unevenly distributed; therefore, these variables were excluded from regression analyses due to limited variability (Table 1).
Table 1.
Baseline characteristics and dietary practices of pregnant women enrolled in the study (n = 328)
| Characteristic | n (%) |
|---|---|
| Age, years | |
| 18–25 | 97 (29.6) |
| 26–35 | 184 (56.1) |
| >35 | 47 (14.3) |
| Mean ± SD (range) | 28.9 ± 5.7 (18–45) |
| Pre-pregnancy body mass index (BMIa), kg/m2 | |
| Underweight (< 18.5) | 41 (12.5) |
| Normal (18.5–22.9) | 139 (42.4) |
| Overweight (23–27.5) | 99 (30.2) |
| Obese (> 27.5) | 49 (14.9) |
| Mean ± SD (range) | 23.2 ± 4.7 (15.6–39.3) |
| Gravidity (number of pregnancies) | |
| 1 | 137 (41.8) |
| 2 | 109 (33.2) |
| ≥3 | 82 (25.0) |
| Mean ± SD (range) | 1.9 ± 1.0 (1–8) |
| Gestational age, weeks | |
| 28–32 | 246 (75.0) |
| 33–35 | 59 (18.0) |
| >35 | 23 (7.0) |
| Mean ± SD (range) | 31.1 ± 2.5 (28–39) |
| Medical history | |
| None | 285 (86.9) |
| Diabetes mellitus and/or hypertension | 43 (13.1) |
| Medications received in the past 2 weeks | |
| None | 7 (2.1) |
| Thiamine-containing supplementation (multivitamin product A, multivitamin product B) | 174 (53.0) |
| Other antenatal medications only (multivitamin product without thiamine, calcium, folic acid, iron, aspirin, etc.) | 147 (44.8) |
| Types of carbohydrates consumed ≥ 4 times per week | |
| White/Jasmine rice or white flour (noodles) | 262 (79.9) |
| Brown/unpolished rice | 66 (20.1) |
| Types of protein consumed ≥ 4 times per week | |
| White meat, red meat, or seafood | 328 (100) |
| None of the above | 0 (0) |
| Innards consumption (e.g. liver) | |
| None | 135 (41.2) |
| 1–3 times per week | 170 (51.8) |
| ≥4 times per week | 23 (7.0) |
| Caffeine consumption (tea, coffee) | |
| None | 147 (44.8) |
| 1–3 times per week | 118 (36.0) |
| ≥4 times per week | 63 (19.2) |
| Alcohol consumption | |
| None | 324 (98.8) |
| 1–3 times per week | 4 (1.2) |
| ≥4 times per week | 0 (0) |
| Fermented food consumption (fermented fish paste, pickled fish, etc.) | |
| None | 157 (47.9) |
| 1–3 times per week | 144 (43.9) |
| ≥4 times per week | 27 (8.2) |
| Betel nut or herb use | |
| None | 323 (98.5) |
| 1–3 times per week | 2 (0.6) |
| ≥4 times per week | 3 (0.9) |
aBMI categorized according to Asia-pacific BMI
To better capture dietary exposure relevant to thiamine status, a composite variable (“Carbohydrate intake and thiamine supplementation”) was created by combining the type of carbohydrate consumed and recent thiamine-containing supplementation, since refined carbohydrate is the main source of energy. Participants were classified into four mutually exclusive categories: refined carbohydrates without supplementation; refined carbohydrates with supplementation; brown or unpolished rice without supplementation; and brown or unpolished rice with supplementation.
Distribution of ETKAC and prevalence of thiamine deficiency
The mean ETKAC was 1.07 ± 0.18 (range 0.63–1.65). The distribution was centered around approximately 1.0 and showed right skewness extending beyond the deficiency threshold (Fig. 1A). Based on predefined cut-offs, 71.0% of participants had adequate thiamine status (ETKAC < 1.15), 11.3% had marginal deficiency (1.15–1.25), and 17.7% met the criteria for thiamine deficiency (> 1.25) (Fig. 1B). For regression analyses, thiamine deficiency was modeled as a binary outcome by combining adequate and marginal categories into a single reference group, as the primary objective was to identify factors associated with biochemical thiamine deficiency.
Fig. 1.
Distribution of erythrocyte transketolase activity coefficient (ETKAC) and thiamine status among pregnant women (n = 328). A Histogram with kernel density overlay showing the distribution of ETKAC values. Dashed vertical lines indicate predefined thresholds for adequate status (< 1.15), marginal deficiency (1.15–1.25), and thiamine deficiency (> 1.25). B Proportion of participants classified as adequate, marginal deficiency, and thiamine deficiency based on ETKAC cut-offs
Factors associated with thiamine deficiency
Among 328 participants, 58 (17.7%) had thiamine deficiency. In multivariable analysis, the composite variable combining carbohydrate intake and thiamine supplementation was the only factor associated with thiamine deficiency. Compared with pregnant women consuming brown or unpolished rice with thiamine-containing supplementation (reference group), those consuming refined carbohydrates without thiamine supplementation had higher odds of thiamine deficiency (aOR: 4.20; 95% CI: 1.30–17.87). No clear associations were observed for other carbohydrate–supplementation categories. Age, pre-pregnancy body mass index, gravidity, gestational age, medical history, intake of innards, caffeine intake, and fermented food consumption were not clearly associated with thiamine deficiency, as confidence intervals for adjusted odds ratios included unity (Table 2).
Table 2.
Factors associated with thiamine deficiency among pregnant women (n = 328)
| Characteristic | Thiamine deficiency (n = 58) |
Non-deficiency (n = 270) |
cOR (95% CI) | aOR (95% CI) |
|---|---|---|---|---|
| n (%) | n (%) | |||
| Age, years | ||||
| 18–25 | 17 (17.5) | 80 (82.5) | 1.39 (0.54–3.94) | 1.37 (0.46–4.40) |
| 26–35 | 35 (19.0) | 149 (81.0) | 1.52 (0.65–4.07) | 1.34 (0.53–3.77) |
| >35 | 6 (12.8) | 41 (87.2) | Reference | Reference |
| Pre-pregnancy body mass index, kg/m2 | ||||
| Underweight (< 18.5) | 8 (19.5) | 33 (80.5) | 1.14 (0.46–2.63) | 1.36 (0.53–3.30) |
| Normal (18.5–22.9) | 25 (18.0) | 114 (82.0) | Reference | Reference |
| Overweight (23–27.5) | 15 (15.2) | 84 (84.8) | 0.82 (0.41–1.63) | 0.85 (0.40–1.77) |
| Obese (> 27.5) | 10 (20.4) | 39 (79.6) | 1.19 (0.52–2.62) | 1.18 (0.49–2.70) |
| Gravidity (number of pregnancies) | ||||
| 1 | 22 (16.1) | 115 (83.9) | Reference | Reference |
| 2 | 19 (17.4) | 90 (82.6) | 1.11 (0.56–2.15) | 1.15 (0.56–2.33) |
| ≥3 | 17 (20.7) | 65 (79.3) | 1.37 (0.68–2.74) | 1.59 (0.73–3.48) |
| Gestational age, weeks | ||||
| 28–32 | 47 (19.1) | 199 (80.9) | Reference | Reference |
| 33–35 | 7 (11.9) | 52 (88.1) | 0.60 (0.24–1.30) | 0.62 (0.25–1.38) |
| >35 | 4 (17.4) | 19 (82.6) | 0.97 (0.29–2.62) | 1.15 (0.34–3.28) |
| Medical history | ||||
| None | 52 (18.2) | 233 (81.8) | Reference | Reference |
| Diabetes mellitus and/or hypertension | 6 (14.0) | 37 (86.0) | 0.77 (0.29–1.76) | 1.47 (0.49–4.18) |
| Carbohydrate intake and thiamine supplementation | ||||
| Brown/unpolished rice with thiamine-containing supplementation | 3 (8.6) | 32 (91.4) | Reference | Reference |
| Refined carbohydrates with thiamine-containing supplementation | 20 (14.5) | 118 (85.5) | 1.61 (0.54–6.34) | 2.06 (0.62–8.84) |
| Brown/unpolished rice without thiamine supplementation | 2 (6.5) | 29 (93.5) | 0.79 (0.12–4.34) | 0.87 (0.14–4.80) |
| Refined carbohydrates without thiamine supplementation | 33 (26.6) | 91 (73.4) | 3.40 (1.18–13.17) | 4.20 (1.30–17.87) |
| Innards consumption (e.g. liver) | ||||
| None | 26 (19.3) | 109 (80.7) | 1.26 (0.70–2.28) | 1.25 (0.68–2.29) |
| 1–3 times per week | 27 (15.9) | 143 (84.1) | Reference | Reference |
| ≥4 times per week | 5 (21.7) | 18 (78.3) | 1.55 (0.51–4.16) | 1.79 (0.56–5.08) |
| Caffeine consumption (tea, coffee) | ||||
| None | 25 (17.0) | 122 (83.0) | 0.85 (0.45–1.58) | 1.06 (0.55–2.06) |
| 1–3 times per week | 23 (19.5) | 95 (80.5) | Reference | Reference |
| ≥4 times per week | 10 (15.9) | 53 (84.1) | 0.80 (0.35–1.74) | 0.82 (0.35–1.82) |
| Fermented food consumption (fermented fish paste, pickled fish, etc.) | ||||
| None | 26 (16.6) | 131 (83.4) | 0.79 (0.44–1.41) | 0.85 (0.47–1.55) |
| 1–3 times per week | 29 (20.1) | 115 (79.9) | Reference | Reference |
| ≥4 times per week | 3 (11.1) | 24 (88.9) | 0.56 (0.14–1.65) | 0.49 (0.12–1.49) |
cOR crude odds ratio, aOR adjusted odds ratio, 95% CI 95% confidence interval
Symptoms according to thiamine status
Symptoms during the preceding week were common in both groups (Table 3). Reduced concentration or memory problems were reported at least once by 48.3% of women with thiamine deficiency compared with 26.6% of those without deficiency, and this difference was statistically significant (p = 0.007). For other symptoms, including irritability, chest pain, fatigue, palpitations, muscle pain, numbness or tingling, cramps, weakness, and gastrointestinal symptoms, the distribution of symptom frequencies did not differ significantly between groups (all p > 0.05).
Table 3.
Self-reported symptoms during the previous week among pregnant women, stratified by thiamine deficiency status (n = 328)
| Symptom | Thiamine deficiency group (n = 58) |
Non-deficiency group (n = 270) |
p-valuea | ||||
|---|---|---|---|---|---|---|---|
| None | 1–3 times | ≥ 4 times | None | 1–3 times | ≥ 4 times | ||
| n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | ||
| Reduced concentration/ memory problems | 30 (51.7) | 23 (39.7) | 5 (8.6) | 198 (73.3) | 50 (18.5) | 22 (8.1) | 0.007* |
| Irritability | 30 (51.7) | 18 (31.0) | 10 (17.2) | 147 (54.4) | 92 (34.1) | 31 (11.5) | 0.357 |
| Chest pain | 47 (81.0) | 9 (15.5) | 2 (3.4) | 241 (89.3) | 20 (7.4) | 9 (3.3) | 0.196 |
| Fatigue | 23 (39.7) | 25 (43.1) | 10 (17.2) | 132 (48.9) | 97 (35.9) | 41 (15.2) | 0.461 |
| Palpitations | 45 (77.6) | 12 (20.7) | 1 (1.7) | 229 (84.8) | 32 (11.9) | 9 (3.3) | 0.180 |
| Muscle pain | 40 (69.0) | 16 (27.6) | 2 (3.4) | 200 (74.1) | 45 (16.7) | 25 (9.3) | 0.112 |
| Numbness or tingling sensation | 39 (67.2) | 18 (31.0) | 2 (3.4) | 187 (69.3) | 65 (24.1) | 18 (6.7) | 0.540 |
| Cramps | 23 (39.7) | 30 (51.7) | 5 (8.6) | 140 (51.9) | 99 (36.7) | 31 (11.5) | 0.178 |
| Weakness | 58 (100) | 0 (0.0) | 0 (0.0) | 256 (94.8) | 11 (4.1) | 3 (1.1) | 0.122 |
| Constipation, loss of appetite, nausea, or vomiting | 37 (63.8) | 16 (27.6) | 5 (8.6) | 180 (66.7) | 67 (24.8) | 23 (8.5) | 0.918 |
a p-values were calculated using the Pearson chi-square test or Fisher’s exact test, as appropriate; *significance at p < 0.05
Clinical and neurological findings according to thiamine status
Vital signs at the time of assessment were comparable between women with and without thiamine deficiency (Fig. 2). Median diastolic blood pressure was 67.0 mmHg (IQR 10.0) in the non-deficiency group and 67.5 mmHg (IQR 10.0) among women with thiamine deficiency (p = 0.274). Median systolic blood pressure was 114.0 mmHg (IQR 12.0) and 116.5 mmHg (IQR 16.0), respectively (p = 0.299). Median heart rate was 96.0 beats/min (IQR 17.0) in the non-deficiency group and 98.0 beats/min (IQR 17.8) in the deficiency group (p = 0.897). Median body temperature was 36.2 °C (IQR 0.2) in both groups (p = 0.090). No statistically significant differences were observed for any measured vital parameter.
Fig. 2.
Vital signs according to thiamine status among pregnant women. Box-and-whisker plots showing body temperature, systolic blood pressure, diastolic blood pressure, and heart rate among women with and without thiamine deficiency. Boxes represent interquartile ranges with medians indicated; whiskers represent 1.5× the interquartile range; points represent individual participants
Neurological examination findings were largely unremarkable (Appendix 2). Overall, 290 women (88.4%) demonstrated normoreflexia at the knee. Hyporeflexia was observed in 36 women (11.0%), while hyperreflexia was rare (2 women, 0.6%). The distribution of reflex categories appeared similar across thiamine status groups. Nystagmus was absent in 267 participants (81.4%) and present in 61 (18.6%) (Appendix 2). The prevalence of nystagmus did not differ meaningfully between women with and without thiamine deficiency. Taken together, routine clinical and neurological assessments did not clearly distinguish women with biochemical thiamine deficiency from those without deficiency in this study. No formal statistical comparisons were performed for neurological examination findings, and results are presented descriptively.
Discussion
This study demonstrates that subclinical thiamine deficiency persists among third-trimester pregnant women in an urban setting in Thailand, even in the context of relatively good access to antenatal care and high rates of supplement use. Nearly one-fifth (17.7%) of third-trimester pregnant women in this cohort had biochemical evidence of thiamine deficiency, as assessed by erythrocyte transketolase activity coefficient. These findings highlight that thiamine deficiency may represent a persistent but under-recognized micronutrient problem among pregnant women, even in urban environments where food availability and healthcare access are generally adequate and multivitamin use was taken into account. Previous studies in Thailand have reported thiamine deficiency primarily in rural or resource-limited settings, particularly among border populations [22, 24] or in socioeconomically unstable regions [30], where deficiency was assessed using dietary recall and reported at higher rates. Our results indicate that thiamine deficiency remains a hidden burden even in urban settings with improved healthcare and food access.
Refined carbohydrate-based dietary habits may play an important role. Polished white rice, the staple carbohydrate source in Thailand, contains minimal thiamine. When combined with the increased metabolic demands of pregnancy, this dietary pattern may predispose women to marginal or functional deficiencies. Although supplementation with two milligrams per day of thiamine was included in multivitamin formulations, supplementation alone did not completely prevent biochemical deficiency. This suggests that additional factors, including dosage adequacy, bioavailability, absorption efficiency, food–nutrient interactions, and potential genetic variation in thiamine transport or utilization [2], may influence maternal thiamine status during pregnancy. Another factor to consider is the increase in glomerular filtration rate during pregnancy [31] since excess thiamine intake was excreted from the urine [32, 33].
An important finding of this study is that subclinical thiamine deficiency was observed despite a high rate of antenatal supplementation. Although almost all participants reported receiving at least one form of supplement, only about half received multivitamin supplements containing thiamine. Even among women who received supplements containing approximately two milligrams of thiamine per day, some individuals continued to demonstrate biochemical evidence of deficiency. In this cohort, 27 pregnant women who reported taking thiamine-containing multivitamins still had ETKAC values consistent with thiamine deficiency. This observation raises the possibility that supplementation alone may not fully correct thiamine insufficiency in certain individuals. Potential explanations include variability in supplement adherence, differences in intestinal absorption, interactions with other dietary components, or different physiological demands during pregnancy [2]. These findings raise concerns regarding the adequacy of current supplementation strategies and highlight the need for urgent evaluation of their effectiveness.
Clinical manifestations of thiamine deficiency are often nonspecific and may therefore be overlooked in routine antenatal care. In this study, most classical symptoms associated with thiamine deficiency were not significantly different between groups, and the only symptom that showed a statistical association with deficiency was reduced concentration or memory problems. Such symptoms are subjective and reported during normal pregnancy and are often attributed to physiological changes rather than micronutrient deficiency [34]. As a result, reliance on clinical symptoms and physical examination findings, such as tachycardia, deep tendon reflexes, and nystagmus, cannot reliably identify the case, potentially leading to under-recognition of subclinical thiamine deficiency.
This study also explored potential demographic and obstetric factors associated with thiamine deficiency, including maternal age, body mass index, gestational weight gain, and parity. None of these factors showed a significant association with biochemical deficiency in the present analysis. Anthropometric measures such as weight and body mass index (BMI) alone were insufficient indicators of micronutrient adequacy in this population. Physiological weight gain during pregnancy may mask underlying micronutrient insufficiency, highlighting the limitation of relying solely on body mass index or anthropometric indicators during antenatal care [35]. Consequently, women who appear nutritionally adequate based on body composition may still experience clinically significant micronutrient deficiencies.
Previous studies have suggested that thiamine deficiency may be more prevalent among individuals with obesity, high carbohydrate intake, diabetes, or medication use such as aspirin for preeclampsia prevention [33, 36, 37]. However, these associations were not observed in this cohort. Cultural practices that may influence thiamine absorption, such as betel nut chewing or the consumption of thiaminase-containing foods, were reported infrequently and therefore could not be evaluated robustly in the statistical analysis.
Subclinical thiamine deficiency in pregnant women is of particular concern because maternal thiamine status directly influences the thiamine concentration of breast milk [21, 22, 38]. Infants who are exclusively breastfed rely entirely on maternal thiamine stores during early life. Although severe manifestations such as infantile cardiac beriberi are currently considered rare in Thailand, mild or subclinical maternal deficiency may still have important consequences, including potential effects on infant neurodevelopment.
The laboratory diagnosis of thiamine deficiency is also challenging. The strength of this study is that we use ETKAC as a biomarker to represent the red blood cell functional activity. Although ThDP measurement is considered a more practical biomarker than other methods, access to such testing remains limited in many clinical settings [38]. As a result, confirming the diagnosis prior to treatment is often impractical in routine antenatal care. These constraints highlight an important gap in current screening approaches. Alternative strategies may therefore be necessary to prevent subclinical thiamine deficiency disorders (TDDs), particularly those that remain clinically silent yet may still affect maternal and infant health outcomes.
This study has several limitations. First, the cross-sectional design limits the ability to determine causal relationships between dietary patterns, supplementation practices, and thiamine status. Second, the study did not assess neonatal outcomes, cord blood thiamine concentrations, or breast milk thiamine levels. In urban Thailand, antenatal care and delivery services are often provided at different hospitals, which limits the feasibility of collecting these data. Future studies incorporating maternal–infant follow-up and breast milk analysis would help clarify the clinical implications of maternal thiamine deficiency.
Despite these limitations, this study provides important evidence that subclinical thiamine deficiency remains present among pregnant women in an urban Thai population with good access to antenatal care. The findings highlight the need for greater awareness of micronutrient deficiencies that may persist despite supplementation and suggest that broader nutritional strategies, including dietary education and potential food fortification, may be required to address this hidden burden.
Conclusions
From a public health perspective, these findings suggest that current antenatal nutritional strategies may not fully address the risk of thiamine deficiency among pregnant women in real-world settings. While supplementation can improve thiamine intake, supplementation practices remain inconsistent, and dietary patterns dominated by polished rice may continue to limit thiamine availability [6]. Food fortification strategies targeting staple carbohydrate sources have been shown to be effective in reducing micronutrient deficiencies in many populations and may represent a complementary approach to individual supplementation [6, 39, 40]. Additionally, greater attention to dietary counselling during antenatal care may help improve maternal micronutrient intake, and education regarding food preparation methods that preserve water-soluble and heat-labile vitamins could further support nutritional adequacy. All these interventions should be combined to enhance maternal thiamine status. Further evaluation of newborn clinical outcome and thiamine status should be further studies.
Supplementary Information
Acknowledgements
We would like to express our sincere appreciation to all the participants who took part in this study, as well as to all staff members who contributed to the study processes.
Authors’ contributions
AT conceived the study. DS, SS and TY contribute to site data collection. IJ, MC, and CN contribute to data preparation. AP, NP, and KK contribute to the laboratory process. All authors read and approved the final manuscript.
Funding
This project was funded by the Early Career Innovator Award (ECIA) from Mahidol-Oxford Translational Innovative Partnership (MOTIP) and the Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University of Thailand.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Ethical approval was obtained from both the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University (approval number MUTM 2025-005-02), and the Rajavithi Hospital Ethics Committee (approval number 069/2568). Written informed consent was obtained from all participants before enrollment in the study. All procedures involving human participants were conducted in accordance with the ethical standards of the institutional research committees and with the Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.