Case Report

Obstetric Medicine
0(0) 1–6
A case series of rare neurological ! The Author(s) 2020
Article reuse guidelines:
and cardio-pulmonary manifestations sagepub.com/journals-permissions
DOI: 10.1177/1753495X20960906
of thiamine deficiency in pregnancy journals.sagepub.com/home/obm

and lactation

Nivedita Hegde1 , AJ Ashwal2, Shrayva Deekonda1 and

KK Suresh3

Abstract
Thiamine (vitamin B1) is a sulfur-containing, water-soluble vitamin that plays an essential role in energy metabolism and the tricarboxylic acid
cycle. There is an increased need for vitamin B1 (1–1.2 mg daily) during pregnancy and lactation. Hyperemesis during pregnancy can cause severe
polyneuropathy (Wernicke’s encephalopathy) as a result of thiamine deficiency. Thiamine deficiency has also been associated with beriberi. A
number of atypical cases with reversible right heart failure and severe pulmonary hypertension have also been reported in non-pregnant
individuals, but have never been reported in pregnancy. Here we present five such cases of thiamine deficiency with neurological and cardio-
pulmonary manifestations.

Keywords
Thiamine deficiency, beriberi, Wernicke’s encephalopathy, right heart failure, pulmonary hypertension
Date Received: 26 June 2020; accepted: 28 August 2020

Introduction hyperemesis gravidarum from six weeks of gestation. There was no

Thiamine (vitamin B1) is a sulfur-containing, water-soluble vitamin
that plays an essential role in energy metabolism and the tricarboxylic
acid cycle. It plays an important role in neurotransmission and sen-
sory nerve conduction. There is an increased need for vitamin B1 (1–
1.2 mg daily) during pregnancy and lactation, and there is a higher
concentration of the vitamin B1 in the fetal blood than in that of the
mother. Thiamine deficiency can result in symptoms within one week.
Hyperemesis during pregnancy can cause severe polyneuropathy
(Wernicke’s encephalopathy).
Neiching, a Chinese doctor in 2697 BC first reported beriberi, but
it was not attributed to thiamine deficiency. In 1890, Eijkman
reported a polyneuropathy in birds fed with rice alone, which was
similar to symptoms of beriberi in humans. It can cause high output
heart failure with pulmonary hypertension. A number of atypical
cases with reversible right heart failure and severe pulmonary hyper-
tension have also been reported in non-pregnant individuals but
never been previously described in pregnancy.
Case 1
A 27-year-old lady with 15 weeks of gestation presented with acute
confusional state (delirium) of one week duration. She had a history
of a spontaneous fetal loss at 16 weeks of gestation in the previous
pregnancy, which was not evaluated. The present pregnancy was the
result of spontaneous conception. Relatives gave a history of
history of fever, headache, or neck pain.
She was hemodynamically stable, conscious but not oriented to
time, place, and person. Initial evaluation showed a GCS score of 7
(E4V2M1). Higher mental functions could not be assessed.
Neurological examination showed decreased power and tone in bilat-
eral upper and lower limbs (lower limb more than upper limb), and
diminished reflexes, multidirectional nystagmus, left lateral rectus
muscle palsy. Pupils were bilaterally equal and reactive. Due to a
deterioration of consciousness (GCS score of 3), the patient was
intubated and ventilated. Laboratory investigations, sonographic,
and radiological findings are given in Table 1. MRI brain was done
and it showed features suggestive of Wernicke’s encephalopathy
(bilateral symmetrical hyperintensity T2/fluid-attenuated inversion
recovery (FLAIR) signals in mammillary bodies, dorsomedial
1
Department of Obstetrics and Gynaecology, Kasturba Medical College,
Manipal Academy of Higher Education, Manipal, India
2
Department of Cardiology, Kasturba Medical College, Manipal Academy
of Higher Education, Manipal, India
3
Department of Radiology, Kasturba Medical College, Manipal Academy
of Higher Education, Manipal, India
Corresponding author:
Nivedita Hegde, Department of Obstetrics and Gynaecology, Kasturba
Medical College, Manipal Academy of Higher Education, Manipal, India.
Email: niveditaashwal@gmail.com
 2

Table 1. Laboratory investigations, sonographic, and radiological findings.

CASE 1 CASE 2 CASE 3 CASE 4 CASE 5

Age (Years) 27 32 35 23 33
Hb (g/dl) 13.3 10.3 10.5 13.4 14
Creatinine (mg/dL) 0.6 0.3 0.37 0.84 0.60
Potassium (mmol/L) 4.4 4.1 3.8 5.1 4.4
Sodium (mmol/L) 142 125 140 140 134
Bilirubin (mg/dL) 0.15 1.13 0.4 0.29 0.42
Calcium 7.6 8.9 8.7 7.8 8.2
Magnesium 2.0 1.7 1.6 2.1 1.8
ALT (IU/L) 13 89 18 10 12
AST (IU/L) 21 58 27 12 16
ALP( U/L) 36 62 97 74 66
D Dimer (mg/ml) 2.4 6.8 5.4
TSH ( micro IU/L) 2.07 3.2 0.63 6.63 4.5
NT PRO (pg/mL) 45 33 56 9476 11236
Vitamin B12 (pg/ml) >2000 1122 450 420.6 688
Vitamin D (ng/ml) 16.6 14.12 13.5 10.22 12.11
Vitamin B1 (nmol/L) 42 32 27 16 21
Other investigations MRI Head MRI head MRI Head Echocardiography Echocardiography
Bilateral symmetrical T2/ Bilateral symmetrical T2/ Bilateral symmetrical T2/ On Admission: On Admission:
FLAIR hyperintensities in FLAIR hyperintensities in FLAIR hyperintensities in PAH 67 mmHg PAH 50 mmHg
mammillary bodies, dorso- mammillary bodies, dorso- mammillary bodies, dorso- After 2 weeks: After 2 weeks:
medial thalami, medial thalami, medial thalami, PAH 47 mmHg PAH 34 mmHg
around third ventricle and around third ventricle and around third ventricle and After 3 months: After 3 months:
dorsal pons showing diffu- dorsal pons showing diffu- dorsal pons showing diffu- PAH 20 mmHg PAH 24 mmHg
sion restriction sion restriction sion restriction CTPA: Mildly dilated CTPA:
MPA/RPA/ Mildly dilated MPA/RPA/
LPA LPA
RV/LV >1 RV/LV >1
Auto immune profile Normal Normal Normal Normal Normal

MPA: main pulmonary artery; RPA: right pulmonary artery; LPA: left pulmonary artery; RV: right ventricle; LV: left ventricle.
Obstetric Medicine: The Medicine of Pregnancy
Hegde et al.
thalami, around third ventricle and dorsal pons (Figure 1(a) to (d)).
Nerve conduction studies (NCS) showed changes consistent with an
axonal neuropathy. Magnetic resonance (MR) venogram was
normal. Cerebrospinal fluid (CSF) analysis was also normal.
MRI and NCS reports were noted and the patient was suspected
to have thiamine deficiency. Serum thiamine levels were low
(42 nmol/L (normal range: 67–200 nmol/L) consistent with deficiency
and the diagnosis of Wernicke’s encephalopathy. She was treated
with 500 mg intravenous thiamine twice daily for three days, and
then she was started on 200 mg of oral thiamine daily supplementa-
tion. She was on ventilator support for four weeks and underwent
tracheostomy. Her neurological condition gradually improved over
four weeks (from GCS score of 3 to 13; E4V4M5) and she was
weaned off the ventilator. Hypotonia and multidirectional nystagmus
persisted.
The patient had a persisting low mood. Montreal cognitive assess-
ment test (MoCA) done showed attention impairment and recent
memory impairment for which she was continued on oral thiamine
supplementation and started on oral agomelatine and memantine.
A fetal scan done showed good cardiac activity and regular ante-
natal check-ups were done. Anomaly scan done at 21 weeks showed
no gross anomalies. The patient was discharged at 27 weeks, after
Figure 1 (a–d) MRI brain showing features suggestive of
Wernicke’s encephalopathy with bilateral symmetrical T2/FLAIR
hyper intensities in mammillary bodies, dorsomedial thalami,
around third ventricle and dorsal pons showing diffusion
restriction.
3
3 months of hospitalization, with tracheostomy (to reduce the likeli-
hood of aspiration as she was confined to bed) and a nasogastric tube
in situ to provide enteral nutrition, as generalized encephalopathy
changes persisted, and she had significant residual muscle weakness
with a GCS score of 13 (E4V4M5).
At 31 weeks of gestation, a regular antenatal ultrasound identified
a short cervix of 2.3 cm and fetal growth restriction (FGR) with an
estimated fetal weight of 1.3 kg. She was admitted and started on
steroid prophylaxis for fetal lung maturity and progesterone supple-
ments. At 34 weeks, the patient was admitted in preterm labor with
breech presentation. She underwent an emergency caesarean section
and delivered a live baby of 1.7 kg. She was continued on oral thia-
mine 100 mg twice daily, oral memantine once daily, and oral pirac-
etam three times daily, in addition to routine postoperative
medications.
She was slowly weaned off tracheostomy support and started on
oral feeding. Nasogastric tube was then removed and she was dis-
charged after 15 days. At the time of discharge, she was still confined
to bed and required assistance for her routine activities.
Case 2
A 32-year-old woman in her first pregnancy was referred to our
center at 17 weeks of gestation following 2 generalized tonic-clonic
seizures. She had no history of seizures in the past and had no sig-
nificant past medical history. There was no history of alcohol con-
sumption. It was a spontaneous conception and initial antenatal
checkups were done at a local hospital. She gave a past history of
hyperemesis in the first trimester at eight weeks, which was managed
medically. She described a new headache that had developed two
days before seizure onset, following which she was told she had
high blood pressure, but repeat values were normal. She had one
seizure episode a day before admission to our hospital, which
lasted for 2–3 min and was managed with intravenous diazepam
and phenytoin at a local hospital, but when these seizures continued,
she was referred to a tertiary care center for management and
evaluation.
On admission, the patient was in an irritable and non-responsive
state. Vitals were normal, the GCS score was 13 (E4V4M5). Pupils
were bilaterally equal and reactive. The muscle tone was normal. The
power, sensory, and cerebellar function could not be assessed initial-
ly. No neck rigidity was noted.
Abdominal examination showed the uterus size was consistent
with her gestation. Ultrasonography showed good cardiac activity
in the fetus.
Blood tests showed mildly deranged liver function tests (see
Table 1). There was concern that these episodes represented atypical
HELLP syndrome, so medical termination of pregnancy was dis-
cussed and then performed. She was started on an infusion of mag-
nesium sulphate after delivery.
An MRI was then performed and was suggestive of Wernicke’s
encephalopathy. There was no evidence of cerebral venous sinus
thrombosis. Serum thiamine levels were 32 nmol/L confirming defi-
ciency and supported the diagnosis of Wernicke’s encephalopathy.
Intravenous thiamine 500 mg twice daily and levetiracetam 750 mg
twice daily were started and continued for three days. This was
then followed by oral supplementation of 200 mg of thiamine per
day and 500 mg levetiracetam twice daily. As the patient’s condition
improved and she started to mobilize, gait ataxia and multi-
directional nystagmus were also noted.
She was discharged in a stable condition on oral levetiracetam
500 mg twice daily and oral thiamine 100 mg twice daily after
two weeks with normal cognitive function, good higher mental func-
tion, and minimal motor/cerebellar deficits.
4 Obstetric Medicine: The Medicine of Pregnancy

Case 3
A 35-year-old woman at 38 weeks of gestation was referred to our
center for further management of pregnancy. She had been previously
diagnosed and treated for Wernicke’s encephalopathy in her second
trimester.
She was in her second pregnancy. Her first pregnancy was
uneventful. In the current pregnancy, she received antenatal care at
a local hospital. At 13 weeks, she had been admitted with a history of
hyperemesis gravidarum, in the semiconscious state along with nys-
tagmus, restricted bilateral convergence of eye, and confusion. MR
venogram was normal and MRI brain was suggestive of Wernicke’s
encephalopathy with bilaterally symmetrical T2/FLAIR hyperinten-
sities showing diffuse restriction with no areas of blooming in medial
thalami, periaqueductal grey matter, mammillary bodies, and tectum.
Outside lab reports revealed serum thiamine levels of 27 nmol/L. She
was treated with intravenous thiamine 500 mg twice daily for three -
days and then followed by an oral maintenance dose of 100–200 mg
thiamine daily. Her clinical condition improved and became fully
conscious and oriented within one week. All the neurological deficits
improved over the next two weeks with thiamine supplementation.
At the time of admission to our center, the patient was fully con-
scious and oriented with no neurological deficits. Repeat MRI brain
in our institute showed significant improvement. Previously noted
changes were significantly reduced and thin symmetrical gyriform
FLAIR hyperintensities involving bilateral frontoparietal lobes
were not seen in the present study.
Fetal ultrasound showed a good biophysical profile and amniotic
fluid index, with an estimated fetal weight being 2.5 kg. She under-
went an elective caesarean section (due to previous caesarean section)
and delivered a healthy baby of 2.4 kg. She was advised to continue
oral thiamine 100 mg twice daily.

Case 4
A 23-year-old woman with 32 weeks of amenorrhea, presented with a
one-month history of progressive dyspnea of NYHA Class 2 to 3 and
generalized edema. There was no history of hyperemesis gravidarum,
any prior lung disease or rheumatological conditions, use of medica- Figure 2. (a and b) A chest CT scan with contrast enhancement
tions that may cause pulmonary pathology such as amiodarone, and showing a slightly enlarged trunk of the pulmonary artery with
she did not smoke, consume excessive alcohol, or used illicit drugs. right ventricle/left ventricle ratio >1 suggestive of right ventric-
Her diet was normal with rice as the main component. On examina- ular strain but was negative for pulmonary embolism.
tion, her blood pressure was 122/64 mmHg, pulse was 110 beats per
minute, and respiratory rate was normal. Physical examination
showed mild jugular venous distension and edema of the face, Intravenous thiamine (500 mg twice daily) was given for three -
upper, and lower limbs. Physical and neurological findings were oth- days and followed by oral supplementation of thiamine (100 mg twice
erwise entirely normal. There was no confabulation on cognitive daily).
assessment. Within one week, there was improvement in her symptoms of
Arterial blood gas (ABG) was normal. Hemoglobin, kidney func- dyspnea and bilateral pitting edema. Repeat 2D Echo after two weeks
tion, liver function, thyroid function tests, and D-dimer were normal showed marked improvement in the pulmonary artery hypertension
(Table 1). NT pro-BNP was increased (9476 ng/ml). ECG showed
(47 mmHg). After three months of follow-up on oral thiamine sup-
normal sinus rhythm with T wave inversion in leads V1-3. A chest
plementation, echocardiography showed normal pulmonary artery
radiograph showed mild cardiomegaly. Echocardiography showed
pressures with normal biventricular function. Her symptoms had
marked right ventricular dilation and flattening of the interventricu-
entirely resolved.
lar septum with a D-shaped deformation of the left ventricle in later
She continued her antenatal care at a local hospital and delivered
systole and throughout diastole, consistent with right ventricular
a healthy baby of 3 kgs at term. She was advised to continue oral
overload. Severe tricuspid regurgitation was found. The estimated
thiamine supplementation for six months.
systolic pulmonary artery pressure as determined on continuous
wave Doppler echocardiography was 67 mmHg. The left ventricular
ejection fraction was normal. Case 5
Chest CT scans with contrast enhancement (Figure 2(a) and (b))
showed a slightly enlarged trunk of the pulmonary artery with right Case 5 was a 33-year-old lactating woman who presented with 15
ventricle/left ventricle ratio greater than one, suggestive of right ven- days history of dyspnea of NYHA class 2 and generalized edema
tricular strain. No pulmonary emboli were identified. The serum thi- after 5 months following the delivery of her first child. Her antenatal
amine levels were found to be low (16 nmol/L). period was uneventful and infant was exclusively breastfed. As in case
Hegde et al.
4, there was no significant medical history and she consumed a
normal diet with rice as the main component. Blood pressure was
112/78 mmHg, pulse was 108 beats per minute, and respiratory rate
was normal. Physical examination findings were also similar to case 4;
mild jugular venous distension and edema of the face, upper, and
lower limbs. There were no abnormal neurological findings. The
infant was asymptomatic and was not evaluated for thiamine
deficiency.
ECG showed normal sinus rhythm with T wave inversion in V1-3
leads. Chest radiograph showed mild cardiomegaly.
Echocardiography showed marked right ventricular dilation and flat-
tening of the interventricular septum with a D-shaped deformation of
the left ventricle in later systole and throughout diastole, which indi-
cated right ventricular overload. Severe tricuspid regurgitation was
found. The estimated systolic pulmonary artery pressure as deter-
mined on continuous wave Doppler echocardiography was 50 mm
Hg. The left ventricular ejection fraction was normal.
The ABG was normal. Hemoglobin, kidney function, liver func-
tion, thyroid function, and D-dimer were normal (Table 1). The NT
pro-BNP level was elevated (11,236 pg/ml). Chest CT scans with con-
trast (Figure 2(a) and (b)) showed a slightly enlarged trunk of the
pulmonary artery with right ventricle/left ventricle ratio greater than
one suggestive of right ventricular strain but were negative for pul-
monary embolism. The serum thiamine levels were low (21 nmol/L).
Intravenous thiamine (500 mg twice daily) was administered for
three days and followed by oral thiamine (100 mg twice daily).
Within one week there was an improvement with reduced dyspnea
and markedly reduced edema. Repeat 2D Echo after two weeks
showed marked improvement in the pulmonary artery hypertension
(34 mmHg). 2D Echo after three months of follow up on oral thia-
mine supplementation showed normal pulmonary artery pressure
with normal biventricular function and complete resolution of
symptoms.
Discussion
Thiamine deficiency is an important health issue in many parts of the
world. Inadequate diets, consumption of foods with anti-thiamine
compounds (thiaminases, tannin-containing or food rich in caffeine,
theobromine, and theophylline), prolonged cooking of foods, chronic
alcoholism, HIV-related disorders, and gastrointestinal diseases are
the main reasons for thiamine deficiency.
Thiamine (vitamin B1) is a water-soluble, sulfur-containing vita-
min. Its only source is diet (beef, poultry, cereals, nuts, and beans).
The maximum stored thiamine in the body is not more than 30 mg
and the minimum average thiamine requirement is 0.66 mg for an
average of 2000 kcalories consumed daily.1 Recommended daily
intake for men and women is around 1.2 and 1.1 mg, respectively.1,2
During pregnancy or breast-feeding, the daily requirement increases
to 1.4 mg/day.1 During lactation, infants have increased risks of
developing beriberi from deficient but asymptomatic mothers.3
White rice consumption is a common cause of thiamine deficiency
in developing countries.3,4 Industrial rice milling and processing strip
away essential nutrients (such as thiamine) within the bran;5 90% of
the rice produced worldwide is consumed by Asian countries, with a
prevalence of thiamine deficiency to the extent of 15% of the adoles-
cent population.6
Wernicke’s encephalopathy is a neurological disorder. The classic
triad of encephalopathy, ophthalmoplegia, and/or nystagmus and
ataxia constitutes Wernicke’s encephalopathy.7 All the three patients
in our case series had this triad. The mechanism which causes brain
lesions is unknown, but neuronal damage begins once the metabolism
in brain regions with high metabolic requirements of thiamine is
inhibited.7 Thiamine is an essential coenzyme and major component
in many biochemical pathways in the brain which include
5
transketolase, alpha-ketoglutarate dehydrogenase, and pyruvate
dehydrogenase enzymes.8 Usually, Wernicke’s encephalopathy is
reversible but major complications can arise in pregnant women
and fetuses. Wernicke’s encephalopathy can cause permanent neuro-
logic deficits and Korsakoff syndrome in mothers which is life-
threatening in 10–20% of cases. It can also cause miscarriage,
preterm birth, and intrauterine growth restriction.9 In case 1, the
patient had preterm delivery and there was evidence of FGR. The
typical lesions in MRI are bilateral symmetrical hyperintensities
involving the thalamus, mammillary bodies, tectal plate, and peria-
queductal areas, although early reversible cytotoxic edema is the most
distinctive.7 The diagnosis of Wernicke’s encephalopathy is mainly
based on the clinical features, MRI findings, and rapid improvement
of symptoms with thiamine replacement.10 Symptomatic improve-
ment often requires months of treatment and complete remission is
rarely obtained possibly due to significant storage depletion and inad-
equate supplementation. In a series by Chiossi et al.,8 complete remis-
sion was obtained in only 14 of the 49 reported cases, along with
spontaneous fetal loss in 37%, and elective termination of pregnancy
in 10%.
Beriberi is characterized by high cardiac output failure due to
arteriolar vasodilatation.11 Pulmonary hypertension can be caused
by increased pulmonary arterial blood flow and elevated left ventric-
ular end-diastolic pressure.12 Left ventricular function is reported to
be normal or hyperkinetic in beriberi. Thiamine deficiency can be a
cause of a reversible form of pulmonary hypertension and it must be
included in the differential diagnosis in patients with a high risk of
nutritional thiamine deficiency.
In our case series, three women presented with Wernicke’s
encephalopathy. They had typical symptoms and typical features
on MRI scans. One of the women had persistent neurological deficits,
while others had a complete recovery. Two other women presented
with severe pulmonary hypertension. They had complete recovery
with thiamine supplementation and had an uneventful postnatal
period.
Thiamine status can be evaluated in two ways, by assessing the
degree of ThDP-saturation of a thiamine-dependent enzyme (eryth-
rocyte transketolase (ETK) assay), and by measuring thiamine
metabolites in the accessible tissues. The ETK assay is considered
to be more informative and demonstrates the actual functionality
of the vitamin. Both methods show thiamine status to be lower in
regions of the world where beriberi occurs than where it does not
occur. However, in populations with beriberi, both affected and non-
affected individuals may have similarly low values.13,14 Plasma thia-
mine level reflects only the recent intake of thiamine and not the
store. Thiamine diphosphate level of the erythrocytes is the biologi-
cally active vitamin form and an indicator of thiamine status.15
However, the tests which assess the biomarkers of thiamine status
are not widely practiced. These tests require temperature controlled
transport of the samples which adds costs and challenges to the diag-
nosis. Clinically, thiamine deficiency can present suddenly and can be
rapidly fatal, so treatment of suspected beriberi patients empirically
with thiamine is advised.15 Plasma thiamine and TMP correlate with
eThDP, and all thiamine forms respond significantly to thiamine
intervention.16
A therapeutic trial is the best test in suspected thiamine deficiency
and the clinical improvement on thiamine supplementation proves
the diagnosis.17 There are no universally accepted guidelines regard-
ing the treatments of thiamine deficiency. European Federation of
Neurological Societies recommends thiamine to be given at a dose
of 200 mg intravenously three times daily, before any carbohydrate,
and to be continued till there is no further improvement in signs/
symptoms.18 RCOG Green Top Guideline 69 advocates thiamine
supplementation (either oral or intravenous form) to all women
admitted with a history of prolonged vomiting, especially before
6 Obstetric Medicine: The Medicine of Pregnancy
administration of dextrose or parenteral nutrition.19 Depending on
the clinical severity, a high thiamine dose of 500 mg twice daily has
been advised by many.10 Hence, in all of our cases, treatment was
started at a similar dose for three days and then converted to oral
supplementation 100–200 mg/day for a minimum of six months.
There are no clinical data that suggest any teratogenicity with high
doses of thiamine.
Conclusion
Thiamine deficiency is very common in pregnant and lactating
women in developing countries. Early diagnosis and treatment can
prevent Wernicke’s encephalopathy as well as pulmonary hyperten-
sion and can prevent major maternal and fetal complications.
Routine supplementation with thiamine during pregnancy is, as a
rule, unnecessary; however, for hyperemesis gravidarum, and
women where dietary information shows they are at high risk of
deficiency, thiamine should be supplemented.
Acknowledgments
None.
Availability of data
It’s a clinically oriented case series and all relevant information have
been submitted.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
Ethical approval
Not taken as it was a retrospective study and it involved reporting a
case series.
Informed consent
Written informed consent was obtained from the patient(s) for their
anonymized information to be published in this article.
Guarantor
Dr. Nivedita Hegde.
Contributorship
Dr. N H: Data collection and manuscript writing, Dr. S D: Data
collection, Dr. K K: Data collection, Dr. A J: Data collection.
ORCID iD
Nivedita Hegde https://orcid.org/0000-0003-2357-2522
References
1. Martin PR, Singleton CK and Hiller-Sturmhofel S. The role of
thiamine deficiency in alcoholic brain disease. Alcohol Res Health
2003; 27: 134–142.
2. Martel JL and Franklin DS. Vitamin B1 (thiamine). In:
StatPearls. Treasure Island, FL, 2018.
3. Lonsdale D. A review of the biochemistry, metabolism, and clin-
ical benefits of thiamin(e) and its derivatives. Evid Based
Complement Alternat Med 2006; 3: 49–59.
4. Lonsdale D and Marrs C. High-calorie malnutrition and its
impact on health. In: Lonsdale D and Marrs C (eds) Thiamine
deficiency disease, dysautonomia, and high-calorie malnutrition.
Cambridge, MA: Academic Press, pp. 213–261, 2017.
5. Scrimshaw NS and Behar M. Malnutrition in underdeveloped
countries. N Engl J Med 1965; 272: 193–198.
6. Whitfield KC, Smith G, Chamnan C, et al. High prevalence of
thiamine (vitamin B1) deficiency in early childhood among a
nationally representative sample of Cambodian women of child-
bearing age and their children. PLoS Negl Trop Dis 2017; 11:
e0005814.
7. GascOn-Bayarri J, Campdelacreu J, GarcIa-Carreira MC, et al.
Wernicke’s encephalopathy in non-alcoholic patients: a series of
8 cases. Neurologia 2011; 26: 540–547.
8. Chiossi G, Neri I, Cavazzuti M, et al. Hyperemesis gravidarum
complicated by Wernicke encephalopathy: background, case
report, and review of the literature. Obstet Gynecol Surv 2006;
61: 255–268.
9. Michel ME, Alanio E, Bois E, et al. Wernicke encephalopathy
complicating hyperemesis gravidarum: a case report. Eur J
Obstet Gynecol Reproduct Biol 2010; 149: 117–123.
10. Berdai MA, Labib S, Harandou M. Wernicke’s Encephalopathy
Complicating Hyperemesis during Pregnancy. Case Rep Crit
Care 2016; 2016: 8783932. DOI:10.1155/2016/8783932.
11. Jeffrey FE and Abelmann WH. Recovery from proved Shoshin
beriberi. Am J Med 1971; 50: 123–128.
12. Okura H and Takatsu Y. High-output heart failure as a cause of
pulmonary hypertension. Intern Med 1994; 33: 363–365.
13. Khounnorath S, Chamberlain K, Taylor AM, et al. Clinically
unapparent infantile thiamin deficiency in Vientiane. PLoS
Negl Trop Dis 2011; 5: e969.
14. Coats D, Shelton-Dodge K, Ou K, et al. Thiamine deficiency in
Cambodian infantswith andwithout beriberi. J Pediatr 2012; 161:
843–847.
15. Whitfield KC, Bourassa MW, Adamolekun B, et al. Thiamine
deficiency disorders: diagnosis, prevalence, and a roadmap for
global control programs. Ann N Y Acad Sci 2018; 1430: 3–43.
16. McCann A, Midttun Ø, Whitfield KC, et al. Comparable perfor-
mance characteristics of plasma thiamine and erythrocyte thia-
mine diphosphate in response to thiamine fortification in rural
Cambodian women. Nutrients 2017; 9: 676.
17. Park JH, Lee JH, Jeong JO, et al. Thiamine deficiency as a rare
cause of reversible severe pulmonary hypertension. Int J Cardiol
2007; 121: e1–e3.
18. Galvin R, Br˚athen G, Ivashynka A, et al. EFNS guidelines for
diagnosis, therapy, and prevention of Wernicke encephalopathy.
Eur J Neurol 2010; 17: 1408–1418.
19. RCOG. The management of nausea and vomiting of pregnancy
and hyperemesis gravidarum. RCOG Greentop Guideline No 69,
2016.