Am J Clin Nutr 2002;76:426–9. Printed in USA. © 2002 American Society for Clinical Nutrition
Vitamin A deficiency in a newborn resulting from maternal
hypovitaminosis A after biliopancreatic diversion for the treatment
of morbid obesity1–3
Sergio Huerta, Lisa M Rogers, Zhaoping Li, David Heber, Carson Liu, and Edward H Livingston
Background: Biliopancreatic diversion (BPD) has been advo-
cated for the treatment of morbid obesity. This procedure has the
theoretical advantage that patients retain normal eating capacity
and lose weight irrespective of their eating habits. However, vita-
min deficiencies may develop because BPD causes malabsorption.
Objective: This report describes a 40-y-old mother and her new-
born infant, who developed vitamin A deficiency as a result of
iatrogenic maternal malabsorption after BPD. Our primary objec-
tive is to show that BPD patients need close follow-up and life-
long micronutrient supplementation to prevent nutrient deficien-
cies in themselves and their offspring.
Design: The medical records of the mother and infant were
reviewed, and their clinical course was followed until 10 mo post-
partum. The mother was also interviewed on several occasions
about her medical care, follow-up, and supplemental vitamin use.
Results: The mother developed night blindness with undetectable
serum vitamin A concentrations in the third trimester of her preg-
nancy. Her vitamin A deficiency was untreated until she delivered
her infant. At delivery, the infant also had vitamin A deficiency.
He may have permanent retinal damage, but this is still unclear
because the ophthalmologic examination performed at 2 mo of age
Conclusions: Complications of BPD may take many years to
develop, and the signs and symptoms may be subtle. Because of
the malabsorption that results from BPD, patients need lifelong
follow-up and appropriate vitamin supplementation to prevent defi-
ciencies.These nutrient deficiencies can also affect the offspring of
female BPD patients.
Am J Clin Nutr 2002;76:426–9.
night blindness, malabsorption, morbid obesity, neonatal
nutrition, hypovitaminosis A
Vitamin A deficiency, biliopancreatic diversion,
The prevalence of obesity is constantly rising, and this has led to
a parallel increase in the number of surgical procedures performed
to treat clinically severe (morbid) obesity. Seventy-five to eighty
percent of patients who have surgical treatment for morbid obesity
are female (1–3). Some physicians have advocated biliopancreatic
diversion (BPD) for the surgical management of obesity. Because
most women who choose BPD are of childbearing age (2–4), preg-
nancy is a frequent event after the surgical intervention. In fact, res-
olution of infertility is a beneficial effect of BPD (5). However, BPD
1From the Department of Surgery,VA Greater Los Angeles Health Care Sys-
tem (CL and EHL), and the UCLA Center for Human Nutrition, Los Angeles
(SH, LMR, ZL, and DH).
2Supported by a training grant from the National Institutes of Health
3Address reprint requests to S Huerta, UCLA Center for Human Nutrition,
900 Veteran Avenue, 12-217 Warren Hall, Box 951742, Los Angeles, CA
90095-1742. E-mail: email@example.com.
Received May 31, 2001.
Accepted for publication August 29, 2001.
patients are at risk of developing deficiencies of protein and fat-
soluble vitamins because this procedure relies on intestinal malab-
sorption. In pregnant women, this becomes an even greater concern
because of the physiologic stress associated with pregnancy. There-
fore, women who have had BPD need additional prenatal nutritional
support. Prenatal vitamins alone are insufficient for preventing
severe vitamin deficiencies during pregnancy in BPD patients (6).
In 1973, Scopinaro et al (3) described BPD for the treatment of
morbid obesity. In BPD, a distal gastrectomy is performed and the
ileum is divided 200 cm proximal to the ileocecal valve. The distal
ileum becomes the alimentary limb and is anastomosed to the gas-
tric pouch, which is the intestinal segment that carries the food for
absorption. The proximal bowel is known as the biliopancreatic
limb because it carries the biliopancreatic secretions to the alimen-
tary limb. The distal end of the biliopancreatic limb is anastomosed
to the alimentary limb 50 cm proximal to the ileocecal valve. Thus,
absorption of nutrients only takes place in the last 50-cm segment
of the intestine (Figure 1). Long-term weight loss independent of
the patient’s eating behaviors has been cited as the major advan-
tage of BPD compared with gastric-restrictive procedures.
In patients who have had BPD, the fat-soluble vitamins (A, D, E,
and K) are poorly absorbed because of fat malabsorption in the
distal intestine. Six percent of patients develop deficiencies of the
fat-soluble vitamins after BPD (7). Consequently, patients who
have had surgery to induce intestinal malabsorption and thereby
treat obesity are at risk of developing night blindness from vitamin
A deficiency, bone loss from calcium malabsorption coupled with
vitamin D deficits, bleeding disorders from lack of vitamin K, and
both ataxia and dry pruritic skin from vitamin E deficiency. Sev-
eral cases of vision disorders secondary to vitamin A deficiency
after BPD have been reported (2, 7–9). Night blindness (impaired
dark adaptation resulting from slowed regeneration of rhodopsin)
is the first ocular symptom observed with vitamin A deficiency
(10), but late symptoms also occur. In addition, vitamin A is
VITAMIN A DEFICIENCY AFTER BILIOPANCREATIC DIVERSION427
FIGURE 1. Diagram of biliopancreatic diversion, showing that the
only intestinal segment available for digestion and absorption is the last
50 cm of the small intestine, where the alimentary limb meets the bil-
required for the differentiation and growth of epithelial cells dur-
ing embryonic development (11), and thus it is an important
micronutrient during pregnancy.
Although BPD is often performed in women of reproductive
age (3), and vitamin A deficiency is common after BPD, adverse
effects resulting from hypovitaminosis A have not been reported
previously in the offspring of BPD patients. The present report was
written to describe the need for close follow-up in patients who
have undergone BPD. Close follow-up is especially important in
pregnant women because their micronutrient deficiencies may also
affect their offspring.
SUBJECTS AND METHODS
Data collection methods
We reviewed the medical care received by the mother and
infant from the date of admission to the UCLA Medical Center at
12 d postpartum until 10 mo postpartum. Information was
obtained from the medical charts and from interviews conducted
in person and by telephone with the mother. We also collected
data regarding her medical condition, vitamin supplementation,
and physician follow-up from the time of her BPD surgery until
10 mo postpartum (1987–2000). The patient provided written,
informed consent for both herself and her child.
The patient had a history of obesity, which was treated surgi-
cally with BPD at a community hospital in 1987. Her weight
before surgery was 127 kg, with a body mass index (in kg/m2) of
50. She lost 68 kg during the first year after her surgery, but even-
tually regained 13.6 kg. Postoperatively, she had a good appetite
and did not experience nausea or vomiting. The patient had mild
chronic diarrhea, with loose bowel movements 3–4 times/d for the
first few months after surgery.
She was in good health until 1994, when she developed fatigue
and weakness. At this time, iron deficiency anemia was diagnosed
by her primary care physician. The anemia did not improve with
oral iron supplementation. The patient eventually required par-
enteral iron (3 doses/y), which she received for 3 y from 1994 to
1997. She did not undergo further testing for other micronutrient
deficiencies and she had no follow-up care from either a surgeon
or a nutritionist from the time following BPD surgery until she
was admitted to the UCLA Medical Center. The only supplements
she took during this time period were one children’s multivitamin
and 600 mg calcium carbonate/d. In addition, she received routine
prenatal vitamins during her pregnancies.
The patient first became pregnant in 1995. This pregnancy was
complicated by preeclampsia, but ultimately resulted in the deliv-
ery of a healthy infant. In 1999, a second pregnancy ended in
spontaneous abortion at 10 wk gestation. In 2000, during a third
pregnancy, the patient developed fatigue, lightheadedness, per-
sistent dizziness, and night blindness during the second trimester.
At this time, she was taking one children’s multivitamin contain-
ing 2500 IU vitamin A (50% of the RDA) daily, 600 mg calcium
carbonate/d, and 325 mg ferrous sulfate 3 times/d.
During her third trimester, the night blindness worsened,
prompting her to seek medical care at the Jules Stein Eye Institute
at UCLA. Ophthalmologic examination revealed a visual acuity
of 20/30 in the right eye and 20/40 in the left eye with normal ocu-
lar motility in both eyes. The intraocular pressure measured by
tonometry was normal at 16 mm Hg in both eyes. Dark adaptom-
etry (SST-1 Scotopic Sensitivity Tester; LKC Technologies,
Gaithersburg, MD) revealed a prolonged dark adaptation time in
both eyes, which is consistent with vitaminA deficiency.An elec-
troretinogram (Visual Evoked Response Imaging System; LKC
Technologies), which measures the electrical response of the
retina to flashes of light, revealed panretinal abnormalities of both
rod- and cone-mediated systems. Rod responses were not detected,
suggesting that the visual loss was a result of vitaminA deficiency.
VitaminA concentrations were not measurable in her serum, lead-
ing to a diagnosis of night blindness secondary to vitamin A defi-
ciency.After the diagnosis of vitaminA deficiency, water-miscible
vitaminA was recommended. However, the patient declined med-
ications because of her fear that they might harm the fetus.
The patient delivered a premature male infant via normal sponta-
(25th percentile; weight-for-age z score = ?0.674) and was 45 cm
circumference was 30 cm (20th percentile; head circumference-for-
age z score = ?0.704) and his APGAR scores were 7 and 9 at 1
and 5 min, respectively. At 2 d of age, he had a plasma vitamin A
concentration <0.1 mg/L (normal range: 0.3–0.9 mg/L). The
patient’s postpartum course was unremarkable except that she did
not breast-feed her infant because she was unable to lactate.
The patient was discharged from the hospital on the second day
after delivery. She was discharged to home with the following
medications: 600 mg ibuprofen every 6 h as needed for pain and
325 mg ferrous sulfate 3 times/d. She was given a prescription for
oral vitamin A (50000 IU/d), but she did not fill the prescription.
428HUERTA ET AL
The mother’s laboratory values during her hospital admission at 12 d postpartum showing evidence of severe anemia; hypoalbuminemia; low plasma
concentrations of vitamin A, 25-hydroxyvitamin D, vitamin E, calcium, and zinc; and elevated liver function tests1
Complete blood countChemistry profileVitamins Minerals Liver function tests
WBC = 9.6 ? 103/?L
(3.28–9.29 ? 103/?L)
RBC = 2.98 ? 106/?L
(3.76–4.93 ? 106/?L)
Hemoglobin = 6.9 g/dL
Hematocrit = 24.2%
Platelets = 256 ? 103/?L
(143–398 ? 103/?L)
Sodium = 138 mmol/L
Potassium = 3.7 mmol/L
Chloride = 108 mmol/L
CO2content = 25 mmol/L
Glucose = 90 mg/dL
Urea nitrogen = 13 mg/dL
Homocysteine = 10 ?mol/L
Vitamin A <0.1 mg/L
25-hydroxyvitamin D = 6 ng/mL
Vitamin E <2.0 mg/L
(5.6–22 mg/L )
Vitamin K = 143 pg/mL
Thiamine = 3.4 ?g/dL
Vitamin B-6 = 5.3 ng/mL
Vitamin B-12 = 153 pg/mL
(160–840 pg/mL )
Folate = 7.8 ng/mL
Iron = 18 ?g/dL
TIBC = 379 ?g/dL
Copper = 81 ?g/dL
Zinc = 45 ?g/dL
Calcium = 8.1 mg/dL
= 1.07 mmol/L
AST = 63 U/L
ALT = 84 U/L
Alkaline phosphatase = 199 U/L
Total bilirubin = 0.4 mg/dL
Total protein = 5.3 g/dL
Albumin = 2.8 g/dL
1Normal ranges are shown in parentheses. WBC, white blood cell count; RBC, red blood cell count; TIBC, total iron-binding capacity; AST, aspartate
aminotransferase; ALT, alanine aminotransferase.
At 12 d postpartum (19 October 2000), the patient was admitted
to the UCLA Medical Center. Her symptoms included fatigue,
lightheadedness, dizziness, dyspnea with minimal exertion, and
bilateral lower-extremity edema. She was only taking ferrous sul-
fate and one children’s vitamin/d. On physical examination, her
body temperature, blood pressure, heart rate, and respiration were
all normal (37?C, 140/80 mm Hg, 78 beats/min, and 16 breaths/min,
respectively). She weighed 73.5 kg (body mass index of 29). She
was pale with dry skin, very fine and crispy hair, and pitting nails.
On examination, her lungs were normal with good air movement.
Her cardiac exam revealed a regular heart rate and rhythm with a
mild systolic murmur at the left sternal border radiating to the
base. Her abdominal exam was also normal without masses or ten-
derness. Bilateral pedal edema and tenderness at both shins were
noted. Mild ataxia and unsteadiness were present on the neuro-
The patient’s laboratory results (Table 1) revealed severe ane-
mia; hypoalbuminemia; low plasma concentrations of vitamin A,
25-hydroxyvitamin D, vitamin E, calcium, and zinc; and elevated
liver function tests.
An abdominal ultrasound showed hepatomegaly and an
abdominal computed tomography scan showed a low-attenuation
lesion in the left hepatic lobe, most likely consisting of fat, and
a right renal angiomyolipoma. A liver biopsy indicated mild
microvesicular steatosis. An echocardiogram was unrevealing.
No evidence of osteomalacia was found on femoral and tibial
On the basis of all of the tests performed, the following diag-
noses were made: vitamin E deficiency resulting in ataxia, vita-
min B-6 deficiency resulting in neuropathy, and vitamin A defi-
ciency with a history of night blindness.
During the hospitalization, the patient was transfused with
2 units of packed red blood cells. Parenteral multivitamins con-
taining thiamin, folic acid, and vitamin D (calcitriol; Abbot Lab-
oratories, Chicago) were administered, and oral vitamin B-6,
vitamin E, and ferrous sulfate were provided. In addition, the
patient received intramuscular vitamin A (100000 IU) 3 times dur-
ing her hospital admission and follow-up for outpatient therapy.
After these interventions, the patient’s hemoglobin and hemat-
ocrit improved.The dizziness, mild neuropathy, dyspnea, and lower
extremity edema resolved. Her night blindness corrected soon after
vitaminA was administered. She was then discharged with the fol-
lowing medications: 325 mg oral ferrous sulfate 3 times/d, 15 IU
tocopherol (vitamin E)/d, 250 mg ascorbic acid (vitamin C)/d, 2 ?g
calcitriol (vitamin D)/d, 250 ?g cyanocobalamin (vitamin B-12)/d,
and protein-rich nutritional shake meal replacements. At a 2-wk
follow-up after her hospitalization, she was asymptomatic.
The child’s course of treatment was as follows. At 9 d of age,
he received 50000 IU vitamin A intramuscularly. At 1 mo of age,
the child’s eyes were fully formed and the mother thought that he
could see to some extent, although probably below the normal
acuity for his age. The mother also stated that he blinked at light
and performed some tracking. At this time, he was evaluated for
retinopathy of prematurity, a proliferative disorder of the retinal
blood vessels. This disorder was excluded as a potential cause of
his visual impairment. At 2 mo of age, his values for plasma
retinol, ?- and ?-tocopherol, and 1,25-dihydroxyvitamin D were
all within the normal ranges. At 7 mo of age, the infant was below
the 10th percentile for length (length-for-age z score = ?1.282),
at the 25th percentile for weight (weight-for-age z score = ?0.674),
and at the 50th percentile for weight-for-length (weight-for-length
z score = 0). The infant may have permanent retinal damage, but
this is still unclear because the ophthalmologic examination per-
formed at 2 mo of age was inconclusive.
BPD reduces the intestinal capacity to absorb fat and starch,
thereby limiting energy absorption and promoting weight loss (2).
In addition, BPD patients are at risk of malabsorption of the fat-
soluble vitamins, calcium, iron, and proteins. Complications of
long-term malabsorption occurring many years after the proce-
dure have been described; these complications include steatohep-
atitis, hepatic failure (7, 12), and secondary hyperparathyroidism
resulting from vitamin D and calcium malabsorption (13).
Micronutrient malabsorption after this operation has also been
VITAMIN A DEFICIENCY AFTER BILIOPANCREATIC DIVERSION 429 Download full-text
reported. Vitamin A deficiency is relatively common in BPD
patients, who often present with night blindness (2, 7–10). In a
large series of 1356 patients who underwent BPD, Scopinaro et al
(2) reported that 37 patients (2.7%) developed night blindness.
In addition to its role in the visual system, vitamin A plays an
In normal gestation, vitaminA is transported rapidly across the pla-
centa from the mother to her fetus (11, 14, 15) by way of retinal-
binding-protein receptors (16). Because an increasing number of
women of childbearing age are undergoing surgical treatment for
obesity, it is important to establish the risk factors for this patient
population to avoid hypovitaminosisA and possible adverse effects
on the fetus. In a series of 1136 BPD patients, there were 239 preg-
who were pregnant at the time of the report. In this 18-y follow-up,
32 patients required parenteral nutrition and the rest received stan-
dard prenatal care (5). Twenty-two infants (15.3%) were born pre-
maturely and 40 (27.8%) were born small for gestational age (5). It
is possible that nutritional deficiencies contributed to the high rates
role of vitaminA in these cases is unclear. The incidence of vitamin
A deficiency in pregnant women after BPD has not been reported.
The present case shows the consequences of iatrogenic vitamin
A deficiency after BPD. Because the patient was eating normal
amounts of food, she was not aware that she might be developing
micronutrient deficiencies. Her medical follow-up was inadequate,
which contributed to the delay in diagnosing her deficiencies. In
addition, the signs and symptoms of vitaminA deficiency are often
subtle.The first symptom noted in the present case was night blind-
ness, which could have been precipitated by the patient’s pregnancy.
The plasma concentration of vitamin A generally does not
decrease during pregnancy, despite fetal uptake (15). This is proba-
bly a result of the increased metabolism of fat that occurs during
pregnancy (15, 17–19). However, in the BPD patient, this physio-
fore vitaminA deficiency may develop in both the mother and fetus,
with adverse effects on the fetus. Animal studies of vitamin A defi-
ciency during pregnancy have found fetal malformations, intrauter-
mothers with hypovitaminosisA have a higher mortality rate, which
ent case, the mother delivered prematurely and the infant was born
small for gestational age.Whether this association can be attributed
to vitaminA deficiency, other nutritional deficits, or both is unclear.
Currently, advocates of BPD recommend 2 g oral calcium car-
bonate daily, 400000 IU vitamin D intramuscularly each month,
325 mg ferrous sulfate 3 times/d, and both thiamin and vitamin A
as needed for nonpregnant patients to avoid deficiencies of these
micronutrients. There are currently no standard guidelines for
vitamin supplementation in pregnant women who have undergone
BPD. Some vitamins, particularly vitamin A, may even be terato-
genic in high doses (> 25 000 IU). Excessive vitamin A during
early pregnancy has been associated with congenital obstructive
lesions of the ureter and malformations of the urinary tract (22).
Thus, it is absolutely imperative for a pregnant woman who has
undergone BPD to have close follow-up to assess nutritional defi-
ciencies and the appropriate supplementation.
This case study describes a severe, late complication of a pro-
cedure used to treat morbid obesity. To our knowledge, this is the
first case of vitamin A deficiency in an infant resulting from iatro-
genic, induced malabsorption in the mother. This case shows the
importance of life-long, close follow-up and vitamin A supple-
mentation after BPD for the treatment of morbid obesity.
1. Printen KJ, Scott D. Pregnancy following gastric bypass for the treat-
ment of morbid obesity. Am Surg 1982;48:363–5.
2. Scopinaro N, Gianetta E, Adami GF, et al. Biliopancreatic diversion
for obesity at eighteen years. Surgery 1996;119:261–8.
3. Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diver-
sion. World J Surg 1998;22:936–46.
4. Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V. Bilio-
pancreatic bypass for obesity. II. Initial experience in man. Br J Surg
5. Friedman D, Cuneo S, Valenzano M, et al. Pregnancies in an
18-year follow-up after biliopancreatic diversion. Obes Surg 1995;
6. Brolin RE. Update: NIH consensus conference. Gastrointestinal sur-
gery for severe obesity. Nutrition 1996;12:403–4.
7. Brolin RE, Leung M. Survey of vitamin and mineral supplementa-
tion after gastric bypass and biliopancreatic diversion for morbid obe-
sity. Obes Surg 1999;9:150–4.
8. Smets RM, Waeben M. Unusual combination of night blindness and
optic neuropathy after biliopancreatic bypass. Bull Soc Belge Oph-
9. Murr MM, Balsiger BM, Kennedy FP, Mai JL, Sarr MG. Malabsorp-
tive procedures for severe obesity: comparison of pancreaticobiliary
bypass and very very long limb Roux-en-Y gastric bypass. J Gas-
trointest Surg 1999;3:607–12.
10. Berson EL. Nutrition and retinal degenerations. Int Ophthalmol Clin
11. Morriss-Kay GM, Sokolova N. Embryonic development and pattern
formation. FASEB J 1996;10:961–8.
12. Grimm IS, Schindler W, Haluszka O. Steatohepatitis and fatal
hepatic failure after biliopancreatic diversion. Am J Gastroenterol
13. Chapin BL, LeMar HJ Jr, Knodel DH, Carter PL. Secondary hyper-
parathyroidism following biliopancreatic diversion. Arch Surg 1996;
14. Chambon P. The retinoid signaling pathway: molecular and genetic
analyses. Semin Cell Biol 1994;5:115–25.
15. Sapin V, Alexandre MC, Chaib S, et al. Effect of vitamin A status at
the end of term pregnancy on the saturation of retinol binding pro-
tein with retinol. Am J Clin Nutr 2000;71:537–43.
16. Sundaram M, SivaprasadaraoA, DeSousa MM, Findlay JB. The trans-
fer of retinol from serum retinol-binding protein to cellular retinol-
binding protein is mediated by a membrane receptor. J Biol Chem
17. Blomhoff R, Green MH, Norum KR. Vitamin A: physiological and
biochemical processing. Annu Rev Nutr 1992;12:37–57.
18. Shah RS, Rajalakshmi R. Vitamin A status of the newborn in relation
to gestational age, body weight, and maternal nutritional status. Am
J Clin Nutr 1984;40:794–800.
19. Shah RS, Rajalakshmi R, Bhatt RV, et al. Liver stores of vitamin A in
human fetuses in relation to gestational age, fetal size and maternal
nutritional status. Br J Nutr 1987;58:181–9.
20. Neela J, Raman L. The relationship between maternal nutritional sta-
tus and spontaneous abortion. Natl Med J India 1997;10:15–6.
21. Humphrey JH, West KP Jr, Sommer A. Vitamin A deficiency and
attributable mortality among under-5-year-olds. Bull World Health
22. Mendelsohn C, Batourina E, Fung S, Gilbert T, Dodd J. Stromal cells
mediate retinoid-dependent functions essential for renal development.