Nutritional Vitamin B12 Deficiency in a Breastfed Infant Following Maternal Gastric Bypass

Breasfed infants of women who have had gastric or intestinal bypass procedures may develop nutritional deficiencies. We describe a 10-month-old exclusively breastfed white male infant who presented with vomiting, failure to thrive, and megaloblastic anemia. He was found to have vitamin B₁₂ deficiency. His mother had undergone a gastric bypass procedure for morbid obesity 2 years Prior to her pregnancy with this child. She had subclinical vitamin B₁₂ deficiency, with an abnormal Schilling test that corrected with the addition of intrinsic factor. Therefore, we believe that the mother's gastric bypass had caused a decrease in available intrinsic factor, resulting in subclinical vitamin B₁₂ deficiency and decreased breast milk B₁₂. Although she was asymptomatic, her breastfed infant developed symptomatic B₁₂ deficiency. This is the first reported case of a maternal gastric bypass resulting in vitamin B₁₂ deficiency in an infant. These mothers should receive vitamin supplements, including vitamin B₁₂ during and after pregnancy, and my require parenterally administered vitamin B₁₂.     

Solid food refusal as the presenting sign of vitamin B<Subscript>12</Subscript> deficiency in a breastfed infant

Dietary vitamin B₁₂ (vitB₁₂) deficiency, although common in the elderly, is rare in childhood. We report on an exclusively breastfed 8-month-old infant, presenting with persistent refusal of solid foods. Three months later, developmental regression and failure to thrive led to the diagnosis of vitB₁₂ deficiency, as a consequence of a subclinical pernicious anaemia with vitB₁₂ deficiency in the mother. Treating the infant with parenteral vitB₁₂ induced prompt recovery including acceptance of weaning food. Conclusion: This case illustrates refusal of complementary foods as a presenting symptom of vitB₁₂ deficiency in a breastfed infant. Symptoms, diagnostic tests and treatment of vitamin B₁₂ deficiency are reviewed. Early diagnosis and treatment are important to prevent irreversible neurological damage.     

Nutritional vitamin B12 deficiency: Two cases detected by routine newborn urinary screening

We describe two asymptomatic newborns with nutritional vitamin B₁₂ deficiency in whom increased urinary methylmalonic acid was detected by routine neonatal screening at 3 weeks of age. Both infants were exclusively breast-fed. One mother suffered from pernicious anaemia, and the other was a strict vegetarian. Both mothers had no clinical or haematological abnormality, aside from a borderline mean corpuscular volume for the vegetarian mother. This report illustrates the early appearance of functional vitamin B₁₂ deficiency in breastfed infants of vitamin B₁₂-depleted mothers. It also demonstrates that urinary methylmalonic acid measurement is a sensitive indicator of tissue vitamin B₁₂ deficiency.     

Vitamin B12 deficiency with intrinsic factor antibodies in an infant with poor growth and developmental delay

Vitamin B₁₂ deficiency is very rare in infants and may lead to serious hematological and neurodevelopmental abnormalities. The present article describes a case involving a seven-month-old boy with severe vitamin B₁₂ deficiency, likely caused by juvenile pernicious anemia, an entity rarely described. The child presented with feeding intolerance, poor growth and developmental delay. He was noted to have macrocytic anemia, a markedly low serum vitamin B₁₂ level, and elevated homocysteine and methylmalonic acid levels. Antibodies to intrinsic factor were positive. The mother was healthy, with normal vitamin B₁₂ status. Therapy with vitamin B₁₂ supplements led to excellent recovery of symptoms. Vitamin B₁₂ deficiency should be considered in children presenting with failure to thrive, especially when compounded with neurological symptoms. Early diagnosis and adequate treatment is essential to avoid serious complications.     

Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature

Vitamin B₁₂ deficiency is one of the major causes of megaloblastic anaemia with or without neurological symptoms. We report on a patient manifesting acute encephalopathy, epilepsy, microcephaly and megaloblastic anaemia at the age of 4 months. Vitamin B₁₂ deficiency in the patient was due to subclinical pernicious anaemia of the mother who exhibited neither haematological nor neurological symptoms. Mother and child both had elevated methylmalonic acid in their urine which is a sensitive parameter of vitamin B₁₂ deficiency. Vitamin B₁₂ therapy resulted in arrest of convulsions within 24 h. There were no further seizures although the patient showed moderate mental retardation at the age of 7 years but a normal head circumference. Long-term MRI follow-up, performed at the age of 7 years, showed moderate enlargement of the ventricles with reduction of myelin and hypoplasia of the corpus callosum. Conclusion:vitamin B₁₂ deficiency due to maternal pernicious anaemia should always be considered in the differential diagnosis of neurological symptoms in infants and especially in combination with megaloblastic anaemia. Since the age of onset and the duration of neurological symptoms may contribute to the development of long-term symptoms, early diagnosis and treatment is important for vitamin B₁₂ deficient children.     

Maternal vegan diet causing a serious infantile neurological disorder due to vitamin B12 deficiency

We present a 9-month-old exclusively breastfed baby of a strict vegetarian mother who had excluded all animal proteins from her diet. The patient's symptoms included dystrophy, weakness, muscular atrophy, loss of tendon reflexes, psychomotor regression and haematological abnormalities. Biochemical investigations revealed severe methylmalonic aciduria and homocystinuria in the patient, slight methylmalonic aciduria in the mother and low concentrations of serum vitamin B₁₂ in both patient and mother.Presented in preliminary form at the Annual Meeting of the Swiss Paediatric Society, Geneva, 12–13 June 1987     

Beziehungen zwischen der Vitamin B6-Versorgung Schwangerer und der Vitamin B6-Ausstattung ihrer Neugeborenen

Zusammenfassung 95 Schwangere erhielten im letzten Schwangerschaftstrimenon zusätzlich zur üblichen Kost eine kontrollierte Vitamin B₆-Zufuhr. Von jeder Schwangeren wurde zur Zeit der Aufnahme in die Studie und zum Zeitpunkt der Entbindung der Vitamin B₆-Status an Hand der Aktivitätsmessung der erythrocytären GOT (EGOT) bestimmt. Während des letzten Schwangerschaftstrimenons lagen deutliche Zeichen eines biochemischen Vitamin B₆-Mangels vor. Bei fehlender zusätzlicher Pyridoxinzufuhr nahm das Defizit signifikant zu, Verabreichung von täglich 3 mg Vitamin B₆ hingegen normalisierte die defizitären Enzymwerte.Bei den Neugeborenen wurde kurz nach der Geburt die Vitamin B₆-Versorgung an Hand der EGOT, am. 3. und 5. Lebenstag zusätzlich durch die Messung der Harnausscheidung von 4-Pyridoxinsäure untersucht. Zwischen der Vitamin B₆-Versorgung der Schwangeren und der des Neugeborenen zeigten sich sowohl kurz nach der Geburt als auch am. 3. und 5. Lebenstag signifikante Abhängigkeiten. Die Retention von einer am 4. Lebenstag parenteral verabreichten Dosis Vitamin B₆ war ebenfalls signifikant abhängig von der Vitamin B₆-Versorgungslage der Mutter. Eine weitere Beziehung bestand zwischen Geburtsgewicht und Vitamin B₆-Versorgung der Schwangeren. Die Geburtsgewichte der Neugeborenen, deren Mütter Vitamin B₆ zusätzlich erhalten hatten, waren signifikant höher als die der Vergleichsgruppe.

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Relations between vitamin, B₆ status of mother and vitamin B₆ nutriture of her newborn infant

The activity of erythrocyte GOT (EGOT) with and without in vitro repletion with pyridoxal phosphate was determined in 95 pregnant women between the 22nd and 30th week of pregnancy. Following controlled vitamin B₆ (P) supplementation, the activity of this enzyme was determined again within 1 hr after delivery. During the last trimester of pregnancy significant P deficiency could be detected. Biochemical deficiency increased in pregnant women not receiving supplementary P.The activity of EGOT was determined in newborn intants sub partu; excretion of 4-pyridoxic acid was measured on the third and fifth day post partum. Significant correlations were found between the P status of the mother and the P nutriture of her newborn infant sub partu and on the third and fifth post partum day. There was also a correlation between P retention after a P load on the fourth post partum day and the P status of mother. Newborn infants of mothers supplemented with P had a significantly higher birth weight than those of the control group.

     

Brain atrophy caused by vitamin B12-deficient anemia in an infant

Vitamin B12 deficiency in infants often presents with nonspecific hematological, gastrointestinal, and neurological manifestations. It is usually caused by inadequate intake, abnormal absorption, or congenital disorders of vitamin B12 metabolism, including transport disorders. We describe a vitamin B12-deficient infant with severe anemia who was breastfed. His mother had undiagnosed vitamin B12 deficiency having undergone total gastrectomy 18 years earlier. The infant developed normally after taking vitamin B12. It is important to suspect vitamin B12 deficiency in mothers who have undergone gastrectomy. Early diagnosis and treatment of vitamin B12 deficiency in infants is important and will help improve long-term prognosis.     

Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings

Vitamin B₁₂ deficiency is known to be associated with signs of demyelination, usually in the spinal cord. Lack of vitamin B₁₂ in the maternal diet during pregnancy has been shown to cause severe retardation of myelination in the nervous system. We report the case of a 14¹/₂-month-old child of strictly vegetarian parents who presented with severe psychomotor retardation. This severely hypotonic child had anemia due to insufficient maternal intake of vitamin B₁₂ with associated megaloblastic anemia. MRI of the brain revealed severe brain atrophy with signs of retarded myelination, the frontal and temporal lobes being most severely affected. It was concluded that this myelination retardation was due to insufficient intake of vitamin B₁₂ and vitamin B₁₂ therapy was instituted. The patient responded well with improvement of clinical and imaging abnormalities. We stress the importance of MRI in the diagnosis and follow-up of patients with suspected diseases of myelination. Received: 19 February 1996 Accepted: 26 March 1996     

Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional vitamin B12 deficiency – What have we learned?

BackgroundMaternal vitamin B₁₂ (Cbl) deficiency causes nutritional Cbl deficiency in breastfed infants.AimsTo analyse clinical presentation and metabolic consequences in 40 breastfed infants with Cbl deficiency.MethodsCbl levels in serum and breast milk were determined by an electrochemiluminescence immunoassay, methylmalonic acid level by GC/MS, plasma homocysteine by HPLC and propionylcarnitine by MS/MS. Profound Cbl deficiency was found in 17 children (69 ± 17 ng/l, controls 200–900), and milder Cbl deficiency in 23 children (167 ± 40 ng/l). Maternal Cbl deficiency was mostly caused by insufficient Cbl absorption. Only six mothers were vegetarian.ResultsThe average age at diagnosis was 4.4 ± 2.5 months. Clinical symptoms included failure to thrive (48% of children), hypotonia (40%), developmental delay (38%) and microcephaly (23%). 63% of children had anaemia (megaloblastic in 28% of all children). All but one patient had methylmalonic aciduria, 80% of patients had hyperhomocysteinemia and 87% had increased aminotransferases. Propionylcarnitine was elevated in two out of 25 infants. Comparing groups with severe and mild Cbl deficiency, a marked difference was found in severity of clinical and laboratory changes.ConclusionMaternal Cbl status and diagnostic delay are the major factors influencing severity and progression of Cbl deficiency in breastfed infants. In our cohort, propionylcarnitine was not sufficiently sensitive marker of Cbl deficiency. Although symptoms are reversible on Cbl substitution, permanent neurological damage can result. Selective screening for Cbl deficiency is indicated in all breastfed infants with failure to thrive, hypotonia, developmental delay, microcephaly or megaloblastic anaemia. The best prevention in future could be the screening of all pregnant women.     

Megaloblastic anaemia in one of monozygous twins breast fed by their vegetarian mother

Megaloblastic anaemia in infancy is uncommon in western countries. We describe a case of an exclusively breast-fed monozygous twin with severe vitamin B₁₂ deficiency with haematologic and neurologic abnormalities. Treatment with vitamin B₁₂ resulted in a rapid haematological and clinical improvement.     

Gastric bypass: a risk factor for neural tube defects? Case report

Gastric bypass surgery has become a safe and acceptable surgical weight loss treatment for individuals who suffer from morbid obesity. Patients who undergo this procedure are subject to vitamin deficiencies due to an iatrogenic malabsorptive state. Folate, a vitamin known for its role in the prevention of neural tube defects (NTDs), can be part of the deficiency spectrum resulting from this procedure. The authors describe the case of a woman who was nonadherent to multivitamin treatment after undergoing gastric bypass surgery. Her lack of understanding and appreciation of the relationship between gastric bypass surgery, folate deficiency, and NTDs may have contributed to her noncompliance with daily multivitamin consumption. As a result, her potential problems with folate absorption could have contributed to her subsequently giving birth to a child with a myelomeningocele. Thus, patient awareness and counseling along with aggressive vitamin supplementation among this particular population may help prevent the occurrence of NTDs after gastric bypass surgery.     

Effect of combined maternal and infant vitamin D supplementation on vitamin D status of exclusively breastfed infants

Severe vitamin D deficiency in mothers and their breastfed infants is a significant health problem in the Middle East. Supplementation of the breastfed infant alone with the recommended dose of vitamin D may be insufficient in high‐risk population. We investigated the effect of combined maternal and infant vitamin D supplementation on vitamin D status of the breastfed infant. We examined also the effect of supplementation on vitamin D antirachitic activity of breast milk in a subset of mothers. Healthy breastfeeding mothers (n = 90) were randomly assigned to 2000 IU daily (group 1) or 60 000 IU monthly (group 2) of vitamin D₂, and all their infants (n = 92) received 400 IU daily of vitamin D₂ for 3 months. Most infants had vitamin D deficiency – 25‐hydroxyvitamin D [25(OH)D] ≤ 37.5 nmol L^?1– at study entry. Serum 25(OH)D concentrations at 3 months increased significantly from baseline in infants of mothers in group 1 (13.9 ± 8.6 vs. 49.6 ± 18.5 nmol L^?1, P < 0.0001) and group 2 (13.7 ± 12.1 vs. 44.6 ± 15.0 nmol L^?1, P < 0.0001). Maternal and infant serum 25(OH)D concentrations correlated positively at baseline (r = 0.36, P = 0.01) and 3 months (r = 0.46, P = 0.002). Milk antirachitic activity increased from undetectable (<20 IU L^?1) to a median of 50.9 IU L^?1. In conclusion, combined maternal and infant vitamin D supplementation was associated with a threefold increase in infants’ serum 25(OH)D concentrations and a 64% reduction in the prevalence of vitamin D deficiency without causing hypervitaminosis D.     

Vitamin B12 absorption and exocrine pancreatic insufficiency in childhood

The absorption of vitamin B₁₂, labelled with radioactive ⁵⁸Co, was measured in 19 patients with cystic fibrosis and one child with the Shwachman-Diamond syndrome using the whole body counting technique. We found vitamin B₁₂ absorption reduced to 7.97% on average, compared to 59.2% for the control group. The low vitamin B₁₂ absorption correlated well with the reduced fat retention coefficients. After adding 0.212 pancreatin to the radioactive vitamin B₁₂ test dose, the absorption quotas improved in all cases, the average being 61%. A meal poor in vitamin B₁₂ tended to increase the absorption of the radioactive test dose to 23% on average. As yet there is no satisfactory explanation for the effect of the diet on the absorption of vitamin B₁₂ in exocrine pancreatic insufficiency. This could be the reason why the malabsorption of vitamin B₁₂ in patients with EPI can go unnoticed for many years and could possibly explain why vitamin B₁₂ malabsorption in exocrine pancreatic insufficiency does not cause symptoms and signs of vitamin B₁₂ deficiency for many years.With the support of the Volkswagen Foundation     

Selective vitamin B12 malabsorption (Imerslund-Gräsbeck Syndrome)

In a girl 10 years of age with selective vitamin B₁₂ malabsorption associated with proteinuria and residual symptoms of funicular myelosis an extensive study of the intestinal and nephrologic functions was done. Repeated Schilling tests pointed to a malabsorption pattern of vitamin B₁₂. Gastric acid and intrinsic factor secretion as well as gastric morphology were normal. There were no antibodies against intrinsic factor and parietal cells in serum. Ileal mucosa showed on light- and electron-microscopy no pathologic changes. Pancreatic exocrine function as well as pH and calcium concentrations in the lumen of the gut were within the normal range. A general malabsorption syndrome could be excluded.A high selective glomerular proteinuria was found through different methods. Inulin clearance was slightly reduced, PAH clearance, however, markedley so. There was no further evidence for renal tubular dysfunction. Renal biopsy showed a minimal proliferative intercapillary glomerulonephritis (minimal changes). In electron-microscopic studies a fusion of a part of the foot processes of the podocytes was found.No familial history of the syndrome could be demonstrated in our patient.

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Zusammenfassung Bei einem zum Zeitpunkt der Untersuchung 10 Jahre alten Mädchen mit selektiver Vitamin B₁₂-Malabsorption und Proteinurie wurden eingehende gastroenterologische und nephrologische Untersuchungen durchgeführt. Die Patientin wies auch nach mehrjähriger, regelmäßiger Vitamin B₁₂-Substitution noch Restzeichen einer funiculären Myelose auf, die durch elektrodiagnostische Untersuchungen objektiviert werden konnten. Die wiederholte Prüfung der Vitamin B₁₂-Resorption mit dem Schilling-Test zeigte eine Vitamin B₁₂-Malabsorption. Antikörper gegen Intrinsic-Faktor und Parietalzellen konnten im Serum nicht nachgewiesen werden. Die Mukosa des terminalen Ileums wies licht- und elektronenmikroskopisch keine pathologischen Veränderungen auf. Die exokrine Pankreasfunktion sowie das pH und die Calcium-Konzentrationen im Duodenalsaft waren im Bereich der Norm. Ein generelles Malabsorptions-Syndrom konnte ausgeschlossen werden.Mit verschiedenen Methoden wurde eine hochselective glomeruläre Proteinurie nachgewiesen. Die Inulin-Clearance war leicht, die PAH-Clearance deutlich erniedrigt. Es bestand sonst kein weiterer Anhalt für eine Störung der Tubulusfunktion. Die Nierenbiopsie ergab lichtmikroskopisch Zeichen einer minimal proliferierenden, intercapillären Glomerulonephritis (minimal changes). Elektronenmikroskopisch wurde eine partielle Verschmelzung der Glomerulumdeckzellen gefunden. Eine Familiarität des Syndroms konnte durch Untersuchung der Eltern und einer Schwester der Patientin ausgeschlossen werden.

     

Vitamin B12 and homocysteine status in asymptomatic Indian toddlers

Low serum vitamin B₁₂ (V B₁₂) and hyperhomocysteinemia have been reported in asymptomatic Asian Indian men. We studied the prevalence of V B₁₂ deficiency and hyperhomocysteinemia in 51 asymptomatic toddlers, from Pune, India. V B₁₂ levels were low and total serum homocysteine was high in 14 % and homocysteine levels were significantly higher in boys. Programming for cardiovascular risk in adulthood possibly starts at a very young age through the homocysteine axis.     

Cranial magnetic resonance imaging findings of nutritional vitamin B12 deficiency in 15 hypotonic infants

BackgroundNutritional vitamin B₁₂ deficieny is common among infants in the developing and underdeveloped countries. There is limited information concerning neuroimaging findings in infants with vitamin B₁₂ deficiency in the literature.AimsThe aim of this study is to evaluate the cranial magnetic resonance imaging (MRI) changes and clinical characteristics of hypotonic infants due to vitamin B₁₂ deficiency. Materials and methods: A total of 15 infants with neuroradiologic investigations were diagnosed with nutritional B₁₂ vitamin deficiency. Cranial MRI was performed on all infants.ResultsFive infants were female (33%) and the mean age of infants was 12.3 ± 5.5 months. Hypotonia and neurodevelopmental retardation were present in all patients. MRI demonstrated thinning of the corpus callosum in 6 (40%), cortical atrophy in 5 (33.3%), large sylvian fissures in 5 (33.3%), ventricular dilatation in 3 (20%), asymetric large lateral ventricle in 2 (13.3%) and delayed in myelination in 2 (13.3%) patients. Four infants had normal MRI findings.ConclusionBecause of the importance of vitamin B₁₂ in the development of the brain, MRI findings may be detected and useful in infants with vitamin B₁₂ deficiency.     

Vitamin B12 treatment reduces mononuclear DNA damage

Background: DNA damage effects of vitamin B₁₂ deficiency were performed in vitro and in adults. Methods: The study group included 32 children (13 girls, 19 boys) with vitamin B₁₂ deficiency (mean age 44 ± 58 months) and their 27 mothers (mean age 30.4 ± 5.3 years). The control group contained 30 healthy children and 25 mothers. DNA strand breaks in peripheral blood mononuclear leukocytes were assayed by single‐cell alkaline gel electrophoresis (comet assay) before and 8 days after the first injection of vitamin B₁₂. Results: Mean DNA damage scores in children with vitamin B₁₂ deficiency and their mothers were significantly higher before treatment than those after treatment. The DNA damage scores of children after treatment were still significantly higher than controls. There were significant negative correlations between the children and their mothers in terms of vitamin B₁₂ levels and DNA damage scores (r = 0.3, P= 0.02; r = 0.58, P= 0.002, respectively). There were correlations between the children's and their mothers' DNA damage and the severity of vitamin B₁₂ deficiency, suggesting that the children and their mothers may play a role in the scarcity of nutritional vitamin B₁₂. Conclusion: DNA damage is increased in children with vitamin B₁₂ deficiency and in their mothers. DNA damage scores were significantly improved through vitamin B₁₂ therapy 8 days after the first injection, however, they were still significantly higher than those of controls.     

Severe hyperhomocysteinemia and peripheral neuropathy as side effects of nitrous oxide in two patients with sickle cell disease

Nitrous oxide (N₂O) is a widely used anesthetic agent. We report two patients with sickle cell disease (SCD) who presented with complications following the use of N₂O. Patient 1, a 15-year-old girl, presented severe hyperhomocysteinemia, pancytopenia, vitamin B₁₂ deficiency, and peripheral polyneuropathy after massive use of N₂O for pain management. At the 1-year follow-up, hyperhomocysteinemia and B₁₂ deficiency had resolved, but she had persisting mild symptoms of polyneuropathy. Patient 2, a 17-year-old boy, presented only severe hyperhomocysteinemia, only partially corrected by initial B₁₂ supplementation. Careful monitoring of N₂O use, especially in patients with SCD, is mandatory to prevent complications.     

Suboptimal maternal and cord plasma pyridoxal 5′ phosphate concentrations are uncommon in a cohort of Canadian pregnant women and newborn infants

Vitamin B₆ is important in fetal development, but little is known of the vitamin B₆ status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5′ phosphate (PLP; an indicator of vitamin B₆ status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B₆ and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B₆ were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CβS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood (p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B₆ intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B₆ deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B₆ supplement use.