Effects of Intravenous Nitroglycerin on Hemodynamics in Neonates with Refractory Congestive Heart Failure of PFC

(1) Continuous intravenous infusion (2–10 μ/kg/min) of nitroglycerin (TNG) was administered to 20 neonates consisting of 17 with refractory congestive heart failure and 3 with PFC (Persistent Fetal Circulation). (2) AT doses of 2–4 μ/kg/min, there were no significant changes in heart rate or systemic blood pressue. (3) At doses of 2–4 μ/kg/min, the CVP was significantly reduced and urnary output increased. (4) Echocardiograms revealed a significant decrease in LVS at 4 – 5 μ/kg/min. In addition, the EF and cardiac output were significantly increased at 2 – 5 μ/kg/min. (5) The right ventricle systolic time interval (STI) was reduced significantly at 2 μ/kg/min. The left ventricle STI was not reduced below doses of 4 μ/kg/min. (6) In the dose range 2 – 5 μ/kg/min, TNG is an effective and safe vasodilator in the treatment of refractory congestive heart failure or PFC in neonates.     

EVALUATION OF A NEW SUSTAINED-RELEASE THEOPHYLLINE TABLET FOR CHILDREN

Abstract. Selvig, K., Alme, A., Rugs tad, H. E., Aas, K. and Bjerve, K. S. (Institute of Clinical Biochemistry, the Allergy Institute Voksentoppen, Department of Paediatrics and Department of Clinical Pharmacology, Rikshospitalet, Oslo 1, Norway). Evaluation of a new sustained-release theophylline tablet for children. Acta Paediatr Scand, 70: 929, 1981.-A new, low dose sustained-release tablet of theophylline has been developed in order to facilitate a correct dose regimen in asthmatic children treated with theophylline. The formulation (Euphyllin® retard mite w/groove) contains 128 mg of theophylline, and can easily be divided. The extent of bioavailability in adults is 0.91, and the peak serum concentration is reached after 8.7 h. 25 children treated with plain theophylline tablets were followed when changing to the sustained-release tablets. Compared to the plain tablets, the serum theophylline concentration before the morning dose was 29 μmol/l higher (range 12–51) when the same daily dose was given as a sustained-release preparation. The serum concentration fluctuations during one dosing interval were reduced with 13 μmol/l (0–26). Mild gastrointestinal side effects reported by the children when using the plain theophylline tablets all disappeared on changing to the sustained-release tablets.     

Hereditary Tyrosinemia of Chronic Course without Rickets and Renal Tubular Dysfunction

ABSTRACT. Three patients with hereditary tyrosinemia type 1, two brothers and one girl, studied at the age of 5, 12 and 15 years, respectively, had neither generalized hyperaminoaciduria, glucosuria nor clinical symptoms of rickets. Untreated the elder brother had only slightly elevated plasma tyrosine level (141 μmol/l, normal <80), and low excretion of p-hydroxyphenyllactate. He presented with pronounced thrombocytopenia (3 × 10⁹/1). At 13 years of age he contracted hepatocellular carcinoma. The younger brother presented with serum tyrosine of 318 μol/l and thrombocyte count 48 × 10⁹/1. Succinylacetone in urine was elevated in both, 30 and 79 μmol/mmol creatinine, respectively. The female patient was investigated for hepatomegaly in infancy, atypical tyrosinemia being considered, but afterwards developed normally without diet or any other treatment until she contracted hepatoma at the age of 15 years. Her plasma tyrosine level was 600-700 μmol/1, and she excreted large amounts of p-hydroxyphenyllactate. Succinylacetone in urine was low but elevated (8 μmol/mmol creatinine). The fumarylacetoacetase activity in fibroblasts from the brothers and in lymphocytes from the girl was less than 5% and 10% of control levels, respectively. In conclusion, the chronic form of hereditary tyrosinemia may occur without evidence of renal tubular dysfunction.     

Potentially Life-Threatening Cardiac Dysrhythmia in a Child with Selenium Deficiency and Phenylketonuria

ABSTRACT. Selenium deficiency is a frequent finding in children with phenylketonuria (PKU) receiving dietary treatment. We report the occurrence of episodic ventricular tachycardia in a 9-month-old infant with PKU. Serum selenium (Se), 0.13 μmol/1 (normal range 0.28–1.12 μmol/1, mean ± 2 SD), and whole blood glutathione peroxidase (GSHPX), 16 U/g Hb (normal range 19.5–34.3 U/g Hb, mean ± 2 SD), were low. Auscultation of cardiac rhythm is recommended during the routine follow-up of young children with PKU. Se deficiency should be considered in the aetiology of a dysrhythmia and corrected with Se supplementation.     

COPPER DEFICIENCY AND HYPOCALCEMIC RICKETS IN A SMALL-FOR-DATE INFANT

ABSTRACT. A case of copper deficiency associated with hypocalcemia, radiological features of rickets and hyperparathyroidism is described in a small-for-date infant (gestational age 39 weeks, B.W. 1240 g). Neonatal serum copper (Cu) levels were found between 223 and 138 μmol/l. She was given daily 2 400 U of vitamin D₂ and a load dose of 80 000 IU at the age of 55 days. At the age of 79 days, X-rays of the legs and wrist showed spread, cupped and frayed metaphyses. Serum Ca was 1.35 mmol/1, P=0.99 mmol/1 with high alkaline phosphatases (A.P.) 590 II/ml. But plasma level of 25 hydroxycholecalciferol (25-OH-CC) was normal = 10.8 ng/ml. Serum Cu was low=3.14 μmol/l and serum immunoreactive parathormone (iPTH) level was elevated: 520 μlEq/ml (N±100). Administration of vitamin D₂ (15 mg) induced an immediate normalization of serum Ca, normal serum iPTH (68 μlEq/ml) in one month, normal X-rays in two months and normal A.P. in four months. Serum Cu and ceruloplasmin levels increased slowly without any supplementation to subnormal levels at the age of eight months (14.9 and 1.65 μmol/1. Serum Cu concentrations were found to be normal (16.0–33.7 μmol/1) in five children with hypocalcemic rickets. These results suggest a role of Cu deficiency in the occurrence of this transient vitamin D-resistant rickets.     

Increased lipid peroxidation in children with autoimmune diseases

To examine the role of oxidative damage in children and adolescents with autoimmune diseases, we compared blood serum levels of the lipid peroxidation (LPO) products 4-hydroxynonenal (HNE) and malondialdehyde (MDA) in 22 children with systemic lupus erythematosus (SLE), 13 children with focal type of scleroderma, and 21 healthy controls. In order to study the influence of disease activity in SLE on serum LPO product levels, the SLE group was divided into one group with active disease ( n = 11) and one group with non-active disease ( n = 11) according to SLEDAI-score, 15.1 and 1.8, respectively. SLE patients with active SLE (146 ± 14nmol/l, median 145nmol/l) have significantly higher HNE levels compared to controls (61 ± 10nmol/l, median 52nmol/l), whereas the MDA serum levels are similar to those of the control group, 1.94 ± 0.18μmol/l (median: 2.02μmol/l) and 1.58 ± 0.11 μmol/1 (median: 1.52 μmol/l), respectively. Children with SCL had HNE and MDA levels similar to the control group.     

Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic-ischemic encephalopathy

Asphyxiated ( n = 27 ) and control infants ( n = 25 ) were subjected to spinal taps. Amino acids were measured with liquid chromatography and the degree of hypoxic-ischemic cncephalopathy was determined in each case. In asphyxiated infants, the concentrations of aspartate and glutamate were 286% and 387% ( p 0.01 and p 0.05) of the control values. respectively. The Cerebrospinal fluid aspartate levels were significantly ( p 0.05) higher in the group with severe (3.4 μmol/l) compared with the group with mild hypoxic-ischemic encephalopathy (1.0 μmol/l). Glutamate was also higher in the group with severe (12.3 μmol/l) than in the groups with mild (2.7 μmol/l) or moderate (3.2 μmol/l) hypoxic-ischemic enccphalopathy ( p 0.05). High concentrations of excitatory amino acids were present in the CSF of asphyxiated infants which may exert excitotoxic effects.     

Jaundice in full term healthy neonates — a population study

Abstract A geographically based population of 498 full term, appropriate for gestational age, healthy, singleton neonates was used to study the effect of obstetric and nursery practices on the occurrence of neonatal jaundice. At 3–4 days 56% of babies became visibly jaundiced (plasma bilrubin (PB)> 100 μmol/l) and 10% were hyperbilirubinaemic (PB > 200 μmol/I). Less mature babies, those slow to pass meconium and those who had lost weight at 4 and 7 days were more likely to be jaundiced. Obstetric practices, drugs given during labour, mother's or baby's blood group, natural illumination, plethora, extravasated blood or mode of feeding were found to have no effect. No benefit from giving supplementary milk or dextrose to breast fed babies was discovered.
At 6–7 days at least 9% of babies, all bout one of whom were breast fed, were visibly jaundiced. The frequency of prolonged jaundice (breast milk jaundice) was 3'.8% of breast fed babies at 3 weeks and zero by 7 weeks. The proportion of babies receiving phototherapy was 2.2%.     

PLASMA CONJUGATED CHOLIC ACID IN PREMATURE AND TERM NEWBORNS AND YOUNG INFANTS

ABSTRACT. Tikanoja, T., Tikanoja, S. and Simell, O. (Children's Hospital, University of Helsinki, Helsinki, Finland). Plasma conjugated cholic acid in premature and term newborns and young infants. Acta Paediatr Scand, 70:491,.–Bile acid handling by neonates, both premature (Group 1, mean gestational age 34.3 weeks; Croup II, 36,6 weeks) and full-term (Group HI, 40.2 weeks) and by 3-month-old infants (Group IV) was assessed by measuring plasma concentrations of conjugated cholic acid (CCA) before and at successive intervals after feeds. The prefeeding CCA concentrations were highest in Group I (log mean 8.2; range 1.8–28.6 μmol/1) and lower in Groups II (7.5; 2.6–22.4 umol/1), III (5.1; 2.1–11.1 μ0mol/1), and IV (2.2; 0.5–6.1 μmol/1). The mean postprandial increments correlated with maturity: the rises for Groups I-IV were 3.7, 4.3, 1.0 and 0.7 μmol/1, respectively. Peak values were consistently reached at 30 min after the start of the feed, i.e., strikingly earlier than in older children and adults. After the peaks the return to prefeeding levels occurred rapidly in Groups II-IV but more slowly in the most premature infants (Group I). The rapid postprandial rise may be due to many factors, e.g., passive jejunal absorption, immature hepatic-clearing mechanisms, or rapid transit of bile acids to the ileum. Hence, measurements of postprandial plasma bile acids would appear ill-suited for detection of disturbed ileal function in young infants. The high concentrations in healthy newborns suggest that caution is necessary in interpreting plasma bile acid concentrations during the first few weeks of life, especially in premature infants.     

Serum inflammatory markers and effects of age and tobacco smoke exposure in young non-asthmatic children

Serum eosinophil cationic protein (ECP), but not serum myeloperoxidase (MPO), has been found to reflect disease activity of asthma and eczema, but no reference values exist for young children. Thus, we aimed to provide values of serum-ECP and serum-MPO in young children without obstructive airways disease (OAD), and determine possible influencing factors. Parental interview was performed and serum was collected from a total of 245 children (207 children aged 24-41 months and 76 children aged 0-23 months) with no history of lower respiratory disease. Repeated serum samples were obtained in 38 subjects. Ten percent of the children had active eczema at examination. All children were controls in the"Environment and Childhood Asthma"study in Oslo. Geometric means (GM ± 1.96 SD) for serum ECP were 11.8 μg/l (2.5-56.0) and 7.9 μg/l (2.0-30.4), respectively, in the 0-23 and 24-41-month-old children, with the corresponding values for serum MPO 453 μg/l (153-1349) and 347 μg/l (142–859), respectively. Age was inversely associated with serum-ECP and serum-MPO, most pronounced in the youngest children. Active eczema and maternal daily smoking adversely affected serum-ECP, but not serum-MPO. Gender and parental atopy did not influence the results. We conclude that serum-ECP in very young children is influenced by age and active eczema and is related to maternal smoking in a dose-dependent fashion. These factors should be considered when assessing inflammatory markers in very young children.     

Aluminium in the neonate related to parenteral nutrition

Moreno A, Domínguez C, Ballabriga A. Aluminium in the neonate related to parenteral nutrition. Acta Pædiatr 1994;83:25–9. Stockholm. ISSN 0803–5253
Sources of aluminium loading and exposure in preterm and full-term newborns were studied. Parenteral nutrition solutions were the main source of aluminium representing 88.7% of total aluminium intake. Blood and urine aluminium levels were followed over a 28-day period in a group of 26 preterm and 9 term infants while receiving parenteral nutrition (duration 15.6 ± 8.7 days) and later when being formula fed. Urine levels were followed up to 13 weeks in a subgroup of the neonates. Serum aluminium levels (0.86 ± 0.38 μmol/l) and urine aluminium/crcatinine ratio (1.52 ± 0.81 μ mol/ mmol) were increased when the infants were receiving parenteral nutrition compared with the control group (p<0.001). The urine aluminium/creatinine ratio remained high up to 10 weeks following withdrawal of parenteral nutrition and suggested tissular loading. This was confirmed after high aluminium levels were found in post-mortem brain and bone samples from two preterm and one full-term infant. We conclude that both preterm and full-term neonates are susceptible to accumulation of aluminium in tissue while receiving parenteral nutrition.     

Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT)

In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor. Thus, anticoagulant treatment with melagatran is of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin. We evaluated the anticoagulant action of increasing amounts of melagatran (0.1–2.0 μmol/l) in both cord and adult plasma by means of calibrated automated thrombography (CAT) with respect to the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. Melagatran exhibited approximately the same ability to prolong lag times or TTPs in both cord and adult plasma. Similar concentrations (IC₅₀) of melagatran were required to double the lag times (0.44±0.04 μmol/l vs. 0.52±0.05 μmol/l) or to double the TTPs (0.91±0.08 μmol/l vs. 1.06±0.09 μmol/l) in cord vs. adult plasma. Melagatran exhibited a higher ability to suppress ETPs or thrombin peak heights in cord vs. adult plasma. Markedly lower concentrations (IC₅₀) of melagatran were required to suppress ETPs (0.27±0.03 μmol/l vs. 0.70±0.06 μmol/l) or thrombin peak heights by 50% (0.29±0.03 μmol/l vs. 0.53±0.04 μmol/l) in cord vs. adult plasma. We conclude that our results suggest a higher ability of melagatran to suppress thrombin formation in cord vs. adult plasma. Thus, lower amounts of melagatran might be required in neonates undergoing antithrombotic therapy.     

Intranasal administration of growth hormone-releasing hormone(1–29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth

The growth-promoting potential of growth hormone-releasing hormone(1— 29)-NH, (GHRH(1–29)- NH,) in a new formulation for intranasal use was examined in a 6-month pilot study of eight short prepubertal children. The maximal plasma concentration of growth hormone (GH) was below 12 μg/l in two stimulation tests (arginine, insulin), but above 12 (24–90) μg/l after intravenous GHRH, 1 μglkg. GHRH, 50 μg/kg, was insufflated intranasally three times per day over 6 months. On day 1, GHRHinsufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 μg/l and from 10 to 85 mIU/l, respectively. Peak amplitudes were variably reduced after 6 weeks in most patients, and further reduced at 6 months. GHRH antibodies (initially negative) were positive in three patients after 6 weeks. The mean knemometric growth rate rose from 0.24 to 0.48 mm/week after 6 weeks of treatment ( p = 0.03) and then rapidly declined; the mean 6-month stadiometric height velocity did not increase. Local tolerance was good in one patient; most others reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients after 6 and 12 weeks. It is concluded that intranasal GHRH, though non-invasive, is not suitable in its present form for use in children, because of decreasing absorption and effectiveness with concomitant development of antibodies and local reactions.     

Growth velocity and serum aminoterminal propeptide of type III procollagen in precocious puberty during gonadotropin-releasing hormone analogue treatment

Growth velocity and serum aminoterminal propeptide of type III procollagen (P-III-NP) were evaluated in 11 girls (age 3.8–8.5 years) with central precocious puberty during luteinizing hormone releasing hormone (LH-RH) analogue treatment (D-Trp⁶-LH-RH, 60 μg/kg im for 28 days, n = 7; D-ser(TBU)⁶-LH-RH, 1600 μg/day intranasally, n = 4). Before treatment, growth velocity (10.2 ± 1.9 cm/ year) and P-III-NP concentrations (12.8 ± 4.3 μg/l) were in the pubertal range. During therapy, growth velocity significantly decreased to the prepubertal levels. P-III-NP concentrations decreased significantly after six months of therapy (7.9 ± 3.7 μg/l, p < 0.001). Three girls with low growth velocity (< 4 cm/year), stimulated growth hormone peak < 10 μg/l, and altered 12-h nocturnal growth hormone secretion at 12 and/or 18 months of treatment, had a more marked decrease in P-III-NP concentrations (patient 3: −65.9%; patient 5: −58.7%; patient 10: −61.0%) after 6 months of therapy. Our results suggest that LH-RH analogue treatment in central precocious puberty may impair growth. In these cases, measurement of serum P-III-NP levels may be an additional marker to- monitor growth.     

Plasminogen activators and plasminogen activator inhibitors in plasma of premature and term newborns

Objective : To compare the plasminogen activators (tPA, uPA) and their inhibitors (PAI-1, PAI-2) at different gestational ages, related to levels in women at term and non-pregnant women. Methods : Blood samples were obtained by puncture of the umbilical cord vein, in gestational weeks 39–40 ( n = 21), 30–32 ( n = 15), and 27–29 ( n = 9). Analyses of PA and PAI antigen concentrations and of PAI-1 activity were performed. Results : The mean tPA antigen level in term newborn infants was 14.5 μg/l compared to the premature newborns (7.0 μg/l) women at term (7.5 μg/l) and non-pregnant women (2.3 μg/l). PAI-1 activity and PAI-2 antigen concentrations were also higher in term newborn than in premature infants. Conclusions : The plasma levels of the plasminogen activators and inhibitors are higher in term newborn compared with premature newborn infants, reflecting maturation of protein synthesis.     

Hypoglycaemia in Childhood Diabetes II.

ABSTRACT. Hypoglycaemia (blood glucose 1.3–2.5 mmol/1) was induced in thirty diabetic children by reduction of their morning meal. Glucagon, 10 or 20 μg/kg was then given by intramuscular or subcutaneous injection. Ten min later, all signs of hypoglycaemia had disappeared and blood glucose concentrations increased by 0.7–3.3 mmol/1. Glucagon plasma concentrations at glucose nadir were low, 23±8 pmol/l, rose to 300±42 ten min after the injection and reached peak values after another ten min. Later, a slow decrease was noted. No significant difference of blood glucose or plasma glucagon concentrations were found after subcutaneous or intramuscular injections of 20 μg/kg. After 10 μg/kg, slightly lower increase of blood glucose was seen, but the clinical effect was equally good. Nausea occurred in four children given 20 μg/kg. The rise of blood glucose did not correlate to the peak glucagon concentration obtained after the injection but showed significant correlations to the lowest glucose concentration and, inversely, to the concentration of free insulin in blood at glucose nadir. It is concluded that glucagon injections are effective in hypoglycaemia in insulin-treated diabetic children and that the injection of 10–20 μg/kg gives long-standing supraphysiological concentrations which make repeated injections unnecessary.     

Clinical application of the measurement of cord plasma lactate and pyruvate in the assessment of high-risk neonates

Lactate levels in combination with lactate/pyruvate (L/P) ratio have been used to measure altered cellular redox states. We measured the cord plasma lactate levels and L/P ratios in 70 normal neonates (40 full-term and 30 preterm neonates) to set up the normal (control) ranges. The control cord plasma lactate levels and L/P ratios were 2660 [700 (SD)] μmol/l, 16 (3) in full-term neonates and 2750 (740) μmol/l, 17 (3) in preterm neonates, respectively. We also measured the lactate levels and L/P ratios in the high-risk full-term (n = 23) and preterm (n = 35) neonates, the results were 4500 (2600) μmol/l, 19 (13), and 5100 (2700) μmol/l, 26 (12), respectively. With the aid of elevated lactate levels and L/P ratios, the occurrence of neonatal encephalopathy can be predicted with a sensitivity of 100% and a specificity of 94.5% in this patient group. In our study, the six cases with abnormal neurodevelopment at 6-9 months of age all had both elevated lactate levels and L/P ratios at birth. We conclude that the measurement of lactate levels in combination with L/P ratios is a useful quantitative tool in assessing the existence and severity of perinatal hypoxia in the high-risk neonates.     

Neonatal plasma vitamin K1 levels following oral and intramuscular administration of vitamin K1

Vitamin K₁ levels were measured by high performance liquid chromatography in cord blood ( n = 33) and at the age of 97–120 h after administration of 2 mg of vitamin K_l orally ( n = 88) or 1 mg of vitamin K₁ by im injection ( n = 88). Vitamin K₁ levels were less than 0.05 μg/l in cord blood. The mean (range), SEM, mode and median values (μg/l) for the infants given oral vitamin K₁ were 17.99 (1–56), 1.25, 8 and 15.5 and those for the infants given im vitamin K_l 15.83(2–57), 1.01, 11and 14, respectively. The t- test showed no significant difference in the mean values ( p = 0.09) in the infants given oral or im vitamin K.     

The international collaborative study of maternal phenylketonuria: status report 1994

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.     

Latent coeliac disease in a child with epilepsy, cerebral calcifications, drug-induced systemic lupus erythematosus and intestinal folic acid malabsorption associated with impairment of folic acid transport across the blood-brain barrier

A 15-year-old boy with epilepsy and cerebral calcifications, treated with valproic acid, ethyl phenylbarbiturate and ethosuximide, was referred for drug induced systemic lupus erythematosus. Anti-gliadin (AGA) and anti-endomysium (EMA) antibody tests were both positive (EMA titre 1:50). Endoscopic duodenal biopsy showed intense chronic inflammation without villous atrophy or crypt hyperplasia. The child was discharged with a gluten-containing diet. The follow-up showed an increase in EMA titre (1:200) and the persistence of AGA. After 15 months, a second endoscopic intestinal biopsy showed flat mucosa and villous atrophy. Three serum folic acid determinations showed 1.8, 2.4, 2.0 ng/ml (reference range 2.5–16.9 ng/ml) prior to the two intestinal biopsies, but returned to normal levels (11.8 ng/ml) after a gluten-free diet and oral supplementation together. Two years later, the frequency of epileptic seizures was unchanged despite ongoing anti-epileptic treatment and a gluten-free diet. As cerebral calcification and epilepsy are reminiscent of the findings in congenital folate malabsorption, oral loading tests with 5 mg folic acid were carried out and showed impaired intestinal absorption and a defect in the transport across the blood-brain barrier. Low CSF folate levels (13.9 and 12.6 ng/ml, reference range 15–40 ng/ml) and an alteration in the CSF/serum folate ratio (1.43 and 1.16, normal ratio 3:1) were also found as well as increased levels of cystathionine both in CSF (40 μmol/l, reference range 18–28 μmol/l) and in serum (32 μmol/l, reference value <0.10 μmol/l). Conclusion Impairment of intestinal folic acid absorption with a defect in folic acid transport across the blood-brain barrier has been demonstrated in a case of epilepsy and cerebral calcifications associated with coeliac disease. Received: 12 November 1998 / Accepted: 29 February 2000