Higher serum alkaline phosphatase activity in infants born to vitamin D-deficient mothers.

Our research shows that the newborns of vitamin D-deficient mothers have higher serum alkaline phosphatase (ALP) activity compared with those of vitamin D-non-deficient mothers, which is likely related to increased bone turnover rather than just being a marker for bone formation. This has a potential negative impact on fetal bone development and subsequent skeletal growth. PURPOSE/INTRODUCTION: Low maternal serum 25-hydroxy vitamin D (25(OH)D) level during pregnancy contributes to vitamin D deficiency in infants at birth, which is associated with multiple potential adverse effects on fetal skeletal mineralization and growth. We studied the relationship between maternal 25(OH)D level and newborn serum alkaline phosphatase activity (ALP) at term. METHODS: In this prospective cross-sectional hospital-based study, venous blood samples of healthy pregnant mothers were drawn to measure 25(OH)D levels within 6 h of delivery. Cord blood samples were examined for calcium, phosphorus levels, and ALP activity immediately after birth. In addition, we also recorded the newborns' anthropometric measurements. RESULTS: Seventy-two percent (n = 108/150) of mothers in our study were vitamin D-deficient (serum 25(OH)2D < 25 nmol/l). In a multivariate logistic regression model, young maternal age (odds ratio (OR) = 0.94, 95% CI 0.88-0.99, p = 0.04) and increased weight (OR = 1.03, 95% CI 1.01-1.07, p = 0.02) as well as decreased milk intake (OR = 0.31, 95% CI 0.13-0.74, p = 0.009) were all significantly associated with maternal vitamin D deficiency. ALP activity was significantly higher in newborns of vitamin D-deficient compared with vitamin D-non-deficient mothers (median = 176 (IQR = 139-221) and 156 (IQR = 132-182), respectively, p = 0.04). A significant inverse correlation (Pearson's coefficient = - 0.18, p = 0.03) was observed between maternal 25(OH)D levels and babies' ALP activities. This association persisted in a multivariate logistic regression model (OR = 3.46, 95% CI 1.18-10.18, p = 0.024). CONCLUSIONS: Our findings indicate that newborns of vitamin D-deficient mothers have higher serum ALP activity than those of non-deficient mothers, which might be related to increased bone turnover rather than just being a marker for bone formation. This could have a potential negative impact on fetal bone development and subsequent skeletal growth.

CFU-megakaryocytic progenitors expanded ex vivo from cord blood maintain their in vitro homing potential and express matrix metalloproteinases.

BACKGROUND: In patients transplanted with cord blood (CB), prolonged thrombocytopenia is a major complication. However, this could be alleviated by supplementing the CB graft with ex vivo-expanded megakaryocytic progenitors (CFU-Meg), provided that the homing properties of these cells are not affected negatively by expansion. METHODS AND RESULTS: We assessed the in vitro homing potential of CFU-Meg progenitors expanded from CB and showed that the combination of thrombopoietin (TPO) with interleukin-3 (IL-3) used for expansion not only results in optimal proliferation of CFU-Meg but also protects these cells from apoptosis. Moreover, we found that ex vivo-expanded CFU-Meg maintained expression of the CXCR4 receptor throughout a 9-day culture and were chemoattracted towards a stromal cell-derived factor-1 (SDF-1) gradient. They also expressed matrix metalloproteinase-9 (MMP-9) and membrane-type (MT) 1-MMP, and transmigrated across the reconstituted basement membrane Matrigel. Finally, we observed that SDF-1 up-regulated the expression of both MMP-9 and MT1-MMP in CB CD34(+) cells and ex vivo-expanded CFU-Meg. DISCUSSION: We suggest that CB-expanded CFU-Meg, in particular those from day 3 of expansion, when their proliferation and in vitro homing potential are maximal, could be employed to supplement CB grafts and speed up platelet recovery in transplant recipients.

Early childhood wheezing symptoms in relation to plasma selenium in pregnant mothers and neonates.

OBJECTIVE: Reduced dietary selenium intake has been linked to the development of asthma. We have investigated whether childhood wheezing symptoms, and asthma up to the age of 5 years are associated with plasma selenium and erythrocyte glutathione peroxidase (GPx) concentrations in pregnant mothers and neonates. METHODS: Two thousand pregnant women were recruited and their 1924 singleton children followed up. Plasma selenium and erythrocyte GPx concentrations were measured in maternal blood during early pregnancy (12 weeks gestation) and in neonatal cord blood. Cohort children were followed up at 1, 2 and 5 years using a respiratory symptom questionnaire and at 5 years children were also invited for spirometry and skin-prick test (SPT). Maternal and neonatal plasma selenium and erythrocyte GPx were related to the childhood outcomes of wheezing, and asthma. RESULTS: At 2 years 1282 children were followed up. At 5 years symptom data were available for 1167 children, 700 children were SPT tested, and forced expiratory volume in 1 s (FEV(1)) was measured in 478. Maternal plasma selenium concentration during early pregnancy was inversely associated with wheezing (odds ratio per 10 microg/kg plasma selenium 0.86, 95% confidence interval 0.76-0.97), and consulting a doctor because of wheeze (0.79, 0.69-0.93) in the second year of life. Cord plasma selenium was also inversely associated with wheezing (0.67, 0.47-0.96), and consulting a doctor because of wheeze (0.62, 0.41-0.93) in the second year of life. By age 5 these associations had disappeared. Maternal and neonatal erythrocyte GPx concentrations were not associated with any childhood outcomes at 2 or 5 years. CONCLUSION: The selenium status of mothers during early pregnancy, and neonates is associated with early childhood wheezing but not asthma or atopic sensitization, furthermore, this association is absent by the age of 5 years.

Protein kinase Czeta: a novel protective neonatal T-cell marker that can be upregulated by allergy prevention strategies.

BACKGROUND: Variations in neonatal T-cell function have been associated with allergic disease. OBJECTIVES: To examine the relationship between neonatal T-cell protein kinase (PKC) expression and subsequent allergic disease. METHODS: T cells were purified from cord blood samples (n = 74) obtained from a cohort of mothers who received either 4 g/d fish oil or a placebo from 20 weeks of gestation. PKC expression was examined in relationship to supplementation, fatty acid levels, cytokine production, and allergic outcomes at 1 year and 2.5 years of age. RESULTS: Neonatal T-cell PKCzeta expression was lower in children who had evidence of allergic disease at 1 year (P = .001) and 2.5 years (P = .052) of age. It was also lower in children with sensitization (positive skin prick test) at each age (P = .02 and P = .072, respectively). PKCzeta expression was inversely correlated to PKCalpha (r = -0.28; P = .025), which was strongly related to IL-5 responses to allergens (ovalbumin, r = 0.59; P = .003; dust mite, r = 0.52; P = .011) at 1 year of age. Fish oil supplementation was associated with significantly higher PKCzeta expression (P = .014), whereas most other isozymes were reduced by fish oil supplementation. CONCLUSION: This is the first study to show that allergic disease is associated with altered expression of T-cell PKC isozymes in the neonatal period. It has also demonstrated that fish oil can modulate expression of PKC isozymes in a potentially favorable direction. CLINICAL IMPLICATIONS: Protein kinase Czeta should be explored further as an early marker and potential target for disease prevention.

Neurologic condition of healthy term infants at 18 months: positive association with venous umbilical DHA status and negative association with umbilical trans-fatty acids.

Prenatal long-chain polyunsaturated fatty acids (LCPUFAs) and trans-fatty acids may affect neurodevelopment. In healthy term children, we determined relationships between relative fatty acid contents of umbilical arteries and veins and neurodevelopment at 18 mo. The study comprised a mixed group of 317 breast-fed, formula-fed, and LCPUFA formula-fed children. Study endpoints were the Hempel neurologic examination resulting in a neurologic classification and neurologic optimality score (NOS), and the Bayley Psychomotor Developmental Index (PDI) and Mental Developmental Index (MDI). Fifteen children showed minor neurologic dysfunction (MND). The umbilical vein trans, trans-18:2n-6 content was higher in children with MND than in the normal group. The NOS was significantly reduced in infants with an umbilical vein docosahexaenoic acid (DHA) content within the lowest quartile. Umbilical vein arachidonic acid (AA) was related to NOS in univariate statistics but not in multivariate analyses. The sum of trans-fatty acids and that of C18 trans-fatty acids showed a negative association with NOS in both univariate and multivariate analyses. No associations were found between AA, DHA and total trans-fatty acids with PDI or MDI. In conclusion, neonates with a relatively low DHA status and those with high trans-fatty acid levels have a less favorable neurologic condition at 18 mo.

Effect of maternal manganese blood levels on erythrocyte calcium-pump activity in newborns.

UNLABELLED: Manganese (Mn) is widely distributed in the biosphere but occurs in only trace amounts in animal tissues. Although Mn deficiency and toxicity both have pathological consequences, the underlying biochemical lesions have not been well defined. In vitro studies suggest that transport proteins are affected by Mn, lead (Pb), and selenium (Se). Among these transport proteins, the calmodulin-regulated calcium pump (Ca(2+)Mg(2+)ATPase) could be inhibited by Mn. In order to understand Mn biochemical pathways, we examined the relationships between Mn blood levels and red blood cell Ca-pump activity among 248 mothers and newborns, environmentally exposed to Mn, Pb, and Se. POPULATION AND METHODS: 248 mother-newborn pairs were recruited at Robert Debré University Hospital (Paris). Blood Mn and Pb concentrations were measured by absorption spectrophotometry. Se was measured by fluorometric method. Red blood cell membrane suspensions were obtained for Ca-pump activity measurements. Linear and quadratic regression models and Pearson correlation were performed. RESULTS: A non-linear parabolic relationship between maternal Mn blood levels and newborn Ca-pump activity was discovered from the analysis of the observed data. The peak level of maternal Mn that corresponded to a maximal activity of the newborn Ca-pump was estimated at 23.9 microg/l with a 95% confidence interval of 17.6 to 32.4 microg/l. An inhibition of this enzyme was observed at low and high levels of maternal Mn. The relationships between the newborn Ca-pump activity and maternal Se and Pb levels became non-significant after adjustment on all the co-factors included in the final model. CONCLUSION: Maternal environmental exposure to Mn, as reflected by maternal blood levels of this metal, is associated with a reduced activity of newborn erythrocyte Ca-pump in a non-linear pattern. Mn levels between 17.6 and 32.4 microg/l in maternal blood probably correspond to the optimal physiological concentration for the metabolism of this enzyme in newborns.

Neonatal screening of glucose-6-phosphate dehydrogenase deficiency in Yanbu, Saudi Arabia.

OBJECTIVE: To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the population tested, and to evaluate the prevalence of neonatal jaundice in newborns with G6PD deficiency. METHODS: Cord blood of all babies born between October 1996 and October 1998 at the Royal Commission Medical Center in Yanbu, Saudi Arabia, was screened for G6PD deficiency by fluorescent spot test. The results of screening of cord blood samples were reported to the physician in charge, and also placed on the files of the babies and their mothers. These babies were observed for 72 h and discharged if no jaundice developed. RESULTS: During this two-year period, 2,505 neonatal cord blood samples from 1,278 boys and 1,227 girls were screened for G6PD. There were 50 positive results for G6PD deficiency (39 boys and 11 girls), and the prevalence was estimated to be around 2%. The sex-specific prevalence for boys was 3.05%, and for girls 0.9%. Male to female ratio was 3:1. Neonatal jaundice developed in six (12%) babies, five male and one female. All were treated with phototherapy and discharged within one week of birth. CONCLUSION: The prevalence of G6PD is relatively high in Yanbu. Routine neonatal screening in areas with a high prevalence of G6PD in Saudi Arabia is justifiable.

Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates.

We performed DNA analysis on cord blood samples of 128 Chinese male neonates diagnosed as G6PD deficiency in Hospital Universiti Kebangsaan Malaysia by a combination PCR-restriction enzyme digest technique, Single Stranded Conformation Polymorphism analysis and DNA sequencing. We found 10 different G6PD-deficient mutations exist. The two commonest alleles were G6PD Canton 1376 G>T (42.3%) and Kaiping 1388 G>A (39.4%) followed by G6PD Gaohe 592 G>A (7.0%), Chinese-5 1024 C>T, Nankang 517 T>C (1.5%), Mahidol 487 G>A (1.6%), Chatham 1003 G>T (0.8%), Union 1360 C>T (0.8%), Viangchan 871 G>A (0.8%) and Quing Yang 392 G>T (0.8%). Sixty eight percent (88/125) neonates in this study had neonatal jaundice and 29.7% developed hyperbilirubinemia >250 micromol/l. The incidence of hyperbilirubinemia >250 micromol/l was higher in G6PD Kaiping (43.8%) than G6PD Canton (22%) (p< 0.05). There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean duration of phototherapy between the two major variants. None of the 88 neonates required exchange transfusion. In conclusion we have completely characterized the molecular defects of a group of Chinese G6PD deficiency in Malaysia. The mutation distribution reflects the original genetic pool and limited ethnic admixture with indigenous Malays.

Identification and molecular characterization of acyl-CoA synthetase in human erythrocytes and erythroid precursors.

Full-length cDNA species encoding two forms of acyl-CoA synthetase from a K-562 human erythroleukaemic cell line were cloned, sequenced and expressed. The first form, named long-chain acyl-CoA synthetase 5 (LACS5), was found to be a novel, unreported, human acyl-CoA synthetase with high similarity to rat brain ACS2 (91% identical). The second form (66% identical with LACS5) was 97% identical with human liver LACS1. The LACS5 gene encodes a highly expressed 2.9 kb mRNA transcript in human haemopoietic stem cells from cord blood, bone marrow, reticulocytes and fetal blood cells derived from fetal liver. An additional 6.3 kb transcript is also found in these erythrocyte precursors; 2.9 and 9.6 kb transcripts of LACS5 are found in human brain, but transcripts are virtually absent from human heart, kidney, liver, lung, pancreas, spleen and skeletal muscle. The 78 kDa expressed LACS5 protein used the long-chain fatty acids palmitic acid, oleic acid and arachidonic acid as substrates. Antibodies directed against LACS5 cross-reacted with erythrocyte membranes. We conclude that early erythrocyte precursors express at least two different forms of acyl-CoA synthetase and that LACS5 is present in mature erythrocyte plasma membranes.

Enzymic evaluation of thiamin, riboflavin and pyridoxine status of parturient mothers and their newborn infants in a Mediterranean area of Spain.

OBJECTIVE: To determine the biochemical status of thiamin, riboflavin and pyridoxine in parturient mothers and their newborn infants in a Mediterranean region. DESIGN: Transveral study. SETTING: St Joan University Hospital and Faculty of Medicine & Health Sciences, Universitat Rovira i Virgili, Reus, Spain. SUBJECTS: 131 healthy parturient mothers, with normal pregnancies and deliveries in St Joan University Hospital, and their newborn infants. INTERVENTIONS: Erythrocyte haemolysates were prepared from maternal blood at delivery and infants' umbilical cord blood and used to measure micronutrient status using the transketolase, glutathione reductase and aspartate aminotransferase coenzyme stimulation tests. RESULTS: Maternal and infant coenzyme activities were significantly correlated, but infant coenzyme status was better than maternal, with significantly higher basal and stimulated activity (P < 0.001) and significantly lower activation coefficients (P < 0.001). Inadequate thiamin, riboflavin or pyridoxine status occured in 38.2 62.6% (50-82) of the mothers and 3.1-37.4% (4 49) of the infants; 85.2% (46/54), 12.9% (4/31) and 24.1% (12/54) of infants born to mothers with biochemical deficiency of either thiamin, riboflavin or pyridoxine, respectively also had inadequate status. Maternal deficiencies in more than one vitamin further increased the risk of infant thiamin and pyridoxine deficiency. Maternal and infant riboflavin status were significantly correlated with fetal development (e.g. length at birth, P < 0.001). The incidence of thiamin deficiency in paturient mothers in Spain was the highest out of a 12-country comparison. CONCLUSIONS: Inadequate status for each vitamin was evident in mothers and infants. Maternal status of each individual vitamin, but especially riboflavin, was affected by maternal status of the other vitamins. Infant thiamin status was the most adversely affected by maternal deficiencies in more than one vitamin. Infant riboflavin status, however, was apparently protected from adverse maternal status.

Efficacy of a food supplement in correcting riboflavin deficiency in pregnant Gambian women.

Pregnant women living in rural Gambian villages, whose natural riboflavin intake is about 0.5 mg/d, have abnormal biochemical riboflavin status and signs of clinical deficiency. A vitamin-fortified food supplement given in one village which increased the riboflavin intake to about 1.3 mg/d was followed by a substantial improvement in biochemical status, although seasonally-related variations in status somewhat complicated the picture. It was calculated that the amount of riboflavin needed to satisfy the requirement, for normal biochemical status, of the majority of pregnant women throughout pregnancy and throughout the year, is about 2.6 mg/d. Clinical signs associated with riboflavin deficiency, especially atrophic lingual papillae, showed significantly reduced incidence in the supplemented, compared with an unsupplemented, village. Cord blood values of the activation coefficient of erythrocyte glutathione reductase were in the abnormal range for 84 per cent of infants before introduction of the supplement, but were abnormal for only one of 12 infants after its introduction. Thus even a suboptimal maternal riboflavin intake of about 1.3 mg/d appears to be sufficient to prevent biochemical deficiency in cord blood, and to reduce considerably the incidence of clinical deficiency signs during pregnancy.

Levels of the glutamic oxaloacetic transaminase of erythrocytes of pregnant women and of cord bloods of newborn infants.

The mean basal specific activity (S.A.) of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) for a group of 64 pregnant women was lower (p less than 0.001) than the value for the cord bloods of newborn infants, and lower (p less than 0.001) than the value for adults who had a top limit of S.A. of EGOT. In establishing the top limit of the S.A., it is important that the mean basal S.A. of the cord bloods from 49 newborn infants was identical to the mean basal S.A. of adults who had an adequate supplement of pyridoxine. There were no differences in the mean basal S.A.'s of the cord bloods between asymptomatic mothers and mothers who had anemia, edema, hypertension, proteinuria and glucosuria. An infant may be born with a top limit of S.A. which is non-deficient in pyridoxal 5'-phosphate, but a mother can have a low level of the transaminase, and which is deficient in the coenzyme.