Loss of endothelial nitric oxide synthase exacerbates intestinal and lung injury in experimental necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) continues to be a devastating condition among preterm infants. Nitric oxide, which is synthesized in the intestine by endothelial nitric oxide synthase (eNOS), acts as a potent vasodilator and antioxidant within the mesentery and may play a role in prevention of NEC. We hypothesized that loss of endothelial nitric oxide would worsen both intestinal and associated lung injury and increase local and systemic inflammation during experimental NEC. METHODS: NEC was induced in five-day-old wild type (WT) and eNOS-knockout (eNOSKO) mouse pups. Experimental groups (n=10) were formula fed and subjected to intermittent hypoxic and hypothermic stress, while control groups (n=10) remained with their mother to breastfeed. Pups were monitored by daily clinical assessment. After sacrifice on day nine, intestine and lung were assessed for injury, and cytokines were measured in tissue homogenates by ELISA. Data were compared with Mann-Whitney, and p<0.05 was significant. RESULTS: Each NEC group was compared to its respective strain's breastfed control to facilitate comparisons between the groups. Both NEC groups were significantly sicker than their breastfed controls. eNOSKO NEC animals had a median clinical assessment score of 3 (IQR=1-5), and the WT NEC animal's median score was 3 (IQR=2-5). Despite similar clinical scores, intestinal injury was significantly worse in the eNOSKO NEC groups compared to WT NEC groups (median injury scores of 3.25 (IQR=2.25-3.625) and 2 (IQR=1-3), respectively (p=0.0474). Associated lung injury was significantly worse in the eNOSKO NEC group as compared to the WT NEC group (median scores of 8.5 (IQR=6.75-11.25) and 6.5 (IQR=5-7.5), respectively, p=0.0391). Interestingly, cytokines in both tissues were very different between the two groups, with varying effects noted for each cytokine (IL-6, IL-1ß, VEGF, and IL-12) in both tissues. CONCLUSION: Nitric oxide from eNOS plays a key role in preventing the development of NEC. Without eNOS function, both intestinal and lung injuries are more severe, and the inflammatory cascade is significantly altered. Further studies are needed to determine how eNOS-derived nitric oxide facilitates these beneficial effects.

Bone Mineral Density According to Dual Energy X-ray Absorptiometry is Associated with Serial Serum Alkaline Phosphatase Level in Extremely Low Birth Weight Infants at Discharge.

BACKGROUND: To examine bone mineral density in extremely low birth weight infants at discharge and investigate whether serial measurements of serum alkaline phosphatase (ALP) and phosphate can predict bone mineralization. METHODS: The individuals were 70 preterm infants. Serum calcium, phosphate, and ALP were measured at weekly intervals during admission in extremely low birth weight infants (mean gestational age, 25.3±2.1 weeks; birth weight, 812.8±141.1 g). Bone mineral apparent density (BMAD) of the lumbar spine was prospectively evaluated by dual energy X-ray absorptiometry at discharge (n=70). RESULTS: BMAD was classified as poor (< 25th percentile) at < 0.014 g/cm3, fair (25th-75th percentile) at < 0.014-0.021 g/cm3, and good (> 75th percentile) at > 0.021 g/cm3, based on the distribution of BMAD values in infants with noncomplicated courses of prematurity (n=43). In a further multivariate analysis, the number of total parenteral nutrition days, phosphate at 2 postnatal weeks and 3 postnatal weeks, and ALP at 4 postnatal weeks and 5 postnatal weeks had an impact on bone mineral density at the lumbar spine, independent of gestational age and body weight. Peak ALP activities exceeding 650 IU/L revealed low bone mineral density with 80% sensitivity and 64% specificity (AUC, 0.70; p=0.005). CONCLUSION: Serial measurements of serum ALP and phosphate are associated with decreased bone mineralization by dual energy X-ray absorptiometry at discharge in extremely low birth weight infants.

Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study.

The p.Thr1406Asn (rs1047891) polymorphism of the carbamoyl-phosphate synthetase 1 (CPS1) gene has been linked to functional consequences affecting the downstream availability of the nitric oxide precursor L-arginine. L-arginine concentrations are decreased in preterm infants with necrotizing enterocolitis (NEC). In this multicenter prospective study, we investigated the association of the p.Thr1406Asn polymorphism with NEC in 477 preterm infants (36 cases of NEC) from 4 European neonatal intensive care units (Maastricht, Las Palmas de Gran Canaria, Mantova, and Milan). Allele and genotype frequencies of the p.Thr1406Asn polymorphism did not significantly differ between the infants with and without NEC. In contrast, the minor A-allele was significantly less frequent in the group of 64 infants with the combined outcome NEC or death before 34 weeks of corrected gestational age than in the infants without the outcome (0.20 vs. 0.31, P = 0.03). In addition, a significant negative association of the A-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.54, 95% CI 0.29-0.99) and the additive (aOR 0.58, 95% CI 0.36-0.93) genetic models. In conclusion, our study provides further evidence that a functional variant of the CPS1 gene may contribute to NEC susceptibility.

UGT1A1*28 Genotypes and Respiratory Disease in Very Preterm Infants: A Cohort Study.

BACKGROUND: Respiratory disease in the very preterm infant is frequent and often severe. Bilirubin is both a potent neurotoxin and antioxidant, and may have a clinical impact on preterm respiratory disease. The Gilbert genotype, the UGT1A1*28 allele, is the major known genetic cause of variation in bilirubin. OBJECTIVES: To study the association between respiratory disease in the very preterm infant and the UGT1A1*28 allele. METHODS: This is a cohort study of 1,354 very preterm infants (gestational age <32 weeks) born in Jutland, Denmark in 1997-2011. Genotypes were obtained from the Danish Neonatal Screening Biobank, and clinical information was obtained from the databases of two tertiary neonatal intensive care units. Outcomes were the need for surfactant therapy, any need for and duration of supplementary oxygen and bronchopulmonary dysplasia (BPD). RESULTS: Per UGT1A1*28 allele, odds were increased for any need of supplementary oxygen (odds ratio 1.26; 1.05-1.50) and for BPD (odds ratio 1.71; 1.23-2.39), the need of supplementary oxygen increased by 6.38 days (1.87-10.89), and chance per day of no longer needing supplementary oxygen was reduced (hazard rate 0.84; 0.76-0.93). No effect was observed for need of surfactant treatment (odds ratio 1.08; 0.91-1.28). Hardy-Weinberg equilibrium was unlikely for the cohort (p < 0.012). This could be explained by death prior to genotype sampling. In tests of robustness this failed to explain the primary results. CONCLUSIONS: Compared to the common genotype, UGT1A1*28 genotypes were associated with an increased need of oxygen supplementation and risk of BPD in very preterm newborns.

Serum neuron-specific enolase levels in preterm and term newborns and in infants 1-3 months of age.

BACKGROUND: Elevated serum levels of neuron-specific enolase (NSE) was initially assumed to be specific to neuronal tumors (particularly neuroblastoma), but is now known to accompany nontumoral conditions and tumors other than neuroblastomas. There is a need to establish normal ranges for NSE, especially in early infancy. The aims of this study were to determine reference values for NSE in newborns and young infants and to assess whether NSE levels in early infancy (i.e., preterm infants and term infants) differ from the adult reference range for this enzyme. METHODS: We enrolled 140 healthy babies, which included 40 preterm newborns (3-15 days old and born at 28-42 weeks gestation), 40 term newborns (< 1 month old and born at term), and 60 young infants 1-3 months old (n = 20 per subgroup of 1-, 2-, and 3-month-old infants). The determination of NSE levels was performed by the electrochemiluminescence immunoassay (ECLIA) method using the Elecysys 2010 device (Roche Diagnostics, Mannheim, Germany). The mean serum NSE levels for the preterm newborns was 21.83 ± 15.06 ng/mL [95% confidence interval (95%CI), 16.95-26.71 ng/mL]; term newborns, 18.06 ± 12.83 ng/mL (95%CI, 13.94-22.19 ng/mL); and young infants, 9.09 ± 4.38 ng/mL (95%CI, 7.96-10.23 ng/mL). The mean serum NSE level for infants 1-3 months old was within the ECLIA kit's normal range (4.7-18 ng/mL for adults), whereas the corresponding means for the preterm and term newborns were higher (p < 0.001, for both). CONCLUSION: Our findings suggest that adult reference values should not be applied to the preterm and term age groups.

Analysis of nitric oxide synthase gene polymorphisms in neonatal respiratory distress syndrome among the Chinese Han population.

AIM: To evaluate the association of NOS1 and NOS3 gene polymorphisms with the risk/severity of neonatal respiratory distress syndrome (RDS) among preterm infants. METHODS: The patient group was 189 preterm infants diagnosed with RDS. The control group was 227 preterm neonates who did not develop RDS. NOS genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique based on LDR. RESULTS: It was found that genotype and allele frequencies of rs2682826 of the NOS1 gene and rs1799983 of the NOS3 gene were not significantly different between the RDS group and the control group. However, when the preterm infants were divided into two and three groups based on gestational age and birth weight, a study of the SNP rs1799983 of the NOS3 gene showed that the GG genotype and G allele frequencies were significantly increased in the RDS groups, the GT genotype and A allele were less frequent among the RDS groups in 26-32.9 weeks of gestational age and in a birth weight subgroup of <1.5 Kg. CONCLUSION: Our study raises the possibility that a genetic variation of NOS3 could be implicated in the pathophysiology of RDS in the Chinese Han population, especially in very preterm and very low birth weight infants.

Detection of pepsin in mouth swab: correlation with clinical gastroesophageal reflux in preterm infants.

OBJECTIVE: To study the relationship between pepsinogen/pepsin in a mouth swab and clinical gastroesophageal reflux (GER) in preterm infants. METHODS: Preterm infants (birth weight ≤ 2000 g) on full enteral feeds were enrolled. Mouth swabs from cheek and below the tongue were collected one, two and three hours after feeding. An enzymatic assay with substrate fluorescein isothiocyanate-casein was used to detect pepsin A and C activities with further confirmation by western blot. Blinded investigators reviewed the infant's medical record to clinically diagnose GER. RESULTS: A total of 101 premature infants were enrolled. Pepsinogen/pepsin was detected in 45/101 (44.5%) infants in at least one sample. A clinical diagnosis of GER was made in 36/101 (35.6%) infants. Mouth swabs were positive in 26/36 (72%) infants with clinical GER and only 19/65 (29%) infants without GER (p < 0.001). Similarly, the levels of pepsinogen/pepsin A and C were higher in the mouth swabs of infants with clinical GER. CONCLUSION: The detection of pepsinogen/pepsin in a mouth swab correlates with clinical GER in premature infants.

High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support.

BACKGROUND: Osteopenia and rickets are common among extremely low birth weight infants (ELBW, <1000 g birth weight) despite current practices of vitamin and mineral supplementation. Few data are available evaluating the usual course of markers of mineral status in this population. Our objectives in this study were to determine the relationship between birth weight (BW) and peak serum alkaline phosphatase activity (P-APA) in ELBW infants and evaluate our experience with the diagnosis of rickets in these infants. METHODS: We evaluated all ELBW infants admitted to Texas Children's Hospital NICU in 2006 and 2007. Of 211 admissions, we excluded 98 patients who were admitted at >30 days of age or did not survive/stay for >6 weeks. Bone radiographs obtained in 32 infants were reviewed by a radiologist masked to laboratory values. RESULTS: In this cohort of 113 infants, P-APA was found to have a significant inverse relationship with BW, gestational age and serum phosphorus. In paired comparisons, P-APA of infants <600 g (957 +/- 346 IU/L, n = 20) and infants 600-800 g (808 +/- 323 IU/L, n = 43) were both significantly higher than P-APA of infants 800-1000 g (615 +/- 252 IU/L, n = 50), p < 0.01. Thirty-two patients had radiographic evaluation for evidence of rickets, based on P-APA greater than 800 IU/L, parenteral nutrition greater than 3 to 4 weeks, or clinical suspicion. Of these, 18 showed radiologic rickets and 14 showed osteopenia without rickets. Infants with BW <600 g were more likely to have radiologic rickets (10/20 infants) compared to those with BW 600-800 g (6/43 infants) and BW 800-1000 g (2/50 infants), p < 0.01 for each. P-APA was not significantly higher in infants with radiologic rickets (1078 +/- 356 IU/L) compared to those without radiologic evidence of rickets (943 +/- 346, p = 0.18). CONCLUSION: Elevation of P-APA >600 IU/L was very common in ELBW infants. BW was significantly inversely related to both P-APA and radiologic rickets. No single value of P-APA was related to radiological findings of rickets. Given the very high risk of osteopenia and rickets among ELBW infants, we recommend consideration of early screening and early mineral supplementation, especially among infants <600 g BW.

Secretory phospholipase A(2) in newborn infants with sepsis.

OBJECTIVE: To investigate secretory phospholipase A(2) (sPLA(2)) activity in neonatal sepsis. STUDY DESIGN: Plasma sPLA(2) activity, C-reactive protein (CRP) concentration, leukocyte count and immature/total neutrophil (I/T) ratio were assessed in a group of 156 infants admitted for neonatal intensive care, who were classified as documented sepsis (n=24), suspected infection (n=77) and controls (n=55). Interleukin-6 (IL-6) concentrations were assessed in a subgroup (n=29). RESULT: sPLA(2) activity, CRP concentration and I/T ratio were higher in sepsis than in suspected infection or control groups. sPLA(2) activity advanced with increasing CRP, I/T ratio and IL-6 was highest in infants with respiratory distress syndrome (RDS). Compared to CRP, sPLA(2) had equal sensitivity and lower specificity. Compared to I/T ratio, sensitivity and specificity of sPLA(2) were higher. CONCLUSION: Plasma sPLA(2) activity is increased in neonatal sepsis and highest in infants with RDS. Further studies should assess the potential of sPLA(2) inhibition in neonatal sepsis.

Early increased levels of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome.

AIM: Matrix metalloproteinases (MMPs) play an eminent role in airway injury and remodelling. We explored the hypothesis that pulmonary MMP levels would differ early after birth (2-4 days) between infants with resolving respiratory distress syndrome (RDS) and infants developing chronic lung disease of prematurity (CLD). METHODS: Thirty-two prematurely born infants (gestational age < or =30 weeks) diagnosed with RDS were included. In 13 infants RDS resolved while 19 developed CLD. MMP-2 and MMP-9 in bronchoalveolar lavage (BAL) fluids collected on postnatal days 2, 4, 7 and 10 were analyzed by zymography and densitometry. Immunochemistry was performed on BAL cells and lung tissue to identify cellular sources of MMP-9 in RDS and CLD. RESULTS: Median MMP-9 levels increased significantly on day 2 in BAL fluid from patients with resolving RDS (median values MMP-9 = 42.0 arbitrary units (AU)) compared to CLD patients (MMP-9 = 5.4 AU). MMP-9 and neutrophil lipocalin-associated MMP-9 (NGAL) were significantly higher on day 4 in BAL fluid from resolving RDS (MMP-9 = 65.8 AU; NGAL = 16.1 AU) compared to CLD (MMP-9 = 25.4 AU; NGAL = 2.0 AU), Levels of MMP-9 and NGAL increased subsequently on days 7 and 10 in CLD. No differences in MMP-2 levels were detected between RDS and CLD. Neutrophils, macrophages and alveolar type-II epithelial cells were identified as potential sources of MMP-9. CONCLUSION: Our findings indicate differences in early MMP-9 BAL fluid levels between resolving RDS and developing CLD, which may relate to the ability to raise an early and adequate response to the initial injury.

Erythrocyte Cu/Zn superoxide dismutase activity in preterm infants with and without bronchopulmonary dysplasia.

BACKGROUND: Erythrocyte Cu/Zn superoxide dismutase is believed to play a major role as a first-line antioxidant defense. Studies have reported varying results from measures of superoxide dismutase activity in cord blood samples from neonates. OBJECTIVE: The study goal was to assess enzyme activity for preterm infants representing a range of gestational ages during the 1st week of life. Clinical data were obtained and correlations with superoxide dismutase activity were examined. METHODS: We collected blood samples from umbilical arterial lines or the radial artery of 44 preterm infants (gestational age range 25-30 weeks) on days 1, 3, and 6 after delivery and evaluated erythrocyte Cu/Zn superoxide dismutase activity. RESULTS: There was no correlation between enzyme activity and gestational age or birth weight. Superoxide dismutase activity gradually increased in preterm infants with bronchopulmonary dysplasia on days 3 and 6, with levels significantly higher than those of preterm infants without bronchopulmonary dysplasia on day 6. We found that packed red cell transfusion did not affect erythrocyte superoxide dismutase activity in either group. However, higher cumulative oxygen administration was noted in preterm infants with bronchopulmonary dysplasia. CONCLUSION: Higher cumulative oxygen administration may be one factor that upregulates the activity of erythrocyte superoxide dismutase.

Glucose-6-phosphate dehydrogenase activity in male premature and term neonates.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term neonates than in adults. Some studies have suggested that activity may be even higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in preterm than term neonates, and whether higher activity would interfere with diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was determined in the first 48 hours after delivery in male premature, term, and near term infants. G6PD deficient neonates were separated, and the remaining premature infants compared with healthy, male, G6PD normal, near term and term neonates. RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8) weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g haemoglobin (Hb), which is clearly in the deficient range with no overlap into the normal range. G6PD activity in the remaining premature infants was significantly higher than in 24 near term and term neonates (gestational age > or = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that significance was limited to those born between 29 and 32 weeks gestation, in which group G6PD activity was significantly higher than in those born before 29 weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation. CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32 weeks gestation than in term neonates. This did not interfere with diagnosis of G6PD deficiency.

Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.

OBJECTIVE: The aims of this study were to determine the impact of expanded newborn screening using tandem mass spectrometry (MS/MS) on the overall detection rate of inborn errors of metabolism in Germany and to assess the outcome for the patients that were diagnosed. METHODS: During the period of study, 250,000 neonates in a German population were investigated for 23 inborn errors of metabolism by electrospray ionization-MS/MS. The overall value of the screening program was estimated by 1) complete ascertainment of all positive tests; 2) definite assignment of all diagnoses including reconfirmation at 12 months; and 3) clinical follow-up of all detected patients in an overall interval of 42 months. The mean observation period was 13.5 months per child. RESULTS: In 106 newborns, confirmed inborn errors of metabolism were found. The disorders were classified as 50 classic forms and 56 variants. A total of 825 tests (0.33%) were false-positives. Seventy of the 106 newborns with confirmed disorders were judged to require treatment. Six children developed symptoms despite treatment. Three children had died. Among 9 children who became symptomatic before report of the results of screening, in 6 the diagnosis had been made in advance of the screening report. In evaluation of the screening program, 61 of the 106 identified children (58% of true-positives, or 1 of 4100 healthy newborns) were judged to have benefited from screening and treatment, because the diagnosis had not been made before screening. None of these infants had died and none developed psychomotor retardation or metabolic crisis during the follow-up period. CONCLUSIONS: The screening by MS/MS for up to 23 additional disorders has approximately doubled the detection rate compared with that achieved by the conventional methods used in Germany. This strategy represents valuable preventive medicine by enabling diagnosis and treatment before the onset of symptoms.

Relationship of serum lactate dehydrogenase, creatine kinase, aspartate aminotransferase concentrations and severe intraventricular hemorrhage/leukomalacia in very low birth body weight preterm neonates.

Estimations of serum enzyme values are widely employed as valuable diagnostic aids in diseases. Most commonly employed enzymes include Aspartate aminotransferase (AST), Lactate dehydrogenase (LDH), and Creatine kinase (CK). The study was designed to determine the relationship of elevated postnatal serum LDH, CK, and AST concentrations within the first day of life and the risk of suffering severe intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) in VLBW preterm newborns. 81 preterm neonates whose birth body weight < 1500 gm were enrolled. Serums were obtained for measurement within the first postnatal day. Cranial ultrasound scans were performed twice per week after birth until their body weight was above 2300 gm or postconceptional age above 40 weeks. Significant difference was noted in serum LDH and CK concentrations in severe IVH/PVL infants (p < 0.05). No difference was found in serum AST values. Compared with the cut-off values of 1933 IU/L of LDH concentration and 652 IU/L of CK, the predictive values revealed a sensitivity, specificity, negative predictive value and positive predictive value of 76.9%, 89.7%, 95.3% and 58.8%, respectively. In conclusion, higher serum LDH and/or CK concentrations within the first day of life were associated with risk for development of severe IVH/PVL.

Biochemical and molecular genetic characteristics of the severe form of tyrosine hydroxylase deficiency.

BACKGROUND: Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of the catecholamines dopamine, norepinephrine, and epinephrine. Recently, mutations were identified in cases of autosomal recessive dopa-responsive dystonia and infantile parkinsonism. We describe a patient with severe symptoms and a new missense mutation in TH. METHODS: Relevant metabolites in urine and cerebrospinal fluid were measured by HPLC with fluorometric and electrochemical detection. All exons of the TH gene were amplified by PCR and subjected to single-strand conformation polymorphism analysis. Amplimers displaying aberrant migration patterns were analyzed by DNA sequence analysis. RESULTS: The patient presented with severe axial hypotonia, hypokinesia, reduced facial mimicry, ptosis, and oculogyric crises from infancy. The major metabolite of dopamine, homovanillic acid, was undetectable in the patient's cerebrospinal fluid. A low dose of L-dopa produced substantial biochemical but limited clinical improvement. DNA sequencing revealed a homozygous 1076G-->T missense mutation in exon 10 of the TH gene. The mutation was confirmed with restriction enzyme analysis. It was not present in 100 control alleles. Secondary structure prediction based on Chou-Fasman calculations showed an abnormal secondary structure of the mutant protein. CONCLUSIONS: We describe a new missense mutation (1076G-->T, C359F) in the TH gene. The transversion is present in all known splice variants of the enzyme. It produces more severe clinical and biochemical manifestations than previously described in TH-deficient cases. Our findings extend the clinical and the biochemical phenotype of genetically demonstrated TH deficiency.

Erythrocyte glutathione S transferase as a marker of oxidative stress at birth.

AIMS: To determine the level of oxidative stress and cell damage as a result of exposure to O(2) at birth. METHODS: Using glutathione S transferase (GST) as an indicator of oxidative stress, GST activity in cord blood was compared with that in samples taken three hours after birth. Twenty four prematurely born infants and eight full term infants were studied. To test whether stronger effects occur under less favourable conditions, the neonates were divided in three groups: healthy premature; sick premature; and healthy full term infants. RESULTS: GST activity three hours after birth was significantly decreased compared with that at birth in all three groups tested. There were no significant differences in the magnitude of this effect among the three groups. CONCLUSIONS: These results indicate that a sudden increase in oxygenation exposes the neonate to oxidative stress. Measurement of GST activity might be useful for the evaluation of protective treatment in trials considering antioxidant strategies.

Early feeding, feeding tolerance, and lactase activity in preterm infants.

OBJECTIVE: We sought to ascertain whether the timing of feeding initiation affected the development of intestinal lactase activity and whether there are clinical ramifications of lower lactase activity. STUDY DESIGN: Preterm infants (26 to 30 weeks' gestation; n = 135) were randomly assigned to begin enteral feedings at either 4 (early group) or 15 days of age (standard group). At 10, 28, and 50 days of age lactase activity was determined by measuring the urinary ratio of lactulose/lactose after the 2 sugars were administered. RESULTS: Lactase activity increased significantly over time. Infants in the early group had greater lactase activity at 10 days of age (by 100%) and 28 days of age (by 60%) than the standard group. At 10 days of age lactase activity was greater in milk- versus formula-fed infants. The time required to achieve full enteral feedings, the number of abnormal abdominal x-ray examinations, and the total number of abdominal x-ray examinations were inversely related to lactase activity. CONCLUSIONS: Early feeding increases intestinal lactase activity in preterm infants. Lactase activity is a marker of intestinal maturity and may influence clinical outcomes. Whether the effects of milk on lactase activity were due to the greater concentration of lactose in human milk compared with that in formula must be determined.

Carbohydrate-deficient glycoprotein syndrome type 1 with profound thrombocytopenia and normal phosphomannomutase and phosphomannose isomerase activities.

We report siblings with a variant of carbohydrate-deficient glycoprotein syndrome, type 1 (CDGS1), characterized by normal phosphomannomutase and phosphomannose isomerase activities, severe thrombocytopenia, and respiratory compromise. Each infant died after a course of intensive care, suggesting that infants with CDGS1 and normal phosphomannomutase and phosphomannose isomerase activities may have a more severe CDGS1 phenotype.

Rickets screening in the preterm infant.

Although rickets in the preterm infant has decreased with improvements in care and nutrition, there continue to be infants at high risk for this disease. Early diagnosis and treatment can prevent fractures and other complications, such as decreased linear growth. Nurses must know which infants are at risk, must be aware of the appropriate screening tests, and must know how to customize care for at-risk neonates.