Usefulness of tissue transglutaminase type 2 antibodies in early pregnancy.

Celiac disease (CD), an autoimmune disease triggered by dietary gluten, is a multi-systemic disorder that primarily results in mucosal damage of the small intestine. Reproductive disorders and pregnancy complications have been associated with CD. Conflicting results have been published concerning CD and the risk of impaired fetal growth with reduced birthweight. The aim of our multicentric, perspective, case-control study was to determine the prevalence of undiagnosed CD in mothers of small for gestational age (SGA) newborns in two regions of Italy. The study included 480 mothers: group A consisted of 284 SGA newborns' mothers and group B consisted of 196 appropriate for gestational age (AGA) newborns' mothers. Tissue transglutaminase type 2 antibodies (TG2) IgA and IgG were measured in blood samples. We diagnosed two new cases of CD in asymptomatic mothers. It may be appropriate to include the TG2 to the panel of prenatal blood test.

Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns.

BACKGROUND AND OBJECTIVES: Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome. METHODS: Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded. RESULTS: We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9-10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7-25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003). CONCLUSIONS: Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age.

Serum calprotectin: an antimicrobial peptide as a new marker for the diagnosis of sepsis in very low birth weight newborns.

To determine the diagnostic utility of serum calprotectin, a mediator of innate immune response against infections, we performed a multicenter study involving newborns with a birth weight < 1500 g and a postnatal age >72 hours of life. The diagnostic accuracy of serum calprotectin was compared with that of the most commonly used markers of neonatal sepsis (white blood cell count, immature-to-total-neutrophil ratio, platelet count, and C-reactive protein). We found that the serum calprotectin concentration was significantly higher (P < .001) in 62 newborns with confirmed sepsis (3.1 ± 1.0 µg/mL) than in either 29 noninfected subjects (1.1 ± 0.3 µg/ml) or 110 healthy controls (0.91 ± 0.58 µg/ml). The diagnostic accuracy of serum calprotectin was greater (sensitivity 89%, specificity 96%) than that of the traditional markers of sepsis. In conclusion, serum calprotectin is an accurate marker of sepsis in very low birth weight newborns.

Plasma levels of conjugated bile acids in newborns after a short period of parenteral nutrition.

BACKGROUND: Patients receiving parenteral nutrition (PN) frequently exhibit liver dysfunction. The authors previously reported that plant sterols of lipid emulsions added to the nutritional solution of newborns receiving PN accumulate in plasma and cell membranes and may contribute to the development of cholestasis. Conjugated bile acids (BA) have been shown to be useful markers of cholestasis. Plasma levels of several BA in newborns were quantified after administration of PN for less than 2 weeks. METHODS: Plasma samples from 15 healthy control infants (CN), 22 patients who had received PN for 3-15 days (T1), and 9 patients scheduled to receive PN (T0) were analyzed. After a simple extraction procedure, plasma BA were analyzed by liquid chromatography-tandem mass spectrometry using a quantitative isotope dilution method. RESULTS: The concentrations of BA did not differ significantly between controls and patients before PN (CN vs T0), with the exception of glycocholic acid (GCA; 2.30 ± 2.60 µM vs 7.29 ± 5.39 µM, respectively). There was a significant difference in several BA between controls and patients after PN (2.30 ± 2.60 µM vs 7.61 ± 6.46 µM for GCA, respectively; 4.02 ± 3.49 µM vs 11.88 ± 11.05 µM for taurocholic acid [TCA], respectively; and 4.81 ± 3.49 µM vs 13.58 ± 12.22 µM for taurochenodeoxycholic + taurodeoxycholic + tauroursodeoxycholic acids [TCDCA+TDCA+TUDCA], respectively). CONCLUSIONS: In newborns receiving PN, a short period of PN is associated with an early increase of some conjugated BA. These results suggest that GCA, TCA, and TCDCA+TDCA+TUDCA levels could be used as early markers of PN-related cholestasis.

Maturation of gastric electrical activity, gastric emptying and intestinal permeability in preterm newborns during the first month of life.

INTRODUCTION: Immaturity of motility, intestinal epithelial barrier function and absorptive capacity may play a role in the pathophysiology of intestinal diseases in preterms. We determined the gastric electrical activity and emptying, and intestinal permeability, in preterm newborns to verify if a maturation pattern exists in preterm newborns during the first month of life. PATIENTS AND METHODS: Eighteen preterm newborns (median 34 wks, range 2 wks) completed the study. They underwent the recording of gastric electrical activity by means of cutaneous electrogastrography, the ultrasound examination of gastric emptying, and the lactulose-to-mannitol ratio from permeability-absorption test on days 3, 7, 15, and 30 after birth. RESULTS: Gastric electrical activity and emptying showed only slight changes between day 3 and day 7. On the contrary, an evident maturation in permeability, expressed as L/Mratio, was evident over time (Friedman Repeated Measures Analysis, p = 0.004). CONCLUSION: In preterm healthy newborns of 34 weeks gestational age, electrical and motor activity are completely developed at birth whilst the intestinal epithelial barrier clearly improves during the first week of life.

Use of real time continuous glucose monitoring and intravenous insulin in type 1 diabetic mothers to prevent respiratory distress and hypoglycaemia in infants.

BACKGROUND: Pregnancy in Type 1 diabetic patients is a precarious condition, both for mother and fetus with increased the risk of prematurity and, immediately after delivery with risk of respiratory distress syndrome and hypoglycaemia in newborns. A strict control and monitoring of diabetes throughout pregnancy is important in reducing the impact of the disease on the fetus and newborn. In recent years many new technologies have been introduced to ameliorate diabetes monitoring, where the last is the Real-time Continuous Glucose Monitoring System (RT-CGMS). METHODS: In the last three years, 72 h continuous glucose monitoring system (RT-CGMS) (Medtronic, CA) was performed in 18 pregnant women with Type 1 diabetes in two moments of pregnancy: during treatment with betamethasone to prevent respiratory distress and during delivery. In both cases insulin was administered intravenous and the dose was changed on the basis of glycaemia. RESULTS: The results present the use of this new technique during two topics moments of pregnancy of type 1 diabetes patients when is very important intensively to monitor diabetes and to obtain the well being of the fetus. No infant experimented hypoglycaemia or respiratory distress syndrome at the moment and in the first hours after the birth. CONCLUSION: We wish to stress the importance reducing glycaemia during administration of betamethasone and during labor. It is conceivable that the scarce attention paid to monitoring glucose levels in diabetic mothers during labor in gynaecological world may be due to the difficulty in glucose monitoring with the devices until now available. Hopefully, our anecdotal account may prompt improvements with RT-CGMS, and may lead to a better approach to the problem, thereby changing the prognosis of infants born to diabetic mothers.

Neonatal onset intestinal failure: an Italian Multicenter Study.

OBJECTIVE: To describe the natural course of intestinal failure with onset in the neonatal period to provide data regarding the occurrence and to provide a population-based survey regarding the spectrum of underlying diseases. STUDY DESIGN: We performed a retrospective chart review including infants admitted to the neonatal intensive care unit of 7 Italian tertiary care centers. Intestinal failure was defined as a primary intestinal disease that induces the need of total parenteral nutrition (PN) for more than 4 weeks or the need of partial PN for more than 3 months. RESULTS: The total number of live births during the study time within the enrolled institutions was 30 353, and the number of newborns admitted to the neonatal intensive care unit was 5088. Twenty-six patients satisfied the definition of intestinal failure; thus the occurrence rate of intestinal failure was 0.1% among live-birth newborns and 0.5% among infants at high risk. The main underlying diseases leading to intestinal failure in neonatal age were congenital intestinal defects (42.3%), necrotizing enterocolitis (30.8%), severe intestinal motility disorder (11.5%), intestinal obstruction (7.7%), structural enterocyte defects (3.8%), and meconium peritonitis (3.8%). After a follow-up of 36 months, 84.6% of patients achieved intestinal competence, 1 patient was still receiving home PN, 1 patient underwent transplantation, and 2 patients died. Cholestatic liver disease was diagnosed in 54% of observed children. CONCLUSION: An understanding of the incidence, causes, and natural history of intestinal failure would be helpful to appropriately allocate resources and to plan clinical trials.

Intravenous magnesium sulphate vs. inhaled nitric oxide for moderate, persistent pulmonary hypertension of the newborn. A Multicentre, retrospective study.

We have compared intravenous magnesium sulphate vs. inhaled nitric oxide in the therapy of moderate persistent pulmonary hypertension of the neonate. A retrospective collection of clinical data from 58 neonates was carried out in six neonatal intensive care units of Southern Italy sharing the same operational protocols. In our setting, both drugs were effective in treating moderate persistent pulmonary hypertension of the neonate but nitric oxide (NO) treatment resulted in much faster amelioration of oxygenation index, taken as a marker of the underlying condition. No significant difference was recorded in immediate or long-term complications. We conclude that, wherever NO facilities are not readily available, magnesium sulphate is a safe and cheaper alternative for first-line treatment of moderate persistent pulmonary hypertension of the neonate.

Development of esophageal peristalsis in preterm and term neonates.

BACKGROUND & AIMS: High-resolution manometry demonstrates a chain of 3 sequential pressure segments that represent esophageal peristalsis in children and adults. We performed high-resolution manometry in preterm and term neonates to determine the ontogenesis of esophageal motility with regard to this segmental architecture. METHODS: Sixteen preterm (gestational age 32.9 +/- 2.6 weeks at examination) and 14 term neonates (38.9 +/- 1.6 weeks) underwent manometry with a 9-lumen perfused catheter having recording side holes spaced at 1-cm intervals. Pressure responses to swallows were evaluated for the presence of peristaltic segments on isobaric contour maps by an investigator who was blinded to gestational age. RESULTS: The second segment was well developed in > or =50% of swallows in all preterm and term neonates. In contrast, the first segment was present in > or =50% of swallows in only 2 preterm neonates (12.5%) and 8 term neonates (57.1%; P < .05 for each compared with second segment) with identical findings for the third segment (12.5% preterm and 57.1% term neonates; P < .05 for each). Completed peristalses with intact segmental contraction sequences throughout the esophageal body were present in 26% +/- 6% of swallows in preterm neonates vs 55% +/- 9% in term neonates (P = .01). CONCLUSIONS: The second pressure segment in the midesophagus (proximal smooth-muscle region) is well developed before term. Presence of other segments significantly improves at term, but peristalsis remains incomplete in nearly half of swallows. Control mechanisms for both striated- and smooth-muscle esophageal regions are incompletely developed in neonates, the outcome of which could participate in infant reflux disease.

Evolution of gastric electrical features and gastric emptying in children with Duchenne and Becker muscular dystrophy.

OBJECTIVES: Although muscular dystrophy (MD) affects primarily striated muscles, smooth muscle cells of the gastrointestinal tract may also be involved. We recorded gastric electrical activity and gastric emptying time (GET) in children with MD at initial presentation and at 3-yr follow-up in order to detect gastric motor abnormalities and study their evolution along the clinical course. METHODS: Twenty children with MD (median age: 4.6 yr; range age: 3-7 yr) were investigated by means of ultrasonography, for measuring GET, and by electrogastrography (EGG); 70 children served as controls. RESULTS: Ten patients had Duchenne muscular dystrophy (DMD) and 10 Becker muscular dystrophy (BMD). GET was significantly more delayed in MD patients (DMD, median: 195 min; range 150-260 min; BMD, median: 197 min; range: 150-250 min) than in controls (median: 150 min; 110-180 min; p < 0.05); it markedly worsened at the follow-up in DMD (median: 270 min; range 170-310 min; p < 0.001 vs controls) but not in BMD patients (median: 205 min; 155-275 min; p < 0.05 vs DMD). Baseline EGG showed a significantly lower prevalence of normal rhythm and significantly higher prevalence of dysrhythmias in both groups of patients as compared to controls (% of normal rhythm: DMD 66.7 +/- 8.2, BMB 67.2 +/- 11.5, controls 85.3 +/- 7.2, p < 0.001; % of tachygastria: DMD 28.4 +/- 8.0, BMB 29.8 +/- 12.3, controls 10.6 +/- 5.1, p < 0.001; % of dominant frequency instability coefficient: DMD 36.1 +/- 6.0, BMB 33.2 +/- 2.9, controls 17.9 +/- 7.1, p < 0.001); furthermore, no difference in fed-to-fasting ratio of the dominant EGG power was found between the two groups and controls (DMD 2.84 +/- 1.27, BMB 2.82 +/- 0.98, controls 3.04 +/- 0.85, ns). However, at the follow-up no significant change in the prevalence of normal rhythm and dysrhythmias occurred in both groups (ns vs baseline values), whereas only DMD patients showed a marked reduction in fed-to-fasting power ratio (0.78 +/- 0.59; p < 0.001 vs controls and BMD; p < 0.05 vs baseline), which correlated with the progressive neuromuscular weakness occurring in DMD subjects (r, 0.75; p < 0.001). CONCLUSIONS: In children with MD, there is an early abnormality in gastric motility that is due to deranged regulatory mechanisms, whereas contractile activity of smooth muscle cells seems to be preserved. At the follow-up, DMD patients exhibited a progressive failure in neuromuscular function, which was accompanied by a gastric motility derangement with worsening in GET and in EGG features suggesting an altered function of gastric smooth muscle cells.