Plasma D-lactate Levels in Necrotizing Enterocolitis in Premature Infants

Background: D-Lactate is normally present in the blood of humans at nanomolar concentrations due to methylglyoxal metabolism; millimolar D-lactate concentrations can arise due to excess gastrointestinal microbial production. Objectives: To examine the levels of plasma D-lactate in the necrotizing enterocolitis in premature infants. Patients and Methods: 128 premature infants were divided into control (group I, n = 69), feeding intolerance (group II, n = 42) and NEC (group III, n = 27) groups. Plasma D-lactate levels were measured at the onset of feeding intolerance or NEC and at weeks 2-3 in control infants (group I) by ELISA. Data were analyzed using descriptive statistics, non-parametric tests and Student’s t-test. Results: In groups I, II, III, median birth weights were 1845.7 ± 267.5 g, 1913.1 ± 306.5 g, and 1898.4 ± 285.3 g, median gestational ages were 34.3 ± 1.7 weeks, 33.9 ± 2.2 weeks and 35.1 ± 2.6 weeks, ages of sampling were 12.3 ± 2.9 days, 14.6 ± 3.7 days and 15.1 ± 1.8 days, respectively. The differences of median birth weights, median gestational ages and ages of sampling were not statistically significant (P > 0.05). The plasma D-lactate levels in groups I, II, III were 3.6 ± 1.9 μg/mL, 12.7 ± 8.3 μg/mL, and 35.4 ± 29.1 μg/mL, respectively, group III had higher plasma D-lactate level than groups I, II, and the difference among these groups was significant (x2 = 21.6, P < 0.01). Conclusions: Plasma D-lactate significantly increased early in NEC. Plasma D-lactate levels were associated with extensive disease in NEC infants. Therefore, it could be used as a diagnosis indicator in the early stage of NEC.

Necrotizing enterocolitis, pathogenesis and the protector effect of prenatal corticosteroids

Necrotizing enterocolitis is the most frequently occurring gastrointestinal disorder in premature neonates. Animal models of necrotizing enterocolitis and prenatal administration of cortisone have demonstrated that cortisone may accelerate maturation of the mucosal barrier, therefore reducing the incidence of this gastrointestinal disorder. The authors present a review of the literature of the most important risk factors associated with necrotizing enterocolitis, such as inflammatory gastrointestinal mediators, enteral feeding and bacterial colonization, and immaturity of the gastrointestinal barrier, and we emphasize the necessity for additional studies to explore the prenatal administration of cortisone as a preventive strategy for necrotizing enterocolitis.

Concomitant involvement of the small intestine and the distal esophagus in an infant with massive necrotizing enterocolitis

Necrotizing enterocolitis is a disease of the newborn that may involve the small intestine and/or the colon, and the stomach. To our knowledge, massive necrosis of the small intestine with concomitant involvement of the esophagus has never been reported. A case of a 6-month-old boy with necrotizing enterocolitis and pan-necrosis of the small intestine, cecum, and the lower third of the esophagus is presented. After 70 days of treatment, intestinal transit was established by an anastomosis between the first centimeter of jejunum and the ascending colon. Finally, esophageal transit was established by a total gastric transposition with cervical esophagogastric anastomosis. The patient was maintained under total parenteral nutrition, and after 19 months he developed fulminant hepatic failure due to parenteral nutrition; he then underwent combined liver and small bowel transplantation. After 2 months, the patient died due to undefined neurologic complications, probably related to infection or immunosuppressive therapy.

Placental vascular obstructive lesions: risk factor for developing necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a severe neonatal disease affecting particularly preterm infants. Its exact pathogenesis still remains unknown. In this study, we have compared the prevalence of vascular obstructive lesions in placentae of premature newborns which developed NEC and of a control group. We further compared separately the findings of placentae of infants of less than 30 weeks of gestation, the age group in which NEC occurs most frequently. We found signs of fetal vascular obstructive lesions in 65% of the placentae of preterm patients developing NEC, compared to only 17% of the placentae of preterm patients in the control group. In the age groups below 30 weeks of gestation, 58.5% of placentae of later NEC patients presented such lesions compared to 24.5% in the control group. The significant difference between NEC and control group suggests a strong association between fetal vascular obstructive lesions and NEC. Therefore, we propose that fetal vascular obstructive lesions might be considered as a risk factor for the development of NEC in premature infants.

16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

OBJECTIVE:: Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. DESIGN:: Descriptive case report. SETTING:: Genetic department and neonatal intensive care unit of a tertiary care children's hospital. INTERVENTIONS:: None. PATIENT:: We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. MEASUREMENTS AND MAIN RESULTS:: An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. CONCLUSIONS:: Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

A simple presurgical necrotizing enterocolitis-mortality scoring system

OBJECTIVE: To assess the relationship between early laboratory parameters, disease severity, type of management (surgical or conservative) and outcome in necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective collection and analysis of data from infants treated in a single tertiary care center (1980 to 2002). Data were collected on disease severity (Bell stage), birth weight (BW), gestational age (GA) and pre-intervention laboratory parameters (leukocyte and platelet counts, hemoglobin, lactate, C-reactive protein). RESULTS: Data from 128 infants were sufficient for analysis. Factors significantly associated with survival were Bell stage (P<0.05), lactate (P<0.05), BW and GA (P<0.01, P<0.001, respectively). From receiver operating characteristics curves, the highest predictive value resulted from a score with 0 to 8 points combining BW, Bell stage, lactate and platelet count (P<0.001). At a cutoff level of 4.5 sensitivity and specificity for predicting survival were 0.71 and 0.72, respectively. CONCLUSION: Some single parameters were associated with poor outcome in NEC. Optimal risk stratification was achieved by combining several parameters in a score.

Is there a correlation between venlafaxine therapy during pregnancy and a higher incidence of necrotizing enterocolitis?

BACKGROUND: Novel antidepressant drugs are increasingly used by women of child bearing age. However, potentially harmful effects on fetus and newborn remain unknown. METHODS: Case report and literature review. RESULTS: We present preterm twins whose mother was treated with venlafaxine, a nonselective serotonin reuptake inhibitor, throughout pregnancy until delivery. The twins developed neonatal necrotizing enterocolitis. CONCLUSION: The question whether there might be a correlation between maternal serotonin reuptake inhibitor therapy and neonatal necrotizing enterocolitis is discussed.

Cardio-pulmonary interaction in premature newborn with nasal continuous positive airways pressure (n-CPAP) respiratory assistance evaluated with echocardiography

Introduction: Nasal continuous positive airways pressure (n-CPAP) is an effective treatment in premature infants with respiratory distress. The cardio-pulmonary interactions secondary to n-CPAP are well studied in adults, but less well described in premature infants. We postulated that there could be important interactions with regard to the patent ductus arteriosus (PDA). Methods: Prospective study, approved by the local ethic committee. Premature infants less than 32 weeks gestation, _7 days-old, needing n-CPAP for respiratory distress, but without the need of additional oxygen were included in the study. Every patient had a first echocardiography with n-CPAP and then n-CPAP was retrieved. 3 hours later the echocardiography was repeated by the same investigator and then the patient replaced on n-CPAP. Results: 14 premature newborn were included, mean gestational age of 28 _ 2 weeks, mean weight 1.1 _ 0.3 Kg and height 39 _ 3 cm. Echocardiographic measurements are depicted in Table 1. Significant finding were observed between measurement on n- CPAP or without n-CPAP: on end diastolic left ventricular diameter (12.8 _ 1.6 mm vs. 13.5 _ 2 mm), on end systolic left ventricular diameter (8.4 _ 1.3 mm vs. 9.1 _ 1.5 mm), left atrium diameter (8.9 _ 2.2 mm vs. 10.4 _ 2.5 mm), maximal velocity on tricuspid valve (46 _ 10 cm/s vs. 51 _ 9 cm/s), calculated Qp (3.7 _ 0.8 L/min/m2 vs. 4.3 _ 0.8 L/min/m2). Only three patients have demonstrated a PDA during the study. Conclusion: Positive end expiratory pressure (Peep) has hemodynamic effects which are: reduction of systemic and pulmonary venous return as shown by the changes on tricuspid valve inflow,on the calculated Qp and finally on the diameter of the left atrium and left ventricle.We found in premature infants the same hemodynamic effects than those described in adults but with lower Peep values. This could be due to the particular elasticity and weakness of the thoracic wall of premature infants. Interestingly the flow through a PDA seems also to be diminished with Peep, but the number of patients is insufficient to conclude. Further investigation will be needed to better understand these interactions. Table 1. Echocardiographic measurement (mean (SD)). With n-CPAP Without n-CPAP p value RV ED diameter (mm) 6.3 (1.7) 6.04 (1.1) NS LV ED diameter (mm) 12.8 (1.6) 13.5 (2.0) _0.05 LV ES diameter (mm) 8.4 (1.3) 9.1 (1.5) _0.05 SF (%) 34 (5) 33 (6) NS Ao valve diameter (mm) 7.4 (1.3) 7.4 (1.2) NS LA diameter (mm) 8.9 (2.2) 10.4 (2.5) _0.05 Vmax Ao (cm/s) 70 (16) 71 (18) NS Vmax PV (cm/s) 69 (15) 72 (16) NS Vmax TV (cm/s) 46 (10) 51 (9) _0.05 Vmax MV (cm/s) 53 (17) 54 (18) NS Qp (L/min/m2) 3.7 (0.8) 4.3 (0.8) _0.05 Qs (L/min/m2) 4.0 (0.8) 4.0 (0.7) NS Qp/Qs 0.92 (0.14) 1.09 (0.23) _0.05 RV: right ventricle, LV: left ventricle, ED: end diastolic, ES: end systolic, SF: shortening fraction,Ao: aortic valve, LA: left atrium,Vmax: maximum Doppler Velocity, Qp: pulmonary output, Qs: systemic output, NS: non significant.

Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with formula.

BACKGROUND/AIMS: Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1). METHODS: In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4-5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 x 10(8)/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. RESULTS: At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. CONCLUSIONS: Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

A meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates

Necrotizing enterocolitis (NEC) is one of the most common acquired diseases of the gastrointestinal tract in preterm infants. Some randomized, controlled trials (RCTs) have indicated that probiotics may potentially lower the incidence of NEC and mortality. However, debate still remains about the safety of probiotics and their influence on normal infant growth. We performed this meta-analysis to assess the safety and benefits of probiotic supplementation in preterm infants. We searched in PubMed, Embase, and Cochrane databases for English references, and in Wanfang, VIP, and CNKI databases for Chinese references. Ultimately, 27 RCTs (including 9 Chinese articles) were incorporated into this meta-analysis. Relative risk (RR) and weighted mean difference (WMD) were calculated using a random-effects or fixed-effects model, depending on the data type and heterogeneity. A total of 6655 preterm infants, including the probiotic group (n=3298) and the placebo group (n=3357), were eligible for inclusion in this meta-analysis. For Bell stage ≥I and gestational age <37 weeks, risk of NEC incidence was significantly lower in the probiotic group [RR=0.35, 95% confidence interval (CI)=0.27-0.44, P<0.00001]. For Bell stage ≥II or gestational age <34 weeks, there were likewise significant differences between the probiotic and placebo groups concerning NEC incidence (RR=0.34, 95%CI=0.25-0.48, P<0.00001; and RR=0.39, 95%CI=0.27-0.56, P<0.00001). Risk of death was significantly reduced in the probiotic group (RR=0.58, 95%CI=0.46-0.75, P<0.0001). In contrast, there was no significant difference concerning the risk of sepsis (RR=0.94, 95%CI=0.83-1.06, P=0.31). With respect to weight gain and the age at which infants reached full feeds, no significant differences were found between the probiotic and placebo groups (WMD=1.07, 95%CI=−0.21-2.34, P=0.10; and WMD=−1.66, 95%CI=−3.6-0.27, P=0.09). This meta-analysis has shown that, regardless of gestational age and NEC stage, probiotic supplementation could significantly reduce the risk of NEC in preterm infants. Analysis also indicated that such supplementation did not increase the incidence risk of sepsis or of mortality. Finally, the study showed that probiotic supplementation may have no adverse effect on normal feeding and growth.

Étude critique de la densité électronique et des températures (excitation et ionisation) d'un plasma d'aluminium induit par laser

La caractérisation de matériaux par spectroscopie optique d’émission d’un plasma induit par laser (LIPS) suscite un intérêt qui ne va que s’amplifiant, et dont les applications se multiplient. L’objectif de ce mémoire est de vérifier l’influence du choix des raies spectrales sur certaines mesures du plasma, soit la densité électronique et la température d’excitation des atomes neutres et ionisés une fois, ainsi que la température d’ionisation. Nos mesures sont intégrées spatialement et résolues temporellement, ce qui est typique des conditions opératoires du LIPS, et nous avons utilisé pour nos travaux des cibles binaires d’aluminium contenant des éléments à l’état de trace (Al-Fe et Al-Mg). Premièrement, nous avons mesuré la densité électronique à l’aide de l’élargissement Stark de raies de plusieurs espèces (Al II, Fe II, Mg II, Fe I, Mg I, Halpha). Nous avons observé que les densités absolues avaient un comportement temporel différent en fonction de l’espèce. Les raies ioniques donnent des densités électroniques systématiquement plus élevées (jusqu’à 50 % à 200 ns après l’allumage du plasma), et décroissent plus rapidement que les densités issues des raies neutres. Par ailleurs, les densités obtenues par les éléments traces Fe et Mg sont moindres que les densités obtenues par l’observation de la raie communément utilisée Al II à 281,618 nm. Nous avons parallèlement étudié la densité électronique déterminée à l’aide de la raie de l’hydrogène Halpha, et la densité électronique ainsi obtenue a un comportement temporel similaire à celle obtenue par la raie Al II à 281,618 nm. Les deux espèces partagent probablement la même distribution spatiale à l’intérieur du plasma. Finalement, nous avons mesuré la température d’excitation du fer (neutre et ionisé, à l’état de trace dans nos cibles), ainsi que la température d’ionisation, à l’aide de diagrammes de Boltzmann et de Saha-Boltzmann, respectivement. À l’instar de travaux antérieurs (Barthélémy et al., 2005), il nous est apparu que les différentes températures convergeaient vers une température unique (considérant nos incertitudes) après 2-3 microsecondes. Les différentes températures mesurées de 0 à 2 microsecondes ne se recoupent pas, ce qui pourrait s’expliquer soit par un écart à l’équilibre thermodynamique local, soit en considérant un plasma inhomogène où la distribution des éléments dans la plume n’est pas similaire d’un élément à l’autre, les espèces énergétiques se retrouvant au cœur du plasma, plus chaud, alors que les espèces de moindre énergie se retrouvant principalement en périphérie.