A porcine model of postoperative hemi-diaphragmatic paresis to evaluate a unilateral diaphragmatic pacemaker.

Unilateral phrenic nerve damage is a dreaded complication in congenital heart surgery. It has deleterious effects in neonates and children with uni-ventricular circulation. Diaphragmatic palsy, caused by phrenic nerve damage, impairs respiratory function, especially in new-borns, because their respiration depends on diaphragmatic contractions. Furthermore, Fontan patients with passive pulmonary perfusion are seriously affected by phrenic nerve injury, because diaphragmatic contraction augments pulmonary blood flow. Diaphragmatic plication is currently employed to ameliorate the negative effects of diaphragmatic palsy on pulmonary perfusion and respiratory mechanics. This procedure attenuates pulmonary compression by the abdominal contents. However, there is no contraction of the plicated diaphragm and consequently no contribution to the pulmonary blood flow. Hence, we developed a porcine model of unilateral diaphragmatic palsy in order to evaluate a diaphragmatic pacemaker. Our illustrated step-by-step description of the model generation enables others to replicate and use our model for future studies. Thereby, it might contribute to investigation and advancement of potential improvements for these patients.

The fetal gastrointestinal tract is exposed to melatonin and superoxide dismutase rich amniotic fluid throughout prenatal development.

Amniotic fluid (AF) is the first fluid to enter the gastrointestinal tract. Preterm birth is leading to a sudden interruption of AF swallowing. Understanding the composition of amniotic fluid is crucial to implement strategies preventing intestinal injury in preterm infants. We hypothesized that the fetal gastrointestinal tract (GIT) is exposed to melatonin and antioxidant enzymes via amniotic fluid throughout prenatal development. Amniotic fluid samples from 76 pregnant women with a median (range) gestational age of 38.0 (14.3-40.1) weeks have been collected. Immediately after birth blood samples were collected from the umbilical vein (n = 53). Median (Interquartile range) melatonin concentration was 30.5 pg/ml (12.7-118.3) and superoxide dismutase 1 (SOD1) concentration was 84 ng/ml (59-123). Extracellular glutathione peroxidase concentration was either not detectable or exceptionally low. We found a positive correlation between melatonin concentration in amniotic fluid and gestational age (Spearman's correlation coefficient, r = 0.570, p<0.001), while SOD1 concentration in amniotic fluid was inversely correlated with gestational age (r = -0.246, p = 0.032). Compared to serum samples, melatonin concentration was statistically significantly higher in amniotic fluid (p<0.001). Our results indicate that the fetal gastrointestinal system is continuously exposed to melatonin and SOD1 via the amniotic fluid throughout prenatal development.

Management of esophageal perforations in infants by endoscopic vacuum therapy: a single center case series.

BACKGROUND: Endoscopic vacuum therapy (EVT) has become a standard treatment method for esophageal perforations in adults. However, experience with EVT in infants is scarce. In this retrospective case series, we report on four very young infants who were successfully treated with EVT for esophageal perforations of different etiology. METHODS: Four infants were diagnosed with esophageal perforations on day 7, 32, 35 and 159 of life, respectively. The youngest one was prematurely born in the 31st week of pregnancy weighing 980 g only. Three infants had perforations due to foreign body insertion (nasogastric tube or pulling through of percutaneous endoscopic gastrostomy (PEG) tube through the esophagus). One child had an anastomotic dehiscence after Foker's surgery for atresia. In three children EVT was applied as first-line therapy for perforation, in one child EVT was a rescue therapy due to persisting leakage after surgical closure involving thoracotomy. Depending on the esophageal diameter, either an open-pore drainage film or polyurethane sponge was attached to a single-lumen 8 Fr suction catheter, endoscopically (or fluoroscopically by wire-guidance) placed into the esophagus (intraluminal EVT) and supplied with continuous negative pressure (ranging between 75 and 150 mmHg). The EVT system was exchanged twice per week. RESULTS: Complete closure of the perforation/leakage could be achieved in all four infants (100%) after 22 days of continuous EVT (median value; range 7-39) and 4.5 EVT exchanges (median value; range 1-12). No serious adverse events occurred. CONCLUSIONS: EVT is an effective and safe addition to our therapeutic armamentarium in the management of esophageal perforations irrespective of its etiology. Here we prove the feasibility of EVT even in very young infants. The use of an extra thin vacuum open-pore drainage film is helpful to cope with the small esophageal diameter. EVT settings and exchange rates similar to those known from adult treatment were used.

Neurological outcome at 24 months corrected age of prematurely born infants after preterm premature rupture of membranes (PPROM) of at least 7 days: a two-center experience in Germany.

Objective: Preterm premature rupture of membranes (PPROM) is a risk factor for chorioamnionitis (CA) and injury to the fetal brain. However, prolongation of gestation prevents morbidity and decreases complications of prematurity. The current investigation is to define risk factors for the adverse neurological outcome from the influence of PPROM of at least 7 days.Methods: A case-control study included three groups of preterm infants born at the University Hospitals Bonn and Essen, Germany. The first group consisted of infants with PPROM of at least 7 days and no chorioamnionitis (CA) (PPROM group), the second included preterm infants with CA (CA group), and the third group consisted of infants without PPROM and CA (control group). The outcome was assessed using Bayley Scales of Infant Development at a corrected age of 24 months. Each group consisted of 20 corresponding infants with an identical birth weight and gestational age at birth.Results: There was no significant difference between the mental development index (MDI) and psychomotor development index (PDI) scores (mean ± SD): the MDI score was 101 ± 14 in the PPROM group, 98 ± 12 in the CA group and 96 ± 17 in the control group; the PDI score 96 ± 10, 89 ± 16, and 90 ± 17, respectively. Multiple regression analysis revealed no significant influence of PPROM and CA on neurological outcome.Conclusions: PPROM of at least 7 days has no influence on neurodevelopmental outcome at a corrected age of 24 months when birth is initiated in the case of beginning CA.

An examination of the factors affecting intestinal wall integrity in newborns at birth.

BACKGROUND: An understanding of the factors that influence intestinal wall integrity during the transition from fetal to neonatal life is important to elucidate and minimize potential contributions to the development of intestinal pathologies in vulnerable newborns. OBJECTIVE: To assess the factors affecting intestinal wall integrity of late preterm and term newborns at birth. METHODS: The concentrations of serum intestinal fatty acid-binding protein (I-FABP) as biomarker of intestinal wall injury, superoxide dismutase (SOD), and glutathione peroxidase (Gpx) as parameters of oxidative stress, and blood gas analyses were measured in the arterial cord blood of 80 newborns, delivered by spontaneous vaginal delivery (labor group) or elective cesarean delivery (non-labor group). RESULTS: Compared with the non-labor group, I-FABP, SOD, and Gpx levels were significantly higher in the labor group. I-FABP concentration was inversely correlated with pH and BE and positively correlated with SOD and Gpx concentrations, second stage of labor duration, and active pushing time. CONCLUSIONS: This study demonstrates that oxidative stress at birth and prolonged second stage of labor may lead to the intestinal injury, which is reflected in increased serum concentration of I-FABP.

Evaluation of two commercially available ELISA kits for the determination of melatonin concentrations in amniotic fluid throughout pregnancy.

Background The aim of the present study is to evaluate the utility of extraction versus non-extraction-based commercial melatonin ELISA kits for determining the melatonin concentration in amniotic fluid obtained in early and late pregnancy. Methods Pregnancy duration less than 28 weeks was defined as early and from 28 weeks until delivery as late gestation. Nine samples were obtained in early and 18 in late pregnancy. Two commercially available melatonin ELISA kits (melatonin ELISA RE54021, including methanol-based extraction and direct saliva melatonin ELISA RE 54041, not including an extraction step, both from IBL-International, Germany) were used to determine melatonin concentrations in amniotic fluid. Results The mean melatonin concentration in ELISAs assayed by the non-extraction was significantly lower than those assayed after extraction. Subgroup analysis showed that there was no significant difference between melatonin concentration measured by non-extraction versus extraction ELISA in early pregnancy (11.2 ± 7.4 vs. 12.2 ± 7.7, respectively, P = 0.463) but that the mean melatonin concentration in late pregnancy was significantly lower when assayed by non-extraction ELISA than when assayed by extraction ELISA (14.8 ± 9.3 vs. 145.1 ± 179.3, respectively; P < 0.001). Agreement between both measurements in late pregnancy was rather poor (r2 = 0.271, P = 0.022), as opposed to the good correlation found in early pregnancy (r2 = 0.929, P < 0.001). Conclusions The present study revealed that a melatonin assay without an extraction step, such as direct saliva ELISA, does not seem to be a valid method to determine the melatonin concentration of amniotic fluid, especially in late gestation.

Melatonin Concentrations and Antioxidative Capacity of Human Breast Milk According to Gestational Age and the Time of Day.

BACKGROUND: While changes in the composition of breast milk throughout the lactation period are well known, little is known about the antioxidative capacity of breast milk and its regulation as a function of time of day. OBJECTIVE: The aim of this study was to evaluate the antioxidative capacity in breast milk and its regulation by time of day. METHODS: Melatonin, superoxide dismutase (SOD), glutathione peroxidase 3 (Gpx3) concentrations, and the total antioxidative capacity (TAOC) were analyzed in 105 breast milk samples and 12 maternal serum samples from 21 healthy nursing mothers. RESULTS: Comparison between daytime breast milk (collected from 1000-2200 h) and nighttime breast milk (collected from 2200-1000 h) revealed significantly higher concentrations of melatonin and Gpx3 in nighttime milk (melatonin: 1.5 pg/mL [1.0-2.1] day vs 7.3 pg/mL [3.8-13.6] night, median [quartiles], with an estimated mean night-to-day ratio of 5.2 [3.9, 7.1], P < .001; Gpx3: 1436 ng/mL [765-2060] day vs 1800 ng/mL [1242-2297] night, night-to-day difference 192.1 [0.6, 383.7], P = .049). Subgroup analysis showed that melatonin had a circadian rhythm in both preterm and term milk, with a significantly higher nighttime concentration ( P < .001), while antioxidant enzymes had a circadian rhythm only in preterm milk, with a significantly higher nighttime concentration for Gpx3 and a significant higher daytime concentration for SOD and TAOC ( P = .041 and P = .049, respectively). We found no significant correlation between the concentration of melatonin and the concentration of SOD, Gpx3, or TAOC. Moreover, there were no significant correlations observed between gestational age and the concentration of melatonin and antioxidant enzymes. CONCLUSION: Because of its higher melatonin and Gpx3 content, future research is needed to determine if preterm nighttime milk ought to be the first choice in the feeding of high-risk preterm infants.

More than fetal urine: enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation.

UNLABELLED: The purpose of our study was to investigate the importance of amniotic fluid (AF) for fetal growth during late gestation using esophageal atresia (EA) patients as a model. In this retrospective cohort study, we compared the z-scores adapted for birth weights (BW z-scores) for each of 517 European newborns with congenital pre-gastric intestinal atresia, i.e., EA, to a European reference population. To account for the influence of the intestinal atresia on fetal growth per se, we compared adapted birth weights for each of 504 European newborns with post colonic intestinal atresia (anorectal malformation (ARM) with atresia of the anus) to the same European reference population. Analysis of the complete cohort showed (i) a significantly higher rate of small for gestational age newborns among EA compared to ARM newborns (p < 0.001) and (ii) significantly lower BW z-scores among EA compared to ARM newborns (p < 0.001). BW z-scores of EA newborns were significantly lower in term compared to preterm newborns with an inverse correlation with gestational age (GA) (Spearman correlation coefficient, r = -0.185, p < 0.001). CONCLUSIONS: Enteral uptake of AF seems to play a pivotal role in fetal growth during late gestation. WHAT IS KNOWN: • Peak velocity of fetal weight gain occurs at 33 weeks of gestation and continues until birth. During this period, fetal growth is mainly characterized by cellular hypertrophy. • Amniotic fluid (AF) comprises large amounts of hormones and growth regulators. What is New: • A significantly higher rate of small for gestational age and lower birth weights and z-scores are observed among newborn infants with congenital pre-gastric intestinal atresia. • These findings suggest that enteral uptake of AF is a major predictor for fetal growth during late gestation.

Antioxidative status and oxidative stress in the fetal circulation at birth: the effects of time of delivery and presence of labor.

BACKGROUND: There are important physiological changes in the maternal, placental, and fetal compartments during pregnancy and labor. Increased oxidative stress has been demonstrated during labor. Melatonin has been reported to serve as an indirect antioxidant via the stimulation and induction of antioxidant enzymes as superoxide dismutase (SOD) and glutathione peroxidase (Gpx) in several tissues. AIM: : To assess whether the melatonin status, presence of labor at the time of birth and the time of delivery influence the extracellular antioxidative enzymes and DNA oxidative stress in newborns. METHODS: The extracellular antioxidative status and oxidative stress were analyzed by measuring the concentrations of the SOD3, Gpx3 and 8-hydroxydeoxyguanosine (8-OHdG) in the cord blood of 135 newborns. Newborns delivered during the day and at night and newborns delivered by spontaneous vaginal delivery (labor group) or elective caesarean section delivery (no labor group) were studied. OUTCOME MEASURES: The concentration of melatonin, SOD3, Gpx3 and 8-OHdG. RESULTS: Independent of the time of delivery, we found significantly higher melatonin, SOD3 and Gpx3 but lower 8-OHdG concentrations in the labor group than in the no labor group. We did not observe a correlation between the concentration of melatonin and SOD3, Gpx3 or 8-OHdG, or a day-night difference in SOD3, Gpx3 or 8-OHdG. CONCLUSION: Our findings suggest that oxidative stress during labor leads to an elevation of melatonin, SOD3 and Gpx3 in the fetal circulation, protecting the newborn from serious impairment, which is reflected by lower 8-OHdG levels. The melatonin status at the time of birth does not influence the extracellular SOD3 or Gpx3 concentrations.