Background Adequate intake of choline is essential for growth and homeostasis, but its supply does often not meet requirements. Choline deficiency decreases phosphatidylcholine (PC) and betaine synthesis, resulting in organ pathology, especially of liver, lung, and brain. This is of particular clinical importance in preterm infants and cystic fibrosis patients. We compared four different choline supplements for their impact on plasma concentration and kinetics of choline, betaine as a methyl donor and trimethylamine oxide (TMAO) as a marker of bacterial degradation prior to absorption. Methods Prospective randomized cross-over study (1/2020–4/2020) in six healthy adult men. Participants received a single dose of 550 mg/d choline equivalent in the form of choline chloride, choline bitartrate, α-glycerophosphocholine (GPC), and egg-PC in randomized sequence at least 1 week apart. Blood was taken from t = − 0.1–6 h after supplement intake. Choline, betaine, TMAO, and total PC concentrations were analyzed by tandem mass spectrometry. Results are shown as medians and interquartile range. Results There was no difference in the AUC of choline plasma concentrations after intake of the different supplements. Individual plasma kinetics of choline and betaine differed and concentrations peaked latest for PC (at ≈3 h). All supplements similarly increased plasma betaine. All water-soluble supplements rapidly increased TMAO, whereas egg-PC did not. Conclusion All supplements tested rapidly increased choline and betaine levels to a similar extent, with egg-PC showing the latest peak. Assuming that TMAO may have undesirable effects, egg-PC might be best suited for choline supplementation in adults. Study registration This study was registered at “Deutsches Register Klinischer Studien” (DRKS) (German Register for Clinical Studies), 17.01.2020, DRKS00020454.
Background Enemas are used in preterm infants to promote meconium evacuation, but frequent high-volume enemas might contribute to focal intestinal perforation (FIP). To replace a regime consisting of frequent enemas of varying volume and composition, we implemented a once-daily, low-volume lipid enema (LE) regimen. We investigated its impact on meconium evacuation, enteral nutrition, and gastrointestinal complications in preterm infants. Methods We performed a single-center retrospective study comparing cohorts of preterm infants < 28 weeks gestation or < 32 weeks, but with birth weight < 10th percentile, before and after implementing LE. Outcomes were rates of FIP, necrotizing enterocolitis (NEC), and sepsis. We assessed stooling patterns, early enteral and parenteral nutrition. We used descriptive statistics for group comparisons and logistic regression to identify associations between LE and gastrointestinal complications and to adjust for group imbalances and potential confounders. Exclusion criteria were gastrointestinal malformations or pre-determined palliative care. Results Data from 399 infants were analyzed, 203 before vs. 190 after implementing LE; in the latter period, 55 protocol deviations occurred where infants received no enema, resulting in 3 groups with either variable enemas, LE or no enema use. Rates of FIP and sepsis were 11.9% vs. 6.4% vs. 0.0% and 18.4% vs. 13.5% vs. 14.0%, respectively. NEC rates were 3.0% vs. 7.8% vs. 3.5%. Adjusted for confounders, LE had no effect on FIP risk (aOR 1.1; 95%CI 0.5–2.8; p = 0.80), but was associated with an increased risk of NEC (aOR 2.9; 95%CI 1.0–8.6; p = 0.048). While fewer enemas were applied in the LE group resulting in a prolonged meconium passage, no changes in early enteral and parenteral nutrition were observed. We identified indomethacin administration and formula feeding as additional risk factors for FIP and NEC, respectively (aOR 3.5; 95%CI 1.5–8.3; p < 0.01 and aOR 3.4; 95%CI 1.2–9.3; p = 0.02). Conclusion Implementing LE had no clinically significant impact on meconium evacuation, early enteral or parenteral nutrition. FIP and sepsis rates remained unaffected. Other changes in clinical practice, like a reduced use of indomethacin, possibly affected FIP rates in our cohorts. The association between LE and NEC found here argues against further adoption of this practice. Trial registration Registered at the German Register of Clinical Trials (no. DRKS00024021; Feb 022021).
Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.
Germinal matrix intraventricular hemorrhage (IVH) remains a severe and common complication in preterm infants. A neonatal care bundle (NCB) was implemented as an in-house guideline at a tertiary neonatal intensive care unit to reduce the incidence of IVH in preterm infants. The NCB was applied either to preterm infants <1250 g birth weight or <30 weeks gestational age or both, and standardized patient positioning, nursing care, and medical procedures within the first week of life. A retrospective cohort study was performed to investigate the effect of the NCB and other known risk factors on the occurrence and severity of IVH. Data from 229 preterm infants were analyzed. The rate of IVH was 26.2% before and 27.1% after implementing the NCB. The NCB was associated neither with reducing the overall rate of IVH (odds ratio (OR) 1.02; 95% confidence interval (CI) 0.57–1.84; p = 0.94) nor with severe IVH (OR 1.0; 95% CI 0.67-1.55; p = 0.92). After adjustment for group differences and other influencing factors, amnion infection syndrome and early intubation were associated with an increased risk for IVH. An NCB focusing on patient positioning, nursing care, and medical interventions had no impact on IVH in preterm infants. Known risk factors for IVH were confirmed.
Background Sepsis is one of the most important complications in preterm infants. For this reason, most preterm infants receive antibiotics during their first postnatal week. Since 2013, a weekly colonization screening has been installed in German neonatal intensive care units (NICUs), including multi-drug resistant organisms (MDRO) and pathogens with increased epidemic potential. We here investigated the impact of early antibiotic exposure on the colonization with these pathogens. Methods Data from 1407 preterm infants with gestational age < 32 + 0 weeks and born in three NICUs in Germany between January 2014 and December 2019 were analysed. Results Antibiotics were administered to 911/1407 (64.7%) participating infants during their first postnatal week. Screening-targeted pathogens were detected in 547/1407 (38.9%). Early antibiotic exposure did not increase the risk of colonization with screening-targeted pathogens. The only independent risk factor for colonisation with potential pathogens was the admitting hospital. Interestingly, longer antibiotic therapy (> 7 days) decreased the risk for acquiring pathogens with increased epidemic potential. Conclusion Early antibiotic exposure did not impact the risk for colonization with MDRO or highly epidemic pathogens in preterm infants. Further studies are needed to identify risk factors for the acquisition of MDRO and highly epidemic pathogens and potential associations with long-term outcome.
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