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Abstract Background Infants with rule-out infections are responsible for the majority of empirical antibiotics treatment (EAT) in neonatal intensive care units (NICUs), particularly very preterm infants (VPIs). Antibiotic overuse has been linked to adverse outcomes. There is a paucity of data on the association between EAT and clinical outcomes (containing the nutritional outcomes) of VPIs without infection-related morbidities. Methods Clinical data of VPIs admitted in 28 hospitals in 20 provinces of China from September 2019 to December 2020 were collected. EAT of VPIs was calculated as the number of days with initial usage in the first week after birth, and then categorized into 3 groups (antibiotic exposure: none, 1-4 days, and > 4 days). Clinical characteristics, nutritional status , and the short-term clinical outcomes among 3 groups were compared and analyzed. Results In total, 1834 VPIs without infection-related morbidities in the first postnatal week were enrolled, including 152 cases (8.3%) without antibiotics, 374 cases (20.4%) with EAT ≤4 days and 1308 cases (71.3%) with EAT > 4 days. After adjusting for the confounding variables, longer duration of EAT was associated with decreased weight growth velocity and increased duration of reach of full enteral feeding in EAT > 4 days group (aβ: -4.83, 95% CI: − 6.12 ~ − 3.53; aβ: 2.77, 95% CI: 0.25 ~ 5.87, respectively) than those receiving no antibiotics. In addition, the risk of feeding intolerance (FI) in EAT > 4 days group was 4 times higher than that in non-antibiotic group (aOR: 4.14, 95%CI: 1.49 ~ 13.56) and 1.8 times higher than that in EAT ≤4 days group (aOR: 1.82, 95%CI: 1.08 ~ 3.17). EAT > 4 days was also a risk factor for greater than or equal to stage 2 necrotizing enterocolitis (NEC) than those who did not receive antibiotics (aOR: 7.68, 95%CI: 1.14 ~ 54.75) and those who received EAT ≤4 days antibiotics (aOR: 5.42, 95%CI: 1.94 ~ 14.80). Conclusions The EAT rate among uninfected VPIs was high in Chinese NICUs. Prolonged antibiotic exposure was associated with decreased weight growth velocity, longer duration of reach of full enteral feeding, increased risk of feeding intolerance and NEC ≥ stage 2. Future stewardship interventions to reduce EAT use should be designed and implemented.

IntroductionAntenatal corticosteroids (ACS) administration is a standardized prenatal care for accelerating fetal maturation before anticipated preterm delivery, however, its effect on nutrition and growth is yet uncertain. This study aimed to examine if ACS application is associated with improvement in postnatal growth and nutrition in very preterm infants (VPIs).MethodsThis was a secondary analysis of a multicenter prospective survey included infants born before 32 weeks gestation and admitted to 28 tertiary neonatal intensive care units throughout China from September 2019 to December 2020. Infants were divided into no ACS, partial ACS and complete ACS groups according to the steroids exposure. For infants exposed to antenatal corticosteroids, complete ACS was defined as receiving all doses of steroids 24 h-7 days before delivery, otherwise it was referred to partial ACS. The primary outcomes of postnatal growth were compared among the 3 groups. The multivariable regression analyses were applied to evaluate the association of different steroids coverage with postnatal growth and nutritional outcomes while adjusting for potential confounders. For each outcome, no ACS coverage was defined as the reference group. Data were presented as unstandardized coefficients or adjusted odds ratios with 95% confidence intervals, P

The gut microbiota plays a key role in the pathogenesis of diseases affecting preterm infants and gestational age is one of the important factors which affect the gut microbiota of infants. To determine the characteristics of the gut microbiota in preterm infants of different gestational ages from birth to 1 year after birth, we collected 622 fecal samples from neonates of different gestational ages at different time points after birth. According to the gestational ages, the samples were divided into four groups, extremely preterm, very preterm, moderate to late preterm, and term group. Meconium and fecal samples at day 14, 28, 120, and 365 after birth were collected. 16S rRNA sequencing was performed and the composition and structure of the gut microbiota in preterm infants of different gestational age was compared with that of term infants. In our study, alpha diversity of meconium in extremely preterm group was higher than very preterm group, moderate to late preterm group and term group and alpha diversity of meconium in preterm group was decreased with increasing of gestational age. At day 14 to day 120 after birth, alpha diversity of term and moderate to late preterm group were significantly higher than other two preterm groups. However, moderate to late preterm group owned the highest alpha diversity which was higher than term group at day 365 after birth. Besides, the results shown the duration of opportunistic pathogen such as Klebsiella and Enterococcus which dominant colonization was different in different gestational age groups. As well as the probiotics, such as Bifidobacterium, which abundance enriched at different time point in different gestational age groups. We profiled the features of dynamic changes of gut microbiome from different gestational ages infants. The results of our research provide new insights for individualized interventions of specific microbes of preterm infants with different gestational ages at different time points after birth.

Background and AimsThis study aimed to detect breast milk sialic acid (SA) content and the changing pattern, to understand the various stages of breastfeeding SA secretion, and the influence factors of the human milk SA content.MethodsWe recruited mothers and their infants as our subjects. At days 7, 14, 30, 120, and 365 after delivery, the contents of SA in breast milk were collected and detected through Fluorescence Detector-High Performance Liquid Chromatography. The participants completed the baseline questionnaire at ≤day 7 and were followed up at days 30, 120, and 365.ResultsA total of 95 mothers with 122 infants were included in the analysis, including 22 mothers with 22 term infants, 25 mothers with 35 late preterm infants, 31 mothers with 39 very preterm infants, and 17 mothers with 26 extremely preterm infants. Similar to previous findings, the results of the study showed that, compared with breast milk of term mothers at the same period, breast milk of preterm mothers contained more SA at each time node, and the content of SA in breast milk increased with decreasing gestational weeks. Moreover, maternal age, pre-pregnancy BMI, and delivery mode had significant effects on total SA in breast milk, especially for the preterm infant breast milk. Significant negative associations occurred between SA contents and infant growth status, especially in preterm infants.ConclusionsWe have confirmed the previous observations showing that with the prolongation of lactation time, the content of SA in breast milk gradually decreased, and the content of SA in the breast milk of preterm mothers was higher than that of term mothers. In addition, SA content was associated with maternal age, pre-pregnancy BMI, and delivery mode.

AimTo investigate the use of human milk fortifier (HMF) for very preterm infants (VPIs) and complications and nutritional status of VPIs due to various breast milk enhancement strategies among the Chinese population.MethodsVPIs with birth weight < 1,800 g and wholly or predominantly breastfed were assigned to the following fortification groups: no HMF, early HMF (adding HMF at an enteral volume of ≤ 80 ml·kg−1·day−1), middle HMF (adding HMF at an enteral volume of 80–100 ml·kg−1·day−1), and late HMF (adding HMF at an enteral volume of ≥100 ml·kg−1·day−1). The growth status and complications for various groups were evaluated.ResultsWe enrolled 985 VPIs, of which 847 VPIs (86.0%) received HMF, whereas 138 VPIs (14.0%) did not. The number of VPIs in the early, middle, and late fortification groups were 89 (9.0%), 252 (25.6%), and 506 (51.4%), respectively. The complete fortification of the early, middle, and late fortification groups was achieved in 13.2 ± 11.0, 13.8 ± 11.7, and 12.3 ± 13.0 days, respectively, without significant differences (p > 0.05). The groups did not exhibit significant differences in the incidence of feeding intolerance, necrotizing enterocolitis (Bell stage ≥ 2), late-onset sepsis, and metabolic bone diseases (p > 0.05). The middle fortification groups exhibited the fastest growth velocity and the least dramatic decrease in the Z-score of weight and length, and the lowest incidence of EUGR (35.7%), whereas the “no HMF” groups exhibited the slowest growth velocity and the largest decline in the Z-score, and the highest incidence of EUGR (61.6%).ConclusionsThe usage rate of HMF was relatively low among Chinese VPIs, fortification often occurred in the late feeding stage, and the time to reach complete fortification was long. Adding HMF and different breast milk enhancement strategies did not increase the incidence of feeding intolerance and necrotizing enterocolitis. The enteral volume of 80–100 ml·kg−1·day−1 with HMF addition led to increased growth in the weight and length and lower EUGR incidence, indicating that the addition of HMF at the specific feeding volume might be the best practice for promoting growth.

Background: Extremely low birth weight (ELBW, 500 IU/L, P ≥4.5 mg/dL), and severe (ALP >500 IU/L, P 4 weeks after birth) according to the time of onset.Results: A total of 142 ELBW infants were included, with a median gestational age of 28.1 (26.5–29.7) weeks and a median birth weight of 875 (818–950) g. Seventy-three cases of MBD were diagnosed, and the total prevalence was 51.4% (mild MBD, 10.6%; and severe MBD, 40.8%). Male sex, breastfeeding, and sepsis would increase the risk of severe MBD. Most MBD in ELBW infants occurred at 3–4 weeks after birth. Sixty-two percent (45/73) of infants were diagnosed as having early MBD, which are diagnosed earlier than late MBD [24 (21–26) vs. 39 (36–41), t = −7.161; P < 0.001]. Male sex [odds ratio (OR), 2.86; 95% confidence interval (CI), 1.07–7.64; P = 0.036], initial high ALP levels (OR, 1.02; 95% CI, 1.01–1.03; P < 0.001), and breastfeeding (OR, 5.97; 95% CI, 1.01–25.12; P = 0.049) are independent risk factors for the development of early MBD.Conclusion: The risk of MBD among ELBW infants is very high. Most cases occurred early and were severe. Male sex, initial high ALP levels, and breastfeeding are closely related to the increased risk of early MBD. Serial screening of serum ALP and P helps early detection of MBD; it is recommended to start biochemical screening for ELBW infants 2 weeks after birth and monitor their biochemical markers weekly.

Microbial colonization of very preterm (VPT) infants is detrimentally affected by the complex interplay of physiological, dietary, medical, and environmental factors. The aim of this study was to evaluate the effects of an infant formula containing the specific prebiotic mixture of scGOS/lcFOS (9:1) and glycomacropeptide (GMP) on the composition and function of VPT infants’ gut microbiota. Metagenomic analysis was performed on the gut microbiota of VPT infants sampled at four time points: 24 h before the trial and 7, 14, and 28 days after the trial. Functional profiling was aggregated into gut and brain modules (GBMs) and gut metabolic modules (GMMs) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Enterococcus faecium, Escherichia coli, Klebsiella aerogenes, and Klebsiella pneumoniae were dominant species in both the test group and the control group. After the 4-week intervention, the abundance of Bifidobacterium in the test group was significantly increased. We found two GBMs (quinolinic acid synthesis and kynurenine degradation) and four GMMs (glutamine degradation, glyoxylate bypass, dissimilatory nitrate reduction, and preparatory phase of glycolysis) were significantly enriched in the test group, respectively. The results of this study suggested that formula enriched with scGOS/lcFOS (9:1) and GPM is beneficial to the intestinal microecology of VPT infants.

Dielectric decrement means that the dielectric constant declines with the increase in the ionic concentration of the system, and it is found that, in the dilute solution, the law of the dielectric decrement is linear. However, the dielectric decrement law is unknown when the concentration of the solution is very high, and the current nonlinear fitting formula about the law of dielectric decrement is only correct in the cases of low or not very high concentrations. However, in the case of extremely high concentrations, its prediction is zero and is obviously unreasonable or incorrect. Therefore, a new expression should be and has been proposed to describe the relation between the dielectric constant and the concentration in this paper. In addition, the numerical calculations show that almost the same results can be obtained by the new and previous formulas when the concentration is not very high, but unlike the previous ones, the dielectric constant predicted by the new formula will tend to be fixed and greater than the zero value in the case of extremely high concentrations.

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Background. Feeding intolerance (FI) is a common complication that may cause great harm to preterm infants. The mechanism of FI remains unclear, but probiotics may help prevent and alleviate its symptoms. We hypothesized that the alteration in gut microbiota may be associated with the development of FI. Our study aimed to investigate the association between gut microbiota and FI in preterm infants. Methods. Ninety-seven preterm infants were divided into the FI group (N=42) and the feeding tolerance (FT) group (N=55) depending on whether the infants were diagnosed with FI. The fecal samples of each infant were collected on the 7th day after birth. Fecal microbiota was analyzed by 16S rRNA sequencing. Plasma motilin were detected on day-1, 7, 14, and 21. Results. The microbial diversity of the FI group was significantly lower than that of the FT group. The abundance levels of phylum Proteobacteria, class Gammaproteobacteria, genera such as Escherichia/Shigella were higher in the FI group than in the FT group. The abundance levels of phylum Firmicutes, class Negativicutes, and genus Veillonella were higher in the FT group than in the FI group. The motilin levels on days 7 and 14 were negatively correlated with the FI-enriched genera Planomicrobium and Vibrio, respectively. Our study also found gut microbiota was correlated with FI clinical characteristics, including gestational age, birth weight, age of FI diagnosis, age of FI disappearance, and FI duration. Conclusions. Altered gut microbiota is associated with FI in preterm infants. FI cases typically have lower microbial diversity, a decreased abundance of beneficial bacteria, and an increased abundance of pathogenic bacteria. Gut microbiota is correlated with the clinical characteristics of FI. The decrease in motilin secretion caused by some bacteria may lead to the occurrence of FI. [ABSTRACT FROM AUTHOR]