Probiotic supplementation modifies the gut microbiota profile of very low birth weight preterm infants during hospitalization.

BACKGROUND: Probiotic supplementation is increasingly being given to very low birth weight (VLBW) preterm infants. This preliminary observational study aimed to investigate the effects of multiple-strain probiotics on the gut microbiota of VLBW preterm infants. METHODS: We collected meconium and stool samples on days 14, 30, and 60 after birth from 49 VLBW infants with a gestational age of <32 weeks. The infants were divided into the probiotics (n = 24) and control (n = 25) groups. The microbial composition and diversity in the gut of the two groups were analyzed using 16 S rRNA gene sequencing. RESULTS: The relative abundance of Bifidobacterium and Lactobacillus was significantly higher in the probiotics group than in the control group on days 14, 30, and 60 (Bifidobacterium: p = 0.002, p < 0.0001, and p < 0.0001, respectively; Lactobacillus: p = 0.012, p < 0.0001, and p < 0.0001, respectively). The control group exhibited a significantly higher proportion of participants with a low abundance (<1%) of Bifidobacterium or Lactobacillus on days 14, 30, and 60 than those in the probiotic group. Moreover, the probiotics group exhibited a significantly lower abundance of Klebsiella on days 14 and 30 (2.4% vs. 11.6%, p = 0.037; and 7.9% vs. 16.6%, p = 0.032, respectively) and of Escherichia-Shigella on day 60 than the control group (6.1% vs. 12.3%, p = 0.013). Beta diversity analysis revealed that the microbiota profile was clearly divided into two groups on days 30 and 60 (p = 0.001). CONCLUSION: Probiotic supplementation significantly increased the relative abundance of Bifidobacterium and Lactobacillus and inhibited the growth of potential pathogens. Furthermore, probiotic supplementation led to a distinct gut microbiota profile. Further research is needed to identify probiotic strains that exert significant influence on the gut microbiome and their long-term health implications in preterm infants.

Association of mode of delivery with short-term and neurodevelopmental outcomes in periviable singleton infants: A nationwide database study.

OBJECTIVE: To evaluate the association of mode of delivery (MOD) with short-term and neurodevelopmental outcomes at 2 years of corrected age (CA) in periviable singleton infants. METHODS: This retrospective cohort study of the Taiwan Premature Infant Follow-up Network database between 2010 and 2016 compared non-anomalous singleton deliveries (cesarean delivery [CD] vs vaginal delivery [VD]) between 22 0/7 and 25 6/7 gestational weeks. Major morbidities, mortality, and neurodevelopmental outcomes were evaluated at 2-year CA. RESULTS: The CD and VD groups included 354 and 472 infants, respectively. The intraventricular hemorrhage (IVH) rate was lower in the CD group (54% vs 66%, P = 0.001), but severe IVH differed non-significantly between groups (20% vs 26%, P = 0.057). In the small-for-gestational age subgroup, CD was associated with lower IVH (56% vs 84%, adjusted odds ratio [aOR] 0.17, 95% confidence interval [CI] 0.04-0.69) and better survival without neurodevelopmental impairment (29% vs 8%, aOR, 6.64, 95% CI 1.02-43.29) after controlling for potential confounders. CONCLUSION: The optimal MOD for periviable singleton birth and its impact are unclear. CD in periviable singleton births is associated with a decreased IVH risk, without improvement in severe IVH, mortality, or neurodevelopment at 2-year CA. The small-for-gestational age subgroup may benefit from CD for better survival without neurodevelopmental impairment.

Genome-Wide Sequencing Modalities for Children with Unexplained Global Developmental Delay and Intellectual Disabilities-A Narrative Review.

Unexplained global developmental delay (GDD) and intellectual disabilities (ID) together affect nearly 2% of the pediatric population. Establishing an etiologic diagnosis is crucial for disease management, prognostic evaluation, and provision of physical and psychological support for both the patient and the family. Advancements in genome sequencing have allowed rapid accumulation of gene-disorder associations and have accelerated the search for an etiologic diagnosis for unexplained GDD/ID. We reviewed recent studies that utilized genome-wide analysis technologies, and we discussed their diagnostic yield, strengths, and limitations. Overall, exome sequencing (ES) and genome sequencing (GS) outperformed chromosomal microarrays and targeted panel sequencing. GS provides coverage for both ES and chromosomal microarray regions, providing the maximal diagnostic potential, and the cost of ES and reanalysis of ES-negative results is currently still lower than that of GS alone. Therefore, singleton or trio ES is the more cost-effective option for the initial investigation of individuals with GDD/ID in clinical practice compared to a staged approach or GS alone. Based on these updated evidence, we proposed an evaluation algorithm with ES as the first-tier evaluation for unexplained GDD/ID.

Effects of erythropoietin in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Minimizing multiple organ dysfunction-related mortality and morbidity is a critical issue for patients with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH). Although erythropoietin (EPO) has demonstrated protective effects on various hypoxic-ischemic organs in animal studies and clinical trials in adults, its effects on neonates with HIE require further investigation. METHODS: This study retrospectively analyzed the medical records of neonates with HIE who received TH with or without EPO (TH+EPO vs TH groups) administration in a tertiary referral hospital from January 2016 to January 2021. Data regarding patient characteristics, medical treatment, and clinical (neurological, cardiac, respiratory, gastrointestinal, hepatic, and renal) function assessments were collected. To control for confounding factors and selection bias between the two groups, a 1:1 propensity matching method was applied. RESULTS: A total of 45 neonates with HIE received TH during the study period, with 24 patients (53%) in the TH+EPO group. After matching, each group enrolled 13 cases. No significant difference in mortality or hospital stay between the two groups was noted. During the first 3 days, the patients in the TH+EPO group showed significantly higher blood pressure (BP) than those in the TH group ( p < 0.05 on day 1). The TH+EPO group showed trends of higher blood hemoglobin ( p > 0.05) and creatinine ( p > 0.05) levels and lower estimated glomerular filtration rate ( p > 0.05) and urine output ( p > 0.05) during the first 2 weeks than TH group. CONCLUSION: The use of EPO in addition to TH is safe for neonates with HIE. The neonates with moderate or severe HIE who received EPO may have a lesser risk of hypotension than those who received TH alone. Further clinical studies on renal and cardiac functions and long-term neurological effects of EPO are required.

Characteristics of Gut Microbiota in Small for Gestational Age Infants with Very Low Birth Weight.

Small for gestational age (SGA) birth is associated with high rates of mortality and morbidity in preterm infants. The aim of this preliminary observational study was to investigate the difference in gut microbiota between SGA and appropriate for gestational age (AGA) preterm infants with very low birth weight (VLBW). We included 20 VLBW preterm infants (SGA, n = 10; AGA, n = 10) in this study. Stool samples were collected on days 7, 14, and 30 after birth. We performed 16S ribosomal DNA sequencing to compare microbiota composition between both groups. The SGA group exhibited a lower abundance of Klebsiella on day 14 (SGA, 0.57%; AGA, 7.42%; p = 0.037). On day 30, the SGA group exhibited a lower abundance of Klebsiella (SGA 3.76% vs. AGA 16.05%; p = 0.07) and Enterobacter (SGA 5.09% vs. AGA 27.25%; p = 0.011) than the AGA group. Beta diversity demonstrated a separation of the bacterial community structure between both groups on day 30 (p = 0.019). The present study revealed that a distinct gut microbiota profile gradually develops in SGA preterm infants with VLBW during the early days of life. The role of changes in gut microbiota structure warrants further investigation.

Subclinical Changes in Left Heart Structure and Function at Preschool Age in Very Low Birth Weight Preterm Infants.

Background: Survivors of preterm birth are at risk of long-term cardiovascular consequences. The objective of this prospective observational study was to assess left heart function at preschool age in preterm children with very low birth weight (VLBW). Methods: We recruited children aged 5-6 years from preterm infants and full-term children. All subjects underwent conventional echocardiography and speckle-tracking echocardiography. The results were compared between the preterm and term groups. Results: Eighty-seven VLBW preterm children and 29 term controls were included in the study. After adjusting for body surface area, the preterm group compared to the full-term group had significantly smaller left ventricular (LV) end-diastolic and end-systolic internal dimensions (31.2 vs. 33.5 mm, p = 0.048; and 20.0 vs. 21.6 mm, respectively; p = 0.024), lower LV end-diastolic and end-systolic volumes (38.8 vs. 46.3 mL, p = 0.024; and 12.8 vs. 15.6 mL, respectively; p = 0.008). Left atrial (LA) maximal and minimal volume were also significantly smaller in the preterm group (15.4 vs. 18.9 mL, p = 0.017; and 6.2 vs 7.5 mL, respectively; p = 0.018). LV global longitudinal strain (-21.4 vs. -23.2%, p < 0.0001) and systolic strain rate (-1.30 vs. -1.37 /s, p = 0.001) were significantly lower in the preterm group than in the term control group. LA longitudinal strain was decreased (43.9 vs. 52.8%, p < 0.0001) and left atrial stiffness index (0.17 vs. 0.14, p < 0.0001) was increased in preterm infants. However, all the measurements in both groups were within normal range. Conclusions: Subclinical changes of left heart structure and function were found in VLBW infants at preschool age. Additional long-term follow-ups of the cardiovascular outcomes are needed in this vulnerable population.

An 18-year retrospective study on the epidemiology of early-onset neonatal sepsis - emergence of uncommon pathogens.

BACKGROUND: Nationwide group B Streptococcus agalactiae (GBS) antepartum screening was instituted in Taiwan in 2012. The impact of the policy on early-onset sepsis (EOS) has not been evaluated. This study aimed to examine the impact of the policy on the incidence of neonatal EOS. METHODS: This was a retrospective study conducted at MacKay Children's Hospital. Patients with culture-proven neonatal EOS were enrolled and divided by birth year in relation to the implementation of GBS prevention policy: Epoch 1, 2001-2004 pre-GBS screening; Epoch 2, 2005-2011 elective GBS screening; and Epoch 3, 2012-2018 universal GBS screening. The pathogens and antimicrobial resistance patterns were reviewed and analyzed. The incidence was modeled using Poisson regression. RESULTS: A total of 128 neonates met the enrollment criteria. The observed incidence of EOS was 1.52‰. The incidence rates of EOS, GBS, and Escherichia coli (E. coli) sepsis were similar in Epoch 1 and Epoch 3. E. coli and non-Enterococcal group D Streptococcus (GDS) infection increased significantly in term infants, whereas the EOS-related mortality rate declined in preterm infants. Approximately 72% of the isolated E. coli were ampicillin-resistant, and the antimicrobial sensitivity remained unaltered during the studied period. CONCLUSIONS: The overall EOS incidence has not changed from 2001 to 2018. However, changes in the causative pathogens were observed in both term and preterm infants. Clinicians should be aware of this evolving epidemiology to provide prompt appropriate perinatal management.

Impact of Early Empiric Antibiotic Regimens on the Gut Microbiota in Very Low Birth Weight Preterm Infants: An Observational Study.

Frequent use of antibiotics in preterm infants disturbs their gut microbial balance. In this preliminary observational study, we investigated the effect of different antibiotic regimens, administered during the first week of life, on microbial composition and diversity in very low birth weight (VLBW) preterm infants. We performed fecal sampling of breastfed VLBW infants on days 7, 14, and 30. After excluding stool samples from infants who received probiotics or who were administered antibiotics beyond the age of 7 days, we compared gut microbiota profiles between infants receiving a combination of ampicillin and gentamicin for 3 days (AG group, n = 10) and those receiving a combination of ampicillin and cefotaxime for 7 days (AC group, n = 14) using 16S ribosomal DNA community profiling. We also assessed the changes over time in each group. Compared to the AG group, Enterococcus species were significantly more abundant in the AC group (P = 0.002), especially in 7-day samples (12.3 vs. 0.6%, respectively, P = 0.032). No difference was observed at phylum and genus level over time within each group. Species richness in the AC group decreased significantly in the 14-day (P = 0.038) and 30-day (P = 0.03) samples compared to that in the 7-day sample. The same was observed for microbial evenness; in contrast, no significant difference in Shannon index and beta-diversity was detected between the two groups. Controlling for relevant confounding variables did not change the results. In conclusion, different antibiotic regimens affect the early development of gut microbiota in VLBW preterm infants. Prolonged use of ampicillin and cefotaxime might result in overabundance of Enterococcus. However, given that no significant differences were observed in 1-month samples, bacterial genera appear to continue colonizing the gastrointestinal tract despite previous exposure to antibiotics. The clinical relevance of these findings should be elucidated by further studies.

Comparisons and Refinements of Neonatal Oro-Tracheal Intubation Length Estimation Methods in Taiwanese Neonates.

Objective: This study aimed to evaluate the efficacy of Tochen's formula [TF, body weight (kg) plus 6 cm], nasal septum to ear tragus length (NTL) + 1 cm, and Neonatal Resuscitation Program gestational age (NRP-GA) and body weight (NRP-BW)-based intubation table in estimating the oro-tracheal intubation length, and to improve the estimation efficacy using anthropometric measurements in Taiwanese neonates. Study design: This was a prospective observational study conducted at a neonatal intensive care unit in Taipei, Taiwan. One hundred intubated neonates were enrolled. The estimated intubation depth was defined as being mid-tracheal concordant if it placed the endotracheal tip between the upper border of the first and the lower border of the second thoracic vertebra. A linear regression model was used to analyze the relationships between mid-tracheal depth and body weight (BW), NTL and gestational age (GA), and to revise the NRP intubation tables using our results. Results: Overall, 56% of the neonates were born at a GA ≤ 28 weeks and 48% had a BW ≤ 1,000 g. The overall mid-tracheal concordance rates for TF, NTL + 1 cm, NRP-GA, and NRP-BW estimations were 51.0, 57.0, 15.0, and 14.0%, and in the infants with a BW ≤ 1,000 g 56.3, 56.3, 8.3, and 8.3%, respectively. Our revisions of the NRP intubation tables based on the anthropometric measurements of our participants improved the efficacy of BW, GA, and NTL estimations to 63, 44, and 61%, respectively. Conclusion: TF and NTL + 1 cm were more reliable than NRP intubation tables in predicting the neonatal mid-tracheal length in neonates of all BW and GA. Considering morphological differences secondary to ethnicity, we recommend using these tailored recommendations during neonatal resuscitation in Asian neonates.