High Versus Low Medium Chain Triglyceride Content of Formula for Promoting Short-Term Growth of Preterm Infants

BACKGROUND: In-hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering. For preterm infants who cannot be fed maternal or donor breast milk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs) or long chain triglycerides (LCTs) may be chosen to support nutrient utilization and to improve growth. MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervous system development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant\u27s short-term growth remain unclear. This is an update of a review originally published in 2002, then in 2007. OBJECTIVES: To determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included all randomized and quasi-randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short-term growth of preterm (\u3c 37 weeks\u27 gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition. DATA COLLECTION AND ANALYSIS: The review authors assessed each study\u27s quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We identified 10 eligible trials (253 infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, or blinding. We found no evidence of differences in short-term growth parameters when high and low MCT formulas were compared. As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of -0.21 g/kg/d (95% confidence interval (CI) -1.24 to 0.83; 6 studies, 118 infants; low-certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d (95% CI -5.93 to 5.93; 1 study, 18 infants; very low-certainty evidence), finding an average weight gain of 20 ± 5.9 versus 20 ± 6.9 g/d for high and low MCT groups, respectively. We found that length gain showed no difference between low and high MCT formulas, with a typical MD of 0.10 cm/week (95% CI -0.09 to 0.29; 3 studies, 61 infants; very low-certainty evidence). Head circumference gain also showed little to no difference during the intervention period, with an MD of -0.04 cm/week (95% CI -0.17 to 0.09; 3 studies, 61 infants; low-certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference (2 studies, 32 infants; very low-certainty evidence). There are conflicting data (5 studies) as to formula tolerance, with 4 studies reporting narrative results of no observed clinical difference and 1 study reporting higher incidence of signs of gastrointestinal intolerance in high MCT formula groups. There is no evidence of effect on the incidence of necrotizing enterocolitis (NEC), based on small numbers in two trials. Review authors found no studies addressing long-term growth parameters or neurodevelopmental outcomes. AUTHORS\u27 CONCLUSIONS: We found evidence of very low to low certainty suggesting no differences among short-term growth data for infants fed low versus high MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short-term growth outcomes or have fewer adverse effects. Further studies are necessary because the results from included studies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence

Predicting Maintenance of Any Breastfeeding from Exclusive Breastfeeding Duration: A Replication Study

OBJECTIVES: To predict the duration of any breastfeeding using the duration of exclusive breastfeeding in a socioeconomically heterogeneous sample of mothers using receiver operator characteristic (ROC) analysis. STUDY DESIGN: The Mother Baby Health Survey, a birth certificate-linked cross-sectional survey was sent at 4-5 months postpartum to a stratified random sample of socioeconomically and racially diverse women in upstate New York; 797 mothers who initiated exclusive breastfeeding were included in this study. Split-sample validation was employed; eligible subjects were divided into training or test samples at random (80% and 20%, respectively). ROC curves were constructed using the training sample and optimal exclusive breastfeeding duration thresholds were tested using the remaining test sample. Logistic regression using the training sample provided estimates of the predictive ability (sensitivity, specificity, positive predictive value) of thresholds in both unadjusted and adjusted analyses (covariates: age, education, parity, marital status, and race). RESULTS: The ROC analysis in this sample demonstrated that 9 weeks of exclusivity was required for maintenance of breastfeeding at 3 months, and 14.9 weeks of exclusivity was required for maintenance at 20 weeks. Unadjusted and adjusted models yielded similar results; women who exclusively breastfed for at least 9 weeks had 2.2 times the risk (95% CI 1.7-2.8) of maintaining any breastfeeding at 3 months. CONCLUSIONS: These results are similar to our previous results, from a less diverse cohort, and support that these thresholds may be useful in clinical settings for helping mothers achieve breastfeeding duration goals

Preterm infant gut microbial patterns related to the development of necrotizing enterocolitis

<p><b>Objectives:</b> To define gut microbial patterns in preterm infants with and without necrotizing enterocolitis (NEC) and to characterize clinical factors related to the composition of the preterm intestinal microbiome.</p> <p><b>Methods:</b> Fecal samples were collected at one-week intervals from infants with gestational ages <30 weeks at a single level IV neonatal intensive care unit. Using 16S rRNA gene sequencing, the composition and diversity of microbiota were determined in samples collected from five NEC infants and five matched controls. Hierarchical linear regression was used to identify clinical factors related to microbial diversity and specific bacterial signatures.</p> <p><b>Results:</b> Low levels of diversity were demonstrated in samples obtained from all preterm infants and antibiotic exposure further decreased diversity among both NEC cases and controls. Fecal microbial composition differed between NEC cases and controls, with a greater abundance of <i>Proteobacteria</i> and bacteria belonging to the class <i>Gammaproteobacteria</i> among NEC infants. Control infants demonstrated a greater abundance of bacteria belonging to the phylum <i>Firmicutes</i>.</p> <p><b>Conclusion:</b> These findings indicate that an association exists between intestinal <i>Proteobacteria</i> and NEC, and strengthens the notion that an overly exuberant response to Gram-negative products, particularly lipopolysaccharide, in the preterm intestine is involved in NEC pathogenesis. Cumulative exposure to antibiotics corresponded to a reduction in microbial diversity in both NEC cases and controls.</p