Effect of SMOF lipid emulsion on physical growth and extrauterine growth retardation in very preterm infants: Insights from a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to investigate the effects of soybean, medium-chain triacylglycerols (MCTs), olive oil, and fish oil (SMOF) on short-term clinical outcomes, physical growth, and extrauterine growth retardation (EUGR) in very preterm infants. METHODS: This was a multicenter retrospective cohort study of very preterm infants hospitalized in neonatal intensive care units at five tertiary hospitals in China between January 2021 and December 2021. According to the type of fat emulsion used in parenteral nutrition (PN), eligible very preterm infants were divided into the MCTs/long-chain triacylglycerol (MCT/LCT) group and SMOF group. Change in weight z-score (weight Δz) between measurements at birth and at 36 wk of postmenstrual age or at discharge, the incidence of EUGR, and short-term clinical outcomes between the two groups were compared and analyzed. RESULTS: We enrolled 409 very preterm infants, including 205 in the MCT/LCT group and 204 in the SMOF group. Univariate analysis showed that infants in the SMOF group had significantly longer duration of invasive mechanical ventilation and PN, longer days to reach total enteral nutrition, and a higher proportion of maximum weight loss than those in MCT/LCT group (all P < 0.05). After adjusting for the confounding variables, multifactorial logistic regression analysis of short-term clinical outcomes showed that SMOF had protective effects on PN-associated cholestasis (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.266-0.831) and metabolic bone disease of prematurity (OR, 0.263; 95% CI, 0.078-0.880). Additionally, SMOF was an independent risk factor for lower weight growth velocity (ß = -0.733; 95% CI, -1.452 to -0.015) but had no effect on the incidence of EUGR (OR, 1.567; 95% CI, 0.912 to -2.693). CONCLUSION: Compared with MCT/LCT, SMOF can reduce the risk for PN-associated cholestasis and metabolic bone disease of prematurity in very preterm infants and has a negative effect on growth velocity but has no effect on the incidence of EUGR.

Osteopenia of prematurity and associated nutritional factors: case-control study.

BACKGROUND: Preterm newborn nutrition affects postnatal skeletal growth and bone mineralization, but studies have not yet fully concluded the relationship between nutrition and osteopenia. This study was intended to investigate the impact of nutritional factors on osteopenia in preterm newborns. METHODS: This is a case-control study with babies born with gestational age ≤ 32 weeks in a high-risk maternity hospital, between 2018 and 2019. The population consisted of 115 newborns, being 46 cases (40%) and 69 controls (60%). Disease outcome was based on serum alkaline phosphatase levels > 900UL/l and hypophosphatemia < 4 mg/dl. Gestational data at birth and clinical and nutritional follow-up data during 8 weeks postnatally were assessed. Variables were assessed using regressive logistic models. FINDINGS: Preterm infants who were fed pasteurized fresh human milk with acidity ≥ 4 ºDornic are 5.36 times more likely to develop osteopenia (p = 0.035). Higher calcium intake, compared to controls, also increased the probability of disease occurrence [OR 1.05 (CI 1.006-1.1); p = 0.025], while the presence of a partner [OR 0.10 (CI 0.02-0.59); p = 0.038] and the shortest time using sedatives [OR 0.89 (CI 0.83-0.98); p = 0.010] were protective factors associated with osteopenia. Extremely low birth weight [OR 5.49 (CI 1.20-25.1); p = 0.028], sepsis [OR 5.71 (CI 1.35-24.2); p = 0.018] and invasive ventilatory support [OR 1.09 (CI 1.03-1.18); p = 0.007] were risk factors. CONCLUSIONS: Acidity and high calcium intake are the main nutritional factors associated with osteopenia of prematurity. Further studies on the use of human milk with lower acidity, recommendation and nutritional supplementation of calcium should be accomplished to guide prevention strategies in newborns at risk for osteopenia during hospital stay.

Postdischarge Iron Status in Very Preterm Infants Receiving Prophylactic Iron Supplementation after Birth.

OBJECTIVE: To determine postdischarge iron status and associated factors in very preterm infants. STUDY DESIGN: A retrospective cohort study was conducted through a provincial database on all very preterm infants born in Nova Scotia between 2005 and 2018. As a standard of care, all infants received prophylactic iron supplements starting at 2-4 weeks of chronological age and were tested for iron deficiency at 4 or 6 months corrected age. Iron deficiency was defined as serum ferritin <20 g/L at 4 months or <12 g/L at 6 months. Multivariate logistic regression analysis identified factors associated with iron deficiency. RESULTS: Among 411 infants, 132 (32.1%) had iron deficiency and 11 (2.7%) had iron deficiency anemia. The prevalence of iron deficiency decreased over time, from 37.6% in 2005-2011 to 25.8% in 2012-2018. Gestational hypertension in the mother (P = .01) and gestational age <27 weeks (P = .02) were independent risk factors for iron deficiency. In addition, the odds of iron deficiency were lower in the mixed-fed group (ie, with breast milk and formula combined) compared with the exclusive formula-fed group (P = .01). CONCLUSIONS: Iron deficiency was prevalent in 32% of the very preterm infants despite early iron prophylaxis. These results demonstrate the importance of monitoring iron stores during preterm follow-up. Information about risk factors is important to mitigate iron deficiency in very preterm infants.

Early vs late initiation of sodium glycerophosphate: Impact on hypophosphatemia in preterm infants <32 weeks.

BACKGROUND & AIMS: Early electrolyte and mineral imbalances have emerged as a conspicuous problem in very preterm babies since the revision of nutrition guidelines and the eventual implementation of early aggressive parenteral nutrition (PN). We opted to carry out a study with the introduction of phosphorus as sodium glycerophosphate in PN from the first day onward to reveal the impact on serum phosphorus and calcium levels following the surge in the incidence of hypercalcemia and hypophosphatemia. METHODS: In this single-center, prospective, observational cohort study, inborn babies <32 gestational weeks and <1500 g between August 2017 and July 2018 were enrolled consecutively. Infants born in the first 6-month of this period were initiated PN (Early phosphorus group) containing phosphorus (1 mmol P as sodium glycerophosphate/100 ml PN) immediately after birth, and in the latter six-months, mineral-free standard PN (Control group) was commenced up until 48 h of life. Parenteral nutritional prescriptions of both groups were similar in terms of macro and micronutrient intakes except for early phosphorus, calcium, and sodium. Serum mineral and electrolyte levels were measured on Days 1-3-7 and compared between the groups. The primary outcome was the presence of hypophosphatemia in the first week of life. The secondary outcome was hypercalcemia, preterm morbidity, and mortality. RESULTS: A total of 261 infants were included in this study. There were 130 babies in Early phosphorus group and 131 in control group. Gestational ages (28.79 ± 2.1 vs 28.46 ± 2.2 weeks, respectively) and birth weights (1138 ± 273 vs 1090 ± 274 g, respectively) were similar in the groups. Mean serum phosphorus levels were higher on all days in Early phosphorus group (p < 0.001). Early phosphorus group had a lower incidence of hypophosphatemia on days 1-3 and 7 (p < 0.001). The percentage of hypercalcemic infants was significantly lower in Early phosphorus group on day 3 (p < 0.001). No difference was noted in terms of hypernatremia in the groups. CONCLUSIONS: Adding phosphorus to PN in the first hours of life reduced the frequency of hypophosphatemia and hypercalcemia without any surge in hypernatremia or morbidity. Nutrition guidelines need to be revised accordingly in terms of early mineral/electrolyte supplementation.

Assessment of morbidity and mortality in newborns with late prematurity: experience of a reference maternity in the northeast of Brazil.

BACKGROUND: Late preterm infants show high rates of adverse perinatal outcomes. The aim of this study is to assess the morbidity and mortality of newborns (NBs) with late preterm birth in a reference maternity hospital in northeastern Brazil. METHODS: Retrospective cohort study from March 1st to July 15th, 2017. A total of 204 NBs with gestational age between 34 and 36 weeks and six days were evaluated and compared to 205 full-term NBs (39 and 40 weeks and six days). Perinatal outcomes including neonatal morbidity were evaluated. The Student's t and ANOVA tests were used for normal variables, and the Wilcoxon, Mann-Whitney and Kruskal-Wallis tests for non-normal variables. RESULTS: Late preterm infants showed significant higher rates of hypothermia, hypoglycemia, respiratory distress syndrome, jaundice in need of phototherapy (67.6%), admission to the neonatal intensive care unit (ICU), and difficulty breastfeeding compared to full-term NBs (P<0.001). Respiratory distress was the main indication for the admission of late preterm infants (P<0.001) to neonatal ICU. Late preterm infants had a longer hospital stay (6.9 vs. 3.7 days, P<0.001). There were three deaths in the group of late preterm NBs, and none in the group of term NBs. CONCLUSIONS: Late preterm NBs presented higher rates of morbidity and mortality when compared to full-term NBs.

Vitamin D Status and Factors Associated with Vitamin D Deficiency during the First Year of Life in Preterm Infants.

We aimed to investigate the changes in vitamin D levels and factors associated with vitamin D deficiency (VDD) during the first year of life in Korean preterm infants. We enrolled 333 preterm infants who were born at Kyungpook National University Children's Hospital between March 2013 and December 2019. 25-hydroxyvitamin D (25-OHD) levels and medical records were collected at birth, 6 months, and 12 months of age. The mean gestational age was 33.4 ± 2.3 weeks and mean 25-OHD levels at birth were 18.2 ± 13.5 ng/mL. The incidence of VDD was 82.8%, 30.6%, and 27.0% at birth, 6 months, and 12 months, respectively. The incidence of severe VDD (25-OHD < 10 ng/mL) was 31.5%, 1.5%, and 0%, at birth, 6 months, and 12 months, respectively. Among infants with severe VDD, the deficiency persisted in 49.6% at 6 months, and 35.3% at 12 months. The strongest predictor of VDD during follow-up was 25-OHD concentration at birth. Vitamin D supplementation at 400 IU/day did not affect vitamin D levels during the first year of life. Therefore, it is important to prevent neonatal VDD through maternal vitamin D supplementation during pregnancy. Further research is needed to determine the optimal vitamin D supplementation dose for Korean preterm infants.

The incidence of osteopenia of prematurity in preterm infants without phosphate supplementation: A prospective, observational study.

ABSTRACT: To meet their requirements for bone mineralization, it is recommended that preterm infants receive nutritional support containing calcium and phosphate. There are no clear data on the incidence of osteopenia of prematurity (OFP) in preterm infants without phosphate supplementation.This study aimed to investigate the incidence of OFP in preterm infants without phosphate supplementation and its relationship with the duration of parenteral nutrition (PN).This was a prospective and observational study.This study included 30 infants aged <32 gestational weeks and weighed <1500 g at birth. All infants received PN according to a standard protocol, beginning on day 1 with calcium, without phosphate. Starting from the first day of life, all infants received human milk without fortifiers. Oral vitamin D (400 IU/d) was administered when enteral nutrition reached 100 mL/kg/d.The diagnosis of OFP was based on radiographs that were taken of both wrists. Serum alkaline phosphatase (ALP) was measured 3 times: at the start of PN (ALP 1), at the end of PN (ALP 2), and at discharge or the expected due date (ALP 3). Radiographs were obtained on the same day as ALP 3. The duration of PN was analyzed in the presence of OFP using receiver operating characteristic curve analysis.Among the 30 infants, 13 (43%) were diagnosed with OFP. The duration of PN was significantly longer in the OFP group than in the group without OFP (16 vs 12 days; P < .05). The provision of PN for >15 days significantly increased the risk of OFP (odds ratio, 5.40; 95% confidence interval, 1.12-26.04; P = .035).We found a high incidence of OFP in preterm infants without phosphate supplementation. An association was found between the duration of PN and the incidence of OFP. Further research is needed to prevent the development of osteopenia in preterm infants.

Oropharyngeal colostrum therapy reduces the incidence of ventilator-associated pneumonia in very low birth weight infants: a systematic review and meta-analysis.

BACKGROUND: Oropharyngeal colostrum (OC) is a novel feeding strategy to prevent complications of prematurity. A meta-analysis was conducted to investigate whether very low birth weight infants (VLBWs) can benefit from OC. METHODS: Randomized controlled trials (RCTs) were searched from Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials from the date of inception until May 2019. RCTs were eligible if they used OC therapy on VLBW infants. The primary outcomes included ventilator-associated pneumonia (VAP), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late-onset sepsis, and death. The secondary outcomes included the time of full enteral feeding and the length of stay. RESULTS: Eight RCTs involving 682 patients (OC group: 332; non-OC group: 350) were included in the meta-analysis. The results suggested that OC was associated with a significantly reduced incidence of VAP [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.17-0.88, P = 0.02] and full enteral feeding days (mean difference = -2.66, 95% CI: -4.51 to -0.80, P = 0.005), a potential significance of NEC (OR = 0.51, 95% CI: 0.26-0.99, P = 0.05), a trend toward downregulating mortality (OR = 0.60, 95% CI: 0.34-1.08, P = 0.09) and proven sepsis (OR = 0.64, 95% CI: 0.40-1.01, P = 0.06). CONCLUSIONS: OC could significantly reduce the occurrence of VAP, and consequently, its routine use should be considered for VLBWs to prevent infectious diseases. IMPACT: OC significantly reduces the occurrence of VAP and NEC in VLBW infants. OC may reduce the incidence of VAP and NEC by increasing IgA levels. Early OC therapy for mechanical ventilation of low-weight infants may prevent the occurrence of VAP.

Thyroid function in preterm infants and neurodevelopment at 2 years.

OBJECTIVES: Postnatal thyroid dysfunction is common in preterm infants but the relationship between mild dysfunction and neurodevelopment is unclear. Our aim is to describe the relationship between thyroid function and neurodevelopment. DESIGN: Cohort analysis. PATIENTS: 1275 infants born under 31 weeks' gestation; there were no exclusion criteria. SETTING: The infants were part of a UK daily iodine supplementation trial. MAIN OUTCOMES: Thyroid-stimulating hormone, thyroid-binding globulin and total thyroxine levels were measured in dried blood spots on postnatal days 7, 14, 28 and the equivalent of 34 weeks' gestation. Neurodevelopment was measured using the Bayley-III Scales of infant development at 2 years of age. RESULTS: No infant was identified as hypothyroid through routine screening. The 3% of infants consistently in the top decile of gestationally age-adjusted thyroid-stimulating hormone levels had a reduction in cognitive score of 7 Bayley units when compared with those not in the top decile (95% CI -13 to -1). A reduction in motor composite score of 6 units (95% CI -12 to <-0.1) and fine motor score of 1 unit (95% CI -2 to -0.1) was also identified. The 0.7% of infants consistently in the bottom decile of age-adjusted thyroxine levels had a reduction in motor composite score of 14 units (95% CI -25 to -2) and its two subset scores, fine and gross motor, of 2 units (95% CI respectively -4.5 to <-0.1 and -4.3 to -0.3). CONCLUSIONS: Preterm infants with consistent 'mild' thyroid dysfunction score less on neurodevelopmental tests at 2 years of age. Many of these infants will not be detected by current clinical protocols or screening programmes.

Necrotizing Enterocolitis Reduction Using an Exclusive Human-Milk Diet and Probiotic Supplementation in Infants With 1000-1499 Gram Birth Weight.

BACKGROUND: Necrotizing enterocolitis (NEC) is a major complication confronting clinicians caring for premature infants. This investigation compares clinical outcomes before and after quality improvement-program interventions in a population of premature infants at intermediate risk for NEC. METHODS: This study is a retrospective single-center chart review of infants admitted with a birth weight of 1000-1499 g, excluding major congenital anomalies, over a 6-year period, beginning with implementation of a donor breast-milk program when mother's own milk was not available. Infants were separated into 2 epochs, before (July 2012-December 2013) and after (April 2014-June 2018) introduction of human milk-derived fortifier (Prolacta) and a daily probiotic (FloraBABY) supplement. RESULTS: Comparing 140 preintervention infants with 265 postintervention infants, NEC was significantly lower in the postintervention group: 5.2% vs 1.1% (P = 0.046). Somatic growth was similar in both epochs. CONCLUSIONS: Quality-improvement initiatives utilizing an exclusive human-milk diet and daily probiotic supplementation were associated with a decreased incidence of NEC in infants with a birth weight of 1000-1499 g. Implementation of the NEC reduction bundle did not affect infant growth.

Multi-component lipid emulsion vs soy-based lipid emulsion for very low birth weight preterm neonates: A pre-post comparative study.

OBJECTIVE: To examine the effectiveness of soybean oil-medium chain triglycerides-olive oil-fish oil lipid emulsion (SMOF-LE) on clinical outcomes of very-low-birth-weight neonates. STUDY DESIGN: We conducted a pre-post comparative study of very-low-birth-weight neonates, dividing them according to lipid emulsion received: Intralipid (soy-based; n = 680) or SMOF-LE (n = 617). Primary outcomes were mortality, chronic lung disease, severe retinopathy, infection, and necrotising enterocolitis. Secondary outcomes were cholestasis, osteopenia, time to full feeds, and time to regain birthweight. RESULTS: Baseline characteristics between groups were comparable. Primary outcomes did not differ significantly between groups, although any retinopathy was significantly lower in the SMOF-LE group. SMOF-LE group had lower odds of cholestasis, osteopenia, and lipid interruption, and reduced times to full feeds and to regain birthweight. CONCLUSIONS: Compared with Intralipid, SMOF-LE was not associated with differences in mortality and major morbidities but was associated with lower odds of any retinopathy, cholestasis, and osteopenia; and improved lipid tolerance.

Fungal Ecology in a Tertiary Neonatal Intensive Care Unit after 16 Years of Routine Fluconazole Prophylaxis: No Emergence of Native Fluconazole-Resistant Strains.

OBJECTIVE: We analyzed the fungal ecology of a neonatal intensive care unit (NICU) over a period of 20 consecutive years following the introduction of routine fluconazole prophylaxis for all very low birth weight (VLBW; <1,500 g at birth) preterm babies. The aim was to detect the possible appearance of any ecological shifts toward the emergence of native fluconazole-resistant (NFR) fungal species. STUDY DESIGN: This was a retrospective analysis of clinical and microbiological data of VLBW preterm neonates admitted to a large tertiary NICU in Italy from 1997 to 2016 and surviving more than 3 days. Colonization and infection incidence rates, both for fluconazole-sensitive Candida spp and NFR Candida spp, were calculated for each year. We compared the first 4-year period without prophylaxis (1997-2000) with the last 16-year period with use of routine fluconazole prophylaxis (2000-2016). RESULTS: Overall, the incidence of fungal colonization significantly decreased after the introduction of prophylaxis (from 43.4% to 16.5%) as well as the systemic fungal infection incidence (from 16% to 3.7%). The proportion of colonization and infection by NFR Candida spp, on the other hand, did not increase, remaining stable throughout the 16 years of exposure to fluconazole. During the prophylaxis period, 42 of 1,172 VLBW neonates were colonized by NFR species (3.6%), and of them 11 developed a systemic infection (0.9%). During the preprophylaxis period, colonization by these particular species affected 11 of 285 VLBW neonates (3.8%), and a systemic infection involved 4 neonates (1.4%). CONCLUSION: Fluconazole prophylaxis is effective in decreasing Candida colonization and systemic infections in preterm neonates in NICU and did not cause emergence or shifts toward NFR Candida spp over a 16-year surveillance period.

Oropharyngeal Colostrum for Preterm Infants: A Systematic Review and Meta-Analysis.

Administration of oropharyngeal colostrum (OPC) is safe, feasible, and potentially beneficial in preterm infants. We aimed to assess the effects of OPC in preterm infants. A systematic review of randomized controlled trials (RCTs) and non-RCTs of OPC administration in preterm infants was conducted. We searched MEDLINE via PubMed and Ovid, EMBASE, the Cochrane Central Register of Controlled Trials, Emcare databases, abstracts of Pediatric Academic Societies meetings, and gray literature in April 2018. Six RCTs (n = 269) and 4 non-RCTs (n = 737) were included. One RCT (n = 40) focused on enteral bovine colostrum and hence was excluded from our review. Five of the 6 RCTs had unclear risk of bias in many domains of assessment. Meta-analysis (random effects model) of RCT data showed no significant difference in ≥stage 2 necrotizing enterocolitis (RR: 0.83; 95% CI: 0.39, 1.75; P = 0.62), late-onset sepsis (RR: 0.78; 95% CI: 0.50, 1.22; P = 0.28), all-cause mortality (RR: 0.74; 95% CI: 0.27, 2.06; P = 0.56); duration of hospital stay (mean difference [MD]: -1.65 d; 95% CI: -10.09, 6.80; P = 0.70), and time to full feeds (MD: -2.86 d; 95% CI: -6.49, 0.77; P = 0.12). Meta-analysis of data from non-RCTs also showed no benefit for any of these outcomes. OPC increased secretory IgA and lactoferrin concentrations (4 RCTs), and had only a transient effect on the oral microbiome (1 RCT). There were no adverse effects (e.g., aspiration) of OPC. The overall quality of evidence (Grades of Recommendation, Assessment, Development, and Evaluation analysis) was very low. Adequately powered RCTs are needed to confirm the nutritional and immunomodulatory benefits of OPC in preterm infants.

Effects of two different lipid emulsions on antioxidant status, lipid peroxidation and parenteral nutrition- related cholestasis in premature babies, a randomized-controlled study.

BACKGROUND: Olive oil-soybean oil (OO/SO) based lipid emulsions (LE) lack ω-3 PUFAs eicosapentaenoic acid -EPA and docosahexaenoic acid- DHA, which have clinical benefits on inflammatory processes. Fish oil based LEs are good sources of DHA and EPA. Fish oil, MCT, Olive oil and Soya oil (FMOS) lipid is one of the fish oil containing LEs supplemented with high levels of α-tocopherol and lower levels of phytosterol compared to OO/SO lipid emulsions. We investigated the effects of OO/SO and FMOS lipid preparations on cholestasis, levels of antioxidant enzymes and lipid peroxidation. METHODS: Preterm neonates ≤32 gestational weeks age and/or ≤1500 g were randomly assigned to receive either FMOS or OO/SO in the first day of life. Catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS) levels in the first day of life, 7th day of lipid use and 28th day of life were measured and cholestasis during parenteral nutrition was recorded. RESULTS: 34 and 33 patients were in FMOS and OO/SO lipid groups respectively. Although the TBARS levels were higher in the first day of life and 7th day of LEs in OO/SO lipid group (p=0.014 and p=0.022), on the 28th day of life TBARS level was similar and SOD level was higher (p=0.014) in OO/SO group. Cholestasis was significantly lower in FMOS lipid group (0% vs. 18.2%), (p=0.011) and neonates regained birth weight earlier (p=0.006). There was no significant difference in other morbidities. CONCLUSIONS: FMOS and OO/SO lipid emulsions have similar effects on lipid peroxidation on 28th day of life and on morbidities in short term period except for cholestasis.

Enhancement of immune response mediated by oropharyngeal colostrum administration in preterm neonates.

BACKGROUND: The immune system of preterm infants is immature, being a significant cause of morbidity and mortality, particularly in the preterm infant. Oropharyngeal colostrum administration could be an immunomodulatory aid. Our aim was to evaluate the effect of oropharyngeal colostrum on the serum levels of immunoglobulins, lactoferrin, and resistin during the first month of life and to track the clinical outcome of the neonates. METHODS: One hundred preterm neonates born at <32 weeks of gestation and/or weighing < 1500 g and assisted in the Neonatal Intensive Care Unit were enrolled and divided into two groups: colostrum (n = 48) and control (n = 52). The subjects assigned to the colostrum group received 0.2 mL of colostrum (oropharyngeal route) every 4 hours for the first 15 days of life, and if mothers have inability to breastfeed, they were included in the control group (no oropharyngeal colostrum). Serum concentrations of IgA, IgM, and IgG1, lactoferrin, and resistin were assessed in both groups at 1, 3, 15, and 30 days of life. Clinical data during hospitalization were collected. RESULTS: IgA and IgM increased in preterm neonates who were administered colostrum for 15 and 30 days. Lactoferrin increased after 30 days, and resistin increased after 15 days of supplying oropharyngeal colostrum. The colostrum group underwent full enteral nutrition before, and no differences were observed in the common neonatal morbidities. CONCLUSION: Oropharyngeal colostrum administration is safe in preterm neonates and improves their immunologic profile, showing a potential role as an immunomodulatory agent.

Standardized Nutrition Protocol for Very Low-Birth-Weight Infants Resulted in Less Use of Parenteral Nutrition and Associated Complications, Better Growth, and Lower Rates of Necrotizing Enterocolitis.

BACKGROUND: We assessed the impact of a standardized nutrition initiative for very low-birth-weight (VLBW) infants on their nutrition and clinical outcomes. METHODS: This was a prospective analysis of VLBW infants born before and after the initiation of a nutrition protocol. This protocol included trophic feeds, feeding advancement, fortification guidelines, parameters on the concentration of parenteral nutrition (PN), and the discontinuation of PN and central lines. Gastric residual monitoring was discontinued. Statistical analyses were performed with Fisher's exact and Student's t-tests. Primary outcome measures were days receiving PN, days made nil per os (NPO) after feeding initiation, necrotizing enterocolitis, and growth parameters. Secondary outcome measures were central-line days, sepsis, blood transfusions, cholestasis, osteopenia, chronic lung disease, and retinopathy of prematurity. RESULTS: 136 VLBW infants were analyzed, including 77 in the preprotocol group and 59 in the postprotocol group. Infants postprotocol were found to have reduced PN days (26.1 versus [vs] 18.4, P < .01), fewer days made NPO after feeding initiation (7.2 vs 4.0, P = .02), NEC (7.8% vs 0%, P = 0.038), central-line days (26.5 vs 18.6, P < .01), cholestasis (16% vs 3%, P = .02), and blood transfusions (5.3 vs 3.1, P = .028). Growth, defined by change in z-score from birth to discharge, improved for weight (-1.3 vs -0.8, P < .01), length (-1.5 vs -1.0, P = .033), and head (-1.1 vs -0.6, P = .024). CONCLUSION: Initiation of a standardized nutrition initiative for VLBW infants significantly improved growth, reduced PN use, and improved patient outcomes.

Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014.

BACKGROUND: Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting. METHODS: We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold. RESULTS: Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor. CONCLUSION: INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can contribute to improve neonatal outcomes.

Standardized feeding and probiotic supplementation for reducing necrotizing enterocolitis in preterm infants in a resource limited set up.

BACKGROUND/OBJECTIVES: Necrotizing enterocolitis (NEC ≥ Stage II) is associated with high mortality and morbidity in preterm infants. To assess if introduction of standardized feeding regimen (SFR) and routine probiotic supplementation (RPS) was associated with reduced incidence of NEC in preterm infants in our nursery in a resource limited set up. SUBJECTS/METHODS: This was a retrospective cohort study assessing the incidence of NEC ≥ Stage II before (Epoch 1: N = 144) vs. after (Epoch 2, N = 144) implementation of SFR and RPS in preterm infants < 35 weeks. RESULTS: The median (IQR) gestation and birth weight in epoch 1 and epoch 2 was [32 (30, 33.5) vs. 31.5 (30, 34) weeks, p = 0.829], and [1350 (1100, 1700) vs. 1370 (1110, 1550) g, p = 0.363] respectively. Both groups had predominantly outborn infants (Epoch 1: 79.2% vs. Epoch 2: 78.2%; p = 1.00). Multivariate analysis after adjusting for potential confounders found a significantly lower incidence of NEC ≥ Stage II after implementing SFR and RPS (Epoch 1: 17.4% vs. Epoch 2:9.0%, adjusted odds ratio aOR: 0.19; 95% CI: 0.05, 0.71, p = 0.013). The incidence of the composite outcome of 'NEC or Mortality' was also significantly lower after the intervention (Epoch 1: 21.5% vs. Epoch 2: 14.6%; aOR 0.24, 95% CI: 0.07, 0.85, p = 0.027). CONCLUSIONS: Introduction of SFR and RPS was associated with significant reduction in NEC ≥ Stage II and the composite outcome of NEC ≥ Stage II /mortality in preterm infants.

Adverse Maternal and Neonatal Outcomes in Indicated Compared with Spontaneous Preterm Birth in Healthy Nulliparas: A Secondary Analysis of a Randomized Trial.

OBJECTIVE: To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB). METHODS: A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity. RESULTS: Of 9,867 women, 10.4% (N = 1,038) were PTBs; 32.7% (n = 340) IPTBs and 67.3% (n = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more frequent in IPTB-4.4% versus 0.9% (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.8), as were blood transfusion and prolonged hospital stay (3.2 and 3.7 times, respectively). The frequency of composite neonatal outcome was higher in IPTBs (aOR, 1.8; 95% CI, 1.1-3.0), as were RDS (1.7 times), small for gestational age (SGA) < 5th percentile (7.9 times), and neonatal intensive care unit (NICU) admission (1.8 times). CONCLUSION: Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB.

Arginine supplementation for prevention of necrotising enterocolitis in preterm infants.

BACKGROUND: Decreased concentration of nitric oxide has been proposed as one of the possible cellular mechanisms of necrotising enterocolitis (NEC). Arginine can act as a substrate for production of nitric oxide in the tissues, and arginine supplementation may help to prevent NEC. OBJECTIVES: To examine the effect of arginine supplementation (administered by any route) on the incidence of NEC in preterm neonates. To conduct subgroup analyses based on the dose of arginine and the gestational age of participants (≤ 32 weeks, > 32 weeks). SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4), MEDLINE via PubMed (from 1966 to 12 May 2016), Embase (from 1980 to 12 May 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982 to 12 May 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of arginine supplementation (administered orally or parenterally for at least seven days, in addition to what an infant may be receiving from an enteral or parenteral source) compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of trials by using information obtained from study reports and through personal communication with study authors. We extracted data on relevant outcomes and estimated and reported the effect size as risk ratio (RR), risk difference (RD) and mean difference (MD), as appropriate. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: We identified three eligible studies that included a total of 285 neonates (140 received arginine) from three countries. We assessed the overall methodological quality of the included studies as good. We noted a statistically significant reduction in risk of development of NEC (any stage) among preterm neonates in the arginine group compared with the placebo group (RR 0.38, 95% confidence interval (CI) 0.23 to 0.64; I2 = 27%) (RD -0.19, 95% CI -0.28 to -0.10; I2 = 0%) and rated the quality of evidence as moderate. The number needed to treat for an additional beneficial outcome (NNTB) as required to prevent the development of NEC (any stage) was 6 (95% CI 4 to 10). Study results showed a statistically significant reduction in risk of development of NEC stage 1 (RR 0.37, 95% CI 0.15 to 0.90; I2 = 52%) (RD -0.07, 95% CI -0.14 to -0.01; I2 = 0%) and NEC stage 3 (RR 0.13, 95% CI 0.02 to 1.03; I2 = 0%) (RD -0.05, 95% CI -0.09 to -0.01; I2 = 89%) in the arginine group compared with the control group; the quality of evidence was moderate.Arginine supplementation was associated with a significant reduction in death related to NEC (RR 0.18, 95% CI 0.03 to 1.00; I2 = 0%) (RD -0.05, 95% CI -0.09 to -0.01; I2 = 87%). Results showed clinical heterogeneity in mortality rates. Mortality due to any cause was not significantly different between arginine and control or no treatment groups (RR 0.77, 95% CI 0.41 to 1.45; I2 = 42%) (RD -0.03, 95% CI -0.10 to 0.04; I2 = 79%). Investigators noted no significant side effects directly attributable to arginine, including hypotension or alterations in glucose homeostasis. Follow-up data from one trial revealed no statistically significant differences in adverse outcomes (cerebral palsy, cognitive delay, bilateral blindness or hearing loss requiring hearing aids) at 36 months. Limitations of the present findings include a relatively small overall sample size. AUTHORS' CONCLUSIONS: Administration of arginine to preterm infants may prevent development of NEC. Because information was provided by three small trials that included 285 participants, the data are insufficient at present to support a practice recommendation. A multi-centre randomised controlled study that is focused on the incidence of NEC, particularly at more severe stages (2 and 3), is needed.