A Case of Neonate with Split Cord Malformation Presenting with Hypoplasia of the Left Lower Extremity.

The frequency of split cord malformation (SCM) is approximately 1 in 5000 births; however, patients are rarely diagnosed with SCM in the neonatal period. Moreover, there have been no reports of SCM with hypoplasia of the lower extremities at birth. A 3-day-old girl was transferred to our hospital for a thorough examination of hypoplasia of the left lower extremity and lumbosacral abnormalities detected after birth. The spinal magnetic resonance imaging (MRI) revealed a split spinal cord in a single dural tube. Based on the MRI findings, the patient was diagnosed with SCM type II. Following discussions with the parents, pediatricians, neurosurgeons, psychologists, and social workers, we decided to perform untethering to prevent further neurological impairment after achieving a sufficient body weight. The patient was discharged on day 25 of life. Early diagnosis and intervention may improve the neurological prognosis in terms of motor function, bladder and bowel function, and superficial sensation; thus, clinicians should report infrequent findings that may lead to SCM diagnosis. SCM should be differentiated in patients with left-right differences in the appearance of the lower extremity, particularly in those with lumbosacral abnormalities.

A COL4A1 variant in a neonate with multiple intracranial hemorrhages and congenital cataracts.

A 2-day-old neonate presented with seizures, multiple intracranial hemorrhages, and bilateral congenital cataracts. Targeted next-generation sequencing of the collagen type IV alpha 1 chain (COL4A1) gene revealed a heterozygous de novo missense variant (NM_001845.6:c.2291G>A/p.Gly764Asp). This missense variant adds to the compendium of COL4A1 variants and is associated with a COL4A1-related disorder.

Growth Trajectories during the First 6 Years in Survivors Born at Less Than 25 Weeks of Gestation Compared with Those between 25 and 29 Weeks.

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (<25 weeks' gestation) up to 6 years of age compared to those of older gestational ages. Preterm infants were divided into two groups: 22−24 weeks' gestation (male (M) 16, female (F) 28) and 25−29 weeks' gestation (M 84, F 59). Z-scores of body weight (BW), body length (BL), and body mass index (BMI) were derived from Japanese standards at 1, 1.5, 3, and 6 years of corrected age. Comparisons between the two groups by sex were made using the Wilcoxon test and linear regression analysis to examine the longitudinal and time-point associations of anthropometric z-scores, the presence of small for gestational age (SGA), and the two gestational groups. BW, BL, BMI, and z-scores were significantly lower in the 22−24 weeks group at almost all assessment points. However, there were no significant differences in BW, BL, BMI, and z-scores between the two female groups after 3 years. BMI z-scores were significantly associated with the youngest gestational age and the presence of SGA at all ages in males, but not in females. The youngest gestational age had a greater influence in males on the z-score of anthropometric parameters up to 6 years of age.

Resistin in Urine and Breast Milk: Relation to Type of Feeding and Anthropometry at 1-Month.

Breast milk contains adipokines such as resistin and leptin and is known for its protective effect against obesity and insulin resistance. This pilot study aims to evaluate the correlation between resistin levels, feeding types (breast milk and formula), and anthropometric parameters in healthy 1-month-old term infants. Urine and breast milk samples were collected from 32 infants and their mothers at 1 month postpartum. Twelve infants were included in the breastfed group, while thirteen infants comprised the breastfed-dominant mix-fed group, and seven infants the formula-dominant mix-fed group. Using ELISA kits, we analyzed resistin levels in the infants' urine and the mothers' breast milk, and leptin levels in breast milk. Urinary resistin levels among the three groups were not significantly different. There was no correlation between the following: urinary resistin levels in the breastfed group with resistin levels in breast milk; resistin levels in urine with infant's body weight and weight gain; resistin levels in breast milk with weight, age, and BMI of mothers and leptin levels in breast milk. This study suggests that the type of feeding does not affect resistin levels in term infants and resistin level does not affect growth in early infancy.

Avoidance of bottles during the establishment of breastfeeds in preterm infants.

BACKGROUND: Preterm infants often start milk feeds by gavage tube. As they mature, sucking feeds are gradually introduced. Women with preterm infants may not always be in hospital to breastfeed their baby and need an alternative approach to feeding. Most commonly, milk (expressed breast milk or formula) is given by bottle. Whether using bottles during establishment of breastfeeds is detrimental to breastfeeding success is a topic of ongoing debate. OBJECTIVES: To identify the effects of avoidance of bottle feeds during establishment of breastfeeding on the likelihood of successful breastfeeding, and to assess the safety of alternatives to bottle feeds. SEARCH METHODS: A new search strategy was developed for this update. Searches were conducted without date or language limits in September 2021 in: MEDLINE, CENTRAL, and CINAHL.  We also searched the ISRCTN trial registry and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.  SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing avoidance of bottles with use of bottles for preterm infants where their mothers planned to breastfeed. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. When appropriate, we contacted study authors for additional information. We used the GRADE approach to assess the certainty of evidence. Outcomes included full breastfeeding and any breastfeeding on discharge home and at three and six months after discharge, as well as length of hospital stay and episodes of infant infection. We synthesised data using risk ratios (RR), risk differences (RD) and mean differences (MD), with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included seven trials with 1152 preterm infants in this updated review. There are three studies awaiting classification. Five included studies used a cup feeding strategy, one used a tube feeding strategy and one used a novel teat when supplements to breastfeeds were needed. We included the novel teat study in this review as the teat was designed to closely mimic the sucking action of breastfeeding. The trials were of small to moderate size, and two had high risk of attrition bias. Adherence with cup feeding was poor in one of the studies, indicating dissatisfaction with this method by staff or parents (or both); the remaining four cup feeding studies provided no such reports of dissatisfaction or low adherence. Avoiding bottles may increase the extent of full breastfeeding on discharge home (RR 1.47, 95% CI 1.19 to 1.80; 6 studies, 1074 infants; low-certainty evidence), and probably increases any breastfeeding (full and partial combined) on discharge (RR 1.11, 95% CI 1.06 to 1.16; studies, 1138 infants; moderate-certainty evidence). Avoiding bottles probably increases the occurrence of full breastfeeding three months after discharge (RR 1.56, 95% CI 1.37 to 1.78; 4 studies, 986 infants; moderate-certainty evidence), and may also increase full breastfeeding six months after discharge (RR 1.64, 95% CI 1.14 to 2.36; 3 studies, 887 infants; low-certainty evidence). Avoiding bottles may increase the occurrence of any breastfeeding (full and partial combined) three months after discharge (RR 1.31, 95% CI 1.01 to 1.71; 5 studies, 1063 infants; low-certainty evidence), and six months after discharge (RR 1.25, 95% CI 1.10 to 1.41; 3 studies, 886 infants; low-certainty evidence). The effects on breastfeeding outcomes were evident at all time points for the tube alone strategy and for all except any breastfeeding three months after discharge for cup feeding, but were not present for the novel teat. There were no other benefits or harms including for length of hospital stay (MD 2.25 days, 95% CI -3.36 to 7.86; 4 studies, 1004 infants; low-certainty evidence) or episodes of infection per infant (RR 0.70, 95% CI 0.35 to 1.42; 3 studies, 500 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: Avoiding the use of bottles when preterm infants need supplementary feeds probably increases the extent of any breastfeeding at discharge, and may improve any and full breastfeeding (exclusive) up to six months postdischarge. Most of the evidence demonstrating benefit was for cup feeding. Only one study used a tube feeding strategy. We are uncertain whether a tube alone approach to supplementing breastfeeds improves breastfeeding outcomes; further studies of high certainty are needed to determine this.

Effect of parenteral lipid emulsion on preterm infant PUFAs and their downstream metabolites.

OBJECTIVE: Oxylipins synthesized by oxidation of long-chain polyunsaturated fatty acids (LCPUFAs) are bioactive downstream lipid mediators. The aim of this study was to describe oxylipin levels in preterm infants born 30 to 33 weeks' gestation who were enrolled in a randomized controlled trial in which peripheral parenteral nutrition (P-PN), including lipid emulsion (containing soy, medium chain triglyceride, olive and fish oil), was compared with 10% glucose on growth during the transition to enteral feeds. METHODS: Of the 92 infants randomized to the P-PN study, the first 72 (P-PN n = 34, control n = 38) had blood taken for fatty acid analyses. P-PN infants received parenteral nutrition including 3% protein, 8% glucose and 17% SMOFlipid® lipid (containing soy, medium chain triglyceride, olive and fish oil), and control infants 10% glucose. Both groups commenced enteral feeds when clinically stable. 32 oxylipins and 5 free fatty acids were screened (using ultra-high-performance liquid chromatography-tandem mass spectrometry), and 5 total LCPUFA were measured (using gas chromatography), on study days 1 (baseline), 2, 4, 7, 14 and 21. RESULTS: Both total and free LA, ALA and EPA were significantly higher in the P-PN group compared with control over the first week of life. Whereas total AA was significantly lower and free DHA significantly higher over the same time period. All LA, ALA, EPA and four DHA derived oxylipins detected were significantly higher in the P-PN group compared with the control group during the first week of life, with three AA derived oxylipins significantly lower and one significantly higher. CONCLUSIONS: Parenteral lipid emulsion resulted in a change in total and free fatty acids and related oxylipins with the profiles suggesting increased omega-6 driven inflammation. Further studies to investigate the association between the oxylipin levels and nutrition and to determine whether the oxylipin profiles influence the clinical outcome in preterm infants are warranted.

The efficacy and safety of peripheral intravenous parenteral nutrition vs 10% glucose in preterm infants born 30 to 33 weeks' gestation: a randomised controlled trial.

BACKGROUND: Preterm infants born 30 to 33 weeks' gestation often require early support with intravenous fluids because of respiratory distress, hypoglycemia or feed intolerance. When full feeds are anticipated to be reached within the first week, risks associated with intravenous delivery mode and type must be carefully considered. Recommendations are for parenteral nutrition to be infused via central venous lines (because of the high osmolarity), however, given the risks associated with central lines, clinicians may opt for 10% glucose via peripheral venous catheter when the need is short-term. We therefore compare a low osmolarity peripheral intravenous parenteral nutrition (P-PN) solution with peripheral intravenous 10% glucose on growth rate in preterm infants born 30 to 33 weeks' gestation. METHODS: In this parallel group, single centre, superiority, non-blinded, randomised controlled trial, 92 (P-PN 42, control 50) infants born 30+ 0 to 33+ 6 weeks' gestation, were randomised within 24 h of age, to receive either P-PN (8% glucose, 30 g/L amino acids, 500 IU/L heparin and SMOFlipid®) or a control of peripheral intravenous 10% glucose. Both groups received enteral feeds according to hospital protocol. The primary outcome was rate of weight gain from birth to 21 days of age. RESULTS: The rate of weight gain was significantly increased in P-PN infants compared with control (P-PN, n = 42, 18.7, SD 6.6 g/d vs control, n = 50, 14.8, SD 6.0 g/d; adjusted mean difference 3.9 g/d, 95% CI 1.3 to 6.6; P = 0.004), with the effect maintained to discharge home. Days to regain birthweight were significantly reduced and length gain significantly increased in P-PN infants. One infant in the P-PN group had a stage 3 extravasation which rapidly resolved. Blood urea nitrogen and triglyceride levels were significantly higher in the P-PN group in the first week of life, but there were no instances of abnormally high levels. There were no significant differences in any other clinical or biochemical outcomes. CONCLUSION: P-PN improves the rate of weight gain to discharge home in preterm infants born 30 to 33 weeks gestation compared with peripheral intravenous 10% glucose. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000925448 . Registered 12 July 2016.

Intravenous fat induces changes in PUFA and their bioactive metabolites: Comparison between Japanese and Australian preterm infants.

OBJECTIVE: Oxylipins are biologically active signaling molecules that initiate and resolve inflammation; they are synthesized by oxidation of polyunsaturated fatty acids (PUFAs) and reflect PUFA intake and status. The PUFA intake in preterm infants differs between countries because of the type of lipid emulsions used and the PUFA content of breast milk. We compared total blood PUFA, free PUFA and their oxylipin levels in dried whole blood samples from preterm infants born in Australia and Japan. METHODS: We enrolled 30 and 14 preterm infants born less than 31 weeks' gestation, from Adelaide and Japan respectively. Blood samples were obtained from cord blood, and on postnatal days 4, 7, 14 and 28. Total PUFAs were measured using gas chromatography, while free fatty acids and oxylipins were screened using ultra high-performance liquid chromatography mass spectroscopy. RESULTS: Differences in the levels of blood PUFA between the centres were found which were in line with the timing and type of lipid emulsion administration. Significant differences in longitudinal levels were seen more often in free PUFA and their oxylipins than in total blood PUFA. This was particularly true for AA and DHA. In contrast, differences in the levels could be seen in total blood EPA, as well as in free EPA and its oxylipins. Further, levels of many free PUFA and their oxylipins were higher in Japanese infants than in Australian infants. CONCLUSION: Differences in total and free fatty acids and unesterified oxylipins, were observed during the first weeks of life and between preterm infants born in Australia and Japan, which were likely a reflection of the type of lipid emulsion and timing of administration. The clinical significance of these changes remains to be explored.

Oxylipins and Free Fatty Acids in Parenteral Lipid Emulsions Currently Used in Preterm Infant Care: An In Vitro Study.

Lipid emulsions used to support nutrition in preterm infants contain long-chain polyunsaturated fatty acids (LCPUFAs) as a source of essential fatty acids; these LCPUFAs and their parent polyunsaturated fatty acid (PUFA) can be oxidized by a variety of mechanisms to bioactive molecules called oxylipins, which are signaling molecules that initiate and/or resolve inflammation. The aim of this study was to explore levels of free LCPUFA and their related oxylipins in 3 commercially available lipid emulsions (Intralipid, SMOFlipid, and ClinOleic) using ultra high-performance liquid chromatography mass spectroscopy. Free LCPUFA were detected in all lipid emulsions tested. Seven, 8, and 9 different oxylipin compounds were detected in the 3 emulsions, respectively. The oxylipins detected were mainly derived from omega-6 PUFAs; these included 13-hydroxyoctadecadienoic acid from linoleic acid and 5-hydroxyeicosatetraenoic acid derived from arachidonic acid. It may be clinically important to know that oxylipins exist in lipid emulsions and to evaluate their potential effects on preterm infants.

Influence of i.v. lipid emulsion on lipoprotein subclass in preterm infants.

BACKGROUND: Lipid emulsions given i.v. are normally rapidly metabolized by apoprotein recruited from high-density lipoprotein (HDL) particles in the blood. Very low-birthweight infants (VLBWI), however, have a low rate of lipid clearance from the blood, and therefore lipid emulsions must be given carefully to minimize the risk of hyperlipidemia. The purpose of this study was to evaluate the influence of i.v. lipid emulsion on lipoprotein subclass profile in VLBWI during the early postnatal period. METHODS: Forty-six VLBWI who had been given different doses of lipid emulsion in the first few days after birth were enrolled in the present study. Triglyceride and cholesterol content of each lipoprotein subclass was measured at 3 weeks after birth, and their correlation with the total dose of lipid emulsion was calculated. RESULTS: There was no correlation between the total dose of lipid emulsion and the triglyceride and cholesterol content in any subclasses of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). There was a significant negative correlation between the total dose of lipid emulsion and the triglyceride content in very large (P < 0.05, r = -0.32), large (P < 0.01, r = -0.47) and medium HDL (P < 0.05, r = -0.34) particles; and the cholesterol content in large (P < 0.01, r = -0.47) and medium HDL (P < 0.01, r = -0.4) particles. CONCLUSION: Lipid emulsion influenced the triglyceride and cholesterol content of HDL particles in VLBWI, suggesting that lipid emulsion can affect lipid metabolism in this infant population in the early postnatal period.

A Systematic Review and Meta-Analysis of Human Milk Feeding and Morbidity in Very Low Birth Weight Infants.

This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks' gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother's own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.

Urinary prostaglandin D2 metabolite excretion during the first six months of life was significantly lower in breast-fed than formula-fed infants.

AIM: The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and breast milk is considered to provide the optimal source of infant nutrition. This pilot study from September 2013 to May 2015 examined the effect of breastfeeding on prostaglandin metabolism in healthy term infants. METHODS: Urine samples were collected from 19 infants at one month of age in the Juntendo University Hospital, Tokyo, Japan. The 13 infants in the breast-fed group received less than 540 mL/week of their intake from formula, and the other six were exclusively fed on formula. At six months, we sampled 14 infants: nine breast-fed and five receiving formula. The infants were from normal single pregnancies and free from perinatal complications. We analysed urinary prostaglandin metabolites-tetranor prostaglandin E2 metabolite (t-PGEM) and tetranor prostaglandin D2 metabolite (t-PGDM)-using liquid chromatography tandem-mass spectrometry. RESULTS: Urinary t-PGDM excretion at one and six months was significantly lower in breast-fed infants than formula-fed infants. However, urinary t-PGEM excretion at one and six months was not significantly different between the groups. CONCLUSION: Our study showed that the type of feeding in early infancy affected prostaglandin metabolism in healthy term infants.

Correlations between feeding type and blood ionized magnesium levels in Japanese preterm infants.

Although magnesium (Mg) contents are different between breast milk and formula, few studies have investigated the blood Mg level in breast fed or formula fed preterm infants. We examined the influence of feeding type on serum Mg and whole blood ionized Mg (iMg) levels in preterm infants soon after birth. We included 115 preterm infants born between gestational weeks 32 and 35. Infants were separated into two groups: breast milk (BM) dominant group (n = 30) receiving ≥70% of Mg intake from BM and mixed-fed (MF) group (n = 85) receiving ≥30% of Mg intake from formula. Blood levels of Mg, iMg, Ca, and iCa at day 1 of age and at discharge from the hospital were compared between the groups. No differences in the Mg and iMg levels at day 1 of age were observed between the two groups. The Mg and iMg levels at discharge were significantly lower (P < 0.05) in the BM group than in the MF group; 0.86 (interquartile range 0.81-0.91) versus 0.91 (0.86-0.99) mmol/L and 0.46 (0.41-0.51) versus 0.52 (0.47-0.57) mmol/L, respectively. There were no differences in the Ca and iCa levels between the two groups. By stepwise multiple regression analysis, the percentage of BM intake was a significant independent predictor of the Mg and iMg levels. The feeding type influenced serum Mg and blood iMg levels in preterm infants soon after birth. Further studies are needed to investigate the influence of Mg on growth and the optimal range of blood Mg levels.

Relationship between insulin-like growth factor 1, leptin and ghrelin levels and catch-up growth in small for gestational age infants of 27-31 weeks during neonatal intensive care unit admission.

AIM: Poor post-natal growth is related to later morbidity and poor cognitive development in preterm infants. We investigated the relationship between plasma insulin-like growth factor 1 (IGF-1), leptin, active ghrelin levels and post-natal growth in preterm infants small for gestational age (SGA). METHODS: Plasma IGF-1, leptin and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 42 very low birthweight (VLBW) infants (born between 27 and 31 weeks of gestation), including 14 SGA infants with extrauterine growth restriction (EUGR), 6 SGA infants without EUGR and 22 appropriate-for-gestational-age infants. RESULTS: At birth, IGF-1 levels in SGA infants without EUGR did not differ significantly from those in SGA infants with EUGR. However, IGF-1 levels in SGA infants without EUGR were as high as those observed in appropriate-for-gestational-age infants and were significantly different from those in SGA infants with EUGR at 4 and 8 weeks of age. Leptin and ghrelin levels did not differ significantly among the three groups at any time point. CONCLUSION: IGF-1 is related to catch-up growth in SGA VLBW infants during neonatal intensive care unit admission; however, this does not appear to be the case for leptin and ghrelin. IGF-1 level monitoring may be useful for predicting EUGR in preterm VLBW infants.

Avoidance of bottles during the establishment of breast feeds in preterm infants.

BACKGROUND: Preterm infants start milk feeds by gavage tube. As they mature, sucking feeds are gradually introduced. Women who choose to breast feed their preterm infant are not always able to be in hospital with their baby and need an alternative approach to feeding. Most commonly, milk (expressed breast milk or formula) is given by bottle. Whether using bottles during establishment of breast feeds is detrimental to breast feeding success is a topic of ongoing debate. OBJECTIVES: To identify the effects of avoidance of bottle feeds during establishment of breast feeding on the likelihood of successful breast feeding, and to assess the safety of alternatives to bottle feeds. 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 2), MEDLINE via PubMed (1966 to July 2016), Embase (1980 to July 2016) and CINAHL (1982 to July 2016). We also searched databases of clinical trials and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing avoidance of bottles with use of bottles in women who have chosen to breast feed their preterm infant. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. When appropriate, we contacted study authors for additional information. Review authors used standard methods of The Cochrane Collaboration and the Cochrane Neonatal Review Group. MAIN RESULTS: We included seven trials with 1152 preterm infants. Five studies used a cup feeding strategy, one used a tube feeding strategy and one used a novel teat when supplements to breast feeds were needed. We included the novel teat study in this review, as the teat was designed to more closely mimic the sucking action of breast feeding. The trials were of small to moderate size, and two had high risk of attrition bias. Adherence with cup feeding was poor in one of the studies, indicating dissatisfaction with this method by staff and/or parents; the remaining four cup feeding studies provided no such reports of dissatisfaction or low adherence. Meta-analyses provided evidence of low to moderate quality indicating that avoiding bottles increases the extent of breast feeding on discharge home (full breast feeding typical risk ratio (RR) 1.47, 95% confidence interval (CI) 1.19 to 1.80; any breast feeding RR 1.11, 95% CI 1.06 to 1.16). Limited available evidence for three months and six months post discharge shows that avoiding bottles increases the occurrence of full breast feeding and any breast feeding at discharge and at six months post discharge, and of full (but not any) breast feeding at three months post discharge. This effect was evident at all time points for the tube alone strategy and for all except any breast feeding at three months post discharge for cup feeding. Investigators reported no clear benefit when the novel teat was used. No other benefits or harms were evident, including, in contrast to the previous (2008) review, length of hospital stay. AUTHORS' CONCLUSIONS: Evidence of low to moderate quality suggests that supplementing breast feeds by cup increases the extent and duration of breast feeding. Current insufficient evidence provides no basis for recommendations for a tube alone approach to supplementing breast feeds.

Avoidance of bottles during the establishment of breast feeds in preterm infants.

BACKGROUND: Preterm infants start milk feeds by gavage tube. As they mature, sucking feeds are gradually introduced. Women who choose to breast feed their preterm infant are not always able to be in hospital with their baby and need an alternative approach to feeding. Most commonly, milk (expressed breast milk or formula) is given by bottle. Whether using bottles during establishment of breast feeds is detrimental to breast feeding success is a topic of ongoing debate. OBJECTIVES: To identify the effects of avoidance of bottle feeds during establishment of breast feeding on the likelihood of successful breast feeding, and to assess the safety of alternatives to bottle feeds. 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 2), MEDLINE via PubMed (1966 to July 2016), Embase (1980 to July 2016) and CINAHL (1982 to July 2016). We also searched databases of clinical trials and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing avoidance of bottles with use of bottles in women who have chosen to breast feed their preterm infant. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. When appropriate, we contacted study authors for additional information. Review authors used standard methods of The Cochrane Collaboration and the Cochrane Neonatal Review Group. MAIN RESULTS: We included seven trials with 1152 preterm infants. Five studies used a cup feeding strategy, one used a tube feeding strategy and one used a novel teat when supplements to breast feeds were needed. We included the novel teat study in this review, as the teat was designed to more closely mimic the sucking action of breast feeding. The trials were of small to moderate size, and two had high risk of attrition bias. Adherence with cup feeding was poor in one of the studies, indicating dissatisfaction with this method by staff and/or parents; the remaining four cup feeding studies provided no such reports of dissatisfaction or low adherence. Meta-analyses provided evidence of low to moderate quality indicating that avoiding bottles increases the extent of breast feeding on discharge home (full breast feeding typical risk ratio (RR) 1.47, 95% confidence interval (CI) 1.19 to 1.80; any breast feeding RR 1.11, 95% CI 1.06 to 1.16). Limited available evidence for three months and six months post discharge shows that avoiding bottles increases the occurrence of full breast feeding and any breast feeding at discharge and at six months post discharge, and of full (but not any) breast feeding at three months post discharge. This effect was evident at all time points for the tube alone strategy and for all except any breast feeding at three months post discharge for cup feeding. Investigators reported no clear benefit when the novel teat was used. No other benefits or harms were evident, including, in contrast to the previous (2008) review, length of hospital stay. AUTHORS' CONCLUSIONS: Evidence of low to moderate quality suggests that supplementing breast feeds by cup increases the extent and duration of breast feeding. Current insufficient evidence provides no basis for recommendations for a tube alone approach to supplementing breast feeds.

Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. METHODS: Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. RESULTS: Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. CONCLUSIONS: No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.

A family having type 2B von Willebrand disease with a novel VWF p.R1308S mutation: Detection of characteristic platelet aggregates on peripheral blood smears as the key aspect of diagnosis.

Type 2B von Willebrand disease (VWD) is frequently associated with distinct platelet morphology. Here we present a familial case of type 2B VWD with a novel VWF mutation (p.R1308S), which caused neonatal thrombocytopenia. The mother had been treated for refractory immune thrombocytopenia (ITP) for more than 20years. The most important hematological features of this case were large platelets and platelet aggregates detected on peripheral blood smears. Hemostatic tests showed enhanced ristocetin-induced platelet agglutination at low-ristocetin concentrations, absence of high-molecular weight von Willebrand factor (VWF) multimers, and low VWF cofactor activity/antigen ratio. In patients with intractable ITP, family history of ITP and consecutive neonatal thrombocytopenia, the differential diagnosis of congenital thrombocytopenia is mandatory. For this purpose, the identification of large platelets and platelet aggregates on peripheral blood smears is the key aspect of type 2B VWD diagnosis.

Measurement of cytokine levels in cerebrospinal fluid over time in neonatal Enterococcal meningitis.

Enterococcus faecalis is rarely involved in neonatal meningitis. Several studies have indicated that the cytokines related to bacterial infection may induce nerve cell damage; therefore, the cytokine levels in cerebrospinal fluid (CSF) could represent a valuable hallmark for rapid recognition of the disease and evaluation of the degree of neurological involvement. We analyzed cytokine levels in the CSF of a neonate with E. faecalis meningitis over time. Tumor necrosis factor-α (TNF-α) tended to be elevated during the acute phase of infection, and then decreased during the convalescent stage after treatment. CSF inflammatory cytokine measurement may provide important clues for predicting the development of complications in the host because some of these cytokines, such as TNF-α, can injure neurons.