Elizabeth A. Nathan

Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in preterm neonates - A randomised double blind placebo controlled trial

Background Probiotic supplementation significantly reduces the risk of necrotising enterocolitis (NEC) and all cause mortality in preterm neonates. Independent quality assessment is important before introducing routine probiotic supplementation in this cohort. Aim To assess product quality, and confirm that Bifidobacterium breve (B. breve) M-16V supplementation will increase fecal B. breve counts without adverse effects. Methods and Participants Strain identity (16S rRNA gene sequencing), viability over 2 year shelf-life were confirmed, and microbial contamination of the product was ruled out. In a controlled trial preterm neonates (Gestation <33 weeks) ready to commence or on feeds for <12 hours were randomly allocated to either B. breve M-16V (3×109 cfu/day) or placebo (dextrin) supplementation until the corrected age 37 weeks. Stool samples were collected before (S1) and after 3 weeks of supplementation (S2) for studying fecal B. breve levels using quantitative PCR (Primary outcome). Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II. Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests, and McNemar and Wilcoxon signed-rank tests for paired comparisons. Results A total of 159 neonates (Probiotic: 79, Placebo: 80) were enrolled. Maternal and neonatal demographic characteristics were comparable between the groups. The proportion of neonates with detectable B. breve increased significantly post intervention: Placebo: [S1:2/66 (3%), S2: 25/66 (38%), p<0.001] Probiotic: [S1: 29/74 (40%), S2: 67/74 (91%), p<0.001]. Median S1 B. breve counts in both groups were below detection (<4.7 log cells.g−1), increasing significantly in S2 for the probiotic group (log 8.6) while remaining <4.7 log in the control group (p<0.001). There were no adverse effects including probiotic sepsis and no deaths. NEC≥Stage II occurred in only 1 neonate (placebo group). Conclusion B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates. Trial Registration Australia New Zealand Clinical Trial Registry ACTRN 12609000374268

Small for gestational age preterm infants and relationship of abnormal umbilical artery Doppler blood flow to perinatal mortality and neurodevelopmental outcomes

Aim: To determine the outcomes of preterm small for gestational age (SGA) infants with abnormal umbilical artery (UA) Doppler studies.

Risk factors for severe perineal trauma during vaginal childbirth: A Western Australian retrospective cohort study

AIM To determine rates and risk factors for third and fourth degree perineal tears (severe perineal trauma) in a Western Australian context. DESIGN AND SETTING A retrospective hospital-based cohort study was performed using computerised data for 10,408 singleton vaginal deliveries from 28 weeks gestation. METHODS Women with severe perineal trauma were compared to those without. Logistic regression analysis, stratified by parity, was used to assess demographic and obstetric factors associated with perineal trauma. RESULTS Severe perineal trauma incidence was 3% (338/10408), 5.4% (239/4405) for primiparas and 1.7% (99/5990) for multiparas (p<0.001). Adjusted risk factors associated with trauma and common across parity included Asian or Indian ethnicity, shoulder dystocia and assisted delivery. Epidural analgesia (OR 0.72, 95% CI 0.54-0.96), preterm birth (OR 0.40, 95% CI 0.23-0.72) and episiotomy (OR 0.54, 95% CI 0.39-0.74) were protective in primiparas, while episiotomy was associated with increased risk in multiparas (OR 2.01, 95% CI 1.18-3.45). Additional factors among primiparas were occipito posterior (OP) delivery (OR 3.35, 95% CI 1.75-6.41) and prolonged second stage (OR 1.98, 95% CI 1.46-2.68), and among multiparas included gestational diabetes (OR 1.78, 95% CI 1.04-3.03) and birth weight >4000g (OR 1.86, 95% CI 1.10-3.15). CONCLUSION Parity differences in risk factors such as episiotomy, infant weight, OP delivery, gestational diabetes and prolonged second stage warrant investigation into clinical management. Although rates differ internationally, and replication evidence has confirmed consistency for certain demographic and obstetric factors, the development of internationally endorsed clinical guidelines and further research around interventions to protect the perineum are recommended.

Voice abnormalities at school age in children born extremely preterm

BACKGROUND AND OBJECTIVES: Voice abnormality is a frequent finding in school age children born at <25 weeks’ gestation in Western Australia. The objective of this study was to determine the frequency of voice abnormality, voice-related quality of life, and demographic and intubation factors in this population. METHODS: Survivors <25 weeks’ gestational age in Western Australia born from 1996 to 2004 were included. Voice assessments (auditory perceptual assessment scale and Pediatric Voice Handicap Index) were carried out by speech pathologists. Intubation history was obtained by retrospective chart review. RESULTS: Of 251 NICU admissions, 154 (61%) survived. Exclusions were based on severe disability (11) or distant residence (13). Of 70 assessed, 67 completed assessments, 4 (6%) were in the normal range and 39 (58%) showed moderate-severe hoarseness. Simultaneous modeling of demographic and intubation characteristics showed an increased odds of moderate-severe voice disorder for children who had more than 5 intubations (odds ratio 6.96, 95% confidence interval 2.07–23.40, P = .002) and for girls relative to boys (odds ratio 3.46, 95% confidence interval 1.12–10.62, P = .030). Tube size and duration of intubation were not significant in the multivariable model. Median scores of parent-reported voice quality of life on the Pediatric Voice Handicap Index were markedly different for preterm (22) and term (3) groups, P < .001. CONCLUSIONS: Voice disorders in this population were much more frequent than expected. Further studies are required to assess voice across a broader range of gestational ages, and to investigate voice-protective strategies in infants requiring multiple episodes of intubation.

Benefits of Bifidobacterium breve M-16V Supplementation in Preterm Neonates - A Retrospective Cohort Study

Background Systematic reviews of randomised controlled trials report that probiotics reduce the risk of necrotising enterocolitis (NEC) in preterm neonates. Aim To determine whether routine probiotic supplementation (RPS) to preterm neonates would reduce the incidence of NEC. Methods The incidence of NEC ≥ Stage II and all-cause mortality was compared for an equal period of 24 months ‘before’ (Epoch 1) and ‘after’ (Epoch 2) RPS with Bifidobacterium breve M-16V in neonates <34 weeks. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. Results A total of 1755 neonates (Epoch I vs. II: 835 vs. 920) with comparable gestation and birth weights were admitted. There was a significant reduction in NEC ≥ Stage II: 3% vs. 1%, adjusted odds ratio (aOR) = 0.43 (95%CI: 0.21–0.87); ‘NEC ≥ Stage II or all-cause mortality’: 9% vs. 5%, aOR = 0.53 (95%CI: 0.32–0.88); but not all-cause mortality alone: 7% vs. 4%, aOR = 0.58 (95% CI: 0.31–1.06) in Epoch II. The benefits in neonates <28 weeks did not reach statistical significance: NEC ≥ Stage II: 6% vs. 3%, aOR 0.51 (95%CI: 0.20–1.27), ‘NEC ≥ Stage II or all-cause mortality’, 21% vs. 14%, aOR = 0.59 (95%CI: 0.29–1.18); all-cause mortality: 17% vs. 11%, aOR = 0.63 (95%CI: 0.28–1.41). There was no probiotic sepsis. Conclusion RPS with Bifidobacterium breve M-16V was associated with decreased NEC≥ Stage II and ‘NEC≥ Stage II or all-cause mortality’ in neonates <34 weeks. Large sample size is required to assess the potential benefits of RPS in neonates <28 weeks.

The long term physical consequences of gastroschisis.

PURPOSE To determine the progress, physical and metabolic outcomes of gastroschisis survivors. METHODS Fifty children born with gastroschisis were assessed with a health questionnaire, physical assessment, bone density and nutritional blood parameters at a median age of 9years (range 5-17). RESULTS After initial abdominal closure, 27/50 (54%) required additional surgical interventions. Ten (20%) children had complex gastroschisis (CG). Abdominal pain was common: weekly in 41%; and requiring hospitalization in 30%. The weight, length and head circumference z-scores improved by a median 0.88 (p=0.001), 0.56 (p=0.006) and 0.74 (p=0.018) of a standard deviation (SD) respectively from birth; 24% were overweight or obese at follow up. However, those with CG had significantly lower median weight z-scores (-0.43 v 0.49, p=0.0004) and body mass index (BMI) (-0.48 v 0.42, p=0.001) at follow up compared to children with simple gastroschisis. Cholesterol levels were elevated in 24% of children. Bone mineral density was reassuring. There were 15 instances of low blood vitamin and mineral levels. CONCLUSIONS Although gastroschisis survival levels are high, many children have significant ongoing morbidity. Children with simple gastroschisis showed significant catch up growth and a quarter had become overweight.

Factors influencing survival in pre-viable preterm premature rupture of membranes

Objective: An observational study of a consecutive case series of pre-viable PPROM (16–24 gestational weeks) was performed between 2001 and 2007 in a single tertiary centre to identify factors that predict neonatal survival. Methods: Detailed obstetric, ultrasound and neonatal data were abstracted from clinical records. Univariate, multivariate and receiver operator curve (ROC) analyses were performed to identify predictors of neonatal survival to discharge. Results: A total of 143 cases of PPROM were identified. Survival to discharge was less with PPROM at 16–20 weeks than 20–24 weeks (17% versus 39%; p = 0.042). GA at PPROM, latency, mode of delivery and electronic foetal monitoring (EFM) were all significant, independent, predictors of survival (p < 0.05). Ultrasound assessed amniotic fluid index (AFI) was a poor predictor of survival (area under ROC = 0.649, 95% CI = 0.532–0.766). A multivariable predictive model, including GA at PPROM, latency, mode of delivery and EFM had an area under the ROC of 0.954 (95% CI = 0.916–0.993, sensitivity 97%, specificity 89% and accuracy 92%). Conclusion: Pre-viable PPROM has a poor prognosis, though modern neonatal management techniques may improve survival in late pre-viable PPROM. The predictive model generated from this consecutive case series of this rare condition provides valuable data for counselling patients with this condition.

The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study.

OBJECTIVES Previous gastroschisis specific neurodevelopmental studies have focused on the first 3years of life. The aim of this study was to assess the intellectual, behavioral and neurological outcomes of older children and adolescents born with gastroschisis. STUDY DESIGN Of 99 gastroschisis survivors born in Western Australia, 1992 to 2005, and who were at least 5years old, 42 agreed to take part in this study. The study assessed: intellectual ability, with age appropriate Wechsler intelligence scales; neurological status; hearing; vision; behavioral status with the Strengths and Difficulties Questionnaire (SDQ); and parenting style with the Parenting Relationship Questionnaire (PRQ). All results were compared to normative means. RESULTS Median age at follow-up was 10years (range 5-17). No child had evidence of cerebral palsy or hearing loss; 1 child had amblyopia. Psychometric tests were completed in 39 children: mean full scale IQ was 98.2 (standard deviation [SD] 10.7); the working memory index was the only subscale to show a significant decrease from the normative mean (mean 95.5, SD 12.4, p=0.038). The mean SDQ behavioral scores were significantly lower for 3 of 5 domains and the Total Difficulties score. PRQ scores were significantly abnormal for 4 of 7 domains: Communication, Discipline, Satisfaction with School and Relational Frustration. CONCLUSIONS Overall intellectual abilities were within a normal range. The decrease in working memory index and the behavioral and parenting relationship impairments could be an effect of perinatal factors, gastroschisis management and complications or the complexity of the socio-economic environment.

Feasibility study: Assessing the influence of macronutrient intakes on preterm body composition, using air displacement plethysmography

Preterm nutrition guidelines target nutrient accretion and growth at intrauterine rates, yet at term equivalent age, the phenotype of the preterm infant differs from that of term infants. Monitoring early changes in preterm body composition (BC) in response to macronutrient intakes may facilitate our understanding of how best to meet preterm nutrition and growth targets.

Feasibility of using ultrasound to measure preterm body composition and to assess macronutrient influences on tissue accretion rates

BACKGROUND AND AIMS To assess ultrasound as a method for (i) measuring body composition (BC) of preterm infants and for (ii) assessing the influence of macronutrient intakes on tissue accretion rates. METHODS Preterm ultrasound studies of four anatomical sites were performed approximately every three weeks from birth to corrected-term age. Preterm measurements were compared to foetal reference data. Duplicate scans at each site were taken on a subset of infants to test the reproducibility of the method, assessed as the coefficient of variation (CV). The influence of measured macronutrient intakes on preterm BC was assessed by regression analysis. RESULTS Median (range) gestation and birth weight of 40 preterm infants were 27 (23-29) weeks and 1022 (480-1475) g, respectively. Accretion rates of adipose and muscle tissues were not uniform across the four sites. Relative to the foetus, preterm adipose tissue thickness was reduced at an equivalent (corrected) gestation, but towards term, a faster accretion rate of subcutaneous abdominal adipose and limb muscle tissue was evident. Timing of fortification (p=0.012), enteral carbohydrate intake (p=0.008) and the protein energy ratio of intakes (p=0.038) moderated the ratio of adipose to muscle tissue accretion over the four sites by -0.004, -0.048 and -0.042, respectively. CONCLUSIONS Ultrasound provides a non-invasive, portable method of assessing changes in subcutaneous adipose tissue and muscle accretion and appears sufficiently sensitive to detect influences of macronutrient intakes on accretion rates from birth. The method warrants further investigation as a bedside tool for measuring BC of preterm infants.