Infant massage and brain maturation measured using EEG: A randomised controlled trial.

BACKGROUND: Very preterm (VPT) infants develop adverse neurological sequelae from early exposure of the immature brain to the extrauterine environment. AIMS: To determine the effects of infant massage on brain maturation in low-risk VPT infants. STUDY DESIGN: A randomised controlled trial of VPT infants, who received standard care or daily massage therapy, administered by the mother, from 34 weeks' to 40 weeks' corrected age (CA). SUBJECTS: VPT infants (born at 28 weeks to 32 + 6 weeks' gestational age, G.A.) and a healthy at term cohort for comparison. OUTCOME MEASURES: At term equivalent age (39 weeks' to 42 weeks' CA), EEG was recorded to calculate global relative power (GRP), using power spectral analysis. RESULTS: Sixty infants were recruited, and EEGs of 25 massage and 20 standard care infants were analysable. There was no difference between groups in primary outcome (beta GRP). There was a significantly higher central alpha relative power measured in the intervention group infants, compared to standard care (SC) group (mean difference = 1.42, 95 % confidence interval (CI): 0.12 to 2.73; p = 0.03). A massage dose effect was shown by a positive correlation between, massage dose and beta, alpha and theta GRP (r = 0.42, 95%CI = 0.12 to 0.64, r = 0.45; 95%CI = 0.16 to 0.66, r = 0.39; 95%CI = 0.10 to 0.62 respectively) and a negative correlation between massage dose and delta GRP (r = -0.41, 95%CI = -0.64 to -0.12), suggesting that a higher dose of massage is associated with more favourable brain maturation. CONCLUSIONS: Central alpha regional relative power was greater in massaged infants compared to SC group infants, suggesting relatively greater brain maturation in this area. A measurable massage dose effect in favour of greater brain maturation, shows promise for verification in a larger clinical trial.

Docosahexaenoic acid supplementation of preterm infants and parent-reported symptoms of allergic disease at 7 years corrected age: follow-up of a randomized controlled trial.

BACKGROUND: Docosahexaenoic acid (DHA, 22:6n-3) supplementation in the prenatal period is associated with a reduction in the incidence of some symptoms of allergic disease. Infants born preterm are at increased risk of allergic disease, but it is unknown if DHA supplementation reduces the risk of childhood allergies. OBJECTIVES: The aim of this study was to determine if supplementation of infants born at <33 wk gestation with high-DHA compared with standard-DHA enteral feeds decreases the incidence and severity of parent-reported allergic disease symptoms at a corrected age (CA) of 7 y. METHODS: This study was a follow-up of an Australian multicenter randomized controlled trial. Infants were given high-DHA (∼1% total fatty acids) or standard-DHA (∼0.3% total fatty acids) enteral feeds from 2-4 d of postnatal age until 40 wk postmenstrual age. Parent-reported incidence of respiratory allergic disease symptoms including wheeze and rhinitis at 7 y CA were the main outcomes. Other outcomes included the incidence of eczema symptoms; severity of any symptoms; and the incidence of wheeze, rhinitis, rhinoconjunctivitis, and eczema from birth to 7 y CA. RESULTS: Data were available for 569 of 657 (87%) children originally randomized. Symptoms of wheeze or rhinitis at 7 y CA did not differ between high- and standard-DHA groups [wheeze: RR: 1.10; 95% CI: 0.73, 1.65; P = 0.66; rhinitis: RR: 1.09; 95% CI: 0.81, 1.46; P = 0.59]. There was no difference in other allergic disease symptoms at 7 y CA or in the severity of symptoms. Parent-reported symptoms of wheeze, rhinitis, rhinoconjunctivitis, or eczema from birth to 7 y CA did not differ between the groups. CONCLUSIONS: High-dose DHA supplementation of infants born at <33 wk gestation did not alter allergic disease symptoms or severity at 7 y CA, or from birth to 7 y CA compared with standard-dose DHA. This trial was registered with the Australian New Zealand Clinical Trials Registry as ANZCTR 12606000327583 (http://www.anzctr.org.au).

PREMM: preterm early massage by the mother: protocol of a randomised controlled trial of massage therapy in very preterm infants.

BACKGROUND: Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety. The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants. Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels.  Effects on maternal mood, anxiety and mother-infant attachment will also be measured. METHODS/DESIGN: A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32 weeks and 6 days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12 months and 24 months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. DISCUSSION: Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massage on neurodevelopment. An early intervention such as massage that is relatively easy to administer and could alter the trajectory of preterm infant brain development, holds potential to improve neurodevelopmental outcomes in this vulnerable population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000335897 . Date registered: 22/3/2012.

Neurodevelopmental outcomes at 7†years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial.

OBJECTIVE: To determine if improvements in cognitive outcome detected at 18 months' corrected age (CA) in infants born <33 weeks' gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. DESIGN: Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. SETTING: Five Australian tertiary hospitals from 2008 to 2013. PARTICIPANTS: 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. INTERVENTIONS: High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2-4 days until term CA. PRIMARY OUTCOME: Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. RESULTS: 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital -0.3, 95% CI -2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. CONCLUSIONS: Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2-4 until term CA showed no evidence of benefit at 7 years' CA. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12606000327583.

Vibroacoustic stimulation for fetal assessment in labour in the presence of a nonreassuring fetal heart rate trace.

BACKGROUND: Fetal vibroacoustic stimulation (VAS) is a simple, non-invasive technique where a device is placed on the maternal abdomen over the region of the fetal head and sound is emitted at a predetermined level for several seconds. It is hypothesised that the resultant startle reflex in the fetus and subsequent fetal heart rate (FHR) acceleration or transient tachycardia following VAS provide reassurance of fetal well-being. This technique has been proposed as a tool to assess fetal well-being in the presence of a nonreassuring cardiotocographic (CTG) trace during the first and second stages of labour. OBJECTIVES: To evaluate the clinical effectiveness and safety of VAS in the assessment of fetal well-being during labour, compared with mock or no stimulation for women with a singleton pregnancy exhibiting a nonreassuring FHR pattern. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 September 2012) and reference lists of all retrieved articles. We sought unpublished trials and abstracts submitted to major international congresses and contacted expert informants. SELECTION CRITERIA: All published and unpublished randomised trials that compared maternal and fetal/neonatal/infant outcomes when VAS was used to evaluate fetal status in the presence of a nonreassuring CTG trace during labour, compared with mock or no stimulation. DATA COLLECTION AND ANALYSIS: Two review authors independently sought to assess for inclusion all the potential studies we identified as a result of the search strategy. We planned to resolve any disagreement through discussion or, if required, to consult a third person. Where there was uncertainty about a particular study, we attempted to contact study authors for additional information. However, these attempts were unsuccessful. MAIN RESULTS: The search strategies yielded six studies for consideration of inclusion. However, none of these studies fulfilled the requirements for inclusion in this review. AUTHORS' CONCLUSIONS: There are currently no randomised controlled trials that address the safety and efficacy of VAS used to assess fetal well-being in labour in the presence of a nonreassuring CTG trace. Although VAS has been proposed as a simple, non-invasive tool for assessment of fetal well-being, there is insufficient evidence from randomised trials on which to base recommendations for use of VAS in the evaluation of fetal well-being in labour in the presence of a nonreassuring CTG trace.

Pre- and post-term growth in pre-term infants supplemented with higher-dose DHA: a randomised controlled trial.

The effect of the dietary n-3 long-chain PUFA, DHA (22 : 6n-3), on the growth of pre-term infants is controversial. We tested the effect of higher-dose DHA (approximately 1 % dietary fatty acids) on the growth of pre-term infants to 18 months corrected age compared with standard feeding practice (0·2-0·3 % DHA) in a randomised controlled trial. Infants born < 33 weeks gestation (n 657) were randomly allocated to receive breast milk and/or formula with higher DHA or standard DHA according to a concealed schedule stratified for sex and birth-weight ( < 1250 and ≥ 1250 g). The dietary arachidonic acid content of both diets was constant at approximately 0·4 % total fatty acids. The intervention was from day 2 to 5 of life until the infant's expected date of delivery (EDD). Growth was assessed at EDD, and at 4, 12 and 18 months corrected age. There was no effect of higher DHA on weight or head circumference at any age, but infants fed higher DHA were 0·7 cm (95 % CI 0·1, 1·4 cm; P = 0·02) longer at 18 months corrected age. There was an interaction effect between treatment and birth weight strata for weight (P = 0·01) and length (P = 0·04). Higher DHA resulted in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age. Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth.

S-adenosyl-L-methionine restores photoreceptor function following acute retinal ischemia.

The survival and function of retinal neurons is dependent on mitochondrial energy generation and its intracellular distribution by creatine kinase. Post ischemic disruption of retinal creatine synthesis, creatine kinase activity, or transport of creatine into neurons may impair retinal function. S-adenosyl-L-methionine (SAMe) is required for creatine synthesis, phosphatidylcholine and glutathione synthesis, and transducin methylation. These reactions are essential for photoreceptor function but may be downregulated after ischemia due to a reduction in SAMe. Our aim was to determine whether administration of SAMe after ischemia could improve retinal function. Unilateral retinal ischemia was induced in adult rats by increasing the intraocular pressure to 110 mm Hg for 60 min. Immediately after the ischemic insult, SAMe was injected into the vitreous (100 microM), followed by oral administration (69 mg/kg/day) for 5 or 10 days. Retinal function (electroretinography), histology, and creatine transporter (CRT-1) expression were analyzed. Photoreceptoral responses (R(mP3), S), rod and cone bipolar cell responses (PII), and oscillatory potentials were reduced by the ischemia/reperfusion insult. Although SAMe treatment ameliorated the ischemia-induced histological damage by day 5, there was no improvement in retinal function and the intensity of CRT-1 labeling in ischemic retinas was markedly reduced. However, 10 days after ischemia, a recovery in CRT-1 immunolabeling was evident and SAMe supplementation significantly restored photoreceptor function and rod PII responses. In conclusion, these data suggest that creatine transport and methylation reactions, such as creatine synthesis, may be compromised by an ischemic insult contributing to retinal dysfunction and injury. Oral SAMe supplementation after retinal ischemia may provide an effective, safe, and accessible neuroprotective strategy.

Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial.

CONTEXT: Uncertainty exists about the benefit of dietary docosahexaenoic acid (DHA) on the neurodevelopment of preterm infants. OBJECTIVE: To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months' corrected age. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind controlled trial enrolling infants born at less than 33 weeks' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals, with follow-up to 18 months. INTERVENTION: High-DHA (approximately 1% total fatty acids) enteral feeds compared with standard DHA (approximately 0.3% total fatty acids) from day 2 to 4 of life until term corrected age. MAIN OUTCOME MEASURES: Bayley Mental Development Index (MDI) at 18 months' corrected age. A priori subgroup analyses were conducted based on randomization strata (sex and birth weight < 1250 g vs > or = 1250 g). RESULTS: Of the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley MDI scores did not differ between the high- and standard-DHA groups (mean difference, 1.9; 95% confidence interval [CI], -1.0 to 4.7). The MDI among girls fed the high-DHA diet was higher than girls fed standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7; 95% CI, 0.5-8.8; adjusted mean difference, 4.5; 95% CI, 0.5-8.5). The MDI among boys did not differ between groups. For infants born weighing less than 1250 g, the MDI in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 95% CI, 0.2-9.2) but did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, -0.5 to 8.0). The MDI among infants born weighing at least 1250 g did not differ between groups. CONCLUSION: A DHA dose of approximately 1% total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12606000327583.

Clinicians' evaluations of fetal oximetry sensor placement in a multicentre randomised trial (the FOREMOST trial).

BACKGROUND: Fetal pulse oximetry (FPO) may improve the assessment of the fetal well-being in labour. Reports of health-care provider's evaluations of new technology are important in the overall evaluation of that technology. AIMS: To determine doctors' and midwives' perceptions of their experience placing FPO sensors. METHODS: We surveyed clinicians (midwives and doctors) following placement of a FPO sensor during the FOREMOST trial (multicentre randomised trial of fetal pulse oximetry). Clinicians rated ease of sensor placement (poor, fair, good and excellent). Potential influences on ease of sensor placement (staff category, prior experience in Birth Suite, prior experience in placing sensors, epidural analgesia, cervical dilatation and fetal station) were examined by ordinal regression. RESULTS: There were 281 surveys returned for the 294 sensor placement attempts (response rate 96%). Sensors were placed by midwives (29%), research midwives (48%), registrars (22%) and obstetricians (1%). The majority of clinicians had 1 or more years' Birth Suite experience, had placed six or more sensors previously, and rated ease of sensor placement as good. Advancing fetal station (P < 0.001) and the presence of epidural analgesia prior to sensor placement (P = 0.029) predicted improved ease of sensor placement. Having a clinician placing a sensor for the first time predicted a lower rating for ease of sensor placement (P = 0.001), compared to having placed one or more sensors previously. CONCLUSIONS: Clinicians with varying levels of Birth Suite experience successfully placed fetal oxygen saturation sensors, with the majority rating ease of sensor placement as good.