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).

Haemophilus influenzae: a potent perinatal pathogen disproportionately isolated from Indigenous women and their neonates.

BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) bacteraemia in pregnant women is strongly associated with pregnancy loss and preterm delivery. However, the clinical significance of isolation of NTHi from nonsterile sites is unknown. AIMS: To examine the hypothesis that isolation of NTHi from any specimen is associated with adverse perinatal outcomes and to investigate the impression that NTHi is disproportionately isolated from indigenous women and their neonates. MATERIALS AND METHODS: Cases where NTHi was isolated from maternal, fetal or neonatal specimens during the period from 1 July 1997 to 1 July 2009 were identified. Demographic and clinical data were extracted from case notes. Histopathological material was re-reviewed by a perinatal pathologist. Demographic and clinical features of the affected group were compared with the hospital obstetric population. RESULTS: NTHi was isolated from maternal, fetal or neonatal specimens in 97 pregnancies. Two women had NTHi isolated during different pregnancies. Two mothers and 10 neonates were bacteraemic. Indigenous women comprised 28% of pregnancies where NTHi was isolated, compared with 6% of the hospital obstetric population (P < 0.001). Pregnancy loss occurred in six cases (6%). Median gestation at delivery was 33 weeks. Of 96 liveborn neonates, 88 (92%) required admission to a neonatal special care unit. Four liveborn neonates died (4%). Chorioamnionitis was confirmed by histology in 31/33 (93.9%) of placentas examined. CONCLUSIONS: Isolation of NTHi occurred more commonly in indigenous women and neonates. Isolation of NTHi from any obstetric or neonatal specimen is associated with chorioamnionitis, preterm birth, pregnancy loss, early-onset neonatal sepsis and neonatal death.

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.

Dysphonia in preterm children: assessing incidence and response to treatment.

BACKGROUND: Mild dysphonia in childhood is surprisingly common, yet moderate to severe dysphonia is rare. The latter has been associated with complex medical conditions and congenital abnormalities. Intubation injury has also been documented as a cause of childhood dysphonia. Children born very preterm may be intubated as part of the intensive care administered in the perinatal and neonatal periods, yet there are few studies investigating dysphonia in this population. This study will be the first to: use an objective acoustic voice assessment in a paediatric study, document the incidence of dysphonia in very preterm children at school age, and conduct a controlled trial of behavioural voice therapy in this population. DESIGN: This study will consist of three phases: assessment of voice quality and its impact on quality of life in up to 200 children born at less than 32 weeks' gestation: assessment of the nature and extent of laryngeal pathology in children with moderate to severe dysphonia; and a non-blinded, randomised controlled trial of behavioural voice therapy in children with moderate to severe dysphonia. DISCUSSION: This study will be the first to use clinical assessment to examine the voice quality of very preterm children, and to use fibre optic endoscopic evaluation of laryngeal function to determine the nature and extent of any laryngeal pathology in such children. Those participants with significant voice difficulties will be randomised to receive treatment immediately or after the eight week assessment. TRIAL REGISTRATION: This study is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12613001015730/ACTRN12613001012763).

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. METHODS: A retrospective cohort study of SGA singleton infants delivered between 24 and 32 weeks gestation at King Edward Memorial Hospital, Perth, who had UA Doppler studies performed within seven days of birth. Main outcomes assessed were perinatal mortality and morbidity, and neurodevelopmental outcomes at >or= 1 year of age. Outcomes were compared by normality of UA blood flow. RESULTS: There were 119 infants in the study: 49 (41%) had normal UA Doppler studies, 31 (26%) had an increased systolic-diastolic ratio >or= 95th centile, 19 (16%) had absent end diastolic blood flow (AEDF) and 20 (17%) had reversed end-diastolic flow (REDF). Infants in the AEDF and REDF groups were delivered significantly more preterm (P = 0.006) and had lower birthweights (P < 0.001). Ninety four per cent (110 of 117) of live born infants survived. Neurodevelopmental follow-up at 12 months of age or more (median 24 months) was available on 87 of 108 (81%) of live children. Twenty-eight per cent (11 of 39) of fetuses who had had AEDF or REDF died or were classified with moderate or severe disability. There was no significant association between abnormality of UA blood flow, perinatal morbidity, perinatal mortality and neurodevelopmental disability after correction for gestational age. CONCLUSION: Fetuses that are SGA with abnormal UA Doppler studies remain at significant risk of perinatal death, perinatal morbidity and long-term neurodevelopmental disability, associated with their increased risk of preterm birth.

The long term neurologic outcome of children from pregnancies complicated by twin-to-twin transfusion syndrome.

OBJECTIVE: To assess long term outcomes of children from pregnancies complicated by twin-to-twin transfusion syndrome. DESIGN: Comparison of children from pregnancies with twin-to-twin transfusion syndrome in Western Australia with a contemporaneous regional comparison cohort of preterm and term infants studied using an identical assessment procedure. POPULATION AND SETTING: All infants aged > or =18 months were identified from a geographically based longitudinal cohort of monochorionic twin pregnancies with an antenatal diagnosis of twin-to-twin transfusion syndrome conducted prospectively since 1992. METHODS: Children were evaluated using age-specific developmental and behavioural assessments. Cerebral palsy was diagnosed clinically and ascertainment confirmed through the Western Australian Cerebral Palsy Register. MAIN OUTCOME MEASURES: Intellectual disability, cerebral palsy, behavioural and cognitive function. RESULTS: Fifty-two children were identified as eligible for study and assessments were performed on 49 (94%). Three surviving children had a diagnosis of cerebral palsy (5.8%). The mean IQ score was 8 points lower in twin-to-twin transfusion syndrome children compared with the comparison cohort although this was mainly due to a decrement of 13 points in those born before 33 weeks of gestation. There was no difference between the donor and the recipient twin in terms of IQ scores (median difference -3, 95% CI -9 to 6). There was no relationship of IQ score to the worst stage of the twin-to-twin transfusion syndrome. Child Behavior Check List and Vineland Adaptive Behavior Scale scores did not differ between twin-to-twin transfusion syndrome children and the comparison group. CONCLUSIONS: Twin-to-twin transfusion syndrome is associated with a significant reduction in IQ score in very preterm survivors. There seems to be no increase in the prevalence of cerebral palsy. Overall behaviour and adaptive behaviour scale scores are similar to a comparison group.

Repeated antenatal corticosteroids: effects on cerebral palsy and childhood behavior.

OBJECTIVE: This study was undertaken to determine the effects of repeated courses of antenatal corticosteroids on childhood behavior and disabilities, including cognitive delay and cerebral palsy. STUDY DESIGN: Nonrandomized regional cohort of 541 very preterm infants born in Western Australia from singleton pregnancies and alive at 3 years were included in the study. MAIN OUTCOME MEASURES: Physical, cognitive, and psychological assessments up to 6 years. RESULTS: Increasing numbers of antenatal corticosteroid courses were associated with a reduction in the rate of cerebral palsy. Three or more courses were also associated with increased rates of aggressive/destructive, distractible, and hyperkinetic behavior and these effects were present at both ages 3 and 6 years. Measures of internalizing behavior and intelligence quotient were unaffected by antenatal corticosteroid use. CONCLUSION: Repeated antenatal courses of corticosteroids may protect against cerebral palsy but are associated with hyperactivity later in childhood.