Exposure to antibiotics in the first 24 months of life and neurocognitive outcomes at 11 years of age.

RATIONALE: Antibiotics are commonly prescribed for infants. In addition to increasing concern about antibiotic resistance, there is a concern about the potential negative impact of antibiotics on the gut microbiota and health and development outcomes. OBJECTIVE: The aim of this study was to investigate the association between early life antibiotic exposure and later neurocognitive outcomes. METHODS: Participants were infants born to mothers enrolled in the probiotics study. The initial study was designed to evaluate the effect of two different probiotics on allergy outcomes in childhood. Antibiotic exposure was based on parent report and categorised according to the following timing of the first exposure: 0-6 months, 6-12 months, 12-24 months or not at all. At 11 years of age, children's neurocognitive outcomes were assessed using psychologist-administered, parent-report and self-report measures. The relationship between the timing of antibiotic exposure and neurocognitive outcomes was examined using regression models. RESULTS: Of the 474 participants initially enrolled, 342 (72%) children had a neurocognitive assessment at 11 years of age. After adjustment for mode of delivery, probiotic treatment group assignment, income and breastfeeding, children who had received antibiotics in the first 6 months of life had significantly lower overall cognitive and verbal comprehension abilities, increased risk of problems with metacognition, executive function, impulsivity, hyperactivity, attention-deficit hyperactivity disorder, anxiety and emotional problems. CONCLUSIONS: These results provide further evidence that early exposure to antibiotics may be associated with detrimental neurodevelopmental outcomes.

Effect of early probiotic supplementation on childhood cognition, behaviour and mood a randomised, placebo-controlled trial.

AIM: To determine whether probiotic supplementation in early life improves neurocognitive outcomes assessed at 11 years of age. METHODS: A total of 474 children who were born March 2004-Aug 2005 participated in a two-centre randomised placebo-controlled trial of infants at risk of developing allergic disease. Pregnant women were randomised to take Lactobacillus rhamnosus strain HN001, Bifidobacterium animalis subsp. lactis strain HN019 or placebo daily from 35 weeks gestation until six months if breastfeeding, and their infants the same treatment from birth to two years. Intelligence, executive function, attention, depression and anxiety were assessed when the children were 11 years of age. RESULTS: A total of 342 (72.2%) children were assessed (HN001 n = 109, HN019 n = 118 and placebo n = 115). Overall, there were no significant differences in the neurocognitive outcomes between the treatment groups. CONCLUSION: HN001 and HN019 given in early life were not associated with neurocognitive outcomes at 11 years of age in this study. However, we cannot exclude that other probiotics may have a beneficial effect. Further clinical trials are indicated.

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial.

BACKGROUND: Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms. OBJECTIVE: The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12months of age. DESIGN, SETTING, PARTICIPANTS: A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14-16weeks gestation. INTERVENTION: Women were randomised to receive either placebo or HN001 daily from enrolment until 6months postpartum if breastfeeding. OUTCOME MEASURES: Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum. TRIAL REGISTRATION: Australia NZ Clinical Trials Registry: ACTRN12612000196842. FINDINGS: 423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean=7·7 (SD=5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p=0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p=0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score>15) were significantly lower in the HN001 treated mothers (OR=0·44 (0·26, 0·73), p=0·002). INTERPRETATION: Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum. FUNDING SOURCE: Health Research Council of New Zealand (11/318) and Fonterra Co-operative Group Ltd.

Breastfeeding and intelligence of preschool children.

AIM: To investigate whether breastfeeding during infancy is a determinant of intelligence at 3.5 y. METHODS: Five hundred and fifty European children enrolled at birth in the Auckland Birthweight Collaborative Study were assessed at 3.5 y of age. Approximately half were small for gestational age (SGA < or =10th percentile) at birth and half were appropriate for gestational age (AGA >10th percentile). Duration of breastfeeding was recorded at maternal interview, and the intelligence of children was assessed using the Stanford Binet Intelligence Scale. Regression analysis was used to calculate estimates of difference in intelligence scores between breastfeeding groups for the total sample and the group of SGA children. Analyses of the total sample were weighted to account for the disproportionate sampling of SGA children. RESULTS: Breastfeeding was not significantly related to intelligence scores in the total sample despite a trend for longer periods of breastfeeding to be associated with higher intelligence scores. However, in the SGA group, breastfeeding was significantly related to IQ at 3.5 y. Small for gestational age children who were breastfed for longer than 12 mo had adjusted scores 6.0 points higher than those who were not breastfed (p=0.06). CONCLUSION: Breastfeeding may be particularly important for the cognitive development of preschool children born small for gestational age.

Maternal stress, social support and preschool children's intelligence.

BACKGROUND: Despite some research suggesting maternal stress may be associated with cognitive impairment in preschool children, there has been little direct investigation of the association between maternal stress, social support and children's intelligence. AIM: To determine whether maternal stress and social support during pregnancy and during the child's early years of life are associated with the intelligence test performance of preschool children. STUDY DESIGN: Five hundred and fifty European mothers and children enrolled in the Auckland Birthweight Collaborative Study at birth were interviewed when the child was 3 1/2 years of age. SUBJECTS: All children were full term gestation and approximately half the sample were small for gestational age at birth (SGA = birthweight < or = 10th percentile). OUTCOME MEASURE: The cognitive ability of children aged 3 1/2 years was assessed using the Stanford Binet Intelligence Scale 4th Edition. RESULTS: In the total sample, maternal stress and lack of social support during pregnancy were significantly associated with lower intelligence test scores of children. In the group of SGA children, maternal stress post pregnancy was significantly associated with lower intelligence test scores in children. There is evidence that for some children the presence of good social support for mothers may reduce the negative effects of maternal stress on children's cognitive development. CONCLUSION: Maternal stress and lack of social support appear to be associated with lower intelligence test scores of preschool children. Social support may attenuate some of the negative effects of maternal stress on intelligence in children born small for gestational age.