Rebecca F. Slykerman

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.

Antibiotics in the first year of life and subsequent neurocognitive outcomes

There may be a link between disruption to the gut microbiota in early life and later neurocognitive outcomes. We hypothesised that antibiotic use in early life is associated with a detrimental effect on later neurocognitive outcomes.

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 12 months 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 14–16 weeks gestation. Intervention Women were randomised to receive either placebo or HN001 daily from enrolment until 6 months 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.

Environmental and genetic determinants of childhood depression: The roles of DAT1 and the antenatal environment

Research on adolescent and adult populations has linked depression to variation in several monoaminergic genes, but genetic association studies on depression in children are limited. Additionally, few studies have investigated whether stressors occurring very early in development moderate the influence of certain genes on depression. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) from monoaminergic genes interacted with measures of early life stress to influence depressive symptoms in children. Participants were members of the Auckland Birthweight Collaborative cohort. Small for gestational age (SGA) and maternal stress during pregnancy were measured at birth and used as indicators of early life stress. At age 11, depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and DNA samples were collected for genotyping. A two-way ANOVA revealed that SGA and a SNP from the dopamine transporter gene DAT1 had an interactive effect on childrens depressive symptoms. Specifically, symptoms were greater in children born SGA who are T homozygous for the rs1042098 SNP. These findings suggest that adverse intrauterine environments leading to low birth weight also seem to exacerbate the effects of certain DAT1 variants on depression.

Associations Between the KIAA0319 Dyslexia Susceptibility Gene Variants, Antenatal Maternal Stress, and Reading Ability in a Longitudinal Birth Cohort.

Maternal stress during pregnancy has been associated with detrimental cognitive developmental outcomes in offspring. This study investigated whether antenatal maternal perceived stress and variants of the rs12193738 and rs2179515 polymorphisms on the KIAA0319 gene interact to affect reading ability and full-scale IQ (FSIQ) in members of the longitudinal Auckland Birthweight Collaborative study. Antenatal maternal stress was measured at birth, and reading ability was assessed at ages 7 and 16. Reading data were available for 500 participants at age 7 and 479 participants at age 16. FSIQ was measured at ages 7 and 11. At age 11, DNA samples were collected. Analyses of covariance revealed that individuals with the TT genotype of the rs12193738 polymorphism exposed to high maternal stress during pregnancy possessed significantly poorer reading ability (as measured by Woodcock-Johnson Word Identification standard scores) during adolescence compared with TT carriers exposed to low maternal stress. TT carriers of the rs12193738 SNP also obtained lower IQ scores at age 7 than C allele carriers. These findings suggest that the KIAA0319 gene is associated with both reading ability and general cognition, but in different ways. The effect on IQ appears to occur earlier in development and is transient, whereas the effect of reading ability occurs later and is moderated by antenatal maternal stress. Copyright

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

To determine whether probiotic supplementation in early life improves neurocognitive outcomes assessed at 11 years of age.

Dopamine transporter (DAT1/SLC6A3) polymorphism and the association between being born small for gestational age and symptoms of ADHD

Abstract Being small for gestational age (SGA) has been established as a risk factor for Attention Deficit Hyperactivity Disorder (ADHD). Likewise, several molecular genetic studies have found a link between DAT1 and ADHD. This study investigated whether SGA moderates the effect of dopamine transporter gene variants on the risk of ADHD. A total of 546 children of European descent were genotyped at age 11 for seven DAT1 SNPs (rs6347, rs11564774, rs40184, rs1042098, rs2702, rs8179029 and rs3863145). The Strengths and Difficulties Questionnaire was used to measure symptoms of ADHD at ages 3.5, 7 and 11. We found significant gene‐environment interactions between birth weight and DAT1 SNPs (rs6347, rs40184, rs1042098, rs3863145) on ADHD symptoms at 3.5 years only. Results suggest that genotypic variation of DAT1 may confer a relative protective effect against ADHD in SGA individuals. This study supports the idea that being born SGA moderates the effect of the DAT1 gene on ADHD symptoms in the preschool years and may help to explain some of the heterogeneity in ADHD outcomes.

Response to a letter to the editor

Renton and Low (1) are unable to accept our conclusions that there is an association between antibiotic use in the first year of life and subsequent neurocognitive outcomes in childhood due to reservations about the methodology and confounding impact of socioeconomic status.(2) We agree that socioeconomic status is an important confounder, as it may be associated both with the exposure (antibiotic use) and neurocognitive outcomes; however, Renton and Low appear to have missed the fact that we did adjust for this factor. Socio-economic status can be measured in different ways, most commonly using occupation, income or education, and it may vary with time. For women who have recently given birth (i.e. when they enrolled in the study) many will not be working. Income is difficult to measure fully and accurately and is of course affected by mothers stopping work or going on maternity leave.(3) We chose education (age mother left school, as stated in the Statistical analysis section). This has the additional advantage of not changing with time. As stated in the paper, 95.6% of respondents answered the question on antibiotic use in the first 12 months of life. We acknowledged as a limitation that inaccuracies in the reporting of antibiotics may have occurred, but noted that such misclassification would weaken the ability to detect an association between antibiotic use and neurocognitive outcomes. It could not produce a systematic bias. We therefore stand by our results. As this was a hypothesis generating study, we were appropriately cautious in our conclusions and our recommendation that other longitudinal studies examine the relationship of antibiotic use in the first year of life and subsequent neurocognitive outcomes.

Breastfeeding and intelligence of preschool children: Breastfeeding and intelligence in 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 (SGA10th 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).