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1.  Fast-food consumption and body mass index in children and adolescents: an international cross-sectional study 
BMJ Open  2014;4(12):e005813.
To investigate whether reported fast-food consumption over the previous year is associated with higher childhood or adolescent body mass index (BMI).
Secondary analysis from a multicentre, multicountry cross-sectional study (International Study of Asthma and Allergies in Children (ISAAC) Phase Three).
Subjects and methods
Parents/guardians of children aged 6–7 completed questionnaires which included questions about their children's asthma and allergies, fast-food consumption, height and weight. Adolescents aged 13–14 completed the same questionnaire. The questionnaire asked “In the past 12 months, how often on average did you (your child) eat fast-food/burgers?” The responses were infrequent (never/only occasionally), frequent (once/twice a week) or very frequent (three or more times per week). A general linear mixed model was used to determine the association between BMI and fast-food consumption, adjusting for Gross National Income per capita by country, measurement type (whether heights/weights were reported or measured), age and sex.
72 900 children (17 countries) and 199 135 adolescents (36 countries) provided data. Frequent and very frequent fast-food consumption was reported in 23% and 4% of children, and 39% and 13% of adolescents, respectively. Children in the frequent and very frequent groups had a BMI that was 0.15 and 0.22 kg/m2 higher than those in the infrequent group (p<0.001). Male adolescents in the frequent and very frequent groups had a BMI that was 0.14 and 0.28 kg/m2 lower than those in the infrequent group (p<0.001). Female adolescents in the frequent and very frequent groups had a BMI that was 0.19 kg/m2 lower than those in the infrequent group (p<0.001).
Reported fast-food consumption is high in childhood and increases in adolescence. Compared with infrequent fast-food consumption, frequent and very frequent consumption is associated with a higher BMI in children. Owing to residual confounding, reverse causation and likely misreporting, the reverse association observed in adolescents should be interpreted with caution.
PMCID: PMC4265088  PMID: 25488096
BMI; Fast food consumption; International; Childhood obesity; Childhood overweight
2.  Associations between Acetaminophen Use during Pregnancy and ADHD Symptoms Measured at Ages 7 and 11 Years 
PLoS ONE  2014;9(9):e108210.
Our aim was to replicate and extend the recently found association between acetaminophen use during pregnancy and ADHD symptoms in school-age children.
Participants were members of the Auckland Birthweight Collaborative Study, a longitudinal study of 871 infants of European descent sampled disproportionately for small for gestational age. Drug use during pregnancy (acetaminophen, aspirin, antacids, and antibiotics) were analysed in relation to behavioural difficulties and ADHD symptoms measured by parent report at age 7 and both parent- and child-report at 11 years of age. The analyses included multiple covariates including birthweight, socioeconomic status and antenatal maternal perceived stress.
Acetaminophen was used by 49.8% of the study mothers during pregnancy. We found significantly higher total difficulty scores (Strengths and Difficulty Questionnaire parent report at age 7 and child report at age 11) if acetaminophen was used during pregnancy, but there were no significant differences associated with any of the other drugs. Children of mothers who used acetaminophen during pregnancy were also at increased risk of ADHD at 7 and 11 years of age (Conners’ Parent Rating Scale-Revised).
These findings strengthen the contention that acetaminophen exposure in pregnancy increases the risk of ADHD-like behaviours. Our study also supports earlier claims that findings are specific to acetaminophen.
PMCID: PMC4177119  PMID: 25251831
3.  No evidence for copy number and methylation variation in H19 and KCNQ10T1 imprinting control regions in children born small for gestational age 
BMC Medical Genetics  2014;15:67.
There is a substantial genetic component for birthweight variation, and although there are known associations between fetal genotype and birthweight, the role of common epigenetic variation in influencing the risk for small for gestational age (SGA) is unknown. The two imprinting control regions (ICRs) located on chromosome 11p15.5, involved in the overgrowth disorder Beckwith-Wiedemann syndrome (BWS) and the growth restriction disorder Silver-Russell syndrome (SRS), are prime epigenetic candidates for regulating fetal growth. We investigated whether common variation in copy number in the BWS/SRS 11p15 region or altered methylation levels at IGF2/H19 ICR or KCNQ10T1 ICR was associated with SGA.
We used a methylation-specific multiplex-ligation-dependent probe amplification assay to analyse copy number variation in the 11p15 region and methylation of IGF2/H19 and KCNQ10T1 ICRs in blood samples from 153 children (including 80 SGA), as well as bisulfite pyrosequencing to measure methylation at IGF2 differentially methylated region (DMR)0 and H19 DMR.
No copy number variants were detected in the analyzed cohort. Children born SGA had 2.7% lower methylation at the IGF2 DMR0. No methylation differences were detected at the H19 or KCNQ10T1 DMRs.
We confirm that a small hypomethylation of the IGF2 DMR0 is detected in peripheral blood leucocytes of children born SGA at term. Copy number variation within the 11p15 BWS/SRS region is not an important cause of non-syndromic SGA at term.
PMCID: PMC4089969  PMID: 24934635
DNA methylation; Imprinting; ICR2; ICR1; H19; KCNQ10T1; Small for gestational age
4.  The Midland and North of England Stillbirth Study (MiNESS) 
The United Kingdom has one of the highest rates of stillbirth in Europe, resulting in approximately 4,000 stillbirths every year. Potentially modifiable risk factors for late stillbirths are maternal age, obesity and smoking, but the population attributable risk associated with these risk factors is small.
Recently the Auckland Stillbirth Study reported that maternal sleep position was associated with late stillbirth. Women who did not sleep on their left side on the night before the death of the baby had double the risk compared with sleeping on other positions. The population attributable risk was 37%. This novel observation needs to be replicated or refuted.
Case control study of late singleton stillbirths without congenital abnormality. Controls are women with an ongoing singleton pregnancy, who are randomly selected from participating maternity units booking list of pregnant women, they are allocated a gestation for interview based on the distribution of gestations of stillbirths from the previous 4 years for the unit. The number of controls selected is proportional to the number of stillbirths that occurred at the hospital over the previous 4 years.
Data collection: Interviewer administered questionnaire and data extracted from medical records. Sample size: 415 cases and 830 controls. This takes into account a 30% non-participation rate, and will detect an OR of 1.5 with a significance level of 0.05 and power of 80% for variables with a prevalence of 57%, such as non-left sleeping position.
Statistical analysis: Mantel-Haenszel odds ratios and unconditional logistic regression to adjust for potential confounders.
The hypotheses to be tested here are important, biologically plausible and amenable to a public health intervention. Although this case–control study cannot prove causation, there is a striking parallel with research relating to sudden infant death syndrome, where case–control studies identified prone sleeping position as a major modifiable risk factor. Subsequently mothers were advised to sleep babies prone (“Back to Sleep” campaign), which resulted in a dramatic drop in SIDS. This study will provide robust evidence to help determine whether such a public health intervention should be considered.
Trial registration number
PMCID: PMC4032501  PMID: 24885461
Stillbirth; Perinatal mortality; Perinatal death; Risk factors; Sleep position; Reduced fetal movements; Fetal growth restriction
5.  A triple risk model for unexplained late stillbirth 
The triple risk model for sudden infant death syndrome (SIDS) has been useful in understanding its pathogenesis. Risk factors for late stillbirth are well established, especially relating to maternal and fetal wellbeing.
We propose a similar triple risk model for unexplained late stillbirth. The model proposed by us results from the interplay of three groups of factors: (1) maternal factors (such as maternal age, obesity, smoking), (2) fetal and placental factors (such as intrauterine growth retardation, placental insufficiency), and (3) a stressor (such as venocaval compression from maternal supine sleep position, sleep disordered breathing). We argue that the risk factors within each group in themselves may be insufficient to cause the death, but when they interrelate may produce a lethal combination.
Unexplained late stillbirth occurs when a fetus who is somehow vulnerable dies as a result of encountering a stressor and/or maternal condition in a combination which is lethal for them.
PMCID: PMC3991879  PMID: 24731396
Stillbirth; Triple risk; Vulnerable fetus
7.  Risk factors for migraine and tension-type headache in 11 year old children 
Though migraine and tension type headache are both commonly diagnosed in childhood, little is known about their determinants when diagnosed prior to puberty onset. Our aim was to determine psychosocial- and health-related risk factors of migraine and tension-type headache in 11 year old children.
871 New Zealand European children were enrolled in a longitudinal study at birth and data were collected at birth, 1, 3.5, 7, and 11 years of age. Primary headache was determined at age 11 years based on the International Headache Society. Perinatal factors assessed were small for gestational age status, sex, maternal smoking during pregnancy, maternal perceived stress, and maternal school leaving age. Childhood factors assessed were sleep duration, percent body fat, television watching, parent and self-reported total problem behaviour, being bullied, and depression.
Prevalence of migraine and tension-type headache was 10.5% and 18.6%, respectively. Both migraine and TTH were significantly associated with self-reported problem behaviour in univariable logistic regression analyses. Additionally, migraine was associated with reduced sleep duration, and both sleep and behaviour problems remained significant after multivariable analyses. TTH was also significantly associated with antenatal maternal smoking, higher body fat, and being bullied. For TTH, problem behaviour measured at ages 3.5 and 11 years both remained significant after multivariable analysis. Being born small for gestational age was not associated with either headache group.
Although they share some commonality, migraine and tension-type headache are separate entities in childhood with different developmental characteristics. The association between primary headache and problem behaviour requires further investigation.
PMCID: PMC4162739  PMID: 25205384
Migraine; Tension-type; Paediatrics; Small for gestational age; Longitudinal; Risk-factors; Paediatric
8.  The Worldwide Association between Television Viewing and Obesity in Children and Adolescents: Cross Sectional Study 
PLoS ONE  2013;8(9):e74263.
Studies exploring the effect of television viewing on obesity throughout childhood are conflicting. Most studies have been confined to single high-income countries. Our aim was to examine the association between television viewing habits and Body Mass Index (BMI) in adolescents and children in a multicentre worldwide sample.
In the International Study of Asthma and Allergies in Children Phase Three, adolescents aged between 12 and 15 years completed questionnaires which included questions on television viewing habits, height and weight. Parents/guardians of children aged between 5 and 8 years completed the same questionnaire on behalf of their children. The questionnaire asked “During a normal week, how many hours a day (24 hours) do you (does your child) watch television?” Responses were categorised as; “short” (<1 hour), “moderate” (1 to ≤3 hours), “long” (3 to ≤5 hours) and “prolonged” (>5 hours).
207,672 adolescents from 37 countries and 77,003 children from 18 countries provided data. Daily television viewing in excess of one hour was reported in 89% of adolescents and 79% of children. Compared with adolescents in the short viewing group, those in the moderate, long and prolonged groups had BMIs that were 0.14 kg/m2, 0.21 kg/m2, 0.30 kg/m2 and 0.08 kg/m2, 0.16 kg/m2 and 0.17 kg/m2 larger for females and males respectively (both P<0.001). Compared with children in the short viewing group, those in the moderate, long and prolonged groups had BMIs that were 0.24 kg/m2, 0.34 kg/m2, 0.36 kg/m2 and 0.19 kg/m2, 0.32 kg/m2 and 0.36 kg/m2 larger for females and males respectively (both P<0.001).
Increased television viewing hours were positively associated with BMI in both adolescents and children with an apparent dose response effect. These findings extend the evidence that television viewing contributes to increased BMI in childhood.
PMCID: PMC3783429  PMID: 24086327
9.  Time trends, ethnicity and risk factors for eczema in New Zealand children: ISAAC Phase Three 
Asia Pacific Allergy  2013;3(3):161-178.
Eczema is a common chronic disease which has significant morbidity and costs for children and their families. Phase One (1993) of the International Study of Asthma and Allergies in Childhood (ISAAC) found a high prevalence of symptoms of eczema in New Zealand.
In Phase Three (2001-3) we aimed to answer these three questions: Is the prevalence of eczema changing over time?; Are there ethnic differences in prevalence?; and What are the risk factors for eczema?
Five New Zealand centres participated in ISAAC Phases One and Three using the same methodology. Questionnaires about ethnicity, symptoms of eczema and environmental factors were completed by parents of 6-7 year olds (children) and self-completed by 13-14 year olds (adolescents). Prevalence and change per year were calculated by centre, ethnicity and gender. Prevalence differences between centres and associations with environmental factors were examined using logistic regression.
There was little change in prevalence over time for the children, and a decrease in prevalence for the adolescents. Prevalence was higher among Māori and even higher among Pacific participants than among European children. Positive associations with current eczema symptoms were found for both age groups for truck traffic in the street of residence, and current paracetamol consumption, and for children only, antibiotics or paracetamol in the 1st year of life. Inverse associations were found with residence in New Zealand less than 5 years, consumption of milk, seafood, and eggs, and presence of a dog in the home.
Eczema remains a significant problem, particularly for young Māori and Pacific New Zealanders in whom less recognition of eczema and poorer access to effective, sustained eczema management may be contributing factors. Reverse causation may explain all the environmental findings apart from truck traffic which is increasing in New Zealand.
PMCID: PMC3736373  PMID: 23956963
Eczema; Children; Adolescents; Ethnicity; New Zealand; Environment
10.  Bed sharing when parents do not smoke: is there a risk of SIDS? An individual level analysis of five major case–control studies 
BMJ Open  2013;3(5):e002299.
To resolve uncertainty as to the risk of Sudden Infant Death Syndrome (SIDS) associated with sleeping in bed with your baby if neither parent smokes and the baby is breastfed.
Bed sharing was defined as sleeping with a baby in the parents’ bed; room sharing as baby sleeping in the parents’ room. Frequency of bed sharing during last sleep was compared between babies who died of SIDS and living control infants. Five large SIDS case–control datasets were combined. Missing data were imputed. Random effects logistic regression controlled for confounding factors.
Home sleeping arrangements of infants in 19 studies across the UK, Europe and Australasia.
1472 SIDS cases, and 4679 controls. Each study effectively included all cases, by standard criteria. Controls were randomly selected normal infants of similar age, time and place.
In the combined dataset, 22.2% of cases and 9.6% of controls were bed sharing, adjusted OR (AOR) for all ages 2.7; 95% CI (1.4 to 5.3). Bed sharing risk decreased with increasing infant age. When neither parent smoked, and the baby was less than 3 months, breastfed and had no other risk factors, the AOR for bed sharing versus room sharing was 5.1 (2.3 to 11.4) and estimated absolute risk for these room sharing infants was very low (0.08 (0.05 to 0.14)/1000 live-births). This increased to 0.23 (0.11 to 0.43)/1000 when bed sharing. Smoking and alcohol use greatly increased bed sharing risk.
Bed sharing for sleep when the parents do not smoke or take alcohol or drugs increases the risk of SIDS. Risks associated with bed sharing are greatly increased when combined with parental smoking, maternal alcohol consumption and/or drug use. A substantial reduction of SIDS rates could be achieved if parents avoided bed sharing.
PMCID: PMC3657670  PMID: 23793691
Prevention; Public Health; Epidemiology; Sids; Bed sharing
11.  Reduced genetic influence on childhood obesity in small for gestational age children 
BMC Medical Genetics  2013;14:10.
Children born small-for-gestational-age (SGA) are at increased risk of developing obesity and metabolic diseases later in life, a risk which is magnified if followed by accelerated postnatal growth. We investigated whether common gene variants associated with adult obesity were associated with increased postnatal growth, as measured by BMI z-score, in children born SGA and appropriate for gestational age (AGA) in the Auckland Birthweight Collaborative.
A total of 37 candidate SNPs were genotyped on 547 European children (228 SGA and 319 AGA). Repeated measures of BMI (z-score) were used for assessing obesity status, and results were corrected for multiple testing using the false discovery rate.
SGA children had a lower BMI z-score than non-SGA children at assessment age 3.5, 7 and 11 years. We confirmed 27 variants within 14 obesity risk genes to be individually associated with increasing early childhood BMI, predominantly in those born AGA.
Genetic risk variants are less important in influencing early childhood BMI in those born SGA than in those born AGA, suggesting that non-genetic or environmental factors may be more important in influencing childhood BMI in those born SGA.
PMCID: PMC3556300  PMID: 23339409
BMI; Childhood obesity; AGA children; SGA children
12.  A postal survey of maternal sleep in late pregnancy 
Sleep disturbances in late pregnancy are common. This study aimed to survey sleep problems in third trimester pregnant women and to compare sleep in the pre-pregnancy period with the third trimester.
Third-trimester women (n=650) were sent a postal survey containing questions relating to sleep experience, including perceived sleep quality, sleep difficulties, night waking, sleep environment, snoring, daytime tiredness and daytime napping. Time periods reported on were before pregnancy and in the last week.
Respondents numbered 244 (38%). Before pregnancy, the mean reported duration of night-time sleep was 8.1 (SD 1.1) hours; in the last week this had decreased to 7.5 (SD 1.8) hours (p<.0001). Only 29% rated their sleep quality in the last week as very good or fairly good, compared with 82% rating their sleep this way before the pregnancy. The main reasons for sleeping difficulties were discomfort (67%) and pain (36%). Snoring increased significantly over the course of the pregnancy, with 37% reporting snoring often or every night in the last week. Those with a pre-pregnancy body mass index of greater than 25 were significantly more likely to snore (p=.01). Only 4% of women had an abnormal Epworth Sleepiness Scale score (i.e. >10) prior to pregnancy, whereas in the last week 33% scored in the abnormal range. Likewise, 5% had regularly napped during the daytime before pregnancy, compared with 41% in the last week.
Sleep problems are common in women in late pregnancy, and increase markedly compared with before pregnancy.
PMCID: PMC3541269  PMID: 23228137
Pregnancy; Sleep disturbances; Sleep quality; Snoring; Daytime sleepiness
13.  Sleep position and risk of late stillbirth 
BMC Pregnancy and Childbirth  2012;12(Suppl 1):A12.
PMCID: PMC3428675
14.  Concluding remarks 
BMC Pregnancy and Childbirth  2012;12(Suppl 1):A14.
PMCID: PMC3428676
16.  Emerging ideas to better understand and prevent stillbirths 
BMC Pregnancy and Childbirth  2012;12(Suppl 1):A1.
PMCID: PMC3428684  PMID: 22950795
17.  Analysis of MMP2 promoter polymorphisms in childhood obesity 
BMC Research Notes  2011;4:253.
Several lines of evidence suggest a possible functional role of Matrix metalloproteinase -2 (MMP-2) in obesity. The aim of this study was to evaluate the role of MMP-2 promoter polymorphisms in percentage body fat (PBF) as a measure of childhood obesity in a New Zealand population.
546 samples from the Auckland Birthweight Collaborative (ABC) study were genotyped for the three MMP-2 promoter SNPs -1306 C/T (rs243865), -1575G/A (rs243866) and -790 T/G (rs243864) using the Sequenom genotyping platform. The results demonstrated that an MMP-2 promoter haplotype is associated with PBF in New Zealand 7 year old children.
We have previously determined that environmental factors are associated with differences in PBF in this study group, and now we have demonstrated a possible genetic contribution.
PMCID: PMC3154167  PMID: 21777433
childhood obesity; percentage body fat; matrix metalloproteinase-2; genetic association
18.  Relationship between obesity, ethnicity and risk of late stillbirth: a case control study 
In high income countries there has been little improvement in stillbirth rates over the past two decades. Previous studies have indicated an ethnic disparity in the rate of stillbirths. This study aimed to determine whether maternal ethnicity is independently associated with late stillbirth in New Zealand.
Cases were women with a singleton, late stillbirth (≥28 weeks' gestation) without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two controls with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Women were interviewed in the first few weeks following stillbirth, or at the equivalent gestation for controls. Detailed demographic data were recorded. The study was powered to detect an odds ratio of 2, with a power of 80% at the 5% level of significance, given a prevalence of the risk factor of 20%. A multivariable regression model was developed which adjusted for known risk factors for stillbirth, as well as significant risk factors identified in the current study, and adjusted odds ratios and 95% confidence intervals were calculated.
155/215 (72%) cases and 310/429 (72%) controls consented. Pacific ethnicity, overweight and obesity, grandmultiparity, not being married, not being in paid work, social deprivation, exposure to tobacco smoke and use of recreational drugs were associated with an increased risk of late stillbirth in univariable analysis. Maternal overweight and obesity, nulliparity, grandmultiparity, not being married and not being in paid work were independently associated with late stillbirth in multivariable analysis, whereas Pacific ethnicity was no longer significant (adjusted Odds Ratio 0.99; 0.51-1.91).
Pacific ethnicity was not found to be an independent risk factor for late stillbirth in this New Zealand study. The disparity in stillbirth rates between Pacific and European women can be attributed to confounding factors such as maternal obesity and high parity.
PMCID: PMC3027197  PMID: 21226915
19.  Risk factors for obesity in 7‐year‐old European children: the Auckland Birthweight Collaborative Study 
Archives of Disease in Childhood  2007;92(10):866-871.
To identify risk factors associated with obesity in primary school children, with a particular focus on those which can be modified. To identify critical periods and growth patterns in the development of childhood obesity.
871 New Zealand European children were enrolled in a longitudinal study at birth and data were collected at birth, 1, 3.5 and 7 years of age. Data collected at 7 years included weight, height, bioelectrical impedance analysis (BIA), television viewing time and a 24 h body movement record (actigraphy). The outcome measure was percentage body fat (PBF), which was calculated at 3.5 and 7 years using BIA. Univariate and multiple regression analyses were carried out using PBF as a continuous variable.
Multivariable analysis found maternal overweight/obesity, maternal age, female gender, sedentary activity time and hours of television viewing to be independently associated with PBF at 7 years. Growth variables (birth weight, rapid weight gain in infancy, early (1–3.5 years) and middle childhood (3.5–7 years)) were also independently associated with adiposity at 7 years. There was a strong correlation between PBF at 3.5 years and PBF at 7 years.
Many primary school aged children start on the trajectory of obesity in the preschool years, which suggests interventions need to start early. Maternal overweight/obesity, television watching, sedentary activity time and rapid weight gain in infancy, early and middle childhood are risk factors for childhood obesity, and are all potentially modifiable.
PMCID: PMC2083229  PMID: 17855436
20.  The continuing decline in SIDS mortality 
Archives of Disease in Childhood  2007;92(7):625-626.
The “Back to Sleep” campaign resulted in a dramatic decrease in sudden infant death syndrome (SIDS) worldwide. SIDS mortality has continued to decline (in New Zealand by 63% from 1993 to 2004), but the reason for this has not been explained. A postal survey found that the proportion of infants sleeping on their back has increased substantially (from 24.4% in 1992 to 72.3% in 2005), and this could account for the 39%–48% decrease in SIDS mortality.
PMCID: PMC2083749  PMID: 17405855
SIDS; sleeping position; mortality trends

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