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1.  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
2.  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
3.  Elevated maternal lipids in early pregnancy are not associated with risk of intrapartum caesarean in overweight and obese nulliparous women 
Maternal overweight and obesity are associated with slower labour progress and increased caesarean delivery for failure to progress. Obesity is also associated with hyperlipidaemia and cholesterol inhibits myometrial contractility in vitro. Our aim was, among overweight and obese nulliparous women, to investigate 1. the role of early pregnancy serum cholesterol and 2. clinical risk factors associated with first stage caesarean for failure to progress at term.
Secondary data analysis from a prospective cohort of overweight/obese New Zealand and Australian nullipara recruited to the SCOPE study. Women who laboured at term and delivered vaginally (n=840) or required first stage caesarean for failure to progress (n=196) were included. Maternal characteristics and serum cholesterol at 14–16 weeks’ of gestation were compared according to delivery mode in univariable and multivariable analyses (adjusted for BMI, maternal age and height, obstetric care type, induction of labour and gestation at delivery ≥41 weeks).
Total cholesterol at 14–16 weeks was not higher among women requiring first stage caesarean for failure to progress compared to those with vaginal delivery (5.55 ± 0.92 versus 5.67 ± 0.85 mmol/L, p= 0.10 respectively). Antenatal risk factors for first stage caesarean for failure to progress in overweight and obese women were BMI (adjusted odds ratio [aOR (95% CI)] 1.15 (1.07-1.22) per 5 unit increase, maternal age 1.37 (1.17-1.61) per 5 year increase, height 1.09 (1.06-1.12) per 1cm reduction), induction of labour 1.94 (1.38-2.73) and prolonged pregnancy ≥41 weeks 1.64 (1.14-2.35).
Elevated maternal cholesterol in early pregnancy is not a risk factor for first stage caesarean for failure to progress in overweight/obese women. Other clinically relevant risk factors identified are: increasing maternal BMI, increasing maternal age, induction of labour and prolonged pregnancy ≥41 weeks’ of gestation.
PMCID: PMC3711839  PMID: 23835080
Cholesterol; Antenatal; Delivery; Obesity; Labour
4.  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
5.  Maternal obesity and postpartum haemorrhage after vaginal and caesarean delivery among nulliparous women at term: a retrospective cohort study 
Increasing rates of postpartum haemorrhage in developed countries over the past two decades are not explained by corresponding changes in risk factors and conjecture has been raised that maternal obesity may be responsible. Few studies investigating risk factors for PPH have included BMI or investigated PPH risk among nulliparous women. The aim of this study was to determine in a cohort of nulliparous women delivering at term whether overweight and obesity are independent risk factors for major postpartum haemorrhage (PPH ≥1000ml) after vaginal and caesarean section delivery.
The study population was nulliparous singleton pregnancies delivered at term at National Women’s Hospital, Auckland, New Zealand from 2006 to 2009 (N=11,363). Multivariable logistic regression was adjusted for risk factors for major PPH.
There were 7238 (63.7%) women of normal BMI, 2631 (23.2%) overweight and 1494 (13.1%) obese. Overall, PPH rates were increased in overweight and obese compared with normal-weight women (n=255 [9.7%], n=233 [15.6%]), n=524 [7.2%], p <.001) respectively. There was an approximate twofold increase in risk in obese nulliparous women that was independent of confounders, adjusted odds ratio [aOR (95% CI)] for all deliveries 1.86 (1.51-2.28). Being obese was a risk factor for major PPH following both caesarean 1.73 (1.32-2.28) and vaginal delivery 2.11 (1.54-2.89) and the latter risk was similar after exclusion of women with major perineal trauma and retained placentae. Three additional factors were consistently associated with risk for major PPH regardless of mode of delivery: increasing infant birthweight, antepartum haemorrhage and Asian ethnicity.
Nulliparous obese women have a twofold increase in risk of major PPH compared to women with normal BMI regardless of mode of delivery. Higher rates of PPH among obese women are not attributable to their higher rates of caesarean delivery. Obesity is an important high risk factor for PPH, and the risk following vaginal delivery is emphasised. We recommend in addition to standard practice of active management of third stage of labour, there should be increased vigilance and preparation for PPH management in obese women.
PMCID: PMC3495044  PMID: 23078042
Nulliparity obesity postpartum haemorrhage
6.  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
7.  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
8.  Obesity and diabetes genes are associated with being born small for gestational age: Results from the Auckland Birthweight Collaborative study 
BMC Medical Genetics  2010;11:125.
Individuals born small for gestational age (SGA) are at increased risk of rapid postnatal weight gain, later obesity and diseases in adulthood such as type 2 diabetes, hypertension and cardiovascular diseases. Environmental risk factors for SGA are well established and include smoking, low pregnancy weight, maternal short stature, maternal diet, ethnic origin of mother and hypertension. However, in a large proportion of SGA, no underlying cause is evident, and these individuals may have a larger genetic contribution.
In this study we tested the association between SGA and polymorphisms in genes that have previously been associated with obesity and/or diabetes. We undertook analysis of 54 single nucleotide polymorphisms (SNPs) in 546 samples from the Auckland Birthweight Collaborative (ABC) study. 227 children were born small for gestational age (SGA) and 319 were appropriate for gestational age (AGA).
Results and Conclusion
The results demonstrated that genetic variation in KCNJ11, BDNF, PFKP, PTER and SEC16B were associated with SGA and support the concept that genetic factors associated with obesity and/or type 2 diabetes are more prevalent in those born SGA compared to those born AGA. We have previously determined that environmental factors are associated with differences in birthweight in the ABC study and now we have demonstrated a significant genetic contribution, suggesting that the interaction between genetics and the environment are important.
PMCID: PMC2928774  PMID: 20712903
9.  Predictors of severe H1N1 infection in children presenting within Pediatric Emergency Research Networks (PERN): retrospective case-control study 
Objective To identify historical and clinical findings at emergency department presentation associated with severe H1N1 outcome in children presenting with influenza-like illness.
Design Multicentre retrospective case-control study.
Setting 79 emergency departments of hospitals associated with the Pediatric Emergency Research Networks in 12 countries.
Participants 265 children (<16 years), presenting between 16 April and 31 December 2009, who fulfilled Centers for Disease Control and Prevention criteria for influenza-like illness and developed severe outcomes from laboratory confirmed H1N1 infection. For each case, two controls presenting with influenza-like illness but without severe outcomes were included: one random control and one age matched control.
Main outcome measures Severe outcomes included death or admission to intensive care for assisted ventilation, inotropic support, or both. Multivariable conditional logistic regression was used to compare cases and controls, with effect sizes measured as adjusted odds ratios.
Results 151 (57%) of the 265 cases were male, the median age was 6 (interquartile range 2.3-10.0) years, and 27 (10%) died. Six factors were associated with severe outcomes in children presenting with influenza-like illness: history of chronic lung disease (odds ratio 10.3, 95% confidence interval 1.5 to 69.8), history of cerebral palsy/developmental delay (10.2, 2.0 to 51.4), signs of chest retractions (9.6, 3.2 to 29.0), signs of dehydration (8.8, 1.6 to 49.3), requirement for oxygen (5.8, 2.0 to 16.2), and tachycardia relative to age).
Conclusion These independent risk factors may alert clinicians to children at risk of severe outcomes when presenting with influenza-like illness during future pandemics.
PMCID: PMC3741086  PMID: 23940290

Results 1-9 (9)