Predictors of vitamin D status in pregnant women in New Zealand.

INTRODUCTION: Newborn vitamin D status is largely determined by maternal vitamin D status during pregnancy. New Zealand has a sun avoidance health policy and minimal dietary vitamin D fortification. Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/L) is present in 57% of a sample of newborns from Christchurch and Wellington. To inform vitamin D supplementation policy, our aim was to describe the frequency of, and factors associated with, vitamin D deficiency during pregnancy. METHODS: We enrolled an ethnically diverse sample of pregnant women from a community maternity clinic in South Auckland, New Zealand, with serum 25(OH)D concentration measured at 27 weeks gestation. We examined the associations of enrolment season, maternal demographics, health, sunlight exposure and vitamin D intake with vitamin D deficiency. RESULTS: Vitamin D deficiency was present in 109/259 (42%). Enrolment season (P<0.001) and ethnicity (P=0.003) were independently associated with the odds of vitamin D deficiency, but not sunlight exposure or dietary vitamin D intake. Of those enrolled in winter (June-August)/spring (September-November), vitamin D deficiency was present in 43% of European, 67% of Maori, 80% of Pacific and 59% of women of other ethnic groups. CONCLUSIONS: These findings suggest that New Zealand's targeted strategy for vitamin D supplementation may miss up to 42% of women with vitamin D deficiency in our population. Supplementation for all pregnant women during winter/spring could be an appropriate intervention for prevention of vitamin D deficiency during pregnancy in New Zealand.

Auditory evoked arousal responses of 3-month-old infants exposed to methamphetamine in utero: a nap study.

AIM: To investigate whether or not infants exposed to methamphetamine prenatally have impaired arousal responses from sleep. METHODS: The polygraphic nap studies involved 42 infants aged 3 months exposed to methamphetamine in utero and a comparison group of 57 infants. A proportion of mothers in both groups smoked cigarettes and/or marijuana and drank alcohol during pregnancy. White noise from 50 to 100 decibels (dB) was administered at 10 dB intervals twice within non-rapid eye movement (NREM) and rapid eye movement (REM) sleep states and arousal thresholds measured. RESULTS: Combining groups, 306 tests were completed (128 and 178 within REM and NREM sleep, respectively) and infants were more likely to wake at lower thresholds in REM than NREM sleep (hazard ratio 5.58; 95% CI, 3.78-8.23 p < 0.0001). No significant differences in arousal threshold were found between methamphetamine and comparison groups, before or after controlling for other substance use (NREM sleep; 0.98, 95% CI, 0.60-1.59 and REM sleep; 1.03, 95% CI, 0.56-1.89). CONCLUSIONS: These findings suggest that arousal responses of methamphetamine-exposed infants remain intact, providing no support for the hypothesis that prenatal exposure could increase their vulnerability to sudden infant death syndrome (SIDS) through arousal deficits.

Beckwith Wiedemann imprinting defect found in leucocyte but not buccal DNA in a child born small for gestational age.

BACKGROUND: Loss of methylation (LOM) at imprinting control region (ICR) 1 or LOM at ICR 2 on chromosome 11p15 in leucocyte DNA is commonly used to diagnose the imprinting disorders Silver Russell syndrome (SRS) characterized by growth restriction or Beckwith Wiedemann syndrome (BWS) characterized by overgrowth, respectively. CASE PRESENTATION: A child was normally conceived and born by caesarian section to a healthy 19 year old smoking mother (G2P1) at 38 weeks gestation, with SGA (birthweight SDS -2.44), placenta weight 250g (normal histology), with an umbilical hernia and transient neonatal hypoglycemia but no other features of BWS.The methylation status at 11p15 region was initially investigated by multiplex ligation dependent probe amplification (MLPA). Subsequently, methylation-specific (ms) PCR was performed to screen for this and other imprinted loci abnormalities at PLAG1 (6q24), IGF2R (6q27), GRB10 (7p12), PEG1/MEST (7q32), DLK1 (14q32), SNRPN (15q11); PEG3 (19q32), NESPAS/GNAS (20q13).Leucocyte DNA methylation was normal at ICR1 but markedly reduced at ICR2 using both MLPA and ms-PCR, and no other anomalies of imprinting were detected. Buccal DNA methylation was normal at all imprinted sites tested. CONCLUSION: This is the first report of an isolated LOM at ICR2 in leucocyte but not buccal DNA in a normally conceived singleton SGA child without overt SRS or BWS.

Time trends and risk factors for rhinoconjunctivitis in New Zealand children: an International Study of Asthma and Allergies in Childhood (ISAAC) survey.

AIM: To investigate prevalence, time trends and factors associated with rhinitis and rhinoconjunctivitis not related to acute infections in New Zealand. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) surveyed children aged 6-7 and 13-14 years for symptoms of these conditions. Five New Zealand centres were surveyed on two occasions (Phase One and Phase Three) 8-10 years apart. In Phase Three, questions were included on environmental factors, which might be associated with rhinoconjunctivitis. We report findings related to symptoms of rhinoconjunctivitis among 24 190 New Zealand children. RESULTS: Symptoms of rhinoconjunctivitis in the past year were reported in 11.4% of 6- to 7-year-old children and 18% of 13- to 14-year-old adolescents in Phase Three compared with 9.5 and 19.1%, respectively, in Phase One. Severe symptoms of rhinoconjunctivitis were reported in 0.5% of children and 0.8% of adolescents. Current symptoms were more common in males at 6-7 years and in females of 13-14 years, and Maori and Pacific Island ethnic groups had higher prevalence compared with those of European descent, especially in the older age group. For immigrant children, there was a very strong positive relationship between symptoms and length of time resident in New Zealand, supporting the probable importance of environmental factors. A positive association was found between symptoms and use of paracetamol in infancy or in the last year, and weaker associations were noted for antibiotic use, exercise, and regular pasta ingestion. CONCLUSIONS: Further study of environmental factors is recommended.

Reanalyses of case-control studies examining the temporal association between sudden infant death syndrome and vaccination.

In this paper we examine different time periods after vaccinations and investigate whether the risk of sudden infant death is different during the post-vaccination period than at other times. Three already published case-control studies are re-examined in this context. Several evaluation approaches are presented. The recently developed self-controled case series (SCCS) method for terminal events, which only takes the cases into account, is used in addition. There is no increased or reduced risk of sudden infant death during the period after the vaccination. The previously reported protective effect seen in case contol studies is based on the inclusion of unvaccinated cases. The results of the case-control analysis of one study is affected by two confounders. The SCCS method for terminal events, in which all time-independent confounders are eliminated, is an alternative to case-control analysis when it comes to the temporal association between exposed time periods and SIDS after vaccination.

Association between maternal sleep practices and risk of late stillbirth: a case-control study.

OBJECTIVES: To determine whether snoring, sleep position, and other sleep practices in pregnant women are associated with risk of late stillbirth. DESIGN: Prospective population based case-control study. SETTING: Auckland, New Zealand CASES: 155 women with a singleton late stillbirth (≥ 28 weeks' gestation) without congenital abnormality born between July 2006 and June 2009 and booked to deliver in Auckland. CONTROLS: 310 women with single ongoing pregnancies and gestation matched to that at which the stillbirth occurred. Multivariable logistic regression adjusted for known confounding factors. MAIN OUTCOME MEASURE: Maternal snoring, daytime sleepiness (measured with the Epworth sleepiness scale), and sleep position at the time of going to sleep and on waking (left side, right side, back, and other). RESULTS: The prevalence of late stillbirth in this study was 3.09/1000 births. No relation was found between snoring or daytime sleepiness and risk of late stillbirth. However, women who slept on their back or on their right side on the previous night (before stillbirth or interview) were more likely to experience a late stillbirth compared with women who slept on their left side (adjusted odds ratio for back sleeping 2.54 (95% CI 1.04 to 6.18), and for right side sleeping 1.74 (0.98 to 3.01)). The absolute risk of late stillbirth for women who went to sleep on their left was 1.96/1000 and was 3.93/1000 for women who did not go to sleep on their left. Women who got up to go to the toilet once or less on the last night were more likely to experience a late stillbirth compared with women who got up more frequently (adjusted odds ratio 2.28 (1.40 to 3.71)). Women who regularly slept during the day in the previous month were also more likely to experience a late stillbirth than those who did not (2.04 (1.26 to 3.27)). CONCLUSIONS: This is the first study to report maternal sleep related practices as risk factors for stillbirth, and these findings require urgent confirmation in further studies.

A structural study of norovirus 3C protease specificity: binding of a designed active site-directed peptide inhibitor.

Noroviruses are the major cause of human epidemic nonbacterial gastroenteritis. Viral replication requires a 3C cysteine protease that cleaves a 200 kDa viral polyprotein into its constituent functional proteins. Here we describe the X-ray structure of the Southampton norovirus 3C protease (SV3CP) bound to an active site-directed peptide inhibitor (MAPI) which has been refined at 1.7 Å resolution. The inhibitor, acetyl-Glu-Phe-Gln-Leu-Gln-X, which is based on the most rapidly cleaved recognition sequence in the 200 kDa polyprotein substrate, reacts covalently through its propenyl ethyl ester group (X) with the active site nucleophile, Cys 139. The structure permits, for the first time, the identification of substrate recognition and binding groups in a noroviral 3C protease and thus provides important new information for the development of antiviral prophylactics.

Getting tangled in red tape: the challenges of doing clinical research in New Zealand.

Regulations and the number of forms that require completion remain a major frustration for researchers attempting to establish a clinical research project. It is essential that clinical research is of the highest standard and abides by ethical principles. However, the duplication of information required and lack of co-ordination between national and local ethics and research committees is a hindrance to conducting clinical research. This publication highlights the pitfalls in our current system with a case study, and suggests changes to the ethical review process that may aid researchers in establishing clinical research.

Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study.

BACKGROUND: 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. METHODS: 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.

Placental chorioamnionitis at term: epidemiology and follow-up in childhood.

The objective was to identify histologic chorioamnionitis ("amnionitis") in the placental disc at term and to investigate associations with demographic, lifestyle, and pregnancy factors and with allergic diseases, atopy, and intelligence quotients in childhood. The setting was a population-based case control study of small-for-gestational age infants at term. One thousand and twelve placentas were assessed histologically for amniocentric inflammation of fetal and/or maternal origin using conservative criteria. Data were collected at birth by maternal interview and from medical records. Follow-up data were obtained from 439 and 418 children at 3.5 and 7 years of age, respectively. Amnionitis was identified in 145 placentas (14.3%), with maternal reaction in 97.2% and fetal reaction in 48.3%. In multivariable analysis any amnionitis was significantly associated with a time from membrane rupture to delivery of 6 to 12 hours, but not with times beyond 12 hours, a duration of total labor exceeding 12 hours, ethnicity (incidences ranging from 8.8% in Indians to 23.5% in Chinese), male infant gender, and anaesthesia during labor, and amnionitis was negatively associated with induction of labor. No associations were found with later allergic disease, atopy, or intelligence quotients. This high incidence of histologic amnionitis at term is similar to historical estimates, despite large reductions in time-related risk factors during labor. Significant ethnic variations contribute to the high incidence and are unexplained, but variation in genetic polymorphisms for susceptibility factors is a possibility. "Silent" histologic amnionitis is a frequent cause of fetal immune activation with potential effects in later life.

Determinants of cognitive ability at 7 years: a longitudinal case-control study of children born small-for-gestational age at term.

The aim of this study was to identify the determinants of children's intelligence at 7 years, including pregnancy, postnatal, demographic factors, and small-for-gestational age (SGA) birth at term. Information was collected at birth (n = 871), 1 year (n = 744), 3.5 years (n = 550), and 7 years (n = 591). Approximately half of the children in this study were born SGA (birthweight

Has the prevalence and severity of symptoms of asthma changed among children in New Zealand? ISAAC Phase Three.

AIM: To investigate time trends in prevalence of symptoms of asthma by repeating, during 2001-3 (Phase Three), the International Study of Asthma and Allergies in Childhood (ISAAC) Phase One study that was conducted in New Zealand in 1992-3. METHODS: ISAAC Phase Three involved repeating the cross-sectional questionnaire survey of two age groups of school children (6-7 years and 13-14 years, children and adolescents respectively) using the same methodology as Phase One. In New Zealand it was conducted in Auckland, Bay of Plenty, Christchurch, Nelson, and Wellington. RESULTS: After 9 years, reported asthma ever increased from 24.6% to 30.2% in children and from 24.1% to 32.4% in adolescents (p<0.001). Current wheeze (written questionnaire) significantly decreased in children from 23.6% to 22.2% (p=0.002) and in adolescents from 29.7% to 26.7% (p=0.047), and for the video questionnaire from 18.1% to 11.1% (p<0.001). There was a significant reduction in wheezing limiting speech from 5.0% to 3.7% in children, and 7.9% to 6.2% in adolescents. Little regional variation was found. A higher proportion of children with asthma symptoms now report having ever had asthma. CONCLUSIONS: The decrease in prevalence and severity of symptoms of asthma is encouraging, but the reasons for these trends are currently unclear. Increases in asthma labelling are likely to be due to greater awareness of asthma. A trend of decreasing prevalence of asthma symptoms, if maintained, has positive implications for lessened burden of disease among asthmatics and lowered cost of treatment.

Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC).

BACKGROUND: Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC) was designed to allow worldwide comparisons of the prevalence of asthma symptoms. In phase III the phase I survey was repeated in order to assess changes over time. METHODS: The phase I survey was repeated after an interval of 5-10 years in 106 centres in 56 countries in children aged 13-14 years (n = 304,679) and in 66 centres in 37 countries in children aged 6-7 years (n = 193,404). RESULTS: The mean symptom prevalence of current wheeze in the last 12 months changed slightly from 13.2% to 13.7% in the 13-14 year age group (mean increase of 0.06% per year) and from 11.1% to 11.6% in the 6-7 year age group (mean increase of 0.13% per year). There was also little change in the mean symptom prevalence of severe asthma or the symptom prevalence measured with the asthma video questionnaire. However, the time trends in asthma symptom prevalence showed different regional patterns. In Western Europe, current wheeze decreased by 0.07% per year in children aged 13-14 years but increased by 0.20% per year in children aged 6-7 years. The corresponding findings per year for the other regions in children aged 13-14 years and 6-7 years, respectively, were: Oceania (-0.39% and -0.21%); Latin America (+0.32% and +0.07%); Northern and Eastern Europe (+0.26% and +0.05%); Africa (+0.16% and +0.10%); North America (+0.12% and +0.32%); Eastern Mediterranean (-0.10% and +0.79%); Asia-Pacific (+0.07% and -0.06%); and the Indian subcontinent (+0.02% and +0.06%). There was a particularly marked reduction in current asthma symptom prevalence in English language countries (-0.51% and -0.09%). Similar patterns were observed for symptoms of severe asthma. However, the percentage of children reported to have had asthma at some time in their lives increased by 0.28% per year in the 13-14 year age group and by 0.18% per year in the 6-7 year age group. CONCLUSIONS: These findings indicate that international differences in asthma symptom prevalence have reduced, particularly in the 13-14 year age group, with decreases in prevalence in English speaking countries and Western Europe and increases in prevalence in regions where prevalence was previously low. Although there was little change in the overall prevalence of current wheeze, the percentage of children reported to have had asthma increased significantly, possibly reflecting greater awareness of this condition and/or changes in diagnostic practice. The increases in asthma symptom prevalence in Africa, Latin America and parts of Asia indicate that the global burden of asthma is continuing to rise, but the global prevalence differences are lessening.

Dietary patterns of New Zealand European preschool children.

AIMS: To record and describe the dietary patterns of a large group of New Zealand (NZ) European preschool children and to compare these with NZ Ministry of Health (MOH) food and nutrition guidelines. METHODS: Mothers were interviewed when children enrolled in the Auckland Birthweight Collaborative (ABC) study were seen at 3.5 years of age. Approximately half of the children in the study were born small for gestational age (SGA =10th percentile) and the remaining were born appropriate for gestational age (AGA >10th percentile). Food frequency information was collected on 549 New Zealand European children. The analysis utilised weighting to allow for the disproportionate sampling of children born SGA. RESULTS: Compared with nutritional guidelines, 27% and 54% of preschool children did not eat the recommended two or more servings of fruit per day or two or more servings of vegetables per day, respectively; 93% of children did not eat breads and cereals the recommended four or more times a day. CONCLUSION: A notable proportion of children were not eating fruit and vegetables at levels recommended by the MOH. Preschool children's food frequency patterns were, however, similar to patterns reported for school-aged children in the National Children's Nutrition Survey.

SIDS-protective infant care practices among Auckland, New Zealand mothers.

AIM: To survey the knowledge and implementation of sudden infant death syndrome (SIDS)-protective infant care practices in mothers of infants aged less than 4 months. METHODS: A postal survey was carried out of knowledge of SIDS risk factors and infant care practices of 200 mothers with infants aged 6-8 weeks and 3-4 months. RESULTS: Mothers who could cite supine sleeping as protective comprised 84%, while 73% knew that smoking was a risk factor. Fewer knew that room sharing, keeping the face clear of bedding, and avoiding bed sharing and overheating are also protective. Fifty-four percent of the infants usually room-share with a parent, while 39% both room-share and sleep in their own bed. Sixteen percent usually co-slept for part or all of the night. Nearly one-third used pacifiers. Mothers who smoked during pregnancy comprised 8%, while 7% had smoked in the last 24 hours. Most infants (97%) had been breastfed at some time. CONCLUSIONS: Maternal education of the benefits of supine sleeping, not smoking, and breastfeeding appear well understood by these mothers. However, more education is needed about other SIDS-protective behaviours such as keeping the face clear and sleeping the infant in their own bed in the parents' room.

Modifiable risk factors for SIDS in Germany: results of GeSID.

BACKGROUND: The incidence of sudden infant death syndrome (SIDS) has been falling in Germany over the last decade. However, little is known about the prevalence and the importance of well-known risk factors in Germany since a local prevention campaign in 1992. DESIGN: A 3-y, population-based, case-control study was conducted in half of Germany, consisting of 333 cases. All sudden and unexpected deaths in infancy, if they fitted the inclusion criteria, were included in the study. Parental interview was carried out soon after the death, and three living control infants, matched for age, gender, region and sleep time, were recruited. RESULTS: The prevalence of placing infants prone to sleep was only 4% in the control group, but this was associated with a markedly increased risk of SIDS (adjusted odds ration, aOR=6.08). Other modifiable risk factors for SIDS were: maternal smoking during pregnancy, breastfeeding for less than 2 wk (aOR=1.71) and co-sleeping (aOR=2.71), while using a pacifier during the last sleep reduced the risk (aOR=0.39). CONCLUSIONS: Previously recognized risk factors for SIDS also occur in Germany. Despite knowledge about the major modifiable risk factors for SIDS, these factors are still present in Germany. To reduce the incidence of SIDS in Germany, a continued effort is needed to inform all parents about preventable risk factors for SIDS.

Quantification of plagiocephaly and brachycephaly in infants using a digital photographic technique.

OBJECTIVES: The aims of the study were: (1) to develop a technique to quantify plagiocephaly that is safe, accurate, objective, easy to use, well tolerated, and inexpensive; and (2) to compare this method with tracings from a flexicurve ruler. DESIGN: A case-control study of 31 case infants recruited from outpatient plagiocephaly clinics and 29 control infants recruited from other pediatric outpatient clinics. PARTICIPANTS: Infants in the study had been diagnosed with nonsynostotic plagiocephaly or brachycephaly and were between 2 and 12 months old. INTERVENTIONS: Infants' head shapes were measured using (a) digital photographs of a head circumference band and (b) a flexicurve ruler. Flexicurve tracings were scanned, and both the digital photos and the scanned flexicurve tracings were analyzed using a custom-written computer program. MAIN OUTCOME MEASURES: The oblique cranial length ratio was used to quantify cranial asymmetry, and the cephalic index was used to quantify the degree of brachycephaly. RESULTS: The infants tolerated the photo technique better than the flexicurve. Also, mothers preferred the photo technique. There was less within-subject variance for the photos than for the flexicurve measurements. The results suggested that an oblique cranial length ratio of >or= 106% can define plagiocephaly and that a cephalic index of >or= 93% can define brachycephaly. CONCLUSIONS: The photographic technique was better accepted and more repeatable than the flexicurve measuring system. We propose that "normal" head shape is indicated in infants with both an oblique cranial length ratio of less than 106% and a cephalic index of less than 93%.

Pulmonary aspiration of gastric contents and the sudden infant death syndrome.

OBJECTIVE: To determine ante-mortem and post-mortem risk factors for the finding of gastric contents in pulmonary airways (aspiration of gastric contents) at post-mortem examination in the sudden infant death syndrome (SIDS). METHODS: There were 217 post-neonatal deaths in the Auckland region of the New Zealand Cot Death Study. No deaths were certified as due to aspiration of gastric contents. There were 138 SIDS cases. The parents of 110 (80%) of these cases were interviewed. Histological sections from the periphery of the lungs in 99 of the 110 cases were reviewed for evidence of aspiration of gastric contents. A wide range of variables were analysed in SIDS cases with and without aspiration to determine risk factors. RESULTS: Aspiration of gastric contents was identified in 37 (37%) of SIDS cases. Aspiration was of mild-to-moderate degree and in no case was severe and a potential cause of death. Finding infants on their backs at death (P = 0.024) and conducting the post-mortem on the day after the death or subsequently (P = 0.033) were statistically significant variables linked to identification of aspiration. Position placed to sleep, symptoms of gastro-oesophageal reflux and other variables were not related to aspiration. CONCLUSIONS: The only determinants for aspiration of gastric contents identified were agonal or post-mortem events, supporting the contention that aspiration has limited relevance to the mechanism of SIDS.

Teenage use of GP care for moderate to severe asthma in Auckland, New Zealand.

OBJECTIVES: To describe and understand teenagers' frequency of attendance for General Practitioner (GP) care of moderate to severe asthma in the Auckland region. METHODS: Ten Auckland schools identified 510 children aged 13-14 years with breathing problems, who were invited to complete a screening questionnaire. 271 children participated, of whom 114 had moderate to severe asthma. RESULTS: 39% of the 114 had made 0-1 GP visit for asthma, and 17% made 'greater than and equal to' 5 visits. Low attendees (0-1 visit) were disproportionately New Zealand European. High attendees ('greater than and equal to' 5 visits) tended to be Maori and/or Pacific Islanders. Half of the teenagers attended GP asthma care as often as it wanted, independently of ethnicity; 62% tell their parents when they cannot manage their asthma; and 29% must pay for GP care. Expected attendance was increased for Maori and Pacific students versus others by 77% (p=0002), and by asthma of increased severity (p<0.001). Teenager resistance to accessing GP asthma care reduced expected attendance by 24% (p=0.003). CONCLUSIONS: Maori and Pacific peoples have traditionally faced barriers to accessing GP care, but their their more frequent attendance (than New Zealand Europeans) in this case, challenges whether such barriers persist, at least for acute care of moderate to severe asthma.