Dietary intakes of iron, folate, and vitamin B12 during pregnancy and correlation with maternal hemoglobin and fetal growth: findings from the ROLO longitudinal birth cohort study.

PURPOSE: Dietary micronutrient intakes of iron, folate and vitamin B12 are known to influence hemoglobin. Low maternal hemoglobin (maternal anemia) has been linked to low birthweight and other adverse health outcomes in the fetus and infant. Our primary aim was to explore relationships between maternal dietary micronutrient intakes, maternal full blood count (FBC) parameters and fetal abdominal circumference (AC) and estimated fetal weight (EFW) growth trajectories. Secondarily, we aimed to assess relationships between maternal dietary micronutrient intakes, maternal hemoglobin values and placental weight and birthweight. METHODS: Mother-child pairs (n = 759) recruited for the ROLO study were included in this analysis. Maternal dietary micronutrient intakes were calculated from food diaries completed during each trimester of pregnancy. FBC samples were collected at 13- and 28-weeks' gestation. Fetal ultrasound measurements were recorded at 20- and 34-weeks' gestation. Growth trajectories for AC and EFW were estimated using latent class trajectory mixture models. RESULTS: Dietary intakes of iron and folate were deficient for all trimesters. Mean maternal hemoglobin levels were replete at 13- and 28-weeks' gestation. Dietary iron, folate and vitamin B12 intakes showed no associations with fetal growth trajectories, placental weight or birthweight. Lower maternal hemoglobin concentrations at 28 weeks' gestation were associated with faster rates of fetal growth and larger placental weights and birthweights. CONCLUSION: The negative association between maternal hemoglobin at 28 weeks' gestation and accelerated fetal and placental growth may be due to greater consumption of maternal iron and hemoglobin by fetuses' on faster growth trajectories in addition to placental biochemical responses to lower oxygen states.

The human tRNA-guanine transglycosylase displays promiscuous nucleobase preference but strict tRNA specificity.

Base-modification can occur throughout a transfer RNA molecule; however, elaboration is particularly prevalent at position 34 of the anticodon loop (the wobble position), where it functions to influence protein translation. Previously, we demonstrated that the queuosine modification at position 34 can be substituted with an artificial analogue via the queuine tRNA ribosyltransferase enzyme to induce disease recovery in an animal model of multiple sclerosis. Here, we demonstrate that the human enzyme can recognize a very broad range of artificial 7-deazaguanine derivatives for transfer RNA incorporation. By contrast, the enzyme displays strict specificity for transfer RNA species decoding the dual synonymous NAU/C codons, determined using a novel enzyme-RNA capture-release method. Our data highlight the broad scope and therapeutic potential of exploiting the queuosine incorporation pathway to intentionally engineer chemical diversity into the transfer RNA anticodon.

De-novo designed ß-lysine derivatives can both augment and diminish the proliferation rates of E. coli through the action of Elongation Factor P.

An investigation into the effect of modified ß-lysines on the growth rates of eubacterial cells is reported. It is shown that the effects observed are due to the post translational modification of Elongation Factor P (EFP) with these compounds catalysed by PoxA. PoxA was found to be remarkably promiscuous, which allowed the activity of a wide range of exogenous ß-lysines to be examined. Two chain-elongated ß-lysine derivatives which differ in aminoalkyl chain length by only 2 carbon units exhibited opposing biological activities - one promoting growth and the other retarding it. Both compounds were shown to operate through modification of EFP.

Ecological factors and childhood eating behaviours at 5 years of age: findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Individual differences in children eating behaviours have been linked with childhood overweight and obesity. The determinants of childhood eating behaviours are influenced by a complex combination of hereditary and ecological factors. This study examines if key ecological predictors of childhood overweight; maternal socio-economic status (SES), children's screen time, and childcare arrangements, are associated with eating behaviours in children aged 5-years-old. METHODS: This is secondary, cross-sectional analysis of the ROLO (Randomized COntrol Trial of LOw glycemic diet in pregnancy) study, using data from the 5-year follow-up (n = 306). Weight, height, and body mass index (BMI) were obtained from mothers and children at the 5-year follow-up. Children's BMI z-scores were calculated. SES was determined using maternal education level and neighborhood deprivation score. Information on children's screen time and childcare arrangements were collected using lifestyle questionnaires. Children's eating behaviours were measured using the Children's Eating Behaviour Questionnaire (CEBQ). Multiple linear regression, adjusted for potential confounders, assessed associations between maternal SES, screen time and children's eating behaviours. One-way ANOVA, independent sample t-tests and Spearman's correlation examined childcare exposure and children's eating behaviour. RESULTS: Mothers in the lowest SES group had higher BMI and were younger than those in the highest SES group (p = < 0.001, p = 0.03 respectively). In adjusted analysis, the lowest SES group was associated with a 0.463-point higher mean score for 'Desire to Drink' (95% CI = 0.054,0.870, p = 0.027) and higher 'Slowness to Eat' (B = 0.388, 95% CI = 0.044,0.733, p = 0.027) when compared with the highest SES group. Screen time (hours) was associated with higher 'Food Fussiness' (B = 0.032, 95% CI = 0.014,0.051, p = 0.001). Those who attended childcare had higher scores for 'Desire to Drink'(p = 0.046). No relationship was observed between longer duration (years) spent in childcare and eating behaviours. CONCLUSIONS: In this cohort, the ecological factors examined had an influence on children's eating behaviours aged 5-years-old. Our results illustrate the complexity of the relationship between the child's environment, eating behaviour and children's body composition. Being aware of the ecological factors that impact the development of eating behaviours, in the pre-school years is vital to promote optimal childhood appetitive traits, thus reducing the risk of issues with excess adiposity long-term.

Maternal dietary quality during pregnancy and child appetitive traits at 5-years-old: Findings from the ROLO longitudinal birth cohort study.

Maternal diet during pregnancy is an important determinant of birth outcomes and offspring health. The relationship between maternal diet quality during pregnancy and the development of appetitive traits in early childhood has not been extensively researched. We examined associations of maternal diet quality during pregnancy with child appetitive traits at 5 years old. This is a secondary analysis of the ROLO longitudinal birth cohort study. We assessed maternal diet during pregnancy using 3-day food diaries and evaluated diet quality using the Alternative Healthy Eating Index, modified for pregnancy (AHEI-P). Children's appetitive traits at 5-years-old were assessed using the Child Eating Behaviour Questionnaire (CEBQ) (n = 306). Average AHEI-P score over trimesters was calculated and stratified into tertiles. Maternal and child characteristics were examined across AHEI-P tertiles. Multiple linear regression was conducted to explore associations between maternal AHEI-P scores in each trimester and child appetitive traits at 5-years-old. Women with low AHEI-P scores were younger at childbirth and had higher BMI. In adjusted linear regression maternal AHEI-P was negatively associated with child 'Desire to Drink' (Trimester 1: B = -0.014, 95% CI = -0.025, -0.002, p = 0.017; Trimester 2: B = -0.013, 95% CI = -0.025, -0.001, p = 0.035). Trimester 3 AHEI-P was not associated with any child appetitive traits. Maternal diet quality in pregnancy may provide an early opportunity to positively influence the development of offspring's appetitive traits.

Stability of child appetitive traits and association with diet quality at 5 years and 9-11 years old: Findings from the ROLO longitudinal birth cohort study.

BACKGROUND: We explored change in child appetitive traits from 5 to 9-11 years old and examined associations between appetitive traits at both timepoints and child diet quality. METHODS: This is secondary analyses of the ROLO longitudinal birth cohort study, including mother-child dyads from the 5 and 9-11-year old follow-up. The Children's Eating Behaviour Questionnaire measured child appetitive traits, with 167 children having matched data for both timepoints. The Healthy Eating Index (HEI) measured diet quality. Linear mixed models and multiple linear regression were completed. RESULTS: Mean (SD) score for 'Emotional Overeating' (1.63 (0.51) vs. 1.99 (0.57), p = <0.001) and 'Enjoyment of Food' (3.79 (0.72) vs. 3.98 (0.66), p = <0.001) increased from 5 to 9-11 years. Mean score for 'Desire to Drink' (2.63 (0.94) vs. 2.45 (0.85), p = 0.01), 'Satiety Responsiveness (3.07 (0.66) vs. 2.71 (0.66), p = <0.001), 'Slowness Eating' (3.02 (0.77) vs. 2.64 (0.78), p = <0.001), and 'Food Fussiness' (3.00 (1.04) vs. 2.81 (0.96), p = 0.001) decreased. At 5-years-old, 'Food Responsiveness' and 'Enjoyment of Food' were positively associated with HEI and 'Desire to Drink', 'Satiety Responsiveness' and 'Food Fussiness' were negatively associated with HEI. At 9-11-years, 'Enjoyment of Food' was positively and 'Desire to Drink' and 'Food 'Fussiness' were negatively associated with HEI. CONCLUSIONS: Food approach appetitive traits increased over time, whereas food avoidant appetitive traits tended to decrease. At both time points 'Food Fussiness' and 'Desire to Drink" were inversely associated with HEI. Further research on how appetitive traits track over childhood and how this relates to dietary quality and weight is warranted.

Including the child's voice in research from a longitudinal birth cohort: insights from the ROLO young person's advisory group.

BACKGROUND: Public and patient involvement (PPI) through Young Person's Advisory Groups (YPAG) enables children to provide guidance and insight into research activities. PPI is an important characteristic of research, however, to date, most collaboration has been with adults. Also, few YPAGs have been established within the Irish setting. The ROLO (Randomised cOntrol trial of a LOw glycaemic index diet in pregnancy to prevent macrosomia) YPAG was established in July 2020 to identify the research priorities of a group of healthy Irish children who are part of a longitudinal birth cohort. We aimed to describe this process and the key insights to date. METHODS: The ROLO study is a longitudinal birth cohort which has followed-up mother-child dyads at multiple timepoints over 10 years. Mothers actively involved in the study were contacted by the research team to invite their ROLO child and older sibling to participate in the YPAG. Meetings were conducted virtually between July 2020 and February 2022. Researchers encouraged free expression of views amongst the children regarding their research interests. Meetings were recorded, transcribed verbatim and analysed for themes based on the topics most frequently discussed and considered important to participants. RESULTS: In all, seven ROLO children and six older siblings attended four ROLO YPAG meetings. Participants were aged between nine to fifteen years old. Four key themes were identified; study children viewed their identity as part of a longitudinal birth cohort as positive and unique; study children considered the fitness test and body measurements as fun aspects related to their participation; all children considered the impact and use of social media as an important form of communication; and all participants expressed interest in attaining new health-related information and learning opportunities. Children suggested topics such as mental health, future viruses, organ transplants, cancer, and the effect of technology and chemicals on the body were important for future research. CONCLUSION: The ROLO YPAG offers promising scope for continued collaboration. The themes identified from the meetings contribute to a gap in the literature which will guide future research activities, particularly with children, in view of study design, relevance, and by communication strategies. Trial Details: ISRCTN54392969 registered at www.isrctn.com .

The ROLO pregnancy study took place in the National Maternity Hospital in Dublin Ireland. It started in 2007 and ended in 2011. The researchers recorded what women were eating. They also measured the weight of the baby at birth. Since then, ROLO mothers and their children were invited to come back to the study. Now the children of the study are 9­11 years of age.The researchers invited members of the ROLO study to speak with them. They wanted to know what research was important to them. They set up a group called the ROLO Family Advisory Committee in 2017. This group of parents and researchers meet once a year. The group thought it was important to include children as well. They made a new group called the ROLO Young Person's Advisory Group in 2020. The group has 7 ROLO children and 6 older siblings. The members are aged between 9 and 15-years-old. The children and researchers have met four times so far.The researchers found four key themes. Study children saw their identity as being part of a longitudinal birth cohort as positive and unique. Study children liked the fitness test and body measurements. All children thought that social media was an important form of communication. All children were interested in learning new information on how their bodies worked.Involving this group of children is important. It will make our research more relevant. Other researchers who want to involve children can learn from our experience.

The impact of macrosomia on cardiometabolic health in preteens: findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Macrosomia (birthweight ≥ 4 kg or ≥ 4.5 kg) is strongly associated with a predisposition to childhood obesity, which in turn is linked with adverse cardiometabolic health. Despite this, there is a lack of longitudinal investigation on the impact of high birthweight on cardiometabolic outcomes in youth. The preteen period represents an important window of opportunity to further explore this link, to potentially prevent cardiometabolic profiles worsening during puberty. METHODS: This is a secondary analysis of 9-11-year-olds (n = 405) born to mothers in the ROLO longitudinal birth cohort study, who previously delivered an infant with macrosomia. Preteens were dichotomised into those born with and without macrosomia, using two common cut-off criteria (birthweight ≥ 4 kg (n = 208) and < 4 kg; ≥ 4.5 kg (n = 65) and < 4.5 kg). Cardiometabolic health was assessed using anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance (20-m shuttle run test), and non-fasting serum biomarkers for a subgroup (n = 213). Statistical comparisons between the two groups were explored using independent t-tests, Mann-Whitney U tests, and Chi-square tests. Crude and adjusted linear regression models investigated associations between macrosomia and preteen cardiometabolic outcomes. RESULTS: In total, 29.3% (n = 119) of preteens had overweight/obesity based on their BMI z-score. Preteens born ≥ 4 kg had lower median (IQR) C3 concentrations (1.38 (1.22, 1.52) g/L vs. 1.4 (1.26, 1.6) g/L, p = 0.043) and lower median (IQR) ICAM-1 concentrations (345.39 (290.34, 394.91) ng/mL vs. 387.44 (312.91, 441.83) ng/mL, p = 0.040), than those born < 4 kg. Those born ≥ 4.5 kg had higher mean (SD) BMI z-scores (0.71 (0.99) vs. 0.36 (1.09), p = 0.016), and higher median (IQR) lean mass (24.76 (23.28, 28.51) kg vs. 23.87 (21.9, 26.79) kg, p = 0.021), than those born < 4.5 kg. Adjusted linear regression analyses revealed birthweight ≥ 4 kg was negatively associated with C3 concentration (g/L) (B = - 0.095, 95% CI = - 0.162, - 0.029, p = 0.005) and birthweight ≥ 4.5 kg was positively associated with weight z-score (B = 0.325, 95% CI = 0.018, 0.633, p = 0.038), height z-score (B = 0.391, 95% CI = 0.079, 0.703, p = 0.014), lean mass (kg) (B = 1.353, 95% CI = 0.264, 2.442, p = 0.015) and cardiorespiratory endurance (B = 0.407, 95% CI = 0.006, 0.808, p = 0.047). CONCLUSION: This study found no strong evidence to suggest that macrosomia is associated with adverse preteen cardiometabolic health. Macrosomia alone may not be a long-term cardiometabolic risk factor. Trial registration ISRCTN54392969 registered at  www.isrctn.com .

No effect of calcium and vitamin D intake on maternal blood pressure in a healthy pregnant population.

OBJECTIVES: Clinical studies have reported an inverse relationship between calcium and vitamin D intake and hypertensive disorders of pregnancy (HDP). The aim of this study was to investigate if there was an association between calcium/vitamin D intake, and vitamin D (25OHD) status, and maternal blood pressure (BP), during pregnancy and at 5-year follow-up. STUDY DESIGN: This was an observational study of 415 women who participated in the ROLO (Randomised cOntrolled trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia) study. Maternal BP measurements were taken during each trimester and at 5-year follow-up. Calcium and vitamin D intake were determined at each trimester and 25OHD was measured in early and late pregnancy. RESULTS: Over two-thirds of the cohort were vitamin D sufficient (25OHD > 30 nmol/L) and had adequate calcium intake (>750 mg/day). There was no correlation between calcium intake or vitamin D intake and maternal BP in trimester 1 to 3 or at 5-year follow-up. Vitamin D status at 13 weeks' gestation negatively correlated with mean arterial pressure in trimester 1 (r = -0.152, p = 0.044). There was no correlation however between 25OHD at 28 weeks' gestation and BP at 28 or 34 weeks' gestation or 25OHD and BP at 5-year follow-up. CONCLUSIONS: In a healthy population of women with adequate calcium and vitamin D intake, no clinically significant correlation existed between calcium and vitamin D and maternal BP.

Coeliac screening in a high-risk population: paediatric type 1 diabetes-a review of current guidelines and practice.

BACKGROUND AND AIMS: Coeliac disease (CD) is more common in those with type 1 diabetes mellitus (T1DM) and may be asymptomatic despite the presence of intestinal histological changes. Optimal screening practice guidelines differ internationally. We undertook a retrospective audit to determine the efficacy of current screening practice for CD in T1DM in our centre. METHODS: All children and adolescents < 16 years, diagnosed with T1DM in our service and continuing to attend the service in January 2017 were included. Data on CD screening was collected and compared to current NICE, NASPGHAN and ESPGHAN guidelines. RESULTS: Of the 355 patients attending our service, 253 attended from T1DM diagnosis and all had CD screening performed in our centre. In 37 of 253 patients, IgA-TTG was positive, providing a cumulative prevalence of 14.6%. Of these, 31(83.78%) with an elevated TTG on screening had no recorded gastrointestinal symptoms or CD-related clinical signs. Of the 35 TTG plus EMA-positive patients, 22/35 (59.46%) had diagnostic endoscopic biopsy. Nineteen (83.4%) had CD confirmed, 1 (4.54%) had negative biopsy and 2 (9%) had equivocal, non-diagnostic changes. CONCLUSIONS: Timely diagnosis of CD can prevent chronic ill health in affected individuals, and in patients with T1DM, CD is an independent risk factor for increased morbidity and mortality. Given the high prevalence of atypical symptoms and silent CD in those with T1DM, in this and other studies, and the benefits of detection and treatment of CD, screening is essential. Large-scale data collection allowing for the development of evidence-based guidelines is required.

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland.

BACKGROUND AND OBJECTIVES: Congenital hypothyroidism (CHT) is one of the most common preventable causes of learning disability. Newborn screening with whole-blood thyroid-stimulating hormone measurements was introduced in the Republic of Ireland in 1979 and is coordinated from a single center with an unchanged protocol since its inception. Our objective in this study was to describe the incidence of CHT in the Republic of Ireland over the past 37 years in the context of a complete national population and an unchanged screening protocol. METHODS: The newborn screening records of all individuals who were diagnosed with CHT between 1979 and 2016 were reviewed. Infants with positive screening results had a whole-blood thyroid-stimulating hormone value of ≥15 mU/L at 72 to 120 hours of life; values of 8 to 15 mU/L required a repeat whole-blood screening test. RESULTS: Of 2 361 174 infants who were screened between July 1979 and December 2016, 1063 (662 girls) were diagnosed with CHT (incidence: 0.45 cases per 1000 live births). The number of detected cases increased from 0.27 cases per 1000 live births treated between 1979 and 1991 to 0.41 cases per 1000 live births treated between 1992 and 2004 to 0.65 cases per 1000 live births treated between 2005 and 2016. The increase in detected cases of CHT was predominantly in the normal or hyperplastic gland category. CONCLUSIONS: The incidence of CHT has increased significantly in the Republic of Ireland over the past 37 years despite a consistent screening cutoff. The increased rate was not explained by an increased survival rate of preterm infants or a changing population heterogeneity.

A novel homozygous deletion in the calcium-sensing receptor ligand-binding domain associated with neonatal severe hyperparathyroidism.

Neonatal severe hyperparathyroidism (NSHPT) is a life-threatening disorder usually caused by homozygous mutations occurring in the calcium-sensing receptor (CaR) gene. We examined an infant hospitalised with NSHPT for mutations in the CaR gene using heterozygous sequence analysis and confirmed this result by a restriction enzyme assay. Clinical management of this case, which was beset by other complications, involved control of the hypercalcemia and the effects of hyperparathyroidism by a combination of treatments prior to parathyroidectomy performed at 10 months. Mutational analysis demonstrated a homozygous 5 base-pair deletion in the CaR gene located at the 5' end of exon 4 which would result in a severely truncated, non-functional receptor with only the first 164 amino acids of the CaR followed by 23 amino acids of aberrant sequence. This is the first report of an out-of-frame deletion in the extracellular domain of the CaR associated with clinical disease.

Primary ovarian failure and deletions of the long arm of chromosome 3.

A 14 year-old girl was found to have a deletion of the distal segment of chromosome 3 [46,XX,Del(3)(q28-29)]. The main features of this presentation were mild intellectual disability, facial dysmorphism, short stature, kypho-scoliosis, and primary ovarian failure, an association that has not been described before in association with chromosome 3 deletion. The phenotype and presentation are compared with those of previous case reports.

Hyperglycemia and externalizing behavior in children with type 1 diabetes.

OBJECTIVE: Ancedotally, parents report behavioral changes in their diabetic children who have fluctuating blood glucose levels. This study aimed to test associations between intercurrent glycemia and child behavior in an ambulant setting. RESEARCH DESIGN AND METHODS: Prepubertal children attending the Royal Children's Hospital, Melbourne, Australia, with type 1 diabetes received glycemic assessment and simultaneous behavioral assessment on two occasions 6 months apart. Subjects wore a continuous glucose monitor over a 72-h period, and parents completed the Behavior Assessment System for Children at the two study time points. RESULTS: There was a high correlation between intra-individual externalizing and internalizing behavior scores (r = 0.88, P < 0.001 and r = 0.81, P < 0.001, respectively) at the two time points. Mean blood glucose (MBG) was significantly associated with the mean externalizing behavior score (beta = 1.7 [95% CI 0.6-2.8], adjusted r(2) = 0.088). Percentage of time in the normal (r = -0.2 [-0.3 to -0.5], adjusted r(2) = 0.068) and high (r = 0.2 [0.07-0.3], adjusted r(2) = 0.089) glycemic ranges were significantly associated with the mean externalizing behavior score. For every 5% increase in time in the normal glycemic range, there was a decrease in the externalizing behavior score of 1.0, and for every 5% increase in time in the high glycemic range there was an increase in the externalizing behavior score of 1.0. There was no significant association between MBG and the mean internalizing behavior score. CONCLUSIONS: Externalizing behaviors were associated with intercurrent glycemic status. These findings underscore the importance of understanding the mechanisms of this association and how it might impact ultimate diabetes outcomes.

Maternal primary hyperparathyroidism: discordant outcomes in a twin pregnancy.

The case reports a neonate (twin 2 of a twin girl pregnancy) presenting with seizures due to hypocalcaemia. The presumptive cause of the hypocalcaemia was maternal hyperparathyroidism with concurrent vitamin D deficiency. The first twin remained free of hypocalcaemia and was vitamin D replete, despite similar exposure in the pregnancy and similar postnatal care.

Diabetic ketoacidosis, hyperosmolarity and hypernatremia: are high-carbohydrate drinks worsening initial presentation?

The case of five pediatric patients who presented to the Royal Children's Hospital, Melbourne with newly diagnosed diabetes mellitus between January 2001 and September 2003 is reported. Each case was complicated by hyperosmolarity and hypernatremia and required intensive therapy. Fluid intake prior to admission in each case was documented and consisted of between 5 and 12 L of carbonated carbohydrate beverages and 'isotonic' sports drinks. At presentation, biochemical results of the four cases (four males and one female), mean age 13.6 yr (range 11.7-15.1 yr) included glucose (mean 1460 mg/dL; range 864-2106), adjusted sodium (mean 176.3 mmol/L; range 165-183), serum osmolarity (mean 399 mmol/kg; range 364-424), anion gap (mean 48 mEq/L; range 42-84), and pH (mean 7.15; range 7.01-7.27). All five cases had evidence of ketonuria on presentation. Treatment in all five cases consisted of replacement of fluids over a prolonged period of 72 h and careful monitoring of electrolyte response. Three of five cases required hemofiltration in the first 48 h postadmission. All five cases made a complete recovery without neurological sequelae. Carbonated carbohydrate fluid intake may precipitate a more severe presentation of type 1 diabetes mellitus (T1DM). Fluid composition and intake should be carefully estimated at admission to help identify and manage similar cases.

Iodine deficiency and goitre in schoolchildren in Melbourne, 2001.

OBJECTIVE: To assess iodine status and goitre prevalence in a sample of schoolchildren in Melbourne. DESIGN: Cross-sectional study of urinary iodine excretion and presence of goitre in a sample of schoolchildren from Years 5-12 attending two urban schools. PARTICIPANTS: 607 children aged 11-18 years consented to thyroid gland palpation and 577 provided a urine sample on the day of examination in August 2001. OUTCOME MEASURE: Iodine status of the study population, based on median urinary iodine values categorised as normal (> or = 100 microg/L), mild (50-99 microg/L) or moderate-severe (< 50 microg/L), and classified according to sex, school year and presence of goitre. RESULTS: 76% (439/577) of students had abnormal urinary iodine values, with 27% (156/577) having values consistent with moderate-severe deficiency. The median urinary iodine excretion for the total group was 70 microg/L, with values for school years 5-12 ranging from 62 microg/L (Year 12) to 76 microg/L (Year 9). The median urinary iodine value in girls was lower than that in boys (64 microg/L v 82 microg/L), and girls had significantly lower urinary iodine values overall (P < 0.002). There was no association between goitre grade and moderate-severe (< 50 microg/L; P = 0.39) or mild (50-99 microg/L; P = 0.07) urinary iodine deficiency. CONCLUSIONS: We found mild iodine deficiency in a cohort of schoolchildren in Melbourne. Our results support other data showing mild iodine deficiency in Sydney and Tasmania and the argument for a national study of iodine nutrition.

A 3-year prospective study to assess uterine growth in girls with Turner's syndrome by pelvic ultrasound.

OBJECTIVE: Adult women with Turner's syndrome who have used the donor ovum IVF programme are reported to have reduced pregnancy outcome with an increased risk for first trimester spontaneous abortion. This is considered to be related to a small uterine size and reduced endometrial thickness. This study examines whether adequate oestrogen replacement during the early adolescent years will result in normal adult uterine dimensions, with consequent reduction in these pregnancy risks. DESIGN: A prospective evaluation of uterine dimensions by pelvic ultrasound examination over 3 years, in a group of 18 girls commencing pubertal induction with oestrogen or entering puberty spontaneously. PATIENTS: Girls with Turner's syndrome attending the outpatient clinc at the Royal Children's Hospital and due to start oestrogen treatment were invited to participate in the study. MEASUREMENTS: Data were collected for clinical parameters of age, pubertal staging, menarche, oestrogen dose and karyotype. Ultrasonographic measurements of uterine length, sagittal and transverse width, endometrial cavity and identification of ovaries were also included. RESULTS: The mean age at commencement of the study was 14.6 years, mean age at final evaluation was 17.1 years. Karyotype was 45XO in 6/18, mosaic in 12/18. Spontaneous pubertal onset occurred in 5/18. One of these later required the addition of oestrogen treatment. Pubertal induction with oestrogen was used in 13/18 girls. A total of 15/18 girls have either achieved spontaneous menarche or are using adult doses of oestrogen and progestogen with regular withdrawal bleeds. All 18 girls have achieved a uterine length of 5.8-8.6 cm (mean 7.04 cm) within the normal adult range (5-8 cm). Mean uterine volume was 30.23 cm3. CONCLUSION: The study suggests that adequate oestrogen replacement in early to mid adolescence mimicking spontaneous timing of puberty results in normal uterine growth and adult uterine dimensions. Further follow-up of uterine growth in these girls is warranted.

K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial phaeochromocytoma and paraganglioma.

OBJECTIVE: Germline mutations in succinate dehydrogenase (SDH)B, SDHC and SDHD, encoding three of the four subunits of mitochondrial complex II, have been implicated in the tumourigenesis of familial paragangliomas and phaeochromocytomas. Twenty-three SDHB mutations have been identified to date. PATIENTS: We present a novel missense SDHB exon 2 mutation (c.118 A > G; K40E) identified in an Australian family. The proband was diagnosed with phaeochromocytoma at an early age following an unexpected hypertensive crisis and was found to be SDHB mutation-positive. Subsequent genetic screening of 26 family members has identified 17 mutation-positive relatives. In addition to the proband, four mutation positive relatives were found to have clinical symptoms or a lesion and/or catecholamine excess after the identification of the mutation led to further evaluation. Both the proband and an uncle have required surgical removal of a tumour. CONCLUSIONS: This family indicates the importance of germline screening of first-degree relatives when a patient presents with an apparently sporadic extra adrenal phaeochromocytoma at a young age or whenever a patient with a nonsecretory paraganglioma is found.