Pediatric diabetes care in Sri Lanka and Bangladesh: Reaching the community.

Diabetes is a major non-communicable disease with long-term complications. Over one million children and adolescents are affected with type 1 diabetes in the world. The number of children and adolescents with type 2 diabetes is also on the rise due to the increase incidence of childhood diabetes. South East Asian (SEA) contributes 184 100 children and adolescents with type 1 diabetes under the age of 20 years for this global health issue as at 2019. Countries of SEA region share same socio demographic, cultural, and economic challenges when it comes to holistic care of affected children. It is timely to discuss common concerns of these countries to give the best possible care for children affected with diabetes to minimize the burden of diabetes related complications, which would potentially affect the socioeconomic development of the respective countries.

Effectiveness and acceptability of a novel school-based healthy eating program among primary school children in urban Sri Lanka.

BACKGROUND: Obesity rates are rising rapidly in low-middle-income-countries (LMICs). School-based interventions have shown moderate efficacy in improving diet and lifestyle associated with obesity in high-income countries. However, there is little data available on effective interventions suitable for LMICs. We devised a novel program for primary school children including a simple storybook and sticker-based food-diary (FD) and conducted a pilot study to evaluate the acceptability and short-term effectiveness of the program. METHODS: This pre-post intervention study included grade 1 and 2 students from four public schools in Colombo, Sri Lanka. Weight and height were assessed, and participating children self-monitored their diet using sticker-based FDs for one week at baseline (pre-test). The following week, class teachers discussed the storybook, which incorporated the benefits/disadvantages of a healthy/unhealthy diet and lifestyle in classrooms. At the end of the intervention, participating children were self-monitoring their diet again for a week (post-test). A simple scoring system was used to derive a weekly score based on the healthiness of the meals consumed each week (FD-score). The primary outcome of the study was change in eating habits following the story book discussion (post-test FD score - pre-test FD score). Acceptability and effectiveness were also assessed by anonymized feedback questionnaires for parents and teachers. RESULTS: One thousand and forty-two students completed the program. There was an improvement in eating habits of participating children, with FD scores improving by 12% from 51 ± 23 at baseline to 63 ± 24 following the intervention (p < 0.001). Further, when considering BMI category of participants: 69.1% were normal weight (NW), 18.3% underweight (UW), 7.4% overweight (OW) and 5.2% obese (OB). Improvement in eating habits were seen among children of all BMI categories (change in FD-score: UW 13.2%, NW 12.3%, OW 10.4% and OB 12.4% (p < 0.001)). Furthermore,> 90% parents(n = 1028) and > 95% teachers(n = 39) strongly agreed/agreed that the intervention was easy to implement, motivated children and led to an observable improvement in healthy eating. CONCLUSION: This novel program led to an immediate improvement in eating habits and was well accepted by parents and teachers making it a potentially suitable intervention for wider implementation in primary schools in urban Sri Lanka.

Gender-role behaviour and gender identity in girls with classical congenital adrenal hyperplasia.

INTRODUCTION: Girls with classical congenital adrenal hyperplasia (CAH) are exposed to excess fetal adrenal androgens in-utero, and often born with masculinised genitalia. They are conventionally reared as females, but show more "boyish" gender-role behaviour (GRB) and gender-identity (GI) issues in childhood and adolescence. Male-rearing is also reported mainly due to delayed treatment and/or socio-cultural factors. We compared GRB/GI in girls with CAH with healthy age matched children, and explored for associations with socio-demographic and diagnosis/treatment related factors. METHODS: GRB and GI were assessed using the Gender Identity Questionnaire for children (GIQC) in 27 girls with classical CAH at a specialised clinic, and compared with 50 age-matched healthy controls, with exploratory-analysis based on socio-demographic and diagnosis/treatment-related factors. RESULTS: Girls with CAH had lower total GIQC scores compared to healthy children (3.29 vs. 4.04, p = < 0.001) with lower GRB score (3.39 vs. 4.23, p < 0.001), and tendency for lower GI score (3.19 vs. 3.5, p = 0.08). Exploratory analysis showed no differences based on diagnosis/treatment factors including age, degree of virilisation at diagnosis and surgical procedures. and only subtle changes based on ethnicity and maternal education. DISCUSSION/CONCLUSION: Girls with CAH managed at a specialised centre showed more masculinised GRB and tendency for ambiguous GI, which did not vary upon diagnosis/treatment related factors, suggesting that prenatal androgen exposure was the likely contributor. Clinicians should be vigilant about the increased risk of gender-related problems in girls with CAH, irrespective of sociocultural background and despite early treatment.

A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development.

Cell lineages of the early human gonad commit to one of the two mutually antagonistic organogenetic fates, the testis or the ovary. Some individuals with a 46,XX karyotype develop testes or ovotestes (testicular or ovotesticular disorder of sex development; TDSD/OTDSD), due to the presence of the testis-determining gene, SRY Other rare complex syndromic forms of TDSD/OTDSD are associated with mutations in pro-ovarian genes that repress testis development (e.g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown. Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function. Loss-of-function changes in NR5A1 in 46,XY individuals are associated with a spectrum of phenotypes in humans ranging from a lack of testis formation to male infertility. Mutations in NR5A1 in 46,XX women are associated with primary ovarian insufficiency, which includes a lack of ovary formation, primary and secondary amenorrhoea as well as early menopause. Here, we show that a specific recurrent heterozygous missense mutation (p.Arg92Trp) in the accessory DNA-binding region of NR5A1 is associated with variable degree of testis development in 46,XX children and adults from four unrelated families. Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis. These unique findings highlight how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represents the first missense mutation causing isolated, non-syndromic 46,XX testicular/ovotesticular DSD in humans.

Nulliparity is associated with subtle adverse metabolic outcomes in overweight/obese mothers and their offspring.

BACKGROUND: We aimed to evaluate metabolic outcomes in overweight/obese nulliparous and multiparous women and their offspring. STUDY DESIGN: Seventy-two overweight and obese women who participated in a randomized controlled trial of exercise in pregnancy were included in the study, comparing 18 nulliparous and 54 multiparous women and their singleton offspring. Women were assessed at 19 and 36 weeks of gestation. Fetal growth was measured using standard obstetric ultrasound techniques. Cord blood was collected at birth. Maternal and offspring body composition was assessed using DXA ~2 weeks after delivery. RESULTS: Nulliparous women had higher HbA1c in the third trimester of pregnancy than multiparous women (5.48% vs 5.29%; P=.002) and were more insulin-resistant based on the surrogate marker sex hormone-binding globulin (354 vs 408 nmol/L; P=.047). Nulliparous women also had higher levels of the inflammatory marker tumour necrosis factor-alpha (4.74 vs 3.62 pg/mL; P=.025). At birth, the offspring of nulliparous women were on average 340 g (P=.013) and 0.69 standard deviation scores (P=.026) lighter than those born of multiparous women. Cord blood data showed lower insulin-like growth factor-II (P=.026) and higher IGF binding protein-1 (P=.002) levels in the offspring of nulliparous women. In addition, a less favourable metabolic profile was observed in the offspring of nulliparous women, as indicated by higher triglyceride (P<.001) and interleukin-6 (P=.039) concentrations. CONCLUSIONS: Infants born of nulliparous overweight and obese women appear to be exposed to a less favourable metabolic environment in utero, with evidence of subtle adverse metabolic outcomes at birth compared to infants of overweight/obese multiparous women.

The sex of the foetus affects maternal blood glucose concentrations in overweight and obese pregnant women.

There is increasing evidence that the sex of the foetus may alter the maternal metabolic milieu during pregnancy. Following a randomized controlled trial of exercise in overweight and obese pregnant women, we assessed whether the sex of the foetus was associated with changes in maternal metabolism. Data were analysed on 74 randomized participants who completed the trial, including 38 mothers carrying males and 36 mothers carrying females. At 19 weeks of gestation, mothers carrying boys had higher blood glucose concentrations than those carrying girls (5.4 vs 4.9 mmol/l; p = .046). At 36 weeks of gestation, differences were more marked, with blood glucose concentrations 15% higher in mothers carrying females (5.7 vs 5.0 mmol/l; p = .004). In addition, mothers carrying girls had higher concentrations of hs-CRP across pregnancy (5.0 vs 3.6 mg/l; p = .029). Our findings provide further evidence that the sex of the foetus appears to influence maternal metabolism.

Exercise in pregnancies complicated by obesity: achieving benefits and overcoming barriers.

An increasing number of women are entering pregnancy in an overweight or obese state. Obese women and their offspring are at increased risk of adverse perinatal outcomes, which may be improved by regular moderate-intensity antenatal exercise. Current guidelines recommend that all pregnant women without contraindications engage in ≥30 minutes of moderate-intensity exercise on a daily basis. However, obese women are usually less physically active and tend to further reduce activity levels during pregnancy. This commentary summarizes the potential short- and long-term benefits of antenatal exercise in obese pregnant women, highlights the challenges they face, and discusses means of improving their exercise levels. In addition, we make recommendations on exercise prescription for pregnancies complicated by obesity.

Antenatal exercise in overweight and obese women and its effects on offspring and maternal health: design and rationale of the IMPROVE (Improving Maternal and Progeny Obesity Via Exercise) randomised controlled trial.

BACKGROUND: Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. Lifestyle interventions in pregnancy such as antenatal exercise, are proposed to improve both short- and long-term health of mother and child. We hypothesise that regular moderate-intensity exercise during the second half of pregnancy will result in improved maternal and offspring outcomes, including a reduction in birth weight and adiposity in the offspring, which may be protective against obesity in later life. METHODS/DESIGN: The IMPROVE (Improving Maternal and Progeny Risks of Obesity Via Exercise) study is a two-arm parallel randomised controlled clinical trial being conducted in Auckland, New Zealand. Overweight and obese women (BMI ≥25 kg/m2) aged 18-40 years, with a singleton pregnancy of <20 weeks of gestation, from the Auckland region, are eligible for the trial. Exclusion criteria are ongoing smoking or medical contra-indications to antenatal exercise.Participants are randomised with 1:1 allocation ratio to either intervention or control group, using computer-generated randomisation sequences in variable block sizes, stratified on ethnicity and parity, after completion of baseline assessments. The intervention consists of a 16-week structured home-based moderate-intensity exercise programme utilising stationary cycles and heart rate monitors, commencing at 20 weeks of gestation. The control group do not receive any exercise intervention. Both groups undergo regular fetal ultrasonography and receive standard antenatal care. Due to the nature of the intervention, participants are un-blinded to group assignment during the trial.The primary outcome is offspring birth weight. Secondary offspring outcomes include fetal and neonatal body composition and anthropometry, neonatal complications and cord blood metabolic markers. Maternal outcomes include weight gain, pregnancy and delivery complications, aerobic fitness, quality of life, metabolic markers and post-partum body composition. DISCUSSION: The results of this trial will provide valuable insights on the effects of antenatal exercise on health outcomes in overweight and obese mothers and their offspring. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000932864.

Health-Related Quality of Life in Children and Adolescents With Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review (SR) and meta-analysis (MA) on health-related quality-of-life (QoL) and associated factors among children/adolescents with congenital adrenal hyperplasia (CAH). METHOD: Following registration in the PROSPERO International Prospective Register of Systematic Reviews(reg no: CRD42022313389), Google Scholar, PubMed, LILACS, Cochrane, and Scopus databases were searched up to March 5, 2022, using predefined search strategy/MESH terms to identify original studies describing/assessing self-reported/parent-reported health-related QoL in patients with CAH ≤21 years. Methodological quality was assessed by Newcastle-Ottawa Quality Assessment Scale (NOS), and heterogeneity by I2 statistics. MA assessed mean difference (MD) in QoL between children/adolescents with CAH and healthy children/adolescents. RESULTS: Among 1308 publications, the 12 studies eligible for the SR (CAH n = 781) showed NOS scales of 3 to 7/9, and the 6 eligible for MA (CAH n = 227) showed moderate-considerable heterogeneity. MA showed that parent-reported psychosocial QoL (MD 9.9 [-12.6,7.3], P ≤ .001) {consisting of school (MD 7.4[-12.2, -2.5], P = .003), emotional (MD 5.6 [-10.2, -0.9], P = .02) and social domains (MD 4.3 [-8.1, -0.5], P = .03), and self-reported school domain QoL (MD 8.5 [-15.9, -1.2], P = .02) was lower in children/adolescents with CAH while parent-reported and self-reported physical QoL were similar to controls.Factors associated with lower QoL among children/ adolescents with CAH included poor disease control, poor medication compliance, and complications including hyperpigmentation, virilization, hypertension, hospital admission, and urinary incontinence. CONCLUSION: Based on available data, children/adolescents with CAH had preserved physical QoL but impaired psychosocial QoL, especially in the school domain. Factors associated with lower QoL included poor disease control and disease/treatment-related complications. There is a need for further high-quality research that investigates the relationship between disease control, provision of psychosocial support, and improvement in QoL in children/adolescents with CAH.

Improved food habits and anthropometry among primary school children following a novel healthy eating programme.

OBJECTIVE: Assess longer-term changes in food habits and anthropometry among Grades 1-2 primary school students from four public schools in Colombo, Sri Lanka, following a 3-week programme including a classroom-based motivational storybook discussion and self-monitoring food diary (FD). METHODS: This follow-up study assessed changes from baseline (pre-intervention) BMI z-scores and food habits (increased healthy food-item consumption/decreased unhealthy food-item consumption reflected by an increase in FD score) and parental perceptions (anonymous questionnaires) among 863 students (aged 6-8 years), between 9 and 12 months after completing the programme (November 2019-February 2020). RESULTS: Food habits showed sustained improvement from baseline mean FD score (baseline vs. follow-up: 51 ± 23% vs. 67 ± 22%, p < 0.001), with children from all BMI subgroups (underweight [UW], normal weight [NW], overweight [OW] and obesity [OB]) showing a significant increase in FD scores (ranging from 14.1% to 17.2%, p < 0.001). BMI z-scores increased in children living with UW (-2.85 to -2.21, p < 0.00) and NW (-0.70 to -0.57, p < 0.001), but did not change in children with OW (+1.5 to +1.49, p = 0.83) and OB (+2.85 to +2.21, p = 0.19). Most parents (n = 497, 97.8%) reported satisfaction with programme outcomes. CONCLUSION: This programme led to sustained improvement in food habits among young primary school children from all BMI categories, increase in BMI towards the median among children living with UW and NW, and stabilization of BMI in children with OW and OB, suggesting it as a useful tool for improving nutritional status of young children in low- and middle-income countries (LMIC) facing the double burden of under- and overnutrition.

Gynecomastia and Its Management In Boys With Partial Androgen Insensitivity Syndrome.

INTRODUCTION: Partial androgen insensitivity syndrome (PAIS) is a rare condition that is reported to be commonly associated with gynecomastia in males. OBJECTIVES: To assess the management of gynecomastia in male PAIS. MATERIALS AND METHODS: Retrospective review of males with PAIS over the age of 10 years in the I-DSD registry. RESULTS: Of the 205 eligible cases, information was available for 57 from 13 centers. An androgen receptor gene variant was confirmed in 45 (79%) with a median age at first presentation of 1.0 year (range 0.1, 26.0). Of the 45 genetically confirmed cases, gynecomastia was present in 41 (91%) with a median age at the time of gynecomastia development of 13.5 years (11.0, 29.0). In the other 4 (9%) with no gynecomastia, the median age at last assessment was 15.7 years (10.6, 17.0). In 30 cases with information available, micropenis was present at the time of gynecomastia development in 23 (77%). Of the 35 with information available, 2 (6%) exhibited spontaneous resolution between the ages of 15 and 21 years and 25 (71%) had breast surgery at a median age of 15.7 years (14.0, 23.0). Of these 25, 9 (26%) had previously received medical therapy. The median clinician score of effectiveness for medical therapy was 3 (1, 8) compared to 10 (3, 10) for surgery (P < .0001). In 31 with information available, 13 (42%) had received psychology support. CONCLUSION: Gynecomastia is common in PAIS but not universal. Surgical management may be more effective than medical therapy, but there is a need for further standardized and systematic studies.

Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022.

Background: It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Aim: Study temporal trends of AI related AE in the I-CAH Registry. Methods: In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019. Results: In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02). Conclusion: The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.

Bone health in childhood and adolescence: an overview on dual-energy X-ray absorptiometry scanning, fracture surveillance and bisphosphonate therapy for low-middle-income countries.

Bone accrual in childhood determines bone health in later life. Loss of bone strength in early life can lead to increased morbidity and reduced quality of life in childhood and adolescence. Increased availability of assessment tools and bisphosphonate therapy, together with increased awareness on the significance of fracture history and risk factors, have led to greater opportunities, to improve detection and optimize management of children and adolescents with bone fragility globally, including those in lower resource settings. Bone mineral density z-scores and bone mineral content are surrogate measures of bone strength, which can be measured by dual-energy X-ray absorptiometry (DXA), in growing individuals. DXA can aid in the diagnosis and management of primary and secondary bone fragility disorders in childhood. DXA helps evaluate children with clinically significant fractures, and monitor those with bone fragility disorders, or at high risk for compromised bone strength. Obtaining DXA images can however be challenging, especially in younger children, due to difficulty in positioning and movement artefacts, while paediatric DXA interpretation can be confounded by effects of growth and puberty. Furthermore, access to DXA facilities as well as appropriate paediatric reference norms and expertise for interpretation, may not be easily available especially in lower resource settings. Pediatric bone experts are now placing increasing emphasis on the fracture phenotype and clinical context to diagnose osteoporosis over bone mineral density (BMD) by DXA. Low trauma vertebral fractures are now recognized as a hallmark of bone fragility, and spinal fracture surveillance by either conventional lateral thoracolumbar radiographs or vertebral fracture assessment by DXA is gaining increasing importance in diagnosing childhood osteoporosis, and initiating bone protective therapy. Furthermore, it is now understood that even a single, low-trauma long bone fracture can signal osteoporosis in those with risk factors for bone fragility. Intravenous bisphosphonate therapy is the mainstay of treatment for childhood bone fragility disorders. Other supportive measures to improve bone strength include optimizing nutrition, encouraging weight bearing physical activity within the limits of the underlying condition, and treating any associated endocrinopathies. With this paradigm shift in childhood osteoporosis evaluation and management, lack of DXA facilities to assess BMD at baseline and/or provide serial monitoring is not a major barrier for initiating IV bisphosphonate therapy in children in whom it is clinically indicated and would benefit from its use. DXA is useful, however, to monitor treatment response and optimal timing for treatment discontinuation in children with transient risk factors for osteoporosis. Overall, there is lack of awareness and paucity of guidelines on utilizing and adopting available resources to manage paediatric bone disorders optimally in lower-resource settings. We provide an evidence-based approach to the assessment and management of bone fragility disorders in children and adolescents, with appropriate considerations for lower resource settings including LMIC countries.

Endocrine manifestations of COVID-19 in children: A scoping review.

In this review, we explore associations between SARS CoV-2 infection and the endocrine system and metabolism in children and adolescents. PubMed, Scopus and Google scholar databases were searched to identify published data on endocrine manifestations of COVID-19 in children up to 31 March 2023, including diabetes, obesity, puberty, thyroid disorders, adrenal disorders and pituitary disorders. Data on changes in disease pattern/ incidence, disease control, and other effects due to the COVID-19 pandemic, as well as effects of pre-existing endocrine conditions on severity of COVID-19 infection are presented, and practice points and research needs provided under each section.

Fetal programming of obesity and type 2 diabetes.

The prevalence of obesity and type 2 diabetes mellitus has increased rapidly over the past few decades, and prevention efforts have not been successful. Fetal programming involves the earliest stage of obesity development, and provides a novel concept to complement other strategies for lifelong prevention of obesity and type 2 diabetes mellitus. The World Health Organization now advocates a life-course approach to prevent/control obesity, starting with pre-conceptional and antenatal maternal health. Maternal overnutrition, gestational diabetes mellitus and excessive gestational weight gain lead to fetal overgrowth, and "programs" the offspring with an increased risk of obesity and type 2 diabetes mellitus in childhood and adulthood. This review summarizes current data on fetal programming of obesity and type 2 diabetes mellitus including potential causative factors, mechanisms and interventions to reduce its impact.

Effects of probiotics combined with dietary and lifestyle modification on clinical, biochemical, and radiological parameters in obese children with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: a randomized clinical trial.

BACKGROUND: Childhood obesity is a global problem associated with metabolic abnormalities. The gut-liver axis is thought to play a major role in its pathogenesis. Probiotics are known to alter the gut microbiota and, therefore, could be a therapeutic option in the management of childhood obesity-related complications. PURPOSE: This double-blind randomized placebo-controlled trial evaluated the effects of probiotics on metabolic derangement in obese children with nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis (NAFLD/NASH). METHODS: Obese children with NAFLD/NASH treated at the nutrition clinic of the University Paediatric Unit at Lady Ridgeway Hospital, Colombo, were recruited. Anthropometry, body fat, metabolic derangement, and liver ultrasound scan (USS) results were evaluated at baseline and after 6 months. Transient elastography (FibroScan) was performed on a subsample of these patients. Eighty-four patients were recruited and randomized into the probiotics (n=43) and placebo (n= 41) groups. The mean age was 11.3±1.9 versus 12.1±1.5 years in the probiotic and placebo groups, respectively. Baseline parameters including liver disease stage on USS, body fat percentage, fasting blood sugar, lipid profile, liver function, and C-reactive protein showed no significant intergroup differences. RESULTS: In the probiotic group, a statistically significant reduction in body mass index was noted from the baseline value. However, the reduction was not significant compared with the placebo group. There was a significant reduction in triglycerides, aspartate transaminase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and alkaline phosphatase in the placebo group over the treatment period. Although the liver disease stage on USS improved from stage II-III to stage I in a small number of patients in the probiotic-treated group, transient elastography performed in a subsample did not demonstrate significant improvement in either group. CONCLUSION: Our results indicate that probiotics have no advantage over lifestyle modification for improving obesityassociated metabolic derangement in children.

Presenting status of children with classical congenital adrenal hyperplasia over two decades (1999-2018) in the absence of newborn screening in Sri Lanka.

OBJECTIVES: Although new-born screening (NBS) for classical congenital adrenal hyperplasia (C-CAH) has been available for decades, it is not widely implemented. We assessed the usefulness of introducing NBS for C-CAH, by analyzing presenting status of infants with C-CAH, over the past two decades, in Sri Lanka. METHODS: This retrospective clinic-based study, from the largest tertiary children's hospital in Sri Lanka, analyzed initial presenting features of children with C-CAH from 1999 to 2018, in the absence of NBS for CAH, and included gender-based comparisons. RESULTS: Features suggestive of impending adrenal-crisis were seen at initial presentation in >80 % (dehydration 70%, hyponatremia 65%, hyperkalemia 47%, vomiting 45%, hypoglycemia 22%, collapse 20%). Hyperpigmentation was seen in 78%, and consanguinity in 27%. There were fewer affected males (n = 12) compared to females (n = 28). Most girls (96%) had virilized genitalia, and 16 faced uncertainty about gender at birth. Median age at diagnosis was 20 days. More than 70% of children had SW-CAH (males = 9 and females = 20). There were fewer males with SW-CAH, and all had features of impending adrenal crisis, including severe hyponatremia in 50%, while 62% of girls also developed hyponatremia and 33% had hyperkalemia, prior to treatment. Treatment of SW-CAH was initiated at a median age of 30 days in boys, and 10 days of age in girls. CONCLUSION: Many boys and girls with C-CAH from Sri Lanka presented late with impending adrenal crisis. Males were diagnosed later, and some possibly succumbed to C-CAH undiagnosed. These findings support including CAH in NBS programs to avert preventable childhood morbidity and mortality.

The associations between maternal BMI and gestational weight gain and health outcomes in offspring at age 1 and 7 years.

In secondary analyses of a randomised controlled trial of exercise during pregnancy, we examined associations between mid-pregnancy maternal body mass index (BMI) and excessive gestational weight gain (GWG) with offspring health. Follow-up data were available on 57 mother-child pairs at 1-year and 52 pairs at 7-year follow-ups. Clinical assessments included body composition and fasting blood tests. At age 1 year, increased maternal BMI in mid-gestation was associated with greater weight standard deviation scores (SDS) in the offspring (p = 0.035), with no observed associations for excessive GWG. At age 7 years, greater maternal BMI was associated with increased weight SDS (p < 0.001), BMI SDS (p = 0.005), and total body fat percentage (p = 0.037) in their children. Irrespective of maternal BMI, children born to mothers with excessive GWG had greater abdominal adiposity (p = 0.043) and less favourable lipid profile (lower HDL-C and higher triglycerides). At 7 years, maternal BMI and excessive GWG had compounded adverse associations with offspring adiposity. Compared to offspring of mothers with overweight/obesity plus excessive GWG, children of normal-weight mothers with adequate and excessive GWG were 0.97 and 0.64 SDS lighter (p = 0.002 and p = 0.014, respectively), and 0.98 and 0.63 SDS leaner (p = 0.001 and p = 0.014, respectively). Both greater maternal BMI in mid-pregnancy and excessive GWG were independently associated with increased adiposity in offspring at 7 years.

Van Wyk-Grumbach syndrome and oligosyndactyly in a 6-year-old girl: a case report.

BACKGROUND: Van Wyk-Grumbach syndrome refers to the development of isosexual precocious pseudopuberty and multicystic enlarged ovaries in the presence of hypothyroidism and delayed bone age. It is a rare presentation of untreated hypothyroidism. The prepubertal response in Van Wyk-Grumbach syndrome is always isosexual and mediated by very high thyroid-stimulating hormone levels acting through the follicle-stimulating hormone receptors inducing a follicle-stimulating hormonal effect. Early recognition and thyroid hormone replacement can completely regress precocious puberty and ovarian enlargement, while improving the final height achievement. Oligosyndactly is a congenital bony abnormality and can manifest either as an isolated malformation or as a component of a syndromic diagnosis. However, development of hypothyroidism in children with this peculiar bony deformity has rarely been described in the medical literature, with the exception of Cenani-Lenz Syndactyly syndrome. CASE PRESENTATION: We report the case of a 6-year-old Sri Lankan girl who presented with a 2-day history of vaginal bleeding and exertional dyspnea. She had marked short stature (well below -3 standard deviations) with an upper segment to lower segment ratio of 1.47. This girl had isolated breast development of Tanner stage 2. She was diagnosed to have acquired hypothyroidism secondary to autoimmune thyroiditis and also had macrocytic anemia, pericardial effusion, gonadotropin-releasing hormone-independent precocious puberty with radiological evidence of pubertal changes in the uterus, and multicystic ovaries. Interestingly, she also had post-axial oligosyndactyly in both feet and right-sided clubfoot. The diagnosis of Van Wyk-Grumbach syndrome was made based on the clinical and laboratory features. Her symptoms were successfully managed with L-thyroxine therapy. CONCLUSIONS: Acquired hypothyroidism is a relatively common endocrine disorder among children and early recognition is important to prevent serious complications like Van Wyk-Grumbach syndrome. Sexual precocity with delayed bone age and stunting should direct our minds toward this unique diagnosis. It is always necessary to identify the other associated anomalies in addition to the primary diagnosis since these features may direct to a syndromic diagnosis.