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European Journal of Endocrinology Jan 2021The current systematic review aimed to provide comprehensive data on the effects of iodine supplementation in pregnancy and investigate its potential benefits on infant... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The current systematic review aimed to provide comprehensive data on the effects of iodine supplementation in pregnancy and investigate its potential benefits on infant growth parameters and neurocognitive development using meta-analysis.
METHODS
A systematic review was conducted on trials published from January 1989 to December 2019 by searching MEDLINE, Web of Science, the Cochrane Library, Scopus, and Google Scholar. For most maternal and neonatal outcomes, a narrative synthesis of the data was performed. For birth anthropometric measurements and infant neurocognitive outcomes, the pooled standardized mean differences (SMDs) with 95% CIs were estimated using fixed/random effect models.
RESULTS
Fourteen trials were eligible for inclusion in the systematic review, of which five trials were included in the meta-analysis. Although the findings of different thyroid parameters are inconclusive, more consistent evidence showed that iodine supplementation could prevent the increase in thyroglobulin concentration during pregnancy. In the meta-analysis, no differences were found in weight (-0.11 (95% CI: -0.23 to 0.01)), length (-0.06 (95% CI: -0.21 to 0.09)), and head circumference (0.26 (95% CI: -0.35 to 0.88)) at birth, or in cognitive (0.07 (95% CI: -0.07 to 0.20)), language (0.06 (95% CI: -0.22 to 0.35)), and motor (0.07 (95% CI: -0.06 to 0.21)) development during the first 2 years of life in infants between the iodine-supplemented and control groups.
CONCLUSION
Iodine supplementation during pregnancy can improve the iodine status in pregnant women and their offspring; however, according to our meta-analysis, there was no evidence of improved growth or neurodevelopmental outcomes in infants of iodine-supplemented mothers.
Topics: Child Development; Clinical Trials as Topic; Congenital Hypothyroidism; Dietary Supplements; Female; Humans; Infant; Infant, Newborn; Iodine; Male; Maternal Nutritional Physiological Phenomena; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Prenatal Care
PubMed: 33112293
DOI: 10.1530/EJE-20-0927 -
American Journal of Medical Genetics.... Jan 2021Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia condition caused by FGFR3 mutations leading to disproportionate short stature. Classically HCH...
Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia condition caused by FGFR3 mutations leading to disproportionate short stature. Classically HCH presents in toddlers or school-age children, as limb-to-trunk disproportion and is often mild and easily overlooked during infancy. We report experiences from a single-center UK HCH-cohort of 31 patients, the rate of antenatal HCH detection in our cohort (13/31, 41.9%) and describe relevant case-data for this subset of 13 patients. Inclusion criteria were patients with confirmed molecular HCH diagnosis (by age 3 years) and presenting with short long-bones or large head size on antenatal ultrasound scan. We then conducted a systematic literature review using PUBMED and MEDLINE, analyzing patients with HCH and related antenatal findings. Antenatally suspected (with subsequent molecular confirmation) HCH has been reported 15 times in the literature (2004-2019). Key markers (consistent in both groups) included reduced; femur length, humeral length and increased; biparietal diameter and head circumference. HCH is increasingly detected both antenatally and in infancy, contrary to previous descriptions. This is likely due to greater HCH awareness, improved imaging, and easier molecular testing. Thus, one should consider HCH outside the classical presenting period. Studying the natural history of younger patients with HCH is important with the advent of several targeted FGFR3 therapies currently in trials for Achondroplasia, that may soon be trialed in HCH.
Topics: Achondroplasia; Bone and Bones; Dwarfism; Early Diagnosis; Female; Femur; Humans; Limb Deformities, Congenital; Lordosis; Mutation; Pregnancy; Receptor, Fibroblast Growth Factor, Type 3; United Kingdom
PubMed: 33051983
DOI: 10.1002/ajmg.a.61912 -
Journal of Pediatric Endocrinology &... Dec 2020Idiopathic short stature (ISS) is a recognized, albeit a controversial indication for treatment with recombinant human growth hormone (rhGH).The objective of the present... (Meta-Analysis)
Meta-Analysis
The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis.
OBJECTIVES
Idiopathic short stature (ISS) is a recognized, albeit a controversial indication for treatment with recombinant human growth hormone (rhGH).The objective of the present study was to conduct a systematic review of the literature and meta-analyses of selected studies about the use of rhGH in children with ISS on linear growth and adult height (AH).
METHODS
A systematic literature search was conducted to identify relevant studies published till February 28, 2017 in the following databases: Medline (PubMed), Scopus and Cochrane Central Registry of Controlled Trials. After exclusion of duplicate studies, 3,609 studies were initially identified. Of those, 3,497 studies were excluded during the process of assessing the title and/or the abstract. The remaining 112 studies were evaluated further by assessing the full text; 21 of them fulfilled all the criteria in order to be included in the current meta-analysis.
RESULTS
Children who received rhGH had significantly higher height increment at the end of the first year, an effect that persisted in the second year of treatment and achieved significantly higher AH than the control group. The difference between the two groups was equal to 5.3 cm (95% CI: 3.4-7 cm) for male and 4.7 cm (95% CI: 3.1-6.3 cm) for female patients.
CONCLUSION
In children with ISS, treatment with rhGH improves short-term linear growth and increases AH compared with control subjects. However, the final decision should be made on an individual basis, following detailed diagnostic evaluation and careful consideration of both risks and benefits of rhGH administration.
Topics: Body Height; Dwarfism; Growth Disorders; Human Growth Hormone; Humans; Recombinant Proteins
PubMed: 33035189
DOI: 10.1515/jpem-2020-0287 -
American Journal of Medical Genetics.... Oct 2020Achondroplasia is a genetic disorder that results in disproportionate short stature. The true prevalence of achondroplasia is unknown as estimates vary widely. This... (Meta-Analysis)
Meta-Analysis
Achondroplasia is a genetic disorder that results in disproportionate short stature. The true prevalence of achondroplasia is unknown as estimates vary widely. This systematic literature review and meta-analysis was conducted to better estimate worldwide achondroplasia birth prevalence. PubMed, Embase, Scielo, and Google Scholar were searched, complemented by manual searching, for peer-reviewed articles published between 1950 and 2019. Eligible articles were identified by two independent researchers using predefined selection criteria. Birth prevalence estimates were extracted for analysis, and the quality of evidence was assessed. A meta-analysis using a quality effects approach based on the inverse variance fixed effect model was conducted. The search identified 955 unique articles, of which 52 were eligible and included. Based on the meta-analysis, the worldwide birth prevalence of achondroplasia was estimated to be 4.6 per 100,000. Substantial regional variation was observed with a considerably higher birth prevalence reported in North Africa and the Middle East compared to other regions, particularly Europe and the Americas. Higher birth prevalence was also reported in specialized care settings. Significant heterogeneity (Higgins I of 84.3) was present and some indication of publication bias was detected, based on visual asymmetry of the Doi plot with a Furuya-Kanamori index of 2.73. Analysis of pooled data from the current literature yields a worldwide achondroplasia birth prevalence of approximately 4.6 per 100,000, with considerable regional variation. Careful interpretation of these findings is advised as included studies are of broadly varying methodological quality.
Topics: Achondroplasia; Europe; Female; Humans; Male; Middle East
PubMed: 32803853
DOI: 10.1002/ajmg.a.61787 -
Journal of Neurointerventional Surgery Feb 2021Microcephalic primordial dwarfism (MPD) is a heterogeneous group of rare disorders. Recent studies have reported a significant percentage of patients with MPD suffering...
BACKGROUND
Microcephalic primordial dwarfism (MPD) is a heterogeneous group of rare disorders. Recent studies have reported a significant percentage of patients with MPD suffering from a spectrum of cerebrovascular abnormalities, including intracranial aneurysms (IAs) and moyamoya syndrome. The neurological literature has not as yet specifically assessed IAs in this population. This systematic review aimed to assess the clinical behavior, characteristics, treatment modalities and outcomes of IAs in patients with MPD.
METHODS
We performed a systematic search in PubMed, Ovid MEDLINE and Ovid EMBASE for cases of MPD with IAs. We included three illustrative cases from our institution.
RESULTS
Twenty-four patients with 71 aneurysms were included in this study. Twelve patients (50%) presented with subarachnoid hemorrhage. The majority of patients were aged ≤18 years (70.8%), with a mean age of 16.2 years at presentation. Median aneurysm size was 3 (IQR 1.8-6) mm, and the most frequent locations were the internal carotid (37.3%) and middle cerebral arteries (23.8%). Concomitant moyamoya disease was reported in nine (37.5%) patients. Median age of aneurysm detection in screened patients was significantly lower than in non-screened patients (P=0.02). Microsurgical clipping (55.3%) and endovascular coiling (26.3%) were the most used modalities. Twenty-two cases were managed conservatively. Overall, mortality occurred in 45.8% of cases.
CONCLUSIONS
Screening for cerebrovascular disease seems reasonable and effective to detect aneurysms at an earlier age in this population. Efforts in the literature to emphasize early and regular screening for these patients can positively impact outcomes in this population, however more evidence is needed.
Topics: Adolescent; Child; Dwarfism; Female; Humans; Intracranial Aneurysm; Male; Microcephaly; Moyamoya Disease; Subarachnoid Hemorrhage; Treatment Outcome; Young Adult
PubMed: 32522788
DOI: 10.1136/neurintsurg-2020-016069 -
Journal of Thoracic Disease Mar 2020Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies... (Review)
Review
Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies have examined these patients when undergoing cardiac surgery or percutaneous intervention. This systematic review examines the literature to determine outcomes following cardiac intervention in this unique population. An electronic search was performed in the English literature to identify all reports of achondroplasia, dwarfism, and cardiac intervention. Of the 5,274 articles identified, 14 articles with 14 cases met inclusion criteria. Patient-level data was extracted and analyzed. Median patient age was 55.5 [interquartile ranges (IQR), 43.8, 59.8] years, median height 102.0 [98.8, 112.5] cm, median BMI 32.1 [27.0, 45.9], and 57.1% (8/14) were male. Of these 14 patients, nine had the following documented skeletal abnormalities: 66.7% (6/9) had scoliosis, 66.7% (6/9) had kyphosis, 11.1% (1/9) had lordosis, 11.1% (1/9) pectus carinatum and 11.1% (1/9) spinal stenosis. Coronary artery disease was present in 53.8% (7/13), and 30.8% (4/13) patients previously suffered a myocardial infarction. Of the eight patients who underwent cardiac surgery, 37.5% (3/8) underwent multivessel coronary artery bypass grafting, 37.5% (3/8) underwent aortic valve replacement, 25.0% (2/8) underwent type A aortic dissection repair, and the remaining 12.5% (1/8) underwent pulmonary thromboendarterectomy. Six patients underwent percutaneous intervention. Median cardiopulmonary bypass time was 136.5 [110.0, 178.8] minutes. Median arterial cannula size was 20.0 [20.0, 24.0] Fr. Bicaval cannulation was performed in all cases describing cannulation strategy (5/5). Median superior vena cava cannula size was 28.0 [28.0, 28.0] Fr, and inferior vena cava cannula size was 28.0 [28.0, 28.0] Fr. No mortality was reported with a median follow up time of 6.0 [6.0, 10.5] months. In conclusion, Common cardiac procedures can be performed with reasonable safety in this patient population. Operative adjustments may need to be made with respect to equipment to accommodate patient-specific needs.
PubMed: 32274169
DOI: 10.21037/jtd.2020.02.05 -
European Journal of Endocrinology Mar 2020To provide an overview of cognitive and motor outcome, and quality of life (QoL) in patients with congenital central hypothyroidism (CH-C). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To provide an overview of cognitive and motor outcome, and quality of life (QoL) in patients with congenital central hypothyroidism (CH-C).
DESIGN
Systematic review with individual patient data (IPD) meta-analysis.
METHODS
OVID MEDLINE, EMBASE and PsycInfo were searched from inception to June 11th, 2019. Studies in patients with CH-C, either isolated or with multiple pituitary hormone deficiency (MPHD), were included if CH-C patients could be separated from any additional patient groups. Primary outcomes were full-scale intelligence quotient (FSIQ) and motor outcome; secondary outcome was QoL. Following data-extraction, one-stage IPD meta-analysis was performed, fitting a linear mixed model with FSIQ as dependent variable. Random intercepts were fitted for each study.
RESULTS
Six studies measuring FSIQ were eligible for meta-analysis, comprising 30 CH-C patients (20 males; 27 MPHD patients). FSIQ range was wide (64-123). Mean weighted FSIQ was 97 (95% CI: 88-105). Twenty-seven percent had an FSIQ below 85 (≥1 s.d. below norm score), and 10% below 70 (≥2 s.d. below norm score). There was no significant association between FSIQ and sex or age. Age at treatment initiation was available from three studies only, thus impeding a reliable analysis of this parameter. Motor outcome and QoL were each studied in one study; no quantitative analyses could be performed for these outcomes.
CONCLUSION
A wide range in FSIQ scores was observed in CH-C patients. Results should be interpreted with caution, because included patients mainly had MPHD and age at treatment initiation was unknown for the majority of patients.
Topics: Adolescent; Child; Child, Preschool; Congenital Hypothyroidism; Female; Humans; Hypopituitarism; Intelligence Tests; Male; Quality of Life; Young Adult
PubMed: 31961799
DOI: 10.1530/EJE-19-0874 -
Clinical Genetics Jan 2020This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We... (Review)
Review
This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We have used a scoping review methodology particularly recommended for mapping and summarizing existing research evidence, and to identify knowledge gaps. The review process was conducted in accordance with the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews). The selection of studies was based on criteria predefined in a review protocol. Twenty-nine publications were included; 2 reviews, and 27 primary studies. Key information such as reference details, study characteristics, topics of interest, main findings and the study author's conclusion are presented in text and tables. Over the past decades, there has only been a slight increase in publications on adults with achondroplasia. The reported morbidity rates and prevalence of medical complications are often based on a few studies where the methodology and representativeness can be questioned. Studies on sleep-related disorders and pregnancy-related complications were lacking. Multicenter natural history studies have recently been initiated. Future studies should report in accordance to methodological reference standards, to strengthen the reliability and generalizability of the findings, and to increase the relevance for implementing in clinical practice.
Topics: Achondroplasia; Adult; Bone Diseases; Female; Female Urogenital Diseases; Humans; Obesity; Otorhinolaryngologic Diseases; Pain; Pregnancy; Quality of Life; Reproducibility of Results; Respiration Disorders; Sleep Wake Disorders; Spinal Stenosis
PubMed: 30916780
DOI: 10.1111/cge.13542 -
The Cochrane Database of Systematic... Nov 2018Iodine deficiency is the main cause of potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is...
BACKGROUND
Iodine deficiency is the main cause of potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world.
OBJECTIVES
To assess the effects of iodine supplementation overall, and of different forms and dosages of iodine supplementation separately, in the prevention of iodine deficiency disorders in children.
SEARCH METHODS
The Cochrane Library, MEDLINE, EMBASE and reference lists, databases of ongoing trials and the Internet were searched.
SELECTION CRITERIA
We included randomised controlled trials and prospective controlled trials not using randomisation of iodine supplementation in children living in areas of iodine deficiency.
DATA COLLECTION AND ANALYSIS
Two reviewers did the initial data selection and quality assessment of trials independently. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format.
MAIN RESULTS
Twenty-six prospective controlled trials were related to our question, assessing a total of 29613 children. Twenty of them were classified as being of low quality, six of moderate quality. Most studies used iodised oil as a supplement, but other supplements were also used. The intervention groups were compared to a non-supplemented control group, different doses or different forms of iodine supplementation.There was a clear tendency towards goitre reduction with iodine supplementation; this was significant in several studies. Significant differences in physical development were not seen, except in one study. Results for differences in cognitive and psychomotor measures were mixed, with only few studies showing a positive intervention effect. One study suggested that infant mortality was lowered after iodine supplementation.Most studies showed a significant increase in urinary iodine excretion and levels recommended by the WHO were reached in most cases after supplementation. Thyroid-stimulating hormone (TSH) levels were significantly reduced in one study. In 1.8% of the children investigated, adverse effects were found, most of them were minor and transient.
AUTHORS' CONCLUSIONS
Despite most of the included studies being of low quality, the results suggest that iodine supplementation, especially iodised oil, is an effective means of decreasing goitre rates and improving iodine status in children. Indications of positive effects on physical and mental development and mortality were seen, although results were not always significant. Adverse effects were generally minor and transient. Insufficient evidence was available on non-oil supplements. High quality controlled studies investigating relevant long term outcome measures are needed to address the question of the best form of iodine supplementation in different population groups and settings.
Topics: Child; Congenital Hypothyroidism; Controlled Clinical Trials as Topic; Dietary Supplements; Goiter; Humans; Iodates; Iodine; Iodized Oil; Myxedema; Potassium Compounds; Potassium Iodide; Sodium Chloride, Dietary
PubMed: 30489630
DOI: 10.1002/14651858.CD003819.pub3 -
Epidemiology (Cambridge, Mass.) Jan 2019Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children, yet its etiology is poorly understood. Early thyroid hormone...
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children, yet its etiology is poorly understood. Early thyroid hormone disruption may contribute to the development of ADHD. Disrupted maternal thyroid hormone function has been associated with adverse neurodevelopmental outcomes in children. Among newborns, early-treated congenital hypothyroidism has been consistently associated with later cognitive deficits.
METHODS
We systematically reviewed literature on the association between maternal or neonatal thyroid hormones and ADHD diagnosis or symptoms. We searched Embase, Pubmed, Cinahl, PsycInfo, ERIC, Medline, Scopus, and Web of Science for articles published or available ahead of print as of April 2018.
RESULTS
We identified 28 eligible articles: 16 studies of maternal thyroid hormones, seven studies of early-treated congenital hypothyroidism, and five studies of neonatal thyroid hormones. The studies provide moderate evidence for an association between maternal thyroid hormone levels and offspring ADHD, some evidence for an association between early-treated congenital hypothyroidism and ADHD, and little evidence for an association between neonatal thyroid hormone levels and later ADHD.
CONCLUSIONS
The reviewed articles suggest an association between maternal thyroid function and ADHD, and possibly between early-treated congenital hypothyroidism and ADHD. Study limitations, however, weaken the conclusions in our systematic review, underlining the need for more research. Importantly, there was much variation in the measurement of thyroid hormone function and of ADHD symptoms. Recommendations for future research include using population-based designs, attending to measurement issues for thyroid hormones and ADHD, considering biologically relevant covariates (e.g., iodine intake), and assessing nonlinear dose-responses.
Topics: Attention Deficit Disorder with Hyperactivity; Child; Congenital Hypothyroidism; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Thyroid Gland; Thyroid Hormones
PubMed: 30299402
DOI: 10.1097/EDE.0000000000000937