Thyroid Stimulating Hormone Level at Diagnosis as a Predictor of Persistent Subclinical Hypothyroidism in Children with Down Syndrome

Objective

To evaluate subclinical hypothyroidism in a cohort of children with Down syndrome and identify a TSH level at the time of diagnosis to predict persistent hypothyroidism.

Methods

192 children (age <3 years) with Down syndrome, registered in the Genetic Clinic of a referral tertiary care Hospital from 2010 to 2015 were evaluated with thyroid function test at initial visits and subsequently based on standard protocol. Children with subclinical hypothyroidism were evaluated at 3 years of age after discontinuation of thyroxine for 3 months.

Results

47 (24.5%) children had elevated TSH and among them 43 (91.5%) had subclinical hypothyroidism. Among the subclinical hypothyroidism group, 25 (73.5%) had transient hypothyroidism and 9 (26.5%) persistent hypothyroidism. Initial TSH level at the time of diagnosis was higher in persistent hypothyroidism group as compared to transient group (P= 0.003). The best cut-off level for prediction of persistent hypothyroidism for initial TSH level was 11.6 mIU/L.

Conclusion

Subclinical hypothyroidism, especially transient, is the commonest form of thyroid dysfunction in children with Down syndrome. The initial TSH level may help to predict the possibility of persistence of hypothyroidism.

     

Non-autoimmune subclinical and overt hypothyroidism in idiopathic steroid-resistant nephrotic syndrome in children

Objective

To evaluate the frequency of non-autoimmune subclinical and overt hypothyroidism in children with idiopathic steroid-resistant nephrotic syndrome (SRNS).

Methods

This cross-sectional study recruited 30 children (age 1–18 y) with idiopathic SRNS; and 30 healthy controls. Serum T3, T4 and TSH were performed in cases as well as controls. Anti-thyroid peroxidase and anti-thyroglobulin antibody tests were performed in all cases.

Results

Non-autoimmune subclinical or overt hypothyroidism was detected in 10 out of 30 children with idiopathic SRNS; 2 had overt hypothyroidism, while 8 patients had subclinical hypothyroidism. Children with SRNS had a mean (SD) TSH value 4.55 (4.64) mIU/L that was higher as compared to controls (1.88 (1.04) mIU/L) (P<0.01). Focal segmental glomerulosclerosis (FSGS) was the commonest histopathological condition, seen in 13 (43.3%). Children with overt hypothyroidism (2 cases) and grade III subclinical hypothyroidism (1 case) were subsequently started on levothyroxine therapy.

Conclusions

The prevalence of subclinical and overt hypothyroidism seems to be high in idiopathic SRNS, with almost one-third of children having overt or subclinical non-autoimmune hypothyroidism.

     

Intelligence Quotient at the Age of Six years of Iranian Children with Congenital Hypothyroidism

Objective

To evaluate the success rate of the National newborn screening program in maintenance of intelligent quotient (IQ) of children with congenital hypothyroidism in Iran.

Design

Retrospective cohort study.

Methods

The IQ scores, in three subsets of verbal, non verbal (Performance) and full scale IQ, of 240 children diagnosed with Transient congenital hypothyroidism (TCH) and Permanent congenital hypothyroidism (PCH), from 5 provinces in 5 different geographical areas of Iran, were measured at the age of 6 years using revised Wechsler pre school and primary scale of intelligence and compared with 240 healthy children. We used independent sample t test and two-way ANOVA for data analysis.

Results

Mean of verbal, performance, and full scale IQ scores were lower in the CH cases (permanent and transient) than the control group. Most of the IQ differences in two studied groups related to the PCH cases (P=0.005). Mean difference of IQs between children in the two groups in Yazd province (center of Iran) was higher than other provinces, and they also had significantly lower IQ than their control (healthy) children (P=0.001). No treated child had IQ<70.

Conclusion

Although mean IQs of CH children was lower than their controls, IQ of all treated CH cases were close to the healthy children.

     

Subclinical Hypothyroidism: A Prospective Observational Study from Southern India

Objective

To assess the natural history and progression of subclinical hypothyroidism and to study factors which help predict evolution of subclinical hypothyroidism into overt hypothyroidism.

Methods

Longitudinal study in 40 children (2-16 yrs) presenting with subclinical hypothyroidism in a tertiary care unit in Chennai, India. Patients showing evidence of overt hypothyroidism or thyroid stimulating hormone ≥15 mIU/mL during follow-up were started on thyroxine. Others were followed up with 3-monthly thyroid function tests up to one year.

Results

At the end of our study period 3 (7.5%) were overtly hypothyroid, 16 (40%) remained as subclinical hypothyroid, and 21 (52.5%) became euthyroid. Evidence of autoimmunity at baseline was a significant (P<0.05) risk factor for progression to overt hypothyroidism.

Conclusions

Subclinical hypothyroidism in children, with thyroid stimulating hormone upto 15 mIU/L and irrespective of thyroid autoimmunity, needs only periodic clinical and biochemical follow up. Thyroid autoimmunity may point to an increased probability of progression to overt hypothyroidism.

     

Neurodevelopmental outcome of children with congenital hypothyroidism diagnosed in a national screening program in Turkey

Objective

To study the factors affecting a neurodevelopmental status of children with congenital hypothyroidism, diagnosed on national screening program.

Methods

The study was performed in the Pediatric Endocrinology Department of Dr. Behcet Uz Children’s Hospital between May 2012 and May 2013. Children with congenital hypothyroidism, aged between 24 and 36 months, diagnosed by national screening program were included in the study group. Healthy subjects at the same age group consisted of the control group. For the neurodevelopmental evaluation, Bayley Scale of Infant Development- II (BSID-II) was used. Factors possibly effective on neurodevelopment were evaluated.

Results

42 patients and 40 healthy children (mean (SD) age, 29.4 (3.7) and 29.2 (3.5), respectively were included in the study. The mean MDI score [92.6 (7.07) vs 97.1 (9.69), P=0.14)] and the mean PDI score [97.8 (15.68) vs 99.1 (10.57), P=0.66)] in the study group and control group were not significantly different. Among the patient, 4.6% and 4.7% children were moderately retarded as per the MDI scores and PPI scores, respectively. The sex, socioeconomic status, birth weight, screening levels of TSH, severity of the congenital hypothyroidism, initiation time and the dosage of thyroid hormone replacement, length of the normalization period of TSH, and adherence to treatment were not found to affect the MDI and PDI scores of the patients.

Conclusion

Some children with congenital hypothyrodism may have mild to moderate neurodevelopmental retardation, despite the early diagnosis and treatment, and thus need to be under regular follow-up for neurodevelopmental status.

     

Neurodevelopmental evaluation of very low birth weight infants with transient hypothyroxinemia at corrected age of 18–24 months

Objective

To perform neurodevelopmental evaluation at 18 to 24 months’ corrected age in very low birth infants (VLBW) with transient hypothyroxinemia.

Design

Cohort study.

Setting

Maternity teaching hospital.

Patients

Premature infants who were previously evaluated for thyroid hormone values in the first weeks of life were included.

Intervention

Data of these infants who weighed ≤1500 g and ≤32 weeks of gestation were retrieved for the current study. Available subjects (n=56) were evaluated for neurodevelopmental status at 18 to 24 months of corrected age. Bayley Scales of Infant Development -Second Edition (BSID-II) was performed to define Mental developmental index (MDI) and Psychomotor developmental index (PDI).

Results

The mean MDI and PDI scores were similar between the infants with and without transient hypothyroxinemia of prematurity (THOP) [79.9 ± 14.9 vs 70 ± 20.7, respectively (P=0.54); and 92.2 ± 16.4 vs 85.6 ± 18.9, respectively (P=0.68)]. After adjustment for gestational age and multiple prenatal, perinatal, and early and late neonatal variables, THOP was not associated with an increased risk of disabling cerebral palsy, or a reduction of MDI and PDI scores.

Conclusions

THOP may not be an important cause of problems in neurologic and mental development detected at the age of 18 to 24 months’ corrected age.

     

Wachstum bei Störungen der Schilddrüsenfunktion im Kindes- und Jugendalter

Background

Disorders of the thyroid function of mother and child can not only irreversibly inhibit maturation of the central nervous system, but may also affect growth and puberty.

Objectives

Review of the consequences of thyroid function disorders on the growth of children and adolescents and the relevance of adequate treatment.

Materials and Methods

This article summarises the current literature concerning the effect of thyroid hormone disorders of mother and child and their therapy on growth.

Results

Every untreated manifestation of congenital or acquired hypothyroidism is associated with a delay of growth and skeletal maturation. In children presenting with acquired hyperthyroidism, height is shifted towards higher values and skeletal maturation is accelerated. Approximately 20?% of children and adolescents with Down syndrome develop primary hypothyroidism, frequently manifesting within the first months of life (approximately 5.5?%). Adequate treatment of the thyroid disorder can normalise growth disorders. About 6?% of children with growth hormone deficiency develop abnormally low free thyroxin (fT4) levels in serum during growth hormone treatment due to increased conversion of T4 to T3. There is no indication for treatment after excluding secondary hypothyroidism.

Conclusions

Early diagnosis and timely, adequate treatment of thyroid function disorders of mother and child are essential to achieving growth that is as age-appropriate as possible in affected children and adolescents

     

Thyroid dysfunction and developmental anomalies in first degree relatives of children with thyroid dysgenesis

Background

Familial clustering in patients with permanent congenital hypothyroidism (CH) caused by thyroid dysgenesis (TD) has been reported in developed countries. There is no information on familial TD from developing countries.

Methods

A total of 312 first degree relatives belonging to 80 families of children with TD (group 1) and 40 families of age-matched normal children (group 2) were screened by thyroid ultrasonography, serum total thyroxine (T4) and thyroid stimulating hormone (TSH).

Results

Thyroid scintigraphy revealed agenesis in 78.7% of the patients, ectopic gland in 15%, and hypoplasia in 6.2%. The mean thyroid volumes were similar in parents and siblings of both groups. Eight (10.6%) mothers in group 1 were identified to have thyroid hypoplasia as compared with none in group 2 (P=0.03). Serum TSH was significantly higher in group 1 than in group 2 (P=0.004). Sixteen (7.8%) subjects (6 mothers, 5 fathers, and 5 siblings) in group 1 were found to have subclinical hypothyroidism as compared to none in group 2 (P<0.05). Four families were identified to have thyroid developmental anomalies and abnormal thyroid functions accounting for 5% of cases of familial TD in our cohort.

Conclusion

Thyroid developmental anomalies and thyroid function abnormalities are more frequent in first degree relatives of children with TD as compared with a control population. These findings suggest that possibly there is a genetic component of TD in Indian patients.

     

Transcutaneous bilirubin nomogram for healthy term and late preterm neonates in first 96 hours of life

Objective

To develop nomogram of Transcutaneous Bilirubin among healthy term and late-preterm neonates during first 96 hours of age.

Design

Longitudinal observational study.

Setting

Neonatal unit of a tertiary care Hospital of Central Gujarat, India.

Participants

1075 healthy term and late preterm neonates (≥35weeks).

Intervention

Six-hourly transcutaneous bilirubin was obtained from birth to 96 hour of life using Drager JM 103 Transcutaneous Bilirubinometer.

Main outcome measures

Nomogram of Transcutaneous Bilirubin with percentile values was obtained, rate of rise of bilirubin was calculated and predictive ability of normative data was analyzed for subsequent need of phototherapy.

Results

The age-specific percentile curves and nomogram were developed from the transcutaneous bilirubin readings of 1,010 neonates. Rate of rise in first 12 hour was 0.2 mg/dL and was 0.17 mg/dL in 12 to 24 hour of life which decreased on second day of life. Neonates who required phototherapy had consistently higher readings of transcutaneous bilirubin and also higher rate of rise in first 48 hrs.

Conclusion

Neonates whose transcutaneous bilirubin is above the 50th percentile should be monitored for the development of significant hyperbilirubinemia.

     

Study of Family Clustering and <Emphasis Type="Italic">PNPLA3</Emphasis> Gene Polymorphism in Pediatric Non Alcoholic Fatty Liver Disease

Objectives

To find association of pediatric NAFLD with metabolic risk factors, and Patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene polymorphism.

Design

Cross-sectional study

Setting

Pediatric Hepatology unit of a tertiary care hospital

Participants

Overweight/obese children (<18 years) with (69 patients) or without (30 patients) NAFLD (ultrasonography based), and their parents.

Intervention

Metabolic screening, PNPLA3 gene polymorphism, and transient elastography

Outcome measure

Association of pediatric NAFLD with parental metabolic risk factors and PNPLA3 gene polymorphism.

Results

In the NAFLD group, there was high parental incidence of metabolic diseases, fatty liver (80%) and low high-density lipoproteins levels (84%). Family history of NAFLD (in any parent), higher alanine aminotransferase levels and higher total cholesterol levels in the child independently predicted possibility of NAFLD, but similar results could not be replicated for PNPLA3 gene polymorphism. Controlled attenuation parameter measurement (by transient elastography) had high sensitivity and specificity to diagnose steatosis.

Conclusion

There is high familial incidence of metabolic diseases in children with NAFLD. Controlled attenuation parameter can be useful as a non-invasive modality to screen fatty liver in children.

     

Endoscopic Management of Vesicoureteral Reflux and Long-term Follow-up

Objectives

To report our experience with endoscopic management of vesicoureteral reflux (VUR) by injection of a tissue bulking substance–Dextranomer/ hyaluronic acid copolymer at vesicoureteric junction.

Design

Retrospective analyses of case records.

Setting

Pediatric Surgery department in a tertiary care government Institute.

Participants

500 children (767 renal units) consecutively referred to the out-patient department with vesicoureteral reflux noted on micturating cysto-urethrogram (MCU) over a period of 13 years (2004-2016).

Intervention

Preoperative VUR grading and renal scars on radionuclide scans were documented. Dextranomer hyaluronic acid copolymer was injected through a cystoscope at the vesicoureteral junction as a day care procedure under short anesthesia. Patients were followed (average duration 27.3 mo) with clinical assessment, periodic urine cultures and renal scans.

Main outcome measure

Cessation of VUR and symptomatic relief / clinical success postoperatively at 3 months.

Results

Complete symptomatic relief was obtained in 482 (96.4%) patients. In 681 units where MCU was available, 614 (90%) units showed resolution of VUR.

Conclusion

Endoscopic injection of tissue bulking substances at vesicoureteric junction to stop VUR seems to be an effective intervention

     

Joint involvement in children with celiac disease

Objective

To determine early joint involvement as detected by ultrasonography in children with newly diagnosed celiac disease, and in children with celiac disease on gluten-free diet for more than 6 months.

Methods

Cross-sectional comparative study evaluating joint abnormalities by ultrasonography.

Results

Ultrasonography showed abnormalities in 19 out of 60 (31.7%) children with newly diagnosed celiac disease as compared to 2 (3.3%) out of 60 in those on a gluten-free diet for more than 6 months.

Conclusion

Subclinical synovitis as detected by ultrasound is a frequent finding in newly diagnosed children with celiac disease.

     

Carnitine Deficiency in Chinese Children with Epilepsy on Valproate Monotherapy

Objective

To explore the incidence and independent risk-factors of secondary carnitine deficiency in Chinese children with epilepsy on valproate monotherapy.

Methods

The free carnitine and acylcarnitines levels in 299 children with epilepsy on valproate monotherapy between June 2014 and September 2015 were compared with age- and sex-matched 299 healthy controls.

Results

Children with valproate monotherapy had lower free carnitine levels [23.86 (10.60) μmol/L] than the controls [36.37 (9.37) μmol/L] (P<0.01). Most acylcarnitines were significantly lower in children with valproate monotherapy than controls. 63 children (21.1%) with epilepsy had carnitine deficiency; 54 were asymptomatic. Female gender (OR 2.1), high alanine aminotransferase levels (OR 1.0) and long duration of VPA treatment (1-12 mo) (OR 1.9) were independent risk factors for secondary carnitine deficiency induced by VPA.

Conclusions

Carnitine deficiency with valproate is more likely in females, those with transaminitis, and those receiving the drug for 1–12 months.

     

Improving First-hour Breastfeeding Initiation Rate After Cesarean Deliveries: A Quality Improvement Study

Objective

To improve the rates of first hour initiation of breastfeeding in neonates born through cesarean section from 0 to 80% over 3 months through a quality improvement (QI) process.

Design

Quality improvement study.

Setting

Labor Room-Operation Theatre of a tertiary care hospital.

Participants

Stable newborns ≥35 weeks of gestation born by cesarean section under spinal anesthesia.

Procedure

A team of nurses, pediatricians, obstetricians and anesthetists analyzed possible reasons for delayed initiation of breastfeeding by Process flow mapping and Fish bone analysis. Various change ideas were tested through sequential Plan-Do- Study-Act (PDSA) cycles.

Outcome measure

Proportion of eligible babies breast fed within 1 hour of delivery.

Results

The rate of first-hour initiation of breastfeeding increased from 0% to 93% over the study period. The result was sustained even after the last PDSA cycle, without any additional resources.

Conclusions

A QI approach was able to accomplish sustained improvement in first-hour breastfeeding rates in cesarean deliveries.

     

Paradoxical Vocal Cord Motion in a Pair of Twin Preterm Infants

Background

Intractable obstructive apneas requiring multiple intubations are rare in newborns.

Case characteristics

We report a pair of twins born at 29 weeks gestation who had severe obstructive apneas due to Paradoxical Vocal Cord Motion (PVCM).

Outcome

The symptoms resolved promptly with ipratropium nebulization. Follow-up at 12 months of age revealed normal development.

Message

PVCM should be considered in the differential diagnosis of intractable obstructive apneas in very low birth weight preterm infants.

     

Early Neurodevelopmental Outcomes After Corrective Cardiac Surgery In Infants

Objective

To assess neurodevelopmental status in Indian infants undergoing corrective surgery for congenital heart disease (CHD) and to analyze factors associated with neurodevelopmental delay.

Design

Cross-sectional study.

Setting

Tertiary-care pediatric cardiology facility.

Participants

Consecutive infants undergoing corrective surgery for CHD (January 2013–December 2014). Palliative procedures, and patients with known genetic syndromes were excluded.

Main outcome measures

Neurodevelopmental evaluation 3 months, and one year after surgery using Developmental Assessment Scales for Indian Infants (DASII); scores were categorized as delayed if ≤70.

Results

Of the 162 children enrolled, delayed PDI and MDI scores were observed in 33.5% and 19.6% of patients at 3 months, respectively; this reduced to 14.5 % on 1-year follow-up. On multivariate analysis, delayed PDI outcome at one year was predicted by early term birth and one-year postoperative head circumference Z-score <–2. Delayed MDI was associated with higher mean perfusion pressure on cardiopulmonary bypass. Cardiac diagnosis and peri-operative factors did not impact neurodevelopmental outcomes.

Conclusions

Neurodevelopmental status is delayed in 14.5% of infants one year after corrective infant heart surgery.

     

Serum Interleukin-6 Levels in Children with Febrile Seizures

Objectives

To compare levels of Interleukin-6 (IL-6) in children with febrile seizures and febrile controls.

Methods

Study conducted in a tertiary-care hospital in Northern India from November 2013 to April 2015, enrolling 160 children (80 each with febrile seizures and febrile controls), aged 6–60 months. Serum IL-6 estimated by ELISA method. Iron study done as per standard technique. All the cases of febrile seizure were followed up at 1 week, 3 months and 6 months for recurrence of seizures.

Results

The mean serum IL-6 levels in children with febrile seizures was 62.0 (63.9) pg/mL and febrile controls was 86.9 (70.6) pg/mL (P=0.025).

Conclusion

Serum IL-6 levels were significantly lower in children with febrile seizures as compared to febrile controls.

     

Disseminated cryptococcosis in an immunocompetent toddler

Background

Immunodeficient children are more prone for invasive cryptococcal infections.

Case characteristics

A 2-year-old boy with disseminated cryptococcosis was evaluated for underlying immunodeficiency without success.

Intervention/outcome

Child was managed successfully.

Message

Immunocompetent children with disseminated cryptococcosis can present diagnostic or therapeutic challenge in resource-limited settings.

     

Outcomes of Children with Severe Acute Malnutrition in a Tribal Daycare Setting

Objective

To describe the nutritional outcomes of children with severe acute malnutrition (SAM) in a village-level intervention.

Methods

This observational longitudinal study on 179 children aged <3 years was conducted in seven tribal blocks of Central and Eastern India with SAM managed in a comprehensive day care program.

Results

76% children with SAM showed improvement over a 4-6 months period, with 37% shifting to normal anthrometric status. There was a significant shift in Z scores.

Conclusions

This community-based intervention showed fair results for management of children with SAM at village level.