Twin–twin transfusion syndrome,coarctation of the aorta and hypoplastic aortic arch: A case series report

Aim: The twin–twin transfusion syndrome (TTTS) complicates 10–30% of monochorionic pregnancies. The incidence of pulmonary stenosis and endocardial fibroelastosis is especially high in the recipient twin. We report a novel finding of four cases of coarctation of the aorta and hypoplastic aortic arch in the donor to raise awareness of cardiac lesions in twins affected by TTTS. Method: Retrospective review of both neonatal database and mortality data from 2002 to 2007 with cross‐validation from the local tertiary cardiology unit data (1998–2006) to identify children presenting with coarctation who were also twins. Results: We identified four monochorionic twin pairs affected by the TTTS, delivered between 25 weeks and 36 weeks' gestation, where the donor was found to have coarctation of the aorta or a hypoplastic aortic arch. In addition, two of the four recipients also had cardiac abnormalities. There was a high mortality rate of 30% for both twins, and a high morbidity rate, especially for neurological sequelae. Conclusion: We believe that the types of abnormalities seen may be explained by the altered fetal blood flow and haemodynamics in TTTS. Given the increased prevalence of congenital heart disease in TTTS, with an increased risk of coarctation in the donor twin and pulmonary stenosis in the recipient, intra‐uterine surveillance and a post‐natal comprehensive cardiac assessment for both twins is warranted.     

Basal insulin and total daily insulin dose in children with type 1 diabetes using insulin pumps

Objective:  To assess the contribution of basal insulin to the total daily dose (CBITDD) and to identify the determinant factors in children with type 1 diabetes mellitus.
Study design:  Cross-sectional study in which the basal insulin requirement was established based on a memory read-out of insulin delivery from pumps. Factors such as glycated haemoglobin A1c (HbA1c), fasting C-peptide, standard deviation score of body mass index (sdsBMI) and demographic data were determined during routine hospital visits. Study group included a total of 90 well-controlled diabetic children with the mean HbA1c 6.6 ± 0.7 (5.2–7.9), age 10.4 ± 4.4 yr (1.1–17.9 yr), diabetes duration 3.0 ± 2.6 yr (0.3–10.9 yr) and sdsBMI 0.08 (−2.27 to 1.79), excluding patients with ketoacidosis or infectious diseases.
Results:  Correlations between CBITDD and age (r = 0.39 and p < 0.005) and diabetes duration (r = 0.61 and p < 0.0001) and an inverse correlation with C-peptide (r = −0.41 and p = 0.0001) were found. C-peptide-positive patients had a significantly lower percentage of basal insulin compared with C-peptide-negative patients (20.6 ± 11 vs. 31.6 ± 11.0%, respectively; p = 0.0004); yet, no significant difference in total insulin daily dose (0.65 ± 0.3 vs. 0.78 ± 0.2 U/kg/d, respectively) was observed.
Conclusions:  The percentage of basal insulin in diabetic children is below 50% and in well-controlled diabetic children is related to the fasting C-peptide level, age of patient and diabetes duration but not to HbA1c and sdsBMI.     

The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

Objective:  To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM)
Research design and methods:  Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10–18 yr, puberty (≥Tanner breast stage 2 or testicular volume >4 mL), insulin dose ≥1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests.
Results:  Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (−0.3 vs. −0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone.
Conclusion:  The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM.     

The Tei index for evaluation of fetal myocardial performance in sick fetuses

OBJECTIVE: The Tei index is a useful, new, noninvasive Doppler index of combined systolic and diastolic function calculated by isovolumic relaxation time plus isovolumic contraction time divided by ejection time. Sick fetuses were evaluated with the Tei index. METHODS: The study group underwent two-dimensional/Doppler echocardiographic measurement of their Tei index and included 10 monochorionic diamniotic (MD) twin pairs with non-twin to twin transfusion syndrome (TTTS), 4 twin pairs with TTTS, 12 fetuses with intrauterine growth retardation (IUGR), 14 fetuses of diabetic mothers, 3 hydrops fetalis fetuses, 8 fetuses of mothers treated with a tocolytic agent, and 40 normal fetuses (control group). RESULTS: The Tei indices in the following groups were significantly higher than the control: recipient fetuses in TTTS, large for gestational age (LGA) fetuses of diabetic mothers, and fetuses with hydrops fetalis. CONCLUSION: The Tei index may be a useful tool for the assessment of fetal cardiac status in a variety of sick fetuses. Recipient fetuses in TTTS, LGA fetuses of diabetic mothers, and hydrops fetalis fetuses may have abnormal myocardial performance. The Tei index readily provides early detection of diminished myocardial function, particularly ventricular dysfunction.     

Monochorionic twin fetuses showing a reversal of donor-recipient phenotypes in severe twin–twin transfusion syndrome without oligo-polyhydramnios sequence

ABSTRACT   Antenatal sonographic diagnosis of twin–twin transfusion syndrome (TTTS) is based on findings of a twin oligo-polyhydramnios sequence (TOPS) observed in monochorionic twin fetuses. However, TTTS can develop without a significant characteristic intertwin discordance in the amniotic fluid volumes. We report an uncommon form of TTTS without TOPS showing severe anemia in one twin and polycythemia in the other. Based on sonographic findings, it is considered that the recipient twin became the donor later in gestation, and vice versa. It is concluded therefore that even in the absence of TOPS, the possibility of severe TTTS with a suspected reversal of donor-recipient phenotypes during pregnancy should not be excluded, and serial Doppler studies including the measurement of the middle cerebral artery peak systolic velocity should be routinely performed even in seemingly uncomplicated monochorionic twin fetuses without TOPS.     

Discordant amino acid profiles in monochorionic twins with twin-twin transfusion syndrome

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n = 12) and without (n = 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p < 0.001), leucine (p < 0.001), iso-leucine (p < 0.05), histidine (p < 0.001) and L-arginine (p < 0. 001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p < 0.001), serine (p < 0.01), glycine (p < 0.001) and tyrosine (p < 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 +/- 64 versus 396 +/- 23 microM; p < 0.001) and the non-TTTS twin pairs (p < 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism.     

Twin-twin transfusion syndrome: report of two cases with hemodynamic complications]

CASE REPORTS: We report two cases of cardiac dysfunction in twin-twin transfusion syndrome (TTTS) evaluated with serial echocardiography. Two cases of TTTS were referred at 27 and 26 weeks. At delivery at 31 weeks, the first recipient twin had evidence of severe cardiac dysfunction with decreased ventricular function and transient systemic hypertension. There was polycythaemia. Favorable outcome was observed after treatment with arterial vasodilating (nicardipine) and inotropic agents (dobutamine, enoximone), and reduction of haematocrit. At 28 weeks the other recipient twin had cardiac dilatation with hypokinetic myocardium. These alterations were cured by dobutamine. CONCLUSION: These cases show that even severe cardiac dysfunction may be reversed after birth unlike in utero natural evolution.     

Cardiac outcomes of hydrops as a result of twin–twin transfusion syndrome treated with laser surgery

Aim:   To determine cardiac outcomes of foetal hydrops as a result of twin–twin transfusion syndrome treated with laser surgery.
Methods:   Hydrops identified in 16 recipient foetuses with twin–twin transfusion syndrome was treated with laser ablation surgery to anastomotic vessels. Prior to laser surgery, the foetuses were assessed by echocardiography for cardiac abnormalities and ventricular and valvular dysfunction. After delivery, echocardiography was performed on 15 of the 16 newborn infants.
Results:   Foetal echocardiography indicated impaired biventricular function in the 16 hydropic foetuses. Five foetuses had little or no forward flow through the pulmonary valve, while four had pulmonary regurgitation. Following laser surgery performed at a mean of 22.9 weeks gestation, hydrops resolved in all cases. Delivery occurred at a mean of 33.6 weeks gestation. Post-natal echocardiography revealed cardiac abnormalities in five neonates, of whom three had right ventricular outflow tract obstruction. One preterm infant with severe pulmonary stenosis died with intractable cardiac failure.
Conclusion:   The majority of hydropic infants with twin–win transfusion syndrome have normal cardiac outcomes following intrauterine laser surgery. As up to one-third may have cardiac abnormalities, cardiological monitoring is recommended during the first year of life.     

Health-related quality of life in intensively treated young patients with type 1 diabetes

Abstract:  This study aimed to analyse the impact of the disease and treatment on health-related quality of life (HRQOL) in intensively treated young patients with diabetes. Our main hypothesis was that metabolic control, gender, age and socio-economic status predict HRQOL. All children and adolescents (n = 400, 191 girls) and parents in a geographic population of two paediatric clinics in Sweden [mean age 13.2 yr, ±SD 3.9, range 2.6–19.6; mean duration of diabetes 5.1 yr, ±SD 3.8, range 0.3–17.6; yr mean haemoglobin A1c (HbA1c) 7.1%, ±SD 1.2, range 4.0–10.7] received the DISABKIDS questionnaire, a validated combined chronic generic and condition-specific HRQOL measure for children, and the EuroQol-5D questionnaire. Parents as proxy perceived HRQOL lower than their children. Adolescents with separated parents reported lower generic HRQOL (GeHRQOL) and diabetes-specific HRQOL (DiHRQOL) than those with parents living together (p = 0.027 and p = 0.043, respectively). Adolescent girls reported lower GeHRQOL (p = 0.041) and DiHRQOL (p = 0.001) than boys did. Parents of girls <8 yr of age reported lower DiHRQOL (p = 0.047) than did parents of boys <8 yr. In addition, a difference was found in HRQOL between centres. Intensive insulin therapy did not seem to lower HRQOL. If anything, along with better metabolic control, it increased HRQOL. A correlation between DiHRQOL and HbA1c was found in adolescents (r = −0.16, p = 0.046) and boys aged 8–12 yr (r = −0.28, p = 0.045). We conclude that the diabetes team can influence the HRQOL of the patients as there was a centre difference and because HRQOL is influenced by glycaemic control and insulin regimen. Girls seem to need extra support.     

Cardiac output and blood volume parameters using femoral arterial thermodilution

Background:  The pulse-induced continuous cardiac output (PiCCO) system is a less invasive method than pulmonary thermodilution for the measurement of cardiac output and estimating blood volume parameters. The normal values in children have not been defined. The purpose of the present paper was therefore to evaluate cardiac output and parameters of blood volume using femoral arterial thermodilution in critically ill children.
Methods:  A prospective study was performed in 17 critically ill children aged between 2 months and 14 years. Two measurements were taken for each determination of cardiac output, global end diastolic volume (GEDVI), intrathoracic blood volume index (ITBI), extravascular lung water index (ELWI), systolic volume index (SVI), stroke volume variation (SVV), cardiac function index (CFI), left ventricular contractility (dp/dt max), and the systemic vascular resistance index (SVRI).
Results:  One hundred and seventeen measurements were performed. The mean cardiac index (CI) was 3.5 ± 1.3 L/min per m². The GEDVI (399.7 ± 349.1 mL/m²), ITBI (574.5 ± 212.2 mL/m²) and dp/dt max (804.6 ± 372.1 mmHg/s) were lower than reported in adults, whereas ELWI (18.9 ± 9.3 mL/m2) and CFI (8 ± 2.5 L/min) where higher. The GEDVI, SVI, dp/dt max and CI increased with the weight of the patients whereas the ELWI values decreased.
Conclusions:  Femoral arterial thermodilution is a suitable technique for the measurement of cardiac output in critically ill children. The intrathoracic and intracardiac volumes are lower than in adults, whereas extrapulmonary water is higher; these values are related to the weight of the patient.     

Renal Tubular Apoptosis in Twin-to-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome (TTTS) is caused by uneven shunting of blood between monochorionic twins, resulting in polycythemia in the recipient twin and growth restriction, anemia, and oliguria in the donor twin. Recent reports have described loss of proximal convoluted tubules in the kidneys of TTTS donor twins. In order to elucidate the pathogenesis of tubular deficiency in TTTS, we have reviewed the renal pathology in 25 twin pairs with autopsy-proven TTTS. Loss of differentiated proximal tubules, associated with atrophy of medullary tubules, was identified in 12/25 donor twins. In seven of these cases (all > 23-wk gestational age), the kidneys showed diffuse or partial tubular atrophy without evidence of cell death, similar to previously reported patterns. In five cases (all between 18- and 22-wk gestation), proximal and medullary tubules showed active injury characterized by markedly increased apoptosis, cell detachment, and intraluminal cell debris associated with calcifications. Tubular apoptosis tended to be more prevalent in donor fetuses with greater inter-twin body weight discordance, consistent with a more severe degree of TTTS. These results extend the spectrum of tubular alterations in TTTS to include an early stage of active apoptotic injury. The temporal distribution of injury patterns suggests that apoptotic injury of proximal and medullary tubules may be a precursor to partial or diffuse tubular atrophy. We speculate that the risk for development of tubular apoptosis in TTTS depends on the severity and timing of the hemodynamic imbalance, whereby early mid-trimester fetuses may be more vulnerable.     

Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient

Despite advances in treatment, twin-to-twin transfusion syndrome (TTTS) still carries a high risk for perinatal mortality and morbidity. Simple blood transfer from the donor to the recipient twin cannot explain all of the features of this disease, in particular the recipient's hypertensive cardiomyopathy. We report a case in which TTTS resulted in preterm delivery with early neonatal death of both twins, allowing assessment of the renin angiotensin system (RAS) status of each fetus, both by cord blood renin and aldosterone assay and by renal immunohistochemistry. The donor had severe oliguria/oligohydramnios, whereas the recipient, in addition to severe polyuria/polyhydramnios, had cardiomyopathy, atrioventricular regurgitation, and ascites. Although immunohistochemistry demonstrated that renal secretion of renin was up-regulated in the donor and down-regulated in the recipient, cord blood levels of renin and aldosterone were similar, with high renin levels in both twins. This observation supports the hypothesis that despite renal RAS down-regulation, the recipient is exposed to RAS effectors elaborated in the donor and transferred via placental shunts. This may contribute to cardiomyopathy and hypertension in the recipient, which cannot be accounted for by hypervolemia alone. We thus hypothesized that in TTTS, the recipient's hypertensive cardiomyopathy could be due to a mechanism similar to the classical model of hypertension referred to as "2 kidneys-1 clip." Thus the hypovolemic donor twin, comparable to the clipped kidney, produces vasoactive hormones that compromise the recipient, comparable to the normal kidney, causing hypertension and cardiomyopathy.     

Twin–twin transfusion syndrome: cerebral ischemia is not the only fetal MR imaging finding

Background Twin–twin transfusion syndrome (TTTS) is a complication of monochorionic/diamniotic twin pregnancies. An imbalance of blood flow occurs through placental anastomoses, causing potentially significant morbidity and mortality in both twins. Although the sonographic findings of TTTS are well documented, we believe that MR imaging is a valuable adjunct. Objective We describe the fetal MR imaging findings associated with TTTS. Materials and methods From 2003 to 2005, 37 consecutive MR imaging studies were performed on multiple-gestation pregnancies. Of the 37, 25 were consistent with TTTS, correlated and confirmed by sonographic criteria. MR fetal abnormalities were documented. Results Cerebral ischemia, which could not be demonstrated by sonography, was delineated well by MR imaging. New findings noted on fetal MR imaging were enlargement of cerebral venous sinuses in both twins, dilatation of the renal collecting system in the recipient, lung lesions in the recipient and cerebral malformations in the donor. Conclusion MR imaging is an important adjunct in TTTS imaging. Its benefit over sonography is its clear definition of cerebral pathology, which is important for intervention and counseling. The new findings, particularly in the urinary tract and cerebral venous sinuses, also help support the diagnosis of TTTS and might reveal additional consequences of the altered hemodynamics that occur in TTTS.     

Effect of Carelink, an internet-based insulin pump monitoring system, on glycemic control in rural and urban children with type 1 diabetes mellitus

Objective:  To determine whether use of the internet-based insulin pump monitoring system, Carelink, improved glycemic control in rural and urban children treated with insulin pump therapy.
Research design:  We reviewed records of 94 children treated with insulin pump therapy between the years 2004 and 2007 and compared glycemic control, diabetes self-care measures, frequency of clinic visits, and geographic location associated with Carelink use.
Results:  Carelink users showed improvement in hemoglobin A1c (HbA1c) levels [8.0 ± 0.1 (SE) vs. 7.7 ± 0.1 (SE), p = 0.002]. Carelink users uploaded pump and glucometer data 2.2 ± 1.8 (SD) times per month over 0.8 ± 0.4 (SD) yr. Patients who had no access to carelink software and were followed in a conventional manner showed no change in HbA1c levels [8.0 ± 0.2 (SE) vs. 8.1 ± 0.2 (SE), p = 0.17] during the study period. Carelink non-users, defined as patients who had Carelink access but did not use it, had a higher HbA1c level at the start of the study and did not change over the study period [8.9 ± 0.2 (SE) vs. 9.0 ± 0.3 (SE), p = 0.82]. Rural Carelink users showed improvement in HbA1c levels following Carelink use [7.9 ± 0.2 (SE) vs. 7.4 ± 0.2 (SE), p = 0.001], yet had significantly fewer clinic visits per year compared with urban patients [2.8 ± 0.2 (SE) vs. 3.5 ± 0.1 (SE), p = 0.001].
Conclusion:  Use of the Carelink system was associated with improved glycemic control in children with type 1 diabetes on insulin pump therapy.     

The use of Doppler tissue imaging to predict cellular and antibody-mediated rejection in pediatric heart transplant recipients

Abstract:  DTI indices have been associated with cellular rejection in adult heart transplant recipients, but their predictive value in pediatric recipients is unknown. The purpose of this study was to evaluate DTI measures in the detection of cellular and AMR in pediatric heart transplant recipients. One hundred and forty-eight pediatric heart transplant recipients who had 267 cardiac catheterization procedures with EMB, echocardiogram with DTI, and BNP level performed on the same day were included in the study. For the mitral and tricuspid valves, the ratios (E/E') between the early diastolic inflow velocity by pulsed Doppler (E, m/s) and the early diastolic annular velocity by DTI (E', m/s) were obtained and compared between subjects with and without rejection. Of the 148 recipients, 30 subjects had a total of 37 episodes of rejection: 10 cellular (≥1B), 17 AMR, and 10 biopsy-negative clinical rejection. Mitral and tricuspid valve E/E' ratios were significantly higher in rejectors than in non-rejectors (5.5 ± 1.3 vs. 4.4 ± 1.4, p < 0.001 and 4.9 ± 2.1 vs. 4.1 ± 1.5, p < 0.01, respectively). By multivariate linear regression, mitral valve E/E' was an independent predictor of rejection. Mitral and tricuspid valve E/E' <5.0 had 93% and 89% NPV, respectively, for rejection. Mitral and tricuspid valve E/E' ratios <5.0 may be useful non-invasive screening measures to exclude rejection in pediatric heart transplant recipients.     

Continuous subcutaneous insulin infusion vs. multiple daily injections in children with type 1 diabetes: a systematic review and meta-analysis of randomized control trials

Objective:  To investigate potential effects of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) on glycemic control in children with type 1 diabetes mellitus (T1DM).
Study design:  Meta-analysis and systematic review of randomized control studies (RCTs). The electronic databases MEDLINE, Cochrane Library, and EMBASE were searched through October 2007.
Results:  Six RCTs involving 165 participants with T1DM met our predefined inclusion criteria. Combined data from all trials showed that the CSII group compared with the MDI group experienced a significant reduction in the level of glycosylated hemoglobin. The pooled weighted mean difference (WMD) was −0.24% [95% confidence interval (95% CI) −0.41 to −0.07, p < 0.001] with a fixed model and remained significant in the random effect model. This effect was reached by slightly decreasing insulin requirement [three RCTs, n = 74, WMD −0.22 IU/kg/d (95% CI −0.31 to −0.14, p < 0.001)]. No differences in the incidences of ketoacidosis and severe hypoglycemic events were found.
Conclusions:  In short-term insulin therapy, CSII compared with MDI is a more effective form of metabolic control and allows reducing the daily insulin requirement. Yet, no conclusions have been made so far whether this effect holds in later years. These results should be approached with caution because of the methodological limitations of the analyzed studies.     

Reducing postprandial hyperglycemia with adjuvant premeal pramlintide and postmeal insulin in children with type 1 diabetes mellitus

Objective:  The purpose of this study was to determine the effect of adjuvant premeal pramlintide with postmeal insulin on postprandial hyperglycemia in children with type 1 diabetes mellitus (T1DM).
Methods:  Eight adolescents with T1DM on intensive insulin therapy participated in an open-label, non-randomized, crossover study, comparing postprandial glucose excursions in study A (prescribed insulin regimen and given premeal) vs. study B (pramlintide + insulin). Prandial insulin dose for study B was decreased by 20% and given postmeal, while pramlintide was given just before the meal. Blood glucose (BG), glucagon, and pramlintide concentrations were measured basally and at timed intervals during a 300-min study period.
Results:  Postprandial incremental BG for the duration of the study was reduced in study B vs. study A with AUC_{(−60 to 300 min)} (area under the curve) at 6600 ± 2371 vs. 20 230 ± 3126 mg/dL/min (367 ± 132 vs. 1124 ± 174 mmol/L/min) (p < 0.001). Glucagon concentration was suppressed for ∼120 min following administration of 30 μg of pramlintide and postmeal insulin (p < 0.003). No severe hypoglycemic episodes were experienced in this study.
Conclusions:  Postprandial hyperglycemia is considerably reduced in adolescents with T1DM when treated with fixed-dose premeal pramlintide, and precisely calculated postmeal insulin, without significant side effects.     

Seropositivity to celiac antigens in asymptomatic children with type 1 diabetes mellitus: association with weight, height, and bone mineralization

Background:  Screening for celiac disease (CD) in children with diabetes is controversial because no studies have demonstrated metabolic complications in asymptomatic, seropositive subjects or beneficial effects of dietary intervention.
Objective:  We hypothesized that seropositivity to celiac antigens is associated with decreased growth and bone mineralization in asymptomatic diabetic children.
Design/Methods:  Asymptomatic diabetic children were screened for seropositivity to tissue transglutaminase. Villous atrophy was assessed by small bowel biopsy in a subset of seropositive subjects. We compared measures of growth and bone mineralization in 30 seropositive subjects, and 34 matched seronegative controls.
Results:  Relative to seronegative controls, the seropositive subjects had reductions in insulin-like growth factor (IGF) binding protein 3 z scores (p < 0.05) and bone mineral density (BMD) z scores (p = 0.05). Weight, body mass index, IGF-I, and bone mineral apparent density (BMAD) z scores were marginally lower, but height z scores were comparable. Seropositive patients with severe villous atrophy had lower weight (−0.91 SDs), height (−1.1 SDs), BMD (−2.0 SDs), and BMAD (−2.0 SDs) z scores and significant increases in parathyroid hormone (all p < 0.05). Four patients with severe villous atrophy maintained strict gluten restriction for at least 12 months. Gluten restriction increased BMD and BMAD z scores.
Conclusions:  High-titer seropositivity to celiac antigens is associated with reductions in weight and BMD in diabetic children, justifying screening of high-risk patients. Results suggest that biopsy is required to confirm the diagnosis and assess the severity of CD; those with severe villous atrophy are more likely to have growth failure and osteopenia. Gluten restriction may reverse these complications.     

Dermatological side effects and complications of continuous subcutaneous insulin infusion in preschool-age and school-age children

Objective:  The objective of this study was to evaluate whether very young children develop more dermatological complications during insulin pump treatment compared with school children.
Study design:  Cross-sectional study in 78 consecutive children using insulin pump treatment >4 months.
Results:  Children in group A [n = 40, 28 males (M) and 12 females (F)] were 2.3 ± 1.3 yr (±SD) and those in group B (n = 38, 13 M and 25 F) were 11.0 ± 2.9 yr old at the start of continuous subcutaneous insulin infusion (CSII). The mean duration of CSII was similar in both groups (23.6 ± 16.5 months in group A and 21.8 ± 16.1 in group B). The most common dermatological complications were scars <3 mm (50% in group A vs. 71% in group B, p < 0.05) and lipohypertrophic areas at the insertion sites (45% in group vs. 47% in group B). Local abscesses and blisters were rare findings in both groups (7.5–12%), none leading to interruption or stop of CSII.
Conclusions:  Dermatological side effects during CSII are not more frequent or severe in very young diabetic children compared with diabetic children in school age.     

C-reactive protein as a marker of serious bacterial infections in hospitalized febrile infants

Objective:  To determine the potential predictive power of C-reactive protein (CRP) as a marker of serious bacterial infection (SBI) in hospitalized febrile infants aged ≤3 months.
Patients and Methods:  Data on blood CRP levels were collected prospectively on admission for all infants aged ≤3 months who were hospitalized for fever from 2005 to 2008. The patients were divided into two groups by the presence or absence of findings of SBI.
Results:  A total of 892 infants met the inclusion criteria, of whom 102 had a SBI. Mean CRP level was significantly higher in the infants who had a bacterial infection than in those who did not (5.3 ± 6.3 mg/dL vs. 1.3 ± 2.2 mg/dL, p < 0.001). The area under the ROC curve (AUC) was 0.74 (95% CI: 0.67–0.80) for CRP compared to 0.70 (95% CI: 0.64–0.76) for white blood cell (WBC) count. When analyses were limited to predicting bacteremia or meningitis only, the AUCs for CRP and WBC were 0.81 (95% CI: 0.66–0.96) and 0.63 (95% CI: 0.42–0.83), respectively.
Conclusion:  C-reactive protein is a valuable laboratory test in the assessment of febrile infants aged ≤3 months old and may serve as a better diagnostic marker of SBI than total WBC count.