THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 156, No. 1

Xylitol syrup can reduce dental cariesprogression in young childrenMilgrom P, Ly KA, Tut OK, Mancl L, Roberts MC, Briand K,et al. Xylitol pediatric topical oral syrup to prevent dentalcaries: a double-blind randomized clinical trial of efficacy.Arch Pediatr Adolesc Med 2009;163:601-7.

Question Among very young children at high risk for earlychildhood caries (ECC), will a xylitol pediatric topical oralsyrup reduce the incidence of dental caries?

Design Double-blind randomized controlled trial.

Setting Communities in the Republic of the Marshall Islandswith very high ambient ECC rates.

Participants A total of 108 children, aged 9 to 15 months,were screened, and 100 were enrolled.

Intervention Xylitol topical oral syrup (administered bytheir parents) twice a day (2 xylitol [4.00-g] doses and 1sorbitol dose) (Xyl-2X group) or thrice per day (3 xylitol[2.67-g] doses) (Xyl-3X group) vs a control syrup (1 xylitol[2.67-g] dose and 2 sorbitol doses) (control group).

Outcomes Primary outcome was the number of decayed pri-mary teeth.

Main Results 94 children (mean age 15.0 months at random-ization) with at least 1 follow-up examination were includedin the intent-to-treat analysis. The mean (SD) follow-upperiod was 10.5 (2.2) months. Fifteen of the 29 children inthe control group (51.7%) had tooth decay compared with13/32 in the Xyl-3X group (40.6%) and 8/33 children inthe Xyl-2X group (24.2%). The mean (SD) numbers ofdecayed teeth were 1.9 (2.4) in the control group, 1.0 (1.4)in the Xyl-3X group, and 0.6 (1.1) in the Xyl-2X group. Com-pared with the control group, there were significantly fewerdecayed teeth in the Xyl-2X group (relative risk, 0.30; 95%confidence interval, 0.13-0.66; P = .003) and in the Xyl-3Xgroup (0.50; 0.26-0.96; P = .04). No statistical differencewas noted between the 2 xylitol treatment groups (P = .22).

Conclusions Xylitol oral syrup administered topically 2 or 3times daily at a total daily dose of 8 g was effective in reducingearly childhood caries progression.

Commentary Worldwide, pediatric dental caries is a preva-lent, persistent, and consequential disease characterized bya low-level chronicity that often belies its significance to in-dividual children and those close to them. It is rampantwithin some subpopulations, both those of poverty and thoseof emerging affluence. In the United States, more than 2 in 5poor children ages 2 to 5 years experience ‘‘early childhoodcaries’’ (ECC), and nearly half of those affected experiencethe severe form of this preventable condition.1 The extremeprevalence, rapidly increasing incidence, and very early onsetof ECC in the Marshall Island population studied by Mil-grom et al provide excellent conditions to validate theshort-term (1 year) salutary impact of a xylitol intervention(16-24 g per day in divided doses) within a small population(n = 100) at high risk. A significant difference in numbers ofnewly decayed teeth, if not in the percentage of children who

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experienced any caries progression, suggests a high potentialclinical utility to this intervention. Yet we must be cautiousabout extrapolation of these results to more typical childpopulations. Prior evidence for cariostatic benefits of xylitolwas sufficiently strong to ethically mandate inclusion of low-level xylitol exposure within the ‘‘control’’ group. This inclu-sion, however, does not diminish the observation that xylitolholds strong promise as a pharmacologic adjunct in the bio-behavioral management of dental caries in early childhood.

Burton L. Edelstein, DDS, MPHCollege of Dental Medicine, Columbia University

New York, New York

Reference

1. Iida H, Auinger P, Billings RJ, Weitzman M. Association between breast-

feeding and early childhood caries in the United States. Pediatr 2007;120:

e944-52.

Ibuprofen elevates total bilirubin in preterminfantsZecca E, Romagnoli C, De Carolis MP, Costa S, Marra R, DeLuca D. Does ibuprofen increase neonatal hyperbilirubine-mia? Pediatrics 2009;124:480-4.

Question Among preterm infants born at <30 weeks gesta-tional age, does prophylaxis for patent ductus arteriosus(PDA) with ibuprofen increase total serum bilirubin (TSB)levels in the first weeks of life?

Design Comparison of 2 retrospective cohorts, before and af-ter implementation of standard ibuprofen dosing to preventPDA.

Setting Single neonatal intensive care unit in Italy.

Participants A total of 418 infants < 30 weeks gestation fromthe study’s center between 2000 and 2007 given ibuprofenprophylaxis compared with 288 infants < 30 weeks gestationborn in the study’s center between 1993 and 1999 not givenprophylactic ibuprofen. The 2 groups were similar with re-spect to gestational age (�27 weeks), birth weight (�1000g), sex, 5-minute Apgar score (�8), clinical risk index forbabies (�2.3), isoimmunization (�2%), and G6PDH defi-ciency (�2%).

Outcomes Comparison of the 2 cohorts for the outcomes ofpeak TSB level, the need for and duration of phototherapy,and the need for exchange transfusion. The unbound (uncon-jugated) bilirubin levels were mathematically calculated fromthe TSB levels using a previously published correlation curve.

Main Results The average peak TSB in the ibuprofenexposed infants was statistically higher than that of thenon-exposed infants (9.0 mg/dL vs 7.3 mg/dL, P < .001).95.2% of the ibuprofen treated infants needed phototherapycompared with 88.2% in the nontreated infants (P < .001,number needed to harm = 15). If needed, the duration ofphototherapy was 7 hours longer in the treated infants than

January 2010 CURRENT BEST EVIDENCE

the untreated infants (94.3 hours vs 87.2 hours, P = .034). Ex-change transfusions were needed by an equivalent percentagein each group (4.5% ibuprofen treated vs 4.8% no-ibuprofentreated, P = .870).

Conclusions Ibuprofen given to premature infants <30weeks gestational age raises the peak TSB, makes the needfor phototherapy more likely and needed for a longer dura-tion, but has no effect on the need for exchange transfusion.

Commentary Zecca et al compared 2 cohorts of infants <30weeks of age before and after their neonatal intensive careunit began a protocol of standard ibuprofen dosing in thisage group to prevent PDA. Although the groups seem similarby the characteristics given, because it was not randomized,the 2 groups are likely not similar with regard to other un-measured or as yet undiscovered factors. This is particularlylikely given that the 2 cohorts were in 2 separate decades.Although TSB is a disease-oriented and not a patient-orientedoutcome, the authors did measure the need for and durationof phototherapy and need for exchange transfusion as out-comes. Follow-up was far too short to measure the ultimatepatient-oriented and clinically relevant outcome of neurode-velopment. A small randomized trial of 46 infants <30 weeksof age by the same group1 showed that those treated for theirPDA with ibuprofen had a statistically higher rate as com-pared with placebo of a closed ductus at 72 hours (87% vs30%), lower need for backup treatment with indomethacin(13% vs 70%), but the same rate statistically of the need forsurgical closure (4% vs 13%). Even though this final differ-ence seems quite large, the study was underpowered to findit statistically significant. Outcomes regarding bilirubin werenot reported in this study. This leaves the clinician wonderingif a closed ductus at 72 hours is worth the higher chance ofneeding phototherapy and for a longer period. A single largerandomized trial comparing ibuprofen, indomethacin, andplacebo in this patient group would help clarify the issue.

Brett Robbins, MDUniversity of Rochester

Rochester, New York

Reference

1. De Carolis MP, Romagnoli C, Polimeni V, Piersigilli F, Zecca E, Papacci P,

et al. Prophylactic ibuprofen therapy of patent ductus arteriosus in pre-

term infants. Eur J Pediatr 2000;159:364-8.

Fever and hypoxia predict radiographicpneumonia among children with wheezingMathews B, Shah S, Cleveland RH, Lee EY, Bachur RG, Neu-man MI. Clinical predictors of pneumonia among childrenwith wheezing. Pediatrics 2009;124:e29-36.

Question Among children with wheezing in the emergencydepartment (ED) setting, what factors predict radiographi-cally-confirmed pneumonia?

Design Prospective cohort study.

Setting Single ED in Boston, Massachusetts.

Participants A total of 526 children #21 years of age (me-dian age 1.9 years) who were evaluated in the ED were foundto have wheezing on examination and underwent chest radi-ography because of possible pneumonia.

Intervention Historical features and examination findingswere collected by treating physicians before knowledge ofthe chest radiography results. Chest radiographs were readindependently by 2 blinded radiologists.

Outcomes Accuracy of the history and physical findings wereassessed by use of likelihood ratios.

Main Results Thirty-six percent of patients were hospital-ized. A history of wheezing was present for 247 patients(47%). Twenty-six patients (4.9% [95% confidence interval[CI]: 3.3-7.3]) had radiographic pneumonia. History of feverat home (positive likelihood ratio [LR]: 1.39 [95% CI: 1.13-1.70]), history of abdominal pain (positive LR: 2.85 [95% CI:1.08 -7.54]), triage temperature of $38�C (positive LR: 2.03[95% CI: 1.34-3.07]), maximal temperature in the ED of$38�C (positive LR: 1.92 [95% CI: 1.48-2.49]), and triageoxygen saturation of <92% (positive LR: 3.06 [95% CI:1.15- 8.16]) were associated with increased risk of pneumo-nia. Among fever-free children (temperature of <38�C)with wheezing, the rate of pneumonia was very low (2.2%[95% CI: 1.0-4.7]).

Conclusions Radiographic pneumonia among children withwheezing is uncommon. Historical and clinical factors maybe used to determine the need for chest radiography forwheezing children. The routine use of chest radiographyfor children with wheezing but without fever should bediscouraged.

Commentary Mathews et al are to be commended for put-ting together this large, well-designed, prospective cohortof wheezing children to evaluate features that predict thepresence of pneumonia on radiography. This study over-comes some of the limitations in prior studies that excludedchildren with known asthma or those older than 2 years ofage. The most important finding from this study is that ra-diographic pneumonia in children with wheezing is verylow (4.9%), and even lower in those younger than 2 yearsold (3%). This article includes a very nice table of multilevellikelihood ratios for different historical features and physicalfindings. For example, the strongest predictor of radio-graphic pneumonia was the presence and height of fever inthe ED. A temperature in the ED $ 38�C was associatedwith a likelihood ratio of 1.92 and a temperature $39�Chad a likelihood ratio of 3.92. However, because of the smallnumber of patients with radiographic pneumonia, the confi-dence intervals around these ratios were quite large. In addi-tion, ruling out the presence of pneumonia by use of thesefindings would be difficult; the absence of fever on arrivalto the ED is associated with a likelihood ratio of only 0.66.Although it may be difficult to use any one of these findingsto rule out pneumonia, these data are the first step in the

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