sntatmtishrbplwnf1tdsbonwmbpdiah

1a2

PpvLpwA

Qtpa

D

St

Po

Isbptg

Oppmbog

Md2(Scic

Ctrw

Cwtpatidmacipsmaahssrtw

1

tudy is congruent with the Cochrane review,1 concluding theull hypothesis for death or cerebral palsy, as well as a reduc-ion in severity of cerebral palsy. Decisions to use magnesiumre made by obstetricians; when dealing with this treatmenthey must consider the potential risk for both infant andaternal harm. Doyle’s meta-analysis suggests significant ma-

ernal adverse outcomes do occur in the treatment group,ncluding maternal tachycardia and hypotension. The lack ofuch finding in this trial is worthy of discussion. If maternalarm occurs, pediatricians must ask whether the potentialisks to 63 mothers (ie, the number needed to treat) arealanced against the value of preventing one case of cerebralalsy? Additionally, it may make biologic sense that neuro-

ogic deaths may be prevented by magnesium, but it is alsoorrisome that magnesium therapy may contribute to neo-atal harm (such as the effect of maternal hypotension on theetus). The data from this study hints at this concern with a.6% reduction in CP incidence (3.5% in control vs 1.9% inreatment group) accompanied by a 1% increase in neonataleath (8.5% in control vs 9.5% in treatment group). Theseeem to be conflicting results when evaluating magnesium’senefits to the neonate. That is, is cerebral palsy preventednly to result in more neonatal deaths? Knowing the cause ofeonatal death would be interesting and is required if one isorried about the intervention being the cause of the incre-ental deaths. If neonatal neurologic death is not prevented

y magnesium, one could question the use of death or cerebralalsy as the principal outcome measure. This underscores theifficulty one encounters in designing such studies. Because it

s a large, well designed and executed study, there should bebundant data available to explore such questions leading toypothesis generation and better designed studies in this area.

Aaron W. Swenson, MDRobert E. Schumacher, MD

University of MichiganAnn Arbor, Michigan

REFERENCE. Doyle LW, Crowther CA, Middleton P, Marret S. Magnesium sulphate for woment risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev007;(3):CD004661.

hysical therapy is effective for deformationallagiocephalyan Vlimmeren LA, van der Graaf Y, Boere-Boonekamp MM,’Hoir MP, Helders PJM, Engelbert RHH. Effect of pediatrichysical therapy on deformational plagiocephaly in childrenith positional preference: a randomized controlled trial.rch Pediatr Adolesc Med 2008;162:712-8.

uestion Among infants with a positional preference forheir head, does physical therapy decrease the prevalence ofositional preference and deformational plagiocephaly (DP)t 6 and 12 months, compared with no active intervention?

esign Randomized controlled trial. p

52

etting Physical therapy department in a single hospital inhe Netherlands.

articipants Sixty-five sequential infants referred at 7 weeksf age to physical therapy with positional DP.

ntervention Infants were randomly assigned (stratified byex) to a 4-week course of 8 physical therapy sessions designedy the authors to address positional preferences, includingarent counseling, exercises for motor development, “tummyime,” and an educational brochure. Those in the placeboroup received only the educational brochure.

utcomes The primary outcome was severe DP assessed bylagiocephalometry. The secondary outcomes were positionalreference, motor development, and cervical passive range ofotion. The physical therapists performing the therapy were

linded to the outcome assessors, but no mention was madef whether the outcome assessors were blinded to treatmentroup.

ain Results The primary outcome of severe plagiocephalyecreased in the treatment group from 55% at age 7 weeks to4% at 12 months compared with 63% to 56% in the controlleaflet-only) group (number needed to treat [NNT] � 4).econdary outcomes were similar between the 2 groups, ex-ept intervention parents were better at positioning theirnfants and gave them more tummy time compared with theontrol group.

onclusions A 4-month standardized pediatric physicalherapy program to treat positional preference significantlyeduced the prevalence of severe deformational plagiocephalyhen initiated by 2 months of age.

ommentary Van Vlimmeren et al randomized 65 childrenith positional plagiocephaly to a 4-month course of physical

herapy or simply receiving a patient education handout. Thearticipants were quite young, at 7 weeks, and although theuthors noted baseline characteristics to be “similar” betweenhe 2 groups, there was a trend toward the control groupnfants having more positional preference. Patients were ran-omized and intention to treat was followed. However, noention of allocation concealment or blinding of outcome

ssessors was made, even for the subjective secondary out-omes. The NNT of 4 is quite impressive for such a benignntervention, and physical therapy can be quite reassuring toarents as a “hands-on” treatment. However, the outcome ofevere plagiocephaly was defined by objective head measure-ents and not by a more clinically meaningful measure such

s parent-reported satisfaction. The improvement in second-ry outcomes is to be expected because it simply measuredow well the parents understood the physical therapists’ in-tructions. A meta-analysis published in the same issuehowed that molding therapy with helmets was superior toepositioning therapy for positional plagiocephaly.1 However,he treatments in the 7 studies included in the meta-analysisere begun at an average age of 6 months, about the age the

atients in the van Vlimmeren trial were completing their

The Journal of Pediatrics • January 2009

cicteeoa2v

1tM

EciiJedr

Qddtm

D

S

Ptodt

Iem

Oed

Mcshsmm1sa1

Ctlh

CivdtAmwatihpco

T

ourse of physical therapy. Thus it makes sense for youngnfants with severe positional plagiocephaly to first undergo aourse of physical therapy. Only if this should fail to producehe desired results after a few months should serious consid-ration and referral for molding therapy be considered. Inter-stingly, the trials in the meta-analysis point toward the sameutcomes for positional treatments as molding by 2 years ofge. Unfortunately, for those children who do not respond byyears of age to any treatment, surgery is usually the only

iable option.

Brett Robbins, MDUniversity of Rochester

Rochester, New York

REFERENCE. Xia J, Kennedy K, Teichgraeber J, Wu K, Baumgartner J, Gateno J. Nonsurgicalreatment of deformational plagiocephaly: A systematic review. Arch Pediatr Adolesc

ed 2008;162:719-27.

scalating dose indomethacin for prophylacticlosure of patent ductus arteriosus does notmprove closure rates and is associated withncreased complicationsegatheesan P, Ianus V, Buchh B, Yoon G, Chorne N, Ewig A,t al. Increased indomethacin dosing for persistent patentuctus arteriosus in preterm infants: A multicenter,andomized, controlled trial. J Pediatr 2008;153:183-9.

uestion Among extremely premature infants whose patentuctus arteriosus (PDA) failed to close with a conventionalosing regimen of indomethacin, does a higher dose increasehe rate of PDA closure without increasing the rate of otherorbidities?

esign Randomized controlled trial.

etting Four university hospitals in the United States.

articipants One hundred five infants (�28 weeks gesta-ion) who received a conventional, prophylactic 3-dose coursef indomethacin who had continued evidence of persistentuctus patency on an echocardiogram obtained before the

hird prophylactic indomethacin dose.

ranslating Best Evidence into Best Care

ntervention Infants received an extended 3-day course ofither low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5g/kg/d) indomethacin.

utcomes Closure of the PDA, as documented by anchocardiogram obtained 24 hours after the last dose of studyrug.

ain Results Despite increasing serum indomethacin con-entrations by 2.9-fold in the higher-dose group, there was noignificant decrease in the rate of persistent PDA (low � 52%;igher � 45%, P � .50). The higher-dose group had aignificantly higher occurrence of serum creatinine above 2g/100 mL (low � 6%, higher � 19%, P � .05) andoderate/severe retinopathy of prematurity (ROP) (low �

5%, higher � 36%, P � .025). The incidence of moderate/evere ROP was directly related to the poststudy indometh-cin concentrations (odds ratio � 1.75, confidence interval:.15-2.68, P � .01).

onclusions Increasing indomethacin concentrations abovehe levels achieved with a conventional dosing regimen hadittle effect on the rate of PDA closure but was associated withigher rates of moderate/severe ROP and renal compromise.

ommentary PDA is a common concern in prematurenfants and can be associated with significant morbidity. Pre-ious studies have suggested greater success with escalating-ose indomethacin. This well-designed, randomized con-rolled trial sought to determine the efficacy of this practice.lthough the increased dose significantly increased indo-ethacin levels, no benefit was seen in terms of ductal closure,ith increased risk of toxicity in the form of renal dysfunction

nd retinopathy of prematurity. Even though it is possiblehat a larger sample size may have resulted in a significantncrease in the rate of ductal closure, the toxicity seen withigher doses precluded further enrollment in this study. It isossible that the treatment effect of higher-dose indometha-in shown in previous studies may have been due to durationf therapy as opposed to increased dose.

Timothy Cotts, MD

University of MichiganAnn Arbor, Michigan

153