Body position

The Effect of Body Positioning on Gastroesophageal Reflux in Premature Infants:Evaluation by Combined Impedance and pH MonitoringL UIGI C ORVAGLIA,MD,R AFFAELLA R OTATORI,MD,M ARIANNA F ERLINI,MD,A RIANNA A CETI,MD,G INA A NCORA,MD,AND G IACOMO F ALDELLA,MDObjective To evaluate the pattern of acid and nonacid gastroesophageal reflux(GER)in different body positions in preterm infants with reflux symptoms by a combined multichannel intraluminal impedance(MII)–pH monitoring,which identifies both acid and nonacid GER.Study design Premature infants with frequent regurgitation and postprandial desaturation(n؍22)underwent a24-hour recording of MII-pH.In a within-subjects design,reflux indexes were analyzed with the infants in4different positions:supine (S),prone(P),on the right side(RS),and on the left side(LS).Results All infants were analyzed for20hours.The mean number of recorded GER episodes was109.7.The mean esophageal exposure to acid and nonacid GER was lower in positions P(4.4%and0.3%,respectively)and LS(7.5%and0.7%, respectively)than in positions RS(21.4%and1.2%,respectively)and S(17.6%and1.3%,respectively).The number of postprandial nonacid GER episodes decreased but the number of acid GER episodes increased over time.The LS position showed the lowest esophageal acid exposure(0.8%)in the early postprandial period,and the P position showed the lowest esophageal acid exposure(5.1%)in the late postprandial period.Conclusion Placing premature infants in the prone or left lateral position in the postprandial period is a simple intervention to limit GER.(J Pediatr2007;151:591-6)G astroesophageal reflux(GER)is common in premature infants.Because it may be linked to serious clinical conse-quences,it is cause for concern in neonatologists and parents and necessitates prolongation of hospitalization.1,2As in term infants,3a conservative approach based on postural treatment has been suggested in preterm infants with GER.1 However,few studies have been performed to investigate the best body position for this approach to GER treatment in premature infants,and results are not ing pH monitoring,Ewer et al4found that prone and left lateral positioning was more effective in preventing GER.Omari et al,5using combined manometry and multichannel intraluminal impedance (MII)recording in preterm infants asymptomatic for GER,found that left lateral positioning was more advantageous than right lateral positioning.These authors analyzed the mechanisms triggering GER and observed an increased number of transient lower esophageal sphincter relaxations(TLESRs)in the right lateral position,despite a gastricemptying rate twice that in the left lateral position.Despite these importantfindings,thisstudy was unable to differentiate acid and nonacid GER.5The effect of positioning is predictable based on previous work,but it is importantto describe this effect using the current state-of-the-art methods for GER measurement.Consequently,the aim of our study was to evaluate the affect of body position on GERin symptomatic premature infants using combining intraluminal impedance and pHmonitoring.MII is based on the intraluminal electrical impedance changes occurring duringthe passage of a bolus through the esophagus.It is measured by electrodes incorpo-rated along a catheter.Impedance is decreased if the bolus is liquid and is increasedif it is air.The direction of the bolus is determined by evaluating changes inintraluminal impedance at various levels over time.6MII can detect gas,mixed,andBEI Bolus exposure indexGER Gastroesophageal refluxLES Lower esophageal sphincterLS Left sideMACT Mean acidic clearing timeMII Multichannel intraluminal impedance P ProneRIpH Reflux indexRS Right sideS SupineTLESR Transient lower esophageal sphincterrelaxationSee editorial,p560andrelated article,p585From the Institute of Preventive Pediatricsand Neonatology,St.Orsola Malpighi Gen-eral Hospital,University of Bologna,Bolo-gna,Italy(L.C.,R.R.,M.F.,A.A.,G.A.,G.F.).Submitted for publication Feb1,2007;lastrevision received Apr27,2007;acceptedJun6,2007.Reprint requests:Luigi Corvaglia,MD,Istitutodi Pediatria Preventiva e Neonatologia,ViaMassarenti11,40138Bologna,Italy.E-mail:luicorva@almadns.unibo.it.0022-3476/$-see front matterCopyright©2007Mosby Inc.All rightsreserved.10.1016/j.jpeds.2007.06.014591liquid GER episodes but cannot differentiate acid and non-acid episodes;for this reason,it is essential to combine MII and pH monitoring to evaluate the role of acid and nonacid GER episodes.METHODSA total of22(16male)symptomatic premature infants with a median gestational age at birth of31weeks(range,24 to32weeks)and a median birth weight of1220g(range,630 to2250g)were enrolled in the study at a median age of29 days(range,12to83days)and a median weight of1747g (range,1150to3215g).The infants exhibited frequent re-gurgitation and postprandial desaturation;in addition,7in-fants had postprandial apnea,4had failure to thrive,1had bradycardia,and1had both postprandial apnea and brady-cardia.All were otherwise healthy at the time of examination. None had malformation or major gastrointestinal problems or was taking drugs influencing gastrointestinal motility or gas-tric acidity.Seven infants were fed extracted human milk fortified with3%FM85(Nestlé,Vevey,Switzerland),3were fed a standard preterm formula,and the remaining12re-ceived both.All22infants tolerated at least100ml/kg per day of milk.The effect of postural intervention on GER was eval-uated in a within-subjects design,taking for each subject measurement of GER in different postural conditions.In a within-subjects design,the same subjects are tested in each condition;therefore,differences among subjects can be sep-arated from error,increasing the power of significance tests.A possible drawback of this method is the“carry-over”effect—a persistent effect in a subsequent treatment period from treat-ment in the previous period.In our study,this could be represented by the effect on GER of each position on the subsequent position.To limit this effect,we randomly as-signed to each enrolled infant a different sequence of the possible postural combinations.Postural InterventionIn the24-hour examination,4positions—supine(S), prone(P),right side(RS),and left side(LS)—were studied. Each position was maintained for6hours,except for2 periods of30minutes each for feeding.The order of different positions was assigned randomly and was not known by the data analysts.Each infant received8meals(1every3hours) through a feeding bottle or an orogastric tube,inserted and removed at each meal.This approach allowed us to include2 meals and2150-minute postprandial periods in each body position.GER MonitoringEach patient underwent a24-hour,continuous,simul-taneous measurement of intraesophageal pH and multichan-nel electrical impedance.The system was calibrated before each measurement using pH buffer solutions of pH4.0and pH7.0.A single-use combined MII–pH probe(Comfortec MII-pH,2.1mm in diameter;Sandhill Scientific,Highlands Ranch,CO)was used.Theflexible catheter contained seven impedance electrodes representing6bipolar impedance chan-nels and1antimony electrode for pH detection.The distance between each impedance electrode was1.5cm,except for the distal couple spaced at2cm.The pH sensor was located1cm above the distal impedance ring,in the middle of the most distal impedance-measurement segment.The catheter was inserted through a nostril without sedation and placed under fluoroscopic guidance.The tip wasfixed1to1.5cm above the gastroesophageal junction.Before removal,the position of the catheter was compared with the initial position by checking the depth mark on the catheter,to exclude possible displace-ment.Data were acquired on a portable Sleuth system(San-dhill Scientific),stored at the end of each test in a personal computer,and analyzed by BioVIEW Analysis software,ver-sion5.0.9(Sandhill Scientific)and by direct visual evaluation of each event.During each GER episode,we recorded the minimum pH value;the height(in cm),calculated by the distance from the lower esophageal sphincter(LES)of the most proximal electrode that detected the reflux;and the duration(in sec-onds),defined as the time between the onset of GER and the recovery of50%of the initial impedance value,measured at the level of the distal impedance bipolar channel(ie,1.5cm). To be detected as MII-GER,the bolus,moving in a retro-grade direction,had to contact at least3impedance elec-trodes,reaching a height of at least4to4.5cm above the gastroesophageal junction.An MII-GER episode was de-fined as acid(aMII-GER)if the pH wasϽ4and as nonacid (NaMII-GER)if the pH wasՆ4.7The total percentage of time with a MII-GER in the esophagus was indicated as bolus exposure index(BEI)and further separated into acid (aMII-GER-BEI)and nonacid(NaMII-GER-BEI)reflux indexes.The number of all acid GERs,including those detected only by pH electrode and those detected by MII as well,was classified as pH-acid-GER.The total percent time of esoph-ageal exposure to a pHϽ4was designated as the reflux index (RIpH).This latter measurement substantially represents a traditional pH monitoring and includes periods of acid esophageal exposure associated with retrograde movement detected by MII and periods with acid esophageal exposure not associated with retrograde movement detected by MII. The mean time(in seconds)required for pH to return to4 after a GER episode was designated the mean acidic clear-ing time(MACT).Because the features of GER change during postpran-dial hours,8we further analyzed and compared GER indexes measured during thefirst75postprandial minutes(first pe-riod)with those measured during the second75postprandial minutes(second period).The study design was approved by the hospital’s Insti-tutional Ethics Committee.Written informed consent was obtained from a parent of each infant enrolled in the study.592Corvaglia et al The Journal of Pediatrics•December2007Statistical AnalysisAll statistical analyses were performed with SPSS13.0 for Windows(SPSS Inc,Chicago IL).Normal distribution wasfirst evaluated by the Kolmogorov-Smirnov test.Reflux variables in each position were analyzed using generalized likelihood model repeated-measures design(1within-subjects factor)and Bonferroni post hoc pairwise comparison;differ-ences between thefirst and second postprandial periods were tested by paired-sample t tests.A P valueϽ.05was consid-ered statistically significant.RESULTSThe test was well tolerated by all of the patients,and their clinical status remained stable.No probe position changes were detected during any examination.We analyzed a total of176postprandial periods(44periods for each position),with a mean duration of149minutes(range,145to 157minutes).RIpH measurements in the22patients are given in Table I.During the20-hour monitoring(24hours minus4 feeding hours),the mean total number of recorded GER episodes was109.7(5.5per hour).The mean numbers of aMII-GER,NaMII-GER,and pH-acid-GER episodes were 11.7,35.9,and73.7,respectively,with corresponding mean percent times of esophageal exposure to reflux of0.3%,0.9%, and12.7%.Effect of Position on the Physical Compositionof RefluxateGER episodes werefirst analyzed regarding physical composition of the refluxate.In each position,most of the GER refluxate was liquid,although some was gaseous or mixed.Liquid refluxate was significantly less frequent in the LS and P positions compared with the RS and S positions (PϽ.01)(Table I).There were no significant differences among positions regarding gaseous and mixed episodes. Effect of Position on Impedance-Detected andpH-Detected RefluxWhen values were analyzed by different positions,we observed a reduction of each type of MII-pH–detected GER in the LS and P positions compared with the RS and S positions(Figures1and2).In particular,acid exposure time (RIpH)and MACT were significantly lower in both the P and LS positions compared with the S and RS positions.We found no difference between the P and LS positions.The P position exhibited significantly fewer Na-MII-GER episodes than the other3positions.Table I.Reflux parameters measured in the22patientsTotal Left side Right side Supine Prone PLiquid GER(n)40.5(20.5)0-877.9(4.8)0-2013.6(8.8)0-3015.9(9.7)0-393.1(2.6)0-10LS vs RS:.012LS vs S:.002P vs RS,S,LS:.001Gaseous GER(n) 4.8(5.2)0-191.7(2.1)0-81.1(1.4)0-50.9(1.2)0-41.1(2)0-8NSMixed GER(n)7.4(5.9)0-222.3(2.6)0-112.5(2.9)0-131.7(1.9)0-70.8(1.4)0-6NSaMII-GER(n)11.7(9.1)1-351.9(2.1)0-84.2(4.4)0-184.3(3.5)0-121.1(1.2)0-3P vs S:.001P vs RS:.019LS vs S:.029NaMII-GER(n)35.9(22)2-918.3(5.8)0-2111.9(8.9)0-3612.9(9.1)1-352.8(2.6)0-8P vs RS,S,LS:.001pH-acid-GER(n)73.7(44.3)3-14917.9(15.7)0-5627.1(18.1)3-6621.9(15.3)0-566.8(5.3)0-17P vs S,RS:.001P vs LS:.006aMII-GER-BEI(%)0.3(0.2)0-0.70.2(0.3)0-10.5(0.5)0-1.70.5(0.5)0-1.70.1(0.1)0-0.4P vs RS:.001P vs S:.006RS vs LS:.015NaMII-GER-BEI(%)0.9(0.5)0-1.80.7(0.6)0-2.11.2(0.9)0-2.61.3(1)0.11-3.30.3(0.3)0-1P vs S,RS:.0001LS vs S:.011RipH(%)12.7(10.5)1.6-37.97.5(8.2)0-32.221.4(19.4)0.4-68.417.6(16.1)0-48.64.4(5.8)0-19.8P vs RS:.001P vs S:.002LS vs RS:.004LS vs S:.014MACT(sec)119.8(116.1)26.4-582.693.2(143.9)0-701.8176.4(245.6)26.4-1216.9162.7(103)17.1-282.994.9(91.1)0-257.1P vs S:.016LS vs RS:.021Mean MII-GER height(cm)3.5(1.2)1.8-7.23.9(1.7)1.7-93.4(1.2)1.5-73.8(1.3)1.7-7.33(1.4)0-7NSNS,not significant.Values are expressed as mean(standard deviation)and range.The Effect of Body Positioning on Gastroesophageal Reflux in Premature Infants:Evaluation by Combined Impedanceand pH Monitoring593Improvement in all GER indexes in the P and LS positions was seen in all patients except 1,who showed better GER indexes in the S and RS positions than in the P and LS positions.In this patient,an upper radiograph study with a barium swallow performed after MII-pH monitoring dem-onstrated a gastric malrotation.We decided not to exclude this patient from the analysis,because the inclusion criteria were fulfilled,and the diagnosis of malrotation was made after the MII-pH monitoring had been performed.Moreover,we verified that the exclusion of this patient would not have affected the global results;in fact,in an analysis performed excluding this patient,all statistical significances did not vary (data not showed).Influence of Position on the Height of GER EpisodesNo difference among positions was found in mean height reached by GER episodes.Changes in the Composition of Postprandial Refluxate Over TimeComparison of the 2postprandial periods (Table II )revealed that acid GER indexes (RIpH and aMII-GER-BEI)were significantly higher in the second postprandial period than in the first postprandial period in all of the positions studied except P.In the first postprandial period,the P and LS positions were associated with a significantly lower RIpH compared with the S and RS positions (P Ͻ.01).RIpH was the lowest in the LS position (with 12of the 22patients having a RipH of 0%),significantly lower than in the P position (LS ϭ0.8%vs P ϭ3.6%;P Ͻ.05)(Figure 3;available at ).During the second postprandial period,the P position was associated with strongly reduced esophageal acid exposure compared with the other 3positions (P Ͻ.01).RIpH was lower in the LS than in the S and RS position (P Ͻ.01);however,RIpH was significantly higher in the LS position than in the P position (14.3%vs 5%;P ϭ.016).In the first postprandial period,Na-MII-GER-BEI was significantly lower in the P position compared with the RS and S positions (P Ͻ.05);in the second postprandial period,Na-MII-GER-BEI was significantly lower in the P position compared withall of the other positions (P Ͻ.01)(Figure 4;available at ).DISCUSSIONIn this study,we found fewer GER episodes when infants were placed in the LS and P positions compared with the RS and S positions.Body position had no influence on the proximal extent of MII-detected GER episodes.In each body position,we noticed a decrease in the number of postprandial nonacid GER episodes and an increase in the number of postprandial acid GER episodes over time.GER is common in preterm infants;the almost fixed lying position promotes the entry of liquid gastric contents into the esophagus when TLESR occurs.Additional risk factors associated with preterm birth include high total fluid enteral intake,frequent handling by nurses,and the use of permanent feeding tubes.9A study in asymptomatic preterm neonates found a median of 71reflux episodes in 24hours.10Although GER is asymptomatic in most preterm infants,in some it may cause such symptoms as desaturation,regurgitation,and bradycar-dia or can lead to such complications as apnea,recurrent desaturation and/or aspiration,difficulties in oral feeding,vomiting,and failure to thrive.1Although acid reflux episodes are considered more likely associated with symptoms in pre-term infants,11recent studies indicate that nonacid reflux can produce these symptoms as well.12For preterm infants with symptomatic GER,a stepwise approach,based mainly on conservative interventions,is the best therapeutic choice.Drugs should be the last option,considering that cisapride was withdrawn from the market because of its possible cardiac side effects,13and treatment with gastric acid inhibitors is not without risk.14,15In a previous study,we found no reduction of GER from thickening human milk with precooked starch.16More-over,a possible relationship between milk thickening and the development of necrotizing enterocolitis has been described in 2preterm infants.17Few studies have evaluated the influence of body posi-tion on acid GER in preterm newborns,and,to the best of our knowledge,none have investigated the influence of body position on nonacid GER.Omari et al 5evaluated the inci-dence of GER in 10newborns with mild prematurity and without GER symptoms using a combined MII and manom-etry catheter and found an advantage of LS over RS position-ing in terms of a reduced number of GER episodes.Although that study provided important data concerning GER patho-logical mechanisms,the presence of a trans-LES catheter could have increased the number of GER episodes,and the absence of a pH sensor did not allow the authors to differ-entiate acid and nonacid episodes.Another study confirmed these findings in 18premature babies with GER symptoms using pH monitoring and comparing the P position with the RS and LS positions.4But that study evaluated only acid episodes with no information about the S position,the most frequently used position in both term and in pretermnew-Figure 1.RIpH in different body positions (—,median;---,95th percentile).594Corvaglia et alThe Journal of Pediatrics •December 2007borns.Recognizing that nonacid reflux episodes are common in premature infants,we believe that combined MII-pH monitoring is the most appropriate method for evaluating GER in preterm newborns.In our study,RIpH was mostly measured only by a pH electrode (placed 1.5to 2cm above the diaphragm),not by MII (with the most distal 2electrodes placed at about 4.5cm above diaphragm).Thus,GER episodes were detected in 2different esophageal sites 3cm apart;this distance is partic-ularly relevant considering the total esophageal length of about 6to 10cm.For this reason,we can state that in symptomatic preterm infants,most GER occurs in the distal half of the esophagus.Even in adults,a 6-fold increase in acid exposure (mean RipH,11.7%vs 1.8%)was found between the more distal and proximal pH measurements.18Our data are not comparable with those from previous studies,due to methodological differences.Wenzl,6Skopnik et al,19and others reported that most GER episodes reached the proximal esophagus because they considered as GER episodes only those detectable by both MII and pH probes.In comparison,we also considered numerous short-segment ep-isodes detected only by the pH probe.Omari et al 11charac-terized most GER episodes as nonacid,because they first detected all GER episodes by manometry just above the LES and then classified them as acid or nonacid by a pH electrode.In contrast,we were able to detect GER episodes just above the LES only by the pH probe.We found that the P and LS positions significantly decreased the number of acid and nonacid GER episodes compared with the S and RS positions.The effect of theLSFigure 2.aMII-BEI and NaMII-BEI in different body positions (—,median;---,95th percentile).(aMII-BEI:P vs RS P ϭ.001,P vs S ϭP ϭ.006,RS vs LS P ϭ.015;NaMII-BEI:P vs RS P ϭ.0001,P vs S ϭP ϭ.0001,RS vs LS P ϭ.011.)Table II.Variation of acid and nonacid GER during postprandial periodsRIpHP aMII-GER-BEI P NaMII-GER-BEI P Left sideFirst period 0.8(1.5)0-5.5.0010(0.1)0-0.3.031.2(1)0-3.7.0001Second period 14.3(16)0-64.40.2(0.5)0-20.2(0.2)0-0.6Right side First period 9.9(21)0-92.1.0010.3(0.5)0-2.2.01 2.2(1.7)0-5.2.0001Second period 32.9(26.1)0.7-84.30.8(0.9)0-2.50.2(0.3)0-0.8SupineFirst period 5.4(13.4)0-54.9.00010.1(0.2)0-0.6.0001 2.2(1.7)0.2-5.5.0001Second period 29.7(25.6)0-72.60.9(0.9)0-3.10.4(0.8)0-3.1ProneFirst period 3.6(8.7)0-37.3NS 0(0.1)0-0.4.040.7(0.6)0-2.0.0001Second period 5.1(7.3)0-33.70.1(0.2)0-0.90(0.1)0-0.5TotalFirst period 4.9(9.3)0-34.3.00010.1(0.1)0-0.5.001 1.6(0.9)0.1-3.5.0001Second period20.5(14.3)0.2-47.80.5(0.4)0-1.40.21(0.3)0-1.0Values are expressed as mean (standard deviation)and range.The Effect of Body Positioning on Gastroesophageal Reflux in Premature Infants:Evaluation by Combined Impedance and pH Monitoring595position in reducing GER is due mainly to a functional factor—reduced TLESR episodes—by laying the gastric con-tents on the gastric body and greater curvature,which to-gether act as a reservoir.5The effect of the P position is related mainly to an anatomic factor.In this position,the LES is above the gastric body,far from the gastric contents;4 thus,when a TLESR occurs,the gastric contents are farther from the LES and are less likely to go back into the esoph-agus.Our separate analysis of the incidence of acid and non-acid GER episodes and the relationship with different body positions in thefirst and second postprandial periods revealed that in thefirst period,the degree of acid esophageal exposure was4-fold higher in the P position compared with the LS position(percent time,3.6%vs0.8%;PϽ.05).In dyspeptic adults,after meals in upright position,a pocket of unbuffered acid juice forms near the gastroesophageal junction;it seems to escape the buffering effects of meals,remaining highly acid compared with the body of the stomach.20The presence of a similar pocket in preterm infants lying in the P position could explain the higher esophageal acid exposure in the P position than in the LS position during thefirst postprandial period. In contrast,in the second postprandial period,esophageal acid exposure was higher in the LS position than in the P position(Pϭ.016).Thesefindings suggest that acid exposure can be optimally reduced by keeping the newborn on the left side during the early postprandial period and in the prone position thereafter.In conclusion,our study suggests that placing prema-ture infants in a prone or left lateral position during the postprandial period is a simple intervention to limit GER. Ourfindings do not provide any information on clinical improvement,because the study was not designed to monitor the effect of postural intervention on GER symptoms.Fur-ther studies are needed to evaluate the effective correlation between postural intervention and improvement of GER symptoms.REFERENCES1.Poets CF.Gastroesophageal reflux:a critical review of its role in preterm infants. 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