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AdvAnces in GeRd

section editor: Joel e. Richter, Md

C u r r e n t D e v e l o p m e n t s i n t h e M a n a g e m e n t o f A c i d - R e l a t e d G I D i s o r d e r s

Treatment of Gastroesophageal Reflux Disease During Pregnancy

Lauren B. Gerson, MD, MScAssociate Professor of Medicine & GastroenterologyStanford University School of MedicineStanford, California

G&H How common is gastroesophageal reflux disease in pregnant women?

LBG Inthebaselinepopulationof individualswhoarenotpregnant,gastroesophagealrefluxdisease(GERD)ispresentinapproximately40%ofAmericansonamonthlybasisandapproximately7–10%ofAmericansonadailyorweeklybasis.ManystudieshavefoundthatGERDisverycommonduringpregnancy;approximately30–50%ofpregnantwomencomplainofheartburn.

G&H What risk factors predispose patients to the development of GERD during pregnancy?

LBG AlthoughmostpregnantwomenwithGERDdonot report having prior heartburn symptoms, one oftheriskfactorsforhavingGERDduringpregnancyisthepresenceofpre-existingGERD.OtherriskfactorsforGERDduringpregnancyincludeincreasedmater-nalageandweightgain,sothatthemoreweightthatapatientgainsduringpregnancy,thehighertheriskofdevelopingGERD.

G&H How safe are proton pump inhibitors for treating GERD in patients who are pregnant?

LBG Except for omeprazole, all proton pump inhibi-tors(PPIs)areclassifiedascategoryBdrugsbytheUSFood and Drug Administration (FDA), which meansthattheyaresafetouseduringpregnancy.OmeprazoleiscurrentlyclassifiedasacategoryCdrug(Animalstudiesshowriskbuthumanstudiesareinadequateorlackingornostudiesinhumansoranimals). However, sincethecategoryratingforomeprazolewasestablished,multiple

studieshavebeenpublisheddemonstratingthatomepra-zoleisassafeasanyotherPPIforpregnantwomen.Forexample,alargestudyfromDenmarkpublishedinTheNew England Journal of Medicinein2010examinedover840,000birthsanddidnotfindanyassociationbetweenPPIusageinthefirsttrimesterandbirthdefects.Inthisstudy, omeprazole was the most commonly prescribedPPI.Inameta-analysisof7studiespublishedin2009,therewasnoevidencelinkingPPIexposureinpregnancytoadverseoutcomessuchascongenitalmalformations,spontaneous abortions, or premature deliveries. Whendata were analyzed separately for omeprazole usage,therewasnochangeintheresults.

Themost interestingfinding from the2010Dan-ish studywas that therewas an increased riskofbirthdefects in women who reported PPI usage 1–4 weeksbefore conception. However, the authors were unableto arrive at the sameconclusionswhen they examinedusageofomeprazolealoneorusageofover-the-counterPPIs.Therefore,moreresearchisneededtodefinitivelyconcludewhetherthereisanincreaseintheriskofbirthdefects in patients who are on PPI therapy prior tobecomingpregnant.

G&H Thus far, is there enough research to conclude whether PPI therapy is safe in pregnant women?

LBG Yes,thereareenoughdatatosuggestthatPPIther-apyissafeduringpregnancy—andthisincludesallPPIs,evenomeprazole.DespitebeinglabeledasapregnancycategoryCdrugbytheFDA,manystudieshavedem-onstrated that omeprazole is safe in pregnant women,as discussed above; in fact, the majority of safety data

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ontheuseofPPItherapy inpregnantGERDpatientsinvolveomeprazolebecauseitwasthefirstPPIthatwasavailable.AsallPPIsaresafeinpregnantwomen—andnosinglePPIissaferthanotherPPIs—thereisnoreasonfor a pregnant woman on PPI therapy to switch to adifferentPPI.

The recent study from Denmark suggested thattherewas an increased riskofbirthdefects inpatientswhowereonPPItherapypriortoconception,andtheresearcherssuggestedthatpatientsshouldstopPPIther-apyiftheywerecontemplatingpregnancy.Thus,ithasbeensuggestedbysomegastroenterologiststhatGERDpatientsshouldtrytodiscontinuePPItherapywhentry-ingtobecomepregnant;however,moredataareneededbefore this guideline should be recommended to allGERDpatientscontemplatingpregnancy.

ManypatientswithGERDhaveintermittentsymp-toms,sotheycanusePPItherapyforsymptomcontrolasneeded.ThismanagementstrategyhasbeendemonstratedtobeeffectiveforalargenumberofpatientswithGERDinthegeneral population.

G&H In your experience, do most doctors currently prescribe PPI therapy to GERD patients who are pregnant or trying to become pregnant?

LBG Inmypractice,Iencounterwomenwhoarecon-templatingpregnancymorecommonlythanwomenwhoarealreadypregnant;oncewomenbecomepregnant,theirobstetricians usually take over management, includingmanagementofGERDsymptoms.TheissueofwhetherPPItherapyshouldbediscontinuedisacommontopicofconversationwithmyGERDpatientswhoarecontem-platingpregnancy.Inthesepatients,Iusuallyrecommendtemporary cessation of PPI therapy during conceptionand pregnancy, if tolerated, but I also explain that theusage of these agents has been demonstrated to be safeand,therefore,theyshouldbeusedifneeded.

G&H How safe are other treatment options in pregnant GERD patients?

LBG If a pregnant woman is experiencing mild-to-moderateGERDsymptomsduringpregnancy,theinitialtreatment options should include either antacids or anH2-receptorantagonistsuchasfamotidineorranitidine.If thepatient’sheartburn is severe, thepatientcouldbestartedonPPItherapy.Forpatientswhoarenotrespond-ing toPPI therapy, aprokinetic agent suchasmetoclo-pramide(pregnancycategoryB)couldbeadded.

The usage of laparoscopic surgery in pregnantpatients is feasiblewhenclinically indicated.Themostcommon scenario would be cholecystectomy for acutecholecystitisorbiliarycolicoranappendectomyinthesettingof acute appendicitis. In some studies,patientswith GERD have successfully undergone laparoscopicNissen fundoplication prior to pregnancy in order todiscontinuePPItherapy,butthiswouldnotberoutinelyrecommended,giventhesafetyofmedicaltherapy.Theeffectiveness and safety of surgical fundoplication inpregnantpatientswithGERDhavenotbeenreported.

G&H Are lifestyle modifications effective for managing GERD in pregnant patients?

LBG Yes, in fact, thefirst treatment recommendationfor patients with pregnancy-induced GERD shouldinclude lifestyle modifications such as eating smallermealsandnoteatinglateatnight(ie,within3hoursofbedtime).Notmuchdatahavebeen found to supporttheavoidanceofcaffeineand/orspicyfoodsinordertoalleviate GERD symptoms, but patients should avoidanyfoodsthattriggersymptoms.Ifpatientshavenight-timeGERD,theyshouldelevatetheheadoftheirbedwithafoamwedge,asdatahaveshownthatthisadjust-mentreducesGERDsymptoms.

G&H What are the next steps in research in this area?

LBG Given the above data, it would be efficacious toconduct additional studies evaluating the safety of PPItherapy during conception, given the recent concernaboutapossibleincreaseinbirthdefectsinthesepatients.It would also be useful to collect more long-term dataregardingwhetherpregnantpatientswithGERDexperi-ence this conditionpostpregnancy andwhen the recur-rencesoccurinthepostpartumperiod.

Suggested Reading

PasternakB,HviidA.Useofprotonpumpinhibitorsinearlypregnancyandtheriskofbirthdefects.N Engl J Med.2010;363:2114-2123.

GersonLB.Protonpumpinhibitorsandsafetyduringpregnancy.Gastroenterology.2011;141:389-391.

MatokI,LevyA,WiznitzerA,UzielE,KorenG,GorodischerR.Thesafetyoffetalexposuretoprotonpumpinhibitorsduringpregnancy.Dig Dis Sci.2012;57:699-705.

GillSK,O’BrienL,EinarsonTR,KorenG.Thesafetyofprotonpumpinhibitors(PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol. 2009;104:1541-1545;quiz1540,1546.

ReyE,Rodriguez-ArtalejoF,HerraizMA, et al.Gastroesophageal reflux symp-toms during and after pregnancy: a longitudinal study. Am J Gastroenterol.2007;102:2395-2400.