Single or double needle insertion in twins amniocentesis

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Single or double needle insertion in twin ’ s amniocentesis: Does the technique in ﬂ uence the risk of complications?

E. Krispin

^a,b,1

, A. Wertheimer

^a,b,

*

^,1

, S. Trigerman

^a,b

, A. Ben-Haroush

^a,b

, I. Meizner

^a,b

, A. Wiznitzer

^a,b

, R. Bardin

^a,b

aHelenSchneiderHospitalforWomen,RabinMedicalCenter–BeilinsonHospital,PetachTikva,Israel

bSacklerFacultyofMedicine,TelAvivUniversity,TelAviv,Israel

ARTICLE INFO Articlehistory:

Received13January2019

Receivedinrevisedform30April2019 Accepted14May2019

Availableonline15May2019 Keywords:

Twinpregnancy Amniocentesis Abortion Needleinsertion

ABSTRACT

Objective: Tocomparecomplication ratesfollowingamniocentesisin twingestations,accordingto samplingtechniqueandnumberofneedleinsertions.

Study design: A retrospectivecohort studyof all women withtwin gestationswho underwent amniocentesis and delivered in a single university afﬁliated medical center during 2002 2016.

Amniocentesiswasperformedeitherthroughoneuterineentrywithpassagethroughtheinter-twin membraneorthroughtwodifferententriestothetwoamnioticsacs.Pregnancyoutcomeofwomenthat underwentsingleneedleinsertionamniocentesis,wascomparedtothisofdoubleneedleinsertion.

Primary outcome was neonatal complications within 4 weeks after amniocentesis (late abortion, chorioamnionitis, preterm premature rupture of membranes, or hospitalization due to related symptoms).Secondaryoutcomesweregestationalweekatdeliveryandlaborcharacteristics.

Results:Thestudygroupcomprised212women.Ofthem,73(34.4%)underwentasingle uterine insertionand139(65.6%)twoseparateneedleinsertions.Baselinecharacteristicsdidnotdifferbetween thegroups.Theamniocentesiscomplicationratewas13.7%inthesingleinsertiongroupand16.5%inthe doubleinsertiongroup(p=0.587).Multivariateanalysisfoundthatasingleinsertionmethodhadno statistically signiﬁcant inﬂuence on complication rate, after making adjustments for potential confounders(OR=1.085,95%CI0.4–2.9;p=0.871).Otherlaborcharacteristicsweresimilarbetween thegroups.

Conclusion:Needleinsertiontechnique intwingestationamniocentesiswasnot associatedwith procedurerelatedcomplications.

Introduction

Duringrecentdecades,therehasbeenasigniﬁcantincreasein theincidenceoftwinpregnancies.[1]Thistrendisaccountedfor bothbytheincreaseinmaternalageindevelopedcountries,and the rise in pregnancies achieved by assisted reproductive technologies. According to the American Society for Assisted Reproductive Technology (SART), approximately 8 percent of pregnanciesconceivedthroughassistedreproductivetechnology in 2016 were twin pregnancies [2]. Patients with multiple gestationspossesshigherriskforfetalgeneticandchromosomal

anomaliescomparedtosingletonpregnancies,anddizygotictwin pregnancies have approximately twice thesingleton risk of an affectedfetus[3].Asaresult,thegeneticworkup,whichinmost casesincludesamniocentesistoobtainfetalcellsforanalysis,has animportantroleintheprenatalevaluationofthesepregnancies.

[4] While the risk of pregnancy loss after amniocentesis in singletonpregnanciesiswellestablished[5,6],apaucityofdata exists regarding the risk in twin pregnancies [7]. Studies have demonstrateddifferentratesofpregnancylossfollowingamnio- centesisintwinpregnancies,rangingfrom0to9percent[4,7–9].

One of the factors that might inﬂuence amniocentesis complications rate isthesamplingtechnique– asingleuterine entrytechniquewithsamplingofbothgestationalsacsfollowing one puncture, versus a double uterine-entry technique and separatepuncturesofeachsac.[7]

Thereisaninsufﬁcientbodyofdataaddressingtherelationship betweensamplingtechniqueandpregnancyoutcome[10].Thus,

* Correspondingauthorat:HelenSchneiderHospitalforWomen,RabinMedical Center,PetahTiqva,4941492,Israel.

E-mailaddress:[email protected](A. Wertheimer).

1 Bothauthorscontributedequallytothiswork.

http://dx.doi.org/10.1016/j.eurox.2019.100051

ContentslistsavailableatScienceDirect

European Journal of Obstetrics & Gynecology and Reproductive Biology: X

j o u r n al h o m e p a g e : w w w . el s e v i e r . c o m / l o c a t e / e u r o x

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weaimed toinvestigate thepotential impactof amniocentesis technique on related complications in a large cohort of twin pregnancies.

Materialsandmethods Studycohort

Aretrospectivecohortstudy ofallwomencarryingtwingestation whounderwentamniocentesisduringpregnancyanddeliveredina singleuniversity-afﬁliatedtertiaryhospital,betweenOctober2002 and February 2016. The cohort was divided into two groups accordingtoamniocentesistechniquewithregardtothenumber oftrans-abdominalneedleapplications.Proceduresin whichasingle trans-abdominalneedleinsertionwasperformedwerecomparedto proceduresusingthedouble insertiontechnique.Amniocentesis relatedcomplicationrateswereinvestigatedinbothgroups.Our localinstitutionalreviewboard(0165-16-RMC)approvedthestudy.

Informedconsentwaswaivedduetotheretrospectivedesignofthe studyandinaccordancewithgoodclinicalpractice.

Ourhospitalisareferralcenterforhigh-riskpregnancies.Thus, we were able to access a large cohort of women with twin pregnancieswhowerecarefullyfollowedduringpregnancyand thendeliveredinthesameinstitution.Someofthesepregnancies underwent amniocentesis. The indications for amniocentesis during twin gestation are variable. Our study included only indicationsthatarerecommendedandfundedbytheMinistryof Health,inaccordancewithIsraeliguidelines:(1)amniocentesisfor fetalkaryotypewhenmaternalageexceeds35years;(2)suspected anatomicalanomaliesdemonstratedbyultrasoundduringprimary or secondary anatomical survey; (3) Cytomegalovirus (CMV) seroconversionwhendiagnosedduringpregnancy.Amniocentesis totraceviruspresenceintheamnioticﬂuidisrecommendedafter 21 weeks of gestation and at least 6 weeks after suspected maternalexposuretovirus;and(4)when recommendedduring geneticcounselinggenerallybecauseof abnormalresultsinthe ﬁrstorsecondtrimesterscreening,orwhentherewashereditary diseaseinthefamily.

Thefollowingcaseswereexcluded:1)methodofamniocentesis was not clear or puncture was made only in a single sac; 2) terminationofpregnancy;3)feticideofasingleembryo;4)fetal chromosomalanomalies;5)monochorionicmonoamniotictwins;

and6)missingdatawewerenotabletoattain.

Thetimingforamniocentesisdependedontheindicationfor theprocedure.Electiveproceduresindicatedduetomaternalage orpathologicalscreeningtestswereheldat17+0–22+6weeksof gestation. Subsequent procedures were initiated as a result of ﬁndingsdiagnosedlaterinpregnancy.

Procedure

Allprocedures wereperformedbywell trained,experienced senior Ob-Gyn physicians specialized in ultrasound. For the investigated cohort, amniocentesis was performed by seven electedphysiciansand84%ofcaseswereperformedbythreeof them.Afterelaboratingontherisksassociatedwithamniocentesis, informedconsentwasobtainedfromthepatient.Theprocedure wasperformedundercontinuousultrasoundvision.Initially,the first selected amniotic sac was punctured and amniotic fluid aspirated.Inmostcases,afteraspiratingtherequiredamountof fluidforgeneticanalysis,colorwasinjectedintothesamesac,to markthefirst-enteredamnioticsac.Theentrancetothesecond amniotic sac involved injecting a needle into the inter-twin membrane(single insertion)ordirectlyintotheuterus(double insertion).Theprocedurewascompletedwhenamnioticfluidfrom thesecondsacwasobtained.

Datacollection

Data regarding the procedure, pregnancy, and birth were retrieved from our departmental comprehensive computerized perinataldatabase, and cross-tabulatedusing an individualized identiﬁcationnumberperpatient.Datafromtheultrasoundunit andtheneonatalintensivecareunit(NICU)wereintegratedinto thedeliverywarddatabase.

Thefollowingbaselinecharacteristicswererecorded:maternal age,gravidity,parity,previouspretermlabor,pregnancyachieved by assisted reproductive technology, twin amnionicity and chorionicity, fetal gender, gestational ageat amniocentesis and placental location.Missing datawas obtainedthroughacareful manual chart review performed by the study personnel or by callingthepatient'spersonalphysicianafterreceiving informed consent.

Primaryoutcomewasdeﬁnedasthecompositecomplications outcome,includinganyoneofthefollowingamniocentesisrelated complications occurring within 4 weeks post procedure: late abortion,chorioamnionitis,prematureruptureofmembranes,or hospitalization for observation in gynecologic ward due to procedureassociatedsymptoms(i.e.feverabove38^oC,premature contractions, abdominal pain and tenderness). Secondary out- comeswerelaborcharacteristics.

Outcomes were stratiﬁed for study groups according to amniocentesistechnique:singlevs.doubleinsertion.

Statisticalanalysis

Pregnancylossratesrelatedtotwinamniocentesisrangefrom 0%andupto9%indifferentstudies[4–9],UsingtheEpi-info^TM, programforthispregnancylossfrequenciesassuring80%power withalimitof0.05fortypeIerror;asamplesizeof116casesfor each subgroup is needed. Since we performed a retrospective designforourstudy,andusedallcaseseligibleaccordingtothe inclusioncriteria,wedeﬁnedaprimaryoutcomecomposedofany procedure associated complications. Post-hoc power analysis calculatedwiththeabove-mentioneddeﬁnitions,foracomplica- tion’sfrequencyof14%,asamplesizeof64casesisneededforeach subgroup.

Data analysis was performed using the SPSS v21.0 package (Chicago, IL). Continuous variables were compared using the Student's t-test and Mann-Whitney U test. The chi-square and Fisher'sexacttestswereusedforcategoricalvariables.Differences wereconsideredsigniﬁcantwhenthep-valuewaslessthan0.05.

Followingthebivariateanalysis,logistic regressionanalysiswas utilized toadjustoutcomesfor potentialconfounders. Variables withclinical impacts or thatdiffered signiﬁcantly betweenthe groups(p<0.05)inthebivariateanalysisenteredtheregression model: maternal age, gravidity, parity, previous preterm labor, gestational age at amniocentesis and composite complications outcome.

Results

Duringthestudyperiod,309motherswithtwinpregnancies underwent amniocentesis and delivery in our institution; 212 (68.6%)mettheinclusioncriteria.In73(34.4%)casesamniocente- siswasperformedbyasingleuterineentry,andin139(65.6%) cases amniocentesis was performedby double uterine entry.A totalof97caseswereexcludedaspresentedinFig.1.

Baselinecharacteristicsofwomeninbothgroupsarepresented inTable1.Nosigniﬁcantdifferencewasfoundbetweenthegroups regardingdemographic characteristics,prior pretermlabor,and indicationforprocedure,orplacentallocation.Themajorityofthe womencarriedabichorionictwinpregnancyandonly20women

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carried a monochorionic diamniotic pregnancy. Of them, four underwent a single uterine entry and 16 underwent a double uterine entry. Thus, chorionicity did not differ between study groups(p=0.149).TheuseofcoloraselaboratedintheMethods sectionwasperformedin190(89.6%)ofallcases;whileahigher rateofitsusewasdocumentedinthesingleinsertiontechnique (95.6%vs.86.3%inthedoubleinsertiontechnique,p=0.03).

Bivariate analysisofindividualand composite complications outcomesispresentedinTable2.Regardingprimaryoutcomeas defined in the Methods section, no significant difference was demonstrated between the groups. A composite complications outcomerateof13.7%wasfoundinthesingleinsertiontechnique vs.16.5%inthedoubleinsertiontechnique(p=0.587).Aspecific analysisof themonochorionic twinsubgroup demonstratedan overallfrequencyofthecompositecomplicationsoutcomeofupto

40%. Moreover, the only one case of abortion ascribed to amniocentesis (0.5%)that was identiﬁedin thecohort andwas found in the double entry group was a monochorionic twin gestation. Thepatient presented at 19weeks of gestation, two weeksfollowingtheprocedure,withnocardiacactivitytoboth twins.

Followingadjustmentforpotentialconfoundersaselaborated in the Methods section, amniocentesis technique was not associated with composite complication outcome (OR=1.085, 95%CI0.4–2.9,p=0.871).

Labor characteristics for the study groups are presented in Table 3. No differences regarding pregnancy complications, inductionoflaborormodeofdeliverywerefoundbetweenthe groups.Themeangestationalageatdeliverywas35.1weeksand birthweightswerestatisticallysimilarinbothstudygroups.

Table1

Baselinecharacteristicsforthestudygroups.

Variable Singleinsertion(N=73) Doubleinsertion(N=139) pvalue

Maternalage(years) 34.74.8 34.94.8 0.828

Gravidity 2.31.4 2.81.7 0.071

Parity 0.90.9 1.21.1 0.147

Previouspretermlabor

<37weeks 5/63(7.9) 11/112(8.9) 0.915

<34weeks 1/63(1.6) 2/123(1.6) 0.984

Assistedreproductivetechnology 41/63(65.1) 71/119(59.7) 0.555

Chorionicity 0.149

Bichorionicdiamniotic 58(93.5) 102(86.4)

Monichorionicdiamniotic 4(6.5) 16

Indicationforamniocentesis 0.914

Maternalage>35years 36/71(50.7) 62/135(45.9) –

Maternalrequest 9/71(12.7) 20/135(14.8) –

Anatomicanomalies 16/71(22.5) 36/135(26.7) –

CMVseroconversion 2/71(2.8) 4/135(3) –

Geneticcounseling 8/71(11.3) 12/135(8.9) –

Maleneonates

Fetus#1 38/65(58.5) 67/118(56.8) 0.379

Fetus#2 35/65(58.3) 48/116(41.4) 0.094

Gestationalageatamniocentesis(weeks) 19.64.1 20.34.68 0.296

Anteriorplacenta

Fetus#1 43/71(60.6) 63/135(46.6) 0.363

Fetus#2 29/68(42.7) 66/134(49.3) 0.477

Useofcolorinamniocentesis 70/73(95.9) 120/139(86.3) 0.030

Forallvariables,categoricaldataarepresentedasn/N(%)andcontinuousvariablesarepresentedasaverage2SD.

CMV,cytomegalovirus.

Fig.1.Studycohortselection.

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Discussion

This study sought to evaluate the association between amniocentesis technique and pregnancy complications in twin pregnancies, comparing single uterine entry to conventional double uterine entry, and foundthe two methods comparable.

Pregnancies complications directly relate to amniocentesis are knowntooccurwithin4weeksfollowingtheprocedure[11–13].

Thus,wepresentedaprimaryoutcomecompositecomprisedof complicationsoccurringupto4weeksfollowingtheprocedure.

Theresultsshowedthatbothtechniquesweresimilarintermsof pregnancyandcomplicationsoutcomes.

A singleuterineentrytechnique,aswasdescribed inseveral studies,requiresgoodvisualizationoftheamnioticmembranesin order toadvance the same needle into both gestational sacs [ 10,14,15].Thisprocedurewasdescribedasbothswiftandeasy,and reducesdiscomforttothepatient[14].

Itiscommonlyacceptedthattheriskforadverseoutcomerises withincreaseinnumberofuterineentriesduringtheprocedure [7].Wehypothesizedthat singleuterineentrytechniquemight presentalowercomplicationsratecomparedtothedoubleuterine entry technique, and might resemble published complications rates in singleton pregnancies. However, single uterine entry techniqueismorecomplexthanthesingletonamniocentesissince

itrequiresthepassagethroughtheinter-twinmembrane,which exposes one of the gestational sacs to two different amniotic punctures(oneattheentryandthesecondthroughtheinter-twin membrane). Moreover, the single-entry technique raises the theoreticalriskofinter-twinmembranerupture,evidenceforthis hypothesisislacking.

Todate,onlyonestudyhasaddressedtheeffectofnumberof uterine entries during amniocentesis of twin pregnancies on pregnancyoutcomes[10].Inthatstudy,theauthorsreviewed100 casesofamniocentesisintwinpregnanciesdescribedtotalfetal lossbefore24weeksorPPROM<34weeksatarate of1(2.7%) (n=37)forsingleentryvs.3(4.76%)(n=63)fordoubleentry,with nostatisticsigniﬁcantdifferences(RR=0.57).Ourstudyofalarger cohortof212pregnancies,showedsimilarresults.Thissamplesize is correlated withthepowercalculations and presentsa much largercohortcomparedtopreviousstudies.Thelackofstatistically signiﬁcantdifferencesbetweenthetwogroups,despiteourlarger samplesizeand adequatepoweraselaboratedinthestatistical analysissection,maybeattributedtotheverylowrateoffetalloss inourstudy(0.5%)whichisconsistentwithsomeearlierstudies[ 14–17].

Ingeneral,ourresultscomparefavorablywiththeliteraturein termsofgestationalageatdelivery,complicationrateandbirth weight[7,8].However,tothebestofourknowledge,ourstudy includes one of the largest cohorts of twin pregnancies who underwentamniocentesisreportedintheliterature.

Anotherpotentialproblemwithsingleuterineentrytechnique, isthatitmaycausesamplingerrorsorcrosscontaminations[4,10].

In ourseries,there werenosuchcomplications. Thismight be attributed toour wellexperienced procedure operators, tothe widely used color injection and to the thorough ultrasound evaluationconductedbothpriortoandduringtheprocedure.

Thestrengthsofourstudyaretherelativelylargesamplesize and the detailed prenatal information wewere able tocollect.

Operator dependent complications bias was diminished by an electedgroupofwellexperiencedoperators.Limitationsinclude theretrospectivedesign,thelackofrandomizationforprocedure techniqueandthesmallnumbersofmonochorionictwingestation thatconstrainedourabilitytoimplysigniﬁcantresultsoverthis subgroup.

Inconclusion,wefoundsimilarpregnancyoutcomesfortwin pregnanciesfollowingamniocentesisbyasingleordoubleuterine entry technique. Both techniques are optional and medically acceptable.Choiceshouldbelefttotheoperatorconsideringtheir skillsandreal-timeultrasoundﬁndings.

Disclosure

Theauthorsreportnoconﬂictofinterest.

Funding None.

References

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Table2

Amniocentesisrelatedcomplicationrates.

Variable Singleinsertion

(N=73)

Doubleinsertion (N=139)

pvalue Complicationswithin4weeksafterAmniocentesis

Lateabortion 0/65(0) 1/125(0.8) 0.470

Chorioamnionitis 0/62(0) 1/118(0.8) 0.655

PPROM 3/62(4.8) 6/122(4.9) 0.981

Hospitalization 6/62(9.7) 16/118(13.6) 0.655 Compositecomplications

outcome^*

9/73(13.7) 24/139(16.5) 0.587

Forallvariables,categoricaldataarepresentedasn/N(%).

PPROM,pretermprematureruptureofmembranes.

*Compositeincludesanyofthefollowingwithin4weeksofamniocentesis:Late abortion, chorioamnionitis, pre-term premature rupture of membranes, or hospitalization.

Table3

Pregnancyandlaborcharacteristicsforthestudygroups.

Variable Single

Insertion (N=73)

DoubleInsertion (N=139)

p value

pvalue

Pregnancycomplications

Pre-eclampsia 5/59(8.5) 12/118(10.2) 0.718 0.718 GestationalDM 7/61(11.5) 15/118(12.7) 0.593 0.593 Suspectedintrauterine

growthrestriction

7/61(11.5) 17/116(14.7) 0.557 0.557 Twintotwintransfusion

syndrome

0/61(0) 1/118(0.8) 0.471 0.471

Laborcharacteristics

Laborinduction 29/61(47.5) 63/118(53.4) 0.298 0.298 Cesareandelivery 51/67(76.1) 101/126(80.2) 0.307 0.307 Gestationalageat

delivery(weeks)

35.13.0 35.12.9 0.973 0.973

Birthweight(grams)

Fetus#1 2169.2506.2 2324.3550.3 0.071 0.071 Fetus#2 2145.5553.5 2198.7502.6 0.529 0.529 Forallvariables,categoricaldataarepresentedasn/N(%);continuousvariablesare presentedasaverage2SD.

DM,diabetesmellitus.

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