Citation/Reference Braeken M.A.K.A., Jones A., Widjaja D., Van Huffel S., Monsieur G.J.Y.J., van Oirschot C.M., Van den Bergh B.R.H., ``Anxious women do not show the expected decrease in cardiovascular stress responsiveness as pregnancy advances'', Biological Psychology, vol. 111, 2015, pp. 83-89
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Biological Psychology
j ou rn a l h o m epa g e : w w w . e l s e v i e r . c o m / l o c a t e / b i o p s y c h o
Anxious women do not show the expected decrease in cardiovascular stress responsiveness as pregnancy advances
M.A.K.A.Braekena,b,c,A.Jonesd,R.A.Ottea,D.Widjajae,S.VanHuffele,G.J.Y.J.Monsieurf, C.M.vanOirschotg,B.R.H.VandenBergha,c,h,∗
aDepartmentofPsychology,TilburgUniversity,TheNetherlands
bREVALRehabilitationResearchCenter,BiomedicalResearchInstitute,FacultyofMedicineandLifeSciences,HasseltUniversity,Belgium
cDepartmentofPsychology,KULeuven,Belgium
dInstituteofCardiovascularScience,UniversityCollegeLondon,UK
eDepartmentofElectricalEngineering,ESAT-STADIUSCenterforDynamicalSystems,SignalProcessingandDataAnalytics,KULeuven,MedicalIT,iMinds, Belgium
fFontysUniversityofAppliedSciences,TheNetherlands
gSintElisabethHospitalTilburg,TheNetherlands
hDepartmentofWelfare,PublicHealthandFamily,FlemishGovernment,Brussels,Belgium
a r t i c l e i n f o
Articlehistory:
Received25July2014
Receivedinrevisedform18August2015 Accepted18August2015
Availableonline24August2015
Keywords:
Stressresponsiveness Pregnancy
Autonomicnervoussystem Heartratevariability Anxiety
a b s t r a c t
Alteredstressresponsivenessisariskfactorformentalandphysicalillness.Innon-pregnantpopulations, itiswell-knownthatanxietycanalterthephysiologicalregulationofstressreactivity.Characterization ofcorrespondingrisksforpregnantwomenandtheiroffspringrequiresgreaterunderstandingofhow stressreactivityandrecoveryareinfluencedbypregnancyandwomen’sanxietyfeelings.Inthecur- rentstudy,womenwerepresentedrepeatedlywithmentalarithmeticstresstasksinthefirstandthird pregnancytrimesterandreportedtheirtraitanxietyusingthestatetraitanxietyinventory.Cardiovas- cularstressreactivityinlatepregnancywaslowerthanreactivityinthefirstpregnancytrimester(heart rate(HR):t(197)=4.98,p<.001;highfrequencyheartratevariability(HFHRV):t(196)=−2.09,p=.04).
Lessattenuationofstressreactivityoccurredinmoreanxiouswomen(HR:b=0.15,SE=0.06,p=.008;
HFHRV:b=−10.97,SE=4.79,p=.02).Thestudydesigndidnotallowtheinfluenceofhabituationto repeatedstresstaskexposuretobeassessedseparatelyfromtheinfluenceofpregnancyprogression.
Althoughthisisalimitation,thecleardifferencesbetweenanxiousandnon-anxiouspregnantwomen areimportant,regardlessoftheextenttowhichdifferinghabituationbetweenthegroupsisresponsible.
Lessdampenedstressreactivitythroughpregnancymayposelong-termrisksforanxiouswomenand theiroffspring.Follow-upstudiesarerequiredtodeterminetheserisks.
©2015ElsevierB.V.Allrightsreserved.
1. Introduction
Pregnantwomen undergo marked changes in maternal car- diovascularfunction during pregnancy,such asincreased basal strokevolume(SV)andheartrate(HR)(Abbas,Lester,&Connolly, 2005;Silversides&Colman,2007).Theautonomicnervoussys- tem(ANS)playsacentralroleinthesechanges.BasalANSactivity isshiftedtowardshighersympathetic(e.g.,shorterpre-ejection period (PEP) and increased skin conductance level (SCL)) and
∗ Correspondingauthorat:FacultyofSocialandBehaviouralSciences,Tilburg University,Warandelaan 2,POBox 90153,5000LETilburg, TheNetherlands.
Fax:+31134662067.
E-mailaddress:Bea.vdnBergh@uvt.nl(B.R.H.VandenBergh).
lowervagalmodulation(e.g.,reducedHRvariability(HRV))over thecourseofpregnancy(DiPietro,Costigan,&Gurewitsch,2005;
Ekholm&Erkkola,1996;Kuo,Chen,Yang,Lo,&Tsai,2000).
These changes go along with attenuated cardiovascular responsestostress,asHRandbloodpressure(BP)reactivityare typicallyattenuatedaspregnancyprogresses(DiPietro,Costigan,
&Gurewitsch, 2003; Entringer et al.,2010; Matthews&Rodin, 1992).StudiesofANSstressresponsivenessduringpregnancyare rare.EvidenceofdecliningSCLstressreactivitybetween24and36 weeksgestationisanimportantfinding(DiPietroetal.,2003)anda reportofdecreasedHRVresponsivenesswithadvancingpregnancy is valuablebut this findinghad marginal statisticalsignificance (Klinkenbergetal.,2009).NostudiesexistexaminingPEPreactiv- itytolaboratorystressorsduringpregnancy.Moreover,studiesof stressreactivityinpregnancyhavegenerallyexaminedthemagni- http://dx.doi.org/10.1016/j.biopsycho.2015.08.007
0301-0511/©2015ElsevierB.V.Allrightsreserved.
84 M.A.K.A.Braekenetal./BiologicalPsychology111(2015)83–89
tudeofphysiologicalchangefollowinganacutestressorandhave generallynotreportedonhowpregnantwomenrecoveredfrom stress(Christian,2012;deWeerth&Buitelaar,2005).
Ifstressreactivityattenuatesduringpregnancy,assuggestedby theseearlystudies,itraisesthequestionofwhythismightoccur.
Onepossibilityisthathighstressreactivityinpregnancycouldbe detrimentaltothemother,thechild,orboth.Therefore,aprotective mechanismmaybeoperatingtolimitstress-inducedchangesin thehormonal,cardiovascularandmetabolicenvironmentsofthe pregnancythatcouldbeharmful.Forexample,previouslyithas beendemonstratedthatstressisassociatedwithvasoconstriction, whichcanalteruteroplacentalbloodflow,reducingoxygenand nutritiondeliverywithpotentiallynegativeeffectsonfetalgrowth (Alder,Fink,Bitzer,Hösli,&Holzgreve,2007;Copperetal.,1996;
McCubbinetal.,1996)andnervoussystemdevelopment(Sjöström, Valentin,Thelin,&Marsál,1997).However,morerecentstudies couldnotreplicatetheassociationbetweenmaternalanxietyand reduceduterinebloodflow(Mendelson,DiPietro,Costigan,Chen,
&Henderson,2011;Monketal.,2012).
In men and non-pregnant women, stress reactivity differs accordingtolevelofanxiety.Highanxietyisassociatedwithexag- geratedcardiovascular (HRandBP) stressresponses(Gramer&
Saria, 2007; Pointer et al., 2012). Thereis some evidence that depressionandanxietyaffectstressresponsivenessduringpreg- nancybutthishasnotbeenstudiedextensively(Christian,2012;
deWeerth&Buitelaar,2005).Findingshavealsobeeninconsistent, suggestingthatanxiouspregnantwomenmayhavelower(Monk etal.,2000;Saisto,Kaaja,Helske,Ylikorkala,&Halmesmäki,2004) orunaltered(Monk,Myers,Sloan,Ellman,&Fifer,2003)HRand BPreactivitytopsychologicalstress.Our studywasdesignedto addressthislackofevidenceandtoassessbothreactivitytoand recoveryfromstress.
Our aims were: (a) to characterize typical autonomic stress responsiveness (i.e., reactivity and recovery) through different pregnancytrimestersand(b)totestthehypothesisthatanxiety mayalterstressresponsivenessduringpregnancy.
2. Methods 2.1. Participants
The prenatal early life stress (PELS) study is a longitudinal studyand focuses onassociations betweenprenatal stress risk factors,birthoutcomesandalteredpregnantwomen’sphysiology andchild’spsychophysiologyandneurodevelopment.Thenational ethics committee and the ethics committee of the Sint Elisa- bethhospital,Tilburg,TheNetherlandsbothapprovedthestudy protocol. Pregnantwomen were recruited from a hospital and midwiferiesaroundTilburg.Theyfilledoutquestionnairesabout theiremotionsandtheirECGwasrecordedduringeachpregnancy trimester.Afterbirth,psychophysiologicalmeasurementsofthe childrenandmotherstookplace.Allparticipantsandtheirpart- nersprovidedwritteninformedconsent.Noneoftheparticipants smoked,drankalcohol,wereundertreatmentforacurrentmental disorder,orusedcardiovascularmedicationsorantidepressants.
Onehundredandseventywomencompletedstresstasksduring thefirst(8–14thweekofgestation,N=133)and/orthirdpregnancy trimester(31–37thpregnancyweek,N=138)and157ofthese170 participantsfilledoutastandardizedanxietyself-reportquestion- naireat15–22weeksofpregnancy.
2.2. Material
2.2.1. Relaxationandstresstasks
In the first and third pregnancy trimesters, each pregnant womanundertooka25-mintaskconsistingoffivetestingphases, lastingfor5mineach.Stresswasinducedinthesecondandfourth
Fig.1.Diagramshowinghowthereactivityandrecoverymeasureswerecalcu- latedfromtheHR/HRVdatacollectedduringthementalarithmeticstresstask.As indicatedinthefigure,themeasurementinthefirstphasewasuseasabaseline measure.
phase,withtheremainderbeingrelaxationphases.Participants viewedpeacefulpicturesandlistenedtorestfulmusicduringthe relaxationphases(Taelman,Vandeput,Vlemincx,Spaepen,&Van Huffel,2011).Duringthestressphases,participantswereaskedto solvecomplexmentalarithmeticproblems,involvingfivemath- ematicaloperationson2–3digitnumberswithoutverbalization (e.g.,361+17/24×2+13).Theywereaskedtochoosethecorrect answerfromthreepossibilitiespresentedbyacomputer.Feedback onthetaskwasgivenaftercompletionofthelastphase(Vlemincx, Taelman,DePeuter,VanDiest,&VandenBergh,2011).
2.2.2. ECGandICGrecording
Maternalelectrocardiography(ECG)andimpedancecardiogra- phy(ICG) wasrecorded withtheVrije Universiteit Ambulatory Monitoringsystem(VU-AMS)duringthestresstaskusingseven Ag/AgClelectrodesplacedaccordingtotheVU-AMSconfiguration guidelines(Goedhart,Sluis,Houtveen,Willemsen,&Geus,2007).
Theskinwascleaned withalcohol tokeep electrode resistance low.Cardiovascularmeasurementsweredeterminedforthethree relaxationphasesandtwostressphases,eachlasting5min.The firstrelaxationphase wasusedasbaselinemeasure.Cardiovas- cularreactivitytothestressphasewascalculatedbysubtracting thecardiovascularmeasurementsofeachofthestressphaseswith thelevel ofthepreviousrelaxation phase.Hence,we explicitly choosetoworkwithtworeactivitymeasures,onederivedfrom thedifferencebetweenphase1and2(i.e.,reactivitytofirststressor presentation),andonebetweenphase3and4(i.e.,reactivitytosec- ondstressorpresentation).Cardiovascularrecoveryfromastressor presentationwasderivedfromthesubtraction betweencardio- vascularmeasurementsintherelaxationphasethat followsthe stressorpresentationandbaselinecardiovascularmeasurements (i.e.,inthefirstrelaxationphase)(Stewart&France,2001).Fig.1 showsagraphicalrepresentationofthecalculationofthereactivity andrecoverymeasures.
2.2.3. Thestatetraitanxietyinventory(STAI)
Inthesecondpregnancytrimestertheparticipantsfilledout thequestionsconstitutingthetraitanxietysubscaleoftheDutch, psychometricallyvalidatedversionofthestatetraitanxietyinven- tory(STAI)(VanderPloeg,Defares,&Spielberger,1980).Thetrait subscale hasbeenidentified recentlyasthebest instrumentto assessgeneralmaternalanxietyduringpregnancy(Nast,Bolten, Meinlschmidt,&Hellhammer,2013).Traitanxietyreferstodiffer- encesinanxietypronenessandisseenasapersonalitytrait.This subscalecontains20itemsscoredfrom1to4andhasareliability coefficient(Cronbach’salpha)of0.75inoursample.
2.3. Dataprocessingandanalyses
ECG data were processed using custom software written in Matlab R2012b (Mathworks, Natick, USA) to obtain indices of parasympatheticandsympatheticANSactivity,accordingtopub- lishedstandards(TaskForceoftheEuropeanSocietyofCardiology theNorth American Societyof Pacing Electrophysiology, 1996).
ThesemeasureswereHR,highfrequency(0.15–0.4Hz,HF)HRV, and the sympathetic measure pre-ejection period (PEP). ECG beatdetectionwascarried outwiththeHilberttransformalgo- rithm(Benitez,Gaydecki, Zaidi,&Fitzpatrick, 2001).Potentially erroneousbeatdetectionswereidentified andscreened usinga standardapproach(Berntson,Quigley,Jang,&Boysen,2007).The powerspectraldensity(PSD)analysisusedforthecalculationof HFHRVwascomputedusingthefastFouriertransform(FFT).Vari- ablesthatwereright-skewedweretransformedtonormality.Data offourwomenwereexcludedduetoextremeHRVvalues;visual inspectionoftheECGssuggestedthattheseoutliersweredueto cardiacarrhythmias.
Inthepresentstudy,RMSSDHRV,thesquarerootofthemean squareddifferencesofsuccessiveinterbeatintervals,hadsimilar relationshipswithoutcomemeasuresasthoseseenwithHFHRV.
Therefore,RMSSDHRVwasnotincludedasanadditionalmeasure ofparasympatheticactivity.
For thecalculationof PEPthe ICGdZ/dt signal(firstderiva- tive)wasensembleaveragedfromconsecutivecardiaccyclesand synchronizedwiththeECGsignal.PEP,whichisanindicatorof sympatheticactivity,wascalculatedfromtheICGastheinterval betweenECG’sR-waveonsetandtheICG’sB-point.TheB-point, whichrepresentstheopeningoftheaorticvalve,wasdeterminedas the15%responsepointofthenegativepeakofthedZ/dtwaveform (dZ/dtmin)fromthebaseline(Onoetal.,2004).
2.4. Statisticalanalysis
All analyses were conducted using Stata 12.1. Repeated measuresANOVAwereconductedtovalidatethatthementalarith- metictaskevokedsignificantresponsesinHR,HRVandPEP.These ANOVAanalyseswerealsousedtodetermineHR,HRVandPEPdif- ferencesbetweenpregnancytrimesters.Differencesinreactivity andrecoverybetweenthefirstandthirdpregnancytrimesterwere testedusingpairedsamplest-tests.
Multilevel(i.e.,pregnancytrimesterand first/secondstressor presentation)regressionanalyseswereconductedtoexaminethe potential association between trait anxiety and cardiovascular responsivenessduringpregnancy.Bothlevelsfitwiththereactiv- ityandrecoverymeasuresdescribedinthematerialsectionand showninFig.1.Two-wayandthree-wayinteractioneffectswere assessedtotestwhetherreactivityandrecoveryinHR,HRVand PEPdifferacrosslevelsofanxiety,pregnancytrimestersandfirst andsecondpresentationofthestressor.
AllregressionmodelswereadjustedforlevelsofHR,HRVor PEP inthe first phase of themental task(baseline), as wellas for common confounders such as age and pre-pregnancy BMI (Vallejo, Márquez,Borja-Aburto,Cárdenas, &Hermosillo, 2005).
Otherpotentialcovariates(i.e.,gravidity,parity,educationallevel andthegestationalageofthefetusatthetimeofmeasurements) weretestedinrepeatedanalysesbutwerenotincludedinthefinal analyses,becausetheydidnotinfluencetheresults.
3. Results
CharacteristicsofthepregnantwomenareshowninTable1.
Therewerenosignificantassociationsbetweentraitanxiety,gra- vidity, parity, marital status, educational level and any of the
cardiovascularbaselinelevels.Pre-pregnancyBMIwaspositively correlated withbaseline HR in third trimester (r=0.23, n=133, p<0.01), and negatively correlated with baseline PEP in both trimesters(trimester1:r=−0.36,n=122, p<0.001;trimester 3:
r=−0.26, n=124, p<0.01). Age was negatively correlated with baselineHFHRVinbothtrimesters(trimester1:r=−0.19,n=138, p=0.02;trimester3:r=−0.23,n=133,p<0.01).
3.1. HR,HRVandPEPdifferencesbetweentaskphasesand betweenpregnancytrimesters
RepeatedmeasuresANOVA(pregnancytrimester×taskphase) wereexecutedtovalidatethatthementalarithmetictaskevoked significantresponsesandindicatedsignificantdifferencesbetween thefivephasesofthementalarithmetictaskforpregnantwomen’s HRandHRV(HR:F(4161)=49.02,p<.001;HFHFV:F(4161)=11.39, p<.001)butnotforPEP(p>.1).HR,HRVandPEPweresignificantly different between pregnancy trimesters (HR: F(1161)=581.87, p<.001;HFHRV:F(1161)=362.44,p<.001;PEP:F(1157)=219.53, p<.001).
3.2. Comparisonofreactivityandrecoverymeasuresbetween trimesters
Differencesinreactivityandrecoverybetweenthefirstandthird pregnancytrimesterweretestedusingpairedsamplest-tests(see Table 1).HRand HRV reactivity, but not PEPreactivity, in late pregnancywerelowerthaninthefirstpregnancytrimester(HR:
t(193)=5.01,p<.001;HFHRV:t(187)=−2.00,p<.05).Furthermore, HR,HRVand PEPrecoveryweregreaterin thethirdpregnancy trimestercomparedtothefirsttrimester(HR:t(201)=2.74,p=.01;
HFHRV:t(187)=−2.24,p=.03;PEP:t(176)=−2.23,p=.03),indi- catingthatthedifferencebetweenHR,HRVorPEPafterastressor presentationandbaselineHR,HRVorPEPwassmallerinthethird pregnancytrimestercomparedtothefirsttrimester.
3.3. Comparisonofreactivityandrecoverymeasuresbetween firstandsecondstressorpresentation
Themultilevelregressionanalysesshowedthatstresspresen- tation wassignificantlyrelated toHR reactivity,indicating that HRreactivitywassignificantlylowerduringthesecondstressor presentation(b=−1.67, SE=0.28, p<.001).Analogously HFHRV decreaseslessduringthesecondstressorpresentation(b=94.27, SE=23.46,p<.001).Recoveryfromthesecondstressorpresenta- tionwassignificantlylargerthanrecoveryfromthefirststressor presentation(HR:b=−1.27,SE=0.26,p<.001;HFHRV:b=43.61, SE=18.11,p=.02),indicatingthatthedifferencebetweenHRor HRVafterthestressorpresentationandbaselineHRorHRVwas smallerafterthesecondpresentationcomparedtoafterthefirst presentation.
3.4. Relationshipbetweenanxietyandstressresponsiveness duringpregnancy
Multilevel regression analyses showed significant two-way interactionsbetweentraitanxietyandpregnancytrimesterforHR andHFHRVreactivity,adjustedforbaselinelevelsofHRandHF HRV(HR:b=0.15,SE=0.06,p=.008;HFHRV:b=−10.97,SE=4.79, p=.02),indicatingthatinthethirdpregnancytrimester,compared tolessanxiouswomen,moreanxiouswomenhavehigherHRand HFHRVresponsestostress,independentofthebaselinelevelof HRorHFHRV(Table2and Fig.2a andb).Giventhesignificant decreaseinHRandHRVreactivitybetweenthefirstandthirdpreg- nancytrimester,thisimpliesthatcomparedtolessanxiouswomen, moreanxiouswomenhavelessdampenedHRandHRVreactivity
86 M.A.K.A.Braekenetal./BiologicalPsychology111(2015)83–89
Table1
Descriptivestatisticsforvariablesrelatedtopregnantwomen.Observeddifferencesbetweenthefirstandthirdpregnancytrimesterweretestedusingpairedsamplest-tests.
Mothers M (SD) %
Traitanxiety 36.67 5.29
BMIbeforepregnancy(kg/m2) 24.19 4.09
Gravidity 1.08 1.29
Parity 0.61 0.65
Maritalstatus
Marriedorcohabiting 97.45
Single 2.55
Educationallevel
Secondaryschool 32.48
Highervocationaleducation 39.49
Universitydegree 28.02
1sttrimester 3rdtrimester
n M (SD) n M (SD) pvalue
Age(years) 125 32.58 (4.26) 129 32.77 (4.33)
Weekspregnantduringmeasurement 125 13.61 (1.28) 129 33.96 (1.80)
BaselineHR(bpm) 125 80.25 (9.45) 129 89.29 (10.01) <.001
BaselineHF(lnms2) 122 6.05 (1.07) 128 5.30 (1.21) <.001
BaselinePEP(ms) 122 74.36 (20.51) 124 60.95 (20.64) <.001
HRreactivity(bpm) 125 4.45 (5.28) 129 2.17 (4.38) <.001
HFreactivity(ms2) 122 −139.16 (456.10) 128 −52.17 (318.10) <.05
PEPreactivity(ms) 122 0.78 (12.60) 124 −0.79 (10.64) >.1
HRrecovery(bpm) 125 .26 (4.29) 129 −.87 (4.27) .01
HFrecovery(ms2) 124 74.94 (462.62) 128 37.80 (263.08) .03
PEPrecovery(ms) 122 −2.71 (15.30) 124 −1.92 (12.98) .03
Table2
MultilevelregressionanalysesbetweentraitanxietyandreactivityofHR,HFHRVandPEP(n=157).
HRreactivity HFHRVreactivity PEPreactivity
Coef. SE p Coef. SE p Coef. SE p
Baselinelevel −0.05 0.02 .04 −0.28 0.03 <.001 −0.07 0.03 <.001
Traitanxiety −0.04 0.06 .51 3.04 4.14 .46 0.15 0.14 .30
Trimester(3rdvs.1st) −6.85 2.16 .008 397.78 178.75 .03 −0.48 7.55 .95
Traitanxiety×trimester 0.15 0.06 .01 −10.97 4.79 .02 −0.06 0.20 .79
Presentationofstressor(2ndvs.1st) −1.67 0.28 <.001 94.27 23.46 <.001 0.13 1.06 .90
Age −0.03 0.06 .63 −0.40 4.27 .92 0.22 0.13 .09
BMI −0.01 0.06 .84 0.61 4.36 .89 −0.01 0.13 .96
Constant 11.32 3.94 .004 −109.41 255.29 .67 −6.24 8.64 .47
Fig.2. Theassociationbetweentraitanxietyandcardiovascularreactivity(a–c)(significantinteraction)andrecovery(d–f).Thelinesintheplotsareconstructedbyconnecting thepointsdisplayingtheestimatedmarginalmeanofareactivity/recoverymeasure(adjustedforthecovariates)ineachpregnancytrimester.Theminimumandmaximum scoresfortraitanxietyinoursample(29and59,respectively)wereusedtomakeseparatelines.
