Fetal pulmonary and cerebral artery Doppler velocimetry in normal and high risk pregnancy

Fetal pulmonary and cerebral artery Doppler velocimetry in normal and high risk pregnancy

Tętniczy przepływ krwi w płucach i OUN płodu w ciąży o przebiegu prawidłowym i w ciąży wysokiego ryzyka

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, Mariusz Dubiel

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1 Division of Reproductive Endocrinology and Infertility, Department of Ob/Gyn & Women’s Health – Montefiore Medical Center Albert Einstein College of Medicine, New York, USA

2 Department of Obstetrics and Gynecology, Collegium Medicum, Nicolaus Copernicus University, Torun, Poland

3 Department of Obstetrics and Women Diseases, Poznań University School of Medical Sciences, Poznań, Poland

4 Department of Perinatology and Gynecology, Poznań University School of Medical Sciences, Poznań, Poland

5 Department of Obstetrics and Gynecology, Malmö University Hospital, Malmö, Sweden

Abstract

Studies on fetal lung/brain circulation by means of power Doppler technique have suggested a marked reduction in lung perfusion in high-risk pregnancies as a sign of circulation redistribution. The ratio between lung/brain perfusion might therefore give a new method to predict fetal circulation centralization.

Objective: The aim of the present study was to obtain fetal lung and cerebral artery ratio in normal and high-risk pregnancies.

Study design: Doppler samples from proximal right pulmonary artery blood velocities and middle cerebral artery (MCA) were recorded cross-sectionally in 228 normal singleton pregnancies at gestational age 22 to 40 weeks.

MCA / right pulmonary artery pulsatility index (PI) ratio was calculated. Doppler samples from proximal right pulmo- nary artery and MCA were also recorded in 89 high-risk singleton pregnancies and the results related to perinatal outcome.

Results: In the normal controls, right pulmonary artery PI remained stable until 30 weeks of gestation with slight increase thereafter until term. The MCA to right pulmonary artery PI ratio increased between 22 and 28 weeks of gestation with the rapid fall towards term. In the high-risk pregnancies group, right pulmonary artery PI showed no significant correlation to perinatal outcome, but signs of brain-sparing in the MCA were correlated to all adverse outcome parameters.

Conclusion: Velocimetry of the middle cerebral artery is better than velocimetry of right pulmonary artery in pre- dicting adverse outcome of pregnancy. The brain/lung PI ratio does not improve the prediction of adverse outcome of pregnancy.

Otrzymano: 18.08.2013

Zaakceptowano do druku: 30.10.2013 Address for correspondence:

Grzegorz H. Bręborowicz

Department of Perinatology and Gynecology, Poznań University School of Medical Sciences ul. Polna 33, 60 535 Poznań, Poland

tel./fax: +48 61 84 19 283 e-mail: gbrebor@wp.pl

Introduction

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Materials and methods

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blood velocities and middle cerebral artery were recorded in a cross-sectional study in 22 normal sinJleton SreJnancies at Jestational aJe 22 to  weeNs $ll SreJnancies Kad an uneventIul course oI SreJnancy, labour and delivery $ll Satients Jave tKeir inIormed consent and tKe study Srotocol Kas been aSSroved by tKe +osSital (tKics &ommittee Malmo-6weden *estational aJe Kad been establisKed in eacK SreJnancy by ultrasound e[amina- tion SerIormed in tKe ¿rst trimester oI SreJnancy

DoSSler samSles Irom tKe Sro[imal riJKt Sulmonary artery and middle cerebral artery were also recorded in  KiJK-risN sin- Jleton SreJnancies reIerred Ior antenatal blood Àow e[amination indicated by intra-uterine JrowtK retardation ,8*5 n= and SreJnancy induced KySertension 3,+ n= 7Ke de¿nition used as SreJnancy-induced KySertension was values oI blood Key words: pulmonary artery / middle cerebral artery / brain-sparing / fetus /

/ Doppler / pregnancy /

Streszczenie

Wstęp: Ocena przepływu krwi przy pomocy metod ddopplerowskich w krążeniu płucnym I mózgowym sugerowała istotny spadek perfuzji płuc w ciążach wysokiego ryzyka jako wykładnik zmienionej redystrybucji krwi w ustroju pło- du. Stworzyło to koncepcję z której wynika, że stosunek perfuzji krwi w płucach i mózgu może być nową metodą oceniającą centralizację krążenia.

Cel pracy: Celem badań było określenie współczynnika określającego stosunek przepływów krwi w płucach i mó- zgu w ciąży o przebiegu prawidłowym i w ciąży wysokiego ryzyka.

Materiał i metody: Przepływ krwi oceniano metodą dopplerowska w proksymalnej części prawej tętnicy płucnej oraz w tętnicy środkowej mózgu w dwóch grupach pacjentek: u 228 ciężarnych z ciążą pojedynczą o przebiegu prawidłowym między 22 a 40 tygodniem ciąży oraz u 89 ciężarnych z ciążą wysokiego ryzyka. W oparciu o uzy- skane wyniki obliczano stosunek wartości PI w naczyniach płucnych i mózgowych. Uzyskane wyniki odnoszono do stanu noworodka po porodzie.

Wyniki: W grupie kontrolnej wartości PI tętnicy płucnej są stabilne aż do 30. tygodnia ciąży z następowym nie- znacznym wzrostem aż do terminu porodu. Wartości stosunku PI w tętnicy środkowej mózgu do PI prawej tętnicy płucnej wzrastają między 22. a 28. tygodniem ciąży z następowym spadkiem do terminu porodu. W grupie ciąż wysokiego ryzyka, nie stwierdzono istotnej zależności między wartościami PI prawej tętnicy płucnej a stanem no- worodka po porodzie. W tej grupie ciąż wykładniki centralizacji krążenia wykazywały zależność w odniesieniu do parametrów charakteryzujących zły stan noworodka po porodzie.

Wnioski: Ocena przepływu krwi w tętnicy środkowej mózgu, w porównaniu z oceną przepływu w tętnicy płucnej, ma większą wartość predykcyjną w prognozowaniu stanu płodu. Analiza współczynnika – PI mózgu/PI płuc – nie poprawia tej oceny.

Słowa kluczowe: tĊtnica páucna / tĊtnica ĞrodNoZa my]gu / centrali]acMa NrąĪenia / / páyd / Doppler / ciąĪa /

Sressure 1 mm+J, an increase oI systolic blood Sressure oI  mm+J and diastolic blood Sressure oI 1 mm+J above tKe basic values ([aminations were reSeated in some cases, but results Irom tKe last e[amination beIore delivery were only cor- related to outcome oI SreJnancy Median Jestational aJe at tKe last e[amination was  weeNs ranJe 2- weeNs 7Ke median interval between tKe e[amination and labour was , days ranJe

- days 7Ke clinicians were only inIormed oI tKe umbilical 8$ and uterine artery 8t$ blood velocimetry, but not oI Ietal cerebral and Sulmonary blood Àow recordinJ, wKicK were Ser- Iormed at tKe same time as

$cuson ;3 and 6eTuoia ultrasound units 6iemens Medical

&o witK Sulsed, color and Sower DoSSler Sossibilities was used durinJ tKe study &onventional %-mode sonoJraSKy was used to visualize tKe Ietal cKest at it¶s transverse, cross-sectional Slane at tKe level oI tKe Sulmonary artery 7Ke main Sulmonary artery was located and tKen tKe riJKt Sulmonary artery Must beyond biIurca- tion oI tKe main Sulmonary artery ¹² 7Ke blood velocity wave- Iorm was obtained by SositioninJ tKe DoSSler samSle volume into Sro[imal Sart oI riJKt Sulmonary artery Must beyond biIurca- tion oI main Sulmonary artery 7Ke riJKt brancK was cKosen Ior tKe measurements as tKere is no diIIerence between waveIorms obtained Irom riJKt and leIt Sulmonary artery >12,1@ &Karac- teristic oI riJKt Sulmonary arterial blood velocity waveIorm is illustrated in )iJure 1

7Ke middle cerebral artery was visualized at tKe level oI circle oI :illis by tKe use oI color DoSSler 7Ke Sulsed DoSSler samSle volume was Slaced in tKe middle cerebral artery at near ⁰ anJles to tKe ultrasound beam and tKe blood velocity waveIorms were obtained and stored &are was taNen not to SusK on tKe Ietal Kead, wKile e[amininJ middle cerebral artery as tKat miJKt in- crease Sressure and, conseTuently reduce cerebral SerIusion >2@

)etal brain sSarinJ eIIect was de¿ned as 3,  mean - 26D

8mbilical artery velocimetry was recorded Irom a Iree Àoat- inJ looS oI tKe cord 7Ke blood velocity waveIorm was analysed Ior 3, and comSared witK normal reIerence values >1@ $ll DoS- Sler e[aminations were made durinJ absence oI Ietal breatKinJ movements

Uterine artery blood velocity was located bilaterally by color Àow maSSinJ in an obliTue scan, witK tKe samSle volume Slaced in tKe artery Must cranial to tKe aSSarent crossinJ oI tKe e[ternal iliac blood vessels 7Kree subseTuent blood velocity waveIorms Ior eacK vessel were analyzed Ior 3, accordinJ to *oslinJ et al, wKicK is an acNnowledJed measure oI downward vascular im- Sedance >1@ 7Ke mean oI botK uterine arteries 3, were calcu- lated, 3, e[ceedinJ 120 was deemed abnormal >1@ Middle ce- rebral artery over riJKt Sulmonary artery 3, ratio M&$53$ 3, ratio was calculated $ll e[aminations oI normal controls were SerIormed by one oSerator MD

,n tKe KiJK-risN SreJnancies, tKe DoSSler results were attrib- uted to Serinatal outcome, includinJ Jestational aJe at delivery, birtKweiJKt, $SJar score at  minute oI liIe, umbilical arterial and venous S+, tKe need Ior oSerative delivery Ior Ietal distress 2D)D, tKe needs Ior admission to neonatal intensive care unit 1,&U, arti¿cial ventilation and Serinatal mortality $ small-Ior- Jestational-aJe 6*$ inIant was de¿ned as birtKweiJKt below tKe tentK Sercentile Ior corresSondinJ Jestational aJe >1@.

7Ke comSuter soItware 6tatistica version 0 6tat6oIt, ,nc was used Ior statistical analysis 1ormal reIerence cKarts

Ior M&$ 3,, 53$ 3, and M&$53$ ratios were constructed by Solynomial reJression analysis by tKe Tuadratic metKod JivinJ mean, 2 and  Sercentiles cut-oII¶s )isKer¶s e[act test was used to determine numeric diIIerences between JrouSs witK normal and abnormal blood Àow velocity 7Ke Mann-:Kitney non-Sarametric test was used to comSare continuinJ variables in tKe two JrouSs

Results

5iJKt Sulmonary artery 3, in tKe normal controls remained stable until 0 weeNs oI Jestation witK sliJKt increase tKereaIter until term )iJure 2 ,n tKe course oI normal SreJnancy tKe mid- dle cerebral artery curve is Tuite similar to tKe curve Sresented by Mari and Deter >1@ )iJure 

7Ke middle cerebral artery to riJKt Sulmonary artery M&$

53$ 3, ratio increased between 22 and 2 weeNs oI Jestation witK tKe raSid Iall towards term )iJure 

,n tKe KiJK-risN SreJnancy JrouS, tKe median Jestational aJe at delivery was  weeNs ranJe 2-1 weeNs

Figure 1. Typical spectrum of blood velocity waveforms of proximal branch right fetal pulmonary artery in normal pregnancy.

Figure 2. Mean and 95% CI of right proximal pulmonary artery pulsatility index (PI) in in the second half of pregnancy.

7Ke mean birtKweiJKt oI inIants was 10“ J and 

1 newborns were small-Ior-Jestational aJe at birtK 7Ke needs Ior 2D)D were in 2 cases and  neonates were admitted to 1,&U, wKere  oI tKem were ventilated $SJar score  at  min was Iound in 1 $rterial S+ 1 and venous S+ 20 was Iound in 2 and 2 cases, resSectively 7Kere were seven Serinatal deatKs ± all aIter delivery due to severe ,U*5 and Srematurity 2 weeNs oI Jestational aJe ± 10J 2 weeNs oI Jestational aJe ± 20J 2 weeNs oI Jestational aJe ± 0J 2 weeNs oI Jestational aJe ± 0J 2 weeNs oI Jestational aJe ± 0J 2 weeNs ± 0J 2 weeNs ± 0J

,n tKe KiJK-risN SreJnancies, 0  Kad a normal Sro[i- mal riJKt Sulmonary artery 3, 7Kere were no siJni¿cant diI- Ierences in Serinatal outcome between cases witK normal and abnormal Sulmonary artery 3, 6iJns oI brain-sSarinJ in M&$

were Iound in   Ietuses and was KiJKly correlated in all adverse outcome Sarameters e[ceSt 6*$ newborns 7Ke JrouS oI KiJK-risN SreJnancies consists oI 1  Ietuses witK abnormal M&$53$ 3, ratio 6iJni¿cance oI diIIerences was Iound in all Sarameters studied e[ceSt 6*$ newborns, ventilation in 1,&U and 2D)D

Discussion

7Ke results demonstrate a cKanJe in Ietal 53$ and M&$

blood Àow witK advancinJ Jestation in second KalI oI SreJnancy

M&$  53$ 3, ratio was also demonstrated Irom 22^nd to 0^th week oI SreJnancy 7he analysis oI blood Àow in hiJh-risk SreJnancies showed that riJht Sulmonary artery 3, seems to be a Soor marker in SredictinJ Serinatal outcome 7here were no diIIerences in Serinatal outcome between Ietus with normal and abnormal riJht Sulmonary artery 3,  +owever, an abnormal M&$53$ ratio was related to adverse outcome, but this was mainly due to chanJes in M&$ 3, 7his study revealed that middle cerebral artery 3, better corresSond with chanJes in Ietal redistribution and adverse outcome oI SreJnancy than does the 53$

$lthouJh 1 Ietuses maniIested abnormal values oI M&$

53$-ratio, M&$-3, seemed to be a better Sredictor oI adverse Serinatal outcome than was M&$53$-3,-ratio )urthermore, the JrouS oI Ietuses with abnormal riJht Sulmonary artery 3, consisted oI 0 Ietuses ± only , oI the hiJh-risk SreJnancy JrouS 7his suJJests that riJht Sulmonary artery blood Àow miJht chanJe durinJ Ietal circulation redistribution, but this reaction is Srobably not constant durinJ this Seriod and miJht occur in the beJinninJ oI this Srocess 5esults by -ensen et al suJJests that lunJ SerIusion miJht be imSroved aIter reSeated hySo[ic insult

>1@

5asanen et aldescribed decrease oI Sulsatility inde[ 3, oI Sro[imal Sulmonary artery with advanced Jestational aJe un- til ^th week oI Jestation >12@ 7he conÀictinJ results between the Sresent study on normal controls and the Srevious study by 5asanen et al may be e[Slained by the diIIerence in number oI investiJated Satients, as their SoSulation JrouS consisted oI only 100 Satients >12@

5en-,nJ /ianJ et al in their study analyzed diIIerences be- tween multiJate sSectral DoSSler scanninJ with the Sower DoS- Sler imaJinJ oStion and traditional sSectral DoSSler ultrasonoJ- raShy with color Àow maSSinJ >1@ 7heir study revealed a siJ- ni¿cant diIIerence between main Sulmonary artery and SeriSheral blood Àow 7his may e[Slain Srevious results in studies on Ietal brain lunJ circulation usinJ diJital analysis oI Sower DoSSler siJnal intensity, where a marked reduction in lunJ SerIusion was seen in hiJh-risk SreJnancies 7he 3ower DoSSler miJht thus re- Àect tissue SerIusion, while sSectral DoSSler reÀects vascular im- Sedance in the vessel 7his miJht e[Slain the conÀictinJ results oI Sresent study and a Srevious results >2@

6tudies on animal and the human Ietus have shown that Ietal cardiac outSut is redistributed durinJ hySo[ia, IavorinJ vital or- Jans such as the brain, heart and adrenals >@ %y reducinJ blood Àow to less imSortant orJans the need Ior o[yJen and nutrients is reduced and the Ietus is able to maintain o[yJen and blood

Figure 3. Mean and 95%CI of middle cerebral artery pulsatility index (PI) in in the second half of pregnancy.

Figure 4. Mean and 95%CI of middle cerebral artery pulsatility index (PI) over right pulmonary artery PI ratio (MCA/RPA) in the second half of pregnancy.

Jas status within normal limits %lood S+ may remain stable due this Shenomenon 7he centralization oI Ietal circulation results in reduced Àow in the kidneys and Jut, which may cause oliJohy- dramnios and necrotizinJ enterocolitis in the newborn &ircula- tion redistribution miJht also lead to asymmetrical Jrowth oI the Ietal body

6tudies Iocused on Ietal suSerior mesenteric and heSatic arteries revealed that siJns oI redistribution in the mesenteric artery miJht be a late siJn oI Ietal comSromise >@ The vascular sSarinJ oI the Ietal liver can be seen at an early staJe oI Ietal comSromise This sSarinJ eIIect seems to disaSSear in severely comSromised Ietuses¹ The velocimetry oI sSlenic artery and 3, values in the course oI hiJh-risk remained within normal values

>20@ $rudini et al revealed in their studies on the renal artery, that blood Àow in this vessel is decreased durinJ lonJ term Ietal hySo[ia >21@ 6tiJter et al studied inÀuence oI chanJes in Ietal renal artery on Ietal condition in the Jrowth-restricted Sreterm Ietus >22@ They revealed that redistribution is reÀected by chanJes oI Seak-systolic velocities rather than by chanJes in Sulsatility inde[ 6Sectrum oI both the renal and Sulmonary blood velocity has low Àow velocities in diastole &hanJes durinJ reduction miJht be diI¿cult to interSret by DoSSler, esSecially in the severely aIIected Ietus where reversal oI venous Àow durinJ atrial contraction miJht be suSerimSosed in the diastolic Àow Sattern

The evaluation oI Slacental and Ietal liver, adrenals, kidney, and lunJ blood Àow by Sower-DoSSler ultrasound has imSroved our knowledJe on Ietal circulation ,n normal SreJnancy, the Sower-DoSSler comSuter analyzed siJnal intensity seems to in- crease in all orJans with Jestation uS to  weeks, aIter which a decline in intensity is noted >11@ The chanJe in the other orJans miJht be e[Slained by centralization oI Ietal circulation second- ary to IailinJ Slacental Iunction ,n hiJh-risk SreJnancies the de- crease in orJan blood Àow is even more Sronounced, suJJestinJ Iurther develoSment oI Ietal circulatory centralization >@ )etal cerebral Sower-DoSSler siJnal intensity and the brainlunJ-ratio increases towards the end oI normal SreJnancy The data Irom the Srevious study shows that Sower DoSSler reSresents centraliza- tion oI Ietal circulation durinJ chronic hySo[ia by evaluation oI Ietal orJan tissue SerIusion, rather than vascular imSedance

Conclusion

The main conclusion oI this study is that velocimetry oI the middle cerebral artery is better than velocimetry oI riJht Sulmo- nary artery in SredictinJ outcome in hiJh-risk SreJnancy M&$

53$ 3, ratio was oI limited value in SredictinJ redistribution oI Ietal circulation in hiJh-risk SreJnancies

Acknowledgements:

The medical faculty, University of Lund, research funds at the University hospital in Malmö and Region Skåne supported the study.

Oświadczenie autorów

1. Andrzej Bręborowicz – autor koncepcji i założeń pracy, zebranie materiału, przygotowanie manuskryptu, analiza wyników, zebranie piśmiennictwa.

2. Mariusz Dubiel – zebranie materiału, analiza statystyczna wyników, przygotowanie manuskryptu.

3. Marek Pietryga – współautor tekstu pracy, współautor protokołu i aktualiza- cja literatury.

4. Grzegorz H. Bręborowicz – autor założeń pracy, analizy i interpretacji wyników, przygotowanie, korekta i akceptacja ostatecznego kształtu pracy – autor zgłaszający i odpowiedzialny za manuskrypt.

5. Saemundur Gudmundsson – udział w przygotowaniu koncepcji badań, korekta oraz ostateczne zatwierdzenie manuskryptu.

Źródło finansowania:

Praca nie była finansowana przez żadną instytucję naukowo-badawczą, stowarzyszenie ani inny podmiot, autorzy nie otrzymali żadnego grantu.

Konflikt interesów:

Autorzy nie zgłaszają konfliktu interesów oraz nie otrzymali żadnego wynagrodzenia związanego z powstawaniem pracy.

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