Rev. Assoc. Med. Bras. vol.55 número2

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* Correspondência: Dr. Adolfo Liao Clínica Obstétrica, 1 0 º andar - Instituto Central Hospital das Clínicas Av. Dr. Enéas de Carvalho Aguiar, 2 5 5

São Paulo, SP CEP 0 5 4 0 3 0 0 0

SUM M ARY

OBJECTI VES. Evaluate the feasibility of transvaginal uterine artery Doppler examination in the first and second trimesters of pregnancy, establish reference ranges in a Brazilian population and examine the correlation betw een these Doppler findings.

METH ODS. Longitudinal prospective study at the antenatal clinic of a tertiary teaching hospital. Uterine artery Doppler examinations w ere carried out transvaginally at 1 1 to 1 4 w eeks and 2 0 to 2 5 w eeks of gestation. Uterine artery mean pulsatility index (PI) distributions w ere determined and the presence or absence of an early diastolic notch w as also noted. The degree of correlation betw een first and second trimester Doppler findings w as examined.

RESU LTS. Three hundred and forty four w omen w ith live singleton pregnancies and normal outcome w ere first examined at a mean gestation of 1 2 .7 w eeks. The values corresponding to the 5 0 th and 9 5 th centiles of mean PI w ere 1 .6 9 and 2 .4 8 . Bilateral notches w ere observed in 4 4 % of cases and unilateral notches w ere present in 1 9 % . Second trimester Doppler examinations w ere carried out at a mean gestation of 2 3 .2 w eeks and corresponding figures for the 5 0 th and 9 5 th centiles w ere 1 .0 3 and 1 .5 7 . Bilateral notches w ere noted in 4 .4 % of the cases. First trimester impedance indices w ere significantly higher and positively correlated to second trimester findings (r = 0 .4 2 , p< 0 .0 0 0 1 ).

CON CLU SI ON. Uterine artery Doppler examination can be successfully performed transvaginally and incorporated into scans that are routinely offered to w omen during their antenatal care in the first and second trimesters. Doppler indices obtained during the first trimester are significantly higher than those of the second trimester and findings at both scans are significantly correlated.

KEYWORDS: Uterine artery. Ultrasonography. Colour oppler. Pregnancy.

CORRELATION

BETWEEN

THE

DOPPLER

VELOCIMETRY

FINDINGS

OF

THE

UTERINE

ARTERIES

DURING

THE

FIRST

AND

SECOND

TRIMESTERS

OF

PREGNANCY

ADOLFO WEN JAW LI AO*1_{, JU LI O TOYAM A}2_{, VERBÊN I A COSTA}2_{, CARLA RAM OS}2 , _{MARI A BRI ZOT}3 _{, MARCELO ZU GAI B}4

Trabalho realizado na Clínica Obstétrica do Hospital das Clínicas, Faculdade de M edicina, Universidade de São Paulo, S.Paulo, SP

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Examination of uterine artery blood flow can be achieved by Doppler ultrasound. The increased impedance to flow in these vessels during the second trimester of pregnancy has been shown to be associated with increased risk of pregnancy complications such as pre-eclampsia and intrauterine fetal growth restriction1_.

Both complications are major causes of maternal and perinatal mortality. In the city of São Paulo, hypertensive disorders account for about one fourth of maternal deaths2_.

Several treatm ents have been proposed to reduce the incidence of such complications during pregnancy. How ever randomized studies evaluating interventions, such as low dose daily aspirin for w omen identified as high-risk, based on second trim ester Doppler findings, have not show n a significant reduction in the rate of these complications3_.

One m ay hypothesize that if such interventions w ere im plem ented at an earlier gestational age, before the trophoblastic invasion process is complete, they might have been more effective.

This study evaluated the feasibility of transvaginal uterine artery Doppler examination in the first and second trimesters of pregnancy, to determine normal reference ranges and findings in a Brazilian population and assess the degree of correlation between first and second trimester findings. Based on these reference ranges, methodologically appropriate uterine artery Doppler screening studies could then be performed in our population.

M

This w as a longitudinal prospective study conducted at the Department of Obstetrics, Hospital das Clínicas, São Paulo

1 . M édico assistente responsável pelo setor de medicina fetal da Clínica Obstétrica do Hospital das Clínicas, Faculdade de M edicina, Universidade de São Paulo, SP 2 . Pós-graduando da Clínica Obstétrica do Hospital das Clínicas, Faculdade de M edicina, Universidade de São Paulo, SP

3 . M édica assistente responsável pelo setor de ultrassonografia da Clínica Obstétrica do Hospital das Clínicas, Faculdade de M edicina, Universidade de São Paulo, SP

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University School of M edicine. The study w as approved by the Hospital ethics committee.

Patients routinely attending the antenatal clinic w ere informed about the study during their first trimester nuchal translucency scan and those w ho agreed to participate in the study gave informed consent. During that scan the number of live fetuses w as determined, gestational age w as confirmed by fetal crow n-rum p length m easurem ent, fetal nuchal translucency thickness w as measured and major fetal structural abnormalities w ere sought. Only live singleton pregnancies w ere included in the study.

U terine artery Doppler exam ination w as perform ed transvaginally on patients in the lithotomy position, w ith an empty bladder. The probe w as inserted into the vagina and placed in the lateral fornix w here color Doppler identified the uterine artery vessels at the level of the internal cervical os. Pulsed Doppler w aveforms w ere obtained and pulsatility index (PI), w as calculated for both uterine arteries. M ean (right + left/ 2 ) indices w ere calculated for each patient and the presence or absence of an early diastolic notch w as also noted4_.

As part of the routine antenatal care, an anomaly scan w as offered to all patients at 2 0 - 2 4 w eeks gestation w hen the transvaginal uterine artery Doppler examination w as repeated as done in the first trimester scan.

The results of the Doppler examinations w ere not disclosed to the obstetricians caring for these patients and no intervention w as implemented on the basis of the Doppler results. Women w ith clinical or obstetrical com plications, those w ith an abnormal fetus or that presented abnormal fetal grow th, w ere excluded from the analysis.

Statistical analysis

M ean uterine artery Doppler indices (right + left/2 ) w ere calculated for each examination and the distribution in the first and second trimesters w as described. Values obtained in the first trimester w ere compared to those of the second trimester using the paired t-test. Spearman´ s correlation test and simple linear regression w ere used to examine the degree of correlation betw een these values. The frequencies of unilateral and bilateral notches w ere calculated for each trimester and compared using the Chi-square or Fisher’s exact test, w hen appropriate.

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During the study, 6 4 5 patients w ith live singleton pregnancies and know n pregnancy outcome w ere recruited and agreed to participate. They w ere first examined at a mean gestation of 1 2 .7 w eeks (SD: 0 .8 , range: 1 1 to 1 3 w eeks 6 days) how ever, transvaginal uterine artery Doppler w aveforms could not be obtained in 6 (0 .9 % ) cases. These w omen w ere re-examined at a mean gestation of 2 3 .2 w eeks (SD: 0 .8 , range: 2 0 to 2 4 w eeks 6 days), and the Doppler scan w as unsuccessful in 1 1 (1 .7 % ) cases during the second trimester.

Uterine artery Doppler index reference ranges and findings w ere calculated based on 3 4 4 pregnancies w ith a normal pregnancy outcome. Cases w ith maternal hypertension (4 7 ), diabetes (1 2 ), thrombophilia (1 1 ), cardiac (2 0 ), auto immune (1 9 ), thyroid (1 8 ), respiratory (1 5 ) and chronic renal diseases (8 ) w ere excluded. Pregnancies w ith fetal structural

abnormalities (1 3 ), intrauterine fetal or unexplained neonatal death (4 ), pre-eclampsia (2 5 ), preterm delivery (8 7 ) and birthw eight below the 1 0th _{centile (1 1 2 ) or above the 9 0}th _centile

(2 1 ) w ere also excluded.

Values corresponding to various mean uterine artery Doppler pulsatility index centiles are show n in Table 1 . First trimester uterine artery Doppler indices w ere significantly higher compared to those of the second trimester (mean PI difference = 0 .6 6 + 0 .4 2 , paired t test p< 0 .0 0 1 ) and these

measurements w ere significantly and positively correlated (r =

0 .4 2 [ 9 5 % confidence interval CI= 0 .3 3 to 0 .5 0 ] , p< 0 .0 0 1 ; Figure 1 ).

Bilateral notches w ere observed in 1 5 1 (4 3 .9 % ) cases during the first trimester and in 1 5 (4 .4 % ) evaluations during the second trimester. The corresponding figures for unilateral notches w ere 6 6 (1 9 .2 % ) and 3 1 (9 .0 % ). Both findings w ere significantly less common in the second trimester (Chi-square test p< 0 .0 0 1 ). Among the 1 5 1 patients w ho had bilateral notches in the first evaluation, 1 3 (8 .6 % ) had persistence of bilateral notches in the second trimester scan, 2 5 (1 6 .6 % ) presented unilateral notches and the rem aining (7 4 .8 % ) show ed no notches. Table 2 summarizes uterine artery notch findings in both scans.

D

This prospective study has show n that Doppler examination of the uterine artery can be successfully achieved transvaginally and included to scans that are offered to w omen during their routine antenatal care, such as the first trim ester nuchal translucency and second trimester anomaly scans5_{. Failure to}

obtain an appropriate Doppler sonogram w as observed in less than 2 % of our study population.

H istorically, uterine arteries have been exam ined transabdominally, in the second trimester of pregnancy, at the level of their “ cross over” w ith the external iliac artery 4_{. How ever}

this technique is not applicable during the first trimester and different techniques have been employed 6 -9_{. The transvaginal}

route w as chosen for this study because it enables easy identification of the uterine arteries at the level of the internal cervical os, during the entire pregnancy. It therefore allow s

Table 1 - Normal values for mean uterine artery Doppler pulsatility indices at 1 1 to 1 3 weeks 6 days and 2 0 to 2 4 weeks 6 days in

3 4 4 normal pregnancies

percentile M ean Pulsatility Index

1 1 - 1 3 weeks 6 days 2 0 - 2 4 weeks 6 days

5 1.10 0.72

25 1.37 0.88

50 1.69 1.03

70 2.00 1.19

75 2.07 1.24

80 2.11 1.31

85 2.23 1.35

90 2.34 1.44

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CORRELATIONBETWEENTH EDOPPLERVELOCIM ETRYFINDINGSOFTH EU TERIN EARTERIESDURIN GTH EFIRSTANDSECONDTRIM ESTEROFPREGN AN CY

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more than half the cases examined. How ever, only less than 1 0 % of them show ed persistence of bilateral notches w hen re-examined in the second trimester w hile 7 0 % did not show any notches. Apparently an absence of notches in the first trimester is highly predictive of the same finding in the second trimester. Similar results w ere observed in tw o other studies conducted betw een 1 1 and 1 4 w eeks of gestation. M artin et al performed transabdominal studies and recorded bilateral notches in 5 5 % of the cases examined and 2 .3 5 as the 9 5th _{centile for mean PI}

(9 ). Góm ez et al applied the transvaginal technique and described bilateral notches in 4 6 % of the cases and mean PI 9 5th _{centile figures betw een 2 .2 4 and 2 .7 0} 1 2_.

Our second trimester findings w ere very similar to those reported by Papageorghiou et al1 _{(mean PI 5 0}th _{centile= 1 .0 5}

vs 1 .0 3 ; mean PI 9 5th _{centile= 1 .6 3 vs 1 .5 7 ). In fact both}

studies w ere carried out transvaginally betw een 2 0 -2 4 w eeks and w ith the same technique. The similarities in the results highlight the im portance of strict standardization of the technique to promote results reproduciblity.

On the other hand, bilateral notches w ere found in around 8 -9 % of the cases examined by Papageorghiou1 _{and only 4 -5 %}

of our cases. This difference is most likely explained because notch assessment is based on subjective criteria. Indeed, the pulsatility index describes the shape of the velocity w aveform much better, as it includes the area below the curve in the formula. Likew ise and for this reason, the PI index indirectly informs about presence or absence of a protodiastolic notch and is the preferred Doppler impedance index in most recent uterine artery Doppler studies.

Several studies have now show n that increased impedance to flow , in the second trimester of pregnancy is associated w ith an increased risk of pregnancy complications, such as pre-eclampsia and fetal grow th restriction1 3_{. How ever randomized}

studies testing prophylactic interventions, such as low -dose aspirin to reduce such complications in patients identified as high-risk, based on mid-second trimester uterine artery Doppler findings, have not proven effective3 ,1 4_{. Perhaps these}

interventions are being tested at a gestational age too far ahead in the trophoblastic invasion process.

Therefore, one may hypothesize that if such interventions w ere implemented at an earlier gestational age, they might have been m ore effective in reducing the rate of pregnancy complications. How ever, our data suggest that if prophylactic interventions w ere to be tested in future studies, based on first trimester uterine artery Doppler findings, such studies w ould have to recruit a large number of w omen screened and the sample size w ould have to be much larger than current second trimester randomized prophylactic studies to show significant reduction of pregnancy complications.

I nterest conflict: none

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CORRELAÇÃO EN TRE OS ACH ADOS DOPPPLERVELOCI M ÉTRI COS DAS ARTÉRI AS U TERI N AS N O PRI M EI RO E SEGU N DO TRI M ESTRES DA GESTAÇÃO

OB JETIVO. Avaliar a aplicabilidade de realizar exam es dopplervelocimétricos endovaginais das artérias uterinas no primeiro e segundo trimestres da gestação, definir valores

Figure 1 - First and second trimester uterine artery Doppler indices scatter plots in 3 4 4 normal pregnancies. PI : pulsatility index

Table 2 - Uterine artery notch findings at 1 1 to 1 3 weeks 6 days and 2 0 to 2 4 weeks 6 days in 3 4 4 normal pregnancies

Uterine notch at Uterine notch at 2 0 -2 4 weeks

1 1 -1 3 weeks no notch unilateral bilateral

(n= 298) (n= 31) (n= 15)

no notch (n= 127) 125 1 1

unilateral (n= 66) 60 5 1

bilateral (n= 151) 113 25 13

direct comparison of results obtained at different stages of pregnancy by this standardized technique.

M oreover the transvaginal route conveys a better assessment of fetal anatomy in the first trimester as w ell as a reliable method for evaluation of the uterine cervix1 0_{. Other}

advantages of this technique include the possibility of obtaining clear w aveforms and a good reproducibility due to the proximity of the transducer to the uterine vessel1 1_.

Our data also show that uterine artery Doppler impedance indices during the first trimester of pregnancy are significantly higher than in the second trimester and that both measurements are significantly and positively correlated. The association betw een uterine artery Doppler findings in the first and second trimesters has also been described in a smaller study involving 5 5 pregnancies6_{. Our results show ed that the group of w omen}

w ith Doppler measurements above the 8 5th _{centile during the}

first trimester comprises approximately half of the cases w ith indices above the 9 5th _{centile in the second trimester.}

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normais na população brasileira e examinar a correlação entre esses achados.

MÉTODOS. Estudo prospectivo longitudinal conduzido em

H osp it al U n iversit ário Terciário. Os exam es dopplervelocim étricos das artérias uterinas foram realizados pela via endovaginal, entre 1 1 a 1 4 sem anas e 2 0 a 2 5 sem anas de gestação. Em cada período gestacional estuda-do, a distribuição dos valores dos índices de pulsatilidade (IP) m édio foi descrita e diferentes percentis calculados. Tam bém foi anotada a presença ou ausência de incisura uterina protodiastólica. Os achados dopplervelocim étricos observados no prim eiro trim estre foram correlacionados com os achados do segundo trim estre.

RESU LTADOS. Trezen t os e q u aren t a e q u at ro m u lh eres com gest ações ú n icas de desfech o n orm al foram exam in a-das in icialm en t e em idade gest acion al m édia de 1 2 , 7 sem an as. Os valores correspon den t es aos percen t is 5 0 e 9 5 para o IP m édio foram de 1 , 6 9 e 2 , 4 8 , respect ivam en t e. In cisu ra bilat eral foi observada em 4 4 % dos casos e u n ila-t eral em 1 9 % . N a segu n da avaliação, realizada em idade gest acion al m édia de 2 3 , 2 sem an as, os valores correspon -den t es aos percen t is 5 0 e 9 5 do IP m édio foram de 1 , 0 3 e 1 , 5 7 , respect ivam en t e. In cisu ra bilat eral foi observada em 4 , 4 % d os casos n a segu n d a avaliação. Os ín d ices dopplervelocim ét ricos do prim eiro exam e se correlacion a-ram de form a sign ificat iva e posit iva com os valores do segu n do t rim est re (r= 0 , 4 2 ; p< 0 , 0 0 0 1 ).

CONCLUSÃO. O estudo dopplervelocimétrico endovaginal das artérias uterinas pode ser realizado de forma satisfatória e incorporado nos exames ultrassonográficos oferecidos como parte da rotina de acompanhamento pré-natal no primeiro e segundo trimestres da gestação. Índices dopplervelocimétricos uterinos médios observados entre 1 1 e 1 4 semanas são significativamente maiores do que entre 2 0 e 2 5 semanas, e esses valores se correlacionam de forma positiva e significativa.

[ Rev Assoc M ed Bras 2 0 0 9 ; 5 5 (2 ): 1 9 7 -2 0 0 ]

UN ITERM OS: Artéria uterina. Ultrassonografia. Doppler colorido. Gravidez.

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1 . Papageorghiou AT, Yu CK, Bindra R, Pandis G, Nicolaides KH. M ulticenter screening for pre-eclam psia and fetal grow th restriction by transvaginal uterine artery Doppler at 2 3 w eeks of gestation. Ultrasound Obstet Gynecol 2 0 0 1 ;1 8 (5 ):4 4 1 -9 .

2 . Vega CE, Kahhale S, Zugaib M . M aternal m ortality due to arterial hypertension in Sao Paulo City (1 9 9 5 -1 9 9 9 ). Clinics 2 0 0 7 ;6 2 (6 ):6 7 9 -8 4 . 3 . Yu CK, Papageorghiou AT, Parra M , Palm a Dias R, N icolaides KH . Random ized controlled trial using low -dose aspirin in the prevention of pre-eclam psia in w om en w ith abnorm al uterine artery Doppler at 2 3 w eeks gestation. Ultrasound Obstet Gynecol 2 0 0 3 ;2 2 (3 ):2 3 3 -9 .

4 . Bew ley S, Cam pbell S, Cooper D. Uteroplacental Doppler flow velocity w aveform s in the second trim ester. A com plex circulation. Br J Obstet Gynaecol 1 9 8 9 ;9 6 (9 ):1 0 4 0 -6 .

5 . Carvalho M H, Brizot M L, Lopes LM , Chiba CH, M iyadahira S, Zugaib M . Detection of fetal structural abnorm alities at the 1 1 -1 4 w eek ultrasound scan. Prenat Diagn. 2 0 0 2 ;2 2 (1 ):1 -4 .

6 . Kam inopetros P, Higueras M T, Nicolaides KH. Doppler study of uterine artery blood flow : com parison of findings in the first and second trim esters of pregnancy. Fetal Diagn Ther. 1 9 9 1 ;6 (1 -2 ):5 8 -6 4 .

7. Van den Elzen HJ, Cohen-Overbeek TE, Grobbee DE, Quartero RW, Wladimiroff JW. Early uterine artery Doppler velocimetry and the outcome of pregnancy in women aged 35 years and older. Ultrasound Obstet Gynecol. 1995;5(5):328-33. 8 . Harrington K, Goldfrad C, Carpenter RG, Cam pbell S. Transvaginal uterine and um bilical artery Doppler exam ination of 1 2 -1 6 w eeks and the subsequent developm ent of pre-eclam psia and intrauterine grow th retardation. Ultrasound Obstet Gynecol. 1 9 9 7 ;9 (2 ):9 4 -1 0 0 .

9 . M artin AM , Bindra R, Curcio P, Cicero S, Nicolaides KH. Screening for pre-eclam psia and fetal grow th restriction by uterine artery Doppler at 1 1 -1 4 w eeks of gestation. Ultrasound Obstet Gynecol. 2 0 0 1 ;1 8 (6 ):5 8 3 -6 . 1 0 . Carvalho M H, Bittar RE, Brizot M L, M aganha PP, Borges da Fonseca ES,

Zugaib M . Cervical length at 1 1 -1 4 w eeks and 2 2 -2 4 w eeks gestation evaluated by transvaginal sonography, and gestational age at delivery. Ultrasound Obstet Gynecol. 2 0 0 3 ;2 1 (2 ):1 3 5 -9 .

1 1 . Papageorghiou AT, To M S, Yu CK, N icolaides KH . Repeatability of m easurem ent of uterine artery pulsatility index using transvaginal color Doppler. Ultrasound Obstet Gynecol. 2 0 0 1 ;1 8 (5 ):4 5 6 -9 .

1 2 . Gom ez O, Figueras F, Fernandez S, Bennasar M , M artinez JM , Puerto B, et al. Reference ranges for uterine artery m ean pulsatility index at 1 1 -4 1 w eeks of gestation. Ultrasound Obstet Gynecol. 2 0 0 8 .

1 3 . Papageorghiou AT, Leslie K. Uterine artery Doppler in the prediction of adverse pregnancy outcome. Curr Opin Obstet Gynecol. 2 0 0 7 ;1 9 (2 ):1 0 3 -9 . 1 4 . Subtil D, Goeusse P, Puech F, Lequien P, Biausque S, Breart G, et al. Aspirin

(1 0 0 m g) used for prevention of pre-eclam psia in nulliparous w om en: the Essai Regional Aspirine M ere-Enfant study (Part 1 ). Br J Obstet Gynecol. 2 0 0 3 ;1 1 0 (5 ):4 7 5 -8 4 .