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ORIGINAL ARTICLE
Year : 2022  |  Volume : 25  |  Issue : 4  |  Page : 406-414

Predictive value of doppler cerebroplacental ratio for adverse perinatal outcomes in postdate pregnancies in Northwestern Nigeria


1 Department of Radiology, Bayero University, Kano, Nigeria
2 Department of Obstetrics and Gynaecology, Federal Medical Centre, Katsina, Nigeria
3 Department of Obstetrics and Gynaecology, Bayero University, Kano, Nigeria

Date of Submission11-Jan-2021
Date of Acceptance25-Jan-2022
Date of Web Publication19-Apr-2022

Correspondence Address:
Dr. A Ismail
Department of Radiology, Bayero University Kano, P.M.B. 3011
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_14_21

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   Abstract 


Background: Postdate pregnancy is a very common obstetric condition, increasing the risk of perinatal morbidity and mortality from uteroplacental insufficiency. Aim: To determine the predictive values of Doppler cerebroplacental ratio (CPR), that is, the ratio between middle cerebral artery (MCA) and UA pulsatility indices (UA PI), and other potential velocimetric predictors of adverse perinatal outcomes in women with postdated pregnancies. Patients and Methods: A prospective cohort study was conducted on consenting 212 low-risk pregnant women beyond 40 weeks' gestational age. The pulsatility indices of MCA, UA, and CPR as well as non-stress tests (NST) and amniotic fluid index (AFI) were measured and recorded. The women were divided into two groups based on the presence or absence of adverse perinatal outcome defined as: meconium stained liquor, meconium aspiration syndrome, perinatal asphyxia, cesarean section for suspected fetal distress, and perinatal death. Results: Of the 200 women whose data were available for analysis, 40 (20%) of them had adverse perinatal outcome and 160 (80%) had normal perinatal outcome. The CPR showed statistically significant difference in predicting adverse perinatal outcome (P < 0.001). CPR had a better predictive value than UA-PI and outperformed MCA-PI and NST for adverse perinatal outcomes. The sensitivity, specificity, negative predictive value (NPV), and accuracy of prediction of adverse perinatal outcomes by CPR were 90%, 81.25%, 97.01%, and 83%, respectively. Conclusion: The Doppler CPR shows the highest diagnostic accuracy in prediction of adverse perinatal outcome in pregnant women after 40 weeks' gestation than UA PI and velocimetric indices when used as stand-alone test.

Keywords: Cerebroplacental ratio, perinatal outcome, postdate pregnancy, Nigeria


How to cite this article:
Ismail A, Ibrahim A L, Rabiu A, Muhammad Z, Garba I. Predictive value of doppler cerebroplacental ratio for adverse perinatal outcomes in postdate pregnancies in Northwestern Nigeria. Niger J Clin Pract 2022;25:406-14

How to cite this URL:
Ismail A, Ibrahim A L, Rabiu A, Muhammad Z, Garba I. Predictive value of doppler cerebroplacental ratio for adverse perinatal outcomes in postdate pregnancies in Northwestern Nigeria. Niger J Clin Pract [serial online] 2022 [cited 2022 May 18];25:406-14. Available from: https://www.njcponline.com/text.asp?2022/25/4/406/343449




   Introduction Top


Postdate pregnancy is defined by the World Health Organization (WHO) as pregnancy with a gestational length of 42 completed weeks or 294 days or more from the first day of the last normal menstrual period or 14 days beyond the estimated day of delivery by obstetric routine ultrasound.[1] The current definition and management of postdate pregnancy have been challenged in some studies as evidences demonstrated that the incidence of complications associated with prolonged pregnancy also increases prior to 42 weeks of gestation.[2],[3]

The incidence of postdate pregnancy varies, ranging from 3% to 14% and had a recurrence rate of 50%.[4],[5],[6],[7] A study conducted at Aminu Kano Teaching Hospital in Kano, found an incidence of 13.1%,[8] while, in Maiduguri and Port Harcourt it accounted for 13%[9] of all deliveries.

Perinatal morbidity and mortality risks are greater than it was originally thought.[10] Furthermore, maternal risks resulting from continuing pregnancy beyond 41 weeks are not negligible. Though medical advances in neonatal and maternal care have decreased perinatal mortality rate, studies of postdate pregnancy have shown an increased risk for both infant and maternal mortality compared to normal pregnancies.[11],[12] The perinatal mortality rate at 40 weeks is about 2–3/1000 deliveries, doubling at 42 weeks, increasing to fourfold at 43 weeks, and then fivefold to sixfold at 44 weeks.[11],[12],[13]

These adverse fetal outcomes have been associated with decreased uteroplacental function resulting in oligohydramnious, intrauterine growth restriction, passage of meconium, intrapartum asphyxia, and potentially stillbirth.[3] In other cases, continued growth of the fetus leads to macrosomia, increasing the risks of prolonged labor, cephalopelvic disproportion, and shoulder dystocia with resultant risks of orthopedic or neurologic injury.[14]

The literature is inconsistent regarding both the type and the frequencies of antenatal surveillance among patient with postdate pregnancies.[15],[16],[17] The principle of antepartum fetal surveillance in postdated pregnancies is to predict fetal compromise secondary to uteroplacental insufficiency and hopefully prevent permanent damage.[18],[19] Currently, Doppler ultrasound, an evolving non-invasive technique, is widely used to assess blood flow in both fetal and maternal hemodynamic circulatory functions. Considering its feasibility and safety, this technology is showing promises in fetal surveillance.[20],[21],[22],[23],[24]

Evaluation of the cerebral blood flow in the fetus has become an integral part of the assessment of high-risk pregnancies. The middle cerebral artery (MCA) has been studied extensively, and its Doppler recordings are incorporated regularly into the management of fetuses at the risk of developing placental compromise and fetal anemia.[21] The cerebroplacental ratio (CPR), that is, the ratio of the pulsatility index (PI) of MCA to that of the UA, can detect hypoxemia occurring via two different mechanisms: (1) reduced resistance in the MCA (brain-sparing effect); and UA (increasing placental resistance).[22] Most of these studies to determine its efficiency in fetal surveillance using Doppler velocimetry were done on the role of MCA and UA Doppler velocimetry with very few on the value of CPR in determining the perinatal outcome in low-risk prolonged pregnancy. Hence, this study was aimed to determine the role of Doppler waveforms of MCA, UA, and CPR in predicting fetal compromise in postdated pregnancies in Nigeria. In addition, the authors also set to determine the best index between MCA-PI, UA-PI, and CPR in prediction of adverse perinatal outcome. Furthermore, we plan to compare the diagnostic accuracy of Doppler indices and other traditional fetal surveillance tests for predicting adverse perinatal outcome and to make recommendations on policy for management of postdate pregnancy.


   Materials and Method Top


It was a prospective cohort study of consenting women with uncomplicated postdate pregnancies who met the inclusion criteria at follow-up visits in the antenatal clinic or as referrals from other hospitals to the obstetric clinic in the labor ward of a tertiary hospital in northern Nigeria. Approval for the study was obtained from the institutional research and ethical committee (NHREC/21/08/2008/1KTH/EC/1954). The sample size was calculated using the Buderer's formula for diagnostic accuracy studies at the required absolute precision level for specificity and using previous studies,[8],[18] the total sample size was 212.

Operational definition of terms

  • Postdate pregnancy was defined as gestational age beyond 40 weeks (280 days) from the first day of the last normal menstrual period.
  • Low Apgar was defined as a score ≤ 6 at 5 min
  • Perinatal asphyxia was defined as persistent low Apgar score with associated CNS manifestation of hypotonia and/or seizures, and biochemical evidence of acidosis.
  • Perinatal death was defined as intrauterine death or death within the first seven days of the neonatal period.
  • Adverse perinatal outcome was defined as presence of any one of the measured outcomes defined as meconium stained liquor, meconium aspiration syndrome, low Apgar ≤6 at 5 min, cesarean section or instrumental delivery for fetal distress, admission into neonatal intensive care unit (NICU), perinatal asphyxia, and perinatal death.
  • Composite fetal outcome was defined as presence of two or more of measured outcomes as meconium stained liquor, meconium aspiration syndrome, low Apgar ≤6 at 5 min, cesarean section or instrumental delivery for fetal distress, admission into NICU, perinatal asphyxia, and perinatal death.


The study subjects were classified into two groups (based on the perinatal outcomes): (1) favorable/normal; and (2) unfavorable/adverse outcomes. The purpose of the study was explained to the women and a written consent was obtained from those who voluntarily agreed to participate in the study. A pretested structured, interviewer administered questionnaire was used to obtain information about age, demographic characteristics of last normal menstrual period, past obstetric history, medical and surgical history, and history of current pregnancy. Basic obstetric ultrasound scan was carried out to determine gestational age, fetal presentation, estimated fetal weight, placental localization, and maturation. The women were rescanned after 1 week if undelivered or when planned for induction of labor based on the departmental protocol at 41 weeks 3 days. The last ultrasound results of the women before delivery were used for data analysis. In addition, non-stress test (NST) was done on all subjects, which was repeated after 1 week if undelivered or when planned for induction of labor. Doppler ultrasound was conducted using 3.5 m Hz convex transducer of the Mindray Digital Ultrasound Imaging System (Model DC-6; Shenzen Mindray Biomed Electronics, China) with the high-pass filter set to 70 Hz and the mechanical and thermal indices kept below 1.9 and 1.5, respectively, via trans-abdominal route. Doppler flow velocity waveforms from the umbilical and MCA were obtained with the subjects in a semi-recumbent position with a 15° tilt to the left side. The angle of insonation was maintained at <30 degrees. Pulsed Doppler wave, also enabling real-time and color-coded imaging, was used for the analysis and the Doppler indices calculated by the built-in fast Fourier Transform Software.

With the patient placed in the semi-recumbent position with left lateral tilt, the uterine contents were quickly scanned to select an area of amniotic cavity with several free-floating loops of umbilical cord. The angle of insonation was aligned with the direction of the umbilical arteries. Using the pulsed wave Doppler, the characteristics sound and shape of the UA waveform were demonstrated and identified. When the screen showed at least four consecutive waveforms of similar height, the image was frozen and the UA PI was estimated using in-built electronic calipers. The recordings were obtained in the absence of fetal breathing or body movements.

The standard plane for measuring the biparietal diameter for estimation of gestational age was used for assessment of fetal MCA. Where the thalami and cavum septum pellucidum were visualized, the color Doppler imaging was then activated to allow visualization of the pulsating MCA at the level of the insula. Using the pulsed wave Doppler, at least four consecutive waveforms of similar height from the proximal part of the MCA were obtained and the MCA-PI was estimated using in-built electronic calipers. Care was taken to apply minimal pressure by the transducer on the maternal abdomen, as fetal head compression could alter fetal intracranial pressure and hence the arterial flow velocity waveforms. The PI of both the umbilical and fetal MCAs was automatically calculated by the ultrasound machine on the pulse Doppler tracings.

The CPR was calculated using the formula:

CPR = MCA-PI/UA-PI

Where MCA-PI = middle cerebral artery pulsatility index

UA-PI = umbilical artery pulsatility index

Gramellini et al.[26] calculated the CPR and found that it remained constant in the last 10 weeks of pregnancy. Therefore, a single CPR cut-off value of 1.08 was used in accordance with other published works.[22],[23] Above this value, Doppler velocimetry was considered normal and, below it, abnormal. Doppler study was also considered abnormal if UA PI ≥2SD and MCA < fifth percentile.

The study subjects were followed up throughout the period of labor, delivery, and early puerperium. The CPR measurement was evaluated for predictability of poor perinatal outcome (s).

Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 20 computer software (SPSS Inc. SPSS Statistics for Windows, Chicago). χ2-test was used for categorical data and t-test for continuous variables. Where criteria for applying χ2-test were not met, Fishers' exact test was used and the P < 0.05 was considered to be statistically significant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and accuracy were calculated for all the measured diagnostic tests.


   Results Top


Out of the 212 pregnant women recruited into the study, one was excluded for major fetal congenital abnormality and up to 11 (5.2%) were lost to follow-up. Therefore, the data from 200 (94.3%) women with 198 live births and 2 perinatal deaths was analyzed.

There were no statistically significant differences in the sociodemographic characteristics between those with adverse perinatal outcome and those with favorable perinatal outcomes. The mean maternal age of the participants was 28.5 ± 5.46 years (17–42 years) with no statistically significant difference between those that had adverse perinatal outcome and those with favorable perinatal outcome (28.2 ± 5.08 vs 28.6 ± 5.56 years; respectively, t = −0.369, P = 0.713).

Up to 92 women had spontaneous onset of labor while 86 (43%) of the subjects were induced. Spontaneous vaginal delivery was the most common mode of delivery accounting for 168 (84%) women of all the cases, followed by 32 (16%) women who had cesarean section. The most common indication for cesarean section was previous cesarean section, followed by suspected fetal distress and failed induction, respectively. The indications for cesarean section differed significantly between those who had a favorable perinatal outcome and those who did not (χ2 = 32.537, P < 0.001). Most of the patients had no complication during delivery but 25 (12.5%) had postpartum hemorrhage (PPH), 1 (0.5%) had shoulder dystocia, and 5 (2.5%) had perineal tear. There was no statistically significant difference of the type of maternal complications found between the two groups (χ2 = 5.053, P = 0.168).

[Table 1] compares the Doppler indices and neonatal outcomes between the two groups. The mean birth weight of the babies was 3.4 ± 0.51 kg (2.1–4.5 kg). There was no statistically significant difference by neonatal birth weight between the group with adverse perinatal outcome and the group with favorable perinatal outcome (3.3 vs 3.4 kg; respectively, t = −1.020, P = 0.309). About 18 babies were admitted into NICU for various indications such perinatal asphyxia, neonatal jaundice, and perinatal death. Majority of the cases, 15 (83.3%) of admitted babies, had perinatal asphyxia. There were 2 (1%) perinatal deaths and 198 (99%) neonates were alive at the time of discharge. Abnormal CPR at 1.08 cut-off was seen in 66 (33%) of the study population while 134 (67%) of the patient had normal values. There was a statistically significant difference between the CPR values in patients with adverse perinatal outcome and patients with favorable perinatal outcome (0.63 ± 0.34 vs 1.54 ± 0.74; respectively, t = −7.531, P < 0.001). Of them, 145 patients had normal MCA-PI values at less than fifth percentile and 55 (27.5%) patients had abnormal MCA-PI findings. The difference between the mean value of MCA-PI for those with normal perinatal outcome and those with abnormal perinatal outcome was not statistically significant (1.81 ± 0.79 vs 1.55 ± 0.61; respectively, t = −1.934, P = 0.054). There were 65 (32.5%) patients with abnormal UA PI > 2SD values while 135 (67.5%) patients had normal values. The mean values of UA PI of those with adverse perinatal outcome and those with normal perinatal showed a statistically significant difference (2.95 ± 1.37 vs 1.44 ± 0.88; respectively, t = 8.529, P < 0.001).
Table 1: The Neonatal Outcomes and Doppler Findings in Relation to Perinatal Outcomes

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[Table 2] displays the comparison of the sensitivity, specificity of CPR, MCA-PI, and UA-PI for predicting the different adverse perinatal outcomes. CPR had a very high sensitivity and a comparatively similar good specificity with UA PI for prediction of meconium stained liquor, perinatal asphyxia, composite fetal outcomes, and admission to NICU. Both CPR and UA PI had an average sensitivity and specificity for predicting cesarean delivery for suspected fetal distress and perinatal death. MCA-PI had a very low sensitivity but a good specificity for all parameters of adverse perinatal outcomes. It had zero sensitivity for prediction of perinatal death.
Table 2: Comparison of Variables to Adverse Outcomes

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[Table 2] also shows the PPV and NPV of CPR, MCA-PI and UA-PI to adverse perinatal outcomes. CPR had a better PPV than UA PI but comparative similar NPV for predicting meconium stained liquor, low APGAR, perinatal asphyxia, and admission into NICU. CPR had a higher NPV than UA PI for prediction of composite fetal outcomes. MCA-PI had a very low PPV and high NPV for all the adverse perinatal outcomes.

CPR had a comparatively similar diagnostic accuracy but a better LR than UA PI for predicting all the measured adverse perinatal outcomes. The fetal MCA-PI test had a very low LR when compared with both CPR and UA PI, but has a good level of accuracy for prediction of adverse perinatal outcomes. The diagnostic accuracy and LR of the Doppler indices were shown on [Table 3].
Table 3: The Overall Performance of Different Diagnostic Tests and Comparison of CPR to Various Adverse Perinatal Outcomes

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In predicting of composite fetal outcomes by CPR, the sensitivity and specificity were very good (87.50% and 71.74%, respectively) and the NPV was also very high (98.5%). Meconium stained liquor prediction by CPR test had a higher NPV (98.5%) but a low PPV (28.79%). The test had a good specificity of 72.47% and a higher NPV (96.27%) in ruling out low Apgar score. In the prediction of perinatal asphyxia, the sensitivity and NPV were found to be very high at 93.7% and 99.2%, respectively. The test had a low sensitivity and very low PPV, but had a high NPV for predicting operation for suspected fetal distress and perinatal death (62.5% vs 50.0%, 7.58% vs 1.52%, 97.7% vs 99.20%, respectively). Overall, the sensitivity, specificity, NPV, and accuracy of prediction of adverse perinatal outcomes by CPR were 90%, 81.25%, 97.01%, and 83%, respectively.

When compared with other parameters, the CPR has therefore a best performance for predicting adverse perinatal outcome as shown on [Table 3]. The amniotic fluid index (AFI) had a very low sensitivity and PPV (17.50% and 36.84%, respectively) and a high specificity and NPV (92.11% and 80.92%, respectively). NST and MCA-PI had the least overall performance for adverse perinatal outcome.

[Figure 1] and [Table 3] also display the overall performance of the Doppler indices and other fetal surveillance tests for predicting adverse perinatal outcomes. CPR had the overall best performance for adverse perinatal outcomes while NST and MCA-PI had the least overall performance for adverse perinatal outcomes.
Figure 1: ROC curve analysis of cerebro-placental ratio for predicting adverse peri-natal outcome. The area under ROC curve = 0.885

Click here to view



   Discussion Top


This present study analyzed 200 pregnant women after 40 weeks of gestation to evaluate the predictive value of CPR for adverse perinatal outcome and also to determine the best index from Doppler indices which can predict adverse perinatal outcome in postdated pregnancies.[36] Doppler velocimetry measurements have been widely used for prenatal diagnosis as well as fetal surveillance for more than two decades now. Most of these studies were done to determine its efficiency in fetal surveillance in Caucasian and Asian population with only few in African countries, which account for the high burden of stillbirths due to prolonged pregnancy. Hence, this study aims to determine the role of Doppler waveforms of MCA, UA, and CPR ratio in predicting fetal compromise in postdated pregnancies.

To improve the quality comparison of the outcomes between the two groups, the authors had ensured that the socio-demographic characteristics between those with adverse and favorable perinatal outcomes are the same.

The mean maternal age of the participants approximates the findings of Abisowo in Lagos, south-west Nigeria (29.30 ± 4.03 years),[25] but is slightly older than the postdated pregnant women reported by Bhriegu et al.[23] in India (23.56 ± 2.75 years).

In predicting the composite fetal outcomes by CPR, the sensitivity and specificity were very good while the NPV was also very high in this study [Table 2]. This partly agrees with the Polish study of Migda et al.,[24] who also reported high sensitivity (0.945) but low specificity (0.1), PPV 0.979, NPV 0.04, and accuracy 0.926.(using a cut-off point of 1.08).

Gramellini et al.[26] as well as other researchers,[27],[28] reported that CPR values are constant throughout the last 10 weeks of pregnancy, and have established a value of 1.08 as a cut-off point, less than which (<1.08) the ratio is regarded as abnormal. It is of paramount importance to properly define the MCA- and UA-PI values as normal or abnormal, since such parameters are to reflect placental insufficiency, especially in prolonged pregnancies at 40 weeks or more, where perinatal morbidity and mortality increase due to frequently postulated placental obsolescence.[29] The noted higher sensitivity, specificity, positive predictive value (PPV), NPV, and LR for adverse perinatal outcome of CPR Doppler index (when compared with UA-PI and outperformed MCA-PI when used separately) is in agreement with those of Ghosh et al.[28] that best results are obtained when we used MCA/UA PI ratio, rather than PIs of MCA and UA separately.

On the other hand, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy of CPR were higher than what was reported by Shaheen et al.[29] in which 62 antenatal women; where they reported an abnormal CPR value had a high incidence of meconium stained liquor, clinical fetal distress, operative delivery, low Apgar scores (at 5 min), NICU admission. and neonatal death of 42.88%, 47.62%, 26.57%, 76.19%, 66.17%, and 66.67%, respectively.

In contrast to the findings of this study with UA-PI showing high sensitivity and specificity in predicting all the adverse perinatal outcomes has lower comparable values for predicting cesarean section for fetal distress and perinatal deaths; Sabdia et al.[30] found the likelihood of having an emergency delivery for foetal compromise increased as the UA-PI increased (OR 4.02; 95% CI 1.7–9.32; P = 0.001). Conversely, a low UA-PI was associated with a decreased risk (OR 0.25; 95% CI 0.11–0.58; P = 0.001). On the other hand, Naveen and Karthikeyan[31] reported that UA had a specificity of 79% and PPV (82%) in predicting adverse perinatal outcome in intra uterine growth-restricted fetuses.

As shown in [Table 1], the mean values of MCA-PI in the present study between those that had adverse perinatal outcome and those with normal outcomes were similar with findings reported by other studies.[24],[27],[28] In agreement with Najam et al.,[32] PI of fetal MCA is not sensitive in predicting perinatal death and low PPV, LR for predicting adverse perinatal outcome. Therefore, a normal MCA-PI may not be an indicator of fetal well-being. Detection of this change from abnormal to normal MCA-PI with prolonged hypoxia is associated with severe growth retardation and predicts perinatal death.[33] The noted very low sensitivity, PPV, and diagnostic accuracy of NST is similar to the findings of an Egyptian study on 60 postdate pregnant women by AbdRabou et al.[34]; who found that CPR had a high predictive value in postdate pregnancy with sensitivity, specificity, PPV, and NPV 85.7%, 73.9%, 50%, 94.4%, respectively, incomparison to Biophysical profile (BPP) (≤6), AFI (≤5 cm), and NST for the prediction of adverse perinatal outcome.

The findings, therefore, suggest for the routine measurements of CPR in advanced pregnancies, to determine the level of perinatal risks. The strength of the study included its prospective design and examination of a large sample size of women from different age groups and diverse ethnic backgrounds with uncomplicated prolonged pregnancy. It also included the Doppler evaluations on the subjects that were done only by the principal investigator, who had been appropriately trained under the supervision of a consultant radiologist and a specialist in vascular and interventional radiology and several Doppler measurements were taken for every woman to reduce inter- and intra-observer errors. Furthermore, the use of wide range of well-acceptable indicators for perinatal outcomes.

The limitations of the study include the use of Apgar score, which consist of subjective elements such as tone, color, and reflex irritability, is associated with poor inter-observer reliability. In addition, the objectivity of the umbilical cord blood gases and acid–base analysis in measurement of perinatal asphyxia, was not used in this study due to its high cost.


   Conclusion Top


The CPR Doppler index is a useful diagnostic test for adverse perinatal outcome and shows the highest diagnostic accuracy in prediction of adverse perinatal outcome in pregnant women after 40 weeks' gestation than did UA-PI or MCA-PI when used as stand-alone test. The use of CPR has a better advantage than other conventional antepartum fetal test for assessing fetal well-being in postdates pregnancy. The inclusion of CPR Doppler as a complimentary test in clinical antepartum care of postdates pregnancy may help better identify fetuses at the risk of adverse outcome.

Acknowledgements

We sincerely appreciate the kindness of the nurses in the labor ward and the NICU for the care of our patients and for supporting us in the course of data collection.

Financial support and sponsorship

The study is self-funded.

Conflicts of interest

There are no conflicts of interest.



 
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