ORIGINAL�ARTICLE ABSTRACT Objective: To determine the diagnostic accuracy of umbilical artery and middle cerebral artery Doppler in detection of intrauterine growth restriction among pregnant women. Study Design: Descriptive cross-sectional study. Place and Duration of Study: The Department of Gynecology and Obstetrics, Fauji Foundation Hospital, Rawalpindi, over a period of six months from May 2019 to October 2019. Materials and Methods: Study participants were 159 pregnant women presented to antenatal clinics. The inclusion criteria were gestational age more than 30 weeks with singleton pregnancies, sure last menstrual period, period of gestation confirmed by dating ultrasonography, small for dates or clinical suspicious of intrauterine growth restriction, and women who provided informed consent. Doppler scan was performed in all those women. Results: Mean age of all the enrolled women was 26.8 (± 6.6) years. Out of 159 women, 32 (20 percent) were nulliparous. On Doppler scan, 29 (18.2 percent) women had intrauterine growth restriction. The mean gestational age at the time of delivery was 35.3 (± 0.95) weeks. Caesarean section was performed in 131 (82.5 percent) of the deliveries. At birth, 24 (15.1 percent) had intrauterine growth restriction. The sensitivity, specificity, positive and negative predictive values of Doppler scan to detect intrauterine growth restriction were 83.3 percent, 93.3 percent, 69.0 percent, and 96.9 percent respectively. The diagnostic accuracy of Doppler scan was 91.8 percent. Conclusion: Our study shows a high sensitivity and specificity of Doppler scan in detecting intrauterine growth restriction. Key Words: Intrauterine Growth Restriction, Middle Cerebral Artery, PulsatilityIndex, Pregnant Women, Resistive Index, Umbilical Artery. 3 Organization criteria for taking public health action. IUGR may be caused by maternal, fetal, placental, 4 and external factors. Early detection of compromised IUGR fetuses and timely intervention is among the major objectives of 5 current prenatal care services. Abnormal findings of fetal size, weight and symmetry ultrasound leads to suspicion of IUGR. Various methods used to determine IUGR comprise of abdominal palpation to measure symphysis-fundal height, fetal ultrasound 6 biometry and ultrasound Doppler flow velocimetry. However, symphysis-fundal height measurements have inadequate accuracy to diagnose an IUGR fetus. However, abdominal circumference and estimated fetal weight are the more accurate sonographic 7 diagnostic measurements to predict IUGR. Nevertheless, recent research has shown that ultrasound Doppler flow velocimetry is the best tool 8 to detect IUGR. However, variations in sensitivity and specificity of Doppler ultrasonography in detecting IUGR have Introduction Intrauterine growth restriction (IUGR) is a condition in which a fetus is unable to attain its genetically 1 predetermined growth potential. Fetuses with intrauterine growth restriction are at higher risk of perinatal mortality, neurological abnormalities, and 2 poor performance at school. It is also one of the major problems in developing countries like Pakistan with incidence of 25%, more than World Health Diagnostic Accuracy of Umbilical Artery and Middle Cereberal Artery Doppler in Detection of Intrauterine Growth Restriction 1 2 3 4 5 6 Asia Raza , Azra Saeed Awan , Seema Gul , Nadia Ahmed Bokhari , Hina Tabassum , Samina Irshaad Correspondence: Dr. Nadia Ahmed Bokhari Assistant Professor Department of Obstetrics & Gynecology Foundation University Medical College, Foundation University, Islamabad E-mail: nadia67bukhari@hotmail.co.uk 1,2,4,5,6 Department of Obstetrics & Gynecology Foundation University Medical College, Foundation University, Islamabad 3 Department of Obstetrics & Gynecology Watim Medical and Dental College, Islamabad Funding Source: NIL; Conflict of Interest: NIL Received: January 12, 2021; Revised: September 17, 2021 Accepted: September 21, 2021 Accuracy of Umbilical artery and Middle Cerebral artery Doppler in IUGRJIIMC 2021 Vol. 16, No.4 219 9 been reported worldwide. Therefore, use of Doppler ultrasonography as a predictive test to detect IUGR in our clinical settings is questionable. Hence, the aim of the present study was to determine the diagnostic value of Doppler in detecting the IUGR among the pregnant women in our clinical settings. This study would help to determine the diagnostic value of Doppler ultrasonography in detecting intrauterine growth restriction in our setup for better management of I U G R fet u s e s . Ea r l y d i a g n o s i s a n d t i m e l y management will help in reduction of perinatal mortality in these fetuses. Materials and Methods A Descriptive cross-sectional study was conducted in Obstetrics and Gynecology Department, Fauji Foundation Hospital, Rawalpindi, over a period of six months from May 2019 to October 2019. A total of 159 pregnant women were selected using nonprobability purposive sampling technique. Women having gestational age more than 30 weeks, visiting antenatal clinics were included in the study. The sample size was estimated by using the World Health Organization (WHO) sample size calculations. The confidence interval level was considered at 95 percent and absolute precision was taken as 10 9 percent. By choosing the sensitivity of 89 percent , 9 specificity of 92 percent and prevalence of 24 10 percent , the required sample size was 159 pregnant women who underwent Doppler scan to detect IUGR. Women having singleton pregnancies beyond 30 weeks of gestation, sure about last menstrual p e r i o d ( L M P ) a n d d a t e s c o n f i r m e d b y ultrasonography in second trimester (before 22 weeks of gestation) and Small for date or clinical suspicious of IUGR (more than 2 weeks difference b e t w e e n g e s t a t i o n a l a g e a n d u l t ra s o u n d parameters) were included in the study. Women having multiple pregnancies, presence of fetal congenital anomalies, unsure about last menstrual period or no dating scan available were excluded. Data was collecting on a predesigned proforma after taking informed verbal consent from the study participants. A brief demographic and clinical history including age, parity, socio-economic status and about the previous obstetric details, and duration of gestation were asked to every enrolled woman. Doppler scan was performed in all women who were diagnosed to have IUGR based on ultrasonography findings. An umbilical artery Doppler abnormality was defined th when the resistive index (RI) was above the 95 centile for gestational age or the presence of an absent end-diastolic flow (AEDF) or reversed end- diastolic flow (REDF). Middle section of the MCA and free loop of umbilical artery were chosen for measurement during periods of fetal apnea. The values of pulsatility indexes (PI) of the MCA and umbilical artery Doppler were calculated. The measurements were taken on weekly basis when doppler values were not normal or fortnightly with growth scan. The measurement before delivery was taken for the analysis. At a minimum, three measurements were obtained, and the mean values were used. All the enrolled women whether with normal or abnormal Doppler findings were followed till the time of delivery to observe the neonatal outcomes for the diagnosis of IUGR based on birth th weight (below the 10 percentile for its gestational age and a term neonate with birth weight less than 2,500 grams). All this information was collected on pre-designed proforma. Data was analyzed using Statistical tests for Social Sciences (SPSS) version 21. Means and standard deviations were calculated for continuous variables while proportions and frequencies were calculated for categorical variables. Results were presented in the form of tables. To examine the accuracy of Doppler scan in detection of IUGR, we calculated the values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) by using the following 2x2 11 table (Table-I). Table I: Calculation of Diagnostic Accuracy of Doppler Scan in Detecting IUGR · Sensitivity = a/ a+c X 100 · Specificity = d/ b+d X 100 · Positive predictive value = a/ a+b X 100 · Negative predictive value = d/ c+d X 100 Results This study was conducted on 159 participants. Mean (SD) age of all the enrolled women in our study was JIIMC 2021 Vol. 16, No.4 Accuracy of Umbilical artery and Middle Cerebral artery Doppler in IUGR Neonatal Birth Weight 220 26.8 (SD = ± 6.6) years. on Doppler ultrasound and had low birth weight on delivery. The sensitivity, specificity, positive and negative predictive values of Doppler scan to detect intrauterine growth restriction were 83.3 percent, 93.3 %, 69.0 % and 96.9 % respectively. The diagnostic accuracy of Doppler scan was 91.8 % (Table-V). Table II: Age Distribution of Enrolled Women (n=159) Out of 159 women, 32 (20 %) were nulliparous and 127 (80%) were parous (Table-III). The mean (SD) gestational age at the time of delivery was 35.3 (± 0.95) weeks, 18 (11.3 %) women were delivered by normal vaginal whereas a great majority, 131 (82.5 %) women were delivered by C-section. In 10 (6.2 %) women, forceps were applied during the delivery time. Values of normal, absent, and reverse diastolic flow in middle cerebral artery are given in Table III. Table III: Descriptive Statistics (n=159) Doppler findings (Umbilical artery and MCA) of all the enrolled women (n=159) are given in Table IV. Table IV: Doppler Findings (Umbilical Artery and MCA) of all the enrolled women (n=159) Note: UA, Umbilical Artery; MCA, Middle Cerebral Artery, RI, Resistance Index; PI, Pulsatility Index; S/D, Systolic to Diastolic Ratio. On Doppler ultrasound, IUGR was present in 29 (18.2 %) pregnant women whereas in 130 (81.8 %) pregnant women IUGR was not detected (Table-V). At birth, 24 (15.1 %) babies were low birth weight whereas in 135 (84.1 %) babies had normal birth weight (no IUGR). So, 20 (12.5%) women had IUGR Table-V: Diagnostic value of Doppler scan to detect IUGR among all the enrolled women (n=159 Discussion Every fetus has a specific growth potential that is inherited from parents. Intrauterine growth restriction (IUGR) may be due to abnormal genetic makeup of the fetus or placental development, maternal medical disorders and environmental 12 factors like toxins and viral infections . IUGR is linked with substantial perinatal morbidity and mortality. Its long-term complications in childhood include cerebral palsy due to permanent brain damage, while in adult life it is found to be associated with noninsulin-dependent diabetes mellitus and hypertension. Diagnosis of intrauterine growth restriction becomes 13 problematic sometimes . Most SGA fetuses are normal, but much unnecessary intervention can be done if they are mistaken as cases of IUGR. On the other hand, growth retarded fetuses may not be 14 SGA . Doppler velocity measurement has been widely used in antenatal diagnosis of IUGR for more than twenty years. Fetal wellbeing is predicted through blood flow in many vessels, particularly in 15 the umbilical artery. In our study, 159 pregnant women with mean age of 26.8 years were enrolled. Out of 159 pregnant women, IUGR was detected in 29 (18.2 %) pregnant JIIMC 2021 Vol. 16, No.4 Accuracy of Umbilical artery and Middle Cerebral artery Doppler in IUGR 221 women on Doppler scan, while based on birth weight 24 (15.1 %) babies were declared as IUGR. The results are like another study where color Doppler Ultrasonography showed the IUGR in 73 (56.59%) patients and birth confirmed IUGR in 71 (55.04%) cases where as 58 (44.96%) patients revealed no 16 IUGR . In our study, the sensitivity, specificity, positive and negative predictive values of Doppler scan to diagnose IUGR were 83.3 percent, 93.3 percent, 69.0 percent, and 96.9 percent respectively. The diagnostic accuracy of Doppler scan was 91.8 percent. In another study, Umbilical artery Doppler ultrasound had sensitivity 85.3%, specificity 72.5%, positive predictive value 84.1%, negative predictive value 74.4% and diagnostic accuracy of 80.1%. Our study showed a substantially high sensitivity and specificity of Doppler scan in detection of IUGR in our clinical settings and our findings are comparable with other similar studies around the world. Similar to our study, a recent study has been carried out in our neighboring country, India, where the diagnostic accuracy of UA and MCA Doppler scan was used in detecting IUGR in their study population. The investigators enrolled 90 pregnant women between gestational ages of 30 weeks and above having fetuses with intrauterine growth restriction, similar to our study population. The diagnostic accuracy of Doppler scan in detecting IUGR in their study population was lower than what we have found in 17 our study. Quite similar to our findings, in United Kingdom, a study enrolled 52 women for Doppler studies of IUGR fetuses, the authors reported a sensitivity and specificity of 96 percent and 84 18 percent respectively. There are several reasons that our study found a higher sensitivity and specificity than what they found. However, the most common reason is that in our study we conducted Doppler scan after 30 weeks of gestation while many studies reported have conducted Doppler in first or second trimester of pregnancy. In a recent study, Doppler studies have been used to detect early onset IUGR in first two trimesters, with detection rates of about 50 percent with false positive rate of 7 percent. However, its use as an isolated screening tool had low sensitivity and positive predictive value if used alone as a screening 19 tool to detect IUGR in first and second trimesters. In fetuses with IUGR, blood flow is redistributed from periphery towards the brain. Umbilical artery (UA) Middle cerebral artery (MCA) is the most studied fetal arteries for Doppler studies due to its easy 20 accessibility. Conclusion Findings of our study suggest high sensitivity and specificity of Doppler scan in detecting IUGR in our study population. However, there is a need to conduct large scale, multicenter randomized controlled trials to determine the diagnostic accuracy of fetal Doppler ultrasonographies in detecting IUGR in our local population. REFERENCES 1. Ross MG, Zion Mansano R. Fetal Growth Restriction: Practice Essentials, Causes of Intrauterine Growth Restriction, Perinatal Implications [Internet]. eMedScape. 2020. Available from: https://emedicine.medscape. com/article/261226-overview. 2. Malhotra A, Allison BJ, Castillo-Melendez M, Jenkin G, Polglase GR, Miller SL. Neonatal morbidities of fetal growth restriction: Pathophysiology and impact. Vol. 10, Frontiers in Endocrinology. 2019. 3. Mohammad N, Sohaila A, Rabbani U, Ahmed S, Ahmed S, Ali SR. Maternal predictors of intrauterine growth retardation. J Coll Physicians Surg Pakistan. 2018;28(9):681–5. 4. Sharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Vol. 10, C l i n i ca l M e d i c i n e I n s i g ht s : Pe d i at r i c s . 2 0 1 6 . p . CMPed.S40070. 5. Tambat AR, Chauhan A. Relationship of the Findings of Colour Doppler and Non-Stress Test with the Perinatal Outcome among the Cases of Intra-Uterine Growth Restriction. MVP J Med Sci. 2016;3(2):115. 6. Cherian, G A. Diagnosis of intrauterine growth restriction Cherian AG - Curr Med Issues. Curr Med Issues. 2017;15(4):267–70. 7. Gutaj P, Wender-Ozegowska E. Diagnosis and Management of IUGR in Pregnancy Complicated by Type 1 Diabetes Mellitus. Vol. 16, Current Diabetes Reports. 2016. 8. Khadija S, Amir Gilani S, Butt S, Yousaf M, Bacha R, Hassan Gilani SZ ul. The Efficacy of Doppler Indices in Third Trimester of IUGR Pregnancies. Obstet Gynecol Res. 2019;03(01):1–9. 9. Cnossen JS, Morris RK, Ter Riet G, Mol BWJ, Van Der Post JAM, Coomarasamy A, et al. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: A systematic review and bivariable meta-analysis. Vol. 178, Cmaj. 2008. p. 701–11. 10. Malik A, Ashraf R, Hanson LA. Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation. Vol. 3, Pakistan Journal of Medical and Health Sciences. 2009. p. 279. 11. Stojanović M, Apostolović M, Stojanović D, Milošević Z, JIIMC 2021 Vol. 16, No.4 Accuracy of Umbilical artery and Middle Cerebral artery Doppler in IUGR 222 Toplaović A, Lakušić VM, et al. Understanding sensitivity, Specificity and predictive values. Vojnosanit Pregl. 2014;71(11):1062–5. 12. Manandhar T, Prashad B, Nath Pal M. Risk Factors for Intrauterine Growth Restriction and Its Neonatal Outcome. Gynecol Obstet. 2018;08(02). 13. Sharma D, Sharma P, Shastri S. Postnatal Complications of Intrauterine Growth Restriction. J Neonatal Biol. 2016;05(04). 14. Kesavan K, Devaskar SU. Intrauterine Growth Restriction: Postnatal Monitoring and Outcomes. Pediatr Clin North Am [ I n t e r n e t ] . 2 0 1 9 ; 6 6 ( 2 ) : 4 0 3 – 2 3 . Av a i l a b l e f r o m : https://doi.org/10.1016/j.pcl.2018.12.009. 15. Figueras F, Gratacós E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther. 2014;36(2):86–98. 16. Mehdi SA, Bukhari H, Dogar IH, Shabbir I. Diagnostic accuracy of Color Doppler of cerebral and umbilical pulsatality in diagnosing IUGR, taking birth weight as gold standard. Prof Med J. 2020;27(03):651–9. 17. Bano S, Chaudhary V, Pande S, Mehta VL, Sharma AK. Color doppler evaluation of cerebral-umbilical pulsatility ratio and its usefulness in the diagnosis of intrauterine growth retardation and prediction of adverse perinatal outcome. Indian J Radiol Imaging. 2010;20(1):20–5. 18. Bamfo JEAK, Kametas NA, Chambers JB, Nicolaides KH. Maternal cardiac function in fetal growth-restricted and n o n - g ro w t h - re s t r i c t e d s m a l l - fo r - g e s ta t i o n a l a g e pregnancies. Ultrasound Obstet Gynecol. 2007;29(1):51–7. 19. Pedroso MA, Palmer KR, Hodges RJ, Costa F da S, Rolnik DL. Uterine artery doppler in screening for preeclampsia and fetal growth restriction. Vol. 40, Revista Brasileira de Ginecologia e Obstetricia. 2018. p. 287–93. 20. Mari G, Hanif F, Kruger M, Cosmi E, Santolaya-Forgas J, Treadwell MC. Middle cerebral artery peak systolic velocity: A new Doppler parameter in the assessment of growth- re st r i c te d fe t u s e s . U l t ra s o u n d O b ste t Gy n e co l . 2007;29(3):310–6. JIIMC 2021 Vol. 16, No.4 Accuracy of Umbilical artery and Middle Cerebral artery Doppler in IUGR 223