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Research Article
Rec. Date: Sep 04, 2019
Acc. Date: Oct 17, 2019
Pub. Date: Oct 24, 2019
Doppler Study of Umbilical and Fetal Middle Cerebral Artery in Severe Preeclampsia and Intra Uterine Growth Restriction and Correlation with Perinatal Outcome
Kavya Kota1*, Mani Deepika Reddy B1 and Manchuru Aruna2
1Junior Resident, Department of Obstetrics and Gynaecology, JJM Medical College, India
2Senior Resident, Department of Obstetrics and Gynaecology, JJM Medical College, India
*Corresponding author: Kavya Kota, Department of Obstetrics and Gynaecology, JJM Medical College, Davangere, Karnataka, India, Tel: +919573416644; E-mail: dr.kavya5@gmail.com
Abstract
Introduction: Doppler velocity study of placental and fetal circulation can provide important information about fetal wellbeing, thus providing an opportunity to improve fetal outcome. 
Objectives: The aim of the study is to determine and compare the diagnostic performance of Doppler sonography of fetal Middle Cerebral Artery (MCA) and Umbilical Artery (UA) in prediction of adverse perinatal outcome in suspected Intrauterine Growth Retardation (IUGR) and severe preeclampsia (PE).
Methods: One hundred singleton pregnancies between 28 and 40 weeks of gestation complicated by IUGR, severe PE or both were prospectively examined with Doppler ultrasonography of the UA and MCA and were correlated with fetal outcome.
Result: Of the 100 cases 52 had elevated umbilical S/D, 58 had elevated umbilical RI, 63 had elevated umbilical PI, 58 had abnormal MCA S/D, 43 had abnormal MCA PI and 57 had CPR<1.08. Birth weight <10th percentile was highest (63.1%) in the abnormal CPR group. LSCS for fetal distress incidence was maximum (30.2%) in the abnormal MCA PI group. 53.4% meconium stained liquor was seen in the elevated umbilical RI group. Maximum perinatal mortality was present in the abnormal MCA PI group (41.8%). NICU stay >48 h was maximum (56.1) in the CPR>1.08 group. CPR had the highest sensitivity (100%) in predicting more than one adverse perinatal outcome.
Conclusion: Doppler studies of multiple vessels in the fetoplacental circulation can help in the monitoring of compromised fetus and can help us predicting neonatal morbidity and mortality. This is helpful in determining the optimal time of delivery in complicated pregnancies.
Keywords: Doppler; Umbilical artery; Middle cerebral artery; Cerebroplacental ratio



1. Introduction 
Hypertensive disorders remain the most common medical complications during pregnancy, leading to a majority of adverse perinatal and maternal outcome, despite numerous efforts have been made at early diagnosis, prevention and treatment [1]. It accounts for a total of 7-10% of perinatal mortality in developed countries and 20% in developing countries. Early detection of preeclampsia may allow vigilant antenatal surveillance and appropriate timing of fetal delivery in order to avoid serious sequelae [2-4].
Pre-eclampsia and IUGR are two conditions that are felt to be the result of abnormal placenta formation involving defective trophoblastic invasion of spiral arteries and a reduction in the vascular resistance in the uteroplacental circulation [5,6]. The decreased uteroplacental perfusion can result in fetal growth restriction, reduced amniotic fluid volume and an inability to tolerate the in utero environment leading to intrauterine death [7,8].
The timely diagnosis of fetal compromise is very important so that delivery can be affected before fetus suffers irreversible damage and dies in utero. Doppler sonography offers a unique tool for the non-invasive evaluation of physiologic, hemodynamic fetoplacental blood flow information. Doppler does correlate well with fetal compromise giving earlier warning sign of fetal distress than other tests [9-13].
Several studies have reported higher sensitivities and specificities for middle cerebral artery/umbilical artery (MCA/UA) Doppler ratio compared with umbilical artery velocimetry alone for the prediction of the fetal prognosis. MCA/UA ratio reflects not only the circulatory insufficiency of the umbilical velocimetry of the placenta manifested by alterations in the umbilical S/D ratio but also the adaptive changes resulting in modifications of the middle cerebral S/D ratio [14-16]. 
2. Objectives
To identify early high risk foetuses by changes in Doppler flow velocity waveforms.
To study S/D ratio, RI, PI and cerebroplacental ratio of fetal umbilical artery and middle cerebral artery in severe preeclampsia and IUGR.
To correlate fetal outcome to Doppler umbilical and middle cerebral artery waveforms in severe preeclampsia and IUGR.
3. Materials and Methods
With a level IV evidence, a prospective study was performed from July 2018 to June 2019 in the department of Obstetrics and Gynaecology, Bapuji hospital, Chigateri Government General hospital, Women and Child Health hospital attached to JJM Medical College, Davangere, Karnataka, India. The patients for this study were recruited by convenient sampling technique. A total of 100 women with singleton pregnancies with vertex presentation between 28 to 40 weeks of gestation who satisfied the inclusion and exclusion criteria were taken for the study. 
Singleton pregnancies with vertex presentation between 28-40 weeks of gestation complicated by severe PE and IUGR were included in the study. Women with anomalous fetus and intrauterine fetal demise and women with medical and obstetric complications were excluded from the study. Intrauterine growth restriction criteria taken as a lag >4 cm in the symphysio fundal height than expected for the period of gestation (calculated by Naegele�s method).
Informed consent was taken from all the patients. Detailed history and through examination was done. All relevant investigations were carried out. The relevant data obtained was recorded in the standard prepared proforma. The doppler waveform analysis of umbilical artery and middle cerebral artery were done.
Umbilical artery: Colour duplex Doppler was used to identify a free floating loop of umbilical cord. The angle of insonation was then optimized and the signals obtained. Umbilical artery S/D ratio was considered abnormal when it was more than 3. Umbilical artery RI and PI were considered elevated when it was more than 95th percentile (Figure 1). 
Middle cerebral artery: It is the largest terminal branch of the internal carotid artery. It was insonated at the level of the greater wing of sphenoid. The angle of insonation can easily be kept at 0 for this vessel (Figure 2).
Systolic flow (A) and the diastolic flow (B) for the above mentioned arteries were obtained. Doppler indices were calculated.

Systolic/Diastolic(S/D) ratio=A/B Resistance index=A-B/A Pulsatality index=A-B/mean
Further management of the cases were decided depending on the clinical status of the patients and the Doppler report and pregnancies were terminated as and when indicated. Patients who continued pregnancy after the Doppler examination, Doppler was repeated at weekly interval. Doppler study done within 7 days prior to termination of pregnancy was taken into consideration for the study.
The mode of termination of pregnancy was decided depending on the clinical condition of patients and the indications. At the time of delivery details such as baby weight, APGAR score, meconium staining of liquor and neonatal intensive care unit admissions were noted.
4. Results
The statistical analysis was done through SPSS for Windows (v 24.0). The descriptive procedure displays univariate summary statistics for several variables in a single table and calculates standardized values (z scores). The Crosstabs procedure forms two-way and multiway tables and provides variety of tests and measures of association for two-way tables. Chi-Square test was used to compare the observed and expected frequencies in each category to test either that all categories contain the same proportion of values or that each category contains a user-specified proportion of values. The results were considered statistically significant if the p value<0.05.
The age of the patients in this study ranges from 18 years to 36 years of which majority belonged to the age group of 21-25 years with a mean age of 22.8 years (SD 3.6 years). The incidence of primigravida (69%) was more than that of multigravida (31%). The study group included patients whose gestational age ranged from 28-40 weeks and the maximum number of patients belonged to 37-40 weeks group (n=60).
Of the 100 cases included in the study 47 patients had only severe PE, 7 patients had only IUGR and the remaining 46 patients were complicated by both severe PE and IUGR.
4.1 Umbilical artery Doppler studies
Out of the 100 patients studied 5 patients had AEDF and 3 patients had REDF, hence S/D ratio could not be calculated in them. Amongst the remaining 92 patients 43.5% (40 patients) had a normal umbilical artery S/D ratio (<3) while the rest 56.5% (52 patients) had elevated S/D ratio (Table 1).
Umbilical artery S/D ratio analysis showed that patients with S/D ratio >3 had a poor perinatal outcome. Perinatal mortality was seen in 13 patients with an elevated S/D ratio, while those with a normal S/D ratio had no perinatal mortality. Birth weight<10th percentile was seen in 30(57.7%) patients in the abnormal S/D group. Thirteen patients with an elevated S/D underwent LSCS for fetal distress, whereas the incidence was only 2(5%) in the normal S/D ratio group. Meconium stained liquor was present in 27 patients (51.9%) and 28 patients (53.8%) had babies with APGAR<7 at 5 min in the elevated S/D ratio group. 41(78.8%) of babies in the elevated S/D group required NICU care of whom 27(51.9%) had to stay for >48 h, whereas in the normal S/D group 8(20%) required NICU care and 3 amongst them had to stay >48 h. The above data shows a strong statistical correlation with poor perinatal outcome and increased perinatal morbidity and mortality with an increased umbilical artery S/D ratio (<3).
After analysis of umbilical artery RI ratio it was seen that 58 patients had elevated RI, whereas 42 of the remaining had normal RI (Table 2).
Umbilical artery RI value analysis showed 34(58.6%) patients delivered babies weighing<10th percentile compared to 11(26.2%) in those with a normal RI. LSCS for fetal distress had to be done in 16 patients in the elevated RI group while only 1 patient with a normal RI underwent LSCS for the same. 31(53.4%) patients had meconium stained liquor in the elevated RI group compared to 6(14.28%) amongst the normal RI group. All babies in the normal RI group had 5 min APGAR values>7 while 33(56.8) babies in the elevated RI group had APGAR<7. NICU care was required in 45(77.5%) and NICU >48 h in 29(50%) in the elevated RI group, compared to 8(19%) and 3(7.1) in the normal RI group. Perinatal mortality rate was 31% (18) in the elevated RI group.
Most of the values were statistically significant (p<.05) except NICU stay >48 h. In this study elevated RI had 100% sensitivity in predicting APGAR<7 at 5 min.
A total of 63 patients of the 100 had elevated PI values whereas remaining 37 patients had normal PI values (Table 3).
Thirty-seven (58.7%) patients with an elevated PI values delivered babies weighing <10th percentile and those with normal PI had 8(21.6%) babies weighing <10th percentile. Sixteen (25.4%) with an elevated PI underwent LSCS for fetal distress while only 1(2.7%) with a normal PI underwent LSCS for the same. 32(50.7%) patients with elevated PI had meconium stained liquor and baby APGAR values<7 at 5 min. Only 5(13.5%) had meconium stained liquor and 1(2.7%) had APGAR<7 in the normal PI group. NICU admission was needed in 46(73%) in the elevated RI group and 29 of them required care for >48 h, whereas 7(18.9%) required NICU care and 3 of them had to stay beyond 48 h in the normal PI group. Perinatal mortality rate was 28.5% (18) in the abnormal PI group, whereas none of the cases with a normal PI had perinatal mortality. 
Statistical correlation was drawn and found to be significant (p<0.05) in most of the parameters (except NICU stay >48 h) in predicting poor perinatal outcome. PI values had highest sensitivity (96.9%) for predicting low APGAR values and highest specificity (63.8%) for predicting NICU admission.
4.2 Absent end diastolic flow in umbilical arteries
Out of the 100 cases studied 5 patients had AEDF in the umbilical arteries.
4.3 AEDF correlation with fetal outcome
Out of the 5 cases with AEDF, 1 delivered a stillborn fetus, 2 babies were deeply asphyxiated and died within 5 h of birth. One of the 3 perinatal mortalities was a preterm baby. 4 out of the 5 live births had meconium stained liquor and all 4 had APGAR<7 at 5 min. 3 cases had babies weighing <10th percentile.
4.4 REDF in umbilical arteries and fetal outcome
Three cases out of 100 studied had REDF in the umbilical arteries. All 3 delivered stillborn babies. 2 out of 3 cases were preterm. A total of 91 patients showed positive diastolic flow and 9 patients showed reversal of flow velocities. 
4.5 Middle cerebral artery Doppler indices MCA S/D ratio
Amongst the 100 cases, 58 had abnormal MCA S/D ratio and the remaining 42 had normal S/D ratio values (Table 4).
In this study it was seen that abnormal MCA S/D ratio was associated with 35(60.3%) babies with birth weight<10th percentile, 15(25.8%) LSCS for fetal distress, 29(50%) patients with meconium stained liquor, 31 babies with APGAR <7 (5 min), 44 NICU admissions amongst which 31 required stay beyond 48h and a perinatal mortality rate of 31% (18). In those cases, with a normal S/D ratio, 10(23.8%) had babies weighing<10th percentile, 2 LSCS for fetal distress, 8(19%) patients with meconium stained liquor, 2 babies with APGAR<7(5 min), 9(21.4%) NICU admissions. No perinatal mortality was seen amongst the normal MCA S/D ratio group.
All data showed statistical significance (<0.05) and MCA S/D had a sensitivity of 96.8% in determining the NICU stay>48 h and a specificity of 70% in determining NICU admissions.
4.6 MCA RI analysis
Forty-seven patients had decreased RI values in the fetal MCA and the remaining 53 had normal values (Table 5).
Forty-seven cases had abnormal MCA RI and 53 had a normal RI. 27(57.4%) of the abnormal group had SGA babies compared to 18(34%) in the normal group. LSCS for fetal distress rate was 25.5% in the abnormal group and 9.4% in the normal. 21 cases had meconium stained liquor and 23 had APGAR<7 at 5 min in abnormal group as against 16 and 10 in the normal group. 36 cases (76.5%) babies of the abnormal group were admitted to NICU and 23 of them hat to stay>48 h, while in the babies of the normal group the incidence of NICU admission was 32.1% (17 cases) and NICU>48 h was 16.9% (9 cases). Perinatal mortality rate in abnormal group was 34% and 3.7% in normal group.
MCA RI had the highest sensitivity (71.8%) for NICU stay >48 h and highest specificity for predicting NICU admissions (76.5%).


4.7 MCA PI values analysis
After analysis of the 100 cases studied it was seen that normal PI values of MCA Doppler was present in 57 cases and the rest 43 had abnormal PI values (Table 6).
In this study it was seen that abnormal MCA PI was associated with 26(60.4%) babies with birth weight<10th percentile, 13(30.2%) LSCS for fetal distress, 19(44.1%) patients with meconium stained liquor, 22 babies with APGAR <7(5min), 33 NICU admissions amongst which 13 required stay beyond 48 h and a perinatal mortality rate of 41.8%(18). In those cases with a normal PI, 19(33.3%) had babies weighing<10th percentile, 4 LSCS for fetal distress, 18(31.5%) patients with meconium stained liquor, 11 babies with APGAR<7(5min), 20(35%) NICU admissions. No perinatal mortality was seen amongst the normal MCA PI ratio group. All data except two showed statistical significance (<0.05) and MCA PI had a sensitivity of 66.6% in determining APGAR<7 at 5 min and a specificity of 78.7% in determining NICU admissions.
4.8 Cerebro-placental ratio analysis
Cerebroplacental ratio is the ratio of PI of MCA to PI of umbilical artery. Fifty-seven cases out of 100 had a CPR <1.08 showing redistribution of blood flow (�BRAIN SPARING EFFECT�) (Table 7).
Thirty-six (63.1%) patients with a CPR<1.08 delivered babies weighing <10th percentile and those with normal CPR had 9(20.9%) babies weighing <10th percentile. 16(28.1%) with a CPR<1.08 underwent LSCS for fetal distress while only 1(2.3%) with a normal CPR underwent LSCS for the same. 30(52.6%) patients in the abnormal group had meconium stained liquor and 33(57.8%) had baby APGAR values <7 at 5 min. Only 7(16.3%) had meconium stained liquor and none had APGAR<7 in the normal CPR group. NICU admission was needed in 46(80.7%) in the abnormal group and 32 of them required care for >48 h, whereas 7(16.2%) required NICU care and none of them had to stay beyond 48h in the normal group. Perinatal mortality rate was 31.5% (18) in the abnormal group, whereas none of the cases with a normal CPR had perinatal mortality.
Statistical correlation was drawn and found to be significant (p<0.05) in all the parameters in predicting poor perinatal outcome. CPR had the highest sensitivity (100%) compared to all other indices.
5. Discussion
The role of Doppler ultrasound in the study of uteroplacental and fetoplacental circulation is well known. It helps in detecting the extent of placental pathology and also predicts the fetal outcome. Numerous studies have been conducted to know the association between Doppler waveforms and perinatal outcome and have had variable results (17-19). The present study showed that abnormal Doppler waveforms were associated with adverse perinatal outcome.
5.1 Umbilical artery waveforms
When umbilical artery velocity was correlated to fetal outcome in the present study, it was shown that there was an increase in the perinatal morbidity and mortality in cases with an abnormal umbilical artery S/D ratio. The present study was compared with study of Yoon et al. [20] (Table 8).
The umbilical artery S/D ratios were compared to the study of Trudinger et al. [21] (Table 9).
The diagnostic performance of UA S/D ratio in detecting birth weight<10th percentile was compared to Adil Fleisher et al. and was noted that the sensitivity was comparable with the present study [22] (Table 10).
Brar et al. noted that when umbilical artery S/D ratio is >3 than there is a greater chance of SGA, APGAR score<7 at 5 min, caesarean section for fetal distress and thick meconium in labour that correlated with the present study [23].
5.2 AEDF or REDF in umbilical arteries
When the fetoplacental flow is severely affected there is an increased impedance to flow resulting in end diastolic flow becoming absent. With further hemodynamic compromise there will be reversal of flow in the umbilical arteries. Such a development is ominous and results in a profoundly adverse perinatal outcome. In our study it was seen that AEDF or REDF correlated with poor perinatal outcome with an increase in the perinatal mortality and morbidity (Table 11).
The perinatal mortality rate in those with a REDF in our was 100%. Hence from the above correlation and the results of the present study it is evident that in women with AEDF/REDF, if the baby is salvageable and NICU facilities are available, it is safer to deliver the baby for a better perinatal outcome.
Delivery can be delayed by 1-2 weeks if desired, with very intensive fetal surveillance in cases of AEDF, but immediate delivery is advocated when REDF sets in. REDF is a terminal event associated with an extremely high perinatal mortality.
5.3 Middle cerebral artery
Redistribution of blood flow occurs as an early stage in fetal adaptation to hypoxemia (brain-sparing reflex), wherein there will be an increased end diastolic flow resulting in decrease in PI and RI. Our study showed similar findings of decrease in the MCA Doppler indices with an elevated umbilical artery resistance.
Low index of pulsatality in the MCA associated fetal compromise has been described by many authors [10,12,13]. In our study it was found that low MCA PI was associated with 60.4% of SGA babies and 41.8% of perinatal mortality (Table 12).
Although our values did not correlate with that of Shahina Bano et al. but we also had a relatively higher sensitivity of the UA PI probably because it directly reflects the resistance in the placental vascular bed [10]. Thus in suspected IUGR cases UA PI may be enough to detect IUGR as recommended in the study of Shahina Bano et al. [10].
5.4 Cerebroplacental ratio
MCA/UA pulsatality index ratio is potentially more advantageous in predicting perinatal outcome as it not only incorporates data on the placental status but also on fetal response. Gramellini et al. calculated the C/U ratio and found that it remains constant in the last 10 weeks of pregnancy [27]. They have also shown that it provides a better diagnostic accuracy than either vessels PI considered alone (Table 13).
The diagnostic performance of CPR in relation to perinatal death was compared with other studies (Table 14).
Our study was comparable to the study of Rozeta et al. although it varied from that of Gramellini et al. [10,27]. In our study CPR had the highest sensitivity (100%) when compared to other indices in predicting NICU stay>48 h and APGAR<7 at 5 min.
6. Conclusion
The present study noted an adverse fetal outcome in cases of severe preeclampsia and or IUGR which showed abnormal Doppler results. The finding of REDF is ominous and AEDF also correlated with poor fetal outcome with a perinatal mortality of 60%. In our study CPR had the highest sensitivity of 100% in predicting adverse fetal outcomes. CPR incorporates data on the placental side and also the fetal response and hence it can be considered potentially more advantageous. Doppler investigation of the fetal circulation plays an important role in monitoring the redistributing fetus and thereby may help to determine the optimal time for delivery.









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