PERINATAL OUTCOME PREDICTION IN PATIENTS WITH PREECLAMPSIA USING FETALDOPPLER STUDIES AT MOI TEACHING AND REFERRAL HOSPITAL

1. Resident,Department of Radiology and Imaging,Moi University, P.O. Box 4606-30100, Eldoret, Kenya. 2. Department of Radiology and Imaging,Moi University, P.O. Box 4606-30100, Eldoret, Kenya. 3. Department of Reproductive Health,Moi University, P.O. Box 4606-30100, Eldoret, Kenya. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 25 April 2020 Final Accepted: 30 May 2020 Published: June 2020


1535
Doppler ultrasonography is done in the third trimester and it is a non-invasive way of evaluating fetal circulation through the umbilical vessels, middle cerebral artery, uterine artery and fetal venous circulation. The umbilical artery (UA) Doppler measurements do not provide information on how the fetus is coping with a compromised supply and therefore will not identify all the compromised fetuses in a population. For this reason, study of systemic vessels such as the middle cerebral artery (MCA) is also carried out 5 .
Although Doppler studies have been shown to improve outcome in high risk pregnancies, they are of no use in low risk pregnancies and should not be used in routine screening of such pregnancies 6 .In Kenya the maternal mortality due to preeclampsia is as high as 16% and preeclampsia has a four-fold increase in preterm births, perinatal mortality and admission to the new born unit 7 .
Umbilical Artery (UA) is the most widely studied vessel and its value well established in several studies. However, there is conflicting data on the the value of Middle Cerebral Artery (MCA) doppler except in assessment of fetal anemia. Some studies have shown assessment of the MCA to have limited predictive accuracy of perinatal out come 8 . Use of the Cerebro-placental Index (CPI) ismore accurate than individual vessel indices in prediction of perinatal outcomes as it gives information on how the fetus is coping with the impaired blood flow 9,10 .
The value of Doppler studies has been established the world over. However, this has not been done in our hospital setup and Biophysical Profile (BPP) is still the main ultrasound fetal surveillance tool.Only two studies have been done in Kenya regarding Doppler in obstetrics and both were done more than 10 years ago 11,5 . None of these studied fetal vessels and both were in private hospitals. Thus, there is general paucity of data in our setup regarding utility of obstetric Doppler studies. Although a study by Ngukuet al in Nairobi showed that umbilical artery Doppler is more sensitive than biophysical profile in prediction of perinatal outcome, this study did not evaluate systemic vessels like the MCA 11 .
Doppler ultrasound provides important information to guide obstetricians in management and time delivery. International guidelines exist on use of Doppler in obstetrics and specifically in preeclampsia but there are no clear local guidelines.
The World Health Organization (WHO)estimated the maternal mortality rate(MMR) in 2015 to be 216 maternal deaths per 100,000 live births with developing regions accounting for 99% and Sub-Saharan Africa alone accounting for roughly 66%. The MMR in Kenya was estimated at 510/100,000 live births 12 . Preeclampsia is second to hemorrhage as a cause of maternal mortality with an estimated 50,000-60,000 preeclampsia related deaths worldwide every year 13,12 .
Preeclampsia is clinically defined as hypertension (BP> 140/90), proteinuria with or without pathological edema 14 . According to the new guideline by American College of Obstetricians and Gynaecologists (ACOG), diagnosis of preeclampsia no longer requires presence of proteinuria or edema for diagnosis 15 . Severity depends on cut-offs for hypertension and proteinuria and clinical or laboratory evidence of end organ damage. In the fetus, it can lead to ischemic encephalopathy, growth retardation and the various sequelae of premature birth.
The umbilical artery (UA) was the first vessel to be evaluated by Doppler velocimetry. Flow velocity waveforms from the umbilical cord have a characteristic saw-tooth appearance of arterial flow in one direction and continuous umbilical venous blood flow in the other. Indices used to asses umbilical artery abnormalities include Systolic/Diastolic (S/D) ratio, resistive index(RI) and pulastility index. These can be used interchanagably with similar predictive values for perinatal outcome 16 .
The umbilical artery (UA) is a low resistance vessel, with preeclampsia increase in vascular resistance leads to reduction in end diastolic velocity. Placental insufficiency can be quantified based on the reduction of end-diastolic Doppler flow velocity into: 1. Reduced end diastolic flow velocity 2. Absent end-diastolic flow velocity 3. Reversed end-diastolic flow velocity The risk of perinatal mortality increases up to 60%, with increasing severity from reduced to reversed end-diastolic flow velocity 17 .
1536 Doppler asesment of the foetal midddle cerebral artery (MCA) is an important part of asssessing fetal cardiovascular distress, fetal anemia or fetal hypoxia. Examination of the MCA is used as an adjunct to UA doppler to monitor those fetuses at risk of perinatal morbidity or mortality due to placental insufficiency. The MCA is a high resistance vessel compared to the umbilical artery with minimal flow in fetal diastole. With mild hypoxia, the resistance in the UA is increased with no change in the resistance in the MCA. With progressive hypoxia, vasodilation occurs to protect the brain, heart and adrenals with reduced flow to the placental and peripheral circulations-brain sparing effect. With brainsparing the doppler waveform depicts increased diastolic flow and reduced pulsatility index. With worsening hypoxia, there is a paradoxical rise in resistance with 'normalisation' of the waveform and this is a poor prognostic sign 18 .
Use of the umbilical artery or the middle cerebral arteries in isolation to predict perinatal outcome has lower sensitivities and positive predictive values 9 . For this reason many studies have been conducted on the use of Cerebro-placental index (CPI)to predict perinatal outcome and it has been shown to be superior than individual vessels 10 . Use of the cerebro-placental index is a valuable predictor of outcome in preeclampsia irrespective of whether the fetus is small or appropriate for gestational age 19 .
Virginia Apgar was an anesthesiologist who invented the Apgar score in 1952 as a method to quickly summarize the health of newborn children. It uses five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10 20 .The test is generally done at one and five minutes after birth, and may be repeated later if the score is and remains low. Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low.A low score on the one-minute test may show that the neonate requires immediate medical attention. An Apgar score that remains below 3 at later times-such as 10, 15, or 30 minutes may indicate longer-term neurological damage, including a small but significant increase in the risk of cerebral palsy.

Methods:-
This was a cross-sectional study with prenatal data collected at one point and post-natal findings also recorded at a single point in time.The study was conducted in the Radiology and Imaging department and the antenatal, labour and neonatal wards in the Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya. The study population included pregnant women with preeclampsia referred for ultrasound. Only patients who planned to deliver in MTRH were recruited in this study so as to reduce loss to follow-up as postpartum results were also required. The study was conducted over a period of 12 months from October 2016 to September 2017.Patients in their third trimester (>28weeks) of pregnancy with a clinical diagnosis of preeclampsia made by the attending clinicians in the reproductive health department were recruited. However, patients with multiple gestation, those in labour and those with fetal congenital malformations like neural tube defects, cardiac malformations, fetal hydrops were excluded.
Consecutive sampling was used in this study. Patients diagnosed with preeclampsia were referred for ultrasound from the antenatal clinic or antenatal ward.All nurses in reproductive health department of MTRHwere formally trained on APGAR scoring and they were further sensitized and updated on accurate APGAR scoring, weighing of new borns and proper recording in patients' files.
A trans-abdominal approach using aMindray M7 ultrasound machine 2016 model with 3.5-5 MHz curvilinear probe was used. The examination was done with the patient lying supine or semi-recumbent on the examination couch.The following ultrasound findings were considered abnormal: The outcomes of interest were whether live or still birth, mode of delivery, gestation at birth, APGAR score at 5 minutes and birth weight. Abnormal outcomes were: 1. Preterm delivery <37 weeks.
1537 APGAR score ≤ 7 at 5 minutes Data was collected using a structured questionnaire. Data was then imported into STATA/MP version 13, where coding, cleaning and analysis was done.

Results:-
The results are based on 165 patients whose age ranged from 15 to 42 years with an average of 29 (SD 6.3) years. The median age was 30 (IQR 24, 34) years. Majority (n=138, 83.6%) of patients were married and 63% had attained secondary level of education   There was a statistically significant association between Doppler findings and overall pregnancy outcome (p<0.001), where majority (80%) who had abnormal Doppler findings were also found to have abnormal overall pregnancy outcome, 25.7% of those who had normal Doppler ended up with overall abnormal pregnancy outcomes. Those with abnormal Doppler findings were 11.5 times more likely to have poor post natal outcomes as compared to those with normal Doppler findings (OR=11.55, p<0.001, 95% CI 4.83, 27.61) Only MCA-RI was not statistically associated with post natal outcomes (p=0.494). There was a statistically significant association between all abnormal Doppler findings and still birth/IUFD except MCA RI. Only MCA RI was not significantly associated with APGAR score ≤ 7 at 5 minutes. Intrauterine Growth restriction (IUGR) was present in 30.3% of the patients and this is similar to what was found by Nguku et al in Nairobi who found IUGR in 30.5% of their pre-eclamptic patients 11 . Similar results were demonstrated in a study done in Pennsylvania which showed 2-4 fold increase in odds of getting IUGR in preeclampsia and incidence increased with severity of preeclampsia 21 . IUGR in preeclampsia is explained by uteroplacental insufficiency which leads to impaired fetal blood supply thus the fetus does not grow to its full genetic potential. 20.61% of the patients were found to have oligohydramnios as measured by the Amniotic Fluid Index (AFI).
Oligohydramnios is a common finding in pregnancies complicated by IUGR and it is explained by decreased fetal blood volume, renal blood flow, and, subsequently, fetal urine output 22  A statistically significant association was demonstrated between Doppler findings and poor perinatal outcomes. This is similar to what was found by a study in India with a similar composition of outcomes 24 . All the specific abnormal Doppler findings were also associated with poor outcomes except MCA RI (P=0.494). A case control study done in Egypt showed no significant difference between individual Doppler indices except CPI in patients with preeclampsia and those without 18 . The same study demonstrated combination of UA and MCA indices as the CPI had better sensitivity, specificity and predictive values. Another study in India also demonstrated that CPI is a better predictor of perinatal outcome compared to UA S/D ratio 28 .
Several studies have sought to validate different antenatal tests but no single test has been shown to accurately provide information on fetal status. Most clinical guidelines advocate combination of clinical findings, laboratory tests and ultrasound findings to make decisions on delivery in patients with preeclampsia 29 . Moreover, poor postnatal outcomes are varied and cord blood pH is considered the most objective method of assessing post-natal outcome 30 .
Having an abnormal Doppler increased odds of having and abnormal outcome 11.5 times. A study in Pennsylvania demonstrated an Odds ratio of 4.2 with CPI threshold of less than 1.08 with an odds ratio (95% confidence interval) 31 . The higher odds in our study can be explained by the use of several Doppler parameters as opposed to using only one (CPI).

Conclusions:-
Majority (78.7%) had abnormal Doppler findings with 51.1% having abnormal umbilical artery spectral flow patterns. Abnormal Doppler findings were significantly associated with poor perinatal outcomes.
Doppler studies of both the Umbilical and Middle Cerebral Arteries including the Cerebro-Placental Index should be included in the prenatal evaluation of pregnancies affected by preeclampsia.