Abnormal Doppler flow velocimetry in the growth restricted foetus as a predictor for necrotising enterocolitis.AB Bhatt, PD Tank, KB Barmade, KR Damania
Department of Obstetrics and Gynaecology, Seth G. S. Medical College, Parel, Mumbai-400 012, India. , India
BACKGROUND: Obstetric decision- making for the growth restricted foetus has to take into consideration the benefits and risks of waiting for pulmonary maturity and continued exposure to hostile intra-uterine environment. Necrotising Enterocolitis (NEC) results from continued exposure to hostile environment and is an important cause of poor neonatal outcome. AIMS: To evaluate the predictive value of abnormal Doppler flow velocimetry of the foetal umbilical artery for NEC and neonatal mortality. SETTINGS AND DESIGN: A retrospective study carried out at a tertiary care centre for obstetric and neonatal care. MATERIALS AND METHOD: Seventy-seven neonates with birth weight less than 2000 gm, born over a period of 18 months were studied. These pregnancies were identified as having growth abnormalities of the foetus. Besides other tests of foetal well-being, they were also subjected to Doppler flow velocimetry of the foeto-placental vasculature. Obstetric outcome was evaluated with reference to period of gestation and route of delivery. The neonatal outcome was reviewed with reference to birth weight, Apgar scores and evidence of NEC. STATISTICAL ANALYSIS USED: Chi square test. RESULTS: In the group of patients with Absent or Reverse End Diastolic Frequencies (A/R EDF) in the umbilical arteries, positive predictive value for NEC was 52.6%, (RR 30.2; OR 264). The mortality from NEC was 50%. When umbilical artery velocimetry did not show A/REDF, there were no cases of NEC or mortality. Abnormal umbilical or uterine artery flow increased the rate of caesarean section to 62.5% as compared to 17.6% in cases where umbilical artery flow was normal. CONCLUSION: In antenatally identified pregnancies at risk for foetal growth restriction, abnormal Doppler velocimetry in the form of A/REDF in the umbilical arteries is a useful guide to predict NEC and mortality in the early neonatal period.
Keywords: Adult, Blood Flow Velocity, physiology,Chi-Square Distribution, Comorbidity, Enterocolitis, Necrotizing, epidemiology,physiopathology,ultrasonography,Female, Fetal Growth Retardation, epidemiology,ultrasonography,Follow-Up Studies, Human, Infant Mortality, trends,Infant, Newborn, Predictive Value of Tests, Pregnancy, Prevalence, Probability, Retrospective Studies, Rheology, methods,Risk Assessment, Ultrasonography, Doppler, methods,Ultrasonography, Prenatal, Umbilical Arteries,
The investigation of the foetal circulation by Doppler studies was first carried out by Fitzgerald and Drumm. This diagnostic modality has gained prime importance in the area of high-risk pregnancy evaluation. Growth abnormalities, a common feature in high-risk pregnancies, have a disproportionately large contribution to perinatal morbidity and mortality. Doppler flow velocimetry as an antenatal surveillance tool in such pregnancies helps us to identify the compromised foetus. This knowledge of deteriorating foetal condition can be used to intervene and eventually improve foetal prognosis. Neonatal complications, particularly Necrotising Enterocolitis (NEC), are reportedly more likely where prenatal umbilical artery Doppler recordings show Absent or Reversed End Diastolic Frequencies (A/R EDF). However, these babies are usually delivered very premature from complicated pregnancies, and existing data do not control for confounding variables.
We studied neonatal outcome at term (in specific relation to NEC and mortality) in a group of women with high-risk pregnancies who underwent Doppler studies as part of foetal well being evaluation.
The records of term neonates weighing less than 2 kg who were admitted to the NICU during the 18-month period beginning January 2000 were analysed. Although the international definition for low birth weight is 2.5 kg or less, in the Indian scenario, the criterion of 2 Kg is used. The exclusion factors were Preterm deliveries, multiple pregnancies and malformed babies.
It was the policy of the obstetric unit to monitor high risk pregnancies for foetal growth compromise, using clinical assessment, ultrasound foetal growth by biometry, Doppler velocimetry and cardiotocographic tracings. The maternal histories were reviewed, taking note of maternal age, parity, previous obstetric and medical histories, complications of present pregnancy like diabetes and hypertension, tobacco use and ingestion of alcohol and drugs taken during pregnancy. Factors influencing obstetric decision-making were analysed.
Doppler velocimetry was performed by experienced sonologists using a GE 400 MD (General Electrics, USA) ultrasound machine. There was a rigorous protocol defining the diagnosis of absent end diastolic frequencies. The high pass filter was set at 50 Hz to minimise artefactual absence of velocities due to concealment under the filter. The uterine artery or its main branch was located at the cervico-corporal junction. Doppler velocimetry measurements were performed at this location for the uterine artery. The umbilical cord was visualised with ultrasound; waveforms were accepted only where a constant venous signal was obtained and the flow velocity waveform was sampled from three points on the umbilical artery to minimise the risk of abnormally high angles of incidence.
The neonatal outcome and the course in the NICU were reviewed with reference to birth weight, Apgar scores and subsequent neonatal morbidity and mortality especially in relation to NEC occurrence. Necrotising enterocolitis was clinically suspected when there was abdominal distension with bile stained gastric aspirate or vomit and blood stained mucoid stools. Radiological findings of reduced bowel gas shadowing, thickening of bowel wall, and pneumatosis coli were used for confirming the diagnosis. The statistical test used was the Chi square test using supportive computer software Microsoft Excel 97.
During the study period, 16,201, births occurred in our institute. The average gestational age was 37.1 weeks and mean birth weight was 2.558 Kg. There were 2,123 admissions to the neonatal intensive care unit of which 544 neonates were term babies weighing 2 Kg or less. Of these, 77 neonates satisfied our selection criteria with adequacy of Doppler documentation in the antenatal period. Late registration or complete lack of antenatal care and admissions of babies born outside the institute contributed to a relatively smaller proportion of infants entering the study. The demographic distribution of the population was uniform as shown in [Table - 1].
Forty-three patients had abnormal Doppler flow velocimetry results: Sixteen had abnormal indices only in the uterine artery and 27 had abnormal flows in the umbilical arteries. Of the latter, 8 patients were identified with Increased Resistance to Diastolic Flows, 10 with Absent End Diastolic Flow and 9 with Reverse End Diastolic Flows in the umbilical artery.
The incidence of operative intervention for delivery correlated to the abnormalities in Doppler, [Table - 2]. Twenty-five patients with abnormal flows were delivered by caesarean section. Of these, 19 patients had Absent or Reversed End Diastolic Frequencies (A/R EDF). The other 6 were taken up for caesarean section in view of a non-reactive foetal heart rate pattern on cardiotocography. Of the patients with increased resistance to flows in the umbilical or uterine arteries, who went into labour spontaneously or by induction, there was a high risk for emergency caesarean section for foetal distress. In the group of patients with increased resistance to the uterine or umbilical flow, the caesarean section rate was 62.5% as compared to the caesarean section rate of 17.6% in the group with normal flows. The difference was statistically significant (P 0.04).
Ten infants developed NEC. All neonates who developed NEC had A/R EDF pattern of umbilical Doppler flow velocimetry in intra-uterine life. The mortality from NEC was 50%. This accounted for 100% of mortality in the population. All these neonatal deaths due to NEC occurred in patients with REDF. A/REDF groups were associated with a significantly increased risk of NEC (P 0.001). The positive predictive value of A/REDF for development of NEC was 52.6% and for mortality was 26.3%. The positive predictive value of Reversed End Diastolic Flow (REDF) for the neonatal mortality is 55.5%.
In contrast, no neonate developed NEC where the pregnancy was characterized by normal flow, abnormal uterine flow or even increased resistance in umbilical artery. Thus, when A/REDF in umbilical artery does not occur, the chances of NEC occurrence and mortality was nil in our study.
The other risk factors were evaluated for their influence on NEC causation and mortality [Table - 3]. Birth weight, Apgar score of less than 7 or presence of meconium in the amniotic fluid were not found to be significant independent parameters for predicting the occurrence of NEC or perinatal mortality.
Absent or reverse end diastolic frequencies in the umbilical artery is thought to result from increased downstream vascular resistance. Circulatory redistribution is associated with decreased blood flow to the lung, intestines, kidneys, skin, and muscle, with blood diverted to the brain, myocardium and adrenals. This reduction in visceral perfusion has been associated with an increased risk of necrotising enterocolitis, cerebral haemorrhage, and neonatal morbidity.,
The terminal villous compartment of the placenta appears to be maldeveloped in intrauterine growth restricted pregnancies where Absent and Reverse End Diastolic Flow velocity is demonstrated in the umbilical artery before delivery. These findings are consistent with an increase in fetoplacental vascular impedance at the capillary level and may account for the impaired gas and nutrient transfer in this disorder.
In foetuses with growth restriction there is a redistribution of blood flow away from the gut towards the vital organs. This reduction in visceral perfusion has been associated with increased risk of NEC. The major determinant of NEC in the term neonate is an insult to the gut mucosa, which alters its permeability. This is most commonly a result of ischaemia of the gut. The increased permeability leads to bacterial colonisation and inadequate neutralization of toxins, which ultimately leads to NEC. The results of our study validate this hypothesis.
The detection of abnormal Colour flow indices influenced decision-making and was often found to be a major determinant of the mode of delivery. This can be readily appreciated from the nearly 4-fold increase in the caesarean section rate in patients with abnormal flow velocimetry.
In this high-risk population, Doppler flow velocimetry was a sensitive tool to predict perinatal mortality. The positive predictive value of abnormal umbilical flow was 18.5% and that of REDF in the umbilical arteries was as high as 55.6% for perinatal mortality. One also needs to emphasize the potential of a normal Doppler flow velocimetry in predicting a normal outcome in terms of NEC occurrence and mortality. There were no cases of NEC or mortality when there was no A/REDF in the umbilical artery.
Doppler flow velocimetry is a great help to the obstetrician and neonatologist. The evolution of our knowledge of foetal physiology has been significantly improved with developing technology. Doppler velocimetry studies of placental and foetal circulation can provide important information regarding foetal well being, yielding an opportunity to improve foetal outcome.
[Table - 1], [Table - 2], [Table - 3]