Can Cerebroplacental Ratio Predict Neonatal Mortality?
By John C. Hobbins, MD
Professor, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora
Dr. Hobbins reports no financial relationships relevant to this field of study.
SYNOPSIS: Recent articles show the cerebroplacental ratio to be a useful predictor of immediate and later neonatal morbidity, particularly, in late-onset intrauterine growth restriction.
SOURCE: Khalil AA, et al. Is fetal cerebroplacental ratio an independent predictor of intrapartum fetal compromise and neonatal unit admission? Am J Obstet Gynecol 2015;213:54.e1-10.
The July issue of the American Journal of Obstetrics and Gynecology included three articles on the cerebroplacental ratio. Back-to-back papers from the same institution, Kings College Hospital in London,1,2 were accompanied by an excellent review on the subject by Gregory DeVore.3 This month I will focus on one of the studies1 by the British authors.
In Doppler wave form analysis, the pulsatility index (PI) and systolic/diastolic (S/D) ratios quantify the relationship between systole and diastole in a cardiac cycle. Normally there is increased resistance in the cerebral circulation, which is reflected in an increased distance between systole and diastole in the waveform, resulting in (normally) high PIs and S/D ratios in the middle cerebral artery (MCA). In contrast, the placental circulation, by necessity, is very lush. This lowered resistance results in proportionally greater diastolic flow in the umbilical artery (UA) as demonstrated by low PIs and S/D ratios, with ratios in the latter of generally less than 3:1 in the third trimester.
In intrauterine growth restriction (IUGR) when the PO2 drops below a certain point in a gradually worsening progression, the fetus will feel a need to protect the brain by vasodilation, thereby increasing flow during diastole. This causes a decrease in the PIs and S/D ratios in the MCA. In early-onset IUGR, the fetal circulation in the placenta has fewer villus branches and terminal villi. The umbilical arteries, therefore, will encounter more resistance downstream, causing lower flow during diastole, thus resulting in an increase in the PIs and S/D ratios. Interestingly, as the fetal condition worsens, the wave forms from the MCA (with diastolic flow trending upward) and the UA (with progressively lower diastolic flow) begin to look very much alike. Since the umbilical artery reflects the adequacy of the placental circulation and the MCA is indicative of how well the fetus tolerates the deprivation process, a ratio of the two PIs, cerebroplacental ratio, has emerged as a way to provide even more useful information than either alone. Any value < 1.08 is thought to be concerning.
The featured retrospective cohort study involved patients who were delivered between 2000 and 2013. Each of these patients had UA and MCA Dopplers done within 2 weeks of delivery. Although the managing physicians were privy to the individual results, the cerebroplacental ratios were calculated later for the purpose of the study. The only Doppler criterion used in decision-making was the UA.
The results should get our attention: The higher the birth weight and the higher the cerebroplacental ratio, the lower the chances of having an operative delivery for fetal distress. Specifically, if the cerebroplacental ratio was reassuring, the risk of operative delivery was significantly lower (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.52-0.77). This association held up even if small for gestational age infants were excluded from the analysis. The cerebroplacental ratio was also an independent predictor of newborn special care unit admissions (OR, 0.55; 95% CI, 0.33-0.92), while birth weight was not. It is of note that operative delivery was more common in appropriate for gestational age babies with low cerebroplacental ratios than small for gestational age babies with normal cerebroplacental ratios.
COMMENTARY
First, it is clear that there are two forms of IUGR: early onset and late onset. The early onset type is associated with an early fall off in fetal growth secondary to insufficient placental flow. Affected fetuses generally have birth weights below the third percentile, have a more predictable course, often are delivered very early, and have a high rate of perinatal mortality and morbidity. Late-onset IUGR is associated with late plateauing of fetal growth and, although perinatal mortality is uncommon, later morbidity is not. Their courses are generally unpredictable and any diagnostic help in managing these pregnancies should be welcomed.
In 1999, Bahado-Singh described cerebroplacental ratio as a way to keep tabs on the placenta and fetus at the same time.4 The concept languished for many years. However, recently there has been a rebirth of its use in IUGR pregnancies, with studies mostly from Europe correlating abnormal MCAs and cerebroplacental ratios with poor neonatal acid base status,5 neurological sequelae after birth,6 neuro-developmental performance at 2 years of age,7 and even, indirectly, with childhood cardiovascular abnormalities.8 Yet, in the United States the concept of brain sparing has been largely ignored, where the only Doppler method that is officially recognized is the UA Doppler — a test that is often within normal range in those late IUGR pregnancies leading to poor neonatal outcome and later neurological morbidity. The latest American College of Obstetricians and Gynecologists (ACOG) practice bulletin on fetal growth restriction (May 2013) makes no mention of early vs late IUGR or the use of MCA Dopplers in the management of IUGR pregnancies. The ACOG bulletin on fetal surveillance (July 2014) also did not distinguish between early and late IUGR, and states that “MCA has not been shown to improve outcome” and its “role remains uncertain.”
Well, if the above studies are not sufficient, there are new data from a large multicenter observational study from Ireland9 to indicate that the cerebroplacental ratio is predictive of immediate outcome and how well the fetus will tolerate labor. Yet with today’s emphasis on “evidence-based medicine,” nothing appears to be put into play until it is first tested through a prospective, randomized, clinical trial. So, we had better act fast while we are still seemingly clueless about the benefit of information derived from the MCA. And don’t bother asking our colleagues in Europe to join us. They already have made up their minds.
REFERENCES
- Khalil AA, et al. Is fetal cerebroplacental ratio an independent predictor of intrapartum fetal compromise and neonatal unit admission? Am J Obstet Gynecol 2015;213:54.e1-10.
- Khalil AA, et al. The association between fetal Doppler and admission to neonatal unit at term. Am J Obstet Gynecol 2015;213:57.e1-7.
- Devore GR. The importance of cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol 2015;213:5-15.
- Bahado-Singh RO, et al. The Doppler cerebroplacental ratio and perinatal outcome in intrauterine growth restriction. Am J Obstet Gynecol 1999;180:750-756.
- Morales-Rosello J, et al. Poor neonatal acid-base status in term fetuses with low cerebroplacental ratio. Ultrasound Obstet Gynecol 2015;45:156-161.
- Figueras F, et al. Neurobehavioral outcomes in preterm, growth-restricted infants with and without prenatal advanced signs of brain sparing. Ultrasound Obstet Gynecol 2011;38:288-294.
- Eixarach E, et al. Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 2008;32:894-899.
- Cruz-Lemini M, et al. A fetal cardiovascular score to predict infant hypertension and arterial remodeling in intrauterine growth restriction. Am J Obstet Gynecol 2015;210:552.e1-22.
- Flood K, et al. The role of brain sparing in prediction of adverse outcomes in intrauterine growth restriction: Results of the multicenter PORTO study. Am J Obstet Gynecol 2014;211:288.e1-5.
Recent articles show the cerebroplacental ratio to be a useful predictor of immediate and later neonatal morbidity, particularly, in late-onset intrauterine growth restriction.
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