Detection and false-positive rates of middle cerebral artery for cesarean delivery for nonreassuring fetal status were 29.5% and 8.7%, whereas they were 45.9% and 21.5% for cerebroplacental ratio. For neonatal acidosis, the detection rate was 37.5% (false-positive of 12.9%) for middle cerebral artery and 37.5% (false-positive of 27.8%) for cerebroplacental ratio.
This study provides evidence that abnormal brain Doppler before the onset of labor induction indentifies small-for-gestational-age fetuses at high risk of emergency cesarean delivery for nonreassuring fetal status and neonatal acidosis. The data suggest that combination of middle cerebral artery Doppler and cerebroplacental ratio may refine prediction and establish subgroups with progressive risk of nonreassuring fetal status. These findings add to the body of evidence suggesting that the diagnostic category of small for gestational age includes a proportion of cases with true growth restriction and mild placental insufficiency, which is not reflected in the umbilical artery Doppler. In this category, in which longitudinal studies have demonstrated that umbilical artery impedance remains normal throughout the fetal monitoring,31 brain redistribution seems to constitute a surrogate of placental insufficiency and hypoxia as suggested by its association with abnormal neonatal neurobehavior10,17 The present study suggests a new clinical application for fetal brain Doppler in the selection of small-for-gestational-age fetuses at risk of nonreassuring fetal status during labor induction.
This study found that middle cerebral artery Doppler had the highest value to predict the individual risk of emergency cesarean delivery for nonreassuring fetal status. The data are in line with Severi et al9 who reported that the risk of cesarean delivery was increased in small-for-gestational-age fetuses with middle cerebral artery vasodilation at the time of diagnosis. Concerning the cerebroplacental ratio, our clinical algorithm shows that decreased cerebroplacental ratio values had a higher sensitivity than middle cerebral artery vasodilation for emergency cesarean delivery for nonreassuring fetal status (45.9% compared with 29.5%) but lower specificity (78.5% compared with 91.3%). These findings are in agreement with previous studies in preterm fetuses with growth restriction showing that cerebroplacental ratio becomes abnormal earlier32–34 and, thus, it has a greater sensitivity for adverse outcome than middle cerebral artery,12–15 but it is less specific.35 As the decision tree algorithm illustrates, combining both middle cerebral artery and cerebroplacental ratio allows an overall detection rate for nonreassuring fetal status of 50% while maintaining a specificity of 76%. Concerning brain tissue perfusion as measured by fractional moving blood volume, this study showed no association with the risk of nonreassuring fetal status or neonatal acidosis. Brain tissue perfusion becomes abnormal earlier than spectral Doppler parameters such as middle cerebral artery and cerebroplacental ratio16 and has shown the greatest sensitivity to detect poor neonatal neurobehavior among term small-for-gestational-age fetuses.17 It can be hypothesized that increased brain perfusion by fractional moving blood volume identifies early stages of fetal hypoxia, when a majority of small-for-gestational-age fetuses are still capable of tolerating uterine contractions. On the contrary, abnormal middle cerebral artery Doppler, which appears only in advanced stages,16,31 would indicate a lower fetal reserve in the presence of uterine contractions. In agreement with this contention, middle cerebral artery was the only brain Doppler parameter associated with neonatal acidosis, which is a major contributor to neonatal neurological morbidity.36
The effect of the identification of small-for-gestational-age fetuses at risk of emergency cesarean delivery after labor induction should not be underestimated. Small for gestational age affects up to 10% of the deliveries in developed countries and represents approximately 400,000 cases per year in the United States.37 Although there are recommendations that term IUGR fetuses should be monitored during delivery as high-risk pregnancies,38 there is no consensus about the best strategy for delivery. A recent multicenter clinical trial failed to demonstrate differences in perinatal outcome between expectant management compared with induction of labor.39 However, this study defined small-for-gestational-age fetuses only by estimated fetal weight percentiles and therefore it remains unclear whether the results might differ in the subgroup of small-for-gestational-age fetuses with signs of late-onset IUGR. The lack of consensus is reflected in a substantial proportion of small-for-gestational-age pregnancies managed by induction of labor.18–20 These numbers may increase as evidence supporting an increased risk of adverse perinatal and neurodevelopmental outcome in term small-for-gestational-age fetuses accumulates.2–7 However, labor induction in small for gestational age carries a higher risk of nonreassuring fetal status and emergency cesarean delivery,9 which in turn are associated with increased maternal and perinatal risks and high resource consumption.40–42 The results of this study may be of help in decision-making at the time of induction of labor. Brain Doppler may allow identifying patients with high risk of emergency cesarean delivery and overall low chances of successful vaginal delivery. Prediction of this risk before labor induction might allow a better patient-individualized counseling and a more efficient provision of resources in cases of suspected small for gestational age. However, it must be stressed that this study does not intend to suggest a single best management strategy for delivering small-for-gestational-age pregnancies presenting with abnormal brain Doppler. For instance, it cannot be ruled out that poor outcome is strongly influenced by intrauterine environmental factors associated with growth restriction, and thus cesarean delivery would not result in any improvement on long-term outcome. In addition, the answer to this question may be strongly influenced by other factors including cervical conditions, parity, and availability of resources. In any event, the data suggest that brain Doppler may help establishing overall risks that could be combined with other clinical information in decision-making processes and opens opportunities for clinical trials addressing these questions. Multicenter clinical studies including evaluation of the mentioned factors might help refining the appropriate application of fetal brain Doppler evaluation in the selection of cases for trial of labor compared with elective cesarean delivery.
Strengths of this study are the prospective design, the inclusion of a well-defined cohort of term small-for-gestational-age fetuses with normal umbilical artery Doppler exposed to labor induction, and that obstetricians in charge of labor monitoring were blinded to the brain Doppler parameters evaluated in this study. Among the limitations of the study, it must be acknowledged that because all brain Doppler measurements were performed by a single expert, this may limit the external validity and therefore the generalizability of the results, although it increases the internal validity of the study. In addition, the sample size of the study did not allow evaluating the contribution of known factors affecting the risk of cesarean delivery such as Bishop score and parity into the clinical algorithm. The fact that most instances of cesarean delivery for nonreassuring fetal status occurred early in the induction process reduces the potential influence of these factors, but larger studies are needed to address this issue. Finally, we acknowledge that the clinical applicability of these findings may be limited because brain Doppler evaluation in advanced gestational ages requires expertise and this may not be readily available in all settings. In addition, like with other Doppler indices, middle cerebral artery vasodilation must be confirmed over 24 hours to avoid false-positive results.43
In conclusion, evaluation of spectral brain Doppler indices allows identification of small-for-gestational- age fetuses with late-onset IUGR and normal umbilical artery Doppler at risk of emergency cesarean delivery for nonreassuring fetal status and metabolic acidosis at birth. These findings support the assessment of brain Doppler in the monitoring of small-for-gestational-age fetuses to improve timely delivery and decision-making regarding induction of labor at term.
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