Obstetrics & Gynecology:
Fetal Brain Doppler to Predict Cesarean Delivery for Nonreassuring Fetal Status in Term Small-for-Gestational-Age Fetuses
Cruz-Martínez, Rogelio MD; Figueras, Francesc MD, PhD; Hernandez-Andrade, Edgar MD, PhD; Oros, Daniel MD; Gratacos, Eduard MD, PhD
From the Department of Maternal-Fetal Medicine, Institute Clínic of Gynecology, Obstetrics and Neonatology (ICGON), Hospital Clinic-IDIBAPS, University of Barcelona and the Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Supported by grants from the Fondo de Investigación Sanitaria (PI/060347) (Spain), Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK), and Thrasher Research Fund (Salt Lake City, UT). R.C. was supported by Marie Curie Host Fellowships for Early Stage Researchers, FETAL-MED-019707-2 and by the Mexican National Council for Science and Technology (CONACyT). E.H.-A. was supported by a Juan de la Cierva postdoctoral fellowship, Fondo de Investigaciones Sanitarias, Spain.
Presented at the 9th World Congress in Fetal Medicine and the Eurofoetus Meeting, Fetal Medicine Foundation of London, June 20–24, 2010, Rhodes, Greece; and at the 20th World Congress on Ultrasound in Obstetrics and Gynecology (ISUOG), October 10–14, 2010, Prague, Czech Republic.
Corresponding author: Eduard Gratacos, PhD, Maternal-Fetal Medicine Department, Hospital Clinic, University of Barcelona, Sabino de Arana 1, 08028 Barcelona, Spain; e-mail: email@example.com.
Financial Disclosure The authors did not report any potential conflicts of interest.
OBJECTIVE: To estimate the value of fetal brain Doppler in predicting the risk of cesarean delivery for nonreassuring fetal status and neonatal acidosis after labor induction in small-for-gestational-age fetuses with normal umbilical artery Doppler.
METHODS: Fetal brain Doppler parameters, including cerebral tissue perfusion measured by fractional moving blood volume, cerebroplacental ratio, and middle cerebral artery pulsatility index, were evaluated before labor induction in a cohort of 210 term small-for-gestational-age fetuses with normal umbilical artery Doppler and 210 control participants matched by gestational age. The value of the cerebral Doppler indices to predict the risk of cesarean delivery, cesarean delivery for nonreassuring fetal status, and neonatal acidosis was analyzed.
RESULTS: Overall, small-for-gestational-age fetuses showed a significant higher incidence of cesarean delivery (37.6% compared with 19.5%, P<.001), cesarean delivery for nonreassuring fetal status (29% compared with 4.8%, P<.001), and neonatal acidosis (7.6% compared with 2.4%, P=.03) than control participants. Within the small-for-gestational-age group, middle cerebral artery vasodilation was associated with the highest risk of cesarean delivery (67.7% compared with 32.4%, P<.001) and cesarean delivery for nonreassuring fetal status (58.1% compared with 24%, P<.001). In the subgroup of normal middle cerebral artery, incorporation of cerebroplacental ratio further distinguished two groups with different risks of cesarean delivery (51.4% compared with 27.5%, P<.01) and cesarean delivery for nonreassuring fetal status (37.8% compared with 20.4%, P=.01). Middle cerebral artery vasodilation was associated with increased risk of neonatal acidosis (odds ratio, 9.0). Fractional moving blood volume was not associated with the risk of cesarean delivery for nonreassuring fetal status or neonatal acidosis.
CONCLUSION: Evaluation of brain Doppler indices before labor induction discriminates small-for-gestational-age fetuses at high risk of cesarean delivery for nonreassuring fetal status and neonatal acidosis.
LEVEL OF EVIDENCE: II
Small-for-gestational age fetuses without signs of placental insufficiency as reflected in the umbilical artery Doppler account for up to 10% of the pregnant population by customized centiles.1 Recent evidence suggests that a proportion of these small-for-gestational-age fetuses have milder forms of late-onset intrauterine growth restriction (IUGR) as suggested by an increased risk of adverse perinatal outcome,2–4 abnormal neonatal neurobehavioral performance,5 and suboptimal neurodevelopment in childhood.6,7 Thus, the identification of small-for-gestational-age fetuses with late-onset IUGR is challenging and cannot only be based on umbilical artery Doppler.
Recent studies suggest that the risk of adverse outcome in these fetuses is best established by means of brain Doppler examination. Thus, brain sparing as measured by the middle cerebral artery Doppler is associated with poorer perinatal outcome,8 higher risk of cesarean delivery for nonreassuring fetal status,9 and increased risk of abnormal neurodevelopmental tests at birth10 and at 2 years of age.11 The combination of middle cerebral artery and umbilical artery Doppler in the cerebroplacental ratio further improves the prediction of adverse perinatal outcome.12–15 In addition, brain tissue perfusion measured by power Doppler and estimated by fractional moving blood volume, as a quantitative methodology to estimate blood tissue perfusion, has been demonstrated to be more sensitive than middle cerebral artery and cerebroplacental ratio for early detection of brain redistribution in term small-for-gestational-age fetuses16 and to identify those cases at risk of abnormal neurobehavior.17
Small-for-gestational-age fetuses are often managed by induction of labor.18–20 However, clinical studies have reported an increased risk of cesarean delivery for nonreassuring fetal status in these fetuses.9 Predicting this risk might allow timely delivery, assist the decision-making process regarding labor induction, and result in a more efficient provision of resources at delivery. The aim of this study was to estimate whether a combination of middle cerebral artery Doppler, cerebroplacental ratio, and brain perfusion by fractional moving blood volume could improve the prediction of cesarean delivery for nonreassuring fetal status and neonatal acidosis after labor induction in term small-for-gestational-age fetuses with normal umbilical artery Doppler.
MATERIALS AND METHODS
Between January 2008 and May 2010, a prospective cohort of consecutive singleton fetuses with an estimated fetal weight below 10th percentile according to local standards,21 normal umbilical artery Doppler (pulsatility index below the 95th percentile),22 and cephalic presentation was selected for labor induction beyond 37 weeks of gestation corrected by first-trimester ultrasound.23 Sample size was estimated according to the formula described elsewhere.24 Exclusion criteria were: 1) congenital malformations and chromosomal abnormalities; and 2) confirmed birth weight above the 10th percentile according to local standards.21 Control participants were selected during the same study period and were defined as singleton pregnancies with labor induction for premature rupture of membranes without clinical suspicion of chorioamnionitis and resulting in a neonatal birth weight between the 10th and 90th percentiles.21 Control participants were individually matched with cases by gestational age at delivery (±1 week). The protocol was approved by the hospital ethics committee and written consent was obtained for the study from all the women involved (Institutional Review Board 2008/4422).
Prenatal Doppler ultrasound examinations were weekly performed by one experienced operator (R.C.M.) using a Siemens Sonoline Antares ultrasound machine equipped with a 6-2-MHz linear curved-array transducer. Doppler recordings were performed in the absence of fetal movements and voluntary maternal suspended breathing. Spectral Doppler parameters were performed automatically from three or more consecutive waveforms with the angle of insonation as close to zero as possible. A high-pass wall filter of 70 Hz was used to record low flow velocities and avoid artifacts. Umbilical artery pulsatility index was performed from a free-floating cord loop. The middle cerebral artery pulsatility index was obtained in a transversal view of the fetal head, at the level of its origin from the circle of Willis, and the cerebroplacental ratio was calculated as a ratio of the middle cerebral artery pulsatility index to the umbilical artery pulsatility index. Using power Doppler ultrasound, fractional moving blood volume was estimated as previously described.25 Briefly, in a sagittal view of the fetal head, the color box was placed to include the whole frontal lobe and thus the anterior cerebral artery, pericallosal artery, median callosal artery, sagittal sinus, and the frontal medial branches. Five consecutive high-quality images with no artifacts were recorded using the following fixed ultrasound setting: gray-scale image for obstetrics, medium persistence, wall filter of 1, gain level of 1, and pulsed repetition frequency of 610 Hz. All images were examined offline and the region of interest was delineated anteriorly by the internal wall of the frontal bone, inferiorly by the base of the skull, and posteriorly by an imaginary line drawn at 90° at the level of the origin of the anterior cerebral artery and crossing at the level of the origin of the internal cerebral vein (Fig. 1). The mean fractional moving blood volume values from all five images was considered as representative for that specific case and expressed as a percentage.
The middle cerebral artery pulsatility index and cerebroplacental ratio values below the fifth percentile and increased fractional moving blood volume above the 95th percentile were considered indicative of cerebral blood flow redistribution.26,27 Doppler indices with confirmed abnormal values at least 24 hours apart were considered as abnormal. In all cases, only the last examination within 24 hours before the onset of labor induction was included in the analysis.
Labor induction was performed at term (37 weeks or greater) for all small-for-gestational-age cases by cervical ripening with a slow-release prostaglandin estradiol vaginal pessary (10 mg). If the onset of labor did not occur within 12 hours, oxytocin induction was performed. All deliveries were attended by a staff obstetrician blinded to the results of the brain Doppler parameters evaluated in this study. Indication of cesarean delivery for nonreassuring fetal status was based on abnormal fetal heart rate tracing28 and abnormal fetal scalp blood pH during intrapartum monitoring. Briefly, continuous fetal heart rate monitoring was performed and tracings were classified as normal, suspicious, or abnormal according to the presence, type, and length of decelerations; bradycardia; tachycardia; and the assessment of variability.28 In cases with two or more criteria of suspicion and one or more criteria of abnormality not responding to fetal scalp digital stimulation, a fetal scalp blood sampling was attempted and considered as abnormal with values below 7.2.
Cases in which cervical conditions did not allow fetal scalp sampling were considered for cesarean delivery for nonreassuring fetal status if abnormal tracing persisted after pessary withdrawal and 10 minutes of intravenous infusion of ritodrine (200 μg/min). Metabolic acidosis was defined as the presence of an umbilical artery pH below 7.15 and base excess greater than 12 mEq/L in the newborn.29 All cases with adverse outcome are evaluated in a confidential enquiry to assure adherence to such guidelines.
Student's t test or paired Student's t and McNemar tests were used to compare independent and paired data, respectively. The association between abnormalities in the brain Doppler parameters and the risk of emergency cesarean delivery for nonreassuring fetal status and metabolic acidosis was analyzed by multiple simple logistic regression (for independent data) or conditional logistic regression (for paired data) adjusted by estimated fetal weight percentile and gestational age at birth using Statistical Package for the Social Sciences 17.0 statistical software.
A predictive model for the occurrence of intrapartum cesarean delivery and emergency cesarean delivery for nonreassuring fetal status was constructed using the Decision Tree Analysis algorithm (SPSS 17.0), which provides clinically comprehensive classification algorithms that allow their use in clinical practice to profile the individual risk for a given patient. The decision tree was developed using the Classification and Regression Trees CHAID method (Quick, Unbiased and Efficient Statistical Tree), which generates binary decision trees with the P inset at .05 (Bonferroni-adjusted for multiple comparisons) and a cutoff selected automatically for all the parameters included.30 The classification and regression tree was constructed by splitting subsets of the data set using all predictor variables to create two child nodes repeatedly. The best predictor was chosen using a variety of impurity and diversity measures. For a parsimonious model, the number of cases to be present for a split has to be greater than 5% of the sample. Thus, the stopping rules for the iterative process were that the tree should have a maximum of three levels, a minimum of 10 cases were to be present for a split to be calculated, and any given split should not generate a group with less than five cases. This allowed sequential analysis of variables to predict the risk of intrapartum cesarean delivery.
During the study period, a total of 232 consecutive small-for-gestational-age fetuses with estimated fetal weight less than the 10th percentile fulfilling the inclusion criteria were recruited. One neonate was excluded because a nondiagnosed congenital malformation and eight additional cases because of a normal birth weight, leaving a total population of 223 cases.
In 13 cases (5.8%), frontal brain perfusion could not be evaluated as a result of the degree of engagement of the fetal head into the pelvis, leaving 210 cases for the analysis that were matched with 210 control participants, resulting in a final population of 420 fetuses.
Table 1 shows the maternal and neonatal clinical characteristics of the population. According to our matched design, gestational age at inclusion and at delivery was similar between cases and control participants. Small-for-gestational-age fetuses showed a significantly higher rate of cesarean delivery, emergency cesarean delivery resulting from nonreassuring fetal status, and neonatal acidosis than control participants. In 64% of the small-for-gestational age group with nonreassuring fetal status (in 39 of 61), the diagnosis was made during the latent phase (in 18 of 39 fetal scalp samplings was not performed as a result of the unfavorable cervical conditions) and in 36% during the first or second stages of labor. The proportion of small-for-gestational-age fetuses with increased fractional moving blood volume, abnormal cerebroplacental ratio, and middle cerebral artery vasodilation was 42.4%, 28.6%, and 14.8%, respectively.
Figures 2 and 3 show the frequency of intrapartum cesarean delivery, cesarean delivery resulting from nonreassuring fetal status, and neonatal acidosis for control participants and for small-for-gestational-age fetuses classified according to the presence or absence of decreased cerebroplacental ratio or middle cerebral artery vasodilation. Within the group of small-for-gestational-age fetuses, those fetuses with middle cerebral artery vasodilation had a significantly higher incidence of intrapartum cesarean delivery (67.7% compared with 32.4%, P<.001), cesarean delivery for nonreassuring fetal status (58.1% compared with 24.0%, P<.001), and neonatal acidosis (19.4% compared with 5.6%, P=.01) than those with normal middle cerebral artery Doppler. Small-for-gestational-age fetuses with abnormal cerebroplacental ratio had a significantly higher incidence of intrapartum cesarean delivery (58.3% compared with 29.3%, respectively, P<.01) and a higher rate of cesarean delivery for nonreassuring fetal status (46.7% compared with 22.0%, respectively, P<.01) than those small-for-gestational-age cases with normal cerebroplacental ratio. Abnormal cerebroplacental ratio was not significantly associated with the risk of neonatal acidosis (10.0% compared with 6.7%, respectively, P=.50). Small-for-gestational-age fetuses with increased or normal fractional moving blood volume had similar risks of intrapartum cesarean delivery (41.6% compared with 34.7%, respectively, P=.22), emergency cesarean delivery for nonreassuring fetal status (33.7% compared with 25.6%, respectively, P=.14), or neonatal acidosis (9.0% compared with 6.6%, respectively, P=.50).
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.
Table 2 shows the odds ratios of emergency cesarean delivery for nonreassuring fetal status and neonatal acidosis according to each brain Doppler parameter with control participants as the reference group.
The decision tree analysis (Fig. 4) profiled three groups with increasing risk of intrapartum cesarean delivery and cesarean delivery secondary to nonreassuring fetal status. Middle cerebral artery pulsatility index was the best initial predictor discriminating a group with the highest risk of CD (67.7% in small-for-gestational-age fetuses with middle cerebral artery vasodilation compared with 32.4% in those with normal middle cerebral artery, P<.001) and cesarean delivery for nonreassuring fetal status (58.1% compared with 24%, respectively, P<.001). In the subgroup of normal middle cerebral artery, incorporation of cerebroplacental ratio identified two groups with different risk of cesarean delivery (51.4% in small-for-gestational-age fetuses with decreased cerebroplacental ratio compared with 27.5% in those with normal cerebroplacental ratio, P<.01) and cesarean delivery for nonreassuring fetal status (37.8% compared with 20.4%, respectively, P=.01).
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.
1. Figueras F, Figueras J, Meler E, Eixarch E, Coll O, Gratacos E, et al. Customised birthweight standards accurately predict perinatal morbidity. Arch Dis Child Fetal Neonatal Ed 2007;92:F277–80.
2. McCowan LM, Harding JE, Stewart AW. Umbilical artery Doppler studies in small for gestational age babies reflect disease severity. BJOG 2000;107:916–25.
3. Doctor BA, O'Riordan MA, Kirchner HL, Shah D, Hack M. Perinatal correlates and neonatal outcomes of small for gestational age infants born at term gestation. Am J Obstet Gynecol 2001;185:652–9.
4. Figueras F, Eixarch E, Gratacos E, Gardosi J. Predictiveness of antenatal umbilical artery Doppler for adverse pregnancy outcome in small-for-gestational-age babies according to customised birthweight centiles: population-based study. BJOG 2008;115:590–4.
5. Figueras F, Oros D, Cruz-Martinez R, Padilla N, Hernandez-Andrade E, Botet F, et al. Neurobehavior in term, small-for-gestational age infants with normal placental function. Pediatrics 2009;124:e934–41.
6. McCowan LM, Pryor J, Harding JE. Perinatal predictors of neurodevelopmental outcome in small-for-gestational-age children at 18 months of age. Am J Obstet Gynecol 2002;186:1069–75.
7. Figueras F, Eixarch E, Meler E, Iraola A, Figueras J, Puerto B, et al. Small-for-gestational-age fetuses with normal umbilical artery Doppler have suboptimal perinatal and neurodevelopmental outcome. Eur J Obstet Gynecol Reprod Biol 2008;136:34–8.
8. Hershkovitz R, Kingdom JC, Geary M, Rodeck CH. Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2000;15:209–12.
9. Severi FM, Bocchi C, Visentin A, Falco P, Cobellis L, Florio P, et al. Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2002;19:225–8.
10. Oros D, Figueras F, Cruz-Martinez R, Padilla N, Meler E, Hernandez-Andrade E, et al. Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2010;35:456–61.
11. Eixarch E, Meler E, Iraola A, Illa M, Crispi F, Hernandez-Andrade 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;32:894–9.
12. Gramellini D, Folli MC, Raboni S, Vadora E, Merialdi A. Cerebral-umbilical Doppler ratio as a predictor of adverse perinatal outcome. Obstet Gynecol 1992;79:416–20.
13. Jain M, Farooq T, Shukla RC. Doppler cerebroplacental ratio for the prediction of adverse perinatal outcome. Int J Gynaecol Obstet 2004;86:384–5.
14. Odibo AO, Riddick C, Pare E, Stamilio DM, Macones GA. Cerebroplacental Doppler ratio and adverse perinatal outcomes in intrauterine growth restriction: evaluating the impact of using gestational age-specific reference values. J Ultrasound Med 2005;24:1223–8.
15. Habek D, Salihagic A, Jugovic D, Herman R. Doppler cerebro-umbilical ratio and fetal biophysical profile in the assessment of peripartal cardiotocography in growth-retarded fetuses. Fetal Diagn Ther 2007;22:452–6.
16. Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Puerto B, Gratacos E. Longitudinal brain perfusion changes in near-term small-for-gestational-age fetuses as measured by spectral Doppler indices or by fractional moving blood volume. Am J Obstet Gynecol 2010;203:42.e1–6.
17. Cruz-Martinez R, Figueras F, Oros D, Padilla N, Meler E, Hernandez-Andrade E, et al. Cerebral blood perfusion and neurobehavioral performance in full-term small-for-gestational-age fetuses. Am J Obstet Gynecol 2009;201:474.e1–7.
18. Larsen T, Larsen JF, Petersen S, Greisen G. Detection of small-for-gestational-age fetuses by ultrasound screening in a high risk population: a randomized controlled study. Br J Obstet Gynaecol 1992;99:469–74.
19. Biran G, Mazor M, Shoham I, Leiberman JR, Glezerman M. Premature delivery of small versus appropriate-for-gestational-age neonates. A comparative study of maternal characteristics. J Reprod Med 1994;39:39–44.
20. McCowan LM, Harding JE, Roberts AB, Barker SE, Ford C, Stewart AW. A pilot randomized controlled trial of two regimens of fetal surveillance for small-for-gestational-age fetuses with normal results of umbilical artery doppler velocimetry. Am J Obstet Gynecol 2000;182:81–6.
21. Figueras F, Meler E, Iraola A, Eixarch E, Coll O, Figueras J, et al. Customized birthweight standards for a Spanish population. Eur J Obstet Gynecol Reprod Biol 2008;136:20–4.
22. Arduini D, Rizzo G. Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med 1990;18:165–72.
23. Robinson HP, Fleming JE. A critical evaluation of sonar ‘crown-rump length’ measurements. Br J Obstet Gynaecol 1975;82:702–10.
24. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996;49:1373–9.
25. Hernandez-Andrade E, Jansson T, Figueroa-Diesel H, Rangel-Nava H, Acosta-Rojas R, Gratacos E. Evaluation of fetal regional cerebral blood perfusion using power Doppler ultrasound and the estimation of fractional moving blood volume. Ultrasound Obstet Gynecol 2007;29:556–61.
26. Baschat AA, Gembruch U. The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol 2003;21:124–7.
27. Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Benavides-Serralde A, Gratacos E. Normal reference ranges of fetal regional cerebral blood perfusion using power Doppler ultrasound as measured by Fractional Moving Blood Volume. Ultrasound Obstet Gynecol 2010 Jun 14 [Epub ahead of print].
28. Altaf S, Oppenheimer C, Shaw R, Waugh J, Dixon-Woods M. Practices and views on fetal heart monitoring: a structured observation and interview study. BJOG 2006;113:409–18.
29. Gregg AR, Weiner CP. ‘Normal’ umbilical arterial and venous acid-base and blood gas values. Clin Obstet Gynecol 1993;36:24–32.
30. Shih Y. Families of splitting criteria for classification tress. Statistics and Computing 1999;9:309–15.
31. Oros D, Figueras F, Cruz-Martinez R, Meler E, Munmany M, Gratacos E. Longitudinal changes in uterine, umbilical and cerebral Doppler in late-onset small-for-gestational age fetuses. Ultrasound Obstet Gynecol. 2010 Jul 8 [Epub ahead of print].
32. Arbeille P, Maulik D, Fignon A, Stale H, Berson M, Bodard S, et al. Assessment of the fetal PO2 changes by cerebral and umbilical Doppler on lamb fetuses during acute hypoxia. Ultrasound Med Biol 1995;21:861–70.
33. Harrington K, Thompson MO, Carpenter RG, Nguyen M, Campbell S. Doppler fetal circulation in pregnancies complicated by pre-eclampsia or delivery of a small for gestational age baby: 2. Longitudinal analysis. Br J Obstet Gynaecol 1999;106:453–66.
34. Turan OM, Turan S, Gungor S, Berg C, Moyano D, Gembruch U, et al. Progression of Doppler abnormalities in intrauterine growth restriction. Ultrasound Obstet Gynecol 2008;32:160–7.
35. Bahado-Singh RO, Kovanci E, Jeffres A, Oz U, Deren O, Copel J, et al. The Doppler cerebroplacental ratio and perinatal outcome in intrauterine growth restriction. Am J Obstet Gynecol 1999;180:750–6.
36. Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis. BMJ 2010;340:c1471.
37. MacDorman MF, Menacker F, Declercq E. Trends and characteristics of home and other out-of-hospital births in the United States, 1990–2006. Natl Vital Stat Rep 2010;58:1–14, 6.
38. Royal College of Obstetricians and Gynaecologists. The Investigation and Management of the Small-for-Gestational-age Fetus. Evidence-based Clinical Guideline No. 31. London: RCOG 2002:1–16.
39. Boers KE, Vijgen SM, Bijlenga D, van der Post JA, Bekedam DJ, Kwee A, et al. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BMJ 2010 Dec 21;341:c7087.
40. Lilford RJ, van Coeverden de Groot HA, Moore PJ, Bingham P. The relative risks of caesarean section (intrapartum and elective) and vaginal delivery: a detailed analysis to exclude the effects of medical disorders and other acute pre-existing physiological disturbances. Br J Obstet Gynaecol 1990;97:883–92.
41. Towner D, Castro MA, Eby-Wilkens E, Gilbert WM. Effect of mode of delivery in nulliparous women on neonatal intracranial injury. N Engl J Med 1999;341:1709–14.
42. Caughey AB, Sundaram V, Kaimal AJ, Cheng YW, Gienger A, Little SE, et al. Maternal and neonatal outcomes of elective induction of labor. Evid Rep Technol Assess (Full Rep) 2009;176:1–257.
43. Figueras F, Fernandez S, Eixarch E, Gomez O, Martinez JM, Puerto B, et al. Middle cerebral artery pulsatility index: reliability at different sampling sites. Ultrasound Obstet Gynecol 2006;28:809–13.
Figure. No caption available.
© 2011 The American College of Obstetricians and Gynecologists
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Looking for ABOG articles? Visit our ABOG MOC II collection. The selected Green Journal articles are free through the end of the calendar year.
ACOG MEMBER SUBSCRIPTION ACCESS
If you are an ACOG Fellow and have not logged in or registered to Obstetrics & Gynecology, please follow these step-by-step instructions to access journal content with your member subscription.
Data is temporarily unavailable. Please try again soon.
Readers Of this Article Also Read