Objective
We sought to evaluate the association between fetal cerebroplacental ratio (CPR) and intrapartum fetal compromise and admission to the neonatal unit (NNU) in term pregnancies.
Study Design
This was a retrospective cohort study in a single tertiary referral center over a 14-year period from 2000 through 2013. The umbilical artery pulsatility index, middle cerebral artery pulsatility index, and CPR were recorded within 2 weeks of delivery. The birthweight (BW) values were converted into centiles and Doppler parameters converted into multiples of median (MoM), adjusting for gestational age using reference ranges. Logistic regression analysis was performed to identify, and adjust for, potential confounders.
Results
The study cohort included 9772 singleton pregnancies. The rates of operative delivery for presumed fetal compromise and neonatal admission were 17.2% and 3.9%, respectively. Doppler CPR MoM was significantly lower in pregnancies requiring operative delivery or admission to NNU for presumed fetal compromise ( P < .01). On multivariate logistic regression, both CPR MoM and BW centile were independently associated with the risk of operative delivery for presumed fetal compromise (adjusted odds ratio [OR], 0.67; 95% confidence interval [CI], 0.52–0.87; P = .003 and adjusted OR, 0.994; 95% CI, 0.992–0.997; P < .001, respectively). The latter associations persisted even after exclusion of small-for-gestational-age cases from the cohort. Multivariate logistic regression also demonstrated that CPR MoM was an independent predictor for NNU admission at term (adjusted OR, 0.55; 95% CI, 0.33–0.92; P = .021), while BW centile was not (adjusted OR, 1.00; 95% CI, 0.99–1.00; P = .794). The rates of operative delivery for presumed fetal compromise were significantly higher for appropriate-for-gestational-age fetuses with low CPR MoM (22.3%) compared to small-for-gestational-age fetuses with normal CPR MoM (17.3%).
Conclusion
Lower fetal CPR, regardless of the fetal size, was independently associated with the need for operative delivery for presumed fetal compromise and with NNU admission at term. The extent to which fetal hemodynamic status could be used to predict perinatal morbidity and optimize the mode of delivery merits further investigation.
Approximately 10-15% of cerebral palsy cases result from intrapartum hypoxia. Despite the clinical importance of intrapartum hypoxia, the antenatal identification of the fetus at risk of cerebral palsy and other hypoxia-related outcomes remains challenging. The widespread use of intrapartum cardiotocography (CTG) has not led to a reduction in the incidence of cerebral palsy. Likewise, admission CTG in early labor and amniotic fluid volume assessment have been shown to be of limited value in identifying fetuses at risk of intrapartum compromise. Adverse events related to fetal hypoxia, such as cerebral palsy and stillbirth, are known to be more frequent in fetal growth restriction (FGR) secondary to placental insufficiency. In clinical practice where fetal size is often used as a proxy for FGR, small-for-gestational-age (SGA) babies have 4 times the incidence of cesarean delivery for nonreassuring fetal status. This approach is limited by the inaccuracy of ultrasound in the detection of SGA fetuses and the finding that the majority of cerebral palsy cases are, in fact, born with a birthweight (BW) appropriate for gestational age (AGA). Antenatal fetal Doppler assessment also appears to be able to predict those SGA pregnancies likely to have cesarean delivery for nonreassuring fetal status. We have recently reported that fetal Doppler assessment might also be of value in detecting pregnancies that are AGA, yet complicated by placental insufficiency. Consistent with these results, Prior et al recently demonstrated in a small prospective study that, independent of fetal size, fetal cerebroplacental ratio (CPR) measured within 72 hours of delivery could identify those likely to require obstetric intervention for intrapartum fetal compromise. The main aim of this study was to investigate the association in term pregnancies between fetal CPR and both intrapartum fetal compromise and admission to the neonatal unit (NNU).
Materials and Methods
This was a retrospective cohort study (retrospective analysis of prospectively collected data) in a single tertiary referral center over a 14-year period from 2000 through 2013. Cases were identified by searching the ViewPoint database (ViewPoint 5.6.8.428; ViewPoint Bildverarbeitung GmbH, Weßling, Germany) in the Fetal Medicine Unit, St. George’s Hospital, London, United Kingdom. The inclusion criteria were singleton morphologically normal fetuses born at term (≥37 weeks’ gestation) that had an ultrasound scan within 2 weeks of delivery. Pregnancies complicated by fetal abnormality, aneuploidy, or stillbirth were excluded from the analysis. Elective cesarean delivery cases were also excluded from the analysis of operative delivery for intrapartum fetal compromise. Gestational age was calculated from the crown-rump length measurement at 11-13 weeks and only one (the last) examination per pregnancy was included in the analysis. For the pregnancies where the first ultrasound performed was in the second trimester (>14 weeks’ gestation), the pregnancy was dated according to the head circumference. Routine fetal biometry was performed according to a standard protocol and the estimated fetal weight (EFW) calculated using the formula of Hadlock et al. The umbilical artery (UA) and middle cerebral artery (MCA) Doppler waveforms were recorded using color Doppler, and the pulsatility index (PI) was calculated according to a standard protocol. The CPR was calculated as the simple ratio between the MCA PI and the UA PI. All Doppler indices were converted into multiples of median (MoM), correcting for gestational age using reference ranges and BW values were converted into centiles. The study cohort was divided into 4 groups according to a combination of a BW cutoff of the 10th centile and a CPR cutoff of 0.6765 MoM to assess the difference between the SGA model, which relies on fetal biometry, and the placental insufficiency model, which relies on fetal hemodynamic assessment.
Intrapartum data included whether the labor was induced or spontaneous, presence or absence of meconium-stained liquor (grade 2 or 3), CTG abnormalities (classified according to National Institute for Health and Clinical Excellence guidelines), ST analysis abnormalities, use of oxytocin for slow progress of labor, intrapartum pyrexia, intrapartum hemorrhage, use of epidural analgesia for labor, and mode of delivery. Data on maternal baseline characteristics and pregnancy outcomes were collected from hospital obstetric and neonatal records. The main outcome in this study was operative delivery for presumed fetal compromise. Operative delivery for fetal compromise included both cesarean delivery and instrumental delivery. The second outcome was admission to the NNU. The diagnosis of fetal compromise was based on CTG abnormalities, ST analysis abnormalities, abnormal fetal scalp blood sample pH, or a combination of these. Pregnancies that had an elective cesarean delivery were excluded from the analysis. The study was exempt from review by Wandsworth Research Ethics Committee.
Statistical analysis
Categorical data were presented as number (%) and were compared using the Fisher exact test or χ 2 test. Continuous data were presented as median (interquartile range). The D’Agostino and Pearson omnibus test was used to assess the normality of the data. Nonparametric analysis using Mann-Whitney U test was then used to compare continuous data between the study groups. Logistic regression analysis was performed to identify, and adjust for, potential confounders. We considered both maternal and intrapartum risk factors as important confounders for the 2 outcomes investigated in this study. As year was not found to be a significant confounder, we decided not to include it as a covariate. Both unadjusted and adjusted odds ratios were calculated. P values < .05 were considered statistically significant. All P values were 2-tailed. We did not perform a sample size calculation a priori as this was a retrospective study. We included all the pregnancies that fit the inclusion criteria and excluded those that fit the exclusion criteria. However, as the sample size was large, we thought that the analysis was adequately powered to address the outcomes chosen. The analysis was performed using the statistical software packages SPSS 18.0 (IBM Corp, Armonk, NY); Stata 11, Release 11.2 (StataCorp LP, College Station, TX); and GraphPad Prism 5.0 for Windows (GraphPad Software Inc, San Diego, CA).
Results
We identified 9772 pregnancies with fetal ultrasound and Doppler assessment within 2 weeks of delivery at term. We excluded 1390 pregnancies because they had aneuploidy, major structural abnormalities, stillbirth, or an elective cesarean delivery, leaving 8382 for the analysis of data related to operative delivery for fetal distress ( Figure 1 ). The prevalence of SGA in this cohort, defined as BW <10th centile, was 15.3%. The overall operative delivery for presumed fetal compromise was 17.2%, which was divided into emergency cesarean delivery (n = 757, 9.0%) and instrumental delivery (n = 684, 8.2%). Women who had operative delivery for presumed fetal compromise were significantly older and more likely to be nulliparous ( P < .01) ( Table 1 ). The rate of admission to NNU for presumed fetal compromise was significantly higher in the operative delivery group (10.0% vs 2.8%, P < .001).
| Pregnancy variables | No operative delivery for fetal compromise, n = 6941 | Operative delivery for fetal compromise, n = 1441 | P value |
|---|---|---|---|
| Antenatal variables | |||
| Maternal age, y, median (IQR) | 31.0 (27.0–35.0) | 32.0 (28.0–35.0) | .003 |
| Body mass index, kg/m 2 , median (IQR) | 24.10 (21.70–27.60) | 24.10 (21.70–27.20) | .714 |
| Nulliparous, n (%) | 3564 (51.3) | 1169 (81.1) | < .001 |
| Ethnicity, n (%) | .135 | ||
| Caucasian | 4211 (60.7) | 928 (64.4) | |
| African | 1167 (16.8) | 225 (15.6) | |
| South Asian | 1180 (17.0) | 217 (15.1) | |
| East Asian | 77 (1.1) | 18 (1.3) | |
| Mixed | 247 (3.6) | 41 (2.9) | |
| Other | 59 (0.9) | 12 (0.8) | |
| Smoker, n (%) | 474 (6.8) | 66 (4.6) | .002 |
| Alcohol use, n (%) | 104 (1.5) | 15 (1.04) | .182 |
| Drug use, n (%) | 47 (0.7) | 8 (0.6) | .602 |
| Ultrasound and Doppler variables | |||
| Gestational age at ultrasound, wk, median (IQR) | 40.4 (38.4–41.4) | 41.3 (39.6–41.4) | < .001 |
| Interval between scan and delivery, d, median (IQR) | 4.0 (2.0–7.0) | 5.0 (2.0–7.0) | .367 |
| Umbilical artery pulsatility index, median (IQR) | 0.82 (0.71–0.93) | 0.81 (0.71–0.93) | .948 |
| Umbilical artery pulsatility index MoM, median (IQR) | 1.00 (0.88–1.13) | 1.01 (0.89–1.16) | .003 |
| Middle cerebral artery pulsatility index, median (IQR) | 1.32 (1.12–1.55) | 1.23 (1.05–1.44) | < .001 |
| Middle cerebral artery pulsatility index MoM, median (IQR) | 1.30 (1.13–1.51) | 1.29 (1.12–1.50) | .237 |
| Cerebroplacental ratio, median (IQR) | 1.63 (1.35–1.95) | 1.53 (1.26–1.84) | < .001 |
| Cerebroplacental ratio MoM, median (IQR) | 0.96 (0.81–1.15) | 0.93 (0.77–1.11) | < .001 |
| Cerebroplacental ratio <0.6765 MoM, n (%) | 649 (9.4) | 188 (13.1) | < .001 |
| Intrapartum variables | |||
| Induction of labor, n (%) | 2549 (40.0) | 755 (52.4) | < .001 |
| Meconium-stained liquor (grade 2 or 3), n (%) | 137 (2.0) | 71 (4.9) | < .001 |
| Oxytocin use for slow progress in labor, n (%) | 1613 (23.2) | 708 (49.1) | < .001 |
| Intrapartum hemorrhage, n (%) | 16 (0.2) | 10 (0.7) | .006 |
| Intrapartum pyrexia, n (%) | 98 (1.5) | 114 (7.9) | < .001 |
| Epidural use, n (%) | 2297 (34.8) | 1094 (75.9) | < .001 |
| Variables at birth | |||
| Gestational age at delivery, wk, median (IQR) | 41.1 (39.4–41.9) | 41.6 (40.4–42.1) | < .001 |
| Fetal sex male, n (%) | 3517 (50.7) | 815 (56.6) | < .001 |
| Birthweight, g, median (IQR) | 3420 (3020–3800) | 3460 (3100–3820) | .01 |
| Birthweight centile, median (IQR) | 44.39 (18.59–73.17) | 45.0 (17.72–74.45) | .941 |
| Small for gestational age, n (%) | 1033 (14.9) | 236 (16.4) | .15 |
| Admission to neonatal unit, n (%) | 194 (2.8) | 139 (10.0) | < .001 |
Doppler ultrasound UA PI MoM was significantly higher and CPR MoM significantly lower in pregnancies requiring operative delivery for presumed fetal compromise ( P < .01) ( Table 1 ). The BW centile and prevalence of SGA were not significantly different between the 2 study groups ( P = .941 and P = .15, respectively). According to the multivariate logistic regression, both CPR MoM and BW centile were independently associated with the risk of operative delivery for presumed fetal compromise ( P < .05) ( Table 2 ). The latter associations persisted even after exclusion of SGA cases from the cohort ( Table 3 ). The overall neonatal admission rate in the study cohort was 3.9% ( Table 3 ). The admission to the NNU was significantly higher in nullipara, smokers, non-Caucasian ethnic origin, and those with larger body mass index ( P < .05) ( Table 4 ). UA PI MoM was significantly higher, while MCA PI and CPR MoM were significantly lower, in pregnancies where the newborn was admitted to the NNU ( P < .05) ( Table 4 ). The BW centile was not significantly different between the 2 groups ( P = .064), while the prevalence of SGA was ( P < .001) ( Table 4 ). According to the multivariate logistic regression, CPR MoM was an independent predictor for neonatal admission at term ( P = .021), while BW centile was not ( P = .794) ( Table 5 ).
| Risk factor | Unadjusted OR | 95% CI | P value | Adjusted OR | 95% CI | P value |
|---|---|---|---|---|---|---|
| Maternal age, y | 1.02 | 1.01–1.03 | .001 | 1.04 | 1.02–1.05 | < .001 |
| Body mass index, kg/m 2 | 1.00 | 0.98–1.01 | .49 | 1.01 | 0.96–1.02 | .182 |
| Multiparous | 0.25 | 0.21–0.28 | < .001 | 0.38 | 0.31–0.45 | < .001 |
| Ethnicity | 0.94 | 0.89–0.99 | .016 | 1.08 | 1.02–1.16 | .013 |
| Smoking | 0.65 | 0.50–0.85 | .002 | 0.83 | 0.61–1.13 | .229 |
| Drug abuse | 0.82 | 0.39–1.74 | .602 | 0.73 | 0.29–1.82 | .501 |
| Alcohol use | 0.69 | 0.40–1.19 | .184 | 0.78 | 0.41–1.49 | .449 |
| Cerebroplacental ratio MoM | 0.59 | 0.48–0.74 | < .001 | 0.67 | 0.52–0.87 | .003 |
| Gestational age at delivery, wk | 1.30 | 1.25–1.36 | < .001 | 1.18 | 1.12–1.25 | < .001 |
| Birthweight centiles | 0.99 | 0.998–1.002 | .941 | 0.994 | 0.992–0.997 | < .001 |
| Intrapartum factors | ||||||
| Induction of labor | 1.88 | 1.67–2.10 | < .001 | 1.28 | 1.12–1.47 | < .001 |
| Epidural use | 5.92 | 5.19–6.75 | < .001 | 4.00 | 3.38–4.70 | < .001 |
| Intrapartum pyrexia | 5.71 | 4.33–7.52 | < .001 | 2.66 | 1.94–3.63 | < .001 |
| Intrapartum hemorrhage | 2.88 | 1.30–6.36 | .009 | 4.34 | 1.64–11.53 | .003 |
| Oxytocin used for slow progress | 3.19 | 2.84–3.59 | < .001 | 1.02 | 0.87–1.19 | .838 |
| Meconium grade 2/3 | 2.53 | 1.89–3.38 | < .001 | 3.31 | 2.32–4.73 | < .001 |
| Risk factor | Unadjusted OR | 95% CI | P value | Adjusted OR | 95% CI | P value |
|---|---|---|---|---|---|---|
| Maternal age, y | 1.02 | 1.01–1.03 | .001 | 1.04 | 1.02–1.05 | < .001 |
| Body mass index, kg/m 2 | 1.00 | 0.98–1.01 | .535 | 1.01 | 1.00–1.03 | .145 |
| Multiparity | 0.24 | 0.21–0.28 | < .001 | 0.39 | 0.32–0.47 | < .001 |
| Ethnicity | 0.92 | 0.87–0.98 | .011 | 1.08 | 1.01–1.16 | .031 |
| Smoking | 0.68 | 0.50–0.92 | .013 | 0.86 | 0.61–1.22 | .394 |
| Drug abuse | 0.56 | 0.20–1.58 | .271 | 0.54 | 0.18–1.59 | .262 |
| Alcohol use | 0.86 | 0.50–1.50 | .603 | 0.89 | 0.46–1.71 | .721 |
| Cerebroplacental ratio MoM | 0.61 | 0.48–0.77 | <.001 | 0.68 | 0.52–0.91 | .009 |
| Gestational age at delivery, wk | 1.40 | 1.33–1.48 | < .001 | 1.21 | 1.14–1.29 | < .001 |
| Birthweight centiles | 1.00 | 0.999–1.003 | .24 | 0.996 | 0.993–0.999 | .007 |
| Intrapartum factors | ||||||
| Induction of labor | 1.86 | 1.64–2.11 | < .001 | 1.24 | 1.07–1.44 | .005 |
| Epidural use | 6.21 | 5.37–7.19 | < .001 | 4.03 | 3.34–4.85 | < .001 |
| Intrapartum pyrexia | 5.66 | 4.23–7.57 | < .001 | 2.67 | 1.92–3.72 | < .001 |
| Intrapartum hemorrhage | 2.20 | 0.89–5.40 | .86 | 3.12 | 1.00–9.75 | .05 |
| Oxytocin used for slow progress | 3.33 | 2.93–3.79 | < .001 | 1.03 | 0.87–1.21 | .761 |
| Meconium grade 2/3 | 2.62 | 1.83–3.47 | < .001 | 2.87 | 1.94–4.24 | < .001 |
| Pregnancy variables | No neonatal admission n = 8842 | Neonatal admission n = 356 | P value |
|---|---|---|---|
| Antenatal criteria | |||
| Maternal age, y, median (IQR) | 31.0 (27.0–35.0) | 30.0 (26.0–33.8) | .001 |
| Body mass index, kg/m 2 , median (IQR) | 24.10 (21.70–27.70) | 24.95 (21.90–28.63) | .033 |
| Nulliparous, n (%) | 4829 (54.6) | 232 (65.2) | < .001 |
| Ethnicity, n (%) | .014 | ||
| Caucasian | 5450 (61.6) | 197 (55.3) | |
| African | 1452 (16.4) | 77 (21.6) | |
| South Asian | 1462 (16.5) | 70 (19.7) | |
| East Asian | 102 (1.2) | 4 (1.1) | |
| Mixed | 301 (3.4) | 8 (2.3) | |
| Other | 75 (0.9) | 0 | |
| Smoker, n (%) | 547 (6.2) | 32 (9.0) | .033 |
| Alcohol use, n (%) | 132 (1.5) | 2 (0.6) | .151 |
| Drug use, n (%) | 51 (0.6) | 4 (1.1) | .19 |
| Ultrasound and Doppler criteria | |||
| Gestational age at ultrasound, wk, median (IQR) | 40.4 (38.3–41.4) | 40.3 (37.7–41.4) | .203 |
| Interval between scan and delivery, d, median (IQR) | 4.0 (2.0–8.0) | 5.0 (2.0–8.0) | .049 |
| Umbilical artery pulsatility index, median (IQR) | 0.82 (0.71–0.93) | 0.84 (0.73–0.96) | .018 |
| Umbilical artery pulsatility index MoM, median (IQR) | 1.00 (0.88–1.13) | 1.01 (0.90–1.15) | .038 |
| Middle cerebral artery pulsatility index, median (IQR) | 1.32 (1.12–1.55) | 1.30 (1.10–1.52) | .385 |
| Middle cerebral artery pulsatility index MoM, median (IQR) | 1.29 (1.13–1.50) | 1.26 (1.08–1.47) | .033 |
| Cerebroplacental ratio, median (IQR) | 1.63 (1.35–1.95) | 1.54 (1.30–1.89) | .005 |
| Cerebroplacental ratio MoM, median (IQR) | 0.96 (0.80–1.15) | 0.92 (0.77–1.10) | .003 |
| Cerebroplacental ratio <0.6765 MoM, n (%) | 857 (9.7) | 51 (14.3) | .004 |
| Intrapartum criteria | |||
| Induction of labor, n (%) | 3163 (39.4) | 146 (44.1) | .087 |
| Meconium-stained liquor (grade 2 or 3), n (%) | 177 (2.0) | 31 (8.7) | < .001 |
| Oxytocin use for slow progress in labor, n (%) | 2200 (24.9) | 124 (34.8) | < .001 |
| Intrapartum hemorrhage, n (%) | 23 (0.3) | 3 (1.0) | .037 |
| Intrapartum pyrexia, n (%) | 177 (2.3) | 34 (11.2) | < .001 |
| Epidural use, n (%) | 2297 (34.8) | 1094 (75.9) | < .001 |
| Criteria at birth | |||
| Gestational age at delivery, wk, median (IQR) | 41.1 (39.3–41.9) | 41.1 (38.5–42.0) | .526 |
| Fetal sex male, n (%) | 4524 (51.2) | 213 (59.8) | .001 |
| Birthweight (g), median (IQR) | 3420 (3012–3800) | 3400 (2860–3780) | .052 |
| Birthweight centile, median (IQR) | 44.33 (18.66–73.28) | 40.37 (12.56–71.99) | .064 |
| Small for gestational age, n (%) | 1328 (15.0) | 78 (21.9) | < .001 |
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