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The association between fetal Doppler and admission to neonatal unit at term Asma A. Khalil, MD, MRCOG; Jose´ Morales-Rosello, MD; Malaz Elsadigg; Naila Khan; Aris Papageorghiou, MD, MRCOG; Amar Bhide, MD, MRCOG; Basky Thilaganathan, PhD, MRCOG OBJECTIVE: Fetal cerebroplacental ratio is emerging as a better proxy
than birthweight for placental insufficiency and as a marker of fetal compromise at term. The extent to which these fetal Doppler changes are related to neonatal outcomes has not been systematically assessed. The main aim of this study was to evaluate the association between estimated fetal weight percentile, cerebroplacental ratio recorded at 34þ0e35þ6 weeks’ gestation, and neonatal unit admission at term. STUDY DESIGN: This was a retrospective cohort study in a tertiary referral center over an 11 year period from 2002 to 2012. The umbilical artery pulsatility index (PI), middle cerebral artery PI, and cerebroplacental ratio were recorded at 34þ0e35þ6 weeks. Weight values were converted into percentiles and Doppler parameters into multiples of the median (MoM), adjusting for gestational age. Logistic regression analysis was performed to identify, and adjust for, potential confounders. RESULTS: We identified 2518 pregnancies in which a scan was performed at 34þ0e35þ6 weeks and delivery occurred at or beyond 37 weeks. In the 2485 pregnancies included in the analysis, the umbilical artery PI MoM was significantly higher, and the middle cerebral artery PI and cerebroplacental ratio MoM significantly lower in
the babies requiring neonatal unit admission (P < .05). However, the estimated fetal weight percentile was not significantly different between those who required neonatal unit admission and those who did not (P ¼ .087). According to multivariate logistic regression, cerebroplacental ratio MoM (odds ratio, 0.39; 95% confidence interval, 0.19e0.79; P ¼ .008) and gestational age at delivery (odds ratio, 0.70; 95% confidence interval, 0.61e0.80; P < .001) were significantly associated with the risk of neonatal unit admission, whereas maternal age and birthweight percentile were not (P ¼ .183 and P ¼ .460, respectively). Irrespective of birthweight or estimated fetal weight percentile, the fetal cerebroplacental ratio appears to be a better predictor of the need for neonatal unit admission (P < .001). CONCLUSION: Lower cerebroplacental ratio and gestational age at
delivery, but not fetal size, were independently associated with the need for admission to the neonatal unit at term in a high-risk patient group. The extent to which fetal hemodynamic assessment could be used to predict perinatal morbidity and optimize the timing of delivery merits further investigation. Key words: birthweight, cerebroplacental ratio, Doppler, neonatal unit admission, small for gestational age
Cite this article as: Khalil AA, Morales-Rosello J, Elsadigg M, et al. The association between fetal Doppler and admission to neonatal unit at term. Am J Obstet Gynecol 2014;212:xx-xx.
S
mall for gestational age (SGA), defined as birthweight (BW) less than the 10th percentile for gestation, is commonly used as a proxy to identify fetuses at risk of adverse outcomes secondary to fetal growth restriction.1,2 However, the majority of SGA babies are not pathologically growth restricted
From the Fetal Medicine Unit, St George’s Hospital, St George’s University of London, London, England, UK. Received June 15, 2014; revised Aug. 23, 2014; accepted Oct. 7, 2014. The authors report no conflict of interest. Corresponding author: Asma Khalil, MD, MRCOG. [email protected] 0002-9378/$36.00 ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2014.10.013
and do not demonstrate signs of placental insufficiency. The clinical definition of SGA is further confused by the finding that a proportion of average for gestational age (AGA) infants also fail to meet their growth potential or, more correctly, suffer from occult placental insufficiency.3,4 We and others have recently reported that fetal Doppler assessment immediately prior to delivery at term might be of value in detecting AGA pregnancies that are at increased risk of adverse outcome from fetal hypoxemia secondary to placental insufficiency and failure to reach growth potential.4,5 Fetal Doppler indices assessed just prior to delivery appear to be a better marker than BW or BW percentile for adverse pregnancy outcomes, such as the need for operative delivery for fetal compromise in an
average risk group for fetal growth restriction (FGR).4,5 However, national guidance in the United Kingdom and the United States does not recommend the use of fetal Doppler as a screening tool for placental insufficiency, except when the fetus is already known to be SGA.1,2 The antenatal diagnosis of FGR using fetal biometry alone has recently been challenged, and the use of fetal Doppler assessment has been proposed as a potentially better marker.4,6,7 It is now increasingly routine in many hospitals and individual practices to undertake a 34-36 week ultrasound scan for fetal assessment. There is a paucity of data to support such routine assessment, but nevertheless its proponents are convinced of its utility. The main aim of this study was to investigate the association between fetal Doppler and
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ultrasound parameters at the 34-36 week growth scan and the need for neonatal unit admission at term.
M ATERIALS
AND
M ETHODS
This was a retrospective cohort study in a single tertiary referral center over an 11 year period from 2002 to 2012. 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. The inclusion criteria were singleton morphologically normal fetuses born at term that had previously had an ultrasound scan at 34þ0e35þ6 weeks’ gestation for a variety of indications such as suspected poor/excessive fetal growth, reduced fetal movements, history of SGA or large for gestational age baby, high midtrimester uterine artery Doppler indices, and gestational diabetes. Therefore, these pregnancies were at risk of fetal growth disorders. Pregnancies complicated by fetal abnormality, aneuploidy, or antepartum stillbirth were excluded from the analysis. Gestational age (GA) was calculated from the crown-rump length measurement at 11-13 weeks, and only 1 examination (the last in the 34þ0e35þ6 week window) per fetus was included in the analysis.8 Routine fetal biometry was performed according to a standard protocol and the estimated fetal weight (EFW) calculated using Hadlock’s formula.9 Data on pregnancy outcomes were collected from hospital obstetric and neonatal records. The umbilical artery (UA) and middle cerebral artery (MCA) Doppler were recorded using color Doppler, and the pulsatility index (PI) calculated according to a standard protocol.10,11 The cerebroplacental ratio (CPR) was calculated as the simple ratio of the MCA PI to the UA PI.12 All Doppler indices were converted into multiples of the median (MoM) correcting for GA using reference ranges, and BW values were converted into percentiles.4,13,14 The study cohort was divided into 4 groups according to a combination of a BW cutoff of the 10th percentile and an optimal CPR cutoff of 0.6765 MoM4 to
ajog.org assess the difference between the SGA model, which relies on fetal biometry, and the placental insufficiency model, which relies on fetal hemodynamic assessment. This was derived from our previous work in which, to define the threshold for the failure to achieve growth potential, we calculated the fifth centile of the CPR in the group least likely to present with failure to achieve growth potential (those with BW greater than the 90th percentile). This value corresponded to 0.6765.4 Data on admission to the neonatal unit were ascertained from the maternity and neonatal records. The indications for admission to the neonatal unit were respiratory complications (defined as respiratory distress syndrome and transient tachypnea of the newborn, use of continuous positive airway pressure, endotracheal intubation), hypoglycemia, sepsis, need for phototherapy, postresuscitation observation, seizures, and hypothermia.
Statistical analysis Categorical data were presented as number (percentage) and were compared using the Fisher exact test or the c2 test. Continuous data were presented as median (interquartile range [IQR]). The D’Agostino and Pearson Omnibus test was used to assess the normality of the data. Nonparametric analysis using the Mann-Whitney U test was then used to compare continuous data between the study groups. A logistic regression analysis was performed to identify, and adjust for, potential confounders. Both unadjusted and adjusted odds ratios (ORs) were calculated. The analysis was performed using the statistical software packages SPSS 18.0 (SPSS Inc, Chicago, IL), Stata 11 (release 11.2; College Station, TX), and GraphPad Prism 5.0 for Windows (InStat; GraphPad Software Inc, San Diego, CA).
R ESULTS We identified 2518 pregnancies with fetal Doppler assessment at 34þ0e35þ6 weeks, in which the delivery occurred at or beyond 37 weeks’ gestation. We excluded 33 pregnancies (1.3%) because they had aneuploidy, major structural
abnormalities, stillbirth, or missing outcome data, leaving 2485 pregnancies included in the analysis. The maternal characteristics, ultrasound, and birth indices in the groups requiring and not requiring admission to the neonatal unit are shown in Table 1. The prevalence of SGA, defined as BW less than the 10th percentile and the fifth percentile, was 25.8% and 14.0%, respectively. The overall neonatal admission rate in the study cohort was 6.7%. This fell with advancing gestation from 16.8% to 8.7%, 4.2% and 4.2% at 37, 38, 39, and longer than 40 weeks, respectively. The most common indications for admission to the neonatal unit were respiratory complications and postresuscitation observation. There were 2 early neonatal deaths and 1 late neonatal death. The scatter plot of CPR MoM values against BW percentiles showed a significant linear relationship (Figure 1: CPR MoM ¼ (0.0019 BW percentile) þ 0.9705, R2 ¼ 0.049). At the ultrasound assessment, UA PI MoM was significantly higher and MCA PI and CPR MoM were significantly lower in the neonates requiring neonatal unit admission (P < .05, Table 1, Figure 2), but the EFW percentile was not significantly different between the 2 study groups (P ¼ .087). The results of the regression analysis are shown in Tables 2 and 3. According to a multivariate logistic regression, CPR MoM, GA at delivery, maternal ethnicity, and male gender were significantly associated with the risk of neonatal unit admission (P < .05), whereas maternal age and BW percentile were not (P ¼ .183 and P ¼ .460, respectively). When divided into 4 groups according to a combination of a BW cutoff of the 10th percentile and an optimal CPR cutoff of 0.6765 MoM, the rates of neonatal unit admission were significantly different (P < .001, Figure 3). The incidence of admission to the neonatal unit in the AGA neonates with low CPR (9.8%) was almost double that in the group of AGA with normal CPR (5.5%). However, the difference in the admission rates between the groups of AGA with low CPR and AGA with
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TABLE 1
Maternal and fetal characteristics in the study cohort according to admission to the neonatal unit Neonatal unit admission (n [ 167)
Characteristic Maternal age, y, median (IQR)
31.0 (27.0e34.0)
No neonatal unit admission (n [ 2318) 31.0 (26.0e34.0)
Ethnicity
P value .133 .276
White, n (%)
101 (60.5)
1230 (53.1)
African, n (%)
30 (18.0)
416 (18.0)
Asian, n (%)
30 (18.0)
522 (22.5)
Mixed, n (%)
4 (2.4)
100 (4.3)
Other, n (%)
2 (1.2)
50 (2.2)
Gestational age at ultrasound (wks), median (IQR) Estimated fetal weight (g), median (IQR) Estimated fetal weight percentile, median (IQR)
34.9 (34.4e35.4)
35.0 (34.4e35.6)
.113
2356 (2085e2651)
2426 (2183e2690)
.025
28.92 (11.45e54.01)
32.89 (15.60e55.77)
.087
0.95 (0.85e1.08)
0.91 (0.80e1.03)
.008
UA PI MoM
1.01 (0.89e1.14)
0.97 (0.85e1.09)
.014
MCA PI
1.73 (1.50e1.98)
1.80 (1.60e2.02)
.002
MCA PI MoM
1.17 (1.00e1.30)
1.21 (1.08e1.37)
.001
Cerebroplacental ratio
1.87 (1.50e2.25)
2.00 (1.70e2.31)
< .001
UA PI
Cerebroplacental ratio MoM
0.95 (0.76e1.15)
Gestational age at delivery (wks), median (IQR) Birthweight (g), median (IQR)
1.02 (0.87e1.18)
< .001
38.9 (37.7e40.0)
39.6 (38.6e40.6)
< .001
2955 (2500e3470)
3140 (2780e3520)
< .001
Birthweight percentile, median (IQR)
19.01 (4.67e57.80)
Fetal sex male, n (%)
98 (59.4)
28.32 (10.09e58.43) 1140 (49.3)
.005 .012
IQR, interquartile range; MCA, middle cerebral artery; PI, pulsatility index; MoM, multiples of median; UA, umbilical artery. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
normal CPR was not statistically significant (P ¼ .203). This could be related to the small number of cases in these 2 groups because admission to the neonatal unit in healthy newborns at term is a relatively uncommon event. We also investigated the association between fetal Doppler parameters and the risk of admission to the neonatal unit in the pregnancies that were SGA (BW less than 10th percentile, n ¼ 640) in which the rate of admission to the neonatal unit was 10%. Compared with those not requiring admission, neonates requiring neonatal unit admission had significantly lower median BW percentile (2.70, IQR, 0.73e5.89 vs 4.69, IQR, 2.34e7.38), GA at delivery in weeks (38.35, IQR, 37.45e39.40 vs 39.10, IQR, 38.30e40.10), MCA PI MoM (1.11, IQR, 0.97e1.24 vs 1.19,
IQR, 1.06e1.35), and CPR MoM (0.84, IQR, 0.67e0.99 vs 0.94, IQR, 0.80e1.09). BW percentile, MCA PI MoM, and CPR MoM were significantly associated with the risk of neonatal unit admission (P < .001, Table 4), whereas the UA PI MoM and EFW percentile were not (P ¼ .115 and P ¼ .213, respectively). According to the multivariate logistic regression in SGA neonates, both BW percentile (OR, 0.87; 96% confidence interval [CI], 0.78e0.96; P ¼ .008) and CPR MoM (OR, 0.21; 96% CI, 0.06e0.77; P ¼ .018) were significantly and independently associated with the risk of neonatal unit admission. The prevalence of SGA, defined as BW less than the third percentile, was 8.5%. The neonatal unit admission rate in this cohort was 15.8%, which was
significantly higher in those with low CPR MoM compared with those with normal CPR MoM (30.2% vs 12.2%, P ¼ .004).
C OMMENT The findings of this study suggest that neonates that were admitted to the neonatal unit at term had significantly lower CPR at 34-36 weeks, whereas both ultrasound EFW and BW percentiles were not significantly different from those not admitted. A multivariate logistic regression demonstrated that CPR MoM at 34-36 weeks was almost twice as likely as GA at delivery to determine the need for neonatal unit admission. It was also the case that, among the SGA neonates at term, those with a lower CPR MoM at 34-36 weeks had a higher risk
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FIGURE 1
Scatter plot of CPR MoM values against BW percentile
Scatter plot of CPR MoM values against BW percentile, showing a significant linear relationship (CPR MoM ¼ [0.0019 BW percentile] þ 0.9705, R2 ¼ 0.049). BW, birthweight; CPR, cerebroplacental ratio; MoM, multiple of median. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
ajog.org of a neonatal unit admission compared with those with normal CPR MoMs.
Findings in term pregnancies The novel observation in our cohort is that CPR, but not BW, percentiles, measured at 34-36 weeks’ gestation, are significantly and independently associated with the need for neonatal unit admission at term. In a recent prospective study including 400 term pregnancies (37-42 weeks), the investigators assessed fetal biometry and Doppler parameters immediately before established labor.5 Fetuses with CPR below the10th percentile were 6 times more likely to be delivered by cesarean delivery for presumed fetal compromise than those with a CPR above the10th percentile.5 Even after the exclusion of cases with a BW below the 10th percentile, the rate of cesarean delivery for presumed fetal compromise remained significantly higher in fetuses with a CPR less than the 10th percentile.5 In the Generation R Study (Rotterdam, The Netherlands, 2003-2007), Roza et al15 reported that, even in the general
FIGURE 2
Cerebroplacental ratio MoM values and percentiles
Box and whisker plots of cerebroplacental ratio MoM values and birthweight percentiles in newborns who were admitted to the neonatal unit and those who were not. The horizontal line in the box represents the median, the box represents the IQR, and the whiskers indicate the minimum and maximum values. IQR, interquartile range; MoM, multiple of median. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
population, an abnormal CPR at term predicts neurobehavioral problems at 18 months of age on internalizing and somatic complaints scales.
Findings in term SGA pregnancies The role of fetal Doppler in term and near-term pregnancies may currently be underestimated because of the rarity of abnormal UA Doppler indices at this gestation and the fact that FGRrelated perinatal morbidity has been noted to occur even when the UA blood flow is normal.16-18 In our cohort the rate of neonatal unit admission was almost 3 times higher in SGA neonates with low CPR MoM compared with those SGA neonates with normal CPR MoM (23% vs 8%). The role of the MCA Doppler in SGA pregnancies at term has been investigated in previous studies.16,18-22 Chang et al18 reported that fetal Doppler PI ratios recorded in the third trimester (aortic/middle cerebral and renal/middle cerebral PI ratios) were superior to predelivery estimates of fetal size in predicting suboptimal perinatal outcome in small fetuses delivering at term. The suboptimal perinatal outcome in the latter study was defined as acidemia at birth, fetal distress requiring emergency cesarean delivery in labor, or admission to the neonatal unit.18 Hershkovitz et al16 also demonstrated an association between MCA blood flow redistribution in structurally normal fetuses with an EFW below the fifth percentile and an increased risk of cesarean delivery and need for neonatal unit admission. CPR has been shown to correlate better with adverse outcome than does UA and MCA Doppler.23,24 Findings in preterm SGA pregnancies In pregnancies with SGA neonates, BW percentiles and CPR MoMs at 34-36 weeks’ gestation, but not EFW percentiles at 34-36 weeks, were independently associated with neonatal unit admission at term. These findings are consistent with the recent Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study, in which in 1200 pregnancies with EFW less than the 10th percentile
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TABLE 2
Results of the logistic regression analysis of factors associated with the risk of admission to the neonatal unit Risk factor
Research
Rates of neonatal unit admission in the 4 study groups
P value
Unadjusted OR
95% CI
Maternal age, y
1.02
(1.00e1.05)
.106
Maternal ethnicity
0.83
(0.70e0.98)
.026
Maternal characteristics
Ultrasound indices EFW percentile
1.00
(0.99e1.00)
.245
UA PI MoM
3.00
(1.23e7.28)
.016
MCA PI MoM
0.26
(0.12e0.55)
< .001
Cerebroplacental ratio MoM
0.83
(0.70e0.98)
< .001
Fetal sex (female)
0.67
(0.48e0.92)
.013
Indices at birth GA at delivery, wk
0.67
(0.59e0.76)
< .001
BW percentile
0.99
(0.99e1.00)
.079
BW, birthweight; CI, confidence interval; EFW, estimated fetal weight; GA, gestational age; MCA, middle cerebral artery; MoM, multiples of median; OR, odds ratio; PI, pulsatility index; UA, umbilical artery. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
prospectively followed up, 95% of those with abdominal circumference below the 10th percentile had a normal pregnancy outcome.25 Importantly, the authors noted that the presence of an abnormal UA Doppler was significantly associated with adverse outcome, irrespective of EFW or abdominal circumference measurement.25 Furthermore, the only sonographic weight-related
parameter that was significantly associated with adverse outcome was EFW below the third percentile.25 Despite the fact that the authors stated in the methodology that MCA Doppler had been performed, these data were not reported in the results.25 The neonatal admission rate in that SGA cohort was 28%, compared with 10% in our cohort of 640 pregnancies with SGA. This
TABLE 3
Results of the multivariate logistic regression analysis of factors associated with the risk of admission to the neonatal unit Risk factor
P value
Adjusted OR
95% CI
Maternal age, y
1.02
(0.99e1.05)
.183
Maternal ethnicity
0.81
(0.68e0.97)
.020
Cerebroplacental ratio MoM
0.39
(0.19e0.78)
.008
Fetal sex (female)
0.67
(0.48e0.94)
.020
GA at delivery, wks
0.70
(0.61e0.80)
< .001
BW percentile
1.00
(0.99e1.00)
.460
Maternal characteristics
Ultrasound indices
Indices at birth
BW, birthweight; CI, confidence interval; GA, gestational age; MoM, multiples of median; OR, odds ratio. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
The rates of neonatal unit admission in the 4 study groups according to a combination of a BW cutoff of the 10th percentile and a CPR cutoff of 0.6765 MoM. AGA, average for gestational age; BW, birthweight; CPR, cerebroplacental ratio; SGA, small for gestational age. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
difference may be due to variations in gestation at assessment and delivery as well as in neonatal unit admission policies in the 2 studies. Despite this discrepancy, the findings of both studies question the currently accepted definition of FGR and emphasize the importance of fetal hemodynamic assessment as a predictor of adverse pregnancy outcome in all fetal weight categories.
Strengths and limitations The strengths of our study include the large number of pregnancies, adjusting for GA, ascertainment of the outcome data, and the narrow GA range at ultrasound assessment. However, the retrospective design, lack of detailed robust data on the intrapartum events, and the higher proportion of SGA (25.8%) in the study population limit the generalizability of our findings. The higher prevalence of SGA in our cohort could be explained by the fact that pregnancies at risk of SGA were more likely to have an ultrasound assessment at 34-36 weeks’ gestation. However, we see this as a strength because despite the bias toward lower BW and higher prevalence of SGA, CPR was more strongly associated with neonatal unit admission. A high proportion of neonatal unit admissions are short term, with full recovery and discharge home. Prolonged neonatal
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TABLE 4
Factors associated with neonatal unit admission in SGA newbornsa Risk factor
P value
Unadjusted OR
95% CI
Maternal age, y
1.03
0.98e1.07
.255
Maternal ethnicity
0.69
0.53e0.91
.008
Maternal characteristics
Ultrasound indices EFW percentile
0.98
0.96e1.01
.213
UA PI MoM
3.06
0.76e12.27
.115
MCA PI MoM
0.88
0.24e0.32
< .001
Cerebroplacental ratio MoM
0.12
0.03e0.42
.001
Fetal sex (female)
0.70
0.42e1.18
.184
Indices at birth GA delivery, wks
0.68
0.55e0.86
.001
BW percentile
0.84
0.76e0.92
< .001
BW less than fifth percentile
2.13
1.22e3.74
.008
BW, birthweight; CI, confidence interval; EFW, estimated fetal weight; GA, gestational age; MCA, middle cerebral artery; MoM, multiples of median; OR, odds ratio; PI, pulsatility index; SGA, small for gestational age (defined as birthweight less than 10th percentile); UA, umbilical artery. a
Determined by logistic regression analysis.
Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
intensive care unit admission and neonatal morbidity are the subjects of a future study. Approximately 10% of term babies may require admission to the neonatal unit.26 The commonest indications include respiratory complications, postresuscitation observation, and hypoglycemia. These adverse events are more likely to occur in FGR babies, or more correctly, babies compromised by placental insufficiency. Admission to the neonatal unit at term is usually an unexpected event for both parents and health care professionals. It also represents a burden on health care resources and reflects the quality of intrapartum care. For these reasons, it is one of the national health care quality measures in many Western countries, including the United Kingdom and the United States. We have shown that lower CPR at 34-36 weeks and GA at delivery, but not BW percentiles at 34-36 weeks, were independently associated with the need for admission to the neonatal unit at term.
These findings support the assertion that fetal Doppler assessment could be of value in detecting fetal hypoxemia secondary to placental insufficiency and failure to reach their genetic growth potential in apparently AGA pregnancies. AGA pregnancies can demonstrate fetal cerebral and placental blood flow redistribution indicative of an increased risk of adverse pregnancy outcome as a consequence of fetal hypoxemia secondary to placental insufficiency.4 Despite this significant association between fetal Doppler and the need for neonatal unit admission at term, its predictive accuracy as an isolated marker is likely to be poor because of the confounding effect of the process of labor and birth.27 Whether fetal Doppler assessment in AGA pregnancies is predictive of perinatal morbidity or neurodevelopmental delay is unknown. The extent to which fetal hemodynamic assessment could be used to optimize the timing of delivery and reduce neurodevelopmental impairment merits further investigation. -
1. American College of Obstetricians and Gynecologists. Intrauterine growth restriction. ACOG practice bulletin no. 12. Int J Gynecol Obstet 2001;72:85-96. 2. Royal College of Obstetricians and Gynaecologists. The investigation and management of the small-for-gestational-age fetus. Green-top guideline number 31. London (UK): Royal College of Obstetricians and Gynaecologists; 2013. 3. Maulik D. Fetal growth compromise: definitions, standards, and classification. Clin Obstet Gynecol 2006;49:214-8. 4. Morales-Roselló J, Khalil A, Morlando M, Papageorghiou A, Bhide A, Thilaganathan B. Changes in fetal Doppler as a marker of failure to reach growth potential at term. Ultrasound Obstet Gynecol 2014;43:303-10. 5. Prior T, Mullins E, Bennett P, Kumar S. Prediction of intrapartum fetal compromise using the cerebroumbilical ratio: a prospective observational study. Am J Obstet Gynecol 2013;208: 124.e1-6. 6. Sebire NJ. Detection of fetal growth restriction at autopsy in non-anomalous stillborn infants. Ultrasound Obstet Gynecol 2014;43:241-4. 7. Figueras F, Gratacós E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther 2014;36:86-98. 8. Robinson HP, Fleming JE. A critical evaluation of sonar “crown-rump length” measurements. BJOG 1975;82:702-10. 9. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements, a prospective study. Am J Obstet Gynecol 1985;151:333-7. 10. Acharya G, Wilsgaard T, Berntsen GK, Maltau JM, Kiserud T. Reference ranges for serial measurements of umbilical artery Doppler indices in the second half of pregnancy. Am J Obstet Gynecol 2005;192:937-44. 11. Bahlmann F, Reinhard I, Krummenauer F, Neubert S, Macchiella D, Wellek S. Blood flow velocity waveforms of the fetal middle cerebral artery in a normal population: reference values from 18 weeks to 42 weeks of gestation. J Perinat Med 2002;30:490-501. 12. Baschat AA, Gembruch U. The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol 2003;21:124-7. 13. Morales Roselló J, Hervás Marín D, Fillol Crespo M, Perales Marín A. Doppler changes in the vertebral, middle cerebral, and umbilical arteries in fetuses delivered after 34 weeks: relationship to severity of growth restriction. Prenat Diagn 2012;32:960-7. 14. Yudkin PL, Aboualfa M, Eyre JA, Redman CW, Wilkinson AR. New birthweight and head circumference percentiles for gestational ages 24 to 42 weeks. Early Hum Dev 1987;15:45-52. 15. Roza SJ, Steegers EA, Verburg BO, et al. What is spared by fetal brain-sparing? Fetal circulatory redistribution and behavioral problems
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20. 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. 21. Fong KW, Ohlsson A, Hannah ME, et al. Prediction of perinatal outcomes in fetuses suspected to have intrauterine growth restriction: Doppler US study of fetal cerebral, renal and umbilical arteries. Radiology 1999;213: 681-9. 22. Harrington K, Carpenter RG, Nguyen M, Campbell S. Changes observed in Doppler studies of the fetal circulation in pregnancies complicated by pre-eclampsia or the delivery of a small-for-gestational-age baby. I. Crosssectional analysis. Ultrasound Obstet Gynecol 1995;6:19-28. 23. Bahado-Singh RO, Kovanci E, Jeffres A, et al. The Doppler cerebroplacental ratio and
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perinatal outcome in intrauterine growth restriction. Am J Obstet Gynecol 1999;180:750-6. 24. 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. 25. Unterscheider J, Daly S, Geary MP, et al. Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol 2013;208:290. e1-6. 26. Alkiaat A, Hutchinson M, Jacques A, Sharp MJ, Dickinson JE. Evaluation of the frequency and obstetric risk factors associated with term neonatal admissions to special care units. Aust N Z J Obstet Gynaecol 2013;53: 277-82. 27. Martinez-Biarge M, Diez-Sebastian J, Wusthoff CJ, Mercuri E, Cowan FM. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics 2013;132:e952-9.
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The association between fetal Doppler and admission to neonatal unit at term Asma A. Khalil, MD, MRCOG; Jose´ Morales-Rosello, MD; Malaz Elsadigg; Naila Khan; Aris Papageorghiou, MD, MRCOG; Amar Bhide, MD, MRCOG; Basky Thilaganathan, PhD, MRCOG OBJECTIVE: Fetal cerebroplacental ratio is emerging as a better proxy
than birthweight for placental insufficiency and as a marker of fetal compromise at term. The extent to which these fetal Doppler changes are related to neonatal outcomes has not been systematically assessed. The main aim of this study was to evaluate the association between estimated fetal weight percentile, cerebroplacental ratio recorded at 34þ0e35þ6 weeks’ gestation, and neonatal unit admission at term. STUDY DESIGN: This was a retrospective cohort study in a tertiary referral center over an 11 year period from 2002 to 2012. The umbilical artery pulsatility index (PI), middle cerebral artery PI, and cerebroplacental ratio were recorded at 34þ0e35þ6 weeks. Weight values were converted into percentiles and Doppler parameters into multiples of the median (MoM), adjusting for gestational age. Logistic regression analysis was performed to identify, and adjust for, potential confounders. RESULTS: We identified 2518 pregnancies in which a scan was performed at 34þ0e35þ6 weeks and delivery occurred at or beyond 37 weeks. In the 2485 pregnancies included in the analysis, the umbilical artery PI MoM was significantly higher, and the middle cerebral artery PI and cerebroplacental ratio MoM significantly lower in
the babies requiring neonatal unit admission (P < .05). However, the estimated fetal weight percentile was not significantly different between those who required neonatal unit admission and those who did not (P ¼ .087). According to multivariate logistic regression, cerebroplacental ratio MoM (odds ratio, 0.39; 95% confidence interval, 0.19e0.79; P ¼ .008) and gestational age at delivery (odds ratio, 0.70; 95% confidence interval, 0.61e0.80; P < .001) were significantly associated with the risk of neonatal unit admission, whereas maternal age and birthweight percentile were not (P ¼ .183 and P ¼ .460, respectively). Irrespective of birthweight or estimated fetal weight percentile, the fetal cerebroplacental ratio appears to be a better predictor of the need for neonatal unit admission (P < .001). CONCLUSION: Lower cerebroplacental ratio and gestational age at
delivery, but not fetal size, were independently associated with the need for admission to the neonatal unit at term in a high-risk patient group. The extent to which fetal hemodynamic assessment could be used to predict perinatal morbidity and optimize the timing of delivery merits further investigation. Key words: birthweight, cerebroplacental ratio, Doppler, neonatal unit admission, small for gestational age
Cite this article as: Khalil AA, Morales-Rosello J, Elsadigg M, et al. The association between fetal Doppler and admission to neonatal unit at term. Am J Obstet Gynecol 2014;212:xx-xx.
S
mall for gestational age (SGA), defined as birthweight (BW) less than the 10th percentile for gestation, is commonly used as a proxy to identify fetuses at risk of adverse outcomes secondary to fetal growth restriction.1,2 However, the majority of SGA babies are not pathologically growth restricted
From the Fetal Medicine Unit, St George’s Hospital, St George’s University of London, London, England, UK. Received June 15, 2014; revised Aug. 23, 2014; accepted Oct. 7, 2014. The authors report no conflict of interest. Corresponding author: Asma Khalil, MD, MRCOG. [email protected] 0002-9378/$36.00 ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2014.10.013
and do not demonstrate signs of placental insufficiency. The clinical definition of SGA is further confused by the finding that a proportion of average for gestational age (AGA) infants also fail to meet their growth potential or, more correctly, suffer from occult placental insufficiency.3,4 We and others have recently reported that fetal Doppler assessment immediately prior to delivery at term might be of value in detecting AGA pregnancies that are at increased risk of adverse outcome from fetal hypoxemia secondary to placental insufficiency and failure to reach growth potential.4,5 Fetal Doppler indices assessed just prior to delivery appear to be a better marker than BW or BW percentile for adverse pregnancy outcomes, such as the need for operative delivery for fetal compromise in an
average risk group for fetal growth restriction (FGR).4,5 However, national guidance in the United Kingdom and the United States does not recommend the use of fetal Doppler as a screening tool for placental insufficiency, except when the fetus is already known to be SGA.1,2 The antenatal diagnosis of FGR using fetal biometry alone has recently been challenged, and the use of fetal Doppler assessment has been proposed as a potentially better marker.4,6,7 It is now increasingly routine in many hospitals and individual practices to undertake a 34-36 week ultrasound scan for fetal assessment. There is a paucity of data to support such routine assessment, but nevertheless its proponents are convinced of its utility. The main aim of this study was to investigate the association between fetal Doppler and
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ultrasound parameters at the 34-36 week growth scan and the need for neonatal unit admission at term.
M ATERIALS
AND
M ETHODS
This was a retrospective cohort study in a single tertiary referral center over an 11 year period from 2002 to 2012. 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. The inclusion criteria were singleton morphologically normal fetuses born at term that had previously had an ultrasound scan at 34þ0e35þ6 weeks’ gestation for a variety of indications such as suspected poor/excessive fetal growth, reduced fetal movements, history of SGA or large for gestational age baby, high midtrimester uterine artery Doppler indices, and gestational diabetes. Therefore, these pregnancies were at risk of fetal growth disorders. Pregnancies complicated by fetal abnormality, aneuploidy, or antepartum stillbirth were excluded from the analysis. Gestational age (GA) was calculated from the crown-rump length measurement at 11-13 weeks, and only 1 examination (the last in the 34þ0e35þ6 week window) per fetus was included in the analysis.8 Routine fetal biometry was performed according to a standard protocol and the estimated fetal weight (EFW) calculated using Hadlock’s formula.9 Data on pregnancy outcomes were collected from hospital obstetric and neonatal records. The umbilical artery (UA) and middle cerebral artery (MCA) Doppler were recorded using color Doppler, and the pulsatility index (PI) calculated according to a standard protocol.10,11 The cerebroplacental ratio (CPR) was calculated as the simple ratio of the MCA PI to the UA PI.12 All Doppler indices were converted into multiples of the median (MoM) correcting for GA using reference ranges, and BW values were converted into percentiles.4,13,14 The study cohort was divided into 4 groups according to a combination of a BW cutoff of the 10th percentile and an optimal CPR cutoff of 0.6765 MoM4 to
ajog.org assess the difference between the SGA model, which relies on fetal biometry, and the placental insufficiency model, which relies on fetal hemodynamic assessment. This was derived from our previous work in which, to define the threshold for the failure to achieve growth potential, we calculated the fifth centile of the CPR in the group least likely to present with failure to achieve growth potential (those with BW greater than the 90th percentile). This value corresponded to 0.6765.4 Data on admission to the neonatal unit were ascertained from the maternity and neonatal records. The indications for admission to the neonatal unit were respiratory complications (defined as respiratory distress syndrome and transient tachypnea of the newborn, use of continuous positive airway pressure, endotracheal intubation), hypoglycemia, sepsis, need for phototherapy, postresuscitation observation, seizures, and hypothermia.
Statistical analysis Categorical data were presented as number (percentage) and were compared using the Fisher exact test or the c2 test. Continuous data were presented as median (interquartile range [IQR]). The D’Agostino and Pearson Omnibus test was used to assess the normality of the data. Nonparametric analysis using the Mann-Whitney U test was then used to compare continuous data between the study groups. A logistic regression analysis was performed to identify, and adjust for, potential confounders. Both unadjusted and adjusted odds ratios (ORs) were calculated. The analysis was performed using the statistical software packages SPSS 18.0 (SPSS Inc, Chicago, IL), Stata 11 (release 11.2; College Station, TX), and GraphPad Prism 5.0 for Windows (InStat; GraphPad Software Inc, San Diego, CA).
R ESULTS We identified 2518 pregnancies with fetal Doppler assessment at 34þ0e35þ6 weeks, in which the delivery occurred at or beyond 37 weeks’ gestation. We excluded 33 pregnancies (1.3%) because they had aneuploidy, major structural
abnormalities, stillbirth, or missing outcome data, leaving 2485 pregnancies included in the analysis. The maternal characteristics, ultrasound, and birth indices in the groups requiring and not requiring admission to the neonatal unit are shown in Table 1. The prevalence of SGA, defined as BW less than the 10th percentile and the fifth percentile, was 25.8% and 14.0%, respectively. The overall neonatal admission rate in the study cohort was 6.7%. This fell with advancing gestation from 16.8% to 8.7%, 4.2% and 4.2% at 37, 38, 39, and longer than 40 weeks, respectively. The most common indications for admission to the neonatal unit were respiratory complications and postresuscitation observation. There were 2 early neonatal deaths and 1 late neonatal death. The scatter plot of CPR MoM values against BW percentiles showed a significant linear relationship (Figure 1: CPR MoM ¼ (0.0019 BW percentile) þ 0.9705, R2 ¼ 0.049). At the ultrasound assessment, UA PI MoM was significantly higher and MCA PI and CPR MoM were significantly lower in the neonates requiring neonatal unit admission (P < .05, Table 1, Figure 2), but the EFW percentile was not significantly different between the 2 study groups (P ¼ .087). The results of the regression analysis are shown in Tables 2 and 3. According to a multivariate logistic regression, CPR MoM, GA at delivery, maternal ethnicity, and male gender were significantly associated with the risk of neonatal unit admission (P < .05), whereas maternal age and BW percentile were not (P ¼ .183 and P ¼ .460, respectively). When divided into 4 groups according to a combination of a BW cutoff of the 10th percentile and an optimal CPR cutoff of 0.6765 MoM, the rates of neonatal unit admission were significantly different (P < .001, Figure 3). The incidence of admission to the neonatal unit in the AGA neonates with low CPR (9.8%) was almost double that in the group of AGA with normal CPR (5.5%). However, the difference in the admission rates between the groups of AGA with low CPR and AGA with
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TABLE 1
Maternal and fetal characteristics in the study cohort according to admission to the neonatal unit Neonatal unit admission (n [ 167)
Characteristic Maternal age, y, median (IQR)
31.0 (27.0e34.0)
No neonatal unit admission (n [ 2318) 31.0 (26.0e34.0)
Ethnicity
P value .133 .276
White, n (%)
101 (60.5)
1230 (53.1)
African, n (%)
30 (18.0)
416 (18.0)
Asian, n (%)
30 (18.0)
522 (22.5)
Mixed, n (%)
4 (2.4)
100 (4.3)
Other, n (%)
2 (1.2)
50 (2.2)
Gestational age at ultrasound (wks), median (IQR) Estimated fetal weight (g), median (IQR) Estimated fetal weight percentile, median (IQR)
34.9 (34.4e35.4)
35.0 (34.4e35.6)
.113
2356 (2085e2651)
2426 (2183e2690)
.025
28.92 (11.45e54.01)
32.89 (15.60e55.77)
.087
0.95 (0.85e1.08)
0.91 (0.80e1.03)
.008
UA PI MoM
1.01 (0.89e1.14)
0.97 (0.85e1.09)
.014
MCA PI
1.73 (1.50e1.98)
1.80 (1.60e2.02)
.002
MCA PI MoM
1.17 (1.00e1.30)
1.21 (1.08e1.37)
.001
Cerebroplacental ratio
1.87 (1.50e2.25)
2.00 (1.70e2.31)
< .001
UA PI
Cerebroplacental ratio MoM
0.95 (0.76e1.15)
Gestational age at delivery (wks), median (IQR) Birthweight (g), median (IQR)
1.02 (0.87e1.18)
< .001
38.9 (37.7e40.0)
39.6 (38.6e40.6)
< .001
2955 (2500e3470)
3140 (2780e3520)
< .001
Birthweight percentile, median (IQR)
19.01 (4.67e57.80)
Fetal sex male, n (%)
98 (59.4)
28.32 (10.09e58.43) 1140 (49.3)
.005 .012
IQR, interquartile range; MCA, middle cerebral artery; PI, pulsatility index; MoM, multiples of median; UA, umbilical artery. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
normal CPR was not statistically significant (P ¼ .203). This could be related to the small number of cases in these 2 groups because admission to the neonatal unit in healthy newborns at term is a relatively uncommon event. We also investigated the association between fetal Doppler parameters and the risk of admission to the neonatal unit in the pregnancies that were SGA (BW less than 10th percentile, n ¼ 640) in which the rate of admission to the neonatal unit was 10%. Compared with those not requiring admission, neonates requiring neonatal unit admission had significantly lower median BW percentile (2.70, IQR, 0.73e5.89 vs 4.69, IQR, 2.34e7.38), GA at delivery in weeks (38.35, IQR, 37.45e39.40 vs 39.10, IQR, 38.30e40.10), MCA PI MoM (1.11, IQR, 0.97e1.24 vs 1.19,
IQR, 1.06e1.35), and CPR MoM (0.84, IQR, 0.67e0.99 vs 0.94, IQR, 0.80e1.09). BW percentile, MCA PI MoM, and CPR MoM were significantly associated with the risk of neonatal unit admission (P < .001, Table 4), whereas the UA PI MoM and EFW percentile were not (P ¼ .115 and P ¼ .213, respectively). According to the multivariate logistic regression in SGA neonates, both BW percentile (OR, 0.87; 96% confidence interval [CI], 0.78e0.96; P ¼ .008) and CPR MoM (OR, 0.21; 96% CI, 0.06e0.77; P ¼ .018) were significantly and independently associated with the risk of neonatal unit admission. The prevalence of SGA, defined as BW less than the third percentile, was 8.5%. The neonatal unit admission rate in this cohort was 15.8%, which was
significantly higher in those with low CPR MoM compared with those with normal CPR MoM (30.2% vs 12.2%, P ¼ .004).
C OMMENT The findings of this study suggest that neonates that were admitted to the neonatal unit at term had significantly lower CPR at 34-36 weeks, whereas both ultrasound EFW and BW percentiles were not significantly different from those not admitted. A multivariate logistic regression demonstrated that CPR MoM at 34-36 weeks was almost twice as likely as GA at delivery to determine the need for neonatal unit admission. It was also the case that, among the SGA neonates at term, those with a lower CPR MoM at 34-36 weeks had a higher risk
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FIGURE 1
Scatter plot of CPR MoM values against BW percentile
Scatter plot of CPR MoM values against BW percentile, showing a significant linear relationship (CPR MoM ¼ [0.0019 BW percentile] þ 0.9705, R2 ¼ 0.049). BW, birthweight; CPR, cerebroplacental ratio; MoM, multiple of median. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
ajog.org of a neonatal unit admission compared with those with normal CPR MoMs.
Findings in term pregnancies The novel observation in our cohort is that CPR, but not BW, percentiles, measured at 34-36 weeks’ gestation, are significantly and independently associated with the need for neonatal unit admission at term. In a recent prospective study including 400 term pregnancies (37-42 weeks), the investigators assessed fetal biometry and Doppler parameters immediately before established labor.5 Fetuses with CPR below the10th percentile were 6 times more likely to be delivered by cesarean delivery for presumed fetal compromise than those with a CPR above the10th percentile.5 Even after the exclusion of cases with a BW below the 10th percentile, the rate of cesarean delivery for presumed fetal compromise remained significantly higher in fetuses with a CPR less than the 10th percentile.5 In the Generation R Study (Rotterdam, The Netherlands, 2003-2007), Roza et al15 reported that, even in the general
FIGURE 2
Cerebroplacental ratio MoM values and percentiles
Box and whisker plots of cerebroplacental ratio MoM values and birthweight percentiles in newborns who were admitted to the neonatal unit and those who were not. The horizontal line in the box represents the median, the box represents the IQR, and the whiskers indicate the minimum and maximum values. IQR, interquartile range; MoM, multiple of median. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
population, an abnormal CPR at term predicts neurobehavioral problems at 18 months of age on internalizing and somatic complaints scales.
Findings in term SGA pregnancies The role of fetal Doppler in term and near-term pregnancies may currently be underestimated because of the rarity of abnormal UA Doppler indices at this gestation and the fact that FGRrelated perinatal morbidity has been noted to occur even when the UA blood flow is normal.16-18 In our cohort the rate of neonatal unit admission was almost 3 times higher in SGA neonates with low CPR MoM compared with those SGA neonates with normal CPR MoM (23% vs 8%). The role of the MCA Doppler in SGA pregnancies at term has been investigated in previous studies.16,18-22 Chang et al18 reported that fetal Doppler PI ratios recorded in the third trimester (aortic/middle cerebral and renal/middle cerebral PI ratios) were superior to predelivery estimates of fetal size in predicting suboptimal perinatal outcome in small fetuses delivering at term. The suboptimal perinatal outcome in the latter study was defined as acidemia at birth, fetal distress requiring emergency cesarean delivery in labor, or admission to the neonatal unit.18 Hershkovitz et al16 also demonstrated an association between MCA blood flow redistribution in structurally normal fetuses with an EFW below the fifth percentile and an increased risk of cesarean delivery and need for neonatal unit admission. CPR has been shown to correlate better with adverse outcome than does UA and MCA Doppler.23,24 Findings in preterm SGA pregnancies In pregnancies with SGA neonates, BW percentiles and CPR MoMs at 34-36 weeks’ gestation, but not EFW percentiles at 34-36 weeks, were independently associated with neonatal unit admission at term. These findings are consistent with the recent Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study, in which in 1200 pregnancies with EFW less than the 10th percentile
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TABLE 2
Results of the logistic regression analysis of factors associated with the risk of admission to the neonatal unit Risk factor
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Rates of neonatal unit admission in the 4 study groups
P value
Unadjusted OR
95% CI
Maternal age, y
1.02
(1.00e1.05)
.106
Maternal ethnicity
0.83
(0.70e0.98)
.026
Maternal characteristics
Ultrasound indices EFW percentile
1.00
(0.99e1.00)
.245
UA PI MoM
3.00
(1.23e7.28)
.016
MCA PI MoM
0.26
(0.12e0.55)
< .001
Cerebroplacental ratio MoM
0.83
(0.70e0.98)
< .001
Fetal sex (female)
0.67
(0.48e0.92)
.013
Indices at birth GA at delivery, wk
0.67
(0.59e0.76)
< .001
BW percentile
0.99
(0.99e1.00)
.079
BW, birthweight; CI, confidence interval; EFW, estimated fetal weight; GA, gestational age; MCA, middle cerebral artery; MoM, multiples of median; OR, odds ratio; PI, pulsatility index; UA, umbilical artery. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
prospectively followed up, 95% of those with abdominal circumference below the 10th percentile had a normal pregnancy outcome.25 Importantly, the authors noted that the presence of an abnormal UA Doppler was significantly associated with adverse outcome, irrespective of EFW or abdominal circumference measurement.25 Furthermore, the only sonographic weight-related
parameter that was significantly associated with adverse outcome was EFW below the third percentile.25 Despite the fact that the authors stated in the methodology that MCA Doppler had been performed, these data were not reported in the results.25 The neonatal admission rate in that SGA cohort was 28%, compared with 10% in our cohort of 640 pregnancies with SGA. This
TABLE 3
Results of the multivariate logistic regression analysis of factors associated with the risk of admission to the neonatal unit Risk factor
P value
Adjusted OR
95% CI
Maternal age, y
1.02
(0.99e1.05)
.183
Maternal ethnicity
0.81
(0.68e0.97)
.020
Cerebroplacental ratio MoM
0.39
(0.19e0.78)
.008
Fetal sex (female)
0.67
(0.48e0.94)
.020
GA at delivery, wks
0.70
(0.61e0.80)
< .001
BW percentile
1.00
(0.99e1.00)
.460
Maternal characteristics
Ultrasound indices
Indices at birth
BW, birthweight; CI, confidence interval; GA, gestational age; MoM, multiples of median; OR, odds ratio. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
The rates of neonatal unit admission in the 4 study groups according to a combination of a BW cutoff of the 10th percentile and a CPR cutoff of 0.6765 MoM. AGA, average for gestational age; BW, birthweight; CPR, cerebroplacental ratio; SGA, small for gestational age. Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
difference may be due to variations in gestation at assessment and delivery as well as in neonatal unit admission policies in the 2 studies. Despite this discrepancy, the findings of both studies question the currently accepted definition of FGR and emphasize the importance of fetal hemodynamic assessment as a predictor of adverse pregnancy outcome in all fetal weight categories.
Strengths and limitations The strengths of our study include the large number of pregnancies, adjusting for GA, ascertainment of the outcome data, and the narrow GA range at ultrasound assessment. However, the retrospective design, lack of detailed robust data on the intrapartum events, and the higher proportion of SGA (25.8%) in the study population limit the generalizability of our findings. The higher prevalence of SGA in our cohort could be explained by the fact that pregnancies at risk of SGA were more likely to have an ultrasound assessment at 34-36 weeks’ gestation. However, we see this as a strength because despite the bias toward lower BW and higher prevalence of SGA, CPR was more strongly associated with neonatal unit admission. A high proportion of neonatal unit admissions are short term, with full recovery and discharge home. Prolonged neonatal
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TABLE 4
Factors associated with neonatal unit admission in SGA newbornsa Risk factor
P value
Unadjusted OR
95% CI
Maternal age, y
1.03
0.98e1.07
.255
Maternal ethnicity
0.69
0.53e0.91
.008
Maternal characteristics
Ultrasound indices EFW percentile
0.98
0.96e1.01
.213
UA PI MoM
3.06
0.76e12.27
.115
MCA PI MoM
0.88
0.24e0.32
< .001
Cerebroplacental ratio MoM
0.12
0.03e0.42
.001
Fetal sex (female)
0.70
0.42e1.18
.184
Indices at birth GA delivery, wks
0.68
0.55e0.86
.001
BW percentile
0.84
0.76e0.92
< .001
BW less than fifth percentile
2.13
1.22e3.74
.008
BW, birthweight; CI, confidence interval; EFW, estimated fetal weight; GA, gestational age; MCA, middle cerebral artery; MoM, multiples of median; OR, odds ratio; PI, pulsatility index; SGA, small for gestational age (defined as birthweight less than 10th percentile); UA, umbilical artery. a
Determined by logistic regression analysis.
Khalil. Doppler and neonatal unit admission. Am J Obstet Gynecol 2014.
intensive care unit admission and neonatal morbidity are the subjects of a future study. Approximately 10% of term babies may require admission to the neonatal unit.26 The commonest indications include respiratory complications, postresuscitation observation, and hypoglycemia. These adverse events are more likely to occur in FGR babies, or more correctly, babies compromised by placental insufficiency. Admission to the neonatal unit at term is usually an unexpected event for both parents and health care professionals. It also represents a burden on health care resources and reflects the quality of intrapartum care. For these reasons, it is one of the national health care quality measures in many Western countries, including the United Kingdom and the United States. We have shown that lower CPR at 34-36 weeks and GA at delivery, but not BW percentiles at 34-36 weeks, were independently associated with the need for admission to the neonatal unit at term.
These findings support the assertion that fetal Doppler assessment could be of value in detecting fetal hypoxemia secondary to placental insufficiency and failure to reach their genetic growth potential in apparently AGA pregnancies. AGA pregnancies can demonstrate fetal cerebral and placental blood flow redistribution indicative of an increased risk of adverse pregnancy outcome as a consequence of fetal hypoxemia secondary to placental insufficiency.4 Despite this significant association between fetal Doppler and the need for neonatal unit admission at term, its predictive accuracy as an isolated marker is likely to be poor because of the confounding effect of the process of labor and birth.27 Whether fetal Doppler assessment in AGA pregnancies is predictive of perinatal morbidity or neurodevelopmental delay is unknown. The extent to which fetal hemodynamic assessment could be used to optimize the timing of delivery and reduce neurodevelopmental impairment merits further investigation. -
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