Ultrasound screening for fetal growth restriction at 36 vs 32 weeks' gestation: a randomized trial (ROUTE) E. Roma, A. Arnau, R. Berdala, C. Bergos, J. Montesinos and F. Figueras Volume 46, Issue 4, pages 391–397 View the free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.14915/full

1. UOG Journal Club: October 2015
Ultrasound screening for fetal growth restriction at 36
vs 32 weeks’ gestation: a randomized trial (ROUTE)
E. Roma, A. Arnau, R. Berdala, C. Bergos, J. Montesinos
and F. Figueras
Ultrasound Obstet Gynecol 2015; 46: 391–397
Journal Club slides prepared by Dr Aly Youssef
(UOG Editor for Trainees)

2. Introduction
• Undetected SGA status significantly increases the risk of adverse perinatal
outcome and stillbirth
• Fetal growth restriction (FGR) in late pregnancy accounts for the largest fraction
of adverse outcomes and stillbirths
• Detecting late onset FGR is therefore central to third-trimester screening
• The optimal method (symphysis–fundus height [SFH] measurement vs
ultrasound) of fetal growth assessment in the third trimester remains unclear
• The optimal gestational age for a third trimester scan, in terms of FGR
detection, has not been addressed previously in any randomized study
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015

3. To assess the utility of routine third-trimester
ultrasound examination at 36 rather than 32 weeks’
gestation for detecting FGR
Aim of the study
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015

4. • This was an open-label parallel randomized trial
• 2586 healthy pregnant women with a singleton non-anomalous fetus
• Enrolled after routine second-trimester scanning
Methods
• Women were randomized for a scan at either 32 (±1) or 36 (±1) weeks
• Following assignment, participants were followed by midwives, including
serial SFH measurements after 26 weeks
• Suspected SGA prompted weekly monitoring
• Timing of elective induction was decided according to (but not limited to)
umbilical artery Doppler findings and suspected fetal acidosis
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015
• Analysis was based on originally-assigned groups (intention-to-treat)

5. Results
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015
3320 assessed for eligibility
2612 eligible
708 excluded
2586 randomized
163 excluded or lost
to follow-up
1272
assigned to ultrasound
examination at 32 weeks
1314
assigned to ultrasound
examination at 36 weeks
1109
analyzed
199 excluded or lost
to follow-up
1115
analyzed
There were two stillbirths before examination (one in each group)

6. Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015
Outcome 32 weeks (n=1109) 36 weeks (n=1115) P
Labor induction, n (%) 364 (32.8) 400 (35.9) 0.13
GA at delivery (days) (mean ± SD) 278.7 ± 9.4 279.1±9.0 0.316
Birth weight (g) (mean ±SD) 3286 ± 459 3272±453 0.467
Birth weight <10th centile, n (%) 109 (9.8) 134 (12) 0.098
Birth weight <3th centile, n (%) 40 (3.6) 49 (4.4) 0.34
Cesarean delivery for non-reassuring
fetal status during labor, n (%)
54 (4.9) 47 (4.2) 0.459
Umbilical artery pH < 7.15, n (%) 49 (4.8) 47 (4.7) 0.944
Neonatal admission, n (%) 99 (8.9) 89 (8.0) 0.42
Results: perinatal outcome in 2224 women randomized to either ultrasound
examination at 32 or 36 weeks to detect FGR
Perinatal outcomes did not differ between groups

7. Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015
Ultrasound examination at 36 weeks: AUC curve,
0.82 (95% CI, 0.78–0.85)
Ultrasound examination at 32 weeks: AUC curve,
0.75 (95% CI, 0.71–0.79)
Accuracy for prediction of FGR illustrated by the area under the receiver–
operating characteristics (AUC) curve
(shaded area indicates a 5–15% range of false-positive rate)

8. Accuracy for prediction of severe FGR (customized birthweight <3rd centile)
(shaded area indicates a 5–15% range of false-positive rate)
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015
Ultrasound examination at 36 weeks: AUC curve,
0.86 (95% CI, 0.80–0.92)
Ultrasound examination at 32 weeks: AUC curve,
0.82 (95% CI, 0.76–0.87)

9. Results
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015
• Despite similar false-positive rates (6.4% vs 8.2%), FGR detection
rates were superior at 36 weeks’ gestation to those at 32 weeks’
gestation (38.8% vs 22.5%; P = 0.006).
• False-positive rates were also similar (8.5% vs 8.7%), with improved
detection of severe FGR at 36 weeks than at 32 weeks (61.4% vs
32.5%; P = 0.008).
• A diagnosis of SGA at 32 weeks had an odds ratio (OR) of 3.27
(95% CI, 1.97–5.43) for FGR and 5.07 (95% CI, 2.52–10.19) for
severe FGR at birth.
• A diagnosis of SGA at 36 weeks, had an OR of 9.31 (95% CI, 6.04–
14.35) for FGR and 17.13 (95% CI, 8.98–32.7) for severe FGR at
birth.

10. Discussion
• A meta-analysis of earlier RCTs failed to demonstrate a benefit
of routine third-trimester scanning
• FGR is associated with a 5- to 10-fold increased risk of stillbirth
• Timely recognition and delivery of FGR fetuses is thought to
play an important role in reducing the risk of stillbirth
• The present study indicates that routine 36 week scans, as
opposed to 32 week scans, yield improved rates of FGR
detection
• A policy of routine 36 week scans has no evident increase in
risk of perinatal complications due to diagnostic delay of SGA
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015

11. • First randomized trial addressing the optimal gestational
age to perform third-trimester assessment of fetal growth
Limitations
• The study may have been underpowered to assess
differences in perinatal outcome, such as perinatal mortality
or neonatal complications
• If fundal height measurement could be performed more
accurately, the differences between scans at 32 and 36
weeks’ gestation in detecting FGR may be less pronounced
Strengths
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015

12. Discussion points
• Should third-trimester ultrasound evaluation of fetal growth
be offered routinely to all women?
• Should it be offered only to women at high risk of FGR
(previous FGR, abnormal uterine artery Doppler, etc.)?
• What is the ideal method for fetal growth assessment in the
third trimester?
• In areas where third-trimester ultrasound is routine, when
and how often should fetal growth assessment be
performed?
• Should ultrasound-based fetal assessment be evaluated
routinely by single or serial evaluations?
Ultrasound screening for fetal growth restriction at 36 vs 32 weeks’ gestation: a randomized trial (ROUTE)
Roma et al., UOG 2015