Clinical Significance Of Intermittently Absent End-Diastolic Flow Of The Fetal Umbilical Artery On Perinatal And Neonatal Outcomes Zeynep Kayaoğlu Yıldırım, Gynecologist and Obstetrician, Perinatologist, İstanbul Başakşehir Çam ve Sakura City Hospital, Drkayaoglu@Hotmail.Com, Alperen İnce, MD, Obstetrics and Gynecology Medical Student, Başakşehir Çam ve Sakura City Hospital,Gökhan Bayanmelek, Gynecologist and Obstetrician, Perinatologist, İstanbul Başakşehir Çam ve Sakura City Hospital,Gökhan Bolluk, Gynecologist and Obstetrician, Perinatologist, Başakşehir Çam ve Sakura City Hospital
Conditions: Absent End-Diastolic Flow Of The Fetal Umbilical Artery
Sponsor: Başakşehir Çam & Sakura City Hospital

 
 
CLINICAL SIGNIFICANCE OF INTERMITTENTLY 
ABSENT END-DIASTOLIC FLOW OF THE FETAL 
UMBILICAL ARTERY ON PERINATAL AND 
NEONATAL OUTCOMES 
 
 
Başakşehir Çam ve Sakura City Hospital Clinical Research Ethics Committee 
(ethics no.2023-561, date 08/11/2023)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
AUTHOR INFORMATION –  
 
-All authors:  
Dr. Zeynep Kayaoğlu Yıldırım, Gynecologist and Obstetrician, Perinatologist, İstanbul 
Başakşehir Çam ve Sakura City Hospital, Department of Obstetrics and Gynecology, 
drkayaoglu@hotmail.com 
Dr. Alperen İnce, Medical Doctor, Obstetrics and Gynecology Medical Student, İstanbul 
Başakşehir Çam ve Sakura City Hospital, Department of Obstetrics and Gynecology, 
alperenince@gmail.com  
Dr Gökhan Bayanmelek, Gynecologist and Obstetrician, Perinatologist, İstanbul Başakşehir 
Çam 
ve 
Sakura 
City 
Hospital, 
Department 
of 
Obstetrics 
and 
Gynecology, 
goldstandart17@gmail.com 
Dr Gökhan Bolluk, Gynecologist and Obstetrician, Perinatologist, İstanbul Başakşehir Çam ve 
Sakura City Hospital, Department of Obstetrics and Gynecology, drgbolluk@hotmail.com 
- Corresponding author: 
 Dr. 
Zeynep 
Kayaoğlu 
Yıldırım, 
drkayaoglu@hotmail.com, 
telephone 
number: 
+905327027341 
 
 
 
 
 
 

Clinical Significance Of Intermittently Absent End-Diastolic Flow Of The Fetal Umbilical 
Artery On Perinatal And Neonatal Outcomes  
 
Zeynep Kayaoğlu Yıldırım, MD, Gynecologist and Obstetrician, Perinatologist, İstanbul 
Başakşehir Çam ve Sakura City Hospital, drkayaoglu@hotmail.com, telephone number: 
+905327027341 
Alperen İnce, MD, Obstetrics and Gynecology Medical Student, İstanbul Başakşehir Çam ve 
Sakura City Hospital, alperenince@gmail.com, telephone number: +905355871592 
Gökhan Bayanmelek, MD, Gynecologist and Obstetrician, Perinatologist, İstanbul Başakşehir 
Çam ve Sakura City Hospital, goldstandart17@gmail.com, telephone number: 
+905052638836 
Dr Gökhan Bolluk, Gynecologist and Obstetrician, Perinatologist, Başakşehir Çam ve Sakura 
City Hospital, drgbolluk@hotmail.com, telephone number: +905065993144 
 
Abstract 
Objective: This study aimed to estimate the risk of adverse perinatal outcomes among pregnant 
patients with intermittently absent (iAEDF) and persistently absent end-diastolic umbilical 
artery flow (pAEDF).  
Study design: We performed a retrospective cohort study of patients diagnosed with the 
iAEDF or pAEDF at our institution from 2020 to 2023. Fetuses were classified under two 
categories:  iAEDF group and pAEDF group.  
Results: Of the 137 patients included, 38 had iAEDF and 99 had pAEDF. In terms of 
pregnancy outcomes, the duration from diagnosis to birth was significantly shorter for women 
diagnosed with pAEDF  compared to women diagnosed with iAEDF. Additionally, 
pregnancies with  iAEDF were associated with a later gestational age at delivery. 

In terms of pregnancy complications, there were no statistically significant differences between 
the two groups. But all four stillborn patients were in the pAEDF group and the percentage of 
fetal distress in women diagnosed with  pAEDF was noticeably greater than the percentage of 
fetal distress in women diagnosed with iAEDF. A comparison of the two groups revealed that 
concerning neoatal outcomes, in the iAEDF group, the Apgar score was significantly greater 
and the percentage of women with an Apgar score in the fifth minute less than seven was lower. 
Conclusion: For fetuses with absent end-diastolic flow-related UA, the absence of flow was 
associated with pregnancy outcome. There was no significant difference between the groups in 
terms of stillbirth, however, all 4 stillborns were in the pAEDF group, which suggested that 
inpatient follow-up of pregnancies with iAEDF allows early intervention. However, the 
average time from diagnosis to delivery in women with an iAEDF was 15.6 days, which 
extended latency from diagnosis to delivery may favor outpatient management of iAEDF. 
These outcomes should be considered when creating an antenatal surveillance plan and 
discussing the potential for outpatient management. 
Key Points  
-Doppler velocity measurements have excellent benefits in the surveillance of risky fetuses.  
-Absent umbilical artery end-diastolic flow is associated with adverse perinatal outcomes. 
- Patterns of end-diastolic flow may inform  management and decision-making for high-risk 
pregnancies 
Keyword: absent end-diastolic flow, Doppler, gestational age, intrauterine growth restriction, 
pregnancy outcome, neonatal outcomes, ultrasound, umbilical artery  
Introduction 
Doppler velocity measurement of the umbilical artery (UA) serves as a crucial clinical tool for 
monitoring feto-placental hemodynamics and assessing fetal well-being in high-risk 
pregnancies1-3. This technique has demonstrated notable advantages in monitoring potentially 

risky fetuses, particularly in pregnancies complicated by placental disorders, such as fetal 
growth restriction (FGR)4,5. Since UA Doppler (UAD) results can deteriorate over the course 
of pregnancy, regular assessments are recommended6,7. However, the frequency of these 
assessments, management protocols, and delivery timing recommendations vary among major 
national obstetric societies7. 
The UA blood velocity waveform is typically characterized by the pulsatility index (PI)8 and 
qualitative information concerning the potential absence or reversal of end-diastolic flow 
(EDF)9. Absent end-diastolic flow (AEDF) signifies increased resistance to flow in the 
placental vascular bed10,11 and is associated with elevated risks of intrauterine death and 
adverse perinatal outcomes12-14. AEDF in the UA can be either persistent (pAEDF), occurring 
in most or all fetal cardiac cycles, or intermittent (iAEDF), manifesting in only some of the 
cardiac cycles. However, standardized definitions for these terms lack and the clinical 
implications of the iAEDF versus the pAEDF remain unclear. 
A previous study indicated that, compared to fetuses with pAEDF, those with iAEDF are 
diagnosed with UAD abnormalities later in pregnancy and are delivered at a later gestational 
age (GA) with higher birth weights15. Consequently, it is plausible that some fetuses with an 
iAEDF may remain in utero for an extended duration without facing an immediate risk of death. 
Identifying this specific subgroup might allow the avoidance of some neonatal risks associated 
with extremely preterm birth. 
In this study, we aimed to assess the risk of adverse perinatal outcomes among pregnant 
patients with intermittently absent and persistently absent end-diastolic umbilical artery flow. 
This investigation seeks to contribute to a better understanding of the fetal risks associated with 
different patterns of absent end-diastolic flow, thereby informing clinical management and 
decision-making for high-risk pregnancies. 
 

Materials and Methods 
We performed a retrospective cohort study of patients with non-anomalous, singleton 
pregnancies diagnosed with intermittent absence of end-diastolic umbilical artery Doppler flow 
or persistent absence of end-diastolic flow at our institution from 2020 to 2023. The study was 
approved by the Başakşehir Çam ve Sakura City Hospital Clinical Research Ethics Committee 
(ethics no.2023-561, date 08/11/2023) and was conducted in accordance with the latest version 
of the Declaration of Helsinki (2019/92). Fetuses were classified into two categories: 
intermittent absent end-diastolic flow and persistent absent end-diastolic flow. 
Patients were excluded if they had major fetal anomalies or aneuploidy diagnosed prenatally 
or if they lacked delivery or neonatal outcome data. Patients were also excluded if they were 
intermittently elevated or if they showed REDF syndrome during pregnancy. All ultrasounds 
were performed and interpreted by a maternal-fetal medicine fellowship-trained obstetrician. 
UAD waveforms were obtained through transabdominal imaging from a free-floating loop of 
the umbilical cord on a Hitachi machine. To improve the accuracy of the measurements, 
waveforms were obtained during a brief pause during maternal breathing. At least three 
separate UAD assessments were performed for each fetus. Doppler waveforms were defined 
as iAEDF if diastolic flow was absent in one or more waveforms during a cycle of images. 
Doppler waveforms were defined as persistently absent if the absence of diastolic flow was 
observed in all waveforms. The REDF was defined as the reversal of flow in the UA in at least 
one fetal cardiac cycle. The patients defined as having an iAEDF were not subdivided based 
on the percentage of patients with no waveforms. The most recent guidelines for the 
management of FGR from the Society for Maternal-Fetal Medicine and American College of 
Obstetricians and Gynecologists (ACOG) were released in 2020. We recommend that pregnant 
patients with AEDF undergo UAD surveillance two to three times weekly and delivery by 33 
to 34 weeks of gestation 6,16. Inpatient management is suggested as an option for AEDF. In our 

study, the management of AEDF included admission of pregnant patients for antenatal 
corticosteroid administration and inpatient monitoring, including daily UAD assessment and 
antenatal testing twice a day. Although previous studies have shown that improvements in 
UAD abnormalities can be observed with the application of corticosteroids to stimulate fetal 
lung maturity17,18, we did not find it necessary to study it since corticosteroids were already 
administered to all patients whose AEDF was detected. Delivery was recommended at the GA 
of 34 weeks following the recommendations of ACOG, or if another indication arose19. If a 
diagnosis of AEDF or REDF was made after the recommended GA for delivery, it was advised 
to proceed with delivery at the time of diagnosis. 
Maternal demographic information, medical complications, prenatal history (including 
additional ultrasound studies), and delivery and neonatal outcomes were taken from medical 
records. 
The primary outcome was a composite of neonatal outcomes, including birth weight, Z-score 
for standardized birth weight, Apgar score in the first minute, Apgar score in the fifth minute, 
Apgar score in the fifth minute lower than seven, admission to the ICU, and the need for 
intubation. 
The secondary outcomes included demographic information, time of AEDF diagnosis, latency 
from the time of AEDF diagnosis to delivery, and pregnancy complications (IUMF, ablatio 
placenta, fetal distress, IUGR, amniotic fluid abnormalities). 
These outcomes were compared between patients with iAEDF and those with pAEDF. 
Statistical Analysis 
Statistical analysis was performed using R statistical software (R Core Team 2021). A score of 
P<0.05 was considered to indicate statistical signiﬁcance. The normality of the distribution of 
the variables was assessed using quantile–quantile plots and the Shapiro–Wilk test. Continuous 
variables were evaluated using the unpaired student’s t test or Mann–Whitney U test (for two 

groups), depending on the normality of the distribution. Categorical variables were analyzed 
using the χ2 test or Fisher’s exact test, depending on the variable count20. 
Results 
Our cohort included 137 pregnancies in the final analysis. A total of 99 (33.0%) patients were 
classified as pAEDF, while 38 (16.0%) were classified as iAEDF. The sociodemographic and 
obstetrical characteristics of the patients in both groups are shown in Tables 1 and 2. 
Table 1 shows the comparisons of age, parity, and gravidity between the groups. There were 
no significant differences in age, parity, or gravidity between the persistent dak group and the 
intermittent dak group. Table 2 shows the results of the comparison of the two groups in terms 
of pregnancy outcomes, including the week of AEDF diagnosis, gestational age at birth, birth 
weight, Z-score for standardized birth weight and the time elapsed from diagnosis to birth. 
There were significant differences between the two groups in terms of gestational age at birth 
and the time elapsed from diagnosis to birth. The mean gestational age at birth among women 
who were diagnosed with persistent dak was 29.6  2.8 years, while the mean gestational age 
at birth was 30.9  2.6 years (p=0.03). The time from diagnosis to birth was significantly shorter 
for women who were diagnosed with persistent dak (mean=7.88, sd=9.99) compared to women 
who were diagnosed with intermittent dak (mean=15.6, sd=11.5) (p=<.0001). 
Table 3 shows the results of the comparison of the two groups in terms of pregnancy 
complications, including AFI abnormalities, stillbirth, ablatio placenta, and fetal distress. There 
were no significant differences between the two groups in terms of pregnancy complications. 
However, the percentage of fetal distress in women who were diagnosed with persistent dak 
(56.6%) was noticeably greater than the percentage of fetal distress in women who were 
diagnosed with intermittent dak (39.5%). Although there was no significant difference between 
the groups in terms of stillbirths, all four stillborns were in the pAEDF group. 

Table 4 shows a comparison of the two groups in terms of adverse neonatal outcomes. There 
were significant differences between the two groups in terms of the Apgar score at the first 
minute and the Apgar score at the fifth minute. Among women who were in the persistent dak 
group, the mean Apgar score in the first minute was 4.2  2.2, while the mean Apgar score in 
the first minute among women in the intermittent dak group was 5.4  1.9 (p=0.004). Similarly, 
the mean Apgar score at the fifth minute was lower in the persistent dak group than in the 
intermittent dak group (6.4  2.2 and 7.6  1.0, respectively). 
We also evaluated the Apgar score at the fifth minute by categorizing patients as being less 
than or more than seven. However, there was a significant difference between the two groups. 
The percentage of women with Apgar scores less than seven in the dak group (33.3%) was 
much greater than the percentage of women with Apgar scores less than seven in the fifth 
minute in the intermittent dak group (13.2%) (p=0.02). 
The significant difference between the two groups in terms of Apgar score was due to higher 
mean gestational age at birth of women diagnosed with pAEDF compared to the mean 
gestational age at birth of women diagnosed with iAEDF. 
There were no significant differences between the two groups in terms of admission to the ICU 
or intubation. 
Discussion 
An improvement in UAD has been associated with longer latency, later GA at delivery, and 
lower rates of acidosis at delivery21,22. 
In the current study conducted on pregnancies with AEDV, pregnancies with iAEDF had 
longer latency from diagnosis to delivery, were delivered at a later gestational age (GA) and 
were less likely to be delivered because of fetal distress. Based on the data that pregnant women 
with iAEDF have a longer latency from diagnosis to delivery and require delivery later in 

gestation, iAEDF is a stage of placental insufficiency progression and likely represents less 
severe UAD abnormality than pAEDVF 
Rosner et al. compared outcomes among 109 pregnancies with an iAEDF or pA/REDF from 
19 to 39 weeks (15). Like our study, they reported that pregnancies with an iAEDF were 
delivered at a later gestational age and were less likely to have a fetal indication for delivery. 
In contrast, they found no difference in latency from AEDV diagnosis to delivery and did not 
observe changes in UAD velocimetry. This may be attributed to the low percentage of 
pregnancies complicated by FGR in this study. Their study included all pregnancies with UAD 
abnormalities, as did ours and only 83% of the subjects had FGR. In our study, 94% of patients 
had UAD abnormalities complicated with FGR. 
Like our study, a recent retrospective study of singletons with fetal growth restriction and 
absent end-diastolic velocity conducted by Katherine H. Bligard et al. has reported that the 
latency to delivery was longer in the iAEDF group than in the pAEDF group and the 
nonreassuring fetal status indication for delivery was greater in the pAEDF group. In that study, 
when the two groups were compared in terms of Apgar scores and birth weights, the Apgar 
scores and birth weights were greater for fetuses complicated with iAEDF23. Our study 
supported these data with approximately twice the number of patients. 
Sophie Green et al. compared outcomes among three Doppler groups (persistently elevated, 
intermittently absent, and persistently absent end-diastolic flow) of growth-restricted fetuses24. 
According to our study, there was no difference in composite neonatal morbidity among the 
three groups. Although the Apgar score was lower in the pAEDF group, there were no 
significant differences between the two groups in terms of admission to the ICU or intubation. 
Our study is limited because subsequent neonatal outcomes are unknown. It is important to 
acknowledge that UAD is a dynamic measurement that changes over time. Green’s study and 

our study could be more powerful if they included data from pregnancies with an iAEDF that 
subsequently progressed to an AEDF in the outcome analyses. 
Conclusion 
In fetuses with AEDF in the UA, the severity of flow absence was associated with pregnancy 
outcomes (gestational age at birth, time elapsed from diagnosis to birth, fetal distress, and 
Apgar scores). Although there was no significant difference between the groups in terms of 
stillbirth, all four stillborns being in the pAEDF group suggested that inpatient follow-up of 
pregnancies with iAEDF allows early intervention in these patients. However, the mean time 
from diagnosis to delivery in women with an iAEDF was 15.6 days, which extended latency 
from diagnosis to delivery may favor outpatient management of iAEDF. However, considering 
the lack of available clinical data on the iAEDF population, we believe that our study 
contributes to the current data as a descriptive study because it involves the largest number of 
patients with AEDF, and the multiple parameters evaluated. 
Conflict of Interest 
None declared. 
Acknowledgments 
The authors would like to thank the staff of the Başakşehir Çam ve Sakura City Hospital for 
their help and support. 
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Tables 
Table 1. Demographic information 
 
 
   iAEDF  (n=38)      pAEDF  (n=99) p-value 
Age 
29.5 (6.1) 
29.5 (6.6) 
0.96* 
Parity 
0.78** 
0 
19 (50.0) 
48 (48.5) 
1 
12 (31.6) 
26 (26.3) 
 

2 
4 (10.5) 
18 (18.2) 
3 
2 (5.3) 
5 (5.1) 
 
4 
0 (0.0) 
1 (1.0) 
5 
1 (2.6) 
1 (1.0) 
Gravidity 
0.69** 
1 
15 (39.5) 
43. (43.4) 
2 
8 (21.1) 
24 (24.2) 
3 
9 (23.7) 
15 (15.2) 
4 
2 (5.3) 
6 (6.1) 
5+ 
4 (10.5) 
11 (11.1) 
 
*The Mann-Whitney U, **Fisher's Exact test, ***Chi-square test, ª Independent Sample T-
test          
Table 1 represents the comparison of age, parity, and gravidity between two groups. There 
were no significant differences in age, parity and gravidity between pAEDF and iAEDF 
group. 
Table 2. Pregnancy outcomes 
 
 
iAEDF (n=38) 
pAEDF (n=99) 
p-value 
The week of AEDF diagnosis 
28.6 (2.8) 
28.5 (2.9) 
0.84ª   
Gestational age at birth   
30.9 (2.6) 
29.6 (2.8) 
0.03* 
Birthweight  
1067 (450) 
929 (441) 
0.09* 
z score for standardized birthweight 
(-3.05) (1.1) 
(-3.0) (1.6) 
0.73* 
The time passed from the diagnosis to the birth 
15.6 (11.5) 
7.88 (9.99) 
<.0001* 
 

*The Mann-Whitney U, **Fisher's Exact test, ***Chi-square test, ª Independent Sample T-test        
Table 2 represents results from the comparison of the two groups in terms pregnancy outcomes 
including the week of AEDF diagnosis, gestational age at birth, birthweight, z score for 
standardized birthweight and the time passed from the diagnosis to the birth. Mean gestational age 
at birth in women who diagnosed with pAEDF was 29.6  2.8 while mean gestational age at birth 
in women who diagnosed with iAEDF 30.9  2.6 (p-value=0.03). The time passed from the 
diagnosis to the birth was much shorter for women who diagnosed with pAEDF (mean=7.88, 
sd=9.99) than for women who diagnosed with iAEDF (mean=15.6, sd=11.5) (p-value=<.0001).   
Table 3. Pregnancy complications 
 
 
  iAEDF (n=38)      pAEDF (n=99) p-value 
AFV 
0.57** 
A 
4 (10.5) 
9 (9.1) 
N 
29 (76.3) 
66 (66.7) 
O 
5 (13.2) 
21 (21.2) 
P 
0 (0.0) 
3 (3.0) 
IUFD 
 
 
0.57** 
+  
0 (0.0) 
4 (4.0) 
 
                 - 38 (100.0) 
95 (96.0) 
 
Placentel Ablatio 
1.00** 
+  
1 (2.6) 
5 (5.1) 
- 
37 (97.4) 
94 (94.9) 
Fetal Distress 
0.07*** 
+  
15 (39.5) 
56 (56.6) 

- 
23 (60.5) 
43 (43.4) 
IUGR 
 
 
1.00** 
+  
36 (94.7) 
93 (93.9) 
- 
2 (5.3) 
6 (6.1) 
 
*The Mann-Whitney U, **Fisher's Exact test, ***Chi-square test, ª Independent Sample T-
test          
Table 3 represents results from the comparison of the two groups in terms pregnancy 
complications including AFV abnormalities (A: anhydramnios O: oligohydramnios, P: 
polyhydramnios), IUFD (intrauterine fetal demise), placental ablation, fetal distress. There 
were no statistically significant differences between two groups in terms of pregnancy 
complications. However, the percentage of fetal distress in women who diagnosed with 
pAEDF (56.6%) was noticeably higher than the percentage of fetal distress in women who 
diagnosed with iAEDF (39.5%).  
Table 4. Adverse neonatal outcomes 
 
iAEDF (n=38)   pAEDF (n=99) p-value 
Apgar score in the first minute 
5.4 (1.9) 
4.2 (2.2) 
0.004* 
Apgar score in the fiftht minute 7.6 (1.0) 
6.4 (2.2) 
0.002* 
Apgar score in the fiftht minute 
0.02*** 
<7 
5 (13.2) 
33 (33.3) 
 
>=7 
33 (86.8) 
66 (66.7) 
admission to the ICU 
0.58** 
+  
0 (0.0) 
4 (4.0) 
- 
38 (100.0) 
95 (96.0) 

to be intubated. 
0.08*** 
+  
20 (52.6) 
68 (68.7) 
 
- 
18 (47.4) 
31 (31.3) 
 
*The Mann-Whitney U, **Fisher's Exact test, ***Chi-square test, ª Independent Sample T-
test          
The comparison of the two groups in terms adverse neoatal outcomes is given in Table 4. 
Among women who were in the pAEDF group, mean Apgar score in the first minute was 4.2 
 2.2, while the mean Apgar score in the first minute among women who were in the iAEDF 
group was 5.4  1.9 (p-value=0.004). Similarly, the mean Apgar score in the fifth minute was 
lower for the pAEDF group than the iAEDF group (6.4 2.2, 7.6 1.0 respectively).  
The percentage of women with Apgar score in the fifth minute less than 7 in the dak group 
(33.3%) was much higher than the percentage the percentage of women with Apgar score in 
the fifth minute less than 7 in the intermittent dak group (13.2%) (p-value=0.02).