Ultrasound Obstet Gynecol 2022; 59: 483–489

Published online 4 March 2022 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.24854

Ophthalmic artery Doppler at 35–37 weeks’ gestation in

pregnancies with small or growth-restricted fetuses
S. ABDEL AZIM1,2 , M. SARNO1,3 , A. WRIGHT4 , N. VIEIRA1 , M. CHARAKIDA1,5 and
K. H. NICOLAIDES1
1
Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK; 2 Department of Obstetrics and Gynaecology,
Medical University of Innsbruck, Innsbruck, Austria; 3 Department of Obstetrics and Gynecology, Federal University of Bahia (UFBA),
Salvador-Bahia, Brazil; 4 Institute of Health Research, University of Exeter, Exeter, UK; 5 School of Biomedical Engineering and Imaging
Sciences, King’s College London, London, UK

K E Y W O R D S: Doppler; ophthalmic artery; small-for-gestational age

CONTRIBUTION (SGA) or growth-restricted (FGR) neonates in the

absence of hypertensive disorders, women who developed
What are the novel findings of this work?
pre-eclampsia (PE) or gestational hypertension (GH) and
In the third trimester, women with small-for-gestational-
those without SGA, FGR, PE or GH. Second, to examine
age (SGA) fetuses in the absence of hypertensive
the association of PSV ratio with placental growth factor
disorders have increased peak systolic velocity (PSV)
(PlGF) and mean arterial pressure (MAP). Third, to
ratio in the ophthalmic artery on Doppler, mildly
assess the associations of PSV ratio, PlGF and MAP
increased mean arterial pressure and decreased serum
with birth-weight Z-score and percentile.
placental growth factor compared to women with
uncomplicated pregnancy. Although the maternal arterial Methods This was a prospective observational study in
changes resemble those seen in hypertensive disorders women attending for a routine hospital visit at 35 + 0
of pregnancy, they differ in magnitude and physiology. to 36 + 6 weeks’ gestation. This visit included recording
Ophthalmic artery waveform analysis revealed that the of maternal demographic characteristics and medical
predominant feature in pregnancies complicated by SGA history, ultrasound examination of fetal anatomy and
is a reduction in the first systolic wave, whereas, in growth, and measurement of maternal ophthalmic artery
those with hypertensive disorders, there is an increase PSV ratio, first (PSV1) and second (PSV2) peaks of systolic
in the second systolic wave. There is a linear (inverse) velocity, MAP and serum PlGF. The values of PSV ratio,
association between PSV ratio and birth-weight Z-score MAP and PlGF were converted to multiples of the median
in non-hypertensive pregnancies. (MoM) or delta values, and the median MoM or delta of
these variables in the SGA, FGR, PE and GH groups were
What are the clinical implications of this work? compared with those in the unaffected group. Regression
The ophthalmic artery PSV ratio and derivative wave- analysis was used to examine the relationship of PSV
forms can provide information about maternal hemo- ratio delta, PlGF MoM and MAP MoM with birth-weight
dynamics. The linear association between PSV ratio Z-score after exclusion of PE and GH cases. Regression
and birth-weight Z-score suggests the presence of a analysis was also used to examine the association of
continuous physiological relationship between fetal size PSV ratio delta with log10 PlGF MoM and log10 MAP
and cardiovascular response rather than a dichoto- MoM.
mous relationship between high peripheral resistance and
Results The study population included 2287 pregnan-
low cardiac output in small compared with non-small
cies, of which 1954 (85.4%) were not affected by FGR,
fetuses.
SGA, PE or GH, 49 (2.1%) were complicated by FGR
in the absence of PE or GH, 160 (7.0%) had SGA in
ABSTRACT the absence of FGR, PE or GH, 60 (2.6%) had PE and
64 (2.8%) had GH. Compared with unaffected preg-
Objectives First, to compare the ophthalmic artery peak nancies, in both the FGR and SGA groups, the means
systolic velocity (PSV) ratio at 35–37 weeks’ gestation of PSV ratio delta (0.042 (95% CI, 0.007–0.076) and
among women who delivered small-for-gestational-age 0.032 (95% CI, 0.016–0.049), respectively) and MAP

Correspondence to: Prof. K. H. Nicolaides, Fetal Medicine Research Institute, King’s College Hospital, 16–20 Windsor Walk, Denmark Hill,
London SE5 8BB, UK (e-mail: kypros@fetalmedicine.com)
Accepted: 29 December 2021

© 2022 International Society of Ultrasound in Obstetrics and Gynecology. ORIGINAL PAPER

484 Abdel Azim et al.

MoM (1.028 (95% CI, 1.006–1.050) and 1.048 (95% CI, In two recent prospective observational studies, we exam-
1.035–1.060), respectively) were increased, while the ined 2853 unselected pregnancies at 19–23 weeks’ gesta-
mean of PlGF MoM was decreased (0.495 (95% CI, tion and 2287 unselected pregnancies at 35–37 weeks5,6 .
0.393–0.622) and 0.648 (95% CI, 0.562–0.747), respec- In both study groups, we found that PSV ratio was
tively). However, the magnitude of these changes was increased in pregnancies that subsequently developed
smaller than in the PE and GH groups. Ophthalmic artery pre-eclampsia (PE) and that it improved the prediction
waveform analysis revealed that the predominant feature of PE provided by maternal factors alone and by combi-
of pregnancies complicated by SGA in the absence of nations of maternal factors with other biomarkers5,6 .
hypertensive disorders was a reduction in PSV1, whereas, Pregnancies complicated by small-for-gestational age
in those with hypertensive disorders, there was an increase (SGA) at birth in the absence of hypertensive disorders
in PSV2. In non-hypertensive pregnancies, there were lin- share features with PE, including impaired placentation
ear inverse associations of PSV ratio delta and MAP and endothelial dysfunction, and are associated with
MoM with birth-weight Z-score, with increased values in an increased long-term risk of development of maternal
small neonates and decreased values in large neonates. cardiovascular disease7–12 . There are limited data on
There was a quadratic relationship between PlGF MoM ophthalmic artery Doppler in SGA pregnancies. A
and birth-weight Z-score, with low PlGF levels in small cross-sectional study of 60 pregnancies with SGA fetuses
neonates and high PlGF levels in large neonates. There at 32–40 weeks’ gestation and 60 normal controls
was a significant correlation of ophthalmic artery PSV reported that maternal ophthalmic artery PSV ratio in the
ratio delta with both log10 MAP MoM (0.124 (95% CI, SGA group was significantly higher than in the control
0.069–0.178)) and log10 PlGF MoM (−0.238 (95% CI, group13 . A prospective observational study involving 499
−0.289 to −0.185)). singleton pregnancies at 11–14 weeks’ gestation reported
that PSV ratio in the group of 27 women who delivered
Conclusion Assuming that the ophthalmic artery PSV
SGA neonates was slightly higher than in the non-SGA
ratio is a reflection of the interplay between cardiac
group14 .
output and peripheral vascular resistance, the linear
association between PSV ratio and birth-weight Z-score The objectives of this study on 2287 unselected
in non-hypertensive pregnancies suggests the presence of pregnancies at 35–37 weeks’ gestation, which have
a continuous physiological relationship between fetal size been examined previously6 , were, first, to compare the
and cardiovascular response rather than a dichotomous ophthalmic artery PSV ratio among women who delivered
relationship between high peripheral resistance and low SGA or growth-restricted (FGR) neonates in the absence
cardiac output in small compared with non-small fetuses. of hypertensive disorders, women who developed PE or
© 2022 International Society of Ultrasound in Obstetrics gestational hypertension (GH) and those unaffected by
and Gynecology. SGA, FGR, PE or GH, second, to examine the association
between PSV ratio and the established biomarkers of PE,
placental growth factor (PlGF) and MAP, and, third, to
examine the association of PSV ratio, PlGF and MAP
INTRODUCTION with birth-weight Z-score or percentile.
The ophthalmic artery, which is the first branch of the
internal carotid artery, has a Doppler velocity waveform
METHODS
with two systolic peaks. The first systolic wave (PSV1) is
created by cardiac systole, with the opening of the aortic Study design and participants
valve and ejection of blood into the aorta, whilst the sec-
ond systolic wave (PSV2) is a reflective wave formed by This was a prospective observational study in women
the systolic pulse wave reaching smaller, higher resistance attending for a routine hospital visit at 35 + 0 to
arterioles and being reflected back towards the heart. At 36 + 6 weeks’ gestation at King’s College Hospital,
the level of the aortic arch, a fraction is diverted cranially London, UK, between June 2019 and March 2020. This
to the cerebral circulation as a forward wave to create visit included, first, recording of maternal demographic
PSV21,2 . In this way, PSV2 is most influenced by periph- characteristics and medical history, second, ultrasound
eral arterial compliance and resistance, whilst PSV1 is examination for fetal anatomy and growth, third, two
more affected by cardiac output. Therefore, an increase recordings of flow velocity waveforms from the left and
in the ratio of PSV2 to PSV1 (PSV ratio) could repre- right maternal ophthalmic arteries and calculating the
sent an increase in peripheral vascular resistance and/or a average of the four measurements for PSV1, PSV2 and
reduction in cardiac output3 . The association between PSV ratio15 , fourth, measurement of MAP by validated
ophthalmic artery PSV ratio and peripheral vascular automated devices following a standardized protocol16 ,
resistance is supported by the findings of a study in hyper- fifth, color flow imaging of the left and right uterine arter-
tensive pregnancies, which reported a high correlation ies (UtA) by transabdominal ultrasound and measurement
between PSV ratio and mean arterial pressure (MAP) and a of mean UtA pulsatility index (PI)17 , color flow imaging
decrease of both MAP and PSV ratio after the administra- of the umbilical artery (UA) and fetal middle cerebral
tion of antihypertensive drugs, such as nifedipine modified artery (MCA) and measurement of UA-PI and MCA-PI18
release and labetalol, which reduce peripheral resistance4 . and, sixth, measurement of serum concentration of

© 2022 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 483–489.
Ophthalmic artery Doppler and small-for-gestational age 485

PlGF in pg/mL by an automated biochemical analyzer artery PSV ratio delta, PSV1 MoM, PSV2 MoM, PlGF
(BRAHMS KRYPTOR compact PLUS, Thermo Fisher MoM and MAP MoM in SGA, FGR, PE and GH
Scientific, Hennigsdorf, Germany). Gestational age was groups were compared with those in the unaffected group
determined by the measurement of fetal crown–rump using t-test. Regression analysis was used to examine the
length at 11–13 weeks or fetal head circumference at relationship of PSV ratio delta, PlGF MoM and MAP
19–24 weeks19,20 . The women gave written informed MoM with birth-weight Z-score. Regression analysis
consent to participate in the study, which was approved was also used to examine the association of PSV ratio
by the NHS research ethics committee. delta with log10 PlGF MoM and log10 MAP MoM.
The inclusion criteria for this study were singleton The statistical software package R was used for data
pregnancy examined at 35 + 0 to 36 + 6 weeks’ gestation analysis23 .
and delivering a non-malformed liveborn neonate. We
excluded pregnancies with aneuploidy or major fetal
abnormalities and those with PE at the time of screening. RESULTS

Study participants
Outcome measures
The study population included 2287 pregnancies, of
Data on pregnancy outcome were collected from the which 1954 (85.4%) were not affected by FGR, SGA,
hospital maternity records or the general medical PE or GH, 49 (2.1%) were complicated by FGR in
practitioners of the women. Outcome measures were the absence of PE or GH, 160 (7.0%) had SGA in the
delivery with SGA, FGR, PE or GH. Diagnosis of SGA in absence of FGR, PE or GH, 60 (2.6%) had PE and 64
the absence of hypertensive disorders was made if birth (2.8%) had GH. Maternal and pregnancy characteristics
weight was < 10th percentile of the The Fetal Medicine of the study population are summarized in Table 1. In
Foundation fetal and neonatal population weight charts21 the SGA group, compared with unaffected pregnancies,
in the absence of PE or GH and in the presence of UtA-PI there was a lower median maternal weight and body
≤ 95th percentile, UA-PI ≤ 95th percentile and MCA-PI mass index, and higher proportions of non-white and
≥ 5th percentile. Diagnosis of FGR in the absence of nulliparous women. In the PE and GH groups, compared
hypertensive disorders was made if birth weight was with unaffected pregnancies, there was a higher median
< 10th percentile in the absence of PE or GH and in maternal weight and body mass index, and a higher rate
the presence of UtA-PI > 95th percentile, UA-PI > 95th of nulliparity and previous PE.
percentile or MCA-PI < 5th percentile. Diagnosis of GH
was based on the finding of hypertension (systolic blood
Distribution of biomarkers in SGA, FGR, PE, GH and
pressure of ≥ 140 mmHg or diastolic blood pressure of
unaffected pregnancies
≥ 90 mmHg on at least two occasions 4 h apart developing
after 20 weeks’ gestation in previously normotensive The median (IQR) of PSV ratio delta and PSV1, PSV2,
women). Diagnosis of PE was based on the finding of PlGF and MAP MoMs according to study group is shown
new onset hypertension or chronic hypertension and at in Figure 1 and the mean (95% CI) of each group com-
least one of the following: proteinuria (≥ 300 mg/24 h pared with unaffected pregnancies is shown in Table 2. In
or protein-to-creatinine ratio ≥ 30 mg/mmol or ≥ 2 + both FGR and SGA groups in the absence of hypertensive
on dipstick testing), renal insufficiency with serum disorders, the PSV ratio delta and MAP MoM were
creatinine > 97 μmol/L in the absence of underlying renal increased and PlGF MoM was decreased compared with
disease, hepatic dysfunction with blood concentration unaffected pregnancies. However, the magnitude of these
of transaminases more than twice the upper limit of changes was smaller than in PE and GH groups. In
normal (≥ 65 IU/L for our laboratory), thrombocytopenia addition, in the SGA group, PSV1 MoM was reduced,
(platelet count < 100 000/μL), neurological complications whereas, in pregnancies complicated by GH, both PSV1
(e.g. cerebral or visual symptoms) or pulmonary edema22 . MoM and PSV2 MoM were increased (Table 2).
The associations of PSV ratio delta, PlGF MoM and
Statistical analysis MAP MoM with birth-weight Z-score or percentile in all
pregnancies after exclusion of PE and GH are shown in
Data were expressed as median (interquartile range Figure 2 and the fitted regression models are presented
(IQR)) for continuous variables and n (%) for categorical in Table 3. There was a linear inverse association of PSV
variables. Student’s t-test and chi-square test or Fisher’s ratio delta and MAP MoM with birth-weight Z-score,
exact test were used for comparing continuous and with increased values in small neonates and decreased
categorical data, respectively, between outcome groups. values in large neonates. There was a quadratic rela-
The measured values of biomarkers were converted to tionship between PlGF MoM and birth-weight Z-score,
multiples of the median (MoM) or delta to remove the with lower PlGF levels in small neonates and higher
effects of characteristics such as gestational age, weight, PlGF levels in large neonates. There was a significant
race, method of conception, medical conditions, obstetric correlation of ophthalmic artery PSV ratio delta with
history and characteristics of the instrument used for the log10 MAP MoM (0.124 (95% CI, 0.069–0.178)) and
measurement. The means with 95% CIs of ophthalmic log10 PlGF MoM (−0.238 (95% CI, −0.289 to −0.185)).

© 2022 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 483–489.
486 Abdel Azim et al.

Table 1 Maternal and pregnancy characteristics of the study population

Unaffected FGR* SGA (no FGR)* PE GH

Characteristic (n = 1954) (n = 49) (n = 160) (n = 60) (n = 64)
Age (years) 33.6 (30.6–36.8) 31.0 (28.4–36.5) 33.9 (31.0–36.8) 34.0 (30.3–37.0) 34.6 (30.8–38.2)
Weight (kg) 78.0 (71.0–87.5) 79.7 (68.0–88.2) 73.0 (65.3–81.9)† 85.5 (76.0–93.4)† 83.7 (71.4–101.7)†
Height (cm) 167 (163–171) 165 (162–168) 164 (159–168)† 166 (163–171) 166 (163–168)
Body mass index (kg/m2 ) 28.2 (25.7–31.3) 29.2 (25.4–31.8) 26.9 (24.6–30.5)† 30.6 (27.7–33.6)† 29.7 (26.5–36.5)†
Gestational age (weeks) 35.7 (35.6–36.0) 35.9 (35.4–36.0) 35.7 (35.4–36.0) 35.8 (35.6–36.0) 35.9 (35.6–36.1)
Racial origin
White 1483 (75.9) 32 (65.3) 108 (67.5)† 45 (75.0) 48 (75.0)
Black 228 (11.7) 11 (22.4) 24 (15.0) 10 (16.7) 13 (20.3)
South Asian 104 (5.3) 4 (8.2) 17 (10.6) 1 (1.7) 0 (0)
East Asian 70 (3.6) 0 (0.0) 4 (2.5) 2 (3.3) 1 (1.6)
Mixed 69 (3.5) 2 (4.1) 7 (4.4) 2 (3.3) 2 (3.1)
Medical history
Chronic hypertension 25 (1.3) 1 (2.0) 7 (4.4) 2 (3.3) 64 (100)
Diabetes mellitus 25 (1.3) 0 (0) 2 (1.3) 3 (5.0) 2 (3.1)
Smoker 7 (0.4) 0 (0) 2 (1.3) 1 (1.7) 0 (0)
Family history of PE 59 (3.0) 1 (2.0) 8 (5.0) 5 (8.3) 3 (4.7)
Method of conception
Spontaneous 1853 (94.8) 46 (93.9) 148 (92.5) 54 (90.0) 58 (90.6)
In-vitro fertilization 94 (4.8) 3 (6.1) 10 (6.3) 6 (10.0) 6 (9.4)
Ovulation drugs 7 (0.4) 0 (0) 2 (1.3) 0 (0) 0 (0)
Parity
Nulliparous 1003 (51.3) 29 (59.2) 104 (65.0)† 49 (81.7)† 39 (60.9)†
Parous, no previous PE 916 (46.9) 18 (36.7) 52 (32.5) 9 (15.0) 20 (31.3)
Parous, previous PE 35 (1.8) 2 (4.1) 4 (2.5) 2 (3.3)† 5 (7.8)†
Interpregnancy interval (years) 2.4 (1.6–4.1) 2.6 (1.4–5.0) 2.9 (1.9–6.7) 3.2 (2.0–5.6) 3.2 (2.2–5.2)

Data are given as median (interquartile range) or n (%). *In non-hypertensive pregnancies. †Significant difference compared with unaffected
pregnancies. Outcome groups were compared using chi-square or Fisher’s exact test for categorical variables and Mann–Whitney U-test for
continuous variables. FGR, fetal growth restriction; GH, gestational hypertension; PE, pre-eclampsia; SGA, small-for-gestational age.

0.4 3.0 3.0 12.0 1.4

8.0
0.3

2.0 2.0
4.0 1.2
0.2
1.6 1.6
0.1 2.0
PSV ratio delta

PSV2 MoM

MAP MoM
PlGF MoM
PSV1 MoM

1.2 1.2
0.0 1.0 1.0
1.0 1.0
−0.1 0.6
0.8 0.8 0.9
0.4
−0.2
0.6 0.6 0.8
0.2
−0.3

0.1
−0.4 0.4 0.4 0.7

Figure 1 Box-and-whiskers plots of ophthalmic artery peak systolic velocity (PSV) ratio delta, first (PSV1) and second (PSV2) systolic
velocities multiples of the median (MoM), placental growth factor (PlGF) MoM and mean arterial pressure (MAP) MoM in unaffected
pregnancies ( ), non-hypertensive pregnancies complicated by fetal growth restriction (FGR) ( ) or by small-for-gestational age without
FGR ( ) and pregnancies with pre-eclampsia ( ) or gestational hypertension ( ). Boxes are median and interquartile range and whiskers are
range. *Significant difference compared with unaffected pregnancies.

DISCUSSION PSV ratio and MAP are increased and serum PlGF is
decreased compared with unaffected pregnancies, but the
Principal findings of this study
magnitude of these changes is smaller than in pregnancies
This prospective non-interventional study of women complicated by PE or GH. Second, the predominant
attending for a routine hospital visit at 35–37 weeks has feature in non-hypertensive pregnancies delivering SGA
four main findings. First, in non-hypertensive pregnancies or FGR neonates is a reduction in PSV1, whereas, in
delivering SGA or FGR neonates, the ophthalmic artery pregnancies complicated by PE or GH, the main feature

© 2022 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 483–489.
Ophthalmic artery Doppler and small-for-gestational age 487

Table 2 Comparison of mean (95% CI) ophthalmic artery (OA) Doppler measurements, placental growth factor (PlGF) multiples of the
median (MoM) and mean arterial pressure (MAP) MoM between adverse outcome groups and the unaffected group

Parameter Unaffected FGR or SGA FGR SGA (no FGR) PE GH

OA PSV ratio delta 0.000 0.035 0.042 0.032 0.114 0.078
(−0.005 to 0.005) (0.020–0.050)* (0.007–0.076)* (0.016–0.049)* (0.084–0.144)* (0.051–0.106)*
OA PSV1 MoM 1.000 0.958 0.971 0.954 1.043 1.084
(0.990–1.010) (0.928–0.988)* (0.904–1.043) (0.923–0.986)* (0.983–1.107) (1.024–1.147)*
OA PSV2 MoM 1.000 1.016 1.035 1.010 1.263 1.224
(0.987–1.013) (0.979–1.054) (0.935–1.146) (0.972–1.051) (1.172–1.360)* (1.131–1.326)*
PlGF MoM 1.000 0.608 0.495 0.648 0.366 0.459
(0.964–1.038) (0.537–0.689)* (0.393–0.622)* (0.562–0.747)* (0.306–0.438)* (0.376–0.559)*
MAP MoM 1.000 1.043 1.028 1.048 1.122 1.124
(0.997–1.003) (1.032–1.054)* (1.006–1.050)* (1.035–1.060)* (1.105–1.140)* (1.104–1.144)*

*Significant difference compared with the unaffected group. FGR, fetal growth restriction; GH, gestational hypertension; PE, pre-eclampsia;
PSV, peak systolic velocity; PSV1, first peak of systolic velocity; PSV2, second peak of systolic velocity; SGA, small-for-gestational age.

(a) BW Z-score (b) BW Z-score (c) BW Z-score

−2 −1 0 1 2 −2 −1 0 1 2 −2 −1 0 1 2
0.075 1.4 1.12

1.2 1.10
0.050
1.08
1.0
0.025
1.06
PSV ratio delta

MAP MoM
PlGF MoM

0.8
0.000 1.04

1.02
−0.025 0.6
1.00

−0.050
0.98

−0.075 0.4 0.96

5 10 30 50 70 90 95 5 10 30 50 70 90 95 5 10 30 50 70 90 95
BW percentile BW percentile BW percentile

Figure 2 Association of ophthalmic artery peak systolic velocity (PSV) ratio delta (a), placental growth factor (PlGF) multiples of the median
(MoM) (b) and mean arterial pressure (MAP) MoM (c) with birth-weight (BW) Z-score or percentile in non-hypertensive pregnancies.

is an increase in PSV2. Third, there is a significant hypertensive disorders are associated with suboptimal
correlation of ophthalmic artery PSV ratio with both placentation24,25 , and this is reflected by our finding of
MAP and PlGF. These findings highlight the presence reduced serum PlGF in these conditions. However, our
of a close inter-relationship between placental function, study also highlights important differences between SGA
systemic perfusion and maternal ophthalmic artery and hypertensive disorders in maternal hemodynamic
Doppler waveform. Fourth, there are linear (inverse) response. Although we did not perform direct assessment
associations of PSV ratio delta and MAP MoM with of cardiac output and peripheral vascular resistance, our
birth-weight Z-score, whereby the values are increased data suggest that the ophthalmic artery PSV ratio can be
in small neonates and decreased in large neonates, used as an indirect marker of both. In both SGA and PE,
and a quadratic relationship between PlGF MoM and the PSV ratio was increased, albeit to a greater degree in
birth-weight Z-score, with low PlGF levels in small the latter; however, the difference in the component waves
neonates and high PlGF levels in large neonates. of PSV1 and PSV2 suggests that the predominant feature
in SGA is reduced cardiac output, whereas the main
Interpretation of results feature of PE is increased peripheral vascular resistance.
The finding of a linear relationship between birth-weight
Pregnancies complicated by hypertensive disorders Z-score and PSV ratio is consistent with the results of a
and those with a SGA fetus in the absence of previous study in uncomplicated pregnancies, in which

© 2022 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 483–489.
488 Abdel Azim et al.

Table 3 Regression models summarizing the relationship of In addition, all our measurements were performed late
ophthalmic artery peak systolic velocity (PSV) ratio, placental in gestation; therefore, our observations may be reflective
growth factor (PlGF) and mean arterial pressure (MAP) with
of the changes seen in term PE and late SGA but not
birth-weight Z-score, in study population after exclusion of
pregnancies with hypertensive disorders representative of the physiology seen in early pregnancy
or mid-gestation in association with early SGA or early PE.
Estimate (95% CI) P

PSV ratio delta Conclusions

Intercept 0.43764 < 0.0001
(0.29319 to 0.58209) Assuming that the ophthalmic artery PSV ratio is
Birth-weight Z-score −0.00872 0.0002 a reflection of the interplay between cardiac output
(−0.01331 to −0.00414) and peripheral vascular resistance, the linear (inverse)
GA at delivery (in weeks) −0.01090 < 0.0001 association between the PSV ratio and birth-weight
(−0.01452 to −0.00728)
PlGF MoM
Z-score in non-hypertensive pregnancies suggests the
Intercept −1.92574 < 0.0001 presence of a continuous physiological relationship
(−2.39866 to −1.45282) between fetal size and cardiovascular response rather
Birth-weight Z-score 0.07420 < 0.0001 than a dichotomous relationship between high peripheral
(0.05923 to 0.08917) resistance and low cardiac output in pregnancies with
(Birth-weight Z-score)2 −0.01012 0.047
small compared with non-small fetuses.
(−0.02012 to −0.00012)
GA at delivery (in weeks) 0.04807 < 0.0001
(0.03625 to 0.05989)
MAP MoM
ACKNOWLEDGMENTS
Intercept 0.11786 0.001
The study was supported by a grant from The Fetal
(0.04567 to 0.19005)
Birth-weight Z-score −0.00424 0.0003 Medicine Foundation (Charity No: 1037116). The
(−0.00653 to −0.00195) reagents and equipment for the measurement of serum
GA at delivery (in weeks) −0.00291 0.002 placental growth factor were provided by Thermo Fisher
(−0.00472 to −0.00110) Scientific. These bodies had no involvement in the study
GA, gestational age; MoM, multiples of the median.
design, collection, analysis and interpretation of data,
writing of the report or decision to submit the article for
publication.
we reported that cardiac output decreased and peripheral
vascular resistance increased linearly with decreasing
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