Third trimester fetal haemodynamics and cardiovascular outcomes in
childhood. The Generation R Study
Running title: Fetal haemodynamics and cardiac outcomes
Marjolein N. KOOIJMAN MSc; Layla L. DE JONGE MD, PhD, MSc; Eric A.P. STEEGERS MD,
PhD; Lennie VAN OSCH-GEVERS MD, PhD; Bero O. VERBURG MD, PhD; Albert HOFMAN
MD, PhD; Willem A. HELBING MD, PhD; Vincent W.V. JADDOE MD, PhD
SUPPLEMENTAL DIGITAL CONTENT 1
Tables: 2
Figures: 1
Table S1. Associations of fetal third trimester vascular resistance parameters with cardiovascular structures and function at the age of 6 years (n=917)
Umbilical artery PI
(SD = 0.16)
U/C ratio (middle cerebral
artery) (SD = 0.12)
Systolic blood
Diastolic blood
Pulse wave
Aortic root
Left ventricular
Fractional
pressure
pressure
velocity
diameter
mass
shortening
(SD = 7.8 mmHg)
(SD = 6.4 mmHg)
(SD = 1.0 m/s)
(SD = 1.8 mm)
(SD = 11.3 g)
(SD = 4.5 %)
0.00
-0.02
0.03
-0.06
-0.07
0.07
(-0.05, 0.06)
(-0.07, 0.03)
(-0.05, 0.11)
(-0.13, 0.00)
(-0.13, -0.01)*
(0.00, 0.14)
0.01
-0.02
0.06
-0.08
-0.06
0.02
(-0.05, 0.06)
(-0.07, 0.03)
(-0.02, 0.15)
(-0.15, -0.02)*
(-0.13, 0.00)*
(-0.04, 0.09)
Values are regression coefficients (95% confidence intervals) and reflect the change in SD score of blood pressure, carotid-femoral pulse wave velocity, left
cardiac structures and fractional shortening per change in SD score of vascular resistance parameters. Models are adjusted for gestational age at third trimester
measurement, child sex and current age. Models with ultrasound outcomes are additionally adjusted for ultrasound device and performing sonographer.
SD = standard deviation
* P<0.05
Table S2. Associations of third trimester fetal cardiac haemodynamics with cardiovascular structures
and function at the age of 6 years (n=917)
Aortic root
Left ventricular
Fractional
diameter
mass
shortening
(SD = 1.8 mm)
(SD = 11.3 g)
(SD = 4.5 %)
0.17
0.11
-0.05
(0.09, 0.24)†
(0.04, 0.17)†
(-0.13, 0.03)
-0.04
0.01
0.01
(-0.10, 0.03)
(-0.05, 0.08)
(-0.06, 0.08)
-0.01
0.02
-0.01
(-0.08, 0.05)
(-0.04, 0.08)
(-0.08, 0.06)
0.12
0.08
-0.04
(SD = 175.4 ml/min)
(0.05, 0.19)†
(0.01, 0.15)*
(-0.12, 0.03)
Mitral valve E wave
-0.06
-0.04
0.02
(-0.12, 0.00)
(-0.10, 0.02)
(-0.05, 0.08)
0.02
-0.02
0.03
(-0.05, 0.08)
(-0.08, 0.04)
(-0.04, 0.09)
-0.10
-0.04
-0.01
(-0.16, -0.04)†
(-0.10, 0.02)
(-0.08, 0.06)
Aorta ascendens diameter (SD
= 7.0 mm)
Aorta ascendens PSV
(SD = 12.4 cm/s)
Aorta ascendens TVI
(SD = 2.1)
Left cardiac output
(SD = 6.3 cm/s)
Mitral valve A wave
(SD = 8.0 cm/s)
Mitral valve E/A ratio
(SD = 0.1)
Values are regression coefficients (95% confidence intervals) and reflect the change in SD score of
left cardiac structures and fractional shortening per change in SD score of fetal cardiac haemodynamic
parameters. Models are adjusted for gestational age at third trimester measurement, child sex and
current age, ultrasound device and performing sonographer.
SD = standard deviation
* P<0.05, † P<0.01
Figure S1. Flow chart of participants included in the analysis.
Singleton live births participating in the Generation R
Focus Cohort
N = 1,216
N = 15 Excluded, due to missing placental and
fetal haemodynamic measurements
Data on placental and fetal haemodynamics
N = 1,201
N = 276 Excluded, due to withdrawal of
consent (N = 35), loss to follow-up (N =15), or
not visiting the research center
Data on 6 year visit
N = 925
(N = 226)
N = 7 Excluded, due to missing cardiovascular
measurements
Data on cardiovascular outcomes
N = 918
N = 1 Excluded, due to echocardiographic
evidence of heart disease
Participation in 6 years visit: N = 917
Cardiac ultrasounds: N = 870
Pulse wave velocity: N = 744
Blood pressure: N = 904