First trimester differences in ultrasound parameters between pregnancies complicated by uteroplacental insufficiency and uncomplicated pregnancies: an observational study

Important pregnancy complications, such as preeclampsia (PE) and fetal growth
restriction (FGR) share uteroplacental insufficiency (UPI) as a common
pathophysiology. PE and FGR represent a major concern in public health,
affecting 2-8% and 5-10% of all pregnancies, respectively, and are a leading
cause of perinatal morbidity and mortality. For UPI and its subsequent
pregnancy conditions, no causal treatment is available, besides adequate fetal
monitoring and timely delivery.
Estimating the risk for UPI and its high-impact pregnancy complications
is challenging in daily practice. Literature demonstrates that predictive
accuracy for FGR (as a consequence of UPI) is minimal to low for FGR-related
biomarkers; at least when independently deployed.(3) It is unknown whether
possible biomarkers related to placental dysfunction are altered in the first
trimester already; before clinical features of UPI are manifest (e.g.
hypertension and proteinuria for PE). At the time of clinical presentation, UPI
is reflected in the resistance to blood flow in the uterine arteries (maternal)
and umbilical (placental) arteries, which can be measured by Doppler US. It is
unknown whether these changes are already present in the first trimester,
especially in fetuses with late-onset FGR (>=32 weeks of pregnancy (as a
consequence of UPI). Especially the accuracy of the diagnosis of FGR with a
late onset is poor.
We aim to investigate whether there are differences in Doppler US
parameters and possible biomarkers measured during the 13-week scan between
pregnancies complicated by UPI and pregnancies not complicated by UPI.
Prospectively evaluating this in the first trimester of pregnancy might be a
stepping stone towards a 1st trimester screening strategy for UPI based on
Doppler US and possible biomarkers could have additional value in this. Such a
newly to develop screening algorithm would allow clinicians to make a risk
assessment, early in pregnancy with the possibility of intervening by means of
antiplatelet agents or intensified fetal monitoring; this might prevent or
milden the consequences of UPI. With the 13-week scan now being part of
standard prenatal care in the Netherlands, clarifying the additional value of
such a strategy could be extremely valuable.

Primary objective:
To investigate whether there are differences in Doppler ultrasound (US)
parameters measured during the routine 13-week scan between pregnancies
complicated by uteroplacental insufficiency (UPI) and pregnancies not
complicated by UPI.
Secondary objective:
To study differences in other possible biomarkers, such as serum samples in
pregnancies complicated by UPI compared to pregnancies not complicated by UPI,
sampled during the routine 13-week scan.

Observational prospective study.

The study population consists of singleton pregnant women undergoing a 13-week
scan in the UMCG in the context of a combined test (cT) and/or indicated
screening anomaly scan. The ultrasound (US) exam and including measurements at
13 weeks gestational age are in the context of a routine cT and/or an indicated
screening anomaly scan. In the context of the study we ask permission of the
participant for including these data in the research database, analyzing the
recorded data and withdrawal of 2 extra bloodsamples (taken during the visit
for the scan).

To evaluate whether uteroplacental insufficiency (UPI) develops during
pregnancy, fetal growth and Doppler profiles should be measured later on in
pregnancy. The US exam and including measurements at 20 weeks gestation is in
the context of standard prenatal care in the Netherlands. In the context of the
study we ask permission of the participant for including these data in the
research database and analyzing the recorded data.
In the context of the study we ask the participant to return for an additional
US of circa 15 minutes at >=32 weeks gestation, where we will again evaluate
fetal growth and Doppler profiles (thus UPI). Blood withdrawal is only
necessary during the 13-week scan.