Study on adequate identification of the term fetus at risk due to intra uterine growth restriction.

Perinatal morbidity and mortality are increased in term fetuses with a birth
weight below the 10th population percentile. Perinatal mortality is around 1%.
Data from the Dutch Perinatal Registry have shown that the risk of perinatal
mortality in term fetuses increases from 0.1% to 0.8% and 2% when the birth
weight percentile decreases from the 75th centile to the 5th-10th percentile
and below the 2.3rd centile, respectively. About 60% of term perinatal
mortality concerns children with a birth weight percentile below the 10th
percentile. A low birth weight has important consequences for future
development, especially for cardiovascular, metabolic and neurological
development. (DOHaD; *Barker hypothesis*).

Term small-for-gestational-age (SGA) fetuses present the obstetrician with at
least two difficulties. Firstly they are difficult to identify. After
identification of the small fetus, the second challenge concerns the
distinction between pathologically small fetuses, most likely accompanied by a
suboptimal placental function, and healthy small fetuses. Such a distinction is
difficult, since most assessment tools fail during the term period.

The importance of being able to identify fetuses at risk resides in the
possibility to target interventions with potential adverse effects if used too
liberally. This has been shown by a recent large randomized trial in which an
unselected population of term fetuses with an estimated fetal weight below the
10th percentile were randomized between immediate induction of labor or
expectant management. The incidence of adverse outcomes did not differ between
both groups. In other words, too many constitutionally small fetuses were
exposed to an unnecessary intervention with risks of complications obscuring
the possible gain of early intervention in fetuses at real risk.
Many parameters have been evaluated to distinguish between constitutionally
small and pathologically small fetuses with little result so far. Doppler
evaluation of flow patterns in the umbilical artery are used routinely in
preterm growth restricted fetuses but are normal in most cases in term
small-for-gestational-age fetuses. This due to the fact that a high placental
resistance occurs only when more than 1/3rd of placenta function is deficient.
Oligohydramnios is not specific enough. Abnormal fetal heart rate patterns can
reliably identify fetal distress but are a late sign of impairment. Monitoring
of fetal movements is subjective and reduced movements are generally also a
late sign of impairment. ,

Recently a number of diagnostics tools have been described in small case
series, which have potential in the early recognition of the term SGA fetus at
risk for adverse neonatal outcome:

Ultrasound:
-Flow patterns and ratio's in maternal and fetal arteries: a. umbilicalis , a.
cerebri media, ductus venosus, a. uterina
Fetal heart rate registration:
- Analysis of the autonomous regulation of the fetal heart rate. Assessed by
relatively new promising methods; spectral analysis or phase rectified signal
averaging (PRSA) of the fetal heart rate, measured by electromyography.

The challenge is to find combinations amongst these new monitoring modalities
that will identify term SGA fetuses at risk, in such a way that targeted
intervention studies can be performed.

Evaluate the potential of these new parameters to identify
small-for-gestational-age fetuses at risk of adverse outcome.

Prospective longitudinal observational study in which multiple antenatal
parameters are correlated to neonatal outcome.

Risks/burden:
During pregnancy all additional measurements will solely be performed during
routine investigation; all of the participating women will receive standard
care. Fetal heart rate recording by the AN24 recorder is completely
non-invasive. Therefore the maternal or fetal risk and time/effort burden for
the patient is negligible.
For the neurological assessment of the child at 3 months, a validated
assessment will be used; Qualitative assessment of general movements according
to Prechtl. This is the only additional examination for these children.
For the further follow up, participants will be contacted after 1 year and
after 2 years for information about growth and neurobehavioral assessment, this
could be considered as a minimal burden.
The risk for participating mothers is classified as negligible. Although the
risk for the participating children is also extremely small, due to the fact
this group is very vulnerable, classification is minimal crossing of a neglible
risk. Risk classification is based on the document "Kwaliteitsborging van
mensgebonden onderzoek' of the NFU, page 36 table 1:Risk classification.

Benefits:
A low birth weight has important consequences for future development,
especially for cardiovascular, metabolic and neurological development. (DOHaD;
*Barker hypothesis*).Identifying true growth restriction may contribute to
adequate timely delivery resulting in prevention of long term
neurodevelopmental and cardiovascular consequences. The importance of being
able to identify fetuses at risk also resides in the possibility to target
interventions with potential adverse effects if used too liberally, for example
unnecessary premature termination of pregnancy with immature long maturation as
a consequence.
Even though participating patients will not benefit personally, due to its
potential large benefit for patients in the future, this study should be
considered ethically acceptable.