Discussion
With the development of medical research in recent years, nomogram is a
new type of multi-factor statistical method, which has better advantages
than the total statistical method. It is widely applied in the medical
fields and provides a visual basis for clinical work. Our study was the
first to use nomogram to explore the risk of fetal distress and
admission to NICU in patients with FGR in china. Using a novel
prediction tool that was the lasso regression screened out more
influential and available variables from the research factors in
patients with FGR.
At present, FGR is the most concerned disease that affects fetal outcome
in the field of fetal medicine 14. In the early stage,
Barker firstly proposed a hypothesis which was ”fetal origins of adult
hypothesis”15, 16 . With the
continuous research and development of the disease, it gradually
transformed into ”developmental origins of health and
disease”17, 18.An unhealthy maternal
intrauterine environment not only affected the growth and development of
the fetus, but also caused adverse consequences for the
fetus19. Therefore, owing to its effective prenatal
monitoring, timing and method of pregnancy termination are particularly
important. However, there are still great controversies about FGR
management due to the lack of effective and gold standard.
Our study started from the maternal disease to explore the outcome of
the fetus, which has important clinical value. In the prediction model
one, six independent variates were presented as predictors of fetal
distress, and nine optimal predictors for staying into the NICU. With
the increase of pregnant women’s age, the decrease of gestational week,
abnormal cord blood flow during pregnancy, the risk of fetal distress
has increased in the fetus of FGR patients. Among them, the risk of
fetal distress in FGR patients at the age of 40 years old was
significantly higher than the others at the age of 35 years old (OR
=4.058, 95% CI 1.872-8.622,P < 0.001). And abnormal
cord blood flow also increased its risk obviously (OR =7.563, 95% CI
3.653-16.146, P < 0.001). FGR patients with placenta
previa could reduce the occurrence of fetal distress (OR =0.330, 95% CI
0.094-0.878, P =0.046). At present, there is no clear and
sufficient evidence to prove that LMWH plays a role in the treatment of
fetal growth restriction, so further research is still under way. Our
study found that the application of LMWH during pregnancy could reduce
the incidence of fetal distress (OR =0.554, 95% CI 0.331-0.895,P =0.020), but not affecting the risk of fetal entered into the
NICU by lasso regression analysis. Therefore, we recommend that LMWH
could reduce the incidence of fetal distress, which is consistent with
the latest research results3, 20.
For the use of clinical aspirin, a meta-analysis of research randomized
controlled trials had shown that aspirin decreased the risk of fetal
growth restriction21. We used the lasso regression to
screen out variates, indicating that aspirin did not decrease the risk
of fetal distress for fetal growth restriction. Our research tentatively
studied that the gestational week decreases would increase the incidence
of admission to NICU after birth (P < 0.001), which was
similar to the research22. The fetus of FGR patients
with HDP, ICP was easier to entry into the NICU (P =0.032,P =0.011). The use of prednisone during pregnancy did not reduce
the incidence of admission to NICU(P =0.120). For the more, it is
interesting that children to be born for FGR patients whose sex is a boy
was not significantly related to the incidence of staying in the
NICU(P =0.244).
Regarding to the delivery method of FGR patients, it is not an absolute
indication of cesarean section. When the cord blood flow was abnormal,
it was recommended to terminate the pregnancy by cesarean section23. However, there was still a lot of controversy
about the timing of delivery and the method of delivery in various
countries 23-26. The innovative findings of this study
were that vaginal delivery, compared with cesarean delivery, could
reduce the incidence of fetal distress and admission to NICU for FGR
patients (P < 0.001, P < 0.001)). A
foreign study showed that most patients with FGR achieved vaginal
delivery, the terrible fetal outcome did not
increase27. Even one research advocated vaginal
delivery28. Therefore, we recommend that FGR patients
chose vaginal delivery without serious emergency complications, and we
monitored the labor process during delivery.
The independent predictors of two nomograms were developed based on
prediction model one and two. We could add up the single points
corresponding to the independent predictors of patients with FGR to get
the total points. Finally, we got the probability of risk of fetal
distress or admission to NICU. It was easier and more intuitive for
clinicians to understand its risks. For example, the nomogram of
prediction model two, a FGR patients of 34 gestational weeks (about 83
point), using the cesarean section to terminate pregnancy (about 40
point), without HDP (0 point) and ICP (0 point). The total points are
120 points, and the corresponding risk of admission to NICU is about
78%. At the same time, when we verified two models, we found that these
had good discrimination and calibration power. The internal verification
results are consistent with the previous ones. When verified two models,
we found that these had good discrimination and calibration power. The
decision curve analysis suggested two models had better clinical
application value. The internal verification results are consistent with
the previous ones.
The current shortcoming of this study is that the timing of LMWH
treatment and the timing of drug withdrawal was not studied, so further
research is needed. In summary, the establishment of an effective
predictive model is the key to prenatal management of the fetal outcome
of FGR patients and provides a reliable basis for clinicians. The
further treatment can reduce the occurrence of adverse maternal and
infant outcomes.