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.