Clinical Significance and Correlation Decomposition of Cord Blood NO, Activin A Levels, and MCA/UA with Fetal Distress.

The clinical significance and correlation of cord blood NO, activin A levels, and middle cerebral artery (MCA)/umbilical artery (UA) with fetal distress are explored. 120 puerperae who delivered in the obstetrics department of our hospital from January 2021 to January 2022 are selected as the examination subjects. According to the diagnostic criteria of fetal distress, they are divided into 70 cases of fetal distress and 50 cases of normal delivery. The parameters of umbilical cord blood NO, activin A, UA, and MCA are contrast between the two sets, then the diagnostic value of umbilical cord blood NO and activin A combined with UA and MCA in fetal distress is analyzed. The experimental results show cord blood NO and activin A combined with UA and MCA have a high diagnostic value for fetal distress, and there is an extensive correlation with the occurrence of fetal distress, which provides a reliable clinical diagnosis of fetal distress in a timely manner.

1. Introduction

Neonatal asphyxia caused by persistent fetal distress is one of the main causes of perinatal death and can be complicated by various systemic diseases. Essentially, it may be complicated by various systemic diseases, especially affecting the cardiovascular system and the central nervous system and can cause permanent neurological consequences after childbirth, threatening not only perinatal life and future quality of life but also a burden on families and society [1, 2]. Although the causes of neonatal asphyxia are relatively clear, some unexplained or chronic intrauterine fetal hypoxia-induced causes of neonatal asphyxia are currently at an unknown stage [3]. Activin is a water-soluble glycoprotein hormone secreted mainly by the gonads and belongs to the family of transforming growth factors. Activin, especially activin A, is a multifunctional cytokine with an anti-infective activity that plays an important role in tissue injury and inflammatory healing, is expressed in multiple tissues and cells in the body, and can affect the functions of a variety of cells, involved in the processes of survival, proliferation, and differentiation [4]. With the continuous development of ultrasound technology, especially the popularization of color Doppler ultrasound in obstetric pregnancy, the prenatal diagnosis of fetal umbilical cord around the neck has been notoriously enhanced. The fetal umbilical cord wraps around the neck. The neck is shown on a two-dimensional ultrasound U, W, or a longitudinal section of the undulating skin depression of the fetal neck. Color Doppler ultrasound shows red and blue “color rings” in the cross-section of the neck [5]. The fetal umbilical artery (UA) and middle cerebral artery (MCA) can be used for clinical prediction [6]. However, there are few studies on the correlation between the levels of cord blood NO, activin A, and the clinical expression of MCA/UA and fetal distress. The level and the expression significance of MCA/UA are intended to provide a theoretical basis for the occurrence and prevention of fetal distress in the future.

The rest of this paper is organized as follows: Section 2 discusses related work, followed by general information and examination methods designed in Section 3. Section 4 shows the results of the contrast experiment, and Section 5 concludes the paper with a summary and future research directions.

2. Related Work

Fetal distress is a critical pathological state of the fetus due to hypoxia and acidosis in utero, of which 2/3 continues to neonatal asphyxia, and 30% to 50% of perinatal morbidity and mortality are related to fetal distress [7]. Therefore, the diagnosis and therapy of fetal distress are more important. Fetal blood oxygen decreases, blood carbon dioxide accumulates, fetal vascular endothelial cells are damaged, NO synthesis is reduced, fetal-placental circulation resistance increases, and fetal hypoxia is further manifested as respiratory acidosis, sympathetic nerve excitation, and heart rate acceleration. If hypoxia continues, the vagus nerve becomes excited, heart rate slows down, anaerobic glycolysis increases, lactic acid accumulates, metabolic acidosis occurs, and fetal blood pH decreases [8].

NO is a new cell messenger molecule discovered in recent years. An extensive number of animal and human studies have found that the production of NO synthase during pregnancy is through various mechanisms and the level of NO metabolites increases. Among them, the placenta and umbilical cord during pregnancy are also part of NO production [9]. High levels of NO can impair the sensitivity of blood to endothelin 1 and thromboxane A2 and reduce vascular tone. NO can activate guanylate cyclase, increase the level of cGMp in the body, meet the needs of vascular smooth muscle without local excretion through the placenta, prevents platelet aggregation and proliferation, and interferes with platelet aggregation in the placenta to maintain the placental cycle. Low resistance increases blood flow to the placenta, ensuring the supply of nutrients and oxygen to the fetus [10, 11]. The present study found that the absence of high levels of maternal blood and umbilical cord blood was notoriously reduced in fetal complications, possibly due to damage to placental trophoblastic and villous endothelial cells by fetal distress pathogens, reducing trophoblast NO concentrations. High levels of NO in maternal blood and umbilical cord blood will not lead to the low resistance of the fetoplacental circulation, leading to reduced placental perfusion, fetal ischemia, and hypoxia, which led to fetal vascular endothelial cell damage, further reducing NO [12]. The experiment also contrasts the umbilical cord blood NO of two sets of pregnant women, and the fetal distress set was higher than the contrast set. The disparity between different blood types is very important and there is also an important relationship. NO is related to the occurrence of fetal distress (P < 0.05). Therefore, by measuring the NO level in the mother's blood during pregnancy, one can directly understand the hypoxia in the fetoplacental circulation, and monitoring the NO level in the mother's blood and bloodstream can be used as a marker for fetal distress diagnosis. Many scientists believe that the pH of the cord blood is the most reliable indicator of fetal and neonatal ischemia and hypoxia, provides a sound framework for managing the medical timing of fetal complications, and plays an important role in preventing and reducing fetal complications at birth, while the continuous deepening of the examination on NO in the cord blood will also bring new information and therapy methods to the rescue of infants [13, 14].

Since UA was the only connection between the placenta and the fetus, it was easily affected by myocardial contraction and peripheral vascular resistance during its changes [15]. In the early pregnancy of pregnant women, due to the small villi, thin blood vessels, high blood flow, and strong and huge arteries, which reduced blood flow, so after the color Doppler ultrasound examination, PI, RI, and S/D Junhui decreased notoriously, guaranteeing adequate blood flow to ensure the normal growth of the fetus. When the umbilical cord is wrapped around the neck of the fetus, there will be symptoms such as hypoxia. In addition to the recovery of the heart and the dilation of cerebral blood vessels, the blood throughout the body is redistributed to provide oxygen to the heart, brain, and other vital organs. It has the function of “protecting the brain” [16]. As the most important blood vessel and the extensive blood supplied source in the fetal brain, MCA notoriously reduces its resistance to bleeding and the development of the fetal brain. Because the neck was wrapped, its resistance to blood flow is further increased under the “protective effect of the brain,” which was reduced in contrast with the degree of change in UA hemodynamic parameters. The results of this study showed that the UA score in fetal distress was notoriously lower than that of the contrast set, the MCA score was notoriously higher than that of the contrast set, and the disparity were statistically extensive (all P < 0.05). The main reason for the decomposition was that the umbilical cord was loosened around the neck, the lack of blood oxygen supplies disappeared, and the “brain protection effect” was also relieved. The continuous expansion of cerebral blood vessels decreased and increased MCA blood pressure to a certain extent. Blood flow in the legs and abdomen was restored, and vasoconstriction levels were increased to restore UV and DV function, which in turn reduced blood resistance [17].

Activin is a water-soluble glycoprotein hormone mainly secreted by the gonads and belongs to the transforming growth factor beta family. Activin, especially activin A, is a multifunctional cytokine with anti-infective activity, plays an important role in tissue damage and inflammation repair, is expressed in many tissues and cells of the body, and can affect the function of a variety of cells, such as survival, proliferation, and differentiation processes. Comparing the levels of activin A between the two sets, it was found that the level of activin A in the fetal distress set was notoriously higher than that in the contrast set, and the disparity was statistically extensive (P < 0.05). Both trophoblasts and their underlying cytotrophoblasts were expressed, indicating that activin A can act through autocrine and paracrine. In early pregnancy, trophoblast cells can synthesize activin A, regulate the differentiation of placental trophoblast cells, rapidly proliferate and continuously infiltrate the endometrium, differentiate into syncytiotrophoblast cells after exposure to maternal blood, and synthesize α-chorionic membrane at the same time. Hormones such as gonadotropins, beta-chorionic gonadotropin, and progesterone play an important role in maintaining pregnancy. With the development of pregnancy, the expression level of activin A mRNA in placental tissue increased notoriously and was positively correlated with the serum activin A level of pregnant women, suggesting that the placenta was the main source of activin A in the blood circulation during pregnancy. In the third trimester, fetal-placental hypoxia as an acute stimulator can cause the secretion of fetal-placental unit activin A, thereby regulating placental blood flow. Activin A also has a potential regulatory effect on fetal hypoxia, increasing fetal circulation and amniotic fluid activin A [18].

3. General Information and Examination Methods

3.1. General Information

A total of 120 puerperae who delivered in the obstetrics department of our hospital from January 2021 to January 2022 are selected as the examination subjects, aged 23–40 years old, with an average age of (26.45 ± 1.56) years; gestational weeks of 37 to 42 weeks, with an average of (39.51 ± 5.75) weeks. Among them, there were 65 cases of primipara and 55 cases of multiparous women; all were singleton pregnancy; 77 cases were vaginal delivery and 45 cases were cesarean section. According to the diagnostic criteria of fetal distress, the sufferers are divided into 70 cases of fetal distress and 50 cases of normal delivery.

FD diagnostic criteria include the following aspects [19]: FD can be determined if one of the following conditions is met: (1) fecal staining of the amniotic fluid of grade II to III with abnormal fetal heart rate monitoring; (2) frequent variable deceleration and/or late deceleration in fetal heart rate monitoring; (3) the pH of postpartum neonatal scalp blood gas decomposition is less than 7.20; (4) the Apgar score of neonates 1 min after birth is ≤7 points.

3.2. Examination Methods

Activin A: the biotin-avidin enzyme-linked immunosorbent assay is used, and the kit is provided by Shanghai West Tang Biotechnology Co. Ltd. The operation steps are carried out in strict accordance with the kit operating instructions.

NO: take 4 ml of cubital venous blood from pregnant women after giving birth, and 5 ml of umbilical venous blood immediately after childbirth, centrifuge at 1500 r/min for 10 minutes, and store the serum in a −20°C refrigerator for testing. The NO test kit is provided by the Academy of Military Medical Sciences. Greiss measures the nitrite content in serum and indirectly measures the NO level. The Beckman Du-type biochemical analyzer measures the absorbance of the tested sample at its absorption peak at 545 nm and compares it with the standard to determine the NO content.

Determination of hemodynamics: V0LUSON E8 and Philips EPIQ 5 high-end four-dimensional color Doppler ultrasound diagnostic instruments from GE Company of the United States are used for detection. During the test, the pregnant woman is placed in a lying position. If necessary, the lateral position is used as a supplementary position. Before the test, the pregnant woman can eat properly, but need to empty the bladder, and placenta and amniotic fluid are routinely examined and measured. UA: after determining the position of the placenta, select a free segment near the root of the placenta that is not tortuous and does not strike, adjust the ultrasound sampling volume to 2 mm, and then correct the ultrasound sampling line and the included angle of the blood vessel (ensure that the included angle is as close to 0° as possible, and the maximum does not exceed 2 mm, obtain more than 5 clear, complete, and consistent pulse Doppler blood flow spectra, and obtain the resistance index (RI), pulsatility index (PI), and systolic to diastolic flow rate ratio (S/D)). MCA: take the horizontal section of the long axis of the brain to clearly display the fetal cerebral basilar artery ring (Circle of Willis), observe the blood flow signal of the intracranial artery by CDFI, and correct the ultrasound sampling line and the included angle of the blood vessel (guarantee the clip angle is as close to 0° as possible, and the maximum is not more than 30°), and more than 5 clear, complete, and consistent pulse Doppler blood flow spectra are obtained, and RI, PI, and S/D are obtained after the machine automatically envelopes them.

3.3. Observation Indicators

There are five observation indicators:

Contrast of NO levels in umbilical cord blood between the two sets;

Compare the levels of activin A between the two sets;

To analyze the diagnostic value of umbilical cord blood NO and activin A combined with UA and MCA in fetal distress;

To analyze the correlation between cord blood NO, activin A, UA, and MCA and fetal distress.

3.4. Statistical Methods

In this study, all the data are organized, a corresponding database is established for it, all the databases are entered into SPSS 26.0 for data processing, and the measurement data are tested for normality. The multiple-set test is F, the repeated measures are analyzed by MANOVA, the independent samples t-test is used for the data between sets, the paired-samples t-test is used for the data within the set, and the Mann–Whitney U test is used for non-normality; the rate is expressed as % in χ2; correlation is analyzed by Pearson; ROC curve is used to compare the diagnostic performance, and when P < 0.05, the disparity between the data is considered to be statistically extensive.

4. Results of Contrast Experiment

4.1. Contrast of NO Levels in Cord Blood between the Two Sets

Table 1 shows the quantitative analysis of NO levels in cord blood between the two sets. Figure 1 shows the contrast of NO levels in cord blood between the two sets. Through the above experimental results, it can be observed that the fetal distress set is notoriously higher than the contrast set, and the disparity is statistically extensive (P < 0.05).

Table 1

Quantitative analysis of NO levels in cord blood between the two sets.

Set	Number of cases	Maternal blood NO (μmol/L)	Cord blood NO (μmol/L)
Fetal distress set	70	2.42 ± 0.31	1.89 ± 0.37
Contrast set	50	3.79 ± 0.52	3.26 ± 0.61
t		8.632	9.617
P		<0.001	<0.001

Figure 1

Contrast of NO levels in cord blood between the two sets.

4.2. Contrast of Activin A Levels between the Two Sets

Table 2 shows the contrast of the levels of activin A between the two sets. As shown in Table 2, the level of activin A in the fetal distress set is notoriously higher than that in the contrast set, and the disparity is statistically extensive (P < 0.05).

Table 2

Contrast of the levels of activin A between the two sets.

Set	Number of cases	Activin A (pg/ml)
Fetal distress set	70	779.61 ± 96.47
Contrast set	50	271.52 ± 47.81
t		10.527
P		<0.001

4.3. Contrast of Fetal UA and MCA Parameters between the Two Sets of Pregnant Women

Table 3 shows the contrast of fetal UA and MCA parameters between the two sets of pregnant women. It can be seen in Table 3 that the parameters of UA in the fetal distress set are notoriously lower than those in the contrast set, and the parameters of MCA are notoriously higher than those in the contrast set, and the disparity is statistically extensive (all P < 0.05).

Table 3

Contrast of fetal UA and MCA parameters between the two sets of pregnant women.

Set	Number of cases	UA			MCA
		RI	PI	S/D	RI	PI	S/D
Fetal distress set	70	0.61 ± 0.13	1.01 ± 0.17	2.69 ± 0.42	0.69 ± 0.17	1.32 ± 0.24	3.52 ± 0.83
Contrast set	50	0.73 ± 0.12	1.35 ± 0.26	3.23 ± 0.65	0.56 ± 0.15	1.05 ± 0.19	2.71 ± 0.62
t		5.129	6.321	4.281	5.671	7.836	6.156
P		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

4.4. The Diagnostic Value of Cord Blood NO, Activin A Combined with UA and MCA in Fetal Distress

Table 4 shows the diagnostic value of cord blood NO and activin A combined with UA and MCA for fetal distress. Figure 2 is the ROC curve of the diagnostic value of cord blood NO and activin A combined with UA and MCA for fetal distress. It can be seen from Table 4 and Figure 2 that the area under the ROC curve of cord blood NO and activin A combined with UA and MCA for the assessment of fetal distress is 0.957, which has high specificity and sensitivity, which is notoriously higher than that of cord blood NO and activin A combined with UA and MCA detection ROC curve. In the lower area, the prediction model is statistically different (Z = 2.235, P < 0.05).

Table 4

The diagnostic value of cord blood NO and activin A combined with UA and MCA for fetal distress.

Index	Accuracy	Sensitivity	Specificity	Cutoff value (%)	AUC
Cord blood NO	76.00	77.50	70.26	65.52	0.675 (0.554 ∼ 0.763)
Activin A	71.00	70.00	76.60	63.35	0.659 (0.562 ∼ 0.847)
MCA	73.33	70.00	75.00	82.50	0.713 (0.603 ∼ 0.875)
UA	72.45	78.50	70.50	80.13	0.696 (0.598 ∼ 0.793)
Joint detection	97.00	97.50	94.20	93.25	0.957 (0.913 ∼ 0.969)

Figure 2

ROC curve of the diagnostic value of cord blood NO and activin A combined with UA and MCA for fetal distress.

4.5. Correlation Decomposition of Cord Blood NO, Activin A, UA, and MCA with Fetal Distress

Table 5 shows the correlation of NO, activin A, UA, and MCA in cord blood with fetal distress. It is clearly evident from Table 5 that there is an extensive positive correlation between cord blood NO, activin A, and MCA and fetal distress, and an extensive negative correlation with UA (all P < 0.05).

Table 5

Correlation of NO, activin A, UA, and MCA in cord blood with fetal distress.

Index	Fetal distress
	R	P
Cord blood NO	0.636	<0.001
Activin A	0.732	<0.001
MCA	0.619	<0.001
UA	−0.658	<0.001

5. Conclusion and Future Work

The clinical significance and correlation of cord blood NO, activin A levels, and MCA/UA with fetal distress are explored. It is clearly evident from the experiment results that cord blood NO, activin A combined with UA and MCA have high diagnostic value for fetal distress, and there is an extensive correlation with the occurrence of fetal distress, which provides a reliable diagnosis for clinically correct and timely diagnosis of fetal distress. This research plays an important role in preventing and reducing the occurrence of neonatal asphyxia, and it is worthy of clinical application.