Skip to main content
Download PDF

Correlation analysis between the amniotic fluid contamination and clinical grading of neonatal hypoxic–ischemic encephalopathy and biomarkers of brain damage

BMC Pediatrics volume 24, Article number: 178 (2024) Cite this article

Abstract

Background

Amniotic fluid contamination (AFC) is a risk factor for neonatal hypoxic ischemic encephalopathy (HIE); however, the correlation between AFC level and the incidence and clinical grading of HIE, in addition to relevant biomarkers of brain damage, have not been assessed.

Methods

This single-center observational study included 75 neonates with moderate-to-severe HIE. The neonates with HIE were divided into four subgroups according to the AFC level: normal amniotic fluid with HIE group (NAF-HIE), I°AFC with HIE group (I°AFC-HIE), II°AFC with HIE group (II°AFC-HIE), and III°AFC with HIE group (III°AFC-HIE). The control groups consisted of 35 healthy neonates. The clinical grading of neonatal HIE was performed according to the criteria of Sarnat and Sarnat. Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay kits. Correlations of serum tau protein and S100B were evaluated using the Pearson correlation analysis.

Results

(1) The incidence of neonatal HIE in the NAF-HIE group was 20 cases (26. 7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42. 7%). The incidence of moderate-to-severe HIE in the I°–III°AFC-HIE groups was 73.3% (55/75). (2) In 44 cases with severe HIE, 26 cases (59.1%) occurred in the III°AFC-HIE group, which had a significantly higher incidence of severe HIE than moderate HIE (p < 0.05). In NAF-HIE and I°AFC-HIE groups, the incidence of moderate HIE was 45.2% and 29.0%, respectively, which was higher than that of severe HIE (X2 = 9.2425, p < 0.05; X2 = 5.0472, p < 0.05, respectively). (3) Serum tau protein and S100B levels in the HIE groups were significantly higher than in the control group (all p < 0.05), and were significantly higher in the III°AFC-HIE group than in the NAF-HIE and I°AFC-HIE groups (all p < 0.05). (4) Serum tau protein and S100B levels in the severe HIE group were significantly higher in the moderate HIE group (all p < 0.05). (5) Serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p < 0.0001).

Conclusion

Among children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased. AFC level might be associated with HIE grading.

Peer Review reports

Background

Neonatal hypoxic–ischemic encephalopathy (HIE) is not uncommon, often resulting in neonatal mortality and permanent neurological disabilities (brain palsy, epilepsy, mental disorders, etc.). In developed countries, the incidence of neonatal HIE is reported to be 1–2/1000 live births [1, 2]. In some economically poor countries, its incidence is higher, at 10–20/1000 live births [3]. There are many risk factors leading to neonatal HIE, with more than 20 risk factors currently reported, which include both maternal and fetal factors [4,5,6,7]. Nevertheless, these risk factors for HIE remain controversial.

Most scholars consider that meconium-stained amniotic fluid (MSAF) is an important factor related to newborn adverse outcomes [6, 7]. Amniotic fluid is very important for fetal growth and development. Many factors can alter the characteristics of amniotic fluid, leading to amniotic fluid contamination (AFC). The incidence of AFC in neonatal HIE was reported to be 47.3% [5], and the incidence of MSAF in neonatal asphyxia was 11.5–56.1% [8, 9]. To date, there are few reports on the assessment of different AFC levels and the incidence of HIE, clinical grading of HIE, and biomarkers of brain damage.

Tau protein is a neuronal scaffolding protein, which functions to promote microtubule assembly and stabilization [10]. S100B, secreted by astrocytes, is a calcium sensor protein, which functions to regulate the biological activities of calcium ions and is associated with cellular apoptosis and necrosis [11, 12]. Upon damage to brain tissue, the levels of tau protein and S100B in the cerebrospinal fluid and blood circulation can act as biomarkers of brain injury [13,14,15,16].

Recently, the serum concentration of tau protein and S100B have been reported to be increased in neonatal HIE (or bilirubin encephalopathy), and are suggested as biomarkers of neonatal brain damage [17,18,19]. This study aimed to further investigate the relationship between the AFC level and incidence of HIE, clinical grading of neonatal HIE, and biomarkers of brain damage, in a cohort of 75 neonates with HIE.

Materials and methods

Subjects and grouping

The single-center observational study included 75 neonates with moderate-to-severe HIE (HIE group) who were admitted to the neonatal intensive care unit of the Handan Maternal and Child Health Care Hospital from August 2018 to August 2022. The diagnostic criteria for neonatal HIE were based on the detailed content created by the Chinese Medical Association [20]. The 75 cases included 40 males and 35 females; and 31 cases with moderate HIE and 44 cases with severe HIE. All neonates were inborn. The control group consisted of 35 healthy neonates.

Inclusion criteria of HIE cases

(1) neonatal HIE diagnosed according to the Chinese Medical Association [20]; (2) abnormal electroencephalograms (moderate abnormalities: predominant or transient discontinuous activity; severe abnormalities: inactive (background activity<5µV) or permanent discontinuous activity (“suppression–burst” or “permanent discontinuous activity plus theta activity”) [21], paroxysmal activity and seizure patterns [22] and the diagnosis of HIE confirmed by cranial computed tomography (diffuse hypodensity in both cerebellar hemispheres and areas of the cerebral cortex, as well as abnormalities in the subcortical white matter and basal ganglia [23]) and magnetic resonance imaging (score 1: abnormal signals in the basal ganglia/thalamus, score 2: abnormal signals in the cortex, score 3: abnormal signals in the areas of cortex and basal nuclei, score 4: abnormal signals in the entire cortex and basal nuclei [22, 24]); and (3) all clinical data were intact.

Exclusion criteria of HIE cases

(1) intracranial hemorrhage; (2) inherited metabolic diseases; (3) congenital deformity and infectious diseases; (4) severe anemia (hemoglobin level < 120 g/L); (5) history of maternal drug abuse; and (6) patients who automatically abandon treatment. The clinical features of neonates with their mothers are shown in Table 1.

Table 1 Clinical features of neonates and their mothers
Full size table

Patients received a series of comprehensive supportive therapies after hospitalization, such as hypothermia [25], reduction of intracranial pressure, correction of acid–base balance disorders, anticonvulsant drugs, and so on. Patients also underwent tests to assess blood glucose levels, and liver and renal function.

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Handan Maternal and Child Health Care Hospital of Hebei Province. Written informed consent for the publication of the patients’ clinical details was obtained from the parents of the enrolled neonates.

Classification of AFC degree

AFC degree was classified according to the method described in the previous study [26]. Normal amniotic fluid (non-amniotic fluid contamination) is clear. The different AFC degrees are divided into three levels: I°AFC, amniotic fluid is light green; II°AFC, amniotic fluid is yellow–green or dark-green and cloudy; and III°AFC, amniotic fluid is brown–yellow, thick, and meconium stained, also known as meconium-stained amniotic fluid (MSAF).

Clinical grading of neonatal HIE

The clinical grading of neonatal HIE was estimated by Sarnat and Sarnat’s scoring methods [27].

Determination of serum tau protein and S100B

A blood sample was taken from the vein within the first 24 h of postnatal life, which was placed in a test tube (5 ml, No. A06277602, Hebei City Zhong Xing Medical Supplies Co. Ltd, China) and kept at room temperature for 30 min, followed by centrifugation (table low speed automatic balancing centrifuge L-400 (Hunan Xiangyi Laboratory Instrument Development Co. Ltd., China)) for 15 min (3000 rpm). The serum was loaded into a test tube and stored at -70 °C. To avoid any influence on the detection results, the neonates did not undergo a blood transfusion before the collection of blood samples. The storage time from blood collection to measurement was 3 months.

Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay (ELISA) kits (Shanghai HuDing Biological Science and Technology Co., Ltd. [R&D Systems, USA]; the purchased kits were Human Tau protein (T-Tau) ELISA kit and Human S-100B protein (S-100B) ELISA kit). Before the assay, the samples were removed from the − 70 °C freezer and placed on an oscillator (FWZ-1 type micro drug device, Guangzhou Fenghua Bioengineering Co. Ltd, China) at room temperature with shock melting for 1 h (1200 rpm). The ELISAs were performed following the manufacturer’s instructions.

Statistical analysis

All data analysis was performed by SPSS 11.5 software (Chicago, IL). Measurement data were described as the mean with standard deviation (SD), and a comparison of two groups was evaluated using the Student’s t-test. Comparisons of multiple groups were performed with the Student-Newman-Keuls test. Counting data were expressed as numbers (%), the comparisons between groups were calculated by the Chi-square (X2) test or Fisher’s test, as appropriate. Correlations of serum tau protein and S100B were tested using Pearson correlation analysis. p < 0.05 was considered to indicate statistical significance.

Results

Incidence of neonatal HIE in different AFC groups

In the 75 patients with HIE, the incidence of neonatal HIE in NAF-HIE group was 20 cases (26.7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42.7%).The incidence of neonatal HIE in I°–III°AFC-HIE groups was 55 cases (73.3%). The incidence of severe HIE in the III°AFC-HIE group was significantly higher than that of moderate HIE (p < 0.05). The incidence of moderate HIE in the NAF-HIE group and I°AFC-HIE group was higher than that of severe HIE (all p < 0.05; Table 2).

Table 2 The incidence of neonatal HIE in different AFC groups n (%)
Full size table

Comparison of serum tau and S100B levels in different HIE groups

The serum level of tau protein and S100B in the HIE group was significantly higher than that of control group (all p < 0.05). Furthermore, the tau protein and S100B level in severe neonatal HIE were significantly higher than that of moderate HIE (all p < 0.05; Table 3).

Table 3 Comparison of serum tau and S100B levels in different HIE groups (mean ± SD)
Full size table

Comparison of serum tau protein and S100B level in different AFC groups

The serum level of tau protein and S100B in the NAF-HIE group, I°AFC-HIE group, II°AFC-HIE group, and III°AFC-HIE group were significantly higher than that of control group (all p < 0.05). The serum tau protein and S100B level in the III°AFC-HIE group were significantly higher than those of the NAF-HIE group and I°AFC-HIE group (all p<,0.05); however, the tau protein and S100B level in the III°AFC-HIE group showed no significant difference to that of the II°AFC-HIE group (all p > 0.05; Table 4).

Table 4 Comparison of serum tau protein and S100B levels in different AFC groups (mean ± SD)
Full size table

Correlation analysis of serum tau protein and S100B level

Our results showed that the levels of serum tau protein and S100B were significantly positively correlated (r = 0.7703, p < 0.0001; Fig. 1).

Fig. 1
figure 1

Correlation between serum tau protein and S100B levels

Full size image

Discussion

Neonatal HIE is characterized by brain injury due to severe ischemia–hypoxia of the cerebrum during the prenatal and perinatal period [28]. A histopathological study has identified that neonatal HIE involves neuronal degeneration and necrosis, periventricular leukomalacia, intracranial hemorrhage, and various pathological changes. According to relevant report on neonates with hypoxic brain injury, approximately 80% of cases occur in the prenatal period and 10–20% of cases occur in the perinatal period [29]. Many risk factors are associated with neonatal HIE, such as AFC [4, 5, 30,31,32,33,34], low birth weight (< 2.5 kg) [33], gestation age ≥ 41 weeks, umbilical cord around neck [35], newborn born to women without reproductive history [5], placental abruption, ruptured uterus [31], placenta previa, dystocia, fetal respiratory distress syndrome, emergency cesarean Sects. [4, 36], growth retardation, large head circumference [30], chorioamnionitis [36], Apgar score [31], and so on. Nevertheless, some inconsistent results remain among these risk factors for HIE.

Normally, the amniotic fluid, which is the internal environment of the growing fetus, is a colorless and transparent liquid. AFC was reported to be an independent risk factor for neonatal HIE [31, 33]; especially, MSAF showed a significant correlation with the occurrence of neonatal HIE [32]. The causal chain of events resulting in AFC and neonatal HIE, influence of the AFC level on the incidence and severity of HIE, as well as the biomarkers of brain damage are not yet fully understood. Research into the mechanisms has gained increasing attention recently.

The clinical grading of neonatal HIE is divided into three levels: mild, moderate, and severe HIE. The AFC level can be divided into three levels: I°AFC, II°AFC, and III°AFC (also known as MSAF). There have been many reports regarding AFC in neonatal asphyxia; the incidence of AFC in neonatal asphyxia was 11.5–56.1% [8, 9], and severe neonatal asphyxia may be involved in multiple organ damage, such as neonatal HIE, respiratory distress syndrome, neonatal necrotizing enterocolitis, renal and liver damage. Among these adverse consequences, neonatal HIE was of the greatest concern to obstetricians and neonatologists. The incidence of AFC causing neonatal HIE has been reported in few studies; the incidence of AFC causing neonatal HIE was 47.3–51.2% [4, 5]. Our study showed that the incidence of neonatal HIE (moderate-to-severe HIE cases) in the I°–III° AFC groups was 73.3% (55/75). This result was significantly higher than the results of Chen et al. (X2 = 12.4198, p = 0.004) and Wang et al. (X2 = 70.1199, p = 0.0000) [4, 5].

III°AFC is also known as MSAF. MSAF is one of the clinical manifestations of the fetus in intrauterine hypoxia. A clinical epidemiological study reported that the incidence of MSAF was 16.6% [37]. MSAF is the most harmful for newborns, and the incidence probability of MSAF in neonatal HIE was higher. Li et al. reported that the incidence of MSAF in neonatal HIE was 49.6% [38]. Torbenson et al. reported that the incidence of MSAF in neonatal HIE was 42.3% [32]. Our data showed that the incidence of neonatal HIE (including moderate-to-severe HIE cases) in the III°AFC (or MSAF) group was 42.7% (32/75); the result was in keeping with those of previous studies. Therefore, we also confirmed that MSAF was a risk factor for neonatal HIE, and that it had an important reference value for judging the severity of neonatal HIE.

Regarding the relationship between the AFC level and HIE clinical grading, our result showed that in the III°AFC-HIE group, the incidence of severe HIE was 59.1% (26/44), which was significantly higher than that of moderate HIE (19.4%, p < 0.05). In the NAF-HIE group, the incidence of moderate HIE was 45.2% (14/31), which was significantly higher than that of severe HIE (13.6%, p < 0.05). In the I°AFC-HIE group, the incidence of moderate HIE was 29% (9/31), which was higher than that of severe HIE (9.1%, p<0.05). These results suggested that the higher the AFC level, the higher the probability of neonatal severe HIE.

When no contamination is present in the amniotic fluid, it is a clear liquid, which is very important to fetal growth and development. If the fetus suffers from intrauterine hypoxia, leading to an enhanced intestinal peristalsis, relaxation of the anal sphincter occurs allowing meconium into the amniotic fluid. As a result, the fetus inhales the contaminated amniotic fluid, causing respiratory tract obstruction and further aggravating the hypoxic–ischemic brain damage. Therefore, amniotic fluid monitoring during pregnancy should be routinely performed.

Of note, in normal amniotic fluid, neonatal HIE can also occur. Recently, Wang JR et al. reported that the incidence of moderate-to-severe HIE in patients with no amniotic fluid contamination was 48.8% [4]. We also observed this in the present study; in the NAF-HIE group (non-amniotic fluid contamination group), the incidence of moderate-to-severe HIE was 26.7% (20/75). This result was lower than that of Wang JR et al. Because a certain number of neonatal HIE cases occurred in the normal amniotic fluid group, this suggests that the risk factors for neonatal HIE are more complex, which requires further study.

To reveal the relationship between the AFC level and severity of neonatal HIE, in addition to biomarkers of brain damage, we performed this preliminary study. Tau protein, a microtubule-associated structural protein family member, it is located in the axons and dendrites of central neurons [39,40,41]. Tau promotes the formation and stability of microtubules, and regulates the growth and development of neurons as well as the communication of axons [42]. S100B is a calcium sensor protein, and a multifunctional member of S100-calmodulin-troponin super-family. S100B functions to regulate the growth and differentiation of cells. In vitro and in vivo experiments showed that S100B may stimulate the proliferation of glial cell [43, 44], and it was considered to be a brain-specific protein. Previous studies have shown that tau protein and S100B have significant value in estimating brain damage, for instance, brain trauma [45,46,47,48,49], ischemic stroke [14, 50, 51], and cerebral hemorrhage [52, 53]. In recent years, tau protein and S100B have also been reported to be associated with newborn hypoxia and newborn brain injury, including neonatal jaundice encephalopathy [17], neonatal asphyxia [54–56], and neonatal HIE [18, 56,57,58]. Our results demonstrate that serum tau and S100B levels of neonates with moderate-to-severe HIE were significantly higher than in the control group. Furthermore, serum tau protein and S100B levels in neonates with severe HIE were significantly higher than those of patients with moderate HIE, suggesting that the levels of serum tau protein and S100B could serve as biomarkers of neonatal brain damage. We showed that the serum level of tau protein and S100B in all HIE groups were significantly higher than in the control group. Furthermore, serum tau and S100B levels in the III°AFC-HIE group were significantly higher than in the NAF-HIE and I°AFC-HIE groups, which is likely related to the higher incidence of severe HIE cases in the III°AFC-HIE group, and the higher incidence of moderate HIE cases in the NAF-HIE and I°AFC-HIE groups; therefore, the higher the AFC level, the more serious the neonatal brain damage.

Serum tau protein and S100B represent the number of neuronal and glial cells, respectively; therefore, their levels in the serum reflect the degree of damage to neuronal and glial cells. In this study, serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p = 0.0001), suggesting that neurons and glial cells in neonatal HIE were affected to a similar degree. How glial cells can be repaired or regenerated, in addition to the functional reconstruction of neurons, in neonatal HIE still needs to be further studied.

However, the study has some limitation. First, this is a retrospective study, and inherent limitations exist in this kind of studies. Second, the grading of AFC relies solely on color, this method is subjective.Factors such as individual differences, variations in color perception, and the influence of lighting conditions can contribute to this subjectivity. Further studies are needed to explore more objective and standardized methods for AFC grading.

In conclusion, our findings showed that among children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased, suggesting that AFC level might be associated with HIE grading.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AFC:

amniotic fluid contamination

HIE:

hypoxic ischemic encephalopathy

NAF:

normal amniotic fluid

MSAF:

meconium stained amniotic fluid

References

  1. Wang Q, Lv H, Lu L, Ren P, Li L. Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury. J Matern Fetal Neonatal Med. 2019;32(21):3685–92. https://doi.org/10.1080/14767058.2018. PMID: 29681183.

    Article  PubMed  Google Scholar 

  2. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010;86(6):329–38. https://doi.org/10.1016/j.earlhumdev.2010.05.010. PMID: 20554402 https://.

    Article  PubMed  Google Scholar 

  3. Greco G, Piva I, Scioscia M, Volta CA, Spadaro S et al. Pathophysiology of hypoxic-ischemic encephalopathy: a review of the past and a view on the future. Acta Neurol Beig. 2020; 120(2): 277–288 PMID: 32112349. https://doi.org/10.1007/s13760-020-01308-3.

  4. Wang JR, Tao EF, Mo MJ, Ding WM, Yuan JH, Wang M et al. Perinatal risk factors influencing neonatal hypoxic ischemic encephalopathy in Southern China: A case-Control study. Am J Perinatol. 2021; 38(S 01):e182-e186 PMID: 32219797. https://doi.org/10.1055/s-0040-1708884.

  5. Chen XX, Chen HX, Jiang DC. Maternal and fetal risk factors for neonatal hypoxic-ischemic encephalopathy: a retrospective study. Int J Gen Med. 2023;16:537–45. https://doi.org/10.2147/IJGM.S394202. PMID: 36818762. PMCID: PMC9936872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kolatat T, Vanprapar N, Thitadilok. Perinatal asphyxia: multivariate analysis of risk factors. J Med Assoc Thai. 2000;83(9):1039–44. PMID: 11075971.

    CAS  PubMed  Google Scholar 

  7. Wang QH, Yang YJ, Wei KL, Yao YJ, Du LZ. Epidemiological survey on newborns born at the obstetric departments in hospitals in mid-southern region of China in 2005. Transl Pediatr. 2013;2(1):21–6. https://doi.org/10.3978/j.issn.2224-4336.2012.05.01. PMID: 26835280 PMCID: PMC4728943.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yu Y, Gao JS, Liu JT, Tang YB, Zhong M, He J, et al. Perinatal maternal characteristics predict a high risk of neonatal asphyxia: a multi-center retrospective cohort study in China. Front Med (Lausanne). 2022;9:944272. https://doi.org/10.3389/fmed.2022.944272. PMID: 36004371. PMCID: PMC9393324 https://.

    Article  PubMed  Google Scholar 

  9. de Dios JG, Benaven MM, Rodoreda AB, Trave TD, Ruiz MJ, Iglesias CC, et al. Neonatal morbidity associated with meconial amniotic fluid. Esp Pediatr. 1998;48(1):54–9. PMID: 9580399.

    Google Scholar 

  10. Avila J, Lucas JJ, Perez M, Hernandez F. Role of tau protein in both physiological and pathological conditions. Physiol Rev. 2004;84(2):361–84. https://doi.org/10.1152/physrev.00024.2003. PMID: 15044677.

    Article  CAS  PubMed  Google Scholar 

  11. Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, et al. S100B’s double life: intracellular regulator and extracellular signal. Biochim Biophys Acta. 2009;1793(6):1008–22. https://doi.org/10.1016/j.bbamcr.2008.11.009. PMID: 19110011.

    Article  CAS  PubMed  Google Scholar 

  12. Van Eldik LJ, Wainwright MS. The janus face of glial-derived S100B: beneficial and detrimental functions in the brain. Restor Neurol Neurosci. 2003;21(3–4):97–108. PMID: 14530573.

    PubMed  Google Scholar 

  13. Wang JW, LI J, Han L, Guo SB, Wang L, Xiong ZJ, et al. Serum T protein as a potential biomarker in the assessment of traumatic brain injury. Exp Ther Med. 2016;11(3):1147–51. https://doi.org/10.3892/etm.2016.3017. PMID: 26998051 PMCID: PMC4774463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bitsch A, Horn C, Kemmling Y, Seipelt M, Hellenbrand U, Stiefel M, et al. Serum tau protein level as a marker of axonal damage in acute ischemic stroke. Eur Neurol. 2002;47(1):45–51. https://doi.org/10.1159/000047946. PMID: 11803192.

    Article  CAS  PubMed  Google Scholar 

  15. Bielewicz J, Kurzepa J, Czekajska-Chehab E, Stelmasiak Z, Bartosik-Psujek H. Does serum tau protein predict the outcome of patients with ischemic stroke? J Mol Neurosci. 2011;43(3):241–5. https://doi.org/10.1007/s12031-010-9403-4. PMID: 20549384.

    Article  CAS  PubMed  Google Scholar 

  16. Liu MD, Luo P, Wang ZJ, Zhou F. Changes of serum tau, GFAP, TNF-α and malonal-dehyde after blast-related traumatic brain injury. Chin J Traumatol. 2014;17(6):317–22. PMID: 25471424.

    CAS  PubMed  Google Scholar 

  17. Okumus N, Turkyilmaz C, Onal EE, Atalay Y, Serdaroglu AS, Elbeg S, et al. Tau and s-100B proteins as biochemical markers of billrubin-induced neurotoxicity in term neonates. Pediatri Neurol. 2008;39(4):245–50. https://doi.org/10.1016/j.pediatrneurol.2008.07.004. PMID: 18805362.

    Article  Google Scholar 

  18. Lv HY, Wu SJ, Gu XL, Wang QL, Ren PS, Ma Y, et al. Predictive value of neurodevelopmental outcome and serum tau protein level in neonates with hypoxic ischemic encephalopathy. Clin Lab. 2017;63(7):1153–62. https://doi.org/10.7754/Clin.Lab.2017.170103. PMID: 28792689.

    Article  CAS  PubMed  Google Scholar 

  19. Pei XM, Gao R, Zhang GY, Lin L, Wan SM, Qiu SQ. Effects of erythropoietin on serum NSE and S-100B levels in neonates with hypoxic-ischemic encephalopathy. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16(7):705–8. PMID: 25008877.

    CAS  PubMed  Google Scholar 

  20. Group of Neonatology; Chinese Pediatric Society; Chinese Medical Association. Diagnostic criteria for neonatal hypoxic ischemic encephalopathy. Zhonghua Er Ke Za Zhi. 2005;43:584–5. https://doi.org/10.3760/j.issn:0578-1310.2005.08.007. http://www.cmaped.org.cn/.

    Article  Google Scholar 

  21. Sefton D, André M. Prognosis of hypoxic ischaemic encephalopathy in full-term newborns-value of neonatal electroencephalography. Neuropediatrics. 1997;28(5):276–80.

    Article  Google Scholar 

  22. Ong LC, Kanaheswari Y, Chandran V, Rohana J, Yong SC, Boo NY. The usefulness of early ultrasonography, electroencephalography, and clinical parameters in predicting adverse outcome in asphyxiated term infants. Singap Med J. 2009;50(7):705–9.

    CAS  Google Scholar 

  23. Voorhies TM, Lipper EG, Lee BC, Vannucci RC, Auld PA. Occlusive vascular disease in asphyxiated newborn infants. J Pediatr. 1984;105(1):92–6.

    Article  CAS  PubMed  Google Scholar 

  24. Barkovich AJ, Hajnal BL, Vigneron D, Sola A, Partridge JC, Allen F, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol. 1998;19(1):143–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Shao XM, Zhang CF. standard version,. Guideline of evidence-based treatment for hypoxic-ischemic encephalopathy in full-term infants (2011). Chin J Evidence-Based Pediatr. 2011; 6(5): 327–335. http://www.cjebp.net. https://doi.org/10.3969/J.issn.1673-5501.200.05.003.

  26. Singh SN, Srivastava R, Singh A, Tahazzul M, Kumar M, Kanta C, Chandra S. Respiratory distress including meconium aspiration syndrome in vigorous neonates born through meconium stained amniotic fluid: incidence, onset, severity and predictors at birth. Indian J Pediatr. 2013;80(7):538–43.

    Article  CAS  PubMed  Google Scholar 

  27. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33(10):696–705. https://doi.org/10.1001/archneur.1976.00500100030012. PMID: 987769.

    Article  CAS  PubMed  Google Scholar 

  28. Mattiesen WR, Tauber SC, Gerber J, Bunkowshi S, Brück W, Nau R. Increased neurogenesis after hypoxic–ischemic encephalopathy in humans is age related. Acta Neuropathol. 2009;117:525–34. https://doi.org/10.1007/s00401-009-0509-0. PMID: 19277687.

    Article  CAS  PubMed  Google Scholar 

  29. Bao KZ, Huang Y, Hu XZ, Xie BC. Risk factors and prognosis analysis of neonatal hypoxic- ischemic encephalopathy. Maternal Child Health Care China. 2016;31:971–3. https://doi.org/10.7620/zgfybj.j.issn.1001-4411.2016.05.30. http://www.cnki.com.cn.

    Article  Google Scholar 

  30. Hayes BC, McGarvey C, Mulvany S, Kennedy J, Geary MP, Matthews TG et al. A case-control study of hypoxic-ischemic encephalopathy in newborn infants at > 36 weeks gestation. Am J Obstet Gynecol. 2013; 209(1):29.e1-29.e19. PMID: 23524176. https://doi.org/10.1016/j.ajog.2013.03.023. Epub 2013 Mar 21.

  31. Peebles PJ, Duello TM, Eickhoff JC, McAdams RM. Antenatal and intrapartum risk factors for neonatal hypoxic ischemic encephalopathy. J Perinatol. 2020;40(1):63–9. https://doi.org/10.1038/s41372-019-0531-6. PMID: 31611618.

    Article  CAS  PubMed  Google Scholar 

  32. Torbenson VE, Tolcher MC, Nesbitt KM, Colby CE, EI-Nashar SA, Gostou BS, et al. Intrapartum factores associated with neonatal hypoxic ischemic encephalopathy: a case -controlled study. BMC Pregnancy Childbirth. 2017;17(1):415. https://doi.org/10.1186/s12884-017-1610-3. PMID: 29228911. PMCID: PMC5725836.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wang YR, Luo SY, Wang KJ, Hou YW, Yan H, Zhang YD. Maternal and neonatal exposure to risk factors for neonates with moderate or severe hypoxic ischemic encephalopathy: a cross-section study. Ital J Pediatr. 2022;48(1):188. https://doi.org/10.1186/s13052-022-01380-w. PMID: 36435902 PMCID: PMC9701427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nadeem G, Rehman A, Bashir H. Risk factors associated with birth asphyxia in term newborns at a Tertiary Care Hospital of Multan. Pakistan Cureus. 2021; 13(10): e18759 PMID: 34796056. PMCID: PMC8590025 https://doi.org/10.7759/cureus.18759.

  35. Martinez-Biarge M, Diez-Sebastian J, Wusthoff CJ, Mercuri E, Cowan FM. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics, 2013, 132(4): e952-959 PMID: 24019409. https://doi.org/10.1542/peds.2013-0511.

  36. Rossi AC, Prefumo F. Antepartum and intrapartum risk factors for neonatal hypoxic ischemic encephalopathy: a systematic review with meta-analysis. Curr Opon Obstet Gynecol. 2019;31(6):410–7. https://doi.org/10.1097/GCO.0000000000000581. PMID: 31567446.

    Article  Google Scholar 

  37. Maymon E, Chaim W, Furman B, Ghezzi F, Vardi IS, Mazor M. Meconium stained amniotic fluid in very low risk pregnancies at term gestation. Eur J Obstet Gynecol Reprod Biol. 1998;80(2):169–73. https://doi.org/10.1016/s0301-2115(98)00122-5. PMID: 9846662.

    Article  CAS  PubMed  Google Scholar 

  38. Li YJ, Yu SZ, Xue J. Meta analysis of risk factors of neonatal hypoxic ischemic encephalopathy. Shandong Med. 2013;53(30):70–1. https://doi.org/10.3969/J.issn.1002-266X.2013.30.030. http://www.cnki.com.cn.https://DOI.

    Article  CAS  Google Scholar 

  39. Lee VM, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci. 2001; 24:11211159 PMID: 11520930. https://doi.org/10.1146/annurev.neuro.24.1.1121.

  40. Trojanowski JQ, Schuck T, Schmidt ML, Lee VM. Distribution of tau proteins in the normal human central and peripheral nervous system. J Histochem Cytochem. 1989;37(2):209–15. https://doi.org/10.1177/37.2.2492045. PMID: 2492045.

    Article  CAS  PubMed  Google Scholar 

  41. Tashiro K, Hasegawa M, Ihara Y, Iwatsubo T. Somatodendritic localization of phosphorylated tau in neonatal and adult rat cerebral cortex. NeuroReport. 1997;8(12):2797–801. https://doi.org/10.1097/00001756-199708180-00029. PMID: 9295120.

    Article  CAS  PubMed  Google Scholar 

  42. Tatebayashi Y, Haque N, Tung YC, Iqbal K, Grundke-Iqbal. Role of tau phosphorylation by glycogen synthase kinase-3betal in the regulation of organelle transport. J Cell Sci. 2004;117(Pt9):1653–63. https://doi.org/10.1242/jcs.01018. PMID: 15075227.

    Article  CAS  PubMed  Google Scholar 

  43. Ravasi T, Hsu K, Goyette J, Schroder K, Yang Z, Rahimi F, et al. Probing the S100 protein family through genomic and functional analysis. Genemics. 2004;84(1):10–22. https://doi.org/10.1016/j.ygeno.2004.02.002. PMID: 15203200.

    Article  CAS  Google Scholar 

  44. Schmidt S. S100B: pathogenetic and pathophysiologic significance in neurology. Nervenarzt. 1998;69(8):639–46. https:/. PMID: 9757414.

    Article  CAS  PubMed  Google Scholar 

  45. Zhou Z, Zeng J, Yu S, Zhao Y, Yang X, Zhou Y, Liang Q. Neurofilament light chain and S100B serum levels are associated with disease severity and outcome in patient with aneurismal subarachnoid hemorrhage. Front Neurol. 2022; 13:956043 PMID: 35989914. PMCID: https://doi.org/10.3389/fneur.2022.956043.

  46. Shaw GJ, Jauch EC, Zemlan FP. Serum cleaved tau protein levels and clinical oucome in adult patients with closed head injury. Ann Emerg Med. 2002;39(3):254–7. https://doi.org/10.1067/mem.2002.121214. PMID: 11867977.

    Article  PubMed  Google Scholar 

  47. Liliang PC, Liang CL, Lu K, Wang KW, Weng HC, Hsieh CH, et al. Relationship between injury severity and serum tau protein levels in traumatic brain injured rats. Resuscitation. 2010;81:1205–8. https://doi.org/10.1016/j.resuscitation.2010.05.016. PMID: 20598429.

    Article  PubMed  Google Scholar 

  48. Stroick M, Fatar M, Ragoschke-Schumm A, Fassbender K, Bertsch T, Hennerici M. Protein S-100B–a prognostic marker for cerebral damage. Curr Med Chem. 2006;13(25):3053–60. https://doi.org/10.2174/092986706778521751. PMID: 17073646.

    Article  CAS  PubMed  Google Scholar 

  49. Honda M, Tsuruta R, Kaneko T, Kasaoka S, Yagi T, Todani M, et al. Serum glial fibrillary acidic protein is a highly specific biomarker for traumatic brain injury in humans compared with S-100B and neuron-specific enolase. J Trauma. 2010;69(1):104–9. https://doi.org/10.1097/TA.0b013e3181bbd485. PMID: 20093985.

    Article  CAS  PubMed  Google Scholar 

  50. Ye H, Wang L, Yang XK, Fan LP, Wang YG, Guo L. Serum S100B levels may be associated with cerebral infarction: a meta-analysis. J Neurol Sci. 2015; 348(1–2):81–88 PMID: 25434713. https://doi.org/10.1016/j.jns.2014.11.010.

  51. Garzelli L, Jacquens A, Amouyal C, Premat K, Sourour N, Cortese J et al. Secondary S100B protein increase following brain arteriovenous malformation rupture is associated with cerebral infarction. Molecule. 2020; 25(21): 5177 PMID: 33172087. PMCID: PMC7664396. https://doi.org/10.3390/molecules25215177.

  52. Hu HT, Xiao F, Yan YQ, Wen SQ, Zhang L. The prognostic value of serum tau in patients with intracerebral hemorrhage. Clin Biochem. 2012;45(16–17):1320–4. https://doi.org/10.1016/j.clinbiochem.2012.06.003. PMID: 22705449.

    Article  CAS  PubMed  Google Scholar 

  53. Lad SP, Hegen H, Gupta G, Deisenhammer F. Proteomic biomarker discovery in cerebrospinal fluid for cerebral vasospasm following subarachnoid hemorrhage. Stroke Cerebrovasec Dis. 2012;21(1):30–41. https://doi.org/10.1016/j.jstrokecerebrovasdis.2010.04.004. PMID: 20851633.

    Article  Google Scholar 

  54. Sofijanova A, Piperkova K, Khalili DA. Predicting outcome after severe brain injury in risk neonates using the serum S100B biomarker: results using single (24 h) time-point. Prilozi. 2012;33(1):147–56. PMID: 22952101.

    CAS  PubMed  Google Scholar 

  55. Takahashi K, Hasegawa S, Maeba S, Maeba S, Fukunaga S, Motoyama M, et al. Serum tau protein level serves as a predictive factor for neurological prognosis in neonatal asphyxia. Brain Dev. 2014;36(8):670–5. https://doi.org/10.1016/j.braindev.2013.10.007. PMID: 24268747.

    Article  PubMed  Google Scholar 

  56. Liu L, Zheng CH, Peng SF, Zhou HY, Su ZY, He L, et al. Evaluation of urinary S100B protein level and lactate/creatinine ratio for early diagnosis and prognostic. Neonatology. 2010;97(1):41–4. https://doi.org/10.1159/000227292. PMID: 19590245.

    Article  ADS  CAS  PubMed  Google Scholar 

  57. Gaulee P, Yang ZH, Sura L, Xu HY, Rossignol C, Weiss MD et al. Concentration of serum biomarkers of brain injury in neonates with a low cord pH with or without mild hypoxic-ischemic encephalopathy. Front Neurol. 2022; 13:934755 PMID: 35873777. PMCID: PMC9301366. https://doi.org/10.3389/fneur.2022.934755.

  58. Ali AG, Arnaez J. Value of brain damage biomarkers in cerebrospinal fluid in neonates with hypoxic-ischemic brain injury. Biomark Med. 2022; https://doi.org/10.2217/bmm-2021-0381. PMID: 35081738. https://DOI:10.2217/bmm-2021-0381.

Download references

Acknowledgements

Not applicable.

Funding

This study is supported by Health and Family Planning Commission of Hebei (No 20150033); Science and Technology Bureau of Handan, City, Hebei Province (No.152810879-6); Science and Technology Department of Hebei Province (No.162777201,; No. 172777209).

Author information

Author notes

  1. Qiuli Wang is considered as co-first authors

Authors and Affiliations

  1. Department of Neonatology, Handan Maternal and Child Health Care Hospital, Handan, 056001, PR China

    Hongyan Lv, Qiuli Wang, Zhiyong Dong, Huiming Zhang & Pengshun Ren

  2. Department of Pediatrics, NICU the 980th Hospital of the People’s Liberation Army Joint Service Support Force (Bethune International Peace Hospital), Shijiazhuang, 050082, PR China

    Fang Liu

  3. Department of Neonatal Pathology, Handan Maternal and Child Health Care Hospital, Handan, 056001, PR China

    Liangxiang Li

  4. Department of Neonatology and Neonatal Pathology, Handan Maternal and Child Health Care Hospital, No. 50, Li Ming Street, Hanshan District, Handan City, Hebei Province, 056001, China

    Hongyan Lv

Authors
  1. Hongyan Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiuli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhiyong Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huiming Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pengshun Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liangxiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Hongyan LV and Qiuli Wang, conceived, designed, performed the study, and wrote the paper; Fang Liu, Qiuli Wang, Zhiyong Dong, and Hunming Zhang, performed the study, collected and analyzed the data, and wrote the paper; Pengshun and Lianxiang Li analyzed and contributed reagents/materials/analysis tools. All authors reviewed the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Hongyan Lv.

Ethics declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki, and was approved by the Medical Ethics Committee of Handan Maternal and Child Health Care Hospital of Hebei Province. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lv, H., Liu, F., Wang, Q. et al. Correlation analysis between the amniotic fluid contamination and clinical grading of neonatal hypoxic–ischemic encephalopathy and biomarkers of brain damage. BMC Pediatr 24, 178 (2024). https://doi.org/10.1186/s12887-024-04663-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12887-024-04663-9

Keywords

BMC Pediatrics

ISSN: 1471-2431

Contact us