Abdelrazek A. A, Tosson A. M. S, Abde-latif A. A, Youness E. R, Zaki M. Evaluation of Oxidative Stress Markers in Relation APGAR Scores to in Egyptian Newborns with Intrauterine Growth Retardation. Biomed Pharmacol J 2023;16(1).

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Manuscript received on :22-10-2022
Manuscript accepted on :25-01-2023
Published online on: 22-02-2023

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Plagiarism Check: Yes
Reviewed by: Dr. Susmitha , Dr. Niharika Kondepudi
Second Review by: Dr S Shahi
Final Approval by: Dr. Anton R Kiselev

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Abderahman A. Abdelrazek¹, Angie M. S. Tosson¹, Ali Abdehafeez Abde-latif², Eman Refaat Youness^3*, Moushira Zaki⁴

¹Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.

²Department of obstetrics and gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt.

³Medical Biochemistry, Departments, Medical Researches and Clinical Studies Institute – National Research Centre Cairo, Egypt

⁴Biological Anthropology Department, Medical Researches and Clinical Studies Institute– National Research Centre Cairo, Egypt.

Corresponding Author E-mail: hoctober2000@yahoo.com

DOI : https://dx.doi.org/10.13005/bpj/2629

Abstract

The study aimed to estimate the status of oxidative stress markers in neonates of both sexes born 37- 41with intrauterine growth restriction (IUGR) comparing them to healthy convenient for gestational. The study included 44 Egyptian neonates with IUGR of both sexes and 45 neonates of both sexes with appropriate for gestational age. In both groups the neonates were delivered vaginally without any assisted vaginal delivery to mothers without known medical conditions affecting placental sufficiency. Malondialdehyde (MDA, total antioxidant capacity (TAC) and paraoxonase-1(PON1) were measured. Obstetric data including mode of delivery, instrumental delivery and gestational age at delivery by ultrasound Neonatal assessment including gestational age by new Ballard, sex of neonate, weight, head circumference, APGAR score at 1 and 5 minutes, length, full general & systemic examinations of newborn. The activity of MDA was increased, whilelevels of TAC and PON1 were significantly lower in IUGR than controls. APGAR score at both 1 min and 5 min and Ballard were significantly decreased in the IUGR group. Mean birth weight, length, maternal gestational age and head circumference of IUGR cases were decreased than control. APGAR scores were negatively correlated with MDA. In conclusion oxidative stress associated with IUGR newborns and antioxidants during pregnancy may be advised. Oxidative stress markers might have early prediction value for diagnosis of these conditions and probable pharmacological intervention with antioxidants may improve the pregnancy conditions.

Keywords

APGAR score; Intrauterine growth retardation; malondialdehyde; Total Antioxidant Capacity; paraoxonase-1

Introduction

IUGR is of distinctive disquiet in developing countries where30% of the neonates are growth retarded. These infants are liable to early neonatal mortality because of complications as birth asphyxia, shock, hyperbilirubinemia, thrombocytopenia, hypoglycaemia, acidosis, septicaemia and hypoxia ¹.Oxidative stress has been detected in both newborn in IUGR and pregnant mother ². Also, it has been found to respond to antioxidants treatment ³.In newborns, maturation in expressions of gestational agemight be a chief factor in the infant’s tolerance against the deleterious impacts of free oxygen radicals. It has been found that disability of maturation of antioxidant defense system in premature infants implicates to the onset and development of bronchopulmonary dysplasia. Oxygen free radicals are highly reactive and able to destruct macromolecules as polyunsaturated fatty acids, proteins, carbohydrates and DNA⁴⁵.  APGAR scoring system based on easily five recognizable discriminators, irritability color, respiratory effort, reflex, muscletone and heart-rate is a premium technique to evaluate a condition of newborn. Low Apgar scores are significantly related with neonatal mortality⁶. The IUGR rate in developing countries according to estimates is about six times higher than that in developed countries ⁷.

Therefore, we carried out the present work to evaluate oxidative injury in IUGR in Egyptian newborns. 

Subjects

This prospective cohort study was performed in the department of obstetrics and gynecology in Kasr El Ainy hospital and El Gala a teaching hospital from May 2017 to January 2018. The research ethics was approved by the scientific ethical committee of the Department of Pediatrics, Faculty of Medicine, Cairo University. The study was conducted on 89 neonates divided into 2 groups Group 1 (intrauterine growth restriction group): included 44 neonates of both sexes born 37- 41with intrauterine growth restriction. Group 2 (appropriate for gestational age group): included 45 neonates of both sexes born 37-41and appropriate for gestational age. In both groups the neonates were delivered vaginally without any assisted vaginal delivery to mothers without known medical conditions affecting placental sufficiency e.g. diabetes, hypertension and preeclampsia. Neonates with congenital anomalies were eliminated from our study.

Methods

All neonates were subjected to the following:

Full maternal data was taken including age of mother, gravidity, parity, abortions, gestational age by early ultrasound and maternal illnesses as pre-eclampsia, hypertension, gestational diabetes, premature rupture of membrane. Obstetric data including mode of delivery, instrumental delivery and gestational age at delivery by ultrasound. Neonatal assessment including gestational age by new Ballard, sex of neonate, head circumference, length, APGAR score at 1 and 5 minutes, weight and full general & systemic examinations of newborn. All the infants were born at term. Gestational age was evaluated from the of last menstrual period date and simultaneous clinical evaluation was done using the New Ballard score⁸

Biochemical Analysis

Lipid peroxides determination

Malondialdehyde was assessed by measuring thiobarbituric reactive species according to Ruiz-Larrea et al. 1994 method in which the thiobarbituric acid reactive sub-stances react with thiobarbituric acid to generate a red colored complex having absorbance peak at 532 nm ⁹.

Total antioxidant capacity determination

Serum total antioxidant activity was measured through the reaction of antioxidants with a definite quantity of hydrogen peroxide (H₂ O₂). The antioxidants eliminate a definite quantity of the provided H₂O₂. The residual H₂O₂ is measured colorimetric ally by an enzymatic reaction in which the 3, 5, dichloro-2-hydroxy benzen sulphonate is converted to a colored product¹⁰.

Paraoxonase-1 (PON-1) activity determination

The activity of arylesterase of PON-1 was assessed via a colorimetric method using substrate phenyl acetate. PON1 catalyzes the phenyl acetate cleavage forming phenol. The phenol formation rate was assessed through observing the absorbance increase at 270 nm. ¹¹. 

Statistical analysis

Data were analyzed using the statistical SPSS program for Windows, release 20.0 (SPSS,USA). Results are given as means ± standard deviation (SD). Independent sample t test was used for comparison of unpaired data. APGAR score is given as median (range). Mann–Whitney U test was used for comparison of Apgar scores (non-parametric data). P-valueless than 0.05 was considered significant. 

Results

APGAR score both at 1 min and 5 min were significantly lower in the IUGR group compared to control group (Table 1). There was no significant difference of each of maternal age, gravity, parity, abortion and early gestation of IUGR cases compared to control group.  Mean Ballad score, birth weight, length and head circumference of IUGR cases were significantly decreased compared to control group.

MDA levels was significantly elevated in the IUGR group than control group (Table 2). Both TAC and PON1 were significantly lower in IUGR cases than control group. Significant negative correlation was observed between MDA and APGAR scores (Table 3).

Table 1: Maternal and newborns characteristics in cases with IUGR and controls

*P for the comparisons between IUGR newborns vs. controls

 Table 2: Oxidative stress markers in IUGR newborns.

*P for the comparisons between IUGR newborns vs. controls

Table 3: Results from the correlation analysis that evaluated the relationships between oxidative stress markers and 1 min and 5 min APGAR scores.

Discussion

It was hypothesized that oxidative stress, expressed as imbalance inoxidant-antioxidant, has a crucial role in the placental-related disorders development, as disorders ofhypertension of IUGR and pregnancy ^12,131415.

Prematurity is a significant public health issue. The main reason for death in children under the age of five is complications from premature birth. It has been suggested that oxidative stress may be a pathophysiological condition that contributes to this undesirable condition. Premature neonates are especially vulnerable to oxidative stress injury because they lack well-developed antioxidant and immunological defense mechanisms. The transmission from intrauterine to the extrauterine environment impressively upsurges production of free radical, which is usually downregulated by the antioxidant defense system¹⁷. Excessive reactive oxygen species (ROS), which are produced when there is an imbalance in this control, lead to oxidative stress. The antioxidant defense system is unable to reverse ROS damage under oxidative stress^17,18 either as a result of an excessive ROS production, a poor ROS inactivation, or both. The majority of the researchers examined in this review demonstrated a connection between higher risk of clinical outcomes, such as neonatal illnesses and morbidity, and elevated levels of oxidative stress biomarkers and/or decreased antioxidant levels in cord blood. IUGR was one of the disorders that shown a stronger correlation with elevated oxidative stress and/or decreased antioxidant levels ¹⁹. Silva and his colleagues conducted an analysis of the vitamin E concentration in umbilical cord serum in 140 newborns (64 premature and 76 term) to examine an association between the biomarker and intrauterine growth, which was one of the studies that evaluated IUGR¹⁹. The findings revealed that premature neonates were more likely to experience IUGR, and the majority of them had low vitamin E levels. Pregnancy complications like as IUGR, which have a prevalence of between 3 and 7% of deliveries, are frequently mentioned when the fetus is thought to be too small for the GA. A relationship between MDA and ROS levels and a higher probability of a poor Apgar score was reported by another studies ²⁰. The research also used antioxidant activity levels as additional indicators. In general, measuring antioxidant activity may be more beneficial than measuring oxidative stress levels since the data provide a better knowledge of potential processes and therapy options. ²¹.

The reason of maternal oxidative stress in IUGR is not obvious yet. Nevertheless, insufficient exudation causes placental hypoxia at the intervillous space and might share in both fetal and maternal oxidative stress. Significant remodeling of the placenta is monitored at the start of the second trimester or at the end of the first trimester that commonly is the starting point of IUGR. Slight insufficiency in diversion of arteries might cause low-grade fluctuations in villous oxygenation that lead to homeostatic responses in the form of protein synthesis inhibition and mild endoplasmic reticulum stress that leads to the reduced functional capacity and the small size of the placenta ^22,23. Oxidative stress represses nitric oxide (NO) bioavailability as it is quickly degenerated by the oxygen-derived free radical superoxide anion. This anion operates as a vasoconstrictor and is a chief determinant of nitric oxide (NO) bioavailability and biosynthesis. Numerous researches have elucidated that hypertension in human is correlated with a decreased bioavailability of NO and an exaggerated ROS amount ^24,2526. The IUGR pathophysiology is multifactorial and in the majority of cases associated with either infectious, fetal, genetic, maternal, or placental pathology²⁷. The increased level of oxidative stress markers as 8-hydroxy-2-deoxyguanosine (8-OHdG) and MDA and the diminished total antioxidant capacity level were illustrated by numerousstudies^13,28–30.

Conclusion

In conclusion, oxidative stress associated with IUGR newborns and antioxidants during pregnancy may be advised. Oxidative stress markers might have early prediction value for diagnosis of these conditions and probable pharmacological intervention with antioxidants may improve the pregnancy conditions.

Acknowledgements

Appreciation is extended to the Kasr El Ainy hospital and El Galaa teaching hospital.

Conflicts of Interest

There is no conflict of interest.

References

1. Gera T, Ramji S. Early predictors of mortality in very low birth weight neonates. Indian Pediatr. 2001;38(6):596-604.
2. Gupta P, Narang M, Banerjee BD, Basu S. Oxidative stress in term small for gestational age neonates born to undernourished mothers: a case control study. BMC Pediatr. 2004;4(1):1-7.
   CrossRef
3. Karowicz-Bilińska A, Suzin J, Sieroszewski P. Evaluation of oxidative stress indices during treatment in pregnant women with intrauterine growth retardation. Med Sci Monit Int Med J Exp Clin Res. 2002;8(3):CR211-6.
4. Wang W, Pang CCP, Rogers MS, Chang AMZ. Lipid peroxidation in cord blood at birth. Am J Obstet Gynecol. 1996;174(1):62-65.
   CrossRef
5. Winterbourn CC, Chan T, Buss IH, Inder TE, Mogridge N, Darlow BA. Protein carbonyls and lipid peroxidation products as oxidation markers in preterm infant plasma: associations with chronic lung disease and retinopathy and effects of selenium supplementation. Pediatr Res. 2000;48(1):84-90.
   CrossRef
6. Casey BM, McIntire DD, Leveno KJ. The continuing value of the Apgar score for the assessment of newborn infants. N Engl J Med. 2001;344(7):467-471.
   CrossRef
7. Imdad A, Yakoob MY, Siddiqui S, Bhutta ZA. Screening and triage of intrauterine growth restriction (IUGR) in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths. BMC Public Health. 2011;11(3):1-12.
   CrossRef
8. Ballard JL, Khoury JC, Wedig KL, Wang L, Eilers-Walsman BL, Lipp R. New Ballard Score, expanded to include extremely premature infants. J Pediatr. 1991;119(3):417-423.
   CrossRef
9. Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H. Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids. 1994;59(6):383-388.
   CrossRef
10. El-Toukhy SE, Abdel-Salam OME, Ibrahim AMM, Youness ER. Oxidative, Inflammatory, Angiogenic Markers and Vitamin D Status in Pre-and Postmenopausal Breast Cancer Egyptian Patients. Biomed Pharmacol J. 2021;14(2):829-844.
    CrossRef
11. Higashino K, Takahashi Y, Yamamura Y. Release of phenyl acetate esterase from liver microsomes by carbon tetrachloride. Clin Chim Acta. 1972;41:313-320. doi:10.1016/0009-8981(72)90526-8
    CrossRef
12. Jauniaux E, Poston L, Burton GJ. Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Update. 2006;12(6):747-755.
    CrossRef
13. Tenório MB, Ferreira RC, Moura FA, Bueno NB, de Oliveira ACM, Goulart MOF. Cross-talk between oxidative stress and inflammation in preeclampsia. Oxid Med Cell Longev. 2019;2019.
    CrossRef
14. Marseglia L, D’Angelo G, Manti S, et al. Oxidative stress-mediated aging during the fetal and perinatal periods. Oxid Med Cell Longev. 2014;2014.
    CrossRef
15. Negre-Salvayre A, Swiader A, Salvayre R, Guerby P. Oxidative stress, lipid peroxidation and premature placental senescence in preeclampsia. Arch Biochem Biophys. 2022:109416.
    CrossRef
16. Bharadwaj SK, Vishnu Bhat B, Vickneswaran V, Adhisivam B, Bobby Z, Habeebullah S. Oxidative stress, antioxidant status and neurodevelopmental outcome in neonates born to pre-eclamptic mothers. Indian J Pediatr. 2018;85(5):351-357.
    CrossRef
17. Bandyopadhyay T, Bhatia BD, Khanna HD. A study of oxidative stress in neonates delivered through meconium-stained amniotic fluid. Eur J Pediatr. 2017;176(3):317-325.
    CrossRef
18. Stefanov G, Briyal S, Pais G, Puppala B, Gulati A. Relationship between oxidative stress markers and endothelin-1 levels in newborns of different gestational ages. Front Pediatr. 2020;8:279.
    CrossRef
19. Silva AB da, Medeiros JFP, Lima MSR, et al. Intrauterine growth and the vitamin E status of full-term and preterm newborns. Rev Paul Pediatr. 2019;37:291-296.
    CrossRef
20. Zheng B, Jiang Z, Wu S, Jin Q, Lin P, Lin Z. Elevated cord blood oxidative stress biomarkers negatively affect neonatal outcomes of mothers with severe preeclampsia: A case-control study. 2020.
21. Moore TA, Ahmad IM, Zimmerman MC. Oxidative stress and preterm birth: an integrative review. Biol Res Nurs. 2018;20(5):497-512.
    CrossRef
22. Burton GJ, Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol. 2018;218(2):S745-S761.
    CrossRef
23. Burton GJ, Yung H-W, Cindrova-Davies T, Charnock-Jones DS. Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia. Placenta. 2009;30:43-48.
    CrossRef
24. Togliatto G, Lombardo G, Brizzi MF. The future challenge of reactive oxygen species (ROS) in hypertension: from bench to bed side. Int J Mol Sci. 2017;18(9):1988.
    CrossRef
25. González J, Valls N, Brito R, Rodrigo R. Essential hypertension and oxidative stress: New insights. World J Cardiol. 2014;6(6):353.
    CrossRef
26. Hula N, Pasha M, Quon A, et al. Prenatal Hypoxia is Associated with Coronary Artery Endothelial Dysfunction in Male and Female Offspring. FASEB J. 2022;36.
    CrossRef
27. Sharma D, Shastri S, Sharma P. Intrauterine growth restriction: antenatal and postnatal aspects. Clin Med Insights Pediatr. 2016;10:CMPed-S40070.
    CrossRef
28. Prejbisz A, Dobrowolski P, Kosiński P, et al. Management of hypertension in pregnancy—prevention, diagnosis, treatment and long-term prognosis. Varia Medica. 2019;3(6):385-448.
    CrossRef
29. Taravati A, Tohidi F. Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia. Taiwan J Obstet Gynecol. 2018;57(6):779-790.
    CrossRef
30. Surmiak P, Wojnarowicz O, Szymkowiak M. Malondialdehyde and Neutrophil Gelatinase-Associated Lipocalin as Markers of Oxidative Stress in Small for Gestational Age Newborns from Hypertensive and Preeclamptic Pregnancies. Biomed Res Int. 2022;2022.
    CrossRef