Ferda ÖZLÜ, Caner HACIOĞLU, Selim BÜYÜKKURT, Hacer YAPICIOĞLU, Mehmet SATAR

Antenatal magnezyum ile prematüre morbiditelerindeki değişiklikler

Amaç: 34 gestasyonel haftadan once doğan bebeklerin annelerine yapılan antenatal magnesiyum sulfatın, bebeklerdeki intraventriküler kanama, beslenme intoleransı, retinopati ya da bronkopulmoner displazi gibi morbiditeler üzerine etkisi henüz tam açıklığa kavuşturulmamıştır. Biz antenatal uygulanan magnezyum sulfatın prematüre bebeklerde erken ve geç morbidite ve mortaliteye etkisini retrospektif olarak araştırmayı amaçladık.Gereç ve Yöntem: Antenatal magnesiyum alan 108 prematüre bebek Mg (+) grubu, ve antenatal magnesiyum almayan 172 prematüre bebek Mg(-) grubu,oluşturdu.Bulgular: Respiratuar Distres sendromu, intraventriküler kanama, ağır intraventriküler kanama (evre 3 ve 4), premature retinopatisi, bronkopulmoner displazi Mg (+) grupta daha düşük saptanmasına ragmen sadece Respiratuar Distres sendromu için istatistiksel olarak anlamlı idi.Sonuç: Bu retrospektif çalışmada antenatal magnezyum uygulamasının premature bebeklerde morbidite ve mortalite üzerine istatistiksel anlamlı bir yararı gösterilemedi.

Anahtar Kelimeler:

antenatal magnesium, premature morbidities, intraventricular hemorrhage, feeding intolerance, patent ductus arteriozus

Changes on preterm morbidities with antenatal magnesium

Purpose: The effect of magnesium sulphate (MgSO4) to mothers with imminent premature birth at <34 weeks on neonatal morbidities like intraventricular hemorrhage, feeding intolerance, retinopathy or bronchopulmoner dysplasia is not clear. We evaluated the effect of antenatal magnesium sulfate exposure on premature early and late morbidities and mortality retrospectively.Materials and Methods: 108 infants ≤ 32 gestational age having antenatal magnesium were grouped as Mg (+) and 172 infants ≤ 32 gestational age not having antenatal magnesium were grouped as Mg (-).Results: Respiratory Distress Syndrome, intraventricular hemorrhage, severe intraventricular hemorrhage (grade 3 and 4), retinopathy of prematurity and bronchopulmonary dysplasia were less in Mg (+) group compared to Mg (-) group but it is not statistically significant, except Respiratory Distress Syndrome.Conclusion: This retrospective study showed that ante natal exposure to MgSO4 did not have statistically significant beneficial effect on either morbidities or mortality in premature infants.

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1. Lorenz JM, Wooliever DE, Jetton JR, Paneth NA. Quantitative review of mortality and developmental disability in extremely premature newborns. Arch Pediatr Adolesc Med. 1998;152:425-35.
2. Drummond PM, Colver AF. Analysis by gestational age of cerebral palsy in singleton births in north-east England 1970-94. Paediatr Perinat Epidemiol 2002;16:172-80.
3. Vohr B, Allan WC, Scott DT, Katz KH, Schneider KC, Makuch RW et al. Early-onset intraventricular hemorrhage in preterm neonates: incidence of neurodevelopmental handicap. Semin Perinatol 1999;23:212-217.
4. Vermeulen GM, Bruinse HW, Gerards LJ, de Vries LS. Perinatal risk factors for cranial ultrasound abnormalities in neonates born after spontaneous labour before 34 weeks. Eur J Obstet Gynecol Reprod Biol 2001;94:290-295.
5. Bolisetty S, Dhawan A, Abdel-Latif M, Bajuk B, Stack J, Lui K; New South Wales and Australian Capital Territory Neonatal Intensive Care Units' Data Collection. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics 2014;133:55-62.
6. Beaino G, Khoshnood B, Kaminski M, Pierrat V, Marret S, Matis J et al. Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study. Dev Med Child Neurol. 2010;52:e119-125.
7. Marret S, Vanhulle C, Laquerriere A. Pathophysiology of cerebral palsy. In: Dulac O, Lassonde M, Sarnat HB, eds. Handbook of clinical neurology; pediatric neurology part I. Elsevier. 2013:169-76.
8. Conde-Agudelo A, Romero R. Antenatal magnesium sulphate for the prevention of cerebral palsy in preterm infants less than 34 weeks’gestation: a systematic review and metaanalysis. Am J Obstet Gynecol. 2009;200:595–609.
9. Costantine M, Weiner SJ. Effects of antenatal exposure to magnesium sulphate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol. 2009;114:354–64.
10. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;1:CD004661.
11. Teela KC, De Silva DA, Chapman K, Synnes AR, Sawchuck D, Basso M et al. MAG-CP Collaborative Group. Magnesium sulphate for fetal neuroprotection: benefits and challenges of a systematic knowledge translation project in Canada. BMC Pregnancy Childbirth. 2015;15:347.
12. Mittendorf R, Dambrosia J, Pryde PG, Lee KS, Gianopoulos JG, Besinger RE et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol. 2002;186:1111-8.
13. Satake K, Lee JD, Shimizu H, Uzui H, Mitsuke Y, Yue H et al. Effects of magnesium on prostacyclin synthesis and intracellular free calcium concentration in vascular cells. Magnes Res. 2004;17:20-7.
14. Havranek T, Ashmeade TL, Afanador M, Carver JD. Effects of maternal magnesium sulfate administration on intestinal blood flow velocity in preterm neonates. Neonatology. 2011;100:44–9.
15. Paradisis M, Osborn DA, Evans N, Kluckow M. Randomized controlled trial of magnesium sulfate in women at risk of preterm delivery-neonatal cardiovascular effects. J Perinatol. 2012;32:665–70.
16. Robel-Tillig E, Knüpfer M, Pulzer F, Vogtmann C. Blood flow parameters of the superior mesenteric artery as an early predictor of intestinal dysmotility in preterm infants. Pediatr Radiol. 2004;34:958-62.
17. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birthweight less than 1500 g. J Pediatr 1978;92:529-34.
18. Kliegman RM, Hack M, Jones P, Fanaroff AA. Epidemiologic study of necrotizing enterocolitis among low-birth-weight infants. Absence of identifiable risk factors. J Pediatr 1982;100:440-4.
19. Moore TA, Wilson ME. Feeding intolerance; a concept analysis. Adv Neonatal Care. 2011;11:149-54.
20. Dodrill P. Feeding difficulties in premature infants. Infant Child Adolesc Nutr. 2011;3:324-31.
21. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723-9.
22. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123:991-9.
23. Burd I, Breen K, Friedman A, Chai J, Elovitz MA. Magnesium sulfate reduces inflammation- associated brain injury in fetal mice. Am J Obstet Gynecol. 2010;202:292-9.
24. McDonald JW, Silverstein FS, Johnston MV. Magnesium reduces N-methyl-D- aspartate (NMDA)- mediated brain injury in perinatal rats. Neurosci Lett. 1990;109:234-8.
25. Favrais G, Tourneux P, Lopez E, Durrmeyer X, Gascoin G, Ramful D et al. Impact of Common Treatments Given in the Perinatal Period on the Developing Brain Neonatology. 2014;106:163-72.
26. Finesmith RB, Roche K, Yellin PB, Walsh KK, Shen C, Zeglis M et al. Effect of magnesium sulfate on the development of cystic periventricular leukomalacia in preterm infants. Am J Perinatol. 1997;14:303–7.
27. Perlman J, Fermandez C, Gee J, LeVeno K, Risser R. Magnesium sulphate administered to mothers with pregnancy-induced hypertension is associated with a reduction in periventricular- intraventricular hemorrhage [abstract]. Pediatric Research. 1994;37:231A.
28. Wiswell TE, Graziani LJ, Caddell JL, Vecchione N, Stanley C, Spitzer AR. Maternally administered magnesium sulphate protects against early brain injury and long-term adverse neurodevelopmental outcomes in preterm infants. A prospective study. Pediatr Res. 1996;39:253A.
29. Canterino JC, Verma UL, Visintainer PF, Figueroa R, Klein SA, Tejani NA. Maternal magnesium sulfate and the development of neonatal periventricular leucomalacia and intraventricular hemorrhage. Obstet Gynecol. 1999;93:396–402.
30. Kimberlin DF, Hauth JC, Goldenberg RL, Bottoms SF, Iams JD, Mercer B et al. The effect of maternal magnesium sulfate treatment on neonatal morbidity in < or = 1000-gram infants. Am J Perinatol. 1998;15:635–41.
31. Paneth N, Jetton J, Pinto-Martin J, Susser M. Magnesium sulfate in labor and risk of neonatal brain lesions andcerebral palsy in low birth weight infants. The Neonatal Brain Hemorrhage Study Analysis Group. Pediatrics. 1997;99:E1.
32. Weintraub Z, Solovechick M, Reichman B, Rotschild A, Waisman D, Davkin O, et al; Israel Neonatal Network. Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2001;85:F13–7.
33. Kuban KC, Leviton A, Pagano M, Fenton T, Strassfeld R, Wolff M. Maternal toxemia is associated with reduced incidence of germinal matrix hemorrhage in premature babies. J Child Neurol. 1992;7:70-6.
34. Gano D, Ho ML, Partridge JC, , Glass HC, Xu D, Barkovich AJ et al. Antenatal exposure to magnesium sulfate is associated with reduced cerebellar hemorrhage in preterm newborns. J Pediatr 2016;178:68-74.
35. Crowther CA, Hiller JE, Doyle LW, Haslam RR; Australasian Collaborative Trial of Magnesium Sulphate (ACTOMg SO4) Collaborative Group. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA. 2003;290:2669-76.
36. Marret S, Marpeau L, Zupan-Simunek V, Eurin D, Lévêque C, Hellot MF et al. PREMAG trial group. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial BJOG 2007;114:310-8.
37. Zeng X, Xue Y, Tian Q, Sun R, An R. effects and safety of magnesium sulfate on neuroprotection: a meta-analysis based on PRISMA guidelines. Medicine 2016;95:e2451.
38. Ohhashi M, Yoshitomi T, Sumiyoshi K, Kawagoe Y, Satoh S, Sameshima H et al. Magnesium sulphate and perinatal mortality and morbidity in very-lowbirthweight infants born between 24 and 32 weeks of gestation in Japan. Eur J Obstet Gynecol Reprod Biol 2016;201:140-5.
39. Dribben WH, Creeley CE, Wang HH, Smith DJ, Farber NB, Olney JW. High dose magnesium sulfate exposure induces apoptotic cell death in the developing neonatal mouse brain. Neonatol. 2009;96:23-32.
40. del Moral T, Gonzalez-Quintero VH, Claure N, Vanbuskirk S, Bancalari E. Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants. J Perinatol. 2007;27:154-7.
41. Belden MK, Gnadt S, Ebert A. Effects of maternal magnesium sulfate treatment on neonatal feeding tolerance. J Pediatr Pharmacol Ther. 2017;22:112-7.
42. Gursoy T, Imamoğlu EY, Ovali F, Karatekin G. Effects of antenatal magnesium exposure on intestinal blood flow and outcome in pretern neonates. Am J Perinatol. 2015;32:1064-9.
43. Elimian A, Verma R, Ogburn P, Wiencek V, Spitzer A, Quirk JG. Magnesium sulfate and neonatal outcomes of preterm neonates. J Matern Fetal Neonatal Med. 2002;12:118-22.
44. Klauser CK, Briery CM, Keiser SD, Martin RW, Kosek MA, Morrison JC. Effect of antenatal tocolysis on neonatal outcomes. J Matern Fetal Neonatal Med. 2012;25:2778-81.