Tocolytic therapy safeness in various gestational terms

Authors

DOI:

https://doi.org/10.15574/HW.2024.4(173).2632

Keywords:

tocolysis, hexoprenaline, nifedipine, hyperglycemia, neuroprotection

Abstract

Hexoprenaline and nifedipine, known for their side effects, are currently most often used for tocolysis. Duration of use and interactions with other drugs require further study.

Aim was to compare the clinical and laboratory manifestations and consequences of tocolysis with hexporenaline and nifedipine in neonates and mothers.

Materials and methods. The results of tocolysis with hexoprenaline and nifedipine for more or less than 48 hours before delivery time were compared in extremely premature terms of labor (EPP group - 22-27 weeks, 77 parturients) and in terms of moderate premature parturition (MPP group - 28-34 weeks, 73 parturients).

Results. 80.0% and 90.9% of newborns survived within a week in the EPP and MPP groups after tocolysis with hexoprenaline for more than 48 hours. After tocolysis with nifedipine - respectively 66.7% and 92.9%, survival after hexoprenaline is 80.0%, nifedipine is 66.7% in the EPP group. Survival after prolonged tocolysis is higher than the average for the group (63.6%), in the MPP group the difference was 90.9 and 92.9%, without tocolysis 90.0%, and the average for the group was 90.4%. Survival in the EPP group with short-term tocolysis with hexoprenaline (50.0%) and nifedipine (60.0%), close to that without tocolysis (55.2%) and less than the average the EPP group (63.6%). All newborns survived after nifedipine, after hexoprenaline 81.8%, without tocolysis 90.0% in the MPP group. Moderate hyperglycaemia (5.6±0.58 mmol/L and 5.3±0.69 mmol/L) was observed after hexaprenaline and nifedipine, 4.2±0.37 mmol/L without tocolysis.

Conclusions. The lower survival rate of extremely preterm infants does not depend on the tocolysis type or its absence and is associated with immaturity in accordance with the term, and not with effectivelessness of therapeutic influences. Survival of moderately preterm infants after tocolysis with nifedipine showed a better outcome. A side effect of tocolysis with both drugs studied was an excess up to 30% of the mean glycemic value. It is desirable to give preference to hexoprenaline at 22-27 weeks, and tocolysis with nifedipine is more appropriate for MPP (28-34 weeks term).

The study was carried out in accordance with the Helsinki Declaration principles. The study protocol was adopted by the Local Ethics Committee of the Bohomolets NMU. Informed consent from the women for the study was obtained.

Authors declare no conflict of interest.

References

Chakraborty RK, Hamilton RJ. (2024, Jan). Calcium Channel Blocker Toxicity. [Updated 2023 Jul 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. URL: https://www.ncbi.nlm.nih.gov/books/NBK537147.

Crowther CA, Ashwood P, Middleton PF, McPhee A, Tran T et al. (2023). Prenatal Intravenous Magnesium at 30-34 Weeks' Gestation and Neurodevelopmental Outcomes in Offspring: The MAGENTA Randomized Clinical Trial. JAMA. 330(7): 603-614. https://doi.org/10.1001/jama.2023.12357

Dias TZ, Fava ML, Passini Júnior R, Cecatti JG, Tedesco RP, Lajos GJ et al. (2018). Tocolysis among Women with Preterm Birth: Associated Factors and Outcomes from a Multicenter Study in Brazil. Tocólise com parto prematuro: fatores associados e desfechos de um estudo multicêntrico no Brasil. Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia. 40(4): 171-179. https://doi.org/10.1055/s-0038-1642025

Hammers AL, Sanchez-Ramos L, Kaunitz AM. (2015). Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis. American journal of obstetrics and gynecology. 212(4). https://doi.org/10.1016/j.ajog.2014.10.1091

Jørgensen JS, Weile LK, Lamont RF. (2014). Preterm labor: current tocolytic options for the treatment of preterm labor. Expert opinion on pharmacotherapy. 15(5): 585-588. https://doi.org/10.1517/14656566.2014.880110

Klauser CK, Briery CM, Tucker AR, Martin RW, Magann EF, Chauhan SP, Morrison JC. (2016). Tocolysis in women with advanced preterm labor: a secondary analysis of a randomized clinical trial. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 29(5): 696-700. https://doi.org/10.3109/14767058.2015.1018171

Korakas E, Ikonomidis I, Markakis K, Raptis A, Dimitriadis G, Lambadiari V. (2020). The Endothelial Glycocalyx as a Key Mediator of Albumin Handling and the Development of Diabetic Nephropathy. Current vascular pharmacology. 18(6): 619-631. https://doi.org/10.2174/1570161118666191224120242

Lamont CD, Jørgensen JS, Lamont RF. (2016). The safety of tocolytics used for the inhibition of preterm labour. Expert opinion on drug safety. 15(9): 1163-1173. https://doi.org/10.1080/14740338.2016.1187128

Leush S, Protsyk M. (2023). Hemostasis in vessels of the umbilical cord in premature and extremely premature newborns. Ukrainian Journal Health of Woman. 4(167): 35-39. https://doi.org/10.15574/HW.2023.167.35

Louis JM, Randis TM. (2023). Intrapartum Magnesium for Neuroprotection: Revisiting Gestational Age Criteria. JAMA. 330(7): 597-598. https://doi.org/10.1001/jama.2023.10673

Motiaa Y, El Otmani W, El Oudghiri N, Tazi AS. (2018). Nicardipin Associated Pulmonary Edema : A Severe Complication of Tocolysis - A Case Report. Integrative Journal of Medical Sciences. 5. https://doi.org/10.15342/ijms.v5ir.200

MOZ Ukrainy. (2024). Pro zatverdzhennia shistnadciatogo vypusku Derzhavnogo formuliara likarskyh zasobiv ta zabezpechennia yogo dostupnosti. Nakaz MOZ Ukrainy vid 12.03.2024 No. 418. Suppl 2. Vzayemodia likarskych zasobiv. URL: https://moz.gov.ua/uploads/10/54241-dn_418_12032024_dod.pdf.

MOZ Ukrainy (2023). Pro vnesennia zmin do deyakyh normatyvno-pravovyh aktiv Ministerstva ohorony zdorovia Ukrainy shchodo pryznachennia ta vidpusku likarskyh zasobiv ta medychnyh vyrobiv za receptom. Nakaz MOZ Ukrainy vid 15.03.2023 No. 494. Suppl 1 Pravyla vypysuvannia receptive ta vymog-zamovlen na likarski zasoby ta medychni vyroby. URL: https://moz.gov.ua/uploads/9/45103-dn_494_15032023_dod1.pdf.

Oliveros-Cubillan A., Reyna-Villasmil E., Santos-Bolívar J., Mejia-Montilla J., Reyna-Villasmil N., Fernández-Ramírez A. (2017).Tocólisis con sulfato de magnesio o clorhidrato de isoxuprina en amenaza de parto pretérmino. Tocolysis with magnesium sulphate or isoxsuprine hydrochloride in threatened pre-term labour. Perinatología y Reproducción Humana. 31(3): 107-112. https://doi.org/10.1016/j.rprh.2017.10.002

Safdar NZ, Kietsiriroje N, Ajjan RA. (2023). The Cellular and Protein Arms of Coagulation in Diabetes: Established and Potential Targets for the Reduction of Thrombotic Risk. International journal of molecular sciences. 24(20): 15328. https://doi.org/10.3390/ijms242015328

Shennan A, Suff N, Jacobsson B. (2021). FIGO good practice recommendations on magnesium sulfate administration for preterm fetal neuroprotection. Int. J. Gynecol.Obstet. 155(1): 31-33. https://doi.org/10.1002/ijgo.13856

Sunil Kumar KS, Shalini B, Apoorva J. (2023). Nifedipine versus magnesium sulfate in the management of preterm labour- A randomised controlled trial. Indian journal of obstetrics and gynecology research (IJOGR). 10(4): 460-468. https://doi.org/10.18231/j.ijogr.2023.088

Verkleij CJ, Bruijn RE, Meesters EW, Gerdes VE, Meijers JC, Marx PF. (2011). The hemostatic system in patients with type 2 diabetes with and without cardiovascular disease. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 17(6): E57-E63. https://doi.org/10.1177/1076029610384112

Wang LP, Jiang Y, Yang H, Peng C, Zhang C, Tao X, Xie HH. (2016). Combination Therapy of Nifedipine and Sulphonylureas Exhibits a Mutual Antagonistic Effect on the Endothelial Cell Dysfunction Induced by Hyperglycemia Linked to Vascular Disease. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 38(6): 2337-2347. https://doi.org/10.1159/000445587

Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A et al. (2022). Tocolytics for delaying preterm birth: a network meta-analysis (0924). The Cochrane database of systematic reviews. 8(8): CD014978. https://doi.org/10.1002/14651858.CD014978.pub2

Published

2024-10-25