INVESTIGATE THE OPTIMAL DOSAGE OF METFORMIN FOR PROLONGING GESTATION IN PRETERM PREECLAMPSIA AND ITS EFFECTS ON MATERNAL AND NEONATAL OUTCOMES
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Keywords
Metformin, preterm preeclampsia, pregnancy prolongation, maternal outcomes, neonatal outcomes
Abstract
Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, particularly when diagnosed preterm, often necessitating early delivery with substantial neonatal risks. Prolonging gestation in such cases can markedly improve neonatal survival and osutcomes. This randomized controlled trial investigated the optimal dosage of metformin for prolonging gestation and improving maternal–neonatal outcomes in women with preterm preeclampsia. Conducted at the Jinnah Postgraduate Medical Centre and Sindh Institute of Child and Maternal Health, Pakistan, between December 2023 and December 2024, 180 women diagnosed with preterm preeclampsia were randomized into three groups: low-dose (500 mg twice daily), moderate-dose (1000 mg twice daily), and high-dose (1500 mg twice daily) metformin, in addition to standard care. The primary outcome was gestational prolongation; secondary outcomes included maternal blood pressure control, maternal complications, neonatal outcomes, and tolerability. Moderate-dose metformin achieved the most significant prolongation of pregnancy (21.4 ± 5.6 days), compared with low- (14.2 ± 4.9 days, p<0.001) and high-dose (18.1 ± 5.2 days, p=0.02) groups. Maternal complications such as eclampsia and HELLP syndrome were lowest in the moderate-dose arm (10%), and neonatal outcomes, including mean birth weight, Apgar scores, and NICU admissions, were most favorable. High-dose metformin was associated with greater gastrointestinal intolerance without additional efficacy. No lactic acidosis was observed. These findings suggest that moderate-dose metformin is optimal for prolonging gestation and improving both maternal and neonatal outcomes, balancing efficacy with tolerability. Larger multicenter trials are warranted to validate these results and establish definitive clinical guidelines.
References
2. Yang, M., Wang, M., & Li, N. (2024). Advances in pathogenesis of preeclampsia. Archives of Gynecology and Obstetrics, 309(5), 1815-1823.
3. Von Dadelszen, P., Vidler, M., Tsigas, E., & Magee, L. A. (2021). Management of preeclampsia in low-and middle-income countries: lessons to date, and questions arising, from the PRE-EMPT and related initiatives. Maternal-Fetal Medicine, 3(2), 136-150.
4. Narkhede, A. M., & Karnad, D. R. (2021). Preeclampsia and related problems. Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine, 25(Suppl 3), S261.
5. Nirupama, R., Divyashree, S., Janhavi, P., Muthukumar, S. P., & Ravindra, P. V. (2021). Preeclampsia: Pathophysiology and management. Journal of gynecology obstetrics and human reproduction, 50(2), 101975.
6. Wang, Y., Wu, N., & Shen, H. (2021). A review of research progress of pregnancy with twins with preeclampsia. Risk management and healthcare policy, 1999-2010.
7. Beardmore-Gray, A., Seed, P. T., Fleminger, J., Zwertbroek, E., Bernardes, T., Mol, B. W., ... & Chappell, L. C. (2022). Planned delivery or expectant management in preeclampsia: an individual participant data meta-analysis. American journal of obstetrics and gynecology, 227(2), 218-230.
8. Wu, P., Green, M., & Myers, J. E. (2023). Hypertensive disorders of pregnancy. Bmj, 381.
9. Daskalakis, G., Pergialiotis, V., Domellöf, M., Ehrhardt, H., Di Renzo, G. C., Koç, E., ... & Jacobsson, B. (2023). European guidelines on perinatal care: corticosteroids for women at risk of preterm birth. The Journal of Maternal-Fetal & Neonatal Medicine, 36(1), 2160628.
10. Dutta, S., Shah, R. B., Singhal, S., Dutta, S. B., Bansal, S., Sinha, S., & Haque, M. (2023). Metformin: a review of potential mechanism and therapeutic utility beyond diabetes. Drug design, development and therapy, 1907-1932.
11. Poniedziałek-Czajkowska, E., Mierzyński, R., Dłuski, D., & Leszczyńska-Gorzelak, B. (2021). Prevention of hypertensive disorders of pregnancy—is there a place for metformin?. Journal of Clinical Medicine, 10(13), 2805.
12. Hao, H., Li, F., Wang, F., Ran, J., Chen, Y., Yang, L., ... & Yang, H. (2024). Protective effect of metformin on the NG-nitro-l-arginine methyl ester (l-NAME)-induced rat models of preeclampsia. Biochemical and Biophysical Research Communications, 739, 150996.
13. Tong, S., Tu’uhevaha, J., Hastie, R., Brownfoot, F., Cluver, C., & Hannan, N. (2022). Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. American journal of obstetrics and gynecology, 226(2), S1157-S1170.
14. Neola, D., Angelino, A., Sirico, A., Murolo, C., Bartolini, G., Vigilante, L., ... & Maruotti, G. M. (2024). Unveiling therapeutic potentials and exploring maternal‐fetal health benefits of metformin in pregnancy: A scoping review. International Journal of Gynecology & Obstetrics, 167(2), 538-546.
15. Paschou, S. A., Shalit, A., Gerontiti, E., Athanasiadou, K. I., Kalampokas, T., Psaltopoulou, T., ... & Goulis, D. G. (2024). Efficacy and safety of metformin during pregnancy: an update. Endocrine, 83(2), 259-269.
16. Tong, S., Tu’uhevaha, J., Hastie, R., Brownfoot, F., Cluver, C., & Hannan, N. (2022). Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. American journal of obstetrics and gynecology, 226(2), S1157-S1170.
17. Cluver, C. A., Hiscock, R., Decloedt, E. H., Hall, D. R., Schell, S., Mol, B. W., ... & Tong, S. (2021). Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial. Bmj, 374.
18. Gordon, H. G., Atkinson, J. A., Tong, S., Mehdipour, P., Cluver, C., Walker, S. P., ... & Hastie, R. M. (2024). Metformin in pregnancy and childhood neurodevelopmental outcomes: a systematic review and meta-analysis. American Journal of Obstetrics and Gynecology, 231(3), 308-314.
19. Raperport, C., Chronopoulou, E., & Homburg, R. (2021). Effects of metformin treatment on pregnancy outcomes in patients with polycystic ovary syndrome. Expert Review of Endocrinology & Metabolism, 16(2), 37-47.
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Dr. Zobia Munaf
Senior Woman Medical Officer, Sindh Government PIB Hospital, Karachi, Pakistan.
Dr. Ana Mehreen Rajput
Assistant Professor, Sindh Institute of Child Health and Neonatology (SICHN), Karachi, Pakistan.
Dr. Zakia Bano
Assistant Professor, Department of Gynaecology, Liaquat College of Medicine and Dentistry, Karachi, Pakistan.
Dr. Anchal Seetlani
Assistant Professor, Sindh Institute of Child Health and Neonatology (SICHN), Karachi, Pakistan.
Dr. Tehseen Tanveer
Medical Specialist, Department of General Medicine, KRL Hospital, Islamabad, Pakistan.