Hasan Ozkan ^1* Nuray Duman ¹ Funda Tuzun ¹ Fatma Narter ² Can Akyildiz ¹ Emel Altuncu ² Mehmet Satar ³ Mustafa Ozdemir ³ Abdullah Kurt ⁴ Ali U. Tugcu ⁴ Murat Konak ⁵ Saime Sundus Uygun ⁵ Seda Yilmaz Semerci ⁶ Rahime T. Dikmen ⁶ Bora Baysal ⁷ Cemile K. Zeybek ⁷ Yasemin Ezgi Kostekci ⁸ Suzan Sahin ⁹ Merve Tutal ¹⁰ Ayse Anik ¹¹ Mehmet Buyuktiryaki ¹² Belma S. Karagol ¹³ Gaffari Tunç ¹⁴ Derya Colak ¹⁵ Hasan Cetin ¹⁶ Aysen Orman ¹⁷ Ozgur Olukman ¹⁸ Mehmet Fatih Deveci ¹⁹ Dilek Sarici ²⁰ Salih C. Cakir ²¹ Pembe Keskinoglu ¹

• ¹ Faculty of Medicine, Dokuz Eylül University, Izmir, Türkiye
• ² Istanbul Kartal Dr.Lutfi Kirdar Education and Research Hospital, Istanbul, Türkiye
• ³ Faculty of Medicine, Cukurova University, Adana, Adana, Türkiye
• ⁴ Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Ankara, Türkiye
• ⁵ School of Medicine, Selcuk University, Konya, Türkiye
• ⁶ İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Istanbul, Türkiye
• ⁷ Usak University, Usak, Türkiye
• ⁸ Faculty of Medicine, Ankara University, Ankara, Sakarya, Türkiye
• ⁹ Other, Aydin, Türkiye
• ¹⁰ Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Eskişehir, Türkiye
• ¹¹ Medical School, Adnan Menderes University, Aydin, Aydin, Türkiye
• ¹² School of International Medicine, Istanbul Medipol University, Istanbul, Türkiye
• ¹³ Gulhane Faculty of Medicine, University of Health Sciences (Turkey), Ankara, Ankara, Türkiye
• ¹⁴ School of Medicine, Cumhuriyet University, Sivas, Sivas, Türkiye
• ¹⁵ Umraniye Research and Training Hospital, University of Health Sciences, Istanbul, Istanbul, Türkiye
• ¹⁶ School of Medicine, Süleyman Demirel University, Isparta, Isparta, Türkiye
• ¹⁷ Faculty of Medicine, Mersin University, Yenişehir, Mersin, Türkiye
• ¹⁸ Izmir Bakircay University, Izmir, Türkiye
• ¹⁹ Faculty of Medicine, İnönü University, Malatya, Malatya, Türkiye
• ²⁰ S.B. Keçiören Eğitim ve Araştırma Hastanesi, Ankara, Ankara, Türkiye
• ²¹ Samsun Training and Research Hospital, Samsun, Samsun, Türkiye

The objective of this study was to evaluate the efficacy and safety of isotonic and hypotonic intravenous fluids in maintenance fluid therapy for term infants. This was a multi-centre, prospective, observational study conducted in 21 participating centres from December 30, 2020, to June 30, 2023. The study included term newborns requiring parenteral fluid therapy for maintenance (NCT04781361). The fluid treatment was divided into two groups based on the concentration of sodium in the parenteral fluid, designated as hypotonic (NaCl < 130 mmol/L) and isotonic (NaCl = 130–154 mmol/L). The primary outcomes were the change in mean plasma sodium (pNa) levels per hour (∆pNa mmol/L/hour), the incidence of hyponatremia (pNa <135 mmol/L) and hypernatremia (pNa >145 mmol/L), and the occurrence of clinically significant changes in sodium levels (∆pNa >0.5 mmol/L/hour). A total of 420 patients from 21 centers were included. The ∆pNa was negative in the hypotonic fluid group and positive in the isotonic fluid group, with a significant difference between the groups [respectively -0.07 ± 0.03 (95% CI: -0.13 to -0.02); 0.04±0.03 (95%CI: -0.02 to 0.09), p=0.04]. There was no difference between the groups in terms of the development of hypernatremia or a clinically meaningful pNa increase. The hypotonic fluid group had a higher incidence of hyponatremia and a clinically meaningful sodium decrease compared to the isotonic fluid group [7.9% vs. 1.2% (OR:6.5, p:0.03)] and [12.2% vs.4.2% (OR:2.9, p=0.03)]. Contrary to current understanding, this large-scale study is the first to demonstrate that the use of hypotonic fluids in maintenance fluid therapy for newborns poses a risk of hyponatremia development, whereas isotonic fluid therapy appears safe.