Comprehensive assessments of incidence, risk factors and short-term outcomes of refeeding syndrome in small-for-gestational-age infants

Comprehensive assessments of incidence, risk factors and short-term outcomes of refeeding syndrome in small-for-gestational-age infants | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comprehensive assessments of incidence, risk factors and short-term outcomes of refeeding syndrome in small-for-gestational-age infants Lingling Dai, Lei Hu, Zhe Lin, Yiyao Bao, Linhua Tan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7899679/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Few studies have studied the refeeding syndrome (RS) in small-for-gestational-age SGA infants, which led to the lack of knowledge in this field. This study aimed to compressively assess the incidence, risk factors and short-term outcomes of RS in SGA infants in order to improve clinical managements of SGA infants. Methods This prospective cohort study enrolled hospitalized SGA infants who received enteral nutrition (EN) and/or parenteral nutrition (PN) within 24h upon admission and with complete clinical data from January 2019 to June 2024. RS was defined according to the ASPEN criteria and as a decrease of ≥ 10% in at least one of phosphorus, potassium and magnesium level during the first five days of EN and/or PN. Binary logistic regression analyses were performed to explore the independent risk factors of RS and associations between RS and short-term outcomes. Results 359 SGA infants were finally included in the study, comprising 175 (48.70%) males and 184 (51.30%) females. The incidence of RS was 203 (56.50%) in SGA infants. Binary logistic regression analyses revealed that high potassium level at baseline (adjusted odds ratio (OR) = 4.842, 95% confidence interval (CI): 2.947 to 7.955, P < 0.001) and premature rupture of membrane (adjusted OR = 3.292, 95%CI: 1.459 to 7.429, P = 0.004) were the independent risk factors for RS; older age (adjusted OR = 0.910, 95%CI: 0.859 to 0.963, P = 0.001) and higher albumin level (adjusted OR = 0.891, 95%CI: 0.821 to 0.966, P = 0.005) were the protective factors, and RS was the independent risk factors for neonatal sepsis (adjusted OR = 3.672, 95%CI: 1.193 to 11.301, P = 0.023) and thrombocytopenia (adjusted OR = 1.921, 95%CI: 1.023 to 3.606, P = 0.042). Conclusions There was a high RS incidence in SGA infants. High potassium level at baseline and premature rupture of membrane were the independent risk factors for RS, and RS was the independent risk factors for neonatal sepsis and thrombocytopenia. These findings suggested RS screening should be performed in routine clinical practice for all SGA infants, and timely monitoring and intervening in neonatal sepsis and thrombocytopenia in SGA infants with RS. Small-for-gestational-age Refeeding syndrome High potassium level at baseline Premature rupture of membrane Neonatal sepsis Thrombocytopenia. Figures Figure 1 Introduction Small-for-gestational-age (SGA) infants are referred to the infants whose birth weight below the 10th percentile of the corresponding gestational age, which affects about 10% of all newborns [ 1 , 2 ]. SGA infants are at increased risk of adverse perinatal outcomes, poor development and prone to long-term sequelae [ 2 ]. Various etiologies can cause SGA, such as maternal medical and nutritional conditions, genetic and structural disorders and infections [ 3 ]. Refeeding syndrome (RS) is a complex of electrolyte changes following administration of enteral nutrition (EN) and/or parenteral nutrition (PN) after a period of malnutrition or starvation, resulting in one or several of the followings: hypophosphatemia, hypomagnesemia and hypokalemia. In addition, RS can also cause dysfunctions of multiple organs and increase the risk of premature death [ 4 , 5 ]. However, the detection rate and diagnosis rate of RS are low due to the poor awareness of RS for clinicians and a proportion of RS characterized by modest to mild electrolyte imbalance without unique clinical symptoms. Due to SGA infants may be in a state of malnutrition for a long time in the uterus, the risks of RS and acute metabolic disorder syndrome will be high after re-intake of nutrients during the perinatal period. A previous case reported an SGA infant suffered from severe hypokalemia, hypomagnesemia and hypophosphatemia (symptoms of RS) and thrombocytopenia after total PN [ 6 ]. However, few studies have studied the RS in SGA infants, which led to the lack of knowledge on incidence and risk factors of RS and long-term and short-term outcomes of RS in SGA infants [ 6 , 7 ]. This study aimed to compressively assess the incidence, risk factors and short-term outcomes of RS in SGA infants based on a large sample in order to help clinicians identify RS and provide timely interventions for SGA infants with high-risk RS early in clinical practice. Materials and Methods Study design and patients This prospective cohort study enrolled hospitalized SGA infants who received EN and/or PN within 24h upon admission at the Children's Hospital of Zhejiang University, School of Medicine from January 2019 to June 2024. The exclusion criteria were as follows: 1) severe diarrhea; 2) severe congenital metabolic disorders (e.g., hyperinsulinism, phenylketonuria); 3) severe congenital malformations (e.g., gastrointestinal anomalies, complex congenital heart disease); 4) incomplete clinical data for analyses (Fig. 1 ). EN and/or PN were administered according to the standardized criteria to maintain adequate fluids, electrolytes, and nutritional intake until achieving adequate feeding, which was defined as a daily intake of ≥ 120 mL/kg and ≥ 80 kcal/kg, and nutrition prescriptions were monitored daily by a physician [ 2 , 8 , 9 ]. Written informed consent was obtained from all guardians, and the study was approved by the Medical Ethics Committee of the Children's Hospital of Zhejiang University, School of Medicine (Approval Number: 2022-IRB-161). Clinical investigation had been conducted according to the principles in the Declaration of Helsinki. SGA: small for gestational age; RS: refeeding syndrome. Data collection Demographic, clinical and laboratory data of each enrolled infant and maternal information were obtained from the electronic medical records system via standardized criteria, including age, gender, birth weight, fetal age, full-term infant, serum potassium, sodium, phosphorus, magnesium, calcium, albumin, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), creatinine, blood urea nitrogen, oxygen inhalation, neonatal pneumonia, neonatal sepsis, neonatal hyperbilirubinemia, neonatal hypoglycemia, patent ductus arteriosus (PDA), retinopathy of prematurity (ROP), hypoxic-ischemic encephalopathy (HIE), respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and death, and maternal information: maternal age, gestational hypertension, gestational diabetes, twin pregnancy, cesarean section, assisted reproductive technology (ART)‌, premature rupture of membrane and cord around neck. Definition and diagnosis SGA infants were defined as​​ the infants whose birth weight below the 10th percentile of the corresponding gestational age [ 2 ]. RS was defined according to the ASPEN criteria and as a decrease of ≥ 10% in at least one of phosphorus, potassium and magnesium level during the first five days of EN and/or PN [ 10 ]. The decrease of phosphorus, potassium and magnesium was calculated as the difference between the baseline value (initial measurement before nutrition support) and the lowest value of the above three electrolytes during the first 5 days of EN and/or PN. In case of a single value of the above three electrolytes during the hospitalization, this was compared to the lab lower normal value (norms potassium level: 3.5-5 mmol/L; phosphorus level: 1.3–1.9 mmol/L; and magnesium level: 0.75–1.1 mmol/L) [ 10 , 11 ]. The definition of thrombocytopenia was the platelet count < 150 × 10⁹/L during the hospitalization [ 1 ]. The definition of full-term infant was the fetal age ≥ 37 weeks [ 12 ]. Statistical analysis SGA infants were dichotomized into the RS and non-RS group. Clinical characteristics were summarized by computing the median (interquartile range), and differences between two groups were tested by the t-test or Mann-Whitney U-test if they were continuous variables. Categorical variables were summarized by proportion (n, %); and differences between two groups were tested by the chi-square test or Fisher's exact test when appropriate. For early detecting RS, binary logistic regression analyses were performed to explore the risk factors with assessing odds ratios (ORs) and 95% confidence intervals (CIs), which were obtained within 24h upon admission at the hospital and with a p-value of < 0.10 in the univariate analyses (i.e., age, birth weight, full-term infant, potassium at baseline, albumin, AST, ALP, creatinine, oxygen inhalation and premature rupture of membrane) and adjusted for gender and other covariates with a p-value of 10 and all VIFs of the above risk factors and covariates were less than 5. For exploring the associations between RS and short-term outcomes in SGA infants, binary logistic regression analyses were performed to explore the associations between RS and short-term outcomes with a p-value of < 0.10 in the univariate analyses (i.e., neonatal sepsis and thrombocytopenia) and adjusted for gender and covariates with a p-value of < 0.10 in the univariate analyses (i.e., age, birth weight, full-term infant, potassium at baseline, albumin, AST, ALP, creatinine, oxygen inhalation and premature rupture of membrane). Collinearity did not exist for all VIFs of the above covariates were less than 5. Due to the limited cases of ROP and BPD in our study, they were excluded from further evaluation. All comparisons were two-sided, with statistical significance defined as P < 0.05. Analyses were calculated using SPSS version 26.0 (IBM, Armonk, New York) Results ​ Clinical characteristics of SGA infants 359 SGA infants were finally included in the study, comprising 175 (48.70%) males and 184 (51.30%) females; 247 (68.80%) full-term infants and 112 (31.20%) preterm infants. Table 1 showed the detail information of clinical characteristics for 359 SGA infants. The mean age was 5.00 (1.00–11.00) days, the mean birth weight was 2280.00 (1820.00-2600.00) g, and the mean fetal age was 37.71 (36.14–39.14) weeks. The birth weight of 190 (52.90%) infants was between 10% and 3%, and 169 (47.10%) infants were below 3% birth weight. The incidence of RS was 203 (56.50%), suggesting a high incidence of RS in SGA infants. Regarding maternal information, the mean maternal age was 30.00 (28.00–33.00) years, and 60 (16.70%) and 39 (10.90%) pregnant women had gestational hypertension and gestational diabetes, respectively. In addition, 30 (8.40%) women underwent ART and 217 (60.40%) underwent cesarean section. Table 1 Baseline clinical characteristics of SGA infants Overall (n = 359) Age (days) 5.00 (1.00–11.00) Fetal age (weeks) 37.71 (36.14–39.14) Female (n, %) 184 (51.30) Birth weight (g) 2280.00 (1820.00-2600.00) Birth weight < 3% (n, %) 169 (47.10) Full-term infant (n, %) 247 (68.80) Potassium at baseline (mmol/L) 4.30 (4.00-4.70) Phosphorus at baseline (mmol/L) 2.18 (1.86–2.54) Magnesium at baseline (mmol/L) 0.85 (0.78–0.95) Calcium at baseline (mmol/L) 2.35 (2.16–2.48) Albumin (g/L) 34.10 (30.80–36.30) ALT (U/L) 12.00 (8.00–16.00) AST (U/L) 40.00 (30.00–56.00) ALP (U/L) 205.00 (162.00-266.00) GGT (U/L) 133.00 (83.00-194.00) Creatinine (umol/L) 40.00 (28.00–63.00) Blood urea nitrogen (mmol/L) 3.37 (2.29–4.42) RS (n, %) 203 (56.50) Oxygen inhalation (n, %) 121 (33.90) PDA (n, %) 76 (21.20) ROP (n, %) 6 (1.70) HIE (n, %) 6 (1.70) RDS (n, %) 22 (6.10) BPD (n, %) 9 (2.50) Neonatal sepsis (n, %) 27 (7.50) Thrombocytopenia (n, %) 104 (29.00) Neonatal hypoglycemia (n, %) 33 (9.20) Neonatal pneumonia (n, %) 56 (15.60) Neonatal hyperbilirubinemia (n, %) 145 (40.40) Death (n, %) 28 (7.80) Maternal age (years) 30.00 (28.00–33.00) Gestational hypertension (n, %) 60 (16.70) Gestational diabetes (n, %) 39 (10.90) ART (n, %) 30 (8.40) Twin pregnancy (n, %) 40 (11.00) Cesarean section (n, %) 217 (60.40) Premature rupture of membrane (n, %) 48 (13.40) Cord around neck (n, %) 56 (15.60) SGA: small for gestational age; ALT: alanine aminotransferase; AST: aspartate transaminase; ALP: alkaline phosphatase; GGT: γ-glutamyl transferase; RS: refeeding syndrome; PDA: patent ductus arteriosus; ROP: retinopathy of prematurity; HIE: hypoxic-ischemic encephalopathy; RDS: respiratory distress syndrome; BPD: bronchopulmonary dysplasia; ART: assisted reproductive technology. Independent risk factors for RS​ Baseline characteristics of RS vs non-RS infants were presented in Table 2 . Compared to non-RS SGA infants, those SGA infants with RS had younger age [3.00 (0.00–8.00) vs 7.50 (3.00–14.00) days, P < 0.001] and lower birth weight [2250.00 (1650.00-2550.00) vs 2300.00 (1953.00-2600.00) g, P = 0.001]. SGA infants with RS were less likely to be full-term infants [130(64.00%) vs 117(75.00%), P = 0.029], and more likely to undergo oxygen inhalation [83 (40.90%) vs 38 (24.40%), P = 0.001], ROP [6 (3.00%) vs 0 (0.00%), P = 0.030], BPD [9 (4.40) vs 0 (0.00%), P = 0.008], neonatal sepsis [23 (11.30%) vs 4 (2.60%), P = 0.002], thrombocytopenia [72 (35.50%) vs 32 (20.50%), P = 0.002] and premature rupture of membrane [35 (17.20%) vs 13 (8.30%), P = 0.014]. In addition, SGA infants with RS had higher potassium level at baseline [4.50 (4.00-4.90) vs 4.20 (4.00-4.50) mmol/L, P < 0.001], higher creatinine level [47.00 (30.00–70.00) vs 34.00 (25.00-49.75) umol/L, P < 0.001] and higher AST level [42.00 (30.00–59.00) vs 39.00 (29.00–52.00) U/L, P = 0.026], and lower albumin level [33.20 (29.90–36.00) vs 35.00 (32.30-36.68) g/L, P < 0.001]. Table 2 Comparisons of RS vs non-RS in SGA infants RS (n = 203) non-RS (n = 156) P Age (day) 3.00 (0.00–8.00) 7.50 (3.00–14.00) <0.001 Fetal age (weeks) 37.57 (35.29–39.29) 38.00 (36.90–39.00) 0.138 Female (n, %) 106 (52.20) 78 (50.00) 0.677 Birth weight (g) 2250.00 (1650.00-2550.00) 2300.00 (1953.00-2600.00) 0.001 Birth weight<3% (n, %) 100 (49.30) 69 (44.20) 0.344 Full-term infant (n, %) 130(64.00) 117(75.00) 0.029 Potassium at baseline (mmol/L) 4.50 (4.00-4.90) 4.20 (4.00-4.50) <0.001 Phosphorus at baseline (mmol/L) 2.15 (1.82–2.58) 2.22 (1.97–2.50) 0.494 Magnesium at baseline (mmol/L) 0.85 (0.77–0.95) 0.86 (0.79–0.95) 0.359 Calcium at baseline(mmol/L) 2.35 (2.16–2.49) 2.36 (2.17–2.47) 0.830 Albumin (g/L) 33.20 (29.90–36.00) 35.00 (32.30-36.68) <0.001 ALT (U/L) 11.00 (7.00–16.00) 12.50 (9.00–16.00) 0.521 AST (U/L) 42.00 (30.00–59.00) 39.00 (29.00–52.00) 0.026 ALP (U/L) 202.00 (156.00-268.00) 217.50 (170.00-264.50) 0.094 GGT (U/L) 127.00 (78.00-189.00) 139.50 (89.00-195.75) 0.769 Creatinine (umol/L) 47.00 (30.00–70.00) 34.00 (25.00-49.75) <0.001 Blood urea nitrogen (mmol/L) 3.61 (2.39–4.66) 3.17 (2.26–4.05) 0.685 Oxygen inhalation (n, %) 83 (40.90) 38 (24.40) 0.001 PDA (n, %) 49 (24.10) 27 (17.30) 0.116 ROP (n, %) 6 (3.00) 0 (0.00) 0.030 HIE (n, %) 5 (2.50) 1 (0.60) 0.182 RDS (n, %) 16 (7.90) 6 (3.80) 0.114 BPD (n, %) 9 (4.40) 0 (0.00) 0.008 Neonatal sepsis (n, %) 23 (11.30) 4 (2.60) 0.002 Thrombocytopenia (n, %) 72 (35.50) 32 (20.50) 0.002 Neonatal hypoglycemia (n, %) 21 (10.30) 12 (7.70) 0.389 Neonatal pneumonia (n, %) 32 (15.80) 21 (15.40) 0.922 Neonatal hyperbilirubinemia (n, %) 86 (42.40) 59 (37.80) 0.384 Death (n, %) 13 (6.40) 15 (9.60) 0.261 Maternal age (year) 31.00 (28.00–34.00) 30.00 (27.00–33.00) 0.226 Gestational hypertension (n, %) 36 (17.70) 24 (15.40) 0.554 Gestational diabetes (n, %) 23 (11.30) 16 (10.30) 0.746 ART (n, %) 16 (7.90) 14 (9.00) 0.711 Twin pregnancy (n, %) 26 (12.80) 14 (9.00) 0.253 Cesarean section (n, %) 129 (63.50) 88 (56.40) 0.170 Premature rupture of membrane (n, %) 35 (17.20) 13 (8.30) 0.014 Cord around neck (n, %) 33 (16.30) 23 (14.70) 0.695 RS: refeeding syndrome; SGA: small for gestational age; ALT: alanine aminotransferase; AST: aspartate transaminase; ALP: alkaline phosphatase; GGT: γ-glutamyl transferase; PDA: patent ductus arteriosus; ROP: retinopathy of prematurity; HIE: hypoxic-ischemic encephalopathy; RDS: respiratory distress syndrome; BPD: bronchopulmonary dysplasia; ART: assisted reproductive technology. Binary logistic regression analyses revealed that high potassium level at baseline (adjusted OR = 4.842, 95%CI: 2.947 to 7.955, P < 0.001) and premature rupture of membrane (adjusted OR = 3.292, 95%CI: 1.459 to 7.429, P = 0.004) were the independent risk factors for RS in SGA infants, and older age (adjusted OR = 0.910, 95%CI: 0.859 to 0.963, P = 0.001) and higher albumin level (adjusted OR = 0.891, 95%CI: 0.821 to 0.966, P = 0.005) were the protective factors for RS (Table 3 ). Table 3 Independent risk factors for RS in SGA infants Unadjusted Adjusted OR (95%CI) P OR (95%CI) P Potassium at baseline 4.622 (2.857, 7.476) <0.001 4.842 (2.947, 7.955) <0.001 Age 0.909 (0.861, 0.959) <0.001 0.910 (0.859, 0.963) 0.001 Premature rupture of membrane 3.245 (1.461, 7.206) 0.004 3.292 (1.459, 7.429) 0.004 Albumin 0.872 (0.806, 0.943) 0.001 0.891 (0.821, 0.966) 0.005 Creatinine 1.020 (1.010, 1.029) <0.001 1.012 (0.997, 1.027) 0.123 Oxygen inhalation 1.601 (0.878, 2.918) 0.125 1.487 (0.803, 2.754) 0.207 AST 1.008 (1.001, 1.015) 0.031 1.003 (0.993, 1.012) 0.580 Full-term infant 0.594 (0.374, 0.942) 0.027 1.239 (0.526, 2.917) 0.624 ALP 0.998 (0.996, 1.000) 0.100 1.000 (0.997, 1.003) 0.872 Birth weight 1.000 (0.999, 1.001) 0.755 1.000 (0.999, 1.001) 0.943 Adjusted for gender, ROP, BPD, neonatal sepsis and thrombocytopenia. RS: refeeding syndrome; SGA: small for gestational age; OR: odds ratio; CI: confidence interval; AST: aspartate transaminase; ALP: alkaline phosphatase; ROP: retinopathy of prematurity, BPD: bronchopulmonary dysplasia. Associations between RS and short-term outcomes in SGA infants​ There were four short-term outcomes (ROP, BPD, neonatal sepsis and thrombocytopenia) with a p-value of < 0.10 in the univariate analyses (Table 1 ). However, due to limited cases of ROP and BPD in our study, they were excluded from further evaluation. Binary logistic regression analyses indicated that RS was the independent risk factors for neonatal sepsis (adjusted OR = 3.672, 95%CI: 1.193 to 11.301, P = 0.023) and thrombocytopenia (adjusted OR = 1.921, 95%CI: 1.023 to 3.606, P = 0.042) (Table 4 ). Table 4 Associations between RS and short-term outcomes in SGA infants Unadjusted Adjusted OR (95%CI) P OR (95%CI) P Neonatal sepsis 4.856 (1.643, 14.348) 0.004 3.672 (1.193, 11.301) 0.023 Thrombocytopenia 2.130 (1.313, 3.454) 0.002 1.921 (1.023, 3.606) 0.042 Adjusted for age, gender, birth weight, full-term infant, potassium at baseline, albumin, AST, ALP, creatinine, oxygen inhalation and premature rupture of membrane. RS: refeeding syndrome; SGA: small for gestational age; OR: odds ratio; CI: confidence interval; AST: aspartate transaminase; ALP: alkaline phosphatase. Discussion In this prospective cohort study, we found there was a high RS incidence (56.50%) in SGA infants. After comprehensive assessments of the risk factors for RS, we found high potassium level at baseline and premature rupture of membrane were the independent risk factors for RS, and older age of SGA infants and higher albumin level were the protective factors for RS in SGA infants. In addition, we also found RS was the independent risk factor for neonatal sepsis and thrombocytopenia. These findings were of great clinical importance and suggested RS screening should be performed for SGA infants in routine clinical practice, especially for SGA infants with high potassium level at admission and/or premature rupture of membrane. When RS occurred in SGA infants, it was necessary to timely monitor and intervene in neonatal sepsis and thrombocytopenia. Due to few studies have investigated RS in SGA infants, the incidence and risk factors of RS and the complications of RS are largely unknown. After comprehensive assessment of RS risk factors in our study, we found high potassium level at baseline and premature rupture of membrane were the risk factors for RS in SGA infants. Previous studies also reported the strongest predictor of severe RS was the pre-feeding serum electrolyte level, which was consistent with our results [ 13 ]. Potassium is vital for cell membrane potential and activity. The increased anabolism secondary to reintroduction of EN and PN results in increased potassium uptake by cells as they increase in size, number, and activity, leading to hypokalemia if potassium intake is inadequate. Therefore, the absence of potassium will contribute to organ dysfunction, such as muscular dysfunction [ 4 , 14 ]. The potential explanation of the seemingly counterintuitive finding for high potassium level at baseline being the risk factors may be the magnitude of decrease in potassium levels is limited when the levels are already very low at the beginning, therefore, SGA infants with high potassium level at baseline have a high probability for potassium drop to meet the RS criteria (a decrease of ≥ 10% in potassium) [ 10 ]. One of the major functions of fetal membrane is to protect the fetus during its growth and development in utero [ 15 , 16 ]. Premature rupture of membrane are often associated with intraamniotic infection and growth restriction [ 17 ]. Growth restriction could contribute to the increased anabolism when reintroduced nutrition and intraamniotic infection could lead to increased immune cells activation and nutrient digestion, both of which could enhance the risk of RS and the consumptions of electrolytes, such as phosphorus and potassium, as phosphorus is required for adenosine triphosphate energy storage, oxygen delivery in tissues, acid-base buffering, and the activation of many enzymes and second messengers, and potassium is essential for cell electrochemical membrane potential and activity [ 4 , 14 ]. In addition, we noticed that previous studies reported lower fetal age and birth weight were the risk factors for RS, however, binary logistic regression analyses in our study demonstrated no associations between lower fetal age and birth weight with RS in SGA infants [ 18 , 19 ]. The differences between our findings and previous studies may be due to the differences in sample sizes and clinical characteristics, however, which needed further examinations. In addition, our study demonstrated RS was the independent risk factors for neonatal sepsis and thrombocytopenia, which were consistent with the previous conclusions [ 20 ]. The potential interpretations for the associations between RS with neonatal sepsis and thrombocytopenia may be the energy failure. The depletion of electrolytes in RS would lead to the deficiency of adenosine triphosphate and inhibition of cell viability, however, the active immune responses and the production of platelet from megakaryocyte are reliant on adenosine triphosphate energy. In the case of electrolytes depletion, phagocytes are unable to undergo an immune response, which would leave the affected infant more vulnerable to sepsis and may lead to immune thrombocytopenia [ 21 , 22 ]. Several limitations of this study should be acknowledged. First, some inherent and potential bias of the observational study should be considered, such as residual confounding, reverse causation, selection bias and recall bias for several covariates and self-reported variables. Second, the small amount of the study sample size and the study population located in a specific region limited the generalizability of the conclusions. Third, the explorations of associations between RS with ROP and BPD were excluded for the limited cases of ROP and BPD in our study, therefore, studies with large sample size containing more ROP and BPD cases were need for further examination. Forth, we only explored the short-term outcomes of RS in SGA due to the lack of data on follow-up, future studies are needed to comprehensively detect the long-term outcomes of RS for further improving the corresponding knowledge. Fifth, the individuals in the study were SGA infants, which limited the extrapolation of the results; therefore, additional investigations are needed to extrapolate the results to other infants with different clinical characteristics and ethnic groups. Conclusions There was a high RS incidence (56.50%) in SGA infants. High potassium level at baseline and premature rupture of membrane were the independent risk factors for RS, and older age of SGA infants and higher albumin level were the protective factors for RS in SGA infants. In addition, RS was the independent risk factors for neonatal sepsis and thrombocytopenia. These findings suggested RS screening should be performed in routine clinical practice for all SGA infants, and timely monitoring and intervening in neonatal sepsis and thrombocytopenia in SGA infants with RS. Declarations Conflicts of Interest The authors declare no conflicts of interest. Funding This research received no funding. Author Contribution Study concept and design: LL Dai; Acquisition of data: LL Dai, L Hu, Z Lin, YY Bao and LH Tan; Analysis and interpretation of data: LL Dai and Z Lin; Drafting of the manuscript: LL Dai, L Hu and YY Bao; Critical revision of the manuscript for important intellectual content: LL Dai and LH Tan. Acknowledgments We gratefully acknowledge the commitment and dedication of the participants for this study. Data Availability Data and materials used to conduct the research are available from the corresponding author by reasonable request. References Takeshita S, Kakita H, Asai S, Asai T, Mori M, Ueda H, Aoki H, Aoyama M, Yamada Y. Thrombocytopenia and insufficient thrombopoietin production in human small-for-gestational-age infants. Pediatr Res. 2023;93:619–24. 10.1038/s41390-022-02107-7 . Saenger P, Czernichow P, Hughes I, Reiter EO. Small for gestational age: short stature and beyond. Endocr Rev. 2007;28:219–51. 10.1210/er.2006-0039 . Fetal Growth Restriction. 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Abrams SA, Hawthorne KM, Pammi M. A systematic review of controlled trials of lower-protein or energy-containing infant formulas for use by healthy full-term infants. Adv Nutr. 2015;6:178–88. 10.3945/an.114.006379 . Adika E, Jia R, Li J, Seres D, Freedberg DE. Evaluation of the ASPEN guidelines for refeeding syndrome among hospitalized patients receiving enteral nutrition: A retrospective cohort study. JPEN J Parenter Enter Nutr. 2022;46:1859–66. 10.1002/jpen.2368 . Knochel JP. The pathophysiology and clinical characteristics of severe hypophosphatemia. Arch Intern Med. 1977;137:203–20. Menon R, Richardson LS. Preterm prelabor rupture of the membranes: A disease of the fetal membranes. Semin Perinatol. 2017;41:409–19. 10.1053/j.semperi.2017.07.012 . Xu L, Yang T, Wen M, Wen D, Jin C, An M, Wang L, Liu Y, Fan J. Frontiers in the Etiology and Treatment of Preterm Premature Rupture of Membrane: From Molecular Mechanisms to Innovative Therapeutic Strategies. Reprod Sci. 2024;31:917–31. 10.1007/s43032-023-01411-9 . Freeman SW, Denoble A, Kuller JA, Ellestad S, Dotters-Katz S. Management of Preterm Premature Rupture of Membranes in the Late Preterm Period. Obstet Gynecol Surv. 2022;77:283–92. 10.1097/OGX.0000000000001024 . Al-Mouqdad MM, Alshaikh B, Sumaily HH, Almotiri AA, Alodhaidan NA, AlMahmoud L, Abdelrahim A, Yousif TE, Alghamdi AS, Albarrak YA, et al. Impact of Refeeding Syndrome on the Short-Term Clinical Outcomes of Very-Premature Infants. Nutrients. 2024;16. 10.3390/nu16203445 . Igarashi A, Okuno T, Ohta G, Tokuriki S, Ohshima Y. Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants. Dis Markers 2017, 2017 , 9748031. 10.1155/2017/9748031 Wright TB, Bloomfield FH, Alexander T, Cormack BE. Association between early phosphate intake and refeeding syndrome in extremely low-birth-weight infants: A retrospective cohort study. JPEN J Parenter Enter Nutr. 2025;49:460–7. 10.1002/jpen.2739 . Bloomfield FH, Jiang Y, Harding JE, Crowther CA, Cormack BE, Pro VTG. Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years. N Engl J Med. 2022;387:1661–72. 10.1056/NEJMoa2204886 . Mahevas M, Gerfaud-Valentin M, Moulis G, Terriou L, Audia S, Guenin S, Le Guenno G, Salles G, Lambotte O, Limal N, et al. Characteristics, outcome, and response to therapy of multirefractory chronic immune thrombocytopenia. Blood. 2016;128:1625–30. 10.1182/blood-2016-03-704734 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7899679","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":545434122,"identity":"6c584a29-40d5-4670-b070-72c7718351aa","order_by":0,"name":"Lingling Dai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYDCCA4yNBx4YSMgBWUAeG3FaGg4kFFgYk6IFiBI+VCQ2gHnEaOE7fhhoi4FE+vzGMwYMH8oOM/DPbsCvRfJMIlhLbmPDGQPGGecOM0jcOYBfi8EBqJZmhjMGzLxthxkMJBIIaDn/EOIwNpCWv0RpuQGxJYEHpIWRGC2SNyC2GM5gOFZwsOdcOo/EDQJa+M6nP3zw4U+dvPyMwxsf/CizluOfQUALAkgcAEcmD7HqgYC/gQTFo2AUjIJRMKIAAJ9oTDP/l8MSAAAAAElFTkSuQmCC","orcid":"","institution":"Zhejiang University School of Medicine, National Clinical Research Center for Child Health","correspondingAuthor":true,"prefix":"","firstName":"Lingling","middleName":"","lastName":"Dai","suffix":""},{"id":545434123,"identity":"88c39cbe-3ea1-40d9-bbc5-54f4846909d8","order_by":1,"name":"Lei Hu","email":"","orcid":"","institution":"Zhejiang University School of Medicine, National Clinical Research Center for Child Health","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Hu","suffix":""},{"id":545434124,"identity":"83a230e8-e345-4acc-9832-e64d40f3cdb7","order_by":2,"name":"Zhe Lin","email":"","orcid":"","institution":"Children’s Hospital, Zhejiang university School of Medicine, National Clinical Research Center for Child Health","correspondingAuthor":false,"prefix":"","firstName":"Zhe","middleName":"","lastName":"Lin","suffix":""},{"id":545434125,"identity":"6e94e5ba-c8a6-4bb4-b3db-64bbdb08c34c","order_by":3,"name":"Yiyao Bao","email":"","orcid":"","institution":"Zhejiang University School of Medicine, National Clinical Research Center for Child Health","correspondingAuthor":false,"prefix":"","firstName":"Yiyao","middleName":"","lastName":"Bao","suffix":""},{"id":545434126,"identity":"5d6c4406-b02d-4e12-88c4-91e6a3811db2","order_by":4,"name":"Linhua Tan","email":"","orcid":"","institution":"Zhejiang University School of Medicine, National Clinical Research 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10:11:19","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":106025,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7899679/v1/4149c12f265e5c642c933233.html"},{"id":96330380,"identity":"d36dbbb1-8091-41d8-a275-789a9bc58091","added_by":"auto","created_at":"2025-11-20 00:49:01","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":77913,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of study participants enrollment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSGA: small for gestational age; RS: refeeding syndrome.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7899679/v1/2c864003921399bf86af85b4.jpeg"},{"id":100654847,"identity":"c63331e2-c746-476f-976e-5423db3eaded","added_by":"auto","created_at":"2026-01-20 07:25:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":891492,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7899679/v1/3b3202ef-0011-4a98-8e4c-30170fc10fd4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comprehensive assessments of incidence, risk factors and short-term outcomes of refeeding syndrome in small-for-gestational-age infants","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSmall-for-gestational-age (SGA) infants are referred to the infants whose birth weight below the 10th percentile of the corresponding gestational age, which affects about 10% of all newborns [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. SGA infants are at increased risk of adverse perinatal outcomes, poor development and prone to long-term sequelae [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Various etiologies can cause SGA, such as maternal medical and nutritional conditions, genetic and structural disorders and infections [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRefeeding syndrome (RS) is a complex of electrolyte changes following administration of enteral nutrition (EN) and/or parenteral nutrition (PN) after a period of malnutrition or starvation, resulting in one or several of the followings: hypophosphatemia, hypomagnesemia and hypokalemia. In addition, RS can also cause dysfunctions of multiple organs and increase the risk of premature death [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, the detection rate and diagnosis rate of RS are low due to the poor awareness of RS for clinicians and a proportion of RS characterized by modest to mild electrolyte imbalance without unique clinical symptoms.\u003c/p\u003e\u003cp\u003eDue to SGA infants may be in a state of malnutrition for a long time in the uterus, the risks of RS and acute metabolic disorder syndrome will be high after re-intake of nutrients during the perinatal period. A previous case reported an SGA infant suffered from severe hypokalemia, hypomagnesemia and hypophosphatemia (symptoms of RS) and thrombocytopenia after total PN [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, few studies have studied the RS in SGA infants, which led to the lack of knowledge on incidence and risk factors of RS and long-term and short-term outcomes of RS in SGA infants [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This study aimed to compressively assess the incidence, risk factors and short-term outcomes of RS in SGA infants based on a large sample in order to help clinicians identify RS and provide timely interventions for SGA infants with high-risk RS early in clinical practice.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and patients\u003c/h2\u003e\u003cp\u003eThis prospective cohort study enrolled hospitalized SGA infants who received EN and/or PN within 24h upon admission at the Children's Hospital of Zhejiang University, School of Medicine from January 2019 to June 2024. The exclusion criteria were as follows: 1) severe diarrhea; 2) severe congenital metabolic disorders (e.g., hyperinsulinism, phenylketonuria); 3) severe congenital malformations (e.g., gastrointestinal anomalies, complex congenital heart disease); 4) incomplete clinical data for analyses (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). EN and/or PN were administered according to the standardized criteria to maintain adequate fluids, electrolytes, and nutritional intake until achieving adequate feeding, which was defined as a daily intake of \u0026ge;\u0026thinsp;120 mL/kg and \u0026ge;\u0026thinsp;80 kcal/kg, and nutrition prescriptions were monitored daily by a physician [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Written informed consent was obtained from all guardians, and the study was approved by the Medical Ethics Committee of the Children's Hospital of Zhejiang University, School of Medicine (Approval Number: 2022-IRB-161). Clinical investigation had been conducted according to the principles in the Declaration of Helsinki.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSGA: small for gestational age; RS: refeeding syndrome.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eDemographic, clinical and laboratory data of each enrolled infant and maternal information were obtained from the electronic medical records system via standardized criteria, including age, gender, birth weight, fetal age, full-term infant, serum potassium, sodium, phosphorus, magnesium, calcium, albumin, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), creatinine, blood urea nitrogen, oxygen inhalation, neonatal pneumonia, neonatal sepsis, neonatal hyperbilirubinemia, neonatal hypoglycemia, patent ductus arteriosus (PDA), retinopathy of prematurity (ROP), hypoxic-ischemic encephalopathy (HIE), respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and death, and maternal information: maternal age, gestational hypertension, gestational diabetes, twin pregnancy, cesarean section, assisted reproductive technology (ART)\u0026zwnj;, premature rupture of membrane and cord around neck.\u003c/p\u003e\n\u003ch3\u003eDefinition and diagnosis\u003c/h3\u003e\n\u003cp\u003eSGA infants were defined as​​ the infants whose birth weight below the 10th percentile of the corresponding gestational age [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRS was defined according to the ASPEN criteria and as a decrease of \u0026ge;\u0026thinsp;10% in at least one of phosphorus, potassium and magnesium level during the first five days of EN and/or PN [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The decrease of phosphorus, potassium and magnesium was calculated as the difference between the baseline value (initial measurement before nutrition support) and the lowest value of the above three electrolytes during the first 5 days of EN and/or PN. In case of a single value of the above three electrolytes during the hospitalization, this was compared to the lab lower normal value (norms potassium level: 3.5-5 mmol/L; phosphorus level: 1.3\u0026ndash;1.9 mmol/L; and magnesium level: 0.75\u0026ndash;1.1 mmol/L) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe definition of thrombocytopenia was the platelet count\u0026thinsp;\u0026lt;\u0026thinsp;150 \u0026times; 10⁹/L during the hospitalization [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe definition of full-term infant was the fetal age\u0026thinsp;\u0026ge;\u0026thinsp;37 weeks [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eSGA infants were dichotomized into the RS and non-RS group. Clinical characteristics were summarized by computing the median (interquartile range), and differences between two groups were tested by the t-test or Mann-Whitney U-test if they were continuous variables. Categorical variables were summarized by proportion (n, %); and differences between two groups were tested by the chi-square test or Fisher's exact test when appropriate.\u003c/p\u003e\u003cp\u003eFor early detecting RS, binary logistic regression analyses were performed to explore the risk factors with assessing odds ratios (ORs) and 95% confidence intervals (CIs), which were obtained within 24h upon admission at the hospital and with a p-value of \u0026lt;\u0026thinsp;0.10 in the univariate analyses (i.e., age, birth weight, full-term infant, potassium at baseline, albumin, AST, ALP, creatinine, oxygen inhalation and premature rupture of membrane) and adjusted for gender and other covariates with a p-value of \u0026lt;\u0026thinsp;0.10 in the univariate analyses (i.e., ROP, BPD, neonatal sepsis and thrombocytopenia). Collinearity was identified by variance inflation factor (VIF)\u0026thinsp;\u0026gt;\u0026thinsp;10 and all VIFs of the above risk factors and covariates were less than 5.\u003c/p\u003e\u003cp\u003eFor exploring the associations between RS and short-term outcomes in SGA infants, binary logistic regression analyses were performed to explore the associations between RS and short-term outcomes with a p-value of \u0026lt;\u0026thinsp;0.10 in the univariate analyses (i.e., neonatal sepsis and thrombocytopenia) and adjusted for gender and covariates with a p-value of \u0026lt;\u0026thinsp;0.10 in the univariate analyses (i.e., age, birth weight, full-term infant, potassium at baseline, albumin, AST, ALP, creatinine, oxygen inhalation and premature rupture of membrane). Collinearity did not exist for all VIFs of the above covariates were less than 5. Due to the limited cases of ROP and BPD in our study, they were excluded from further evaluation. All comparisons were two-sided, with statistical significance defined as P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were calculated using SPSS version 26.0 (IBM, Armonk, New York)\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e​\u003cb\u003eClinical characteristics of SGA infants\u003c/b\u003e\u003c/p\u003e\u003cp\u003e359 SGA infants were finally included in the study, comprising 175 (48.70%) males and 184 (51.30%) females; 247 (68.80%) full-term infants and 112 (31.20%) preterm infants. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e showed the detail information of clinical characteristics for 359 SGA infants. The mean age was 5.00 (1.00\u0026ndash;11.00) days, the mean birth weight was 2280.00 (1820.00-2600.00) g, and the mean fetal age was 37.71 (36.14\u0026ndash;39.14) weeks. The birth weight of 190 (52.90%) infants was between 10% and 3%, and 169 (47.10%) infants were below 3% birth weight. The incidence of RS was 203 (56.50%), suggesting a high incidence of RS in SGA infants.\u003c/p\u003e\u003cp\u003eRegarding maternal information, the mean maternal age was 30.00 (28.00\u0026ndash;33.00) years, and 60 (16.70%) and 39 (10.90%) pregnant women had gestational hypertension and gestational diabetes, respectively. In addition, 30 (8.40%) women underwent ART and 217 (60.40%) underwent cesarean section.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline clinical characteristics of SGA infants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;359)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.00 (1.00\u0026ndash;11.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFetal age (weeks)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37.71 (36.14\u0026ndash;39.14)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e184 (51.30)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight (g)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2280.00 (1820.00-2600.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight\u0026thinsp;\u0026lt;\u0026thinsp;3% (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e169 (47.10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFull-term infant (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e247 (68.80)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePotassium at baseline (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.30 (4.00-4.70)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhosphorus at baseline (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.18 (1.86\u0026ndash;2.54)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium at baseline (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.85 (0.78\u0026ndash;0.95)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium at baseline (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.35 (2.16\u0026ndash;2.48)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34.10 (30.80\u0026ndash;36.30)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12.00 (8.00\u0026ndash;16.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e40.00 (30.00\u0026ndash;56.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALP (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e205.00 (162.00-266.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGGT (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e133.00 (83.00-194.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine (umol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e40.00 (28.00\u0026ndash;63.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood urea nitrogen (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.37 (2.29\u0026ndash;4.42)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRS (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e203 (56.50)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOxygen inhalation (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e121 (33.90)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePDA (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e76 (21.20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eROP (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (1.70)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIE (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (1.70)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRDS (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (6.10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBPD (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (2.50)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal sepsis (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27 (7.50)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThrombocytopenia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e104 (29.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal hypoglycemia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33 (9.20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal pneumonia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e56 (15.60)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal hyperbilirubinemia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e145 (40.40)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeath (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28 (7.80)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaternal age (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30.00 (28.00\u0026ndash;33.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational hypertension (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60 (16.70)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational diabetes (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e39 (10.90)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eART (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30 (8.40)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTwin pregnancy (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e40 (11.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCesarean section (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e217 (60.40)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePremature rupture of membrane (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e48 (13.40)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCord around neck (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e56 (15.60)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSGA: small for gestational age; ALT: alanine aminotransferase; AST: aspartate transaminase; ALP: alkaline phosphatase; GGT: γ-glutamyl transferase; RS: refeeding syndrome; PDA: patent ductus arteriosus; ROP: retinopathy of prematurity; HIE: hypoxic-ischemic encephalopathy; RDS: respiratory distress syndrome; BPD: bronchopulmonary dysplasia; ART: assisted reproductive technology.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eIndependent risk factors for RS​\u003c/h2\u003e\u003cp\u003eBaseline characteristics of RS vs non-RS infants were presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Compared to non-RS SGA infants, those SGA infants with RS had younger age [3.00 (0.00\u0026ndash;8.00) vs 7.50 (3.00\u0026ndash;14.00) days, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] and lower birth weight [2250.00 (1650.00-2550.00) vs 2300.00 (1953.00-2600.00) g, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001]. SGA infants with RS were less likely to be full-term infants [130(64.00%) vs 117(75.00%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029], and more likely to undergo oxygen inhalation [83 (40.90%) vs 38 (24.40%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001], ROP [6 (3.00%) vs 0 (0.00%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030], BPD [9 (4.40) vs 0 (0.00%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008], neonatal sepsis [23 (11.30%) vs 4 (2.60%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002], thrombocytopenia [72 (35.50%) vs 32 (20.50%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002] and premature rupture of membrane [35 (17.20%) vs 13 (8.30%), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014]. In addition, SGA infants with RS had higher potassium level at baseline [4.50 (4.00-4.90) vs 4.20 (4.00-4.50) mmol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], higher creatinine level [47.00 (30.00\u0026ndash;70.00) vs 34.00 (25.00-49.75) umol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] and higher AST level [42.00 (30.00\u0026ndash;59.00) vs 39.00 (29.00\u0026ndash;52.00) U/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026], and lower albumin level [33.20 (29.90\u0026ndash;36.00) vs 35.00 (32.30-36.68) g/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparisons of RS vs non-RS in SGA infants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRS (n\u0026thinsp;=\u0026thinsp;203)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enon-RS (n\u0026thinsp;=\u0026thinsp;156)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.00 (0.00\u0026ndash;8.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.50 (3.00\u0026ndash;14.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFetal age (weeks)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37.57 (35.29\u0026ndash;39.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38.00 (36.90\u0026ndash;39.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.138\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e106 (52.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e78 (50.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.677\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight (g)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2250.00 (1650.00-2550.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2300.00 (1953.00-2600.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight\u0026lt;3% (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e100 (49.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e69 (44.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.344\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFull-term infant (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e130(64.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e117(75.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePotassium at baseline (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.50 (4.00-4.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.20 (4.00-4.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhosphorus at baseline (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.15 (1.82\u0026ndash;2.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.22 (1.97\u0026ndash;2.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.494\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium at baseline (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.85 (0.77\u0026ndash;0.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.86 (0.79\u0026ndash;0.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.359\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium at baseline(mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.35 (2.16\u0026ndash;2.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.36 (2.17\u0026ndash;2.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.830\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33.20 (29.90\u0026ndash;36.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e35.00 (32.30-36.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11.00 (7.00\u0026ndash;16.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12.50 (9.00\u0026ndash;16.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.521\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e42.00 (30.00\u0026ndash;59.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e39.00 (29.00\u0026ndash;52.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.026\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALP (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e202.00 (156.00-268.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e217.50 (170.00-264.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGGT (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e127.00 (78.00-189.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e139.50 (89.00-195.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.769\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine (umol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e47.00 (30.00\u0026ndash;70.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34.00 (25.00-49.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood urea nitrogen (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.61 (2.39\u0026ndash;4.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.17 (2.26\u0026ndash;4.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.685\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOxygen inhalation (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e83 (40.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38 (24.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePDA (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e49 (24.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (17.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.116\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eROP (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (3.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIE (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (2.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.182\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRDS (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (7.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (3.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.114\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBPD (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (4.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal sepsis (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (11.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (2.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThrombocytopenia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e72 (35.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32 (20.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal hypoglycemia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (10.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12 (7.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.389\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal pneumonia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e32 (15.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21 (15.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.922\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal hyperbilirubinemia (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e86 (42.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e59 (37.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.384\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeath (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13 (6.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15 (9.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.261\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaternal age (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e31.00 (28.00\u0026ndash;34.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30.00 (27.00\u0026ndash;33.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.226\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational hypertension (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e36 (17.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24 (15.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.554\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational diabetes (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (11.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16 (10.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.746\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eART (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (7.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (9.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.711\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTwin pregnancy (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e26 (12.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (9.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.253\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCesarean section (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e129 (63.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e88 (56.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePremature rupture of membrane (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35 (17.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13 (8.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCord around neck (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33 (16.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23 (14.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.695\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRS: refeeding syndrome; SGA: small for gestational age; ALT: alanine aminotransferase; AST: aspartate transaminase; ALP: alkaline phosphatase; GGT: γ-glutamyl transferase; PDA: patent ductus arteriosus; ROP: retinopathy of prematurity; HIE: hypoxic-ischemic encephalopathy; RDS: respiratory distress syndrome; BPD: bronchopulmonary dysplasia; ART: assisted reproductive technology.\u003c/p\u003e\u003cp\u003eBinary logistic regression analyses revealed that high potassium level at baseline (adjusted OR\u0026thinsp;=\u0026thinsp;4.842, 95%CI: 2.947 to 7.955, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and premature rupture of membrane (adjusted OR\u0026thinsp;=\u0026thinsp;3.292, 95%CI: 1.459 to 7.429, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) were the independent risk factors for RS in SGA infants, and older age (adjusted OR\u0026thinsp;=\u0026thinsp;0.910, 95%CI: 0.859 to 0.963, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and higher albumin level (adjusted OR\u0026thinsp;=\u0026thinsp;0.891, 95%CI: 0.821 to 0.966, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) were the protective factors for RS (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eIndependent risk factors for RS in SGA infants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnadjusted\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAdjusted\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePotassium at baseline\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.622 (2.857, 7.476)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.842 (2.947, 7.955)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.909 (0.861, 0.959)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.910 (0.859, 0.963)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePremature rupture of membrane\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.245 (1.461, 7.206)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.292 (1.459, 7.429)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAlbumin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.872 (0.806, 0.943)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.891 (0.821, 0.966)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCreatinine\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.020 (1.010, 1.029)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.012 (0.997, 1.027)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOxygen inhalation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.601 (0.878, 2.918)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.125\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.487 (0.803, 2.754)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.207\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAST\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.008 (1.001, 1.015)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.003 (0.993, 1.012)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.580\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFull-term infant\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.594 (0.374, 0.942)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.239 (0.526, 2.917)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.624\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eALP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.998 (0.996, 1.000)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000 (0.997, 1.003)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.872\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBirth weight\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.000 (0.999, 1.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.755\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000 (0.999, 1.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.943\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAdjusted for gender, ROP, BPD, neonatal sepsis and thrombocytopenia.\u003c/p\u003e\u003cp\u003eRS: refeeding syndrome; SGA: small for gestational age; OR: odds ratio; CI: confidence interval; AST: aspartate transaminase; ALP: alkaline phosphatase; ROP: retinopathy of prematurity, BPD: bronchopulmonary dysplasia.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAssociations between RS and short-term outcomes in SGA infants​\u003c/h3\u003e\n\u003cp\u003eThere were four short-term outcomes (ROP, BPD, neonatal sepsis and thrombocytopenia) with a p-value of \u0026lt;\u0026thinsp;0.10 in the univariate analyses (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). However, due to limited cases of ROP and BPD in our study, they were excluded from further evaluation. Binary logistic regression analyses indicated that RS was the independent risk factors for neonatal sepsis (adjusted OR\u0026thinsp;=\u0026thinsp;3.672, 95%CI: 1.193 to 11.301, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023) and thrombocytopenia (adjusted OR\u0026thinsp;=\u0026thinsp;1.921, 95%CI: 1.023 to 3.606, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociations between RS and short-term outcomes in SGA infants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnadjusted\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAdjusted\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNeonatal sepsis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.856 (1.643, 14.348)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.672 (1.193, 11.301)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.023\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eThrombocytopenia\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.130 (1.313, 3.454)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.921 (1.023, 3.606)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAdjusted for age, gender, birth weight, full-term infant, potassium at baseline, albumin, AST, ALP, creatinine, oxygen inhalation and premature rupture of membrane.\u003c/p\u003e\u003cp\u003eRS: refeeding syndrome; SGA: small for gestational age; OR: odds ratio; CI: confidence interval; AST: aspartate transaminase; ALP: alkaline phosphatase.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this prospective cohort study, we found there was a high RS incidence (56.50%) in SGA infants. After comprehensive assessments of the risk factors for RS, we found high potassium level at baseline and premature rupture of membrane were the independent risk factors for RS, and older age of SGA infants and higher albumin level were the protective factors for RS in SGA infants. In addition, we also found RS was the independent risk factor for neonatal sepsis and thrombocytopenia. These findings were of great clinical importance and suggested RS screening should be performed for SGA infants in routine clinical practice, especially for SGA infants with high potassium level at admission and/or premature rupture of membrane. When RS occurred in SGA infants, it was necessary to timely monitor and intervene in neonatal sepsis and thrombocytopenia.\u003c/p\u003e\u003cp\u003eDue to few studies have investigated RS in SGA infants, the incidence and risk factors of RS and the complications of RS are largely unknown. After comprehensive assessment of RS risk factors in our study, we found high potassium level at baseline and premature rupture of membrane were the risk factors for RS in SGA infants. Previous studies also reported the strongest predictor of severe RS was the pre-feeding serum electrolyte level, which was consistent with our results [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Potassium is vital for cell membrane potential and activity. The increased anabolism secondary to reintroduction of EN and PN results in increased potassium uptake by cells as they increase in size, number, and activity, leading to hypokalemia if potassium intake is inadequate. Therefore, the absence of potassium will contribute to organ dysfunction, such as muscular dysfunction [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The potential explanation of the seemingly counterintuitive finding for high potassium level at baseline being the risk factors may be the magnitude of decrease in potassium levels is limited when the levels are already very low at the beginning, therefore, SGA infants with high potassium level at baseline have a high probability for potassium drop to meet the RS criteria (a decrease of \u0026ge;\u0026thinsp;10% in potassium) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. One of the major functions of fetal membrane is to protect the fetus during its growth and development in utero [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Premature rupture of membrane are often associated with intraamniotic infection and growth restriction [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Growth restriction could contribute to the increased anabolism when reintroduced nutrition and intraamniotic infection could lead to increased immune cells activation and nutrient digestion, both of which could enhance the risk of RS and the consumptions of electrolytes, such as phosphorus and potassium, as phosphorus is required for adenosine triphosphate energy storage, oxygen delivery in tissues, acid-base buffering, and the activation of many enzymes and second messengers, and potassium is essential for cell electrochemical membrane potential and activity [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn addition, we noticed that previous studies reported lower fetal age and birth weight were the risk factors for RS, however, binary logistic regression analyses in our study demonstrated no associations between lower fetal age and birth weight with RS in SGA infants [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The differences between our findings and previous studies may be due to the differences in sample sizes and clinical characteristics, however, which needed further examinations.\u003c/p\u003e\u003cp\u003eIn addition, our study demonstrated RS was the independent risk factors for neonatal sepsis and thrombocytopenia, which were consistent with the previous conclusions [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The potential interpretations for the associations between RS with neonatal sepsis and thrombocytopenia may be the energy failure. The depletion of electrolytes in RS would lead to the deficiency of adenosine triphosphate and inhibition of cell viability, however, the active immune responses and the production of platelet from megakaryocyte are reliant on adenosine triphosphate energy. In the case of electrolytes depletion, phagocytes are unable to undergo an immune response, which would leave the affected infant more vulnerable to sepsis and may lead to immune thrombocytopenia [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSeveral limitations of this study should be acknowledged. First, some inherent and potential bias of the observational study should be considered, such as residual confounding, reverse causation, selection bias and recall bias for several covariates and self-reported variables. Second, the small amount of the study sample size and the study population located in a specific region limited the generalizability of the conclusions. Third, the explorations of associations between RS with ROP and BPD were excluded for the limited cases of ROP and BPD in our study, therefore, studies with large sample size containing more ROP and BPD cases were need for further examination. Forth, we only explored the short-term outcomes of RS in SGA due to the lack of data on follow-up, future studies are needed to comprehensively detect the long-term outcomes of RS for further improving the corresponding knowledge. Fifth, the individuals in the study were SGA infants, which limited the extrapolation of the results; therefore, additional investigations are needed to extrapolate the results to other infants with different clinical characteristics and ethnic groups.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThere was a high RS incidence (56.50%) in SGA infants. High potassium level at baseline and premature rupture of membrane were the independent risk factors for RS, and older age of SGA infants and higher albumin level were the protective factors for RS in SGA infants. In addition, RS was the independent risk factors for neonatal sepsis and thrombocytopenia. These findings suggested RS screening should be performed in routine clinical practice for all SGA infants, and timely monitoring and intervening in neonatal sepsis and thrombocytopenia in SGA infants with RS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflicts of Interest\u003c/h2\u003e\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis research received no funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eStudy concept and design: LL Dai; Acquisition of data: LL Dai, L Hu, Z Lin, YY Bao and LH Tan; Analysis and interpretation of data: LL Dai and Z Lin; Drafting of the manuscript: LL Dai, L Hu and YY Bao; Critical revision of the manuscript for important intellectual content: LL Dai and LH Tan.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e\u003cp\u003eWe gratefully acknowledge the commitment and dedication of the participants for this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData and materials used to conduct the research are available from the corresponding author by reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTakeshita S, Kakita H, Asai S, Asai T, Mori M, Ueda H, Aoki H, Aoyama M, Yamada Y. 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Blood. 2016;128:1625\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood-2016-03-704734\u003c/span\u003e\u003cspan address=\"10.1182/blood-2016-03-704734\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Small-for-gestational-age, Refeeding syndrome, High potassium level at baseline, Premature rupture of membrane, Neonatal sepsis, Thrombocytopenia.","lastPublishedDoi":"10.21203/rs.3.rs-7899679/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7899679/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eFew studies have studied the refeeding syndrome (RS) in small-for-gestational-age SGA infants, which led to the lack of knowledge in this field. This study aimed to compressively assess the incidence, risk factors and short-term outcomes of RS in SGA infants in order to improve clinical managements of SGA infants.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis prospective cohort study enrolled hospitalized SGA infants who received enteral nutrition (EN) and/or parenteral nutrition (PN) within 24h upon admission and with complete clinical data from January 2019 to June 2024. RS was defined according to the ASPEN criteria and as a decrease of \u0026ge;\u0026thinsp;10% in at least one of phosphorus, potassium and magnesium level during the first five days of EN and/or PN. Binary logistic regression analyses were performed to explore the independent risk factors of RS and associations between RS and short-term outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003e359 SGA infants were finally included in the study, comprising 175 (48.70%) males and 184 (51.30%) females. The incidence of RS was 203 (56.50%) in SGA infants. Binary logistic regression analyses revealed that high potassium level at baseline (adjusted odds ratio (OR)\u0026thinsp;=\u0026thinsp;4.842, 95% confidence interval (CI): 2.947 to 7.955, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and premature rupture of membrane (adjusted OR\u0026thinsp;=\u0026thinsp;3.292, 95%CI: 1.459 to 7.429, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) were the independent risk factors for RS; older age (adjusted OR\u0026thinsp;=\u0026thinsp;0.910, 95%CI: 0.859 to 0.963, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and higher albumin level (adjusted OR\u0026thinsp;=\u0026thinsp;0.891, 95%CI: 0.821 to 0.966, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) were the protective factors, and RS was the independent risk factors for neonatal sepsis (adjusted OR\u0026thinsp;=\u0026thinsp;3.672, 95%CI: 1.193 to 11.301, P\u0026thinsp;=\u0026thinsp;0.023) and thrombocytopenia (adjusted OR\u0026thinsp;=\u0026thinsp;1.921, 95%CI: 1.023 to 3.606, P\u0026thinsp;=\u0026thinsp;0.042).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThere was a high RS incidence in SGA infants. High potassium level at baseline and premature rupture of membrane were the independent risk factors for RS, and RS was the independent risk factors for neonatal sepsis and thrombocytopenia. These findings suggested RS screening should be performed in routine clinical practice for all SGA infants, and timely monitoring and intervening in neonatal sepsis and thrombocytopenia in SGA infants with RS.\u003c/p\u003e","manuscriptTitle":"Comprehensive assessments of incidence, risk factors and short-term outcomes of refeeding syndrome in small-for-gestational-age infants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-20 00:48:57","doi":"10.21203/rs.3.rs-7899679/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"02e1f7ca-4c88-4080-b2f1-49d6b49c7428","owner":[],"postedDate":"November 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T07:39:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-20 00:48:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7899679","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7899679","identity":"rs-7899679","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}