Kidney health and blood pressure after very preterm birth. A cohort study at school age

Kidney health and blood pressure after very preterm birth. 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A cohort study at school age Juliette Delbreil, Valérie Leroy, Simon Lorrain, Marie Trigolet, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7636338/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Background Very preterm infants (VPI, < 32 weeks of gestation) are at increased risk of chronic kidney disease and hypertension in later life, and biological abnormalities of kidney function may precede clinically apparent disease. We evaluated kidney function and blood pressure (BP) at school age in VPI and explored their association with perinatal and postnatal factors, including neonatal nutrition and growth. Methods VPI included since birth in a cohort to evaluate kidney function were followed-up at 4–6 years. Standardized assessments included anthropometry, BP, cystatin-C, urea, plasma and urinary creatinine and electrolytes, and urinary albumin-to-creatinine ratio. Biological kidney abnormalities were defined as one among: estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m², macroalbuminuria, or microalbuminuria. Results In total, 69 children (mean age 5.1 ± 0.3 years) attended follow-up and 39 (56.5%) had at least one biological kidney abnormality: eGFR < 90 mL/min/1.73 m² (33.8%), macroalbuminuria (1.4%), or microalbuminuria (26.1%). Hight systolic and diastolic pressure (dBP) occurred in 10.1% and 8.7% of children, respectively. Any neonatal variable, including nutritional intakes, was associated with biological kidney abnormalities. High dBP was significantly associated with lower birth weight, lower birth weight Z-score, higher weight Z-score at 36 weeks post-conception, and higher BMI at follow-up, and the association remained significant after adjustment for gestational age. Conclusions Biological kidney abnormalities and elevated BP are frequent in ex-VPI at school age. The association between high dBP and rapid early catch-up growth underscores the need to monitor growth trajectories as part of early renal and cardiovascular risk assessment in this population. Very preterm infants follow-up in childhood chronic kidney disease hypertension Figures Figure 1 Introduction Thanks to improvements in neonatal care, the survival of very premature infants (VPI), born before 32 weeks of gestational age (GA), has risen sharply over the last decades, in parallel with the decreasing rate of severe comorbidities in surviving preemies [ 1 ]. Recent studies have shown that prematurity and very low birth weight (VLBW, birth weight less than 1500 g) are associated with a 2 to 3 times higher risk of developing chronic kidney disease (CKD) at young adulthood [ 2 – 5 ]. The pathogenesis of the renal consequences of very preterm birth can be explained by both the antenatal alteration in kidney development, that leads to a poor nephron endowment at birth, and the exposure to several neonatal factors that may contribute to worsen the congenital nephron deficit [ 6 ]. Nephrogenesis ends at around 36th weeks of gestation, thus preterm birth interrupts this process. Moreover, in case of preterm birth, whatever the GA, nephrogenesis ceases by the end of the first 40 days of life, leading to a lower nephron number compared to full term birth [ 7 ]. According to the Brenner’s hypothesis [ 8 ], low birth weight infants can be exposed to compensatory glomerular hyperfiltration, an adaptive mechanism inducing nephron hypertrophy, which in turn may lead to glomerulosclerosis. Moreover, in preterm-born children, the risk for glomerulosclerosis may also be due to “kidney-independent” mechanisms, such as vascular remodeling, which can impact vascular resistance and blood pressure (BP) [ 9 ]. The trajectory leading from low nephron number to progression towards CKD may be clinically silent over many years, and it can be preceded by mild biological alterations of kidney function. Thus, the “Low Birth and Nephron Number Working Group” has underlined the need of regular monitoring of preterm and low birth weight individuals throughout life [ 4 ]. Another point of matter is that this trajectory is a heterogeneous - not mandatory - process, which can be modulated by the occurrence of acute kidney injury (AKI) and other morbidities in the neonatal intensive care unit (NICU) [ 10 – 12 ], as also by environmental postnatal factors [ 13 , 14 ], not completely elucidated. In particular, the effect of early postnatal nutrition on long-term kidney function in preterm infants remains a controversial topic. Experimental findings from animal studies suggest that both under- and overnutrition may alter long-term kidney function. Very few clinical studies explored the association between early protein or nutrient intake and mean- or long-term kidney function in ex-preterm human babies, with contrasting results [ 14 ]. Thus, the main objective of this study was to describe the prevalence of abnormal markers of kidney function in a cohort of former VPI, who had been followed during their first month of life regarding the evolution of renal function in the NICU [ 15 ], and who underwent systematic screening of kidney function at 4 to 6 years of life. Secondary objectives were to explore potential associations of both biological markers of kidney function and blood pressure values at school age with various perinatal factors, including neonatal nutritional intakes and postnatal growth. Materials and methods Setting We performed a longitudinal follow-up of VPI enrolled in the PROTIPREMA study [15], which had explored the relationship of the urine protein-to-creatinine ratio (Upr/Cr) during the first month of life with several perinatal variables and morbidities. In Reunion Island University Hospital, all preterm infants born before 32 weeks of gestation undergo a systematic follow-up consultation between 4 to 6 years, and assessment of kidney function is conducted as part of their routine medical monitoring. Study population All infants included in the PROTIPREMA study and discharged alive form the NICU were invited to participate to the present investigation. These infants were born during the period from March 2018 to February 2020. Patients were excluded if they met any of the following conditions: lost to follow-up, parental refusal for the use of their child’s medical data. The follow-up consultations were performed during the period from September 2023 to September 2024. The study visit was performed by the pediatrician in charge of VPI follow-up. In case of abnormal biological findings of kidney function or systolic and/or diastolic hypertension, infants were referred to the pediatric nephrologist or cardiologist for further examination and management. Data collection The following perinatal and neonatal data were collected: GA, birth weight, sex, mode of delivery, APGAR score at 1 and 5 minutes and neonatal morbidities. These included: severe birth asphyxia, acute anemia at birth, respiratory distress syndrome (RDS) requiring surfactant administration, sepsis, hemodynamically significant patent ductus arteriosus (HsPDA) requiring treatment, bronchopulmonary dysplasia (BPD), cerebral ultrasound abnormalities such as intraventricular hemorrhage (IHV) or periventricular leukomalacia (PVL), and AKI. Information regarding exposure to potential nephrotoxic agents, such as aminoglycosides and nonsteroidal anti-inflammatory drugs (NSAIDs), was also documented. All nutritional data were collected, focusing on protein and caloric intakes, and postnatal growth during hospitalization. At the follow-up consultation, anthropometric measures were recorded, including weight, height, and head circumference at 6, 12, 18, and 24 months, as well as weight and height at the time of the consultation. Information on past medical history was gathered, particularly regarding urinary tract infections and the use of nephrotoxic drugs (NSAIDs or aminoglycosides) beyond the discharge from the NICU. Data on breastfeeding were also collected, specifying whether the child was breastfed and, if so, the duration of breastfeeding (more or less than 6 month). BP was taken as following: systolic and diastolic BP was measured three times in seated children after a 5-min rest. The width of the cuff was 2/3 the arm’s length. The device used to measure BP was the EDAN IM3 vital signs monitor. Systolic and diastolic BP (sBP and dBP) analyzed was the mean of the three measures of BP. Blood pressure percentiles were calculated using the calculator of the Baylor college of medicine (https://www.bcm.edu/bodycomplab/BPappZjs/BPvAgeAPPz.html) according to Flynn’s et al. guidelines for managing hypertension [16]. Kidney function was assessed through plasma creatinine measurement, cystatin-C, urea, electrolyte measures, and venous blood gas. Glomerular filtration rate (GFR) was estimated using the Schwartz CKiD formula [17]. Urinary analysis was performed to evaluate proteinuria and microalbuminuria, urine creatinine and electrolytes. Outcome measures The primary objective of this study was to describe biological abnormalities of kidney function at school age. The main outcome of interest was defined by the presence of one among the following: An estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73m², calculated using the Schwartz CKiD formula (17,18); Microalbuminuria greater than 2 mg/mmol [19]; Macroalbuminuria with an albumin-to-creatinine ratio above 20 mg/mmol [18]. The secondary outcomes were the proportion of infants with systolic and/or diastolic hypertension (respectively sBP and/or dBP >= 95 th percentile, according to Flynn et al [16], and the description of perinatal and neonatal factors associated with biological kidney abnormalities or with high BP at school age. Ethics approval Data collection was in compliance with French regulation for clinical studies ( Loi Jardé ) and the principles of the Declaration of Helsinki. Parental consent for the use of infant clinical data collected at school age was obtained. This study was approved by the Institutional Research Ethics Committee (CER-BDX 2025-72) and the project was declared on Health Data Hub (reference N°F20231120123113). Statistical analysis Results were presented using frequencies and proportions for discrete variables, and mean and standard deviations (SD) or median and interquartile range for continuous variables. In a first bivariate analysis, we described variables associated with biological abnormalities of kidney function or with systolic and/or diastolic hypertension at school age. In a second analysis we performed a regression model to obtain variables associated with diastolic hypertension. Comparisons of categorical variables were made with the χ2 test or with the Fisher's exact test. Comparisons of continuous variables were made with Wilcoxon–Mann–Whitney or ANOVA. A p-value below 0.05 was considered significant. Statistical analysis was conducted using SAS® software (Version 9.4, SAS Institute, North Carolina, United States). Results Sixty-nine children were examined at the school age follow-up, and represented our study population. Among the 162 VPI included in the PROTIPREMA study (15), 15 died before hospital discharge, 67 were lost to follow-up, and 11 were excluded due to lack of parental consent. A flow-chart of the study population is presented in Fig. 1 . All the included infants had at least one visit by the pediatrician in charge of VPI follow-up, with a blood and urinary test performed the day of the clinical exam. Neonatal characteristics of the children included in the follow-up study are presented in Table 1 . Children were born at (mean ± SD) 29.1 ± 1.9 weeks of gestation, with a birth weight of 1158 ± 326 g. Only one newborn had AKI during hospital stay in the NICU, and kidney function recovered before discharge at home. Age at the follow-up visit was at mean 5.1 ± 0.3 years. Anthropometric measures at the follow-up exam, growth data and medical history between the discharge from the NICU and the study consultation are shown in Table 2 . No infant had experienced AKI during the timeframe from discharge to follow-up visit. In total, 39 children (56.5%) presented with at least one biological abnormality of kidney function. Among them, 23 (33.8%) had an eGFR below 90 mL/min/1.73m², 1 (1.4%) had macroalbuminuria and 18 (26.1%) had pathological microalbuminuria. Seven children (10.1%) had a sBP ≥ 95th percentile and 6 (8.7%) a dBP ≥ 95th percentile. These data are presented in Table 3 . Both pathological eGFR and systolic or diastolic hypertension were confirmed at the consultation with the paediatric nephrologist or cardiologist. In the children with macroalbuminuria, this was not detected at repeated urine analysis, and a persistent microalbuminuria over two urine samples was observed only in 1 patient over 18. Other data of kidney function and electrolyte analyses are shown in Table 4 . At the bivariate analyses, there was no statistically significant association between eGFR below 90 mL/min/1.73 m 2 , macroalbuminuria, microalbuminuria, or systolic hypertension and any of the neonatal variables, including nutritional intakes or postnatal growth data (data not shown). At the bivariate analysis, the following variables were significantly associated with diastolic hypertension at school age: birth weight, birth weight Z-score, delta Z-score birth-36wks post-conception age (PCA), BMI Z-score at school age. These associations remained significant after adjustment for GA (Table 5 ). Table 1 Neonatal characteristics and morbidities in the NICU of 69 preterm infants born less than 32 weeks of gestation Study population n = 69 Neonatal characteristics Gestational age (weeks), mean (± SD) 29.1 (± 1.9) Birth weight (g), mean (± SD) 1158.7 (± 326.8) Small for gestational age*, n (%) 7 (10) Male sex, n (%) 35 (51) Medical history Severe birth asphyxia, n (%) 1 (1.4) Vaginal way of delivery, n (%) 48 (69) RDS requiring surfactant, n (%) 41 (59) Treated hypotension, n (%) 16 (23) HsPDA, n (%) 19 (28) Early or Late Onset Sepsis, n (%) 10 (14) AKI**, n (%) 1 (1.4) IVH (any stage), n (%) 17 (24) PVL, n (%) 2 (4.6) BPD at 36 weeks of GA, n (%) 8 (12) Drug exposure during the first month of life Exposure to vancomycin, n (%) Duration of treatment in exposed infants (days), mean (± SD) 14 (20) 11.1 (± 8.4) Exposure to Gentamycin, n (%) Duration of treatment in exposed infants (days), mean (± SD) 48 (69) 2.5 (± 1.2) Exposure to Ibuprofen, n (%) Duration of treatment in exposed infants (days), mean (± SD) 18 (26) 1.9 (± 0.9) Nutritional intakes in first weeks of life Daily amino acid intake during the 2 first weeks of life (g/kg), mean (± SD) 3.35 (± 0.37) Daily amino acid intake from week 3 to 6 of life (g/kg), mean (± SD) 2.87 (± 0.51) Daily caloric intake during the 2 first weeks of life (Kcal/kg), mean (± SD) 105 (± 9.3) Daily caloric intake from week 3 to 6 of life (Kcal/kg), mean (± SD) 125 (± 26.9) Acronyms: AKI, acute kidney injury; BPD, bronchopulmonary dysplasia; GA, gestational age; HsPDA, hemodynamically significant patent ductus arteriosus; IVH, intraventricular hemorrhage; PVL periventricular leukomalacia. RDS, respiratory distress syndrome; SD, standard deviation; * defined according to AUDIPOG ( https://www.audipog.net ); ** defined as absolute serum creatinine > 130 µmol/L after the third day of life. Table 2 Anthropometric measures, growth data and medical history after the NICU discharge Study population n = 69 Anthropometric measures Age at follow-up (years), mean (± SD) 5.1 (± 0.3) Weight at follow-up (kg), mean (± SD) 17.9 (± 2.9) Height at follow up (cm), mean (± SD) 108.3 (± 4.7) BMI Z-score at the follow-up exam, mean (± SD) -0,37 (± 1,29) Growth data Delta Z-score 36wks PCA-6months, mean (± SD) 0.62 (± 1.28) Delta Z-score 36wks PCA-12months, mean (± SD) 0.70 (± 1.17) Delta Z-score 36wks PCA-24months, mean (± SD) 0.74 (± 1.24) Delta Z-score 36wks PCA-follow-up exam, mean (± SD) 0.50 (± 1.20) Breastfeeding after discharge, n (%) Any 18 (26.1) Yes, < 6 months 28 (40.6) Yes, ≥ 6 months 23 (33.3) Medical history after NICU discharge Urinary tract infection, n (%) 7 (10.1) Acute renal failure, n (%) 0 (0) Ultrasound kidney abnormalities, n (%) 1 (1.4) Exposure to nephrotoxic drug (NSAIDs or aminoglycosides), n (%) 3 (4.3) Exposure to diuretics, n (%) 0 (0) Hospitalization in the PICU, n (%) 7 (10.1) Viral infection (EBV, CMV), n (%) 2 (2.9) Acronyms: BMI, body mass index; CMV, cytomegalovirus postnatal infection, EBV, Epstein-Barr virus; NSAIDs, nonsteroidal anti-inflammatory drugs; PCA, postconceptional age; PICU, pediatric intensive care unit; SD, standard deviation; wks, weeks. Table 3 Abnormal kidney findings, systolic and diastolic hypertension at follow-up visit (school age) Study population n = 69 Abnormal kidney findings, n (%) eGFR* below 90 mL/min/1.73m² 23 (33.3) Macroalbuminuria** 1 (1.4) Microalbuminuria*** 18 (26.1) Systolic blood pressure ≥ p95% at-follow-up visit 7 (10.1) Diastolic blood pressure ≥ p95% at-follow-up visit 6 (8.7) * eGFR using Schwartz CKiD formula with Cystatine C ** Macroalbuminuria, defined as an albumin-to-creatinine ratio above 20 mg/mmol, *** Microalbuminuria greater than 2 mg/mmol. Blood pressure percentiles determined according to Flynn et al [ 16 ]. Table 4 Kidney function, electrolytic blood and urinary analyses at follow-up visit (school age) Study population n = 69 Biological markers, mean (± SD) [min; max] Plasma creatinine concentration (µmol/L) 35.7 (± 10.7) [4.6; 92.0] Plasmatic Cystatine C concentration (mg/L) 0.9 (± 0.1) [0.6; 1.1] eGFR with Schwartz CKiD formula, using Cystatine C (ml/min/1.73m 2 ) 96.8 (± 14.9) [51.7; 130.1] eGFR with Schwartz formula without Cystatine C (ml/min/1.73m 2 ) 114.2 (± 24.2) [43.0; 171.0] Plasma pH 7.4 (± 0.0) [7.3; 7.5] Plasma bicarbonates (mmol/L) 23.2 (± 1.9) [19.5; 27.3] Plasma urea concentration (mmol/L) 4.32 (± 1.08) [2.0; 6.8] Plasma protein concentration (g/L) 66.3 (± 5.0) [32.0; 74.0] Plasma sodium concentration (mmol/L) 138.0 (± 1.8) [133.0; 143.0] Plasma potassium concentration (mmol/L) 3.4 (± 0.24) [3.4; 4.8] Urinary protein to creatinine ratio (mg/mmol) 20.7 (± 17.3) [8.5; 133.4] Urinary creatinine (mmol/L) 7.7 (± 3.7) [2.1; 20.7] Urinary sodium concentration (mmol/L) 146.4 (± 70.0) [26.0; 298.0] Acronyms: CKiD, chronic kidney disease; eGFR, estimated glomerular filtration rate; SD, standard deviation. Table 5 Perinatal and postnatal variables associated with diastolic blood pressure at school age dBP < p95 n = 63 dBP ≥ p95 n = 6 p p adjusted for GA Perinatal and postnatal variables GA (weeks), mean (± SD) 29.2 (± 1.8) 28.4 (± 1.7) 0.35 Birth weight (g), mean (± SD) 1184 (± 323) 892 (± 245) 0.04 0.04 Male sex, n (%) 31 (± 49) 3 (± 50) 0.60 RDS requiring surfactant, n (%) 40 (± 63) 4 (± 67) 0.80 Treated hypotension, n (%) 18 (± 28) 0 (± 0) 0.32 HsPDA, n (%) 20 (± 32) 0 (± 0) 0.24 AKI, n (%) 43 (± 68) 0 (± 0) 0.81 IVH (any stage), n (%) 17 (± 27) 2 (± 33) 0.87 BPD at 36 weeks of GA, n (%) 9 (± 14) 0 (± 0) 0.75 Vancomycin (days of treatment), mean (± SD) 2.4 (± 6) 4.3 (± 7.7) 0.45 Gentamycin (days of treatment), mean (± SD) 1.9 (± 1.5) 2 (± 1.8) 0.76 IBU (days of treatment), mean (± SD) 0.54 (± 0.98) 0 (± 0) 0.14 Birth weight Z-score, mean (± SD) − 0.30 (± 0.96) − 1.19 (± 0.88) 0.03 0.03 Weight Z-score at 36 weeks of PCA, mean (± SD) − 0.94 (± 0.81) − 0.94 (± 1.24) 0.98 Weight Delta Z-score 36wks PCA-birth, mean (± SD) − 0.62 (± 0.78) 0.24 (± 1.02) 0.01 0.03 Weight Delta Z-score 36wks PCA-6months, mean (± SD) 0.63 (± 1.20) 0.53 (± 2.06) 0.86 Weight Delta Z-score 36wks PCA-12months, mean (± SD) 0.74 (± 1.13) 0.30 (± 1.58) 0.39 Weight Delta Z-score 36wks PCA-24months, mean (± SD) 0.77 (± 1.20) 0.43 (± 1.66) 0.53 Weight Delta Z-score 36wks PCA-follow-up, mean (± SD) 0.43 (± 1.17) 1.31 (± 1.20) 0.08 BMI Z-score at follow-up, mean (± SD) − 0.49 (± 1.21) 0.90 (± 1.51) 0.01 0.02 Total caloric intake in NICU (Kcal/kg), mean (± SD) 4926 (± 824) 5383 (± 392) 0.08 Total amino acid intake in NICU (g/kg), mean (± SD) 126 (± 21) 140 (± 7) 0.06 Total sodium intake in NICU (mmol/kg), mean (± SD) 118 (± 29) 134 (± 13) 0.07 Total potassium intake in NICU (mmol/kg), mean (± SD) 88 (± 18) 96 (± 11) 0.11 Acronyms: AKI, acute kidney injury; BPD, bronchopulmonary dysplasia; BMI, body mass index; GA, gestational age; HsPDA, hemodynamically significant patent ductus arteriosus; IBU, Ibuprofen; IVH, intraventricular hemorrhage; NICU, neonatal intensive care unit; PCA, postconceptional age; RSD, respiratory distress syndrome; SD, standard deviation; wks, weeks. Discussion This study reported the prevalence of abnormal findings of kidney function and high blood pressure in a cohort of VPI followed-up at school age, and their relationship with several neonatal and postnatal factors. Our results showed that in childhood, more than 50% of children born very preterm presented with at least one biological abnormality of kidney function, according to some criteria used in the literature [ 18 , 19 ], and almost 20% had high systolic or diastolic blood pressure. These findings are particularly noteworthy, given that none of the children in the cohort had abnormal renal function at the end of the neonatal period or experienced AKI before the school age follow-up. A majority of the studies that have investigated the short-term consequences of preterm birth on kidney health addressed the impact of neonatal AKI on kidney outcome during early childhood [ 20 – 23 ]. These studies reported several degrees of abnormal kidney function, ranging from mild impairment to end-stage renal failure in extremely low birth weight (ELBW), VLBW infants or VPI aged from 3 to 7.5 years, who had experienced neonatal AKI. Actually, even in absence of neonatal AKI, it seems very important to find early and subtle changes in kidney function in infants born very preterm. First, this helps providing primary information about the risk of CKD in later life, and thus intensifying the kidney follow-up by a pediatric nephrologist in at-risk children. Second, short-term investigations allow to recognize the impact on impaired outcome of neonatal and postnatal factors, that can be prevented or modulated by clinical intervention. Our findings on biological kidney abnormalities are consistent with those of previous studies. In a cohort of 66 preterm infants born at less than 33 weeks of gestation and aged 2 to 4 years, Ojala et al. [ 24 ] found an abnormal eGFR (< 89 ml/min/1.73 m 2 ) in two infants (3%), and kidney abnormalities at ultrasound in ten infants (15%). In a previous cohort study of 48 VLBW infants followed up at 6.3 to 8.2 years of age, we reported an 8.3% rate of pathological microalbuminuria (ACR > 20 mg/g) [ 25 ]. In a representative, longitudinal cohort of infants born at 27–31 weeks of gestation, Vieux et al. [ 26 ] described high albuminuria (urine albumin level > 17.7 mg/g urine creatinine) in 14% of five-year-old children. Despite concordant conclusions, these data underline that follow-up protocols of kidney function are not very standardized in VPI, and biomarkers used to detect early signs of kidney disease are very heterogenous across studies. Moreover, in our study, as in that of Vieux et al. [ 26 ] micro- and macroalbuminuria levels were fluctuating a lot in the same children over time, and this questions the validity of these markers in the follow-up of renal function in VPI. In contrast with previous investigations [ 24 – 26 ], we did not find any significant association between reduced eGFR, microalbuminuria, or macroalbuminuria and perinatal factors or neonatal morbidities. Moreover, our data did not reveal any relationship between postnatal growth, nutritional intakes and abnormal kidney function. According to previous studies in human preterm infants, both suboptimal and excessive growth, like under- and overnutrition, can alter kidney function. The work of Bacchetta et al. [ 27 ] showed that in infants born with ELBW or at less than 30 weeks of gestation, intrauterin and extrauterine growth retardation, compared with adequate intrauterine and postnatal growth, were associated with reduced GFR (as measured by inulin clearance) at 4 years of age. Similarly, in 78 ELBW infants evaluated at a mean age of 6.7 years, the only independent risk factor for renal complications in multivariate logistic regression was lower weight gain in the NICU [ 28 ]. On the contrary, other observations in VLBW or ELBW infants reported that rapid catch-up growth at 6 months of life, higher weight Z-score at 1 year, and higher BMI at the time of renal assessment, were factors significantly associated with abnormal renal function or progressive kidney disease in childhood [ 20 , 25 ]. Data on kidney outcome in relationship with neonatal nutritional intakes are scarce. One previous study had reported an association between higher neonatal protein intakes and reduced kidney size or renal function later in childhood, concluding for a potential adverse effect of excessive early protein supply [ 29 ]. On the contrary with these results, our study demonstrated that there is any effect of protein and caloric intakes during neonatal life on later kidney function, and in particularly on the glomerular filtration, as the relationship between neonatal nutrition and eGFR at childhood was for the first time analyzed in our cohort. This result is interesting, because protein intakes during the neonatal period were notably higher in our cohort compared to previous studies, as nutritional management was based on updated 2018 ESPGHAN guidelines [ 30 , 31 ] recommending increased protein and caloric delivery in VPI. Almost 20% of children in our cohort had high systolic or diastolic pressure, which may be one of the first detectable signs of perinatal imprinting on metabolic syndrome in VPI. In our cohort, high measures of BP were confirmed in subsequent nephrologist and/or cardiologist consultations, and occurred in absence of abnormal biological findings of kidney function. These results are consistent with a recent meta-analysis highlighting the association of prematurity with elevated systolic and diastolic BP [ 32 ], without concomitant alterations of serum levels of blood urea nitrogen, creatinine, and cystatin-C. In our cohort, infants with high dBP did not present with abnormal eGFR according to our definition, thus we can speculate that other mechanisms then glomerular hyperfiltration be implicate in the alteration of vascular resistances and BP in the cohort. Elevated dBP (≥ 95th percentile) was observed in 8.7% of the children, and was significantly associated with growth parameters at birth, growth velocity during the stay in the NICU and BMI in childhood. Interestingly, lower birth weight and Z-score for weight at birth, as also higher Z-score at 36wks PCA and BMI at school age, remained factors associated with diastolic hypertension at follow-up even after adjustment for gestational age. These results underline the deleterious effects on cardiovascular function of an early rapid catch-up growth, especially in tiny babies, as observed by other authors [ 33 ]. Few studies investigated the possible association of early protein intakes and BP at 5 to 6.5 years of life in VPI and they agree in concluding that higher protein intakes during postnatal weeks 1–8 [ 34 ] or at 28 days of life [ 26 ] are associated with respectively higher diastolic or systolic BP. In our cohort, higher caloric and protein intakes had no adverse effects on kidney function or BP at school age. Thus, our findings provide additional insight into the ongoing debate on the long-term effects of high protein and caloric intakes in early life, suggesting that these are not detrimental to metabolic outcomes in VPI. However, direct comparisons with previous studies remain challenging, due to differences in the parameters assessed and to the absence of a term-born control group in our cohort. Also, the absence of a deleterious effect in our cohort could reflect a short follow-up period, where early-stage renal alterations remain subclinical or undetectable by standard markers. One of the major strengths of this study lies in its prospective design, with systematic and standardized follow-up of a well-defined cohort of VPI according to current recommendations [ 4 , 18 ]. The biological screening was performed in a uniform manner. The timing of the follow-up, in early childhood, adds value to the literature by focusing on a developmental period that is often overlooked in favor of adolescence or young adulthood. This age window is particularly relevant as it may represent a critical phase where subclinical renal or cardiovascular changes can first emerge, offering opportunities for early intervention. However, several limitations must be acknowledged. First, the sample size was relatively small, and this limits the statistical power to detect more subtle associations or rare outcomes. Second, the absence of a term-born control group prevents direct comparison and limits the ability to attribute abnormalities solely to prematurity. Third, renal abnormalities were based on isolated biological parameters, and transient or context-dependent findings (e.g., microalbuminuria) may have influenced prevalence estimates. Moreover, our study did not include data on renal volume and no systematic ultrasound assessments were performed, although previous studies have reported smaller kidney volumes in former preterm infants [ 32 , 35 – 36 ], which may represent an early marker of long-term renal dysfunction. Finally, loss to follow-up and selection bias may also affect the generalizability of the results. Despite these limitations, the findings of our study reinforce the importance of structured and early screening of kidney function and BP in children born very preterm, regardless of their neonatal renal status. In line with the recommendations of the Low Birth Weight and Nephron Number Working Group [ 4 ], our data support the need for integrated follow-up strategies that include kidney function monitoring as part of routine pediatric care. The significant association between elevated dBP and growth patterns suggests that growth trajectories may serve as an early indicator of cardiovascular or renal vulnerability in this population. From a clinical standpoint, early identification of children with elevated diastolic pressure could indicate the need for a targeted nephrological monitoring and preventive interventions. More studies with larger sample sizes and term-born control groups are needed to improve comparisons and strengthen current knowledge. Longitudinal cohort designs with repeated assessments would be especially valuable to distinguish persistent abnormalities from transient findings, and to evaluate whether early markers predict adolescent or adult kidney disease. Statements and Declarations The authors have no conflict of interest to declare. This research received no specific grant from any funding agency. References Shah PS, Sankaran K, Aziz K, Allen AC, Seshia M, Ohlsson A et al (2012) Outcomes of preterm infants < 29 weeks gestation over 10-year period in Canada: a cause for concern? J Perinatol févr 32(2):132–138 Harer MW, Charlton JR, Tipple TE, Reidy KJ (2020) Preterm birth and neonatal acute kidney injury: implications on adolescent and adult outcomes. J Perinatol sept 40(9):1286–1295 Carmody JB, Charlton JR (2013) Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatr juin 131(6):1168–1179 Luyckx VA, Perico N, Somaschini M, Manfellotto D, Valensise H, Cetin I et al (2017) A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group. 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Pediatr Nephrol juin 32(6):1067–1076 Ojala R, Ala-Houhala M, Ahonen S, Harmoinen A, Turjanmaa V, Ikonen S et al (2001) Renal follow up of premature infants with and without perinatal indomethacin exposure. Arch Dis Child Fetal Neonatal Ed janv 84(1):F28–33 Iacobelli S, Loprieno S, Bonsante F, Latorre G, Esposito L, Gouyon JB (2007) Renal function in early childhood in very low birthweight infants. Am J Perinatol nov 24(10):587–592 Vieux R, Gerard M, Roussel A, Sow A, Gatin A, Guillemin F et al (2017) Kidneys in 5-year-old preterm-born children: a longitudinal cohort monitoring of renal function. Pediatr Res déc 82(6):979–985 Bacchetta J, Harambat J, Dubourg L, Guy B, Liutkus A, Canterino I et al (2009) Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int août 76(4):445–452 Kwinta P, Klimek M, Drozdz D, Grudzień A, Jagła M, Zasada M et al (2011) Assessment of long-term renal complications in extremely low birth weight children. Pediatr Nephrol 26(7):1095–1103 Galu SC, Hascoet JM, Vieux R (2015) Impact of neonatal factors and nutrition on kidney size in 5-year-old preterm-born children. Am J Perinatol févr 32(3):219–224 van Goudoever JB, Carnielli V, Darmaun D, Sainz de Pipaon M (2018) ESPGHAN/ESPEN/ESPR/CSPEN working group on pediatric parenteral nutrition. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Amino acids. Clin Nutr déc 37(6 Pt B):2315–2323 Agostoni C, Decsi T, Fewtrell M, Goulet O, Kolacek S, Koletzko B et al (2008) Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr janv 46(1):99–110 Heo JS, Lee JM (2021) The Long-Term Effect of Preterm Birth on Renal Function: A Meta-Analysis. Int J Environ Res Public Health 13 mars 18(6):2951 Eriksson JG, Forsén T, Tuomilehto J, Osmond C, Barker DJ (2001) Early growth and coronary heart disease in later life: longitudinal study. BMJ. 21 avr. ;322(7292):949–53 Zamir I, Stoltz Sjöström E, Edstedt Bonamy AK, Mohlkert LA, Norman M, Domellöf M (2019) Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm. Pediatr Res juill 86(1):115–121 Kandasamy Y, Smith R, Wright IMR, Lumbers ER (2013) Extra-uterine renal growth in preterm infants: oligonephropathy and prematurity. Pediatr Nephrol sept 28(9):1791–1796 Rakow A, Laestadius Å, Liliemark U, Backheden M, Legnevall L, Kaiser S et al (2019) Kidney volume, kidney function, and ambulatory blood pressure in children born extremely preterm with and without nephrocalcinosis. Pediatr Nephrol oct 34(10):1765–1776 Cite Share Download PDF Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Major Revisions Needed 21 Oct, 2025 Reviewers agreed at journal 19 Sep, 2025 Reviewers invited by journal 18 Sep, 2025 Editor assigned by journal 18 Sep, 2025 First submitted to journal 16 Sep, 2025 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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1","display":"","copyAsset":false,"role":"figure","size":12940,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7636338/v1/402a0ae16580dbd3817a8bab.png"},{"id":103765825,"identity":"486393f6-b702-44de-b09c-0f3c24fed242","added_by":"auto","created_at":"2026-03-02 16:09:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":854371,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7636338/v1/a380916d-f07e-46b4-a62f-23fc42e156ed.pdf"}],"financialInterests":"","formattedTitle":"Kidney health and blood pressure after very preterm birth. A cohort study at school age","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThanks to improvements in neonatal care, the survival of very premature infants (VPI), born before 32 weeks of gestational age (GA), has risen sharply over the last decades, in parallel with the decreasing rate of severe comorbidities in surviving preemies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Recent studies have shown that prematurity and very low birth weight (VLBW, birth weight less than 1500 g) are associated with a 2 to 3 times higher risk of developing chronic kidney disease (CKD) at young adulthood [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The pathogenesis of the renal consequences of very preterm birth can be explained by both the antenatal alteration in kidney development, that leads to a poor nephron endowment at birth, and the exposure to several neonatal factors that may contribute to worsen the congenital nephron deficit [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nephrogenesis ends at around 36th weeks of gestation, thus preterm birth interrupts this process. Moreover, in case of preterm birth, whatever the GA, nephrogenesis ceases by the end of the first 40 days of life, leading to a lower nephron number compared to full term birth [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. According to the Brenner\u0026rsquo;s hypothesis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], low birth weight infants can be exposed to compensatory glomerular hyperfiltration, an adaptive mechanism inducing nephron hypertrophy, which in turn may lead to glomerulosclerosis. Moreover, in preterm-born children, the risk for glomerulosclerosis may also be due to \u0026ldquo;kidney-independent\u0026rdquo; mechanisms, such as vascular remodeling, which can impact vascular resistance and blood pressure (BP) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe trajectory leading from low nephron number to progression towards CKD may be clinically silent over many years, and it can be preceded by mild biological alterations of kidney function. Thus, the \u003cem\u003e\u0026ldquo;Low Birth and Nephron Number Working Group\u0026rdquo;\u003c/em\u003e has underlined the need of regular monitoring of preterm and low birth weight individuals throughout life [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAnother point of matter is that this trajectory is a heterogeneous - not mandatory - process, which can be modulated by the occurrence of acute kidney injury (AKI) and other morbidities in the neonatal intensive care unit (NICU) [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], as also by environmental postnatal factors [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], not completely elucidated. In particular, the effect of early postnatal nutrition on long-term kidney function in preterm infants remains a controversial topic. Experimental findings from animal studies suggest that both under- and overnutrition may alter long-term kidney function. Very few clinical studies explored the association between early protein or nutrient intake and mean- or long-term kidney function in ex-preterm human babies, with contrasting results [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThus, the main objective of this study was to describe the prevalence of abnormal markers of kidney function in a cohort of former VPI, who had been followed during their first month of life regarding the evolution of renal function in the NICU [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and who underwent systematic screening of kidney function at 4 to 6 years of life. Secondary objectives were to explore potential associations of both biological markers of kidney function and blood pressure values at school age with various perinatal factors, including neonatal nutritional intakes and postnatal growth.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSetting \u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a longitudinal follow-up of VPI enrolled in the PROTIPREMA study [15], which had explored the relationship of the urine protein-to-creatinine ratio (Upr/Cr) during the first month of life with several perinatal variables and morbidities. \u003c/p\u003e\n\u003cp\u003eIn Reunion Island University Hospital, all preterm infants born before 32 weeks of gestation undergo a systematic follow-up consultation between 4 to 6 years, and assessment of kidney function is conducted as part of their routine medical monitoring.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy population\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll infants included in the PROTIPREMA study and discharged alive form the NICU were invited to participate to the present investigation. These infants were born during the period from March 2018 to February 2020. Patients were excluded if they met any of the following conditions: lost to follow-up, parental refusal for the use of their child’s medical data. The follow-up consultations were performed during the period from September 2023 to September 2024. The study visit was performed by the pediatrician in charge of VPI follow-up. \u003c/p\u003e\n\u003cp\u003eIn case of abnormal biological findings of kidney function or systolic and/or diastolic hypertension, infants were referred to the pediatric nephrologist or cardiologist for further examination and management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData collection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe following perinatal and neonatal data were collected: GA, birth weight, sex, mode of delivery, APGAR score at 1 and 5 minutes and neonatal morbidities. These included: severe birth asphyxia, acute anemia at birth, respiratory distress syndrome (RDS) requiring surfactant administration, sepsis, hemodynamically significant patent ductus arteriosus (HsPDA) requiring treatment, bronchopulmonary dysplasia (BPD), cerebral ultrasound abnormalities such as intraventricular hemorrhage (IHV) or periventricular leukomalacia (PVL), and AKI. Information regarding exposure to potential nephrotoxic agents, such as aminoglycosides and nonsteroidal anti-inflammatory drugs (NSAIDs), was also documented. All nutritional data were collected, focusing on protein and caloric intakes, and postnatal growth during hospitalization.\u003c/p\u003e\n\u003cp\u003eAt the follow-up consultation, anthropometric measures were recorded, including weight, height, and head circumference at 6, 12, 18, and 24 months, as well as weight and height at the time of the consultation. Information on past medical history was gathered, particularly regarding urinary tract infections and the use of nephrotoxic drugs (NSAIDs or aminoglycosides) beyond the discharge from the NICU. Data on breastfeeding were also collected, specifying whether the child was breastfed and, if so, the duration of breastfeeding (more or less than 6 month). \u003c/p\u003e\n\u003cp\u003eBP was taken as following: systolic and diastolic BP was measured three times in seated children after a 5-min rest. The width of the cuff was 2/3 the arm’s length. The device used to measure BP was the EDAN IM3 vital signs monitor. Systolic and diastolic BP (sBP and dBP) analyzed was the mean of the three measures of BP. Blood pressure percentiles were calculated using the calculator of the Baylor college of medicine (https://www.bcm.edu/bodycomplab/BPappZjs/BPvAgeAPPz.html) according to Flynn’s et al. guidelines for managing hypertension [16]. \u003c/p\u003e\n\u003cp\u003eKidney function was assessed through plasma creatinine measurement, cystatin-C, urea, electrolyte measures, and venous blood gas. Glomerular filtration rate (GFR) was estimated using the Schwartz CKiD formula [17]. Urinary analysis was performed to evaluate proteinuria and microalbuminuria, urine creatinine and electrolytes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOutcome measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary objective of this study was to describe biological abnormalities of kidney function at school age. \u003c/p\u003e\n\u003cp\u003eThe main outcome of interest was defined by the presence of one among the following: \u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eAn estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73m², calculated using the Schwartz CKiD formula (17,18); \u003c/li\u003e\n\u003cli\u003eMicroalbuminuria greater than 2 mg/mmol [19];\u003c/li\u003e\n\u003cli\u003eMacroalbuminuria with an albumin-to-creatinine ratio above 20 mg/mmol [18].\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe secondary outcomes were the proportion of infants with systolic and/or diastolic hypertension (respectively sBP and/or dBP \u0026gt;= 95\u003csup\u003eth\u003c/sup\u003e percentile, according to Flynn et al [16], and the description of perinatal and neonatal factors associated with biological kidney abnormalities or with high BP at school age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collection was in compliance with French regulation for clinical studies (\u003cem\u003eLoi Jardé\u003c/em\u003e) and the principles of the Declaration of Helsinki. Parental consent for the use of infant clinical data collected at school age was obtained. This study was approved by the Institutional Research Ethics Committee (CER-BDX 2025-72) and the project was declared on Health Data Hub (reference N°F20231120123113).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis \u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResults were presented using frequencies and proportions for discrete variables, and mean and standard deviations (SD) or median and interquartile range for continuous variables. In a first bivariate analysis, we described variables associated with biological abnormalities of kidney function or with systolic and/or diastolic hypertension at school age. In a second analysis we performed a regression model to obtain variables associated with diastolic hypertension. Comparisons of categorical variables were made with the χ2 test or with the Fisher's exact test. Comparisons of continuous variables were made with Wilcoxon–Mann–Whitney or ANOVA. A p-value below 0.05 was considered significant. Statistical analysis was conducted using SAS® software (Version 9.4, SAS Institute, North Carolina, United States).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eSixty-nine children were examined at the school age follow-up, and represented our study population. Among the 162 VPI included in the PROTIPREMA study (15), 15 died before hospital discharge, 67 were lost to follow-up, and 11 were excluded due to lack of parental consent. A flow-chart of the study population is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All the included infants had at least one visit by the pediatrician in charge of VPI follow-up, with a blood and urinary test performed the day of the clinical exam. Neonatal characteristics of the children included in the follow-up study are presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Children were born at (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) 29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 weeks of gestation, with a birth weight of 1158\u0026thinsp;\u0026plusmn;\u0026thinsp;326 g. Only one newborn had AKI during hospital stay in the NICU, and kidney function recovered before discharge at home. Age at the follow-up visit was at mean 5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 years. Anthropometric measures at the follow-up exam, growth data and medical history between the discharge from the NICU and the study consultation are shown in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. No infant had experienced AKI during the timeframe from discharge to follow-up visit. In total, 39 children (56.5%) presented with at least one biological abnormality of kidney function. Among them, 23 (33.8%) had an eGFR below 90 mL/min/1.73m\u0026sup2;, 1 (1.4%) had macroalbuminuria and 18 (26.1%) had pathological microalbuminuria. Seven children (10.1%) had a sBP\u0026thinsp;\u0026ge;\u0026thinsp;95th percentile and 6 (8.7%) a dBP\u0026thinsp;\u0026ge;\u0026thinsp;95th percentile. These data are presented in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Both pathological eGFR and systolic or diastolic hypertension were confirmed at the consultation with the paediatric nephrologist or cardiologist. In the children with macroalbuminuria, this was not detected at repeated urine analysis, and a persistent microalbuminuria over two urine samples was observed only in 1 patient over 18. Other data of kidney function and electrolyte analyses are shown in Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. At the bivariate analyses, there was no statistically significant association between eGFR below 90 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, macroalbuminuria, microalbuminuria, or systolic hypertension and any of the neonatal variables, including nutritional intakes or postnatal growth data (data not shown). At the bivariate analysis, the following variables were significantly associated with diastolic hypertension at school age: birth weight, birth weight Z-score, delta Z-score birth-36wks post-conception age (PCA), BMI Z-score at school age. These associations remained significant after adjustment for GA (Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\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\u003eNeonatal characteristics and morbidities in the NICU of 69 preterm infants born less than 32 weeks of gestation\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=\"left\" 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\u003eStudy population\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;69\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational age (weeks), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.1 (\u0026plusmn;\u0026thinsp;1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight (g), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1158.7 (\u0026plusmn;\u0026thinsp;326.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmall for gestational age*, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (51)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedical history\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere birth asphyxia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVaginal way of delivery, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (69)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRDS requiring surfactant, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (59)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreated hypotension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (23)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHsPDA, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (28)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEarly or Late Onset Sepsis, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (14)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAKI**, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVH (any stage), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePVL, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (4.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBPD at 36 weeks of GA, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDrug exposure during the first month of life\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExposure to vancomycin, n (%)\u003c/p\u003e\u003cp\u003eDuration of treatment in exposed infants (days), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (20)\u003c/p\u003e\u003cp\u003e11.1 (\u0026plusmn;\u0026thinsp;8.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExposure to Gentamycin, n (%)\u003c/p\u003e\u003cp\u003eDuration of treatment in exposed infants (days), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (69)\u003c/p\u003e\u003cp\u003e2.5 (\u0026plusmn;\u0026thinsp;1.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExposure to Ibuprofen, n (%)\u003c/p\u003e\u003cp\u003eDuration of treatment in exposed infants (days), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (26)\u003c/p\u003e\u003cp\u003e1.9 (\u0026plusmn;\u0026thinsp;0.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNutritional intakes in first weeks of life\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaily amino acid intake during the 2 first weeks of life (g/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.35 (\u0026plusmn;\u0026thinsp;0.37)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaily amino acid intake from week 3 to 6 of life (g/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.87 (\u0026plusmn;\u0026thinsp;0.51)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaily caloric intake during the 2 first weeks of life (Kcal/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e105 (\u0026plusmn;\u0026thinsp;9.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaily caloric intake from week 3 to 6 of life (Kcal/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e125 (\u0026plusmn;\u0026thinsp;26.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eAcronyms: AKI, acute kidney injury; BPD, bronchopulmonary dysplasia; GA, gestational age; HsPDA, hemodynamically significant patent ductus arteriosus; IVH, intraventricular hemorrhage; PVL periventricular leukomalacia. RDS, respiratory distress syndrome; SD, standard deviation;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e* defined according to AUDIPOG (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.audipog.net\u003c/span\u003e\u003cspan address=\"https://www.audipog.net\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e);\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e** defined as absolute serum creatinine\u0026thinsp;\u0026gt;\u0026thinsp;130 \u0026micro;mol/L after the third day of life.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\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\u003eAnthropometric measures, growth data and medical history after the NICU discharge\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=\"left\" 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\u003eStudy population\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;69\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnthropometric measures\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at follow-up (years), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.1 (\u0026plusmn;\u0026thinsp;0.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight at follow-up (kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17.9 (\u0026plusmn;\u0026thinsp;2.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight at follow up (cm), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e108.3 (\u0026plusmn;\u0026thinsp;4.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI Z-score at the follow-up exam, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0,37 (\u0026plusmn;\u0026thinsp;1,29)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGrowth data\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta Z-score 36wks PCA-6months, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.62 (\u0026plusmn;\u0026thinsp;1.28)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta Z-score 36wks PCA-12months, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.70 (\u0026plusmn;\u0026thinsp;1.17)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta Z-score 36wks PCA-24months, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.74 (\u0026plusmn;\u0026thinsp;1.24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta Z-score 36wks PCA-follow-up exam, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.50 (\u0026plusmn;\u0026thinsp;1.20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBreastfeeding after discharge, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAny\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (26.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes, \u0026lt; 6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (40.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes, \u0026ge; 6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (33.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedical history after NICU discharge\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary tract infection, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (10.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute renal failure, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasound kidney abnormalities, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExposure to nephrotoxic drug (NSAIDs or aminoglycosides), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (4.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExposure to diuretics, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospitalization in the PICU, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (10.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eViral infection (EBV, CMV), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eAcronyms: BMI, body mass index; CMV, cytomegalovirus postnatal infection, EBV, Epstein-Barr virus; NSAIDs, nonsteroidal anti-inflammatory drugs; PCA, postconceptional age; PICU, pediatric intensive care unit; SD, standard deviation; wks, weeks.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\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\u003eAbnormal kidney findings, systolic and diastolic hypertension at follow-up visit (school age)\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\u003eStudy population\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;69\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbnormal kidney findings, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR* below 90 mL/min/1.73m\u0026sup2;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (33.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMacroalbuminuria**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMicroalbuminuria***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18 (26.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSystolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;p95% at-follow-up visit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7 (10.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiastolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;p95% at-follow-up visit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (8.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e* eGFR using Schwartz CKiD formula with Cystatine C\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e** Macroalbuminuria, defined as an albumin-to-creatinine ratio above 20 mg/mmol,\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e*** Microalbuminuria greater than 2 mg/mmol. Blood pressure percentiles determined according to Flynn et al [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\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\u003eKidney function, electrolytic blood and urinary analyses at follow-up visit (school age)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\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\u003eStudy population\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;69\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiological markers, mean (\u0026plusmn;\u0026thinsp;SD) [min; max]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma creatinine concentration (\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e35.7 (\u0026plusmn;\u0026thinsp;10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[4.6; 92.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasmatic Cystatine C concentration (mg/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.9 (\u0026plusmn;\u0026thinsp;0.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[0.6; 1.1]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR with Schwartz CKiD formula, using Cystatine C (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e96.8 (\u0026plusmn;\u0026thinsp;14.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[51.7; 130.1]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR with Schwartz formula without Cystatine C (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e114.2 (\u0026plusmn;\u0026thinsp;24.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[43.0; 171.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma pH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e7.4 (\u0026plusmn;\u0026thinsp;0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[7.3; 7.5]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma bicarbonates (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e23.2 (\u0026plusmn;\u0026thinsp;1.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[19.5; 27.3]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma urea concentration (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4.32 (\u0026plusmn;\u0026thinsp;1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[2.0; 6.8]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma protein concentration (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e66.3 (\u0026plusmn;\u0026thinsp;5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[32.0; 74.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma sodium concentration (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e138.0 (\u0026plusmn;\u0026thinsp;1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[133.0; 143.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma potassium concentration (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.4 (\u0026plusmn;\u0026thinsp;0.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[3.4; 4.8]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary protein to creatinine ratio (mg/mmol)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e20.7 (\u0026plusmn;\u0026thinsp;17.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[8.5; 133.4]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary creatinine (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e7.7 (\u0026plusmn;\u0026thinsp;3.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[2.1; 20.7]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary sodium concentration (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e146.4 (\u0026plusmn;\u0026thinsp;70.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e[26.0; 298.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eAcronyms: CKiD, chronic kidney disease; eGFR, estimated glomerular filtration rate; SD, standard deviation.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePerinatal and postnatal variables associated with diastolic blood pressure at school age\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" 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\" colname=\"c2\"\u003e\u003cp\u003edBP\u0026thinsp;\u0026lt;\u0026thinsp;p95\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;63\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003edBP\u0026thinsp;\u0026ge;\u0026thinsp;p95\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;6\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep adjusted for GA\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePerinatal and postnatal variables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGA (weeks), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e29.2 (\u0026plusmn;\u0026thinsp;1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e28.4 (\u0026plusmn;\u0026thinsp;1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight (g), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1184 (\u0026plusmn;\u0026thinsp;323)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e892 (\u0026plusmn;\u0026thinsp;245)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e31 (\u0026plusmn;\u0026thinsp;49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3 (\u0026plusmn;\u0026thinsp;50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRDS requiring surfactant, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e40 (\u0026plusmn;\u0026thinsp;63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e4 (\u0026plusmn;\u0026thinsp;67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreated hypotension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e18 (\u0026plusmn;\u0026thinsp;28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0 (\u0026plusmn;\u0026thinsp;0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHsPDA, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e20 (\u0026plusmn;\u0026thinsp;32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0 (\u0026plusmn;\u0026thinsp;0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAKI, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e43 (\u0026plusmn;\u0026thinsp;68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0 (\u0026plusmn;\u0026thinsp;0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVH (any stage), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e17 (\u0026plusmn;\u0026thinsp;27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2 (\u0026plusmn;\u0026thinsp;33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBPD at 36 weeks of GA, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e9 (\u0026plusmn;\u0026thinsp;14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0 (\u0026plusmn;\u0026thinsp;0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVancomycin (days of treatment), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e2.4 (\u0026plusmn;\u0026thinsp;6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e4.3 (\u0026plusmn;\u0026thinsp;7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGentamycin (days of treatment), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1.9 (\u0026plusmn;\u0026thinsp;1.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2 (\u0026plusmn;\u0026thinsp;1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIBU (days of treatment), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.54 (\u0026plusmn;\u0026thinsp;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0 (\u0026plusmn;\u0026thinsp;0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight Z-score, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;\u0026thinsp;0.30 (\u0026plusmn;\u0026thinsp;0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;\u0026thinsp;1.19 (\u0026plusmn;\u0026thinsp;0.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight Z-score at 36 weeks of PCA, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;\u0026thinsp;0.94 (\u0026plusmn;\u0026thinsp;0.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;\u0026thinsp;0.94 (\u0026plusmn;\u0026thinsp;1.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight Delta Z-score 36wks PCA-birth, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;\u0026thinsp;0.62 (\u0026plusmn;\u0026thinsp;0.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.24 (\u0026plusmn;\u0026thinsp;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight Delta Z-score 36wks PCA-6months, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.63 (\u0026plusmn;\u0026thinsp;1.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.53 (\u0026plusmn;\u0026thinsp;2.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight Delta Z-score 36wks PCA-12months, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.74 (\u0026plusmn;\u0026thinsp;1.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.30 (\u0026plusmn;\u0026thinsp;1.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight Delta Z-score 36wks PCA-24months, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.77 (\u0026plusmn;\u0026thinsp;1.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.43 (\u0026plusmn;\u0026thinsp;1.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight Delta Z-score 36wks PCA-follow-up, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.43 (\u0026plusmn;\u0026thinsp;1.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.31 (\u0026plusmn;\u0026thinsp;1.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI Z-score at follow-up, mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;\u0026thinsp;0.49 (\u0026plusmn;\u0026thinsp;1.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.90 (\u0026plusmn;\u0026thinsp;1.51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal caloric intake in NICU (Kcal/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4926 (\u0026plusmn;\u0026thinsp;824)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5383 (\u0026plusmn;\u0026thinsp;392)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal amino acid intake in NICU (g/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e126 (\u0026plusmn;\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e140 (\u0026plusmn;\u0026thinsp;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal sodium intake in NICU (mmol/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e118 (\u0026plusmn;\u0026thinsp;29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e134 (\u0026plusmn;\u0026thinsp;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal potassium intake in NICU (mmol/kg), mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e88 (\u0026plusmn;\u0026thinsp;18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e96 (\u0026plusmn;\u0026thinsp;11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAcronyms: AKI, acute kidney injury; BPD, bronchopulmonary dysplasia; BMI, body mass index; GA, gestational age; HsPDA, hemodynamically significant patent ductus arteriosus; IBU, Ibuprofen; IVH, intraventricular hemorrhage; NICU, neonatal intensive care unit; PCA, postconceptional age; RSD, respiratory distress syndrome; SD, standard deviation; wks, weeks.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study reported the prevalence of abnormal findings of kidney function and high blood pressure in a cohort of VPI followed-up at school age, and their relationship with several neonatal and postnatal factors. Our results showed that in childhood, more than 50% of children born very preterm presented with at least one biological abnormality of kidney function, according to some criteria used in the literature [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and almost 20% had high systolic or diastolic blood pressure. These findings are particularly noteworthy, given that none of the children in the cohort had abnormal renal function at the end of the neonatal period or experienced AKI before the school age follow-up. A majority of the studies that have investigated the short-term consequences of preterm birth on kidney health addressed the impact of neonatal AKI on kidney outcome during early childhood [\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. These studies reported several degrees of abnormal kidney function, ranging from mild impairment to end-stage renal failure in extremely low birth weight (ELBW), VLBW infants or VPI aged from 3 to 7.5 years, who had experienced neonatal AKI. Actually, even in absence of neonatal AKI, it seems very important to find early and subtle changes in kidney function in infants born very preterm. First, this helps providing primary information about the risk of CKD in later life, and thus intensifying the kidney follow-up by a pediatric nephrologist in at-risk children. Second, short-term investigations allow to recognize the impact on impaired outcome of neonatal and postnatal factors, that can be prevented or modulated by clinical intervention.\u003c/p\u003e\u003cp\u003eOur findings on biological kidney abnormalities are consistent with those of previous studies. In a cohort of 66 preterm infants born at less than 33 weeks of gestation and aged 2 to 4 years, Ojala et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] found an abnormal eGFR (\u0026lt;\u0026thinsp;89 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e) in two infants (3%), and kidney abnormalities at ultrasound in ten infants (15%). In a previous cohort study of 48 VLBW infants followed up at 6.3 to 8.2 years of age, we reported an 8.3% rate of pathological microalbuminuria (ACR\u0026thinsp;\u0026gt;\u0026thinsp;20 mg/g) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In a representative, longitudinal cohort of infants born at 27\u0026ndash;31 weeks of gestation, Vieux et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] described high albuminuria (urine albumin level\u0026thinsp;\u0026gt;\u0026thinsp;17.7 mg/g urine creatinine) in 14% of five-year-old children. Despite concordant conclusions, these data underline that follow-up protocols of kidney function are not very standardized in VPI, and biomarkers used to detect early signs of kidney disease are very heterogenous across studies. Moreover, in our study, as in that of Vieux et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] micro- and macroalbuminuria levels were fluctuating a lot in the same children over time, and this questions the validity of these markers in the follow-up of renal function in VPI. In contrast with previous investigations [\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], we did not find any significant association between reduced eGFR, microalbuminuria, or macroalbuminuria and perinatal factors or neonatal morbidities. Moreover, our data did not reveal any relationship between postnatal growth, nutritional intakes and abnormal kidney function. According to previous studies in human preterm infants, both suboptimal and excessive growth, like under- and overnutrition, can alter kidney function. The work of Bacchetta et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] showed that in infants born with ELBW or at less than 30 weeks of gestation, intrauterin and extrauterine growth retardation, compared with adequate intrauterine and postnatal growth, were associated with reduced GFR (as measured by inulin clearance) at 4 years of age. Similarly, in 78 ELBW infants evaluated at a mean age of 6.7 years, the only independent risk factor for renal complications in multivariate logistic regression was lower weight gain in the NICU [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. On the contrary, other observations in VLBW or ELBW infants reported that rapid catch-up growth at 6 months of life, higher weight Z-score at 1 year, and higher BMI at the time of renal assessment, were factors significantly associated with abnormal renal function or progressive kidney disease in childhood [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eData on kidney outcome in relationship with neonatal nutritional intakes are scarce. One previous study had reported an association between higher neonatal protein intakes and reduced kidney size or renal function later in childhood, concluding for a potential adverse effect of excessive early protein supply [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. On the contrary with these results, our study demonstrated that there is any effect of protein and caloric intakes during neonatal life on later kidney function, and in particularly on the glomerular filtration, as the relationship between neonatal nutrition and eGFR at childhood was for the first time analyzed in our cohort. This result is interesting, because protein intakes during the neonatal period were notably higher in our cohort compared to previous studies, as nutritional management was based on updated 2018 ESPGHAN guidelines [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] recommending increased protein and caloric delivery in VPI.\u003c/p\u003e\u003cp\u003eAlmost 20% of children in our cohort had high systolic or diastolic pressure, which may be one of the first detectable signs of perinatal imprinting on metabolic syndrome in VPI. In our cohort, high measures of BP were confirmed in subsequent nephrologist and/or cardiologist consultations, and occurred in absence of abnormal biological findings of kidney function. These results are consistent with a recent meta-analysis highlighting the association of prematurity with elevated systolic and diastolic BP [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], without concomitant alterations of serum levels of blood urea nitrogen, creatinine, and cystatin-C. In our cohort, infants with high dBP did not present with abnormal eGFR according to our definition, thus we can speculate that other mechanisms then glomerular hyperfiltration be implicate in the alteration of vascular resistances and BP in the cohort. Elevated dBP (\u0026ge;\u0026thinsp;95th percentile) was observed in 8.7% of the children, and was significantly associated with growth parameters at birth, growth velocity during the stay in the NICU and BMI in childhood. Interestingly, lower birth weight and Z-score for weight at birth, as also higher Z-score at 36wks PCA and BMI at school age, remained factors associated with diastolic hypertension at follow-up even after adjustment for gestational age. These results underline the deleterious effects on cardiovascular function of an early rapid catch-up growth, especially in tiny babies, as observed by other authors [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFew studies investigated the possible association of early protein intakes and BP at 5 to 6.5 years of life in VPI and they agree in concluding that higher protein intakes during postnatal weeks 1\u0026ndash;8 [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] or at 28 days of life [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] are associated with respectively higher diastolic or systolic BP. In our cohort, higher caloric and protein intakes had no adverse effects on kidney function or BP at school age. Thus, our findings provide additional insight into the ongoing debate on the long-term effects of high protein and caloric intakes in early life, suggesting that these are not detrimental to metabolic outcomes in VPI. However, direct comparisons with previous studies remain challenging, due to differences in the parameters assessed and to the absence of a term-born control group in our cohort. Also, the absence of a deleterious effect in our cohort could reflect a short follow-up period, where early-stage renal alterations remain subclinical or undetectable by standard markers.\u003c/p\u003e\u003cp\u003eOne of the major strengths of this study lies in its prospective design, with systematic and standardized follow-up of a well-defined cohort of VPI according to current recommendations [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The biological screening was performed in a uniform manner. The timing of the follow-up, in early childhood, adds value to the literature by focusing on a developmental period that is often overlooked in favor of adolescence or young adulthood. This age window is particularly relevant as it may represent a critical phase where subclinical renal or cardiovascular changes can first emerge, offering opportunities for early intervention.\u003c/p\u003e\u003cp\u003eHowever, several limitations must be acknowledged. First, the sample size was relatively small, and this limits the statistical power to detect more subtle associations or rare outcomes. Second, the absence of a term-born control group prevents direct comparison and limits the ability to attribute abnormalities solely to prematurity. Third, renal abnormalities were based on isolated biological parameters, and transient or context-dependent findings (e.g., microalbuminuria) may have influenced prevalence estimates. Moreover, our study did not include data on renal volume and no systematic ultrasound assessments were performed, although previous studies have reported smaller kidney volumes in former preterm infants [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], which may represent an early marker of long-term renal dysfunction. Finally, loss to follow-up and selection bias may also affect the generalizability of the results.\u003c/p\u003e\u003cp\u003eDespite these limitations, the findings of our study reinforce the importance of structured and early screening of kidney function and BP in children born very preterm, regardless of their neonatal renal status. In line with the recommendations of the \u003cem\u003eLow Birth Weight and Nephron Number Working Group\u003c/em\u003e [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], our data support the need for integrated follow-up strategies that include kidney function monitoring as part of routine pediatric care.\u003c/p\u003e\u003cp\u003eThe significant association between elevated dBP and growth patterns suggests that growth trajectories may serve as an early indicator of cardiovascular or renal vulnerability in this population. From a clinical standpoint, early identification of children with elevated diastolic pressure could indicate the need for a targeted nephrological monitoring and preventive interventions.\u003c/p\u003e\u003cp\u003eMore studies with larger sample sizes and term-born control groups are needed to improve comparisons and strengthen current knowledge. Longitudinal cohort designs with repeated assessments would be especially valuable to distinguish persistent abnormalities from transient findings, and to evaluate whether early markers predict adolescent or adult kidney disease.\u003c/p\u003e"},{"header":"Statements and Declarations","content":"\u003cp\u003eThe authors have no conflict of interest to declare.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis research received no specific grant from any funding agency.\u0026nbsp;\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShah PS, Sankaran K, Aziz K, Allen AC, Seshia M, Ohlsson A et al (2012) Outcomes of preterm infants\u0026thinsp;\u0026lt;\u0026thinsp;29 weeks gestation over 10-year period in Canada: a cause for concern? J Perinatol f\u0026eacute;vr 32(2):132\u0026ndash;138\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHarer MW, Charlton JR, Tipple TE, Reidy KJ (2020) Preterm birth and neonatal acute kidney injury: implications on adolescent and adult outcomes. J Perinatol sept 40(9):1286\u0026ndash;1295\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarmody JB, Charlton JR (2013) Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatr juin 131(6):1168\u0026ndash;1179\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLuyckx VA, Perico N, Somaschini M, Manfellotto D, Valensise H, Cetin I et al (2017) A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group. Lancet. 22 juill. ;390(10092):424\u0026ndash;8\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrump C, Sundquist J, Winkleby MA, Sundquist K (2019) Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: national cohort study. BMJ 1 mai 365:l1346\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIacobelli S, Guignard JP (2022) When the progresses in neonatology lead to severe congenital nephron deficit: is there a pilot in the NICU? Pediatr Nephrol. juin. ;37(6):1277\u0026ndash;84\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRodr\u0026iacute;guez MM, G\u0026oacute;mez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE (2004) Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 7(1):17\u0026ndash;25\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrenner BM (1989) Chronic renal failure: a disorder of adaptation. Perspect Biol Med 32(3):434\u0026ndash;444\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLigi I, Grandvuillemin I, Andres V, Dignat-George F, Simeoni U (2010) Low birth weight infants and the developmental programming of hypertension: a focus on vascular factors. Semin Perinatol juin 34(3):188\u0026ndash;192\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarmody JB, Swanson JR, Rhone ET, Charlton JR (2014) Recognition and reporting of AKI in very low birth weight infants. Clin J Am Soc Nephrol 5 d\u0026eacute;c 9(12):2036\u0026ndash;2043\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerico N, Askenazi D, Cortinovis M, Remuzzi G (2018) Maternal and environmental risk factors for neonatal AKI and its long-term consequences. 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J Matern Fetal Neonatal Med sept 27(14):1485\u0026ndash;1490\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTrigolet M, Bonsante F, Guignard JP, Gouyon JB, Iacobelli S (2023) Urinary protein to creatinine ratio during the first month of life in very preterm infants-a prospective cohort study (PROTIPREMA). Pediatr Nephrol mars 38(3):721\u0026ndash;727\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFlynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR et al (2017) Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Pediatr sept 140(3):e20171904\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchwartz GJ, Mu\u0026ntilde;oz A, Schneider MF, Mak RH, Kaskel F, Warady BA et al (2009) New equations to estimate GFR in children with CKD. 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Pediatr Nephrol sept 18(9):887\u0026ndash;893\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaqsood S, Fung N, Chowdhary V, Raina R, Mhanna MJ (2017) Outcome of extremely low birth weight infants with a history of neonatal acute kidney injury. Pediatr Nephrol juin 32(6):1035\u0026ndash;1043\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBruel A, Roz\u0026eacute; JC, Quere MP, Flamant C, Boivin M, Roussey-Kesler G et al (2016) Renal outcome in children born preterm with neonatal acute renal failure: IRENEO-a prospective controlled study. Pediatr Nephrol d\u0026eacute;c 31(12):2365\u0026ndash;2373\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHarer MW, Pope CF, Conaway MR, Charlton JR (2017) Follow-up of Acute kidney injury in Neonates during Childhood Years (FANCY): a prospective cohort study. Pediatr Nephrol juin 32(6):1067\u0026ndash;1076\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOjala R, Ala-Houhala M, Ahonen S, Harmoinen A, Turjanmaa V, Ikonen S et al (2001) Renal follow up of premature infants with and without perinatal indomethacin exposure. Arch Dis Child Fetal Neonatal Ed janv 84(1):F28\u0026ndash;33\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIacobelli S, Loprieno S, Bonsante F, Latorre G, Esposito L, Gouyon JB (2007) Renal function in early childhood in very low birthweight infants. Am J Perinatol nov 24(10):587\u0026ndash;592\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVieux R, Gerard M, Roussel A, Sow A, Gatin A, Guillemin F et al (2017) Kidneys in 5-year-old preterm-born children: a longitudinal cohort monitoring of renal function. Pediatr Res d\u0026eacute;c 82(6):979\u0026ndash;985\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBacchetta J, Harambat J, Dubourg L, Guy B, Liutkus A, Canterino I et al (2009) Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int ao\u0026ucirc;t 76(4):445\u0026ndash;452\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKwinta P, Klimek M, Drozdz D, Grudzień A, Jagła M, Zasada M et al (2011) Assessment of long-term renal complications in extremely low birth weight children. Pediatr Nephrol 26(7):1095\u0026ndash;1103\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGalu SC, Hascoet JM, Vieux R (2015) Impact of neonatal factors and nutrition on kidney size in 5-year-old preterm-born children. Am J Perinatol f\u0026eacute;vr 32(3):219\u0026ndash;224\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Goudoever JB, Carnielli V, Darmaun D, Sainz de Pipaon M (2018) ESPGHAN/ESPEN/ESPR/CSPEN working group on pediatric parenteral nutrition. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Amino acids. Clin Nutr d\u0026eacute;c 37(6 Pt B):2315\u0026ndash;2323\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAgostoni C, Decsi T, Fewtrell M, Goulet O, Kolacek S, Koletzko B et al (2008) Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr janv 46(1):99\u0026ndash;110\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHeo JS, Lee JM (2021) The Long-Term Effect of Preterm Birth on Renal Function: A Meta-Analysis. Int J Environ Res Public Health 13 mars 18(6):2951\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEriksson JG, Fors\u0026eacute;n T, Tuomilehto J, Osmond C, Barker DJ (2001) Early growth and coronary heart disease in later life: longitudinal study. BMJ. 21 avr. ;322(7292):949\u0026ndash;53\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZamir I, Stoltz Sj\u0026ouml;str\u0026ouml;m E, Edstedt Bonamy AK, Mohlkert LA, Norman M, Domell\u0026ouml;f M (2019) Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm. Pediatr Res juill 86(1):115\u0026ndash;121\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKandasamy Y, Smith R, Wright IMR, Lumbers ER (2013) Extra-uterine renal growth in preterm infants: oligonephropathy and prematurity. Pediatr Nephrol sept 28(9):1791\u0026ndash;1796\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRakow A, Laestadius \u0026Aring;, Liliemark U, Backheden M, Legnevall L, Kaiser S et al (2019) Kidney volume, kidney function, and ambulatory blood pressure in children born extremely preterm with and without nephrocalcinosis. Pediatr Nephrol oct 34(10):1765\u0026ndash;1776\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Very preterm infants, follow-up in childhood, chronic kidney disease, hypertension","lastPublishedDoi":"10.21203/rs.3.rs-7636338/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7636338/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eVery preterm infants (VPI, \u0026lt;\u0026thinsp;32 weeks of gestation) are at increased risk of chronic kidney disease and hypertension in later life, and biological abnormalities of kidney function may precede clinically apparent disease. We evaluated kidney function and blood pressure (BP) at school age in VPI and explored their association with perinatal and postnatal factors, including neonatal nutrition and growth.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eVPI included since birth in a cohort to evaluate kidney function were followed-up at 4\u0026ndash;6 years. Standardized assessments included anthropometry, BP, cystatin-C, urea, plasma and urinary creatinine and electrolytes, and urinary albumin-to-creatinine ratio. Biological kidney abnormalities were defined as one among: estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;90 mL/min/1.73 m\u0026sup2;, macroalbuminuria, or microalbuminuria.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn total, 69 children (mean age 5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 years) attended follow-up and 39 (56.5%) had at least one biological kidney abnormality: eGFR\u0026thinsp;\u0026lt;\u0026thinsp;90 mL/min/1.73 m\u0026sup2; (33.8%), macroalbuminuria (1.4%), or microalbuminuria (26.1%). Hight systolic and diastolic pressure (dBP) occurred in 10.1% and 8.7% of children, respectively. Any neonatal variable, including nutritional intakes, was associated with biological kidney abnormalities. High dBP was significantly associated with lower birth weight, lower birth weight Z-score, higher weight Z-score at 36 weeks post-conception, and higher BMI at follow-up, and the association remained significant after adjustment for gestational age.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eBiological kidney abnormalities and elevated BP are frequent in ex-VPI at school age. The association between high dBP and rapid early catch-up growth underscores the need to monitor growth trajectories as part of early renal and cardiovascular risk assessment in this population.\u003c/p\u003e","manuscriptTitle":"Kidney health and blood pressure after very preterm birth. A cohort study at school age","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-30 12:23:08","doi":"10.21203/rs.3.rs-7636338/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2025-10-21T23:28:50+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-09-19T12:35:13+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-18T23:02:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-18T15:35:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-09-17T02:22:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0c0f0f6b-eabe-4bfc-96ba-cf572080b322","owner":[],"postedDate":"September 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:06:45+00:00","versionOfRecord":{"articleIdentity":"rs-7636338","link":"https://doi.org/10.1007/s00467-026-07190-0","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2026-02-26 15:59:38","publishedOnDateReadable":"February 26th, 2026"},"versionCreatedAt":"2025-09-30 12:23:08","video":"","vorDoi":"10.1007/s00467-026-07190-0","vorDoiUrl":"https://doi.org/10.1007/s00467-026-07190-0","workflowStages":[]},"version":"v1","identity":"rs-7636338","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7636338","identity":"rs-7636338","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}