Low phosphatemia in extremely low birth weight neonates: A risk factor for hyperglycemia?

Dreyfus, Lélia; Fumeaux, Céline J. Fischer; Remontet, Laurent; Owono, Murielle Christine Essomo Megnier Mbo; Laborie, Sophie; Maucort-Boulch, Delphine; Claris, Olivier

doi:10.1016/j.clnu.2015.07.019

Cited by 13 publications

(9 citation statements)

References 24 publications

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“…29 Electrolyte disturbances consistent with RS have been described previously in smaller preterm cohorts and reported to be associated with sepsis, 6 hyperglycemia, 23 chronic lung disease, 23 enhanced nutrition intakes, 6 and lower phosphate intakes. 24,44 Similarly, intrauterine growthrestricted piglets fed an enteral feed containing 50% more protein than standard sow milk without additional electrolytes developed RS symptoms, and 32% died. 45 We found that severe hypophosphatemia was associated with a 5-fold increased rate of severe IVH.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Refeeding Syndrome and Clinical Outcome in Extremely Low‐Birth‐Weight Babies: Secondary Cohort Analysis From the ProVIDe Trial

Cormack

Jiang

Harding

et al. 2020

J Parenter Enteral Nutr

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Background Refeeding syndrome (RS) following preterm birth has been linked to high intravenous (IV) protein intake in the presence of low electrolyte supply. In extremely low‐birth‐weight (ELBW) babies, we aimed to determine the incidence of RS and associations with birth characteristics and clinical outcomes. Method Prospective cohort study of ELBW ProVIDe Trial participants in 6 New Zealand neonatal intensive care units. RS was defined as serum phosphate < 1.4 mmol.L−1 and total calcium > 2.8 mmol.L−1. Relationships between RS and other factors were explored using 2‐sample tests and logistic regression adjusted for sex, gestation, and birth‐weight z‐score. Results Of 338 babies (mean [SD] birth‐weight, 780 (134) g, gestational age, 25.9 [1.7] weeks), 68 (20%) had RS. Mortality was greater in babies with RS (32% vs 11%; P < .0001). More small‐ than appropriate‐for‐gestational‐age babies developed RS (22% vs 8%; P = .001). Growth from birth to 36 weeks’ corrected age was not different between babies who did and did not have RS. In logistic regression, the odds of RS decreased by 70% for each 1 mmol per kg−1.d−1 IV phosphate intake (odds ratio [OR], 0.3; CI, 0.1–0.6; P = .002) and increased by 80% for each 1 g.kg−1.d−1 IV protein intake (OR, 1.8; CI, 1.3–2.7; P = .002). Conclusions Neonatal RS is common in this cohort of ELBW babies and is associated with increased morbidity and mortality. Optimizing phosphate and calcium intakes in IV nutrition solutions may reduce RS and its consequences.

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Section: Discussionmentioning

confidence: 99%

Neonatal Refeeding Syndrome and Clinical Outcome in Extremely Low‐Birth‐Weight Babies: Secondary Cohort Analysis From the ProVIDe Trial

Cormack

Jiang

Harding

et al. 2020

J Parenter Enteral Nutr

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“…The beneficial effect of insulin use to prevent severe ROP development therefore remains unclear. Alternative strategies aiming at improving glycemic control in the first weeks of life by stimulating endogenous insulin secretion, such as early provision of sufficient protein intake [39][40][41] and early enteral feeding [41,42], as well as preventing hypophosphatemiawhich is associated with an increased risk of hyperglycemia [43]-may be interesting to explore, possibly in an integrated approach to prevention.…”

Section: Plos Medicinementioning

confidence: 99%

Thresholds of glycemia, insulin therapy, and risk for severe retinopathy in premature infants: A cohort study

et al. 2020

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Background Hyperglycemia in preterm infants may be associated with severe retinopathy of prematurity (ROP) and other morbidities. However, it is uncertain which concentration of blood glucose is associated with increased risk of tissue damage, with little consensus on the cutoff level to treat hyperglycemia. The objective of our study was to examine the association between hyperglycemia and severe ROP in premature infants. Methods and findings In 2 independent, monocentric cohorts of preterm infants born at <30 weeks’ gestation (Nantes University Hospital, 2006–2016, primary, and Lyon-HFME University Hospital, 2009–2017, validation), we first analyzed the association between severe (stage 3 or higher) ROP and 2 markers of glucose exposure between birth and day 21—maximum value of glycemia (MaxGly1–21) and mean of daily maximum values of glycemia (MeanMaxGly1–21)—using logistic regression models. In both the primary (n = 863 infants, mean gestational age 27.5 ± 1.4 weeks, boys 52.5%; 38 with severe ROP; 54,083 glucose measurements) and the validation cohort (n = 316 infants, mean gestational age 27.4 ± 1.4 weeks, boys 51.3%), MaxGly1–21 and MeanMaxGly1–21 were significantly associated with an increased risk of severe ROP: odds ratio (OR) 1.21 (95% CI 1.14–1.27, p < 0.001) and OR 1.70 (95% CI 1.48–1.94, p < 0.001), respectively, in the primary cohort and OR 1.17 (95% CI 1.05–1.32, p = 0.008) and OR 1.53 (95% CI 1.20–1.95, p < 0.001), respectively, in the validation cohort. These associations remained significant after adjustment for confounders in both cohorts. Second, we identified optimal cutoff values of duration of exposure above each concentration of glycemia between 7 and 13 mmol/l using receiver operating characteristic curve analyses in the primary cohort. Optimal cutoff values for predicting stage 3 or higher ROP were 9, 6, 5, 3, 2, 2, and 1 days above a glycemic threshold of 7, 8, 9, 10, 11, 12, and 13 mmol/l, respectively. Severe exposure was defined as at least 1 exposure above 1 of the optimal cutoffs. Severe ROP was significantly more common in infants with severe exposure in both the primary (10.9% versus 0.6%, p < 0.001) and validation (5.2% versus 0.9%, p = 0.030) cohorts. Finally, we analyzed the association between insulin therapy and severe ROP in a national population-based prospectively recruited cohort (EPIPAGE-2, 2011, n = 1,441, mean gestational age 27.3 ± 1.4, boys 52.5%) using propensity score weighting. Insulin use was significantly associated with severe ROP in overall cohort crude analyses (OR 2.51 [95% CI 1.13–5.58], p = 0.024). Adjustment for inverse propensity score (gestational age, sex, birth weight percentile, multiple birth, spontaneous preterm birth, main pregnancy complications, surfactant therapy, duration of oxygen exposure between birth and day 28, digestive state at day 7, caloric intake at day 7, and highest glycemia during the first week) and duration of oxygen therapy had a large but not significant effect on the association between insulin treatment and severe ROP (OR 0.40 [95% CI 0.13–1.24], p = 0.106). Limitations of this study include its observational nature and, despite the large number of patients included compared to earlier similar studies, the lack of power to analyze the association between insulin use and retinopathy. Conclusions In this study, we observed that exposure to high glucose concentration is an independent risk factor for severe ROP, and we identified cutoff levels that are significantly associated with increased risk. The clinical impact of avoiding exceeding these thresholds to prevent ROP deserves further evaluation.

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“…En el caso de hipofosfemia severa puede producir falla respiratoria, falla miocárdica por depleción de ATP del miocito, rabdomiólisis , anemia por aumento de la rigidez de los eritrocitos que resulta en hemólisis, convulsiones, acidosis metabólica 21,23 , pero estas últimas no han sido reportadas en el período neonatal actual. También se ha asociado hiperglicemia, y una hipótesis es que esta alteración metabólica precedería a la hiperglicemia a través de dos mecanismos: la hipofosfemia conduciría a un déficit de ATP intracelular que afectaría a las células beta del páncreas, que reduciría la producción de insulina y por otro lado estaría afectada la fosforilación del receptor de insulina, lo cual disminuiría su efectividad 25 . De acuerdo a estos resultados el riesgo de hiperglicemia persistente (> 150 mg/dl) aumenta en 3 veces con una disminución de 1,2 mg/dl de la fosfemia 25 .…”

Section: Síndrome De Realimentación En Prematurosunclassified

“…También se ha asociado hiperglicemia, y una hipótesis es que esta alteración metabólica precedería a la hiperglicemia a través de dos mecanismos: la hipofosfemia conduciría a un déficit de ATP intracelular que afectaría a las células beta del páncreas, que reduciría la producción de insulina y por otro lado estaría afectada la fosforilación del receptor de insulina, lo cual disminuiría su efectividad 25 . De acuerdo a estos resultados el riesgo de hiperglicemia persistente (> 150 mg/dl) aumenta en 3 veces con una disminución de 1,2 mg/dl de la fosfemia 25 .…”

Section: Síndrome De Realimentación En Prematurosunclassified

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal

Celis

Nannig

2018

Rev. chil. pediatr.

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New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

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Low phosphatemia in extremely low birth weight neonates: A risk factor for hyperglycemia?

Cited by 13 publications

References 24 publications

Neonatal Refeeding Syndrome and Clinical Outcome in Extremely Low‐Birth‐Weight Babies: Secondary Cohort Analysis From the ProVIDe Trial

Neonatal Refeeding Syndrome and Clinical Outcome in Extremely Low‐Birth‐Weight Babies: Secondary Cohort Analysis From the ProVIDe Trial

Thresholds of glycemia, insulin therapy, and risk for severe retinopathy in premature infants: A cohort study

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal

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