BackgroundEarly aggressive parenteral nutrition (PN), consisting of caloric and nitrogen intake soon after birth, is currently proposed for the premature baby. Some electrolyte disturbances, such as hypophosphatemia and hypercalcemia, considered unusual in early life, were recently described while using this PN approach. We hypothesize that, due to its impact on cell metabolism, the initial amino acid (AA) amount may specifically influence the metabolism of phosphorus, and consequently of calcium. We aim to evaluate the influence of AA intake on calcium-phosphorus metabolism, and to create a calculation tool to estimate phosphorus needs.MethodsProspective observational study. Phosphate and calcium plasma concentrations and calcium balance were evaluated daily during the first week of life in very preterm infants, and their relationship with nutrition was studied. For this purpose, infants were divided into three groups: high, medium and low AA intake (HAA, MAA, LAA). A calculation formula to assess phosphorus needs was elaborated, with a theoretical model based on AA and calcium intake, and the cumulative deficit of phosphate intake was estimated.Results154 infants were included. Hypophosphatemia (12.5%) and hypercalcemia (9.8%) were more frequent in the HAA than in the MAA (4.6% and 4.8%) and in the LAA group (0% and 1.9%); both p<0.001.DiscussionCalcium-phosphorus homeostasis was influenced by the early AA intake. We propose to consider phosphorus and calcium imbalances as being part of a syndrome, related to incomplete provision of nutrients after the abrupt discontinuation of the placental nutrition at birth (PI-ReFeeding syndrome).We provide a simple tool to calculate the optimal phosphate intake. The early introduction of AA in the PN soon after birth might be completed by an early intake of phosphorus, since AA and phosphorus are (along with potassium) the main determinants of cellular growth.

BackgroundTo investigate the ongoing controversy on the effect of BMI (body mass index) on EOP (early onset preeclampsia) vs LOP (late onset), especially focusing on diabetes and maternal booking/pre-pregnancy BMI as possible independent variables.Methods18 year-observational cohort study (2001–2018). The study population consisted of all consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity (ap. 4,300 birth per year, only level 3 maternity in the south of Reunion Island, sole allowed to follow and deliver all preeclampsia cases of the area). History of pregnancies, deliveries and neonatal outcomes have been collected in standardized fashion into an epidemiological perinatal data base.ResultsChronic hypertension and, history of preeclampsia in multigravidas, were the strongest risk factors for EOP. Primiparity, age over 35 years and BMI ≥ 35 kg/m² were rather associated with LOP. In a multivariate analysis with EOP or LOP as outcome variables compared with controls (normotensive), maternal age and pre-pregnancy BMI were independent risk factors for both EOP and LOP (p < 0.001). However, analyzing by increment of 5 (years of age, kg/m² for BMI) rising maternal ages and incidence of preeclampsia were strictly parallel for EOP and LOP, while increment of BMI was only associated with LOP. Controlling for maternal ages and booking/pre-pregnancy BMI, diabetes was not an independent risk factor neither for EOP or LOP.ConclusionsMetabolic factors, other than diabetes, associated with pre-pregnancy maternal corpulence are specifically associated with LOP. This may be a direction for future researches on the maternal preeclamptic syndrome. This may explain the discrepancy we are facing nowadays where high-income countries report 90% of their preeclampsia being LOP, while it is only 60–70% in medium-low income countries.

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Background: Several reports indicate a decreased cortisol response to adrenocorticotropic hormone in preterm infants developing chronic lung disease and in preterm infants with refractory hypotension. Low-dose hydrocortisone (HC) may allow for beneficial effects. Objective: Our aim was to assess whether HC is able to increase survival without chronic lung disease. Methods: We performed a double-blind, randomized, placebo-controlled trial. Fifty mechanically ventilated infants (birth weight: 500–1,249 g) were randomized to receive treatment (HC 0.5 mg/kg/12 h for 9 days, then HC 0.5 mg/kg/24 h for 3 days) or placebo. Major outcome was survival without oxygen dependence at 36 weeks of postconceptional age (O₂-free survival). Results: The basic characteristics were similar between the two groups. O₂-free survival was higher in the HC group (64 vs. 32%). The advantage was particularly evident among infants without antenatal steroids. The mortality rate was 16% in the HC group versus 40% in the control group (difference not significant). Hypotension after recruitment was reduced by HC (0 vs. 30%). The incidence of gastrointestinal perforation and other adverse effects was similar between the two groups. Conclusions: HC prophylaxis improved O₂-free survival and early cardiocirculatory function in our population, without important short-term effects. The neurodevelopmental outcome will be assessed at 2 years.

Objective To assess the effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone on survival without bronchopulmonary dysplasia (BPD) in very preterm infants using an individual patient data meta-analysis. Study design All existing randomized controlled trials testing the efficacy of the prophylaxis of early adrenal insufficiency using low-dose hydrocortisone on survival without BPD were considered for inclusion when data were available. The primary outcome was the binary variable survival without BPD at 36 weeks of postmenstrual age. Results Among 5 eligible studies, 4 randomized controlled trials had individual patient data available (96% of participants identified; n = 982). Early low-dose hydrocortisone treatment for 10-15 days was associated with a significant increase in survival without BPD (OR, 1.45; 95% CI, 1.11-1.90; P = .007; I 2 = 0%), as well as with decreases in medical treatment for patent ductus arteriosus (OR, 0.72; 95% CI, 0.56-0.93; P = .01; I 2 = 0%) and death before discharge (OR, 0.70; 95% CI, 0.51-0.97; P = .03; I 2 = 0%). The therapy was associated with an increased risk of spontaneous gastrointestinal perforation (OR, 2.50; 95% CI, 1.33-4.69; P = .004; I 2 = 31.9%) when hydrocortisone was given in association with indomethacin exposure. The incidence of late-onset sepsis was increased in infants exposed to hydrocortisone (OR, 1.34; 95% CI, 1.02-1.75; P = .04; I 2 = 0%), but no adverse effects were reported for either death or 2-year neurodevelopmental outcomes as assessed in an aggregate meta-analysis. Conclusions This individual patient data meta-analysis showed that early low-dose hydrocortisone therapy is beneficial for survival without BPD in very preterm infants.

Background: Dexamethasone treatment is associated with an increased risk of cerebral palsy (CP). Early hydrocortisone (HC) treatment may decrease the incidence of bronchopulmonary dysplasia; however, the long-term effects are still under evaluation. Follow-up of randomized studies concerning early HC treatment is essential to confirm the long-term safety. Objective: We hypothesized that early HC treatment in very preterm infants does not impair the neurologic outcome. Methods: We report follow-up data from a randomized trial of early HC given for 10 days. Before the HC or placebo treatment, serum cortisol levels were measured. Receiver-operating characteristic was defined. Values below the median were classified as low endogenous cortisol and those above the median as high endogenous cortisol. A meta-analysis was performed. Results: Altogether 98% of the 46 surviving infants participated in a follow-up study at a corrected age of 2 years. The growth characteristics were similar between the study groups. The developmental quotients (DQs) of the children with high endogenous cortisol and placebo treatment shortly after birth (100 ± 13) and those with low endogenous cortisol and HC (97 ± 7) were not lower than the DQs of the children with high endogenous cortisol and HC (92 ± 3) or low cortisol and placebo (96 ± 2). According to a meta-analysis of three available trials (411 children), the rate of CP and survival without neurosensory or cognitive impairment was not influenced by HC. Conclusion: Early low-dose HC administration had no adverse effects at 2 years of age. Further studies are required to define the target group for neonatal HC.

Background: Parenteral nutrition is commonly given to premature infants. It has previously been suggested that standardized parenteral nutrition (SPN) may offer nutritional advantages compared to individualized parenteral nutrition (IPN). However, whether the same level of biochemical control is assured with SPN and with IPN remains uncertain. Objectives: To compare fluid and electrolyte balance in preterm infants receiving IPN versus SPN in the first week of life. Methods: 107 infants born at <33 weeks gestation were prospectively evaluated. Serum and urinary creatinine and electrolyte concentration, urine volume, body weight, fluid, electrolyte and energy intakes were recorded daily. Results: 40 infants received IPN and 67 SPN. Infants in IPN had significantly more water and less sodium intake than those receiving SPN. Energy and amino acid intakes were significantly lower in IPN than in SPN groups. Incidence of hypernatremia and hyponatremia was similar in both groups. Nonoliguric hyperkalemia (NOHK) was significantly more frequent in IPN than in SPN (20.0 vs. 2.9%) and mean serum K⁺ peak over the first 3 days was higher in IPN than in SPN (5.63 ± 1.05 vs. 4.91 ± 0.78 mmol/l). Weight loss (% of birth weight) at day 7 was significantly higher in IPN than in SPN (7.7 ± 5.8 vs. 4.2 ± 6.5) without differences in urine output/input fluid intake ratio and glomerular renal function between the two groups. Conclusions: There were no significant differences in water and sodium balance in preterm infants who received IPN versus SPN. The risk of NOHK was higher in IPN. Also, SPN significantly increased amino acid and caloric intakes, and it reduced early weight loss.

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