Effect of fortification on the osmolality of human milk.

BACKGROUND: It is known that human milk fortifiers (HMF) increases osmolality of human milk (HM) but some aspects of fortification have not been deeply investigated. Our aim was to evaluate the effect of fortification on the osmolality of donor human milk (DHM) and mother's own milk (MOM) over 72 h of storage using two commercial fortifiers and medium-chain triglycerides (MCT) supplementation. METHODS: Pasteurized DHM and unpasteurized preterm MOM were fortified with 4% PreNAN FM85, 4% PreNAN FM85 plus 2% MCT, or 4% Aptamil BMF. Osmolality was measured in unfortified DHM and MOM and, moreover, just after fortification (T0), and after 6 (T6), 24 (T24) and 72 h (T72) to determine the effect of mixing and storage. RESULTS: Unfortified DHM and MOM did not show changes of osmolality. Fortification increased osmolality of DHM and MOM without changes during the study period, except for Aptamil BMF which increased osmolality of MOM. The addition of MCT to fortified human milk (FHM) did not affect its osmolality. CONCLUSIONS: Changes of osmolality in the 72 h following fortification of both DHM and MOM did not exceed the safety values supporting the theoretically possibility of preparing 72 h volumes of FHM. Supplementation with MCT of FHM does not change osmolality suggesting that increasing energy intake in preterm infants via this approach is safe.

Splanchnic oxygenation during phototherapy in preterm infants with hyperbilirubinemia.

BACKGROUND: It has been reported that preterm infants can develop feeding intolerance during phototherapy (PT) and that PT can affect mesenteric perfusion in these patients. AIMS: Our aim was to assess if PT can decrease regional splanchnic oxygenation (rSO2S) measured by near infrared spectroscopy (NIRS). STUDY DESIGN: We prospectively studied infants with gestational age of 25-34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO2S), oxygen extraction fraction (FOES), and cerebrosplanchnic oxygenation ratio (CSOR) were recorded before, during, and after PT discontinuation. RESULTS: During PT rSO2S and CSOR significantly decreased and this effect lasted for some hours after its interruption. FOES contemporary increased, although this effect was not statistically significant. CONCLUSIONS: PT treatment decreases splanchnic oxygenation in preterm infants likely due to peripheral vasodilation which triggers a redistribution of blood flow. These results can help explain the association between PT and the development of feeding intolerance in preterm infants.

Feeding intolerance during phototherapy in preterm infants.

OBJECTIVE: Many very preterm infants are treated with phototherapy (PT) for hyperbilirubinemia and it has been reported that PT can negatively affect gut perfusion. Thus, our aim was to evaluate the occurrence of feeding intolerance in the course of PT in these patients. METHODS: We retrospectively studied infants born at 25+0-31+6 weeks from November 2017 to April 2020 who required PT during the first two weeks of life. Patients were used as their own controls recording for each one the occurrence of feeding intolerance after starting PT and the resumption of feeding tolerance after its termination. RESULTS: We studied 125 preterm infants of whom 58 (46%) developed a feeding intolerance which disappeared in 47 (81%) of them at the end of PT. Regression analysis showed a trend toward a not significant decrease of risk of feeding intolerance in infants with higher birth weight and age at the start of the first course of PT. CONCLUSION: We found that about half of our patients developed a transient feeding intolerance during PT that ceased in the vast majority of them after termination of the therapy. Further studies are necessary to confirm the correlation between PT and feeding intolerance.

Midwife-to-newborn ratio and neonatal outcome in healthy term infants.

AIM: To assess the effect of midwife-to-infant ratio on healthy term infant outcome. METHODS: Infants were enrolled in an inhospital midwife-led centre and an obstetrician-led centre with different midwife-to-infant ratios (1:2.5-1:5 vs 1:7-1:15). The primary endpoint was exclusive breastfeeding rate; secondary endpoints were neonatal admission in neonatal care unit rate and length of hospital stay. RESULTS: One hundred and ten infants were enrolled in both midwife- and obstetrician-led centre. Exclusive breastfeeding rate at discharge was higher (88% vs 78%, P = .048) in infants born in the midwife- than in the obstetrician-led centre. Admission rate in neonatal care units (9% vs 2%, P = .017) and stay in hospital duration (3.1 ± 1.8 vs 2.6 ± 0.8 days, P = .008) were higher in the obstetrician- than in the midwife-led centre. Birth in the midwife-led centre increased the likelihood of exclusive breastfeeding (OR: 2.04, 1.07-3.92), while newborns' admission in neonatal care units decreased it (OR : 0.17, 0.07-0.43). CONCLUSION: Healthy term infants' neonatal outcome is negatively associated with a low midwife-to-infant ratio which decreases exclusive breastfeeding rate and is associated with a higher likelihood of admission in neonatal care units and longer stay in hospital.

Changes in total serum bilirubin during phototherapy in late preterm and term infants with non-haemolytic hyperbilirubinemia.

BACKGROUND: There is no standardized method for total serum bilirubin (TSB) monitoring during phototherapy for neonatal hyperbilirubinemia and national guidelines give heterogeneous indications. AIM: To assess the hypothesis that TSB values do not exceed exsanguino-transfusion (EXT) threshold during phototherapy and that it is possible to decrease its monitoring frequency in jaundiced infants. STUDY DESIGN: We carried out a prospective observational study in which changes in TSB during phototherapy for non-haemolytic hyperbilirubinemia were recorded in a cohort of late preterm and term infants. TSB values after 6, 12, 18, and 24 h of phototherapy were compared to the EXT threshold matched to infants' gestational and postnatal age according to the specific nomogram of the Italian Society of Neonatology guidelines. RESULTS: We studied 105 infants who started phototherapy at a mean age of 89 ±â€¯37 h when mean TSB was 17.1 ±â€¯2.5 mg/dL. We found that TSB decreased during phototherapy and the difference between mean TSB and EXT threshold progressively increased during phototherapy; TSB exceeded EXT threshold in none of our patients (0%). CONCLUSIONS: Our study demonstrates that differences between mean TSB and EXT threshold increased during phototherapy in late preterm and term infants with non-haemolytic hyperbilirubinemia; in none of our patients TSB exceeded EXT threshold. Our findings support the possibility of safely decreasing TSB monitoring during phototherapy, thus limiting noxious painful stimuli in neonates.

Comparison of the transcutaneous bilirubinometers BiliCare and Minolta JM-103 in late preterm and term neonates.

OBJECTIVES: To assess the agreement of transcutaneous bilirubin (TcB) measurement with the Bilicare™ System in comparison to TcB measured with JM-103™ and total serum bilirubin (TSB). METHODS: Caucasian infants with gestational age ≥35 weeks with non-hemolytic jaundice received TcB measurement with both Bilicare™ and JM-103™ devices. TSB was also obtained in infants at risk of phototherapy. RESULTS: We studied 458 infants measuring TcB with Bilicare™ and JM-103™, correlating the results and with TSB. The mean difference ± 2SD between Bilicare™ and JM-103™ TcB was 2.02 ± 4.46 mg/dL and decreased from 2.88 ± 3.17 to 1.20 ± 4.55, and to -0.95 ± 4.58 mg/dL at mild, moderate and high TcB values, respectively. CONCLUSIONS: Bilicare™ and JM-103™ TcB measurements are well correlated, but Bilicare™ over-estimates TcB for mild and moderate values and under-estimates it for high values compared to JM-103™. This could increase the prescription of TSB measurements for less serious cases and decrease them in the most worrisome.

Broad-spectrum light versus blue light for phototherapy in neonatal hyperbilirubinemia: a randomized controlled trial.

Phototherapy is standard care for treatment of neonatal hyperbilirubinemia. Our aim was to compare the effectiveness of broad-spectrum light (BSL) to that of blue light emitting diodes (LED) phototherapy for the treatment of jaundiced late preterm and term infants. Infants with gestational age from 35(+0) to 41(+6) weeks of gestation and nonhemolytic hyperbilirubinemia were randomized to treatment with BSL phototherapy or blue LED phototherapy. A total of 20 infants were included in the blue LED phototherapy group and 20 in the BSL phototherapy group. The duration of phototherapy was lower in the BSL than in the blue LED phototherapy group (15.8 ± 4.9 vs. 20.6 ± 6.0 hours; p = 0.009), and infants in the former group had a lower probability (p = 0.015) of remaining in phototherapy than infants in the latter. We concluded that BSL phototherapy is more effective than blue LED phototherapy for the treatment of hyperbilirubinemia in late preterm and term infants. Our data suggest that these results are not due to the different irradiance of the two phototherapy systems, but probably depend on their different peak light emissions.

Antioxidant strategies and respiratory disease of the preterm newborn: an update.

Preterm newborns are challenged by an excessive oxidative burden, as a result of several perinatal stimuli, as intrauterine infections, resuscitation, mechanical ventilation, and postnatal complications, in the presence of immature antioxidant capacities. "Oxygen radical disease of neonatology" comprises a wide range of conditions sharing a common pathway of pathogenesis and includes bronchopulmonary dysplasia (BPD) and other main complications of prematurity. Antioxidant strategies may be beneficial in the prevention and treatment of oxidative stress- (OS-) related lung disease of the preterm newborn. Endotracheal supplementation or lung-targeted overexpression of superoxide dismutase was proved to reduce lung damage in several models; however, the supplementation in preterm newborn failed to reduce the risk of BPD, although long-term respiratory outcomes were improved. Also melatonin administration to small cohorts of preterm newborns suggested beneficial effects on lung OS. The possibility to identify single nucleotide polymorphism affecting the risk of BPD may help to identify specific populations with particularly high risk of OS-related diseases and may pose the basis for individually targeted treatments. Finally, surfactant replacement may lead to local anti-inflammatory and antioxidant effects, thanks to specific enzymatic and nonenzymatic antioxidants naturally present in animal surfactants.

Nutrition and bronchopulmonary dysplasia.

We aimed to assess the current knowledge on the nutritional management of preterm infants at risk of developing bronchopulmonary dysplasia (BPD) or with BPD. We considered the evidence supporting the actual fluid and energy intake, proteins, lipids, and electrolytes requirement, and need for other nutrients in preterm infant at risk of developing BPD or with BPD. We concluded that, although many areas remain to be investigated, early nutrition support and careful adjustment of parenteral nutrition and appropriate enteral feeding selection may enhance the growth and contribute a better neurodevelopment in these patients.

Lutein and zeaxanthin supplementation in preterm infants to prevent retinopathy of prematurity: a randomized controlled study.

OBJECTIVES: Lutein and its isomer zeaxanthin (L/Z) function in the eye as antioxidant agents and blue-light filters. Our aim was to evaluate whether their administration could help decrease the occurrence of retinopathy of prematurity (ROP) in preterm infants. METHODS: Infants with gestational age ≤32 weeks were randomly assigned to receive a daily dose of L/Z (0.14 + 0.006 mg) or placebo until discharge. RESULTS: ROP occurrence was similar in the L/Z (11/58; 19%) and placebo (15/56; 27%) groups, as the occurrence of ROP at each stage and the need of eye surgery. CONCLUSION: L/Z supplementation was ineffective in preventing ROP in preterm infants and did not affect the outcome at discharge of our patients.

New therapeutic strategies for the treatment of patent ductus arteriosus in preterm infants.

A high percentage of preterm infants fails to respond to a single course of indomethacin or ibuprofen. Thus, it has been suggested that the actual dose regimens of these drugs could be inadequate because of large interindividual pharmacokinetics variations in premature infants. We tested the hypothesis that a high-dose regimen of ibuprofen was more effective than the current regimen in closing PDA. We demonstrated that a single course of ibuprofen at 20-10-10 mg/kg/day is more effective than a 10-5-5 mg/kg/day course in closing PDA without significant adverse effects. Many other questions regarding the pharmacological treatment of PDA are still debated.

Current Italian practices regarding the management of hyperbilirubinaemia in preterm infants.

AIM: To assess the current practices existing in Italy for the management of jaundice in preterm infants as preliminary achievement to a call for national guidelines and establishment of a kernicterus registry. METHODS: A questionnaire (in Supporting Information online) was sent to the 109 level III neonatal units in Italy to ascertain existing guidelines for total bilirubin monitoring and treatment of hyperbilirubinaemia in preterm infants and occurrence of kernicterus. RESULTS: There was a 61% (67/109) response rate. Eighty-five per cent of responding units had either written guidelines coming from different literature sources or locally developed. The monitoring of bilirubin varied greatly in timing before, during and after jaundice development. Phototherapy and exchange transfusion were given to 56.0 ± 21.0% and 0.2 ± 0.4% of admitted preterm infants in participating centres. Five cases of kernicterus in preterm infants and eleven cases in term infants were documented over the last 10 years. CONCLUSION: The management of hyperbilirubinaemia in preterm infants is not uniform in Italy and would benefit from shared national guidance together with establishment of a kernicterus registry to guide therapy.

Superoxide dismutase and catalase activity in naturally derived commercial surfactants.

Despite the role of reactive oxygen species in the development of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants, the anti-oxidant properties of commercial surfactants have never been studied. We measured the superoxide dismutase (SOD) and catalase (CAT) activity, the scavenger activity against hydrogen peroxide (H(2)O(2)), and its changes after the addition of SOD and CAT in four natural surfactants, namely Infasurf, Curosurf, Survanta, and Alveofact. We found that they contain measurable amount of SOD and CAT. Curosurf and Survanta seem to have higher antioxidant effect than Infasurf and Alveofact. Moreover, the highest phospholipid concentration and recommended dose of Curosurf imply that its scavenger activity for each treatment dose in preterm infants is likely higher than that of Survanta. Finally, the supplementation with SOD and CAT induced a remarkable increase of antioxidant action in all studied surfactants.

Transcutaneous bilirubin measurement: evaluation of Bilitest.

OBJECTIVE: The early discharge of neonates from hospitals makes transcutaneous measurement of total serum bilirubin concentration a useful tool to monitor neonatal jaundice. The objective of this study was to evaluate the Bilitest BB 77trade mark (Bertocchi SRL Elettromedicali, Cremona, Italy), a new device for noninvasive transcutaneous total bilirubin measurement. METHODS: We studied 241 newborn infants > or =32 weeks of gestation admitted to the Neonatal Nursery of Careggi University Hospital, Florence. These infants had total serum bilirubin (TSB) levels measured by a standard laboratory test [corrected] as part of their normal care, and transcutaneous bilirubin (TcB) levels were obtained within 10 min after heel pricking. RESULTS: There was a good correlation between TSB and TcB values. The linear regression plot showed a general underestimation of Bilitest BB 77 measurement compared to standard laboratory test; the negative difference between Bilitest BB 77 values and TSB increased at higher bilirubin levels, as confirmed by the Bland-Altman error plot. To visualize the accuracy of the Bilitest BB 77 measurements, ROC curves plot sensitivity versus specificity and the maximum range of difference between Bilitest BB 77 and TSB were considered. Pearson correlation analysis demonstrated that Bilitest BB 77 accuracy was independent of gestational and postnatal age of newborns. CONCLUSION: We conclude that the Bilitest BB 77, a new device for bilirubin transcutaneous measurement, shows a good correlation with standard laboratory method and has the merit to be quite inexpensive and does not need calibration with consumable or disposable parts. However, because TcB measurements with Bilitest BB 77 underestimated STB levels particularly at STB > or =12 mg/dl, serum bilirubin measurements are still required when treatment with phototherapy or exchange transfusion is being considered.

Transepidermal water loss and cerebral hemodynamics in preterm infants: conventional versus LED phototherapy.

The aim of our study was to evaluate whether high-intensity gallium nitride light-emitting diode (LED) phototherapy (LPT) influences transepidermal water loss (TEWL) and cerebral hemodynamics in preterm neonates in comparison with conventional phototherapy (CPT). Thirty-one preterm infants were randomized for conventional (n = 14) and for LED (n = 17) phototherapy. All infants were studied using a Tewameter TM 210 and cerebral Doppler ultrasound immediately before phototherapy (time 0), 30 min (time 1), 1-6 h (time 2), and 12-24 h (time 3) after the start of phototherapy, and 6-12 h after discontinuing phototherapy (time 4). The study shows that LPT does not induce significant changes in TEWL (time 0: 2.75 +/- 4.71 ml/m(2)/h; time 3: 14.45 +/- 3.68 ml/m(2)/h), in peak systolic, end diastolic and mean cerebral blood flow velocity (CBFV), and in the resistence index (RI). On the contrary, CPT is associated with a significant increase of TEWL (time 0: 13.22 +/- 5.61 ml/m(2)/h; time 3: 20.94 +/- 3.21 ml/m(2)/h), which disappeared at time 4, when phototherapy had stopped. The peak systolic and mean CBFV increased, respectively, from 0.11 +/- 0.03 m/s at time 0 to 0.16 +/- 0.07 m/s at time 3. We conclude that LPT, emitting light within the 450-470-nm spectrum for optimal bilirubin degradation, can be preferable to CPT for the therapy of hyperbilirubinemia in preterm infants.

Bronze baby syndrome and the risk of kernicterus.

AIM: The problem of kernicterus in infants with bronze baby syndrome (BBS) has been reviewed on the basis of cases reported in the literature. In addition, a new case concerning an infant with severe Rh haemolytic disease, who presented with BBS and who has developed neurological manifestations of kernicterus with magnetic resonance images showing basal ganglia abnormalities, is presented. In this patient, the total serum bilirubin (TSB) concentration ranged from 18.0 to 22.8 mg/dl (306 to 388 micromol/l) and the bilirubin/albumin (B/A) ratio was 6.0 (mg/g) (6.8 is the value at which an exchange transfusion should be considered). The case presented is important due to the fact that kernicterus appeared after an exchange transfusion was performed when the TSB level reached 22.8 mg/dl (388 micromol/l) on 6th day of life while the haematocrit was 30%. From this case and from other cases reported in the literature, we must stress that, even if the level at which hyperbilirubinemia poses a threat remains undefined, BBS may constitute an additional risk of developing kernicterus. CONCLUSION: The possible strategies for implementing an approach to the management of hyperbilirubinemia (especially the haemolytic kind) in the presence of BBS may include an exchange transfusion carried out at lower TSB concentration than previously recommended or an early administration of Sn-mesoporphyrin.

Pericentric inversion of chromosome 2 and echogenic vasculature in the basal ganglia: a new finding?

Linear branching echogenicities in the thalamus or basal ganglia have been reported in infants with several genetic and nongenetic disorders. In this article, we report 2 cases of newborns with a neurosonographic diagnosis of thalamic/basal ganglia vasculopathy and karyotype analysis showing pericentric inversion of chromosome 2. To our knowledge, there has been no previous mention of an association between these entities.

Effects of phototherapy on cerebral haemodynamics in preterm infants: is fibre-optic different from conventional phototherapy?

We hypothesized that conventional phototherapy (CPT) and fibre-optic phototherapy (FPT) could exert different effects on cerebral blood perfusion. Our aim was to assess this hypothesis in a prospective study of the cerebral haemodynamics in preterm infants. Twenty-three infants (gestational age <34 weeks) were randomized for CPT (n=12) and for FPT (n=11). Cerebral Doppler ultrasounds were performed on all infants immediately before phototherapy (time 0), 6-12 hours (time 1) and 24-36 hours (time 2) after the start of phototherapy, and 6-12 hours after discontinuing phototherapy (time 3). CPT and FPT were associated with a significant increase of peak-systolic blood flow velocity and mean blood flow velocity at time 1 and 2, which disappeared at time 3, whereas end-diastolic blood flow velocity and resistance index were unchanged. No difference was shown between the groups. CPT and FPT were found to exert similar effects on cerebral haemodynamics. Both were associated with an increase of cerebral blood flow velocity which ended when phototherapy was stopped.

Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study.

BACKGROUND: It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. METHODS: A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor), Dicofarm, Rome, Italy) in a dose of 6 x 10(9) colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo. RESULTS: Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 +/- 26.0 and 48.2 +/- 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. CONCLUSION: Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations.

Changes in skin temperature of hyperbilirubinemic newborns under phototherapy: conventional versus fiberoptic device.

The purpose of this study is to determine the changes in skin temperature of hyperbilirubinemic term newborns under conventional and fiberoptic phototherapy. The study included a group of 41 hyperbilirubinemic, but otherwise healthy, term infants, all of appropriate size for gestational age. The study was devised to include two separate groups: group 1 of 21 infants (51.2%) received conventional phototherapy, and group 2 of 20 infants (48.8%) received fiberoptic phototherapy. In both groups the surface temperature on the forehead, abdomen, left leg and back was calculated by infrared radiation thermometer (Cyclops Compac 3, Minolta, Land, England). A "Photo-Therapie 800 Heraeus" unit (Drager, Lübeck, Germany) was used for conventional phototherapy (CPT). A "Biliblanket PT system" (Ohmeda, Louisville, KY) was used for fiberoptic phototherapy (FO-PT). In our study we did not find significant differences of skin temperature in the four areas examined in the two groups prior to phototherapy. During conventional phototherapy, mean values of skin temperature were found to be significantly higher than those found before phototherapy. During fibreoptic phototherapy no statistically significant temperature differences were found on the forehead, abdomen, leg, and back before and during phototherapy. Furthermore, a statistically significant increase in skin temperature was found during phototherapy on the forehead, abdomen, leg, and back in patients of group 1 with respect to patients of group 2. We demonstrated that fibreoptic phototherapy, in contrast to conventional phototherapy, does not induce a significant increase in skin temperature.