A structured programme to promote breastfeeding improved the rates in very preterm infants at discharge.

AIM: We developed the Promotion of Breastfeeding (PROBREAST) programme and evaluated what effect it had on the breastfeeding rate in infants born at less than 32 weeks of gestation or weighing ≤1500 grams. METHODS: We compared the breastfeeding rate in two cohorts of patients who were born before (n = 72; January 2017 to June 2018) and after (n = 80; July 2018 to December 2019) the application of the programme. Moreover, we compared the correlation between type of feeding at discharge and post-discharge breastfeeding rate, between exclusive breastfeeding, postnatal growth and neurodevelopment. RESULTS: Infants in the PROBREAST group had an exclusive breastfeeding rate at discharge higher (42 vs. 16%, p < 0.001) than that in the historical control group. Exclusive breastfeeding was negatively correlated with weight z-score at discharge, but not at 12 and 24 months corrected age, and was positively correlated with cognitive score at 24 months corrected age. CONCLUSION: The application of a structured programme for the promotion of breastfeeding improved the breastfeeding rate in very preterm infants. We demonstrated that exclusive breastfeeding at discharge improved their neurodevelopment without impairing growth.

Morphine exposure and neurodevelopmental outcome in infants born extremely preterm.

AIM: To investigate the association between morphine exposure in the neonatal period and neurodevelopment at 2 and 5 years of age while controlling for potential confounders. METHOD: We performed a retrospective, single-centre cohort study on 106 infants (60 males, 46 females; mean gestational age 26 weeks [SD 1]) born extremely preterm (gestational age < 28 weeks). Morphine administration was expressed as cumulative dose (mg/kg) until term-equivalent age. Neurodevelopmental outcome was assessed at 2 years with the Bayley Scales of Infant and Toddler Development, Third Edition, Dutch version and at 5 years with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, Dutch version. Multiple linear regression analysis was used to assess the association between morphine exposure and outcome. RESULTS: Sixty-four out of 106 (60.4%) infants included in the study received morphine. Morphine exposure was not associated with poorer motor, cognitive, and language subscores of the Bayley Scales of Infant and Toddler Development, Third Edition, Dutch version at 2 years. Morphine exposure was associated with lower Full-Scale IQ scores (p = 0.008, B = -9.3, 95% confidence interval [CI] = -15.6 to -3.1) and Performance IQ scores (p = 0.005, B = -17.5, 95% CI = -27.9 to -7) at 5 years of age. INTERPRETATION: Morphine exposure in infants born preterm is associated with poorer Full-Scale IQ and Performance IQ at 5 years. Individualized morphine administration is advised in infants born extremely preterm.

The management of late preterm infants: effects of rooming-in assistance versus direct admission to neonatal care units.

Late preterm infants (LPIs) represent a significant percentage of all neonates (6-8%), but there are limited published data on their postnatal management. Our aim was to compare the frequency of neonatal intensive care unit (NICU) admission and the breastfeeding rate of LPIs born at 35+0-36+6 weeks of gestation who were cared for by initial rooming in strategy rather than directly admitted to the special care unit (SCU) and, eventually, to the NICU. We carried out a retrospective study in the perinatal centers of Careggi University Hospital (CUH) and San Giovanni di Dio Hospital in Florence, Italy, where the first and second strategies were applied, respectively. Main outcomes were LPIs admission rate at SCU/NICU and breastfeeding rate at discharge. We studied 190 LPIs born at SGDH and 240 born at CUH. The admission rate in SCU (81 vs. 43%; P < 0.001) and NICU (20 vs. 10%; P = 0.008) was higher in SGDH than in CUH, as was the exclusive breastfeeding rate (36 vs. 22%; P < 0.001). However, infants who were assisted in rooming-in at CUH and infants with similar clinical characteristics at SGDH had similar mixed (60 vs. 69%) and exclusive (35 vs. 31%) breastfeeding rates.  Conclusion: Postnatal assistance of LPIs in rooming-in, eventually followed by admission in SCU/NICU based on their clinical conditions, allowed to safely halve their hospitalization. The assistance of infants in rooming-in did not negatively affect their breastfeeding rate. These results support the possibility of assisting LPIs in rooming-in. What is Known: • Late preterm infants represent a significant percentage of all neonates. • Early rooming-in and breastfeeding is recommended for late preterm infants. What is New: • Postnatal assistance of late preterm infants in rooming-in, followed when necessary by admission in neonatal units based on clinical conditions, allowed to safely avoid about half the number of hospitalizations in comparison with direct admission in neonatal units. • This strategy did not affect breastfeeding rate. Infants who were admitted to SCU/NICU after initial rooming-in had worst breastfeeding rate.

Effect on splanchnic oxygenation of breast milk, fortified breast milk, and formula milk in preterm infants.

BACKGROUND: Enteral feeding induces mesenteric hemodynamic changes in preterm infants, which may vary according to the milk used. Our aim in this study was to evaluate changes of splanchnic regional oxygenation (rSO2S) measured by near-infrared spectroscopy (NIRS) in infants fed with mother's own milk (MOM), fortified human milk (FHM), or preterm formula (PTF). METHODS: Infants born at 25-31 weeks of gestational age (n = 54) received a bolus of MOM, FHM, or PTF. rSO2S and splanchnic fractional oxygen extraction ratio (FOES) were recorded 60 min before (T0), and 30 min (T1) and 120 min (T2) after the beginning of bolus feeding. RESULTS: In the MOM group, rSO2S and FOES did not change during the study period. In the FBM group, rSO2S decreased from T0 to T1 and increased from T1 to T2, while FOES changed in reverse. In the PTF group, rSO2S decreased from T0 to T1 and from T1 to T2, while FOES changed in reverse. CONCLUSIONS: Splanchnic oxygenation was not affected by MOM feeding, was transiently decreased by FBM feeding, and was persistently decreased by PTF. These results suggest that preterm infants who received PTF has higher splanchnic tissue oxygen extraction compared to those who received MOM or FBM. IMPACT: Human milk feeding is associated to a lower splanchnic energy expenditure than preterm formula feeding. Fortified human milk transiently increases splanchnic energy expenditure. Preterm formula should be used only in the absence of human milk.

Lung ultrasound findings in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) occurs in approximately 1 in 2500 to 5000 infants. The use of lung ultrasound (LUS) for its diagnosis has been reported in only two case reports. The aim of this study was to report the LUS pattern of CDH in a case series of infants with respiratory distress. This case series was part of a cohort enrolled in a larger prospective observational study. LUS was performed at the point-of-care during the first 24 h of life of the neonates and its operation time was measured. Seven cases (six left and one right CDH) were diagnosed. We found that the pattern of LUS for CDH diagnosis includes (1) partial absence of the hyperechoic line representing the normal diaphragmatic profile, (2) partial absence of the pleural line in the affected hemithorax, (3) absence of A lines in the affected area, (4) presence of multi-layered area with hyperechoic contents in motion (normal gut), and (5) possible presence of parenchymatous organs inside the thorax (i.e., liver or spleen).Conclusion: A description of LUS pattern in infants with CDH is provided. LUS at the point-of-care may allow the prompt diagnosis of CDH and this is particularly useful in cases of missed prenatal diagnosis. What is Known: • Congenital diaphragmatic hernia occurs in approximately 1 in 2500 to 5000 infants but the use of lung ultrasound for its diagnosis has been reported in only two case reports. What is New: • Research provided a description of lung ultrasound pattern in infants with congenital diaphragmatic hernia. • Lung ultrasound at the point-of-care may allow a prompt diagnosis of congenital diaphragmatic hernia, particularly useful in cases of missed prenatal diagnosis.

Effects of early nutrition and growth on brain volumes, white matter microstructure, and neurodevelopmental outcome in preterm newborns.

BackgroundThis study aimed to investigate the effect of nutrition and growth during the first 4 weeks after birth on cerebral volumes and white matter maturation at term equivalent age (TEA) and on neurodevelopmental outcome at 2 years' corrected age (CA), in preterm infants.MethodsOne hundred thirty-one infants born at a gestational age (GA) <31 weeks with magnetic resonance imaging (MRI) at TEA were studied. Cortical gray matter (CGM) volumes, basal ganglia and thalami (BGT) volumes, cerebellar volumes, and total brain volume (TBV) were computed. Fractional anisotropy (FA) in the posterior limb of internal capsule (PLIC) was obtained. Cognitive and motor scores were assessed at 2 years' CA.ResultsCumulative fat and enteral intakes were positively related to larger cerebellar and BGT volumes. Weight gain was associated with larger cerebellar, BGT, and CGM volume. Cumulative fat and caloric intake, and enteral intakes were positively associated with FA in the PLIC. Cumulative protein intake was positively associated with higher cognitive and motor scores (all P<0.05).ConclusionOur study demonstrated a positive association between nutrition, weight gain, and brain volumes. Moreover, we found a positive relationship between nutrition, white matter maturation at TEA, and neurodevelopment in infancy. These findings emphasize the importance of growth and nutrition with a balanced protein, fat, and caloric content for brain development.

Painful procedures can affect post-natal growth and neurodevelopment in preterm infants.

AIM: This Italian study evaluated whether painful procedures during the first four weeks of life were related to subsequent weight gain, head circumference (HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated the number of invasive procedures that infants born at less than 32 weeks of gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi Hospital, Florence, from January to December 2015. Weight and HC were recorded at birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler Development - Third Edition. RESULTS: We studied 83 preterm infants with a GA of 28 ± 2 weeks and birth weight of 1098 ± 340 g. A higher number of invasive painful procedures were related to a lower HC standard deviation score at 36 weeks of PMA and six and 12 months of CA and with lower cognitive scores at six months. At 12 months, the relationship only remained significant for infants born at less than 28 weeks (p < 0.001). CONCLUSION: Invasive painful procedures affected regular HC growth and short-term cognitive scores in preterm infants in the first year of life.

Change of Cerebral Oxygenation during Surfactant Treatment in Preterm Infants: "LISA" versus "InSurE" Procedures.

Objectives The aim of the study was to compare the effects on cerebral oxygenation in preterm infants of two different procedures for surfactant administration: the LISA (low-invasive method of surfactant administration) and the InSurE (Intubation, SURfactant administration, Extubation). Study Design Twenty premature infants with respiratory distress syndrome were assigned to receive surfactant either by "LISA" (n = 10) or "InSurE" (n = 10) procedure. Patients were continuously studied by near-infrared spectroscopy (NIRS) for the measurement of cerebral regional oxygenation (rSO2C) and calculation of cerebral fractional oxygen extraction rate (cFTOE), and NIRS data were recorded 30 minutes before (T0) surfactant administration, during the procedure (Tproc), and 30 (T1), 60 (T2T2), and 120 minutes (T3) afterward. Cerebral blood flow velocity (CBFV) was studied in the anterior cerebral artery at T0, T1, and T3. Results SpO2 significantly decreased at Tproc in comparison with T0, T1, T2, and T3 and the decrease was higher in the LISA than in the InSurE group. rSO2C was lower at tproc and T3 in the LISA than in the InSurE group. cFTOE was higher at tproc, t2, and t3 in the LISA group than in the InSurE group. CBFV did not change during the study periods in both groups. Conclusions The LISA and InSurE procedures transiently decreased rSO2C in our population, and the decrease was higher in the LISA group. Consistently, there was a contemporary increase in cFTOE that was higher in the LISA than in the InSurE group, suggesting that it represents a compensatory mechanism.

Perfusion index and left ventricular output correlation in healthy term infants.

Perfusion index (PI) is a non-invasive marker of peripheral perfusion which is detected by an oximeter. We aimed to assess the correlation between PI and left ventricular output (LVO) in healthy term infants at the time of the screening for congenital heart disease (CHD). PI was measured at 48±2 h of life in the infant's right hand (PIrh) and in one foot (PIf) contemporary to SpO2 for CHD screening. Heart ultrasound was performed immediately after the screening procedure for measuring LVO. Forty-nine healthy term infants were studied. PIrh and PIf were 1.9 ± 0.6 and 1.9 ± 0.8, respectively, and their values were significantly correlated (p < 0.0001) with a coefficient r = 0.8. Bland-Altman analysis shows a mean difference of -0.06 ± 0.47 (95%LOA -0.98-0.86). PIrh correlates with LVO (r = 0.68) and LVO/kg (r = 0.61) with an increase of 151 mL/min (95%CI 103-198) of LVO and 42 mL/kg/min (95%CI 26-58) of LVO/kg per point of PIrh. PIf correlates with LVO (r = 0.74) and LVO/kg (r = 0.73) with an increase of 123 mL/min (95%CI 90-155) of LVO and 37 mL/kg/min (95%CI 27-47) of LVO/kg per point of PIf. CONCLUSION: PI is significantly correlated with LVO in healthy term infants. These results support the theoretical potential role of PI in the CHD screening. What is Known: • Perfusion index is an indirect measure of perfusion which depends on cardiac output and peripheral vascular resistance whose normal values have been documented in term and preterm infants in the first days of life. • Perfusion index has been proposed for the screening of congenital heart disease with duct-dependent systemic circulation in term infants. What is New: • Perfusion index shows a significant correlation with the left ventricular output in term infants at the moment of the screening for congenital heart disease. • Perfusion index might have a theoretical role in improving the accuracy of pulse oximetry in the screening of CHD associated to low systemic flow.

Morphine exposure and prematurity affect flash visual evoked potentials in preterm infants.

Objective: The present study aimed to explore first the impact of perinatal risk factors on flash-VEP waves and morphology in a group of preterm infants studied at term equivalent age (TEA). Second, to correlate VEP morphology with neurological outcome at 2 years corrected age (CA). Methods: Infants with a gestational age (GA) at birth <32 weeks, without major brain injury, were enrolled. Multivariate regression analyses were performed, and the models were run separately for each dependent variable N2, P2, N3 latencies and P2 amplitude. Logistic regression was applied to study N4 component (present/absent) and VEP morphology (regular/irregular). The predictors were GA, bronchopulmonary dysplasia (BPD), postmenstrual age at VEP registration, cumulative morphine and fentanyl dose, and painful procedures. Lastly, linear regression models were performed to assess the relation between the Bayley-III cognitive and motor scores at 2 years CA and VEP morphology, in relation to GA, BPD, painful procedures and cumulative morphine dose. Results: Eighty infants were enrolled. Morphine was the predictor of N2 (R2 = 0.09, p = 0.006), P2 (R2 = 0.11, p = 0.002), and N3 (R2 = 0.13, p = 0.003) latencies. Younger GA was associated with lower amplitude (R2 = 0.05, p = 0.029). None of the independent variables predicted the presence of N4 component, nor VEP morphology in the logistic analysis. VEP morphology was not associated with cognitive and motor scores at 2 years. Conclusions: Morphine treatment and prematurity were risk factors for altered VEPs parameters at TEA. In our cohort VEP morphology did not predict neurological outcome. Significance: Morphine administration should be evaluated according to potential risks and benefits, and dosage individually accustomed, according to pain and comfort scores, considering the possible risk for neurodevelopmental impairment.

Evaluation of the Relationship between Pain Exposure and Somatosensory Evoked Potentials in Preterm Infants: A Prospective Cohort Study.

BACKGROUND AND AIM: First, to compare somatosensory evoked potentials (SEPs) in preterm newborns without major brain injury studied at term equivalent age (TEA) with a term historical control group. Second, to investigate the impact of pain exposure during the first 28 days after birth on SEPs. Third, to evaluate the association between SEPs and Bayley-III at 2 years corrected age (CA). METHODS: Infants born at <32 weeks' gestational age (GA) were studied with continuous-SEPs. First, SEP differences between preterm and term infants were analyzed. Second, regression analyses were conducted to explore the association between SEPs and painful procedures, and then between SEPs and neurodevelopment. RESULTS: 86 preterm infants were prospectively enrolled. Preterm infants exhibited prolonged N1 latencies, central conduction times (CCTs), lower N1-P1 amplitudes, and more recurrently abnormal SEPs compared to term infants. Higher pain exposure predicted longer N1 latency and slower CCT (all p < 0.005), adjusting for clinical risk factors. Younger GA and postmenstrual age (PMA) at SEP recording were associated with longer N1 latency and lower N1-P1 amplitude (all p < 0.005). A normal SEP at TEA positively predicted cognitive outcome at 2 years CA (p < 0.005). CONCLUSION: Pain exposure and prematurity were risk factors for altered SEP parameters at TEA. SEPs predicted cognitive outcome.

Cardiac Hypertrophy Associated with Insulin Therapy in Extremely Preterm Infants.

BACKGROUND: In the neonatal period, cardiac hypertrophy (CH) has been commonly associated with hyperinsulinemic pathologies, and the first case of CH in an extremely preterm infant treated with insulin infusion has recently been reported. To confirm this association, we report a case series of patients who developed CH after insulin therapy. METHODS: Infants with gestational age < 30 weeks and birth weight < 1500 g, born from November 2017 to June 2022, were studied if they developed hyperglycemia requiring treatment with insulin and had echocardiographic diagnosis of CH. RESULTS: We studied 10 extremely preterm infants (24.3 ± 1.4 weeks) who developed CH at a mean age of 124 ± 37 h of life, 98 ± 24 h after the initiation of insulin therapy. All surviving patients had resolution of CH at discharge, while three of four (75%) of the deceased patients had persistent CH. CONCLUSIONS: Our case series supports the association between the development of CH and insulin therapy in extremely preterm infants and suggests further caution and the need for echocardiographic monitoring when treating these fragile patients with insulin.

Platelet Count and Volume and Pharmacological Closure with Paracetamol of Ductus Arteriosus in Preterm Infants.

Background: Low platelet count might promote resistance to pharmacological closure with indomethacin and ibuprofen of a hemodynamically significant patent ductus arteriosus (hsPDA). However, no studies have investigated if this occurs with paracetamol. Methods: We retrospectively assessed the correlation between platelet count, mean platelet volume (MPV), and plateletcrit (PCT), as well as the effectiveness of paracetamol in closing hsPDA in infants born at 23+0-31+6 weeks of gestation who were treated with 15 mg/kg/6 h of i.v. paracetamol for 3 days. Results: We studied 79 infants: 37 (47%) Had closure after a course of paracetamol and 42 (53%) did not. Platelet count and PCT did not correlate with paracetamol success or failure in closing hsPDA, while MPV was lower at birth (10.7 ± 1.4 vs. 9.5 ± 1.1; p < 0.001) and prior to starting therapy (11.7 ± 1.9 vs. 11.0 ± 1.6; p = 0.079) in refractory infants. Regression analysis confirmed that the low MVP measured prior to starting the treatment increased the risk of hsPDA paracetamol closure failure (OR 1.664, 95% CI 1.153-2.401). Conclusions: The greater MPV correlated positively with the effectiveness of paracetamol in closing hsPDA, while platelet count and PCT did not influence closure rates. Additional studies are needed to confirm our results.

Oxidative Stress Biomarkers and Early Brain Activity in Extremely Preterm Infants: A Prospective Cohort Study.

Early brain activity, measured using amplitude-integrated EEG (aEEG), is correlated with neurodevelopmental outcome in preterm newborns. F2-isoprostanes (IPs) are early biomarkers predictive for brain damage. We aimed to investigate the relationship between perinatal IPs concentrations and quantitative aEEG measures in preterm newborns. Thirty-nine infants (gestational age (GA) 24-27 ± 6 weeks) who underwent neuromonitoring using aEEG during the first two days after birth were enrolled. The rate of spontaneous activity transients per minute (SAT rate) and inter-SAT interval (ISI) in seconds were computed. Two postnatal time-points were examined: within 12 h (day 1) and between 24 and 48 h (day 2). IPs were measured in plasma from cord blood (cb-IPs) and between 24 and 48 h (pl-IPs). Multivariable regression analyses were performed to assess the correlation between IPs and brain activity. Cb-IPs were not associated with SAT rate and ISI at day 1. Higher pl-IPs were followed by longer ISI (R = 0.68; p = 0.034) and decreased SAT rate (R = 0.58; p = 0.007) at day 2 after adjusting for GA, FiO2 and IVH. Higher pl-IPs levels are associated with decreased functional brain activity. Thus, pl-IPs may represent a useful biomarker of brain vulnerability in high-risk infants.

Cerebral and splanchnic oxygenation during automated control of inspired oxygen (FiO2 ) in preterm infants.

OBJECTIVES: Our aim in this study was to assess the effect of the Predictive Intelligent Control of Oxygenation (PRICO® ) system on cerebral (rSO2 C) and splanchnic (rSO2 S) oxygenation in a cohort of preterm infants with frequent desaturations. METHODS: Twenty infants with gestational age <32 weeks (n = 20) were assigned in random sequence to 12 h of automated or manual adjustment of FiO2 . Over this period, they were studied continuously by near-infrared spectroscopy (NIRS). RESULTS: We found that rSO2 C [68.0% (60.5%-74.7%) vs. 68.5% (62%-72%); p = .824] and rSO2 S [27.0% (17.3%-45.7%) vs. 27.0% (15%-53%); p = .878] were similar during automatic and manual control of FiO2 . Time spent with SpO2 90%-95% was higher during the automatic than manual control of FiO2 , while time spent with SpO2 <80% or >95% was lower. CONCLUSIONS: Automated control of FiO2 with PRICO® system did not improve brain and splanchnic oxygenation in comparison with manual control in a cohort of preterm infants, but it significantly decreased SpO2 fluctuations and limited the duration of both hypoxemia and hyperoxemia.

In vivo magnetic resonance imaging evidence of olfactory bulbs changes in a newborn with congenital Citomegalovirus: a case report.

BACKGROUND: Citomegalovirus (CMV) infects approximately 1% of live newborns. About 10% of the infants affected by congenital CMV infection are symptomatic at birth and up to 60% of these infants will develop permanent neurological disabilities. Depending on gestational age (GA) at the time of infection, the involvement of central nervous system (CNS) can lead to malformations of cortical development, calcifications, periventricular white matter lesions and cysts, ventriculomegaly and cerebellar hypoplasia. CASE PRESENTATION: We report the MRI findings in a Caucasian female born at 32 weeks of post-menstrual age with post-birth diagnosis of congenital CMV infection showing an unusual and peculiar marked T2 hyperintensity of the inner part of olfactory bulbs in addition to the CMV related diffuse brain involvement. Despite the known extensively described fetal and neonatal Magnetic Resonance Imaging (MRI) findings in CMV infected fetuses and newborns, any in vivo MRI depiction of olfactory system damage have never been reported so far. Nevertheless, in murine studies CMV is known to infect the placenta during pregnancy showing particular tropism for neural stem cells of the olfactory system and previous neuropathologic study on CMV infected human fetal brains from 23 to 28 weeks of GA reported damage in the olfactory bulbs (OB) consisting in disseminated cytomegalic cells, inflammation, necrosis and neuronal and radial glial cell loss. Therefore, we assume an OB involvement and damage in congenital CMV infection. CONCLUSION: To our knowledge this is the first in vivo MRI evidence of OB damage in a newborn with congenital CMV infection that may give new insights on CMV infection.

Incidence and risk factors of retinopathy of prematurity in an Italian cohort of preterm infants.

OBJECTIVE: Non-negligible differences in retinopathy of prematurity (ROP) and its risk factors between different neonatal intensive care units (NICUs) are reported. Our aim was to assess the incidence and risk factors for ROP development in a large cohort of very preterm infants who were assisted in two Italian NICUs. METHODS: Preterm infants with gestational age between 23+ 0 and 29+ 6 weeks were stratified into subgroups of infants who developed ROP and those who did not; their clinical characteristics were compared with univariate and multivariable logistic regression analyses. RESULTS: We studied a total of 178 infants of whom 67 (38%) developed ROP (stage 1: n = 12; stage 2: n = 41; stage 3: n = 14). Regression analysis demonstrated that maternal milk (OR 0.979, 95% Cl 0.961-0.998) decreased the risk of developing ROP, while intraventricular hemorrhage (IVH) (OR 2.055, 95% Cl 1.120-3.772) increased it. Moreover, maternal milk was found to decrease (OR 0.981, 95% Cl 0.964-0.997) the risk of ROP at discharge, while RBC transfusion increased it (OR 1.522, 95% Cl 1.208-1.916). CONCLUSIONS: In our cohort the occurrence of ROP was similar to that previously reported. Strategies for promoting the use of mother's own milk, preventing IVH, and standardizing the approach to RBC transfusions could contribute to decreasing the risk of ROP in very preterm infants.