Ventilatory Support, Extubation, and Cerebral Perfusion Changes in Pre-Term Neonates: A Near Infrared Spectroscopy Study.

Early extubation is considered to be beneficial for pre-term neonates. On the other hand, premature extubation can cause lung derecruitment, compromised gas exchange, and need for reintubation, which may be associated with severe brain injury caused by sudden cerebral blood flow changes. We used near infrared spectroscopy (NIRS) to investigate changes in cerebral oxygenation (rScO2) and fractional tissue oxygen extraction (+) after extubation in pre-term infants. This is a single-center retrospective study of NIRS data at extubation time of all consecutive pre-term neonates born at our institution over a 1-year period. Comparison between subgroups was performed. Nineteen patients were included; average gestational age (GA) was 29.4 weeks. No significant change was noted in rScO2 and cFTOE after extubation in the whole population. GA and germinal matrix hemorrhage (GMH)-intraventricular hemorrhage (IVH) showed a significant change in rScO2 and cFTOE after extubation. A significant increase in cFTOE was noted in patients with previous GMH-IVH (+0.040; p = 0.05). To conclude, extubation per se was not associated with significant change in cerebral oxygenation and perfusion. Patients with a diagnosed GMH-IVH showed an increase in cFTOE, suggesting perturbation in cerebral perfusion suggesting further understanding during this challenging phenomenon. Larger studies are required to corroborate our findings.

Intubation Rate Evaluation of Inborn Versus Outborn Premature Newborns Affected by Respiratory Distress Syndrome: Impact of Neonatal Transport.

OBJECTIVE: The aim of this study was to compare the management of preterm newborns with respiratory distress both in the delivery room and during transportation. METHODS: We retrospectively evaluated the intubation rate in preterm newborns (inborn vs. outborn), gestational age (GA) < 34 weeks, admitted to the Gaslini neonatal intensive care unit, Genoa, Italy (January 2019-December 2020). RESULTS: A total of 251 newborns were included (202 inborn and 49 outborn). The intubation rate was significantly higher in outborn newborns (69.4% vs. 42.1%, P = .001) in the GA 30- to 34- week subgroup (63.2% vs 20.6%, P = .001) but not in the GA < 30-week subgroup (90.9% vs. 81.7%, P = .68). CONCLUSION: Although the medical staff members involved in neonatal transport were the same who work both in the neonatal intensive care unit and the delivery room, we found a significantly higher intubation rate in outborn newborns, probably due to the transport itself. It is fundamental to encourage in utero transportation to reduce the risk linked to invasive ventilation due to neonatal transportation.

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Background: The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI-) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI- PWMLs. Materials and Methods: MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database. Results: A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI (p = 0.003 and p = 0.0001, respectively). Conclusions: Our results suggest a nosological difference between SWI+ and SWI- PWMLs. Other prospective studies are warranted to corroborate these observations.

Neonatal cerebral sinovenous thrombosis.

Cerebral sinovenous thrombosis (CSVT) is a focal or diffuse disruption of cerebral blood flow secondary to occlusion of cerebral veins and/or sinuses. The challenge of CSVT during the neonatal age has led to a great interest in this condition among neonatologists, child neurologists, and pediatric neuroradiologists. The highly variable clinical spectra, etiologies, and prognosis require fine medical skills and a high level of suspicion. Nevertheless, the diagnosis is often delayed or missed altogether. Differences in brain vulnerability at different stages of maturation may explain the spectrum of associated brain lesions, which varies with gestational age. Treatment is controversial and reported clinical outcomes vary widely. The controversial treatment of CSVT with anticoagulant therapy is based only on case series and expert consensus, there is lack of safety data.

Punctate white matter lesions of preterm infants: Risk factor analysis.

AIM: Punctate white matter lesions (PWML) are frequently detected in preterm infants undergoing brain MRI at term equivalent age (TEA). The aims of this study were to assess prevalence of PWML and to identify risk factors for PWML in VLBW infants. METHODS: Brain MRI scans obtained at TEA and clinical charts of a consecutive sample of very low birth weight (VLBW) infants admitted to Gaslini Children's Hospital NICU between 2012 and 2016 were retrospectively analyzed. MRI protocol included Susceptibility Weighted Imaging (SWI) sequence in order to identify hemosiderin depositions as a result of previous microbleeds. PWML were classified according to their number (≤6 lesions and >6 lesions) and signal characteristics (SWI+ lesions and SWI- lesions). Univariate and multivariable analysis were performed in order to identify risk factors for PWML (as a whole) and for each subgroup of PWML. RESULTS: 321 VLBW infants were included. PWML were identified in 61 subjects (19%), 26 of whom (8% of the study population) had more than 6 lesions. Risk factors for PWML (as a whole) were higher birth weight (OR = 1.001; p = 0.04) and absent or incomplete antenatal steroid course (OR = 2.13; p = 0.02). Risk factors for >6 PWML were need for intubation (OR = 11.9; p = 0.003) and higher Apgar score at 5 min (OR = 1.8; p = 0.02). Presence of GMH-IVH was the only identified risk factor for SWI + lesions. CONCLUSIONS: Our results confirm the high prevalence of PWML among VLBW infants. Differentiation between SWI+ and SWI- lesions is crucial as they have different risk factors and may likely represent two different entities.

Oxidative Stress as a Primary Risk Factor for Brain Damage in Preterm Newborns.

The risk of oxidative stress is high in preterm newborns. Room air exposure of an organism primed to develop in a hypoxic environment, lacking antioxidant defenses, and subjected to hyperoxia, hypoxia, and ischemia challenges the newborn with oxidative stress production. Free radicals can be generated by a multitude of other mechanisms, such as glutamate excitotoxicity, excess free iron, inflammation, and immune reactions. Free radical-induced damage caused by oxidative stress appears to be the major candidate for the pathogenesis of most of the complications of prematurity, brain being especially at risk, with short to long-term consequences. We review the role of free radical oxidative damage to the newborn brain and propose a mechanism of oxidative injury, taking into consideration the particular maturation-dependent vulnerability of the oligodendrocyte precursors. Prompted by our observation of an increase in plasma Adenosine concentrations significantly associated with brain white matter lesions in some premature infants, we discuss a possible bioenergetics hypothesis, correlated to the oxidative challenge of the premature infant. We aim at explaining both the oxidative stress generation and the mechanism promoting the myelination disturbances. Being white matter abnormalities among the most common lesions of prematurity, the use of Adenosine as a biomarker of brain damage appears promising in order to design neuroprotective strategies.

Semipermeable membranes and hypernatremic dehydration in preterms. A randomized-controlled trial.

BACKGROUND: Hypernatremic dehydration is a complication of preterm infants with reportedly high morbility. In preterm infants, this happens due to a combination of low fluid intake, transepidermal water loss (TEWL), and immaturity of kidney function. Semipermeable membranes are self-adhesive membranes that can be applied as an artificial skin to reduce TEWL. AIMS: To test the hypothesis that early application of a semipermeable membrane (Tegaderm™) in preterm infants ≤30 weeks could result in a significant reduction of hypernatremia (serum Na > 145 mEq/l) during the first 15 days of life. STUDY DESIGN: Randomized controlled trial (UMIN000010515). SUBJECTS: 164 consecutive newborns with gestational age ≤ 30 weeks, absence of congenital skin defects, and duration of admission ≥ 15 days. Patients were randomized to receive semipermeable membrane (n = 82) or no membrane (n = 82) for the first 15 days of life. OUTCOME MEASURES: The primary endpoint of the study was the incidence reduction of hypernatremia (Na > 145 mEq/l). Secondary endpoints included: postnatal weight loss (WL) and time to birth weight (BW) recovery. RESULTS: Incidence of hypernatremia in the control and semipermeable membrane group was 59.7% and 41.6%, respectively (p = 0.030). Postnatal WL was larger in the control group (13.9 ±â€¯5.6% vs 11.1 ±â€¯3.4%, p = 0.005) and occurred later than the semipermeable membrane group (5.4 ±â€¯2.3 vs 4.5 ±â€¯1.4 days, p = 0.005). Time to BW recovery was also longer for control group (13.5 ±â€¯4.3 vs 11.9 ±â€¯3.2 days, p = 0.016). CONCLUSIONS: Early application of skin semipermeable membrane to ≤30 week preterm is associated with decreased incidence of hypernatremia, decreased %WL, and earlier BW recovery. No complications were observed with membrane application.

Anti-Rh(c), "little c," isoimmunization: the role of rHuEpo in preventing late anemia.

The overall prevalence of non-Rh-D isoimmunization seems to lie between 0.15% and 1.1%. Anti-Rh(c) alloimmunization, "little c," occurs in 0.07% of pregnancies and shows a quite broad clinical presentation. Late anemia is a frequent problem occurring in the setting of isoimmunization. It occurs more frequently after intrauterine blood transfusions or exsanguinotransfusion, and it can be thought as a hyporegenerative anemia. The authors describe the use of human recombinant erythropoietin in preventing late anemia in a case of anti-Rh(c) isoimmunization. The use of human recombinant erythropoietin is a valid tool for preventing late-onset anemia due to either anti-Rh-D or non-anti-Rh-D isoimmunization.

Development and validation of serum bilirubin nomogram to predict the absence of risk for severe hyperbilirubinaemia before discharge: a prospective, multicenter study.

BACKGROUND: Early discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB) nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before discharge. METHODS: A percentile-based hour-specific nomogram for TSB values was performed using TSB data of 1708 healthy full term neonates. The nomogram's predictive ability was then prospectively assessed in five different first level neonatal units, using a single TSB value determined before discharge. RESULTS: The 75 th percentile of hour specific TSB nomogram allows to predict newborn babies without significant hyperbilirubinemia only after the first 72 hours of life. In the first 48 hours of life the observation of false negative results did not permit a safe discharge from the hospital. CONCLUSION: The hour-specific TSB nomogram is able to predict all neonates without risk of non physiologic hyperbilirubinemia only after 48 to 72 hours of life. The combination of TSB determination and risk factors for hyperbilirubinemia could facilitate a safe discharge from the hospital and a targeted intervention and follow-up.

Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study.

BACKGROUND: Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia. AIMS: To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia. STUDY DESIGN: prospective, observational, multicenter. SUBJECTS: 2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy. METHODS: All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin >17 mg/dL or need for phototherapy. RESULTS: Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age. CONCLUSIONS: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead.

Infants born to mothers under phenobarbital treatment: correlation between serum levels and clinical features of neonates.

OBJECTIVE: Phenobarbital crosses the placenta quickly, and the balance between maternal and fetal blood is achieved in a few minutes. Data on the clinical outcomes of infants born to mothers under phenobarbital treatment during pregnancy show that they are at risk of adverse events, such as sedation and abstinence syndrome. The aim of this study was to analyse the correlation between serum levels of phenobarbital and clinical features of neonates. STUDY DESIGN: Twenty-three infants born between 2001 and 2008 were studied. Maternal, neonatal and pharmacological variables were considered. RESULTS: Eleven infants displayed symptoms related to phenobarbital. Withdrawal syndrome was seen in seven infants and sedation syndrome was seen in four infants. One infant had severe cardiorespiratory depression at birth. None of the infants had severe neonatal abstinence syndrome. No statistically significant differences were found between symptomatic and asymptomatic infants. At birth, the mean serum level of phenobarbital of the 23 infants was 15.4 [standard deviation (SD) 6.2] µg/ml. A peak (16.1 µg/ml, SD 5.5) was seen on Day 3, followed by a gradual decrease to non-therapeutic levels (<10 µg/ml) by Day 8 (9.3 µg/ml, SD 1.0). Phenobarbital levels were higher in symptomatic infants than asymptomatic infants, although the difference was not statistically significant. CONCLUSIONS: Serum levels of phenobarbital remained in the therapeutic range for both mothers and infants, and reduced gradually in infants. However, some infants displayed symptoms related to phenobarbital. As such, a clinical pharmacological surveillance protocol is necessary.

Safety and efficacy of galactogogues: substances that induce, maintain and increase breast milk production.

Poor production of breast milk is the most frequent cause of breast lactation failure. Often, physician prescribe medications or other substances to solve this problem. The use of galactogogues should be limited to those situations in which reduced milk production from treatable causes has been excluded. One of the most frequent indication for the use of galactogogues is the diminution of milk production in mothers using indirect lactation, particularly in the case of preterm birth. The objective of this review is to analyze to the literature relating to the principal drugs used as galactogogues (metoclopramide, domperidone, chlorpromazine, sulpiride, oxytocin, growth hormone, thyrotrophin releasing hormone, medroxyprogesterone). Have been also analyzed galactogogues based on herbs and other natural substances (fenugreek, galega and milk thistle). We have evaluated their mechanism of action, transfer to maternal milk, effectiveness and potential side effects for mother and infant, suggested doses for galactogogic effect, and recommendation for breastfeeding.

Maternal and neonatal characteristics of an immigrant population in an Italian hospital.

OBJECTIVE: The objective of this study was to evaluate clinical and epidemiological characteristics of the maternal and neonatal immigrant population and to compare it with the Italian population in the Agostino Gemelli Hospital (Rome). METHODS: This study was a prospective population-based study. We compared 595 newborns from immigrant mothers with 2413 newborns from Italian mothers. Neonatal characteristics included in this study were sex, gestational age, birth weight, Apgar score, transfer to pathology units, minor pathologies, and type of breastfeeding at discharge. Maternal characteristics included nationality, age, parity, type of delivery, twin birth, and pathology during the pregnancy. RESULTS: Immigrant newborns comprised 20% of the total births included in the study. No statistically significant differences were found between immigrant and Italian newborns in gestational age, birth weight, or Apgar score. Immigrant newborns were transferred to the Paediatric Infectious Disease Unit more frequently than Italian newborns, had a significantly higher incidence of hyperbilirubinemia and a higher rate of exclusive and prevalent breastfeeding at discharge. Immigrant mothers came predominantly from Eastern Europe, were younger and had caesarean sections less frequently than Italian mothers. CONCLUSION: No significant differences in biological and clinical characteristics or in medical practice were found between groups, except for a higher frequency of neonatal hyperbilirubinemia and an inclination among immigrant mothers toward breastfeeding.

ABO hemolytic disease of the fetus and newborn: an iatrogenic complication of heterologous assisted reproductive technology-induced pregnancy.

BACKGROUND: ABO hemolytic disease of the fetus and newborn (ABO HDFN) may manifest itself in cases of mothers belonging to blood group O and newborns of groups A or B and more frequently in group A and less so in group B. CASE STUDY: The case subjects are twin-birth newborns with ABO HDFN, of group AB born to a mother of group O. These cases of ABO HDFN prove inconsistent with Mendel's law of segregation. RESULTS AND CONCLUSION: This case study finds its explanation in new methods of assisted reproduction, particularly heterologous in vitro fertilization with ovodonation.

Different fetal-neonatal outcomes in siblings born to a mother with Graves-Basedow disease after total thyroidectomy: a case series.

INTRODUCTION: We describe three different fetal or neonatal outcomes in the offspring of a mother who had persistent circulating thyrotropin receptor antibodies despite having undergone a total thyroidectomy several years before. CASE PRESENTATION: The three different outcomes were an intrauterine death, a mild and transient fetal and neonatal hyperthyroidism and a severe fetal and neonatal hyperthyroidism that required specific therapy. CONCLUSIONS: The three cases are interesting because of the different outcomes, the absence of a direct correlation between thyrotropin receptor antibody levels and clinical signs, and the persistence of thyrotropin receptor antibodies several years after a total thyroidectomy.

Weight loss and jaundice in healthy term newborns in partial and full rooming-in.

BACKGROUND: An inadequate start of breastfeeding has been associated with reduced caloric intake, excessive weight loss and high serum bilirubin levels in the first days of life. The rooming-in has been proposed as an optimal model for the promotion of breastfeeding. AIM: The aim of this study was to compare two different feeding models (partial and full rooming-in) to evaluate differences as regard to weight loss, hyperbilirubinemia and prevalence of exclusive breastfeeding at discharge. METHODS: A total of 903 healthy term newborns have been evaluated; all the newborns were adequate for gestational age, with birth weight > or = 2800 g and gestational age > or = 37 weeks. RESULTS: The maximum weight loss (mean +/- SD), expressed as percent of birth weight, was not different in the two models (partial vs. full rooming-in 5.8% +/- 1.7%vs. 6% +/- 1.7%). A weight loss > or = 10% occurred in less than 1% in both groups. There were no statistical differences neither as mean of total serum bilirubin (partial vs. full rooming-in 10.5 +/- 3.3 vs. 10.1 +/- 2.9 mg/dl), nor as prevalence of hyperbilirubinemia (total serum bilirubin > or = 12 mg/dl). The prevalence of severe hyperbilirubinemia (total serum bilirubin > or = 18 mg/dl) and the use of phototherapy were not statistically different. Maximum weight loss was similar in the two models, even dividing by total serum bilirubin levels. At the discharge, exclusively breastfed newborns were 81% in full rooming-in and 42.9% in partial rooming-in. CONCLUSIONS: In conclusion, our results allow considering our assistance models similar as regards to severe hyperbilirubinemia and pathological weight loss in term healthy newborns even if full rooming-in is associated with higher prevalence of exclusive breastfeeding at the discharge.