Hearing Loss and Risk Factors in Very Low Birth Weight Infants.

The incidence of sensorineural hearing loss (SNHL) is still high in very low birth weight (VLBW) infants. The purpose of our study was to provide the prevalence rates of SNHL and to analyze the risk factors of hearing impairment and changes in hearing thresholds in a cohort of VLBW infants. A retrospective observational study was conducted in our neonatal intensive care unit (NICU) from 2012 to 2016. All VLBW infants included were screened by transient evoked otoacoustic emissions (TEOAEs) and diagnostic auditory brainstem response (ABR). In total, we enrolled 316 infants and SNHL was diagnosed in 68, leading to an early incidence of 21.5% as 36 infants out of 68 improved. Finally, SNHL was confirmed in 20 patients (6.3%) who needed hearing aids. They were significantly smaller, sicker, had longer hospitalizations, and received more ototoxic therapies. Logistic regression analysis showed that gestational age (GA) influenced the association between drugs and SNHL. The results underlined how the total exposure to antibiotics is significantly associated with SNHL, even after GA correction. In conclusion, GA, birth weight and, above all, the length and complexity of NICU stay quantify the risk of SNHL and should be considered at the individual level for parent counseling.

Brain Growth Evaluation Assessed with Transfontanellar (B-GREAT) Ultrasound. Old and New Bedside Markers to Estimate Cerebral Growth in Preterm Infants: a Pilot Study.

OBJECTIVE: We aimed to investigate the feasibility of evaluating overall preterm brain growth using a gathered set of measurements of brain structures in standard cranial ultrasound planes. We called this method of assessment Brain Growth Evaluation Assessed with Transfontanellar ultrasound (B-GREAT). STUDY DESIGN: In this prospective observational cohort study, cranial ultrasound was regularly performed (on day 1, 2, 3, and 7 of life, and then weekly until discharge, and at term) in preterm infants born with gestational age (GA) less than 32 weeks. We evaluated corpus callosum length, corpus callosum-fastigium length, anterior horn width, frontal white matter height, total brain surface, deep grey matter height, hemisphere height, transverse cerebellar diameter in the axial view, and transverse cerebellar diameter coronal view. Measurements obtained were used to develop growth charts for B-GREAT markers as a function of postmenstrual age. Reproducibility of B-GREAT markers was studied. RESULTS: A total of 528 cranial ultrasounds were performed in 80 neonates (median birth GA: 28+5 weeks and interquartile range: 27+3-30+5). The intraclass correlation coefficients for intra-observer and inter-observer analyses showed substantial agreement for all B-GREAT markers. Growth curves for B-GREAT markers were developed. CONCLUSION: B-GREAT is a feasible and reproducible method for bedside monitoring of the growth of the main brain structures in preterm neonates. KEY POINTS: · Overall neonatal brain growth is not routinely monitored using ultrasound.. · Old and new markers were used to build a standardized and non-invasive tool to monitor brain growth.. · All B-GREAT measurements had a good intra-observer and inter-observer agreement..

Lutein supplementation and retinopathy of prematurity: a meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP. OBJECTIVE: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates. STUDY DESIGN: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates ≤32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP. RESULT: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial.

Growth of Head Circumference and Body Length in Preterm Infants Receiving a Multicomponent vs a Soybean-Based Lipid Emulsion: A Randomized Controlled Trial.

BACKGROUND: The growth of very low-birth-weight (VLBW) infants relies, to a large extent, on parenteral nutrition (PN) during the early weeks of life. Despite the parenteral nutrients supply, extrauterine growth restriction remains the main concern for these infants. A parenteral multicomponent lipid emulsion (MLE) might improve growth and neurological outcomes, delivering fats for brain growth that the traditional soybean-based lipid emulsion (SLE) fails to provide. We hypothesize that the use of an MLE in PN may reduce the loss of head circumference (HC) z-score from birth to 36 weeks' postmenstrual age (PMA) or at discharge compared with the use of an SLE in VLBW infants. METHODS: Infants with BW ≤1250 g, without malformations or chromosomal abnormalities, were randomly assigned to receive an MLE or an SLE. The primary outcome was the change in HC z-score (HC Δ z-score) from birth to 36 weeks' PMA or at discharge. Secondary outcomes included the change in weight and length z-score (W Δ z-score and L Δ z-score) as well as incidence of late-onset sepsis and PN-associated cholestasis (PNAC). RESULTS: Of the 128 infants randomized, 51 infants in the MLE group and 50 infants in the SLE group were analyzed. The MLE was significantly associated with a decreased loss in HC and length z-scores from birth to 36 weeks' PMA or at discharge. CONCLUSIONS: This is the first randomized controlled trial providing the evidence that an MLE is associated with improved HC growth in comparison with a pure SLE.

A modified physiologic test for bronchopulmonary dysplasia: a clinical tool for weaning from CPAP and/or oxygen-therapy the premature babies?

BACKGROUND: A physiologic test for estimating BPD rate has been developed by Walsh and collaborators. Actually there are not standard criteria for weaning from CPAP and/or oxygen therapy the premature babies. Aim of this study was to verify if a physiologic test, modified respect to that developed by Walsh and collaborators for estimating BPD rate, can be used as a clinical tool for weaning the premature babies from CPAP and/or oxygen therapy. METHODS: Neonates with BW 500-1250 g and GA ≤ 32 weeks, receiving FiO2 ≤ 0.30 by hood or CPAP, were prospectively studied at 28 days of life and at 36 weeks of postmestrual age. The test was performed in 3 steps: baseline, challenge (FiO2 and CPAP reduction to room air) and post test (room air). Monitoring of transcutaneous CO2 was added to SpO2 and the newborns passing the test were left in room air. RESULTS: Six of 23 tested babies (26%) passed the challenge at 28 days of life, 4 of 10 tested babies (40%) passed the challenge at 36 weeks. Median values of SpO2 were significantly higher in the neonates passing the test, respect to the failing patients. At the same time median values of TcPCO2 were significantly higher in the latter babies. CONCLUSION: TcPCO2 monitoring appeared to be a new useful parameter for failure prediction of weaning. The test represented a clinical guide because the newborns passing it were left in room air.

Mother-to-child transmission of hepatitis C virus.

This review reinforces the lack of a single maternal risk factor that is highly associated with vertical transmission (VT) of the infection with hepatitis C virus (HCV): indeed HCV RNA levels, mode of delivery, breast feeding, viral genotype or maternal IL28B status were not associated with HCV VT.

Extubation from high-frequency oscillatory ventilation in extremely low birth weight infants: a prospective observational study.

OBJECTIVE: To evaluate if weaning from high-frequency oscillatory ventilation (HFOV) directly to a non-invasive mode of respiratory support is feasible and results in successful extubation in extremely low birth weight (ELBW) infants. DESIGN: Prospective observational study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: One hundred and eight ELBW infants of 26.2±1.4 weeks of gestational age (GA) directly extubated from HFOV. INTERVENTIONS: All infants were managed with elective HFOV and received surfactant after a recruitment HFOV manoeuvre. Extubation was attempted at mean airways pressure (MAP) ≤6 cm H2O with FiO2 ≤0.25. After extubation, all infants were supported by nasal continuous positive airway pressure (6-8 cm H2O). MAIN OUTCOME MEASURES: Extubation failure (clinical deterioration requiring reintubation) was defined as shorter than 7 days. RESULTS: Ninety patients (83%) were successfully extubated and 18 (17%) required reintubation. No significant differences were found between the two groups in terms of birth weight, day of life and weight at the time of extubation. Multivariable analysis showed that GA (OR 1.71; 95% CI 1.04, 2.08) and higher MAP prior to surfactant (OR 1.51; 95% CI 1.06, 2.15) were associated with successful extubation. CONCLUSIONS: In ELBW infants, direct extubation from HFOV at MAP ≤6 cm H2O with FiO2 ≤0.25 is feasible. Our extubation success rate (83%) is higher than conventional mechanical ventilation in this very vulnerable class of infants.

T-cell polarization: Potential serological markers in preterm and term infants.

BACKGROUND: The immaturity of immune system characterizes newborn infants. Possible serological markers of Th1 and Th2 immune response are the lymphocyte activation gene-3 (CD223) and soluble CD30, respectively (sCD30). AIMS: The aim of our study was to evaluate the relationship between Th1 and Th2 immune response and gestational age (GA), comparing data in preterm and term neonates. STUDY DESIGN: Cord blood from 20 preterm (GA: 33±2weeks, BW 1950±490g) and 20 term infants (GA: 38±1weeks, BW: 3177±330g) were tested for sCD30 and CD223 levels by ELISA. IFNγ levels produced by cord blood lymphocytes were also analyzed, both before and after stimulation with phytohaemagglutinin (PHA). RESULTS: sCD30 resulted significantly higher in preterm neonates when compared with term neonates (60±7.6 vs 42.6±3.9U/ml p<0.05). CD223 was undetectable in preterm neonates while resulting at a level of 176.1±112.6ng/ml in term neonates. After stimulation with PHA, a significant increase in IFNγ levels was only observed in term neonates (326.6±72.7pg/ml p<0.05). CONCLUSIONS: Our findings show that sCD30 is present and measurable in term and preterm infants, while CD223 is detectable only in term infants and that Th-cell polarization could also depend on gestational age. Our data suggest that a Th2 immune response seems predominant in preterm neonates.

Clinical examination and pulse oximetry as screening for congenital heart disease in low-risk newborn.

OBJECTIVE: To assess sensitivity, specificity, positive predictive value and negative predictive value of the cardiovascular physical examination (CPE) and of pulse oximetry in screening for congenital heart diseases (CHD) in asymptomatic newborn when prenatal ultrasound evaluation is negative for structural cardiac abnormalities. METHODS: In this observational cohort study, 5750 asymptomatic newborns, admitted to nursery in a period of 2 years, underwent to CPE and determination of arterial oxygen saturation by pulse oxymetry between 48th and 72nd h of life. RESULTS: Two hundred and ninty-eight newborns presented a suspected CPE; in 70% of cases, we found a transitional alteration and in only 17% of cases, the echocardiography examination performed for suspected CPE were completely negative. Three newborns were positive to pulse oximetry screening test but negative at CPE. After discharge, one case of critical CHD was diagnosed. CONCLUSIONS: An accurate CPE performed by trained and experienced pediatricians is indicative of important cardiac structural alteration in more than 25%. The association of CPE and pulse oximetry allows to further improve the diagnostic accuracy.

BiliCheck vs JM-103 in identifying neonates not at risk of hyperbilirubinaemia.

BACKGROUND: Transcutaneous bilirubinometry is widely used to predict hyperbilirubinemia by using several devices. The aim of this study was to compare the predictive ability of BiliCheck vs JM-103 in identifying neonates not at risk of significant hyperbilirubinemia, putting the data obtained with the two instruments on our transcutaneous bilirubin nomogram built with the BiliCheck. METHODS: Transcutaneous bilirubin (TcB) measurement was performed when jaundice appeared in newborn babies and/or just before discharge from the hospital. It was performed at the forehead with the two instruments within 5 minutes by two experienced neonatologists, each one blind to the value obtained by the other. Blood samples were drawn to obtain total serum bilirubin (TSB) levels soon after TcB measurements. RESULTS: A total of 627 paired-sample measurements were obtained from 298 newborn babies. Out of the total population studied, 16 newborn babies (5.4%) showed significant hyperbilirubinemia defined as TSB value >17 mg/dL, or as need for phototherapy treatment according to the AAP guidelines. TcB measurements showed false negative results in the first 60 hours of life using both devices. After the 60th hour of life, TcB measurements using both devices successfully predicted newborn babies not at risk of significant hyperbilirubinemia, being the JM-103 more reliable than BC because of fewer false positive results. CONCLUSIONS: Our study shows that both BC and JM-103 can exclude subsequent significant hyperbilirubinemia when the measurements are performed after the 60th hour of life. Nevertheless, the transcutaneous pre-discharge screening should be considered only as the first step, and it has to be followed by a follow-up through the first days after discharge.

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.

Transcutaneous bilirubin measurement: comparison of Respironics BiliCheck and JM-103 in a normal newborn population.

OBJECTIVES: To compare the accuracy of BiliCheck™ (Respironics, Marietta, GA) and Konica-Minolta Air Shield JM-103 (Drager Medical Inc, Telford, PA) to evaluate total serum bilirubin (TSB). METHODS: Prospective blinded study comparing two diagnostic devices in 630 neonates requiring TSB measurement. RESULTS: Linear regression analysis showed a good correlation between BiliCheck™ and TSB (r=0.8212) as well as between JM-103 and TSB (r=0.8686). BiliCheck shows a tendency to underestimate TSB. The mean difference in TSB-TcB was -1.4 mg/dL for BC (-4.7/+1.8 mg/dL) and 0.3 mg/dL for JM-103 (-2.6/+3.2mg/dL). ROC analysis for TSB≥ 12 mg/dL showed area under the curve for BiliCheck™ significantly lower than those for JM-103 (p<0.0001). JM-103 resulted less time expensive than BiliCheck. CONCLUSIONS: In spite of similar diagnostic accuracy JM-103 could be preferred for some practical advantages, but its suitability in performing universal screening for severe hyperbilirubinemia deserves further investigations.

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.

Ophthalmia neonatorum: what kind of prophylaxis?

OBJECTIVE: Conjunctivitis during neonatal period occurs in 1-12% of all babies. Ophthalmia neonatorum is an acute muco-purulent conjunctivitis occurring in the first month of birth. It is essentially an infection acquired during vaginal delivery. The most frequent infectious agents involved in ophthalmia neonatorum are Chlamydia trachomatis and Neisseria gonorrhoeae. METHODS: Topical ocular prophylaxis must be instituted early after birth. Recommended prophylactic regimen are: 1% nitrate solution; 1% tetracycline solution; 1% erythromycin solution; 2.5% povidone-iodine solution; and fusidic acid. RESULTS: Evidence suggests better outcomes using 1% tetracycline solutions even if there is the risk of selecting drug resistant bacteria. However, even the widespread used nitrate solution can cause a chemical conjunctivitis, arguing against its widespread use. CONCLUSIONS: Fusidic acid is a relatively new promising therapy even if there are still few data about its use. None of the used regimens has the optimal risk-benefit profile to suggest a widespread use.

Toward a bioethical issue: induced multiple pregnancies and neonatal outcomes.

Assisted reproductive technology has made great progress during the last three decades. After the initial enthusiasm, many ethical, legal and social issues related to the application of these procedures began to evolve. Multifetal pregnancy and fetal reduction, embryo cryopreservation, preimplantation genetic diagnosis, risks of birth defects and other adverse outcome associated with assisted reproductive technology are issues that have to be addressed building future collaborative studies and continuing the debate on related ethical issues.