A systematic review and meta-analysis of human population studies on the association between exposure to toxic environmental chemicals and left ventricular dysfunction (LVD).

BACKGROUND: Exposure to environmental chemicals has been associated with an elevated risk of heart failure (HF). However, the impact on early markers of HF, such as left ventricular dysfunction (LVD), remains limited. OBJECTIVE: To establish a foundation of evidence regarding early HF markers and their association with environmental pollutants, a systematic review and meta-analysis was conducted. METHODS: The search, conducted on October 13th, 2023, encompassed PubMed, Embase, and Web of Science without filters, focusing on observational studies reporting myocardial geometrical, structural, or functional alterations in individuals without a history of heart disease. This included the general adult population, workers, young people, and the elderly. The risk of bias was assessed using the ROBINS-I tool at both study and item levels. RESULTS: The systematic review included 17 studies involving 43.358 individuals exposed to air pollution and 2038 exposed to heavy metals. Approximately 41% of the effect measures of associations reported significant abnormalities in myocardial structure or function. The metanalyses by pollutants categories indicated positive associations between LV systolic and diastolic abnormalities and exposure to PM2.5 [-0.069 (-0.104, -0.033); -0.044 (-0.062, -0.025)] and PM10 [-0.055 (-0.087, -0.022); -0.030 (-0.050, -0.010)] and NO2 [-0.042 (-0.071, -0.013); -0.021 (-0.037, -0.004)], as well as positive associations between lead exposure and LV systolic abnormalities [-0.033 (-0.051, -0.016)]. CONCLUSIONS: Existing evidence shows that specific early markers of HF may be associated with exposure to chemical pollutants. It is recommended to include such endpoints in new longitudinal and case-control studies to confirm further risk associations. These studies should consider co-exposures, account for vulnerable groups, and identify cardiotoxic compounds that may require regulation. When examining the link between myocardial abnormalities and environmental exposure, it is also advisable to explore the supportive use of Adverse Outcome Pathway (AOP) approaches to confirm a causal relationship.

Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference.

Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.

Propranolol concentrations after oral administration in term and preterm neonates.

OBJECTIVE: While propranolol pharmacokinetics has been extensively studied in adults, this study reports the first evaluation of propranolol pharmacokinetics in term and preterm neonates. METHODS: Propranolol concentrations were measured in four term and 32 preterm newborns treated with oral propranolol at the dose of 0.5 or 0.25 mg/kg every 6 h by serial dried blood spots. RESULTS: The levels of propranolol, although with high inter-individual variability, were proportional with the administered dose. Pharmacokinetic parameters evaluated at the steady state in newborns treated with 0.5 mg/kg/6 h showed values of maximal (71.7 ± 29.8 ng/mL), minimal (42.2 ± 20.8 ng/mL) and average concentration (60.8 ± 25.0 ng/mL), time of maximal concentration (2.6 ± 0.9 h) and area under the time-concentration curve (364.7 ± 150.2 ng/mL/h) similar to those observed in adults. In both dosing groups, elimination half-life was significantly longer (14.9 ± 4.3 and 15.9 ± 6.1 h), and apparent total body clearance (27.2 ± 13.9 and 31.3 ± 13.3 mL/kg/min) lower than those reported in adults, suggesting a slower metabolism in newborns. No differences were observed between newborns with different gestational age or different sex. CONCLUSIONS: Neonates treated with propranolol-exhibited drug concentrations proportional with the dose, with significant long half-life.

Sildenafil as “first line therapy” in pulmonary persistent hypertension of the newborn?

Despite the recent advances, the clinical approach to persistent pulmonary hypertension of the newborn (PPHN) still represents an important challenge for neonatologists. The care of newborns with PPHN requires meticulous therapeutic and ventilation strategies including, besides the stabilization of the newborn, the use of nitric oxide and high-frequency ventilation. However, not all the neonates with PPHH are responsive to this clinical approach. Recent studies have proposed the use of sildenafil, a phosphodiesterase 5 inhibitor, in refractory forms of PPHN. The aim of this study is to review the cases and the clinical approach of PPHN in the Neonatal Intensive Care Unit of Meyer Children Hospital in the year 2009 and to discuss the possible role of sildenafil in the management of PPHN.

Insulin-resistant hyperglycaemia complicating neonatal onset of methylmalonic and propionic acidaemias.

BACKGROUND: Insulin-resistant hyperglycaemia may occasionally complicate the clinical course of organic acidaemias. STUDY DESIGN: Clinical observation. RESULTS: Two term infants, one suffering from acute early-onset methylmalonic acidaemia, the other suffering from acute early-onset propionic acidaemia, presented acutely with dehydration, ketoacidosis, and hyperammonaemia. Urinary organic acid, plasma amino acids, and blood and plasma acylcarnitine analysis allowed the diagnosis of methylmalonic and propionic acidaemias. The detection of the novel c.481G>A (p.Gly161Arg) and the known c.655A>T (p.Asn219Tyr) MUT gene mutations identified the first patient as affected by methylmalonic acidaemia mut type. The high increase of propionylcarnitine after carnitine administration in both patients suggested a greatly elevated metabolic intoxication. Both newborns showed insulin-resistant hyperglycaemia. Patient 1 died, but patient 2, after a strong reduction of glucose administration, survived. To our knowledge, this is the only patient with this complication who survived. CONCLUSION: Insulin-resistant hyperglycaemia complicating neonatal onset of methylmalonic and propionic acidaemias is probably a marker of a serious disease. One patient with this complication survived after a strong reduction of glucose administration. Even if this is probably only a partial intervention, we hypothesize that in this situation a reduction of glucose administration can reduce almost the risk of persistent hyperglycaemia. Further studies are required to confirm our hypothesis.

High-resolution cry analysis in preterm newborn infants.

Infant monitoring is a common procedure in clinical practice in neonatal critical care units. A number of vital functions are monitored, such as heart beat, breathing, blood flow, etc. Specifically, preterm and/or low-birth-weight infants often present respiratory problems that require monitoring. These may range from insufficient ventilation to apnoea. One of the most common events that may affect the respiratory flow is crying, a physiological action made by the infant to communicate and draw attention, but, for a preterm infant, this action requires great effort, which may cause distress and even may have an adverse impact on blood oxygenation. Acoustic analysis of newborn infant cry is thus of importance, since it is related to other basic neuro-physiological parameters. Being easy to perform, cheap and completely non-invasive, it can be successfully applied in many circumstances. The newborn infant cry is characterised by very high fundamental frequency (F(0)) and resonance frequency (RFs) values, with abrupt changes and voiced/unvoiced features of very short duration in a single utterance. To deal with such signals, a new user-friendly software tool has been developed, that allows robust tracking of main acoustic parameters on very short and time-varying signal frames. The software developed provides the user with a high-resolution picture of the cry signal characteristics.

Non-invasive distress evaluation in preterm newborn infants.

With the increased survival of very preterm infants, there is a growing concern for their developmental outcomes. Infant cry characteristics reflect the development and possibly the integrity of the central nervous system. In this paper, relationships between fundamental frequency (F(0)) and vocal tract resonance frequencies (F(1)-F(3)) are investigated for a set of preterm newborns, by means of a multi-purpose voice analysis tool (BioVoice), characterised by high-resolution and tracking capabilities. Also, first results about possible distress occurring during cry in preterm newborn infants, as related to the decrease of central blood oxygenation, are presented. To this aim, a recording system (Newborn Recorder) has been developed, that allows synchronised, non-invasive monitoring of blood oxygenation and audio recordings of newborn infant's cry. The method has been applied to preterm newborns at the Intensive Care Unit, A.Meyer Children Hospital, Firenze, Italy.

Comparison between pulse oximetry and transthoracic impedance alarm traces during home monitoring.

OBJECTIVE: To compare transthoracic impedance (TTI/ECG) and pulse oximetry alarm traces detected during home monitoring in infants at risk of apnoea, bradycardia and hypoxaemia. STUDY DESIGN: A retrospective evaluation of the monitor downloads of 67 infants who had undergone either TTI/ECG or pulse oximetry home monitoring using a device which can detect both parameters. METHODS: The patients were categorised as: apparent life-threatening events (n = 39), preterm infants (n = 21) and miscellaneous (n = 7). TTI/ECG and pulse oximetry alarm traces were scored as either true or false alarms. Classification criteria were based on visual analysis of the impedance and plethysmographic waveforms captured by the memory monitor every time alarm thresholds were violated. RESULTS: 5242 alarms occurred over 3452 days of monitoring: 4562 (87%) were false and 680 (13%) true. The mean duration of monitoring was 51 days (range 5-220 days). There were 2982 TTI/ECG false alarms (65% of the total) and 1580 pulse oximetry false alarms (35%) (p = 0.0042). Of the 680 true alarms, 507 (74%) were desaturations not attributable to central apnoea and 173 (26%) were true TTI/ECG alarms (p = 0.0013). CONCLUSIONS: Comparison of pulse oximetry and TTI/ECG alarm traces shows that true events were mostly attributable to desaturations, while false alarms were mainly provoked by TTI/ECG. The total number of false alarms is lower than reported in other studies using TTI/ECG only, thus indicating that monitoring using both pulse oximetry and TTI/ECG is suitable for home use. When the combination of both techniques is not feasible or not required, we recommend the use of motion resistant pulse oximetry alone.

[Intensive care at extremely low gestational age: ethical issues and treatment choices]. / Cure intensive nelle bassissime età gestazionali: riflessioni sulle basi etiche delle scelte assistenziali.

With the continuing progress of obstetrical and neonatal care, the limit of human viability has continued to shift towards younger gestational ages. The survival rate as well as the survival without disability increases with each additional week of gestation but, for infants born from 22 to 25 w GA, it is still really low, and the threshold of human viability appears to be limited to the physiological development of the lungs, which take place around the 23rd-24th w GA. At present, the care of such infants, born at the threshold of human viability, presents a variety of complex medical, social, and economical decisions assuming the characteristics of ethical decisions in that the limits between benefits and disadvantages is not so clearcut. What is the true infant's best interest is far to be understood and concern about the ethical basis of providing such intensive care is arising in the scientific community. In this paper the authors provide a review of the ethical basis of decisions related to the care of such infants: to treat, not to treat, intensive or compassionate care, withhold or withdraw treatment.

Polycyclic aromatic hydrocarbons (PAHs) in human milk from Italian women: influence of cigarette smoking and residential area.

The presence of PAH in breast milk collected from 32 smoking and non-smoking lactating women, residing in urban and rural areas of Tuscany (Italy) was investigated. The results indicated a significant contribution of tobacco smoke to the PAH contamination of milk: the condensate contained in the cigarettes smoked daily by each subject was strongly related with the polynuclear hydrocarbon content (R(2)=0.92, P<0.005). An experiment carried out under controlled exposure conditions to cigarette smoke allowed to demonstrate that individual metabolic activity and smoking habits affect the PAH concentration in milk samples. Mothers living in rural environments showed significantly lower PAH concentrations than those observed in urban subjects. The risk evaluation due to PAH ingestion via breast milk was assessed on the basis of the acceptable daily intake of Benzo(a)pyrene in drinking water, evidencing that a hazard cannot be excluded for heavy smokers residing in urban areas.

[Esophageal atresia with distal tracheo-esophageal fistula. Evolution of the treatment in the period of 1955-2000 at the Anna Meyer Children's Hospital of Florence]. / Atresia dell'esofago con fistola esofago-tracheale distale. Evoluzione del trattamento nel periodo 1955-2000 nell'Ospedale Pediatrico Anna Meyer di Firenze.

BACKGROUND: Over the past decades the esophageal atresia (EA) has represented the greatest challenging malformation encountered by the pediatric surgeon. Since then, there have been considerable advancements in the treatment of EA. In this paper the experience at the "Anna Meyer Children's Hospital of Florence" in regards to the surgical treatment of the EA from 1955 to present day is reported, so that the analysis of the various medical and surgical choices followed by the authors and their predecessors in this long period, can be an important learning tool for the EA management. METHODS: From 1955 to 2000, 223 newborns affected by EA with tracheoesophageal fistula (TEF) have been operated on out of a total of 250 cases of EA. Our experience has been subdivided into periods on the basis of homogeneous medical and surgical treatment adopted in that determined time. We have analyzed particularly the data of the last period 1995-2000, where there has been a well standardized protocol of treatment from the medical, surgical and intensive care points of view. RESULTS: The mortality rate has decreased from 44.8 to 3.4% with a significant reduction (p<0.001) between the years 1979-1983 and 1984-2000, due to the introduction of a perioperative treatment in the newborn intensive care unit. Moreover, a significant correlation (p<0.05) has been shown between low birthweight and associated malformations, two risk factors that however do not negatively influence the results of the treatment in the last period 1995-2000. CONCLUSIONS: A full integration between the surgeon and neonatologist is necessary in order to guarantee a good result. The risk connected to EA is not as much the surgical procedure as the presence or absence of associate malformations that are undetected in the prenatal diagnosis. It is suggested that, in order to further reduce the mortality and morbidity rate after EA correction, the number of prenatal diagnoses should be increased.

International Child Care Practices Study: infant sleeping environment.

BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Catch-up growth in short-at-birth NICU graduates.

The statural catch-up growth, defined as reaching at least tenth length/height percentile (P10) for normal population standards (-1.28 SD score, SDS), was studied in 73 infants short at birth (length < P10 for gestational age) admitted to NICU. Mean gestational age at birth was 35.2 weeks (range 29-41) and mean birth length standard deviation score -2.31 (-4.52/-1.46). Infants were measured at birth, at 3, 6, 12, 18, and 24 months corrected age and then once a year until 6 years chronological age. Statural catch-up growth was studied, with reference both to normal population standards and to individual genetic target. With reference to normal population standards, 44% of infants had caught-up at 3 months of age, 51% at 3 years, 66% at 4 years and 73% at 6 years. In the case of individual genetic targets, a similar trend was present, but the absolute values were slightly higher from 4 to 6 years (73 vs. 66% and 78 vs. 73%, respectively). Statistically significant changes in mean standard deviations score for chronological age were present from birth to 3 months, 3 to 12 months, 3 to 4 years and 5 to 6 years (p<0.05). No differences were found in this trend of recovery when considering ponderal index (PI) at birth (symmetrical vs. asymmetrical), sex (male vs. female) or gestational age (p>0.05). In the majority of cases infants with short stature at birth admitted to a NICU had a statural catch-up growth within the first years of life. This is more evident when considered in relation to individual genetic target rather than to normal population standards.

[Evaluation of cerebral oxygenation in newborns with prematurity apnea: new frequency domain NIR oximeter]. / Valutazione dell'ossigenazione cerebrale in neonati con apnea della prematurità: nuovo Ossimetro NIR nel dominio delle frequenze.

Near infrared spectroscopy (NIRS) is a non invasive, portable, safe technique for monitoring cerebral oxygenation and haemodynamics. A new frequency-domain tissue oximeter based on a multi-distance measurement protocol is presented. The effects of apneic episodes on cerebral and peripheral arterial oxygen saturation (SatO2) in preterm newborns, as monitored by NIRS and by pulse oximetry, are reported. The study population consist of 5 preterms (26 to 30 weeks of gestational age), in the second week of postnatal age, affected by apnea of prematurity. NIRS and pulse oximetric measurements were made contemporarily for a 40-minutes period for each infant. All monitorized apneic events were associated with bradicardia, and resolved spontaneously or after tactile stimulation. As results: a) there was always cerebral deoxygenation in association with apneic events, b) the mean SatO2 as measured by NIRS was slightly lower than the pulse oximeter readings, c) cerebral SatO2 decreased faster and the absolute value of the cerebral SaO2 decrease was greater than that measured peripherally (mean value of 27 versus 13%), d) increases of cerebral deoxyhemoglobin and total hemoglobin and a decrease of oxyhemoglobin were also observed. These preliminary results show that peripheral oxygen saturation measurements as measured by pulse oximetry could not always reflect brain oxygenation.

[Percutaneous catheterization of the newborn: control of pain and easy insertion with brachial plexus block]. / Cateterismo percutaneo nel neonato: controllo del dolore e facilità d'esecuzione col blocco del plesso brachiale.

The increasingly prolonged survival of extremely premature infants who required long-term venous access means that this is often a major problem in modern neonatal unit. The insertion of central venous catheters has become an established practice and the development of silastic catheters inserted by newer percutaneous techniques through a peripheral vein is, now, the choice technique in awake non sedated critically-ill infants. Such technique has an high percentage of failure. We have undertaken a retrospective study to determine whether the brachial plexus block performed via the axillary approach could improve the success rate for the insertion of central venous catheter from a peripheral vein of the upper limb in infants minimizing physical and emotional stress to the neonates. Data from 157 low and very low birthweight infants, submitted or not submitted to the axillary block, were examined. The failure rate for the insertion of the central venous catheter was 27% without using the brachial plexus block vs. 9% in the patients that underwent the block. Use of the brachial plexus block via the axillary route, although retrospectively evaluated, improves the success rate and the pain control for the insertion of small diameter central venous silicon catheter from a peripheral vein of the upper limb in low and very low birthweight infants.

Congenital conduction defects in children born to asymptomatic mothers with anti-SSA/SSB antibodies: report of two cases.

It is very difficult to identify pregnant asymptomatic mothers carrying anti-SSA/SSB antibodies. We report two cases of neonatal lupus erythematosus, born to asymptomatic mothers with anti-SSA/Ro antibody, who developed isolated complete congenital cardiac heart block and transient second degree conduction defect associated with cardiac abnormalities, respectively. The first died suddenly of acute myocarditis at the age of 20 months, while the second underwent surgery at the age of 10 years for a ventricular septal defect, after two episodes of second degree atrioventricular block in infancy. We believe that in both cases the diagnosis could have been made in utero after correct heart beat analysis. We propose careful monitoring of fetal heart beat in all pregnant mothers. The occurrence of heart beat modification should prompt clinicians to test the mother for antibody positivity. This approach may permit early diagnosis and in utero treatment in order to spare the child from cardiac conduction defects. We provide the evidence of these cases and propose a flow chart for all physicians dealing with pregnancy.