Pattern of drug use among preterm neonates: results from an Italian neonatal intensive care unit.

BACKGROUND: Drug use in preterm neonates admitted to Neonatal Intensive Care Unit (NICU) has been investigated, so far, in terms of unauthorized or off-label use; very little is known on the use of combinations of different active substances, which is frequently required in this population (prophylaxis of infections, treatment of concomitant diseases). The aim of this study was to describe the most common patterns of drug use in an Italian NICU, focusing on those with nephrotoxic potential. METHODS: Medical records of preterm neonates (<37 weeks of gestational age) weighing less than 1,500 g at birth and admitted to an Italian NICU were scrutinized in a 3-year retrospective investigation. Analysis included drug exposure, duration of therapies, co-administration of drugs with potential renal side effects; also daily protein supplement was calculated from parenteral nutrition. RESULTS: A cohort of 159 preterm neonates was selected; 68 were born weighing less than 1,000 g (extremely low birth weight infants, ELBW, Group A), 91 weighed between 1,000 and 1,500 g at birth (Group B). Compared to Group B, neonates of Group A were more likely to receive pharmacological treatments: the most used drugs were antibiotics (especially ampicillin and amikacin, p = .07 and p < .001, respectively), antifungals (especially fluconazole, p < .001), and diuretics (especially furosemide, p < .001). Analysis of co-administration of drugs with potential nephrotoxicity showed ampicillin and amikacin as the most reported combination (94.1% of Group A and 31.9% of Group B), the combination of furosemide with antibacterials (ampicillin or amikacin) was also frequently reported, with average period of combination shorter than 2 days. CONCLUSIONS: ELBW infants were exposed to a higher number of drugs compared to other neonates and were more likely to receive associations of drugs with nephrotoxic potential (e.g. furosemide and amikacin), though only for short cycles. Further studies should evaluate the safety profile (especially potential renal side effects) related to most commonly used combinations.

Comparison of two different neonatal skin care practices and their influence on transepidermal water loss in healthy newborns within first 10 days of life.

AIM: Physiologic post-partum skin adaptation to the relative dry extra-uterine environment is a dynamic process which begins immediately after birth. Considering the differences from adult skin, the neonatal skin is more prone to damage by environmental factors; therefore, skin care regimens should be age adapted to ensure a good epidermal maturation. The effects of two different skin care practices were evaluated by transepidermal water loss (TEWL) measurement in 94 newborns aged ≤ 10 days: group 1 (G1), newborns washed only with a cotton washcloth moistened with water; group 2 (G2), newborns washed with liquid baby cleansers and hydrated with moisturizers. These recordings were compared to TEWL baseline values of the same neonates and to adults' values. METHODS: A prospective study was conducted in healthy full-term newborns, measuring TEWL with TEWAMETER® TM300. The areas tested were the volar forearm and the popliteal fossa. RESULTS: In G1 (52 subjects), TEWL mean values were 6.65 ± 2.81 SD (g/m2/h) at volar forearm and 7.49 ± 2.47 SD (g/m2/h) at popliteal fossa. In G2 (42 subjects), TEWL mean values were 8.83 ± 3.05 SD (g/m2/h) at volar forearm and 10.18 ± 3.64 SD (g/m2/h) at popliteal fossa. There were statistically significant differences of TEWL mean values between G1 and G2, newborns and adults, baseline and post-skin care procedures. CONCLUSION: Tested skin care regimens could influence the process of functional adaptation of skin, in the early postnatal period. We could hypothesize that daily washing with liquid baby cleansers and moisturizing may delay the natural maturation of skin barrier function.

Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling.

INTRODUCTION: MRI, proton magnetic resonance spectroscopy (¹H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on ¹H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). METHODS: Twenty infants treated with BC underwent conventional MRI and (1)H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. RESULTS: Adverse outcome was observed in 6/20 newborns. Both ¹H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100% PPV and 93% NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91%, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. CONCLUSION: Selective BC in HIE neonates does not affect the early and accurate prognostic value of ¹H-MRS and DTI, which outperform conventional MRI.

Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

[Skin antisepsis in premature infants]. / Problemi di antisepsi nei neonati prematuri.

In some premature newborns, 7 months old and with less than 1 kg of body wheight, total parenteral nutrition is used for weeks, so that good antiseptics can cooperate to the prevention of nosocomial infections, associating the best biocide effects to the best topical tolerability. Details are reported on the biocide cutaneous properties of some chloro-derivates, as sodium hypochlorite and NaDCC, of ethyl and propyl alcohols, of chlorhexidine, of iodophors and also of triclosan and octenidine (even if these latter biocids are not normally available in Italy as cutaneous antiseptics).

The efficacy of sodium alginate (Gaviscon) for the treatment of gastro-oesophageal reflux in preterm infants.

BACKGROUND: Gastro-oesophageal reflux is common in preterm newborns; at present, no studies have evaluated the efficacy of sodium alginate in this population. AIM: To evaluate the effect of sodium alginate on gastro-oesophageal reflux features in preterm newborns by combined pH and impedance monitoring (pH-MII). METHODS: Thirty-two symptomatic preterm newborns underwent a 24 h pH-MII, during which each baby was fed eight times. Sodium alginate was given four times at alternate meals [drug-given (DG) vs. drug-free (DF) meals]. Gastro-oesophageal reflux features (i.e. number, acidity, duration and height of gastro-oesophageal reflux) after DG and DF meals were compared by Wilcoxon signed ranks test. RESULTS: Sodium alginate significantly decreased the number of acid gastro-oesophageal reflux detected either by pH monitoring (DG vs. DF: median 17.00 vs. 29.00, P = 0.002) and MII (DG vs. DF: 4.0 vs. 6.00, P = 0.050), and also acid oesophageal exposure (DG vs. DF: 4.0% vs. 7.6%, P = 0.030), without any influence on non-acid gastro-oesophageal reflux. Furthermore, it decreased the number of gastro-oesophageal reflux reaching proximal oesophagus (DG vs. DF: 5.50 vs. 7.50, P = 0.030). CONCLUSIONS: The use of sodium alginate in preterm infants seems to be promising, because this drug decreases gastro-oesophageal reflux acidity and height with the advantage of a nonsystemic way of action and a more favourable safety profile over H2 blockers and PPIs.

The frequency of apneas in very preterm infants is increased after non-acid gastro-esophageal reflux.

BACKGROUND: To evaluate whether physical and/or chemical features of gastro-esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP). METHODS: Fifty-eight preterm newborns (GA ≤ 33 weeks) with recurrent apneas were studied by simultaneous polysomnography and combined impedance and pH monitoring, to analyze whether the correlation between GER and AOP varies according to the acidity, duration and height of GERs. KEY RESULTS: The frequency of apnea (number apnea/min) occurring after-GER [median (range) 0.07 (0-0.25)] was higher than the one detected in GER-free period [0.06 (0.04-0.13), P = 0.015], and also than the one detected before-GER [0 (0-0.8), P = 0.000]. The frequency of apneas detected in the 30'' after pH-GER [median (range), 0 min(-1) (0-1.09)] was higher than the frequency detected in the 30'' before [0 (0-0.91), P = 0.04]; even more, the frequency of apneas detected after non-acid MII-GER episodes [0 (0-2)] was significantly higher than the one detected before [0 (0-1), P = 0.000], whereas the frequency of apneas detected before acid MII-GER episodes [0 (0-0.67)] did not differ from the one detected after [0 (0-2), P = 0.137]. The frequency of pathological apneas detected in the 30'' after-GER (0 min(-1), range 0-0.55) was higher than the frequency detected before (0, range 0-0.09; P = 0.001). No difference in mean height or in mean duration was found between GERs correlated and those non-correlated to apnea. CONCLUSIONS & INFERENCES: Non-acid GER is responsible for a variable amount of AOP detected after-GER: this novel finding must be taken into consideration when a therapeutic strategy for this common problem is planned.

The effect of gestational age on developmental outcomes: a longitudinal study in the first 2 years of life.

BACKGROUND: Extremely low and very low gestational age (ELGA and VLGA) constitutes a risk factor for development even in absence of cerebral damage, as an immature central nervous system is exposed to invasive and inadequate stimulation. We tested the hypothesis that GA impacts developmental outcomes and trajectories of preterms without major cerebral damage in the first 2 years of life, expecting poorer developmental outcomes and higher rate of impairment with the decreasing of GA. We also evaluated whether GA, together with developmental outcomes in the first year of life, was related to developmental outcomes at 24 months. METHODS: Eighty-eight infants, divided into three GA groups (ELGA: ≤28 weeks; VLGA: 29-32 weeks; full term: >37 weeks) were assessed longitudinally at 6, 12, 18 and 24 months using the Griffiths Mental Development Scales. RESULTS: Use of a repeated measure multivariate analysis of variance resulted in several significant findings. GA was associated with the developmental quotient (DQ) scores (P= 0.006); and locomotor (P < 0.001), eye and hand co-ordination (P= 0.016) and performance (P= 0.040) sub-scale quotient (SQ) scores; age of evaluation was also associated with DQ scores (P= 0.002), and locomotor (P < 0.001) and performance (P < 0.001) SQ scores. In particular, ELGAs exhibited lower DQ and SQ scores compared with the VLGA and full-term groups; some ELGAs showed mild, moderate or severe cognitive impairments, while few VLGAs mild impairments. Linear regression analysis showed that GA (P= 0.034) and 12-month developmental outcome (P < 0.001) were related to 24-month developmental outcome. CONCLUSIONS: Different developmental trajectories emerged in relation to GA, with poorer developmental outcomes and higher rates of impairment in ELGAs and few mild impairments in VLGAs. The relevance of taking into account both GA and repeated assessments in the first 2 years of life was shown.

Hospitalization for lower respiratory tract disease in preterm infants: effects of prophylaxis with palivizumab.

To evaluate the effect of palivizumab prophylaxis on hospitalization for acute respiratory tract infections (RTI) in preterm infants, a prospective study was performed on a cohort of preterm infants [gestational age (GA) <32 weeks], admitted at birth to a Neonatology Intensive Care Unit (NICU) (follow-up: 30-month after discharge). 154 palivizumab-recipients and 71 palivizumab-non-recipients were evaluated. During follow-up, a similar rate of hospitalization for RTI was found in the two groups (11.3% in palivizumab-non-recipients and 15.58% in palivizumab-recipients, p=0.39). However, when only infants hospitalized during their first respiratory syncytial virus (RSV) epidemic season and with a chronological age <6 months at admission were considered, the incidence rates for hospitalization was six-fold lower in the palivizumab-recipients (p=0.007). This study contributes to the definition of epidemiological data on RTI among preterm infants in Italy. These data support the usefulness of palivizumab prophylaxis for prevention of hospitalization for RTI in young preterm infants during the expected RSV epidemic season.

Combined oesophageal impedance-pH monitoring in preterm newborn: comparison of two options for layout analysis.

Gastro-oesophageal reflux (GOR) is common in preterm infants. Combined multichannel intraluminal impedance and pH monitoring (pH-MII) is emerging as an useful tool to study both acid and non-acid GOR in this population. We aimed to highlight main advantages and limits of pH-MII in preterm infants and to test whether the inclusion of GOR episodes detected only by pH monitoring details better the features of GOR. Fifty-two symptomatic preterm infants underwent a 24-hour, continuous and simultaneous measurement of pH-MII. Each layout was analyzed using two different options: option 1 included GOR episodes detected by MII and then classified as acid or non-acid according to the associated pH change; option 2 included GOR episodes detected by MII and also GOR episodes detected only by pH sensor. By adopting option 1, a total number of 2834 GOR episodes was detected by MII: 2162 of them were characterized as non-acid and 672 were characterized as acid. The median (range) number of acid MII-GOR episodes was 10 (1-52); the median (range) number of non-acid MII-GOR episodes was 36.5 (2-119). Median (range) acid MII-GOR-bolus exposure index was 0.28% (0.02-2.73%); median (range) non-acid MII-GOR-bolus exposure index was 1.03% (0.06-38.15%). By adopting option 2, an average of 53.2 acid GOR episodes and an average of 11% oesophageal exposure to acid GOR more than by option 1 was detected. An accurate and detailed description of GOR in preterm infants can be obtained only by including in the analysis all acid GOR episodes detected by pH sensor.

Influence of gestational age on the EDIN score: an observational study.

BACKGROUND AND AIM: Hospitalised neonates, particularly if preterm, may be exposed to prolonged pain. At present the only validated scale to assess prolonged pain in preterms is the EDIN (Echelle Douleur Inconfort Nouveau-Né) scale. Gestational age has been shown to influence the response of infants to acute pain but its potential effect in the setting of prolonged pain has not been investigated. The aim of the present study was to evaluate whether neonatal maturity as expressed by gestational age and/or postnatal age influences their expression of prolonged pain. METHODS: In a 1 year period, 84 neonates (gestational age 25-41 weeks), referred to the authors' neonatal intensive care unit were evaluated using the EDIN scale two to three times a day (1571 scores). The EDIN scores were categorised as indicative (>6) or not indicative (< or =6) of pain. Gestational age and postnatal age were included in a logistic regression analysis along with some painful situations and analgesic treatment to identify the impact on the EDIN scores. RESULTS: Logistic regression analysis showed that the EDIN scores were positively associated with gestational age (odds ratio 1.166; 95% CI 1.123 to 1.211). Postnatal age, sepsis and presence of respiratory support also influenced the EDIN score. CONCLUSIONS: Gestational age influences expression of prolonged pain. Content validity of the EDIN scale could be improved by adding categories for gestational age and attributing higher basal scores to less mature newborns.

Gastro-oesophageal reflux increases the number of apnoeas in very preterm infants.

OBJECTIVE: To document the existence of a relationship between apnoea of prematurity (AOP) and gastro-oesophageal reflux (GER) in preterm infants. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-six preterm infants (gestational age < or =32 weeks) with recurrent apnoeas. INTERVENTION: Simultaneous and synchronised recording of polysomnography and pH-impedance monitoring (pH-MII). Polysomnography detects and characterises apnoeas, by recording of breathing movement, nasal airflow, electrocardiogram and pulse oximeter saturation. pH-MII is the state-of-the-art methodology for GER detection in preterm newborns. MAIN OUTCOME MEASURES: Relationship between AOP and GER, which were considered temporally related if both started within 30 seconds of each other. RESULTS: One hundred and fifty-four apnoeas out of 1136 were temporally related to GER. The frequency of apnoea during the 1-minute time around the onset of GER was significantly higher than the frequency detected in the GER-free period (p = 0.03). Furthermore, the frequency of apnoea in the 30 seconds after GER (GER-triggered apnoeas) was greater than that detected in the 30 seconds before (p = 0.01). A great inter-individual variability was documented in the proportion of GER-triggered apnoeas. A strong correlation between total number of apnoeas and the difference between apnoeas detected 30 seconds after and before GER was found (p = 0.034). CONCLUSIONS: Our data show that a variable rate of apnoeas can be triggered by GER in very preterm infants. Further studies are needed to recognise clinical features that identify those patients who are more susceptible to GER-triggered apnoeas.

Antenatal syphilis serology in pregnant women and follow-up of their infants in northern Italy.

Positive syphilis serology was noted in 119 (0.49%) of the 24 053 pregnant women delivering at St Orsola Hospital in Bologna, Italy, from November 2000 through July 2007. Six presumptive cases of congenital syphilis with IgM western blot positive results were found. Two infants had a positive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory test result (one also had a positive CSF PCR result), another presented long-bone lesions, and the remaining three were preterm. These observations confirmed that antenatal syphilis screening facilitates treatment during pregnancy and offsets vertical transmission; moreover, the use of IgM western blot and careful CSF examination allowed the identification and treatment of high-risk newborns.

Environmental factors associated with stress in mothers of preterm newborns.

AIM: In this study the effects of environmental and structural features of two different neonatal intensive care unit (NICU) settings on the time course of psychological distress in mothers of preterm infants were investigated. METHODS: Levels of psychological distress in 21 mothers of premature infants hospitalized in the NICU of the Salesi Hospital were compared with levels of psychological distress in 21 mothers of premature infants from the NICU of the Sant'Orsola Hospital at three different times during hospitalization. RESULTS: Data showed that mothers from the NICU of the Salesi Hospital, where there is no presence of any specialized figure and the access for parents to the unit is ruled by time schedules, reported higher levels of psychological distress than mothers from the NICU of the Sant'Orsola Hospital, characterized by the continuous presence and contact with the medical staff, which included physiotherapists and clinical psychologists, and free access to the unit for parents. Moreover, levels of psychological distress increased over time in mothers from the Salesi Hospital while levels of distress decreased or were simply maintained over time in mothers from the Sant'Orsola Hospital. CONCLUSIONS: The present findings suggest that providing mothers with the opportunity of discussing the infant's clinical state with health professionals and receiving psychological support on a regular basis may reduce stressful feelings.

Near-infrared reflectance analysis to evaluate the nitrogen and fat content of human milk in neonatal intensive care units.

OBJECTIVE: To validate near-infrared reflectance analysis (NIRA) as a fast, reliable and suitable method for routine evaluation of human milk's nitrogen and fat content. SETTING: One neonatal intensive care unit. PATIENTS: 124 samples of expressed human milk (55 from preterm mothers and 69 from term mothers). INTERVENTION: Measurement of nitrogen and fat content by NIRA and traditional methods (Gerber method for fat and Kjeldahl method for nitrogen). MAIN OUTCOME MEASURES: Agreement between NIRA and traditional methods. Variability in fat and nitrogen content of human milk. RESULTS: A strong agreement was found between the results of traditional methods and NIRA for both fat and nitrogen content (expressed as g/100 g of milk) in term (mean fat content: NIRA = 2.76; Gerber = 2.76; mean nitrogen content: NIRA = 1.88; Kjeldahl = 1.92) and preterm (mean fat content: NIRA = 3.56; Gerber = 3.52; mean nitrogen content: NIRA = 1.91; Kjeldahl = 1.89) mothers' milk. Nitrogen content of the milk samples, measured by NIRA, ranged from 1.18 g/100 g to 2.71 g/100 g of milk in preterm milk and from 1.48 g/100 g to 2.47 g/100 g in term milk; fat content ranged from 1.27 g/100 g to 6.23 g/100 g of milk in preterm milk and from 1.01 g/100 g to 6.01 g/100 g of milk in term milk. CONCLUSION: NIRA can be used as a quick and reliable tool for routine monitoring of macronutrient content of human milk and for devising individualised human milk fortification regimens in the feeding of very premature infants.

Is the ABC pain scale reliable for premature babies?

AIM: We recently developed the ABC scale to assess pain in term newborns. The aim of the present study was to assess the reliability of the scale in preterm babies. MATERIAL AND METHODS: The scale consists of three cry parameters: (a) pitch of the first cry, (b) rhythmicity of the bout of crying and (c) cry constancy. Changes in these parameters were previously found to distinguish medium and high levels of pain as evaluated by spectral analysis of crying. We enrolled 72 babies to perform the steps usually requested to validate a scale, namely the study of the concurrent validity, specificity and sensibility. Moreover, we assessed the interjudge reliability and the clinical utility and ease of the scale. RESULTS: A good correlation (r = 0.68; r(2)= 0.45; p < 0.0001) was found between scores obtained with the ABC scale and the premature infant pain profile (PIPP) scale, demonstrating a good concurrent validity. The scale also showed good sensitivity and specificity (we found statistically significant differences between mean values of scores obtained in babies who underwent pain and babies who underwent non-painful stimulus.) Interobserver reliability was good: Cohen's kappa = 0.7. CONCLUSION: The good correlation between the two scales shows that the ABC scale is also reliable for premature babies.

Prenatal syphilis infection is a possible cause of preterm delivery among immigrant women from eastern Europe.

OBJECTIVE: to evaluate the prevalence of maternal syphilis at delivery and neonatal syphilis infection in an Italian urban area, in connection with the increased flow of immigration. STUDY DESIGN: A prospective surveillance study was carried out in Bologna, Italy, from November 2000 to March 2006. All pregnant women were screened for syphilis at delivery. Infants born to seropositive mothers were enrolled in a prospective follow-up. RESULTS: During the study period 19,205 women gave birth to 19,548 infants. A total of 85 women were seropositive for syphilis at delivery. The overall syphilis seroprevalence in pregnant women was 0.44%, but it was 4.3% in women from eastern Europe and 5.8% in women from Central-South America. Ten women were first found positive at delivery, as they did not receive any prenatal care. Nine of these were from eastern Europe. All their infants were asymptomatic, but six had both reactive immunoglobulin (Ig)M western blot and rapid plasma reagin tests and were considered prenatally infected. Three of six were preterm (gestational age <37 weeks). CONCLUSIONS: In Italy, congenital syphilis infection is strictly related to immigration from eastern Europe. Although it is asymptomatic, it could cause premature delivery. Therefore, it is necessary to perform serological tests during the third trimester in mothers coming from endemic areas to adequately treat syphilis in pregnancy and prevent congenital infection. If the mother's test results are not available at delivery, it is necessary to investigate the newborn, especially if it is born prematurely.

Diffuse and severe ischemic injury of the extremities: a complication of umbilical vein catheterization.

We report a case of severe, peripheral, and diffuse tissue ischemia after umbilical vein catheterization (UVC) in a preterm newborn born to a preeclamptic mother. Nitroglycerin ointment was used to treat lesions. The recovery was good but partial loss of the distal phalange of one finger and one toe occurred. This is the first report of peripheral vasospasm occurring after UVC. Topical nitroglycerin, traditionally used to treat peripheral artery catheter-induced ischemic injury, may be useful to treat the same lesions occurring after UVC.