Luigi Gagliardi

Weight Growth Velocity and Postnatal Growth Failure in Infants 501 to 1500 Grams: 2000–2013

BACKGROUND: Very low birth weight infants often gain weight poorly and demonstrate growth failure during the initial hospitalization. Although many of the major morbidities experienced by these infants during their initial NICU stays have decreased in recent years, it is unclear whether growth has improved. METHODS: We studied 362 833 infants weighing 501 to 1500 g without major birth defects born from 2000 to 2013 and who were hospitalized for 15 to 175 days at 736 North American hospitals in the Vermont Oxford Network. Average growth velocity (GV; g/kg per day) was computed by using a 2-point exponential model on the basis of birth weight and discharge weight. Postnatal growth failure and severe postnatal growth failure were defined as a discharge weight less than the 10th and third percentiles for postmenstrual age, respectively. RESULTS: From 2000 to 2013, average GV increased from 11.8 to 12.9 g/kg per day. Postnatal growth failure decreased from 64.5% to 50.3% and severe postnatal growth failure from 39.8% to 27.5%. The interquartile ranges for the hospitals participating in 2013 were as follows: GV, 12.3 to 13.4 g/kg per day; postnatal growth failure, 41.1% to 61.7%; and severe postnatal growth failure, 19.4% to 36.0%. Adjusted and unadjusted estimates were nearly identical. CONCLUSIONS: For infants weighing 501 to 1500 g at birth, average GV increased and the percentage with postnatal growth failure decreased. However, in 2013, half of these infants still demonstrated postnatal growth failure and one-quarter demonstrated severe postnatal growth failure.

Necrotising Enterocolitis in Very Low Birth Weight Infants in Italy: Incidence and Non-nutritional Risk Factors

Incidence and non-nutritional risk factors were estimated for necrotising enterocolitis in 2035 very low birth weight infants, admitted to 14 tertiary-level neonatal intensive care units in Lombardy, northern Italy. There were 62 necrotising enterocolitis cases, with an overall incidence of 3.1%. After adjustment for gestational age and centre, the risk factors were mechanical ventilation, patent ductus arteriosus, and late-onset sepsis, whereas surfactant treatment was associated with decreased risk. Significant variations in necrotising enterocolitis incidence among hospitals were found.

Clinical pharmacology of netilmicin in preterm and term newborn infants

Sixty-four neonates, with gestational age ranging from 27 1/2 to 40 weeks, postnatal age from 1 to 15 days, and birth weight from 800 to 3400 gm, were given netilmicin 2.5 mg/kg intramuscularly two or three times per day according to postnatal age, for 5 to 14 days. Serum concentrations were measured before and 1 hour after a dose at least twice during treatment. The serum washout profile of the drug was observed in 22 neonates after discontinuation of therapy. Renal function was studied in 37 infants by measuring serum creatinine concentrations and in 27 by urinary excretion of N-acetyl-glucosaminidase during and up to 15 days after therapy. Behavioral and impedance audiometry, and in infants failing those, auditory brainstem evoked response tests, were performed between 6 and 12 months of age. In 23.5% of the neonates, trough serum levels were greater than 3 micrograms/ml. The serum washout followed a multiexponential decay, accounting for distributional, rapid (initial), and slow (tissue) elimination phases. Linear regression analysis performed between each kinetic parameter and gestational age or birth weight showed that initial elimination half-life, steady-state volume of distribution, and total body clearance were significantly correlated with both variables. Netilmicin did not cause detectable renal or auditory damage.

Anxious and depressive components of Edinburgh Postnatal Depression Scale in maternal postpartum psychological problems1)

Abstract Background: The Edinburgh Postnatal Depression Scale (EPDS) is a widely used instrument for screening for postpartum depression, but it might also detect anxiety symptoms. Objective: To investigate the factor structure of the EPDS administered immediately after delivery and to understand which factors predict a high EPDS score 3 months later. Methods: A cohort of 594 Italian mothers delivering a healthy baby at Versilia Hospital completed the EPDS at two points in time: 2 days after delivery (T0) and 3 months later (T1) by telephone interview. Results: EPDS scores were higher at T0 than at T1. Overall, 15.7% of women at 2 days postpartum and 7.6% at 3 months later reported a score >9. The factor analysis of EPDS at T0 indicated a three-factor structure: “depression” (items 7–10), “anxiety” (items 3–6) and “anhedonia” (items 1–2). Anxious symptoms were quantitatively more important than depressive ones (mean 3.9 vs. 1.2) but tended to spontaneously ameliorate at T1, whereas total EPDS score at T1 was better predicted by depressive symptoms at T0 (discriminative ability 0.75 vs. 0.68). Conclusions: This study suggests that EPDS subscales immediately after delivery help understand the spectrum of maternal postpartum psychological problems. Anxious symptoms immediately after delivery are frequent but transient, linked probably to maternity blues or atypical depression, whereas the presence of depressive symptomatology at T0 suggests higher risk of later depressive disorders.

Bronchopulmonary dysplasia and brain white matter damage in the preterm infant: a complex relationship

We analysed the relationship between bronchopulmonary dysplasia (BPD) and brain white matter damage (WMD) in very preterm infants, adjusting for common risk factors and confounders. We studied a cohort of infants <32 weeks gestational age (GA) and <1500 g, admitted to 12 hospitals in Northern Italy in 1999-2002. The association between BPD and WMD was estimated by generalised estimating equations and conditional logistic models, adjusting for centre, GA, propensity score for prolonged ventilation and other potential confounders. Directed acyclic graphs (DAG) were used to depict the underlying causal structure and guide analysis. Of the 1209 infants reaching 36 weeks, 192 (15.8%) developed BPD (supplemental oxygen at 36 weeks) and 88 (7.3%) ultrasound-defined WMD (cystic periventricular leukomalacia). In crude analysis, BPD was a strong risk factor for WMD [odds ratio (OR) = 5.9]. With successive adjustments, the OR progressively decreased to 3.88 when adjusting for GA, to 2.72 adding perinatal risk factors, and further down to 2.16 [95% confidence interval 1.1, 3.9] when ventilation was also adjusted for. Postnatal factors did not change the OR. Significant risk factors for WMD, in addition to BPD, were a low GA, a lower Apgar score, a higher illness severity score, ventilation and early-onset sepsis, while antenatal steroids, being small for GA, and surfactant were associated with a reduced risk. In conclusion, our data suggest that BPD is associated with an increased risk of WMD; most of the effect is due to shared risk factors and causal pathways. DAGs helped clarify the complex confounding of this scenario.

Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus

The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long‐term pulmonary and/or neurosensory outcomes reported moderate‐to‐low predictive values regardless of the BPD criteria.

Respiratory rate and body mass in the first three years of life

The correlation between respiratory rate and body mass in the first three years of life was examined in 635 infants and children, aged between 15 days and 3.5 years. Assessments were made during quiet sleep and when awake and calm. Their body weight (2.8-20.5 kg) was measured at the same time.  Respiratory rate decreased exponentially with increasing body weight. After log transformation of the data, a linear correlation was found between log(respiratory rate) and log(body weight) both during the sleeping and the wakeful states. For each body weight group, boys had about a 6.5% higher respiratory rate than girls, but both the boys’ and the girls’ lines were parallel. The slope of the line was -0.43 during sleep and -0.41 during wakefulness, indicating that the respiratory rate: body weight ratio is not a constant in either state, and that it decreases as body weight increases. Adding age to the model did not significantly increase the precision of the fitting.  A simple equation of the form respiratory rate=a·body weightb, can accurately describe the decrease in respiratory rate with growth. Smaller (hence younger) infants and children have a higher respiratory rate per unit body weight than larger (hence older) children.

Changes in ventilator strategies and outcomes in preterm infants

Background Although life-saving, intubation and mechanical ventilation can lead to complications including bronchopulmonary dysplasia (BPD). In order to reduce the incidence of BPD, non-invasive ventilation (NIV) is increasingly used. Objective The aim of our study was to describe changes in ventilator strategies and outcomes between 2006 and 2010 in the Italian Neonatal Network (INN). Design Multicentre cohort study. Settings 31 tertiary level neonatal units participating in INN in 2006 and 2010. Patients 2465 preterm infants 23–30 weeks gestational age (GA) without congenital anomalies. Main outcomes measures Death, BPD and other variables defined according to Vermont Oxford Network. Logistic regressions, adjusting for confounders and clustering for hospitals, were used. Results Similar numbers of infants were studied between 2006 and 2010 (1234 in 2006 and 1231 in 2010). The baseline risk of populations studied (GA, birth weight and Vermont Oxford Network Risk-Adjustment score) did not change. After adjusting for confounding variables, infants receiving invasive mechanical ventilation decreased (OR=0.72, 95% CI 0.58 to 0.89) while NIV increased (OR=1.75, 95% CI 1.39 to 2.21); intubation in delivery room decreased (OR=0.64, 95% CI 0.51 to 0.79). Considering outcomes, there was a significant reduction in mortality (OR=0.73, 95% CI 0.55 to 0.96) and in the combined outcome mortality or BPD (OR=0.76, 95% CI 0.62 to 0.94). Conclusions Despite a stable baseline risk, from 2006 to 2010, we observed a lower level of invasiveness, a reduction of mechanical ventilation and an increase of NIV use, and this was accompanied by a decrease in risk-adjusted mortality and BPD.

Do differences in delivery room intubation explain different rates of bronchopulmonary dysplasia between hospitals

Objective To investigate whether the wide variation in the frequency of bronchopulmonary dysplasia (BPD) between hospitals is due to differences in delivery room intubation rates. Methods Data on 1260 infants of birth weight <1500 g and 23–31 weeks gestational age, born in 1999–2002 and surviving to 36 weeks, were collected; 196 (15.6%) developed BPD defined as oxygen need at 36 weeks postmenstrual age. Generalised estimating equations and conditional logistic models adjusting for centre, gestational age, propensity score for intubation, and other potential confounders were used. Results Rates of BPD, delivery room intubation and mechanical ventilation for >24 h differed significantly between hospitals. Centres with high delivery room intubation rates had higher ventilation and BPD rates. Hospitals ventilating more often also did so for a longer time. Although delivery room intubation was associated with BPD in unadjusted analyses, neither delivery room intubation nor brief (<24 h) mechanical ventilation were risk factors for BPD in multivariate analyses adjusting for gestational age, case mix and other pre- and perinatal factors, indicating no causal effect or unmeasured confounding. Significant risk factors for developing BPD were low gestational age, prolonged ventilation (>24 h: adjusted OR (aOR) 2.4; >7 days: aOR 14.9), male sex (aOR 1.7), being small for gestational age (SGA; aOR 4.3) and late-onset sepsis (aOR 2.2). After taking into account these variables/procedures, centre differences remained significant but explained only about 5% of variance. Conclusions Differences in BPD frequency between hospitals are explained by differences in procedures, chiefly mechanical ventilation, rather than by differences in initial management or case mix. Delivery room intubation and brief mechanical ventilation did not increase BPD risk.

Symptoms of maternal depression immediately after delivery predict unsuccessful breast feeding

Objective Postnatal depression may interfere with breast feeding. This study tested the ability of the Edinburgh Postnatal Depression Scale (EPDS) to predict later breast feeding problems, hypothesising that risk of unsuccessful breast feeding increased with increasing EPDS scores, even at low values. Design The authors administered the EPDS on days 2–3 after delivery to 592 mothers of a healthy baby. Feeding method was recorded at 12–14 weeks. Results Median EPDS score was 5 (IQR 2 -8); 15.7% of women scored >9. At 12–14 weeks, 50.7% of infants received full breast feeding, 21.0% mixed breast feeding and 28.4% bottle feeding. Mothers with higher EPDS scores were more likely to bottle feed at 3 months; the odds of bottle feeding increased with EPDS result, even at low scores (OR 1.06, 95% CI 1.01 to 1.11). Conclusions Higher EPDS scores immediately after delivery were associated with later breast feeding failure.