Vincenzo Zanardo

Neonatal respiratory morbidity risk and mode of delivery at term: influence of timing of elective caesarean delivery

Aim: To establish whether the timing of delivery between 37 + 0 and 41 + 6wk gestation influences neonatal respiratory outcome in elective caesarean delivery, following uncomplicated pregnancy, thus providing information that can be used to aid planning of elective delivery at term. Methods: All pregnant women who were delivered by elective caesarean delivery at term during a 3‐y period were identified from a perinatal database and compared retrospectively with pregnant women matched for week of gestation, who were vaginally delivered. Maternal characteristics, neonatal outcome, incidence of respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN) were analysed. During this time, 1284 elective caesarean section deliveries occurred at or after 37 + 0 wk of gestation. Results: Neonatal respiratory morbidity risk (odds ratio, OR), including RDS and TTN, was significantly higher in the infant group delivered by elective caesarean delivery compared with vaginal delivery (OR 2.6; 95% CI: 1.35–5.9; p < 0.01). While TTN risk in caesarean delivery was not increased (OR 1.19; 95% CI: 0.58–2.4; p > 0.05), the RDS risk was significantly increased (OR 5.85; 95% CI: 2.27–32.4; p < 0.01). This RDS risk is greatly increased in weeks 37 + 0 to 38 + 6 (OR 12.9; 95% CI: 3.57–35.53; p < 0.01). After 39 + 0 wk, there was no significant difference in RDS risk.

Elective Cesarean Delivery: Does It Have a Negative Effect on Breastfeeding?

BACKGROUND Cesarean delivery has negative effects on breastfeeding. The objective of this study was to evaluate breastfeeding rates, defined in accordance with World Health Organization guidelines, from delivery to 6 months postpartum in infants born by elective and emergency cesarean section and in infants born vaginally. METHODS Delivery modalities were assessed in relation to breastfeeding patterns in 2,137 term infants delivered at a tertiary center, the Padua University School of Medicine in northeastern Italy, from January to December 2007. The study population included 677 (31.1%) newborns delivered by cesarean section, 398 (18.3%) by elective cesarean, 279 (12.8%) by emergency cesarean section, and 1,496 (68.8%) delivered vaginally. RESULTS Breastfeeding prevalence in the delivery room was significantly higher after vaginal delivery compared with that after cesarean delivery (71.5% vs 3.5%, p < 0.001), and a longer interval occurred between birth and first breastfeeding in the newborns delivered by cesarean section (mean ± SD, hours, 3.1 ± 5 vs 10.4 ± 9, p < 0.05). No difference was found in breastfeeding rates between the elective and emergency cesarean groups. Compared with elective cesarean delivery, vaginal delivery was associated with a higher breastfeeding rate at discharge and at the subsequent follow-up steps (7 days, 3 mo, and 6 mo of life). CONCLUSIONS   Emergency and elective cesarean deliveries are similarly associated with a decreased rate of exclusive breastfeeding compared with vaginal delivery. The inability of women who have undergone a cesarean section to breastfeed comfortably in the delivery room and in the immediate postpartum period seems to be the most likely explanation for this association.

Laryngeal Mask Airway Used as a Delivery Conduit for the Administration of Surfactant to Preterm Infants with Respiratory Distress Syndrome

Background: The laryngeal mask airway (LMATM, Laryngeal Mask Co. Ltd, Jersey, UK) is a supraglottic device used to administer positive pressure ventilation (PPV) in adults, pediatric and neonatal patients. Objectives: To avoid endotracheal intubation, we evaluated the feasibility and practicality of administering surfactant via the LMATM in preterm infants with respiratory distress syndrome (RDS). Methods: Infants less than 72 h old with a gestational age of ≤35 weeks and a birth weight of >800 g, treated with nasal continuous positive airway pressure (CPAP, 5 cm H2O) for RDS were eligible for inclusion in the study if the arterial-to-alveolar oxygen tension ratio (a/APO2) was <0.20 over a period of >60 min. Results: Eight preterm infants, median gestational age 31 (range 28–35) weeks; birth weight 1,700 (880–2,520) g, treated with nasal CPAP for RDS were enrolled. Three hours after surfactant instillation, the mean a/APO2 was significantly increased (0.13 ± 0.04 to 0.34 ± 0.11; p < 0.01) without complications. Conclusions: The LMATM may be a useful and noninvasive conduit for the administration of surfactant therapy. A large randomized comparative clinical trial will be required to confirm the efficacy of this technique.

Metabolomics in newborns with intrauterine growth retardation (IUGR): urine reveals markers of metabolic syndrome

To date, we have little knowledge on the overall metabolic status of neonates with intrauterine growth retardation (IUGR). In the last few years, the analysis of metabolomics has assumed an important clinical role in identifying “disorders” in the metabolic profile of patients. The aim of this work has been to analyze the urine metabolic profiles of neonates with IUGR and compare them with controls to define the metabolic patterns associated with this pathology. To our knowledge, this is the first study of metabolomics performed on neonates with IUGR. Recruited for the study were 26 neonates with IUGR diagnosed in the neonatal period and with weight at birth below the 10th percentile and 30 neonates of proper gestational weight at birth (controls). In the first 24 hours (prior to feeding) (T1) and about 4 days after birth (T2), a urine sample was taken non-invasively from each neonate. The samples were then frozen at −80°C up to the time of the analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). The data contained in the NMR spectra obtained from the single samples were statistically analyzed using the Principal Components Analysis and the Partial Least Squares-Discriminate Analysis. By means of a multivariate analysis of the NMR spectra obtained, it was possible to highlight the differences between the two groups (IUGRs and controls) owing to the presence of different metabolic patterns. The discriminants in the urine metabolic profiles derived essentially from significant differences in certain metabolites such as: myo-inositol, sarcosine, creatine and creatinine. The metabolomic analysis showed different urine metabolic profiles between neonates with IUGR and controls and made it possible to identify the molecules responsible for such differences.

Aortic intima media thickness in fetuses and children with intrauterine growth restriction.

OBJECTIVE: To measure aortic intima media thickness and diameter by ultrasonography in fetuses with intrauterine growth restriction (IUGR) and in appropriate for gestational age (AGA) fetuses and in the same children after a mean follow-up of 18 months. METHODS: This was a prospective study performed between January 2006 and August 2008. Fetuses were classified as having IUGR if the estimated fetal weight was below the 10th percentile and umbilical artery pulsatility index was greater than 2 standard deviations; they were classified as AGA if the estimated fetal weight was between the 10th and 90th percentiles. Abdominal aortic intima media thickness and diameter were measured in each fetus with IUGR and in each AGA fetus at a mean gestational age of 32 weeks. The same measurements were taken in the children after a mean follow-up of 18 months. RESULTS: Thirty-eight fetuses with IUGR and 32 AGA fetuses were enrolled in the study. Aortic intima media thickness median values were significantly higher in IUGR than in AGA both in utero (1.9 mm compared with 1.15 mm; P<.001) and after birth (2.4 mm compared with 1.03 mm; P<.001) and were significantly correlated (P=.018, r=0.48). At 32 weeks of gestation, aortic intima media thickness in fetuses with IUGR was inversely correlated with estimated fetal weight (P<.003; r=−0.58). Median diameter of the abdominal aorta and blood-flow velocity at 32 weeks of gestation were significantly higher in fetuses with IUGR compared with AGA fetuses (median diameter 4.5 mm compared with 3.6 mm, P<.001, blood-flow velocity 42.5 cm/s compared with 23.3 cm/s, P<.001). At follow-up, in 25 children who had had IUGR and 25 children who had been AGA, there was no significant difference in median diameter of the abdominal aorta (6.8 mm compared with 7.5 mm, P=.21). CONCLUSION: Aortic wall thickening in fetuses and children with IUGR shows differences with respect to those who were AGA. This may reflect a correlation between impaired growth in utero, Doppler abnormalities, low birth weight, and early signs of vascular dysfunction. LEVEL OF EVIDENCE: II

Cord blood metabolomic profiling in intrauterine growth restriction

A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR). Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis of cord blood collected soon after birth. Samples were collected from 22 IUGR and 21 appropriate for gestational age (AGA) fetuses. Birth weight differed significantly between IUGR and AGA fetuses (p < 0.001). Serum samples were immediately obtained and deproteinized by mixing with methanol at room temperature and centrifugation; supernatants were lyophilized and reconstituted in water for analysis. LC-HRMS analyses were performed on an Orbitrap mass spectrometer linked to a Surveyor Plus LC. Samples were injected into a 1.0 × 150-mm Luna C18 column. Spectra were collected in full-scan mode at a resolution of approximately 30,000. Data were acquired over the m/z range of 50–1,000, with measurements performed in duplicate. To observe metabolic variations between the two sets of samples, LC-HRMS data were analyzed by a principal component analysis model. Many features (e.g., ionic species with specific retention times) differed between the two classes of samples: among these, the essential amino acids phenylalanine, tryptophan, and methionine were identified by comparison with available databases. Logistic regression coupled to a receiver-operating characteristic curve identified a cut-off value for phenylalanine and tryptophan, which gave excellent discrimination between IUGR and AGA fetuses. Non-targeted LC-HRMS analysis of cord blood collected at birth allowed the identification of significant differences in relative abundances of essential amino acids between IUGR and AGA fetuses, emerging as a promising tool for studying metabolic alterations.

Intrauterine growth restriction is associated with persistent aortic wall thickening and glomerular proteinuria during infancy

Low birth weight, caused either by preterm birth or by intrauterine growth restriction, has recently been associated with increased rates of adult renal and cardiovascular disease. Since aortic intima–media thickening is a noninvasive marker of preclinical vascular disease, we compared abdominal aortic intima–media thickness among intrauterine growth restricted and equivalent gestational age fetuses in utero and at 18 months of age. The relationship between intrauterine growth restriction, fetal aortic thickening, and glomerular function during infancy was measured by enrolling 44 mothers with single-fetus pregnancies at 32 weeks gestation: 23 growth restricted and 21 of appropriate gestational age as controls. Abdominal aortic intima–media thickness was measured by ultrasound at enrollment and again at 18 months of age. Fetuses with intrauterine growth restriction had significantly higher abdominal aortic intima–media thickness compared with age controls when measured both in utero and at 18 months. At 18 months, the median urinary microalbumin and median albumin–creatinine ratio were significantly higher in those infants who experienced intrauterine growth restriction compared to the controls. Our results show that intrauterine growth restriction is associated with persistent aortic wall thickening and significantly higher microalbuminuria during infancy.

Knowledge gained by pediatric residents after neonatal resuscitation program courses

Background:  The efficacy of the Neonatal Resuscitation Program (NRP) courses was previously evaluated, demonstrating good retention of knowledge in the participants. However, there is a lack of information regarding the participants’ performance in relation to the different steps of neonatal resuscitation. We aimed to assess the knowledge gained and retained by pediatric residents who participated in a NRP course in relation to the different steps.

Neurodevelopmental outcome in preterm histological chorioamnionitis

The role of histological chorioamnionitis in neonatal neurological outcome is not yet fully understood. The present study aimed to assess the neurodevelopmental outcome of preterm babies born after pregnancy complicated by histological chorioamnionitis. Clinical data were prospectively collected for consecutive premature neonates born before 32 weeks of gestation, admitted to Neonatal Intensive Care Unit of Padua University from January 1998 to December 2001. Placental histology was performed. Outcome at 18 months of corrected age was evaluated by a standardized postal parental questionnaire. Among 104 placentas examined, 41 (39.4%) were diagnosed with histological chorioamnionitis. Reply to the postal questionnaire was available from 76.1% of the families. The relative risk of disability in vision, hearing, speech and motor development was higher in the histological chorioamnionitis than in the non-histological chorioamnionitis group, with statistical significance in speech delay (relative risk 2.37; 95% confidence interval: 1.33-4.22) and hearing loss (relative risk 2.76; 95% confidence interval:1.64-4,64). To our knowledge this is the first report suggesting preterm histological chorioamnionitis as a possible risk factor for hearing loss and speech delay.

Methylxanthines Increase Renal Calcium Excretion in Preterm Infants

To determine the effect of a short course of methylxanthines on renal function and on urinary calcium excretion, 20 premature neonates affected by apnea or moderate respiratory distress syndrome were randomly assigned to either a theophylline treatment or to a caffeine treatment group. The protocol included a 24-hour pretreatment study period (I) and a subsequent 24-hour period (II) following 5 days of theophylline (loading dose 5 mg/kg i.v., maintenance dose 2.5 mg/kg/12 h) or caffeine (loading dose 10 mg/kg i.v., maintenance dose 2.5 mg/kg/12 h) administration. Pre- and postxanthine treatment serum sodium, potassium, calcium and phosphorus remained stable, while serum creatinine decreased significantly (p < 0.05). Furthermore, from period I to period II, sodium urine excretion, fractional Na excretion and creatinine clearance remained statistically comparable in both study groups, along with a significant increase (p < 0.05) in calciuria, urinary Ca/creatinine and urinary Ca/Na. Predose caffeine and theophylline serum levels, assessed on the 5th day of treatment, were 12.8 +/- 1.8 and 7.9 +/- 1.7 micrograms/ml, respectively. Compared to control healthy untreated prematures, the studied premature infants showed a statistically significant increase in urine calcium excretion (10- to 15-fold), which was more evident in the theophylline group. Our data suggest further investigation to determine the long-term renal effects of methylxanthines in premature neonates, to improve assessment of the risk of nephrocalcinosis and osteopenia, in particular in association with various diuretic therapies.