Respiratory symptoms in preterm infants: burden of disease in the first year of life.

OBJECTIVE: While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. METHODS: Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. MAIN OUTCOME MEASURES: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). PATIENTS: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. RESULTS: Cough occurred in 80%, wheeze in 44%, re-hospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR- and CRIB-Score. CONCLUSIONS: Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.

Congenital diaphragmatic hernia : a European population-based study of epidemiology, prenatal diagnosis and mortality

Aim: To study the epidemiology and the impact of prenatal diagnosis on mortality and morbidity in infants with isolated congenital diaphragmatic hernia (CDH). Methods: Cases were identified in eight population-based registries of congenital malformations (Eurocat) in Europe. Results: A total of 183 live births were included in the study. Sixty per cent died and 67% of all deaths were during the first day of life. CDH was diagnosed prenatally in 39% of cases. Both mortality and morbidity were significantly higher for infants diagnosed prenatally compared to those diagnosed postnatally. The Apgar score was a very sensitive indicator for survival. Gestational age at birth was significantly lower for infants diagnosed prenatally compared to those diagnosed postnatally (37.6 weeks vs. 38.8 weeks, p < 0.01). At the end of follow-up, half of the survivors were leading a normal life. The most frequently reported health problems were respiratory and gastrointestinal symptoms. Conclusions: In this population-based study, mortality for infants with CDH was high (60%) and early prenatal diagnosis was a risk factor for survival. Intervention at the time of birth seems too late for the majority of newborn infants with CDH.

Adverse obstetrical and neonatal outcomes in elective and medically indicated inductions of labor at term.

OBJECTIVE: To compare the adverse neonatal and maternal outcomes after medically indicated and elective labor induction. Both induction groups were also compared to women with spontaneous onset of labor. METHOD: Retrospective cohort study of 13 971 women with live, cephalic singleton pregnancies who delivered at term (from 1997 to 2007). Adverse maternal and neonatal outcomes were compared between women who underwent an induction of labor in the presence and absence of standard medical indications. RESULTS: Among 5090 patients with induced labor, 2059 (40.5%) underwent elective labor inductions, defined as inductions without any medical or obstetrical indication. Risks of cesarean or instrumental delivery, postpartum hemorrhage >500 ml, prolonged maternal hospitalization >6 days, Apgar<7 at 5 min of life, arterial umbilical cord pH<7.1, admission in neonatal intensive care unit (NICU) and prolonged NICU hospitalization >7 days were similar between nulliparous who underwent elective and medical labor induction. Similar results were obtained for multiparous. All the above mentioned risks, but the Apgar<7 at 5 min of life, were significantly increased after induction in comparison to spontaneous labor. CONCLUSION: Elective induction of labor carries similar obstetrical and neonatal risks as a medically indicated labor induction. Thus, elective induction of labor should be strongly discouraged.

Effect of physical activity during pregnancy on mode of delivery.

OBJECTIVE: The purpose of this study was to evaluate the effect of structured physical exercise programs during pregnancy on the course of labor and delivery. STUDY DESIGN: We conducted a systematic review and metaanalysis using the following data sources: Medline and The Cochrane Library. In our study, we used randomized controlled trials (RCT) that evaluated the effects of exercise programs during pregnancy on labor and delivery. The results are summarized as relative risks. RESULTS: In the 16 RCTs that were included there were 3359 women. Women in exercise groups had a significantly lower risk of cesarean delivery (relative risk, 0.85; 95% confidence interval [CI], 0.73-0.99). Birthweight was not significantly reduced in exercise groups. The risk of instrumental delivery was similar among groups (relative risk, 1.00; 95% CI, 0.82-1.22). Data on Apgar score, episiotomy, epidural anesthesia, perineal tear, length of labor, and induction of labor were insufficient to draw conclusions. With the use of data from 11 studies (1668 women), our analysis showed that women in the exercise groups gained significantly less weight than women in control groups (mean difference, -1.13 kg; 95% CI, -1.49 to -0.78). CONCLUSION: Structured physical exercise during pregnancy reduces the risk of cesarean delivery. This is an important finding to convince women to be active during their pregnancy and should lead the physician to recommend physical exercise to pregnant women, when this is not contraindicated.

Association of moderate alcohol use and binge drinking during pregnancy with neonatal health.

Background:  Heavy drinking and smoking during pregnancy are known to have a negative impact on the unborn child. However, the impact of low-to-moderate alcohol consumption and binge drinking has been debated recently. The aim of this study was to examine the relationship of moderate prenatal drinking and binge drinking with birthweight, being small for gestational age (SGA) at birth, preterm birth, and neonatal asphyxia. Methods:  Moderate alcohol drinking, binge drinking, and several possible confounders were assessed in 1,258 pregnant women; information on neonatal health was obtained at birth. Results:  Results indicate that 30.8% of the women drank at low levels (<2 glasses/wk), 7.9% drank moderately (2 to 4 glasses/wk), and 0.9% showed higher levels of drinking (≥5 glasses/wk); 4.7% reported binge drinking (defined as ≥3 glasses/occasion). 6.4% of the children were SGA (<10th percentile of birthweight adjusted for gestational age), 4.6% were preterm (<37th week of gestation), and 13.0% showed asphyxia (arterial cord pH <7.10 and/or arterial cord lactate >6.35 mmol and/or Apgar score <7 at 5 minutes). When controlling for maternal age, citizenship, occupational status, parity, smoking, use of prescription/over-the-counter drugs, illicit drug use, and child gender moderate drinking was related to lower birthweight (p < 0.01), and moderate drinking and binge drinking were associated with neonatal asphyxia at trend level (p = 0.06 and p = 0.09). Moderate drinking and binge drinking were not related to length of gestation. Conclusions:  In contrast to recent reviews in the field, our results assume that moderate drinking and binge drinking are risk factors for neonatal health.

Cell death and autophagy after severe hypoxic-ischemic encephalopathy in term newborns

Introduction: Various studies from hypoxic-ischemic animals haveinvestigated neuroprotection by targeting necrosis and apoptosis with inconclusive results. Three types of cell death have been described: apoptosis, necrosis and more recently, autophagic cell death. While autophagy is a physiological process of degradation of cellular components, excessive autophagy may be involved in cell death. Recent studies showed that inhibition of autophagy is neuroprotective in rodent neonatal models of cerebral ischemia. Furthermore, neonatal hypoxia-ischemia strongly increased neuronal autophagic flux which is linked to cell death in a rat model of perinatal asphyxia. Following our observations in animals, the aim of the present study was to characterize the different neuronal death phenotypes and to clarify whether autophagic cell death could be also involved in neuronal death in the human newborns after perinatal asphyxia. Methods: we selected retrospectively and anonymously all newborns who died in our unit of neonatology between 2004 and 2009, with the following criteria: gestational age >36 weeks, diagnosis of perinatal asphyxia (Apgar <5 at 5 minutes, arterial pH <7.0 at 1 hour of life and encephalopathy Sarnat III) and performed autopsy. The brain of 6 cases in asphyxia group and 6 control cases matching gestational age who died of pulmonary or other malformations were selected. On histological sections of thalamus, frontal cortex and hippocampus, different markers of apoptosis (caspase 3, TUNEL), autophagosomes (LC3-II) and lysosomes (LAMP1, Cathepsin D) were tested by immunohistochemistry. Results: Preliminary studies on markers of apoptosis (TUNEL, caspase 3) and of autophagy (Cathepsin D, LC3II, LAMP1) showed an expected increase of apoptosis, but also an increase of neuronal autophagic flux in the selected areas. The distribution seems to be region specific. Conclusion: This is the first time that autophagic flux linked with cell death is shown in brain of human babies, in association with hypoxicischemic encephalopathy. This work leads to a better understanding of the mechanisms associated with neuronal death following perinatal asphyxia and determines whether autophagy could be a promising therapeutic target.

Diagnostic and prognostic value of cerebral 31P magnetic resonance spectroscopy in neonates with perinatal asphyxia.

The impact of depressed neonatal cerebral oxidative phosphorylation for diagnosing the severity of perinatal asphyxia was estimated by correlating the concentrations of phosphocreatine (PCr) and ATP as determined by magnetic resonance spectroscopy with the degree of hypoxic-ischemic encephalopathy (HIE) in 23 asphyxiated term neonates. Ten healthy age-matched neonates served as controls. In patients, the mean concentrations +/- SD of PCr and ATP were 0.99 +/- 0.46 mmol/L (1.6 +/- 0.2 mmol/L) and 0.99 +/- 0.35 mmol/L (1.7 +/- 0.2 mmol/L), respectively (normal values in parentheses). [PCr] and [ATP] correlated significantly with the severity of HIE (r = 0.85 and 0.9, respectively, p < 0.001), indicating that the neonatal encephalopathy is the clinical manifestation of a marred brain energy metabolism. Neurodevelopmental outcome was evaluated in 21 children at 3, 9, and 18 mo. Seven infants had multiple impairments, five were moderately handicapped, five had only mild symptoms, and four were normal. There was a significant correlation between the cerebral concentrations of PCr or ATP at birth and outcome (r = 0.8, p < 0.001) and between the degree of neonatal neurologic depression and outcome (r = 0.7). More important, the outcome of neonates with moderate HIE could better be predicted with information from quantitative 31P magnetic resonance spectroscopy than from neurologic examinations. In general, the accuracy of outcome predictability could significantly be increased by adding results from 31P magnetic resonance spectroscopy to the neonatal neurologic score, but not vice versa. No correlation with outcome was found for other perinatal risk factors, including Apgar score.