Mortality and major morbidities in very preterm infants born from assisted conception or naturally conceived: results of the area-based ACTION study.

BACKGROUND: The use of assisted conception (AC) has been associated with higher risk of adverse perinatal outcome. Few data are available on the outcome of AC-neonates when pregnancy ends before 32 weeks of gestational age.The aim of this study was to compare the short-term outcome of AC- and naturally conceived preterm infants <32 weeks gestation. METHODS: The area-based cohort study ACTION collected data on births 22-31 weeks gestation occurred in 2003-05 in 6 Italian regions. Infants born to 2529 mothers with known mode of conception were studied. The main outcomes were hospital mortality and survival free from major morbidities (IVH grade 3-4, cPVL, ROP stage ≥3, BPD), and were assessed separately for single and multiple infants. Other outcomes were also investigated. Multivariable logistic analyses were used to adjust for maternal and infants' characteristics. To account for the correlation of observations within intensive care units, robust variance and standard error estimates of regression parameters were computed. RESULTS: AC was used in 6.4% of mothers. Infants were 2934; 314 (10.7%) were born after AC. Multiples were 86.0% among AC and 21.7% among non-AC babies. In multivariable analysis no statistically significant difference in hospital mortality and survival without major morbidities was found between AC and non-AC infants. The risk of BPD was lower in AC than in non-AC multiples (aOR 0.41, CI 0.20-0.87), and this finding did not change after controlling for mechanical ventilation (aOR 0.42, CI 0.20-0.85) or presence of a patent ductus arteriosus (aOR 0.39, CI 0.18-0.84). CONCLUSION: When the analysis is restricted to very preterm infants and stratified by multiplicity, no significant associations between AC and increased risk of short-term mortality and survival without major morbidities emerge. This result is consistent with previous studies, and may confirm the hypothesis that the adverse effects of AC are mediated by preterm birth. However, larger appropriately powered studies are needed before definitely excluding the possibility of adverse events linked to AC in infants born before 32 weeks gestation.

Cause-specific mortality of very preterm infants and antenatal events.

OBJECTIVE: To assess the relationship between antenatal factors and cause-specific risk of death in a large area-based cohort of very preterm infants. STUDY DESIGN: The ACTION (Accesso alle Cure e Terapie Intensive Ostetriche e Neonatali) study recruited during an 18-month period all infants 22-31 weeks' gestational age admitted to neonatal care in 6 Italian regions (n=3040). We analyzed the data of 2974 babies without lethal or acutely life-threatening malformations. Cause-specific risks of death adjusted for competing causes were calculated, and region-stratified multiple Cox regression analyses were used to study the association between cause-specific mortality and infants' characteristics, pregnancy complications, antenatal steroids, and place of birth. RESULTS: Deaths attributable to respiratory problems and intraventricular hemorrhage prevailed in the first 2 weeks of life, and those attributable to infections and gastrointestinal diseases afterwards. Antepartum hemorrhage was associated with respiratory deaths (hazard ratio [HR] 1.6, 95% CI 1.1-2.4), and maternal infection with deaths attributable to asphyxia (HR 32.5, 95% CI 4.1-259.4) and to respiratory problems (HR 2.8, 95% CI 1.6-5.2). Preterm premature rupture of membranes increased the likelihood of deaths due to neonatal infection (HR 1.8, 95% CI 1.0-3.1), and preterm labor/contractions of those due to respiratory (HR 1.5, 95% CI 1.1-2.0) and gastrointestinal diseases (HR 5.8, 95% CI 2.1-16.3). In addition, a birth weight z-score<-1 was associated with increasing hazards of death resulting from asphyxia, late infections, respiratory, and gastrointestinal diseases. CONCLUSIONS: Different complications of pregnancy lead to different cause-specific mortality patterns in very preterm infants.

Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study.

BACKGROUND: We examined the relationships between -pregnancy disorders leading to very preterm birth -(spontaneous preterm labor, prelabor premature rupture of -membranes (PPROM), hypertension/preeclampsia, -intrauterine growth restriction (IUGR), antenatal hemorrhage, and maternal -infection), both in isolation and grouped together as -"disorders of placentation" (hypertensive disorders and IUGR) vs. -"presumed infection/inflammation" (all the others), and several unfavorable neonatal outcomes. METHODS: We examined a population-based prospective cohort of 2,085 singleton infants of 23-31 wk gestational age (GA) born in six Italian regions (the Accesso alle Cure e Terapie Intensive Ostetriche e Neonatali (ACTION) study). RESULTS: Neonates born following disorders of placentation had a higher GA and better overall outcomes than those born following infection/inflammation. After adjustment for GA, however, they showed higher risk of mortality (odds ratio, OR: 1.4; 95% confidence interval, CI: 1.0-2.0), bronchopulmonary dysplasia (BPD) (OR: 2.5; CI: 1.8-3.6), and retinopathy of prematurity (ROP) (OR: 2.0; CI: 1.1-3.5), especially in growth-restricted infants, and a lower risk of intraventricular hemorrhage (IVH) (OR: 0.5; CI: 0.3-0.8) and periventricular leukomalacia (PVL) (OR: 0.6; CI: 0.4-1.1) as compared with infants born following -infection/inflammation disorders. CONCLUSION: Our data confirm the hypothesis that, in very preterm infants, adverse outcomes are both a function of immaturity (low GA) and of complications leading to preterm birth. The profile of risk is different in different pregnancy disorders.

Timeliness of routine immunization in a population-based Italian cohort of very preterm infants: results of the ACTION follow-up project.

BACKGROUND: Although very preterm infants are recommended to receive immunizations, according to their chronological age, immunization start in these infants is often delayed. Aim To measure coverage and timeliness of routine immunizations in Italian very preterm infants and to assess determinants of delay. METHODS: We followed up infants 22-31 completed weeks of gestational age discharged from intensive care. We measured the proportion of children with one dose of diphtheria-tetanus-pertussis-poliohepatitis, B-Hib vaccine (DTP-Pol-HBV-Hib), measles-mumps-rubella vaccine (MMR), conjugate pneumococcal vaccine (Pnc), conjugate meningococcal C vaccine (MenC), and varicella vaccine (Var) by 24 months. We used the Kaplan Meier method and Cox proportional hazard models to estimate the age, at immunization start and determinants of timeliness for each vaccine. RESULTS: Data on 1102 (92.1%) children out of 1196 included in the cohort were analyzed. Immunization start by 24 months of age occurred in 95.9% of children for DTP-Pol-HBV-Hib; 84.0% for MMR; 49.7% for Pnc; 38.5% for MenC; and 4.1% for Var. Eighty-seven percent of participants received the first dose of DTP-Pol-HBV-Hib by 6 months of age, and 66.7% had their first MMR administered by 18 months. Hospitalization was associated with delay for all vaccines with the exception of MenC and Var. Maternal employment was associated with earlier immunization for MMR, Pnc, and MenC. DTP-Pol-HBV-Hib timeliness improved with increasing birthweight and paternal employment and decreased with a larger number of siblings in the household. MMR was delayed in children with cerebral palsy, and in those with a larger number of children in the household. Immunization for Pnc was delayed in children with larger number of siblings. CONCLUSIONS: Immunization start for all vaccines was considerably delayed in many very preterm infants. Public health strategies taking into account determinants of delay should be implemented to improve coverage and timeliness of vaccination in this group of infants.

Interaction of child disability and stressful life events in predicting maternal psychological health. Results of an area-based study of very preterm infants at two years corrected age.

This study aimed at exploring the relationship between severe neuromotor and/or sensory disability in very preterm infants assessed at 2 years corrected age and their mothers' psychological health. Data on 581 Italian singletons born at 22-31 weeks of gestation in five Italian regions and their mothers were analyzed. Maternal psychological distress was measured through the General Health Questionnaire short version (GHQ-12). The prevalence of any maternal distress (GHQ scores ≥ 2) and of clinical distress (scores ≥ 5) were 31.3% and 8.1% respectively. At multivariable analysis, we found a statistically significant association between child's disability and mothers' GHQ scoring ≥ 5 (OR 3.45, 95% CI 1.07-11.15). Also lower maternal education appeared to increase the likelihood of psychological distress (OR 1.38, 95% CI 1.14-1.66). The impact of child disability was weaker in women who had experienced additional stressful life events since delivery, pointing to the existence of a "ceiling" effect. Maternal psychological assessment and support should be included in follow-up programs targeting very preterm infants.

Increased morbidity and mortality in very preterm/VLBW infants with congenital heart disease.

PURPOSE: To study the association between congenital heart diseases (CHD) and in-hospital mortality and morbidity of very preterm/very low birth weight (VLBW) infants. METHODS: The area-based prospective cohort study ACTION included all infants with gestational age (GA) 22-31 weeks or birth weight <1,500 g admitted to neonatal care between July 2003 and June 2005 in six Italian regions (n = 3,684). CHD were coded according to ICD9-CM. Cluster multivariable logistic regression analyses were used to assess the relationship between CHD and mortality and selected morbidities [neonatal infection, ultrasound brain abnormalities, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD)] adjusting for potential confounders. RESULTS: Seventy-one patients had CHD [19.3 ‰, 95 % confidence interval (CI) 15.1-24.2 ‰]. The most common lesions were isolated atrial and ventricular septal defects (31.1 and 26.8 %, respectively), pulmonary valvar stenosis (12.7 %), and tetralogy of Fallot (5.6 %). Compared with other infants, CHD patients showed significantly higher GA and frequency of small for gestational age (SGA, i.e., birth weight ≤3rd centile). After adjustment for GA, sex, SGA, presence of extracardiac malformations or chromosomal anomalies, and region of birth, CHD patients had a significantly higher likelihood of infection, BPD, ROP, and, after 27 weeks gestation only, hospital mortality. The increased risk of ROP appeared to be partly due to infection. CONCLUSIONS: In very preterm/VLBW infants CHD are more prevalent than in the general liveborn population, and confer an increased risk of death and serious morbidities independently of other risk factors. These results may be useful to better tailor prognostic assessment and diagnostic and therapeutic interventions for these children.