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Objectives: To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children., Patient and Methods: Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39-40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents., Results: Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five., Conclusions: Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores.

Background: A considerable local variability in the rate of bronchopulmonary dysplasia (BPD) has been recorded previously., Objectives: The objectives of the present study were to describe regional differences in the rate of BPD in very preterm neonates from a European population-based cohort and to further delineate risk factors., Methods: 4,185 survivors to 36 weeks' postmenstrual age of 4,984 live-born infants born at 24+0-31+6 weeks' gestation in 2003 (the MOSAIC cohort) in 10 European regions were enrolled using predefined structured questionnaires., Results: Overall median gestational age of preterms without BPD was 30 weeks (range 23-31), median birth weight 1,320 g (range 490-3,150) compared with 27 weeks (23-31) and 900 g (370-2,460) in those with BPD. The region-specific crude rate of BPD ranged from 10.2% (Italian region) to 24.8% (UK Northern region). Maternal hypertension, immaturity, male gender, small for gestational age, Apgar <7 and region of care were associated with an increased incidence of BPD on multivariate analysis., Conclusion: A wide variability of BPD between European regions may be explained by different local practices; the strongest association however was with degree of immaturity., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To assess evolution in the care and health of very preterm babies between 1998 and 2003 after implementation of a regionalisation policy in France., Design: Comparison of two population-based cohorts., Setting: The Parisian region., Patients: All live births at 24-31 weeks of gestation in 1997 (EPIPAGE study, n=488) and in 2003 (MOSAIC study, n=580). Interventions Implementation of regionalised perinatal networks. Main outcome measures In-hospital mortality and morbidity, including intraventricular haemorrhage (IVH) grade III and IV, cystic periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD)., Results: Over this period, babies born in level III units rose from 67% to 77% and use of antenatal corticosteroids, indicated deliveries and surfactant increased. In-hospital mortality and IVH grades III/IV declined, ORs of 0.66 (95% CI 0.46 to 0.95) and 0.27 (95% CI 0.15 to 0.47), respectively, while PVL and BPD stayed constant. The rate of very preterm babies discharged alive per 1000 total births increased by 18%, but declined for babies with severe brain lesions., Conclusions: The authors found improvements in mortality and morbidity for very preterm babies and changes in their care over a 6-year period following reinforcement of regionalisation policies.

Objective: To describe obstetric intervention for extremely preterm births in ten European regions and assess its impact on mortality and short term morbidity., Design: Prospective observational cohort study., Setting: Ten regions from nine countries participating in the 'Models of Organising Access to Intensive Care for Very Preterm Babies in Europe' (MOSAIC) project., Population: All births from 22 to 29 weeks of gestation (n = 4146) in 2003, excluding terminations of pregnancy., Methods: Comparison of three obstetric interventions (antenatal corticosteroids, antenatal transfer and caesarean section for fetal indication) rates at 22-23, 24-25 and 26-27 weeks to that at 28-29 weeks and the association of the level of intervention with pregnancy outcome., Main Outcome Measures: Use of antenatal corticosteroids, antenatal transfer and caesarean section by two-week gestational age groups as well as a composite score of these three interventions. Outcomes included stillbirth, in-hospital mortality and intraventricular haemorrhage (IVH) grades III and IV and/or periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD)., Results: There were large differences between regions in interventions for births at 22-23 and 24-25 weeks. Differences were most pronounced at 24-25 weeks; in some regions these babies received the same care as babies of 28-29 weeks, whereas elsewhere levels of intervention were distinctly lower. Before 26 weeks and especially at 24-25 weeks, there was an association between the composite intervention score and mortality. No association was observed at 26-27 weeks. For survivors at 24-25 weeks, the intervention score was associated with higher rates of BPD, but not with IVH or PVL., Conclusions: There are large differences between European regions in obstetric practices at the lower limit of viability and these are related to outcome, especially at 24-25 weeks.

Background: Little is known about the influence of anaesthesia for caesarean section on outcome in very preterm infants., Methods: A prospective, population-based, cohort study (the EPIPAGE cohort) included all births before 33 weeks in nine French regions in 1997. Of 2360 infants live-born between 27 and 32 weeks, 1338 were delivered by caesarean section with general anaesthesia (n=711, 53.1%), spinal anaesthesia (n=419, 31.3%), or epidural anaesthesia (n=208, 15.6%). Neonatal mortality was compared among these three groups using bi- (according to gestational age and to anaesthetic technique) and multivariate analyses., Results: Neonatal mortality was 10.1% with general anaesthesia, 12.2% with spinal anaesthesia and 7.7% with epidural anaesthesia. After adjustment for gestational age and characteristics of pregnancy, delivery and neonate, spinal anaesthesia was associated with a higher risk of neonatal death than general anaesthesia (adjusted odds ratio, 1.7; 95% confidence interval 1.1 to 2.6)., Conclusion: In this population-based study, spinal anaesthesia was associated with an increased risk of neonatal mortality in very preterm infants compared to general anaesthesia (and epidural anaesthesia), independently from gestational age and characteristics of the pregnancies, deliveries and neonates. Although this multivariate analysis does not prove a causal relationship, the results suggest it could exist, particularly if maternal haemodynamics are poorly controlled. With recent significant change in the conduct of spinal anaesthesia, further studies are needed to investigate potential harmful effects of anaesthesia on very preterm infants delivered by caesarean section.

Objective: To describe the long-term outcome of very preterm infants receiving prolonged sedation and/or analgesia and examine the relationship between prolonged sedation and/or analgesia and this long-term outcome., Design: A prospective population-based study (Etude EPIdémiologique sur les Petits Ages GEstationnels [EPIPAGE]). To reduce bias, the propensity score method was used., Setting: Nine regions of France., Participants: The study population included very preterm infants of fewer than 33 weeks' gestational age, born in 1997, who received mechanical ventilation and/or surgery. Main Exposure Prolonged exposure to sedative and/or analgesic drugs in the neonatal period, defined as exposure of more than 7 days to sedative and/or opioid drugs., Main Outcome Measure: Presence of moderate or severe disability at 5 years of age., Results: The analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and/or analgesia in the neonatal period was available. A total of 115 were exposed and 1457 were not exposed. There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and/or analgesia and the group who were not. Exposed very preterm infants had severe or moderate disability at 5 years (41/97; 42%) more often than those who were not exposed (324/1248; 26%). After adjustment for gestational age and propensity score, this association was no longer statistically significant (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.2)., Conclusion: Prolonged sedation and/or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score.

Objective: In a previous multicenter, randomized trial, elective use of high-frequency oscillatory ventilation was compared with the use of conventional ventilation in the management of respiratory distress syndrome in preterm infants <30 weeks. No difference in terms of respiratory outcome was observed, but concerns were raised about an increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group. To evaluate outcome, a follow-up study was conducted until a corrected age of 2 years. We report the results concerning neuromotor outcome., Methods: Outcome was able to be evaluated in 192 of the 212 infants who survived until discharge from the neonatal unit: 97 of 105 infants of the high-frequency group and 95 of 104 infants of the conventional ventilation group., Results: In the infants reviewed, mean birth weight and gestational age were similar in the 2 ventilation groups. As in the overall study population, the following differences were observed between the high-frequency ventilation group and the conventional ventilation group: lower 5-minute Apgar score, fewer surfactant instillations, and a higher incidence of severe intraventricular hemorrhage. At a corrected age of 2 years, 93 of the 97 infants of the high-frequency group and 79 of the 95 infants of the conventional ventilation group did not present any neuromotor disability, whereas 4 infants of the high-frequency group and 16 infants of the conventional ventilation group had cerebral palsy., Conclusions: Contrary to our initial concern about the increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group, these data suggest that early use of high-frequency ventilation, compared with conventional ventilation, may be associated with a better neuromotor outcome. Because of the small number of patients studied and the absence of any explanation for this finding, we can conclude only that high-frequency oscillatory ventilation is not associated with a poorer neuromotor outcome.

Objective: To estimate the prevalence of cerebral palsy at 2 years of age among children born very preterm, according to gestational age, infant gender, plurality, and neonatal cranial ultrasound abnormalities., Methods: All infants born between 22 and 32 weeks of gestation in 9 regions of France in 1997 were included in this prospective, population-based, cohort study. The main outcome measure was cerebral palsy prevalence at 2 years. Of the 2364 survivors eligible for follow-up evaluation, 1954 (83%) were assessed at 2 years of age., Results: Among the 1954 children assessed at 2 years, 8.2% had cerebral palsy. Bilateral spastic cerebral palsy, hemiplegia, and monoplegia accounted for 72%, 9%, and 10% of cases, respectively. Fifty percent of the children with cerebral palsy walked independently at the age of 2, 31% were unable to walk but could sit independently, and 19% could not sit (unable to maintain head and trunk control). The prevalence of cerebral palsy was 20% at 24 to 26 weeks of gestation, compared with 4% at 32 weeks. On the basis of ultrasound findings in the neonatal period, we found that 17% of children with isolated grade III intraventricular hemorrhage and 25% of children with white matter damage (ie, ventricular dilation, persistent echodensities, or cystic periventricular leukomalacia) had cerebral palsy, compared with 4% of children with normal ultrasound scans., Conclusions: Despite recent improvements in survival rates, cerebral palsy remains highly prevalent among very preterm children. Severe cranial ultrasound abnormalities predict motor disability strongly, but one third of infants with cerebral palsy had no ultrasound abnormalities.

Study Objective: To analyse the relation between preterm birth and working conditions in Europe using common measures of exposure and to test whether employment related risks varied by country of residence., Design: A case-control study in which cases included all consecutive singleton preterm births and controls included one of every ten singleton term births in each participating maternity unit. Data about working conditions were obtained by interview from women after delivery., Setting: Sixteen European countries., Participants: The analysis included 5145 preterm and 7911 term births of which 2369 preterm and 4098 term births were to women employed during pregnancy. Analyses of working conditions were carried out for women working through at least the third month of pregnancy., Main Results: Employed women did not have an excess risk of preterm birth. Among working women, a moderate excess risk was observed for women working more than 42 hours a week (OR = 1.33, CI = 1.1 to 1.6), standing more than six hours a day (OR = 1.26, CI = 1.1 to 1.5), and for women with low job satisfaction (OR = 1.27, CI = 1.1 to 1.5). There were stronger links in countries with a lower overall level of perinatal health and a common practice of long prenatal leaves., Conclusion: These findings show that specific working conditions affect the risk of preterm birth. They also suggest employment related risks could be mediated by the social and legislative context.

This review describes European health policies related to the place of birth of very preterm babies, and the organizational context in which these policies were enacted using data from two European studies. It also compiles available information on the place of birth of very preterm babies from the published literature. In Europe, there is significant diversity in approaches to the provision of intensive care services for the small proportion of pregnant women and babies that need it, both in terms of health policies and the supply and characteristics of maternity and neonatal units. These diverse models in countries with similar levels of development and medical technology could offer an opportunity to understand how different organizational characteristics affect access to care, health outcomes and resource use.

Objective: To evaluate the outcome for all infants born before 33 weeks gestation until discharge from hospital., Design: A prospective observational population based study., Setting: Nine regions of France in 1997., Patients: All births or late terminations of pregnancy for fetal or maternal reasons between 22 and 32 weeks gestation., Main Outcome Measure: Life status: stillbirth, live birth, death in delivery room, death in intensive care, decision to limit intensive care, survival to discharge., Results: A total of 722 late terminations, 772 stillbirths, and 2901 live births were recorded. The incidence of very preterm births was 1.3 per 100 live births and stillbirths. The survival rate for births between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of live births, and 89% of infants admitted to neonatal intensive care units. Survival increased with gestational age: 31% of all infants born alive at 24 weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among live births was lower for small for gestational age infants, multiple births, and boys. Overall, 50% of deaths after birth followed decisions to withhold or withdraw intensive care: 66% of deaths in the delivery room, decreasing with increasing gestational age; 44% of deaths in the neonatal intensive care unit, with little variation with gestational age., Conclusion: Among very preterm babies, chances of survival varies greatly according to the length of gestation. At all gestational ages, a large proportion of deaths are associated with a decision to limit intensive care.

Objective: To evaluate the prevalence of cranial ultrasound abnormalities in very preterm infants as a function of gestational age, plurality, intrauterine growth restriction, and death before discharge., Study Design: A prospective, population-based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in nine regions of France, transferred to a neonatal intensive care unit, for whom at least one cranial ultrasound scan was available., Results: The frequencies of white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL), periventricular parenchymal hemorrhagic involvement, and intraventricular hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%, respectively. The risk of WMD increased with decreasing gestational age. Mean age at diagnosis of cystic PVL was older for the most premature infants. Intraventricular hemorrhage with ventricular dilatation was associated with a higher risk of cystic PVL. Intrauterine growth restriction was not associated with a lower prevalence of cystic PVL., Conclusion: The frequency of WMD is high in very preterm babies and is strongly related to gestational age. The incidence of cystic PVL did not differ between babies with intrauterine growth restriction and babies who were appropriate for gestational age.

Objective: Early ultrasound scanning estimation of gestational age is known to increase the reported preterm delivery rate (<37 completed weeks) compared with estimation by date of the last normal menstrual period, but it is unclear how this systematic difference arises., Study Design: This study was a hospital-based study of 44,623 women who delivered a live-born or stillborn infant between January 1, 1978, and March 31, 1996, and who had both last normal menstrual period-based and early (usually at 16-18 weeks) ultrasound scan-based gestational age estimates. Cross-classification of the 2 estimates by completed weeks was used to examine the direction and magnitude of the differences between them and to compare the resulting classifications of preterm birth., Results: The early ultrasound scan-based gestational age distribution was shifted uniformly to the left (ie, lower gestational age) relative to the last normal menstrual period gestational age distribution; the early ultrasound scan-based preterm delivery rate was 9.1%, which was 19.5% (n = 659 births) higher than the 7.6% rate by last normal menstrual period (P <.0001). The last normal menstrual period estimate exceeded the early ultrasound scan estimate far more often than the reverse, up to and including early ultrasound scan estimates of 40 weeks. No concentration of 4-week discrepancies was observed in either direction, as would be expected with random or systematic errors in recall of the last normal menstrual period. The absolute number of births at 37 to 39 weeks of gestation (by last normal menstrual period) that were reclassified as preterm (n = 1206 births) was much higher than the number of preterm births at 34 to 36 weeks of gestation that were reclassified as term (n = 581 births). The net increase of 625 preterm births (from 581 to 1206 births) that resulted from reclassification of births at 37 to 39 last normal menstrual period weeks accounted for 95% of the total 659-birth increase in early ultrasound scan-based preterm births at all last normal menstrual period gestational ages., Conclusion: Early ultrasound scanning reduces the gestational age estimate across the entire gestational age range; early ultrasound scan-based reclassification of gestational age results in a substantial increase in the prevalence of preterm births. Small downward reclassifications exceed upward reclassifications of similar magnitude, which is consistent with previous reports that delayed (>14 days) ovulation is more frequent than early (<14 days) ovulation.

We hypothesized that prophylactic treatment with a porcine-modified lung surfactant (PLS) reduces the rate of peri-intraventricular haemorrhage (PIVH) more than rescue treatment. We performed a meta-analysis of three prophylactic versus rescue trials conducted with PLS in four countries using individual data. Overall (grades 1-4) or severe (grades 3 and 4) PIVH of 671 newborns was the outcome. A logistic regression analysis was performed. Prophylactic exposure to PLS was a significant independent factor in reducing the incidence of overall (OR 0.65; 95% CI 0.47-0.90) and severe (OR 0.56; 95% CI 0.35-0.89) PIVH. Moreover, for severe PIVH, the adjusted OR for outborn babies exposed to prophylactic treatment with PLS was highly significant (OR 0.11; 95% CI 0.02-to 0.49). The results we obtained show that prophylactic treatment with PLS reduces the rate of PIVH more than rescue treatment., (Copyright 2002 S. Karger AG, Basel)

We studied the consequences of misdiagnosis of intrauterine growth retardation (IUGR) for preterm elective cesarean section among live singleton newborns in two teaching hospitals in Paris between 1978 and 1983. The population studied comprised the 16,540 babies who were normal for date, according to the 10th percentile of the reference curve established in this population. For 118 of these infants, IUGR had been diagnosed during pregnancy. The preterm elective cesarean section rate was 12.7% among newborns for whom IUGR was erroneously diagnosed, compared to 1.2% among those for whom IUGR was not diagnosed. The relationship between preterm cesarean section and misdiagnosis of IUGR still existed (odds ratio: 5.2, 95% CI: 2.1-12.9) after taking into account obstetric history and hypertension during pregnancy. Our results show that after diagnosis of IUGR, supplementary tests are essential to confirm fetal distress and consequently avoid unnecessary interventions.