Obstetric interventions for babies born before 28 weeks of gestation in Europe: results of the MOSAIC study.

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.

[The usefulness of the hospital standardized mortality ratio as an indicator of hospital mortality]. / Het gestandaardiseerde ziekenhuissterftecijfer (HSMR) bruikbaar voor het volgen van ziekenhuissterfte.

In 2007, a patient safety programme was started to reduce hospital mortality in the Netherlands. The hospital standardized mortality ratio (HSMR) seems to be a promising indicator for monitoring the reduction of hospital mortality within hospitals. It is questionable, however, whether the HSMR can be used to compare the performance of hospitals. It has been shown that certain specialized procedures such as percutaneous transluminal coronary angioplasty (PTCA) and open heart surgery have an impact on the HSMR. Although this hampers a fair comparison between cardiac centres and general hospitals, the HSMR may still indicate whether a cardiac centre could improve its performance. Moreover, the impact of cardiac procedures on the HSMR is relatively modest, which shows that it is a robust indicator to monitor the intended decrease of hospital mortality on a national scale.

[At the limits of viability: Dutch referral policy for premature birth too reserved]. / Op de grens van levensvatbaarheid: Nederlands verwijsbeleid bij vroeggeboorte te terughoudend.

OBJECTIVE: Evaluation of policy and treatment of deliveries at the limits of viability in the Netherlands and resulting survival figures. DESIGN: Cohort study. METHOD: Within the framework of the European 'Models of organising access to intensive care for very preterm births in Europe' (MOSAIC) study, data was collected on all 512 births in 2003 (terminations excluded) following 22-31 weeks gestation in the catchment areas of the perinatal centres in Nijmegen and Utrecht, the Netherlands. RESULTS: Gynaecologists and neonatologists practised a reserved policy for the active treatment of pregnancies under 25 weeks (5/77; 6%); all infants died. At 25 weeks, an active obstetric policy was used in one quarter of pregnancies, but none of the infants survived. Even at 26 weeks pregnancy, the obstetric policy was reserved and the mortality relatively high (9/31; 29%). From the neonatal deaths, 86 out of 92 (93%) were preceded by a decision either not to start or to discontinue treatment. CONCLUSION: Dutch obstetricians and neonatologists practised a reserved policy at the limits of neonatal viability. There is more need for active antenatal transfer to perinatal centres for those at the lower limit of neonatal viability to enable well-balanced decisions to take place. The parents' wishes should always be taken into account.

Is attrition bias a problem in neonatal follow-up?

AIM: To assess whether attrition rate influences outcome in the follow-up of very preterm infants. STUDY DESIGN: In a national follow-up study of infants born alive in 1983 in the Netherlands with a gestational age less than 32 weeks and/or a birth weight less than 1500 g, outcome was assessed separately for adolescents who responded early or late to a follow-up invitation at age 14 years. Neonatal data and outcome results of earlier assessments from early and late responders were compared to those of non-responders by univariate and nominal (polytomous logistic) regression analysis. SUBJECTS: There were 723 (76%) early responders, 130 (14%) late responders and 109 (11%) non-responders. RESULTS: We found significantly more non-Dutch origin and more disabilities and school problems at age 10 years in late- and especially in non-responders. At age 14 years, the health utility index was significantly lower in late responders compared to early responders. School outcome did not show difference in relation to the response groups. CONCLUSION: The results suggest that the incidence of adverse outcome in very preterm infants is underestimated when follow-up is incomplete and hence response rate is not a negligible problem in the assessment of late outcome. Therefore, follow-up studies should include a drop-out analysis to enable comparison to other studies.

Ethnic differences in congenital malformations in the Netherlands: analyses of a 5-year birth cohort.

Congenital malformations are among the major causes of perinatal mortality and morbidity at present. Research into the ethnic diversity of congenital malformations can form a basis both for aetiological studies and for health care advice and planning. This study compared the overall prevalence of congenital malformations, the prevalence in different organ systems and of several specific malformations between different maternal ethnic groups in the Netherlands using a 5-year national birth cohort (1996-2000) containing 881 800 births. Maternal ethnic groups considered were Dutch; Mediterranean (Moroccan/Turkish); other European; Black; Hindu and Asian. Mediterranean women had a 20% higher risk of having a child with a congenital malformation than Dutch women (age-adjusted OR = 1.21 [95% CI 1.16, 1.27]). They showed an increased risk of malformations in several organ systems such as the central nervous system and sensory organs, the urogenital system and skin and abdominal wall. Further, they had an increased risk of the group of chromosomal malformations/multiple malformations/syndromes. For the specific group of multiple malformations the maternal age adjusted OR was 1.80 [95% CI 1.47, 2.20]. The Black group showed a significantly increased risk of skeletal and muscular malformations (age adjusted OR = 1.76 [95% CI 1.53, 2.02]) with a sixfold increased risk of polydactyly compared with the Dutch group. For Mediterranean women, the largest and fastest growing group of immigrants in the Netherlands, this study demonstrated an increased risk of congenital malformations.

Development and evaluation of a follow up assessment of preterm infants at 5 years of age.

BACKGROUND: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. AIMS: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life. METHODS: A total of 431 very premature infants, mean gestational age 30.2 weeks, mean birth weight 1276 g, were studied at age 5 years. Children with severe handicaps were excluded. The percentage of children with a correctly identified developmental disturbance in the domains cognition, speech and language development, neuromotor development, and behaviour were determined. RESULTS: The follow up instrument classified 67% as optimal and 33% as at risk or abnormal. Of the children classified as at risk or abnormal, 60% had not been identified at earlier follow up assessments. The combined set of standardised tests identified a further 30% with mild motor, cognitive, or behavioural disturbances. The paediatrician's assessment had a specificity of 88% (95% CI 83-93%), a sensitivity of 48% (95% CI 42-58%), a positive predictive value of 85% (95% CI 78-91%), and a negative predictive value of 55% (95% CI 49-61%). CONCLUSIONS: Even after standardised and thorough assessment, paediatricians may overlook impairments for cognitive, motor, and behavioural development. Long term follow up studies that do not include detailed standardised tests for multiple domains, especially fine motor domain, may underestimate developmental problems.

Congenital malformations in 4224 children conceived after IVF.

BACKGROUND: The percentage of children born after IVF will continue to increase due to demographic changes such as increasing maternal age and new developments in assisted reproduction techniques. IVF conceptions may carry an increased risk of congenital malformations. METHODS: We compared overall and specific congenital malformation rates calculated for IVF children (n = 4224) and naturally conceived children (n = 314 605), using records from the same Dutch national database for the years 1995 and 1996 and controlling for confounding maternal factors. RESULTS: The overall crude odds ratio (OR) for the risk of any malformation for IVF children compared with naturally conceived children was 1.20 [95% confidence interval (CI): 1.01-1.43]. After correction for differences in maternal age, parity and ethnicity between the IVF and control population the OR was 1.03 (95% CI: 0.86-1.23). The crude OR for IVF children appeared higher for the cardiovascular organ system and for several specific minor congenital malformations. However, these could be chance findings due to comparison of many malformation categories or may result from remaining differences in ascertaining malformations between IVF and naturally conceived children. CONCLUSIONS: The small increase in overall congenital malformations observed in the IVF children appears to be attributable to differences in maternal characteristics and not to any aspect of the IVF procedure.

Randomised clinical trial on the effect of the Dutch obstetric peer review system.

The project "Obstetric Peer Review Interventions" (Verloskundige Onderlinge Kwaliteitsspiegeling Interventies, VOKSINT) was set-up in The Netherlands in 1994. It provided annual comparison data (quality ranking, league tables) for secondary care obstetric departments adjusted for population differences, based on the data registered in the Perinatal Database of The Netherlands (Landelijke Verloskunde Registratie, LVR). The aim of the so-called VOKS reports was to influence obstetricians' interventions in such a way that they led to a more homogeneous policy. To assess this influence, a trial was set-up, with departments randomly assigned to be or not to be informed about the VOKS results. Obstetric intervention rates and the morbidity of newborns including neonatal neurological examinations (NNEs) were assessed. Obstetric intervention rates were similar in the report group and the control group. Practice in the report group became more homogeneous (adjusted for population differences) than in the control departments, but this was only statistically significant for term caesarean section.

The reliability of perinatal and neonatal mortality rates: differential under-reporting in linked professional registers vs. Dutch civil registers.

Official Dutch perinatal mortality rates are based on birth and death certificates. These civil registration data are not detailed enough for international comparisons or extensive epidemiological research. In this study, we linked and extrapolated three national, incomplete, professional registers from midwives, obstetricians and paediatricians, containing detailed perinatal information. This linkage and extrapolation resulted in one detailed professional database which is representative of all Dutch births and from which gestational age-specific perinatal mortality rates could be calculated. The reliability of these calculated mortality rates was established by comparing them with the rates derived from the national civil registers. The professional database reported more perinatal deaths and fewer late neonatal deaths than the civil registers. The under-reporting in the civil registers amounted to 1.2 fewer perinatal deaths per 1000 births and was most apparent in immature newborns. We concluded that under-reporting of perinatal and neonatal deaths depends on the data source used. Mortality rates for the purpose of national and international comparison should, therefore, be defined with caution. This study also demonstrated that combining different incomplete professional registers can result in a more reliable database containing detailed perinatal information. Such databases can be used as the basis for extensive perinatal epidemiological research.

Behavioural problems in children who weigh 1000 g or less at birth in four countries.

BACKGROUND: The increased survival chances of extremely low-birthweight (ELBW) infants (weighing <1000 g at birth) has led to concern about their behavioural outcome in childhood. In reports from several countries with different assessments at various ages, investigators have noted a higher frequency of behavioural problems in such infants, but cross-cultural comparisons are lacking. Our aim was to compare behavioural problems in ELBW children of similar ages from four countries. METHODS: We prospectively studied 408 ELBW children aged 8-10 years, whose parents completed the child behaviour checklist. The children came from the Netherlands, Germany, Canada, and USA. The checklist provides a total problem score consisting of eight narrow-band scales. Of these, two (aggressive and delinquent behaviour) give a broad-band externalising score, three (anxious, somatic, and withdrawn behaviour) give a broad-band internalising score, and three (social, thought, and attention problems) indicate difficulties fitting neither broad-band dimension. For each cohort we analysed scores in ELBW children and those in normal- birthweight controls (two cohorts) or national normative controls (two cohorts). Across countries, we assessed deviations of the ELBW children from normative or control groups. FINDINGS: ELBW children had higher total problem scores than normative or control children, but this increase was only significant in European countries. Narrow-band scores were raised only for the social, thought, and attention difficulty scales, which were 0.5-1.2 SD higher in ELBW children than in others. Except for the increase in internalising scores recorded for one cohort, ELBW children did not differ from normative or control children on internalising or externalising scales. INTERPRETATION: Despite cultural differences, types of behavioural problems seen in ELBW children were very similar in the four countries. This finding suggests that biological mechanisms contribute to behavioural problems of ELBW children.

Measuring health status using the Health Utilities Index: agreement between raters and between modalities of administration.

The aim of this study was to evaluate interrater and intermodality agreement in assessing health status using the Health Utilities Index. A random sample from a Dutch cohort of 14-year-old Very Low Birth Weight children and their parents were invited to participate in a face-to-face (n = 150) or telephone (n = 150) interview. All 300 participants were also sent a questionnaire by mail. Response rate was 68%. Interrater and intermodality agreement were high for the physical HUI3 attributes and poor for the psychological attributes. Children and parents reported more dysfunction in the psychological attributes when interviewed than when completing the mailed questionnaire. High agreement on the physical attributes may have resulted from the fact that hardly any dysfunction was reported in these attributes, and poor agreement in the psychological attributes may have been a result of the fact that in these attributes much more dysfunction was reported. In measuring children's health status using the HUI3, the results and their interpretation vary with the source of information and the modality of administration. For maximum comparability between studies, written self-report questionnaires seem the preferred option.

Measuring health-related quality of life in adolescents: agreement between raters and between methods of administration.

The aim of this study was to evaluate the agreement between children and proxies as well as the agreement between methods of administration in assessing Health-Related Quality of Life (HRQoL) using the TNO AZL Children's Quality Of Life (TACQOL) questionnaire. A random sample from a Dutch cohort of 14-year-old very low birth weight children and their parents were invited to participate in a face-to-face (n = 150) or telephone interview (n = 150). Participants were also sent a questionnaire by mail. The response rate was 83%. Inter-rater and intermethod agreement were generally good in observable HRQoL domains, and moderate in less readily observable, and possibly less stable, domains such as moods, pain and physical symptoms, and social functioning. In measuring children's HRQoL using the TACQOL, the results and their interpretation are dependent on the source of information and the method of administration.

Health status development in a cohort of preterm children.

OBJECTIVE: To determine the impact of preterm birth on health status (HS) development at the ages of 5 and 10 years in a cohort of children born before term. SAMPLE: Six hundred eighty-eight children, born in 1983 with a gestational age of <32 weeks and a birth weight of <1500 g. DESIGN: Prospectively collected HS variables, obtained from the parents, were analyzed in a longitudinal perspective by using principal component analyses. RESULTS: One third of the sample had minor to severe HS problems at both ages of measurement. One third had problems on one assessment only. The remainder of the sample had no HS problems at either age. The analyses grouped the HS variables into 3 combinations. Problems in basic functioning, such as mobility or speech, decreased with age. Negative moods substantially increased, and concentration problems increased slightly. Specifically at risk were preterm born children with handicaps, boys, and children who were small for gestational age. CONCLUSION: According to the parents, one third of the cohort had no HS problems at either age. The pattern of HS problems of the preterm born children changed between 5 and 10 years of age.

[Prevalence of neural tube defects in births before and after promotion of periconceptional folic acid supplementation]. / Geboorteprevalentie van neuralebuisdefecten voor en na campagne voor periconceptioneel foliumzuurgebruik.

OBJECTIVE: To describe the incidence and the expected clinical picture of neural tube defects (NTD) in years when periconceptional folic acid use increased. DESIGN: Descriptive. METHOD: Data on the prevalence of NTD in the Netherlands in 1994-1998 and on the prognosis at the time of the report obtained from the Nederlands Signalerings Centrum Kindergeneeskunde (Netherlands Paediatric Spotting Centre), where all practising physicians in the Netherlands monthly report children in whom a rare disease has been diagnosed. Prevalence figures from before and after 1996 were compared, because periconceptional use of folic acid increased since late 1996. RESULTS: In 1994-1998, 414 children with NTD were reported, 164 boys, 191 girls and 59 unreported. The prevalence of NTD was 4.6 per 10,000 live births (95% confidence interval (CI): 3.7-5.6) compared with 3.8 per 10,000 live births (95% CI: 2.9-4.6) in the period 1997-1998. Of the 414 children, 257 had a meningomyelocele; the early mortality in this group amounted to 37%. Hydrocephalus was found in 84.8% of the infants, 40.9% of the infants were believed never be able to sit, stand, and walk. CONCLUSION: The prevalence of NTD was lower in the period 1997-1998 than in the period 1994-1996 although the difference was not statistically significant.

Looking back in time: outcome of a national cohort of very preterm infants born in The Netherlands in 1983.

In 1983, Dutch pediatricians collaborated on a national level and collected perinatal data on 1338 liveborn infants with a gestational age <32 weeks and/or a birthweight <1500 g (project on preterm and small for gestational age infants, POPS). Their outcome was assessed at 2 years of age by their pediatricians, at 5 years by a team of investigators, and at 9-14 years by questionnaires completed by parents, teachers, and children themselves. The overall picture that emerges from this 14-year follow-up is that a low percentage of these very preterm infants (10%) has a severe disability or handicap at school age. Although 90% of the children are without severe disabilities at school age, many of them meet serious difficulties in everyday life and the burden of mild developmental abnormalities, behavioral and learning disorders increases with age. In adolescents, it is likely that as many as 40% of the survivors will not be able to become fully independent adults. Abnormalities found during early, standardized clinical neurological examination are highly predictive for these later problems.

Self-reported physical disabilities in children in the Netherlands.

PURPOSE: To assess the prevalence of self-reported physical disabilities in school children, through the Child Health Monitoring System. METHODS: In 1992/1993. data were obtained in mainstream education (n = 5484), and in 1994/1995 in special education (n = 2622). The data were weighted to calculate estimates representative of the Dutch population. RESULTS: Physical disabilities were reported in 21% [20.9%; 99% confidence interval 20.0-21.8], and 5% [4.7%; 99% confidence interval 4.3-5.2] had a severe disability. Severe physical disabilities were more frequent in the youngest age group, and certain of these disabilities may be related to normal development. In older children, accidents are an important cause of disabilities. Boys had disabilities more often than girls, especially speech disabilities. Disabilities were more common among children whose parents had a low level of education. Only a minority (14%) of the children with a severe disability, reported to be restricted in the daily pursuits. CONCLUSIONS: Physical disabilities are a common health problem in school children, but they do not usually cause a handicap.

[Determination of one national standard for children with congenital anomalies in the National Obstetrical Registry and in the National Neonatal Registry]. / Opzetten van een landelijk bestand van kinderen met congenitale afwijkingen uit de Landelijke Verloskunde Registratie en de Landelijke Neonatologie Registratie.

OBJECTIVE: To determine if the birth prevalence data on congenital malformations in the national perinatal registries, the Landelijke Verloskunde Registratie (LVR) (National Obstetrical Registry) and the Landelijke Neonatologie Registratie (LNR) (National Neonatological Registry), can be combined into one nationwide database, and if so to determine the validity of this database. DESIGN: Descriptive. SETTING: TNO Prevention and Health, Leiden, the Netherlands. METHODS: Investigation of the registered number of congenital malformations in the LVR/LNR, the amount of overlapping and the possibility of combining the LVR and LNR into one nationwide database. The validity of this database was evaluated by comparing the total number of registered children with the total number expected in the Netherlands. Furthermore the total number of children registered in the nationwide database was compared with children registered by the European registration of congenital anomalies and twins (EUROCAT) in the Northern Netherlands. RESULTS: The LVR and LNR were mostly complementary with respect to the registration of congenital anomalies and could be combined to one nationwide database. For sixteen important diagnoses this nationwide database contained approximately 87% of the total number expected in the Netherlands. Comparing this database with the data of EUROCAT in the Northern Netherlands showed that one-third of these congenital malformations (n = 229 in 217 children) were registered in both systems, while 99 (43%) were only registered by EUROCAT and 50 (22%) only by the nationwide database. CONCLUSION: It was possible to create a nationwide database, which can supplement the regional EUROCAT data with nationwide data on sixteen important diagnoses of congenital malformations.

[Impediments to incubator home care in The Netherlands]. / Belemmeringen voor couveuse-thuiszorg in Nederland.

OBJECTIVE: To determine whether incubator home care is desirable and feasible. DESIGN: Inventory. SETTING: Four neonatal units representative of the type of care in general hospitals in the Netherlands. METHOD: The relevant data on all infants with a birth weight < or = 2000 g admitted in the last 3 months of 1996 to one of four hospitals were analysed. Conditions for incubator home care were determined (e.g. absence of need for special care, vital function monitoring or nasogastric tube feeding). RESULTS: Forty-nine infants were enrolled. Mean hospital stay was 28.7 days in an incubator plus 19.7 days in a cot. When infants were placed in a cot they usually still needed tube feeding and monitoring of vital functions and sometimes parenteral nutrition, medication or extra oxygen which made home discharge impossible. Therefore a pilot study of actual home care could not be carried out. CONCLUSION: Although early home discharge is very desirable for newborn infants, the number of infants eligible for incubator home care is so small that further attempts to organise it are not useful.

[Increase in perinatal referral to regional centers of premature birth in The Netherlands: comparison 1983 and 1993]. / Toename van perinatale verwijzing naar regionale centra bij vroeggeboorte in Nederland: vergelijking van 1983 en 1993.

OBJECTIVE: To determine changes in referral of preterm newborns. DESIGN: Descriptive. SETTING: Foundation for Perinatal Epidemiology the Netherlands, Leiden. METHODS: Data regarding hospital of birth, referral, need of intensive care and mortality of the infants < 32 weeks and (or) < 1500 g birth weight born in 1993 from the National Neonatology Register were supplemented with data from a questionnaire for hospitals not included in the register. The data were compared with those of similar infants from the 'Project on preterm and small for gestational age', born in 1983. RESULTS: In 1983, 61% of the preterm infants were treated in a perinatal centre: 39% were not referred. In 1993 these numbers were 89% and 11%, respectively. The contribution of antenatal referral increased from 29% to 47% while that of postnatal referral decreased from 41% to 25%. Mortality decreased from 25.4% in 1983 to 14.3% in 1993. CONCLUSION: Regionalization of high risk perinatal care resulted in concentration of care for preterm infants. At the same time, in-hospital mortality decreased by almost 50%.

[Sequelae of premature birth: substantial medical consumption and physical limitations; survey among parents of 10-year-olds]. / Gevolgen van vroeggeboorte: veel medische consumptie en lichamelijke beperkingen; enquête onder ouders van 10-jarigen.

OBJECTIVE: To determine health and disabilities of preterm infants at age 10. DESIGN: Prospective follow-up study. SETTING: TNO Preventive en Gezondheid, sector Jeugd. Leiden, the Netherlands. METHOD: A questionnaire on medical consumption and physical disabilities was sent to the parents of a Dutch cohort of infants born alive in 1983 with a gestational age < 32 weeks and (or) a birth weight < 1500 g. The data were compared with outcomes at 5 years of age and with a peer group in mainstream education (data collected in a representative sample from the school health care system). RESULTS: Questionnaires on 75% of the eligible children were returned. Almost 40% of the preterm children had been admitted to hospital after the age of 5. Children in special education were significantly more often treated by a physiotherapist and (or) speech therapist. Overall 45% of the children suffered from a physical disability. This was six times as frequent as in a peer group from the school health survey. Although the assessment of physical disabilities was based on a paediatric examination at age 5 and on a parental questionnaire at age 10, differences were small. CONCLUSION: Mild developmental problems and learning disabilities are frequent in preterm infants. Research of preventive methods and timely interventions are needed and should be incorporated in the facilities for neonatal intensive care.