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Objective: The Hypertension and Preeclampsia Intervention Trial At near Term-I (HYPITAT-I) randomized controlled trial showed that, in women with gestational hypertension or mild pre-eclampsia at term, induction of labor, compared with expectant management, was associated with improved maternal outcome without compromising neonatal outcome. The aim of the current study was to evaluate the impact of these findings on obstetric management and maternal and perinatal outcomes in The Netherlands., Methods: We retrieved data for the period 2000-2014 from the Dutch National Perinatal Registry, including 143 749 women with gestational hypertension or pre-eclampsia and a singleton fetus in cephalic presentation, delivered between 36 + 0 and 40 + 6 weeks of gestation (hypertensive disorder of pregnancy (HDP) group). Pregnant women without HDP were used as the reference group (n = 1 649 510). The HYPITAT-I trial was conducted between 2005 and 2008. To study the impact of HYPITAT-I, we compared rate of induction of labor, mode of delivery and maternal and perinatal outcomes in the periods before (2000-2005) and after (2008-2014) the trial. We also differentiated between hospitals that participated in HYPITAT-I and those that did not., Results: In the HDP group, the rate of induction of labor increased from 51.1% before the HYPITAT-I trial to 64.2% after it (relative risk (RR), 1.26; 95% CI, 1.24-1.27). Maternal mortality decreased from 0.022% before the trial to 0.004% after it (RR, 0.20; 95% CI, 0.06-0.70) and perinatal death decreased from 0.49% to 0.27% (RR, 0.54; 95% CI, 0.45-0.65), which was attributable mostly to a decrease in fetal death. Both the increase in induction rate and the reduction in hypertensive complications were more pronounced in hospitals that participated in the HYPITAT-I trial than in those that did not. Following HYPITAT-I, the rate of induction of labor also increased (by 4.6 percentage points) in the reference group; however, the relative increase in the HDP group (13.1 percentage points) was significantly greater (P < 0.001 for the interaction). The reduction in maternal and perinatal deaths did not differ significantly between the HDP and reference groups. There was a decreased incidence of placental abruption in both HDP and reference groups, which was significantly greater in the HDP than in the reference group (P < 0.001 for the interaction). There was also an increased incidence of emergency Cesarean section in both HDP and reference groups; however, this change was significantly greater in the reference than in the HDP group (P < 0.001 for the interaction)., Conclusion: Following the HYPITAT-I trial, there was a higher rate of induction of labor and improved obstetric outcome in term pregnancies complicated by HDP in The Netherlands. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Study the association between the introduction of tobacco control policies in the Netherlands and changes in perinatal outcomes., Design: National quasi-experimental study., Method: We used Netherlands Perinatal Registry data (now called Perined) for the period 2000-2011. We studied whether the introduction of smoke-free legislation in workplaces plus a tobacco tax increase and mass media campaign in January 2004, and extension of the smoke-free law to the hospitality industry accompanied by another tax increase and media campaign in July 2008, was associated with changes in perinatal outcomes. We studied all singleton births (gestational age: 24+0 to 42+6 weeks). Our primary outcome measures were: perinatal mortality, preterm birth and being small-for-gestational-age (SGA). Interrupted time series logistic regression analyses were performed to investigate changes in these outcomes occurred after the introduction of the aforementioned tobacco control policies (ClinicalTrials.gov: NCT02189265)., Results: Among 2,069,695 singleton births, 13,027 (0.6%) perinatal deaths, 116,043 (5.6%) preterm live-births and 187,966 (9.1%) SGA live-births were observed. The policies introduced in January 2004 were not associated with significant changes in any of the primary outcome measures. A -4.4% (95% CI: -6.4 to -2.4; p < 0.001) decrease in odds of a SGA birth was observed after the policy extension in July 2008 to include a smoke-free hospitality industry, a further tax increase and another media campaign. This translates to an estimated over 500 cases of SGA being averted per year., Conclusion: A reduction in SGA births, but not preterm birth or perinatal mortality, was observed in the Netherlands after extension of the smoke-free workplace law to include bars and restaurants, in conjunction with a tax increase and media campaign in 2008.

Objective: To identify risk indicators for referral during labor from community midwife to a gynecologist in a prospective cohort of women with a singleton term pregnancy, starting labor with a community midwife between 2000 and 2007, registered in the Dutch national perinatal registry., Main Outcome Measures: Referral from community midwife to a gynecologist during labor, because of fetal distress, failure to progress in second stage of labor, meconium stained amniotic fluid, failure to progress in first stage of labor, wish for pain relief, a combination of other less urgent reasons or no referral (reference)., Results: A total of 241 595 (32%) were referred from community midwife to a gynecologist during labor, because of fetal distress (FD;5%), failure to progress in second stage of labor (FTP2;14%), meconium stained amniotic fluid (MSAF;24%), failure to progress in first stage of labor (FTP1;17%), wish for pain relief (WFPR;7%) or a combination of other less urgent reasons, for example, malpresentation (e.g. breech) or other nonspecified problems (OTHER;33%). The strongest overall risk indicators were gestational age (lower risk of referral because of FD, FTP2, MSAF, FTP1 and WFPR and a higher risk of referral because of OTHER at a gestational age between 37(+0) and 37(+)(6) weeks, and higher risks of referral for all reasons at a gestational age ≥41(+)(0) when compared to a gestational age between 38 (+)(0) and 40 (+)(6) weeks and no referral), the intended place of delivery (higher risk of all types of referral compared to no referral when the intended place of delivery was either at a midwife-led birth center or a hospital instead of at home) and birth history (higher risk of all types of referral compared to no referral when women had a history of instrumental vaginal delivery or when they were nulliparous instead of being multiparous without a history of an instrument vaginal delivery). Risk indicators associated with specific reasons of referral were maternal age, ethnicity, degree of urbanization, social economic status, neonatal gender and birth weight., Conclusions: Among low-risk pregnant women, a referral during labor is associated with readily available risk indicators. These risk indicators may be used to increase referral risk awareness and to counsel women for the intended place to start labor.

Introduction: An increase of postpartum hemorrhage (PPH) has been reported in many high-income countries. In addition to this data, this study reports on trends in the incidence of PPH in the Netherlands in 2000-2013, and examines the extent to which temporal changes in risk indicators could explain a possible change in incidence of PPH., Material and Methods: We used data from the Dutch Perinatal Registry, which contains prospectively collected antenatal, peripartum and neonatal data of 95-99% of all women and neonates in the Netherlands. We selected births ≥22 weeks of gestation from January 2000 until December 2013. Changes in the incidence of PPH and its risk indicators were studied over time. Main outcome measure was PPH, defined as blood loss >1000 mL within 24 h following delivery., Results: The data comprised 2 406 784 women. The incidence of PPH rose significantly from 4.1% in 2000 to 6.4% in 2013 (p < 0.0001). The incidence of previously identified risk indicators for PPH increased over time. Manual removal of placenta was strongly associated with PPH (OR 29.3, CI 28.8-29.8). The incidence of PPH-related blood transfusion decreased remarkably., Conclusions: In line with international observations, Dutch data suggest a considerable increase in the incidence of PPH which can only partly be explained by the studied risk indicators. The decreasing incidence of obstetric blood transfusion suggests an increased incidence of blood loss of 1000-1500 mL., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: In 2006, the Dutch guideline for active treatment of extremely preterm neonates advised to lower the gestational age threshold for active intervention from 26 0/7 to 25 0/7 weeks gestation., Objective: To evaluate the association between the guideline modification and early neonatal outcome., Design: National cohort study, using prospectively collected data from The Netherlands Perinatal Registry., Patients: The study population consisted of 9713 infants with a gestational age between 24 0/7 and 29 6/7 weeks, born between 2000 and 2011. Three gestational age subgroups were analysed: 24 0/7 to 24 6/7 weeks (n=269), 25 0/7 to 25 6/7 weeks (n=852) and 26 0/7 to 29 6/7 weeks (n=8592)., Main Outcome Measures: Neonatal intensive care unit (NICU) admission, live births, neonatal in-hospital mortality, morbidity and favourable outcome (no mortality or morbidity) before (2000-2005; period 1) and after (2007-2011; period 2) introduction of the modified guideline, using χ(2) tests and univariable and multivariable logistic regression analyses., Results: In the second period, the proportion of live births and NICU admissions increased and the proportion of neonatal and in-hospital mortality decreased significantly in all subgroups. Morbidity in surviving infants of 25 weeks increased significantly, although the association between guideline modification and morbidity became non-significant after case-mix adjustment. Overall, favourable outcome did not change significantly after guideline modification in all subgroups when adjusted for variation in case-mix., Conclusions: Overall, the trend in mortality gradually declined at all gestational ages, starting before 2006. This suggests that the guideline modification was a formalisation of already existing daily practice., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To compare maternal and perinatal outcomes in dizygotic twin pregnancies conceived after medically assisted reproduction (MAR) with outcomes after natural conception (NC)., Design: Nationwide registry based study., Setting: Academic medical center., Patient(s): Primiparous women who delivered opposite sex twins between January 2000 and December 2012 in the Netherlands, comprising dizygotic twin pregnancies: 6,694 women, 470 after ovulation induction (OI), 511 after intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), 2,437 after in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), and 3,276 after NC., Intervention(s): None., Main Outcome Measure(s): Multivariable logistic regression and generalized linear mixed models to evaluate differences in outcomes: maternal outcomes of hypertension, preeclampsia, preterm delivery, hemorrhage, and delivery mode, perinatal outcomes including small for gestational age (SGA) with birth weight <10th percentile, birth weight <1,500 g, 5-minute Apgar score <7, admission to neonatal intensive care unit, congenital anomalies, and perinatal mortality., Result(s): We found no statistically significant differences in maternal or perinatal outcomes after OI compared with NC. Women pregnant after IVF-ICSI had a lower risk for hypertension (adjusted odds ratio [aOR] 0.74; 95% confidence interval [CI], 0.66-0.83) compared with women pregnant after NC. After IUI-COH more children had Apgar scores <7 (adjusted odds ratio (aOR) 1.38; 95% confidence interval (CI) 1.05-1.81) and perinatal mortality rates were higher (aOR 1.56; 95% CI, 1.04-2.33) compared with NC. We found no differences in perinatal outcomes after IVF-ICSI compared with NC., Conclusion(s): Overall, maternal and perinatal risks other than those due to multiplicity are similar for twin pregnancies conceived after MAR and after NC., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Descriptive population-based birthweight standards possess low sensitivity in detecting infants with growth impairment. A prescriptive birthweight standard based on a 'healthy' subpopulation without risk factors for intrauterine growth restriction might be superior. We created two birthweight standards based on live born, singleton infants with gestational age 24-42 weeks and born in The Netherlands between 2000 and 2007. Inclusion criteria for the prescriptive birthweight standard were restricted to infants without congenital malformations, born to healthy mothers after uncomplicated pregnancies. We defined small-for-gestational-age (SGA) as birthweight <10th percentile and assessed the ability of both standards to predict adverse neonatal outcomes. The prescriptive birthweight standard identified significantly more infants as SGA, up to 38.0 % at 29 weeks gestation. SGA infants classified according to both standards as well as those classified according to the prescriptive birthweight standard only, were at increased risk of both major and minor adverse neonatal outcomes. The prescriptive birthweight standard was both more sensitive and less specific, with a maximum increase in sensitivity predicting bronchopulmonary dysplasia (+42.6 %) and a maximum decrease in specificity predicting intraventricular haemorrhage (-26.9 %) in infants aged 28-31 weeks., Conclusion: Prescriptive birthweight standards could improve identification of infants born SGA and at risk of adverse neonatal outcomes., What Is Known: • Descriptive birthweight standards possess low sensitivity in detecting growth restricted infants at risk of adverse neonatal outcomes. • Prescriptive standards could improve identification of very preterm small-for-gestational-age (SGA) infants at risk of intraventricular haemorrhage. What is New: • Prescriptive standards identify more preterm and term SGA infants at risk of major adverse neonatal outcomes. • Late preterm and term SGA infants classified according to the prescriptive standard are at increased risk of minor adverse neonatal outcomes with potentially harmful implications.

We investigated whether changes in perinatal outcomes occurred following introduction of key tobacco control policies in the Netherlands: smoke-free legislation in workplaces plus a tobacco tax increase and mass media campaign (January-February 2004); and extension of the smoke-free law to the hospitality industry, accompanied by another tax increase and mass media campaign (July 2008). This was a national quasi-experimental study using Netherlands Perinatal Registry data (2000-2011; registration: ClinicalTrials.gov NCT02189265). Primary outcome measures were: perinatal mortality, preterm birth, and being small-for-gestational age (SGA). The association with timing of the tobacco control policies was investigated using interrupted time series logistic regression analyses with adjustment for confounders. Among 2,069,695 singleton births, there were 13,027 (0.6%) perinatal deaths, 116,043 (5.6%) preterm live-births and 187,966 (9.1%) SGA live-births. The 2004 policies were not associated with significant changes in the odds of developing any of the primary outcomes. After the 2008 policy change, a -4.4% (95% CI -2.4; -6.4, p < 0.001) decrease in odds of being SGA was observed. A reduction in SGA births, but not preterm birth or perinatal mortality, was observed in the Netherlands after extension of the smoke-free workplace law to bars and restaurants in conjunction with a tax increase and mass media campaign.

Objective: to study whether an increase in intrapartum referrals in primary midwife-led care births in the Netherlands is accompanied by an increase in caesarean sections., Design: nationwide descriptive study., Setting: The Netherlands Perinatal Registry., Participants: 807,437 births of nine year cohorts of women with low risk pregnancies in primary midwife-led care at the onset of labour between 2000 and 2008., Measurements: primary outcome is the caesarean section rate. Vaginal instrumental childbirth, augmentation with oxytocin, and pharmacological pain relief are secondary outcomes. Trends in outcomes are described. We used logistic regression to explore whether changes in the planned place of birth and other maternal characteristics were associated with the caesarean section rate., Findings: the caesarean section rate increased from 6.2 to 8.3 per cent for nulliparous and from 0.8 to 1.1 per cent for multiparous women. After controlling for maternal characteristics the year by year increase in the caesarean section rate was still significant for nulliparous women (adj OR 1.03; 95% CI 1.02–1.03). The vaginal instrumental birth declined from 18.2 to 17.4 per cent for nulliparous women (multiparous women: 1.7–1.5 per cent). Augmentation of labour and/or pharmacological pain relief increased from 23.1 to 38.1 per cent for nulliparous women and from 5.4 to 9.6 per cent for multiparous women., Conclusion: the rise in augmentation of labour, pharmacological pain relief and electronic fetal monitoring in the period 2000–2008 among women in primary midwife-led care was accompanied by an increase in caesarean section rate for nulliparous women. The vaginal instrumental deliveries declined for both nulliparous and multiparous women., Implications for Practice: primary care midwives should evaluate whether they can strengthen the opportunities for nulliparous women to achieve a physiological birth, without augmentation or pharmacological pain relief. If such interventions are considered necessary to achieve a spontaneous vaginal birth, the current disadvantage of discontinuity of care should be reduced. In a more integrated care system, women could receive continuous care and support from their own primary care midwife, as long as only supportive interventions are needed.

Objective: Our objective is to study the association between potentially influential determinants and first-trimester combined test (FCT) uptake rates in the central region of the Netherlands., Methods: Data were extracted from the national prenatal screening database Peridos and the Netherlands Perinatal Registry and compared at the level of the health care provider. Univariable and multivariable linear regression analysis was used to determine the effect of determinants (maternal age, parity, socio-economic status (SES), mode of conception, ethnicity and urbanisation) on uptake., Results: Prenatal screening data were available for 24 657 women and overall uptake rate was 25.7%. The strongest association with FCT uptake was found for advanced maternal age (β 2.2; 95% CI [1.7, 2.8]). Grand multiparity had a significantly negative association with FCT uptake (β -4.3; 95% CI [-5.9, -2.7]). Positive associations were found for very high urbanisation (β 0.3; 95% CI [0.1, 0.4]) and high SES (β 0.2; 95% CI [0.0, 0.3])., Conclusion: Advanced maternal age is strongly associated with participation in prenatal testing. The role of age related risk perception should be incorporated in future policy making to support women in informed and autonomous decision making. The negative association of grand multiparity and FCT might be religion based but requires further research. © 2015 John Wiley & Sons, Ltd., (© 2015 John Wiley & Sons, Ltd.)

Objective: Whether areas affected by Q fever during a large outbreak (2008-2010) had higher rates of adverse pregnancy outcomes than areas not affected by Q fever., Design: Nationwide registry-based ecological study., Setting: Pregnant women in areas affected and not affected by Q fever in the Netherlands, 2003-2004 and 2008-2010., Participants: Index group (N=58,737): pregnant women in 307 areas with more than two Q fever notifications. Reference group (N=310,635): pregnant women in 921 areas without Q fever notifications. As a baseline, pregnant women in index and reference areas in the years 2003-2004 were also included in the reference group to estimate the effect of Q fever in 2008-2010, and not the already existing differences before the outbreak., Main Outcome Measures: Preterm delivery, small for gestational age, perinatal mortality., Results: In 2008-2010, there was no association between residing in a Q fever-affected area and both preterm delivery (adjusted OR 1.01 (95% CI 0.94 to 1.08)), and perinatal mortality (adjusted OR 0.87 (95% CI 0.72 to 1.05)). In contrast, we found a weak significant association between residing in a Q fever-affected area in 2008-2010 and small for gestational age (adjusted OR 1.06 (95% CI 1.01 to 1.12)), with a population-attributable fraction of 0.70% (95% CI 0.07% to 1.34%). We observed no dose-response relation for this outcome with increasing Q fever notifications, and we did not find a stronger association for women who were in their first trimester of pregnancy during the months of high human Q fever incidence., Conclusions: This study found a weak association between residing in a Q fever-affected area and the pregnancy outcome small for gestational age. Early detection of infection would require mass screening of pregnant women; this does not seem to be justified considering these results, and the uncertainties about its efficacy and the adverse effects of antibiotic treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The incidence of severe postpartum hemorrhage (PPH) is increasing. Regional variation may be attributed to variation in provision of care, and as such contribute to this increasing incidence. We assessed reasons for regional variation in severe PPH in the Netherlands., Methods: We used the Netherlands Perinatal Registry and the Dutch Maternal Mortality Committee to study severe PPH incidences (defined as blood loss ≥ 1000 mL) across both regions and neighborhoods of cities among all deliveries between 2000 and 2008. We first calculated crude incidences. We then used logistic multilevel regression analyses, with hospital or midwife practice as second level to explore further reasons for the regional variation., Results: We analyzed 1599867 deliveries in which the incidence of severe PPH was 4.5%. Crude incidences of severe PPH varied with factor three between regions while between neighborhoods variation was even larger. We could not explain regional variation by maternal characteristics (age, parity, ethnicity, socioeconomic status), pregnancy characteristics (singleton, gestational age, birth weight, pre-eclampsia, perinatal death), medical interventions (induction of labor, mode of delivery, perineal laceration, placental removal) and health care setting., Conclusions: In a nationwide study in The Netherlands, we observed wide practice variation in PPH. This variation could not be explained by maternal characteristics, pregnancy characteristics, medical interventions or health care setting. Regional variation is either unavoidable or subsequent to regional variation of a yet unregistered variable.

Background: The primary aim of this study was to describe the variation in intrapartum referral rates in midwifery practices in the Netherlands. Secondly, we wanted to explore the association between the practice referral rate and a woman's chance of an instrumental birth (caesarean section or vaginal instrumental birth)., Methods: We performed an observational study, using the Dutch national perinatal database. Low risk births in all primary care midwifery practices over the period 2008-2010 were selected. Intrapartum referral rates were calculated. The referral rate among nulliparous women was used to divide the practices in three tertile groups. In a multilevel logistic regression analysis the association between the referral rate and the chance of an instrumental birth was examined., Results: The intrapartum referral rate varied from 9.7 to 63.7 percent (mean 37.8; SD 7.0), and for nulliparous women from 13.8 to 78.1 percent (mean 56.8; SD 8.4). The variation occurred predominantly in non-urgent referrals in the first stage of labour. In the practices in the lowest tertile group more nulliparous women had a spontaneous vaginal birth compared to the middle and highest tertile group (T1: 77.3%, T2:73.5%, T3: 72.0%). For multiparous women the spontaneous vaginal birth rate was 97%. Compared to the lowest tertile group the odds ratios for nulliparous women for an instrumental birth were 1.22 (CI 1.16-1.31) and 1.33 (CI 1.25-1.41) in the middle and high tertile groups. This association was no longer significant after controlling for obstetric interventions (pain relief or augmentation)., Conclusions: The wide variation between referral rates may not be explained by medical factors or client characteristics alone. A high intrapartum referral rate in a midwifery practice is associated with an increased chance of an instrumental birth for nulliparous women, which is mediated by the increased use of obstetric interventions. Midwives should critically evaluate their referral behaviour. A high referral rate may indicate that more interventions are applied than necessary. This may lead to a lower chance of a spontaneous vaginal birth and a higher risk on a PPH. However, a low referral rate should not be achieved at the cost of perinatal safety.

Objective: The use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for perinatal mortality rates. The objective of this study was to investigate the distribution and timing (antenatal, intrapartum or neonatal) of perinatal mortality and morbidity in relation to birth weight and gestational age at delivery., Methods: Data from over 1 million births occurring at 28-43 weeks' gestation from singleton pregnancies without congenital abnormalities in the period from 2002 to 2008 were collected from The Netherlands Perinatal Registry. The distribution of perinatal mortality according to birth-weight centile and gestational age at delivery was studied., Results: In the 1 170 534 pregnancies studied, there were 5075 (0.43%) perinatal deaths. The highest perinatal mortality occurred in those with a birth weight below the 2.3(rd) centile (25.4/1000 births) and the lowest mortality was in those with birth weights between the 80(th) and 84(th) centiles (2.4/1000 births), according to routinely used growth charts. Antepartum deaths were lowest in those with birth weight between the 90(th) and 95(th) centiles. Data were almost identical when the analysis was restricted to infants born at ≥ 37 weeks' gestation., Conclusion: From an immediate survival perspective, optimal fetal growth requires a birth weight between the 80(th) and 84(th) centiles for the population. Median birth weight in the population is, by definition, substantially lower than these centiles, implying that the majority of fetuses exhibit some form of maternal constraint on growth. This finding is consistent with adaptations that have evolved in humans in conjunction with a large head and bipedalism, to reduce the risk of obstructed delivery. These data also fit remarkably well with those on long-term adult cardiovascular and metabolic health risks, which are lowest in cases with a birth weight around the 90(th) centile., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To describe trends in the use of epidural analgesia (EA) and to evaluate the association of EA with operative deliveries., Study Design: In this population-based, retrospective cohort study, women with an intention to deliver vaginally of a term, cephalic, singleton between 2000 and 2009 (n=1378458) were included. Main outcome measures were labor EA rates, unplanned caesarean section (CS), and instrumental vaginal delivery (IVD) including deliveries by either vacuum or forceps. Data were obtained from the Perinatal Registry of The Netherlands and logistic regression analyses were used., Results: Among nulliparous, EA use almost tripled over the 10-year span (from 7.7% to 21.9%), while rates of CS and IVD did not change much (+2.8% and -3.3%, respectively). Among multiparous, EA use increased from 2.4% to 6.8%, while rates of CS and IVD changed slightly (+0.8% and -0.7%, respectively). Multivariable analysis showed a positive association of EA with CS, which weakened in ten years, from an adjusted OR of 2.35 (95% CI, 2.18 to 2.54) to 1.69 (95% CI, 1.60 to 1.79; p<0.001) in nulliparous, and from an adjusted OR of 3.17 (95% CI, 2.79 to 3.61) to 2.56 (95% CI, 2.34 to 2.81; p<0.001) in multiparous women. A weak inverse association between EA and IVD was found among nulliparous (adjusted OR, 0.76; 95% CI, 0.75 to 0.78), and a positive one among multiparous women (adjusted OR, 2.08; 95% CI, 2.00 to 2.16). Both associations grew slightly weaker over time., Conclusions: A near triplication of EA use in The Netherlands in ten years was accompanied by relatively stable rates of operative deliveries. The association between EA and operative delivery became weaker. This supports the idea that EA is not an important causal factor of operative deliveries., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the maternal and neonatal outcome of non-anonymous oocyte donation compared to in vitro fertilization. Study design We compared 84 oocyte donation pregnancies with a 251 matched in vitro fertilization cohort. Maternal and neonatal outcomes were retrieved from a nationwide perinatal registry. Oocyte donation and in vitro fertilization pregnancies were matched for maternal age, study center, ZIP code and embryo transfer date. Both maternal and neonatal complications and outcome were compared between oocyte donation and in vitro fertilization with univariate and multivariate logistic regression analyses, adjusting for maternal age, donor age, socio-economic status, ethnicity, and parity., Results: In total, 277 women underwent 541 oocyte donation cycles. The median recipient age was 34.9 years (IQR: 31.5-38.5), while the median donor age was 34.4 years (IQR: 31.7-37.0). Clinical pregnancy rate was 26.6%, which is comparable to standard in vitro fertilization treatment. Donor age in years (OR 0.93, 95% CI 0.88-0.99) and a previous pregnancy of the recipient (OR 1.69, 95% CI 1.02-2.78) were significantly associated with clinical pregnancy rate. Both singleton and multiple oocyte donation pregnancies were associated with pregnancy-induced hypertension compared with in vitro fertilization singleton and multiple pregnancies (OR 1.99, 95%CI 1.02-3.89, OR 6.43, 95% CI 1.67-24.72, respectively). No significant differences in neonatal outcome were observed., Conclusion: Oocyte donation pregnancies are associated with an increased incidence of pregnancy-induced hypertension compared with age-matched in vitro fertilization controls. However, no significant differences in neonatal outcome were observed between oocyte donation and in vitro fertilization., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: to study whether an increase in intrapartum referrals in primary midwife-led care births in the Netherlands is accompanied by an increase in caesarean sections., Design: nationwide descriptive study., Setting: the Netherlands Perinatal Registry., Participants: 789,795 births of nine year cohorts of women with low risk pregnancies in primary midwife-led care at the onset of labour between 2000 and 2008., Measurements: primary outcome is the caesarean section rate. Vaginal instrumental delivery, augmentation with oxytocin, and pharmacological pain relief are secondary outcomes. Trends in outcomes are described. We used logistic regression to explore whether changes in the planned place of birth and other maternal characteristics influenced the caesarean section rate., Findings: the caesarean section rate did not increase and was 5.5 per cent (range 4.9-6.3 per cent) for nulliparous women, and 1.0 per cent (range 0.8-1.1 per cent) for multiparous women. After controlling for the decline in planned home births and other maternal characteristics no increase in the caesarean section rate was found. The vaginal instrumental birth rate showed no increase, and was 18.1 per cent (range 17.9-18.5 per cent) for nulliparous women and 1.5 per cent (range 1.4-1.7 per cent) for multiparous women. Augmentation of labour and/or pharmacological pain relief increased from 24.0 to 38.8 per cent for nulliparous women, and from 5.4 to 10.0 per cent for multiparous women., Conclusion: the rise in intrapartum referrals was not accompanied by an increase in caesarean section rate over the period 2000-2008. Despite a considerable rise in the use of pain relief and augmentation, the rate of spontaneous vaginal birth remained high for low risk women who started labour in primary midwife-led care., Implications for Practice: the current strict role division between primary care midwives and the obstetrician-led team increasingly results in a change in care provider during labour. In a more integrated care system, more women can receive continuous support of labour from their own primary care midwife, as long as only supportive interventions are needed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To analyse if from 2000-2010 the rate of elective caesarean sections (CS) before 39 0/7 weeks of gestation declined when compared with all elective CS, and to evaluate the possible associated factors., Design: Retrospective cohort study., Method: Using data from The Netherlands Perinatal Registry, all term elective CS (n = 59,653) from 2000-2010 were selected. Trends in patient characteristics and in performing an elective CS before 39 0/7 weeks were analysed using regression analysis, and differences between hospitals using the χ2 test. Using multiple logistic regression analysis it was analysed which factors were associated with performing an elective CS before 39 0/7 weeks., Results: The percentage of elective CS before 39 0/7 weeks decreased from 56% in 2000 to 43% in 2010 (p < 0.0001). In peripheral hospitals an elective SC was performed more often before 39+0 weeks than in academic hospitals; 53% in peripheral teaching hospitals, 57% in peripheral non-teaching hospitals, and 46% in academic hospitals. Adjusted odds ratios and 95% confidence intervals were 1.38 (1.30-1.47) in peripheral teaching hospitals, and 1.55 (1.46-1.65) in peripheral non-teaching hospitals. In hospitals where the number of deliveries per year was situated in the lower quartile, elective CS before 39 0/7 weeks was carried out more often than in hospitals where deliveries per year were in the upper quartile, 60% versus 52% (p < 0.0001)., Conclusion: In the period 2000-2009 the timing of elective CS improved marginally. In 2010 the trend began to decline, even though 43% of elective caesarean sections were still carried out before 39 0/7 weeks. This results in a higher risk of neonatal morbidity and health problems in long-term.

Objective: To compare the change in foetal and neonatal mortality in the Netherlands between 2004 and 2010 with the change in other European countries., Design: Descriptive, population-based study., Method: Data from the Euro-Peristat project on foetal and neonatal mortality in European countries were analysed for changes between 2004 and 2010. The Netherlands was compared with 26 other European countries and regions. International differences in registration and policy were taken into account using figures on foetal mortality starting at 28 weeks of pregnancy and neonatal mortality starting at 24 weeks of pregnancy., Results: Foetal mortality in the Netherlands declined by 33%, from 4.3 per 1000 births in 2004 to 2.9 per 1000 births in 2010 while neonatal mortality declined by 21%, from 2.8 per 1000 live births in 2004 to 2.2 per 1000 live births in 2010. Perinatal mortality (the sum of foetal mortality and neonatal mortality) declined by 27%, from 7.0 to 5.1 per 1000. In the European ranking, the Netherlands shifted from 23rd to 13th place for foetal mortality; it remained the same for neonatal mortality (15th of 22 countries) and virtually the same for perinatal mortality (from 15th to 13th of 22 countries)., Conclusions: Both foetal mortality at 28+ weeks and neonatal mortality at 24+ weeks declined in the Netherlands between 2004 and 2010. However, the relatively unfavourable position of the Netherlands in the European ranking for foetal and neonatal mortality improved only for foetal mortality. In that respect, the Netherlands holds an average position.

Background: Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous studies show conflicting results in the association between pre-eclampsia and postpartum haemorrhage. The primary objective of this study was to investigate the association between pre-eclampsia and postpartum haemorrhage. Our secondary objective was to identify other risk indicators for postpartum haemorrhage in the Netherlands., Methods: A nationwide cohort was used, containing prospectively collected data of women giving birth after 19 completed weeks of gestation from January 2000 until January 2008 (n =  1,457,576). Data were extracted from the Netherlands Perinatal Registry, covering 96% of all deliveries in the Netherlands. The main outcome measure, postpartum haemorrhage, was defined as blood loss of ≥1000 ml in the 24 hours following delivery. The association between pre-eclampsia and postpartum haemorrhage was investigated with uni- and multivariable logistic regression analyses., Results: Overall prevalence of postpartum haemorrhage was 4.3% and of pre-eclampsia 2.2%. From the 31 560 women with pre-eclampsia 2 347 (7.4%) developed postpartum haemorrhage, compared to 60 517 (4.2%) from the 1 426 016 women without pre-eclampsia (odds ratio 1.81; 95% CI 1.74 to 1.89). Risk of postpartum haemorrhage in women with pre-eclampsia remained increased after adjusting for confounders (adjusted odds ratio 1.53; 95% CI 1.46 to 1.60)., Conclusion: Women with pre-eclampsia have a 1.53 fold increased risk for postpartum haemorrhage. Clinicians should be aware of this and use this knowledge in the management of pre-eclampsia and the third stage of labour in order to reach the fifth Millenium Developmental Goal of reducing maternal mortality ratios with 75% by 2015.

Background: There are concerns about the Dutch maternity care system, characterized by a strict role division between primary and secondary care. The objective of this study was to describe trends in referrals and in perinatal outcomes among labors that started in primary midwife-led care., Methods: We performed a descriptive study of all 789,795 labors that started in primary midwife-led care during 2000 to 2008 in The Netherlands. Referrals to obstetrician-led care or pediatrician were classified as urgent or nonurgent. Perinatal safety was described by perinatal mortality (intrapartum or neonatal 0-7 days), admission to neonatal intensive care unit 0-7 days, and Apgar score < 7 at 5 minutes., Results: The proportion of referrals during labor or after birth declined from 52.6 to 42.6 percent for nulliparous women and from 83.2 to 76.7 percent for multiparous women. Especially nonurgent referrals during the first stage increased, for nulliparous women from 28.7 to 40.7 percent and for multiparous women from 10.5 to 16.5 percent. Referrals were less frequent in planned home births. Perinatal mortality was 0.9 per thousand births for nulliparous women, and 0.6 per thousand for multiparous women. A low Apgar score was registered in 8.6 per thousand births for nulliparous women, and 4.1 per thousand for multiparous women., Conclusions: There was a considerable rise in nonurgent referrals to obstetrician-led care in primary midwife-led care during labor. Perinatal safety did not improve significantly over time. The persisting rise in referrals challenges the sustainability of the current strict role division between primary and secondary maternity care in The Netherlands., (© 2013, Copyright the Authors Journal compilation © 2013, Wiley Periodicals, Inc.)

Objective: To compare the incidences of preterm delivery, cervical incompetence treated by cerclage, placental implantation or retention problems (ie, placenta praevia, placental abruption and retained placenta) and postpartum haemorrhage between women with and without a history of pregnancy termination., Design:  A retrospective cohort study using aggregated data from a national perinatal registry., Setting: All midwifery practices and hospitals in the Netherlands., Participants: All pregnant women with a singleton pregnancy without congenital malformations and a gestational age of ≥20 weeks who delivered between January 2000 and December 2007., Main Outcome Measures: Preterm delivery, cervical incompetence treated by cerclage, placenta praevia, placental abruption, retained placenta and postpartum haemorrhage., Results: A previous pregnancy termination was reported in 16 000 (1.2%) deliveries. The vast majority of these (90-95%) were performed by surgical methods. The incidence of all outcome measures was significantly higher in women with a history of pregnancy termination. Adjusted ORs (95% CI) for cervical incompetence treated by cerclage, preterm delivery, placental implantation or retention problems and postpartum haemorrhage were 4.6 (2.9 to 7.2), 1.11 (1.02 to 1.20), 1.42 (1.29 to 1.55) and 1.16 (1.08 to 1.25), respectively. Associated numbers needed to harm were 1000, 167, 111 and 111, respectively. For any listed adverse outcome, the number needed to harm was 63., Conclusions: In this large nationwide cohort study, we found a positive association between surgical termination of pregnancy and subsequent preterm delivery, cervical incompetence treated by cerclage, placental implantation or retention problems and postpartum haemorrhage in a subsequent pregnancy. Absolute risks for these outcomes, however, remain small. Medicinal termination might be considered first whenever there is a choice between both methods.

Study Question: To what degree do records registered in the Netherlands Perinatal Registry (PRN) agree with self-report in a study questionnaire on pregnancy outcomes in childhood cancer survivors (CCSs)?, Summary Answer: This study suggests that self-reported pregnancy outcomes of CCSs agree well with registry data and that outcomes reported by CCSs agree better with registry data than do those of controls., What Is Known Already: Many studies have shown that childhood cancer treatment may affect fertility outcomes in female CCSs; however, these conclusions were often based on questionnaire data, and it remains unclear whether self-report agrees well with more objective sources of information., Study Design, Size, Duration: In an nationwide cohort study on fertility (inclusion period January 2008 and April 2011, trial number: NTR2922), 1420 CCSs and 354 sibling controls were invited to complete a questionnaire regarding socio-demographic characteristics and reproductive history. In total, 879 CCSs (62%) and 287 controls (81%) returned the questionnaire., Participants/materials, Setting, Methods: The current validation study compared the agreement between pregnancy outcomes as registered in the PRN and self-reported outcomes in the study questionnaire. A total of 589 pregnancies were reported in CCSs, and 300 pregnancies in sibling controls, of which 524 could be linked to the PRN., Main Results and the Role of Chance: A high intra-class correlation coefficient (ICC) was found for birthweight (BW) (0.94 and 0.87 for CCSs and controls, respectively). The self-reported BWs tended to be higher than reported in the PRN. For gestational age (GA), the ICC was high for CCSs (0.88), but moderate for controls (0.49). CCSs overestimated GA more often than controls. The Kappa values for method of conception and for method of delivery were moderate to good. Multilevel analyses on the mean difference with regard to BW and GA showed no differences associated with time since pregnancy or educational level., Limitations, Reasons for Caution: Not all pregnancies reported could be linked to the registry data. In addition, the completeness of the PRN could not be assessed precisely, because there is no information on the number of missing records. Finally, for some outcomes there were high proportions of missing values in the PRN registry., Wider Implications of the Findings: Our study suggests that questionnaires are a reliable method of data collection, and that for most variables, self-report agrees well with registry data., Study Funding/competing Interest: This work was supported by the Dutch Cancer Society (grant no. VU 2006-3622) and by Foundation Children Cancer Free. None of the authors report a conflict of interest., Trial Registration Number: NTR2922 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922.

Objective: We sought to assess neonatal morbidity and mortality of elective cesarean section (CS) of uncomplicated twin pregnancies per week of gestation >35(+0)., Study Design: We performed a retrospective cohort study in our nationwide database including all elective CS of twin pregnancies. Two main composite outcome measures were defined, ie, severe adverse neonatal outcome and mild neonatal morbidity., Results: We report on 2228 neonates. More than 17% were born <37(+0) weeks of gestation. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for severe adverse neonatal outcome at 35(+0-6), 36(+0-6), and 37(+0-6) weeks were, OR, 9.4; 95% CI, 3.2-27.6; OR, 1.7; 95% CI, 0.5-5.3; and OR, 0.7; 95% CI, 0.2-2.0, respectively; and for mild neonatal morbidity, OR, 4.7; 95% CI, 2.6-8.7; OR, 4.9; 95% CI, 3.1-7.9; and 1.4; 95% CI, 0.9-2.1, respectively, compared to neonates born ≥38(+0) weeks of gestation., Conclusion: In uncomplicated twin pregnancies elective CS can best be performed between 37(+0) and 39(+6) weeks of gestation., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Studies have demonstrated a higher risk of adverse outcomes among infants born or admitted during off-hours, as compared to office hours, leading to questions about quality of care provide during off-hours (weekend, evening or night). We aim to determine the relationship between off-hours delivery and adverse perinatal outcomes for subgroups of hospital births., Methods: This retrospective cohort study was based on data from the Netherlands Perinatal Registry, a countrywide registry that covers 99% of all hospital births in the Netherlands. Data of 449,714 infants, born at 28 completed weeks or later, in the period 2003 through 2007 were used. Infants with a high a priori risk of morbidity or mortality were excluded. Outcome measures were intrapartum and early neonatal mortality, a low Apgar score (5 minute score of 0-6), and a composite adverse perinatal outcome measure (mortality, low Apgar score, severe birth trauma, admission to a neonatal intensive care unit)., Results: Evening and night-time deliveries that involved induction or augmentation of labour, or an emergency caesarean section, were associated with an increased risk of an adverse perinatal outcome when compared to similar daytime deliveries. Weekend deliveries were not associated with an increased risk when compared to weekday deliveries. It was estimated that each year, between 126 and 141 cases with an adverse perinatal outcomes could be attributed to this evening and night effect. Of these, 21 (15-16%) are intrapartum or early neonatal death. Among the 3100 infants in the study population who experience an adverse outcome each year, death accounted for only 5% (165) of these outcomes., Conclusion: This study shows that for infants whose mothers require obstetric interventions during labour and delivery, birth in the evening or at night, are at an increased risk of an adverse perinatal outcomes.

Objective: To assess the recurrence risk of late-preterm hypertensive disease of pregnancy, and to determine whether potential risk factors are predictive., Design: Retrospective cohort study., Setting: Three secondary and three tertiary care hospitals in the Netherlands., Population: We identified women with a hypertensive disorder in the index pregnancy and delivery at 34-37 weeks of gestation, between January 2000 and December 2002., Methods: Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. An adverse outcome was defined as the recurrence of a hypertensive disorder in the next subsequent pregnancy., Main Outcome Measures: Absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive for adverse outcome., Results: We identified 425 women who matched the criteria, of whom 351 could be contacted. Of these women, 189 (54%) had had a subsequent pregnancy. Hypertensive disorders recurred in 96 (51%, 95% CI 43-58%) women, of whom 17 (9%, 95% CI 5-14%) delivered again before 37 weeks of gestation. Chronic hypertension and maternal age were the strongest predictors for recurrence. Women undergoing recurrence had a nine-fold chance of developing chronic hypertension (37% versus 6%, OR 8.7, 95% CI 3.3-23)., Conclusions: Women with hypertensive disorders and late-preterm delivery have a 50% chance of recurrence, but only a 9% chance of recurrence resulting in delivery before 37 weeks of gestation. Women with chronic hypertension are prone to develop recurrence, and women with a recurrence more often developed chronic hypertension., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Objectives: To validate externally 2 prognostic models for stillbirth and neonatal death in very preterm infants who are either known to be alive at the onset of labor or admitted for neonatal intensive care., Patients and Methods: All infants, with gestational age 22 to 32 weeks, of European ethnicity, known to be alive at the onset of labor (n = 17 582) and admitted for neonatal intensive care (n = 11 578), who were born in the Netherlands between January 1, 2000, and December 31, 2007. The main outcome measures were stillbirth or death within 28 days for infants known to be alive at the onset of labor and death before discharge from the NICU for infants admitted for intensive care. Model performance was studied with calibration plots and c statistic., Results: Of the infants known to be alive at the onset of labor, 16.7% (n = 2939) died during labor or within 28 days of birth, and 7.8% (n = 908) of the infants admitted for neonatal intensive care died before discharge from intensive care. The prognostic model for infants known to be alive at the onset of labor showed good calibration and excellent discrimination (c statistic 0.92). The prognostic model for infants admitted for neonatal intensive care showed good calibration and good discrimination (c statistic 0.82)., Conclusions: The 2 prognostic models for stillbirth and neonatal death in very preterm Dutch infants showed good performance, suggesting their use in clinical practice in the Netherlands and possibly other Western countries.

Objective: The purpose of this study was to evaluate whether the association between short interpregnancy intervals and perinatal outcome varies with maternal age., Study Design: We performed a retrospective cohort study among 263,142 Dutch women with second deliveries that occurred between 2000 and 2007. Outcome variables were preterm delivery (<37 weeks of gestation), low birthweight in term deliveries (<2500 g) and small-for-gestational age (<10th percentile for gestational age on the basis of sex- and parity-specific Dutch standards)., Results: Short interpregnancy intervals (<6 months) was associated positively with preterm delivery and low birthweight, but not with being small for gestational age. The association of short interpregnancy interval with the risk of preterm delivery was weaker among older than younger women. There was no clear interaction between short interpregnancy interval and maternal age in relation to low birthweight or small for gestational age., Conclusion: The results of this study indicate that the association of short interpregnancy interval with preterm delivery attenuates with increasing maternal age., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Q fever has become a major public health problem in The Netherlands. Infection with Coxiella burnetii (Q fever) during pregnancy has resulted in adverse pregnancy outcome in the majority of reported cases. Therefore, we aimed to quantify this risk by examining the earliest periods corresponding to the epidemic in The Netherlands., Methods: Serum samples that had been collected from the area of highest incidence by an existing national prenatal screening programme and data from the Netherlands Perinatal Registry (PRN) on diagnosis and outcome were used. We performed indirect immunofluorescence assay to detect the presence of IgM and IgG antibodies against C. burnetii in the samples. The serological results were analyzed to determine statistical association with recorded pregnancy outcome., Results: Evaluation of serological results for 1174 women in the PRN indicated that the presence of IgM and IgG antibodies against phase II of C. burnetii was not significantly associated with preterm delivery, low birth weight, or several other outcome measures., Conclusion: The present population-based study showed no evidence of adverse pregnancy outcome among women who had antibodies to C. burnetii during early pregnancy.

Background: Most midwives in the Netherlands work in primary care where they are the lead professionals providing care to women with 'normal' or uncomplicated pregnancies, while some midwives work in hospitals ("clinical midwives"). The actual involvement of midwives in maternity care in hospitals is unknown, because in all statistics births in secondary care are registered as births assisted by gynaecologists. The aim of this study is to gain insight in the involvement of midwives with births in secondary care, under supervision of a gynaecologist. This is done using data from the PRN (The Netherlands Perinatal Registry), a voluntary registration of births in the Netherlands. The PRN covers 97% to 99% of all births taking place under responsibility of a gynaecologist., Methods: All births registered in secondary care in the period 1998-2007 (1,102,676, on average 61% of all births) were selected. We analyzed trends in socio-demographic, obstetric and organisational characteristics, associated with the involvement of midwives, using frequency tables and uni- and multivariate logistic regression analyses. As main outcome measure the percentage of births in secondary care with a midwife 'catching' the baby was used., Results: The proportion of births attended by a midwife in secondary care increased from 8.3% in 1998 to 26.06% in 2007, the largest increase involving spontaneous births of a second or later child, on weekdays during day shifts (8.00-20.00 hr) from younger mothers with a gestational age (almost) at term. After 2002, parallel to the growing numbers of midwives working in hospitals, the percentage of instrumental births decreased., Conclusions: In 2007 more midwives are assisting with more births in secondary care than in 1998. Hospital-based midwives are primarily involved with uncomplicated births of women with relatively low risk demographical and obstetrical characteristics. However, they are still only involved with half of the less complicated births, indicating that there may be room for more midwives in hospitals to care for women with relatively uncomplicated births. Whether an association exists between the growing involvement of midwives and the decreasing percentage of instrumental births needs further investigation.

Objective: To compare incidences of perinatal mortality and severe perinatal morbidity between low risk term pregnancies supervised in primary care by a midwife and high risk pregnancies supervised in secondary care by an obstetrician., Design: Prospective cohort study using aggregated data from a national perinatal register., Setting: Catchment area of the neonatal intensive care unit (NICU) of the University Medical Center in Utrecht, a region in the centre of the Netherlands covering 13% of the Dutch population., Participants: Pregnant women at 37 weeks' gestation or later with a singleton or twin pregnancy without congenital malformations., Main Outcome Measures: Perinatal death (antepartum, intrapartum, and neonatal) or admission to a level 3 NICU., Results: During the study period 37 735 normally formed infants were delivered at 37 weeks' gestation or later. Sixty antepartum stillbirths (1.59 (95% confidence interval 1.19 to 1.99) per 1000 babies delivered), 22 intrapartum stillbirths (0.58 (0.34 to 0.83) per 1000 babies delivered), and 210 NICU admissions (5.58 (4.83 to 6.33) per 1000 live births) occurred, of which 17 neonates died (0.45 (0.24 to 0.67) per 1000 live births). The overall perinatal death rate was 2.62 (2.11 to 3.14) per 1000 babies delivered and was significantly higher for nulliparous women compared with multiparous women (relative risk 1.65, 95% confidence interval 1.11 to 2.45). Infants of pregnant women at low risk whose labour started in primary care under the supervision of a midwife had a significant higher risk of delivery related perinatal death than did infants of pregnant women at high risk whose labour started in secondary care under the supervision of an obstetrician (relative risk 2.33, 1.12 to 4.83). NICU admission rates did not differ between pregnancies supervised by a midwife and those supervised by an obstetrician. Infants of women who were referred by a midwife to an obstetrician during labour had a 3.66 times higher risk of delivery related perinatal death than did infants of women who started labour supervised by an obstetrician (relative risk 3.66, 1.58 to 8.46) and a 2.5-fold higher risk of NICU admission (2.51, 1.87 to 3.37)., Conclusions: Infants of pregnant women at low risk whose labour started in primary care under the supervision of a midwife in the Netherlands had a higher risk of delivery related perinatal death and the same risk of admission to the NICU compared with infants of pregnant women at high risk whose labour started in secondary care under the supervision of an obstetrician. An important limitation of the study is that aggregated data of a large birth registry database were used and adjustment for confounders and clustering was not possible. However, the findings are unexpected and the obstetric care system of the Netherlands needs further evaluation.

Background: The number of childhood cancer survivors has dramatically increased and consequently, an increasing number of survivors may now wish to conceive. Recently, several studies have described that previous treatment with abdominal radiotherapy may increase the risk of adverse pregnancy outcome., Methods: We conducted a retrospective single centre cohort study of childhood cancer survivors with a singleton live birth between January 2000 and December 2005. Pregnancy outcome was compared with data from the Netherlands Perinatal Registry, a nationwide database of pregnancy outcome parameters of all births in the Netherlands registered by midwives, obstetricians and paediatricians., Results: Data were available on 40 survivors and 9031 controls. Median age at diagnosis was 6.9 years (range 0.1-16.8 years). The median interval between diagnosis and date of delivery was 21.6 years (range 7.4-36.1 years). In the whole cohort, pregnancy outcome was not different between survivors and controls. However, survivors treated with abdominal radiotherapy delivered preterm and had post-partum haemorrhage (mean gestational age in survivors = 34.9 versus 39.2 weeks in controls, P = 0.001; 33% in survivors versus 5% in controls, P = 0.007, respectively). The offspring of survivors had normal birthweight after adjustment for gestational age (mean birthweight in offspring of survivors 2503 versus 1985 g; P = 0.22)., Conclusion: Childhood cancer survivors irradiated to the abdomen have an earlier delivery and higher incidence of post-partum haemorrhage. This stresses the need for close monitoring of the delivery, including inpatient perinatal care, in this group of childhood cancer survivors.

Objective: We sought to evaluate number and timing of elective cesarean sections at term and to assess perinatal outcome associated with this timing., Study Design: We conducted a recent retrospective cohort study including all elective cesarean sections of singleton pregnancies at term (n = 20,973) with neonatal follow-up. Primary outcome was defined as a composite of neonatal mortality and morbidity., Results: More than half of the neonates were born at <39 weeks of gestation, and they were at significantly higher risk for the composite primary outcome than neonates born thereafter. The absolute risks were 20.6% and 12.5% for birth at <38 and 39 weeks, respectively, as compared to 9.5% for neonates born > or = 39 weeks. The corresponding adjusted odds ratios (95% confidence interval) were 2.4 (2.1-2.8) and 1.4 (1.2-1.5), respectively., Conclusion: More than 50% of the elective cesarean sections are applied at <39 weeks, thus jeopardizing neonatal outcome., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objective: Comparison of perinatal mortality in The Netherlands with that in other European countries (Peristat-II), and with data collected 5 years previously (Peristat-I)., Design: Descriptive study., Method: Indicators ofperinatal mortality which were developed for Peristat-I were used again in Peristat-II. Data on perinatal mortality in 2004 were delivered by 26 European countries. The Dutch data originated from national registers of midwives and gynaecologists and the National Neonatology Register., Results: In Peristat-I, from 22 weeks gestation, The Netherlands had the highest fetal mortality rate (7.4 per 1,000 total number of births). Furthermore, after Greece, The Netherlands had the highest early neonatal mortality rate (3.5 per 1,000 live births). In Peristat-II from 22 weeks gestation, after France, The Netherlands had the highest fetal mortality rate (7.0 per 1,000 total number of births). Of all western European countries, The Netherlands had the highest early neonatal mortality rate (3.0 per 1,000 live births). Over the past 5 years the perinatal mortality rate in The Netherlands has dropped from 10.9 to 10.0 per 1,000 total births but this drop has been faster in other countries., Conclusion: The Netherlands has a relatively high number of older mothers and multiple pregnancies, but this only partly explains the high Dutch perinatal mortality rate which still ranks unfavourably in the European tables. More research is necessary to gain insight into the prevalence of risk factors for perinatal mortality compared with other European countries. In addition, perinatal health and the quality ofperinatal healthcare deserve a more prominent position in Dutch research programmes.

Randomised controlled trials have demonstrated that mild hypothermia reduces mortality and morbidity in full-term neonates who experience perinatal asphyxia. Hypothermia can be applied to the head or entire body, maintaining a temperature of 33-34 degrees C for 72 hours. Treatment should be started within 6 hours after birth. An estimated 180-200 neonates may be eligible for this novel approach to neuroprotection each year in the Netherlands.

Objectives: To describe the modeling techniques used for early prediction of outcome in traumatic brain injury (TBI) and to identify aspects for potential improvements., Study Design and Setting: We reviewed key methodological aspects of studies published between 1970 and 2005 that proposed a prognostic model for the Glasgow Outcome Scale of TBI based on admission data., Results: We included 31 papers. Twenty-four were single-center studies, and 22 reported on fewer than 500 patients. The median of the number of initially considered predictors was eight, and on average five of these were selected for the prognostic model, generally including age, Glasgow Coma Score (or only motor score), and pupillary reactivity. The most common statistical technique was logistic regression with stepwise selection of predictors. Model performance was often quantified by accuracy rate rather than by more appropriate measures such as the area under the receiver-operating characteristic curve. Model validity was addressed in 15 studies, but mostly used a simple split-sample approach, and external validation was performed in only four studies., Conclusion: Although most models agree on the three most important predictors, many were developed on small sample sizes within single centers and hence lack generalizability. Modeling strategies have to be improved, and include external validation.

Objective: Various prognostic models have been developed to predict outcome after traumatic brain injury (TBI). We aimed to determine the validity of six models that used baseline clinical and computed tomographic characteristics to predict mortality or unfavorable outcome at 6 months or later after severe or moderate TBI., Study Design and Setting: The validity was studied in two selected series of TBI patients enrolled in clinical trials (Tirilazad trials; n = 2,269; International Selfotel Trial; n = 409) and in two unselected series of patients consecutively admitted to participating centers (European Brain Injury Consortium [EBIC] survey; n = 796; Traumatic Coma Data Bank; n = 746). Validity was indicated by discriminative ability (AUC) and calibration (Hosmer-Lemeshow goodness-of-fit test)., Results: The models varied in number of predictors (four to seven) and in development technique (two prediction trees and four logistic regression models). Discriminative ability varied widely (AUC: .61-.89), but calibration was poor for most models. Better discrimination was observed for logistic regression models compared with trees, and for models including more predictors. Further, discrimination was better when tested on unselected series that contained more heterogeneous populations., Conclusion: Our findings emphasize the need for external validation of prognostic models. The satisfactory discrimination indicates that logistic regression models, developed on large samples, can be used for classifying TBI patients according to prognostic risk.

Background and Objective: The Marshall computed tomographic (CT) classification identifies six groups of patients with traumatic brain injury (TBI), based on morphological abnormalities on the CT scan. This classification is increasingly used as a predictor of outcome. We aimed to examine the predictive value of the Marshall CT classification in comparison with alternative CT models., Methods: The predictive value was investigated in the Tirilazad trials (n = 2269). Alternative models were developed with logistic regression analysis and recursive partitioning. Six month mortality was used as outcome measure. Internal validity was assessed with bootstrapping techniques and expressed as the area under the receiver operating curve (AUC)., Results: The Marshall CT classification indicated reasonable discrimination (AUC = 0.67), which could be improved by rearranging the underlying individual CT characteristics (AUC = 0.71). Performance could be further increased by adding intraventricular and traumatic subarachnoid hemorrhage and by a more detailed differentiation of mass lesions and basal cisterns (AUC = 0.77). Models developed with logistic regression analysis and recursive partitioning showed similar performance. For clinical application we propose a simple CT score, which permits a more clear differentiation of prognostic risk, particularly in patients with mass lesions., Conclusion: It is preferable to use combinations of individual CT predictors rather than the Marshall CT classification for prognostic purposes in TBI. Such models should include at least the following parameters: status of basal cisterns, shift, traumatic subarachnoid or intraventricular hemorrhage, and presence of different types of mass lesions.

The early prediction of outcome after traumatic brain injury (TBI) is important for several purposes, but no prognostic models have yet been developed with proven generalizability across different settings. The objective of this study was to develop and validate prognostic models that use information available at admission to estimate 6-month outcome after severe or moderate TBI. To this end, this study evaluated mortality and unfavorable outcome, that is, death, and vegetative or severe disability on the Glasgow Outcome Scale (GOS), at 6 months post-injury. Prospectively collected data on 2269 patients from two multi-center clinical trials were used to develop prognostic models for each outcome with logistic regression analysis. We included seven predictive characteristics-age, motor score, pupillary reactivity, hypoxia, hypotension, computed tomography classification, and traumatic subarachnoid hemorrhage. The models were validated internally with bootstrapping techniques. External validity was determined in prospectively collected data from two relatively unselected surveys in Europe (n = 796) and in North America (n = 746). We evaluated the discriminative ability, that is, the ability to distinguish patients with different outcomes, with the area under the receiver operating characteristic curve (AUC). Further, we determined calibration, that is, agreement between predicted and observed outcome, with the Hosmer-Lemeshow goodness-of-fit test. The models discriminated well in the development population (AUC 0.78-0.80). External validity was even better (AUC 0.83-0.89). Calibration was less satisfactory, with poor external validity in the North American survey (p < 0.001). Especially, observed risks were higher than predicted for poor prognosis patients. A score chart was derived from the regression models to facilitate clinical application. Relatively simple prognostic models using baseline characteristics can accurately predict 6-month outcome in patients with severe or moderate TBI. The high discriminative ability indicates the potential of this model for classifying patients according to prognostic risk.

Objective: To investigate whether triage for direct admission of patients with traumatic brain injury to a trauma center is facilitated by predicting the risk of potentially removable lesions or raised intracranial pressure (ICP)., Design and Setting: Cohort study in a level I university trauma center., Patients and Participants: A prospective cohort of primarily (n=200) and secondarily (n=75) referred patients with moderate or severe traumatic brain injury., Measurements and Results: Predictive characteristics for the risk of surgically removable lesions and the risk of raised ICP (repeatedly > or = 20 mmHg) were identified and included in prognostic models. These models were validated internally with bootstrapping techniques and externally on a historic sample (n=205) regarding discriminative ability (AUC). Among the cohort patients, 67% had raised ICP and 54% had surgically removable lesions. Both outcomes occurred more frequently in patients secondarily referred, but the incidence in patients primarily referred was also high (62% and 33% respectively). No strong predictors of raised ICP were identified. Age and pupillary reactivity were significant predictors of surgically removable lesions. The models discriminated reasonably for surgically removable lesions (AUC=0.78 at development and AUC=0.67 at external validation) but not for raised ICP (AUC=0.59 at development and AUC=0.50 at external validation)., Conclusions: It is difficult accurately to identify patients in need of specialized intensive care using baseline characteristics. The high incidence of both outcomes in patients primarily referred support direct admission of more and particularly older patients with severe or moderate brain trauma to level I trauma centers.

Object: Increasing age is associated with poorer outcome in patients with closed traumatic brain injury (TBI). It is uncertain whether critical age thresholds exist, however, and the strength of the association has yet to be investigated across large series. The authors studied the shape and strength of the relationship between age and outcome, that is, the 6-month mortality rate and unfavorable outcome based on the Glasgow Outcome Scale., Methods: The shape of the association was examined in four prospective series with individual patient data (2664 cases). All patients had a closed TBI and were of adult age (96% < 65 years of age). The strength of the association was investigated in a metaanalysis of the aforementioned individual patient data (2664 cases) and aggregate data (2948 cases) from TBI studies published between 1980 and 2001 (total 5612 cases). Analyses were performed with univariable and multivariable logistic regression. Proportions of mortality and unfavorable outcome increased with age: 21 and 39%, respectively, for patients younger than 35 years and 52 and 74%, respectively, for patients older than 55 years. The association between age and both mortality and unfavorable outcome was continuous and could be adequately described by a linear term and expressed even better statistically by a linear and a quadratic term. The use of age thresholds (best fitting threshold 39 years) in the analysis resulted in a considerable loss of information. The strength of the association, expressed as an odds ratio per 10 years of age, was 1.47 (95% confidence interval [CI] 1.34-1.63) for death and 1.49 (95% CI 1.43-1.56) for unfavorable outcome in univariable analyses, and 1.39 (95% CI 1.3-1.5) and 1.46 (95% CI 1.36-1.56), respectively, in multivariable analyses. Thus, the odds for a poor outcome increased by 40 to 50% per 10 years of age., Conclusions: An older age is continuously associated with a worsening outcome after TBI; hence, it is disadvantageous to define the effect of age on outcome in a discrete manner when we aim to estimate prognosis or adjust for confounding variables.

Object: Regional differences have been shown in patient characteristics and case management within multiple unselected series of patients suffering from traumatic brain injury (TBI). One might expect that such regional heterogeneity would be small in a more selected population of a randomized clinical trial. The goal of this study was to examine what regional differences in patient characteristics, case management, and outcomes exist between continents and among countries within a patient population included in a randomized clinical trial., Methods: Data were extracted from two concurrently conducted randomized clinical trials of the drug tirilazad; the designs of these studies were similar. The studies included 1701 patients with severe and 476 patients with moderate TBI. Differences were primarily investigated between studies performed in Europe and North America, but also among European regions and between Canada and the United States. Associations among regions and outcomes (6-month mortality rate and Glasgow Outcome Scale scores) were studied using multivariable logistic regression analysis. Comparisons between continents and among regions within Europe showed differences in the distribution of patient ages, causes of injury, and several clinical characteristics (motor score, pupillary reactivity, hypoxia, hypotension, intracranial pressure [ICP]). and findings on computerized tomography scans. Secondary referrals occurred 2.5 times more frequently in Europe. Within Europe secondary referral was mainly associated with an increased proportion of patients with mass lesions (46% in the European Study compared with 40% in the North American Study). Therapy for lowering ICP was more frequently applied in North America. After adjustments for case mix and management, mortality and unfavorable outcomes were significantly higher in Europe (odds ratios = 1.58 and 1.46, respectively). Significant differences in outcome between regions within Europe or within North America were not observed., Conclusions: Despite the use of a strict study protocol, considerable differences in patient characteristics and case management exist between continents and among countries, reflecting variations in social, cultural, and organizational aspects. Outcomes of TBI may be worse in Europe compared with North America, but this finding requires further study.