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Objective To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach‐bladder distance, using three‐dimensional (3D) ultrasound. Methods This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis. We calculated stomach volumes (n = 223) using Sonography‐based Automated Volume Count. The shortest stomach‐bladder distance (n = 241) was determined using multiplanar visualization of the volume datasets. We used linear mixed modelling to evaluate the effect of gestational age and type of gastroschisis (simple or complex) on fetal stomach volume and stomach‐bladder distance. Results We included 79 affected fetuses. Sixty‐six (84%) had been assessed with 3D ultrasound at least once; 64 of these 66 were liveborn, nine (14%) had complex gastroschisis. With advancing gestational age, stomach volume significantly increased, and stomach‐bladder distance decreased (both P, What's already known about this topic? Infants with complex gastroschisis have a higher risk of morbidity than those with simple gastroschisis.Many attempts have been made to prenatally predict complex gastroschisis, using two‐dimensional ultrasound parameters. What does this study add? This longitudinal prospective multicenter study is the first to evaluate the possible benefit of the use of three‐dimensional ultrasound in fetuses with gastroschisis.Fetal stomach volume and stomach‐bladder distance, measured during pregnancy using three‐dimensional ultrasound, cannot predict complex gastroschisis.

Objective: We aimed to evaluate the relationship between chorionicity, placental abnormalities and necrotizing enterocolitis in multiple pregnancies. We hypothesized that unbalanced interfetal transfusion through vascular anastomoses in monochorionic placentation causes hypoperfusion of the intestinal mucosa, increasing the risk of developing necrotizing enterocolitis. Material and methods: All women with multiple pregnancies who delivered at the University Medical Center Utrecht between January 1995 and December 2015 were retrospectively selected. We compared baseline characteristics and neonatal and maternal outcomes. Secondly, we analyzed ultrasound and placental pathology findings of monochorionic multiples with and without necrotizing enterocolitis. Finally, we compared illness characteristics of necrotizing enterocolitis in monochorionic multiples with necrotizing enterocolitis in dichorionic multiples. Results: We included 2859 dichorionic and 817 monochorionic neonates. Necrotizing enterocolitis occurred significantly more often in monochorionic as compared to dichorionic neonates (3.3% and 1.6% respectively), also after correction for birthweight, gestational age and nulliparity (OR 1.7, 95% CI 1.0 - 2.8). Ultrasound abnormalities were not associated with necrotizing enterocolitis. Histopathology showed that necrotizing enterocolitis was significantly associated with the presence of unbalanced interfetal transfusion (76.9% of monochorionic with necrotizing enterocolitis versus 31.4% of cases without necrotizing enterocolitis, P = 0.001). Conclusion: Necrotizing enterocolitis is more common in monochorionic multiples as compared to dichorionic multiples, at least in part due to the presence of and related to the presence of unbalanced interfetal transfusion through arterial-venous anastomoses in the placenta. Possibly, subtle ischemic damage caused by intra-uterine fetal hypotension or anemia plays a key role in the development of necrotizing enterocolitis in monochorionic twins.

BACKGROUND: Reintroduction of enteral nutrition in neonates with necrotizing enterocolitis (NEC) should take place when the gut is ready for its normal function. Too early a start of oral feeding might lead to disease relapse, whereas prolonged discontinuation of enteral nutrition is associated with impaired gut function and parenteral nutrition-related complications. This study evaluated whether noninvasive urinary measurement of intestinal fatty acid binding protein (I-FABP) at the time of refeeding can predict clinical outcome in neonates with NEC.METHODS: Urinary I-FABP concentrations were measured in 21 infants with NEC just before reintroducing enteral nutrition. Poor outcome was defined as unsuccessful reintroduction of enteral feeding (EF), (re)operation for NEC, or death related to NEC after reintroduction of EF.RESULTS: Median urinary I-FABP levels in neonates with poor outcome (n = 5) were significantly higher as compared with I-FABP levels in neonates with good outcome (n = 16) (P CONCLUSION: Noninvasive urinary I-FABP measurement at time of refeeding differentiates neonates with poor outcome from neonates with good outcome in NEC. Urinary I-FABP measurement may therefore be helpful in the timing of EF in neonates with NEC.

Objective To assess substandard care factors in the case of delivery-related asphyxia. Design Prospective cohort study. Setting Catchment area of the Neonatal Intensive Care Unit (NICU) of the University Medical Center Utrecht; a region in the middle of the Netherlands covering 13% of the Dutch population. Population Term infants, without congenital malformations, who died intrapartum or were admitted to the Neonatal Intensive Care Unit due to asphyxia. Methods During a two-year period, cases were prospectively collected and audited by an expert panel. Main outcome measures Substandard care factors. Results 37 735 term infants without congenital malformations were born. There were 19 intrapartum deaths, and 89 NICU admissions of which 12 neonates died. In 63 (58%) cases a substandard care factor was identified that was possibly (n= 47, 43%) or probably (n= 16, 15%) related to perinatal death or NICU admission. In primary care, substandard care factors were mainly the low frequency of examination during labor and delay in referral to secondary care. In secondary care, misinterpretation of cardiotocography and failure to respond adequately to clinical signs of fetal distress were the most common substandard care factors. Conclusions Substandard care is present in a substantial number of cases with delivery-related asphyxia resulting in perinatal death or NICU admission. Improving the organization of obstetric care in the Netherlands as well as training of obstetric caregivers might reduce adverse outcomes.

Contains fulltext : 168757.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To determine outcome of children born with isolated gastroschisis (no extra-gastrointestinal congenital abnormalities). STUDY DESIGN: International cohort study and meta-analysis. PRIMARY OUTCOME: time to full enteral feeding (TFEF); secondary outcomes: Duration of mechanical ventilation, length of stay (LOS), mortality and differences in outcome between simple and complex gastroschisis (complex; born with bowel atresia, volvulus, perforation or necrosis). To compare the cohort study results with literature three databases were searched. Studies were eligible for inclusion if cases were born in developed countries with isolated gastroschisis after 1990, number of cases >20 and TFEF was reported. RESULTS: The cohort study included 204 liveborn cases of isolated gastroschisis. The TFEF, median duration of ventilation and LOS was, 26days (range 6-515), 2days (range 0-90) and 33days (range 11-515), respectively. Overall mortality was 10.8%. TFEF and LOS were significantly longer (P

Objective. To assess substandard care factors in antepartum stillbirths at term. Design. Prospective cohort study. Setting. A region in the middle of the Netherlands covering 13% of the Dutch population. Population. Antepartum stillbirths (≥37 weeks) without congenital malformations. Methods. During a two-year period, all antepartum term stillbirths were prospectively collected and audited by an expert panel. Main outcome measures. Substandard care factors. Results. During the study period, 37 735 normally formed infants were delivered ≥37 weeks of gestation. There were 60 antepartum stillbirths (1.59 per 1 000, 95%CI 1.19–1.99). Most stillbirths occurred during apparently uncomplicated pregnancies. Twenty-one infants (35%) were small-for-gestational age but growth restriction was only suspected in 10 (47.6%) of these cases. Substandard care factors were identified in 21 (35%) cases. A relation between these factors and fetal demise was possible in nine (15%) and probable in seven (12%) of these cases. Inadequate management and recognition of suspected growth restriction (n=9) or hypertension (n=6) were the most common substandard care factors. Ten (16.7%) women felt none or decreased fetal movements for 24 hours or more before they consulted a doctor or midwife. Conclusion. Twenty-seven percent of all stillbirths were possibly or probably avoidable. Special attention to the recognition and adequate management of suspected growth restriction and hypertension as well as guidelines about patient information and management of decreased fetal movements might result in a reduction of stillbirths in the Netherlands.

UNLABELLED In a recently published randomized clinical trial on intrapartum fetal monitoring, fetal blood samples were obtained in 879 women. One serious complication of fetal blood sampling (FBS) was reported, a case in which physical examination of the neonate after delivery revealed clear fluid loss from the incision site. Four layers of the scalp appeared to be incised. The subarachnoid space was closed with 2 sutures, and antibiotics were started due to the risk of meningitis. The patient was discharged in good clinical condition. In this article, the case is presented and the literature reviewed. We found 12 articles reporting 37 cases of a complication due to FBS, none concerning leakage of cerebrospinal fluid. In conclusion, complications of FBS are rare but can be serious. Excessive fetal bleeding is most frequently reported and often associated with an underlying coagulopathy in the neonate. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES After completion of this educational activity, the obstetrician/gynecologist should be better able to assess the chance of possible complications due to fetal blood sampling; select fetuses at risk for complications due to fetal blood sampling; and evaluate certain technical precautions when performing this procedure.

Objective To evaluate the management of imminent preterm delivery with respect to prescription of antenatal corticosteroids (ACS) and referral to a tertiary center. Study Design A retrospective cohort study existing of 1 perinatal center and 9 referring hospitals. All women who received their first dose of ACS in 1 of the 10 hospitals between 24+0 and 32+0 weeks of gestation and/or delivered before 32 weeks of gestation from 2005 until 2010. Patients were identified using the electronic database of hospital pharmacies. Main outcome measures were time interval from administration to delivery for different indications and number of women who were not referred in time to a tertiary center. Results In total, 1375 women received ACS. Main indications were suspected preterm labor (44.7%), preterm prelabor rupture of membranes (15.9%), maternal indication (12.8%), fetal indication (9.2%) and vaginal blood loss (8.4%). Overall, 467 (34.0%) women delivered ≤7 days after ACS administration; 8.7% of women with vaginal blood loss and 54.5% of women with maternal indication. Among the 931 women who received ACS in the secondary hospitals, 452 (48.5%) women were referred to a tertiary hospital and 89 (6.5%) women delivered in a secondary hospital with a gestational age of less than 32 weeks. Conclusion One-third of all women receiving ACS delivered within 7 days and half of the women who received ACS in a secondary hospital were referred to a tertiary center. There seems to be room for improvement regarding the timing of ACS administration and subsequently referral to a tertiary center.

Background: In preterm ventilated infants, irreversible damage to the airway mucosa in the neonatal period might be related to the development of bronchial hyperresponsiveness (BHR) in subsequent years. Aims: To evaluate whether neonatal indicators of long-term respiratory morbidity, respiratory system compliance (Crs) and resistance (Rrs), were causally related to bronchial responsiveness at the age of 2 and whether these relationships were affected by other factors. Study design: Mean neonatal Crs and Rrs of the first 3 days of life were assessed using the single breath occlusion technique. Bronchial challenge tests were performed at 2 years of age. When wheezing occurred during chest auscultation or oxygen saturation decreased below 90%, the provocative concentration of methacholine was recorded. Subjects: Forty-five preterm infants of

Since severity of acute respiratory distress syndrome (RDS) has been decreasing, the aetiology of long-term respiratory problems may have changed in preterm infants. We investigated whether early neonatal respiratory resistance (Rrs) and compliance (Crs) were important determinants of respiratory morbidity and lung function abnormalities during the 1st year of life in ventilated preterm infants. In 70 infants of less than 37 weeks gestation, mechanically ventilated within 24 h after birth, Rrs and Crs were assessed daily during the first 3 days of life and medians were calculated subsequently (Rrsneo and Crsneo). Rrs and Crs were reassessed 1 year later in 57 of 70 infants (Rrs(1 year) and Crs(1 year)). After correction for endotracheal tube size, increased Rrsneo was significantly related to respiratory morbidity during the 1st year of life (OR 1.20, 95% CI 1.04 to 1.38; P = 0.013), increased Rrs(1 year) (multiplicative beta per kPa/l x s 1.017, 95% CI 1.000 to 1.034; P = 0.045), and decreased Crs(1 year) (multiplicative beta per kPa/l x s 0.986, 95% CI 0.974 to 0.998; P = 0.023). Associations were not adversely affected by degree of prematurity, neonatal disease and treatment. Crsneo did not show any significant associations. In the current surfactant era, increased Rrsneo, and not Crsneo was associated with poor respiratory outcome during the 1st year of life in preterm ventilated infants. Relationships were not adversely affected by measures reflecting degree of prematurity, neonatal disease, and ventilator conditions.our results indicate that inborn properties of the respiratory system have become increasingly important in relation to respiratory outcome instead of neonatal disease and treatment conditions.

OBJECTIVE: To evaluate the value of biomarkers to detect severe NEC. SUMMARY BACKGROUND DATA: The time point of surgery in necrotizing enterocolitis (NEC) is critical. Therefore, there is a need for markers that detect severe NEC, because clinical signs of severe NEC often develop late. This study evaluated the value of biomarkers reflecting intestinal cell damage and inflammation to detect severe NEC. METHODS: 29 neonates with NEC were included. Two definitions of moderate versus severe NEC were analyzed: medical NEC (n = 12) versus surgical or fatal NEC (n = 17); and Bell stage II NEC (n = 13) versus stage III NEC (n = 16). Urinary intestinal fatty acid binding protein (I-FABP), serum amyloid A (SAA), C3a and C5a, and fecal calprotectin were measured. C-reactive protein (CRP), white blood cell count (WBC) and platelet count data were measured in blood. RESULTS: In both definitions of moderate versus severe NEC, urinary SAA levels were significantly higher in severe NEC. A cut-off value of 34.4 ng/ml was found in surgical NEC versus medical NEC (sensitivity, 83%; specificity, 83%; LR+, 4.88 (95% CI, 1.37-17.0); LR-, 0.20 (95% CI, 0.07-0.60)) at diagnosis of NEC and at one day prior to surgery in neonates who were operated later on. Combination of urinary SAA and platelet count increased the accuracy, with a sensitivity, 94%; specificity, 83%; LR+, 5.53 (95% CI, 1.57-20.0); and LR-, 0.07 (95% CI, 0.01-0.48). CONCLUSION: Urinary SAA is an accurate marker in differentiating severe NEC from moderate NEC; particularly if combined with serum platelet count.

ObjectiveTo assess the implementation and first results of a term perinatal internal audit by a standardised method.DesignPopulation-based cohort study.SettingAll 90 Dutch hospitals with obstetric/paediatric departments linked to community practices of midwives, general practitioners in their attachment areas, organised in perinatal cooperation groups (PCG).PopulationThe population consisted of 943 registered term perinatal deaths occurring in 2010–2012 with detailed information, including 707 cases with completed audit results.Main outcome measuresParticipation in the audit, perinatal death classification, identification of substandard factors (SSF), SSF in relation to death, conclusive recommendations for quality improvement in perinatal care and antepartum risk selection at the start of labour.ResultsAfter the introduction of the perinatal audit in 2010, all PCGs participated. They organised 645 audit sessions, with an average of 31 healthcare professionals per session. Of all 1102 term perinatal deaths (2.3/1000) data were registered for 86% (943) and standardised anonymised audit results for 64% (707). In 53% of the cases at least one SSF was identified. Non-compliance to guidelines (35%) and deviation from usual professional care (41%) were the most frequent SSF. There was a (very) probable relation between the SSF and perinatal death for 8% of all cases. This declined over the years: from 10% (n=23) in 2010 to 5% (n=10) in 2012 (p=0.060). Simultaneously term perinatal mortality decreased from 2.3 to 2.0/1000 births (pConclusionsThe perinatal audit is implemented nationwide in all obstetrical units in the Netherlands in a short time period. It is possible that the audit contributed to the decrease in term perinatal mortality.

Purpose: To determine the effects of surfactant replacement therapy (SRT), high-frequency oscillatory ventilation (HFOV), and general improvements in quality of care on the incidence of severe retinopathy of prematurity (ROP). Methods: Retrospective comparison of the incidence and severity of ROP in two groups of preterm infants admitted to our neonatal intensive care unit (NICU) in two consecutive 5-year periods (1986-1995) and screened for ROP. During the second study period, natural surfactant was introduced in the treatment of respiratory distress syndrome (RDS) and HFOV was used for treatment of respiratory insufficiency of any origin. The effects of these developments and general improvements on the incidence of severe ROP were analyzed with stepwise logistic regression. Results: The overall incidence of ROP from 19861990 was not significantly different from the incidence of ROP from 1 991 -1 995. The incidence of severe ROP (ROP stage 3 or greater) was significantly lower in the second period (15.7% versus 6.4%, P=.015). For infants Conclusion: Of the recent new developments in neonatology, only SRT was associated with a decreased risk for severe ROP. Journal of Pediatric Ophthalmology and Strabismus 2000;37:142-148.

To evaluate the prescribing patterns of the first antenatal corticosteroids (ACS) course in our tertiary referral centre from 2005 until 2010.We conducted a retrospective cohort study including all women who received ACS between 24(+0) and 34(+0) weeks of gestation. Main outcome measure was the number of women who delivered within 7 d after ACS administration. The time interval from administration to delivery was compared between women with different indications. Furthermore, all women delivering between 24(+0) and 34(+0) weeks of gestation who did not receive ACS were identified.1008 women received ACS, 15 (1.5%) women were lost to follow up. Main indications were suspected preterm labour, preterm prelabour rupture of membranes, maternal indication, foetal indication and vaginal blood loss (VBL). Overall, 447 (45.4%) women delivered ≤7 d after ACS administration. This percentage was 13.6% in women with VBL and 61.5% in women with maternal indication. During the study period, 1267 women delivered before 34 weeks of gestation, 126 (9.9%) women did not receive ACS.The time interval from ACS administration to delivery differs per indication. Women with VBL are most often over treated. The timing of the first ACS course should be improved.

To assess substandard care factors in the case of delivery-related asphyxia.Prospective cohort study.Catchment area of the Neonatal Intensive Care Unit (NICU) of the University Medical Center Utrecht; a region in the middle of the Netherlands covering 13% of the Dutch population.Term infants, without congenital malformations, who died intrapartum or were admitted to the Neonatal Intensive Care Unit due to asphyxia.During a two-year period, cases were prospectively collected and audited by an expert panel.Substandard care factors.37 735 term infants without congenital malformations were born. There were 19 intrapartum deaths, and 89 NICU admissions of which 12 neonates died. In 63 (58%) cases a substandard care factor was identified that was possibly (n= 47, 43%) or probably (n= 16, 15%) related to perinatal death or NICU admission. In primary care, substandard care factors were mainly the low frequency of examination during labor and delay in referral to secondary care. In secondary care, misinterpretation of cardiotocography and failure to respond adequately to clinical signs of fetal distress were the most common substandard care factors.Substandard care is present in a substantial number of cases with delivery-related asphyxia resulting in perinatal death or NICU admission. Improving the organization of obstetric care in the Netherlands as well as training of obstetric caregivers might reduce adverse outcomes.

To assess substandard care factors in antepartum stillbirths at term. Design. Prospective cohort study.A region in the middle of the Netherlands covering 13% of the Dutch population.Antepartum stillbirths (≥ 37 weeks) without congenital malformations.During a two-year period, all antepartum term stillbirths were prospectively collected and audited by an expert panel.Substandard care factors.During the study period, 37 735 normally formed infants were delivered ≥ 37 weeks of gestation. There were 60 antepartum stillbirths (1.59 per 1,000, 95%CI 1.19-1.99). Most stillbirths occurred during apparently uncomplicated pregnancies. Twenty-one infants (35%) were small-for-gestational age but growth restriction was only suspected in 10 (47.6%) of these cases. Substandard care factors were identified in 21 (35%) cases. A relation between these factors and fetal demise was possible in nine (15%) and probable in seven (12%) of these cases. Inadequate management and recognition of suspected growth restriction (n=9) or hypertension (n=6) were the most common substandard care factors. Ten (16.7%) women felt none or decreased fetal movements for 24 hours or more before they consulted a doctor or midwife.Twenty-seven percent of all stillbirths were possibly or probably avoidable. Special attention to the recognition and adequate management of suspected growth restriction and hypertension as well as guidelines about patient information and management of decreased fetal movements might result in a reduction of stillbirths in the Netherlands.

To investigate differences in perinatal mortality between Dutch provinces and to determine the significance of risk factors including travel time from home to the hospital during labour.Cohort study.The study was based on 1,242,725 singleton births in 2000-2006 as recorded in the Netherlands Perinatal Registry. The influence of province on perinatal mortality was estimated, with logistic regression analysis adjusting for risk factors (age, parity, ethnicity, socioeconomic status) and care factors such as start of antenatal care and travel time.The perinatal mortality rate in the Netherlands was 9.9 per 1000 births. The provinces with the highest mortality rates were Friesland (11.3‰), Groningen (11.1‰), Zeeland (10.6‰) and Flevoland (10.4‰). Noord-Brabant (9.2‰) and Limburg (9.2‰) had the lowest mortality rates. These differences were significantly higher for Friesland (odds ratio: 1.16; 95%-CI: 1.05-1.28) and Groningen (odds ratio: 1.13; 95%-CI: 1.02-1.26). Starting late with perinatal care, at 18 weeks of gestation or later was an important risk factor (adjusted odds ratio 1.8; 95%-CI: 1.7-1.8). Low socio-economic status could partly be associated with the higher mortality risk in Groningen. Longer travel time (≥ 20 minutes) was an independent risk factor associated with perinatal mortality. On average 19% of the women travelled ≥ 20 minutes to the hospital. In the provinces Groningen, Friesland, Flevoland and Zeeland these percentages ranged between 32 and 36%. The adjusted odds ratio of travel time was 1.7 (95%-CI 1.6-1.7).The perinatal mortality differs per province. This can be explained by longer travel time to the hospital during labour. Late start of perinatal care and low socio-economic status also affect the mortality rate. These risk factors need to be taken into account during registration, investigation, audit and obstetric policy.

Contains fulltext : 89807.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To improve diagnosis of necrotizing enterocolitis (NEC) by noninvasive markers representing gut wall integrity loss (I-FABP and claudin-3) and gut wall inflammation (calprotectin). Furthermore, the usefulness of I-FABP to predict NEC severity and to screen for NEC was evaluated. METHODS: Urinary I-FABP and claudin-3 concentrations and fecal calprotectin concentrations were measured in 35 consecutive neonates suspected of NEC at the moment of NEC suspicion. To investigate I-FABP as screening tool for NEC, daily urinary levels were determined in 6 neonates who developed NEC out of 226 neonates included before clinical suspicion of NEC. RESULTS: Of 35 neonates suspected of NEC, 14 developed NEC. Median I-FABP, claudin-3, and calprotectin levels were significantly higher in neonates with NEC than in neonates with other diagnoses. Cutoff values for I-FABP (2.20 pg/nmol creatinine), claudin-3 (800.8 INT), and calprotectin (286.2 microg/g feces) showed clinically relevant positive likelihood ratios (LRs) of 9.30, 3.74, 12.29, and negative LRs of 0.08, 0.36, 0.15, respectively. At suspicion of NEC, median urinary I-FABP levels of neonates with intestinal necrosis necessitating surgery or causing death were significantly higher than urinary I-FABP levels in conservatively treated neonates. Of the 226 neonates included before clinical suspicion of NEC, 6 developed NEC. In 4 of these 6 neonates I-FABP levels were not above the cutoff level to diagnose NEC before clinical suspicion. CONCLUSIONS: Urinary I-FABP levels are not suitable as screening tool for NEC before clinical suspicion. However, urinary I-FABP and claudin-3 and fecal calprotectin are promising diagnostic markers for NEC. Furthermore, urinary I-FABP might also be used to predict disease severity. 01 juni 2010

To gain an insight into perinatal mortality and morbidity in full-term infants without congenital abnormalities admitted to a neonatal intensive care unit (NICU).Retrospective analysis.In this study, all full-term infants, who were born in the period 1997-2003 without congenital disorders and admitted to the NICU at the Wilhelmina Children's Hospital in Utrecht, the Netherlands were included. Information about the delivery, NICU-admission and follow-up until the age of 18 months was obtained from the hospital charts.In total 597 full-term neonates were admitted to the NICU during the study period; this is equivalent to 3-4 per 1,000 full-term neonates in the Utrecht region. Of these, 47% were admitted on account of asphyxia, 17% with respiratory problems and 12% with infections. In 79% of all NICU admissions the delivery had taken place under secondary care; in 29% labour had started under exclusive care of a primary level midwife, because the pregnancy had been defined as low-risk. 21% of the neonates were admitted to the NICU following delivery under exclusive primary care. Almost 15% of the infants died in the NICU, in 89% due to asphyxia. Of the surviving infants following perinatal asphyxia, 15% had a permanent disability at the age of 18 months.Post-partum admission of a fundamentally healthy full-term neonate to the NICU is a serious adverse perinatal outcome, and warrants further investigation. The various factors that influence these admissions should be analysed in more detail, for instance by means of perinatal audits.

Background Perinatal mortality is an important indicator of health. European comparisons of perinatal mortality show an unfavourable position for the Netherlands. Our objective was to study regional variation in perinatal mortality within the Netherlands and to identify possible explanatory factors for the found differences. Methods Our study population comprised of all singleton births (904,003) derived from the Netherlands Perinatal Registry for the period 2000–2004. Perinatal mortality including stillbirth from 22+0 weeks gestation and early neonatal death (0–6 days) was our main outcome measure. Differences in perinatal mortality were calculated between 4 distinct geographical regions North-East-South-West. We tried to explain regional differences by adjustment for the demographic factors maternal age, parity and ethnicity and by socio-economic status and urbanisation degree using logistic modelling. In addition, regional differences in mode of delivery and risk selection were analysed as health care factors. Finally, perinatal mortality was analysed among five distinct clinical risk groups based on the mediating risk factors gestational age and congenital anomalies. Results Overall perinatal mortality was 10.1 per 1,000 total births over the period 2000–2004. Perinatal mortality was elevated in the northern region (11.2 per 1,000 total births). Perinatal mortality in the eastern, western and southern region was 10.2, 10.1 and 9.6 per 1,000 total births respectively. Adjustment for demographic factors increased the perinatal mortality risk in the northern region (odds ratio 1.20, 95% CI 1.12–1.28, compared to reference western region), subsequent adjustment for socio-economic status and urbanisation explained a small part of the elevated risk (odds ratio 1.11, 95% CI 1.03–1.20). Risk group analysis showed that regional differences were absent among very preterm births (22+0 – 25+6 weeks gestation) and most prominent among births from 32+0 gestation weeks onwards and among children with severe congenital anomalies. Among term births (≥ 37+0 weeks) regional mortality differences were largest for births in women transferred from low to high risk during delivery. Conclusion Regional differences in perinatal mortality exist in the Netherlands. These differences could not be explained by demographic or socio-economic factors, however clinical risk group analysis showed indications for a role of health care factors.

To study respiratory outcome in preterm small for gestational age (SGA) fetuses with or without signs of intrauterine growth restriction due to placental insufficiency, and with or without maternal hypertension.This was a retrospective study of 187 neonates with birth weight10(th) percentile and gestational age34 weeks. Results from umbilical artery Doppler velocimetry were used to identify the abnormal Doppler subgroup.No significant difference in respiratory outcome between SGA fetuses with normal (SGA-N) or abnormal (SGA-A) umbilical artery Doppler examination was found. Within the SGA-A group, the respiratory distress syndrome (RDS) incidence (OR 5.6, 95% CI 1.7-18.3), RDS grade (OR 6.7, 95% CI 1.2-38.5), and need for surfactant (OR 5.3, 95% CI 1.1-24.4) were higher in infants of women with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome as compared to those of normotensive mothers.Lung maturation is not accelerated with placental insufficiency. SGA-A fetuses of mothers with HELLP syndrome have a significantly poorer respiratory outcome than those with healthy mothers. Possibly, fetuses of mothers with HELLP syndrome are subjected to 'oxidative stress' causing lung damage rather than lung maturation.

textabstractObjective: To assess the effects of different oxygen concentrations and flow rates on the measurement errors of neonatal pneumotachometers in heated and unheated situations and to develop correction factors to correct for these effects. Design: Prospective laboratory study. Setting: Outpatient clinic with equipment in a standardized setting. Subjects: Neonatal pneumotachometers. Interventions: In standardized conditions, the tested pneumotachometer was calibrated at a flow rate of 3 L/min with 60% oxygen and was set in series with a closed spirometer system being used as a reference. Different air-flow levels (1-9 L/min) and oxygen concentrations (21-100%) were infused into the closed system with the pneumotachometer and spirometer. Measurements and Main Results: The pneumotachometers were significantly affected by changing oxygen concentrations (p < .01) and increasing flow rates (p < .01), increasing the actually measured flow rate. Correction factors, developed by multiple regression analysis, significantly reduced the overall maximum errors of the pneumotachometers from -1.1 to 0.6 L/min to -0.5 to 0.4 L/min. Conclusions: The effects of changes in oxygen concentrations and flow rates on neonatal pneumotachometers could be considerably decreased by the use of correction factors such as were calculated in this study. This will preclude frequent calibration procedures with actual flow and oxygen levels during changes in experimental settings. Copyright

University Children's Hospital Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.Growth failure is a well-known problem in infants with bronchopulmonary dysplasia (BPD). We studied BPD infants' total daily energy expenditure (Ee), nutritional balance, and growth in relation to their past and current clinical status. Applying the doubly labelled water technique, Ee was measured in nine preterm infants with BPD receiving supplemental oxygen (postnatal age 61 +/- 13 days) and nine matched controls (36 +/- 21 days) during a 6-day period. Energy and protein balance, past and present respiratory status, and growth were assessed as well. The results show that Ee was higher in the BPD infants compared to controls (73 +/- 9 vs 63 +/- 8 kcal/kg/day, P < 0.05), but their faecal energy loss was lower (P < 0.01). Weight gain, energy intake, energy cost of growth, protein retention, and physical activity were not different. The respiratory frequency (RR) in the BPD infants was elevated in comparison with controls (P < 0.01). Within the BPD group, RR was positively correlated with energy expenditure (regression equation: Ee [kcal/kg/day] = 26.3 + 0.71*RR [min-1]; r2 = 0.82, P < 0.001), and was the single most significant determinant of Ee. CONCLUSION: Total energy expenditure in BPD infants is elevated and is strongly associated with their respiratory status. These findings could be of practical value for the nutritional management in infants with severe BPD.

To assess the effect of surfactant replacement therapy (SRT) on the prevalence and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT-treated preterm infants with data from 230 historic controls. The prevalence of ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and 20.3% of the ROP patients in the control group. Surfactant therapy had no influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797--2.459, p = 0.242). However, SRT was associated with a decreased risk for severe ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905, p = 0.036). These data suggest that SRT is associated with a decreased risk for severe ROP.

We documented the prevalence of retinopathy of prematurity (ROP) in a group of 46 infants suffering from a moderate or severe respiratory distress syndrome and treated with surfactant replacement therapy (SRT) and 61 controls admitted in the year prior to the institution of SRT. Mortality in the treatment group was lower than in the control group (15.5% versus 23.8;P=0.29). The ROP prevalence in the treatment group was 47.8% and in the control group was 47.8% and in the control group 27.9%. To analyse the contribution of SRT alone to the prevalence of ROP, multivariate analysis using logistic regression technique was used. The odds ratio for SRT was 5.2 with a 95% confidence interval of 1.3–20.7,P=0.02. The prevalence of severe ROP in the surfactant treated group was not increased compared to the control group. From our data we conclude that SRT increases the risk of developing ROP but is not associated with more severe forms of ROP.

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.

Item does not contain fulltext BACKGROUND: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, such as serum amyloid A (SAA) and fecal calprotectin. PURPOSE: The aim of the present study was to evaluate which combination of noninvasive measurement of inflammatory markers and I-FABP improves the diagnostic accuracy in neonates suspected for NEC. METHODS: In 62 neonates with clinical suspicion of NEC (29 with final diagnosis of NEC), urinary I-FABP, urinary SAA, and fecal calprotectin levels were determined quantitatively. Diagnostic accuracy was calculated for the combinations I-FABP-SAA and I-FABP-fecal calprotectin, using a multivariable logistic regression model. RESULTS: The combination of SAA and I-FABP did not increase the diagnostic accuracy of I-FABP. However, the combination of fecal calprotectin and I-FABP improved accuracy significantly. The combination of urinary I-FABP and fecal calprotectin measurement produced a sensitivity of 94%, a specificity of 79%, a positive likelihood ratio of 4.48, and a negative likelihood ratio of 0.08. CONCLUSION: The combination of noninvasive measurement of I-FABP and fecal calprotectin seems promising for diagnosing NEC at an early time point. Prospective analysis is required to confirm this finding and to evaluate better treatment strategies based on noninvasive measurement of I-FABP and calprotectin. 01 september 2012

Objective. To explore the feasibility of a national perinatal audit organization. Design. Validation study. Setting. Three regions in the Netherlands. Population. 228 cases of perinatal mortality. Methods. Narratives of perinatal mortality cases were assessed by a panel of representatives of all perinatal care provider groups. 123 cases were assessed twice. Consensus was defined as 75% agreement. For the chance corrected agreement Cohen's kappa statistic was used. Main outcome measures. Consensus and the chance corrected agreement on three cause of death classifications. The presence or absence of substandard factors (SSF) with the care provider, the organization of care and the relation of the SSF with perinatal death. Results. Consensus rates and chance corrected agreement for three cause of death classifications ranged from 92 to 96% and kappa 0.87 to kappa 0.93 (very good agreement), with comparable confidence intervals and similar values in the validation subset of 123 cases. On the presence of SSF at the level of the care provider consensus and chance corrected agreement was 68% and kappa 0.53 (moderate), with comparable values in the subset of 123 cases. Consensus for the relation between SSF at the level of the care provider and perinatal death was 81.4% and kappa 0.68 (good). Conclusion. Perinatal audit on a national level with relatively large audit groups with many different care providers is feasible.

Infant respiratory distress syndrome (IRDS) and subsequent partial liquid ventilation (PLV) cause increased pulmonary vascular resistance, thus raising afterload. In nine newborn lambs the effects of IRDS and subsequent PLV on right (RV) and left ventricular (LV) contractility and systolic pump function were assessed using indices derived from RV and LV pressure-volume relations, obtained by micromanometric and conductance catheters during transient inferior vena cava occlusion. Pulmonary function deteriorated during IRDS with a significant decrease in the ratio of arterial oxygen pressure to fraction of inspired oxygen (Pa(O(2))/FI(O(2))) whereas pulmonary artery pressure (Ppa) showed a significant increase and pulmonary vascular resistance showed a substantial though not significant increase. Cardiac output (Q), stroke volume (SV), and end-diastolic volume (EDV) did not change. RV contractility showed a significant increase during IRDS: the slope of the end-systolic pressure-volume relation (RV-E (ES)) increased whereas its volume intercept at 5 kPa (RV-V(5)) decreased. The preload-corrected time derivative of ventricular pressure (RV-dP/dt(max)), however, did not change significantly. LV pump function and contractility were unchanged. During PLV pulmonary function showed a recovery but Ppa and pulmonary vascular resistance remained high; indices for RV contractility showed a sustained significant increase compared with baseline conditions whereas indices for LV pump function and contractility remained unchanged. These results show that the right ventricle of the newborn heart, in the face of increased pulmonary vascular resistance, is able to maintain cardiac output through homeometric autoregulation.