NEOnatal Central-venous Line Observational study on Thrombosis (NEOCLOT): evaluation of a national guideline on management of neonatal catheter-related thrombosis.

BACKGROUND: In critically ill (preterm) neonates, central venous catheters (CVCs) are increasingly used for administration of medication or parenteral nutrition. A serious complication, however, is the development of catheter-related thrombosis (CVC-thrombosis), which may resolve by itself or cause severe complications. Due to lack of evidence, management of neonatal CVC-thrombosis varies among neonatal intensive care units (NICUs). In the Netherlands an expert-based national management guideline has been developed which is implemented in all 10 NICUs in 2014. METHODS: The NEOCLOT study is a multicentre prospective observational cohort study, including 150 preterm and term infants (0-6 months) admitted to one of the 10 NICUs, developing CVC-thrombosis. Patient characteristics, thrombosis characteristics, risk factors, treatment strategies and outcome measures will be collected in a web-based database. Management of CVC-thrombosis will be performed as recommended in the protocol. Violations of the protocol will be noted. Primary outcome measures are a composite efficacy outcome consisting of death due to CVC-thrombosis and recurrent thrombosis, and a safety outcome consisting of the incidence of major bleedings during therapy. Secondary outcomes include individual components of primary efficacy outcome, clinically relevant non-major and minor bleedings and the frequency of risk factors, protocol variations, residual thrombosis and post thrombotic syndrome. DISCUSSION: The NEOCLOT study will evaluate the efficacy and safety of the new, national, neonatal CVC-thrombosis guideline. Furthermore, risk factors as well as long-term consequences of CVC-thrombosis will be analysed. TRIAL REGISTRATION: Trial registration: Nederlands Trial Register NTR4336 . Registered 24 December 2013.

A comparison of perinatal outcomes in singletons and multiples born after in vitro fertilization or intracytoplasmic sperm injection stratified for neonatal risk criteria.

OBJECTIVE: To compare perinatal singleton and multiple outcomes in a large Dutch in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) population and within risk subgroups. Newborns were assigned to a risk category based on gestational age, birthweight, Apgar score and congenital malformation. DESIGN: Register-based retrospective cohort study. SETTING: Netherlands Perinatal Registry data. SAMPLE: A total of 3041 singletons and 1788 multiple children born from IVF/ICSI in 2003-2005. METHODS: Student's t-test or Mann-Whitney U-test was used to analyze continuous data, chi-squared analyses were used for categorical data. Multivariate logistic and linear regression analysis was performed to analyze whether the risk stratification criteria were associated with neonatal hospital admission and length of stay. MAIN OUTCOME MEASURES: Start of labor, mode of delivery, gestational age, birthweight, 5-min Apgar score, congenital malformation, neonatal hospital admission, neonatal intensive care unit admission and mortality. RESULTS: IVF/ICSI-conceived multiples had considerably poorer outcomes than singletons in terms of cesarean section rate, preterm birth, birthweight, being small-for-gestational-age, Apgar score, neonatal hospital admission, neonatal intensive care unit admission and neonatal mortality. As opposed to the results found in the total study population and the low-risk and moderate-risk populations, high-risk multiples showed better outcomes than high-risk singletons regarding cesarean section rate, birthweight and Apgar score. All risk stratification variables were associated with being hospitalized after birth. Length of stay was associated with all risk stratification criteria except Apgar score. CONCLUSIONS: Perinatal outcomes in IVF/ICSI-conceived multiples are considerably poorer than in singletons. This finding mainly pertains to low-risk children. High-risk multiples had significantly better perinatal outcomes than high-risk singletons.

Increase in treatment of retinopathy of prematurity in the Netherlands from 2010 to 2017.

PURPOSE: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. METHODS: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared. RESULTS: Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born <25 weeks increased by factor 1.23 and higher oxygen saturation levels were aimed at in most centres. At treatment decision, 59.6% (P1) versus 83.5% (P2) (p = 0.263) infants were classified as Type 1 ROP (ETROP classification). Infants were treated with laser photocoagulation (98 versus 96%) and intravitreal bevacizumab (2 versus 4%). Retreatment was necessary in 10 versus 21 (p = 0.160). Retinal detachment developed in 6 versus 13 infants (p = 0.791) of which 2 versus 6 bilateral (p = 0.599). CONCLUSION: In period 2, the number of infants treated according to the ETROP criteria (Type 1) increased, the number of ROP treatments, retinal detachments and retreatments doubled and the absolute number of retinal detachments increased. Neonatal data did not provide a decisive explanation, although changes in neonatal policy were reported.

Cost-effectiveness of recurrence risk guided care versus care as usual in women who suffered from early-onset preeclampsia including HELLP syndrome in their previous pregnancy (the PreCare study).

BACKGROUND: Preeclampsia and HELLP syndrome may have serious consequences for both mother and fetus. Women who have suffered from preeclampsia or the HELLP syndrome, have an increased risk of developing preeclampsia in a subsequent pregnancy. However, most women will develop no or only minor complications. In this study, we intend to determine cost-effectiveness of recurrence risk guided care versus care as usual in pregnant women with a history of early-onset preeclampsia. METHODS/DESIGN: We developed a prediction model to estimate the individual risk of recurrence of early-onset preeclampsia and the HELLP syndrome. In a before-after study, pregnant women with preeclampsia or HELLP syndrome in their previous pregnancy receiving care as usual (before introduction of the prediction model) will be compared with women receiving recurrence risk guided care (after introduction of the prediction model). Eligible and pregnant women will be recruited at six university hospitals and seven large non-university tertiary referral hospitals in the Netherlands. The primary outcome measure is the recurrence of early-onset preeclampsia or HELLP syndrome in women allocated to the regular monitoring group. For the economic evaluation, a modelling approach will be used. Costs and effects of recurrence risk guided care with those of care as usual will be compared by means of a decision model. Two incremental cost-effectiveness ratios will be calculated: 1) cost per Quality Adjusted Life Year (mother unit of analysis) and 2) cost per live born child (child unit of analysis). DISCUSSION: This is, to our knowledge, the first study that evaluates prospectively the efficacy of a multivariable prediction rule for recurrent hypertensive disease in pregnancy. Results of this study could either be integrated into the current guideline on Hypertensive Disorders in Pregnancy, or be used to develop a new guideline.

Comparison of planned caesarean delivery and planned vaginal delivery in women with a twin pregnancy: A nation wide cohort study.

OBJECTIVE: To compare, in women with twin pregnancy with the first twin in cephalic position, neonatal morbidity and mortality rates after planned caesarean delivery (CD) versus planned vaginal delivery (VD). STUDY DESIGN: A nationwide cohort study on women pregnant with twins and the first child in cephalic position, who delivered between 32 + 0-41 + 0 weeks between 2000 and 2012 in the Netherlands, using multivariate logistic regression analysis to compare neonatal morbidity and mortality according to planned delivery mode, and looking at subgroups 32 + 0-36 + 6 and 37 + 0-41 + 0 weeks. RESULTS: We included 21,107 women, of whom 1384 (6.6%) had a planned CD. Of the 19,723 women (93.4%) who had a planned VD, 19.7% delivered by intrapartum CD. We found no significant differences in 'any mortality' (aOR planned CD vs. planned VD 1.34 (95% CI 0.63-2.60)), the outcome 'Apgar score (AS) < 4 or death within 28 days' (aOR 1.28 (95% CI 0.77-2.11) or asphyxia-related morbidity (aOR 0.57 (95% CI 0.32-1.03)). After planned CD more prematurity-related morbidity (aOR 1.55 (95% CI 1.21-1.98)), other morbidity (aOR 1.50 (95% CI 1.26-1.78)) and 'any morbidity or mortality' (aOR 1.41 (95% CI 1.20-1.66) was noted. Trauma-associated morbidity was absent after planned CD and occurred 45 times (0.2%) after planned VD. Before 36 + 6 weeks, planned CD resulted in more perinatal mortality (aOR 2.10 (95% CI 0.92-4.76)), while asphyxia-related morbidity did not differ (aOR 0.80 (95% CI 0.41-1.54). Planned CD resulted in more 'any morbidity or mortality' (aOR 1.52 (95% CI 1.25-1.84)), 'AS < 4 or death within 28 days' (aOR 1.77 (95% CI 1.02-3.09)), prematurity-related morbidity (aOR 1.73 (95% CI 1.34-2.23)), and 'other morbidity' (aOR 1.56 (95% CI 1.28-1.90)). After 37 weeks, no significance differences in mortality, 'any morbidity or mortality <28 days' (aOR 0.96 (95% CI 1 (0.67-1.38)), or 'AS < 4 or death within 28 days' (aOR 0.41 (95% CI (0.10-1.70)) were found. There was less asphyxia-related morbidity after planned CD (aOR 0.24 (95% CI 0.06-1.002)). CONCLUSION: Planned VD results in comparable neonatal outcomes as planned CD for twin pregnancy with the first twin in cephalic position, even with a low intrapartum CD rate of 19.7%. At term, a planned CD may result in less asphyxia- and trauma-related outcomes.

Outcome of isolated gastroschisis; an international study, systematic review and meta-analysis.

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<0.0001) and mortality was fourfold higher in the complex group. Seventeen studies, amongst the current study, were included for further meta-analysis comprising a total of 1652 patients. Mean TFEF was 35.3±4.4days, length of ventilation was 5.5±2.0days, LOS was 46.4±5.2days and mortality risk was 0.06 [0.04-0.07 95%CI]. Outcome of simple and complex gastroschisis was described in five studies. TFEF, ventilation time, LOS were significant longer and mortality rate was 3.64 [1.95-6.83 95%CI] times higher in complex cases. CONCLUSIONS: These results give a good indication of the expected TFEF, ventilation time and LOS and mortality risk in children born with isolated gastroschisis, although ranges remain wide. This study shows the importance of dividing gastroschisis into simple and complex for the prediction of outcome.

Obesity in childhood: A secular trend or an epidemic disease?

The concern about obesity in children has increased worldwide. The question arises, whether this trend to obesity already starts during the prenatal period and to what extent the increase of weight is related to a secular trend in height. For neonatal data, three studies, performed in The Netherlands, with neonatal data of birth weights were compared. For postnatal data, weight, height and body mass index (BMI) of two nationwide studies, performed in the Netherlands, were analyzed. No differences between birth weights were found between 1970 and 2007. In postnatal data a trend of increasing weight and BMI in both boys and girls starts from five years onwards. The secular trend in height starts from the age of two and a half years onward in both boys and girls. The increase in weight is more pronounced than the increase in height. No prenatal secular trend could be detected in The Netherlands. Postnatal, the secular trend is obvious for weight, height and BMI. The increase in skewness of the weight distribution may be ascribed to a metabolic disturbance of the population.

Long-term neurodevelopmental outcome of monochorionic and matched dichorionic twins.

BACKGROUND: Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years. METHODS: This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. FINDINGS: Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin. CONCLUSIONS: There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death.

Physician medical decision-making at the end of life in newborns: insight into implementation at 2 Dutch centers.

OBJECTIVE: Decisions regarding end-of-life care in critically ill newborns in The Netherlands have received considerable criticism from the media and from the public. This might be because of a lack of proper information and knowledge. Our purpose was to provide detailed information about how and when the implementation of end-of-life decisions, which are based on quality-of-life considerations, takes place. METHODS: We reviewed the charts of all infants who died within the first 2 months of life at 2 university hospitals in The Netherlands from January to July 2005 and extracted all relevant information about the end-of-life decisions. We interviewed the responsible neonatologists about the end-of-life decisions and the underlying quality-of-life considerations and about the process of implementation. RESULTS: Of a total of 30 deaths, 28 were attributable to withholding or withdrawing life-sustaining treatment. In 18 of 28 cases, the infant had no chance to survive; in 10 cases, the final decision was based on the poor prognosis of the infant. In 6 patients, 2 successive different end-of-life decisions were made. The arguments that most frequently were used to conclude that quality of life was deemed poor were predicted suffering and predicted inability of verbal and nonverbal communication. Implementation consisted of discontinuation of ventilatory support and alleviation of pain and symptoms. Neuromuscular blockers were added shortly before death in 5 cases to prevent gasping, mostly on parental request. CONCLUSIONS: The majority of deaths were attributable to withholding or withdrawing treatment. In most cases, the newborn had no chance to survive and prolonging of treatment could not be justified. In the remaining cases, withholding or withdrawing treatment was based on quality-of-life considerations, mostly the predicted suffering and predicted inability of verbal and nonverbal communication. Potentially life-shortening medication played a minor role as a cause of death.