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Abstract Background Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. Methods The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. Discussion The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. Trial registration ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.

Introduction Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin

Summary: Background: Fetal growth restriction (FGR) can negatively affect lung development, leading to increased respiratory morbidity and reduced lung function later in life. Studies regarding the impact of FGR on lung function in singletons are influenced by genetic, obstetric, and maternal factors. To overcome these confounding factors, we aim to investigate lung function in identical twins with selective FGR (sFGR). Methods: Lung function assessments were performed in identical twins with sFGR born in our centre between March 1, 2002, and December 31, 2017, aged between 5 and 17 years. sFGR was defined as birthweight discordance ≥20%. Outcome measures consisted of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (DLCO) and were compared between the smaller and larger twin. Findings: Thirty-nine twin pairs performed spirometry of sufficient quality. Median gestational age at birth was 34.3 (interquartile range (IQR) 32.1–36.0) weeks with median birthweights of 1500 (IQR 1160–1880) grams and 2178 (IQR 1675–2720) grams for the smaller and larger twin, respectively. Smaller twins had significantly lower z-scores for FEV1 (−0.94 versus −0.41, p = 0.0015), FVC (−0.56 versus −0.06, p

Introduction Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage.Methods and analysis We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at

Abstract Background Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research. Methods We conducted a rapid literature review of case reports and series, observational retrospective and prospective cohort studies, and trials describing pregnancies or children affected by Rh(D)- or K-mediated HDFN published between 2005 and 2021. Information relevant to the treatment of HDFN and clinical outcomes was extracted. Medline, ClinicalTrials.gov and EMBASE were searched for relevant studies by two independent reviewers through title/abstract and full-text screening. Two independent reviewers extracted data and assessed methodological quality of included studies. Results Forty-three studies reporting postnatal data were included. The median frequency of exchange transfusions was 6.0% [interquartile range (IQR): 0.0–20.0] in K-mediated HDFN and 26.5% [IQR: 18.0–42.9] in Rh(D)-mediated HDFN. The median use of simple red blood cell transfusions in K-mediated HDFN was 50.0% [IQR: 25.0–56.0] and 60.0% [IQR: 20.0–72.0] in Rh(D)-mediated HDFN. Large differences in transfusion rates were found between centers. Neonatal mortality amongst cases treated with intrauterine transfusion(s) was 1.2% [IQR: 0–4.4]. Guidelines and thresholds for exchange transfusions and simple RBC transfusions were reported in 50% of studies. Conclusion Most included studies were from middle- to high-income countries. No studies with a higher level of evidence from centers in low-income countries were available. We noted a shortage and inconsistency in the reporting of relevant data and provide recommendations for future reports. Although large variations between studies was found and information was often missing, analysis showed that the postnatal burden of HDFN, including need for neonatal interventions, remains high. Systematic review registration PROSPERO 2021 CRD42021234940. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021234940 .

Abstract Background International guidelines recommend delayed umbilical cord clamping (DCC) up to 1 min in preterm infants, unless the condition of the infant requires immediate resuscitation. However, clamping the cord prior to lung aeration may severely limit circulatory adaptation resulting in a reduction in cardiac output and hypoxia. Delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) allows for an adequately established pulmonary circulation and results in a more stable circulatory transition. The decline in cardiac output following time-based delayed cord clamping (TBCC) may thus be avoided. We hypothesise that PBCC, compared to TBCC, results in a more stable transition in very preterm infants, leading to improved clinical outcomes. The primary objective is to compare the effect of PBCC on intact survival with TBCC. Methods The Aeriation, Breathing, Clamping 3 (ABC3) trial is a multicentre randomised controlled clinical trial. In the interventional PBCC group, the umbilical cord is clamped after the infant is stabilised, defined as reaching heart rate > 100 bpm and SpO2 > 85% while using supplemental oxygen

Abstract. Twin anemia polycythemia sequence (TAPS) is a chronic form of unbalanced feto-fetal transfusion through minuscule placental anastomoses in monochorionic twin pregnancies, leading to anemia in the donor twin and polycythemia in the recipient twin. TAPS can occur spontaneously in up to 5% of monochorionic twins or can arise in 2%–16% of cases after incomplete laser surgery for twin-twin transfusion syndrome. TAPS can develop across the entire second and third trimester. Antenatal diagnosis for TAPS is reached via Doppler measurement of the fetal middle cerebral artery peak systolic velocity, showing an increased velocity in the donor, combined with a decreased velocity in the recipient. Treatment options for TAPS include expectant management, preterm delivery, intrauterine blood transfusion with or without a partial exchange transfusion, fetoscopic laser surgery and selective feticide. The best treatment option is unclear and is currently being investigated in an international multicenter randomized trial (the TAPS trial). Spontaneous fetal demise occurs in 5%–11% of TAPS twins, more often in donors (8%–18%) than in recipients (2%–5%). Severe long-term neurodevelopmental impairment is seen in 9% of TAPS twins, with donors having an increased risk for cognitive impairment and hearing problems (15%).

Abstract. Objective:. To review the literature on long-term neurodevelopmental outcome after fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Methods:. A literature search in PubMed, Embase, Emcare, Web of Science, Cochrane library, and Academic Search Premier was performed. Inclusion criteria were studies between 2009 and 2019 in TTTS-survivors treated with fetoscopic laser surgery and followed-up after the neonatal period with cognitive developmental tests and neurologic exams. Exclusion criteria were non-English articles and reviews, case reports, letters, and guidelines. Results:. Nineteen articles were included. Long-term severe neurodevelopmental impairment (NDI) was reported by seven and ranged from 4.0% to 18.0% with a mean of 9.7% (95% confidence interval (CI): 7.8–11.5). The prevalence of cerebral palsy ranged from 1.6% to 18.2%, with a mean of 5.1% (95% CI: 4.1–6.2). The mean prevalence of minor impairment was 13.7% (95% CI: 11.4–16.0). However, only 78.9% (15/19) studies used a validated neurodevelopmental test. As studies lack uniform definitions of primary outcome, timing of follow-up, inclusion criteria, and methods, adequate comparison is hampered. Conclusion:. The prevalence of severe NDI and cerebral palsy after fetoscopic laser surgery for TTTS in the last decade remains stable around 9.7% and 5.1%, respectively. International agreements on primary outcomes, methods, and follow-up are necessary to improve the knowledge of NDI in TTTS-survivors.

Abstract Background Selective fetal growth restriction in monochorionic twin pregnancies is associated with an increased risk of perinatal mortality and morbidity and represents a clinical dilemma. Interventions include expectant management with early preterm delivery if there are signs of fetal compromise, selective termination of the compromised twin, fetoscopic laser coagulation of the communicating placental vessels or termination of the whole pregnancy. Previous studies evaluating interventions have reported many different outcomes and outcome measures. Such variation makes comparing, contrasting, and combining results challenging, limiting ongoing research on this uncommon condition to inform clinical practice. We aim to produce, disseminate, and implement a core outcome set for selective fetal growth restriction research in monochorionic twin pregnancies. Methods An international steering group, including professionals, researchers, and lay experts, has been established to oversee the development of this core outcome set. The methods have been guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. Potential core outcomes will be developed by undertaking a systematic review of studies evaluating interventions for selective fetal growth restriction in monochorionic twin pregnancies. Potential core outcomes will be entered into a three-round Delphi survey and key stakeholders including clinical professionals, researchers, and lay experts will be invited to participate. Repeated reflection and rescoring of individual outcomes should encourage group and individual stakeholder convergence towards consensus outcomes which will be entered into a modified Nominal Group Technique to finalize the core outcome set. Once core outcomes have been agreed, we will establish standardized definitions and recommend high-quality measurement instruments for each outcome. Discussion The development, dissemination, and implementation of a core outcome set for selective fetal growth restriction should ensure that future research protocols select, collect, and report outcomes and outcome measures in a standardized manner. Data synthesis will be possible on a broad level and rigorous implementation should advance the quality of research studies and their effective use in order to guide clinical practice, improve patient care, maternal, short-term perinatal outcomes, and long-term neurodevelopmental outcomes. Trial registration Core Outcome Measures in Effectiveness Trials (COMET) registration number: 998. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42018092697. 18th April 2018.

Background: Fetal growth restriction (FGR) is thought to negatively affect lung development resulting in increased respiratory morbidity. However, research performed in singletons is often limited by a certain level of bias caused by individual differences in genetic constitution, obstetrical and maternal factors. Methods: Respiratory morbidity was compared between the smaller and the larger twin in monochorionic twins with selective fetal growth restriction (sFGR), defined as a birth weight discordance ≥ 20%, born in our center between 2010 and 2019 in this retrospective study. Respiratory distress syndrome (RDS) was diagnosed based on the clinical picture of a neonate with respiratory failure requiring mechanical ventilation and/or surfactant, confirmed by a chest X-ray. Bronchopulmonary dysplasia (BPD) was diagnosed when the neonate required treatment with >21% oxygen for at least 28 days. Findings: Median gestational age at birth for the 94 included pregnancies was 32.4 (IQR 30.4–34.3) weeks. Within-pair analyses showed that the prevalence of RDS was lower in the smaller twin compared to the larger twin, 19.1% (18/94) vs 34.0% (32/94), respectively (p = 0.004). The odds of RDS for the larger twin was doubled (OR 2.1 (CI95% 1.3–3.5). In contrast, the rate of BPD in the smaller twin was higher as opposed to the larger twin, 16.7% (15/90) vs 6.7% (6/89), respectively (p = 0.008), with a more than doubled odds (OR 2.5 (CI95% 1.3–4.9)). Interpretation: Despite being genetically identical, sFGR twins have different respiratory outcomes. Adverse growth condition in utero in the smaller twin is associated with a reduced odds of RDS at birth but a more than doubled odds of BPD, reflecting the pathophysiologic adverse effect of growth restriction on lung development. Funding: The Dutch Heart Foundation (2017T075).

Background Selective fetal restriction growth (sFGR) is one of the common diseases of monochorionic diamniotic (MCDA) twin pregnancies, resulting in many adverse outcomes. At present, second trimester ultrasonography is widely used in the prenatal diagnosis of sFGR, but the diagnostic effectiveness is still uncertain. The aim of this study is to assess the diagnostic accuracy of second trimester Doppler ultrasound measurements for sFGR. Methods A retrospective study included 280 pregnant women (118 with and 162 without sFGR) with MCDA pregnancies was conducted in the fetal medicine center from Leiden University Medical Center from January 2008 to December 2013. The women participating had already undergone an ultrasound examination in the second trimester. The postnatal criteria of sFGR was a single birth weight (BW) 95th percentile). According to the diagnosis of sFGR after birth, we evaluate diagnostic effectiveness of Doppler ultrasound in the second trimester for sFGR. Results Of these 280 participants, the mean age was 32.06 ± 4.76 years. About 43.9% of pregnant women were primiparas. The ability of second trimester Doppler ultrasound to accurately diagnosed sFGR is 75.4%, missed diagnosis rate and the misdiagnosis rate were 24.6% and 10.5% respectively. The ROC curve indicated that the combination of AC discordance, EFW discordance, and small fetal UA blood flow was the best diagnostic indicator of sFGR in MCDA pregnancy with the AUC was 0.882 (95%CI, 0.839–0.926). Conclusions Second trimester Doppler and ultrasound measurements is an effective method for early prenatal diagnosis of sFGR. The combined indicator of AC discordance, EFW discordance, and the small fetal UA blood flow reaches highest diagnostic value.

Introduction Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may lead to severe fetal or neonatal bleeding and/or perinatal death. Maternal alloantibodies, targeted against fetal human platelet antigens (HPAs), can result thrombocytopenia and bleeding complications. In pregnancies with known immunisation, fetal bleeding can be prevented by weekly maternal intravenous immunoglobulin infusions. Without population-based screening, immunisation is only detected after birth of an affected infant. Affected cases that might have been prevented, when timely identified through population-based screening. Implementation is hampered by the lack of knowledge on incidence, natural history and identification of pregnancies at high risk of bleeding. We designed a study aimed to obtain this missing knowledge.Methods and analysis The HIP (HPA-screening in pregnancy) study is a nationwide, prospective and observational cohort study aimed to assess incidence and natural history of FNAIT as well as identifying pregnancies at high risk for developing bleeding complications. For logistic reasons, we invite rhesus D-negative or rhesus c-negative pregnant women, who take part in the Dutch population-based prenatal screening programme for erythrocyte immunisation, to participate in our study. Serological HPA-1a typing is performed and a luminex-based multiplex assay will be performed for the detection of anti-HPA-1a antibodies. Results will not be communicated to patients or caregivers. Clinical data of HPA-1a negative women and an HPA-1a positive control group will be collected after birth. Samples of HPA-1a immunised pregnancies with and without signs of bleeding will be compared with identify parameters for identification of pregnancies at high risk for bleeding complications.Ethics and dissemination Ethical approval for this study has been obtained from the Medical Ethical Committee Leiden-The Hague-Delft (P16.002). Study enrolment began in March 2017. All pregnant women have to give informed consent for testing according to the protocol. Results of the study will be disseminated through congresses and publication in relevant peer-reviewed journals.Trial registration number NCT04067375.

Background: Infants are currently stabilized at birth with initial low FiO2 which increases the risk of hypoxia and suppression of breathing in the first minutes after birth. We hypothesized that initiating stabilization at birth with a high O2 concentration, followed by titration, would improve breathing effort when compared to a low O2 concentration, followed by titration.Methods: In a bi-center randomized controlled trial, infants 95%. 8-iso-prostaglandin F2α (8iPGF2α) was measured to assess oxidative stress in cord blood and 1 and 24 h after birth.Results: Fifty-two infants were randomized and recordings were obtained in 44 infants (100% O2-group: n = 20, 30% O2-group: n = 24). Minute volumes were significantly higher in the 100% O2-group (146.34 ± 112.68 mL/kg/min) compared to the 30% O2-group (74.43 ± 52.19 mL/kg/min), p = 0.014. Tidal volumes and MIFR were significantly higher in the 100% O2-group, while the duration of mask ventilation given was significantly shorter. Oxygenation in the first 5 min after birth was significantly higher in infants in the 100% O2-group [85 (64–93)%] compared to the 30% O2-group [58 (46–67)%], p < 0.001. The duration of hypoxemia was significantly shorter in the 100% O2-group, while the duration of hyperoxemia was not different between groups. There was no difference in oxidative stress marker 8iPGF2α between the groups.Conclusion: Initiating stabilization of preterm infants at birth with 100% O2 led to higher breathing effort, improved oxygenation, and a shorter duration of mask ventilation as compared to 30% O2, without increasing the risk for hyperoxia or oxidative stress.Clinical Trial Registration: This study was registered in www.trialregister.nl, with registration number NTR6878.

Abstract 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.

Abstract Background Twin–Twin Transfusion Syndrome (TTTS) is associated with an increased risk of perinatal mortality and morbidity. Several treatment interventions have been described for TTTS, including fetoscopic laser surgery, amnioreduction, septostomy, expectant management, and pregnancy termination. Over the last decade, fetoscopic laser surgery has become the primary treatment. The literature to date reports on many different outcomes, making it difficult to compare results or combine data from individual studies, limiting the value of research to guide clinical practice. With the advent and ongoing development of new therapeutic techniques, this is more important than ever. The development and use of a core outcome set has been proposed to address these issues, prioritising outcomes important to the key stakeholders, including patients. We aim to produce, disseminate, and implement a core outcome set for TTTS. Methods An international steering group has been established to oversee the development of this core outcome set. This group includes healthcare professionals, researchers and patients. A systematic review is planned to identify previously reported outcomes following treatment for TTTS. Following completion, the identified outcomes will be evaluated by stakeholders using an international, multi-perspective online modified Delphi method to build consensus on core outcomes. This method encourages the participants towards consensus ‘core’ outcomes. All key stakeholders will be invited to participate. The steering group will then hold a consensus meeting to discuss results and form a core outcome set to be introduced and measured. Once core outcomes have been agreed, the next step will be to determine how they should be measured, disseminated, and implemented within an international context. Discussion The development, dissemination, and implementation of a core outcome set in TTTS will enable its use in future clinical trials, systematic reviews and clinical practice guidelines. This is likely to advance the quality of research studies and their effective use in order to guide clinical practice and improve patient care, maternal, short-term perinatal outcomes and long-term neurodevelopmental outcomes. Trial registration Core Outcome Measures in Effectiveness Trials (COMET), 921 Registered on July 2016. International Prospective Register of Systematic Reviews (PROSPERO), CRD42016043999 . Registered on 2 August 2016.

Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age

Background: Most preterm infants fail to aerate their immature lungs at birth and need respiratory support for cardiopulmonary stabilization. Cord clamping before lung aeration compromises cardiovascular function. Delaying cord clamping until the lung has aerated may be beneficial for preterm infants by optimizing hemodynamic transition and placental transfusion. A new purpose-built resuscitation table (the Concord) has been designed making it possible to keep the cord intact after preterm birth until the lung is aerated and the infant is respiratory stable and breathing [Physiological-Based Cord Clamping (PBCC)]. The aim of this study is to test the hypothesis whether stabilizing preterm infants by PBCC is at least as effective as the standard approach using time-based Delayed Cord Clamping (DCC).Study design: This is a randomized controlled non-inferiority study including 64 preterm infants born at

The observation, by Ray Owen and colleagues in 1954, that D-negative women were less likely to form anti-D antibodies against their D-positive fetus if their mother possessed the D-antigen, was not found in all later studies. We hypothesized that breastfeeding, received by the mother, may affect her immunity against non-inherited maternal red blood cell antigens. We studied a cohort of 125 grandmother-mother-child combinations, from a follow-up study of mothers after intrauterine transfusion of the fetus for alloimmune hemolytic disease. For mismatched red blood cell antigens the mother was exposed to, whether or not antibodies were formed, we determined whether her mother, the grandmother, carried these antigens. The duration for which the mothers were breastfed was estimated by way of a questionnaire. Using multivariate logistic regression analyses, the interaction term (non-inherited maternal antigen exposure by categorized breastfeeding period) showed that a longer breastfeeding period was associated with decreased alloimmunization against non-inherited maternal antigens (adjusted odds ratio 0.66; 95% confidence interval 0.48–0.93). Sensitivity analysis with dichotomized (shorter versus longer) breastfeeding periods showed that this lower risk was reached after two months (aOR 0.22; 95% CI 0.07–0.71) and longer duration of breastfeeding did not seem to provide additional protection. These data suggest that oral neonatal exposure to non-inherited maternal red blood cell antigens through breastfeeding for at least two months diminishes the risk of alloimmunization against these antigens when encountered later in life.

BackgroundVenous blood gas (VBG) is frequently used in the neonatal unit as alternative for capillary blood gas (CBG). However, studies reporting correlation are conflicting and data on interchangeability in neonates are lacking.ObjectiveWe investigated the correlation and interchangeability of the components between VBG and CBG in infants admitted to the neonatal intensive care unit.MethodsIn a prospective study in the neonatal unit in Leiden University Medical Center (Netherlands), simultaneously VBG and CBG were withdrawn in neonates when both venous puncture and intravenous access as blood gas monitoring was indicated. From each blood gas analysis, a Pearson correlation, intraclass correlation, and Bland–Altman analysis was performed. Clinically acceptable difference for each blood gas value was defined up-front by means of an absolute difference: pH ± 0.05; partial pressure of carbon dioxide (pCO2) (±0.67 kPa = 5 mmHg); partial pressure of oxygen (pO2) (±0.67 kPa = 5 mmHg); base excess ± 3 mmol/l; and bicarbonate (HCO3−) ± 3 mmol/l.ResultsIn 93 patients [median gestational age 31 (IQR 29–34) weeks], 193 paired samples of VBG and CBG were collected. The Pearson correlation between VBG and CBG was very strong for pH (r = 0.79; P

Central venous catheters (CVCs) in neonates are associated with a risk of central line-associated bloodstream infections (CLABSI). Most reports on the incidence of CLABSI in neonates focus on umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs). We evaluated the incidence and risk factors for CLABSI in a cohort of neonates with femoral venous catheters (FVCs), UVCs, and PICCs, with a gestational age ≥34 weeks born between January 1, 2006 and June 30, 2013. We included 2,986 neonates with a total of 656 catheters. The CLABSI incidence rate varied from 12.3 per 1,000 catheter-days in FVCs to 10.6 per 1,000 catheter-days in UVCs and 5.3 per 1,000 catheter-days in PICCs. In a Kaplan–Meier survival analysis, we did not find a difference in CLABSI risk between the catheter types (p = 0.29). The following factors were independently associated with an increased risk of CLABSI: parenteral nutrition [hazard ratio (HR) 2.60, 95% confidence interval (CI) 1.25–5.41], male gender (HR 2.63, 95% CI 1.17–5.90), and higher birth weight (HR 1.04, 95% CI 1.002–1.09), whereas antibiotic treatment at birth (HR 0.25, 95% CI 0.12–0.52) was associated with a decreased risk. Conclusion: In our cohort, we did not find a difference between the CLABSI incidence in FVCs, PICCs, and UVCs. Occurrence of CLABSI is associated with parenteral nutrition, male gender, and higher birth weight. Antibiotic treatment at birth was associated with a decreased risk of CLABSI.

Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis.A cohort study was carried out among all neonates with proven culture positive sepsis that were admitted to a tertiary NICU between 2006 and 2015 (n = 460). The occurrence, severity and duration of thrombocytopenia were recorded, as well as major bleedings and potential risk factors for mortality in neonatal sepsis.Sepsis was diagnosed in 460 of 6551 neonates (7%). Severe thrombocytopenia (platelets ≤50*109/L) occurred in 20% (92/460) of septic neonates. The median time for platelets to rise >100*109 was 6.0 days (interquartile range 4.0-7.0). On multivariate analysis, maternal hypertension, intravascular thrombosis and Gram negative (as opposed to Gram positive) sepsis were independently associated with thrombocytopenia in neonatal sepsis. In severe thrombocytopenia, 10% (9/92) suffered a severe IVH, compared to 5% (20/356) in neonates with platelets >50*109/L (p = 0.125). 10% (9/92) suffered a pulmonary hemorrhage, compared to 2% (9/368) in neonates with platelets >50*109/L (p = 0.001). On multivariate analysis, thrombocytopenia and Gram negative (as opposed to Gram positive) sepsis were independently associated with neonatal mortality.Thrombocytopenia is independently associated with maternal hypertension, intravascular thrombosis and Gram negative sepsis. Thrombocytopenia in neonatal sepsis increases the risk of mortality nearly four-fold, with another six-fold increase in mortality in case of Gram negative sepsis.

Hypothermia is associated with increased morbidity and mortality rates. Preterm infants frequently have hypothermia when they are admitted to the NICU, but there is no data on the occurrence of hypothermia during the first hours after admission.To investigate the occurrence of hypothermia in preterm infants in the first three hours of admission and to identify risk factors.Infants < 32 weeks of gestation included in a randomized trial with admission temperature as primary outcome were retrospectively analyzed for the occurrence of hypothermia (< 36.5°C) in the first three hours after admission. Risk factors were identified using linear regression analysis and logistic regression.In total 80 infants were included with a median (IQR) gestational age at birth of 29 (27-30) weeks. In 93% of the infants hypothermia occurred in the first three hours after admission. The median (IQR) duration of hypothermia was 101 (34-162) minutes, of which 24 (7-52) minutes the hypothermia was mild, 45 (4-111) minutes moderate, severe hypothermia hardly occurred. Gestational age and the occurrence of hypothermia at birth were independent risk factors for the occurrence of moderate and severe hypothermia and significantly correlated with duration of hypothermia.Hypothermia occurred often and for a long period in preterm infants in the first three hours of life, low gestational age and admission temperature were independent risk factors.

To test the ability of the Ages and Stages Questionnaire, Third Edition (ASQ3) to help identify or exclude neurodevelopmental impairment (NDI) in very preterm-born children at the corrected age of two.We studied the test results of 224 children, born at

High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.Controlled-Trials.com ISRCTN74465643.

This study compares the methods of Dunn and Shukla in determining the appropriate insertion length of umbilical catheters. In July 2007, we changed our policy for umbilical catheter insertions from the method of Dunn to the method of Shukla. We report our percentage of inaccurate placement of umbilical-vein catheters (UVCs) and umbilical-artery catheters (UACs) before and after the change of policy. In the Dunn-group, 41% (28/69) of UVCs were placed directly in the correct position against 24% (20/84) in the Shukla-group. The position of the catheter-tip of UVCs in the Dunn-group and the Shukla-group was too high in 57% (39/69) and 75% (63/84) of neonates, respectively. UACs in the Dunn-group were placed directly in the correct position in 63% (24/38) compared to the 87% (39/45) of cases in Shukla-group. The position of the catheter-tip of UACs in the Dunn-group and the Shukla-group was too high in 34% (13/38) and 13% (6/45) of neonates, respectively. In conclusion, the Dunn-method is more accurate than the Shukla-method in predicting the insertion length for UVCs, whereas the Shukla-method is more accurate for UACs.

BACKGROUND: New national guidelines recommend more restricted fluid intake and early initiation of total parenteral nutrition (TPN) in very preterm infants. The aim was study the effect of these guidelines on serum sodium and potassium levels and fluid balance in the first three days after birth. METHODS: Two cohorts of infants

BACKGROUND: In the period immediately after birth, preterm infants are highly susceptible to lung injury. Early nasal continuous positive airway pressure (ENCPAP) is an attempt to avoid intubation and may minimize lung injury. In contrast, ENCPAP can fail, and at that time surfactant rescue can be less effective. OBJECTIVE: To compare the pulmonary clinical course and outcome of very preterm infants (gestational age 25-32 weeks) with respiratory distress syndrome (RDS) who started with ENCPAP and failed (ECF group), with a control group of infants matched for gestational age, who were directly intubated in the delivery room (DRI group). Primary outcome consisted of death during admission or bronchopulmonary dysplasia (BPD). RESULTS: 25 infants were included in the ECF group and 50 control infants matched for gestational age were included in the DRI group. Mean gestational age and birth weight in the ECF group were 29.7 weeks and 1,393 g and in the DRI group 29.1 weeks and 1,261 g (p = NS). The incidence of BPD was significantly lower in the ECF group than in the DRI group (4% vs. 35%; P