Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study.

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO2) 10-13 kPa and peripheral oxygen saturation (SpO2) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO2). A total of 181 infants were included. The median FiO2 was 0.43 (IQR 0.34-0.56) and the maximum FiO2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO2 > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO2 > 30 kPa. SpO2 was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO2 < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO2 < 6.7 kPa. SpO2 was < 92% in 169/181 (93%) infants for 1.6% (0.5-4.3%) of the iNO time.    Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients. What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition. What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range.

The effect of imposed resistance in neonatal resuscitators on pressure stability and peak flows: a bench test.

BACKGROUND: The importance of neonatal resuscitator resistance is currently unknown. In this study we investigated peak flows and pressure stability resulting from differences in imposed resistance during positive pressure ventilation(PPV) and simulated spontaneous breathing (SSB) between the r-PAP, low-resistance resuscitator, and Neopuff™, high-resistance resuscitator. METHODS: In a bench test, 20 inflations during PPV and 20 breaths during SSB were analysed on breath-by-breath basis to determine peak flow and pressure stability using the Neopuff™ with bias gas flow of 8, 12 or 15 L/min and the r-PAP with total gas flow of 15 L/min. RESULTS: Imposed resistance of the Neopuff™ was significantly reduced when the bias gas flow was increased from 8 to 15 L/min, which resulted in higher peak flows during PPV and SSB. Peak flows in the r-PAP were, however, significantly higher and fluctuations in CPAP during SSB were significantly smaller in the r-PAP compared to the Neopuff™ for all bias gas flow levels. During PPV, a pressure overshoot of 3.2 cmH2O was observed in the r-PAP. CONCLUSIONS: The r-PAP seemed to have a lower resistance than the Neopuff™ even when bias gas flows were increased. This resulted in more stable CPAP pressures with higher peak flows when using the r-PAP. IMPACT: The traditional T-piece system (Neopuff™) has a higher imposed resistance compared to a new neonatal resuscitator (r-PAP). This study shows that reducing imposed resistance leads to smaller CPAP fluctuations and higher inspiratory and expiratory peak flows. High peak flows might negatively affect lung function and/or cause lung injury in preterm infants at birth. This study will form the rationale for further studies investigating these effects. A possible compromise might be to use the traditional T-piece system with a higher bias gas flow (12 L/min), thereby reducing the imposed resistance and generating more stable PEEP/CPAP pressures, while limiting potentially harmful peak flows.

Clinical outcomes of preterm infants while using automated controllers during standard care: comparison of cohorts with different automated titration strategies.

OBJECTIVE: To compare short-term clinical outcome after using two different automated oxygen controllers (OxyGenie and CLiO2). DESIGN: Propensity score-matched retrospective observational study. SETTING: Tertiary-level neonatal unit in the Netherlands. PATIENTS: Preterm infants (OxyGenie n=121, CLiO2 n=121) born between 24+0-29+6 weeks of gestation. Median (IQR) gestational age in the OxyGenie cohort was 28+3 (26+3.5-29+0) vs 27+5 (26+5-28+3) in the CLiO2 cohort, respectively 42% and 46% of infants were male and mean (SD) birth weight was 1034 (266) g vs 1022 (242) g. INTERVENTIONS: Inspired oxygen was titrated by OxyGenie (SLE6000) or CLiO2 (AVEA) during respiratory support. MAIN OUTCOME MEASURES: Mortality, retinopathy of prematurity (ROP), bronchopulmonary dysplasia and necrotising enterocolitis. RESULTS: Fewer infants in the OxyGenie group received laser coagulation for ROP (1 infant vs 10; risk ratio 0.1 (95% CI 0.0 to 0.7); p=0.008), and infants stayed shorter in the neonatal intensive care unit (NICU) (28 (95% CI 15 to 42) vs 40 (95% CI 25 to 61) days; median difference 13.5 days (95% CI 8.5 to 19.5); p<0.001). Infants in the OxyGenie group had fewer days on continuous positive airway pressure (8.4 (95% CI 4.8 to 19.8) days vs 16.7 (95% CI 6.3 to 31.1); p<0.001) and a significantly shorter days on invasive ventilation (0 (95% CI 0 to 4.2) days vs 2.1 (95% CI 0 to 8.4); p=0.012). There were no statistically significant differences in all other morbidities. CONCLUSIONS: In this propensity score-matched retrospective study, the OxyGenie epoch was associated with less morbidity when compared with the CLiO2 epoch. There were significantly fewer infants that received treatment for ROP, received less intensive respiratory support and, although there were more supplemental oxygen days, the duration of stay in the NICU was shorter. A larger study will have to replicate these findings.

Comparison of neonatal morbidity and mortality between single-room and open-bay care: a retrospective cohort study.

OBJECTIVE: In response to the increasing focus on family-centred care, neonatal intensive care unit (NICU) environments have gradually shifted towards the single-room design. However, the assumed benefits of this emerging design remain a subject of debate. Our goal was to evaluate the impact of single-room versus open-bay care on the risk of neonatal morbidity and mortality in preterm neonates. DESIGN: Retrospective cohort study. SETTING: Level III NICU. PATIENTS: Neonates born <32 weeks' gestation between 15 May 2015 and 15 May 2019. MAIN OUTCOME MEASURES: Mortality and morbidities of a cohort of neonates admitted to a new, single-room unit (SRU) were compared with a historical cohort of neonates admitted to an open-bay unit (OBU). Group differences were evaluated and multivariable logistic regression analyses were performed. RESULTS: Three-hundred and fifty-six and 343 neonates were admitted to the SRU and OBU, respectively. No difference in neonatal morbidities and mortality were observed between cohorts (bronchopulmonary dysplasia: OR 1.08, 95% CI 0.73 to 1.58, p=0.44; retinopathy of the prematurity stage ≥2: OR 1.36, 95% CI 0.84 to 2.22, p=0.10; intraventricular haemorrhage: OR 0.89, 95% CI 0.59 to 1.34, p=0.86; mortality: OR 1.55, 95% CI 0.75 to 3.20, p=0.28). In adjusted regression models, single-room care was independently associated with a decreased risk of symptomatic patent ductus arteriosus (adjusted OR 0.54, 95% CI 0.31 to 0.95). No independent association between single-room care and any of the other investigated outcomes was observed. CONCLUSIONS: Implementation of single-rooms in our NICU did not lead to a significant reduction in neonatal morbidity and mortality outcomes.

The Effect of a Higher Bias Gas Flow on Imposed T-Piece Resistance and Breathing in Preterm Infants at Birth.

Objective: The resistance created by the PEEP-valve of a T-piece resuscitator is bias gas flow dependent and might affect breathing in preterm infants. In this study we investigated the effect of a higher bias gas flow on the imposed inspiratory and expiratory T-piece resistance and expiratory breaking manoeuvres (EBM) in preterm infants during spontaneous breathing on CPAP at birth. Methods: In a retrospective pre-post implementation study of preterm infants <32 weeks gestation, who were stabilised with a T-piece resuscitator, a bias gas flow of 12 L/min was compared to 8 L/min. All spontaneous breaths on CPAP within the first 10 min of starting respiratory support were analysed on a breath-by-breath basis to determine the breathing pattern of each breath and to calculate the imposed inspiratory and expiratory T-piece resistance (Ri, Re), flow rates and tidal volume. Results: In total, 54 infants were included (bias gas flow 12 L/min: n = 27, 8 L/min: n = 27) with a median GA of 29+6 (28+4-30+3) and 28+5 (25+6-30+3), respectively (p = 0.182). Ri and Re were significantly lower in the 12 L/min compared to 8 L/min bias flow group [Ri: 29.6 (26.1-33.6) vs. 46.4 (43.0-54.1) cm H2O/L/s, p < 0.001; Re: 32.0 (30.0-35.1) vs. 48.0 (46.3-53.9) cm H2O/L/s, p < 0.001], while the incidence of EBM [77% (53-88) vs. 77% (58-90), p = 0.586] was similar. Conclusion: During stabilisation of preterm infants at birth with a T-piece resuscitator, the use of a higher bias gas flow reduced both the imposed inspiratory and expiratory T-piece resistance for the infant, but this did not influence the incidence of EBMs.

Large Hemoglobin Differences at Birth in Monochorionic Twins with a Placental Chorangioma and Delayed Cord Clamping.

We report a case of a monochorionic diamniotic twin with an uncomplicated pregnancy, but with an unexpected large intertwin hemoglobin (Hb) difference at birth. Twin 1 was delivered vaginally and had an uneventful neonatal course. The umbilical cord of Twin 1 was clamped approximately 5 min after birth. After the birth of Twin 1, Twin 2 developed severe bradycardia and showed limited cardiac output on ultrasound, for which an emergency cesarean section was performed. A full blood count revealed an Hb of 20.1 g/dL for Twin 1 and 10.2 g/dL for Twin 2 (intertwin difference 9.9 g/dL). Reticulocyte counts were similar, 40‰ and 38‰, respectively. Placental examination revealed 10 vascular anastomoses, including one arterio-arterial anastomosis with a diameter of 1.4 mm. Additionally, a large chorangioma was present on the placental surface of Twin 2. There was no color difference on the maternal side of the placenta. Based on the reticulocyte count ratio and the placental characteristics, twin anemia polycythemia sequence was ruled out as the cause of the large intertwin Hb difference. In this report, we discuss the various potential causes that could explain the large intertwin Hb difference including the role of delayed cord clamping in Twin 1, and the role of a large chorangioma, which may have attracted blood from the fetal circulation of Twin 2.

Sustained Inflation Versus Intermittent Positive Pressure Ventilation for Preterm Infants at Birth: Respiratory Function and Vital Sign Measurements.

OBJECTIVE: To characterize respiratory function monitor (RFM) measurements of sustained inflations and intermittent positive pressure ventilation (IPPV) delivered noninvasively to infants in the Sustained Aeration of Infant Lungs (SAIL) trial and to compare vital sign measurements between treatment arms. STUDY DESIGN: We analyzed RFM data from SAIL participants at 5 trial sites. We assessed tidal volumes, rates of airway obstruction, and mask leak among infants allocated to sustained inflations and IPPV, and we compared pulse rate and oxygen saturation measurements between treatment groups. RESULTS: Among 70 SAIL participants (36 sustained inflations, 34 IPPV) with RFM measurements, 40 (57%) were spontaneously breathing prior to the randomized intervention. The median expiratory tidal volume of sustained inflations administered was 5.3 mL/kg (IQR 1.1-9.2). Significant mask leak occurred in 15% and airway obstruction occurred during 17% of sustained inflations. Among 34 control infants, the median expiratory tidal volume of IPPV inflations was 4.3 mL/kg (IQR 1.3-6.6). Mask leak was present in 3%, and airway obstruction was present in 17% of IPPV inflations. There were no significant differences in pulse rate or oxygen saturation measurements between groups at any point during resuscitation. CONCLUSION: Expiratory tidal volumes of sustained inflations and IPPV inflations administered in the SAIL trial were highly variable in both treatment arms. Vital sign values were similar between groups throughout resuscitation. Sustained inflation as operationalized in the SAIL trial was not superior to IPPV to promote lung aeration after birth in this study subgroup. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02139800.

A multi-centre randomised controlled trial of respiratory function monitoring during stabilisation of very preterm infants at birth.

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.

Respiratory distress syndrome and bronchopulmonary dysplasia after fetal growth restriction: Lessons from a natural experiment in identical twins.

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).

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: a review of current concepts.

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, the physiological changes occurring during the fetal-to-neonatal transition in CDH, novel delivery room strategies and early predictors of adverse outcomes. The combination of improvements in the perinatal stabilisation period and early prediction of adverse outcomes may mitigate the need for specific postnatal management strategies.

Leukocyte Counts and Other Hematological Values in Twin-Twin Transfusion Syndrome and Twin Anemia-Polycythemia Sequence.

OBJECTIVE: The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). METHODS: We performed a retrospective cohort study in monochorionic twin pairs with TTTS or TAPS. TTTS and TAPS cases treated with fetoscopic laser surgery were excluded. Primary outcome was the difference in leukocyte levels at birth between donor and recipient twins and the presence of leukopenia (defined as leukocyte count <4 × 109/L). Secondary outcomes included early-onset sepsis, necrotizing enterocolitis, use of antibiotics during admission, and neonatal mortality. RESULTS: We included 99 twins pairs, of which 61 twin pairs were affected by TAPS and 38 twin pairs by TTTS. The mean leukocyte count at birth in donors and recipients was 7.5 × 109/L versus 7.4 × 109/L (p = 0.936), respectively. Leukopenia was significantly more common in donor twins compared to recipient twins (7.1% [7/99] vs. 0% [0/99], p = 0.016). Of the 7 donors with leukopenia, 6 were affected by TAPS and 1 by TTTS. Overall, donors were more often affected by early-onset sepsis than recipients, 23.7% (23/97) versus 13% (13.7/95) (p = 0.049), respectively. CONCLUSIONS: Leukocyte counts at birth in twins with TTTS or TAPS are similar between donors and recipients, but TAPS donors are at an increased risk of leukopenia. Overall, TTTS and TAPS donors seem to be at an increased risk of early-onset neonatal sepsis compared to recipient twins.

Short report: Post-operative wound infections after the gentle caesarean section.

OBJECTIVES: Worldwide, the caesarean section (CS) is the most performed type of surgery and numbers are still rising. The gentle CS has become a more common procedure as it allows the parents to experience birth. Early and continuous skin-to-skin contact between the mother and her newborn is pursued. Parents are not separated from their newborns and stay with their child in the operation theatre and recovery room. However, data are limited on the incidence of surgical site infections (SSI) after gentle CS. The aim of our study was to examine the risk of postoperative wound infections after gentle CS. Secondary outcomes included other maternal complications and neonatal outcomes. STUDY DESIGN: In this multicenter prospective cohort study, all women who underwent an elective gentle CS between January 2015 and January 2017 were eligible. Demographics, per procedural data, maternal complications and neonatal outcomes were collected. The follow-up lasted until six weeks post partum. RESULTS: Of the 243 performed CSs, two (0.8%) SSIs occurred; one superficial and one deep wound infection. One patient (0.4%) was readmitted for treatment of endometritis. In total, 20 (8.2%) maternal complications were identified. Median time to skin-to-skin contact was 3 minutes (IQR 2-4.25) with a median neonatal oxygen saturation 10 minutes after birth of 95% (IQR 92-98). Mean gestational age was 274 ±â€¯4.1 days (39 + 1 weeks) and mean neonatal pH was 7.28 (±SD 0.07). All children had Apgar scores >7 at 5 minutes after birth. Neonatal admission occurred in 19 cases (7.8%) and neonatal readmission in 10 cases (4.1%). CONCLUSION: The gentle CS seems to be a safe procedure for both mother and child and is not associated with an increased risk of surgical site infections or direct suboptimal neonatal outcomes. Therefore, more intensive mother-child interaction during CS is allowed.

Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking. Objective: To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants. Design, Setting, and Participants: Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017. Interventions: Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190). Main Outcomes and Measures: The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age. Results: Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%). Conclusions and Relevance: Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication. Trial Registration: Netherlands National Trial Register Identifier: NTR2768.

Respiratory morbidity was an important consequence of prematurity in the first two years after discharge in three cohorts from 1996 to 2009.

AIM: This study aimed to evaluate the respiratory morbidity of preterm infants in the first two years after discharge in three cohorts from 1996 to 2009. METHODS: We included infants with a gestational age from 25 + 0 to 29 + 6 weeks, who were born in 1996-1997, 2003-2004 and 2008-2009 at the Leiden University Medical Center in the Netherlands. The following parameters were recorded: bronchopulmonary dysplasia (BPD), defined as oxygen demand or positive pressure at 36 weeks, mortality, duration of supplemental oxygen, discharge with supplemental oxygen and a nasogastric feeding tube, rehospitalisation and the use of inhaled medication. RESULTS: In line with our protocols, 106, 120 and 156 infants were analysed in the three study periods and 29%, 22% and 18% were diagnosed with BPD. Respiratory morbidity did not change over time in infants with and without BPD, except for an increase in rehospitalisation for respiratory issues in infants with BPD. This decreased in infants without BPD. Respiratory morbidity occurred more frequently in infants with BPD than without BPD, but this was not statistically significant. CONCLUSION: This study showed that when cohorts of preterm infants were compared over time, respiratory morbidity in the first two years of life remained an important consequence after discharge.

Femoral Vein Catheter is an Important Risk Factor for Catheter-related Thrombosis in (Near-)term Neonates.

Central venous catheters (CVCs) in neonates are associated with an increased risk of thrombosis. Most reports focus on umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs), whereas data available on femoral venous catheters (FVCs) are limited. We performed a retrospective cohort study in all neonates (gestational age ≥34 wk) with CVCs. The primary outcome was the occurrence of thrombosis in CVCs. The secondary outcomes were possible risk factors for thrombosis, the thrombotic incidence in FVCs, UVCs, and PICCs, and clinical aspects of thrombosis in these groups. A total of 552 neonates received a total of 656 catheters, including 407 (62%) UVCs, 185 (28%) PICCs, and 64 (10%) FVCs. Thrombosis was detected in 14 cases, yielding an overall incidence of 2.1% or 3.6 events per 1000 catheter days. FVC was significantly associated with the occurrence of thrombosis when compared with UVC (P=0.02; odds ratio, 3.8; 95% confidence interval, 1.2-12.0) and PICC (P=0.01; odds ratio, 8.2; 95% confidence interval, 1.6-41.7). The incidence of thrombosis was higher in FVCs than in UVCs and PICCS, that is, 7.8% (5/64), 1.7% (7/407), and 1.1% (2/185), respectively (P<0.01). The number of thrombotic events per 1000 catheter days was 12.3 in FVCs, 3.2 in UVCs, and 1.5 in PICCs (P<0.05). We concluded that thrombosis occurs more frequently in FVCs than in other CVCs.

Persistent Pulmonary Hypertension of the Newborn in Twin-Twin Transfusion Syndrome: A Case-Control Study.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is associated with severe morbidity and mortality. Twin-twin transfusion syndrome (TTTS) is suggested to increase the risk of PPHN. OBJECTIVES: To describe the incidence of PPHN in TTTS twins and to identify risk factors in TTTS twins for the development of severe PPHN. METHODS: Cases with severe PPHN were extracted from our monochorionic twin database (2002-2016). Severe PPHN was defined as severe hypoxaemia requiring mechanical ventilation and inhaled nitric oxide (iNO) treatment, confirmed by strict echocardiographic criteria. A case-control comparison within TTTS survivors was conducted to identify risk factors for PPHN. RESULTS: The incidence of PPHN in TTTS twins was 4% (24/598, 95% confidence interval [CI] 2.7-5.9%) and 0.4% (2/493, 95% CI 0.1-1.5%) in uncomplicated monochorionic twins (odds ratio [OR] 10.3, 95% CI 2.4-43.9; p = 0.002). Two risk factors were independently associated with PPHN: severe prematurity (OR 3.3, 95% CI 1.0-11.4) and recipient status (OR 3.9, 95% CI 1.4-11.0). In TTTS recipients, another risk factor for PPHN is anaemia at birth (OR 7.2, 95% CI 1.8-29.6). CONCLUSION: Clinicians caring for neonates with TTTS should be aware of the 10-fold increased risk of PPHN compared to uncomplicated monochorionic twins. PPHN occurs more often in case of premature delivery and in recipient twins, particularly in the presence of anaemia at birth. As the development of severe PPHN is difficult to predict, we advise that all TTTS twins should be delivered in a tertiary care centre with iNO treatment options.

The effect of breathing on ductus arteriosus blood flow directly after birth.

Spontaneous breathing at birth influences ductus arteriosus (DA) flow. This study quantifies the effect of breathing on DA shunting directly after birth. In healthy term infants born by elective cesarean section, simultaneous measurements of DA shunting and tidal volumes during spontaneous breathing were performed at 2-5, 5-8, and 10-13 min after birth. Eight infants with a mean (SD) gestational age of 40 (1) weeks and 3216 (616) grams were studied. Inspiratory tidal volume was 5.8 (3.3-7.7), 5.7 (4.0-7.1), and 5.2 (4.3-6.1) mL/kg at 2-5, 5-8, and 10-13 min. The velocity time integral of left-to-right shunting significantly increased during inspiration when compared to expiration (8.4 (5.2) vs. 3.7 (2.3) cm, 8.9 (4.4) vs. 5.6 (3.4) cm, and 14.0 (6.7) vs. 8.4 (6.9) cm; all p < 0.0001) at 2-5, 5-8, and 10-13 min, respectively. In contrast, right-to-left shunting was not different between inspiration and expiration at 2-5 and 10-13 min (11.1 (2.4) vs. 11.1 (2.6) cm and 10.7 (2.3) vs. 10.6 (3.0) cm; p > 0.05), but there was a small increase at 5-8 min (12.1 (2.4) vs. 10.8 (2.9) cm; p = 0.001) during expiration. CONCLUSION: Directly after birth, ductal shunting is influenced by breathing effort, predominantly with an increase in left-to-right shunt due to inspiration. What is Known: • Spontaneous breathing at birth influences ductus arteriosus flow and pulmonary blood flow. • Crying causes a significant increase in left-to-right ductus arteriosus shunting. What is New: • Left-to-right ductus arteriosus shunting increases during inspiration compared to expiration. • Breathing is important for ductal shunting and contributes to pulmonary blood flow.

Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion.

BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days' gestation to induce a left-sided DH. Kittens were delivered at 30 days' gestation, intubated, and ventilated to achieve a tidal volume (Vt) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.

Caffeine to improve breathing effort of preterm infants at birth: a randomized controlled trial.

BackgroundCaffeine promotes spontaneous breathing by antagonizing adenosine. We assessed the direct effect of caffeine on respiratory effort in preterm infants at birth.MethodsThirty infants of 24-30 weeks of gestation were randomized for receiving caffeine directly after birth in the delivery room (caffeine DR group) or later in the neonatal intensive care unit (control group). Primary outcome was respiratory effort, expressed as minute volume, tidal volumes, respiratory rate, rate of rise to maximum tidal volume, and recruitment breaths at 7-9 min after birth.ResultsAfter correction for gestational age, minute volumes ((mean±SD; 189±74 vs. 162±70 ml/kg/min; P<0.05) and tidal volumes ((median (interquartile range (IQR)) 5.2 (3.9-6.4) vs. 4.4 (3.0-5.6) ml/kg) were significantly greater in the caffeine DR group. Although respiratory rates were similar ((mean±SD) 35±10 vs. 33±10), RoR increased significantly ((median (IQR) 14.3 (11.2-19.8) vs. 11.2 (7.9-15.2) ml/kg/s), and more recruitment breaths were observed (13 vs. 9%).ConclusionCaffeine increases respiratory effort in preterm infants at birth, but the effect on clinical outcomes needs further investigation.

Sustained Lung Inflation: Physiology and Practice.

Lung aeration is the most critical task newborns must accomplish after birth. Almost all extremely preterm infants require respiratory support during this process, but the best method to promote lung aeration in preterm infants is unknown. The current standard practice is intermittent positive pressure ventilation with positive end-expiratory pressure. Sustained inflation is a promising alternative strategy for lung liquid clearance and aeration. Here we review the physiologic rationale for sustained inflation and the available clinical evidence for sustained inflation in preterm infants.