Thiopurine Exposure During Pregnancy is Not Associated With Anemia in Infants Born to Mothers With IBD.

Background: Thiopurines are commonly used to treat inflammatory bowel disease (IBD). Thiopurines are considered safe throughout pregnancy. However, a published study suggested the risk of neonatal anemia was increased if exposed to thiopurines in utero. This prospective cohort study aimed to determine if there is an increased risk of cytopenia among infants born to pregnant people with IBD, exposed or unexposed to thiopurines, compared to infants born to those without IBD. Methods: Pregnant IBD patients, with and without thiopurine exposure, and one cohort of control individuals were recruited over a 5-year period. Consenting individuals completed a questionnaire and infants had a complete blood cell count at the newborn heel prick. Anemia was defined as hemoglobin (Hb) < 140g/L. Descriptive statistics were used to characterize the study population. Fisher exact tests were used to examine differences in outcomes between groups, a P-value of < 0.05 was deemed significant. Results: Three cohorts were recruited: 19 IBD patients on thiopurines, 50 IBD patients not on thiopurines, and 37 controls (total of 106). Neonatal median Hb was not different with 177g/L (IQR 38g/L) for the IBD thiopurine group, 180.5g/L (IQR 40g/L) for the IBD non-thiopurine group, and 181g/L (IQR 37g/L) for the controls. Nineteen infants (18%) were cytopenic with 12 (11%) anemic, 6 (5.6%) thrombocytopenic, and 1 (0.94%) lymphopenic. Thiopurine exposure was only in one, mildly anemic, infant. Conclusions: These findings further support physicians and IBD patients contemplating pregnancy that current guidelines recommending thiopurine adherence do not lead to increased perinatal risk of anemia or cytopenia.

Advanced neonatal procedural skills: a simulation-based workshop: impact and skill decay.

BACKGROUND: Trainees aiming to specialize in Neonatal Perinatal Medicine (NPM), must be competent in a wide range of procedural skills as per the Royal College of Canada. While common neonatal procedures are frequent in daily clinical practice with opportunity to acquire competence, there are substantial gaps in the acquisition of advanced neonatal procedural skills. With the advent of competency by design into NPM training, simulation offers a unique opportunity to acquire, practice and teach potentially life-saving procedural skills. Little is known on the effect of simulation training on different areas of competence, and on skill decay. METHODS: We designed a unique simulation-based 4-h workshop covering 6 advanced procedures chosen because of their rarity yet life-saving effect: chest tube insertion, defibrillation, exchange transfusion, intra-osseus (IO) access, ultrasound-guided paracentesis and pericardiocentesis. Direct observation of procedural skills (DOPS), self-perceived competence, comfort level and cognitive knowledge were measured before (1), directly after (2), for the same participants after 9-12 months (skill decay, 3), and directly after a second workshop (4) in a group of NPM and senior general pediatric volunteers. RESULTS: The DOPS for all six procedures combined for 23 participants increased from 3.83 to 4.59. Steepest DOPS increase pre versus post first workshop were seen for Defibrillation and chest tube insertion. Skill decay was evident for all procedures with largest decrease for Exchange Transfusion, followed by Pericardiocentesis, Defibrillation and Chest Tube. Self-perceived competence, comfort and cognitive knowledge increased for all six procedures over the four time points. Exchange Transfusion stood out without DOPS increase, largest skill decay and minimal impact on self-assessed competence and comfort. All skills were judged as better by the preceptor, compared to self-assessments. CONCLUSIONS: The simulation-based intervention advanced procedural skills day increased preceptor-assessed directly observed procedural skills for all skills examined, except exchange transfusion. Skill decay affected these skills after 9-12 months. Chest tube insertions and Defibrillations may benefit from reminder sessions, Pericardiocentesis may suffice by teaching once. Trainees' observed skills were better than their own assessment. The effect of a booster session was less than the first intervention, but the final scores were higher than pre-intervention. TRIAL REGISTRATION: Not applicable, not a health care intervention.

Cord-Blood Derived Chemistry Reference Values in Preterm Infants for Sodium, Chloride, Potassium, Glucose, and Creatinine.

OBJECTIVES: International guidelines recommend that preterm infants should be supported to maintain their serum electrolytes within "normal" ranges. In term babies, cord blood values differed in pathological pregnancies from healthy ones. STUDY DESIGN: We examined cord blood sodium, chloride, potassium, glucose, and creatinine to derive maturity-related reference intervals. We examined associations with gestational age, delivery mode, singleton versus multiple, and prenatal maternal adverse conditions. We compared preterm cord values to term, and to adult reference ranges. RESULTS: There were 591 infants, 537 preterm and 54 term. Preterm cord glucose levels were steady (3.7 ± 1.1 mmol/L), while sodium, chloride, and creatinine increased over GA by 0.17, 0.14 mmol/L/week, and 1.07 µmol/L/week, respectively (p < 0.003). Average preterm cord potassium and chloride were higher than the term (p < 0.05). Compared with adult reference intervals, cord preterm reference intervals were higher for chloride (100-111 vs. 98-106 mmol/L), lower for creatinine (29-84 vs. 62-115 µmol/L), and more variable for potassium (2.7-7.9 vs. 3.5-5.0 mmol/L) and sodium (130-141 vs. 136-145 mmol/L). Cesarean section was associated with higher potassium and lower glucose, multiple births with higher chloride and creatinine and lower glucose, and SGA with lower glucose. CONCLUSIONS: Cord blood values varied across the GA range with increases in sodium, chloride, and creatinine, while glucose remained steady. Average preterm reference values were higher than term values for potassium and chloride. Preterm reference values differed from published adults' reference values. The changes across GA and by delivery mode, SGA, and being a multiple, which may have direct implications for neonatal care and fluid management. KEY POINTS: · Cord blood electrolyte, creatinine, and glucose values vary across neonatal gestational age.. · Average preterm cord values of potassium and chloride were higher than term values.. · Cord reference values differ by delivery mode, growth, and multiple impacting neonatal care decisions..

Antimicrobial Stewardship at Birth in Preterm Infants: Not Just About a Decrease!

BACKGROUND: Early-onset sepsis results in increased morbidity and mortality in preterm infants. Antimicrobial Stewardship Programs (ASPs) address the need to balance adverse effects of antibiotic exposure with the need for empiric treatment for infants at the highest risk for early-onset sepsis. METHODS: All preterm infants <34 weeks gestational age born during a 6-month period before (January 2017-June 2017) and a 6-month period after (January 2019-June 2019) implementation of ASP in May 2018 were reviewed. The presence of perinatal sepsis risk factors, eligibility for, versus treatment with initial empiric antibiotics was compared. RESULTS: Our cohort comprised 479 infants with a mean of 30 weeks gestation and birth weight of 1400 g. Demographics were comparable, with more Cesarean section deliveries in the post-ASP cohort. Any sepsis risk factor was present in 73.6% versus 68.4% in the pre- versus post-ASP cohorts (P = 0.23). Fewer infants were treated with antibiotics in the later cohort (60.4%) compared with the earlier cohort (69.7%; P = 0.04). Despite the presence of risk factors (preterm labor in 93% and rupture of membranes in 60%), 42% of infants did not receive initial antibiotics. Twenty percent with no perinatal sepsis risk factors were deemed low-risk and not treated. CONCLUSIONS: Implementation of a neonatal ASP decreased antibiotic initiation at birth. Antibiotic use decreased (appropriately) in the subgroup with no perinatal sepsis risk factors. Of concern, some infants were not treated despite risk factors, such as preterm labor/rupture of membrane. Neonatal ASP teams need to be aware of potentially unintended consequences of their initiatives.

Use of Inhaled Nitric Oxide in Preterm Infants: Is There Sufficient Evidence?

Nitric oxide (NO) is a potent vasodilator. The inhaled form (iNO) improves outcomes in term infants with persistent pulmonary hypertension of the newborn (PPHN) or bronchopulmonary dysplasia-associated pulmonary hypertension in preterm infants. However, in preterm infants, the risks and benefits of iNO use are controversial. Substantial evidence reveals no significant impact on survival or other morbidities in preterm infants with iNO treatment, independent of indication, timing, or duration of use. Many scientific organizations do not recommend the use of iNO in preterm infants, except in unique clinical circumstances with echocardiographic findings of PPHN in the setting of presumed pulmonary hypoplasia.

Fluid handling and blood flow patterns in neonatal respiratory distress syndrome versus transient tachypnea: a pilot study.

BACKGROUND: Cardiovascular and renal adaptation in neonates with Respiratory Distress Syndrome (RDS) and Transient Tachypnea of the Newborn (TTN) may be different. METHODS: Neonates ≥32 weeks were diagnosed with RDS or TTN based on clinical, radiologic and lung sonographic criteria. Weight loss, feeding, urine output, and sodium levels were recorded for the first 3 days, and serial ultrasounds assessed central and organ Doppler blood flow. A linear mixed model was used to compare the two groups. RESULTS: Twenty-one neonates were included, 11 with TTN and 10 with RDS. Those with RDS showed less weight loss (- 2.8 +/- 2.7% versus - 5.6 +/- 3.4%), and less enteral feeds (79.2 vs 116 ml/kg/day) than those with TTN, despite similar fluid prescription. We found no difference in urine output, or serum sodium levels. Doppler parameters for any renal or central parameters were similar. However, Anterior Cerebral Artery maximum velocity was lower (p = 0.03), Superior Mesenteric Artery Resistance Index was higher in RDS, compared to TTN (p = 0.02). CONCLUSION: In cohort of moderately preterm to term neonates, those with RDS retained more fluid and were fed less on day 3 than those with TTN. While there were no renal or central blood flow differences, there were some cerebral and mesenteric perfusion differences which may account for different pathophysiology and management.

Simulation-Based Structured Education Supports Focused Neonatal Cranial Ultrasound Training.

OBJECTIVES: Brain injury in preterm neonates may cause clinical deterioration and requires timeous bedside diagnosis. Teaching cranial ultrasound (US) skills using fragile preterm neonates is challenging. The purpose of this study was to test the effectiveness and feasibility of using task-trainer computer-based simulators and US-suitable cranial phantoms in combination with teaching sessions in teaching novices to perform focused cranial US evaluations for identifying substantial intraventricular hemorrhage. METHODS: This was a prospective interventional educational study targeting participants with no prior skills in neonatal cranial US. Participants attended a 2-day training workshop, with didactic and hands-on interactive sessions using computer-based and 3-dimensional printed phantom simulators. Participants then performed a cranial US scan on a healthy neonate to assess the diagnostic quality of the images acquired. Individual precourse and postcourse knowledge tests were compared. To test recall, participants also submitted US images acquired on neonates within 3 and 6 months of attending the course. RESULTS: Forty-five participants completed the training modules. Mean knowledge scores increased significantly (in brain anatomy, brain physiology, intracranial disorders, and US physics domains). Thirty-eight cranial US scans were acquired during the course, 22 within 3 months after completion, and 34 within 6 months after completion. Thirty-two (84%) of the initial 38 case images, 17 (77%) of 22 images submitted within 3 months, and 32 (94%) of 34 images submitted within 6 months after course completion were of diagnostic quality. CONCLUSIONS: A structured training module with didactic and hand-on training sessions using simulators and phantoms is feasible and supports training of clinicians to perform focused cranial US examinations.

Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants.

Introduction: Extremely premature infants are susceptible to fluctuations in cerebral blood flow due to immaturity of cerebral autoregulation. Inotropes may cause rapid changes to systemic blood pressure and consequently cerebral blood flow, especially within the first 72 hours of life. This period is recognized to carry the greatest risk for cerebral hemorrhage. This study evaluates the incidence of death and/or severe brain injury in extremely preterm infants treated with inotropes in the first 72 hours of life.Methods: Prospective cohort study of infants born ≤29+0 weeks gestational age (GA) between January 2013 and December 2016. Severe brain injury was defined based on head ultrasound as presence of: grade III or IV intraventricular hemorrhage (IVH), moderate to severe post-hemorrhagic ventricular dilatation (PHVD), or cystic periventricular leukomalacia (cPVL). The association between inotrope use and death and/or brain injury was explored via logistic regression controlling for predefined confounding risk factors.Results: Of 497 eligible infants, 97 (19.5%) received inotropes during the first 72 hours. GA at birth, birth weight (BW), and 5-minute Apgar scores were lower among infants who received early inotropes compared to those not treated with inotropes. A stepwise logistic regression of the predefined confounding factors showed GA, exposure for antenatal steroids, and admission hypothermia to be significant confounding factors. Adjusting for those factors, early use of inotropes was associated with increased risk of death and/or severe brain injury (AOR 4.5; 95%CI: 2.4-8.5), severe brain injury (AOR 4.2; 95% CI: 1.9-8.9), and IVH of any grade (AOR 2.9; 95%CI: 1.7-4.9).Conclusion: Early inotropes use was associated with higher risk of death and/or severe brain injury. Strict indications and strategies for minimizing inotrope use while preventing hypotension should be implemented in the early postnatal care of infants at risk for severe brain injury.

Intraventricular Hemorrhage: Risk Factors and Association With Patent Ductus Arteriosus Treatment in Extremely Preterm Neonates.

Objectives: To assess maternal and neonatal risk factors for intraventricular hemorrhage (IVH). To examine the association of patent ductus arteriosus (PDA) and its treatment, with IVH and its severity. Study design: In this retrospective cohort study, we included preterm neonates born at <29 weeks, admitted to a tertiary level III Neonatal Intensive Care Unit in Calgary, Canada, between 2013 and 2016, who had a head ultrasound in the first 7 days of life. A subset analysis included neonates who also had cardiac ultrasound in the first 3 days of life. Results: Of the 495 neonates, 121 (24.4%) had IVH of any grade and 48 (9.7%) had severe IVH. Identified risk factors were small birth gestation and weight, lack of antenatal corticosteroids, maternal chorioamnionitis, Apgar score <5 at 5 min, umbilical cord pH < 7, respiratory distress syndrome, early onset sepsis, hypercapnia, pCO2 fluctuations, prolonged intubation, inhaled nitric oxide, inotropes or normal saline boluses, metabolic derangements, opioids infusions, and bicarbonate/THAM therapy. In a primary analysis of the total cohort, when the decision to treat a PDA was used as a surrogate marker of its clinical significance, a PDA requiring treatment was associated with a higher risk of IVH. There was no significant difference in the incidence of IVH between neonates with early treatment of a clinically significant PDA compared to late, however early indomethacin treatment was associated with reduced severity of IVH. In the subset analysis, the presence of a hemodynamically significant PDA (hs-PDA) was not associated with a higher probability of IVH. Of those with severe IVH, 18 (55%) had a hs-PDA; this is clinically but not statistically significant. Conclusions: Identified risk factors should be the target of IVH reduction bundles. Early indomethacin treatment for a clinically significant PDA may reduce IVH severity.

Neonatal Transport Clinician Performed Ultrasound Evaluation of Cardiac Function.

BACKGROUND: Limited point-of-care ultrasound skills for ultrasound-naïve neonatal transport clinicians could enhance clinical evaluation and decision making. Teaching Respiratory Therapists and Nurses to assess cardiac filling and contractility may be feasible. METHODS: Prospective educational study using educational materials, didactic theoretical, and hands-on practical sessions, followed by assessment of practical and theoretical skills. RESULTS: A total of 18 participants completed the study meeting the predefined standard, proving feasibility. Nine (50%) participants had ≤ 10 years of NICU experience. The mean time required for complete training was 8.6 ±â€¯2.1 hours. Time was spent on average on 269 ±â€¯104 minutes for hands-on practice, 171 ±â€¯96 minutes on didactic training, and 76 ±â€¯16 minutes on testing sessions. The median number of hands-on sessions per participant was 5 [Interquartile range (IQR) 5, 7]. The median number of infants required to complete training was 9 infants (IQR 7, 11). RRTs required less time than RNs. Evaluations and feedback from participants on the training program was positive. CONCLUSION: Neonatal RNs and RTs can be trained to perform focused cardiac ultrasound examinations with average time of 8.6 hours. This skill could enhance clinical care on neonatal transport with appropriate interventions to manage suspected hypotension or shock.

Arterial flow patterns in healthy transitioning near-term neonates.

OBJECTIVE: Significant haemodynamic changes occur at delivery impacting organ blood flow distribution. We aimed to characterise Doppler indices patterns over time in three different organs (brain, gut and kidney) and test them as measures of vascular resistance. DESIGN: Observational cohort study. Serial Doppler interrogations of the anterior cerebral, superior mesenteric and renal arteries within 2 hours, 2-6, and 24 hours of life, in combination with central haemodynamic data. PATIENTS: Healthy, near-term (>36 weeks of gestation) neonates. OUTCOME MEASURES: Pulsatility (PI) and Resistance Indices (RI) patterns and organ-specific conductances, detailed echocardiographic haemodynamic measures. RESULTS: Twenty-one babies were studied. Doppler morphology and adaptation patterns were distinctly different between the organs (brain, gut and kidney) supporting autonomous vascular regulatory effects. The PI differentiated especially between kidney and other organ flow consistently over time. PI and RI for all three organs decreased. The variance in organ conductance did not explain the variance in 1/PI, indicating that PI is not a measure of resistance. Superior mesenteric artery had the highest velocity with 72 cm/s. Non-invasively acquired pilot serial values in a normal population are given. Patent ductus arteriosus flow remained open at discharge for 36%. CONCLUSIONS: Haemodynamic transitioning patterns assessed by serial Dopplers in healthy near-term neonates differ in brain, gut and kidney: Doppler waveform morphology differs, and PI differentiates renal Doppler morphology, compared with the other organs. While PI and RI decline for all organs, they do not measure resistance. Brain artery velocity increases, mesenteric perfusion is variable and renal Vmax decreases.

Does Postmenstrual Age Affect Medical Patent Ductus Arteriosus Treatment Success in Preterm Infants?

OBJECTIVE: Patent ductus arteriosus (PDA) is the most common cardiovascular problem of prematurity. Our objective was to examine the effect of postmenstrual age (PMA) on response to medical PDA treatment. STUDY DESIGN: This retrospective cohort study included infants ≤ 32 weeks' gestational age (GA) who received nonsteroidal anti-inflammatory drugs (NSAIDs) for PDA treatment. Response was positive if echocardiogram showed closed or small PDA or no further treatment was required. Baseline characteristics between responders and nonresponders were compared. Multivariable logistic regression analysis with generalized estimating equations was used to analyze the association between PMA and response. RESULTS: A total of 183 infants with a mean GA of 26.4 ± 2.2 weeks and birth weight of 870 ± 313 g received 257 courses of NSAIDs. Positive response rate to the first course was 65.6%. Two and three courses were given in 62 and 12 infants, with response rates of 48.4 and 50%, respectively. Surgical ligation of PDA occurred in 30 (16.4%) infants. Multivariable logistic regression analysis with generalized estimating equations revealed that PMA was not associated with a positive response (adjusted odds ratio [aOR]: 0.88; 95% confidence interval [CI]: 0.71-1.10). GA at birth remained the most influential factor (aOR: 1.33; 95% CI: 1.02-1.73). CONCLUSION: GA rather than PMA is the strongest predictor for a positive response in medical PDA treatment.

Prospective study of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the prevalence, risk factors, and optimal timing of echocardiogram for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD). DESIGN: In this prospective study, infants with gestational age (GA) <30 weeks admitted to a tertiary NICU between July 2015 and June 2017 who required positive pressure ventilation or oxygen therapy at ≥28 days of life were evaluated with serial echocardiograms at study enrollment (4-6 weeks of age), 32 weeks (only for ≤25 weeks), 36, and 40 weeks post-menstrual age (PMA) for PH. RESULTS: Of 126 infants (mean birth weight 858 ± 221 g; mean GA 26.1 ± 1.6 wks), 48 (38%) developed PH at any time during their hospital stay. The first study echocardiogram was performed at a median age of 31 weeks PMA. The prevalence of PH was 36/126 (28.5%) at enrollment, at 6/30 (20%) at 32 weeks, 24/111 (21.6%) at 36 weeks, and 10/59 (17%) at 40 weeks. No new cases of PH were identified at 40 weeks. At 36 weeks, none of the infants with mild BPD had PH, whereas 20% of moderate and 32% of severe BPD infants had PH. After controlling for confounding variables severe BPD (OR 3.31, 95%CI 1.12, 9.74), and ventilator associated pneumonia (VAP) (OR 17.9, 95%CI 3.9, 82.11) remained independent risk factors for BPD-associated PH. CONCLUSION: Echocardiographic screening for PH can be safely restricted to infants with moderate or severe BPD at 36 weeks PMA. We identified VAP as an independent risk factor for PH.