Maternal-fetal-neonatal microbiome and outcomes associated with prematurity.

Our understanding of the premature gut microbiome has increased rapidly in recent years. However, to advance this important topic we must further explore various aspects of the maternal microbiome, neonatal microbiota, and the opportunities for microbiome modulation. We invite authors to contribute research and clinical papers to the Collection "Maternal-fetal-neonatal microbiome and outcomes associated with prematurity".

Blood culture collection practices in NICU; A national survey.

Background: Sepsis is the leading cause of mortality and morbidity in neonates. Blood cultures are the gold standard in diagnosing neonatal sepsis; however, there are currently no consensus guidelines for blood culture collection in neonates and significant practice variation exists in Neonatal Intensive Care Units (NICUs) globally. Objective: To examine current practices in obtaining blood cultures in the evaluation of neonatal sepsis in NICUs across Canada. Methods: A nine-item electronic survey was sent to each of the 29 level-3 NICUs in Canada, which are equipped to provide highly specialized care for newborns. Results: Responses were received from 90% (26/29) of sites. Sixty-five percent (17/26) of sites have blood culture collection guidelines for the investigation of neonatal sepsis. Forty-eight percent (12/25) of sites routinely target 1.0 mL per culture bottle. In late-onset sepsis (LOS), 58% (15/26) of sites process one aerobic culture bottle, whereas four sites routinely add anaerobic culture bottles. In early-onset sepsis (EOS) in very low birth weight infants (BW <1.5 kg), 73% (19/26) of sites use umbilical cord blood, and 72% (18/25) use peripheral venipuncture. Two sites routinely collect cord blood for culture in EOS. Only one site applies the concept of differential time-to-positivity to diagnose central-line-associated bloodstream infection. Conclusions: There is significant practice variation in methods used to obtain blood cultures in level-3 NICUs across Canada. Standardization of blood culture collection practices can provide reliable estimates of the true incidence of neonatal sepsis and help to develop appropriate antimicrobial stewardship strategies.

Impact of Perinatal Exposure to SARS-CoV-2 Infection on Early Health Outcomes among Infants Born from 2020 to 2021 in British Columbia, Canada.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has impacted healthcare services and outcomes. We aimed to investigate healthcare resource utilization and early health outcomes of infants born to mothers with perinatal SARS-CoV-2 infection. Methods: The study included all infants born alive between February 1, 2020, and April 30, 2021, in British Columbia. We used linked provincial population-based databases including data on COVID-19 testing, birth, and health information for up to one year from birth. Perinatal COVID-19 exposure for infants was defined being born to mothers with a positive test for SARS-CoV-2 infection during pregnancy or at delivery. Cases of COVID-19-exposed infants were matched with up to four non-exposed infants by birth month, sex, birthplace, and gestational age in weeks. Outcomes included hospitalizations, emergency department visits, and in-/outpatient diagnoses. Outcomes were compared between groups using conditional logistic regression and linear mixed effects models including effect modification by maternal residence. Results: Among 52,711 live births, 484 infants had perinatal exposure to SARS-CoV-2, an incidence rate of 9.18 per 1000 live births. Exposed infants (54.6% male) had a mean gestational age of 38.5 weeks, and 99% were born in hospital. Proportions of infants requiring at least one hospitalization (8.1% vs. 5.1%) and at least one emergency department visit (16.9% vs. 12.9%) were higher among the exposed vs. unexposed infants, respectively. Among infants from the urban area, those with exposure were more likely to have respiratory infectious diseases (odds ratio: 1.74; 95% confidence intervals: 1.07, 2.84), compared with those without exposure. Interpretation. In our cohort, infants born to mothers with SARS-CoV-2 infection have increased healthcare demands in their early infancy, which warrants further investigation.

Maternal and neonatal trauma following operative vaginal delivery.

BACKGROUND: Operative vaginal delivery (OVD) is considered safe if carried out by trained personnel. However, opportunities for training in OVD have declined and, given these shifts in practice, the safety of OVD is unknown. We estimated incidence rates of trauma following OVD in Canada, and quantified variation in trauma rates by instrument, region, level of obstetric care and institutional OVD volume. METHODS: We conducted a cohort study of all singleton, term deliveries in Canada between April 2013 and March 2019, excluding Quebec. Our main outcome measures were maternal trauma (e.g., obstetric anal sphincter injury, high vaginal lacerations) and neonatal trauma (e.g., subgaleal hemorrhage, brachial plexus injury). We calculated adjusted and stabilized rates of trauma using mixed-effects logistic regression. RESULTS: Of 1 326 191 deliveries, 38 500 (2.9%) were attempted forceps deliveries and 110 987 (8.4%) were attempted vacuum deliveries. The maternal trauma rate following forceps delivery was 25.3% (95% confidence interval [CI] 24.8%-25.7%) and the neonatal trauma rate was 9.6 (95% CI 8.6-10.6) per 1000 live births. Maternal and neonatal trauma rates following vacuum delivery were 13.2% (95% CI 13.0%-13.4%) and 9.6 (95% CI 9.0-10.2) per 1000 live births, respectively. Maternal trauma rates remained higher with forceps than with vacuum after adjustment for confounders (adjusted rate ratio 1.70, 95% CI 1.65-1.75) and varied by region, but not by level of obstetric care. INTERPRETATION: In Canada, rates of trauma following OVD are higher than previously reported, irrespective of region, level of obstetric care and volume of OVD among hospitals. These results support a reassessment of OVD safety in Canada.

Antenatal corticosteroid administration and attention-deficit/hyperactivity disorder in childhood: a regression discontinuity study.

BACKGROUND: Antenatal corticosteroids reduce respiratory morbidity in preterm infants, but their use during late preterm gestation (34-36 weeks) is limited because their safety for longer-term child neurodevelopment is unclear. We sought to determine if fetuses with higher probability of exposure to antenatal corticosteroids had increased rates of prescriptions for attention-deficit/hyperactivity disorder (ADHD) medication in childhood, using a quasiexperimental design that better controls for confounding than existing observational studies. METHODS: We identified 16 358 children whose birthing parents were admitted for delivery between 31 + 0 (31 weeks, 0 days) and 36 + 6 weeks' gestation in 2000-2013, using a perinatal data registry from British Columbia, Canada, and linked their records with population-based child ADHD medication data (2000-2018). We used a regression discontinuity design to capitalize on the fact that pregnancies presenting for delivery immediately before and immediately after the clinical cut-off for antenatal corticosteroid administration of 34 + 0 weeks' gestation have very different levels of exposure to corticosteroids, but are otherwise similar with respect to confounders. RESULTS: Over a median follow-up period of 9 years, 892 (5.5%) children had 1 or more dispensations of ADHD medication. Children whose birthing parents were admitted for delivery just before the corticosteroid clinical cut-off of 34 + 0 weeks' gestation did not appear to be more likely to be prescribed ADHD medication than those admitted just after the cut-off (rate ratio 1.1, 95% confidence interval [CI] 0.8 to 1.6; 1.3 excess cases per 100 children, 95% CI -2.5 to 5.7). INTERPRETATION: We found little evidence that children with higher probability of exposure to antenatal corticosteroids have higher rates of ADHD prescriptions in childhood, supporting the safety of antenatal corticosteroids for this neurodevelopmental outcome.

Factors Associated with Umbilical Venous Catheter Malposition in Newborns: A Tertiary Center Experience.

OBJECTIVE: Umbilical venous catheters (UVC) are widely used in neonatal intensive care (NICU). Noncentral catheter position is known to be associated with multiple adverse complications; however, risk factors for catheter malposition are unclear. This work aimed to identify clinical risk factors and complications associated with UVC malposition in neonates admitted in an NICU. STUDY DESIGN: A retrospective chart review was performed of inborn babies admitted to BC Women's Hospital NICU with UVC inserted in their first 7 days between July 2016 and June 2018. Infant and maternal demographic, radiograph, UVC-related data, and complications were reviewed. RESULTS: A total of 257 infants had UVC placed; 158 (61%) and 99 (39%) were in central and noncentral positions after initial placement, respectively. Of initially central-placed UVCs, a further 35 (22%) were pulled back or migrated to malposition on follow-up X-ray. Multivariable logistic regression analysis revealed the use of larger UV (5 Fr) catheter (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.1-5.6, p = 0.026) and escalation of respiratory support mode (OR: 1.7, 95% CI: 1.0-2.8, p = 0.049) as significant predictors of catheter malposition. CONCLUSION: Noncentral UVC position as well as migration were common after initial placement in this cohort. The use of larger size UV catheters and increasingly invasive respiratory support were risk factors associated with higher incidence of UVC malposition. Ongoing surveillance of UVC position is thus recommended. KEY POINTS: · More than one-third of UV catheters were not in central position after the initial placement.. · Large size UV catheters and increasingly invasive respiratory support were risk factors for UV malposition.. · High incidence of UVC migration was found after initial central placement, warranting surveillance..

Quantifying Proximal Collecting Tubule Deficiency in Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Fetopathy.

INTRODUCTION: Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers (AAs) are used for several indications, with cessation recommended in pregnancy due to toxic effects. AA fetopathy phenotype is similar to renal tubular dysgenesis including reduced proximal convoluted tubules (PCTs). Our study aimed to quantify the reduction of PCTs in fetuses and infants with prenatal exposure to AAs. MATERIALS AND METHODS: We identified 5 fetal AA exposure cases that underwent autopsy at our institution between 2011 and 2018 and compared with 5 gestational age-matched controls. Immunohistochemistry with CD10 and epithelial membrane antigen (EMA) was utilized. RESULTS: CD10 and EMA identified a median PCT density of 19.0% ± 12.3% in AA fetopathy patients, significantly less than controls (52.8% ± 4.4%; p < 0.0001). One case with in utero cessation had a PCT density of 34.2% ± 0.2%. Among other AA fetopathy findings, 1 case demonstrated unilateral renal vein thrombosis and 4 had hypocalvaria. CONCLUSIONS: We have quantified the reduction in AA fetopathy PCT density, and demonstrated in utero cessation may recover PCT differentiation. Future studies may benefit from calculating PCT percentage as a potential biomarker to correlate with post-natal renal function and maternal factors including medication type, dosage, duration, and time from medication cessation.

A national survey of the enteral feeding practices in Canadian neonatal intensive care units.

AIM: Nutrition affects the growth and neurodevelopmental outcomes of preterm infants, yet controversies exist about the optimal enteral feeding regime. The objective of this study was to compare enteral feeding guidelines in Canadian neonatal intensive care units (NICUs). METHOD: The research team identified key enteral feeding practices of interest. Canadian Neonatal Network site investigators at 30 Level 3 NICUs were contacted to obtain a copy of their 2016 to 2017 feeding guidelines for infants who weighed less than 1,500 g at birth. Each guideline was reviewed to compare recommendations around the selected feeding practices. RESULTS: Five of the 30 NICUs did not have a feeding guideline. The other 25 NICUs used 22 different enteral feeding guidelines. The guidelines in 40% of those NICUs recommend commencing minimal enteral nutrition (MEN) within 24 hours of birth and maintaining that same feeding volume for 24 to 96 hours. In 40% of NICUs, the guideline recommended that MEN be initiated at a volume of 5 to 10 mL/kg/day for infants born at <1,000 g. Guidelines in all 25 NICUs recommend the use of bovine-based human milk fortifier (HMF), and in 56% of NICUs, it is recommended that HMF be initiated at a total fluid intake of 100 mL/kg/day. Guidelines in only 16% of NICUs recommended routine gastric residual checks. Donor milk and probiotics are used in 76% and 72% of the 25 NICUs, respectively. CONCLUSION: This study revealed substantial variability in recommended feeding practices for very low birth weight infants, underscoring the need to establish a national feeding guideline for this vulnerable group.

Use of sildenafil in an infant with persistent pulmonary hypertension secondary to lung and renal hypoplasia - a case report.

BACKGROUND: Premature preterm rupture of membranes (PPROM) is reported to be associated with high rates of neonatal mortality and morbidity. Sildenafil has been used in infants with persistent pulmonary hypertension of newborn (PPHN) due to congenital diaphragmatic hernia (CDH) and bronchopulmonary dysplasia (BPD). Recently, Sildenafil has been evaluated as an alternative or adjunctive pulmonary vasodilator. This case report illustrates the use of early sildenafil for PPHN and right ventricular dysfunction in an unusual setting of lung and renal hypoplasia. CASE PRESENTATION: A male infant was born at 37 weeks with a birth weight of 2840 g. Rupture of membranes developed at approximately 24 weeks of gestational age (GA). Bilateral small kidneys (< 2 standard deviations below average) were detected on ultrasound (US) examination at 30 weeks of gestation. The baby developed pneumothorax and pulmonary hypertensive crisis towards the end of the first day. An echocardiogram showed a dilated right ventricle, moderate right ventricular systolic dysfunction, hypoplastic pulmonary arteries and a large patent ductus arteriosus with bidirectional flow. The patient was sedated, paralyzed, and inhaled nitric oxide was administered to decrease the pulmonary resistance. In anticipation of persistent pulmonary hypertension due to the hypoplastic lungs and small calibre of pulmonary arteries, sildenafil was started on day of life (DOL) 5 at a dosage of 0.25 mg/kg/dose Q8H and gradually increased to 2 mg/kg/dose Q8H on DOL 9. The patient was finally extubated on DOL 7 and weaned off of non-invasive respiratory support on DOL 26. Sildenafil was gradually weaned beginning on DOL 21 and discontinued on DOL 48. Repeat echocardiogram assessment at 3 months showed complete resolution of PHT and right ventricular dilatation. CONCLUSIONS: We describe the early use of sildenafil in treating pulmonary hypertension associated with lung and renal hypoplasia in a non-CDH patient. Following this treatment the patient made a full recovery from right ventricular dysfunction.

Antenatal glucocorticoids, magnesium sulfate, and mode of birth in preterm fetal small for gestational age.

A diagnosis of fetal growth restriction and subsequent preterm birth is associated with increased risks of adverse perinatal and neurodevelopmental outcomes and potentially long-lasting effects to adulthood. Most such cases are associated with placental insufficiency and the fetal response to chronic intrauterine hypoxemia and nutrient deprivation leads to substantial physiological and metabolic adaptations. The management of such pregnancies, especially with respect to perinatal interventions and birth mode, remains an unresolved dilemma. The benefits from standard interventions for threatened preterm birth may not be necessarily translated to pregnancies with small-for-gestational-age fetuses. Clinical trials or retrospective studies on outcomes following administration of antenatal glucocorticoids and magnesium sulfate for neuroprotection when preterm birth is imminent either have yielded conflicting results for small-for-gestational-age fetuses, or did not include this subgroup of patients. Experimental models highlight potential harmful effects of administration of antenatal glucocorticoids and magnesium sulfate in the pregnancies with fetal small for gestational age although clinical data do not substantiate these concerns. In addition, heterogeneity in definitions of fetal small for gestational age, variations in the inclusion criteria, and the glucocorticoid regime contribute to inconsistent results. In this review, we discuss the physiologic adaptions of the small-for-gestational-age fetus to its abnormal in utero environment in relation to antenatal glucocorticoids; the impact of antenatal glucocorticoids and intrapartum magnesium sulfate in pregnancies with fetal small for gestational age; the current literature on birth mode for pregnancies with fetal small for gestational age; and the knowledge gaps in the existing literature.

Intrapartum magnesium sulfate is associated with neuroprotection in growth-restricted fetuses.

BACKGROUND: Intrapartum magnesium sulfate administration is recommended for fetal neuroprotection in women with imminent very preterm birth. However, previous studies have not included or separately analyzed the outcomes of pregnancies with fetal growth restriction that were treated with intrapartum magnesium sulfate. OBJECTIVE: We sought to evaluate the neonatal and neurodevelopmental outcomes of growth-restricted fetuses born <29 weeks' gestation and exposed to maternal intrapartum magnesium sulfate. STUDY DESIGN: We conducted a retrospective cohort study of infants born <29 weeks' gestation from 2010 through 2011, admitted to participating Canadian Neonatal Network units, and followed by the Canadian Neonatal Follow-up Network centers. Growth restriction was defined either as estimated fetal or actual neonatal birthweight <10th percentile according to fetal or neonatal growth standards for gestational age and sex, respectively. Infants exposed to intrapartum magnesium sulfate were compared with unexposed infants. The primary outcome was composite of death or significant neurodevelopmental impairment at 18-36 months' corrected age. Secondary outcomes were death or any neurodevelopmental impairment at 18-36 months' corrected age. Neonatal morbidities were also compared. RESULTS: Of the 336 growth-restricted fetuses, 112 (33%) received magnesium sulfate and of the 177 growth-restricted infants, 61 (34%) received magnesium sulfate. Administration of magnesium sulfate was at the discretion of the treating physician. Intrapartum magnesium sulfate was associated with reduced odds of composite of death or significant neurodevelopmental impairment for infants classified according to both fetal standards (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.80) and neonatal standards (adjusted odds ratio, 0.44; 95% confidence interval, 0.20-0.98). CONCLUSION: Intrapartum administration of magnesium sulfate to women with growth-restricted fetuses born <29 weeks' gestation was associated with reduced odds of composite of death or significant neurodevelopmental impairment.

Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming.

OBJECTIVE: This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). METHODS: Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4-5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified. RESULTS: Twenty neonates at median gestation and birth weight of 40 weeks (interquartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106-159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48-42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours. CONCLUSION: Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation.

Association of Antibiotic Utilization and Neurodevelopmental Outcomes among Extremely Low Gestational Age Neonates without Proven Sepsis or Necrotizing Enterocolitis.

OBJECTIVE: The objective is to evaluate the association between antibiotic utilization and neurodevelopmental outcomes at 18 to 21 months' corrected age among extremely low gestational age neonates without culture-proven sepsis or necrotizing enterocolitis (NEC). STUDY DESIGN: We conducted a retrospective cohort study of infants born between April 2009 and September 2011 at <29 weeks' gestation and admitted to the neonatal intensive care units contributing data to the Canadian Neonatal Network. Multivariable analysis was performed to examine the primary composite outcome of death or significant neurodevelopmental impairment (sNDI) in infants with various antibiotic utilization rates (AURs). RESULT: There were 1,373 infants who fulfilled our inclusion criteria. Compared with infants in the lowest AUR quartile (Q1), those in the highest quartile (Q4) had higher odds of death or sNDI (adjusted odds ratio [AOR] = 7.44; 95% confidence interval [CI]: 4.55, 12.2) and death (AOR = 39.3; 95% CI: 16.1, 95.9). CONCLUSION: Our results indicate an association between high AUR and a composite outcome of death or adverse neurodevelopmental outcomes at 18 to 21 months' corrected age.

A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge.

OBJECTIVES: To test the hypothesis that a patent ductus arteriosus (PDA) severity score (PDAsc) incorporating markers of pulmonary overcirculation and left ventricular (LV) diastolic function can predict chronic lung disease or death before discharge (CLD/death). STUDY DESIGN: A multicenter prospective observational study was conducted for infants <29 weeks gestation. An echocardiogram was carried out on day 2 to measure PDA diameter and maximum flow velocity, LV output, diastolic flow in the descending aorta and celiac trunk, and variables of LV function using tissue Doppler imaging. Predictors of CLD/death were identified using logistic regression methods. A PDAsc was created and a receiver operating characteristic curve was constructed to assess its ability to predict CLD/death. RESULTS: We studied 141 infants at a mean (SD) gestation and birthweight of 26 (1.4) weeks and 952 (235) g, respectively. Five variables were identified that were independently associated with CLD/death (gestation at birth, PDA diameter, maximum flow velocity, LV output, and LV a' wave). The PDAsc had a range from 0 (low risk) to 13 (high risk). Infants who developed CLD/death had a higher score than those who did not (7.3 [1.8] vs 3.8 [2.0], P < .001). PDAsc had an area under the curve of 0.92 (95% CI 0.86-0.97, P < .001) for the ability to predict CLD/death. A PDAsc cut-off of 5 has sensitivity and specificity of 92% and 87%, and positive and negative predictive values of 92% and 82%, respectively. CONCLUSIONS: A PDAsc on day 2 can predict the later occurrence of CLD/death further highlighting the association between PDA significance and morbidity.

Should we "eliminate" PDA shunt in preterm infants? A narrative review.

The patent ductus arteriosus frequently poses a significant morbidity in preterm infants, subjecting their immature pulmonary vascular bed to substantial volume overload. This, in turn, results in concurrent hypoperfusion to post-ductal organs, and subsequently alters cerebral blood flow. In addition, treatment has not demonstrated definitive improvements in patient outcomes. Currently, the optimal approach remains a subject of considerable debate with ongoing research controversy regarding the best approach. This article provides a comprehensive review of existing literature.

Hemodynamic management of congenital diaphragmatic hernia: the role of targeted neonatal echocardiography.

Congenital diaphragmatic hernia (CDH) is a major congenital anomaly, resulting from the herniation of abdominal contents into the thoracic cavity, thereby impeding the proper development of the lungs and pulmonary vasculature. CDH severity correlates with a spectrum of pulmonary hypoplasia, pulmonary hypertension (PHT), and cardiac dysfunction, constituting the pathophysiological triad of this complex condition. The accurate diagnosis and effective management of PHT and cardiac dysfunction is pivotal to optimizing patient outcomes. Targeted neonatal echocardiography is instrumental in delivering real-time data crucial for the bespoke, pathophysiology-targeted hemodynamic management of CDH-associated PHT.

The impact of a care bundle with an emphasis on hemodynamic assessment on the short-term outcomes in neonates with congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the short-term outcomes of implementing a care bundle emphasizing frequent hemodynamic assessments by echocardiography in neonates with congenital diaphragmatic hernia (CDH). STUDY DESIGN: This was a retrospective cohort study of infants with CDH admitted to a quaternary perinatal unit from January 2013 to March 2021. The primary composite outcome was defined as mortality or use of extracorporeal membrane oxygenation or need for respiratory support at discharge. RESULTS: We identified 37 and 20 CDH infants in Epoch I and II, respectively. More patch repairs (50% vs. 21.9%, p = 0.035) and echocardiograms (6[4-8] vs. 1[0-5], p = 0.003) were performed in Epoch II. While there were no differences in the primary outcome, there was a reduction in mortality in Epoch II (0% vs. 27%, p = 0.01). CONCLUSION: With the implementation of a CDH care bundle with an emphasis on hemodynamic assessment, we demonstrated a significant reduction in mortality.

Long-Term Neurodevelopmental Impairment among Very Preterm Infants with Sepsis, Meningitis, and Intraventricular Hemorrhage.

INTRODUCTION: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. METHODS: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. RESULTS: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. CONCLUSION: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.

Neonatal abstinence syndrome and infant mortality and morbidity: a population-based study.

Background: Infant health among newborns with neonatal abstinence syndrome (NAS) has been understudied. We examined infant mortality and hospitalizations among infants diagnosed with NAS after birth. Methods: All live births in British Columbia (BC), Canada, for fiscal years from 2004-2005 to 2019-2020, were included (N = 696,900). NAS was identified based on International Classification of Diseases, version 10, Canadian modification (ICD-10-CA) codes; the outcomes included infant death and hospitalizations during the first year of life, ascertained from BC linked administrative data. Generalized estimating equation models were used to adjust for maternal factors. Results: There were 2,439 infants with NAS (3.50 per 1,000 live births). Unadjusted for other factors, infant mortality was 2.5-fold higher in infants with vs. without NAS (7.79 vs. 3.08 per 1,000 live births, respectively) due to increased post-discharge mortality NAS (5.76 vs. 1.34 per 1,000 surviving infants, respectively). These differences diminished after adjustment: adjusted odds ratio (AOR) for infant death was 0.85 [95% confidence interval (CI): 0.52-1.39]; AOR for post-discharge death was 1.75 (95% CI 1.00-3.06). Overall, 22.3% infants with NAS had at least one hospitalization after post-neonatal discharge, this proportion was 10.7% in those without NAS. During the study period, discharge to foster care declined from 49.5% to 20.3% in infants with NAS. Conclusion: Unadjusted for other factors, infants with NAS had increased post-discharge infant mortality and hospitalizations during the first year of life. This association diminished after adjustment for adverse maternal and socio-medical conditions. Infants with NAS had a disproportionately higher rate of placement in foster care after birth, although this proportion declined dramatically between 2004/2005 and 2019/2020. These results highlight the importance of implementing integrated care services to support infants born with NAS and their mothers during the first year of life and beyond, even though NAS itself is not independently associated with increased infant mortality.

Universal access to ambulance does not increase overall demand for ambulance services in Queensland, Australia.

OBJECTIVE: To determine the impact of the introduction of universal access to ambulance services via the implementation of the Community Ambulance Cover (CAC) program in Queensland in 2003-04. METHOD: The study involved a 10-year (2000-01 to 2009-10) retrospective analysis of routinely collected data reported by the Queensland Ambulance Service (QAS) and by the Council of Ambulance Authorities. The data were analysed for the impact of policy changes that resulted in universal access to ambulance services in Queensland. RESULTS: QAS is a statewide, publically funded ambulance service. In Queensland, ambulance utilisation rate (AUR) per 1000 persons grew by 41% over the decade or 3.9% per annum (10-year mean=149.8, 95% CI: 137.3-162.3). The AUR mean after CAC was significantly higher for urgent incidents than for non-urgent ones. However projection modelling demonstrates that URs after the introduction of CAC were significantly lower than the projected utilisation for the same period. CONCLUSIONS: The introduction of universal access under the Community Ambulance Cover program in Queensland has not had any significant independent long-term impact on demand overall. There has been a reduction in the long-term growth rate, which may have been contributed to by an 'appropriate use' public awareness program.