Effectiveness of Alberta Family Integrated Care on infant length of stay in level II neonatal intensive care units: a cluster randomized controlled trial.

BACKGROUND: Parents of infants in neonatal intensive care units (NICUs) are often unintentionally marginalized in pursuit of optimal clinical care. Family Integrated Care (FICare) was developed to support families as part of their infants' care team in level III NICUs. We adapted the model for level II NICUs in Alberta, Canada, and evaluated whether the new Alberta FICare™ model decreased hospital length of stay (LOS) in preterm infants without concomitant increases in readmissions and emergency department visits. METHODS: In this pragmatic cluster randomized controlled trial conducted between December 15, 2015 and July 28, 2018, 10 level II NICUs were randomized to provide Alberta FICare™ (n = 5) or standard care (n = 5). Alberta FICare™ is a psychoeducational intervention with 3 components: Relational Communication, Parent Education, and Parent Support. We enrolled mothers and their singleton or twin infants born between 32 0/7 and 34 6/7 weeks gestation. The primary outcome was infant hospital LOS. We used a linear regression model to conduct weighted site-level analysis comparing adjusted mean LOS between groups, accounting for site geographic area (urban/regional) and infant risk factors. Secondary outcomes included proportions of infants with readmissions and emergency department visits to 2 months corrected age, type of feeding at discharge, and maternal psychosocial distress and parenting self-efficacy at discharge. RESULTS: We enrolled 654 mothers and 765 infants (543 singletons/111 twin cases). Intention to treat analysis included 353 infants/308 mothers in the Alberta FICare™ group and 365 infants/306 mothers in the standard care group. The unadjusted difference between groups in infant hospital LOS (1.96 days) was not statistically significant. Accounting for site geographic area and infant risk factors, infant hospital LOS was 2.55 days shorter (95% CI, - 4.44 to - 0.66) in the Alberta FICare™ group than standard care group, P = .02. Secondary outcomes were not significantly different between groups. CONCLUSIONS: Alberta FICare™ is effective in reducing preterm infant LOS in level II NICUs, without concomitant increases in readmissions or emergency department visits. A small number of sites in a single jurisdiction and select group infants limit generalizability of findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02879799 , retrospectively registered August 26, 2016.

Family Integrated Care (FICare): Positive impact on behavioural outcomes at 18 months.

BACKGROUND: Children born very preterm demonstrate behavioural challenges due to clinical factors, exposure to the high stress environment of intensive care, and separation from parents during neonatal hospitalization at a critical stage in development. Family Integrated Care (FICare) significantly reduced parent stress and anxiety, and improved neonatal outcomes. AIMS: To examine the impact of FICare on behavioural outcomes at 18-21 months corrected age (CA), and assess possible mediation through parenting or infant growth. STUDY DESIGN AND METHODS: A prospective cohort study enrolling infants under 33 weeks gestation and parents from the FICare cluster randomized controlled trial. Primary outcome was behaviour assessed by the Infant Toddler Social Emotional Assessment (ITSEA). Parent child variables were measured with the Nursing Child Assessment Satellite Training (NCAST), Parenting Stress Index (PSI) and infant growth. RESULTS: Subjects included 123 FICare infants and 62 standard care controls evaluated at 18-21 months CA. FICare infants demonstrated lower ITSEA Dysregulation, indicating better self-regulation skills, compared with the control group (T-score 41.7 vs 46.6, p < 0.01). At 12 months CA, the NCAST Child subtotal score was higher and the PSI-Child Domain score was lower in FICare infants than non-FICare infants. The PSI-Child domain was identified as a possible mediator of FICare on child behaviour (mediation effect 1.28, -2.96-0.02, p = 0.044). CONCLUSION: FICare in the NICU has a sustained effect on child behaviour, improving self-regulation at 18-21 months CA.

Umbilical venous catheter insertion depth estimation using birth weight versus surface measurement formula: a randomized controlled trial.

OBJECTIVE: To determine if umbilical venous catheter (UVC) insertion depth estimated by surface measurement (SM) results in optimal catheter tip position on ultrasound as compared with formula using birth weight (BW). METHODS: In this randomized controlled trial, eligible infants were randomized to UVC insertion depth estimated by SM or BW method. We compared proportion of optimum UVC position on ultrasound read by neonatologist masked with group assignment. RESULTS: UVC was inserted to estimated depth in 164 of 200 enroled infants. There was no difference in the proportion of correctly positioned UVCs between the groups (SM 33/82 (40.2%) vs BW 27/82 (32.9%), p = 0.33). Among BW < 1000 g, SM method had higher correctly positioned UVC (43.7% vs 22.5%, p = 0.07). CONCLUSION: There was no difference in the rate of optimally positioned UVC tip between the two methods for estimating UVC insertion depth. However, SM method results in more optimal positioning of UVC tip among BW < 1000 g infants.

Association of Deferred vs Immediate Cord Clamping With Severe Neurological Injury and Survival in Extremely Low-Gestational-Age Neonates.

Importance: Deferred cord clamping (DCC) is recommended for term and preterm neonates to reduce neonatal complications. Information on the association of DCC with outcomes for extremely low-gestational-age neonates is limited. Objective: To compare neonatal outcomes after DCC and immediate cord clamping (ICC) in extremely low-gestational-age neonates. Design, Setting, and Participants: In this retrospective cohort study, eligible neonates born between January 1, 2011, and December 31, 2015, were divided into 2 groups: DCC and ICC. Neonates were recruited from tertiary neonatal intensive care units participating in the Canadian Neonatal Network, and analysis began in January 2018. Neonates were eligible if they were born at 22 to 28 weeks' gestational age and admitted to a participating Canadian Neonatal Network neonatal intensive care unit during the study period. Neonates who were born outside a tertiary-level neonatal intensive care unit, were moribund at birth, needed palliative care before delivery, had major congenital anomalies, or lacked cord clamping information were excluded. Main Outcomes and Measures: Composite of severe neurological injury (intraventricular hemorrhage grade ≥3 with or without persistent periventricular echogenicity) or mortality before discharge. Results: Of 8221 admitted neonates, 4680 were included in the study, of whom 1852 (39.6%) received DCC and 2828 (60.4%) received ICC. There were 974 (52.7%) male neonates in the DCC group and 1540 (54.5%) male neonates in the ICC group. Median (interquartile range) gestational age was 27 (25-28) weeks for the DCC group and 26 (25-27) weeks for the ICC group. Median (interquartile range) birth weight was 930 (760-1120) g and 870 (700-1060) g for DCC and ICC groups, respectively. Neonates who received DCC had significantly reduced odds of the composite outcome of severe neurological injury or mortality (adjusted odds ratio [AOR], 0.80; 95% CI, 0.67-0.96), mortality (AOR, 0.74; 95% CI, 0.59-0.93), and severe neurological injury (AOR, 0.80; 95% CI, 0.64-0.99). The odds of bronchopulmonary dysplasia (AOR, 1.00; 95% CI, 0.84-1.19), retinopathy of prematurity stage 3 or higher (AOR, 0.94; 95% CI, 0.71-1.25), necrotizing enterocolitis stage 2 or higher (AOR, 0.86; 95% CI, 0.66-1.12), late-onset sepsis (AOR, 1.02; 95% CI, 0.85-1.22), and receipt of 2 or more blood transfusions (AOR, 0.93; 95% CI, 0.79-1.10) did not differ between the groups. Propensity score-matched analyses revealed lower odds of mortality (AOR, 0.79; 95% CI, 0.65-0.95), late-onset sepsis (AOR, 0.81; 95% CI, 0.69-0.95), and treatment for hypotension (AOR, 0.75; 95% CI, 0.60-0.95) in the DCC group. Conclusions and Relevance: In this study of extremely low-gestational-age neonates who received DCC or ICC, DCC was associated with reduced risk for the composite outcome of severe neurological injury or mortality.

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.

Risk factors and outcomes of early pulmonary hypertension in preterm infants.

PURPOSE: Data on early pulmonary arterial hypertension (PAH) in preterm infants is limited and outcomes are conflicting. Our objectives are to examine the risk factors and neonatal outcomes of early onset PAH (EOPAH) diagnosed in the first 2 weeks of age in preterm infants in a large perinatal center. METHODS: We performed a case-control study to assess the risk factors and clinical outcomes of preterm infants with EOPAH. Preterm infants (<34 weeks) admitted to NICU between 2009 and 2013 with a diagnosis of PAH in the first 2 weeks of age were matched to two consecutive controls for gestational age, birth weight, and year of birth. We performed univariate and multivariate analyses. RESULTS: Of 1798 eligible infants, 60 (3.3%) had EOPAH with 57/60 (95%) diagnosed in the first 7 d of age. Infants with early PAH had higher incidence of prolonged rupture of membrane (47% versus 29%), oligohydramnios (37% versus 16%) and received less antenatal steroids (78% versus 91%). Fifty-one infants received inhaled nitric oxide (iNO) and all responded well. The overall mortality rate was not significantly different between two groups (13.3% versus 8%). After adjusting for potential confounding variables, early PAH is associated with bronchopulmonary dysplasia (BPD) (aOR 3.06, 95% CI 1.43, 6.54) and BPD/death (aOR 2.65, 95% CI 1.25, 5.64) and severe intraventricular hemorrhage (aOR 3.08, 95% CI 1.28, 7.39). CONCLUSION: Early onset pulmonary arterial hypertension in preterm is not uncommon and is associated with bronchopulmonary dysplasia and severe intraventricular hemorrhage. Inhaled nitric oxide was used to treat in majority of cases with good response and survival is high.

Neonatal Pneumopericardium in a Nonventilated Term Infant: A Case Report and Review of the Literature.

Neonatal pneumopericardium (PPC) is a rare form of neonatal air leak syndrome with high morbidity and mortality. Air leak syndrome in the newborn is usually associated with active resuscitation, respiratory distress syndrome, meconium aspiration syndrome, mechanical ventilation, or trauma associated with labour. Neonatal PPC can be associated with other air leak syndromes such as pneumomediastinum, pneumothorax, pneumoperitoneum, and subcutaneous and interstitial emphysema. Spontaneous PPC is a rare event in the neonatal period. We report a case of PPC in association with pneumothorax in a nonventilated term infant. The infant responded to thoracocentesis without the need for pericardiocentesis.

Does High Protein Intake During First Week of Life Improve Growth and Neurodevelopmental Outcome at 18 months Corrected Age in Extremely Preterm Infants?

OBJECTIVE: To examine whether high protein intake during the first week of life alters the growth and neurodevelopmental outcomes at 18 mo corrected age (CA) in preterm infants born < 29 wk. METHODS: This was a retrospective cohort study of preterm infants (<29 wk) before and after introduction of nutritional policy targeting higher protein intake during the first week of life. The authors compared the growth and neurodevelopmental outcomes at 18 mo CA between infants born before (epoch 1) and after (epoch 2) the introduction of nutrition policy. RESULTS: Of 171 eligible infants who completed follow-up at 18 mo CA, 87 (51 %) were in post intervention group (epoch 2). The mean (± SD) gestational age (26.3 ± 1.49 wk vs. 26.2 ± 1.48 wk) and birth weight (947 ± 220 g vs. 924 ± 225 g) were similar between the two groups. At 18 mo CA, there were no significant differences in the growth and neurodevelopmental impairment rates between the two groups. Logistic regression analysis revealed that high protein intake (>3.5 g/kg/d) was not associated with improved neurodevelopmental outcome (OR 1.49, 95 % CI 0.52-4.26). CONCLUSIONS: High protein intake during the first week of age was not associated with better growth or neurodevelopmental outcome at 18 mo CA in preterm infants.

Utility of Targeted Neonatal Echocardiography in the Management of Neonatal Illness.

OBJECTIVES: To describe the impact of targeted neonatal echocardiography on management of neonatal illness in a tertiary perinatal center neonatal intensive care unit (NICU). METHODS: We conducted a retrospective analysis of consecutive targeted neonatal echocardiographic studies that were performed over an 18-month period in a regional perinatal center NICU in Canada. All studies were performed with a cardiovascular ultrasound machine and transducer and read on a workstation with storage and analysis software. Reporting was done on a standardized document, and any management change resulting from targeted neonatal echocardiography was documented. RESULTS: A total of 303 consecutive targeted neonatal echocardiographic studies were performed on 129 neonates. The mean gestational age ± SD was 27.8 ± 4.3 weeks (range, 23-41 weeks), and the mean birth weight ± SD was 1196 ± 197 g (range, 490- 4500 g). The median number of studies per neonate was 2 (range, 1-8), with most repeated studies for a patent ductus arteriosus (PDA). The most common indication for echocardiography was assessment of a PDA (52.1%), followed by early global hemodynamic assessment of very low birth weight (16.2%) and pulmonary hypertension (12.2%). Of the 303 studies, 126 (41.5%) resulted in management changes. The contribution to management was significantly related to the timing of echocardiography. Around half of the echocardiographic examinations during first the week of life resulted in management changes, compared to 22% of studies after 1 week of age (P = .002). Patent ductus arteriosus management accounted for almost half of the interventions. CONCLUSIONS: Targeted neonatal echocardiography is a valuable tool in the NICU and can contribute substantially to hemodynamic management in the first week of life, PDA management in the first 2 weeks of life, and cases of hypotension or shock at any time during the hospital stay.

Azithromycin and other macrolides for prevention of bronchopulmonary dysplasia: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Ureaplasma spp. infection has been associated with bronchopulmonary dysplasia (BPD) in preterm infants. Macrolides have been used for the treatment of Ureaplasma spp. infection, with an intention to prevent BPD. The objective of this meta-analysis is to evaluate the use of macrolides in the prevention of BPD in preterm infants. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, abstracts of the major pediatric society meetings and bibliographies of retrieved articles. We included randomized controlled trials assessing the effects of macrolides therapy on BPD in preterm infants. A random/fixed-effect model was used to synthesize predefined outcomes. RESULTS: Six studies involving 469 preterm infants were eligible for the analysis. Macrolides when used prophylactically (4 studies) did not show significant reduction in BPD (risk ratio, RR, 0.88, 95% confidence interval, CI, 0.75-1.03), death (RR 0.89, 95% CI 0.79-1.01) or in the composite outcome of BPD/death. Similarly, there was no significant reduction in BPD (RR 0.64, 95% CI 0.31-1.31) or the composite outcome of BPD/death (RR 0.41, 95% CI 0.05-3.13), when macrolides were used in Ureaplasma-positive infants. However, prophylactic azithromycin therapy (3 studies) was associated with significant reduction in BPD (RR 0.83, 95% CI 0.71-0.97; number needed to treat, NNT, 10) and composite outcome of BPD/death (RR 0.86, 95% CI 0.77-0.97; NNT 10). CONCLUSION: This meta-analysis demonstrates prophylactic azithromycin therapy was associated with statistically significant reduction in BPD and the composite outcome of BPD/death in preterm infants. However, given the limited information on pharmacokinetics and potential harmful effects, further studies should be done before routine use of azithromycin in the neonatal population.

Neonatal outcomes following extensive cardiopulmonary resuscitation in the delivery room for infants born at less than 33 weeks gestational age.

AIM: To examine the neonatal mortality and morbidity of infants born at <33 weeks gestational age (GA) who received extensive delivery room cardiopulmonary resuscitation (DR-CPR) immediately after birth. DESIGN/METHODS: In this retrospective cohort study, we performed secondary analyses of data from infants born at <33 weeks GA and admitted to participating NICUs in the Canadian Neonatal Network between January 2010 and December 2011. Infants were divided into two groups based on birth weight (<1000 g and ≥1000 g) and neonatal morbidity and mortality compared using bivariate and multivariate analyses. RESULTS: Of the 8033 eligible infants, 419 (5.2%) received DR-CPR. For infants weighing <1000 g at birth, 10.9% (outborn: 21.6%, inborn: 7.6%) received DR-CPR, whereas 3.4% (outborn: 9.6%, inborn: 2.2%) of those weighing ≥1000 g received DR-CPR. If infants received DR-CPR there was increased risk of mortality, bronchopulmonary dysplasia (BPD) and severe brain injury. Logistic regression analysis showed DR-CPR was associated with increased mortality (adjusted odds ratio [aOR]: 2.09, 95% CI [1.39, 3.14]) in infants born weighing <1000 g. Among infants born weighing ≥1000 g, DR-CPR was associated with increased mortality (aOR: 7.16, 95% CI [3.88, 13.2]), severe brain injury (aOR: 3.08, 95% CI [1.82, 5.22]), BPD (aOR: 2.14, 95% CI [1.25, 3.65]), pneumothorax (aOR: 3.11, 95% CI [1.53, 6.31]) and intestinal perforation (aOR: 3.47, 95% CI [1.46, 8.24]). CONCLUSIONS: DR-CPR is associated with increased risk of mortality and morbidity especially in preterm infants born weighing ≥1000 g. Long-term neurodevelopmental follow up is warranted for these infants.

Citrobacter freundii brain abscess in a preterm infant: a case report and literature review.

Intracranial abscesses are serious conditions but uncommon in preterm neonates. Citrobacter species are an uncommon cause of bacterial meningitis in neonates, but are associated with brain abscesses in a majority of cases. We report a preterm infant who developed Citrobacter freundii meningitis with brain abscess, who was successfully treated with antibiotics and surgical drainage. The infant had normal neurological outcome at follow-up. We report this case to highlight the importance of serial neuroimaging in the diagnosis of cerebral abscess in infants with Citrobacter meningitis.

Effectiveness and safety of indomethacin versus ibuprofen for the treatment of patent ductus arteriosus in preterm infants.

OBJECTIVE: To compare the incidence of medical closure of patent ductus arteriosus (PDA) and adverse events (acute renal dysfunction, necrotizing enterocolitis, spontaneous intestinal perforation, and gastrointestinal bleeding) between preterm infants who received indomethacin and ibuprofen for the treatment of PDA. STUDY DESIGN: A retrospective comparative effectiveness evaluation study was conducted on preterm infants (≤32 weeks) who received indomethacin or ibuprofen for treatment of symptomatic PDA. RESULTS: Of the 124 eligible infants, 54 received indomethacin and 70 received ibuprofen. The overall incidence of medical PDA closure with indomethacin was 37/54 (68.5%) as compared with 42/70 (60%) in the ibuprofen group (p = 0.32). The proportion of infants with surgical PDA ligation was similar between the two groups (18.5% in both the groups). There was no difference in the incidences of acute renal dysfunction, necrotizing enterocolitis stage ≥ 2, spontaneous intestinal perforation, and gastrointestinal bleeding between indomethacin and ibuprofen groups. CONCLUSION: Ibuprofen is as effective as indomethacin in the treatment of symptomatic PDA in preterm infants. This study also shows that both agents have similar adverse effects and the choice of one agent over the other should be based on local availability and dosing preference.

Incidence and timing of presentation of necrotizing enterocolitis in preterm infants.

OBJECTIVES: To examine the variation in the incidence and to identify the timing of the presentation of necrotizing enterocolitis (NEC) in a cohort of preterm infants within the Canadian Neonatal Network (CNN). METHODS: This was a population-based cohort of 16 669 infants with gestational age (GA) <33 weeks, admitted to 25 NICUs participating in the CNN between January 1, 2003, and December 31(,) 2008. Variations in NEC incidence among the participating NICUs for the study period were examined. We categorized early-onset NEC as occurring at <14 days of age and late-onset NEC occurring at ≥14 days. Multivariate logistic regression analysis was performed to identify risk factors for early-onset NEC. RESULTS: The overall incidence of NEC was 5.1%, with significant variation in the risk adjusted incidence among the participating NICUs in the CNN. Early-onset NEC occurred at a mean of 7 days compared with 32 days for late-onset NEC. Early-onset NEC infants had lower incidence of respiratory distress syndrome, patent ductus treated with indomethacin, less use of postnatal steroids, and shorter duration of ventilation days. Multivariate logistic regression analysis identified that greater GA and vaginal delivery were associated with increased risk of early-onset NEC. CONCLUSIONS: Among infants <33 weeks' gestation, NEC appears to present at mean age of 7 days in more mature infants, whereas onset of NEC is delayed to 32 days of age in smaller, lower GA infants. Further studies are required to understand the etiology of this disease process.

Neonatal withdrawal syndrome due to maternal codeine use.

Neonatal withdrawal from maternal drugs and medications is not uncommon. Codeine-containing analgesic preparations given to pregnant mothers for headache have been identified as a cause of neonatal withdrawal syndrome. The present case highlights the importance of obtaining a detailed maternal drug history including prescription and nonprescription drugs, and highlights the need for prenatal counselling for women who are taking narcotic-containing analgesics.

Il n'est pas rare de sevrer un nouveau-né des drogues et médicaments qu'a consommés la mère. Il est établi que les préparations analgésiques qui contiennent de la codéine et qui sont données aux femmes enceintes pour soulager les maux de tête représentent une cause de syndrome de sevrage néonatal. Le présent cas fait ressortir l'importance d'obtenir les antécédents détaillés de la mère quant à ses médicaments, qu'ils soient sur ordonnance ou en vente libre, ainsi que la nécessité de donner des conseils prénatals aux femmes qui prennent des analgésiques contenant des narcotiques.

Perinatal lethal Gaucher disease.

Perinatal Lethal Gaucher Disease (PLGD) is a rare form of Gaucher disease and is often considered a distinct form of type 2 Gaucher disease. The authors report on an infant who presented with progressive hepatosplenomegaly, ichthyosis, generalized skin edema and neonatal encephalopathy and died at 6 h of age. Autopsy revealed massive hepatosplenomegaly, ichthyosis, a diffuse collodion picture and histological evidence of infiltration by Gaucher cells in the liver, spleen, lung, thymus, lymph node and bone marrow. Genetic testing of the parents revealed both to be carriers of Gaucher disease.