Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Postnatal Steroids Use for Bronchopulmonary Dysplasia in a Quaternary Care NICU.

OBJECTIVE: Intercenter variation and trends in postnatal steroids (PNS) use among preterm infants for prevention or treatment of bronchopulmonary dysplasia (BPD) is known. Understanding intracenter PNS use patterns facilitate implementation of center-specific change interventions to optimize outcomes.This study aimed to (i) quantify the proportion of infants who received PNS, and describe the timing, type, trends over time, regimen used, and deviations, and (2) describe the clinical characteristics and unadjusted outcomes of infants who received PNS. STUDY DESIGN: This was a cohort study in a quaternary neonatal intensive care unit including infants born at less than 33 weeks, and who received PNS for prevention or treatment of BPD between 2011 and 2021. Following data were included: proportion of babies who received PNS; type of PNS; age at initiation and duration; trends over time; deviation from published regimen; morbidity, mortality, and cointerventions. RESULTS: One hundred and eighty four infants (8% of <33 week' infants) received PNS. The median (interquartile range [IQR]) gestational age and birth weight were 25 (24-26) weeks and 720 (625-841) grams, respectively. The median (IQR) day of initiation and duration of PNS use were 29 (19-38) and 10 (10-22) days, respectively. One hundred and fifty-seven (85%) infants received dexamethasone (DX) and 22 (12%) received hydrocortisone as the first PNS course, and 71 (39%) infants received multiple courses. The proportion of infants receiving PNS remained unchanged, but the cumulative median dose received for BPD per patient increased by 56%. Nearly one-third of cumulative PNS dose came from PNS used for non-BPD indications. Forty-six percent infants had a deviation from published regimen (±20% deviation in duration or ±10% deviation in dose). Survival, survival without major morbidity, moderate-to-severe BPD, and technology dependence at discharge were 87, 2, 91, and 67%, respectively. CONCLUSION: Increased variation in PNS use, deviation from published regimen, and concurrent PNS exposure from non-BPD indication offer insights into implementing interventions to improve processes. KEY POINTS: · In this quaternary NICU, 8% of infants born before 33 weeks were administered postnatal steroids (PNS).. · The percentage of infants given PNS remained stable; however, the cumulative dose per patient for BPD rose.. · The study identified targeted interventions to minimize clinical practice variations at the center..

Potential Neurologic Manifestations of COVID-19 Infection in Neonates.

In contrast to adults, neonates and infants with coronavirus disease 2019 (COVID-19) infection have milder symptoms and are less likely to require hospitalization. However, some neonates with COVID-19 can present with significant symptoms. Recent evidence suggests that neurologic manifestations of neonatal COVID-19 infection may be higher than initially thought. In this comprehensive review of the current literature, we summarize the clinical, laboratory, and radiologic findings, as well as potential management strategies for COVID-19-related neurologic illness in neonates. Although the growing brain may be affected by neurologic disease associated with COVID-19 infection, the few published studies on the long-term outcomes after COVID-19 infection in neonates and infants provide conflicting results. Larger collaborative clinical studies are needed to determine whether COVID-19 infection in neonates has long-term neurodevelopmental outcomes.

Neurodevelopmental outcomes of preterm neonates receiving rescue inhaled nitric oxide in the first week of age: a cohort study.

OBJECTIVE: To assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF). METHODS: In this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18-24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO. RESULTS: Of the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18-24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12). CONCLUSIONS: In preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18-24 months CA.

Neurodevelopmental Outcomes of Preterm Infants Born <29 Weeks with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: A Multicenter Study.

OBJECTIVE: This study aimed to determine neurodevelopmental outcomes of preterm infants born at <29 weeks' gestational age (GA) with bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) at 18 to 24 months' corrected age (CA). STUDY DESIGN: In this retrospective cohort study, preterm infants born at <29 weeks' GA between January 2016 and December 2019, admitted to level 3 neonatal intensive care units, who developed BPD and were evaluated at 18 to 24 months' CA in the neonatal follow-up clinics were included. We compared demographic characteristics and neurodevelopmental outcomes between the two groups: Group I: BPD with PH and Group II: BPD with no PH, using univariate and multivariate regression models. The primary outcome was a composite of death or neurodevelopmental impairment (NDI). NDI was defined as any Bayley-III score < 85 on one or more of the cognitive, motor, or language composite scores. RESULTS: Of 366 eligible infants, 116 (Group I [BPD-PH] =7, Group II [BPD with no PH] = 109) were lost to follow-up. Of the remaining 250 infants, 51 in Group I and 199 in Group II were followed at 18 to 24 months' CA. Group I and Group II had median (interquartile range [IQR]) birthweights of 705 (325) and 815 g (317; p = 0.003) and median GAs (IQR) were 25 (2) and 26 weeks (2; p = 0.015) respectively. Infants in the BPD-PH group (Group I) were more likely to have mortality or NDI (adjusted odds ratio: 3.82; bootstrap 95% confidence interval; 1.44-40.87). CONCLUSION: BPD-PH in infants born at <29 weeks' GA is associated with increased odds of the composite outcome of death or NDI at 18 to 24 months' CA. KEY POINTS: · Long-term neurodevelopmental follow-up of preterm infants born <29 weeks' GA.. · Association of neurodevelopmental outcomes with BPD-associated PH.. · Need for longitudinal follow-up of children with BPD-associated PH..

Congenital SARS-CoV-2 Infection in Two Neonates with Confirmation by Viral Culture of the Placenta in One Case.

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.

Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial: a protocol for a multicentre, stepped-wedge cluster randomized trial.

BACKGROUND: Evidence-based Practice for Improving Quality (EPIQ) is a collaborative quality improvement method adopted by the Canadian Neonatal Network that led to decreased mortality and morbidity in very preterm neonates. The Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial aims to evaluate the impact of EPIQ collaborative quality improvement strategies in moderate and late preterm neonates in Alberta, Canada. METHODS: In a 4-year, multicentre, stepped-wedge cluster randomized trial involving 12 neonatal intensive care units (NICUs), we will collect baseline data with the current practices in the first year (all NICUs in the control arm). Four NICUs will transition to the intervention arm at the end of each year, with 1 year of follow-up after the last group transitions to the intervention arm. Neonates born at 32 + 0 to 36 + 6 weeks' gestation with primary admission to NICUs or postpartum units will be included. The intervention includes implementation of respiratory and nutritional care bundles using EPIQ strategies, including quality improvement team building, quality improvement education, bundle implementation, quality improvement mentoring and collaborative networking. The primary outcome is length of hospital stay; secondary outcomes include health care costs and short-term clinical outcomes. Neonatal intensive care unit staff will complete a survey in the first year to assess quality improvement culture in each unit, and a sample will be interviewed 1 year after implementation in each unit to evaluate the implementation process. INTERPRETATION: The ABC-QI Trial will assess whether collaborative quality improvement strategies affect length of stay in moderate and late preterm neonates. It will provide detailed population-based data to support future research, benchmarking and quality improvement. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT05231200.

Nutritional Management of Short Bowel Syndrome.

Short bowel syndrome (SBS) of infancy is a cause of prolonged morbidity with intolerance to enteral feeding, specialized nutritional needs, and partial/total dependence on parenteral nutrition. These infants can benefit from individualized nutritional strategies to support and enhance the process of intestinal adaptation. Early introduction of enteral feeds during the period of intestinal adaptation is crucial, even though the enteral feedings may need to be supplemented with an effective, safe, and nutritionally adequate parenteral nutritional regimen. Newer generation intravenous lipid emulsions can be effective in preventing and treating intestinal failure-associated liver disease. Prevention of infection(s), pharmaceutical interventions to enhance bowel motility and prevent/mitigate bacteria overgrowth, and specialized multidisciplinary care to minimize the injury to other organs such as the liver, kidneys, and the brain can assist in nutritional rehabilitation and lower the morbidity in SBS.

Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants.

Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Daily administration of the mixture accelerated the transition into a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Bifidobacterium-driven microbiome maturation was also linked to an anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains are ecosystem engineers that lead to an acceleration of microbiome maturation and immunological consequences in extremely premature infants.

Evaluation of family and staff experiences with virtual rounding and bedside presence in a tertiary neonatal intensive care unit during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic-related visitation restrictions started in March 2020 in Alberta, Canada. In the Neonatal Intensive Care Unit, we implemented a Virtual Communications initiative to allow parents to continue to be present with their infants, attend daily rounds, and communicate with the medical team. The purpose of this survey study was to describe our approach and evaluate the experience for families and staff. METHODS: The study surveys consisted of 13-18 questions directed toward understanding staff and family experience with the process and emotional impact using Likert scale and open-ended questions. The study team reviewed results and implemented changes in real time. Analysis was mixed quantitative and qualitative design, with descriptive data organized into themes. RESULTS: Twenty-six surveys were completed by 16 staff (62%) and 10 parents (38%). About 50% to 100% of respondents agreed or strongly agreed with statements addressing the quality and value of the virtual sessions. Staff identified challenges with slow devices and need for awareness and education. Both staff and parents expressed gratitude for the initiative and an overall positive experience. DISCUSSION: Offering Virtual Rounds and Bedside Presence in the Neonatal Intensive Care Unit is a well-received and feasible alternative to in-person presence that allows parents to stay involved and connected to their infants. Families have a better understanding of their babies' clinical status and plans with an overall positive experience.

Multi-strain probiotics for extremely preterm infants: a randomized controlled trial.

BACKGROUND: Effects of probiotics on intestinal microbiota and feeding tolerance remain unclear in extremely low-birth-weight (ELBW) infants. METHODS: ELBW infants were randomly assigned to receive probiotics or no intervention. Stool samples were collected prior to, 2 and 4 weeks after initiation, and 2 weeks after probiotics cessation for infants in the probiotics group, and at matched postnatal age time points for infants in the control group. RESULTS: Of the 102 infants assessed for eligibility, sixty-two were included. Infants who received probiotics reached full enteral feeds sooner (Mean difference (MD) -1.8; 95% CI:-3.7 to -0.01 day), had a tendency toward lower incidence of hematochezia before hospital discharge (22.6% vs 3.2%; P = 0.053), and were less likely to require extensively hydrolyzed- or amino acids-based formulas to alleviate signs of cow's milk protein intolerance in the first 6 months of life (19.4% vs 51.6%; P = 0.008). Infants on probiotics were more likely to receive wide-spectrum antibiotics (64.5% vs 32.2%; P = 0.01). Multi-strain probiotics resulted in significant increase in fecal Bifidobacterium (P < 0.001) and Lactobacillus (P = 0.005), and marked reduction in fecal candida abundance (P = 0.04). CONCLUSION: Probiotics sustained intestinal Bifidobacterium and reduced time to achieve full enteral feeds in extremely preterm infants. Probiotics might improve tolerance for cow's milk protein supplements. CLINICAL TRIAL REGISTRATION: This trial has been registered at www. CLINICALTRIALS: gov (identifier NCT03422562). IMPACT: Probiotics may help extremely preterm infants achieve full enteral feeds sooner. Probiotics may improve tolerance for cow's milk protein supplements. Multi-strain probiotics can sustain intestinal Bifidobacterium and Lactobacillus until hospital discharge.

Lower Maternal Chronic Physiological Stress and Better Child Behavior at 18 Months: Follow-Up of a Cluster Randomized Trial of Neonatal Intensive Care Unit Family Integrated Care.

OBJECTIVE: To assess whether Family Integrated Care (FICare) in the neonatal intensive care unit improves maternal chronic physiological stress and child behavior at 18 months of corrected age for infants born preterm. STUDY DESIGN: Follow-up of a multicenter, prospective cluster-randomized controlled trial comparing FICare and standard care of children born at <33 weeks of gestation and parents, stratified by tertiary neonatal intensive care units, across Canada. Primary outcomes at 18 months of corrected age were maternal stress hormones (cortisol, ie, hair cumulative cortisol [HCC], dehydroepiandrosterone [DHEA]) assayed from hair samples. Secondary outcomes included maternal reports of parenting stress, child behaviors (Internalizing, Externalizing, Dysregulation), and observer-rated caregiving behaviors. Outcomes were analyzed using multilevel modeling. RESULTS: We included 126 mother-child dyads from 12 sites (6 FICare sites, n = 83; 6 standard care sites, n = 43). FICare intervention significantly lowered maternal physiological stress as indicated by HCC (B = -0.22 [-0.41, -0.04]) and cortisol/DHEA ratio (B = -0.25 [-0.48, -0.02]), but not DHEA (B = 0.01 [-0.11, 0.14]). Enrollment in FICare led to lower child Internalizing (B = -0.93 [-2.33, 0.02]) and Externalizing behavior T scores (B = -0.91 [-2.25, -0.01]) via improvements to maternal HCC (mediation). FICare buffered the negative effects of high maternal HCC on child Dysregulation T scores (B = -11.40 [-23.01, 0.21]; moderation). For mothers reporting high parenting stress at 18 months, FICare was related to lower Dysregulation T scores via maternal HCC; moderated mediation = -0.17 (-0.41, -0.01). CONCLUSIONS: FICare has long-term beneficial effects for mother and child, attenuating maternal chronic physiological stress, and improving child behavior in toddlerhood. CLINICAL TRIAL REGISTRATION: NCT01852695.

Recent Update on Neonatal Resuscitation.

Every 5 y, the International Liaison Committee on Resuscitation publishes consensus on cardiopulmonary resuscitation, and emergency cardiovascular science and treatment recommendations. The latest update on neonatal resuscitation guidelines was published in 2020. Here, the authors review the important changes in the recent recommendations, including initial steps of resuscitation, umbilical cord management, management of nonvigorous infants born through meconium-stained amniotic fluid, sustained inflation in preterm infants, epinephrine, vascular access, timing of discontinuation of resuscitative effort, and team briefing and debriefing.

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. METHODS AND ANALYSIS: A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days.Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). OUTCOMES: The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. SITES AND SAMPLE SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student's t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. TRIAL REGISTRATION NUMBER: NCT04347720.

Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology.

BACKGROUND: There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited. OBJECTIVE: This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally. STUDY DESIGN: This retrospective cohort study included inborn, nonanomalous infants, born at <29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment. RESULTS: Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88). CONCLUSION: Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at <29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

Sustained Lung Inflations During Neonatal Resuscitation at Birth: A Meta-analysis.

CONTEXT: The International Liaison Committee on Resuscitation prioritized review of sustained inflation (SI) of the lung at birth. OBJECTIVE: To complete a systematic review and meta-analysis comparing strategies using 1 or more SI ≥1 second with intermittent inflations <1 second for newborns at birth. DATA SOURCES: Medline, Embase, and Evidence-Based Medicine Reviews were searched from January 1, 1946, to July 20, 2020. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages. DATA EXTRACTION: Reviewers extracted data, appraised risk of bias, and assessed certainty of evidence for each outcome. RESULTS: Ten trials enrolling 1502 preterm newborns were included. Five studies included newborns who did not receive assisted ventilation at the outset. There were no differences between SI and control groups for death before discharge or key morbidities. For death within the first 2 days, comparing SI with the controls, risk ratio was 2.42 (95% confidence interval = 1.15-5.09). In subgroup analysis of preterm infants ≤28 + 0 weeks' gestation, for death before discharge, risk ratio was 1.38 (95% confidence interval = 1.00-1.91). Together, these findings suggest the potential for harm of SI. LIMITATIONS: The certainty of evidence was very low for death in the delivery room and low for all other outcomes. CONCLUSIONS: In this systematic review, we did not find benefit in using 1 or more SI >5 seconds for preterm infants at birth. SI(s) may increase death before discharge among the subgroup born ≤28 + 0 weeks' gestation. There is insufficient evidence to determine the likely effect of SI(s) on other key morbidities.

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.

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.