Association of epidural analgesia in labor with neurodevelopmental outcomes in premature infants born at <29 weeks of gestational age.

OBJECTIVE: To explore associations between epidural administration to mothers in labor with neurodevelopmental outcomes at 3 years corrected age in preterm infants born <29 weeks gestational age. STUDY DESIGN: Infants born <29 weeks gestational age between 2006 and 2012 were included. Our primary outcome was a composite of death or neurodevelopmental impairment at 3 years corrected age. Infants were divided into those whose mothers did or did not receive epidural analgesia in labor. Univariable and multivariable regression was used for analysis. RESULTS: There were 548 infants in the no epidural analgesia group and 121 in the epidural analgesia group. The adjusted odds ratio (95%CI) of neurodevelopmental impairment or death in the epidural group was 1.25 (0.82-1.93). Propensity score-matched results were 1.32 (0.79-2.22). CONCLUSION: Preterm infants born <29 weeks gestational age to mothers who received epidural analgesia during labor were not associated with poor neurodevelopmental outcomes at 3 years corrected age.

Parental perception of neonatal retro-transfers from level 3 to level 2 neonatal intensive care units.

OBJECTIVE: The primary objective of this study was to determine the overall parental satisfaction with retro-transfers from a level 3 to a level 2 Neonatal Intensive Care Unit (NICU). The secondary objectives were to explore factors that caused parental satisfaction associated with retro-transfer and investigate the factors that could be modified to improve the retro-transfer process. METHODS: This is a retrospective cross-sectional study. Questionnaires were mailed to all parents of infants transferred from level 3 to level 2 NICUs from 2016 to 2017. Independent samples t-tests, Spearman's rank correlations, and multiple logistic regression analyses were conducted to identify factors associated with parental retro-transfer satisfaction. RESULTS: Our response rate was 39.1% (n = 140). Of all parents, 64.29% parents were extremely satisfied with the overall retro-transfer process. In our bivariate analyses, multiple factors were found to be strongly associated with parental retro-transfer satisfaction, including parental level of education, the amount of notice and rationale given for the retro-transfer and the level of parental communication and engagement with their infant's healthcare team before and after transfer. Multiple logistic regression analyses revealed that when questions regarding the retro-transfer were answered and the level 2 NICU team demonstrated a concrete understanding of the infant's medical issues and history, parental satisfaction increased. CONCLUSION: Majority of parents were satisfied with the retro-transfer process. However, close collaboration and ongoing and open lines of communication between parents and the level 3 NICU healthcare teams will increase parental retro-transfer satisfaction rates.

Correction to: Oral propranolol in prevention of severe retinopathy of prematurity: a systematic review and meta-analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Oral propranolol in prevention of severe retinopathy of prematurity: a systematic review and meta-analysis.

OBJECTIVE: To systematically assess the efficacy of oral beta blockage treatment in primary (before established) and secondary (in threshold stages) prevention of severe retinopathy of prematurity (ROP) in premature infants born ≤32 weeks gestational age. STUDY DESIGN: Following the PRISMA guidelines, published literature was systematically assessed up to April 27, 2018. Trials and observational studies, in which beta blockage was used to prevent severe ROP (defined as stage ≥3, or requiring treatment) were included. Meta-analyses including random effects models were conducted to determine the overall effect of oral beta blockage on prevention of ROP. RESULTS: Six studies (five clinical trials and one observational study) including 461 infants met inclusion criteria using propranolol. The pooled relative risk (RR) of severe ROP in the primary and secondary prophylaxis groups were 0.65 (95% CI 0.43-0.98, NNT = 7) and 0.48 (95% CI 0.35-0.65, NNT = 6) in RCTs, respectively. The RR of severe ROP in one observational study was 0.21 (95% CI 0.08-0.55) with a NNT of 3. There were low heterogeneity and publication bias. Side effects occurred in 8.4% of participants on propranolol. CONCLUSIONS: Systematic assessment of studies showed that prophylactic oral propranolol appeared to be effective in preventing severe ROP in premature infants ≤32 weeks gestational age. Additional well powered, multinational, randomized control trials reporting on long-term outcomes are needed.

The association between vascular complications during pregnancy in women with Type 1 diabetes and congenital malformations.

AIMS: To assess the association between vascular complications of diabetes and the risk of congenital malformations in pregnant women with Type 1 diabetes. METHODS: We conducted an observational retrospective cohort study in women with Type 1 diabetes who received care consecutively from three tertiary care diabetes-in-pregnancy clinics in Calgary, Alberta, Canada. Multivariable logistic regression was used to assess the association between vascular complications (retinopathy, nephropathy and pre-existing hypertension) and congenital malformations in offspring of women with Type 1 diabetes. RESULTS: Of 232 women with Type 1 diabetes, 49 (21%) had at least one vascular complication and there were 52 babies with congenital malformations. Maternal age (31.8 ± 5.0 vs. 29.4 ± 4.7 years, P < 0.01), diabetes duration (20.9 ± 6.7 vs. 11.2 ± 7.4 years, P < 0.01) and pre-eclampsia rate (12.5% vs. 1.3%, P < 0.01) were higher in mothers with vascular complications than in those without. Multivariable analyses showed that vascular complications were not associated with an increased risk of congenital malformations (odds ratio 1.16, 95% confidence interval 0.46 to 2.88). CONCLUSIONS: Vascular complications are common, occurring in one-fifth of pregnant women with Type 1 diabetes, and in this study do not appear to be associated with an increased risk of congenital malformations in children.

Does duration of caffeine therapy in preterm infants born ≤1250 g at birth influence neurodevelopmental (ND) outcomes at 3 years of age?

OBJECTIVE: To evaluate the effect of duration of caffeine use on long-term neurodevelopmental (ND) outcomes at 3 years corrected age (CA) in preterm infants with birthweights (BW) ≤ 1250 g. DESIGN/METHODS: All surviving infants with BW ≤ 1250 g admitted to the Foothills Medical Center neonatal intensive care unit (NICU) from January 2002 to December 2009 who received the first dose of caffeine in the first week of life and were followed up at three years CA were included in the study. Demographics and follow-up outcomes were compared based on early cessation of caffeine ≤ 14 days (ECC), intermediate cessation of caffeine 15-30 days (ICC), and late cessation of caffeine >30 days (LCC). The primary outcome of ND impairment was present if a child had any one of the following: cerebral palsy, cognitive delay, visual impairment, or hearing impairment or deafness. Univariate and logistic regression analyses were performed. RESULTS: Of the 508 eligible infants, 448 (88%) were seen at 3 years CA at follow-up. ECC (n = 139), ICC (n = 122) and LCC (n = 187) groups had a median (range) BW of 979 (560-1250), 1010 (530-1250), and 980 (520-1250) g (p = 0.524) and median (range) gestational age (GA) of 27 (23-33), 28 (24-33), and 27 (24-32) weeks, respectively (p = 0.034). In logistic regression models adjusting for GA, maternal smoking, and each neonatal risk factor separately (IVH, NEC, sepsis, blood transfusions, BPD, postnatal dexamethasone, SNAP-II, and ventilator days), none of the models showed a statistically significant association between caffeine duration and ND impairment. CONCLUSION: The duration of caffeine use in premature infants in the NICU does not impact on long-term ND outcomes at 3 years CA.

Neurodevelopmental outcomes of preterm infants resuscitated with different oxygen concentration at birth.

OBJECTIVE: To compare the neurodevelopmental outcomes at 18 to 21 months corrected age (CA) of infants born at <29 weeks that received room air, an intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. STUDY DESIGN: In this retrospective cohort study, we compared neonatal and neurodevelopmental outcomes at 18 to 21 months CA among inborn infants born before 29 weeks' gestation that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. RESULTS: Of 1509 infants, 445 received room air, 483 received intermediate oxygen concentrations and 581 received 100% oxygen. Compared to infants that received room air, the primary outcome of death or neurodevelopmental impairment (NDI) was not different in intermediate oxygen (adjusted odds ratio (aOR) 1.01; 95% confidence interval (CI) 0.77, 1.34) or 100% oxygen (aOR 1.03; 95% CI 0.78, 1.35). Compared to room air, there was no difference in odds of death or severe NDI in intermediate oxygen (aOR 1.14; 95% CI 0.82, 1.58) or 100% oxygen group (aOR 1.22; 95% CI 0.90, 1.67). The odds of severe NDI among survivors were significantly higher in infants that received 100% oxygen as compared to room air (aOR 1.57, 95% CI 1.05, 2.35). CONCLUSIONS: We observed no significant difference in the primary composite outcomes of death or NDI and death or severe NDI at 18 to 21 months CA between infants that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. However, use of 100% oxygen was associated with increased odds of severe NDI among survivors as compared to room air.

Twenty-four-hour in-house neonatologist coverage and long-term neurodevelopmental outcomes of preterm infants.

OBJECTIVES: To compare short- and long-term neurodevelopmental outcomes at 3 years of corrected age of preterm infants cared for by 24-hour in-house staff neonatologists and those cared for by staff neonatologists during daytime only. METHODS: Retrospective analysis of prospectively collected follow-up data on all nonanomalous preterm infants from 1998 to 2004 excluding year 2001 as a washout period. Infants were divided into two groups based on care provided by staff neonatologists: 24-hour in-house coverage (24-hour coverage 1998-2000) and daytime coverage (day coverage 2002-2004). Short- and long-term outcomes were compared. RESULTS: A total of 387 (78%) of the screened infants were included. Twenty-four-hour coverage (n=179) and day coverage (n=208) groups had a median birth weight (BW) of 875 g (range 470-1250) and 922 g (480-1530; P=0.028), respectively, and both had a median gestational age of 27 weeks. In the day coverage group, a smaller proportion of mothers had chorioamnionitis (20% vs. 30%; P=0.025), received less antibiotics (62% vs. 73%; P=0.023), and infants had fewer cases of confirmed sepsis (14% vs. 23%; P=0.022). In the day coverage group, a larger number of infants had respiratory distress syndrome (87% vs. 77%; P=0.011) and required prolonged mechanical ventilation (median 31 vs. 21 days; P=0.002). The incidence of major neurodevelopmental impairment was not significantly different between the two groups (odds ratio 0.76; 95% confidence interval 0.34-1.65). CONCLUSIONS: Duration of mechanical ventilation was reduced with 24-hour in-house coverage by staff neonatologists. However, 24-hour coverage was not associated with any difference in neurodevelopmental (ND) outcomes at 3-year corrected age.

Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis.

AIM: To assess the short- and long-term maternal and fetal impact of metformin in pregnancy compared with insulin. METHODS: We performed a comprehensive literature search of MEDLINE, EMBASE, BIOSIS, Cochrane Database of Systematic Reviews and ClinicalTrials.gov. Eligible studies were randomized control trials (RCTs) or follow-up of an RCT that: (1) compared metformin with insulin in pregnancy in women with gestational diabetes mellitus or Type 2 diabetes; and (2) reported maternal or fetal outcomes of interest. Two reviewers extracted the data, evaluated study quality and calculated pooled estimates. RESULTS: Sixteen studies (n = 2165 in quantitative analysis) were included. Metformin lowered the risk of neonatal hypoglycaemia [risk ratio (RR) = 0.63; 95% confidence interval (95% CI), 0.45 to 0.87], large for gestational age babies (RR = 0.80; 95% CI, 0.64 to 0.99), pregnancy-induced hypertension (RR = 0.56; 95% CI, 0.37 to 0.85) and total maternal pregnancy weight gain [mean difference (MD) -2.07; 95% CI -2.88 to -1.27]. Metformin did not increase preterm delivery (RR = 1.18; 95% CI 0.67 to 2.07), small for gestational age babies (RR = 1.20; 95% CI, 0.67 to 2.14), perinatal mortality (RR = 0.82; 95% CI, 0.17 to 3.92) or Caesarean section (RR = 0.97; 95% CI, 0.80 to 1.19). Long-term outcome information is limited. CONCLUSIONS: Our review found that metformin had no short-term adverse effects on pregnancy, potential benefits in the neonatal period, but limited long-term follow-up information. Prior to routine use, we recommend further follow-up studies of offspring exposed to metformin in utero.

Effect of Nasal Continuous Positive Airway Pressure (NCPAP) Cycling and Continuous NCPAP on Successful Weaning: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of nasal continuous positive airway pressure (NCPAP) cycling with continuous NCPAP in the successful weaning of preterm infants of 25(0)-28(6) wk gestation to nasal prongs. METHODS: A total of 30 infants with a gestational age (GA) of 25(0)-28(6) wk, ventilated for respiratory distress syndrome (RDS) and extubated to NCPAP were eligible for the study. They were randomized to NCPAP cycling [Group A: cycling between NCPAP of 4 cm and 1 liter per minute (LPM) of nasal prongs] or to continuous NCPAP at 4 cm of H2O (Group B). Primary outcome was successful weaning off NCPAP to nasal prongs at the end of 72 h of the intervention and remaining off NCPAP for the next 72 h. RESULTS: The demographic characteristics were similar in both the groups. Infants were randomized to Group A (n = 13) and Group B (n = 17). The primary outcome was not significantly different between the groups (successful weaning to nasal prongs: 31 vs. 41 %; p 0.71). CONCLUSIONS: In this pilot, feasibility study there were no differences in the rates of successful weaning of NCPAP to nasal prongs using either cycling NCPAP or continuous NCPAP in preterm infants. A need exists for a large randomized controlled trial (RCT) to determine the role of cycling NCPAP on neonatal outcomes.

Does chronic oxygen dependency in preterm infants with bronchopulmonary dysplasia at NICU discharge predict respiratory outcomes at 3 years of age?

OBJECTIVE: To determine whether chronic oxygen dependency at the time of discharge from the neonatal intensive care unit (NICU) in infants with bronchopulmonary dysplasia (BPD) predicts respiratory outcomes at 3 years. STUDY DESIGN: Preterm infants ⩽1250 g without BPD, BPD and BPD with chronic oxygen dependency were identified from the Southern Alberta Perinatal Follow-up clinic database (1995-2007). Respiratory outcomes at 4, 8, 18 and 36 months corrected age following NICU discharge were examined. Univariate analyses were done. RESULTS: Out of 1563 infants admitted to the NICU, 1212 survived. Complete follow-up data at 36 months were available for 1030 (85%) children. Children with BPD with or without chronic oxygen dependency had significantly (P<0.001) lower birth weights and gestational ages, and greater post-natal steroid use, compared with those with no BPD. At 4, 8 and 18 months follow-up, the use of respiratory medications and supplemental oxygen were both significantly higher in the BPD infants with chronic oxygen dependency group compared with the no-BPD group and BPD group. At 36 months, children in the BPD with chronic oxygen dependency group were more likely to use respiratory medications and supplemental oxygen vs the no-BPD or the BPD groups. At 4, 8 and 36 months of age, more children in the BPD with chronic oxygen dependency group had post-neonatal chronic lung disease (PNCLD) than children in the other groups, but at 36 months the difference was significant only for the BPD with chronic oxygen dependency vs no-BPD group (P<0.001). CONCLUSIONS: At 36 months, children diagnosed with BPD with chronic oxygen dependency at NICU discharge were more likely to need respiratory medications and supplemental oxygen in the previous 12 months, as compared with no-BPD or BPD groups. They were also more likely to require frequent physician visits and have PNCLD at 3 years, as compared with the no-BPD group.

Mothers' and health care providers' perspectives of the barriers and facilitators to attendance at Canadian neonatal follow-up programs.

BACKGROUND: Despite the benefits of Neonatal Follow-Up (NFU) programs for infants at risk for developmental problems subsequent to preterm birth, non-attendance continues to be a problem within Canada and beyond. This study investigated the barriers and facilitators to attendance at Canadian NFU programs from mothers' and health care providers' (HCP) perspectives. METHODS: In this multi-site qualitative descriptive study, we conducted semi-structured individual interviews with 12 mothers, six from each of two NFU programs; and focus groups with 20 HCPs from nine NFU programs. Interviews were audio-recorded and transcribed and then subjected to thematic analysis. RESULTS: The predominant barriers represented a complex interplay of cumulative factors: mothers' isolation and feeling overwhelmed, with limited support, experiencing difficulty attending because of limited resources, who viewed NFU as not needed until problems arose for their child. Other barriers included vulnerability and fear of bad news. Mothers reported the need to protect their vulnerable child from risks, whereas HCPs reported creating vulnerability by monitoring the child's development over time. HCPs perceived fear of bad news as a barrier, whereas mothers viewed that impending bad news increased their need to attend to address the issue. The predominant facilitators were support, family centred-care and mothers with adequate resources. CONCLUSIONS: Attendance is most problematic for mothers with limited support, capacity and resources. First and foremost, targeted approaches to NFU service provision are needed to address the cumulative barriers and improve experiences for mothers who find it difficult to attend NFU. A continuous relationship with a single point of contact is needed and merits further investigation - a provider who works across the traditional silos of neonatal intensive care, NFU and community services, minimizes duplication and navigates transitions.

Coagulase-negative staphylococcus sepsis in preterm infants and long-term neurodevelopmental outcome.

OBJECTIVE: The objective of this study was to examine the impact of Coagulase-negative staphylococcus (CoNS) sepsis in preterm infants on the neurodevelopmental outcomes at 30 to 42 months corrected age (CA). STUDY DESIGN: This is a retrospective cohort study. All preterm infants born at <29 weeks gestational age between 1995 and 2008 and had a neurodevelopmetnal assessment at 30 to 42 months CA were eligible. The neurodevelopmetnal outcomes of infants exposed to CoNS sepsis were compared with infants unexposed to any type of neonatal sepsis. RESULT: A total of 105 eligible infants who were exposed to CoNS sepsis were compared with 227 infants with no neonatal sepsis. In univariate analysis, infants with CoNS sepsis were more likely to have total major disability (odds ratio (OR)=1.9; 95% CI: 1.07 to 3.38) and cognitive delay (OR=2.53; 1.26 to 5.14).There was no significant difference in the incidence of cerebral palsy, blindness and deafness between the two groups. After correcting for potential confounders, CoNS sepsis was associated with increased risk of cognitive delay (adjusted odds ratio (aOR)= 2.23; 95% CI 1.01 to 4.9), but not with the total major disability (aOR=1.14; 95% CI: 0.55 to 2.34). CONCLUSION: Our study suggests that CoNS sepsis in preterm infants might be associated with increased risk for cognitive delay at 36 months CA.

Synthesis of mesoporous silica nanoparticles and drug loading of poorly water soluble drug cyclosporin A.

Mesoporous silica nanoparticles (MSNs) are introduced as chemically and thermally stable nanomaterials with well-defined and controllable morphology and porosity. It is shown that these particles possess external and internal surfaces that can be selectively functionalized with multiple organic and inorganic groups. Silica nano-particles were synthesized by chemical methods from tetraethylorthosilicate (TEOS), methanol (CH3OH) and deionised water in the presence of sodium hydroxide as catalyst at 80°C temperature. The nature and morphology of particles was investigated by scanning electron microscopy (SEM), N2 adsorption/desorption method using BET instrument and X-ray diffraction (XRD). Silica nanoparticles are applicable to a wide range of therapeutic entities from small molecule to peptides and proteins including hydrophobic and hydrophilic entities. Drug loading does not require chemical modification of the molecule; there are no changes in the drug structure or activity after loading and subsequent release of the drug. Thus, well suited to solve formulation problems associated with hydrophobic drugs such as peptide and protein drugs like cyclosporine A. Silica nanoparticles improved the solubility of poorly water soluble drugs and enhanced the absorption and bioavailability of these compounds.

Formulation, process development and evaluation of artemether and lumefantrine soft gelatin capsule.

Artemether and Lumefantrine capsules are indicated for the treatment of P. falciparum malaria cases resistant to both chloroquine and sulphadoxine, pyrimethamine combination. Both artemether and lumefantrine act as blood schizontocides. Artemether is a sesquiterpene lactone derived from artemisinin. Artemisinin is a compound derived from the sweet wormwood plant and has been used for centuries in traditional Chinese medicine to treat fever. Lumefantrine is a synthetic aryl-amino alcohol antimalarial (quinine, mefloquine and halofantrine are members of the same group). Artemether is absorbed fairly rapidly with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag period of up to 2 hours, with peak plasma concentration about 6-8 hours after dosing. In order to overcome this problem, we have observed that when the drug is given in the soft gelatin dosage form, the bioavailability of the drug is increased. Thus, increasing the absorption of the drug and peak plasma concentration is reached earlier then the conventional dosage form.

Formulation and evaluation of transparent ibuprofen soft gelatin capsule.

The compound ibuprofen, 2-(4-isobutylphenyl) propionic acid, has been known e.g. from Martindale, the Extra Pharmacopoeia, 28(th) edition, 1982, p.256, as a drug which had anti-inflammatory and analgesic properties. It is used for the treatment of rheumatoid arthritis or other inflammatory diseases of joints, soft tissue rheumatism and gout. Ibuprofen, because of its analgesic properties, has been widely used as anodyne, e.g. against pain or discomfort associated with headache, toothache or menstruation.A medication suitable to combat acute pain is demanded to display its effects fast which action, in turn, is only achieved by a quick release and good bio-availability of the active-ingredient. It is for the commercial forms in particular that the conditions of preparation must be strictly observed, as minor alterations in production procedures such as mixing, pressure of compression and type of machine will affect the physical properties of the particles of he active ingredient and will deteriorate its bio-availability. It is an object of this presentation to provide a medicament that can be readily taken that contains an active amount of ibuprofen in a carrier, that is simple to prepare and that will quickly display a high activity.

Late-onset Leclercia adecarboxylata bacteraemia in a premature infant in the NICU.

UNLABELLED: Late-onset sepsis is a unique entity in the neonatal intensive care unit (NICU), as organisms involved are, by definition, nosocomial. As such, a limited number of microbes are characteristically involved. Leclercia adecarboxylata is a gram-negative bacillus rarely cultured in a clinical context, with the few published cases primarily involving immunocompromised adults. We present an ex-26-week newborn girl who developed late-onset sepsis with Leclercia adecarboxylata bacteraemia in the NICU. The infection was successfully treated with gentamicin and cefotaxime. This is the fifth paediatric report of Leclercia adecarboxylata infection, and the first in a neonate. The case raises the possibility that prior courses of antibiotics may have predisposed this individual to a rare infection essentially limited to immunocompromised individuals. CONCLUSION: Leclercia adecarboxylata is a rare infection, particularly in immunocompetent individuals. In neonates, the clinical course can be good with timely initiation of appropriate antibiotics.

Physicians' attitudes towards self-treatment of latent tuberculosis.

We conducted a cross-sectional study to assess physicians' attitudes towards self-treatment of latent tuberculosis infection (LTBI) based on real-time responses related to actual purified protein derivative (PPD) results, in addition to using hypothetical situations for those who were PPD-negative. We also obtained information on physicians' recommendations for their patients to treat this condition. Although the physicians claimed to recommend optimal treatment to their patients, the majority of them had different attitudes when considering treatment for themselves. There appears to be a discrepancy between physicians' attitudes to self-treatment and their management of patients with LTBI.

Clinics in diagnostic imaging (132). Vein of Galen malformation.

A two-day-old, full-term male infant was admitted to the neonatal intensive care unit with heart failure. He was found to be non-dysmorphic, with no clinical evidence of sepsis. Physical examination was significant for hepatomegaly, active precordium, pansystolic murmur and hypotension requiring ionotropic support. A cranial bruit was detected on auscultation. Chest radiography revealed cardiomegaly and pulmonary oedema due to heart failure. Electrocardiogram and two-dimensional echocardiography were normal. Magnetic resonance imaging of the brain showed a large vein of Galen malformation, extensive cerebral ischaemia and multiple cerebral infarcts. This case illustrates the importance of auscultation of the cranium to rule out vein of Galen malformation, a potential cause of high-output cardiac failure in neonates in the absence of other common causes of heart failure.