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.

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.

Association between Peripherally Inserted Central Venous Catheter Insertion Site and Complication Rates in Preterm Infants.

Objective To examine whether there is an association between peripherally inserted central venous catheter (PICC) insertion site and complication rates among preterm infants. Design We performed a retrospective analysis of the first PICCs placed in preterm infants in a tertiary neonatal intensive care unit between January 2006 and December 2010. The PICC-related complications resulting in catheter removal were compared based on site of insertion. Results Of the 827 PICCs, 593 (72%) were inserted in upper extremity. Lower extremity PICC group infants had higher illness severity (SNAP-II) score and more likely to be inserted later as compared with the upper extremity group. There was no significant difference in the total PICC-related complications between upper and lower extremity PICCs (31.3 vs. 26%; p > 0.05). Logistic regression analysis after adjusting for gestational age, day of line insertion, and SNAP-II score revealed that upper extremity PICCs were associated with increased risk of line infiltration (adjusted odds ratio [aOR], 2.41; 95% confidence interval [CI], 1.36-4.29) but not the total PICC complication (aOR, 1.29; 95% CI, 0.91-1.83). Conclusion There is no difference in total PICC-related complication between upper and lower extremity PICCs; however, the PICC-related mechanical complications vary depending on the site of insertion in preterm infants.

Trends and Variations in the Use of Inhaled Nitric Oxide in Preterm Infants in Canadian Neonatal Intensive Care Units.

Objective To determine the proportion of infants who receive inhaled nitric oxide (iNO), and to characterize the variations in its use by gestational age (GA) and center in infants <34 weeks' gestation. Design Retrospective analysis was performed in infants born at <34 weeks' gestation and admitted to neonatal intensive care units participating in the Canadian Neonatal Network between January 2010 and December 2013. Results Of 19,525 infants, 831 (4.2%) received iNO. A total of 369 infants (44%) received iNO during the first 2 days after birth. The proportion of neonates who received iNO in the 22 to 25, 26 to 29, and 30 to 33 weeks' GA groups was 16.1, 6.0, and 1.3%, respectively. Infants in whom iNO was initiated in the first 2 days of age received it for a shorter duration (median, 3 days; interquartile range [IQR], 2-5) as compared with those who started after 2 days (median, 5 days; IQR, 2-11). The use of iNO varied by center, ranging from 0 to 15.5% (p < 0.001). Conclusion Out of every 25 infants born at <34 weeks' gestation in Canada received iNO, with the highest rate of use in infants born at lower gestation. Further research to identify reasoning, efficacy, and safety of iNO in preterm infants is warranted.

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.

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.

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.

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.

Antenatal indomethacin tocolysis is associated with an increased need for surgical ligation of patent ductus arteriosus in preterm infants.

OBJECTIVE: To examine the effect of antenatal indomethacin (AI) exposure on the incidence, response to postnatal indomethacin (PI), and need for surgical ligation of patent ductus arteriosus (PDA) in preterm infants. METHODS: We performed a retrospective matched cohort study of infants born at < or = 30 weeks' gestation after exposure to AI administered because of preterm labour. Control subjects were infants unexposed to AI but with similar gestational age and birth weight. We compared the incidence of PDA, response to treatment with PI, and surgical PDA ligation rate between the two groups. RESULTS: There was no difference in the incidence of PDA between AI infants (67.6%) and control subjects (66.6%). Only 22 of 54 (41%) infants in the AI group responded to PI therapy for symptomatic PDA closure, compared to 34 of 52 (65%) infants in the control group (P = 0.012). Thirty-two (59%) infants in the AI group required surgical PDA ligation after indomethacin therapy, compared with 18 infants in the control group (35%) (P = 0.01). Multivariate logistic regression analysis showed that AI exposure was independently associated with surgical ligation of PDA (adjusted odds ratio 3.07; 95% CI 1.46 to 6.45). CONCLUSION: In infants born preterm (< or = 30 weeks) with a PDA, antenatal exposure to indomethacin was associated with an increased rate of therapeutic failure of PI and an increased rate of surgical PDA ligation compared with controls without such antenatal exposure.

A multicenter study on the clinical outcome of chorioamnionitis in preterm infants.

OBJECTIVE: The purpose of this study was to examine the effects of clinical maternal chorioamnionitis on morbidity and mortality rates among infants who are at < 33 weeks of gestation, adjusted for patient characteristics that included admission neonatal illness severity (Score for Neonatal Acute Physiology, version II; SNAP-II). STUDY DESIGN: With multivariate logistic regression analysis, prospectively collected hospital outcomes from the Canadian Neonatal Network of singleton infants with birth gestational age of < 33 weeks and clinical chorioamnionitis were compared retrospectively with nonexposed infants. RESULTS: Of 3094 infants, 477 infants (15.4%) who were exposed to clinical chorioamnionitis had significantly higher admission SNAP-II scores. Bivariate analysis revealed that the neonatal mortality rate was increased significantly in the chorioamnionitis group (10.6% vs 6.1%). Multivariate regression analysis with adjustment for illness severity indicated that chorioamnionitis was associated with an increased risk of early sepsis (odds ratio, 5.54; 95% confidence interval, 2.87-10.69) and severe intraventricular hemorrhage (odds ratio, 1.62; 95% confidence interval, 1.17-2.24) but not neonatal death. CONCLUSION: Preterm infants who are exposed to clinical chorioamnionitis have an increased risk of early-onset sepsis and severe intraventricular hemorrhage.

Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis.

AIM: This study aimed to compare the long-term neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birth weight < or = 1250 gm) who received supplementation with L-arginine during the first 28 days of life with controls. METHODS: Surviving infants enrolled in a randomised control study of L-arginine supplementation were prospectively followed longitudinally to determine their neurodevelopmental outcomes at 36 months of adjusted age. Neurologic examination and neurodevelopmental assessments were performed by examiners who were unaware of the original treatment assignments. RESULTS: A total of 132 children (95% of survivors) were evaluated at 36 months adjusted age. In the group given L-arginine, 5 of 61 (8.1%) had major neurodevelopmental disabilities, defined as the presence of one or more of cerebral palsy, cognitive delay (cognitive index <70), bilateral blindness or bilateral hearing loss requiring hearing aids as compared with 9 of 71 (12.6%) in the placebo group (relative risk, 0.64; 95 % confidence interval, 0.22-1.82; P= 0.40). CONCLUSIONS: There is no increase in neurodevelopmental disability in preterm infants who received L-arginine supplementation.

Effect of single loading dose of intravenous caffeine infusion on superior mesenteric artery blood flow velocities in preterm infants.

AIM: To evaluate the effects of a single loading dose of caffeine base (10 mg/kg) on superior mesenteric artery (SMA) blood flow velocities (BFV). METHODS: Eighteen preterm infants of gestational age

Effectiveness of Injectable Ibuprofen Salts and Indomethacin to Treat Patent Ductus Arteriosus in Preterm Infants: Observational Cohort Study.

BACKGROUND: There is no injectable ibuprofen product marketed to treat patent ductus arteriosus (PDA) in newborns in Canada. The authors' institution has used ibuprofen arginine in the past. In the absence of published evidence supporting use of this salt form of ibuprofen for neonatal PDA, a retrospective analysis was undertaken. OBJECTIVE: To compare the effectiveness and adverse effects of ibuprofen arginine, ibuprofen tromethamine, and indomethacin in the treatment of PDA. METHODS: This retrospective observational cohort study, for patients admitted between 2009 and 2015, included preterm infants with symptomatic PDA who received at least one dose of injectable indomethacin, ibuprofen tromethamine, or ibuprofen arginine. Three effectiveness end points were analyzed: closure after one course of treatment, repeat medical treatment, and surgical ligation. The secondary end points included acute kidney injury, necrotizing enterocolitis, chronic lung disease, and time to full enteral feeding. RESULTS: A total of 179 infants were included. There were no differences among groups in terms of closure after one course of treatment (37/54 [69%] with indomethacin, 42/70 [60%] with ibuprofen tromethamine, and 28/55 [51%] with ibuprofen arginine; p = 0.21) or surgical ligation (10/54 [19%] with indomethacin, 13/70 [19%] with ibuprofen tromethamine, and 12/55 [22%] with ibuprofen arginine; p = 0.88). However, there was a difference regarding use of a repeat course of treatment, ibuprofen arginine having the highest rate (8/54 [15%] with indomethacin, 18/70 [26%] with ibuprofen tromethamine, and 20/55 [36%] with ibuprofen arginine; p = 0.04). After adjustment for gestational age, the association between ibuprofen arginine and increased use of a repeat course of treatment remained significant. The groups did not differ with respect to adverse effects. CONCLUSION: These results highlight the potential for differences in effectiveness among various salt forms of injectable ibuprofen and indomethacin. Because of the small sample size and retrospective methodology, confirmation of the present results through a larger prospective study is needed.

CONTEXTE: Il n'y a pas sur le marché de produit injectable à base d'ibuprofène pour traiter la persistance du canal artériel (PCA) chez le nouveau-né au Canada. L'ibuprofène arginine a été utilisé auparavant dans l'établissement de santé des auteurs. En l'absence de données publiées appuyant l'utilisation de ce médicament sous forme de ce sel pour traiter la PCA chez le nouveau-né, une analyse rétrospective a été réalisée. OBJECTIF: Comparer l'efficacité et les effets indésirables de l'ibuprofène arginine, de l'ibuprofène trométhamine et de l'indométhacine dans le traitement de la PCA. MÉTHODES: Cette étude de cohorte observationnelle rétrospective, au sujet de patients hospitalisés entre 2009 et 2015, incluait des nourrissons prématurés atteints d'une PCA symptomatique ayant reçu par injection au moins une dose d'indométhacine, d'ibuprofène trométhamine ou d'ibuprofène arginine. Trois paramètres d'évaluation de l'efficacité ont été analysés : la fermeture après un seul traitement, la répétition du traitement médical et la ligature chirurgicale. Les paramètres d'évaluation secondaires étaient les cas d'insuffisance rénale aiguë, d'entérocolite nécrosante et de maladie pulmonaire chronique ainsi que le temps pour atteindre l'alimentation entérale complète. RÉSULTATS: Au total, 179 nourrissons ont été admis à l'étude. Aucune différence n'a été relevée entre les groupes en ce qui touche à la fermeture après un seul traitement (37/54 [69 %] pour l'indométhacine, 42/70 [60 %] pour l'ibuprofène trométhamine et 28/55 [51 %] pour l'ibuprofène arginine; p = 0,21) ou à la ligature chirurgicale (10/54 [19 %] pour l'indométhacine, 13/70 [19 %] pour l'ibuprofène trométhamine et 12/55 [22 %] pour l'ibuprofène arginine; p = 0,88). Cependant, une différence a été observée pour ce qui est de la répétition du traitement et l'ibuprofène arginine a obtenu le taux le plus élevé (8/54 [15 %] pour l'indométhacine, 18/70 [26 %] pour l'ibuprofène trométhamine et 20/55 [36 %] pour l'ibuprofène arginine; p = 0,04). Après ajustement pour l'âge gestationnel, l'association entre l'utilisation de l'ibuprofène arginine et une augmentation du recours à un second traitement demeurait significative. Il n'y avait pas de différence entre les groupes en ce qui touche aux effets indésirables. CONCLUSION: Ces résultats soulignent la possible différence d'efficacité parmi les divers sels d'ibuprofène injectable et l'indométhacine. Cependant, en raison de la petite taille de l'échantillon et de l'emploi d'une méthodologie rétrospective, une étude prospective plus importante doit être menée pour confirmer les résultats de la présente étude.

Ultrasound assessment of umbilical venous catheter migration in preterm infants: a prospective study.

OBJECTIVES: To evaluate the umbilical venous catheter (UVC) tip position by ultrasound and compare it with standard radiograph findings and to examine the catheter tip migration rates during the first week of life. DESIGN: Prospective observational study of inborn preterm infants who had an UVC placed and its position radiographically confirmed. The first ultrasound was done on UVC placement at median (IQR) age of 2 hours (1-4) and follow-up scans at a median (IQR) age of 34 hours (27-44 hours), 77 hours (70-94 hours) and 6 days (5-7 days) after insertion. Catheter tip was considered in optimum position if tip was lying in the inferior vena cava up to the right atrium opening. RESULTS: We studied 65 infants at a mean (±SD) gestational age and birth weight of 26.4 (±2.1) weeks and 808 (±289) g, respectively. Ultrasound confirmed optimum position of UVC tip in 25/65 (38.5%) infants. Majority (38/40) of the malpositioned catheters were located inside the heart with 15 reaching the left atrium. Catheter tip migration occurred in 29 of 58 infants (50%) at any time during the first week. The proportions of UVC migration were found to be 17%, 31% and 29% on subsequent ultrasound with a trend to outward movement over time. CONCLUSION: UVC tip localisation by standard radiography is very imprecise, and catheter tip migration occurs in a significant proportion of infants during first weeks of age. We suggest ultrasound as the best modality to assist localisation and follow-up of UVC tip in preterm infants.

Probiotics and prebiotics: role in prevention of nosocomial sepsis in preterm infants.

Nosocomial sepsis is associated with increased mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay. Prevention of sepsis especially in the preterm infants in the neonatal intensive care unit remains a major challenge. The gastrointestinal tract is an important source of potential pathogens causing nosocomial sepsis as the immature intestinal epithelium can permit translocation of bacteria and yeast. The intestinal tract and its microflora play an important role in the immunity. Altering the gut microflora has been extensively studied for immunomodulation in preterm infants. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Probiotics have been used for prevention and treatment of various medical conditions in children and adults. Studies on probiotics in premature infants have focused on normalizing intestinal flora, improvement in feeding intolerance, prevention of necrotizing enterocolitis and sepsis. In this paper, we discuss the intestinal bacterial colonization pattern; the rational for probiotics and prebiotic therapy with special focus on the prevention of nosocomial sepsis in preterm infants.

Advances in the management of meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) is a common cause of severe respiratory distress in term infants, with an associated highly variable morbidity and mortality. MAS results from aspiration of meconium during intrauterine gasping or during the first few breaths. The pathophysiology of MAS is multifactorial and includes acute airway obstruction, surfactant dysfunction or inactivation, chemical pneumonitis with release of vasoconstrictive and inflammatory mediators, and persistent pulmonary hypertension of newborn (PPHN). This disorder can be life threatening, often complicated by respiratory failure, pulmonary air leaks, and PPHN. Approaches to the prevention of MAS have changed over time with collaboration between obstetricians and pediatricians forming the foundations for care. The use of surfactant and inhaled nitric oxide (iNO) has led to the decreased mortality and the need for extracorporeal membrane oxygenation (ECMO) use. In this paper, we review the current understanding of the pathophysiology and management of MAS.

Choice and duration of antimicrobial therapy for neonatal sepsis and meningitis.

Neonatal sepsis is associated with increased mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay. Signs and symptoms of sepsis are nonspecific, and empiric antimicrobial therapy is promptly initiated after obtaining appropriate cultures. However, many preterm and low birth weight infants who do not have infection receive antimicrobial agents during hospital stay. Prolonged and unnecessary use of antimicrobial agents is associated with deleterious effects on the host and the environment. Traditionally, the choice of antimicrobial agents is based on the local policy, and the duration of therapy is decided by the treating physician based on clinical symptoms and blood culture results. In this paper, we discuss briefly the causative organism of neonatal sepsis in both the developed and developing countries. We review the evidence for appropriate choice of empiric antimicrobial agents and optimal duration of therapy in neonates with suspected sepsis, culture-proven sepsis, and meningitis. Moreover, there is significant similarity between the causative organisms for early- and late-onset sepsis in developing countries. The choice of antibiotic described in this paper may be more applicable in developed countries.

Indomethacin tocolysis and neurodevelopmental outcome.

OBJECTIVE: To compare the neurodevelopmental outcomes, at 30-42 months adjusted age, between infants exposed to antenatal indomethacin and those unexposed to antenatal indomethacin. METHODS: This was a retrospective cohort study. The study cohort consisted of all nonanomalous infants with birth weight ≤ 1250 g and/or gestational age ≤ 28 wks born between 2000 and 2003, who completed neurodevelopmental assessments between 30-42 months adjusted age. The authors compared the neurodevelopmental outcomes of infants exposed and unexposed to antenatal indomethacin. RESULTS: Of the 321 infants, 75 infants (23%) exposed to antenatal indomethacin were lower in gestational age (26.4 vs 27.8 wks). In univariate analysis, infants exposed to antenatal indomethacin had significantly increased incidence of patent ductus arteriosus (PDA) (60% vs. 39%), surgical PDA ligation (40% vs. 18%) and bronchopulmonary dysplasia (81% vs. 60%). There was no significant difference in cerebral palsy, cognitive delay, deafness, blindness and major disability between the two groups. In multivariable logistic regression analysis, antenatal indomethacin exposure was not associated with cerebral palsy (OR, 0.70; 95% CI, 0.22-2.18), cognitive delay (OR, 0.56; 95% CI, 0.28-1.12) or neurodevelopmental disability (OR, 0.50; 95% CI, 0.21-1.19). CONCLUSIONS: Neurodevelopmental outcome of preterm infants exposed to antenatal indomethacin is equivalent to those unexposed to antenatal indomethacin, despite being born earlier.

Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight < or =1250 g?

AIM: To compare the long-term growth and neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birthweight (BW) < or = 1250 g) with necrotising enterocolitis (NEC) with BW-matched controls. METHODS: This is a case control study performed at a regional tertiary care neonatal intensive care unit. Infants with stage II or III NEC admitted to a regional tertiary care neonatal unit between 1995 and 2000 were identified. Each infant with NEC was matched by BW (+/-100 g) to next two infants admitted in the unit without NEC. Growth and neurodevelopmental outcomes at 36 months are compared. RESULTS: In total, 51 infants with NEC and 102 controls met study eligibility criteria and 146/153 (94.3%) were prospectively followed for 36 months. Infants with NEC had more culture-proven sepsis (35.3% vs. 10.8%, P < 0.001); patent ductus arteriosus requiring therapy (64.7% vs. 45%, P = 0.02), chronic lung disease (60.7% vs. 45%, P = 0.04) and longer hospital stay (84 days vs. 71 days, P < 0.0001). There were no significant differences in growth outcomes between the two groups at 36 months. Overall 24% of infants with NEC had one major neurodevelopmental disability compared with 10% among control infants. Infants who developed NEC had significantly higher cognitive delay (i.e. cognitive index <70) and visual impairment. A logistic regression model identified NEC as a predictor of cognitive delay. CONCLUSION: Preterm infants who develop NEC are at a significantly higher risk for developing neurodevelopmental disability. We recommend close neurodevelopmental follow up for all < or =1250 g infants who develop stage II or III NEC.