Lenticulostriate Vasculopathy in Very-Low-Birth-Weight Preterm Infants: A Longitudinal Cohort Study

Background: The pathogenesis and clinical significance of lenticulostriate vasculopathy (LSV) are unclear. Our study aimed to determine the prevalence, presentation, and evolution of LSV, and the perinatal risk factors associated with LSV among very-low-birth-weight (VLBW) preterm infants. Methods: One-hundred-and-thirty VLBW preterm infants were retrospectively enrolled in this study. Serial cranial ultrasound examinations were performed regularly from birth until a corrected age of 1 year. Infants with LSV were assigned to early-onset (≤10 postnatal days) and late-onset (>10 postnatal days) groups. Data describing the infants’ perinatal characteristics, placental histopathology, and neonatal morbidities were collected, and the groups were compared. Results: Of the VLBW infants, 39.2% had LSV before they were 1 year old. Linear-type LSV was the most common presentation, and >50% of the infants had bilateral involvement. LSV was first detected at 112 ± 83 postnatal days, and its detection timing correlated negatively with gestational age (GA) (R2 = 0.153, p = 0.005) and persisted for 6 months on average. The infants with and without LSV had similar perinatal characteristics, placental pathologies, cytomegalovirus infection rates, and clinical morbidities. The late-onset LSV group comprised 45 (88.2%) infants who had a significantly higher rate of being small for gestational age (SGA) and used oxygen for longer than the infants without LSV. After adjusting a multivariable regression model for GA and SGA, analysis showed that the duration of oxygen usage was an independent risk factor for late-onset LSV development in VLBW infants (odds ratio: 1.030, p = 0.032). Conclusion: LSV may be a nonspecific marker of perinatal insult to the developing brains of preterm infants. Prolonged postnatal oxygen usage may predispose VLBW preterm infants to late-onset LSV development. The long-term clinical impacts of LSV should be clarified.

Framework for considering abnormal heart rate characteristics and other signs of sepsis in very low birth weight infants

Objective: A heart rate characteristics index (HeRO score), incorporating low variability and superimposed decelerations, was developed as a sepsis risk indicator for preterm infants in the NICU. A rise in the risk score should prompt consideration of other clinical changes that may be signs of sepsis to decide whether a workup and antibiotics are indicated. We aimed to develop a framework to systematically consider signs potentially indicating sepsis in very low birth weight (VLBW) infants. Study Design We developed easy-recall acronyms for ten signs of sepsis in VLBWs. Over 12 months in a level IV NICU, Neonatology Fellows completed a brief survey after each shift to document changes prompting sepsis work-ups. We analyzed associations between survey data, hourly HRC data, and the diagnosis of the work-up, grouped as culture-positive sepsis (CXSEP, positive blood or urine culture), clinical sepsis (CLINSEP, negative cultures treated with antibiotics ≥5 days), or sepsis ruled out (SRO, negative cultures, <3 days antibiotics). Results We analyzed 93 sepsis work-ups in 48 VLBW infants (35 CXSEP, 20 CLINSEP, 38 SRO). The most frequently cited changes prompting the work-ups were heart rate patterns and respiratory deterioration, which were common in all three categories. Low blood pressure and poor perfusion were uncommonly cited but were more likely to be associated with CXSEP than the other signs. A rise in the HeRO score ≥1 from 0-12h before the blood culture compared to 12-72h prior occurred in 31% of work-ups diagnosed as CXSEP, 16% CLINSEP, and 31% SRO. Conclusion The HeRO score can alert clinicians to VLBW infants at high or increasing risk for a sepsis-like illness, but HRC patterns are highly variable in individual babies. The easy-recall NeoSEP-10 framework can assist clinicians in considering other clinical changes when making decisions about sepsis work-ups and the duration of antibiotics.

Scalability of the Basic Care Model for Very Low Birth Weight Infants and Implementation Research Considerations

Objectives: To study the scalability of the rural hospital (RH) model of basic newborn care in a general hospital (GH) by including very low birth weight (VLBW) infants, and to assess the implementation aspects. Study design: Observational Settings: RH (1988-1992) and General Hospital, (GH) (2010-2013). Subjects: VLBW infants with birth weight ranging from 1000 g to 1500 g. Interventions: (1) RH: Basic care including warmth, feeding, antibiotics, and oxygen (2) GH: Basic plus circulatory care (2010-12), and continuous positive airway pressure (CPAP) support (2013). Mechanical ventilation and surfactant therapy were not available. Main outcome measure: Mortality Results: The cumulative mortality (38.5%) with basic neonatal care in the RH model declined to 26.6% at the GH with the addition of circulatory support and a “home-made” CPAP system. Conclusions: The RH package may be scaled up by adding CPAP and circulatory support to reduce the mortality among VLBW infants. The RH model is scalable horizontally and vertically. What is already known about this subject? Implementation research constitutes a relatively new and underdeveloped field, One of the facets of health system research is the implementation research. Implementation research aims at bridging the gaps between knowledge and action. What does this study add? Tertiary care center can help in developing basic newborn care at a rural hospital. The rural hospital model can be upscaled vertically as well as horizontally. Addition of circulatory support and CPAP to basic newborn care can significantly lower neonatal mortality. How might it impact on clinical practice in the foreseeable future? The study may encourage tertiary care centers to facilitate the development of basic newborn care centers at the rural hospitals. These centers, in turn, can spread horizontally.

Prevalence of hearing impairment and language and cognition delay in very low birth weight babies and their risk factors

Background: Very low birth weight infants are at increased risk of language, cognition delay and also hearing impairment disorder. Identification is essential for early intervention. Aims and Objectives: To estimate the burden of language, cognition delay and hearing impairment at 24 months of corrected gestation and to test the association of examination at 6 months and 12 months with the language and cognitive outcome of very low birth weight (VLBW) infants at 24 months and to identify the perinatal and neonatal risk factors for atypical outcome. Materials and Methods: It is a prospective cohort study. Consecutive 120 VLBW infants were enrolled in a single centre level III neonatal unit of a teaching hospital. Hearing assessment was done before discharge and 3 monthly. Language and cognitive assessment was done by DASII Scale neu at 6 months and BSIDIII Scale at 12 months and 24 months at neurodevelopmental clinic. Language assessment was further done by REELS-3 Subscale at 24 months. All assessment ages were corrected for prematurity. Results: At 24 months 7.8% infants developed Language delay and 4.7% had cognition delay. Four infants developed cerebral palsy at 24 months. Shock in neonatal period had significant association with suboptimal Hearing, Language and Cognitive outcome at 12 months of corrected gestation. Conclusion: Early anticipation and early identification of abnormal hearing, language and cognitive outcome of VLBW infants can be used as simple and cost-effective measures for preventing long-term morbidity at resource limited countries.

Blood pressure changes during the first 24 hours of life and the association with the persistence of a patent ductus arteriosus and occurrence of intraventricular haemorrhage

Very low birthweight (VLBW) infants are at risk of intraventricular haemorrhage (IVH) and delayed closure of ductus arteriosus. We investigated mean arterially recorded blood pressure (MAP) changes during the first day of life in VLBW infants as potential risk factors for a patent ductus arteriosus (PDA) and IVH. This retrospective cohort study exploring MAP changes during adaption and risk factors for a PDA and IVH comprised 844 VLBW infants admitted to the Helsinki University Children’s Hospital during 2005–2013. For each infant, we investigated 600 time-points of MAP recorded 4–24 hours after birth. Based on blood pressure patterns revealed by a data-driven method, we divided the infants into two groups. Group 1 (n = 327, mean birthweight = 1019 g, mean gestational age = 28 + 1/7 weeks) consisted of infants whose mean MAP was lower at 18–24 hours than at 4–10 hours after birth. Group 2 (n = 517, mean birthweight = 1070 g, mean gestational age = 28 + 5/7 weeks) included infants with a higher mean MAP at 18–24 hours than at 4–10 hours after birth. We used the group assignments, MAP, gestational age at birth, relative size for gestational age, surfactant administration, inotrope usage, invasive ventilation, presence of respiratory distress syndrome or sepsis, fluid intake, and administration of antenatal steroids to predict the occurrence of IVH and use of pharmacological or surgical therapy for a PDA before 42 weeks of gestational age. Infants whose mean MAP is lower at 18–24 hours than at 4–10 hours after birth are more likely to undergo surgical ligation of a PDA (odds ratio = 2.1; CI 1.14–3.89; p = 0.018) and to suffer from IVH (odds ratio = 1.83; CI 1.23–2.72; p = 0.003).

Antibiotic spectrum index: A new tool comparing antibiotic use in three NICUs

Background: Antibiotics are widely used in very low-birth-weight infants (VLBW, <1500 g), and excess exposure, particularly to broad-spectrum antibiotics, is associated with significant morbidity. An antibiotic spectrum index (ASI) quantifies antibiotic exposure by relative antimicrobial activity, adding information to exposure measured by days of therapy (DOT). We compared ASI and DOT across multiple centers to evaluate differences in antibiotic exposures. Methods: We extracted data from patients admitted to 3 level-4 NICUs for 2 years at 2 sites and for 1 year at a third site. We calculated the ASI per antibiotic days and DOT per patient days for all admitted VLBW infants <32 weeks gestational age. Clinical variables were compared as percentages or as days per 1,000 patient days. We used Kruskal-Wallis tests to compare continuous variables across the 3 sites. Results: Demographics were similar for the 734 VLBW infants included. The site with the highest DOT per patient days had the lowest ASI per antibiotic days and the site with the highest mortality and infection rates had the highest ASI per antibiotic days. Antibiotic utilization varied by center, particularly for choice of broad-spectrum coverage, although the organisms causing infection were similar. Conclusion: An antibiotic spectrum index identified differences in prescribing practice patterns among 3 NICUs unique from those identified by standard antibiotic use metrics. Site differences in infection rates and unit practices or guidelines for prescribing antibiotics were reflected in the ASI. This comparison uncovered opportunities to improve antibiotic stewardship and demonstrates the utility of this metric for comparing antibiotic exposures among NICU populations.

Length of Nutritional Transition Associates Negatively with Postnatal Growth in Very Low Birthweight Infants

Very low birthweight (VLBW, <1500 g) infants may be predisposed to undernutrition during the nutritional transition phase from parenteral to enteral nutrition. We studied the associations among the length of the transition phase, postnatal macronutrient intake, and growth from birth to term equivalent age in VLBW infants. This retrospective cohort study included 248 VLBW infants born before 32 weeks of gestation and admitted to the Children’s Hospital, Helsinki, Finland during 2005–2013. Daily nutrient intakes were obtained from computerized medication administration records. The length of the transition phase correlated negatively with cumulative energy, protein, fat, and carbohydrate intake at 28 days of age. It also associated negatively with weight and head circumference growth from birth to term equivalent age. For infants with a long transition phase (over 12 d), the estimates (95% CI) for weight and head circumference z-score change from birth to term equivalent age were −0.3 (−0.56, −0.04) and −0.44 (−0.81, −0.07), respectively, in comparison to those with a short transition phase (ad 7 d). For VLBW infants, rapid transition to full enteral feeding might be beneficial. However, if enteral nutrition cannot be advanced, well-planned parenteral nutrition during the transition phase is necessary to promote adequate growth.

Routine Administration of a Multispecies Probiotic Containing Bifidobacterium and Lactobacillus to Very Low Birth Weight Infants Had No Significant Impact on the Incidence of Necrotizing Enterocolitis

Background: Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity in preterm infants, and prevention and treatment strategies have remained largely unchanged over the past several decades. As understanding of the microbiome has increased, probiotics have been hypothesized as a possible strategy for decreasing rates of NEC, and several studies have noted significant decreases in rates of NEC after initiation of probiotics in preterm infants. However, a recent AAP report cited caution on the use of probiotic use in part because studies of probiotic use in ELBW infants are lacking. As our unit began routine use of probiotics for all infants &lt;33 weeks in 2015 and we are a leading institution for intact survival of ELBW infants, we attempted to answer if probiotic use can impact the rate of NEC in VLBW and ELBW infants.Methods: We conducted a single-center retrospective chart review of infants with modified Bell's stage ≥2a NEC for the 4 years prior to and 5 years after initiation of a protocol involving routine supplementation of a multispecies probiotic to premature infants at the University of Iowa, Stead Family Children's Hospital. The primary outcome measures were rates of modified Bell's stage ≥2a NEC and all-cause pre-discharge mortality at our institution before and after initiation of routine probiotic supplementation in 2015.Results: In our institution, neither the rates of modified Bell's stage ≥2a NEC, nor the rates of all-cause mortality were significantly altered in very low birth weight (VLBW) infants by the initiation of routine probiotic use (NEC rates pre-probiotic 2.1% vs. post-probiotic 1.5%; all-cause mortality rates pre-probiotic 8.4% vs. post-probiotic 7.4%). Characteristics of our two cohorts were overall similar except for a significantly lower 5-minute APGAR score in infants in the post-probiotic epoch (pre-probiotic 8 vs. post-probiotic 6 p = 0.0316), and significantly more infants in the post-probiotic epoch received probiotics (pre-probiotics 0% vs. post-probiotics 65%; p &lt; 0.0001). Similarly, probiotic use had no impact on the incidence of NEC when we restricted our data to only extremely low birth weight (ELBW) infants (pre-probiotics 1.6% vs post-probiotics 4.1%). When we restricted our analysis to only inborn infants, probiotics still had no impact on NEC rates in VLBW infants (1.5% pre- and 1.1% post-probiotic, p = 0.61) or ELBW infants (2% pre- and 2.1% post-probiotic, p = 0.99)Conclusions: Contrary to other studies, we found no significant difference in rates of modified Bell's stage ≥2a NEC or all-cause pre-discharge mortality in VLBW infants following routine administration of a multispecies probiotic supplement.

Risk factors and prognosis in very low birth weight infants treated for hypotension during the first postnatal week from the Korean Neonatal Network

Hypotension in the early stages of life appears in 20% of very low birth weight (VLBW) infants. The gestational age and birth weight are the risk factors highly related to the postnatal hypotension. Other risk factors slightly differ between different studies. So, we evaluated the risk factors and prognosis that are associated with infants treated with hypotension in the early stages of life, after excluding the influences of gestational age and small for gestational age (SGA). VLBW infants registered in the Korean Neonatal Network between 2013 and 2015 treated for hypotension within a week after their birth were selected as study subjects. The rest were used as a control group. Risk factors and the prevalence of severe complications, including mortality, were investigated and compared after matching for gestational age and SGA. The treatment rate for hypotension within the first postnatal week was inversely related to decreasing gestational ages and birth weights. In particular, 63.4% of preterm infants born at ≤ 24 weeks’ gestation and 66.9% of those with a birth weight < 500 g were treated for hypotension within a week of birth. Regression analysis after matching showed that 1-minute Apgar score, neonatal cardiac massage or epinephrine administration, symptomatic patent ductus arteriosus, early onset sepsis, and chorioamnionitis were significantly associated with hypotension. In the hypotension group, mortality, grade 3 or higher intraventricular hemorrhage, periventricular leukomalacia, and moderate to severe bronchopulmonary dysplasia rates were significantly higher after the matching for gestational age and SGA. Hypotension during the first postnatal week is very closely related to the prematurity and the condition of the infant shortly after birth. Regular prenatal care including careful monitoring and appropriate neonatal resuscitation are very crucial to decrease the risk of hypotension in the early stages of life.

Umbilically and Peripherally Inserted Thin Central Venous Catheters Have Similar Risks of Complications in Very Low Birth Weight Infants

In order to compare the complications associated with thin (1-2F) umbilical vein catheters (tUVC) and peripherally inserted central catheters (PICC) in very low birth weight (VLBW) infants, the frequencies and causes of the non-elective removal of first tUVCs and PICCs were evaluated in 195 VLBW infants born in one hospital. Data were collected from patient records. Risk factors for catheter complications were analysed using logistic regression analysis. Altogether, 92 (47%) infants had tUVCs, and 103 (53%) PICCs. In total, 78 (40%) infants underwent the non-elective removal of their first catheters, most commonly due to suspected infection (n=42) or catheter dislocation (n=30). Infants with complications had lower birth weights and gestational ages than those without. The frequencies and causes of the non-elective catheter removal were similar in the tUVC and PICC groups. True catheter infection was diagnosed in 31 infants. The number of infections/1,000 catheter days was higher in the tUVC than in the PICC group. In a multivariable analysis, gestational age was found to be associated with catheter infection, but catheter type was not. Conclusion: The odds of catheter complications seem to decrease with increasing gestational age, but no clear association with thin catheter type was found.