Screening for Delayed Thyroid Stimulation Hormone Rise and Atypical Congenital Hypothyroidism in Infants Born Very Preterm and Infants with Very Low Birth Weight.

OBJECTIVE: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age. STUDY DESIGN: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 µIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database. RESULTS: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 µIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 µIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 µIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity. CONCLUSIONS: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy.

Lactation support in neonatal intensive care units in Germany from the mothers' perspective - a mixed-method study of the current status and needs.

BACKGROUND: Establishing successful lactation in mothers of very low birth weight (VLBW, <1500g) infants requires structured lactation support. Little is known about mothers' perspectives on lactation support in German neonatal intensive care units (NICUs). METHODS: This paper features a convergent mixed-method approach that includes a retrospective, cross-sectional questionnaire and interview data to showcase mothers' perceptions of lactation support in NICUs. Content analysis of the interviews (n = 12) and a descriptive analysis of quantitative data (n = 533) were performed to illustrate the current status and need for lactation support in German NICUs. RESULTS: The results show that lactation support in German NICUs is often inadequate and does not comply with recommendations based on the existing literature to encourage pumping and breastfeeding in mothers. The data imply that even if lactation is successfully initiated in most cases, it is often not maintained over time, which may be due to a lack of personal support and consistent information. CONCLUSION: The overall structures and institutional guidelines for lactation support should be encouraged to promote nutrition with mother´s own milk in German NICUs.

Kidney replacement therapy in neonates: utilization trends and outcomes.

BACKGROUND: We aimed to assess prevalence and clinical characteristics of newborns receiving kidney replacement therapy (KRT). METHODS: We used the National Inpatient Sample (NIS) dataset for the years 2000-2017. Newborns treated with peritoneal dialysis (PD), hemodialysis (HD), and continuous KRT (CKRT) were included. Trend analysis using the Cochran-Armitage test was used to assess prevalence over the years. RESULTS: A total of 64,532,552 hospitalized newborns were included. Among the 4281 infants treated with KRT, 2501 (58.4%) were treated with PD, 997 (23.3%) had HD, and 783 (18.3%) used CKRT. Associated diagnoses included congenital kidney anomalies (37.4% vs. 15% vs. 9.5%), urinary tract anomalies (35% vs. 12.5% vs. 6.3%), and congenital heart disease (68% vs. 25.7% vs. 72.3%). Median length of stay was longest in PD patients (39 days vs. 18 days vs. 26 days), respectively. However, cost of hospitalization was greatest in CKRT patients (US $490,916 vs. US $218,514 vs. US $621,554), respectively. In the entire cohort, 54,424 newborns had acute kidney injury (AKI); of them 16,999 (31%) died. KRT was used in 2,688 (4.9%) of infants with AKI. Over the study period, trends for utilization of PD (from 0.042 to 0.06%) and CKRT (from 0.03 to 0.21%) increased whereas the hemodialysis trend decreased (from 0.021 to 0.013%). CONCLUSIONS: Congenital heart disease (CHD) and congenital anomalies of the kidneys and urinary tract (CAKUT) are the major diagnoses in newborns receiving KRT. Utilization of PD was greater than HD and CKRT. Trends of PD and CKRT utilization increased over time. Less than 5% of infants diagnosed with AKI received KRT.

Circular RNAs expression profiles and bioinformatics analysis in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) has long been considered the most challenging chronic lung disease for neonatologists and researchers due to its complex pathological mechanisms and difficulty in prediction. Growing evidence indicates that BPD is associated with the dysregulation of circular RNAs (circRNAs). Therefore, we aimed to explore the expression profiles of circRNAs and investigate the underlying molecular network associated with BPD. METHODS: Peripheral blood was collected from very-low-birth-weight (VLBW) infants at 5-8 days of life to extract PBMCs. Microarray analysis and qRT-PCR tests were performed to determine the differentially expressed circRNAs (DEcircRNAs) between BPD and non-BPD VLBW infants. Simultaneous analysis of GSE32472 was conducted to obtain differentially expressed mRNAs (DEmRNA) from BPD infants. The miRNAs were predicted by DEcircRNAs and DEmRNAs of upregulated, respectively, and then screened for overlapping ones. GO and KEGG analysis was performed following construction of the competing endogenous RNA regulatory network (ceRNA) for further investigation. RESULTS: A total of 65 circRNAs (52 upregulated and 13 downregulated) were identified as DEcircRNAs between the two groups (FC >2.0 and p.adj <0.05). As a result, the ceRNA network was constructed based on three upregulated DEcircRNAs validated by qRT-PCR (hsa_circ_0007054, hsa_circ_0057950, and hsa_circ_0120151). Bioinformatics analysis indicated these DEcircRNAs participated in response to stimulus, IL-1 receptor activation, neutrophil activation, and metabolic pathways. CONCLUSIONS: In VLBW infants with a high risk for developing BPD, the circRNA expression profiles in PBMCs were significantly altered in the early post-birth period, suggesting immune dysregulation caused by infection and inflammatory response already existed.

Risk factor analyses for intraventricular hemorrhage in preterm infants: A retrospective cohort study.

BACKGROUND: Very-low-birthweight (VLBW) infants can experience severe intraventricular hemorrhage (IVH) that can lead to life-long disability by impairing neurodevelopment. The aim of this study was to identify the risk and protective factors for severe IVH in VLBW infants. METHODS: A retrospective, cross-sectional review of VLBW infants born at 22-28 weeks' gestation between January 2003 and December 2012 and listed in the Database of Neonatal Research Network in Japan was performed using a statistical model incorporating an odds ratio (OR) and medical center variation as a center variance ratio (CVR). A two-dimensional analysis using a combination of OR and the CVR described evolving measures of a clinical trial (for OR > 1) and standardization (for CVR > 1) concerning a factor of interest. RESULTS: The noteworthy significant protective factors were antenatal steroids (ANS) with and without premature rupture of membrane (OR: 0.43, CVR: 1.08, and OR: 0.68, CVR: 1.14, respectively) and the number of neonatal beds (OR: 0.94, CVR: 0.99) and staff nurses per neonatal bed (OR: 0.89, CVR: 0.99). CONCLUSIONS: Active promotion of ANS administration and consolidation of perinatal medical centers can mitigate the development of severe IVH in VLBW infants.

Trends and racial disparities for acute kidney injury in premature infants: the US national database.

BACKGROUND: To assess prevalence and outcomes of acute kidney injury (AKI) in very-low-birth-weight infants. METHODS: This cross-sectional study utilized the National Inpatient Sample (NIS) dataset for years 2000-2017. All premature infants with birth weight (BW) <1500g and/or gestational age (GA) ≤32 weeks were included. Analyses were conducted for overall population and two BW categories: <1000g and 1000-1499g. Adjusted odds ratios were calculated after controlling for confounding variables in logistic regression analysis. Cochrane-Armitage test was used to assess for statistically significant trends in AKI frequency over the years. RESULTS: In total, 1,311,681 hospitalized premature infants were included; 19,603 (1.5%) were diagnosed with AKI. The majority (74.3%) were BW <1000g and 63.9% ≤28 weeks gestation. Prevalence of AKI differed by ethnicity; White had significantly less AKI than Black (OR=0.79, p<0.001) and Hispanic (OR=0.83, p<0.001). AKI was significantly associated with higher mortality compared to controls (35.1 vs. 3.0%, p<0.001). AKI was associated with comorbidities such as necrotizing enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, intraventricular hemorrhage, and septicemia. In a regression model, AKI was associated with higher mortality after controlling confounding factors (aOR=7.79, p<0.001). AKI was associated with significant increase in length of stay (p<0.001) and cost of hospitalization in survivors (p<0.001). There is a significant trend for increased AKI frequency over the years (Z score=4.33, p<0.001). CONCLUSION: AKI is associated with increased mortality and comorbidities in preterm infants, especially in infants with BW <1000g. Further studies are needed to understand precipitating factors and assess preventative measures for this serious complication.

Do isolates from pharyngeal and rectal swabs match blood culture bacterial pathogens in septic VLBW infants? A pilot, cross-sectional study.

Serial body site swabbing is used to monitor horizontal spread of aggressive bacterial species in the neonatal intensive care unit (NICU). Since colonization/carriage is thought to precede systemic infection, one might expect to retrieve colonizing pathogens from blood cultures. This hypothesis, however, has not been fully investigated in very low birth weight (VLBW) infants that are at high sepsis' risk. The primary outcome was, in a population of VLBW infants with late-onset sepsis, the matching between blood culture results and pathogens isolated from rectal and nose/pharyngeal surveillance swabs in the preceding 2 weeks. The secondary outcomes were the site of swabbing and time interval from colonization to blood culture positivity. Out of 333 VLBW neonates, 80 (24%) were diagnosed with bacterial sepsis. In 46 (57%) neonates, the blood culture showed the same pathogen species cultured from a swab. Of these, 30 were isolated from infants with both body sites colonized with an average time interval of 3.5 days; 2/16 were isolated from rectal swabs and 14 /16 from nose/pharyngeal samples.Conclusion: Our data show a fair correspondence between bacteria colonizing the nasopharynx and/or the rectum and pathogens later isolated from blood cultures. This association depends on the swabbing site, number of sites, and pathogen species. Although these data constitute valuable results, they are not sufficient for providing the sole base of a thoughtful clinical decision. What is Known: • Body site's colonization may precede systemic infection. • Little is known on this mechanism in VLBW infants that are at higher sepsis' risk. What is New: •Colonizing bacteria partially correspond to pathogens of blood cultures in VLBW infants with sepsis. • Correspondence depends on swabbing site, number of sites, and pathogen species.

Nucleated red blood cells and serum lactate values on days 2 and 5 are associated with mortality and morbidity in VLBW infants.

AIM: To correlate nucleated red blood cell counts and serum lactate concentrations on day 2 and 5 of life with morbidity and mortality in very low birth weight infants and to determine corresponding cutoff values. METHODS: Retrospective analysis in a cohort of very low birth weight infants. RESULTS: 250 very low birth weight infants were included in this study. Gestational age ranged from 23 to 35 weeks (mean 29.04) and birth weight was 320-1500 g (mean 1047.9). 55 (22%) patients developed intraventricular hemorrhage, 55 (22%) bronchopulmonary dysplasia, 12 (4.8%) periventricular leukomalacia, 93 (37.2%) retinopathy of prematurity, and 1 (0.4%) necrotizing enterocolitis. Mortality rate was 25/250 (10%). Nucleated red blood cells and serum lactate on day 2 of life were associated with mortality (p < 0.001). Serum lactate on day 5 of life demonstrated an association with retinopathy of prematurity (p = 0.017), bronchopulmonary dysplasia (p = 0.044), and intraventricular hemorrhage (p < 0.001). Cutoff values predicting mortality were >89.5 nucleated red blood cells/100 leucocytes (sensitivity 68.2%, specificity 89.0%) and serum lactate concentrations >8.5 mmol/l (sensitivity 69.6%, specificity 93.5%) on day 2 of life. CONCLUSION: We conclude that both nucleated red blood cell count and serum lactate concentration are valuable biomarkers in predicting important outcome parameters in very low birth weight infants.

Nutritional adequacy of a novel human milk fortifier from donkey milk in feeding preterm infants: study protocol of a randomized controlled clinical trial.

BACKGROUND: Fortification of human milk is a standard practice for feeding very low birth weight infants. However, preterm infants often still experience suboptimal growth and feeding intolerance. New fortification strategies and different commercially available fortifiers have been developed. Commercially available fortifiers are constituted by a blend of ingredients from different sources, including plant oils and bovine milk proteins, thus presenting remarkable differences in the quality of macronutrients with respect to human milk. Based on the consideration that donkey milk has been suggested as a valid alternative for children allergic to cow's milk proteins, due to its biochemical similarity to human milk, we hypothesized that donkey milk could be a suitable ingredient for developing an innovative human milk fortifier. The aim of the study is to evaluate feeding tolerance, growth and clinical short and long-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk, in comparison to an analogous population fed with traditional fortifier and protein supplement containing bovine milk proteins. METHODS: The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born <1500 g and <32 weeks of gestational age were randomized to receive for 21 days either a combination of control bovine milk-based multicomponent fortifier and protein supplement, or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The fortification protocol followed is the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. Weight, length and head circumference are measured; feeding tolerance is assessed by a standardized protocol. The occurrence of sepsis, necrotizing enterocolitis and adverse effects are monitored. DISCUSSION: This is the first clinical study investigating the use of a human milk fortifier derived from donkey milk for the nutrition of preterm infants. If donkey milk derived products will be shown to improve the feeding tolerance or either of the clinical, metabolic, neurological or auxological outcomes of preterm infants, it would be an absolute innovation in the field of feeding practices for preterm infants. TRIAL REGISTRATION: ISRCTN - ISRCTN70022881 .

Lung function in very low birth weight infants after pharmacological and surgical treatment of patent ductus arteriosus - a retrospective analysis.

BACKGROUND: The indications and strategies for treatment of patent ductus arteriosus (PDA) are controversial, and the safety and long-term benefits of surgical PDA closure remain uncertain. The aim of this study was to compare the lung function of very low birth weight (VLBW) infants after successful PDA treatment with a cyclooxygenase inhibitor or secondary surgical ligation. METHODS: A total of 114 VLBW infants (birth weight < 1500 g), including 94 infants (82%) with a birth weight < 1000 g, who received treatment for hemodynamically significant PDA (hsPDA), were examined at a median postmenstrual age of 48 weeks. All infants were initially given pharmacological treatment, and 40 infants (35%) required PDA ligation. Lung function testing (LFT) included tidal breathing measurements, measurement of respiratory mechanics assessed by the occlusion test, whole-body plethysmography, SF6 multiple breath washout, forced expiratory flow (V'maxFRC) by the rapid thoracoabdominal compression technique, exhaled NO (FeNO), and arterialized capillary blood gas analysis. RESULTS: On the day of the LFT, the 2 groups had similar postconceptional age and body weight. However, the PDA ligation group was more immature at birth (p < 0.001) and had reduced respiratory compliance (p < 0.001), lower V'maxFRC (p = 0.006), increased airway resistance (Raw) (p < 0.001), and impaired blood gases (p < 0.001). Multivariate analysis showed that PDA surgery was an independent risk factor for increased Raw. CONCLUSION: PDA ligation after failed pharmacological treatment is associated with impaired lung function as compared to successful pharmacological closure in infants at a postmenstrual age of 48 weeks. However, only Raw was independently affected by PDA ligation, while all other differences were merely explained by patient characteristics.

Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure.

UNLABELLED: Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3-7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 25(1/7) weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %. CONCLUSION: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective.

Association between two different lipid injectable emulsions and parenteral nutrition-associated cholestasis in very low birth weight infants: A retrospective cohort study.

BACKGROUND: Using soybean oil-based lipid emulsions (Intralipid), which contain higher amounts of ω-6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (parenteral nutrition-associated cholestasis [PNAC]). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW infants receiving SMOFlipid vs Intralipid. METHODS: The study was conducted in Sir Run Run Shaw Hospital of the Zhejiang University School of Medicine, Hangzhou, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, length of stay, weight 28 days after birth, severity of PNAC, and the time to reversal of PNAC. RESULTS: Forty-four VLBW infants (35.5%) in the SMOFlipid group vs 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [interquartile range] 55.6 [36.4] vs 118.4 [77.2] µmol/L; P < 0.001), and the time to reversal of PNAC was shorter (44 [49] vs 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. CONCLUSION: SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition.

Diuretic drug utilization in neonates: a French prescription database analysis.

Background: The use of diuretics is extremely common in infants cared for in neonatal wards, despite the lack of proven efficacy for many conditions. The main objective of this study was to assess the rate of diuretics exposure in a multicenter French cohort. The secondary objectives were to describe the evolution of this exposure over time, the indications, the prescription practices, and the exposure rates among centers. Methods: An observational study was conducted in 40 Level 3 French neonatal intensive care units using the same computerized order-entry system. Neonates hospitalized between January 2017 to December 2021 with a corrected age between 24 and 44 weeks of gestation at admission were eligible. Results: A total of 86,032 patients were included. The exposure rate was 8.5%, more specifically 29.4% for children born at < 32 weeks of gestation and 3.7% for neonates born at term. There was no significant variation over the study period, but the exposure ranged from 2.4% to 26.5% depending on the center. The main drugs prescribed were furosemide, spironolactone and dopamine with a diuretic purpose. The main indications were "fluid retention," and to a lesser extent "bronchopulmonary dysplasia" and "post-transfusion." For furosemide, the first exposure occurred in mean at 16.5 (±17.8) days of life, mean duration of exposure was 6.2 (±9.5) days, and the cumulative dose was in mean 10.7 (23.9) mg/kg. Conclusion: Diuretic prescription practices vary between centers. The administration of these drugs is often non-evidence based, doses and duration of treatment easily exceed toxic thresholds.

Admission hypothermia among VLBW infants in Malaysian NICUs.

This study aimed to determine the prevalence of admission hypothermia (AH) among very-low-birth-weight (≤1500 g) infants in 32 Malaysian neonatal intensive care units (NICUs). This was a retrospective analysis of prospectively collected data of all very-low-birth-weight infants admitted and a questionnaire survey of the practice of AH prevention. Of the 3768 (99.8%) infants with admission temperature recorded, 64.8% (n = 2440) were hypothermic: 40.3% (n = 983) mildly (36.0-36.4°C), 58.5% (n = 1428) moderately (32.0-35.9°C) and 1.2% (n = 29) severely (<32.0°C). Mean ambient temperature of these NICUs was 22.8°C (SD = 2.7, n = 28) in labour rooms and 20.1°C (SD = 1.6, n = 30) in operation theatres. None of the NICUs practised complete care bundle against AH at birth (i.e. use of pre-warmed radiant warmer and cling wrap, ambient temperature of at least 25°C and use of pre-warmed transport incubator). Care bundle against neonatal hypothermia should be actively promoted in Malaysian labour rooms and operation theatres.

Supplementation of Mother's Own Milk with Preterm Donor Human Milk: Impact on Protein Intake and Growth in Very Low Birth Weight Infants-A Randomized Controlled Study.

This randomized study investigates whether feeding very low birth weight (VLBW) infants with mother's own milk (MOM) supplemented with either preterm (PDM) or term donor milk (TDM), when MOM is insufficient, has a positive impact on infants' protein intake and growth. A hundred and twenty VLBW infants were randomized into two groups. Group A (43 infants) received MOM supplemented with PDM, whereas Group B (77 infants) was fed with MOM supplemented with TDM, for the first three weeks of life (donor milk period). Breast milk fortifier was added when milk feeds exceeded 50 mL/Kg/day. After the donor milk period, both groups were fed with formula when MOM was not available or the milk bank was unable to provide TDM. Protein intake was higher in Group A than in Group B at initiation of milk fortification (p = 0.006), as well as during the 3-week donor milk period (p = 0.023) and throughout hospitalization (p = 0.014). Moreover, Group A presented higher Δz-score for body weight (p = 0.019) and head circumference (p = 0.001) from birth to the end of donor milk period, and higher mean body weight at discharge (p = 0.047) compared to Group B. In conclusion, when donor milk is required, PDM positively impacts protein intake and growth in VLBW infants (NCT05675397).

Impact of Early Fortification in Very Low Birth Weight Infants on the Incidence of Malnutrition During a Trophamine Shortage.

OBJECTIVE: The devastation of pharmaceutical production facilities from Hurricane Maria caused a national shortage of parenteral amino acids in October 2017. Our institution decreased trophamine in very low birth weight (VLBW) infants and initiated human milk fortification at a lower feeding volume to increase enteral protein intake more quickly. The objective of this study was to assess how protein management during the shortage period affected the incidence of malnutrition. METHODS: This was a retrospective cohort study of infants admitted to 2 neonatal intensive care units from June 1, 2017 to May 31, 2018. Infants between 23 and 32 weeks' gestation were included in this study. The primary outcome was the incidence of malnutrition at 14 days, defined as a z score decline of ≥0.8 SDs, in the pre-shortage period compared with the shortage period. Clinical data regarding adverse effects associated with early fortification and pharmacy costs were recorded. RESULTS: There were 68 infants prior to and 65 during the shortage who met inclusion criteria. There was no difference in malnutrition between the pre-shortage and shortage groups; however, a significant increase in malnutrition was observed in infants who did not receive early fortification during the shortage. No difference in time to full enteral feeds or necrotizing enterocolitis was observed with early fortification. CONCLUSIONS: Early fortification in VLBW infants receiving less trophamine during the shortage was not associated with an increase in malnutrition. Restricting trophamine in neonates during the shortage allowed for distribution to other critically ill patients.

Contaminated Incubators: Source of a Multispecies Enterobacter Outbreak of Neonatal Sepsis.

The genus Enterobacter includes species responsible for nosocomial outbreaks in fragile patients, especially in neonatal intensive care units (NICUs). Determining the primary source of infection is critical to outbreak management and patient outcomes. In this investigation, we report the management and control measures implemented during an Enterobacter outbreak of bloodstream infections in premature babies. The study was conducted in a French NICU over a 3-year period (2016 to 2018) and included 20 premature infants with bacteremia. The clinical and microbiological characteristics were identified, and whole-genome sequencing (WGS) was performed on bacteremia isolates. Initially, several outbreak containment strategies were carried out with no success. Next, outbreak investigation pinpointed the neonatal incubators as the primary reservoir and source of contamination in this outbreak. A new sampling methodology during "on" or "in use" conditions enabled its identification, which led to their replacement, thus resulting in the containment of the outbreak. WGS analysis showed a multiclonal outbreak. Some clones were identified in different isolation sources, including patients and neonatal incubators. In addition, microbiological results showed a multispecies outbreak with a high prevalence of Enterobacter bugandensis and Enterobacter xiangfangensis. We conclude that the NICU health care environment represents an important reservoir for Enterobacter transmission and infection. Finally, extracting samples from the neonatal incubator during active use conditions improves the recovery of bacteria from contaminated equipment. This method should be used more frequently to achieve better monitoring of the NICU for HAIs prevention. IMPORTANCE Neonatal incubators in the NICU can be an important reservoir of pathogens responsible for life-threatening outbreaks in neonatal patients. Traditional disinfection with antiseptics is not sufficient to eradicate the microorganisms that can persist for long periods in the different reservoirs. Identification and elimination of the reservoirs are crucial for outbreak prevention and control. In our investigation, using a new strategy of microbiological screening of neonatal incubators, we demonstrated that these were the primary source of contamination. After their replacement, the outbreak was controlled. This new methodology was effective in containing this outbreak and could be a viable alternative for infection prevention and control in outbreak situations involving incubators as a reservoir.

Improving clinical outcomes of very low birth weight infants: Implementation of standardized management guidelines in tertiary care hospital in Haryana.

BACKGROUND: Standardized written guidelines and protocols in NICU are known to impact neonatal outcomes and improve survival. OBJECTIVE: To study and compare the morbidity and mortality outcomes of very low birth weight (VLBW) neonates before and after introduction of structured approach to standardized management guidelines on four interventions in a tertiary care hospital in North India. METHODOLOGY: Structured approach to standardized management guidelines on four interventions were implemented for VLBW infants in NICU. a) Humidified and Heated High Flow Nasal Cannula (HHHFNC) as the initial mode of ventilator support in preterm VLBW babies. b) Expressed breast milk for feeding preterm VLBW babies and absolutely no formula milk. c) Hand washing and following "Bundle Care Approach" for Central lines as the cardinal cornerstones for maintaining strict asepsis. d) Development and supportive care to be regularly followed. Data was collected prospectively from July 2015 to December 2016 (Intervention Group) and compared with retrospective matched controls from the previous year (July 2014-June 2015) (Control Group). RESULTS: There was a significant decrease in culture positive sepsis in the intervention group compared to control group (3 (2.97%) CI:0.006-0.08 vs 11 (19.64%) CI:0.10-0.32; P = .0004). There was no significant difference in the mortality (5.35% vs3.96% P = .74) amongst the two groups. CONCLUSION: Implementing structured approach to above mentioned interventions in the form of standardized management guidelines for preterm VLBW neonates was associated with significant reduction in culture proven sepsis and mechanical ventilation days without affecting mortality or other co-morbidities.

Clinical and Nutritional Determinants of Extrauterine Growth Restriction Among Very Low Birth Weight Infants.

PURPOSE: To identify the clinical and nutritional factors associated with extrauterine growth restriction (EUGR) among very low birth weight infants (VLBW) in a tertiary hospital in Jordan. PATIENTS AND METHODS: We conducted a retrospective analysis of all VLBW infants admitted at King Abdullah University Hospital between July 2015 and June 2020. Clinical factors, nutritional intake, and growth parameters were collected and analyzed. A multilogistic regression model was applied to identify factors associated with EUGR. RESULTS: Of the 247 VLBW infants included in analysis, 112 (45%) were males, 30 (12%) were below 1000 g, and 72 (29%) were small for gestational age (SGA). EUGR was diagnosed in 198 (80%) at discharge. The rates of EUGR among SGA and non-SGA infants were 97% and 73%, respectively. The EUGR infants had a higher gestational age (30.7 vs 29.8 weeks, p=0.04), a lower birth weight (1209 vs 1300 g, p=0.005), a longer ventilatory support (5.7 vs 2.2 days, p=0.03), a higher incidence of sepsis (23% vs 10%, p=0.05), and a longer hospitalization (46 vs 38 days, p=0.03). With multilogistic regression model, the factors associated with EUGR include small-for-gestational age (AOR 9, 95% C.I. 2, 50), >3-day delay in feeding initiation (AOR 3.8, 95% C.I. 1.2,10), >14-day delay in achieving full feeds (AOR 3.3, 95% C.I. 1.2, 8), <3 g/kg of protein intake on the 8th day (AOR 2.1, 95% C.I. 1.1, 4.1), <100 kcal/kg of total caloric intake on the 15th day (AOR 3.8, 95% C.I. 1.6, 8.9), and occurrence of sepsis (AOR 3, 95% C.I. 1.1, 9). CONCLUSION: The rate of EUGR in our unit is high. In addition to being SGA at birth, sepsis and suboptimal protein and caloric intake in the first two weeks of life were significantly associated with this complication. A more aggressive enteral and parenteral nutritional approach is needed to minimize postnatal growth delay.

Effect of Fluid Bolus on Clinical Outcomes in Very Low Birth Weight Infants.

OBJECTIVE: Administration of fluid bolus in very low birth weight (VLBW) infants is a common practice in the NICU, but one without clear evidence demonstrating benefits in clinical outcomes. On the contrary, recent observational studies have suggested a potential detrimental effect of empiric fluid bolus in preterm infants, especially in the absence of clear indications. The aim of this study was to assess the impact of fluid bolus on various clinical outcomes in VLBW infants. METHODS: Retrospective cohort study of VLBW infants born at ≤34 weeks' gestation and/or ≤1500-g birth weight at a single level III NICU from January 1, 2008, to December 31, 2013, and who received at least one fluid bolus within the first 48 hours of life. Outcomes studied were in-hospital mortality, need for home oxygen, incidence of chronic lung disease (CLD), prevalence of patent ductus arteriosus (PDA), and intraventricular hemorrhage (IVH). RESULTS: Of 516 infants, 112 (21.7%) received a fluid bolus within the first 48 hours of life for various indications. Propensity models suggested no statistical difference for CLD or mortality, but exposed infants had an increased incidence of home on oxygen (p = 0.018), PDA prevalence (p = 0.008), and IVH prevalence (p = 0.038). CONCLUSIONS: Fluid bolus in the first 48 hours of life may be associated with increased incidence of need for home oxygen and higher prevalence of PDA and IVH in VLBW infants. Future studies are needed to address these important adverse outcomes.