Publications by authors named "Aloka L Patel"

55 Publications

Evaluation of vitamin D protocol in the neonatal intensive care unit at Rush University Medical Center.

JPEN J Parenter Enteral Nutr 2021 Jun 14. Epub 2021 Jun 14.

Division of Neonatology, Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA.

Background: In 2017, the neonatal intensive care unit (NICU) at Rush University Medical Center (RUMC) implemented a protocol to provide individualized vitamin D supplementation dosing for very low-birth-weight (VLBW) and very preterm infants. This study evaluated the association of demographic and socioeconomic factors, vitamin D dose, and health indicators, including bone mineral status, measured by alkaline phosphatase and phosphorus levels; linear growth velocity; and occurrence of fractures.

Method: This retrospective cross-sectional study included 227 VLBW or very preterm infants (34 VLBW, 12 very preterm, and 181 VLBW and very preterm) born in and discharged from the RUMC NICU between February 1, 2017, and October 31, 2019. Vitamin D dose was classified as adjusted (supplemental dose of 800 IU/day, n = 169) or standard (recommended dose of 400 IU/day, n = 58), per the protocol. Binary logistic and linear regression models were constructed to test the associations between infant and maternal characteristics and vitamin D dose group and between vitamin D dose group and health indicators.

Results: The analysis found a statistically significant association between maternal age, gestational age, infant birth weight, and race/ethnicity and receipt of an adjusted vitamin D dose. No significant associations were found between health indicators and vitamin D dose.

Conclusion: Sociodemographic factors may influence vitamin D deficiency in VLBW and very preterm infants in the NICU. At this time, there is insufficient evidence to support a tailored approach, but further research in this area is warranted.
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http://dx.doi.org/10.1002/jpen.2138DOI Listing
June 2021

Maternal production of milk for infants in the neonatal intensive care unit.

Semin Perinatol 2021 Mar 2;45(2):151381. Epub 2021 Jan 2.

Department of Pediatrics, Division of Neonatology, Rush University Medical Center, Chicago, USA.

Mother's own milk (MOM) feeding is a cost-effective strategy to reduce risks of comorbidities associated with prematurity and improve long-term health of infants hospitalized in the Neonatal Intensive Care Unit (NICU). Significant racial and socioeconomic disparities exist in MOM provision in the NICU, highlighting the importance of developing strategies to reduce these disparities. Mothers of infants in the NICU experience many health concerns which may negatively impact lactation physiology. Objective measures of lactation physiology are limited but may assist in identifying mothers at particular risk. Several strategies to assist mothers of hospitalized infants are essential, including maternal education, qualified lactation professionals, early and frequent milk expression with a hospital-grade double electric breast pump, and providing support for transitioning to direct breastfeeding prior to discharge from the NICU.
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http://dx.doi.org/10.1016/j.semperi.2020.151381DOI Listing
March 2021

Neurodevelopmental Outcome in Very Low Birth Weight Infants Exposed to Donor Milk.

Am J Perinatol 2021 Jan 6. Epub 2021 Jan 6.

Department of Pediatrics, Rush University Children's Hospital, Chicago, Illinois.

Objective:  This study was aimed to evaluate the impact of donor milk (DM) received in the first 28 days of life (DOL) on neurodevelopmental (ND) outcome at 20-months corrected age (CA) in very low birth weight (VLBW) infants.

Study Design:  A total of 84 infants born in 2011 to 2012 who received only mother's own milk (MOM) and/or preterm formula (PF) was compared with 69 infants born in 2013 to 2014 who received MOM and/or DM. Daily enteral intake of MOM, DM, and PF was collected through 28 DOL. ND outcomes were assessed with the Bayley-III. Multiple regression analyses adjusted for the effect of social and neonatal risk factors alongside era of birth on ND outcome.

Results:  Infants exposed to DM were born to older mothers ( < 0.01) and had higher incidence of severe brain injury ( = 0.013). Although DM group infants received first feed at earlier DOL ( < 0.001), there were no differences in MOM intake at DOL 14 or 28 between the two groups. In regression analyses, DM group did not predict 20-month ND outcome.

Conclusion:  There were no differences in ND outcome between infants born before and after the introduction of DM. This may have been due to the similar percent of MOM at DOL 14 and 28 in the two eras.

Key Points: · Donor milk use is increasing in VLBW infant. The impact of donor milk on neurodevelopment is unclear.. · Provision of mother's own milk was high at days of life 14 and 28 for both groups of infants.. · Donor milk was not associated with improved neurodevelopmental outcome..
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http://dx.doi.org/10.1055/s-0040-1722597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257749PMC
January 2021

Randomized Controlled Trial of Early Docosahexaenoic Acid and Arachidonic Acid Enteral Supplementation in Very Low Birth Weight Infants.

J Pediatr 2021 May 20;232:23-30.e1. Epub 2021 Feb 20.

Department of Pediatrics, NorthShore University HealthSystem, Evanston, IL; Department of Pediatrics, University of Chicago Pritzker School of Medicine, Chicago, IL.

Objective: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation.

Study Design: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks.

Results: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003).

Conclusions: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life.

Trial Registration: Clinicaltrials.gov: NCT03192839.
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http://dx.doi.org/10.1016/j.jpeds.2020.12.037DOI Listing
May 2021

The Interaction of Donor Human Milk Availability and Race/Ethnicity on Provision of Mother's Own Milk for Very Low Birth Weight Infants.

Breastfeed Med 2021 Jan 16;16(1):46-53. Epub 2020 Dec 16.

Section of Neonatology, Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA.

To compare (1) differences in mother's own milk (MOM) provision and enteral feeding outcomes, (2) differences in preterm formula and donor human milk (DHM) uses as bridges to exclusive MOM feedings at discharge, and (3) MOM and enteral feeding outcomes for racial/ethnic subgroups before and after the implementation of a hospital DHM feeding program. Retrospective data from 313 very low birth weight (VLBW; birth weight <1,500 g) infants born between January 2011 to December 2012 (pre-DHM,  = 157) and April 2013 to March 2015 (DHM,  = 156) were analyzed. For this predominantly low-income and minority VLBW infant cohort, the percent of enteral fed hospitalization days was higher in the DHM group (pre-DHM 94% [88, 97] versus DHM 98% [95, 99],  < 0.001). Although MOM remained the predominant first enteral feeding type, significantly fewer DHM infants received MOM (pre-DHM 89% versus DHM 75%,  = 0.001). During days of life 1-14, a lower percentage of DHM infants received 100% MOM (pre-DHM 68% versus DHM 55%,  = 0.02). For the entire cohort, the risk for MOM discontinuation was significantly associated with maternal young age, multiparity, non-Hispanic Black race/ethnicity, and low income. Implementation of a DHM program did not predict duration of MOM feedings. However, non-Hispanic White infants had a longer duration of MOM feedings with DHM availability. Our findings highlight the importance of using precise dose and exposure period methodology to determine the impact of DHM on MOM provision. In addition, DHM availability may be associated with varying effects on MOM provision among racial/ethnic groups.
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http://dx.doi.org/10.1089/bfm.2020.0212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826434PMC
January 2021

Breastfeeding and the origins of health: Interdisciplinary perspectives and priorities.

Matern Child Nutr 2021 04 19;17(2):e13109. Epub 2020 Nov 19.

MRC Integrative Epidemiology Unit and Department of Population Health Sciences, University of Bristol, Bristol, UK.

Breastfeeding and human milk (HM) are critically important to maternal, infant and population health. This paper summarizes the proceedings of a workshop that convened a multidisciplinary panel of researchers to identify key priorities and anticipated breakthroughs in breastfeeding and HM research, discuss perceived barriers and challenges to achieving these breakthroughs and propose a constructive action plan to maximize the impact of future research in this field. Priority research areas identified were as follows: (1) addressing low breastfeeding rates and inequities using mixed methods, community partnerships and implementation science approaches; (2) improving awareness of evidence-based benefits, challenges and complexities of breastfeeding and HM among health practitioners and the public; (3) identifying differential impacts of alternative modes of HM feeding including expressed/pumped milk, donor milk and shared milk; and (4) developing a mechanistic understanding of the health effects of breastfeeding and the contributors to HM composition and variability. Key barriers and challenges included (1) overcoming methodological limitations of epidemiological breastfeeding research and mechanistic HM research; (2) counteracting 'breastfeeding denialism' arising from negative personal breastfeeding experiences; (3) distinguishing and aligning research and advocacy efforts; and (4) managing real and perceived conflicts of interest. To advance research on breastfeeding and HM and maximize the reach and impact of this research, larger investments are needed, interdisciplinary collaboration is essential, and the scientific community must engage families and other stakeholders in research planning and knowledge translation.
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http://dx.doi.org/10.1111/mcn.13109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988860PMC
April 2021

Racial and socioeconomic disparities in breast milk feedings in US neonatal intensive care units.

Pediatr Res 2021 01 13;89(2):344-352. Epub 2020 Nov 13.

Department of Pediatrics, Rush University Children's Hospital, Chicago, IL, USA.

Very low birth weight (VLBW; <1500 g birth weight) infants are substantially more likely to be born to black than to non-black mothers, predisposing them to potentially preventable morbidities that increase the risk for costly lifelong health problems. Mothers' own milk (MOM) may be considered the ultimate "personalized medicine" since milk composition and bioactive components vary among mothers and multiple milk constituents provide specific protection based on shared exposures between mother and infant. MOM feedings reduce the risks and associated costs of prematurity-associated morbidities, with the greatest reduction afforded by MOM through to NICU discharge. Although black and non-black mothers have similar lactation goals and initiation rates, black VLBW infants are half as likely to receive MOM at NICU discharge in the United States. Black mothers are significantly more likely to be low-income, single heads of household and have more children in the home, increasing the burden of MOM provision. Although rarely considered, the out-of-pocket and opportunity costs associated with providing MOM for VLBW infants are especially onerous for black mothers. When MOM is not available, the NICU assumes the costs of inferior substitutes for MOM, contributing further to disparate outcomes. Novel strategies to mitigate these disparities are urgently needed. IMPACT: Mother's own milk exemplifies personalized medicine through its unique biologic activity. Hospital factors and social determinants of health are associated with mother's own milk feedings for very low-birth-weight infants in the neonatal intensive care unit. Notably, out-of-pocket and opportunity costs associated with providing mother's own milk are borne by mothers. Conceptualizing mother's own milk feedings as an integral part of NICU care requires consideration of who bears the costs of MOM provision-the mother or the NICU?
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http://dx.doi.org/10.1038/s41390-020-01263-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662724PMC
January 2021

Mother's Own Milk Biomarkers Predict Coming to Volume in Pump-Dependent Mothers of Preterm Infants.

J Pediatr 2021 01 9;228:44-52.e3. Epub 2020 Sep 9.

Division of Neonatology, Department of Pediatrics, Rush University Medical Center, Chicago, IL; College of Nursing, Rush University Medical Center, Chicago, IL.

Objective: To assess serial secretory activation biomarker concentrations (sodium [Na], potassium [K], Na:K, protein, lactose, and citrate) in mother's own milk (MOM) from breast pump-dependent mothers of preterm infants to determine associations with coming to volume (CTV), defined as producing at least 500 mL/day MOM by day 14 postpartum.

Study Design: We collected serial MOM samples and pumped MOM volume data for 14 days postpartum in mothers who delivered at <33 weeks of gestation. Regression models and the Mann-Whitney U test were used to evaluate associations.

Results: Among 40 mothers, 39 (mean gestational age, 28.8 weeks; 67% overweight/obese; 59% nonwhite) had paired MOM volume and biomarker data; 33% achieved CTV between postpartum days 6 and 14. In univariate models, MOM Na on postpartum day 5 and Na:K on days 3 and 5 were associated with CTV. Mothers achieving CTV were more likely to have postpartum Na:K ≤1 on day 3 (75% vs 25%; P = .06) and ≤0.8 on day 5 (69% vs 10%; P < .01). In a multivariable regression model, day 5 Na:K (1 unit decrease in Na:K: OR, 18.7; 95% CI, 1.13-311.41; P = .049) and maternal prepregnancy body mass index (BMI) (1 unit increase in BMI: OR, 0.88; 95% CI, 0.78-0.99; P = .04) were associated with CTV between postpartum days 6 and 14.

Conclusions: Secretory activation and CTV were compromised in breast pump-dependent mothers with preterm delivery. CTV was predicted by MOM Na level and Na:K. These biomarkers have potential as objective point-of-care measures to detect potentially modifiable lactation problems in a high-risk population.
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http://dx.doi.org/10.1016/j.jpeds.2020.09.010DOI Listing
January 2021

Strategies to increase the use of mother's own milk for infants at risk of necrotizing enterocolitis.

Pediatr Res 2020 08;88(Suppl 1):21-24

Necrotizing Enterocolitis (NEC) Society, Davis, CA, USA.

High-dose mother's own milk (MOM) feedings during the first 14 days post birth reduce the risk of necrotizing enterocolitis in very low birthweight (VLBW; <1500 g birthweight). However, high-dose MOM feedings are only possible if mothers provide sufficient quantities of MOM in a timely manner, and data indicate that the lack of MOM during the early post-birth period is a global problem. This paper reviews the modifiable and unmodifiable barriers to accessing adequate quantities of MOM during the early post-birth period and proposes evidence-based strategies to increase and improve the use of MOM during the neonatal intensive care unit (NICU) hospitalization with an emphasis on the critical first 2 weeks post birth.
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http://dx.doi.org/10.1038/s41390-020-1075-3DOI Listing
August 2020

REVIEW OF OPHTHALMIC AND BREASTFEEDING MEDICINE EVIDENCE: Real and Theoretical Risks of Intravitreal Anti-Vascular Endothelial Growth Factor Administration in Lactating Women.

Retina 2020 Nov;40(11):2065-2069

Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background/purpose: There is limited research regarding the consequences of treating lactating mothers with intravitreal anti-vascular endothelial growth factor (VEGF) agents. Balancing the need for vision-saving treatment, the benefits of breastfeeding, and the concern for affecting the newborn can present a conflict for both mothers and ophthalmologists. This review summarizes the state of the literature regarding the use of intravitreal anti-VEGF agents during breastfeeding along with details about their pharmacology.

Results: Bevacizumab and aflibercept have Fc domains subjecting them to FcRn recycling and extending their half-life compared with ranibizumab which is an antibody fragment and lacks the Fc domain. Case reports and small studies have shown that ranibizumab has the lowest serum concentration after intravitreal injection and the least effect on plasma-free VEGF concentrations and breastmilk VEGF levels.

Conclusion: Clinical and pharmacologic data suggest that ranibizumab has less systemic circulation and effect on maternal serum and breastmilk VEGF levels when compared to bevacizumab and aflibercept. However, there is significant need for further research on the degree and duration to which intravitreal agents circulate systemically, what fraction is transferred into breastmilk and is absorbed, and whether this results in any functional adverse effects to the infant. Other factors to consider in the medical decision-making of lactating mothers necessitating intravitreal anti-VEGF treatment include the gestational and post-natal age of the child and whether it is feasible to avoid breastfeeding for the half-life duration of the intravitreal agent rather than ceasing breastfeeding altogether.
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http://dx.doi.org/10.1097/IAE.0000000000002946DOI Listing
November 2020

The Economic Impact of Donor Milk in the Neonatal Intensive Care Unit.

J Pediatr 2020 09 15;224:57-65.e4. Epub 2020 Jul 15.

Department of Pediatrics, Section of Neonatology, Rush University Medical Center, Chicago, IL.

Objective: To assess the cost-effectiveness of mother's own milk supplemented with donor milk vs mother's own milk supplemented with formula for infants of very low birth weight in the neonatal intensive care unit (NICU).

Study Design: A retrospective analysis of 319 infants with very low birth weight born before (January 2011-December 2012, mother's own milk + formula, n = 150) and after (April 2013-March 2015, mother's own milk + donor milk, n = 169) a donor milk program was implemented in the NICU. Data were retrieved from a prospectively collected research database, the hospital's electronic medical record, and the hospital's cost accounting system. Costs included feedings and other NICU costs incurred by the hospital. A generalized linear regression model was constructed to evaluate the impact of feeding era on NICU total costs, controlling for neonatal and sociodemographic risk factors and morbidities. An incremental cost-effectiveness ratio was calculated for each morbidity that differed significantly between feeding eras.

Results: Infants receiving mother's own milk + donor milk had a lower incidence of necrotizing enterocolitis (NEC) than infants receiving mother's own milk + formula (1.8% vs 6.0%, P = .048). Total (hospital + feeding) median costs (2016 USD) were $169 555 for mother's own milk + donor milk and $185 740 for mother's own milk + formula (P = .331), with median feeding costs of $1317 and $936, respectively (P < .001). Mother's own milk + donor milk was associated with $15 555 lower costs per infant (P = .045) and saved $1812 per percentage point decrease in NEC incidence.

Conclusions: The additional cost of a donor milk program was small compared with the cost of a NICU hospitalization. After its introduction, the NEC incidence was significantly lower with small cost savings per case. We speculate that NICUs with greater NEC rates may have greater cost savings.
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http://dx.doi.org/10.1016/j.jpeds.2020.04.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484385PMC
September 2020

Early Use of Antibiotics Is Associated with a Lower Incidence of Necrotizing Enterocolitis in Preterm, Very Low Birth Weight Infants: The NEOMUNE-NeoNutriNet Cohort Study.

J Pediatr 2020 12 14;227:128-134.e2. Epub 2020 Jun 14.

Department of Neonatology, Shenzhen Bao'an Maternal and Child Health Hospital, Shenzhen, China.

Objective: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC).

Study Design: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition.

Results: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001).

Conclusions: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686259PMC
December 2020

Measures of Secretory Activation for Research and Practice: An Integrative Review.

Breastfeed Med 2020 04 9;15(4):191-212. Epub 2020 Mar 9.

Department of Women and Children's Nursing, College of Nursing, Rush University, Chicago, Illinois.

Maternal concern about inadequate milk volume commonly emerges in the first 2 weeks postpartum, a critical lactation period that includes secretory activation. This review summarizes the biology of secretory activation and evaluates the accuracy and feasibility of published measures of secretory activation. A systematic search of measures of secretory activation for mothers of healthy term and preterm infants yielded 62 abstracts. Following additional screening, 15 publications qualified for quantitative synthesis review and were evaluated with respect to accuracy (validated with another measure of secretory activation in the same mother) and feasibility (accessibility, cost, and ease of use). (MP) is the most feasible measure, but its accuracy has not been established. have been validated with maternal milk-borne biomarkers in breastfeeding, and breast pump-dependent mothers and normal values have been published. Accuracy of concentrations has not been established for secretory activation and lacks feasibility. are the accurate standard to which other measures are compared but currently lack feasibility for routine use. Use of secretory activation measures can personalize lactation care by matching maternal risk with appropriate diagnostics. Priorities for research and practice include validation of MP as a population-based screening tool, implementation of techniques that measure patterns of increase in milk volume for moderate risk populations, and the development of milk biomarker science for point-of-care use in the most complicated lactation scenarios.
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http://dx.doi.org/10.1089/bfm.2019.0247DOI Listing
April 2020

Mother's own milk dose is associated with decreased time from initiation of feedings to discharge and length of stay in infants with gastroschisis.

J Perinatol 2020 08 28;40(8):1222-1227. Epub 2020 Jan 28.

Section of Neonatology, Department of Pediatrics, Rush University Medical Center, Chicago, IL, 60612, USA.

Objective: To determine if mother's own milk (MOM) dose after gastroschisis repair is associated with time from feeding initiation to discharge. Secondary outcomes included parenteral nutrition (PN) duration and length of stay (LOS).

Study Design: Retrospective study of 44 infants with gastroschisis examined demographics, gastroschisis type, PN days, timing of nutrition milestones, feeding composition, and LOS.

Results: MOM dose was significantly associated with shorter time to discharge from feeding initiation (adjusted hazard ratio [HR] for discharge per 10% increase in MOM dose, 1.111; 95% CI, 1.011-1.220, p = 0.029). MOM dose was also significantly associated with shorter LOS (adjusted HR for discharge per 10% increase in MOM dose, 1.130; 95% CI, 1.028-1.242, p = 0.011).

Conclusions: MOM dose was significantly associated with a decrease in time to discharge from feeding initiation and LOS in a dose-dependent manner. Mothers of gastroschisis patients should receive education and proactive lactation support to optimize MOM volume for feedings.
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http://dx.doi.org/10.1038/s41372-020-0595-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223788PMC
August 2020

Correction: Mediators of racial and ethnic disparity in mother's own milk feeding in very low birth weight infants.

Pediatr Res 2019 Dec;86(6):786

Department of Pediatrics, Rush University Children's Hospital, Chicago, IL, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41390-019-0576-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312630PMC
December 2019

Infant, Maternal, and Neighborhood Predictors of Maternal Psychological Distress at Birth and Over Very Low Birth Weight Infants' First Year of Life.

J Dev Behav Pediatr 2019 Oct/Nov;40(8):613-621

Department of Pediatrics, Rush University Medical Center, Chicago, IL.

Objective: To use a social-ecological conceptualization to analyze change of maternal distress, defined as depression, anxiety, and perinatal-specific post-traumatic stress (PPTS), across very low birth weight (VLBW) infants' first year of life and to identify infant, maternal, and neighborhood predictors of these changes over time.

Methods: Mothers of VLBW infants (n = 69) completed psychological distress questionnaires 2 to 4 weeks after infant birth, 2 weeks before infant discharge from neonatal intensive care unit, and at infants' 4- and 8-month corrected age (age adjusted for prematurity). Infant and maternal sociodemographic data were collected from medical chart review. Neighborhood data were obtained through US census data. Multilevel linear growth modeling was used to (1) predict unstandardized estimates of mothers' initial levels of depression, anxiety, and PPTS at the time of infant's birth and the rate of change of these markers of distress over time and (2) model unstandardized estimates of infant, maternal, and neighborhood as predictors of distress at infants' birth and change over time.

Results: Unstandardized estimates from multilevel linear growth modeling revealed depression (-2.8), anxiety (-1.4), and PPTS (-0.7) declined over infants' first year of life (<0.001). Mothers residing in lower-income homes and neighborhoods, respectively, reported lower anxiety (-11.2, p = 0.03) and PPTS (-31.1, p = 0.01) at infant birth. Greater infant birth weight predicted both lower anxiety (-0.02, p = 0.02) and lower PPTS (-0.02, p = 0.005).

Conclusion: Mothers psychologically recover over VLBW infants' first year of life. Results add to a building literature about socioeconomically disadvantaged mothers of preterm infants, reporting lower distress; this warrants additional research.
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http://dx.doi.org/10.1097/DBP.0000000000000704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800614PMC
August 2020

Priorities for Contraception and Lactation Among Breast Pump-Dependent Mothers of Premature Infants in the Neonatal Intensive Care Unit.

Breastfeed Med 2019 09 23;14(7):448-455. Epub 2019 May 23.

Rush University College of Nursing, Chicago, Illinois.

Determine the knowledge and priorities for postpartum contraception and lactation in mothers of premature infants. Twenty-five mothers of premature infants (mean gestational age = 29.9 weeks) hospitalized in a tertiary neonatal intensive care unit (NICU) participated in a multi-methods study using a multiple-choice contraceptive survey and qualitative interview in the first 2 weeks postpartum. Data were analyzed using content analysis and descriptive statistics. Although 60% of mothers planned to use contraception, all questioned the timing of postpartum contraceptive counseling while recovering from a traumatic birth and coping with the critical health status of the infant. All mothers prioritized providing mothers' own milk (MOM) over the use of early hormonal contraception because they did not want to "take any risks" with their milk. They had limited knowledge of risks for repeat preterm birth (e.g., prior preterm birth:  = 13, 52%; multiple birth:  = 9, 36%; no knowledge:  = 3, 12%); only two mothers (0.08%) were counseled about the risks of a short interpregnancy interval. The context of the infants' NICU admission and the mother's desire to "do what is best for the baby" by prioritizing MOM should be integrated into postpartum contraceptive counseling for this population.
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http://dx.doi.org/10.1089/bfm.2019.0007DOI Listing
September 2019

Mediators of racial and ethnic disparity in mother's own milk feeding in very low birth weight infants.

Pediatr Res 2019 04 18;85(5):662-670. Epub 2019 Jan 18.

Department of Pediatrics, Rush University Children's Hospital, Chicago, IL, USA.

Background: Despite high initiation rates for mother's own milk (MOM) provision, MOM feeding at discharge from the neonatal intensive care unit (NICU) drops precipitously and reveals a racial/ethnic disparity. This study sought to identify factors that (1) predict MOM feeding at NICU discharge, and (2) mediate racial/ethnic disparity in MOM feeding at discharge.

Methods: Secondary analysis of prospective cohort study of 415 mothers and their very low birth weight infants. Variables were grouped into five categories (demographics, neighborhood structural, social, maternal health, and MOM pumping). Significant predictors from each category were entered into a multivariable logistic regression model.

Results: Although 97.6% of infants received MOM feedings, black infants were significantly less likely to receive MOM feeding at discharge. Positive predictors were daily pumping frequency, reaching pumped MOM volume ≥500 mL/day by 14 days, and maternal age. Negative predictors were low socioeconomic status (SES) and perceived breastfeeding support from the infant's maternal grandmother. Low SES, maternal age, and daily pumping frequency mediated the racial/ethnic differences.

Conclusions: Multiple potentially modifiable factors predict MOM feeding at NICU discharge. Importantly, low SES, pumping frequency, and maternal age were identified as the mediators of racial and ethnic disparity. Strategies to mitigate the effects of modifiable factors should be developed and evaluated in future research.
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http://dx.doi.org/10.1038/s41390-019-0290-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435382PMC
April 2019

Impact of Donor Milk on Short- and Long-Term Growth of Very Low Birth Weight Infants.

Nutrients 2019 Jan 22;11(2). Epub 2019 Jan 22.

Department of Pediatrics, Section of Neonatology, Rush University Medical Center, Chicago, IL 60612, USA.

Mother's own milk (MOM) reduces the risk of morbidities in very low birth weight (VLBW) infants. When MOM is unavailable, donor breastmilk (DM) is used, with unclear impact on short- and long-term growth. This retrospective analysis compared anthropometric data at six time points from birth to 20⁻24 months corrected age in VLBW infants who received MOM supplements of preterm formula ( = 160) versus fortified DM ( = 161) during neonatal intensive care unit (NICU) hospitalization. The cohort was 46% female; mean birth weight and gestational age (GA) were 998 g and 27.3 weeks. Multilevel linear growth models assessed changes in growth -scores short-term (to NICU discharge) and long-term (post-discharge), controlling for amount of DM or formula received in first 28 days of life, NICU length of stay (LOS), birth GA, and sex. -scores for weight and length decreased during hospitalization but increased for all parameters including head circumference post-discharge. Short-term growth was positively associated with LOS and birth GA. A higher preterm formula proportion, but not DM proportion, was associated with slower rates of decline in short-term growth trajectories, but feeding type was unrelated to long-term growth. In conclusion, controlling for total human milk fed, DM did not affect short- or long-term growth.
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http://dx.doi.org/10.3390/nu11020241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412258PMC
January 2019

Time to Full Enteral Feeding for Very Low-Birth-Weight Infants Varies Markedly Among Hospitals Worldwide But May Not Be Associated With Incidence of Necrotizing Enterocolitis: The NEOMUNE-NeoNutriNet Cohort Study.

JPEN J Parenter Enteral Nutr 2019 07 22;43(5):658-667. Epub 2018 Nov 22.

Department of Neonatology, Shenzhen Bao'an Maternal and Child Health Hospital, Shenzhen, China.

Background: Transition to enteral feeding is difficult for very low-birth-weight (VLBW; ≤1500 g) infants, and optimal nutrition is important for clinical outcomes.

Method: Data on feeding practices and short-term clinical outcomes (growth, necrotizing enterocolitis [NEC], mortality) in VLBW infants were collected from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2947). Specifically, 5 NICUs in Guangdong province in China (GD), mainly using formula feeding and slow feeding advancement (n = 1366), were compared with the remaining NICUs (non-GD, n = 1581, Oceania, Europe, United States, Taiwan, Africa) using mainly human milk with faster advancement rates.

Results: Across NICUs, large differences were observed for time to reach full enteral feeding (TFF; 8-33 days), weight gain (5.0-14.6 g/kg/day), ∆z-scores (-0.54 to -1.64), incidence of NEC (1%-13%), and mortality (1%-18%). Adjusted for gestational age, GD units had longer TFF (26 vs 11 days), lower weight gain (8.7 vs 10.9 g/kg/day), and more days on antibiotics (17 vs 11 days; all P < .001) than non-GD units, but NEC incidence and mortality were similar.

Conclusion: Feeding practices for VLBW infants vary markedly around the world. Use of formula and long TFF in South China was associated with more use of antibiotics and slower weight gain, but apparently not with more NEC or higher mortality. Both infant- and hospital-related factors influence feeding practices for preterm infants. Multicenter, randomized controlled trials are required to identify the optimal feeding strategy during the first weeks of life.
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http://dx.doi.org/10.1002/jpen.1466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531355PMC
July 2019

NICU human milk dose and health care use after NICU discharge in very low birth weight infants.

J Perinatol 2019 01 19;39(1):120-128. Epub 2018 Oct 19.

Rush University Medical Center, Chicago, IL, USA.

Objective: To determine the association between human milk (HM) dose and health care utilization at one and 2 years of life in very low birth weight (birth weight < 1500 g; VLBW) infants.

Study Design: This study included 345 VLBW infants enrolled in a prospective observational cohort study (2008-2012) who completed a neonatal high-risk follow-up clinic visit. Subsequent health care utilization included hospitalizations, emergency department visits, pediatric subspecialists, and specialized therapies.

Results: Each 10 mL/kg/day increase in HM in the first 14 days of life was associated with 0.26 fewer hospitalizations (p = 0.04) at 1 year and 0.21 fewer pediatric subspecialist types (p = 0.04) and 0.20 fewer specialized therapy types (p = 0.04) at 2 years.

Conclusion: HM dose in early life for VLBW infants was an independent predictor of the number of hospitalizations at 1 year and types of pediatric subspecialists and specialized therapies at 2 years of life.
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http://dx.doi.org/10.1038/s41372-018-0246-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298834PMC
January 2019

Predictors of Prolonged Breast Milk Provision to Very Low Birth Weight Infants.

J Pediatr 2018 11 28;202:23-30.e1. Epub 2018 Aug 28.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Department of Pediatrics, Duke University School of Medicine, Durham, NC. Electronic address:

Objective: To identify factors associated with prolonged maternal breast milk (BM) provision in very low birth weight (VLBW) infants.

Study Design: This was a cohort study of VLBW infants who initially received maternal BM and were born at one of 197 neonatal intensive care units managed by the Pediatrix Medical Group from 2010 to 2012. We used multivariable logistic regression to identify demographic, clinical, and maternal factors associated with provision of maternal BM on day of life (DOL) 30 and at discharge.

Results: Median gestational age for all infants was 28 weeks (25, 75 percentiles: 26, 30), and median maternal age was 28 years (23, 33). Of 8806 infants, 6261 (71%) received maternal BM on DOL 30, and 4003 of 8097 (49%) received maternal BM at discharge to home. Predictors of maternal BM provision at DOL 30 included increased maternal age, white maternal race, absence of history of necrotizing enterocolitis or late-onset sepsis, higher household income, lower education level, lack of donor BM exposure, and lower gestational age.

Conclusions: Our results suggest that maternal-infant demographic and clinical factors and household neighborhood socioeconomic characteristics were associated with provision of maternal BM at 30 postnatal days to VLBW infants. Identification of these factors allows providers to anticipate mothers' needs and develop tailored interventions designed to improve rates of prolonged maternal BM provision and infant outcomes.
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http://dx.doi.org/10.1016/j.jpeds.2018.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203611PMC
November 2018

High-Dose Human Milk Feedings Decrease Oxidative Stress in Premature Infant.

JPEN J Parenter Enteral Nutr 2019 01 15;43(1):126-132. Epub 2018 May 15.

Department of Pediatrics, Section of Neonatology, Rush University Children's Hospital, Chicago, Illinois, USA.

Background: Premature infants are susceptible to oxidative stress, increasing the risk for serious morbidities. High-dose human milk (HM) feedings decrease morbidity risks and may reduce oxidative stress in this population. The purpose of this study was to compare oxidative stress using serial urinary F -isoprostane concentrations in predominantly HM and preterm formula (PF)-fed premature infants over the first 21 days of life (DOL), while controlling for perinatal oxidative stress exposures including bovine-based human milk fortifier (HMF) or PF introduction to predominantly HM-fed infants.

Methods: This was a quasi-experimental design that categorized 22 premature infants into mutually exclusive comparison groups based on exposure to HM and PF. Serial urine samples (before and after first feeding, and DOL 7, 14, and 21) were used to determine urine F -isoprostane concentrations measured by enzyme-linked immunosorbent assays. We analyzed data using Mann-Whitney U test, Wilcoxon rank test, and multilevel models.

Results: Comparing the predominantly HM-fed and predominantly PF-fed groups over time, median F -isoprostane concentrations decreased significantly in the predominantly HM group (P = .003) and increased significantly in the predominantly PF group (P = .01). Perinatal oxidant exposures and the introduction of HMF did not affect results.

Conclusions: Our results demonstrate that predominantly HM feedings were associated with decreased oxidative stress, whereas PF feedings increased oxidative stress in premature infants, even after controlling for perinatal oxidant exposures of HMF or PF introduction.
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http://dx.doi.org/10.1002/jpen.1178DOI Listing
January 2019

Human Milk Biomarkers of Secretory Activation in Breast Pump-Dependent Mothers of Premature Infants.

Breastfeed Med 2018 06 30;13(5):352-360. Epub 2018 Apr 30.

1 Department of Pediatrics, Section of Neonatology, Rush University Medical Center , Chicago, Illinois.

Objective: Mothers of premature infants confront barriers to coming to volume (CTV; ≥500 mL/day mother's own milk [MOM] by postpartum day 14), a strong predictor of continued MOM provision at neonatal intensive care unit (NICU) discharge. We sought to determine concentrations of secretory activation biomarkers (MOM sodium, total protein, lactose, and citrate) during the first 14 postpartum days and to describe relationships among these biomarkers, pumped MOM volume, CTV, and pumping frequency.

Study Design: This descriptive observational study collected serial MOM samples, pumped MOM volume, and pumping frequency during the first 14 postpartum days in 16 breast pump-dependent mothers who delivered <33 weeks gestation. Daily biomarker concentrations were compared to published normal values for mothers of term infants. Relationships among biomarkers, pumped MOM volume, and pumping frequency were determined.

Results: On postpartum day 5, only 40% of MOM samples revealed normal concentrations of all four biomarkers, and normalcy was not maintained throughout the first 14 days. All eight mothers (50%) who achieved CTV had normal concentrations for four biomarkers at 5.4 ± 3.5 days postpartum and had more cumulative pumping sessions by day 5 (p = 0.03). A dose-response relationship between number of normal biomarkers and pumped MOM volume was demonstrated for postpartum days 3 (p = 0.01) and 5 (p = 0.04).

Conclusion: Secretory activation is delayed in mothers who deliver prematurely and is closely tied to CTV, MOM volume, and pumping frequency. MOM biomarkers hold promise as objective research outcome measures and for point-of-care testing to identify and proactively manage mothers at risk for compromised lactation.
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http://dx.doi.org/10.1089/bfm.2017.0183DOI Listing
June 2018

Milk Volume at 2 Weeks Predicts Mother's Own Milk Feeding at Neonatal Intensive Care Unit Discharge for Very Low Birthweight Infants.

Breastfeed Med 2018 03 29;13(2):135-141. Epub 2018 Jan 29.

1 Section of Neonatology, Department of Pediatrics, Rush University Medical Center , Chicago, Illinois.

Objective: This study sought to determine the maternal prepregnancy, pregnancy, and delivery risk factors that predicted coming to volume (CTV; achieving pumped mother's own milk [MOM] volume ≥500 mLs/day) and the continuation of MOM provision through to discharge from the neonatal intensive care unit (NICU) in mothers and their very low birthweight (VLBW; <1,500 g at birth) infants.

Study Design: Secondary analysis of prospectively collected data from 402 mothers of VLBW infants admitted to an urban NICU, including detailed MOM pumping records for a subset (51%) of the cohort. Analyses included inverse probability weighting, multivariate regression, and chi-square statistics.

Results: In this high-risk cohort (51.2% black, 27.1% Hispanic, 21.6% white/Asian; 72.6% low income; 61.4% overweight/obese prepregnancy), CTV by day 14 was the strongest predictor of MOM feeding at NICU discharge (odds ratio [OR] 9.70 confidence interval [95% CI] 3.86-24.38, p < 0.01.). Only 39.5% of mothers achieved CTV by postpartum day 14, an outcome that was predicted by gestational age at delivery (OR 1.41, 95% CI 1.15-1.73, p < 0.01), being married (OR 3.66, 95% CI 1.08-12.39, p = 0.04), black race (OR 7.70, 95% CI 2.05-28.97, p < 0.01), cesarean delivery (OR 0.22, 95% CI 0.08-0.63, p = 0.01), and chorioamionitis (OR 0.14, 95% CI 0.02-0.82, p = 0.03).

Conclusion: Continued provision of MOM at NICU discharge can be predicted in the first 14 postpartum days on the basis of achievement of CTV. We posit that CTV can serve as a quality indicator for improving MOM feedings in the NICU and that lactation support resources should target this early critical postbirth period.
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http://dx.doi.org/10.1089/bfm.2017.0159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863077PMC
March 2018

Human milk and necrotizing enterocolitis.

Semin Pediatr Surg 2018 Feb 6;27(1):34-38. Epub 2017 Nov 6.

Divisions of Neonatology & Pediatric Gastroenterology, Hepatology and Nutrition, University of California San Diego, Rady Children's Hospital of San Diego, San Diego, California.

NEC is a multifactorial disease that occurs when multiple risk factors and/or stressors overlap, leading to profound inflammation and intestinal injury. Human milk feedings, both from the infant's mother and donor human milk, have been associated with reductions in NEC in preterm infants. This article will review the protective factors in human milk, clinical studies of human milk and NEC, and practices to enhance human milk use in neonatal intensive care units.
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http://dx.doi.org/10.1053/j.sempedsurg.2017.11.007DOI Listing
February 2018

Reducing Incidence of Necrotizing Enterocolitis.

Clin Perinatol 2017 09 5;44(3):683-700. Epub 2017 Jul 5.

Department of Pediatrics, Rush University Children's Hospital, 1653 West Congress Parkway, Pavilion 357, Chicago, IL 60612, USA.

Necrotizing enterocolitis (NEC) is a multifactorial disease that occurs when multiple risk factors and/or stressors overlap, leading to profound inflammation and intestinal injury. Due to its multifactorial nature, there has been much uncertainty in identifying clear strategies for prevention of NEC. Despite these obstacles, the incidence of NEC has gradually been decreasing over the past 10 years, in part due to quality improvement (QI) initiatives to prevent NEC. Current QI strategies primarily target the various predisposing conditions. This article reviews the evidence on which QI interventions to prevent NEC have been based and provides examples of successful QI interventions.
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http://dx.doi.org/10.1016/j.clp.2017.05.004DOI Listing
September 2017

NICU Human Milk Dose and 20-Month Neurodevelopmental Outcome in Very Low Birth Weight Infants.

Neonatology 2017 3;112(4):330-336. Epub 2017 Aug 3.

Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.

Background: The association between human milk (HM) feeding in the NICU and neurodevelopmental (ND) outcome in very low birth weight (VLBW) infants is unclear. Limitations of previous studies include a lack of exact estimates of HM dose and of generalizability to minority populations.

Objective: To determine the impact on ND outcome of an exact dose of HM received in the NICU in a diverse, contemporary cohort of VLBW infants.

Methods: We included 430 VLBW infants born in the period 2008-2012 for whom the mean daily dose (DD) of HM received during the stay in the NICU (NICU HM-DD) was calculated prospectively from the daily nutritional intake from admission to discharge. Outcomes included Bayley-III index scores at 20 months' corrected age (CA) as assessed upon ND follow-up, which were collected retrospectively. Multivariable linear regression analyses controlled for neonatal and social risk factors.

Results: Each 10 mL/kg/day increase in NICU HM-DD was associated with a 0.35 increase in cognitive index score (95% CI [0.03-0.66], p = 0.03), but no significant associations were detected for the language or motor indices.

Conclusions: There is a significant dose-dependent association between NICU HM intake and cognitive scores at 20 months' CA. Further follow-up will determine whether these findings persist at school age, and could help alleviate the special-education and health-care burden in this population.
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http://dx.doi.org/10.1159/000475834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683911PMC
July 2018

A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants.

Neonatology 2017 3;112(4):354-358. Epub 2017 Aug 3.

Department of Pediatrics, Children's Mercy, Kansas City, MO, USA.

Background: The genetic basis of sepsis susceptibility in preterm infants remains understudied. Herein, we investigated the nucleotide binding-oligomerization domain (NOD)-like receptor (NLR) family of immune receptors as putative loci for preterm sepsis susceptibility.

Objective: To determine whether single nucleotide polymorphisms (SNPs) in NLR genes are associated with blood stream infections (BSI) in premature infants.

Methods: An international cohort of infants with gestational age (GA) <35 weeks were genotyped for SNPs in the ATG16L1, CARD8, NLRP3, NOD2, and NOD1 genes. χ2 and logistic regression analyses were used to examine relationships between NLR variants and BSI.

Results: Among 764 infants, 138 developed BSI, 113 had gram-positive bacterial (GPB) BSI, and 28 had gram-negative bacterial (GNB) BSI. Infants with BSI had a lower birth weight and GA (p < 0.001), but did not differ in gender, race, or chorioamnionitis. NLR variants were not associated with GPB or GNB BSI in the entire cohort. The CC genotype of the NOD1 SNP (rs6958571) was associated with increased GPB BSI in extremely low birth weight (ELBW, birth weight <1,000 g) infants (OR = 3.3, 95% CI: 1.4-7.5, p = 0.003, n = 362) and in Caucasian infants (OR = 2.5, 95% CI: 1.2-5.4, p = 0.016, n = 535). Regression models adjusting for clinical variables identified ELBW status and the NOD1 CC genotype as risk factors for GPB BSI in Caucasian infants.

Conclusions: In this study investigating relationships between NLR variants and sepsis in infants with GA <35 weeks, the NOD1 (rs6958571) SNP was associated with GPB BSI in Caucasian infants and ELBW infants. Replication of our results in an independent cohort would support a role for NLR variants in determining sepsis risk in ELBW infants.
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http://dx.doi.org/10.1159/000477433DOI Listing
July 2018
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