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. 2016 Sep 6;19(1):36–44. doi: 10.1177/1099800416664585

Maternal Interleukin Genotypes Are Associated With NICU Outcomes Among Low-Birth-Weight Infants

Kelley L Baumgartel 1,✉, Maureen W Groer 2,3, Susan M Cohen 1, Dianxu Ren 4, Diane L Spatz 5, Yvette P Conley 1
PMCID: PMC5406263  NIHMSID: NIHMS856210  PMID: 27605567

Abstract

Background:

Maternal interleukin (IL) single nucleotide polymorphisms (SNPs) are associated with obstetrical outcomes. Conversely, infant SNPs are associated with subsequent neonatal intensive care unit (NICU) outcomes. Little is known about relationships between maternal SNPs and neonatal outcomes.

Purpose:

To examine the relationships between maternal IL genotypes and neonatal outcomes.

Methods:

An ancillary study was conducted among mothers (N = 63) who delivered very low-birth-weight infants (N = 74). Maternal DNA was extracted from breast milk and genotyped. Outcomes included fecal calprotectin, length of stay, scores for neonatal acute physiology with perinatal extension (SNAPPE-II), weight gain, oxygen needs, necrotizing enterocolitis, intraventricular hemorrhage, sepsis, retinopathy of prematurity, blood transfusions, and feeding intolerance. Multivariate analyses examined the relationships between maternal IL SNPs and outcomes, controlling for gestational age and the ratio of maternal milk to total milk.

Results:

Absence of a minor allele in 2 IL6 SNPs was associated with fecal calprotectin (p = .0222, p = .0429), length of stay (p = .0158), SNAPPE-II (p = .0497), weight gain (p = .0272), and days on oxygen (p = .0316). IL6 genotype GG (rs1800795) was associated with length of stay (p = .0034) and calprotectin (p = .0213). Minor-allele absence in 2 IL10 SNPs was associated with days on oxygen (p = .0320). There were associations between IL10 genotype TT (rs1800871) and calprotectin (p = .0270) and between IL10 genotypes AA (rs1800872 and rs1800896) and calprotectin (p = .0158, p = .0045).

Conclusion:

Maternal IL SNPs are associated with NICU outcomes. A potential clinical application includes an antenatal risk profile to identify neonatal needs.

Keywords: prematurity, single nucleotide polymorphism, interleukin, calprotectin, SNAPPE-II, human milk

Prematurity-related complications are the leading cause of death for children under 5 years old, and preterm births continue to increase worldwide (World Health Organization, n.d.). Complications from prematurity include, but are not limited to, retinopathy, necrotizing enterocolitis (NEC), and respiratory distress, and the associated stays in the neonatal intensive care unit (NICU) cost the U.S. health-care system more than US $26 billion annually (Behrman & Butler, 2007).

Particular maternal cytokines have been implicated in obstetrical complications including preterm birth (Neta et al., 2010; Sorokin et al., 2010) and small-for-gestational-age (SGA) infant (Neta et al., 2010). Cytokines are an integral part of the inflammatory cascade. Interleukin (IL)-4, a proinflammatory cytokine, induces both antibody and immunoglobulin E production. Single nucleotide polymorphisms (SNPs) in the promoter region of the IL4 gene have been associated with varying levels of IL-4 (Cabantous et al., 2009; Cabantous et al., 2015; Nguyen et al., 2004); furthermore, particular maternal IL4 genotypes are associated with obstetrical complications, including preterm birth (Harmon et al., 2013) and infant SGA (Engel et al., 2005). IL-6 is a pleiotropic cytokine that is poorly regulated in preterm infants (Currie et al., 2011) and induces monoclonal antibody growth. SNPs in the promoter region of the IL6 gene influence IL-6 levels (Malarstig, Lindahl, Wallentin, & Siegbahn, 2006), and altered maternal IL-6 production is associated with obstetrical complications, including preterm labor (Chaemsaithong et al., 2016; Lee et al., 2007). Particular maternal genetic variations of IL6 are also associated with spontaneous preterm birth (Moura et al., 2009) and SGA among term infants (Harmon et al., 2014). IL-10 is a regulatory cytokine, and SNPs in the promoter region of the IL10 gene are associated with IL-10 levels (Capasso et al., 2007; Lowe, Galley, Abdel-Fattah, & Webster, 2003; Qaddourah et al., 2014; Yilmaz, Yentur, & Saruhan-Direskeneli, 2005). Maternal IL10 genetic variation has been associated with pregnancy loss (Cochery-Nouvellon et al., 2009; Qaddourah et al., 2014), perhaps due to the role of IL-10 in maintaining maternal–fetal tolerance (Denney et al., 2011).

Much of the work surrounding maternal IL polymorphisms and/or IL levels focuses on obstetrical outcomes. To our knowledge, there has never been a study that examined the relationship between maternal IL4, IL6, and/or IL10 genotypes and subsequent NICU complications. The purpose of this study was to examine the relationships between maternal IL4, IL6, and IL10 genotypes and NICU outcomes. The potential utility of this research includes infant prognoses and precision care for high-risk infants.

Material and Method

Subjects

This ancillary study included women (N = 64) who delivered infants (N = 73, including multiples) with a birth weight <1,500 g at Tampa General Hospital (Tampa, FL; Groer et al., 2014). The purpose of the parent study was to examine health outcomes of preterm infants in relationship to the volume of maternal milk and exposure to cytokines, chemokines, and growth factors. Mothers with HIV and infants with major congenital anomalies were excluded from enrollment. Also excluded were infants whom the neonatologist determined to be too critical to survive. The University of South Florida’s Institutional Review Board (IRB) approved all aspects of the parent study. We obtained material transfer permission from the University of Pittsburgh prior to shipping samples from the University of South Florida College of Nursing to the University of Pittsburgh and obtained separate IRB approval from the University of Pittsburgh, which added genomic data collection to the parent project.

The following maternal variables had been collected by the parent-study research staff and were available for analyses: maternal age, parity, income, education, ethnicity, race, marital status, working status, and pregnancy history. Medical records provided information about the labor and delivery of the infant(s), and the following information about infants were collected from the NICU medical record: sex, ethnicity, gestational age at birth, birth weight, Apgar scores, scores for neonatal acute physiology with perinatal extension-II (SNAPPE-IIs), ratio of mother’s own milk to total milk administered, length of stay, weight gain at 6 weeks, and days on oxygen. Dichotomous NICU outcome variables included sepsis, retinopathy of prematurity, NEC, intraventricular hemorrhage, blood transfusions, and feeding intolerance. Infants were enrolled in the study as soon as possible after NICU admission. Weekly maternal milk and infant stool samples were collected in tandem longitudinally, and we included 3 weeks of data in this ancillary study.

DNA Extraction and Genotyping

Maternal genomic DNA was extracted from breast milk whey using Qiagen DNA Extraction Mini Kit (Baumgartel, 2016). We collected genotype data using TaqMan allele discrimination assays to genotype seven functional promoter polymorphisms of IL4 (rs2070874, rs2243250), IL6 (rs1800795, rs1800796), and IL10 (rs1800871, rs1800872, rs1800896). We performed TaqMan allelic discrimination with the ABI Prism 7000 Sequence Detection System and SDS software v1.2.3 (Applied Biosystems Inc., Carlsbad, CA). We included negative controls and repeated a portion of the samples to confirm that they repeatedly discriminated into the same genotype. We also included duplicates and performed independent blinded double calls. For each SNP, we evaluated Hardy–Weinberg equilibrium (HWE), reexamining blinded raw data for the SNPs where HWE was violated to rule out genotyping error.

Infant Fecal Calprotectin

Researchers have used fecal calprotectin as a biomarker of inflammation within the preterm population, as calprotectin is an accurate indicator of neutrophil migration toward the gastrointestinal (GI) tract (Kapel et al., 2005). Weekly stool samples were stored at room temperature until they were transported to the laboratory for processing and frozen at −80°C until analysis (Groer, Ashmeade, Louis-Jacques, Beckstead, & Ming, 2016). Investigators weighed out 100 mg of stool, placed it in a 15-ml conical tube, and agitated it with a wooden stirrer. Extraction buffer was added and the sample vortexed to form a fine slurry, then placed on a shaker for 25 min. From this slurry, 1 ml was removed and centrifuged at 10,000 g for 20 min. The supernatant was removed for analysis by ELISA (Calprest, Eurospital, Trieste, Italy). Calprotectin was expressed as microgram/gram of stool. Every assay included a standard curve and quality controls, and all samples were done in duplicate. Intra-assay coefficient of variation was 7.7%.

SNAPPE-II

SNAPPE-II is a physiology-based admission score that uses neonatal vital signs and blood results to characterize neonatal mortality risk within the first 12 hr of life (Richardson, Cocoran, Escobar, & Lee, 2001). SNAPPE-II is an extension of the score for neonatal acute physiology-II and has a higher discrimination than that score. University of South Florida College of Nursing research staff calculated the SNAPPE-II for each participating infant from data available in the medical record.

Statistical Analyses

We performed all statistical analyses using SAS (v. 9.4). We assessed univariate outliers using frequency tables and graphical methods including histograms and normal probability plots and multivariate outliers using scatterplots. We assessed missing data for both amount (percentage) and pattern (random vs. nonrandom). In addition to the Shapiro–Wilk test, we evaluated normality graphically and at each weekly time point with frequency histograms and normal probability plots. To assess linearity, independence, and homoscedasticity, we evaluated bivariate scatterplots.

We first performed univariate analyses for each association and included any relationship with a p value ≤ .20 in multivariate regression models, where we considered p ≤ .05 significant. To examine the relationships between maternal SNPs and categorical infant outcomes, we used Fisher’s exact test. Due to the small sample size and the need for subset analyses based on race/ethnicity, we included analyses for minor-allele absence. We examined multivariate models that included the total population using both minor-allele absence and genotype as an independent variable. We chose this method because including the total population increased our sample size, giving more power to examine genotype-specific relationships. Multivariate analyses controlled for both gestational age and the ratio of maternal milk to total milk administered. We examined continuous outcomes using multiple linear regression and binary outcomes with multiple logistical regression.

Results

The average maternal age of participants was 28.3 years, and more of the mothers identified themselves as African American (39.7%) than any other race or ethnicity (see Table 1 for maternal demographic and delivery characteristics). The average gestational age of infants at delivery was 28 weeks, and average birth weight was 1,069 g (see Table 2 for infant characteristics and NICU outcomes). The cesarean section rate was approximately 76%. Three SNPs violated HWE: rs2070874, rs2243250, rs1800796 (see Table 3 for genotype frequencies and HWE). The mean day of life for entry into Week 1 of data collection was 5.4 ± 0.04 days and the mean corrected gestational age at that time was 29 ± 0.36 weeks.

Table 1.

Maternal Demographic and Delivery Characteristics.

Characteristic n (%) or Mean ± SD
Age, years 28.3 ± 6.8
Total pregnancies 3.1 ± 2.4
Prepregnancy BMI, kg/m2 27.8 ± 7.3
Ethnicity
 Caucasian 21 (32.8)
 African American 25 (39.1)
 Hispanic 13 (20.3)
 Asian 2 (3.1)
 Other 1 (1.6)
 Missing 2 (3.1)
Highest educational level completed
 Grammar/elementary school 4 (6.3)
 Middle school 6 (9.4)
 High school 36 (56.5)
 College 14 (21.9)
 Postgraduate degree 4 (6.5)
Delivery method
 Vaginal 15 (23.4)
 Cesarean section 49 (76.6)
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Note. N = 64. BMI = body mass index.

Table 2.

Infant Characteristics and NICU Outcomes.

Characteristic or Outcome Mean ± SD
Gestational age at delivery, weeks 28.3 ± 2.4
Birth weight, g 1,069.6 ± 216.8
Apgar 1 min 6.0 ± 1.9
Apgar 5 min 7.4 ± 1.5
Days on oxygen 15.2 ± 21.3
Length of NICU stay, days 70.5 ± 37.0
n (%)
Sex, male 38 (52.0)
ROP, yes 13 (19.1)
BPD, yes 4 (5.6)
Sepsis, yes 10 (14.1)
NEC, yes 3 (4.2)
IVH, yes 9 (12.9)
Blood transfusion, yes 33 (45.2)
Feeding intolerance, yes 15 (21.1)
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Note. N = 73. BPD = bronchopulmonary dysplasia; IVH = intraventricular hemorrhage; NEC = necrotizing enterocolitis; ROP = retinopathy of prematurity; NICU = neonatal intensive care unit.

Table 3.

Genotype Frequency and Hardy–Weinberg Equilibrium (HWE), Total Population.

SNP n (%) Study MAF HWE
rs2070874 T = 0.148 p = .001*
 CC 45 (70.31)
 TT 8 (12.5)
 CT 11 (17.19)
rs2243250 n/a p = .00001*
 CC 28 (43.75)
 TT 20 (31.25)
 CT 16 (25)
rs1800795 C = 0.195 p = .3011
 CC 5 (7.81)
 GG 39 (60.94)
 CG 20 (31.25)
rs1800796 C = 0.109 p = .0423*
 CC 3 (4.69)
 GG 50 (78.13)
 CG 11 (17.19)
rs1800871 T = 0.227 p = .252
 TT 7 (11.11)
 CC 34 (53.97)
 CT 22 (34.92)
rs1800872 A = 0.242 p = .1232
 CC 32 (50.79)
 AA 9 (14.29)
 AC 22 (34.92)
rs1800896 G = 0.313 p = .7227
 GG 11 (17.46)
 AA 23 (36.51)
 AG 29 (46.03)
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Note. N = 64. MAF = minor-allele frequency; SNP = single nucleotide polymorphism.

*Significant at p < .05.

When controlling for gestational age at delivery and ratio of maternal milk to total milk received, we found a significant association between IL6 SNP (rs1800795) minor-allele absence and the number of days on oxygen (p = .0316) in the total population (see Table 4). Minor-allele absence for IL6 (rs1800795) was also associated with fecal calprotectin at Week 2 (p = .0222), though only among Caucasians. Additionally, among the total population, there were significant inverse relationships between IL6 SNP (rs1800796) genotype GG and length of stay (p = .0034) and fecal calprotectin at Week 3 (p = .0213). Among Caucasians, there was a significant association between IL6 (rs1800796) minor-allele absence and calprotectin at Week 3 (p = .0429). Among African Americans, there were significant relationships between IL6 (rs1800796) minor-allele absence and length of stay (p = .0158) and SNAPPE-II (p = .0497). There was a significant relationship among Hispanics between IL6 (rs1800796) minor-allele absence and weight at 6 weeks of life (p = .0272).

Table 4.

Multivariate Model for Continuous Infant Outcomes With Maternal Minor-Allele Presence and/or Genotype.

Gene/SNP/Population Infant Outcome Predictor Estimate p Value
IL6
 rs1800795
  Caucasian Calprotectin Week 2a MAP—no −0.743 .0222*
  MAP—yes (ref)
Gestational age 0.011 .9038
Ratio of MOM to total milk −0.535 .3383
  Total population Days on oxygen MAP—no −9.588 .0316*
MAP—yes (ref)
Gestational age −5.048 <.001*
Ratio of MOM to total milk 1.02 .9076
 rs1800796
  Caucasian Calprotectin Week 3a MAP—no 0.815 .0429*
MAP—yes (ref)
Gestational age 0.167 .0530
Ratio of MOM to total milk 0.252 .5708
  African American Length of stay MAP—no −32.318 .0158*
MAP—yes (ref)
Gestational age −9.142 <.001
Ratio of MOM to total milk −10.227 .5371
SNAPPE-IIa MAP—no −0.668 .0497*
MAP—yes (ref)
Gestational age −0.059 .1350
Ratio of MOM to total milk 0.579 .1310
  Hispanic Weight at 6 weeksa MAP—no −0.195 .0272*
MAP—yes (ref)
Gestational age 0.089 .0027*
Ratio of MOM to total milk −0.519 .0822
  Total population Length of stay Genotype GG 69.376 .0034*
Genotype AA −7.257 .4626
Genotype AG (ref)
Gestational age −8.411 <.0001*
Ratio of MOM to total milk −12.07 .4194
Calprotectin Week 3a Genotype GG 0.974 .0213*
Genotype AA −0.063 .7730
Genotype AG (ref)
Gestational age 0.065 .0968
Ratio of MOM to total milk 0.257 .4826
IL10
 rs1800871
  Total population Calprotectin Week 3a Genotype TT 0.732 .0270*
Genotype CC 0.143 .4381
Genotype CT (ref)
Gestational age 0.059 .1299
Ratio of MOM to total milk 0.174 .6452
 rs1800872
  Caucasian Calprotectin Week 1a MAP—no −0.997 .0196*
MAP—yes (ref)
Gestational age −0.202 .0987
Ratio of MOM to total milk −0.044 .9474
  Total population Calprotectin Week 3a Genotype CC 0.203 .2892
Genotype AA 0.768 .0158*
Genotype AC (ref)
Gestational age 0.063 .1466
Ratio of MOM to total milk 0.074 .8523
 rs1800896
  African American Days on oxygen MAP—no 21.589 .0320*
MAP—yes (ref)
Gestational age −4.699 .0016*
Ratio of MOM to total milk −5.597 .7021
  Total population Calprotectin Week 2a MAP—no 0.644 .0057*
MAP—yes (ref)
Gestational age 0.058 .2023
Ratio of MOM to total milk −0.251 .5478
Calprotectin Week 2a Genotype GG 0.220 .3795
Genotype AA 0.741 .0045*
Genotype AG (ref)
Gestational age 0.055 .2297
Ratio of MOM to total milk −0.379 .3928
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Note. MAP = minor-allele presence; MOM = mom’s own milk; ref = reference; SNP = single nucleotide polymorphism; SNAPPE-II = scores for neonatal acute physiology with perinatal extension.

aNatural log transformed.

*Significant association at p < .05.

When examining the relationships between maternal IL10 and infant outcomes, we found a significant relationship between rs1800871 genotype TT and Week 3 calprotectin in the total population (p = .0270). We also found a significant association between IL10 (rs1800872) minor-allele absence among Caucasians and Week 1 calprotectin (p = .0196). We observed a similar relationship in the total population but with genotype AA and Week 3 calprotectin (p = .0158). There was a significant association between IL10 (rs1800896) minor-allele absence and days on oxygen (p = .0320) among African Americans. Within the total population, there were significant associations between both IL10 (rs1800896) genotype AA and minor-allele absence and Week 2 calprotectin (p = .0045 and p = .0057, respectively).

Discussion

Our findings in the present study suggest that maternal IL SNPs may predict NICU outcomes in very low-birth-weight (VLBW) infants. Previous work has examined the relationships between maternal IL SNPs and obstetrical complications (Engel et al., 2005; Harmon et al., 2014; Moura et al., 2009; Qaddourah et al., 2014; Sowmya et al., 2014). Other studies have focused on the NICU infant’s IL genotype/s and subsequent outcomes, including respiratory distress syndrome (RDS; Capasso et al., 2007; Li et al., 2015; Shen, Du, Wang, & Zeng, 2014), abnormal periventricular ultrasound findings (Dordelmann et al., 2006), and bronchopulmonary dysplasia (Yanamandra, Boggs, Loggins, & Baier, 2005). Similar to our work, which examined the relationship between maternal genotype and infant outcome, Pogliani, Muggiasca, Arrigoni, Rossi, and Zuccotti (2010) examined maternal methylenetetrahydrofolate reductase (MTHFR) genotypes and subsequent neonatal cerebral lesions. The authors reported that perinatal prothrombotic disorders are different in their presentation and suggested that maternal genotyping of MTHFR may predict outcomes. Chaemsaithong et al. (2016) suggested that a bedside test that measures IL-6 in amniotic fluid from an amniocentesis may identify inflammation among women who subsequently experience preterm labor. Both of these studies are exemplars of antenatal identification of complications, and the present study further supports this approach.

Infection and inflammation are probable biological determinants of preterm birth (Brown, Speechley, Macnab, Natale, & Campbell, 2015; Romero et al., 2006), suggesting that infants born preterm were in an inflammatory-enhanced environment in utero. This presumption is especially relevant when examining the relationship between IL6 SNPs and SNAPPE-II scores. The infant’s vital signs and lab results used to calculate SNAPPE-II scores are collected within hours of birth, thus this score may reflect the immediately preceding in utero environment. Previous work has identified relationships between IL6 SNPs and SGA infants (Harmon et al., 2014) and preterm birth (Moura et al., 2009; Sugita et al., 2012; Velez, Fortunato, Williams, & Menon, 2008). Interestingly, both Velez, Fortunato, Williams, and Menon (2008) and Harmon et al. (2014) uncovered these relationships only among African Americans, an observation that our findings share. IL-6 is a pleiotropic cytokine that may influence the ability of the placenta to become adequately implanted (Conde-Agudelo, Romero, Kusanovic, & Hassan, 2011), and higher levels of IL-6 are associated with preterm labor (Chaemsaithong et al., 2016). The maternal IL6 SNP associated with SNAPPE-II scores is a functional SNP, with CG genotypes associated with higher IL-6 levels (Malarstig, Wallentin, & Siegbahn, 2007). IL-6 production during pregnancy may influence neonatal outcomes, and mortality risk may be reflected in the SNAPPE-II score, as we observed in the African American subset. NICU length of stay was also associated with this SNP in both African Americans and the total study population.

Maternal IL SNPs were also associated with infant oxygen requirements in the present study, and recent evidence suggests that elevated umbilical cord IL-6 levels are positively associated with RDS (Sorokin et al., 2014). Tracheal aspirate IL-6 levels are used as a biomarker for lung inflammation in ventilated preterm infants (Lista et al., 2008). The underlying pathophysiology of respiratory deterioration in the NICU may implicate IL-6, and our findings suggest that antenatal identification of infant risk may inform postnatal care plans. For example, delayed cord clamping (45 s) is associated with lower rates of RDS in preterm infants (Chiruvolu et al., 2015). The NICU team is usually present for preterm infant births, and this simple and promising intervention can be prioritized for women with genotypes associated with high-acuity NICU respiratory needs.

Infant fecal calprotectin was frequently associated with maternal IL alleles, with significant relationships found at all 3 weeks and in all but the Hispanic subset. Preterm infants with NEC symptoms experience a transient rise in fecal calprotectin when compared with preterm infants of the same gestational age without NEC (Campeotto et al., 2007). The identification of infants who are at risk for a hyperinflamed GI environment may inform the NICU nurse’s care plan to minimize this inflammation, including an exclusive human milk diet (Kantorowska et al., 2016) and probiotics (Olsen, Greisen, Schroder, & Brok, 2016). Maternal milk provides an extrauterine immunological link to preterm infants and contains each of the three ILs examined in this study. Variable exogenous IL levels from human milk could help explain the disparity we observed in infant outcomes, particularly the calprotectin findings. The relationship between maternal IL SNPs and longitudinal NICU outcomes among the present cohort of VLBW infants receiving human milk suggests that milk composition may mediate the relationship between maternal SNPs and neonatal outcomes. This possibility is especially relevant now because more donor milk is being used in the NICU setting, and one feeding represents milk from multiple mothers. It may be that the relationships we uncovered in this study are a result of the effects of maternal SNPs on IL production that influenced the milk’s immunological profile. Future studies should examine appropriate pathways of bioactive milk components and their influence on neonatal outcomes. The unique symbiotic nature of the mother and the human milk–fed preterm infant suggests that we examine both as a dyad rather than as separate entities.

Limitations

There were several limitations to this study, including a small sample size. Due to differences in allele frequencies across races, we further decreased our power by doing subgroup analyses of Caucasians, Hispanics, and African Americans, although for an exploratory study, we believe this subgroup analysis was necessary. Much of this study is based on self-reported variables, including ethnicity. Self-reported ethnicity does not adequately capture inherent biological differences, and ancestral markers are a more reliable way of obtaining biologically relevant information that accounts for admixture (Yaeger et al., 2008). Additionally, the cesarean section rates were high (nearly 76%), though this finding is similar to that in a recent study of a nearly 71% cesarean section rate among VLBW infants (Griffin, Lee, Profit, & Tancedi, 2015).

HWE was violated for three SNPs (rs2070874, rs2243250, and rs1800796). We were able to eliminate genotyping error; therefore, we believe HWE violation was due to a biased sample of women who delivered preterm infants, which enriched for the alleles under investigation. The SNPs included in this study have been implicated in a variety of obstetrical complications including SGA (rs2070874 and rs2243250; Engel et al., 2005), spontaneous preterm birth (rs1800795; Wu et al., 2013), and pregnancy loss (rs1800871 and rs1800872; Cochery-Nouvellon et al., 2009).

Relevance to Nursing Practice

Nurses are well positioned to implement precision evidence-based bedside techniques. This study suggests that maternal IL genotypes play a role in clinical outcomes among VLBW infants. Findings from this study may contribute to the development of a specific antenatal risk profile of high-risk obstetrical patients that informs the neonatal nurse’s care plan. In addition, this study provides further evidence that nurses and other health professionals should have an understanding of how human milk protects infants. This research also has implications for considering the use of donor milk in the NICU. Additionally, since breast milk may be influenced by maternal genotypes, findings from this study may impact how donor milk is batched at milk banks for pasteurization. Perhaps more global to the impact of this study’s findings on nursing is the importance of preparedness in nurse-scientists in genomics (Conley et al., 2015), particularly as to how genetics/genomics informs screening and prognoses (Calzone & Jenkins, 2011).

Footnotes

Author Contribution: K. Baumgartel contributed to conception, design, acquisition, analysis, and interpretation; drafted the manuscript; critically revised the manuscript; gave final approval; and agrees to be accountable for all aspects of work ensuring integrity and accuracy. M. Groer contributed to conception, design, acquisition, and interpretation; critically revised the manuscript; gave final approval; and agrees to be accountable for all aspects of work ensuring integrity and accuracy. D. Spatz contributed to conception, design, and interpretation; critically revised the manuscript; gave final approval; and agrees to be accountable for all aspects of work ensuring integrity and accuracy. S. Cohen contributed to conception and design, critically revised the manuscript, gave final approval, and agrees to be accountable for all aspects of work ensuring integrity and accuracy. D. Ren contributed to conception, design, acquisition, analysis, and interpretation; critically revised the manuscript; gave final approval; and agrees to be accountable for all aspects of work ensuring integrity and accuracy. Y. Conley contributed to conception, design, acquisition, analysis, and interpretation; critically revised the manuscript; gave final approval; and agrees to be accountable for all aspects of work ensuring integrity and accuracy.

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Targeted Research and Academic Training of Nurses in Genomics (NR00975909); Sigma Theta Tau Research Award, University of Pittsburgh; Judith A. Erlen Research Award; International Society of Nurses in Genetics Research Award; Corrine M. Barnes Award; NINR, R21 NR01309401A1.

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