Abstract
Objectives:
Determine the prevalence of glucose concentrations below the Pediatric Endocrine Society (PES) term and late preterm-focused guideline target for mean glucose concentrations (≥70 mg/dL) among preterm NICU infants on full enteral nutrition and assess the impact on monitoring practices.
Study Design:
Retrospective cohort-study.
Results:
We analyzed 1,717 infants who were at least 2 days-old and 48 hours after parenteral fluids were discontinued. Glucose concentrations were ≥70, 60–69, 50–59, and <50 mg/dL in 76.6, 16.2, 5.9, and 1.3% of measurements, respectively. In multivariate models, concentrations <60 mg/dL were common among male infants at lower postnatal age, small-for-gestational age, and born to women with hypertension (p<0.05). After PES guideline, infants were more likely to have >3 glucose measurements (p<0.05).
Conclusions:
Glucose concentrations <70 mg/dL are not uncommon among preterm infants receiving full enteral nutrition. Monitoring increased after guideline publication. Applying PES threshold to well-appearing preterm infants may promote increased monitoring and intervention without clear long-term benefit.
Keywords: Neonatal hypoglycemia, glucose, preterm infants, newborn
INTRODUCTION
At birth, infants transition from a reliance on maternal glucose supply to innate mechanisms for glucose homeostasis (1). Glucose concentrations in the first 48 hours are typically lower than later in life (2). However, definitions of hypoglycemia, as well as the clinical thresholds for treatment of neonatal hypoglycemia, remain controversial (3) (4) (5).
The American Academy of Pediatrics (AAP) guideline for hypoglycemia management, most recently updated in 2011, focused exclusively on term and late preterm infants <24 hours of age and recommends glucose concentrations >40 mg/dL in the first 4 hours and >45 mg/dL thereafter on the first day (6). The AAP provided no specific recommendations for glucose targets after 24 hours of age or for infants of lower gestational age. In 2015, the Pediatric Endocrine Society (PES) published a guideline intended to recognize “persistent hypoglycemia disorders” resulting from congenital or genetic defects in the metabolism of glucose, glycogen, and fatty acids in neonates, infants, and children (7). This guideline concluded that mean glucose concentrations in the post-absorptive state in normal neonates after 48 hours of age should not differ from adult concentrations (serum glucose concentrations 70 – 100 mg/dL) (7). For infants without a suspected genetic or persistent hypoglycemia disorder, the guideline recommends a fasting evaluation (minimum 6–8 hours) to determine whether further testing and treatment is needed for infants over 48 hours of age unable to maintain glucose concentrations >60 mg/dL; infants with severe hypoglycemia (i.e. symptomatic hypoglycemia or need for IV dextrose treatment); and infants considered at-risk without a suspected persistent hypoglycemia disorder that will likely resolve within a short time, (i.e. those with perinatal stress, infants who are large- or small-for-gestational age, premature, or born to diabetic women). (7). Recovering preterm infants on full enteral feeds may be included in this final category, however, whether the guidelines should be applied to these preterm infants has not been established. Furthermore, whether lower glucose concentrations (50–59 mg/dL) in otherwise asymptomatic infants after 2 days of age affect long-term outcomes is not known.
While it was not necessarily the intent of the 2015 PES guideline writers to address the care of preterm infants in the intensive care setting, clinical and laboratory evaluation of recovering preterm infants in the NICU may reveal glucose concentrations that fall slightly below the PES target intended for term neonates. This approach may result in more glucometer testing, “critical” laboratory results, endocrinology consultation, parenteral glucose infusions, and longer NICU stays (3). In the absence of data, practice has been guided by extrapolation of guidelines developed to evaluate healthy infants (such as those by the AAP and PES), locally developed protocols, and individual provider choice. Our hypotheses were 1) recovering preterm infants receiving full enteral nutrition often would not meet the glucose concentrations targeted by the PES guideline (in part because it was not designed for them) and 2) despite the fact that the PES guideline was intended for a different group of infants, that providers would increase glucose monitoring among these infants in the post PES-guideline era potentially due to heightened attention to hypoglycemia among infants more globally. Our objectives were the following: (1) to determine the proportion of glucose concentrations among preterm infants below the goal mean glucose concentration (≥ 70 mg/dL) as well as below the threshold for evaluation and possible treatment (≥ 60 mg/dL); (2) to identify predictors associated with lower glucose concentrations; (3) to provide data regarding glucose concentrations in preterm infants on full enteral feeding; and finally, (4) to assess whether the intensity of glucose concentration monitoring and length of stay (LOS) among these infants changed with the publication of the PES guideline.
SUBJECTS AND METHODS
Study Population
We performed a retrospective cohort study of infants born between February 2008 and April 2019 at a tertiary perinatal center and cared for in the Newborn Intensive Care Unit (NICU). We included a convenience sample of preterm infants <36 weeks of gestation, the threshold for NICU admission, who were admitted to and discharged from the NICU. We selected this time period because electronic data were available. We included all glucose concentrations that were measured after two days of age and at least 48 hours after parenteral fluids, if initiated, were discontinued.
Glucose measurement and covariate ascertainment
We extracted from the electronic medical record glucose concentrations obtained using an Abbott Precision Xceed-Pro point-of-care glucose analyzer. Point-of-care (POC) measurements were obtained either according to the NICU protocol for measurement in all infants less than 36 weeks gestation, other risk factors for hypoglycemia, or clinician judgement. Covariate data obtained from the electronic medical record included infant gestational age, birth weight, age in days at time of glucose screen, multiple versus singleton gestation, and maternal factors including age, race/ethnicity, diabetes, and hypertension. Birth weight-for-gestational age Z scores using the Fenton 2013 growth curves (8) were calculated. We categorized infants whose birth weights were below the 10th percentile for gestational age and sex as small-for-gestational age (SGA) and those above the 90th percentile as large-for-gestational age (LGA).
Statistical analysis
Descriptive analyses of baseline demographic variables and potential predictors of low glucose concentrations were performed. These data were summarized using frequency and percentages for categorical variables and mean and standard deviation for continuous variables. Chi-square and t-tests were used to determine whether the frequency of low glucose concentrations varied among variables as appropriate. To assess for potential predictors of glucose concentrations 60–69 mg/dL, 50–59 mg/dL, and <50 mg/dL, we developed multivariate generalized linear models with cumulative logit transformation clustered by infants to account for repeated glucose measurements. Inverse probability weighting was used to address multiple gestations. Age at the time of glucose measurement (in days of age), gestational age at birth, birth weight-for-gestational age, sex, multiple gestation, race/ethnicity, maternal age, maternal hypertension, and maternal diabetes served as covariates, and the analysis was repeated to determine if results were similar with respect to the final glucose measured during the NICU stay. Additionally, a logistic regression model adjusting for gestational age and birth weight-for-gestational age was used to determine whether the number of glucose measurements per infant changed after PES guideline publication, and another model adjusting for gestational age and glucose monitoring was used to determine if length of stay increased in our population after PES guideline publication in 2015. Finally, we manually reviewed infants above the 95th percentile with respect to the number of glucose measurements obtained. This study was approved by the Beth Israel Deaconess Medical Center institutional review board. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC).
RESULTS
We analyzed 5,917 measurements of glucose concentration in 1,717 preterm infants who were at least 2 days old and who had not received parenteral fluids at all or for at least 48 hours. Table 1 summarizes baseline participant characteristics. The majority of the infants were singletons (64.0%), male (51.6 %), and appropriate birth weight-for-gestational age (AGA) (83.0%). Twelve percent were small-for-gestational age (SGA) and 5% were large-for-gestational age (LGA). Mean gestational age at birth was 32 weeks (SD 2.9) and mean birth weight was 1,782 grams (SD 600). In the cohort, 7.1% of infants were born to women with diabetes and 18.2% with hypertension (Table 1).
Table 1.
Characteristics of 1,717 preterm infants (< 36 weeks) in the NICU receiving full enteral feeding and without parenteral dextrose containing fluids from 2008 to 2019
| Characteristic | n (%) | |||
| Singleton gestation | 1,098 (64.0) | |||
| Male | 886 (51.6) | |||
| Birth weight-for-gestational age | ||||
| Appropriate-for-gestational age (AGA) | 1,424 (83.0) | |||
| Small-for-gestational age (SGA) | 205 (12.0) | |||
| Large-for-gestational age (LGA) | 88 (5.0) | |||
| Gestational age | ||||
| < 28 weeks | 177 (10.3) | |||
| 28 to < 32 weeks | 449 (26.2) | |||
| 32 to < 36 weeks | 1,091 (63.5) | |||
| Race/ethnicity | ||||
| Non-Hispanic white | 839 (48.9) | |||
| Non-Hispanic black | 215 (12.5) | |||
| Hispanic | 90 (5.2) | |||
| Asian | 176 (10.3) | |||
| Other/multiple races | 397 (23.1) | |||
| Diabetes | 122 (7.1) | |||
| Maternal hypertension | 313 (18.2) | |||
| mean (SD) | ||||
| Maternal Age (years) | 32 (5.6) | |||
| Birth weight (grams) | 1,782 (600) | |||
| Birth weight for gestational age (Z score) | −0.18 (0.9) | |||
| Gestational age (weeks) | 32 (2.9) | |||
| Gestational age (weeks)- range | 23 to 35 | |||
| Median | Mode | IQR (Q1-Q3) | max | |
| Day of life of glucose measured | 19 | 13 | 11–36 | |
| Day of life of final glucose measured | 11 | 14 | 6–17 | |
| Number of times glucose measured | 3 | 1 | 1–9 | 97 |
| Length of stay (days) | 33 | 10 | 18–58 | 153 |
Abbreviation: NICU = Newborn Intensive Care Unit
Most POC glucose measurements (76.6%) were ≥70 mg/dL. Of the remainder, 16.2% were 60–69 mg/dL, 5.9% were 50–59 mg/dL, and 1.3% were <50 mg/dL (Table 2). The last glucose concentration recorded during the NICU stay was often drawn at two weeks of age (mode 14 days, median 11 days, IQR 6–17 days) concurrent with the state mandated newborn metabolic screen. The final measured glucose concentrations prior to discharge were ≥70 mg/dL, 60–69 mg/dL and 50–59 mg/dL in 84.3%, 13.8% and 1.9% of infants, respectively. We found no final concentrations below 50 mg/dL. In a sub-analysis by birth weight-for-gestational age, overall glucose concentrations <70 were more common among SGA (35.5%) and LGA (21%) infants compared to AGA (19.4 %). A higher proportion of SGA infants (28.8%) had a final glucose concentration <70 mg/dL compared to AGA (14.0%) and LGA infants (12.5%) (p <0.0001). Overall glucose concentrations <60 were more common among SGA (13.9%) compared to LGA (4.9%) infants and AGA (5.1 %). Finally, 4.9% of SGA and 1.6% of AGA infants had a final glucose concentration <60 mg/dL (p <0.0001).
Table 2.
Categories of glucose concentrations in 1,717 preterm infants* (< 36 weeks of gestational age) in the NICU from 2008 to 2019
| < 50 mg/dL | 50 – 59 mg/dL | 60 – 69 mg/dL | ≥ 70 mg/dL | |
|---|---|---|---|---|
| All glucose (n= 5,917), n (%) | 78 (1.3) | 347 (5.9) | 956 (16.2) | 4,536 (76.6) |
| < 28 weeks | 6 (0.4) | 43 (2.8) | 146 (9.5) | 1,346 (87.3)) |
| 28 to < 32 weeks | 25 (1.6) | 66 (4.3) | 183 (11.9) | 1,260 (82.0 |
| 32 to < 36 weeks | 47 (1.7) | 238 (8.4) | 627 (22.1)) | 1,930 (67.8) |
| Final glucose (n= 1,717), n (%) | - | 33 (1.9) | 237 (13.8) | 1,447 (84.3) |
| < 28 weeks | 1 (0.6) | 11 (6.2) | 165 (93.2)) | |
| 28 to < 32 weeks | 8 (1.8) | 33 (7.3) | 408 (90.9)) | |
| 32 to < 36 weeks | 24 (2.2) | 193 (17.7) | 874 (80.1)) | |
Total glucose measures observed in 1,717 infants: 5,917
Multivariate generalized linear models of all glucose concentrations revealed that infants at older postnatal ages were less likely to have a glucose concentration 60 to 69 mg/dL (per day of life adjusted OR: 0.97, 95% CI: 0.97 – 0.98) while infants with higher gestational age at birth (per week adjusted OR: 1.05, 95% CI: 1.01 – 1.10), SGA infants (versus AGA) (adjusted OR 1.57, 95% CI: 1.24 – 2.00), and infants born to women with hypertension (adjusted OR 1.34, 95% CI: 1.06 – 1.69) were more likely to have glucose concentrations in that range (Table 3). Older infants were also less likely to have a glucose concentration 50 to 59 mg/dL (per day of life adjusted OR: 0.96, 95% CI: 0.94 – 0.98), while male infants (adjusted OR: 1.53, 95% CI: 1.10 – 2.14), SGA infants (adjusted OR 2.50, 95% CI: 1.75 – 3.59), and infants born to women with hypertension (adjusted OR 1.62, 95% CI: 1.08 – 2.44) were more likely to have glucose concentrations in that range. Finally, glucose levels <50 mg/dL were more common in SGA infants (adjusted OR 5.49, 95% CI: 3.14 – 9.59) and black infants (adjusted OR 2.58, 95% CI: 1.28 – 5.21).
Table 3.
Associations of infant and maternal characteristics with glucose concentration categories among 1,717 preterm infants on full enteral nutrition recovering in a Newborn Intensive Care Unit
| Glucose < 50 mg/dL | Glucose 50 – 59 mg/dL | Glucose 60 – 69 mg/dL | |
|---|---|---|---|
| Infant characteristic | Adjusted OR (95% CI) versus ≥ 70 mg/dL^ | ||
| Gestational age (per week) | 1.11 (0.98 – 1.26) | 1.04 (0.97 – 1.12) | 1.05 (1.01 – 1.10) * |
| Day of life at glucose (per day) | 0.98 (0.95 – 1.02) | 0.96 (0.94 – 0.98) * | 0.97 (0.97 – 0.98) * |
| Male (vs. female) | 1.65 (0.89 – 3.05 | 1.53 (1.10 – 2.14) * | 1.03 (0.85 – 1.26) |
| SGA (vs. AGA) | 5.49 (3.14 –9.59) * | 2.50 (1.75 – 3.59) * | 1.57 (1.24 – 2.00) * |
| LGA (vs. AGA) | † | 0.98 (0.47 – 2.03) | 1.04 (0.69 – 1.57) |
| Maternal characteristic | |||
| Age (per year) | 1.01 (0.95 – 1.06) | 0.99 (0.96 – 1.02) | 0.99 (0.98 – 1.01) |
| Race (black vs. white) | 2.58 (1.28 – 5.21) * | 1.32 (0.81 – 2.14) | 1.13 (0.82 – 1.55) |
| Hypertension (vs. no) | 0.92 (0.45 – 1.88) | 1.62 (1.08 – 2.44) * | 1.34 (1.06 – 1.69) * |
| Diabetes (vs. no) | 0.31 (0.03 – 2.50) | 0.50 (0.20 – 1.27) | 0.60 (0.35, 1.04) |
Models mutually adjusted for all variables listed
Statistically significant p<0.05
not calculated due to small number of values (3 LGA infants with glucose concentration <50)
SGA, small-for-gestational age; AGA, appropriate-for-gestational age; LGA, large-for-gestational age
Multivariate models of the final glucose concentration measured prior to discharge showed that older infants (higher postnatal age) were less likely to have a glucose concentration 60 to 69 mg/dL (per day of life adjusted OR: 0.98, 95% CI: 0.97 – 0.99), while SGA infants were more likely to have glucose concentrations in that range (adjusted OR 2.11, 95% CI: 1.39 – 3.20) (Table 4). Finally, infants born to younger women were less likely to have a glucose concentration 50 to 59 mg/dL (adjusted OR 0.89, 95% CI: 0.82 – 0.95), while SGA infants were more likely to have glucose concentrations in that range (adjusted OR 3.79, 95% CI: 1.62 – 8.87).
Table 4.
Associations of infant and maternal characteristics with final glucose concentration among 1,717 preterm infants on full enteral nutrition recovering in a Newborn Intensive Care Unit.
| Glucose 50 – 59 mg/dL | Glucose 60 – 69 mg/dL | |
|---|---|---|
| Adjusted OR (95% CI) versus ≥ 70 mg/dL^ | ||
| Infant characteristic | ||
| Gestational age (per week) | 1.00 (0.77 – 1.31) | 1.09 (0.98 – 1.20) |
| Day of life at glucose (per day) | 0.97 (0.94 – 1.00) | 0.98 (0.97 – 0.99) * |
| Male (vs. female) | 1.98 (0.91 – 4.30) | 1.08 (0.80 – 1.45) |
| SGA (vs. AGA) | 3.79 (1.62 – 8.87) * | 2.11 (1.39 – 3.20) * |
| LGA (vs. AGA) | † | 1.12 (0.57 – 2.21) |
| Maternal characteristic | ||
| Age (per year) | 0.89 (0.82 – 0.95) * | 0.97 (0.94 – 1.00) |
| Race (black vs. white) | 1.21 (0.39 – 3.76) | 0.86 (0.52 – 1.43) |
| Hypertension (vs. no) | 0.95 (0.37 – 2.41) * | 1.24 (0.85 – 1.82) |
| Diabetes (vs. no) | 0.53 (0.07 – 4.05) | 0.54 (0.27, 1.09) |
Models mutually adjusted for all variables listed
OR = Odds Ratio
Statistically significant p< 0.05
Not calculated due to small number of values (3 LGA infants with glucose concentration < 50)
SGA, small-for-gestational age; AGA, appropriate-for-gestational age; LGA, large-for-gestational age
The frequency of glucose determinations in each infant ranged from 1 to 97 (IQR 1 – 9). Almost half of infants (46.2%) had only 1 glucose measurement, 22.0% had 2, and 10.0% had 3 measurements. Overall, 95% of infants had up to 13 measurements. Among the remaining 5% with 13 or more measurements (n=76), 13 had insulin levels measured. Of those, 70% had hyperinsulinemia (9/13) and 76% were born SGA (10/13). None of these infants required treatment for hypoglycemia at the time of discharge home. The proportion of infants with insulin levels measured before 2015 was 0.4% (5/1309) comparared to 2.0% (8/392) in the years after the PES guideline was published (p <0.001). The mean concentration of the last glucose measured before discharge was 82 (SD 1.49, range 80 to 85 mg/dL) with no significant difference over time (data not shown). However, during the 10 years with complete data (2008–2018), the proportion of infants with at least 4 glucose measurements during hospitalization significantly increased after the PES guideline publication in 2015 compared to before (Figure 1 and Supplemental Table 2). This association persisted after adjustment for gestational age at delivery and birth weight-for-gestational age (adjusted OR 1.76, 95% CI: 1.31 – 2.36) (Supplemental Table 1). Infants admitted in the post guideline period had a longer length of stay than infants admitted before the guidelines (5.94 extra days (CI: 2.36 – 9.53). This association remained significant after adjusting by gestational age and by infants with multiple glucose measurements (at least 4 measurements) during admission (2.84 extra days, CI: 1.26 – 4.42). No significant change in LOS was observed when infants with hyperinsulinemia were removed from the model.
Figure 1.
Proportion of infants before and after the PES guideline publication by number of glucose measurements. The proportion of infants with 4 or more measurements increased after publication of the guidelines (p value from χ2 test)
DISCUSSION
We found in a cohort of 1,717 preterm infants at least 2 days of age, who had never received parenteral glucose or had not received parenteral glucose for more than 48 hours, that more than 23% of bedside glucose measurements were below 70 m/dL and 7% were below 60 mg/dL. Our data also demonstrate that, unlike full term LGA infants who are known to have lower glucose concentrations in the newborn period (6) (9), LGA status was not a risk factor for lower glucose levels once these preterm infants were taking full enteral nutrition and not receiving parenteral fluids.
In the absence of data and formal guidance regarding the screening and evaluation of glucose levels among recovering, well-appearing, hospitalized preterm infants receiving full feeds, we found evidence of increased glucose monitoring in this population after the publication of the 2015 PES hypoglycemia guideline, even though the guideline was developed for a different group of infants at risk for persistent hypoglycemia conditions. Although we do not know whether the increase in surveillance was due to the publication of the guideline, we speculate that providers may have been more aware that mild hypoglycemia is worthy of attention. While a few glucose measurements may not be considered particularly invasive (and 78% of infants had ≤ 3 glucose concentrations measured after 48 hours off of parenteral glucose), a glucose level below the goal mean level of 70 mg/dL or persistently below 60 mg/dL may raise provider concern in the post PES guideline era in the absence of clinical symptoms, even though the guideline was not targeted at hospitalized preterm infants. These concerns could potentially prolong length of stay for an extended period of observation. Evidence is sparse regarding changes in health care utilization following the PES guidelines. However, a study of infants diagnosed with persistent hypoglycemia found increased utilization of endocrinology consultations after publication of the PES guideline (10), suggesting that the guideline may affect provider practice. Although the population was not the same as the infants in our study, that report noted that increased screening resulted in more diagnoses of hypoglycemia that were treated with diazoxide.
Although the potentially adverse impact of hypoglycemia is of concern, the optimal range of glucose concentration in otherwise thriving preterm infants in the NICU is not established and results of studies are conflicting. Several studies have shown early hypoglycemia in asymptomatic infants, even if transient, was associated with adverse long-term outcomes and developmental delay, including acute electrophysiological changes in the brain (11), smaller mean head circumference without EEG or mean IQ differences (12), poor academic performance and lower achievement test scores at age 10 years (13). However, other studies have shown no adverse neurodevelopmental outcomes associated with lower blood glucoses in the neonatal period (17,18,19). As an example, a recent secondary analysis of data from the Infant Health and Development Program on outcomes of preterm infants <2,500 grams birth weight and <37 weeks gestational age found no significant differences between those with neonatal hypoglycemia and normoglycemic controls in intellectual or academic achievement at 3 to 18 years of age (14). Most recently, a multicenter, randomized, noninferiority trial of healthy full term and late preterm infants with hypoglycemia, excluding infants with severe hypoglycemia, showed that treating physiological transitional hypoglycemia at two different thresholds (lower threshold of <36 mg/dL and the traditional of <47 mg/dL) showed that the lower threshold was not inferior to the traditional threshold with respect to psychomotor development at 18 months. (15)(16)
Our study adds to the literature by contributing NICU population-based glucose data on recovering preterm infants, but it cannot answer the question of whether slightly low glucose concentrations matter for long-term neurodevelopment among preterm infants already at increased risk of adverse outcomes (17) (18) (19).
The major strength of our study is the large sample size and adjustment for potential confounding variables. Data collection spanned over a decade and reflected practice before and after publication of the PES guideline. Our data show that publication of the guideline was associated with an increased proportion of infants with multiple glucose measurements.
We found that 7% of POC glucose values were 50–59 mg/dL and 1.3% of all were less than 50 mg/dl. Whether these values prompted more intensive monitoring or intervention is not known, but none of these infants were treated for hypoglycemia up to the time of their discharge home. Although the PES guideline raised concerns with the goal of helping physicians recognize persistent hypoglycemia disorders (7), whether this concern applies to well-appearing hospitalized preterm infants is uncertain. More frequent glucose testing and evaluation of mild hypoglycemia must be weighed against risks and costs. For example, longer lengths of stay to evaluate and treat slightly low glucoses values could increase risk for infection, prompt unnecessary intervention, and further stress families (20) (21).
Our study has several limitations. As a retrospective study in a single center practice, our findings may not be generalizable to other NICUs. In particular, to avoid multiple blood draws, glucose measurements were often obtained at the time of other scheduled blood draws. For example, day 14, the most frequent day glucose samples were obtained, corresponds to the timing of routine newborn state metabolic screening in Massachusetts for infants who remain hospitalized. This suggests that most samples were drawn during routine blood draws and not in symptomatic infants. A key limitation is that all samples were analyzed using a bedside point-of-care glucometer that analyzes whole blood glucose. Measurements could potentially be inaccurate or may be affected by other intrinsic factors like polycythemia or extrinsic factors such as poor sampling techniques and are recommended for screening and not diagnosis of hypoglycemia. (22) (23) (24). Laboratory glucose measurements, while recommended for confirmation of hypoglycemia disorders, are less efficient for screening and may have inaccurate results when samples sit in laboratories awaiting analysis(25) (26). Additionally, feeding protocols may vary across units and affect glucose concentrations. In our center, goal feeds were 150 ml/kg/day of expressed breastmilk or preterm formula, fortified to 24 kcal/ounce and then titrated to achieve optimal growth. Despite our large sample size, among infants with hypoglycemia that required further testing including insulin levels, evaluation did not prompt any further work up or follow up after discharge. However, that does not rule out the possibility that more severe cases would have been identified in an even larger cohort. Finally, no systematic long-term follow-up data are available to assess possible associations with neurodevelopmental outcomes.
CONCLUSION
We found that among hospitalized preterm infants in the NICU receiving enteral feedings and who either never received or were not receiving any glucose infusions for more than 48 hours, glucose concentrations <70 (60–69) mg/dL and 50–59 mg/dL are not uncommon. Assessment and management of hypoglycemia, including critical values, for further evaluation and treatment, is not standardized in feeding and growing preterm infants. Although not the express intent of the PES guideline, in the absence of alternative guidance, providers may apply the PES standard of evaluation and treatment at <70 mg/dl or <60 mg/dL to recovering preterm infants. Doing so could increase the utilization of services and extend the hospital stay of otherwise well-appearing preterm infants. More research is needed to assess the optimal thresholds for evaluation and treatment and of hypoglycemia in these infants.
Supplementary Material
Supplemental Table 1. Odds of frequencies of glucose measurements before and after Pediatric Endocrine Society guideline publication in 2015 among 1,701preterm infants from 2008-2018
Supplemental Table 2. Frequency of glucose concentrations measured per infant among 1,717 preterm infants on full enteral nutrition before and after PES guideline was published in 2015
Supplemental Table 3. Infants with Insulin levels checked (n=13) before and after the PES guidelines (Data from 2008 to 2018)
ACKNOWLEDGMENTS
We acknowledge the contributions and support of the Harvard Neonatal-Perinatal Medicine Fellowship program as well as the Harvard-wide Pediatric Health Services Research Fellowship at Boston Children’s Hospital.
Funding Source: Dr. Burris’s time was funded by NIH/NIEHS K23ES022242.
Abbreviations:
- NICU
Neonatal Intensive Care Unit
Footnotes
Financial Disclosures: The authors have no financial relationships relevant to this article to disclose.
CONFLICT OF INTEREST
The authors have no conflicts of interest of any competing financial interests to disclose.
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Associated Data
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Supplementary Materials
Supplemental Table 1. Odds of frequencies of glucose measurements before and after Pediatric Endocrine Society guideline publication in 2015 among 1,701preterm infants from 2008-2018
Supplemental Table 2. Frequency of glucose concentrations measured per infant among 1,717 preterm infants on full enteral nutrition before and after PES guideline was published in 2015
Supplemental Table 3. Infants with Insulin levels checked (n=13) before and after the PES guidelines (Data from 2008 to 2018)