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Blood glucose levels within 7 days after birth in preterm infants according to gestational age

Blood glucose levels within 7 days after birth in preterm infants according to gestational age Original article http://dx.doi.org/10.6065/apem.2015.20.4.213 Ann Pediatr Endocrinol Metab 2015;20:213-219 Blood glucose levels within 7 days after birth in preterm infants according to gestational age Purpose: This study investigated blood glucose levels in preterm babies according Ju Young Yoon, MD , to gestational age (GA). Hye Rim Chung, MD, PhD , Methods: Subjects were 141 preterm infants with a GA<34 weeks. Data on blood Chang Won Choi, MD, PhD , glucose levels, GA, body weight, glucose infusion rate, and other contributing Sei Won Yang, MD, PhD , factors in the first 7 days after birth were analyzed. Hypoglycemia was defined as Beyong Il Kim, MD, PhD , a blood glucose level of <40 mg/dL up to 24 hours after birth and as <50 mg/dL Choong Ho Shin, MD, PhD thereafter. Hyperglycemia was defined as a blood glucose level >180 mg/dL. Results: During the 7 days after birth, hypo- and hyperglycemia occurred in 29 (29 Department of Pediatrics, Seoul of 141, 20.6%) and 42 (42 of 141, 29.8%) neonates, respectively. During the first 2 National University Children’s Hospital, hours, 18 neonates (12.8%) exhibited hypoglycemia, and only 2 (2 of 141, 1.4%) Seoul, Department of Pediatrics, developed hyperglycemia. From 6 to 24 hours, hypo- and hyperglycemia were Seoul National University Bundang observed in 0 and 9 (9 of 141, 6.4%) neonates, respectively. Infants small for their Hospital, Seongnam, Korea GA (SGA) were at risk for hypoglycemia both within 24 hours (odds ratio [OR], 2.718; P=0.045) and during days 2 to 7 (OR, 4.454; P=0.006), and hyperglycemia during days 2 to 7 (OR, 3.200; P=0.005). Low 1-minite Apgar score was risk factor for both hypo- and hyperglycemia during days 2 to 7 (OR, 0.756; P=0.035 for hypoglycemia and OR, 0.789; P=0.016 for hyperglycemia). Both hypo- and hyperglycemia within 24 hours were less common in those who started feeding (OR, 0.294; P=0.013 for hypoglycemia and OR, 0.162; P=0.011 for hyperglycemia). Conclusion: Careful blood glucose level monitoring is required in preterm infants, especially SGA infants or those with low Apgar score. Early feeding could be beneficial for maintaining euglycemia. Keywords: Blood glucose level, Preterm, Birth weight, Gestational age Introduction Preterm infants have limited supplies and stores of energ y sources for carbohydrate metabolism. In addition, the organs involved in the regulation of energ y metabolism, 1) which include the liver, pancreas, brain, and endocrine organs, are immature . Therefore, Received: 23 November, 2015 hypo- and hyperglycemia are more common in preterm infants than in full-term neonates. Revised: 4 December, 2015 2) Hypoglycemia is also common in infants who are small for gestational age (SGA) , as well as Accepted: 14 December, 2015 3) in those with perinatal asphyxia . Hyperglycemia occurs more frequently under conditions Address for correspondence: of excess glucose and lipid infusion, as well as under stressful conditions such as mechanical Hye Rim Chung, MD, PhD ventilation and hypoxia. Department of Pediatrics, Seoul Persistent and recurrent hypoglycemia in neonates is associated with long-term neurological National University Bundang 4) 5-7) complications such as visual defects , localization-related epilepsy , and cognitive dysfunc- Hospital, 82 Gumi-ro 173beon-gil, 8-10) tion . Complications of hyperglycemia include intraventricular hemorrhage, prema ture Bundang-gu, Seongnam 13620, 11) retinopathy, and bronchopulmonary dysplasia . Korea However, little is known about prevalence of hypo- or hyperglycemia in preterm infants, Tel: +82-31-787-2034 Fax: +82-31-787-4054 resulting in challenges for prevention and management. e Th present study aimed to provide E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// ISSN: 2287-1012(Print) creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any ISSN: 2287-1292(Online) medium, provided the original work is properly cited. ©2015 Annals of Pediatric Endocrinology & Metabolism Yoon JY, et al. • Blood glucose levels in preterm infants 2. Methods useful data for the prevention and treatment of hypo- or hyper- glycemia in preterm infants by investigating blood glucose levels for a period of 7 days ae ft r birth, as well as the prevalence of and Blood glucose levels were measured irrespective of feeding risk factors for these conditions. time at least twice a day for the first 3 days after birth and at least once a day from days 4 to 7. Whole blood samples were Materials and methods obtained from the heel using the OneTouch SureStep Hospital Meter (LifeScan Inc., Milpitas, CA, USA). Because there is no 1. Subjects consensus about den fi ition of hypo and hyperglycemia, we used our target blood glucose level for cutoff value. Hypoglycemia was den fi ed as a blood glucose measurement <2.22 mmol/L (40 Preterm infants born at a gestational age (GA) of <34 weeks mg/dL) within 24 hours of birth and <2.78 mmol/L (50 mg/ at Seoul National University Bundang Hospital, Korea, were dL) thereafter. Hyperglycemia was defined as a blood glucose enrolled in this study. Of the 156 preterm infants born at a GA measurement >9.99 mmol/L (180 mg/dL) regardless of the of <34 weeks between March 2010 and December 2011, 15 were sampling time. excluded from the study (due to death within 7 days of birth Patients were infused with a glucose-containing fluid at an [n=8] or maternal diabetes mellitus [n=7]). Finally, a total of 141 initial glucose infusion rate (GIR) of 4 mg/kg/min. The GIR infants were enrolled in this study. was titrated by 0.5 to 1 mg/kg/min daily up to 12 to 15 mg/kg/ min, to maintain blood glucose levels within target range of Table 1. Characteristics of the patients and mothers according to gestational age group Characteristic Overall (n=141) GA (wk)<28 (n=21) 28≤GA (wk)<30 (n=15) 30≤GA (wk)<32 (n=39) 32≤GA (wk)<34 (n=66) Birthweight (kg) 1.53±0.56 0.80±0.21 1.02±0.29 1.44±3.43 1.94±0.42 GA (wk) 31.0±2.6 26.2±1.3 28.7±0.4 31.0±0.5 33.1±0.6 Male sex 81 (57.4) 13 (61.9) 11 (73.3) 18 (46.2) 39 (59.1) Multiple pregnancy 30 (21.3) 4 (19.0) 4 (26.7) 8 (20.5) 14 (21.2) Vaginal delivery 45 (31.9) 8 (38.1) 4 (26.7) 7 (17.9) 26 (39.4) SGA 37 (26.2) 6 (28.6) 7 (46.7) 10 (25.6) 14 (21.2) Breast milk feeding 72 (55.0) 6 (28.6) 8 (57.1) 27 (75.0) 31 (47.0) a) Feeding start within 24 hours 98 (69.5) 8 (38.1) 6 (40.0) 23 (59.0) 61 (92.4) a),b) Full feeding within 7 days 137 (97.2) 21 (100) 15 (100) 37 (94.9) 64 (97.0) Time to full feeding (day) 3.9±1.3 4.9±1.5 4.7±1.5 3.8±1.1 3.5±1.0 Initial blood glucose (mmol/L) 3.9±1.4 4.8±2.1 3.5±0.9 3.4±1.3 3.9±1.3 GIR (mg/kg/min) Day 1 3.9±0.7 3.9±0.7 4.1±0.9 3.9±0.9 4.0±0.7 Days 2–7 4.5±2.4 6.0±1.1 6.3±1.9 4.7±2.4 3.4±2.3 Peak GIR (mg/kg/min) 6.4±2.2 7.3±1.5 8.0±2.3 6.6±2.4 5.7±2.0 Hypoglycemia <24 hours 20 (14.2) 2 (9.5) 3 (20.0) 8 (20.5) 7 (10.6) Days 2–7 16 (11.3) 4 (19) 2 (13.3) 7 (17.9) 3 (4.5) Hyperglycemia <24 hours 10 (7.1) 4 (19) 1 (6.7) 2 (5.1) 3 (4.5) Days 2–7* 36 (25.5) 16 (76.2) 5 (33.3) 9 (23.1) 6 (9.1) Apgar score 1 minute 5.0±2.0 3.0±1.8 4.9±2.4 4.6±1.6 5.8±1.7 5 minutes 6.9±1.7 5.1±1.9 6.8±1.9 6.7±1.3 7.6±1.3 RDS 56 (39.7) 19 (90.5) 8 (53.3) 18 (46.2) 11 (16.7) Sepsis 4 (2.8) 3 (14.3) 0 (100) 1 (2.6) 0 (0) Free T4 (pmol/L) 19.1±4.0 15.2±4.1 17.7±3.0 19.3±3.6 20.8±3.5 17-OHP (pmol/L) 358±519 846±1150 310±205 295±217 250±210 PIH 31 (22.0) 3 (14.3) 5 (33.3) 9 (23.1) 14 (21.2) Maternal steroid 122 (86.5) 19 (90.5) 14 (93.3) 32 (82.1) 57 (86.4) Values are presented as mean±standard deviation or number (%). GA, gestational age; SGA, small for GA; GIR, glucose infusion rate; RDS, respiratory distress syndrome; 17-OHP, 17-hydroxyprogesterone; PIH, pregnancy- induced hypertension. * a) b) P<0.05 between groups. Time from birth. Full feeding: oral intake more than 100 mL/kg/day. 214 www.e-apem.org Yoon JY, et al. • Blood glucose levels in preterm infants 2.78–9.99 mmol/L (50–180 mg/dL). Hypo- and hyperglycemia cond fi ence intervals (CIs). were managed by adjusting glucose infusion rate. Feeding was Analys es were p erformed using the IBM SPSS Statistics initiated on the first day, if tolerable. ver. 19.0 (IBM Co., Armonk, NY, USA). A P-value <0.05 was In addition to the measurement of blood glucose le vels, considered statistically signic fi ant. sex, GA, birth weight, multiple pregnancies, method of deli- ver y, prenatal steroid use, and maternal hypertension were Results recorded. We further collected information on perinatal fac- tors a ss o c i ate d w it h blo o d g luc os e le vels , including G I R , 1. Patient characteristics feeding (bre ast milk or whole milk), and Apgar s cores. In order to evaluate the hormonal status, free thyroxine (T4) and The mean birth weight of all subjects was 1.53±0.56 kg. Of 17-hydroxyprogesterone (17-OHP) levels were measured on these, 37 infants (26.2%) were classie fi d as SGA. day 7 by serum radioimmunoassay and the neonatal screening The subjects were divided into 4 groups according to GA: test, respectively. <28, 28 to <30, 30 to <32, and ≥32 weeks. No die ff rences were This study was approved by the Institutional Review Board observed between groups in terms of characteristics such as sex, of S eoul National University Bund ang Hospital (IRB No.: multiple births, and method of delivery (vaginal vs. Cesarean B-1203/148-101). section). With regards to those perinatal factors that could ae ff ct blood 3. Statistical analysis glucose levels, as the group was younger, Apgar scores at 1 and 5 minutes were significantly lower, free T4 levels were lower, 17- Results are expressed as the mean±standard deviation. Inter- OHP levels were higher, and a greater proportion of subjects group comparisons were conducted using independent t-tests de veloped respirator y distress syndrome. Feeding method, or the chi-square test where appropriate. In addition, stepwise GIR during d ay 1, and materna l f ac tors such a s materna l logistic regression analysis was performed to determine those hypertension or steroid use were not significantly different factors inu fl encing the occurrence of hypo- or hyperglycemia. between the 4 groups (Table 1). These results are expressed as the odds ratios (ORs) with 95% We grouped the subjects according to presence of hypo- and Table 2. Characteristics of the patients and mothers according to presence of hypo- and hyperglycemia Hypoglycemia within 24 hours Hypoglycemia during days 2-7 Overall Characteristic (n=141) Yes (n=20) No (n=121) Yes (n=16) No (n=125) Yes (n=10) No (n=131) Yes (n=36) No (n=105) Birthweight (kg) 1.53±0.56 1.54±0.68 1.53±0.54 1.13±0.48 1.58±0.55 1.28±0.74 1.55±0.54 1.06±0.56 1.69±0.47 GA (wk) 31.0±2.6 31.0±0.6 31.0±2.6 29.7±3.1 31.2±2.5 29.2±3.4 31.2±2.5 28.7±2.9 31.8±1.8 Male sex 81 (57.4) 11 (55) 70 (57.9) 9 (56.3) 72 (57.6) 7 (70.0) 74 (56.5) 18 (50.0) 63 (60.0) Multiple pregnancy 30 (21.3) 7 (35.0) 23 (19.0) 2 (12.5) 28 (22.4) 1 (10.0) 29 (22.1) 7 (19.4) 23 (21.9) Vaginal delivery 45 (31.9) 3 (15.0) 42 (34.7) 3 (18.8) 42 (33.6) 0 (0) 45 (34.4) 8 (22.2) 37 (35.2) * * SGA 37 (26.2) 9 (45.0) 28 (23.1) 9 (56.3) 28 (22.4) 4 (40.0) 33 (25.2) 16 (44.4) 21 (20/0) Breast milk feeding 72 (55.0) 12 (60.0) 60 (49.6) 10 (62.5) 62 (49.6) 6 (60.0) 66 (50.4) 15 (41.7) 57 (53.3) a) * * Feeding start within 24 hours 98 (69.5) 9 (45.0) 89 (73.6) - - 3 (30.0) 95 (72.5) - - b) Time to full feeding (day) 3.9±1.3 4.0±1.1 3.9±1.3 3.9±1.0 3.9±1.3 4.3±1.5 3.9±1.3 4.3±1.5 3.8±1.2 Initial blood glucose (mmol/L) 3.9±1.4 2.3±1.2 4.1±1.3 3.3±1.8 3.9±1.4 4.2±1.4 3.8±1.4 4.1±1.7 68.2±24.2 GIR (mg/kg/min) Day 1 3.9±0.7 3.8±0.6 4.0±0.8 3.8±0.5 4.0±0.8 4.0±0.8 3.9±0.7 3.9±0.9 3.9±0.7 Days 2–7 4.5±2.4 4.3±2.3 4.5±2.4 6.2±1.7 4.3±2.4 5.5±1.3 4.4±2.4 5.9±2.0 4.0±2.3 Apgar score 1 minute 5.0±2.0 4.8±1.7 5.0±2.1 3.9±1.7 5.1±2.0 4.0±1.9 5.0±2.0 4.3±2.2 5.2±1.9 5 minutes 6.9±1.7 6.9±1.7 6.9±1.7 5.9±1.5 7.0±1.7 5.9±1.6 7.0±1.7 6.3±1.9 7.1±1.5 * * RDS 56 (39.7) 5 (25.0) 51 (42.1) 8 (50.0) 48 (38.4) 9 (90.0) 47 (35.9) 22 (61.1) 34 (32.4) Sepsis 4 (2.8) 0 (0) 4 (3.3) 2 (12.5) 2 (1.6) 1 (10.0) 3 (2.3) 3 (8.3) 1 (1.0) Free T4 (pmol/L) 19.1±4.0 18.9±5.0 19.2±3.8 19.7±3.3 19.1±4.1 17.0±5.1 19.3±3.9 17.8±5.0 19.6±3.5 17O-HP (pmol/L) 358±519 291±317 368±545 631±1268 323±313 363±419 357±527 679±912 247±184 PIH 31 (22.0) 5 (25.0) 26 (21.5) 5 (31.3) 26 (20.8) 2 (20) 29 (22.1) 10 (27.8) 21 (20.0) Maternal steroid 122 (86.5) 17 (85.0) 105 (86.8) 15 (93.8) 107 (85.6) 10 (100) 112 (85.5) 35 (97.2) 87 (82.9) Values are presented as mean±standard deviation or number (%). GA, gestational age; SGA, small for gestational age; GIR, glucose infusion rate; RDS, respirator y distress syndrome; 17- OHP, 17-hydroxyprogesterone; PIH, pregnancy-induced hypertension. * a) b) P<0.05 between groups. Time from birth. Full feeding: oral intake more than 100 mL/kg/day www.e-apem.org 215 Yoon JY, et al. • Blood glucose levels in preterm infants 3. Blood glucose levels according to GA hyperglycemia. Infants who developed hypoglycemia within 24 hours had lower Apgar s core t han who did not. Thos e who developed hypoglycemia during days 2 to 7 had lower At 1 hour ae ft r birth, median blood glucose levels were lowest birthweight and Apgar score, and were younger than those in infants with a GA of 30 to <32 weeks and highest in those who did not. Group with hyperglycemia during days 2 to 7 had with a GA <28 weeks (3.27 and 4.72 mmol/L, respectively) (Fig. higher proportion of SGA, and also reported higher prevalence 1). Median blood glucose levels were lower on the first day in of respiratory distress syndrome and sepsis (Table 2). all GA groups. Median blood glucose levels peaked at day 7 in infants with a GA <32 weeks and showed steady levels, ranging 2. Blood glucose levels from 3.67 to 5.44 mmol/L (66 to 98 mg/dL), in those with a GA≥32 weeks (Fig. 2). An average of 17.5 s amples per infant were done within 7 days of birth. The median blood glucose level 1 hour after 4. Hypo-/hyperglycemia according to GA birth was 3.66 mmol/L (66 mg/dL), the lowest level recorded throughout the study period, whereas the highest measurement D uring t he f irst 24 hours , hy p o g lyc emic e pis o des were was 6.38 mmol/L (115 mg/dL), obtained on day 7. The 2.5th- most common in the GA 30 to <32 weeks group (20%, 3 of percentile level was lowest at 1.05 mmol/L (19 mg/dL) at 2 15 patients) and least common in those with a GA<28 weeks hours, and peaked at 3.4 mmol/L (62 mg/dL) on day 6. The (9.5%, 2 of 21 patients), although these intergroup differences 97.5th-percentile blood glucose level was 6.71 mmol/L (120.7 were not statistically significant. Hyperglycemia was higher in mg/dL) at 1 hour and peaked at 15.4 mmol/L (276.5 mg/dL) at the younger GA group (19%, 6.7%, 5.1%, and 4.5% in GA< 28, day 7 (Figs. 1, 2). e Th 5th blood glucose levels were lowest at 2 28 to <30, 30 to <32, and ≥32 weeks, respectively), although not hours ae ft r birth at 1.89 mmol/L (34 mg/dL) (data not shown). statistically signic fi ant (Table 1). During t he f irst 2 hours, 18 neonates (12.8%) exhibited During days 2 to 7, hyperglycemia occurred more frequently hy p o g l y c e m i a , w h i l e hy p e r g l y c e m i a d e v e l op e d i n ju s t 2 in the younger age groups; 16 of 21 neonates (76.2%) with a neonates (1.4%). From 6 to 24 hours, hypo- and hyperglycemia GA<28 weeks developed hyperglycemia, while only 6 of 66 were obser ved in 0 (0%) and 9 neonates (6.4%), respectively. neonates (9.1%) with a GA≥32 weeks exhibited hyperglycemia. Overall, 29 (20.6%) and 42 neonates (29.8%) developed hypo- No significant die ff rences regarding the incidence of hypogly - and hyperglycemia over 7 days, respectively. Eleven infants cemia were observed among the groups (Table 1). (7.8%) developed both hypo- and hyperglycemia, whereas 81 (57.4%) showed neither. (A) Postnatal age (hr) (B) Postnatal age (hr) (C) Postnatal age (hr) Fig. 1. Blood glucose levels within 24 hours. (A) In all the subjects; (B) subjects with gestational age<28 weeks; (C) 28 to <30 weeks; (D) 30 to <32 weeks; and (E) ≥32 weeks. Lower and upper limit are mean±2standard deviation. Bars express inter quartile range. *Outlier. (D) Postnatal age (hr) (E) Postnatal age (hr) 216 www.e-apem.org Yoon JY, et al. • Blood glucose levels in preterm infants (A) Postnatal age (day) (B) Postnatal age (day) (C) Postnatal age (day) Fig. 2. Blood glucose levels over 7 days. (A) In all the subjects; (B) subjects with gestational age <28 weeks; (C ) 28 to <30 weeks; (D) 30 to <32 weeks; and (E) ≥32 weeks. Lower and upper limit are mean±2standard deviation. Bars express inter quartile range. *Outlier. (D) Postnatal age (day) (E) Postnatal age (day) 5. Risk factors for hypoglycemia than in full-term neonates. One of the reasons for this is a reduced ability to suppress endogenous glucose production in the body during glucose infusion. Another common mecha nism Univariate logistic regression analysis was performed to responsible for hyperglycemia in preterm infants is the lack of determine risk factors for hypoglycemia. The results showed 12) insulin-sensitive tissues such as muscle and adipose tissue . In that SGA was signic fi ant risk factors for hypoglycemia within 24 addition, condition such as sepsis and necrotising enterocolitis hours (OR, 2.718; 95% CI, 1.023–7.219). Having started feeding can induce both hepatic and peripheral insulin resistance, which was related with decreased hypoglycemia within 24 hours (OR, 13) lead to stress induced hyperglycemia . There is no consensus 0.294; 95% CI, 0.112–0.775). For hypoglycemia during days 2 to for definition of hypo- and hyperglycemia in neonates. In 7, SGA and low 1-minute Apgar score were risk factors (Table 3). previous studies definition of hypoglycemia ranges from 1.7 to 14) 2.6 mmol/L . For defining hyperglycemia in preterm infants, 6. Risk factors for hyperglycemia 15,16) cutoff value of 150 mg/dL or 180 mg/dL is commonly used . In our study, hypo- and hyperglycemia was defined by values In order to evaluate the risk factors for hyperglycemia, univa- outside target blood glucose level used in our center. riate logistic regression analysis was performed using the same The present study investigated blood glucose levels shortly independent variables as those used for hypoglycemia. Risk of ae ft r birth in preterm neonates, as well as associated risk factors hyperglycemia within 24 hours decreased in those who had for hypo- and hyperglycemia. The median blood glucose level started feeding feeding (OR, 0.162; 95% CI, 0.040–0.662). The was lowest 1 hour after birth, consistent with results from a risk of hyperglycemia 2 to 7 days ae ft r birth increased in SGA 17) study by Srinivasan et al. on blood glucose levels in full- infants and those with low 1-minute Apgar score (Table 4). term neonates. In that study, both the 5th- and 95th-percentile 1 8 ) b l o o d g lu c o s e l e ve l s we re l o we s t f rom 1 0 to 1 4 h ou r s . Discussion However, in our study, the 5th-percentile blood glucose level was lowest at 2 hours after birth. This discrepanc y is likely Shortly ae ft r birth, the response of hormones regulating blood attributable to differences in glucose infusion as glucose was glucose levels is less sensitive because of the immaturity of infused intravenously only when a neonate presented with 17) cyclic adenosine monophosphate, a second messenger related to hypoglycemia in Srinivasan et al. 's study, whereas intravenous glucose metabolism. In addition, preterm neonates have a lower glucose was given to all cases in our study. In the present study, glycogen storage capacity than full-term neonates. Therefore, prevalence of hypoglycemia peaked on day 2, consistent with 17) postnatal hypoglycemia is common in preterm neonates. the results obtained by Srinivasan et al. . In the first 1 hour Hyperglycemia too is more common in preterm neonates ae ft r birth, blood glucose level was the highest in GA<28 weeks www.e-apem.org 217 Blood glucose concentration Blood glucose concentration (mmol/L) (mmol/L) Blood glucose concentration Blood glucose concentration (mmol/L) (mmol/L) Blood glucose concentration (mmol/L) Yoon JY, et al. • Blood glucose levels in preterm infants group. This is explained by immaturity of beta cell enzymatic 4 hours after birth. The relationship of feeding with blood 12) pathways and shortage of insulin sensitive tissue . glucose level is not well known in preterm infants, and further In the present study, the incidence of hypoglycemia was investigation is required. higher in SGA infants than in infants with weights appropriate The major strengths of the present study lie in its single- 2) for GA (AGA). Concordantly, Lubchenco and Bard reported center design, standardized blood glucose level measurement the incidences of hypoglycemia in preterm and full-term SGA method, and relatively large sample size. Furthermore, we not neonates to be 67% and 25%, respectively, higher than those only investigated the incidence of hypo- and hyperglycemia but obser ved in AGA infants. Increased risk of hypoglycemia in also recorded detailed temporal changes in blood glucose levels. SGA infants can be explained by decreased glycogen stores, Ne ver theless, a limitation of this study is that the ef fect 19) increased insulin sensitivity and higher energy requirements . of i nt r ave nous g luc os e i n f usion w a s i nve st i g ate d on l y i n The incidence of hyperglycemia in the present study was conjunction with oral intake and was not analyzed in detail. 20) 29.1%. Hays et al. previously reported an incidence of 60% Furthermore, we did not continuously measure blood glucose within 7 days of birth. This difference may be accounted for le vels; inste ad, blo o d g luc os e le vels were me asure d inter- by that study’s inclusion of only infants with a birth weight <1 mittently, usually once per day from 4 days onwards. e Th refore, kg and a lower cutoff value of 8.33 mmol/L (150 mg/dL) for the overall incidence of hypo- and hyperglycemia may have den fi ing hyperglycemia. been underestimated when compared to the incidence observed In our study, 1-minute Apgar score was associated with both wit h c ontinuous blo o d gluc os e monitoring. Howe ver, t he hypo- and hyperglycemia. This is in accordance with previous prevalence of hypo- and hyperglycemia at each individual time findings that neonates with perinatal distress are prone to both point may have been overestimated, as blood glucose levels 21) 22) hypoglycemia and hyperglycemia . were me asured more f requently in cases where hypo- and Both hypo- and hyperglycemia within 24 hours decreased hyperglycemia developed. in those who started feeding within 24 hours. On the contrary, In c onclusion, hy p o- and hy p erg lyc emi a is c ommon in in recent study of 203 SGA infants, feeding did not prevent preterm infants and careful blood glucose level monitoring 19) hypoglycemia . But this study included full term infants and is required especially in SGA infants or those with low Apgar investigated effect of early feeding defined as feeding before score. Early feeding could be beneci fi al for prevention of hypo- Table 3. Factors influencing hypoglycemia (univariate analysis, grouped by GA) Hypoglycemia within 24 hours Hypoglycemia during days 2-7 All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) Variable P- P- P- P- P- P- OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) value value value value value value SGA 2.718 0.045 2.269 0.190 3.273 0.155 4.454 0.006 3.354 0.054 8.500 0.091 (1.023–7.219) (0.667–7.723) (0.639–16.771) (1.522–13.03) (0.981–11.474) (0.711–101.6) Apgar score 0.941 0.608 0.959 0.785 1.078 0.763 0.756 0.035 0.824 0.236 0.854 0.613 (1 min) (0.746–1.187) (0.707–1.299) (0.660–1.761) (0.583–0.980) (0.598–1.135) (0.464–1.573) Feeding start 0.294 0.013 0.247 0.048 0.436 0.489 - - - - - - a) within 24 hours (0.112–0.775) (0.062–0.986) (0.042–4.565) Time to full - - - - - - 1.014 0.947 0.787 0.333 1.575 0.397 b) feeding (day) (0.671-1.532) (0.485-1.278) (0.550-4.507) GA, gestational age; SGA, small for GA; OR, odds ratio; CI, confidence interval. a) b) Time from birth. Full feeding: oral intake more than 100 mL/kg/day. Table 4. Factors influencing hyperglycemia (univariate analysis, grouped by GA) Hyperglycemia within 24 hours Hyperglycemia during days 2–7 All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) Variable P- OR P- OR P- P- P- P- OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) value (95% CI) value (95% CI) value value value value SGA 1.980 0.312 3.439 0.127 0.000 (-) 0.999 3.200 0.005 3.500 0.016 2.000 0.453 (0.526–7.450) (0.703–16.83) (1.419–7.214) (1.257–9.742) (0.327–12.24) Apgar score 0.780 0.124 0.678 0.098 1.253 0.589 0.789 0.016 0.873 0.267 1.077 0.782 (1 min) (0.569–1.070) (0.427–1.075) (0.553–2.838) (0.651–0.956) (0.687–1.11) (0.637–1.822) Feeding start 0.162 0.011 0.148 0.085 0.136 0.133 - - - - - - a) within 24 hours (0.040–0.662) (0.017–1.297) (0.010–1.835) Time to full - - - - - - 1.308 0.071 1.234 0.228 0.543 0.220 b) feeding (day) (0.977–1.751) (0.877–1.736) (0.204–1.443) GA, gestational age; SGA, small for GA; OR, odds ratio; CI, confidence interval. a) b) Time from birth. Full feeding: oral intake more than 100 mL/kg/day. 218 www.e-apem.org Yoon JY, et al. • Blood glucose levels in preterm infants and hyperglycemia. neurological dysfunction and neonatal hypoglycaemia ae ft r diabetic pregnancy. Arch Dis Child Fetal Neonatal Ed 1998;79:F174-9. Coni fl ct of interest 11. Ka o L S , Mor r i s BH , L a l l y K P, Ste w ar t C D, Hu s eby V, Kennedy KA. Hyperglycemia and morbidity and morta- No potential conflict of interest relevant to this article was lity in extremely low bir t h weight inf ants. J Perinatol reported. 2006;26:730-6. 12. Mitanche z D. Glucose regulation in preterm ne w born References infants. Horm Res 2007;68:265-71. 13. McCowen KC, Malhotra A, Bistrian BR. Stress-induced 1. Kim EY. Glucose metabolism and evaluation of hypoglyce- hyperglycemia. Crit Care Clin 2001;17:107-24. mia in neonates. Korean J Pediatr 2007;50:223-9. 14. Harris DL, Weston PJ, Harding JE. Incidence of neonatal 2. Lubchenco LO, Bard H. Incidence of hypoglycemia in hyp oglycemi a in babies identif ied as at risk. J Pedi atr newborn infants classified by birth weight and gestational 2012;161:787-91. age. Pediatrics 1971;47:831-8. 15. Ogilvy-Stuart AL, Beardsall K. Management of hypergly- 3. Schultz K, Soltesz G. Transient hyperinsulinism in asphyxia- caemia in the preterm infant. Arch Dis Child Fetal Neonatal ted newborn infants. Acta Paediatr Hung 1991;31:47-52. Ed 2010;95:F126-31. 4. Tam EW, Widjaja E, Bl as er SI, Macgregor DL, Sato di a 16. Pati NK, Maheshwari R, Pati NK, Salhan RN. Transient P, Moore AM. Occipital lobe injur y and cortical visual neonatal hyperglycemia. Indian Pediatr 2001;38:898-901. outcomes ae ft r neonatal hypoglycemia. Pediatrics 2008;122: 17. Srinivasan G, Pildes RS, Cattamanchi G, Voora S, Lilien LD. 507-12. Plasma glucose values in normal neonates: a new look. J 5. Udani V, Munot P, Ursekar M, Gupta S. Neonatal hypogly- Pediatr 1986;109:114-7. cemic brain - injur y a common cause of infantile onset 18. Heck LJ, Erenberg A. Serum glucose levels in term neonates remote symptomatic epilepsy. Indian Pediatr 2009;46:127- during the first 48 hours of life. J Pediatr 1987;110:119-22. 19. Bragg JJ, Green R, Holzman IR. Does early enteral feeding 6. C arab a l lo RH, Sa k r D, Mozzi M, Guerrero A, Adi JN, prevent hypoglycemia in small for gestational age neonates? Cersosimo RO, et al. Symptomatic occipital lobe epilepsy J Neonatal Perinatal Med 2013;6:131-5. following neonatal hypoglycemia. Pediatr Neurol 2004;31: 20. Hays SP, Smith EO, Sunehag AL. Hyperglycemia is a risk 24-9. factor for early death and morbidity in extremely low birth- 7. Montassir H, Maegaki Y, Ohno K, Ogura K. Long term weight infants. Pediatrics 2006;118:1811-8. prognosis of symptomatic occipital lobe epilepsy secondary 21. Saha D, Ali MA, Haque MA, Ahmed MS, Sutradhar PK, to neonatal hypoglycemia. Epilepsy Res 2010;88:93-9. Latif T, et al. Association of hypoglycemia, hypocalcemia 8. Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental and hypomagnesemia in neonates with perinatal asphyxia. outc ome of mo d e r ate ne on at a l hy p o g l yc a e m i a . B M J Mymensingh Med J 2015;24:244-50. 1988;297:1304-8. 22. Marque z-Gonzale z H, Munoz-R amire z MC, R amire z- 9. Duvanel CB, Fawer CL, Cotting J, Hohlfeld P, Matthieu Garcia MA, Pineda-Frutos MF, Hernandez-R amirez C, JM. Long-term ee ff cts of neonatal hypoglycemia on brain Villa-Romero AR , et al. Hyperglycemia as a risk factor g row t h and ps ychomotor d e vel opme nt i n s m a l l - for- for mortality in critically ill neonates. Rev Med Inst Mex gestational-age preterm infants. J Pediatr 1999;134:492-8. Seguro Soc 2014;52 Suppl 2:S104-9. 10. Stenninger E, Flink R, Eriksson B, Sahlen C. Long-term www.e-apem.org 219 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Pediatric Endocrinology & Metabolism Pubmed Central

Blood glucose levels within 7 days after birth in preterm infants according to gestational age

Yoon, Ju Young; Chung, Hye Rim; Choi, Chang Won; Yang, Sei Won; Kim, Beyong Il; Shin, Choong Ho
Annals of Pediatric Endocrinology & Metabolism , Volume 20 (4) – Dec 31, 2015
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Original article http://dx.doi.org/10.6065/apem.2015.20.4.213 Ann Pediatr Endocrinol Metab 2015;20:213-219 Blood glucose levels within 7 days after birth in preterm infants according to gestational age Purpose: This study investigated blood glucose levels in preterm babies according Ju Young Yoon, MD , to gestational age (GA). Hye Rim Chung, MD, PhD , Methods: Subjects were 141 preterm infants with a GA<34 weeks. Data on blood Chang Won Choi, MD, PhD , glucose levels, GA, body weight, glucose infusion rate, and other contributing Sei Won Yang, MD, PhD , factors in the first 7 days after birth were analyzed. Hypoglycemia was defined as Beyong Il Kim, MD, PhD , a blood glucose level of <40 mg/dL up to 24 hours after birth and as <50 mg/dL Choong Ho Shin, MD, PhD thereafter. Hyperglycemia was defined as a blood glucose level >180 mg/dL. Results: During the 7 days after birth, hypo- and hyperglycemia occurred in 29 (29 Department of Pediatrics, Seoul of 141, 20.6%) and 42 (42 of 141, 29.8%) neonates, respectively. During the first 2 National University Children’s Hospital, hours, 18 neonates (12.8%) exhibited hypoglycemia, and only 2 (2 of 141, 1.4%) Seoul, Department of Pediatrics, developed hyperglycemia. From 6 to 24 hours, hypo- and hyperglycemia were Seoul National University Bundang observed in 0 and 9 (9 of 141, 6.4%) neonates, respectively. Infants small for their Hospital, Seongnam, Korea GA (SGA) were at risk for hypoglycemia both within 24 hours (odds ratio [OR], 2.718; P=0.045) and during days 2 to 7 (OR, 4.454; P=0.006), and hyperglycemia during days 2 to 7 (OR, 3.200; P=0.005). Low 1-minite Apgar score was risk factor for both hypo- and hyperglycemia during days 2 to 7 (OR, 0.756; P=0.035 for hypoglycemia and OR, 0.789; P=0.016 for hyperglycemia). Both hypo- and hyperglycemia within 24 hours were less common in those who started feeding (OR, 0.294; P=0.013 for hypoglycemia and OR, 0.162; P=0.011 for hyperglycemia). Conclusion: Careful blood glucose level monitoring is required in preterm infants, especially SGA infants or those with low Apgar score. Early feeding could be beneficial for maintaining euglycemia. Keywords: Blood glucose level, Preterm, Birth weight, Gestational age Introduction Preterm infants have limited supplies and stores of energ y sources for carbohydrate metabolism. In addition, the organs involved in the regulation of energ y metabolism, 1) which include the liver, pancreas, brain, and endocrine organs, are immature . Therefore, Received: 23 November, 2015 hypo- and hyperglycemia are more common in preterm infants than in full-term neonates. Revised: 4 December, 2015 2) Hypoglycemia is also common in infants who are small for gestational age (SGA) , as well as Accepted: 14 December, 2015 3) in those with perinatal asphyxia . Hyperglycemia occurs more frequently under conditions Address for correspondence: of excess glucose and lipid infusion, as well as under stressful conditions such as mechanical Hye Rim Chung, MD, PhD ventilation and hypoxia. Department of Pediatrics, Seoul Persistent and recurrent hypoglycemia in neonates is associated with long-term neurological National University Bundang 4) 5-7) complications such as visual defects , localization-related epilepsy , and cognitive dysfunc- Hospital, 82 Gumi-ro 173beon-gil, 8-10) tion . Complications of hyperglycemia include intraventricular hemorrhage, prema ture Bundang-gu, Seongnam 13620, 11) retinopathy, and bronchopulmonary dysplasia . Korea However, little is known about prevalence of hypo- or hyperglycemia in preterm infants, Tel: +82-31-787-2034 Fax: +82-31-787-4054 resulting in challenges for prevention and management. e Th present study aimed to provide E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// ISSN: 2287-1012(Print) creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any ISSN: 2287-1292(Online) medium, provided the original work is properly cited. ©2015 Annals of Pediatric Endocrinology & Metabolism Yoon JY, et al. • Blood glucose levels in preterm infants 2. Methods useful data for the prevention and treatment of hypo- or hyper- glycemia in preterm infants by investigating blood glucose levels for a period of 7 days ae ft r birth, as well as the prevalence of and Blood glucose levels were measured irrespective of feeding risk factors for these conditions. time at least twice a day for the first 3 days after birth and at least once a day from days 4 to 7. Whole blood samples were Materials and methods obtained from the heel using the OneTouch SureStep Hospital Meter (LifeScan Inc., Milpitas, CA, USA). Because there is no 1. Subjects consensus about den fi ition of hypo and hyperglycemia, we used our target blood glucose level for cutoff value. Hypoglycemia was den fi ed as a blood glucose measurement <2.22 mmol/L (40 Preterm infants born at a gestational age (GA) of <34 weeks mg/dL) within 24 hours of birth and <2.78 mmol/L (50 mg/ at Seoul National University Bundang Hospital, Korea, were dL) thereafter. Hyperglycemia was defined as a blood glucose enrolled in this study. Of the 156 preterm infants born at a GA measurement >9.99 mmol/L (180 mg/dL) regardless of the of <34 weeks between March 2010 and December 2011, 15 were sampling time. excluded from the study (due to death within 7 days of birth Patients were infused with a glucose-containing fluid at an [n=8] or maternal diabetes mellitus [n=7]). Finally, a total of 141 initial glucose infusion rate (GIR) of 4 mg/kg/min. The GIR infants were enrolled in this study. was titrated by 0.5 to 1 mg/kg/min daily up to 12 to 15 mg/kg/ min, to maintain blood glucose levels within target range of Table 1. Characteristics of the patients and mothers according to gestational age group Characteristic Overall (n=141) GA (wk)<28 (n=21) 28≤GA (wk)<30 (n=15) 30≤GA (wk)<32 (n=39) 32≤GA (wk)<34 (n=66) Birthweight (kg) 1.53±0.56 0.80±0.21 1.02±0.29 1.44±3.43 1.94±0.42 GA (wk) 31.0±2.6 26.2±1.3 28.7±0.4 31.0±0.5 33.1±0.6 Male sex 81 (57.4) 13 (61.9) 11 (73.3) 18 (46.2) 39 (59.1) Multiple pregnancy 30 (21.3) 4 (19.0) 4 (26.7) 8 (20.5) 14 (21.2) Vaginal delivery 45 (31.9) 8 (38.1) 4 (26.7) 7 (17.9) 26 (39.4) SGA 37 (26.2) 6 (28.6) 7 (46.7) 10 (25.6) 14 (21.2) Breast milk feeding 72 (55.0) 6 (28.6) 8 (57.1) 27 (75.0) 31 (47.0) a) Feeding start within 24 hours 98 (69.5) 8 (38.1) 6 (40.0) 23 (59.0) 61 (92.4) a),b) Full feeding within 7 days 137 (97.2) 21 (100) 15 (100) 37 (94.9) 64 (97.0) Time to full feeding (day) 3.9±1.3 4.9±1.5 4.7±1.5 3.8±1.1 3.5±1.0 Initial blood glucose (mmol/L) 3.9±1.4 4.8±2.1 3.5±0.9 3.4±1.3 3.9±1.3 GIR (mg/kg/min) Day 1 3.9±0.7 3.9±0.7 4.1±0.9 3.9±0.9 4.0±0.7 Days 2–7 4.5±2.4 6.0±1.1 6.3±1.9 4.7±2.4 3.4±2.3 Peak GIR (mg/kg/min) 6.4±2.2 7.3±1.5 8.0±2.3 6.6±2.4 5.7±2.0 Hypoglycemia <24 hours 20 (14.2) 2 (9.5) 3 (20.0) 8 (20.5) 7 (10.6) Days 2–7 16 (11.3) 4 (19) 2 (13.3) 7 (17.9) 3 (4.5) Hyperglycemia <24 hours 10 (7.1) 4 (19) 1 (6.7) 2 (5.1) 3 (4.5) Days 2–7* 36 (25.5) 16 (76.2) 5 (33.3) 9 (23.1) 6 (9.1) Apgar score 1 minute 5.0±2.0 3.0±1.8 4.9±2.4 4.6±1.6 5.8±1.7 5 minutes 6.9±1.7 5.1±1.9 6.8±1.9 6.7±1.3 7.6±1.3 RDS 56 (39.7) 19 (90.5) 8 (53.3) 18 (46.2) 11 (16.7) Sepsis 4 (2.8) 3 (14.3) 0 (100) 1 (2.6) 0 (0) Free T4 (pmol/L) 19.1±4.0 15.2±4.1 17.7±3.0 19.3±3.6 20.8±3.5 17-OHP (pmol/L) 358±519 846±1150 310±205 295±217 250±210 PIH 31 (22.0) 3 (14.3) 5 (33.3) 9 (23.1) 14 (21.2) Maternal steroid 122 (86.5) 19 (90.5) 14 (93.3) 32 (82.1) 57 (86.4) Values are presented as mean±standard deviation or number (%). GA, gestational age; SGA, small for GA; GIR, glucose infusion rate; RDS, respiratory distress syndrome; 17-OHP, 17-hydroxyprogesterone; PIH, pregnancy- induced hypertension. * a) b) P<0.05 between groups. Time from birth. Full feeding: oral intake more than 100 mL/kg/day. 214 www.e-apem.org Yoon JY, et al. • Blood glucose levels in preterm infants 2.78–9.99 mmol/L (50–180 mg/dL). Hypo- and hyperglycemia cond fi ence intervals (CIs). were managed by adjusting glucose infusion rate. Feeding was Analys es were p erformed using the IBM SPSS Statistics initiated on the first day, if tolerable. ver. 19.0 (IBM Co., Armonk, NY, USA). A P-value <0.05 was In addition to the measurement of blood glucose le vels, considered statistically signic fi ant. sex, GA, birth weight, multiple pregnancies, method of deli- ver y, prenatal steroid use, and maternal hypertension were Results recorded. We further collected information on perinatal fac- tors a ss o c i ate d w it h blo o d g luc os e le vels , including G I R , 1. Patient characteristics feeding (bre ast milk or whole milk), and Apgar s cores. In order to evaluate the hormonal status, free thyroxine (T4) and The mean birth weight of all subjects was 1.53±0.56 kg. Of 17-hydroxyprogesterone (17-OHP) levels were measured on these, 37 infants (26.2%) were classie fi d as SGA. day 7 by serum radioimmunoassay and the neonatal screening The subjects were divided into 4 groups according to GA: test, respectively. <28, 28 to <30, 30 to <32, and ≥32 weeks. No die ff rences were This study was approved by the Institutional Review Board observed between groups in terms of characteristics such as sex, of S eoul National University Bund ang Hospital (IRB No.: multiple births, and method of delivery (vaginal vs. Cesarean B-1203/148-101). section). With regards to those perinatal factors that could ae ff ct blood 3. Statistical analysis glucose levels, as the group was younger, Apgar scores at 1 and 5 minutes were significantly lower, free T4 levels were lower, 17- Results are expressed as the mean±standard deviation. Inter- OHP levels were higher, and a greater proportion of subjects group comparisons were conducted using independent t-tests de veloped respirator y distress syndrome. Feeding method, or the chi-square test where appropriate. In addition, stepwise GIR during d ay 1, and materna l f ac tors such a s materna l logistic regression analysis was performed to determine those hypertension or steroid use were not significantly different factors inu fl encing the occurrence of hypo- or hyperglycemia. between the 4 groups (Table 1). These results are expressed as the odds ratios (ORs) with 95% We grouped the subjects according to presence of hypo- and Table 2. Characteristics of the patients and mothers according to presence of hypo- and hyperglycemia Hypoglycemia within 24 hours Hypoglycemia during days 2-7 Overall Characteristic (n=141) Yes (n=20) No (n=121) Yes (n=16) No (n=125) Yes (n=10) No (n=131) Yes (n=36) No (n=105) Birthweight (kg) 1.53±0.56 1.54±0.68 1.53±0.54 1.13±0.48 1.58±0.55 1.28±0.74 1.55±0.54 1.06±0.56 1.69±0.47 GA (wk) 31.0±2.6 31.0±0.6 31.0±2.6 29.7±3.1 31.2±2.5 29.2±3.4 31.2±2.5 28.7±2.9 31.8±1.8 Male sex 81 (57.4) 11 (55) 70 (57.9) 9 (56.3) 72 (57.6) 7 (70.0) 74 (56.5) 18 (50.0) 63 (60.0) Multiple pregnancy 30 (21.3) 7 (35.0) 23 (19.0) 2 (12.5) 28 (22.4) 1 (10.0) 29 (22.1) 7 (19.4) 23 (21.9) Vaginal delivery 45 (31.9) 3 (15.0) 42 (34.7) 3 (18.8) 42 (33.6) 0 (0) 45 (34.4) 8 (22.2) 37 (35.2) * * SGA 37 (26.2) 9 (45.0) 28 (23.1) 9 (56.3) 28 (22.4) 4 (40.0) 33 (25.2) 16 (44.4) 21 (20/0) Breast milk feeding 72 (55.0) 12 (60.0) 60 (49.6) 10 (62.5) 62 (49.6) 6 (60.0) 66 (50.4) 15 (41.7) 57 (53.3) a) * * Feeding start within 24 hours 98 (69.5) 9 (45.0) 89 (73.6) - - 3 (30.0) 95 (72.5) - - b) Time to full feeding (day) 3.9±1.3 4.0±1.1 3.9±1.3 3.9±1.0 3.9±1.3 4.3±1.5 3.9±1.3 4.3±1.5 3.8±1.2 Initial blood glucose (mmol/L) 3.9±1.4 2.3±1.2 4.1±1.3 3.3±1.8 3.9±1.4 4.2±1.4 3.8±1.4 4.1±1.7 68.2±24.2 GIR (mg/kg/min) Day 1 3.9±0.7 3.8±0.6 4.0±0.8 3.8±0.5 4.0±0.8 4.0±0.8 3.9±0.7 3.9±0.9 3.9±0.7 Days 2–7 4.5±2.4 4.3±2.3 4.5±2.4 6.2±1.7 4.3±2.4 5.5±1.3 4.4±2.4 5.9±2.0 4.0±2.3 Apgar score 1 minute 5.0±2.0 4.8±1.7 5.0±2.1 3.9±1.7 5.1±2.0 4.0±1.9 5.0±2.0 4.3±2.2 5.2±1.9 5 minutes 6.9±1.7 6.9±1.7 6.9±1.7 5.9±1.5 7.0±1.7 5.9±1.6 7.0±1.7 6.3±1.9 7.1±1.5 * * RDS 56 (39.7) 5 (25.0) 51 (42.1) 8 (50.0) 48 (38.4) 9 (90.0) 47 (35.9) 22 (61.1) 34 (32.4) Sepsis 4 (2.8) 0 (0) 4 (3.3) 2 (12.5) 2 (1.6) 1 (10.0) 3 (2.3) 3 (8.3) 1 (1.0) Free T4 (pmol/L) 19.1±4.0 18.9±5.0 19.2±3.8 19.7±3.3 19.1±4.1 17.0±5.1 19.3±3.9 17.8±5.0 19.6±3.5 17O-HP (pmol/L) 358±519 291±317 368±545 631±1268 323±313 363±419 357±527 679±912 247±184 PIH 31 (22.0) 5 (25.0) 26 (21.5) 5 (31.3) 26 (20.8) 2 (20) 29 (22.1) 10 (27.8) 21 (20.0) Maternal steroid 122 (86.5) 17 (85.0) 105 (86.8) 15 (93.8) 107 (85.6) 10 (100) 112 (85.5) 35 (97.2) 87 (82.9) Values are presented as mean±standard deviation or number (%). GA, gestational age; SGA, small for gestational age; GIR, glucose infusion rate; RDS, respirator y distress syndrome; 17- OHP, 17-hydroxyprogesterone; PIH, pregnancy-induced hypertension. * a) b) P<0.05 between groups. Time from birth. Full feeding: oral intake more than 100 mL/kg/day www.e-apem.org 215 Yoon JY, et al. • Blood glucose levels in preterm infants 3. Blood glucose levels according to GA hyperglycemia. Infants who developed hypoglycemia within 24 hours had lower Apgar s core t han who did not. Thos e who developed hypoglycemia during days 2 to 7 had lower At 1 hour ae ft r birth, median blood glucose levels were lowest birthweight and Apgar score, and were younger than those in infants with a GA of 30 to <32 weeks and highest in those who did not. Group with hyperglycemia during days 2 to 7 had with a GA <28 weeks (3.27 and 4.72 mmol/L, respectively) (Fig. higher proportion of SGA, and also reported higher prevalence 1). Median blood glucose levels were lower on the first day in of respiratory distress syndrome and sepsis (Table 2). all GA groups. Median blood glucose levels peaked at day 7 in infants with a GA <32 weeks and showed steady levels, ranging 2. Blood glucose levels from 3.67 to 5.44 mmol/L (66 to 98 mg/dL), in those with a GA≥32 weeks (Fig. 2). An average of 17.5 s amples per infant were done within 7 days of birth. The median blood glucose level 1 hour after 4. Hypo-/hyperglycemia according to GA birth was 3.66 mmol/L (66 mg/dL), the lowest level recorded throughout the study period, whereas the highest measurement D uring t he f irst 24 hours , hy p o g lyc emic e pis o des were was 6.38 mmol/L (115 mg/dL), obtained on day 7. The 2.5th- most common in the GA 30 to <32 weeks group (20%, 3 of percentile level was lowest at 1.05 mmol/L (19 mg/dL) at 2 15 patients) and least common in those with a GA<28 weeks hours, and peaked at 3.4 mmol/L (62 mg/dL) on day 6. The (9.5%, 2 of 21 patients), although these intergroup differences 97.5th-percentile blood glucose level was 6.71 mmol/L (120.7 were not statistically significant. Hyperglycemia was higher in mg/dL) at 1 hour and peaked at 15.4 mmol/L (276.5 mg/dL) at the younger GA group (19%, 6.7%, 5.1%, and 4.5% in GA< 28, day 7 (Figs. 1, 2). e Th 5th blood glucose levels were lowest at 2 28 to <30, 30 to <32, and ≥32 weeks, respectively), although not hours ae ft r birth at 1.89 mmol/L (34 mg/dL) (data not shown). statistically signic fi ant (Table 1). During t he f irst 2 hours, 18 neonates (12.8%) exhibited During days 2 to 7, hyperglycemia occurred more frequently hy p o g l y c e m i a , w h i l e hy p e r g l y c e m i a d e v e l op e d i n ju s t 2 in the younger age groups; 16 of 21 neonates (76.2%) with a neonates (1.4%). From 6 to 24 hours, hypo- and hyperglycemia GA<28 weeks developed hyperglycemia, while only 6 of 66 were obser ved in 0 (0%) and 9 neonates (6.4%), respectively. neonates (9.1%) with a GA≥32 weeks exhibited hyperglycemia. Overall, 29 (20.6%) and 42 neonates (29.8%) developed hypo- No significant die ff rences regarding the incidence of hypogly - and hyperglycemia over 7 days, respectively. Eleven infants cemia were observed among the groups (Table 1). (7.8%) developed both hypo- and hyperglycemia, whereas 81 (57.4%) showed neither. (A) Postnatal age (hr) (B) Postnatal age (hr) (C) Postnatal age (hr) Fig. 1. Blood glucose levels within 24 hours. (A) In all the subjects; (B) subjects with gestational age<28 weeks; (C) 28 to <30 weeks; (D) 30 to <32 weeks; and (E) ≥32 weeks. Lower and upper limit are mean±2standard deviation. Bars express inter quartile range. *Outlier. (D) Postnatal age (hr) (E) Postnatal age (hr) 216 www.e-apem.org Yoon JY, et al. • Blood glucose levels in preterm infants (A) Postnatal age (day) (B) Postnatal age (day) (C) Postnatal age (day) Fig. 2. Blood glucose levels over 7 days. (A) In all the subjects; (B) subjects with gestational age <28 weeks; (C ) 28 to <30 weeks; (D) 30 to <32 weeks; and (E) ≥32 weeks. Lower and upper limit are mean±2standard deviation. Bars express inter quartile range. *Outlier. (D) Postnatal age (day) (E) Postnatal age (day) 5. Risk factors for hypoglycemia than in full-term neonates. One of the reasons for this is a reduced ability to suppress endogenous glucose production in the body during glucose infusion. Another common mecha nism Univariate logistic regression analysis was performed to responsible for hyperglycemia in preterm infants is the lack of determine risk factors for hypoglycemia. The results showed 12) insulin-sensitive tissues such as muscle and adipose tissue . In that SGA was signic fi ant risk factors for hypoglycemia within 24 addition, condition such as sepsis and necrotising enterocolitis hours (OR, 2.718; 95% CI, 1.023–7.219). Having started feeding can induce both hepatic and peripheral insulin resistance, which was related with decreased hypoglycemia within 24 hours (OR, 13) lead to stress induced hyperglycemia . There is no consensus 0.294; 95% CI, 0.112–0.775). For hypoglycemia during days 2 to for definition of hypo- and hyperglycemia in neonates. In 7, SGA and low 1-minute Apgar score were risk factors (Table 3). previous studies definition of hypoglycemia ranges from 1.7 to 14) 2.6 mmol/L . For defining hyperglycemia in preterm infants, 6. Risk factors for hyperglycemia 15,16) cutoff value of 150 mg/dL or 180 mg/dL is commonly used . In our study, hypo- and hyperglycemia was defined by values In order to evaluate the risk factors for hyperglycemia, univa- outside target blood glucose level used in our center. riate logistic regression analysis was performed using the same The present study investigated blood glucose levels shortly independent variables as those used for hypoglycemia. Risk of ae ft r birth in preterm neonates, as well as associated risk factors hyperglycemia within 24 hours decreased in those who had for hypo- and hyperglycemia. The median blood glucose level started feeding feeding (OR, 0.162; 95% CI, 0.040–0.662). The was lowest 1 hour after birth, consistent with results from a risk of hyperglycemia 2 to 7 days ae ft r birth increased in SGA 17) study by Srinivasan et al. on blood glucose levels in full- infants and those with low 1-minute Apgar score (Table 4). term neonates. In that study, both the 5th- and 95th-percentile 1 8 ) b l o o d g lu c o s e l e ve l s we re l o we s t f rom 1 0 to 1 4 h ou r s . Discussion However, in our study, the 5th-percentile blood glucose level was lowest at 2 hours after birth. This discrepanc y is likely Shortly ae ft r birth, the response of hormones regulating blood attributable to differences in glucose infusion as glucose was glucose levels is less sensitive because of the immaturity of infused intravenously only when a neonate presented with 17) cyclic adenosine monophosphate, a second messenger related to hypoglycemia in Srinivasan et al. 's study, whereas intravenous glucose metabolism. In addition, preterm neonates have a lower glucose was given to all cases in our study. In the present study, glycogen storage capacity than full-term neonates. Therefore, prevalence of hypoglycemia peaked on day 2, consistent with 17) postnatal hypoglycemia is common in preterm neonates. the results obtained by Srinivasan et al. . In the first 1 hour Hyperglycemia too is more common in preterm neonates ae ft r birth, blood glucose level was the highest in GA<28 weeks www.e-apem.org 217 Blood glucose concentration Blood glucose concentration (mmol/L) (mmol/L) Blood glucose concentration Blood glucose concentration (mmol/L) (mmol/L) Blood glucose concentration (mmol/L) Yoon JY, et al. • Blood glucose levels in preterm infants group. This is explained by immaturity of beta cell enzymatic 4 hours after birth. The relationship of feeding with blood 12) pathways and shortage of insulin sensitive tissue . glucose level is not well known in preterm infants, and further In the present study, the incidence of hypoglycemia was investigation is required. higher in SGA infants than in infants with weights appropriate The major strengths of the present study lie in its single- 2) for GA (AGA). Concordantly, Lubchenco and Bard reported center design, standardized blood glucose level measurement the incidences of hypoglycemia in preterm and full-term SGA method, and relatively large sample size. Furthermore, we not neonates to be 67% and 25%, respectively, higher than those only investigated the incidence of hypo- and hyperglycemia but obser ved in AGA infants. Increased risk of hypoglycemia in also recorded detailed temporal changes in blood glucose levels. SGA infants can be explained by decreased glycogen stores, Ne ver theless, a limitation of this study is that the ef fect 19) increased insulin sensitivity and higher energy requirements . of i nt r ave nous g luc os e i n f usion w a s i nve st i g ate d on l y i n The incidence of hyperglycemia in the present study was conjunction with oral intake and was not analyzed in detail. 20) 29.1%. Hays et al. previously reported an incidence of 60% Furthermore, we did not continuously measure blood glucose within 7 days of birth. This difference may be accounted for le vels; inste ad, blo o d g luc os e le vels were me asure d inter- by that study’s inclusion of only infants with a birth weight <1 mittently, usually once per day from 4 days onwards. e Th refore, kg and a lower cutoff value of 8.33 mmol/L (150 mg/dL) for the overall incidence of hypo- and hyperglycemia may have den fi ing hyperglycemia. been underestimated when compared to the incidence observed In our study, 1-minute Apgar score was associated with both wit h c ontinuous blo o d gluc os e monitoring. Howe ver, t he hypo- and hyperglycemia. This is in accordance with previous prevalence of hypo- and hyperglycemia at each individual time findings that neonates with perinatal distress are prone to both point may have been overestimated, as blood glucose levels 21) 22) hypoglycemia and hyperglycemia . were me asured more f requently in cases where hypo- and Both hypo- and hyperglycemia within 24 hours decreased hyperglycemia developed. in those who started feeding within 24 hours. On the contrary, In c onclusion, hy p o- and hy p erg lyc emi a is c ommon in in recent study of 203 SGA infants, feeding did not prevent preterm infants and careful blood glucose level monitoring 19) hypoglycemia . But this study included full term infants and is required especially in SGA infants or those with low Apgar investigated effect of early feeding defined as feeding before score. Early feeding could be beneci fi al for prevention of hypo- Table 3. Factors influencing hypoglycemia (univariate analysis, grouped by GA) Hypoglycemia within 24 hours Hypoglycemia during days 2-7 All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) Variable P- P- P- P- P- P- OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) value value value value value value SGA 2.718 0.045 2.269 0.190 3.273 0.155 4.454 0.006 3.354 0.054 8.500 0.091 (1.023–7.219) (0.667–7.723) (0.639–16.771) (1.522–13.03) (0.981–11.474) (0.711–101.6) Apgar score 0.941 0.608 0.959 0.785 1.078 0.763 0.756 0.035 0.824 0.236 0.854 0.613 (1 min) (0.746–1.187) (0.707–1.299) (0.660–1.761) (0.583–0.980) (0.598–1.135) (0.464–1.573) Feeding start 0.294 0.013 0.247 0.048 0.436 0.489 - - - - - - a) within 24 hours (0.112–0.775) (0.062–0.986) (0.042–4.565) Time to full - - - - - - 1.014 0.947 0.787 0.333 1.575 0.397 b) feeding (day) (0.671-1.532) (0.485-1.278) (0.550-4.507) GA, gestational age; SGA, small for GA; OR, odds ratio; CI, confidence interval. a) b) Time from birth. Full feeding: oral intake more than 100 mL/kg/day. Table 4. Factors influencing hyperglycemia (univariate analysis, grouped by GA) Hyperglycemia within 24 hours Hyperglycemia during days 2–7 All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) All subjects (n=141) GA (wk)<32 (n=75) GA (wk)≥32 (n=66) Variable P- OR P- OR P- P- P- P- OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) value (95% CI) value (95% CI) value value value value SGA 1.980 0.312 3.439 0.127 0.000 (-) 0.999 3.200 0.005 3.500 0.016 2.000 0.453 (0.526–7.450) (0.703–16.83) (1.419–7.214) (1.257–9.742) (0.327–12.24) Apgar score 0.780 0.124 0.678 0.098 1.253 0.589 0.789 0.016 0.873 0.267 1.077 0.782 (1 min) (0.569–1.070) (0.427–1.075) (0.553–2.838) (0.651–0.956) (0.687–1.11) (0.637–1.822) Feeding start 0.162 0.011 0.148 0.085 0.136 0.133 - - - - - - a) within 24 hours (0.040–0.662) (0.017–1.297) (0.010–1.835) Time to full - - - - - - 1.308 0.071 1.234 0.228 0.543 0.220 b) feeding (day) (0.977–1.751) (0.877–1.736) (0.204–1.443) GA, gestational age; SGA, small for GA; OR, odds ratio; CI, confidence interval. a) b) Time from birth. 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Journal

Annals of Pediatric Endocrinology & Metabolism – Pubmed Central

Published: Dec 31, 2015

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