Maternal and Neonatal Risk Factors for Hypoglycemia in Preterm

Infants

Bugis Mardina Lubis

Beby Syofiani Hasibuan

Faculty of Medicine, Division of Neonatology Department of Child Health, Universitas Sumatera Utara,

Jl.. Dr. Mansyur, Haji Adam Malik General Hospital, Medan, Indonesia

Keywords: Maternal, Hypoglycemia, Preterm Infants, Birth Weight, Gestational Age

Abstract: Hypoglycemia is a common morbidity in preterm infants. It might cause transient and permanent disturbances

in brain structural and have impact on neurological development. The criteria for identifying preterm infants

who are at risk of hypoglycemia remain unclear. This study was conducted to determine incidence of

hypoglycemia in preterm infants and associated with maternal and neonatal risk factors. A cross-sectional

study on 50 consecutive preterm infants on hospitals in Medan, Indonesia from June to August 2018. Maternal

and neonatal risk factors were recorded. Blood glucose levels were obtained from venous blood sample and

were checked serial from the time of delivery within the first hour of life until discharged from hospital or 72

hours of age. Univariate and bivariate (Chi square and Fisher exact test) analysis were performed with 95%

CI and P value <0.05 were considered statistically significant. Out of 50 preterm infants, there were 13 infants

experienced hypoglycemia (26%). Preterm infants with birth weight <2500 gr and 32-<35 weeks of

gestational age were significantly increased the risk of developing hypoglycemia (p=0.010, PR=4.69;

p=0.021, PR= 3.11, respectively). There were significant associations between birth weight <2500 gr and

gestational age 32-<35 weeks with hypoglycemia.

1 INTRODUCTION

Prematurity is one of the highest causes of perinatal

death in addition to low birth weight (LBW) infants,

asphyxia or respiratory disorders. Neonatal mortality

rates in Asia due to prematurity amounted to 413,000

or 30% of total neonatal deaths in 2000-2003.Caring

premature infants is still a challenge. The biggest

challenge is how to reduce the risk of morbidity

which will reduce neurological disorders and long-

term growth and development disorders so that these

preterm infants can grow optimally (Howson, 2012).

One of the most common morbidity in premature

infants is hypoglycemia. The immaturity of the

glucose formation system, inadequate energy storage,

and hyperinsulinism conditions can affect the

occurrence of hypoglycemia, even severe and

recurrent hypoglycemia in preterm infants (Zanardo,

1999).

Symptoms of hypoglycemia in neonates include

jitteriness, convulsions, hypotonia, coma, refusal to

feed, cyanosis, high pitched cry, hypothermia and

even asymptomatic in mostcases. Therefore detection

of hypoglycemia must always be confirmed

biochemically (Dhananjaya, 2011). Hypoglycemia

conditions have an effect on transient and permanent

disturbances in the brain structural and have an

impact on neurological development. (Goode, 2016).

Research on risk factors for hypoglycemia in

premature infants is still limited and shows

controversial results. The purpose of this study is to

determine incidence of hypoglycemia in preterm

infants and associated maternal and neonate risk

factors for hypoglycemia.

2 METHODS

This was a cross sectional study. We examined 50

moderate to late preterm labor infants with 32-36

weeks of gestational age through normal vaginal

delivery and section caesarean. Patients were

obtained consecutively. Minimum sample size

calculated using one population sample formula.

Stillbirth infants and severe congenital abnormalities

were excluded. This study conducted from June to

August 2018 in five hospitals, Adam Malik General

Hospital, Universitas Sumatera Utara Hospital, Stella

924

Lubis, B. and Hasibuan, B.

Maternal and Neonatal Risk Factors for Hypoglycemia in Preterm Infants.

DOI: 10.5220/0010101709240928

In Proceedings of the International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches (ICOSTEERR 2018) - Research in Industry 4.0, pages

924-928

ISBN: 978-989-758-449-7

Maris Mother and Child Hospital, Sarah Hospital, and

Bunda Thamrin Hospital. All hospitals are located in

Medan, Indonesia.

Maternal characteristics such as maternal age,

weight, gravidity and parity, and delivery methods

were recorded as maternal risk factors. Neonate

characteristics such as gender, birthweight,

gestational age, one-minute Apgar score, five-minute

Apgar score were recorded as neonate risk factors.

Blood glucose levels were obtained from venous

blood sample and were checked serial from the time

of delivery within the first hour of life until

discharged from hospital or 72 hours of age. Blood

glucose levels of 40 mg/dL or lower were considered

as hypoglycemia. All patients gave informed consent.

This study was approved by the Institutional Review

Board of Universitas Sumatera Utara. Statistical data

composed of univariate and bivariate were analyzed

using SPSS version 22 (SPSS Inc., Chicago) with

95% confidence interval. The analysis was carried out

using chi square and fisher exact test. P value <0.05

were considered statistically significant.

3 RESULT

3.1 Baseline Maternal Characteristics

of Subjects

Mean of maternal age were 30.9 years with mean of

body weight were 69.3 kgs. A total of 96% gave birth

through cesarean delivery where 58% having medical

indications. There were 54% of premature

infantshadLBW.About66% were 35–37 weeks

ofgestational age. (Table1).

Table 1: Basic maternal characteristicofsubjects.

Characteristics n = 50

Maternal age, years, mean + SD

>31 years

<31 years

30.9 + 5.23

21 (42%)

29 (58%)

Maternal weight, kg, mean + SD

>69 kg

<69 kg

69.3 + 10.87

25 (50%)

Maternal parity, times, median (min-

max)

1 (0 – 2)

8 (16%)

(

84%

)

–

Delivery, n (%)

Vaginal delivery

Sectiocaesarean

2 (4%)

48 (96%)

Indication of preterm labor, n (%)

Medical indication

Spontaneous

29 (58%)

21 (42%)

Gender, n (%)

Male

Female

25 (50%)

Birthweight, gram, mean+ SD

<2500

>2500

2,503.5 +

542.21

27 (54%)

(

46%

)

Gestational age, weeks, n (%)

32 – <35 weeks

–

<37 weeks

17 (34%)

33 (66%)

One-minute Apgar score, n (%)

4-6

1 (2%)

9 (18%)

(

80%

)

Five-minute Apgar score, n (%)

4-6

0 (0%)

1 (2%)

(

98%

)

n = total numberofsubjects

3.2 Association between Maternal and

Neonate Characteristics with

Hypoglycemia in Preterm Infants

Out of 50 preterm infants, there were 13 infants who

had hypoglycemia (26%). Table 2 showed

association between maternal characteristics and

hypoglycemia in preterm infants. There were

significant association between birth weight and

prematurity with hypoglycemia. Infants with a birth

weight <2500 gr were increasedrisk of 4.69 times

experiencing hypoglycemia compared to birth

weight> 2500 gr (p=0.010). Infants with 32- <35

weeks of gestational age had 3.11 times higher risk to

had hypoglycemia than 35-<37 weeks (p=0.021).

There were no significant association between

maternal age, weight, gravidity, parity, indication of

preterm labor, gender, 1-minute and 5-minute Apgar

score with hypoglycemia in preterm infants.



Maternal and Neonatal Risk Factors for Hypoglycemia in Preterm Infants

925

Table 2: Association Between Maternal and NeonatalCharacteristics with Hypoglycemia in Preterm Infants

*p<0.05

4 DISCUSSION

Hypoglycemia is common in neonates. The lowest

blood glucose level in 2 hours of life which is

generally due to physiological rather than pathological

factors (Sperling, 2012; Mitanchez, 2007; Aggarwal,

2010). Previous studies reported prevalence of

hypoglycemia varied in neonates, approximately15.1-

29.1% (Lodhi, 2006; Dashti, 2007; Osiet, 2003;

Dalgic, 2002). The prevalence of hypoglycemia is

significantly higher in preterm infants. Singh. showed

the prevalence of hypoglycemia in preterm infants and

term infants were 19.05% vs 14.42%

(Singh, 2014).

This recentstudy found theprevalence of

hypoglycemia in preterm infantswas 26%. This

prevalence difference is due to differences in the

definition of hypoglycemia, inclusion criteria, sample

size, and detection method of hypoglycemia.There

were significant association between LBW

andprematuritywith hypoglycemia. Infants with a

birth weight <2500 gr were significantly increased

risk of 4.69 times experiencing hypoglycemia

compared to birth weight> 2500 gr. Infantswith 32 –

<35 weeksofgestationalage were significantly

increased risk of 3.11 times experiencing

hypoglycemia compared to 35 – <37 weeks

ofgestational age. This result is in line with previous

studies (Singh, 2014; Rasmussen, 2007).

Variable

Hypoglycemia Total

n (%)

(95% CI)

Yes

(

)

(

)

Maternal age

0.097

2.21 (0.84-

5.81)

>31 years 8 (38.1) 13 (61.9) 21 (100)

<31 years 5 (17.2) 24 (82.8) 29 (100)

Maternal wei

0.747

0.86 (0.34-

2.19)

>69 k

(

)

(

)

(

100

)

<69 kg 7 (28) 18 (72) 25 (100)

Maternal gravidity

–

2 (15.4)

(

29.7

)

11 (84.6)

(

70.3

)

13 (100)

(

100

)

0.469

0.52 (0.13-

2.03

)

Maternal parity

–

0 (0%)

(

)

8 (100)

(

)

8 (100)

(

100

)

0.093

1.45 (1.18-

1.77

)

Indication of preterm

labo

0.340

1.63

(0.58 – 4.59)

Medical 9 (31) 20 (69) 29 (100)

Spontaneous 4 (19) 17 (81) 21 (100)

Gender

Male

Female

6 (24)

(

)

19 (76)

(

)

25 (100)

(

100

)

0.747

0.86

(

0.34-2.19

)

Birthweight

<2,500 gr

>2,500

11 (40.7%)

(

8.7%

)

16 (59.3)

(

91.3

)

27 (100)

(

100

)

0.010*

4.69

(

1.16-19

)

Gestational age

32 – <35 weeks

35 – <37 weeks

8 (47.1)

5 (15.2)

9 (52.9)

28 (84.8)

17 (100)

33 (100)

0.021*

3.11

(1.2-8.05)

One-minute Apgar score

4 (40)

9 (22.5)

6 (60)

31 (77.5)

10 (100)

40 (100)

0.420

1.78

(0.69-4.61)

Five-minute Apgar score

1,000

1.36

(1.15-1.61)

<7 0

(

)

(

100

)

(

100

)

>7 13 (26.5) 36 (73.5) 49 (100)

ICOSTEERR 2018 - International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches

926

In the first week of life, premature infants are at

risk of developing glucose homeostasis. Premature

and LBW infantsare prone to hypoglycemia because

their small reserves and immature metabolic

pathways. After birth, the transplacental glucose

supply is interrupted, while vital organs require

continuous glucose supply to meet nutritional needs.

Simultaneously glycogenic hormones (e.g. glucagon,

catecholamines, glucocorticoids) increase, partially

suppressing insulin secretion. In preterm and LBW

infants prone to hypoglycemia because of these

adaptive changes and premature metabolic pathways.

Premature infants become prone to hypoglycemia due

to the limited glycogen and fat stores, lack of ability

to generate glucose through the gluconeogenesis

pathway, have a high metabolic demand due to

relatively higher brain size, and have a poorly

developed counter-regulatory mechanisms to prevent

hypoglycemia

(Ramzan, 2017; Bromiker, 2017; Sharma, 2017). The

American Academy of Pediatrics (AAP) recommends

hypoglycemia screening in high-risk populations

including premature infants (Adamkin, 2011).

Neonatal patients with hypoglycemia are mostly

asymptomatic. Hypoglycemic neonates were

asymptomatic due to increased utilization of

alternative substrates, such as lactate, in combination

with intracerebral storage of glycogen. All neonates

with hypoglycemia should receive careful

surveillance including glucose monitoring and therapy

because of possible adverse long-term effects (Dashti,

2007; Jain, 2008).

This study showsthatthere were no significant

association between maternal age, weight, gravidity,

parity, indication of preterm labor, gender, 1-minute

and 5-minute Apgar score with hypoglycemia in

preterm infants. Neonates from diabetic mothers,

including type 1 diabetes, type 2, and gestational

diabetes, have a high risk of developing hypoglycemia

due to the relative fetal hyperinsulinism resulting in a

feedback mechanism for the balance of high glucose

levels induced by maternal diabetes (Stanescu, 2014).

There was only 1 diabetic mother in this study where

her infant had hypoglycemia. The limitation of this

study is that infant of diabetic mother was not

analyzed as a risk factor for hypoglycemia in preterm

infants because there was only 1 case of diabetic

mother in this study and breastfeeding in the delivery

room could not be anticipated even though the amount

are expected to be almost negligible (Dollberg, 2001).

5 CONCLUSIONS

Infants with birth weight <2500 grand 32-<35 week

sofgestation a lage were significantly increased risk

to had hypoglycemia.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge that the present

research is supported by Ministry of Research and

Technology and Higher Education Republic of

Indonesia. The support is under the research grant

TALENTA USU of Year 2018 Contract Number

300/UN5.2.3.1/PPM/KP-TALENTA USU/2018.

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