ORIGINAL ARTICLE

Association between neonatal hypoglycaemia and prediabetes in postpartum women with a history of gestational diabetes Sununta Youngwanichsetha and Sasitorn Phumdoung

Aims and Objectives. To determine the association between hypoglycaemia among neonates born to mothers with gestational diabetes mellitus and their postpartum prediabetes. Background. Infants born to mothers with diabetes who experienced hyperglycaemia are more likely to develop hypoglycaemia. Design. A prospective–descriptive research was conducted in three tertiary hospitals in southern Thailand. Methods. One hundred and fifty matched pairs of mothers and their newborns were included in the study. Data were analysed using descriptive statistic, odds ratio, Spearman’s rho correlation and binary logistic regression. Results. The incidence of neonatal hypoglycaemia was 42
37% and odds ratio was 0
30. The findings showed the significant association between neonatal hypoglycaemia and postpartum blood sugar levels of women with a history of gestational diabetes mellitus. Conclusions. Neonatal hypoglycaemia was associated with maternal hyperglycaemia and prediabetes. Relevance to clinical practice. Neonatal hypoglycaemia might be used to predict prediabetes of postpartum women with a history of gestational diabetes mellitus.

What does this paper contribute to the wider global clinical community?

• Most neonates born to diabetic •

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Key words: gestational diabetes mellitus, neonatal hypoglycaemia, postpartum women, prediabetes

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mothers with hyperglycaemia experienced hypoglycaemia. Newborn infants of mothers with diabetes are at risk of developing hypoglycaemia because of high insulin levels and a lack of glucose from the mothers after birth. Neonates born to mothers with a history of diabetes should be assessed for hypoglycaemia during the first two hours after birth. Manifested symptoms of neonatal hypoglycaemia include hypothermia, poor body tone, tachypnea, pallor, cyanosis, tremors, convulsion and cardiac arrest. The study finding showed the significant association between neonatal hypoglycaemia and postpartum blood sugar levels of women with a history of gestational diabetes mellitus. Nurses and midwives should be alert to detect both neonatal hypoglycaemia and maternal hyperglycaemia in order to provide appropriate care.

Accepted for publication: 14 August 2013

Authors: Sununta Youngwanichsetha, PhD, RN, Faculty of Nursing, Prince of Songkla University, Hat Yai, Songkhla; Sasitorn Phumdoung, PhD, RN, Faculty of Nursing, Prince of Songkla University, Hat Yai, Songkhla, Thailand

© 2013 John Wiley & Sons Ltd Journal of Clinical Nursing, 23, 2181–2185, doi: 10.1111/jocn.12488

Correspondence: Sununta Youngwanichsetha, Faculty of Nursing, Department of Obstetric-Gyneocological Nursing and Midwifery, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand. Telephone: +66 074 286537. E-mails: [email protected], [email protected]

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S Youngwanichsetha and S Phumdoung

Introduction Most neonates born to diabetic mothers who could do not achieve the recommended target of glycaemic control experience hypoglycaemia, whereas some mothers with diabetes deliver healthy newborns. Three explanations of neonatal hypoglycaemia have previously been reported, namely chronic hyperglycaemia in utero, transient neonatal hyperinsulinemia and genetic hyperinsulinaemic hypoglycaemia (Straussman & Levitsky 2012). Infants born to mothers with diabetes are at risk of developing hypoglycaemia because of high insulin levels in their blood and a lack of glucose from the mothers. Prior study has shown that mothers’ high fasting and postprandial blood glucose are associated with the newborn body weight and incidence of hypoglycaemia (Durnwald et al. 2011). Macrosomic neonates, bodyweight between 4000–4500 g, are more likely to develop hypoglycaemia (Weissmann-Brenner et al. 2012). In addition, infants born before 37 weeks of gestation are also prone to develop hypoglycaemia (Knight et al. 2012). In Thailand, pregnant women with gestational diabetes mellitus (GDM) class A1 (fasting plasma glucose lower than 105 mg/dl and postprandial plasma glucose lower than 120 mg/dl) are managed with medical nutrition therapy, and pregnant women with GDM class A2 (fasting plasma glucose of 105 mg/dl or higher and postprandial plasma glucose of 120 or higher) are treated with insulin to achieve the recommended target of glycaemic control. Neonatal hypoglycaemia can be prevented through good control of plasma glucose in pregnant women during pregnancy and intrapartum. The mothers should be advised to monitor their blood glucose to maintain within normal limits. However, some of the mothers with diabetes are unable to achieve good glycaemic control, and their newborn infant is then at risk of developing hypoglycaemia.

ment of the newborn (Gataullina et al. 2012). Therefore, nurses and midwives should be alert to detect the condition early and provide appropriate treatment for newborns at risk. Gestational diabetes mellitus is known to be associated with insulin resistance before becoming pregnant, during pregnancy and can exist during the postpartum period by leading to the development of prediabetes or type 2 diabetes (Flores-Le Roux et al. 2010). Prediabetes is diagnosed by either impaired fasting glucose or impaired glucose tolerance. Fasting plasma glucose concentration of 100–125 mg/ dl and plasma glucose after taking a 75-g glucose tolerance test or postprandial of between 140–199 mg/dl are considered prediabetes, which might develop type 2 diabetes within three to 10 years postpartum (Abdul-Ghani & DeFronzo 2009). The researchers hypothesised that the trajectory of gestational diabetes, prediabetes and diabetes may affect insulin resistance, beta-cell function, glycaemic control and neonatal hypoglycaemia.

The purpose of the study The purpose of this study was to determine the association between neonatal hypoglycaemia and prediabetes in postpartum women with a history of gestational diabetes.

Methods Design A descriptive, prospective, research was employed in this study. It was conducted in three tertiary hospitals in southern Thailand, Songkhla province, which were the referral hospitals for pregnant women complicated with diabetes. This project was reviewed and approved by the institutional review board and ethics committee of Prince of Songkla University and studied hospitals.

Background A risk of neonatal hypoglycaemia is considered the consequence of being born to mothers with diabetes. Neonates born to mothers with a history of diabetes should be assessed for their blood glucose level during the first two hours after birth. Blood glucose of lower than 40 mg/dl is diagnosed as hypoglycaemia (Jain et al. 2010). Most hypoglycaemic neonates showed no symptoms. Manifested symptoms of neonatal hypoglycaemia include jitter, hypothermia, poor body tone, tremors, tachypnea, pallor, cyanosis, convulsion and cardiac arrest (Hay 2012). These complications may affect neurological and mental develop-

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Data collection and analysis Postpartum mothers with a history of GDM and their newborns who met the inclusion criteria were recruited to the study. Inclusion criteria were as follows: (1) postpartum mothers diagnosed within 24–72 hours with a history of GDM class A1 or class A2, (2) type of delivery included normal labour, vacuum extraction or caesarean section, (3) ethnicity of mothers included Thai Buddhist and Thai Muslim and (4) term newborn infants delivered by mothers with a history of gestational diabetes within 24–72 hours after birth. Exclusion criteria were as follows: (1) mothers with © 2013 John Wiley & Sons Ltd Journal of Clinical Nursing, 23, 2181–2185

Original article

other health problems such as preterm labour, pre-eclampsia, heart disease, HIV infection; and (2) infants born before 37 weeks of gestation. The potential participants were approached by a coordinating staff nurse. They were informed about the objective of the study and activities needed to take part. Participants’ rights protection was considered throughout the study. Data were collected after obtaining participants’ informed consent. First, demographic data, gestational age, type of delivery and maternal plasma glucose levels including fasting, postprandial and intrapartum blood glucose values in medical records were reviewed and collected. Second, newborn birth weight, blood glucose levels within six hours after birth, using a glucometer were recorded. Finally, six-week postpartum plasma glucose levels after taking a 75-g glucose tolerance test were collected. Data were organised using SPSS, version 14 (SPSS Inc., Chicago, IL, USA). Descriptive statistics, mean and standard deviation were used to analyse demographic and plasma glucose levels. Pearson’s and/or Spearman’s rho correlation was applied to determine the association between neonatal hypoglycaemia and maternal plasma glucose. The odds ratio of neonatal hypoglycaemia among mothers with GDM class A1 and class A2 was calculated. Then, binary logistic regression was used to test the association between neonatal hypoglycaemia and postpartum prediabetes.

Neonatal hypoglycemia and maternal prediabetes Table 1 Characteristics of women with a history of gestational diabetes mellitus (n = 118) Characteristics

Minimum–maximum

Mean (SD)

Age (years) Prepregnancy body mass index (kg/m2) Fasting plasma glucose (mg/dl) Postprandial plasma glucose (mg/dl) Intrapartum plasma glucose (mg/dl) Postpartum oral glucose tolerance teat (mg/dl)

19–47 20
28–35
80

32
60 (6
84) 27
85 (4
02)

82–116

100
37 (11
37)

102–145

125
83 (12
80)

50–158

109
47 (28
51)

98–338

186
33 (80
48)

Table 2 Characteristics of infants born to mothers with a history of gestational diabetes mellitus (n = 118) Characteristics Gestational age (weeks) Body weight (g) Blood glucose levels (mg/dl) Duration of NICU admission (days) Length of hospital stay (days)

Minimum–maximum

Mean (SD)

37–41

38
85 (0
80)

2270
00–4790
00 10
00–80
00

3549
67 (515
93) 43
13 (16
94)

1–8

2
13 (1
50)

1–8

4
13 (1
71)

Table 3 Occurrences of neonatal hypoglycaemia (n = 118)

Results Data of 118 newborn–mother pairs were analysed. Sixtytwo women (52
54%) were classified as GDM class A1 and 56 (47
46%) as GDM class A2. Thirty-five women (29
66%) were primiparas and 83 (70
34%) were multiparas. Most of the women (75 of 118, 63
56%) delivered by caesarean section, 26
28% by normal labour and 10
16% by vacuum extraction. Other maternal characteristics and plasma glucose levels are presented in Table 1. Newborn characteristics and plasma glucose levels are shown in Table 2. Overall incidence of neonatal hypoglycaemia was 42
37%. The occurrences of neonatal hypoglycaemia in mothers with GDM class A1 and class A2 are summarised in Table 3. The odds ratio of neonatal hypoglycaemia for A1 vs. A2 was 0
30, 95% CI 0
14–0
66. There were three factors related to neonatal hypoglycaemia, maternal fasting plasma glucose, postprandial plasma glucose and postpartum plasma glucose after taking a 75-g glucose tolerance test. The strongest association was between neonatal hypoglycaemia and maternal postpartum plasma glucose (Tables 4 and 5). © 2013 John Wiley & Sons Ltd Journal of Clinical Nursing, 23, 2181–2185

Occurrences of neonatal hypoglycaemia

Mothers with GDM class A1 n (%)

Mothers with GDM class A2 n (%)

Total

Hypoglycaemia Did not happen Total

18 (29
0) 44 (71
0) 62 (100
0)

32 (57
1) 24 (42
9) 56 (100
0)

50 68 118

GDM, gestational diabetes mellitus.

Discussion The results showed that neonatal hypoglycaemia was associated with maternal plasma glucose during pregnancy and the six-week postpartum period. These findings supported the concept that maternal hyperglycaemia stimulates neonatal hyperinsulinaemia. As a result, their newborns experienced hypoglycaemia after birth. However, for the mothers with GDM class A1 who could achieve glycaemic control, their infants showed a lower incidence of hypoglycaemia than those of infants born to mothers with GDM class A2. It can be explained that women with GDM class A2 had more prolonged insulin resistance than those with GDM

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S Youngwanichsetha and S Phumdoung Table 4 Correlation coefficient of neonatal hypoglycaemia with maternal and newborn characteristics (n = 118) Maternal and newborn characteristics

Correlation coefficients

Maternal age Gravidity Maternal fasting plasma glucose Maternal postprandial plasma glucose Intrapartum plasma glucose Postpartum plasma glucose after taking a 75-g glucose tolerance test Newborn body weight Duration of NICU admission Length of hospital stay

p-values

0
24 0
11 0
41*

0
180 0
540 0
024

0
42*

0
020

0
35

0
227

0
59**

0
001

0
23 0
19 0
25

0
904 0
301 0
178

insulin use during pregnancy (Ramos et al. 2011). Most women diagnosed with GDM class A2 were treated with insulin because of their high plasma glucose level over the normal limit. It is interesting that neonatal hypoglycaemia was also associated with maternal postpartum prediabetes. This finding suggests that women with GDM might have prediabetes before becoming pregnant.

Conclusion The occurrences of neonatal hypoglycaemia are more likely in neonates born to mothers with GDM class A2. Factors related to neonatal hypoglycaemia are maternal fasting plasma, postprandial plasma glucose and postpartum plasma glucose after taking a 75-g glucose tolerance test. Neonatal hypoglycaemia can be used to predict prediabetes of postpartum women with a history of gestational diabetes mellitus.

*Correlation is significant at the 0
05 level (2-tailed); **Correlation is significant at the 0
01 level (2-tailed).

Relevance to clinical practice Table 5 Binary logistic regression of neonatal hypoglycaemia and maternal plasma glucose (n = 118) Factors

Beta

SE

Wald

df

p-values

Fasting plasma glucose Postprandial plasma glucose Postpartum plasma glucose after taking a 75-g glucose tolerance test

0
066 0
66

0
036 0
033

3
282 4
060

1 1

0
047 0
044

0
101

0
044

5
284

1

0
022

To promote self-management of women with a history of GDM, mother whose infant experienced hypoglycaemia after birth should be informed that they are at risk of developing prediabetes. All postpartum women with a history of GDM, particularly class A2, should be screened for prediabetes using a 75-g glucose tolerance test within six to 12 weeks as recommended.

Disclosure

class A1 manifesting through higher fasting and postprandial plasma glucose (Durnwald et al. 2011). Research evidence indicates that higher fasting plasma glucose of mothers had impacts on neonatal fat mass, body weight and plasma glucose (London et al. 2011). In addition, previous study suggested that neonatal hypoglycaemia was associated with

The authors have confirmed that all authors meet the ICMJE criteria for authorship credit (www.icmje.org/ethical_1author.html), as follows: (1) substantial contributions to conception and design of, or acquisition of data or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version to be published.

References Abdul-Ghani M & DeFronzo RA (2009) Pathophysiology of prediabetes. Current Diabetes Reports 9, 193–199. Durnwald CP, Mele L, Spong CY, Ramin SM, Varner MW, Rouse DJ, Sciscione A, Catalano P, Saade G, Sorokin Y, Tolosa JE, Casey B & Anderson GD (2011) Glycemic characteristics and neonatal outcomes of women treated for mild gestational diabetes.

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Obstetetrics and Gynecology 117, 819–827. Flores-Le Roux JA, Chillaron JJ, Goday A, de Dou JP, Paya A, Lopez-Vilchez MA & Cano JF (2010) Peripartum metabolic control in gestational diabetes. American Journal of Obstetrics and Gynecology 202, 568e1–568e6. Gataullina S, Dellatolas G, Perdry H, Robert JJ, Valayannopoulos V, Touati

G, Ottolenghi C, Dulac O & de Lonlay P (2012) Comorbidity and metabolic context are crucial factors determining neurological sequelae of hypoglycemia. Developmental Medicine and Child Neurology 54, 1012– 1017. Hay WW (2012) Care of the infant of the diabetic mother. Current Diabetes Reports 12, 4–15.

© 2013 John Wiley & Sons Ltd Journal of Clinical Nursing, 23, 2181–2185

Original article Jain A, Aggarwal R, Sankar MJ, Agarval R, Deorari AK & Paul VK (2010) Hypoglycemia in the newborn. Indian Journal of Pediatrics 77, 1137–1142. Knight KM, Pressman EK, Hackney DN & Thornburg LL (2012) Perinatal outcomes in type 2 diabetes patients compared with non-diabetic patients matched by body mass index. The Journal of Maternal-Fetal & Neonatal Medicine 12, 611–615. London MB, Mele L, Spong C, Wapner RJ, Rouse DJ, Thorp JM, Sciscione A, Cata-

Neonatal hypoglycemia and maternal prediabetes lano P, Harper M, Saade G, Caritis SN, Sorokin Y, Peaceman AM, Tolosa JE & Anderson GD (2011) The relationship between maternal glycemia and perinatal outcome. Obstetrics and Gynecology 117, 218–224. Ramos GA, Hanley AA, Agnayo J, Warshak CR, Kim JH & Moore TR (2011) Neonatal chemical hypoglycemia in newborns from pregnancies complicated by type 2 and gestational diabetes: the importance of neonatal ponderal index. The Journal of Mater-

nal- Fetal & Neonatal Medicine 25, 267–271. Straussman S & Levitsky LL (2012) Neonatal hypoglycemia. Current Opinion in Endocrinology, Diabetes, and Obesity 17, 20–24. Weissmann-Brenner A, Simchen MJ, Zilberberg E, Kalter A, Weisz B, Achirom R & Dulitzky M (2012) Maternal and neonatal outcomes of large for gestational age pregnancies. Acta Obstetricia et Gynecologica Scandinavica 91, 844–849.

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