# Risk Factors for Recurrence of Gestational Diabetes Mellitus and Its Correlation with Maternal and Infant Prognosis

Authors: Xiaohui Wei; Ruihong Hu; Ying Gao; Zhongqin Yu; Xin Zhang
Journal: Evidence-Based Complementary and Alternative Medicine
 (2022)

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## Abstract

Objective. To explore and analyze the risk factors of recurrence of gestational diabetes mellitus (GDM) and its correlation with maternal and infant prognosis. Methods. The clinical data of 128 GDM patients admitted to our hospital from May 2018 to May 2020 were retrospectively analyzed, and they were divided into a recurrence group (n = 65) and a nonrecurrence group (n = 63) according to the presence or absence of recurrence after one year of follow-up. The general data and clinical data of the two groups of patients were compared by single factor, and the factors with statistical significance were analyzed by logistic regression, and the maternal and infant outcomes and prognosis of the two groups of patients were compared. Results. Compared with the nonrecurrence group, the recurrence group had a higher proportion of patients aged ≥35 years, with first fasting blood glucose ≥7.0 mmol/L, and with BMI value index ≥25 kg/m2 during repregnancy, and the differences were statistically significant (p<0.05). Multivariate logistic regression analysis showed that elder maternal age, high blood glucose level in the previous pregnancy, and high BMI index during this pregnancy were all high-risk factors for GDM recurrence (p<0.05). Compared with the nonrecurrence group, the recurrence group had a lower rate of vaginal delivery, lower rate of premature rupture of membranes, lower rate of premature birth, lower rate of macrosomia, lower rate of neonatal asphyxia, lower rate of postpartum hemorrhage, and lower Apgar score within 1 minute of delivery (p<0.05). Conclusion. Older maternal age, high blood glucose level in the previous pregnancy, and high BMI index during the present pregnancy are high-risk factors for GDM recurrence that can further lead to adverse outcomes for mothers and infants. Clinicians should place sufficient emphasis on targeted early measures responding to high-risk factors to minimize the risk of GDM recurrence and optimize maternal and infant outcomes.


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## Body

## 1. Introduction

A great deal of evidence show that the occurrence and development of gestational diabetes mellitus (GDM) is highly associated with adverse pregnancy outcomes. Although the blood glucose of most pregnant women with GDM can return to normal levels after delivery, there remains a high risk of developing type 2 diabetes [1, 2]. Recently, with the change of population policy in China, an increasing number of women with a history of GDM tend to have another pregnancy, and the blood sugar of these women received extra attention. The principles of management are to maintain a normal glycaemic range, reduce maternal and infant complications and reduce perinatal mortality. Patients are usually advised to start with diet and exercise therapy, and insulin is recommended if blood glucose is not well controlled [3]. Recurrent GDM is determined if a woman with a history of GDM has abnormal glucose metabolism during pregnancy again and meets the diagnostic criteria for GDM [4]. Patients with gestational diabetes may return to normal blood glucose for a certain period after delivery, but more than half of patients with GDM will eventually become type 2 diabetic within the next 10–20 years, and there is growing evidence that their offspring are at risk of developing obesity and diabetes, with an increased risk of adverse cardiovascular events [5]. In addition to that, hyperglycaemia can cause abnormal embryonic development and even death, with a 15%–30% incidence of miscarriage [6]. In this study, the risk factors of recurrent GDM are discussed, and the correlation between recurrent GDM and maternal and infant prognosis is analyzed, gearing to providing more clinical evidence for obstetrics treatment.


## 2. Materials and Methods

### 2.1. Study Population

The clinical data of 128 GDM patients admitted to our hospital from May 2018 to May 2020 were retrospectively analyzed, and they were divided into a recurrence group (n = 65) and a nonrecurrence group (n = 63) according to whether recurrence occurred after 1-year follow-up.


### 2.2. Inclusion and Exclusion Criteria

#### 2.2.1. Inclusion Criteria

(1)
The clinical symptoms and signs examination and laboratory index met the diagnostic criteria for GDM in Obstetrics and Gynecology (9th edition) [4].(2)
Average-dimensional singleton pregnancy.(3)
Complete clinical data had a strong desire to reproduce again.(4)
The male partner had normal reproductive function.(5)
All signed the informed consent form.


#### 2.2.2. Exclusion Criteria

(1)
Those with diabetes mellitus before this pregnancy.(2)
Those with other pregnancy complications.(3)
Those with missing clinical data.


### 2.3. Methods

Firstly, the general data and clinical data of the two groups of patients were collected for univariate analysis, and then the logistic regression analysis was performed on the factors with statistical significance to analyze the maternal and infant outcomes and prognosis of the two groups of patients.(1)
General and clinical information including maternal age (≥35 or <35 years), number of pregnancies (≥3 or <3), number of deliveries (≥3 or <3), gestational interval, prepregnancy BMI (≥25 kg/m2 or <25 kg/m2), prepregnancy weight, previous fasting glucose (≥7.0 mmol/L or <7.0 mmol/L), weight gain in early pregnancy, second pregnancy weight gain, and first use of insulin were recorded.(2)
The delivery methods of the two groups of patients, including vaginal delivery, vaginal midwifery, and cesarean section were recorded and analyzed.(3)
The maternal and infant outcomes of the two groups of patients, including premature rupture of membranes, premature birth, macrosomia, neonatal asphyxia, and postpartum hemorrhage were recorded and compared.(4)
Apgar scores within 1 minute postpartum [7] was evaluated. The whole body skin color, pulse, respiratory rate, stimulation response, and muscle tone of the neonate were scored. The total score was 10 points. The lower the risk of neonatal asphyxia, the higher the score.


### 2.4. Statistical Analyses

Data were expressed as the mean ± standard deviation and cases (%). Statistical analysis was performed using SPSS 22.0 (IBM, Armonk, NY, USA). Differences between groups were compared using Student’st-test and chi-square test. A p value < 0.05 was considered statistically significant. Univariate and multivariate logistic regression analysis was used to analyze the factors affecting GDM recurrence.


## 2.1. Study Population

The clinical data of 128 GDM patients admitted to our hospital from May 2018 to May 2020 were retrospectively analyzed, and they were divided into a recurrence group (n = 65) and a nonrecurrence group (n = 63) according to whether recurrence occurred after 1-year follow-up.


## 2.2. Inclusion and Exclusion Criteria

### 2.2.1. Inclusion Criteria

(1)
The clinical symptoms and signs examination and laboratory index met the diagnostic criteria for GDM in Obstetrics and Gynecology (9th edition) [4].(2)
Average-dimensional singleton pregnancy.(3)
Complete clinical data had a strong desire to reproduce again.(4)
The male partner had normal reproductive function.(5)
All signed the informed consent form.


### 2.2.2. Exclusion Criteria

(1)
Those with diabetes mellitus before this pregnancy.(2)
Those with other pregnancy complications.(3)
Those with missing clinical data.


## 2.2.1. Inclusion Criteria

(1)
The clinical symptoms and signs examination and laboratory index met the diagnostic criteria for GDM in Obstetrics and Gynecology (9th edition) [4].(2)
Average-dimensional singleton pregnancy.(3)
Complete clinical data had a strong desire to reproduce again.(4)
The male partner had normal reproductive function.(5)
All signed the informed consent form.


## 2.2.2. Exclusion Criteria

(1)
Those with diabetes mellitus before this pregnancy.(2)
Those with other pregnancy complications.(3)
Those with missing clinical data.


## 2.3. Methods

Firstly, the general data and clinical data of the two groups of patients were collected for univariate analysis, and then the logistic regression analysis was performed on the factors with statistical significance to analyze the maternal and infant outcomes and prognosis of the two groups of patients.(1)
General and clinical information including maternal age (≥35 or <35 years), number of pregnancies (≥3 or <3), number of deliveries (≥3 or <3), gestational interval, prepregnancy BMI (≥25 kg/m2 or <25 kg/m2), prepregnancy weight, previous fasting glucose (≥7.0 mmol/L or <7.0 mmol/L), weight gain in early pregnancy, second pregnancy weight gain, and first use of insulin were recorded.(2)
The delivery methods of the two groups of patients, including vaginal delivery, vaginal midwifery, and cesarean section were recorded and analyzed.(3)
The maternal and infant outcomes of the two groups of patients, including premature rupture of membranes, premature birth, macrosomia, neonatal asphyxia, and postpartum hemorrhage were recorded and compared.(4)
Apgar scores within 1 minute postpartum [7] was evaluated. The whole body skin color, pulse, respiratory rate, stimulation response, and muscle tone of the neonate were scored. The total score was 10 points. The lower the risk of neonatal asphyxia, the higher the score.


## 2.4. Statistical Analyses

Data were expressed as the mean ± standard deviation and cases (%). Statistical analysis was performed using SPSS 22.0 (IBM, Armonk, NY, USA). Differences between groups were compared using Student’st-test and chi-square test. A p value < 0.05 was considered statistically significant. Univariate and multivariate logistic regression analysis was used to analyze the factors affecting GDM recurrence.


## 3. Results

### 3.1. Univariate Analysis of Factors Affecting GDM Recurrence

Compared with the nonrecurrence group, the recurrence group had a higher proportion of patients aged ≥35 years, with first fasting blood glucose ≥7.0 mmol/L, and with BMI value index ≥25 kg/m2 during repregnancy, and the differences were statistically significant (p<0.05). There were no significant differences in pregnancy times, parity, pregnancy interval, prepregnancy weight, weight gain during early pregnancy, weight gain during middle pregnancy, and first use of insulin between the two groups (p>0.05) (see Table 1).Table 1
Univariate analysis of factors affecting GDM recurrence.
FactorsRecurrence group (n = 65)Nonrecurrence group (n = 63)χ2/tp valueAge (≥35 year/<35 year)56/933/3017.225≤0.001Pregnancy (≥3/<3 times)9/567/560.2190.640Parity (≥3/<3times)7/585/580.3020.583First fasting blood sugar (≥7.0 mmol/L/<7.0 mmol/L)51/1435/287.6140.006BMI during pregnancy (≥25 kg/m2/<25 kg/m2)53/1237/267.9730.005Pregnancy interval (month)51.20 ± 12.5848.33 ± 13.541.2410.108Prepregnancy body mass (kg)70.26 ± 15.1469.37 ± 17.600.3060.380Weight gain in early pregnancy (kg)1.88 ± 0.941.85 ± 0.800.1950.423Weight gain during the second trimester (kg)7.54 ± 2.117.10 ± 2.231.1460.127First use of insulin (yes/no)18/4713/500.8680.351


### 3.2. Multivariate Logistic Regression Analysis of Factors Affecting GDM Recurrence

Multivariate logistic regression analysis showed that elder maternal age, high blood glucose level in the previous pregnancy, and high BMI index during this pregnancy were all high-risk factors for GDM recurrence (p<0.05) (see Table 2).Table 2
Multivariate logistic regression analysis of factors affecting GDM recurrence.
VariablesαS.E.Waldp valueOR95% CIMaternity age0.3211.4714.258<0.052.3041.156∼3.657Previous pregnancy blood sugar level0.3651.4024.339<0.052.6571.095∼3.345BMI during the present pregnancy0.3231.3584.268<0.052.2581.125∼3.658


### 3.3. Comparison of Maternal and Infant Outcomes and Prognosis between the Two Groups of Patients

Compared with the nonrecurrence group, the recurrence group had a lower rate of vaginal delivery, lower rate of premature rupture of membranes, lower rate of premature birth, lower rate of macrosomia, lower rate of neonatal asphyxia, lower rate of postpartum hemorrhage, and lower Apgar score within 1 minute of delivery (p<0.05). There was no significant difference in the rates of vaginal delivery and cesarean section between the two groups (p>0.05) (see Table 3).Table 3
Comparison of maternal and infant outcomes and prognosis between the two groups of patients.
GroupsnVaginal birth rate (n (%))Rate of midwifery (n (%))Cesarean section rate (n (%))Premature rupture of membranes (n (%))Preterm birth rate (n (%))Macrosomia rate (n (%))Neonatal asphyxia rate (n (%))Postpartum hemorrhage rate (n (%))Apgar score at 1 min of delivery (point)Recurrence group6540 (61.54)9 (13.85)14 (21.54)8 (12.31)9 (13.85)10 (15.38)8 (12.31)8 (12.31)8.21 ± 0.48Nonrecurrence group6354 (85.71)3 (4.76)6 (9.52)1 (1.59)2 (3.17)2 (3.17)1 (1.59)1 (1.59)8.78 ± 0.52χ2/t9.5863.1073.5034.1044.6385.6144.1044.1046.439p value0.0020.0780.0610.0430.0310.0180.0430.043≤0.001


## 3.1. Univariate Analysis of Factors Affecting GDM Recurrence

Compared with the nonrecurrence group, the recurrence group had a higher proportion of patients aged ≥35 years, with first fasting blood glucose ≥7.0 mmol/L, and with BMI value index ≥25 kg/m2 during repregnancy, and the differences were statistically significant (p<0.05). There were no significant differences in pregnancy times, parity, pregnancy interval, prepregnancy weight, weight gain during early pregnancy, weight gain during middle pregnancy, and first use of insulin between the two groups (p>0.05) (see Table 1).Table 1
Univariate analysis of factors affecting GDM recurrence.
FactorsRecurrence group (n = 65)Nonrecurrence group (n = 63)χ2/tp valueAge (≥35 year/<35 year)56/933/3017.225≤0.001Pregnancy (≥3/<3 times)9/567/560.2190.640Parity (≥3/<3times)7/585/580.3020.583First fasting blood sugar (≥7.0 mmol/L/<7.0 mmol/L)51/1435/287.6140.006BMI during pregnancy (≥25 kg/m2/<25 kg/m2)53/1237/267.9730.005Pregnancy interval (month)51.20 ± 12.5848.33 ± 13.541.2410.108Prepregnancy body mass (kg)70.26 ± 15.1469.37 ± 17.600.3060.380Weight gain in early pregnancy (kg)1.88 ± 0.941.85 ± 0.800.1950.423Weight gain during the second trimester (kg)7.54 ± 2.117.10 ± 2.231.1460.127First use of insulin (yes/no)18/4713/500.8680.351


## 3.2. Multivariate Logistic Regression Analysis of Factors Affecting GDM Recurrence

Multivariate logistic regression analysis showed that elder maternal age, high blood glucose level in the previous pregnancy, and high BMI index during this pregnancy were all high-risk factors for GDM recurrence (p<0.05) (see Table 2).Table 2
Multivariate logistic regression analysis of factors affecting GDM recurrence.
VariablesαS.E.Waldp valueOR95% CIMaternity age0.3211.4714.258<0.052.3041.156∼3.657Previous pregnancy blood sugar level0.3651.4024.339<0.052.6571.095∼3.345BMI during the present pregnancy0.3231.3584.268<0.052.2581.125∼3.658


## 3.3. Comparison of Maternal and Infant Outcomes and Prognosis between the Two Groups of Patients

Compared with the nonrecurrence group, the recurrence group had a lower rate of vaginal delivery, lower rate of premature rupture of membranes, lower rate of premature birth, lower rate of macrosomia, lower rate of neonatal asphyxia, lower rate of postpartum hemorrhage, and lower Apgar score within 1 minute of delivery (p<0.05). There was no significant difference in the rates of vaginal delivery and cesarean section between the two groups (p>0.05) (see Table 3).Table 3
Comparison of maternal and infant outcomes and prognosis between the two groups of patients.
GroupsnVaginal birth rate (n (%))Rate of midwifery (n (%))Cesarean section rate (n (%))Premature rupture of membranes (n (%))Preterm birth rate (n (%))Macrosomia rate (n (%))Neonatal asphyxia rate (n (%))Postpartum hemorrhage rate (n (%))Apgar score at 1 min of delivery (point)Recurrence group6540 (61.54)9 (13.85)14 (21.54)8 (12.31)9 (13.85)10 (15.38)8 (12.31)8 (12.31)8.21 ± 0.48Nonrecurrence group6354 (85.71)3 (4.76)6 (9.52)1 (1.59)2 (3.17)2 (3.17)1 (1.59)1 (1.59)8.78 ± 0.52χ2/t9.5863.1073.5034.1044.6385.6144.1044.1046.439p value0.0020.0780.0610.0430.0310.0180.0430.043≤0.001


## 4. Discussion

GDM is a common metabolic disease during pregnancy and also regarded as one of the complications of pregnancy that has a normal glucose metabolism before pregnancy, and diabetes during pregnancy [8]. It is predominantly caused by a series of physiological changes after pregnancy, increased glucose requirements, increased insulin resistance, and relatively low insulin secretion [9]. A survey revealed that the incidence of GDM accounts for 17.5% and 18.9% in China [10]. In recent years, the release of the two-child policy leads to an increased average age of pregnant women with a second child. Concurrently, the repregnancy rate of pregnant women with a history of GDM also rises, imposing substantially adverse impact on maternal and infant outcomes [11, 12]. The impact of GDM on the mother and child depends on the condition of the diabetes and the level of glycaemic control. The severe cases or those with poor glycaemic control have a negatively significant impact on the mother and child, with a higher incidence of near- and long-term complications [13]. Therefore, it is extremely imperative to take corresponding measures to prevent the recurrence of GDM by analyzing the correlation between its risk factors and the prognosis of mothers and infants.In this study, multivariate logistic regression analysis showed that high maternal age, high blood glucose levels in previous pregnancy, and high BMI index during this pregnancy were all high-risk factors for inducing GDM recurrence. Among them, maternal age can significantly increase the risk of GDM recurrence, which is largely consistent with previous research [14]. As early as 2014, the Chinese guidelines for the diagnosis and treatment of gestational diabetes mellitus clearly stipulated that advanced age is a high-risk factor for the occurrence of GDM in Chinese pregnant women. Therefore, for older pregnant women scheduled to be repregnant, it is necessary to formulate a pregnancy plan and shorten the pregnancy interval, thereby reducing the risk of GDM recurrence [15, 16]. Additionally, the high blood sugar in the former pregnancy is likely to experience GDM recurrence. It is attributed to the fact that higher blood sugar leads to more severe insulin resistance followed by impaired secretion function of pancreatic β cells and abnormal glucose metabolism [17, 18]. Moreover, a high BMI index during present pregnancy can also increase the risk of GDM. The possible explanation is that overweight pregnant woman is associated with high blood pressure and blood lipid levels, and further higher blood sugar [19]. In pregnant women, hyperglycaemia can cause abnormal embryonic development or even death, with a miscarriage rate of 15%–30%, and the likelihood of hypertensive disorders in pregnancy are two to four times higher than nondiabetic women, which is possibly due to the presence of severe insulin resistance and hyperinsulinemia [20]; when diabetes is associated with microangiopathy, especially in combination with renal disease, the incidence of hypertension and pre-eclampsia in pregnancy would exceed 50% [21]. Therefore, it has significant implications to control weight, and strengthen diet, and exercise intervention for pregnant women with GDM demanding for repregnancy [22].Our study also observed that compared with the nonrecurrence group, the recurrence group had a lower rate of vaginal delivery, a lower rate of premature rupture of membranes, a lower rate of premature rupture of membranes, a lower rate of preterm birth, a low rate of macrosomia, a low rate of neonatal asphyxia, a lower rate of postpartum hemorrhage, and a lower Apgar score within 1 minute of delivery. It is clear that the maternal and infant pregnancy outcomes in the GDM recurrence group are generally poor, which is attributable to the adverse effects on maternal and infant outcomes. Since the fetus is in an environment of hyperinsulinemia caused by maternal hyperglycaemia for a long time, it promotes protein and fat synthesis and inhibits lipolysis, resulting in the overdevelopment of the body into a macrofetus [23]. Hyperglycemia stimulates increased fetal insulin secretion resulting in hyperinsulinemia, which antagonizes glucocorticoids and promotes the synthesis and release of alveolar type II cell surface active substances, resulting in decreased fetal lung surface active substance production and secretion and delayed fetal lung maturation [24]. In neonates, the incidence of neonatal respiratory distress syndrome is increased and hyperinsulinemia persists after the neonate is removed from the maternal hyperglycaemic environment, which can predispose the neonate to hypoglycaemia if sugar is not replenished in a timely manner, putting the neonate’s life at risk in severe cases [25]. Fetal hyperinsulinemia increases the body’s oxygen consumption, causing chronic intrauterine ischaemia and inducing increased production of erythropoietin, which stimulates extrafetal bone marrow haematopoiesis and causes increased erythropoiesis [26]. As a result, it requires a strict monitoring on various indicators such as glucose metabolism, dietary habits, and prepregnancy body mass of high-risk pregnant women in clinical work, and a reasonable dietary guidance and exercise to ensure reasonable indicators of puerperae, finally reducing the recurrence rate of GDM and achieving favorable pregnancy outcomes for both mothers and infants [27].TCM syndrome differentiation types can be mainly divided into deficiency of Qi (breath power)-Yin, deficiency of spleen-kidney and liver-kidney, deficiency of heart-spleen and heart-lung, and deficiency of spleen-stomach [28]. In the treatment of GDM, according to the principle of identification, the physical condition of GDM belongs to the category of “deficiency of Qi-Yin,” and the common manifestations are polyuria, easy thirst, easy hunger, and fatigue [29]. “Deficiency of the spleen-kidney” is accompanied by soreness in the waist and knees, fear of cold, loose stools, etc. Accordingly, the treatment should strengthen the spleen and kidney, and the prescriptions can be Shenqi Dihuang Decoction and Buzhong Yiqi Decoction [30] and Siwu Decoction and Danggui Buxue Decoction et al. [31]; for those with “heart-spleen deficiency,” the prescription can be Guipi Decoction [32]; for the “heart-lung deficiency” type, Yupingfeng San and Shengmai San can be used in the prescription [33]; for those with excessive Yin deficiency and heat, Danggui Liuhuang Decoction can be used, and for the “spleen-stomach deficiency” type, Shenling Baizhu Powder can be used [34, 35].


## 5. Conclusion

Taken together, older maternal age, high blood glucose level in the previous pregnancy, and high BMI index during the present pregnancy are high-risk factors for GDM recurrence that can further lead to adverse outcomes for mothers and infants. Clinicians should place sufficient emphasis on targeted early measures responding to high-risk factors to minimize the risk of GDM recurrence and optimize maternal and infant outcomes.



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