Maternal Gestational Diabetes and Early Childhood Obesity: A Retrospective Cohort Study

Abstract

Background:

Recently, childhood obesity has become one of the most serious public health problems in the world. Gestational diabetes mellitus (GDM) is considered a risk factor for childhood overweight and obesity. The study aimed at investigating the relationship between maternal GDM and childhood obesity in children aged from 1 to 3 years.

Methods:

In this retrospective cohort study, 237 GDM and 296 non-GDM mothers and their offspring who were followed up by Family Medicine Clinics in Rize province of Turkey were assessed. World Health Organization (WHO) criteria were used for the diagnosis of maternal GDM. Crude and adjusted logistic regression models were calculated for the association of gestational diabetes and childhood overweight/obesity. Gender and age-specific percentile tables were used for the categorization of BMI.

Results:

Statistical analysis carried out with adjustment for potential confounders (mother's age, educational status, smoking status, BMI, gestational weight gain, children's gender, and gestational birth weight) provided results with an odds ratio of 2.99; 95% CI 1.14–7.94 and 7.77; 95% CI 1.92–31.37 for the impact of gestational diabetes on childhood overweight and obesity at 2 and 3 years of age, respectively.

Conclusions:

This study found evidence for maternal GDM to cause the risk of early childhood obesity. Therefore, proper intervention strategies are required for this high-risk population.

Introduction

Childhood obesity is one of the most serious public health problems of the 21st century. The problem is global and constantly affects many low- and middle-income countries, and especially the urban settings.¹ According to the OECD (Organization for Economic Cooperation and Development) 2017 report, one in six children are overweight or obese.² According to the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative 2016 (COSI), 22.5% of children in Turkey are obese or overweight (14.2% overweight, 8.3% obese).³ Since early childhood obesity poses a risk for many diseases that may occur in adulthood such as diabetes mellitus, cardiac diseases, and adult obesity,^4–9 it is important to explain the mechanisms that cause it.

It has been proposed that childhood obesity is affected by prenatal, perinatal, and postnatal environmental factors.¹⁰ Maternal metabolic conditions such as obesity and insulin resistance during pregnancy affect the risk of long-term obesity in children.¹¹ According to the study in Sweden, diabetes mellitus during pregnancy increased the children's BMI at 12 years of age.¹² In another study by Kaseva et al., prenatal metabolism-related factors, including overweight/obesity, excessive gestational weight gain (GWG), and gestational diabetes mellitus (GDM), might increase the risk of childhood obesity.¹³ However, some other studies did not find a clear relationship between mother's GDM and obesity in children older than 5 years.^14–15

Studies to date generally evaluated the relationship between GDM and childhood obesity in children aged 5 years and older.^16–18 This caused the extent of other factors affecting childhood obesity, such as lifestyle, dietary habits, and exercise, to gain prominence. Our study aimed at minimizing the impact of such environmental factors by assessing the weight of the children aged 1, 2, and 3 years.

Our study is one of the few in the whole literature, and the first one in Turkey, investigating the effect of GDM on early childhood obesity. This study aimed at assessing the relationship between the risks of being overweight and obesity in children up to 3 years of age, and it was born from mothers diagnosed with GDM by also considering other risk factors such as maternal obesity, birth weight, and weight gain during pregnancy.

Materials and Methods

Study Population

This large retrospective cohort study was conducted in 45 family medical clinics located in Rize, Turkey. Data collection centers were distributed in a wide geographical area, both urban and rural. In this study, 326 pregnant women diagnosed with GDM and 444 pregnant women without GDM who were pregnant between 2011 and 2016 are included. Women with multiple pregnancies, hypothyroid disease, lacking regular follow-up, and diabetes before pregnancy; and children diagnosed with diseases potentially affecting childhood BMI (e.g., hypothyroidism, phenylketonuria, congenital heart disease), born prematurely, and those lacking regular follow-up were excluded from the study. In addition, fasting blood glucose was checked in all women planning a pregnancy in family health centers, and women with fasting glucose (>100 mg/dL) were excluded from the study. Consequently, 237 GDM mothers, 296 mothers without GDM, and their children up to 3 years old were analyzed in this study (Fig. 1).

Figure 1.

Flow diagram for selection of participants.

All pregnant women and children included in this study were clinically assessed regularly according to the official follow-up of the protocol of the Family Medicine Practice of Turkey. Pregnant women were followed up regularly for at least four times, and children who were up to 3 years old were followed up regularly for at least 12 times. In these follow-up rounds, both mothers' and children's anthropometric measurements were recorded. Mothers' educational status, gestational age, and employment status were recorded in face-to-face conversations, and their medical history was obtained.

GDM Diagnostic Criteria

One-step 75-g oral glucose tolerance test (OGTT) was applied to all pregnant women included in our study during their 24th to 30th gestational weeks, as recommended by the WHO. Pregnant women who met the 1999 WHO diabetes mellitus criteria (fasting glucose ≥7 mmol/L [126 mg/dL] or second-hour glucose ≥11.1 mmol/L [200 mg/dL] or random glucose measurement 11.1 mmol/L [>200 mg/dL]) were diagnosed with GDM.¹⁹

Maternal BMI Analysis

The most clinically meaningful definition of obesity is based on BMI. BMI is calculated by the division of weight in kilograms by the square of height in meters (kg/m²).²⁰ BMIs of pregnant women were calculated no later than the eighth week of their pregnancy to prevent the possible influence of pregnancy-related weight gain. Mothers with BMIs of <18.5, 18.5 to ≤25, 25≤ to <30, and ≥30 kg were categorized as underweight, normal, overweight, and obese, respectively. In our study, there are three reasons why the BMIs of mothers are calculated in no later, yet up to the eighth week of pregnancy, and not before pregnancy. First, we did not have clear information about the prepregnancy period. Second, it is reported in the literature that there was a strong correlation between the prepregnancy period and the first 8 weeks of pregnancy in terms of maternal BMIs.²¹ Third, we took all anthropometric measurements manually, not based on the patient's verbal statement as opposed to former studies.

GWG Analysis

GWG is calculated by subtracting prepregnancy weight from maternal weight at the time of delivery and categorized according to the recommendations of the Institute of Medicine and National Research Council.²² Underweight, normal, overweight, and obese mothers who gained, respectively, 12.7–18.1, 11.3–15.9, 6.8–11.3, and 5.0–9.1 kg, were regarded as adequate GWG; whereas those gaining weight above or below specified values were categorized as excessive or inadequate GWG, respectively.

Children's BMI Analysis

BMIs of the children included in the study were calculated by dividing the weight (kg) by squares of height (m²) measured when they were 1, 2, and 3 years old (kg/m²). Normal BMI is relative to age and gender for children and adolescents and is often referred to as “BMI for Age.” Children's weight status is determined by using age- and gender-specific percentile tables for BMI, different than the absolute BMI intervals used for adults. According to the recommendations of the CDC, age-related BMI percentiles for children 2 and 3 years of age and weight for age percentiles are calculated for up to 1 year of age to determine the status of the weight of the children (whether they are overweight or obese or in normal limits, etc.). Categorization was based on the recommendations of the CDC: Those below 5 percentile were considered to be underweight, between 5 and 85th percentile normal weight, between 85th and 95th percentiles overweight, and more than 95 percentile obese, respectively.²³ Weight measurements of babies are made with scales that are sensitive to ±0.01 kg. Before measurement, clothes and diapers are removed and the weight is recorded at the moment the subject is stationary. For height measurements, an infantometer (inpatient height gauge) is used in children up to 2 years of age. In children older than 2 years of age, measurement is done vertically barefooted. Measurements of length were carried out with 0.1 cm sensitivity.

Breastfeeding Period

Breastfeeding was determined based on maternal self-reports during their follow-up sessions at the 12th and 24th months. Accordingly, children fell into two groups: those breast-fed <12 and >12 months.

Statistical Analysis

Distribution of the mothers' sociodemographic characteristics and some of their and their children's clinical features against the prevalence of GDM and the prevalence of obesity in the children during 1 to 3 years of age were calculated. The continuous variables were expressed in mean and standard deviation, and the categorical variables were expressed in numbers and percentages. In the evaluation of the relationship between the prevalence of mothers' GDM and the sociodemographic and some clinical features of mothers and children, the distribution properties of continuous variables were first assessed by using the Kolmogorov–Smirnov test. Those without a normal distribution pattern were re-analyzed with the Mann–Whitney U test. Chi-square test was used to determine the relationship with categorical variables.

Relationships between the prevalence of mothers' GDM and children's obesity from 1 to 3 years old were evaluated through the chi-square test. Three different models were created, and binary logistic regression analysis was used to determine the factors affecting the obesity of children who were up to 3 years old. The variables used in the first model were analyzed without being adapted for other variables. In the second model, the same variables were put into analysis after they were adapted according to the age of the mother, the education level of the mother, the smoking status of the mother, and the gender of the baby and were only then put into logistic regression analysis. In the third model, GWG, birth weight, and mother weight values were added to the analysis as confounding factors.

Data were analyzed by using SPSS 18.0 package program, and the significance limit was taken as <0.05 for all analyses.

Ethical Procedure

Ethical approval was taken from the Ethics Committee of Recep Tayyip Erdoğan University Faculty of Medicine, with protocol number 2019/151. In addition, informed consent forms are obtained from the mothers.

Results

Table 1 presents the features of mothers and children according to mothers' status of GDM. The data show that mothers with GDM are older at birth than those without GDM. Also, they are less educated and have a higher weight at the beginning of pregnancy. Further, women with GDM have gained less weight during pregnancy. There was no difference between the pregnancy numbers of mothers with and without GDM.

Table 1.

Characteristics of Study Participants by Maternal Gestational Diabetes Mellitus Status

	GDM (n = 237)	Non-GDM (n = 296)	p
Maternal characteristic
Age at delivery, years	36.6 ± 6.2	32.0 ± 5.9	<0.001
Educational status, n (%)
Primary school	128 (54.0)	165 (55.7)	<0.003
High school	62 (26.2)	84 (28.4)
University	47 (19.8)	47 (15.9)
Pregnancy BMI (up to 8 weeks)	28.4 ± 5.7	26.3 ± 4.4	<0.001
Pregnancy BMI, kg/m², n (%)
<18.5	3 (1.3)	2 (0.7)	<0.001
18.5–24.9	53 (22.4)	131 (44.3)
25–29.9	97 (40.9)	107 (36.1)
≥30	84 (35.4)	56 (18.9)
GWG, kg, n (%)
Inadequate	61 (25.7)	80 (27.0)	<0.001
Adequate	118 (49.8)	89 (30.1)
Excessive	58 (24.5)	127 (42.9)
Child characteristic
Gender, n (%)
Male	123 (51.9)	164 (55.4)	<0.462
Female	114 (48.1)	132 (44.6)
Birth weight, g	3374.9 ± 520.8	3356.8 ± 478.7	<0.732
Birth weight, grams, n (%)
<2500	13 (5.5)	11 (3.7)	<0.101
2500–4000	200 (84.4)	266 (89.9)
≥4000	24 (10.1)	19 (6.4)
Mode of infant-feeding, months, n (%)
Exclusive breastfeeding	120 (50.6)	150 (50.7)	<0.469
Not exclusive breastfeeding	117 (49.4)	146 (49.3)
Total breastfeeding duration, months, n (%)
<12	104 (43.9)	60 (20.3)	<0.001
≥12	133 (56.1)	236 (79.7)
Total breastfeeding duration, months	13.2 ± 6.5	19.4 ± 11.2	<0.001

Bold denotes statistical significance, p < 0.05.

GDM, gestational diabetes mellitus; GWG, gestational weight gain.

When all the children are categorized according to the percentile values recommended by CDC, it is found that GDM was effective on the prevalence of overweight or obese children upto 2 and 3 years old. However, it was not found to be effective in the prevalence of overweight or obese children who were 1 year old (Table 2).

Table 2.

Obesity Status of Children at 1, 2, and 3 Years According to the Mothers' Gestational Diabetes Mellitus Status

	GDM		Non-GDM		p
	N	%	N	%	p
Obesity/overweight at age 1 years					0.047
Underweight or normal	205	86.5	269	90.9
Overweight or obese	32	13.5	27	9.1
Obesity/overweight at age 2 years					<0.001
Underweight or normal	154	65	260	87.8
Overweight or obese	83	35	36	12.2
Obesity/overweight at age 3 years					<0.001
Underweight or normal	157	66.2	266	89.9
Overweight or obese	80	33.8	30	10.1

In Table 3, we utilized odds ratios from a multinomial logistic regression model that allowed us to adjust for the possible influence of potentially important covariates. In the crude analysis, GDM poses a risk for both 2 years (OR: 3.30; 95% CI 2.04–5.32) and 3 years of age groups (OR: 4.01; 95% CI 2.44–6.86) for obesity or overweight. We found that the high birth weight of children is causative for obesity or excess weight in the future years for all age groups. The risk of overweight or obesity decreased slightly after adjustment for the mother's age, and education status and smoking status, and the gender of the baby. However, the risk remained significantly higher for the groups of overweight (OR: 3.03; 95% CI 1.11–8.78) and obese children at 2 years and 3 years of age (OR: 7.75; 95% CI 1.92–31.23) . There was no significant association between GDM status and children's obesity at 1 year of age (OR: 2.35; 95% CI 0.64–8.69). When we added GWG, maternal BMI, and birth weight to the confounding factors, the correlation between GDM and obesity or overweight continued in children aged 2 and 3 years of age (Model 3) (OR: 2.99; 95% CI 1.14–7.94, OR: 7.77; 95% CI 1.92–31.37).

Table 3.

Associations of the Maternal Metabolic Factors and Birthweight with Obesity/Overweight Risk at Age 1, 2, and 3 Years in Children

Model 1	Obesity/overweight at age 1 years, OR (95% CI)	p	Obesity/overweight at age 2 years, OR (95% CI)	p	Obesity/overweight at age 3 years, OR (95% CI)	p
GDM
No	1 [Ref.]		1 [Ref.]		1 [Ref.]
Yes	0.58 (0.32–1.07)	0.083	3.30 (2.04–5.32)	<0.001	4.01 (2.44–6.86)	<0.001
Birth weight, grams
<4000	1 [Ref.]		1 [Ref.]		1 [Ref.]
≥4000	1.01 (1.00–1.02)	0.033	0.99 (0.98–0.99)	0.004	0.99 (0.98–0.99)	<0.001
Model 2	AOR1 (95% CI)		AOR1 (95% CI)		AOR1 (95% CI)
GDM
No	1 [Ref.]		1 [Ref.]		1 [Ref.]
Yes	2.35 (0.64–8.69)	0.679	3.03 (1.11–8.78)	0.030	7.75 (1.92–31.23)	0.004
Birth weight, grams
<4000	1 [Ref.]		1 [Ref.]		1 [Ref.]
≥4000	1.01 (1.01–1.02)	0.044	0.99 (0.98–0.01)	0.051	0.99 (0.98–0.99)	0.015
Model 3	AOR2 (95% CI)		AOR2 (95% CI)		AOR2 (95% CI)
GDM
No	1 [Ref.]		1 [Ref.]		1 [Ref.]
Yes	3.42 (0.85–13.74)	0.083	2.99 (1.14–7.94)	0.026	7.77 (1.92–31.37)	0.004

Bold denotes statistical significance, p < 0.05.

AOR1, adjusted for maternal age, education, smoking status, and child sex; AOR2, further adjusting for the potential mediators, including birth weight, maternal BMI, and GWG; CI, confidence interval; OR, odds ratio.

Discussion

In our retrospective cohort study, we found gestational diabetes to be causative for obesity or overweight in children who were 2 and 3 years old. This relationship is independent of other confounding factors such as maternal BMI, child's birth weight, and weight of the mother during pregnancy.

Recent studies show that the investigations conducted by Lowe et al,¹⁵ Hillier et al.,²⁴ and Skrypnik et al.²⁵ demonstrate a significant relationship between maternal GDM and childhood obesity; whereas in some other studies, this relationship remained weak.^14–15 Most of these studies were conducted in high-income countries, and many of them are cross-sectional. Besides, no confounding factors were taken into account in these studies. However, our study was the first one carried out in Turkey, which is a developing country.

It is difficult to differentiate the causative effects of maternal obesity and GDM on childhood obesity separately, because maternal obesity often appears as a precursor of GDM. Therefore, GDM can be a mediator in the relationship between mother and child obesity. For example, in a study published by Voerman et al.,²⁶ it is shown that pregestational obesity was a more prominent risk factor than GDM for children. Santangeli et al. also showed that the mother's obesity is a significant risk factor for the child's obesity.²⁷

In our study, we determined the effect of GDM on obesity in 2- and 3 year-old children separately by inserting the mothers' BMI into regression analysis, thus making our results independent of the possible causative effects of the mother's BMI. Also, we adapted our analysis for factors such as the age, the education level, and the smoking status of the mother; and the gender of the baby for multivariate analysis.

The Diabetes in Pregnancy Study conducted by Northwestern University reported that the relative weight in the children of mothers with GDM increased dramatically after 5 years of age, and half of the GDM mothers' children were >90th percentile after 8 years of age.¹² Another study conducted in China found that maternal GDM increased cardiometabolic risk at the age of 8 in early childhood, but not at 15 years of age.²⁸ The EPOCH Study (The Exploring Perinatal Outcomes among Children) found that maternal GDM was associated with higher BMI, larger waist circumference, more visceral and subcutaneous fat, and a more central fat distribution pattern at the age of 6 and 13 years.²⁹ Children who were up to 3 years old were included in our study. This limited the possible confounding effect of environmental factors on the risk of obesity in children as well as the effect of maternal GDM. Therefore, we obtained more precise and relevant data on the relationship between childhood obesity and GDM for evaluation.

The mechanisms by which diabetes mellitus exposure in the utero increases the risk of childhood obesity are not yet fully understood. However, obese women with GDM tend to have much higher insulin resistance compared with normal-weight women with GDM or obese women without GDM.³⁰ Maternal insulin resistance and corresponding hyperglycemia can cause fetal hyperinsulinemia, which can lead to excessive fetal growth associated with macrosomia and increased adiposity.³¹ Recent evidence suggests that even if glucose levels are well controlled, maternal hypertriglyceridemia from insulin resistance can also cause increased birth size and adiposity.³² Excessive adiposity of the mother at the time of delivery can affect the long-term adiposity of infants.³³ GDM can cause epigenetic changes that affect the expression of genes regulating the accumulation of body fat or related metabolic pathways.³⁴ Also, exposure to maternal diabetes results in increased leptin synthesis in offspring.³⁵

There are many studies showing the effect of GWG on childhood obesity.^36,37 Contrary to these results, we found that high GWG did not have an effect on obesity or overweight in children aged between one and three, which may be due to fact that the mothers with GDM in our study gained less weight than the mothers without GDM and the fact that mothers with GDM gained less weight in our study may be explained by the closer medical control of these mothers after their diagnosis with GDM. This closer medical approach and the psychology of illness on mothers might have affected their individual behavior and this might have caused less weight gain during pregnancy. Besides, since the prepregnancy weights of mothers diagnosed with GDM in our study were significantly higher than those of the mothers without GDM, mothers with GDM might have been more careful in terms of weight control during pregnancy.

Our retrospective cohort study had many strengths. It consisted of a sample prepared from medical records of Family Medicine Practice in Rize province. Data were obtained from 42 different Family Medicine Clinics in Rize province, all of which included pregnant women's and their children's standardized anthropometric measurements that were performed by the same Family Medicine health workers with appropriate protocols for 3 years.

The GDM diagnoses in our study were made with tests that meet the criteria of the WHO at the Family Medicine Clinics where the data were collected,

Our findings should be interpreted in light of the following limitations. There is a lack of information about the treatment (insulin or diet) given to the mother after their diagnosis with GDM. This leaves out the intrauterine effects of insulin and any medications taken by the child. The absence of the child's dietary habits, lifestyle, and physical activity information up to 3 years old may cause us to ignore the environmental factors affecting the child's weight. However, in an evaluation made at an early age such as 3 years old, these possible effects may not be fully apparent yet. Therefore, the effects of these environmental factors on our results are expected to be minimal. Another limitation of our study may be the lack of triglyceride levels of mothers. This may lead us to not detect the effect of hypertriglyceridemia, which is a risk factor for childhood obesity.

Conclusions

This study provides evidence for the impact of maternal GDM on the risk of early childhood obesity. Therefore, appropriate intervention strategies are needed for this high-risk pregnant patient group and their offspring.

Footnotes

Acknowledgments

The authors would like to thank all participating research nurses and collaborators within the family medicine clinics.

Funding Information

This work has not received any funding.

Author Disclosure Statement

No competing financial interests exist.

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