Introduction
Gestational diabetes mellitus (GDM) is a common pregnancy disorder and has long been defined as any degree of abnormal glucose metabolism, first detected or with first onset, during pregnancy [
1]. The prevalence of GDM has been rising over the last decade [
2,
3], making GDM a serious global health issue today.
Gestational diabetes mellitus has adverse short- and long-term effects on the pregnant woman and her child, both during pregnancy and later in life [
4,
5], with maternal obesity augmenting the adverse effects on neonatal outcomes [
6]. Some well-known risk factors for GDM include increase in maternal age, genetic predisposition for diabetes mellitus, non-Caucasian ethnicity, as well as maternal obesity [
7], possibly also lifestyle and dietary related factors, parental smoking and an early age at menarche [
7,
8]. A recent study emphasizes the importance of recognizing GDM as a heterogenic disorder with also non-obese women being affected—indicating the importance of a large number of risk factors [
9]. Further, studies have shown that maternal stature alters glucose metabolism and that short women are at increased risk for GDM [
10].
According to the Developmental Origins of Health and Disease (DOHaD) hypothesis prenatal environmental conditions might have long-lasting effects and affect an individual´s morbidity in adulthood [
11], influencing for example the risk for cardiovascular and metabolic disturbances [
12]. In several previous studies, a negative linear association between birth weight and risk for type 2 diabetes (T2D) has been observed [
13,
14], although some findings indicating a U-shaped relationship between birth weight and risk of T2D exist [
15]. The relationship between birth weight and risk for GDM has also been studied. The results have been conflicting as both studies indicating an inverse association [
16‐
18], as well as a U-shaped relationship have been reported [
19‐
21]. However, birth weight is a very crude measurement of body size at birth. Interestingly, only one recent study has assessed the relationship between maternal birth size using ponderal index (PI) as a measurement of body size at birth and risk for GDM, showing an inverse association [
22].
In 2016, we initiated a long-term follow-up study in the city of Vantaa, Finland, to assess both short- and long-term consequences of glucose metabolism on pregnant women and their offspring’s health. The relationship between body size at birth and future risk for GDM has previously been studied using primarily birth weight as a measure of body size at birth. Body surface area (BSA) is an anthropometric measurement used to make a more accurate evaluation of metabolic mass and body size. The aim of this study is to evaluate how BSA at birth affects the future risk for GDM.
Discussion
According to our study findings, there is a linear inverse association between BSA at birth, and later risk for GDM in primiparous women. The prevalence of GDM was highest (18.1%), among those with the smallest BSA at birth, and lowest (9.5%), among those with the largest BSA at birth. Similarly, the OR for GDM in the group with the largest BSA, compared to the group with the smallest BSA was 0.46. We also used another marker of body size at birth, i.e., ponderal index to evaluate the relationship between body size at birth and risk for GDM. Ponderal index at birth did not predict future risk of GDM. Further, BSA at birth and adult anthropometry correlated, although weakly, with the strongest correlation observed between BSA at birth and adult height.
The GDM prevalence in our study cohort was 12% and the mean age of the primiparous women was 22 years. The mean age of primiparas in Finland during the study period between 2010 and 2015 was 29 years [
28]. The nationwide prevalence of GDM in Finland during 2016 was 18% [
28], which is higher than the prevalence in the present study. This is probably explained by the fact that the women in our study cohort were primiparas of rather young age, due to restrictions of our register-based study setting as the data is limited to women born after 1987, when the Finnish Medical Birth Register was founded.
To the best of our knowledge, this is the first study to investigate the relationship between BSA at birth and later risk for GDM in primiparous women. We aimed to investigate the relationship using BSA at birth as a more accurate estimate for body size at birth than for example birth weight, in order to approximate the metabolic tissue and body size as a whole. Further, we assessed the relationship between both BSA and ponderal index as parameters on risk for GDM. Comparisons between our findings and previous publications are based on studies that have assessed the relationship between birth weight only or ponderal index, and risk for GDM.
Similar to previous studies that have shown birth weight to be inversely associated with risk for GDM [
16‐
18,
29,
30], and a more recent study from 2017 that reported ponderal index to be inversely associated with GDM [
22], we also found an increased risk for GDM in women with a small BSA at birth and a lower risk for women with a large BSA at birth. However, we did not detect a similar statistically significant relationship between ponderal index and risk for GDM. Further, we did not detect a U-shaped relationship between small and large infants and risk for GDM, as some previous studies have reported with respect to low and high birth weight and risk for GDM [
19‐
21,
31,
32].
The conflicting results between former studies with regard to a linear inverse versus a U-shaped relationship between birth weight and risk for GDM have, at least to some extent, been thought to reflect differences in study settings, with some studies lacking a big enough comparison group of macrosomic infants. In addition, the relationship has also been explained by ethnic differences; as Williams showed in 1999, women of African-American ethnicity showed a U-shaped relationship between birth weight and risk for GDM, while women of other ethnicities, showed an inverse linear relationship [
33]. Moreover, offspring born to pregnant women who have been diagnosed with GDM are more prone to be macrosomic, and maternal GDM has been recognized as a risk factor for future metabolic disturbances in the offspring [
5].
There are several factors affecting fetal growth such as gestational age, parity, infant sex, in utero metabolism, and genetic factors [
34,
35]. Furthermore, a small body size at birth can be explained by malnutrition during pregnancy [
36], or maternal constraints [
37], due to limited space in utero as a result of a narrow pelvis.
A small birthweight has been thought to affect morbidity in adulthood and has formed the basis for the DOHaD hypothesis [
38]—the concept that the in utero environment, developmental plasticity, and possible epigenetic mechanisms during critical periods of early organ development can have long-lasting effects on health [
38]. Moreover, low birth weight has been linked to insulin resistance [
39]. In 1991, Hales and Barker proposed in their Hertfordshire study that infants born small have an impaired glucose tolerance in adulthood and that this might be due to impaired development of the endocrine pancreas and result in impaired beta cell function later in life [
40]. Further, insulin is recognized to be an important growth factor and studies indicate that there could be genetic alleles that might both reduce fetal growth and cause an impaired insulin secretion and hence, predispose to diabetes [
41].
Why did we think it was important to assess the relationship between maternal body size as a whole, also taking birth length into account, and risk for GDM? Compared to birth weight, birth length has been considered to be an even stronger predictor of adult height [
42,
43], and height has been shown to influence the risk for GDM [
10].
In 2005, Eide et al. concluded that as birth length predicts adult stature and adult stature is associated with several non-communicable disorders—birth length might be a better predictor of adult health than birth weight [
42]. Adult weight is to a greater degree influenced by environmental factors and appears to have a weaker hereditary component than height [
42]. Therefore, in order to have a more accurate measurement of maternal body size at birth, taking both birth weight and birth length into account and to further dilute the effect of birth weight as the only measurement of birth size in assessing the risk of disease burden in adulthood, we wanted to evaluate the risk for GDM using both BSA and ponderal index at birth as measurements. According to our results, BSA has a stronger effect on predicting risk for GDM than ponderal index has. Our findings suggest that risk for GDM is inversely associated with BSA at birth. Ponderal index at birth showed no significant effect on risk for GDM.
The strength of the study is that it encompasses all primiparous Finnish women from Vantaa city, the fourth biggest city in Finland, who delivered during a 7-year follow-up period and of whom we had complete data about their own birth length and weight based on register data. To avoid the confounding effect of previous GDM or parity, we included only primiparas in the study. The diagnosis of GDM is based on a standardized 2-h 75-g OGTT and the diagnostic criteria have remained the same during the whole study period. Finally, the Finnish Medical Birth Register is considered to be of high quality [
44].
The study also has some limitations. We missed information about some well-known risk factors for GDM; such as family history of diabetes, gestational weight gain, dietary habits, and physical activity. All study participants had Finnish background, and therefore the generalization of the results globally can be restricted. Most importantly, it was only in 1987 when the Finnish Medical Birth Register started to collect information on a nationwide basis, thereby, this cohort consisted only of rather young primiparas and the results cannot be generalized to older pregnant women.
In conclusion, BSA at birth is inversely associated with future risk for GDM in primiparous women. Special attention should be paid to pregnant women who have been born small, in order to follow-up and if possible reduce the risk for GDM. Likewise, to encourage a healthy and nutritious pregnancy diet and to aim for an optimal fetal growth are important in any pregnancy to reduce transgenerational transmission of GDM and to prevent an infant’s risk for being born small and thereby at risk for future metabolic disturbances.