Gestational Diabetes Mellitus—A Brief Overview and Current Situation in Romania

Abstract

Background: Gestational diabetes mellitus (GDM) represents a pregnancy-specific associated pathology that bears a heavy burden on patients and also on the healthcare system. GDM displays an increasing incidence and short- and long-term materno-fetal consequences. Its prevention strategies include lifestyle interventions, diet changes, gestational weight gain control, moderate-intensity exercise, and smoking cessation. GDM screening is performed in the second half of pregnancy between 24 and 28 gestational weeks. Treatment options include medical nutrition therapy and pharmacologic therapy. In most cases, optimum glycemic control is obtained by medical nutrition therapy alone. Although there are screening and treatment options, the medical system in Romania lacks homogeneity in the diagnosis and further management of pregnancies complicated with GDM. There is an urgent need to improve the healthcare system and the basic medical knowledge of the population and to find efficient strategies, which include a national diabetes in pregnancy guideline to ensure pregnancy monitoring, GDM screening, and the diagnosis and personalized management of cases in order to promote good pregnancy outcomes and minimize adverse pregnancy events.

1. Introduction

Gestational diabetes mellitus (GDM) is a distinct type of diabetes mellitus (DM), being identified during the second or third trimester. GDM diagnosis is confirmed only after ruling out other forms of DM: pre-existing diabetes, type 1 DM (T1DM), or any other type that may affect the pregnancy outcome [1]. Regarding the specific population with the related demographic characteristics, the prevalence has been reported to be between 2% and 38% [2]. An increasing trend has been observed in the number of cases of GDM which have been associated with an elevated pre-pregnancy body mass index (BMI), increased maternal age, or the obesity pandemic [3]. GDM remains an important healthcare issue as it is associated with significant materno-fetal short- and long-term complications. Although the risk of congenital anomalies in the fetus and DM-related vasculopathies is reduced compared with pre-existing DM, given the limited time from the onset of the disease, GDM presents with short-term complications such as the following: large for gestational age (LGA) fetuses and macrosomic newborns [4,5]; polyhydramnios [6]; gestational hypertension [7] or preeclampsia [8] that lead to preterm birth, neonatal pathologies (hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia, hypomagnesemia, respiratory disorders) that require neonatal intensive care unit admissions and are associated with a higher cost on the healthcare system [9]; and, the most rare complication—stillbirth [10]. GDM maternal long-term complications include impaired glucose tolerance [11], metabolic syndrome [12], T1DM [13], type 2 DM [14], and cardiovascular disease [15]. Patients with GDM are at high risk of developing type 2 DM, as a meta-analysis estimated an almost 10-fold higher risk of progressing to type 2 DM for these patients compared with normoglycemic pregnancies [14]. GDM also affects the infant’s health status, as infants from GDM-complicated pregnancies are at risk of abnormal glucose tolerance or obesity [16], T1DM [17], type 2 DM [18], and even possible affected cognitive development [19]. Therefore, a critical action is to identify patients that are the most susceptible to developing GDM. High-risk pregnant patients include those that have had GDM in the past, being associated with a 40% recurrence rate [20]; have had a glycated hemoglobin (HbA1c) value of ≥5.7% or a raised fasting glucose level; or present impaired glucose tolerance [21]. Other high-risk factors include the following: previous birth of a macrosomic newborn [22], a family history of DM [23], pre-pregnancy BMI ≥ 30 kg/m² [24], more than 35 years at conception [25], and maternal pathologies associated with insulin resistance such as polycystic ovary syndrome [26]. In contrast, pregnant patients at low risk of developing GDM include the following characteristics: maternal age < 25 years, BMI < 25 kg/m², non-Hispanic white pregnant women, and no family or personal history of DM or impaired glucose tolerance [27]. Considering these criteria and the fact that fewer women nowadays meet all the criteria, the rationale for universal screening for GDM is fundamentally correct.

1.1. GDM Prevention

Firstly, the pre-conceptional consultation should include weight loss counselling, especially in overweight or obese women with other risk factors of developing GDM, to reduce the risk of GDM and its complications during pregnancy [28]. This intervention is necessary especially in cases of pathologies associated with insulin resistance such as polycystic ovary syndrome [26]. Basically, weight loss consists of dietary intervention and an increased level of exercise. A meta-analysis [29] reported a 20% risk reduction in GDM among high-risk patients who underwent lifestyle intervention compared with those who underwent standard care. Lifestyle intervention consisted of diet adjustment, an exercise plan (during pregnancy the plan included fifty or sixty minutes of moderate-intensity exercise at least biweekly), or both; the time of debut was ideally before conception and it continued throughout pregnancy. The diet adjustment permitted weight gain accordingly to the standard recommendations [30] presented in

Table 1. Recommendations of gestational weight gain in singleton pregnancies.

Pre-Pregnancy BMI (kg/m2)	Total Weight Gain (kg)	Mean and Ranges of Weight Gain During the Second and Third Trimester * (kg)
<18.5	12.5–18	0.51 (0.44–0.58)
18.5–24.9	11.5–16	0.42 (0.35–0.5)
25.0–29.9	7–11.5	0.28 (0.23–0.33)
≥30.0	5–9	0.22 (0.17–0.27)

BMI—body mass index. * During the first trimester the recommendations include 0.5–2 kg weight gain.

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Lifestyle intervention includes adopting a balanced diet and sustained physical exercise. Although a statistically significant association between smoking cessation and GDM has not been observed [31], a healthy lifestyle should also include smoking cessation. A systematic review published in 2022 [32] regarding the role of physical activity in the prevention and treatment of GDM concluded that the recommended frequency is at least three times a week for moderate-intensity aerobic and resistance or strength training. Concerning the best dietary advice, an optimum diet represents the Mediterranean diet. Besides its strong cardio-protective features, in randomized controlled trials a reduction in the incidence of GDM in patients who followed the Mediterranean diet has been demonstrated (odds ratio 0.56 with 95% confidence interval (CI): 0.34, 0.93) [33]. A systematic review and meta-analysis of 40,940 patients regarding interventions that might prevent GDM [34] concluded that diet, physical activity, both combined, metformin, or myoinositol have a positive effect on reducing the incidence of GDM. In contrast, another review [35] concluded that the success of GDM prevention by metformin administration or lifestyle interventions relies on different individual characteristics. Another review [36] reported that by improving the metabolic milieu of the patient through time-restricted eating or physical activity, adverse pregnancy outcomes such as preeclampsia, small for gestational age, large for gestational age, fetal death, or GDM could be prevented.

1.2. GDM Diagnosis

The most recent guidelines issued by the American Diabetes Association (ADA) underscore the critical importance of screening for dysglycemia, particularly in women who are planning a pregnancy [1]. The ADA recommends glucose testing in this population, especially in the presence of established risk factors such as overweight or obesity, physical inactivity, atherogenic dyslipidemia, hypertension, a personal history of GDM or prediabetes, individuals belonging to high-risk ethnic populations, or evidence of insulin resistance. Furthermore, the ADA recommends that all females of reproductive age should be evaluated for previously undiagnosed prediabetes or DM, ideally pre-conceptionally or, if this is not the case, during the initial prenatal visit.

Screening during early pregnancy, specifically before 15 gestational weeks, aims to identify underlying glucose metabolism disorders. Elevated glycemic parameters during this period are associated with increased risks of adverse maternal and neonatal outcomes, a heightened likelihood of requiring insulin therapy, or a future GDM diagnosis [37]. Early dysglycemia identified in the first trimester is defined by fasting plasma glucose levels between 110 and 125 mg/dL or HbA1c levels ranging from 5.9% to 6.4%. In the absence of pre-existing DM or early-pregnancy glycemic abnormalities, universal screening for GDM is recommended between 24 and 28 gestational weeks [1]. Postpartum, individuals diagnosed with GDM should undergo screening for prediabetes or DM within 4–12 weeks after birth using a 75 g oral glucose tolerance test (OGTT). Continued surveillance is advised thereafter, with glucose status reassessed every 1 to 3 years, to monitor for the development of prediabetes or overt DM. These interventions are intended to optimize maternal and fetal health outcomes and reduce the long-term risk of metabolic disease [38].

At present, two principal diagnostic strategies are employed for GDM detection: the one-step and the two-step approaches. The one-step approach implies at least one exceeded measurement during the 75 g OGTT: fasting plasma glucose ≥ 92 mg/dL, one-hour plasma glucose ≥ 180 mg/dL, or two-hour plasma glucose value ≥ 153 mg/dL [1]. The two-step approach refers to a 50 g glucose screening test. If the result after one hour reaches or exceeds 140 mg/dL, a 100 g OGTT is required [1]. While both have been evaluated in terms of their implications for maternal and neonatal outcomes, a standardized global diagnostic criterion has yet to be approved, and currently longitudinal studies examining long-term outcomes are in progress [39,40]. The advantages of the 75 g OGTT are as follows: a single appointment that can diagnose GDM, with increased efficiency and patient compliance, allowing timely management and intervention. The disadvantages include a higher cost compared with the two-step approach, and a prolonged fasting period for the patient before the test.

1.3. GDM Monitoring

There are two important elements that assure optimum surveillance: glycemic monitoring and fetal monitoring. Classic glycemic monitoring consists of home blood glucose monitoring in which the patient checks their fasting blood glucose and every two hours after every meal. The glycemic targets are as follows: <95 mg/dL for fasting blood glucose, <140 mg/dL for one-hour postprandial glucose level, and <120 mg/dL for the two-hour postprandial glucose level [41]. At the same time, the ADA recommends different glycemic targets for insulin-treated GDM: 70–95 mg/dL for fasting glucose, 110–140 mg/dL for one-hour postprandial glucose, and 100–120 mg/dL for two-hour postprandial glucose concentration [41]. Due to the intensified red blood cell turnover that is a physiologic mechanism in pregnancy, after the first trimester, HbA1c is not a reliable postprandial hyperglycemia marker, so it should be integrated as a secondary glycemic marker after blood glucose monitoring. Several studies have reported that HbA1 < 6% in the second and third trimester of pregnancy with DM has been associated with a lower risk of LGA [42,43], preeclampsia [44], and preterm delivery [45]. Another method of blood glucose monitoring is represented by continuous glucose monitoring systems (CGMSs). Regarding the monitoring of pregnant women with T1DM, CGMSs have been a real aid in optimizing glycemic control and therefore, pregnancy outcomes. The Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes Trial (CONCEPTT) [46] has proven neonatal benefits: a decrease in the number of LGA infants, a reduction in the number of days spent in the hospital for the infants, and also a decrement in the number of severe neonatal hypoglycemia. Unfortunately, the data available at the moment is insufficient to ensure the use of CGMSs in all patients with T2DM or GDM [47] and current international guidelines need updating and standardizing. Another hyperglycemia marker is represented by skin autofluorescence. Although an easy-to-use and reproductible method, the current data is quite heterogenous and it requires further investigation for validating skin autofluorescence’s use in GDM complicated pregnancies [48].

Fetal surveillance consists of markers that confirm fetal wellbeing and also fetal growth assessment [21]. Fetal monitoring in GDM patients with nutritional therapy and good glycemic control and without other pregnancy complications (polyhydramnios, preeclampsia, macrosomia, etc.) should debut at 36 gestational weeks with a nonstress test, amniotic fluid index, or fetal biophysical profile, as there has not been an association between these pregnancies and stillbirth. In addition, the American College of Obstetricians and Gynecologists recommends only amniotic fluid index assessment [21]. In contrast, fetal surveillance should begin at 32 gestational weeks for patients requiring insulin treatment or for patients with nutritional intervention and suboptimal glycemic control. The monitoring consists of biweekly nonstress test and amniotic fluid index determination [49]. Fetal growth is usually evaluated after 36 weeks of gestation [50], but there is a gap in the literature in which there is no consensus regarding the perfect timing to estimate fetal weight [51]. Fetal weight estimation is challenging and there is no method to perfectly and without error identify LGA with high sensitivity and specificity [52].

1.4. GDM Treatment

The two approaches regarding GDM treatment include medical nutrition therapy and, if necessary, pharmacologic therapy for patients with suboptimal glycemic control. Firstly, the ADA [41] recommends lifestyle and behavioural changes in pregnant patients with GDM, medical nutritional therapy, physical exercise, and weight management depending on the weight before pregnancy. These goals can be realized in telehealth visits or in-person visits, or both. The recommendations regarding diet are a minimum 175 g carbohydrate intake, 28 g of fibre, and at least 71 g protein [53]. Physical activity consists of a minimum 150 min per week of moderate-intensity aerobic activity [54].

The main and most preferred substance used in the pharmacologic therapy of DM in pregnancy is represented by insulin. After the first trimester of pregnancy, around 16 gestational weeks, the insulin requirement begins to increase by 5% per week until the 36th gestational week, due to the increasing trend of insulin resistance. Therefore, insulin requirements double compared with pre-pregnancy doses [55]. Other substances include metformin and glyburide. These two agents are not supported as first-line treatments due to the fact that they cross the placenta and have long-term consequences for offspring (for metformin: an increased risk of small for gestation age [56], a higher BMI, and a higher prevalence of overweight and obesity in infants [57]; for glyburide: a higher risk of neonatal hypoglycemia [58]) [21] and also the diminished effectiveness of glycemic control). Two randomized controlled trials [59,60] investigating the efficacy of glyburide and metformin in maintaining optimum glycemic control in pregnancy reported that these substances did not achieve glycemic targets in 23% and 25–28%, respectively, of patients with GDM. In contrast, the ADA also recommends discontinuing metformin by the end of the first trimester if metformin was used in polycystic ovary syndrome treatment and ovulation induction [41].

1.5. Current Situation of GDM Screening and Diagnosis in Romania

In the Methodology of Performing the Prenatal Consultation clinical guideline, revised in 2024, the Romanian Society of Obstetrics and Gynecology recommends testing fasting plasma glucose in the first trimester, followed by an OGTT or HbA1c between 24 and 28 + 6 gestational weeks, and another fasting plasma glucose measurement in the third trimester [61]. Usually, after the diagnosis of hyperglycemia, DM, or GDM, these patients undergo double surveillance by an obstetrician and a diabetologist. The data provided by the National Public Health Institute shows that in 2020 there were 102,063 pregnancies, among which there were 194 reported cases of DM in pregnancy: 17 cases of pregnant patients with type 1 DM, 8 cases of pregnant patients with type 2 DM, and 169 cases of GDM, representing 87.11% of the cases of DM in pregnancy [62].

In practice, due to urban–rural inequalities, teen pregnancies, and the lack of sexual education in schools or medical education, there is heterogeneity in the screening and diagnosis of GDM. In this direction, our recently published study [63] reported a 74.19% rate of pregnant patients who received insufficient prenatal care belonging to rural areas of Romania in 2024. Approximatively 30% of pregnancies are unmonitored, and, unfortunately, few of the monitored pregnant patients complete GDM screening using the OGTT due to the fact that the patients are not willing to monitor their pregnancy and also because some practitioners do not recommend testing for GDM. Another aspect is that some practitioners apply other guidelines that recommend OGTT only to pregnant patients that present risk factors of developing OGTT, therefore suppressing the universal screening role of OGTT. Finally, these issues contribute to the underdiagnosis of GDM, putting the mother and fetus at risk, and they place a burden on the healthcare system.

Future strategies could involve raising awareness through campaigns on the neurological sequelae that can be caused by severe neonatal hypoglycemia. In addition, mobile applications are promising and could be a practical solution. More and more countries are using mobile applications that improve the communication and collaboration between the patient, general practitioner, diabetologist, and obstetrician such as Diasend [64] or Glooko [65] in order to obtain the best pregnancy outcome, therefore minimizing the number of visits to the hospital. In Romania, there is Diabeta [66], a mobile application based on local guidelines and enriched by artificial intelligence that aids diabetologists in accessing international and local protocols faster. Moreover, a national practice guideline on DM in pregnancy could be a solution to standardize pre-conceptional, prenatal, and also postpartum care in both pregestational DM and GDM, aligned with the ADA’s recommendations [41]. Other obstetrics guidelines should include prenatal counselling based on proper nutrition and physical activity, an adequate and standardized screening method, patient education on DM monitoring, DM management in association with the diabetologist, as well as the care of associated complications, clear criteria for insulin therapy initiation, standardized timing of birth as well as the route of birth, and finally postpartum and lifelong care for patients with a history of GDM by also addressing mental wellbeing, separately from physical wellbeing, for the prevention type 2 DM in these patients [67].

2. Conclusions

In conclusion, there is a critical need for a national DM in pregnancy guideline that should govern current medical practice starting from prenatal counselling, screening, and diagnosis; the multidisciplinary management of the pathology and associated complications; standardized DM treatment; and the homogenized timing of birth and route of birth according to comprehensive and clear criteria, so that mothers and fetuses can receive professional care, therefore minimizing adverse pregnancy outcomes.