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Article

Association Between Hypoglycaemia at the 24–28th-Week OGTT and Obstetric and Neonatal Outcomes in Women with Gestational Diabetes

by
Maria Luís Mazeda
1,†,
Bruna Silva
1,†,
Catarina Cidade-Rodrigues
1,
Filipa Moreira
1,
Vânia Benido-Silva
1,
Vânia Gomes
1,
Catarina Chaves
1,
Catarina A. Pereira
1,
Cláudia Machado
1,
Odete Figueiredo
2,
Anabela Melo
2,
Mariana Martinho
3,
Anabela Ferreira
2,
Ana Morgado
2,
Maria do Céu Almeida
4,5,
Ana Saavedra
1,
Margarida Almeida
1 and
Filipe M. Cunha
1,*
1
Endocrinology Department, Unidade Local de Saúde Tâmega e Sousa, 4560-136 Penafiel, Portugal
2
Gynecology and Obstetrics Department, Unidade Local de Saúde Tâmega e Sousa, 4560-136 Penafiel, Portugal
3
Endocrinology Department, Unidade Local de Saúde Vila Nova de Gaia/Espinho, 4434-502 Vila Nova de Gaia, Portugal
4
Obstetrics Department, Maternidade Bissaya Barreto, Unidade Local de Saúde de Coimbra, 3000-061 Coimbra, Portugal
5
Grupo de Estudos de Diabetes e Gravidez, Sociedade Portuguesa de Diabetologia, 1250-198 Lisboa, Portugal
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Diabetology 2025, 6(10), 106; https://doi.org/10.3390/diabetology6100106
Submission received: 20 June 2025 / Revised: 8 August 2025 / Accepted: 16 September 2025 / Published: 2 October 2025
Browse Figure
Review Reports Versions Notes

Abstract

Introduction: Women with gestational diabetes mellitus (GDM) can present with hypoglycaemia during the oral glucose tolerance test (OGTT), which has been associated with adverse perinatal outcomes. Objectives: We studied whether the presence of hypoglycaemia during the OGGT (HdOGTT) was associated with adverse perinatal outcomes. Methods: Retrospective study of a national database of women diagnosed with GDM in the 24–28th week OGTT. Excluded: women with missing OGTT or the primary outcomes data. HdOGGT: any glucose value < 70 mg/dL. Primary outcomes: hypertensive disease of pregnancy, preterm delivery, caesarean section (CSA), small-for-gestational-age, large-for-gestational-age, neonatal hypoglycaemia, respiratory distress syndrome, and intensive care unit admission. Women with and without hypoglycaemia were compared. Predictors of HdOGTT and the association between HdOGTT and the primary outcomes were studied using a multivariate logistic regression analysis. Results: We analysed 7704 women, 10.7% with HdOGTT. Most of them (94.8%) presented fasting hypoglycaemia, and 3.2% had blood glucose values < 54 mg/dL. There were no differences between groups regarding the primary outcomes, except for women with HdOGTT, who had a lower rate of CSA (34.1% vs. 29.0%, p = 0.001), large-for-gestational-age newborns (9.7% vs. 13.8%, p < 0.001), and a higher rate of small-for-gestational-age newborns (11.0% vs. 6.9%, p < 0.001) than those without HdOGTT. Age, BMI, previous miscarriage, and chronic hypertension were associated with lower risk of HdOGTT. HdOGTT was only associated with increased risk of SGA [OR (95% CI): 1.25 (1.00–1.56), p = 0.047] after adjustment for confounders. Conclusions: The prevalence of HdOGTT was 10.7%. Age, BMI, previous miscarriage, and chronic hypertension were associated with lower risk of HdOGTT. HdOGTT was associated with 25% higher risk of SGA newborns.

1. Introduction

Gestational diabetes mellitus (GDM) is a common pregnancy complication defined by the onset of hyperglycaemia first detected during pregnancy [1,2]. The increased demand for insulin is driven by a number of factors, including elevated levels of placental hormones, increased maternal nutrient intake, and other metabolic changes [3,4,5]. In circumstances where pancreatic β-cells are unable to meet the body’s elevated demand, a state of relative insulin insufficiency ensues. This, in turn, leads to the onset of GDM [1,6]. International guidelines recommended that a 75 g 2 h oral glucose tolerance test (OGTT) be conducted during the 24th to 28th week of pregnancy for the purpose of GDM diagnosis [7].
Epidemiological factors, notably the escalating incidence of obesity in women and delayed childbearing, have contributed to the rising prevalence of GDM [4,8,9]. It is evident that a number of additional risk factors contribute to the development of gestational diabetes. These factors are well documented in the literature and include a previous history of GDM, family history of diabetes, previous birth of a foetus ≥ 4000 g, excessive weight gain, and cigarette smoking [10,11]. Genetic factors are also implicated in the cause of GDM, although data remain scarce [12].
GDM affects approximately 14% of pregnancies globally and is associated with neonatal and obstetric complications [1,13,14]. Evidence from the literature indicates that GDM substantially increases the risk of pre-eclampsia, type 2 diabetes, and cardiovascular disease later in life [2]. Furthermore, a hyperglycaemic intrauterine environment elevates the risk of macrosomia, birth injuries, and long-term complications in the offspring such as childhood obesity, impaired glucose tolerance, and vascular dysfunction [12,13].
A small proportion of pregnant women experience hypoglycaemia during oral glucose tolerance test (OGTT) in pregnancy. This is generally not considered to be abnormal, although the implications of this condition for the pregnancy and foetus remain unclear [15].
The foetus is supplied with glucose and other nutrients by the mother through the placenta via concentration-dependent mechanisms [1]. Consequently, the maternal blood glucose levels are directly associated with the volume of glucose delivered to the foetus [16]. It is evident that a reduction in maternal glucose concentration has the potential to restrict glucose supply to the foetus, which may result in deleterious growth consequences [16,17]. As stated by Abel et al. in 1979, there is an established association between maternal hypoglycaemia during pregnancy and foetal growth restriction, as well as increased overall perinatal mortality [18]. A cohort study conducted in 2020 revealed that levels less than 70 mg/dL, as determined by a 75-g OGTT during pregnancy, were associated with lower birth weight, smaller head circumference, and shorter body length in newborns of women without GDM, compared to the normoglycaemic group [19]. According to Budak et al., women with glycaemia below 90 mg/dL had an increased SGA rate, reduced caesarean section rates, and decreased 5 min Apgar score [20]. Furthermore, a smaller-scale study demonstrated elevated rates of neonatal intensive care unit (NICU) admission and foetal complications in women with HdOGTT [21].
The presence of an HdOGTT in which some glycaemic values meet the diagnostic criteria for GDM represents a clinically significant and potentially unexpected phenomenon for healthcare providers managing these pregnancies [15,22]. The association of this condition with adverse obstetric or neonatal outcomes remains uncertain. However, should this pattern be demonstrated to associate with negative outcomes, early clinical intervention at diagnosis may be warranted to mitigate potential risks. Additionally, the predictors of this phenomenon have been scarcely investigated [18,23], and the impact of HdOGTT in an OGTT that also has other glucose values that meets the diagnostic criteria for GDM on subsequent obstetric and neonatal outcomes has not yet been investigated. This study aimed to identify predictors of hypoglycaemia during the OGTT and to evaluate whether HdOGTT is associated with adverse obstetric and neonatal outcomes.

2. Material and Methods

A retrospective study was performed based on the Portuguese national GDM registry of the Diabetes and Pregnancy Study Group of the Portuguese Society of Diabetology (DPSGPSD). This registry includes women with GDM who were followed at 33 hospitals across Portugal between 2012 and 2021. Data collection and anonymisation were carried out by each participating institution and subsequently transmitted to the DPSGPSD for consolidation and validation. The data collected encompassed demographic, anthropometric, past medical and obstetrical history, glucose values at GDM diagnosis, glycated haemoglobin (HbA1c), obstetric and neonatal complications, and the 6–8-week post-partum OGTT. In our country, GDM diagnosis is performed in accordance with the criteria established by International Association of Diabetes and Pregnancy Study Groups (IADPSG) [7] and the World Health Organization (WHO) [24]. In essence, all pregnant women are screened in their first trimester with fasting plasma glucose, and, if the result is normal, they undergo a 75 g OGTT at 24 to 28 weeks’ gestation.
For the purposes of this analysis, the inclusion criteria were as follows: women diagnosed with gestational diabetes mellitus (GDM) in the second trimester (24–28 weeks of gestation) who underwent a 75 g OGTT, with singleton pregnancies who delivered a live newborn. The exclusion criteria for this study included women with a glucose value on the OGTT suggestive of pre-existing diabetes mellitus (fasting glucose ≥ 126 mg/dL or 120-min glucose ≥ 200 mg/dL), as well as those with missing values at any OGTT time point. Women with missing data for any of the primary outcomes were also excluded. Additionally, women with missing data on maternal age, body mass index (BMI), gestational weight gain (GWG), family history of type 2 diabetes mellitus (T2DM), previous GDM, parity, history of miscarriage, pharmacotherapy, or HbA1c were excluded (Figure 1).
HdOGTT was defined as the presence of any glucose value < 70 mg/dL during the 75 g OGTT conducted between the 24th and 28th weeks of gestation [25]. This definition aligns with the recommendations of the American Diabetes Association, who define hypoglycaemia as blood glucose concentrations of less than 70 mg/dL (<3.9 mmol/L) and sensor glucose concentrations of less than 63 mg/dL (<3.5 mmol/L) [25].
GDM was diagnosed based on at least one elevated glucose levels at any OGTT time point. All women included in this analysis had at least one elevated glucose value in the OGTT, and some women, concomitantly, had a glucose value < 70 mg/dL in other glucose values of the OGTT—most commonly glucose at 0 min. As previously reported in the literature, hypoglycaemia and GDM diagnosis can co-occur [22,26].
BMI was calculated using pre-pregnancy maternal weight (kg)/height (m) squared. Excessive GWG definition follows the Institute of Medicine recommendations: GWG above 18 kg, 16 kg, 11.5 kg, and 9 kg for women with BMI below 18.5 kg/m2, between 18.5 to 24.9 kg/m2, between 25.0 to 29.9 kg/m2, and above 30.0 kg/m2, respectively [27]. Nulliparous and multiparous women were defined as no previous birth and 2 or more births, respectively. Hypertensive disorders of pregnancy (HDP) included a composite of pre-eclampsia and/or gestational hypertension. Large-for-gestational-age (LGA) and small-for-gestational-age (SGA) were defined as newborn weight above the 95th percentile and below the 5th percentile according to the Fenton growth curves, respectively [17].
The primary outcomes are HDP, preterm delivery, caesarean section, SGA, LGA, neonatal hypoglycaemia, respiratory distress syndrome, and intensive care unit admission.
The study respects the Declaration of Helsinki on medical protocol and ethics. It is a retrospective observational study using data from a well-established anonymous national GDM database. No formal approval from a Bioethics committee was needed.

Statistical Analysis

Women with GDM with and without HdOGTT were compared using the χ2 test for categorical variables and the Mann–Whitney U test for continuous variables with a with non-normal distributions. Normality was assessed using the 1-sample Kolmogorov–Smirnov (K-S) test, supplemented by visual inspection of histograms to evaluate distribution patterns.
A multivariate logistic regression analysis was performed to identify predictors of the HdOGTT. The model included variables showing significant differences between groups. Multivariate logistic regression was also employed to evaluate the association between HdOGTT and obstetric and maternal outcomes. This model included all variables with different distributions between groups as well as variables known to be associated with each primary endpoint.
Given the potential structural relationship between maternal height and BMI, collinearity between these two variables was assessed prior to model inclusion. Collinearity was evaluated using both the Variance Inflation Factor (VIF) and Collinearity Diagnostics within a linear regression framework. Both variables had VIF values of 1.000, indicating no significant linear dependence. Although a high condition index (64.3) was observed for one dimension in the collinearity diagnostics, only maternal height had a high variance proportion in that dimension (99%), while BMI had a low variance proportion (1%), suggesting the absence of problematic multicollinearity.
Statistical significance was considered when p-value is <0.05. Data were stored and analysed using SPSS® software (IBM Corp, Armonk, NY, USA, version 29.0).

3. Results

We analysed 7704 women, 824 (10.7%) with HdOGTT. The majority—781 (94.8%)—experienced hypoglycaemia during the fasting period, while 8 women (1.0%) had hypoglycaemia at 60 min and 41 (5.0%) at 120 min. Additionally, six women exhibited hypoglycaemia at two separate time points during the OGTT. Twenty-six (3.2%) had a glucose value < 54 mg/dL. The characteristics of the women, their pregnancies, and the comparation between those with and without hypoglycaemia are presented in Table 1. In summary, women with HdOGTT were younger, had lower BMI and shorter stature, were less likely to exceed recommended gestational weight gain, and more frequently gained an inadequate amount of weight during pregnancy. They were more often nulliparous, less frequently multiparous, and more commonly reported a previous history of miscarriage. They were also less likely to have chronic arterial hypertension. The mean HbA1c during pregnancy was lower in women with HdOGTT compared to those without. Treatment with metformin and/or insulin during pregnancy was also less common among these women. There were no differences between women with and without HdOGTT concerning the rate of hypertensive disease of pregnancy, preterm delivery, neonatal hypoglycaemia, respiratory distress syndrome, and admission to an intensive care unit. Women with HdOGTT had a lower rate of caesarean delivery [2388 (34.1%) vs. 239 (29.0%), p = 0.001], a lower rate of LGA newborns [669 (9.7%) vs. 114 (13.8%), p < 0.001], and a higher rate of SGA newborns [760 (11.0%) vs. 57 (6.9%), p < 0.001], compared to those without HdOGTT.
We investigated the predictors of HdOGTT using a multivariate regression analysis (Table 2). After adjustments for age, BMI, maternal height, weight gain during pregnancy, previous miscarriage, parity, chronic arterial hypertension, HbA1c, insulin and metformin treatment, and presence of hypertensive disease of pregnancy (and for preterm delivery and newborn weight in the case of the CSA), the occurrence of HdOGTT was associated with the increased risk of SGA [OR (95% CI): 1.25 (1.00–1.56), p = 0.047] but not with LGA [OR (95% CI): 0.82 (0.61–1.09), p = 0.18] or CSA [OR (95% CI): 0.88 (0.75–1.04), p = 0.13].
We used a multivariate regression analysis to study the association between the occurrence of HdOGTT and SGA, LGA, and CSA (Table 3). After adjustments for age, BMI, maternal height, weight gain during pregnancy, previous miscarriage, parity, chronic arterial hypertension, HbA1c, insulin and metformin treatment, and presence of hypertensive disease of pregnancy (and for preterm delivery and newborn weight in the case of the CSA), the occurrence of HdOGTT was associated with increased risk of SGA [OR (95% CI): 1.25 (1.00–1.56), p = 0.047] but not with LGA [OR (95% CI): 0.82 (0.61–1.09), p = 0.18] or CSA [OR (95% CI): 0.88 (0.75–1.04), p = 0.13].

4. Discussion

Our analysis of the national registry of women with GDM suggests that increased maternal age, higher BMI, a history of miscarriage, and chronic arterial hypertension are associated with a lower risk of HdOGTT. For each year increase in maternal age and 1 kg/m2 increase in BMI, there were a 3% and 8% reduction in the risk of HdOGTT, respectively. Similarly, previous miscarriage and history arterial hypertension were associated with an 18% and 47% decreased risk of HdOGTT, respectively. We also found that women presented with HdOGTT had 25% higher risk of delivering a newborn SGA.
Predictors of HdOGTT were previously analysed in a smaller study involving 436 hypoglycaemic women and 434 normoglycaemic controls [28]. The authors reported that younger and obese women were less likely to develop hypoglycaemia and that pre-existing medical conditions, including chronic arterial hypertension, were associated with an increased risk of HdOGTT. They found that younger and obese women were less likely to have hypoglycaemia and that previous medical conditions including chronic arterial hypertension were associated with increased risk HdOGTT [28]. These findings differ from those of our study in which younger maternal age was associated with higher risk of HdOGTT, and the presence of comorbidities such as chronic arterial hypertension was associated with a reduced risk of HdOGTT. The only consistent finding between the two studies was that obese women were less likely to develop HdOGTT. However, it is important to note that the participants in the previous study did not have GDM, and the definition of hypoglycaemia used (<88 mg/dL) differed from ours, limiting the comparability of results [28]. Bayraktar et al. also reported that women with HdOGTT were younger and had a higher prevalence of low birth weight, though the difference between the groups was not statistically significant [19]. In addition to maternal age, our study identified BMI, a history of chronic hypertension, and previous miscarriage as factors associated with a lower risk of HdOGTT, a novel finding that, to our knowledge, has not been previously reported.
To the best of our knowledge, this is the first study to investigate the association between hypoglycaemia during an OGTT and obstetric and neonatal outcomes in cases where other glucose values fulfil the diagnostic criteria for GDM. Previous studies have established a correlation between lower glycaemic values and obstetric and neonatal outcomes in women diagnosed with GDM. However, these studies were conducted in the context of overall glycaemic control during pregnancy rather than specifically assessing the presence of hypoglycaemia during the diagnostic OGTT [26,29]. Langer et al. aimed to determine the association between different levels of glycaemic control and neonatal weight in women with GDM. Their findings demonstrated that women with lower glycaemic levels (<87 mg/dL) had more than double the odds of delivering a neonate with low birth weight (OR 2.56, 95% CI: 1.24–5.29) [29]. However, their analysis did not specifically address hypoglycaemia, nor did it adjust for potential cofounders such as hypoglycaemic agents. Furthermore, glycaemia measurements were taken randomly from capillary blood samples, thereby differing substantially in methodology from our approach. Although their results align in part with ours, these methodological differences preclude direct comparisons. A further retrospective study that included 489 women with GDM undergoing pharmacological treatment (metformin or glyburide) also explored the relationship between hypoglycaemia and pregnancy outcomes [26]. In that study, 19.4% of participants experienced hypoglycaemia, which was associated with 69% increased risk of adverse neonatal outcomes, including a 5 min Apgar score < 7, birth trauma, and neonatal hypoglycaemia, when compared to women without hypoglycaemia [26]. Even though the same hypoglycaemia threshold (<70 mg/dL) was applied, the study exclusively included pharmacologically treated women, and the glycaemic data were collected from weekly self-monitoring logs, further complicating comparison with our results [26].
The association between hypoglycaemia in pregnant women with neonatal and obstetric outcomes is well documented in the extant literature [15,18,21,22,28,30,31]. However, these previous studies predominantly examined the association between low glycaemic values at the OGTT and neonatal and obstetric outcomes in women without a diagnosis of GDM. The methodologies of these studies varied considerably, particularly in the definitions of hypoglycaemia employed and the glucose loads used during the OGTT, which ranged from 50 to 100 g. As such, direct comparison with our findings is inherently limited. Nevertheless, most of these investigations reported a significant association between lower glycaemic values and an increased risk of delivering SGA newborns, consistent with our findings [18,22,30,31]. In contrast, a smaller study failed to observe this relationship [21].
Others have reported an association between maternal hypoglycaemia and neonatal hypoglycaemia [21,26]. A more recent retrospective analysis also found an association between HdOGTT and increased rates of NICU admissions and polyhydramnios. However, these associations were not consistently observed across studies [21] and were not replicated in our data. Nevertheless, the association between HdOGTT and adverse obstetric outcomes remains to be elucidated as the reported results are heterogeneous [23]. For instance, a correlation has been proposed between HdOGTT and elevated risk of pre-eclampsia during pregnancy; however, this has not been substantiated in our larger national cohort [24].
In our study, it was observed that the majority of women with HdOGTT (over 80%) exhibited hypoglycaemia at the fasting timepoint at the OGTT, which may suggest early impairment of glucose counterregulatory responses.
The mechanism behind these findings is not completely understood, but differences in insulin secretion, insulin resistance, insulin clearance, and counterregulatory response might be involved [30]. Pregnancy is associated with progressive insulin resistance, which is typically compensated by increased insulin secretion [31]. Some authors suggest that there is a reduction in insulin clearance during the third trimester, which could impair recovery from hypoglycaemia [32]. Also, counterregulatory hormonal response to hypoglycaemia is attenuated in women with diabetes: epinephrine responses are reduced during pregnancy compared to the post-partum period, and growth hormone responses are progressively diminished during pregnancy in comparison with non-pregnant women [30]. Moreover, both insulin secretion and insulin sensitivity tend to decline with advancing maternal age [33,34] and increasing BMI [35].
The predominance of hypoglycaemic values occurring during the fasting phase of the OGTT suggests that the affected women may have relatively greater insulin sensitivity despite their diagnosis of gestational diabetes mellitus. This increased sensitivity is more evident when compared to older women or those with higher BMI, who typically exhibit greater insulin resistance. Consequently, during the fasting period of the OGTT, younger women or those with lower BMI may be more susceptible to hypoglycaemia due to their comparatively heightened insulin responsiveness [36]. Additionally, leaner women may have reduced hepatic glycogen reserves, potentially impairing the counterregulatory hormonal response to hypoglycaemia. This, when combined with lower insulin resistance and potentially decreased insulin clearance, may account for the increased risk of post-load hypoglycaemia in this subgroup. Moreover, it has been shown that women with chronic hypertension exhibit higher degrees of insulin resistance compared to normotensive individuals [37]. A similar rationale may be applicable in this context as evidence suggests that women with a history of miscarriages may display increased insulin resistance [38]. This fact aligns with our findings, which demonstrate that women suffering from chronic hypertension and previous miscarriages are less prone to experiencing HdOGTT.
Pregnancy represents a distinct metabolic condition in which the mother must meet her own energy requirements while also supporting the metabolic demands of the developing foetus [30]. Glucose is an essential nutrient to the developing foetus and is transported via facilitated diffusion from the placenta. Consequently, the foetal glucose supply is contingent on the maternal blood glucose concentration. Therefore, maternal hypoglycaemia may compromise foetal glucose supply, potentially resulting in restricted foetal growth [39].
Our findings confirmed that younger and leaner women were at an increased risk of HdOGTT and exhibited a 25% higher likelihood of delivering a small-for-gestational-age (SGA) newborn. As such, this subgroup of GDM patients may benefit from enhanced foetal growth surveillance and comprehensive maternal nutritional assessment and counselling. In particular, dietary strategies should be implemented to avoid prolonged fasting and excessive postprandial insulin responses. Since the primary focus of most GDM care is on the prevention of macrosomia, HdOGTT may indicate a shift in focus towards growth restriction, which requires a change in the monitoring priorities [36].
This investigation is not without limitations, which merit careful consideration. As a retrospective study based on clinical data, it is inherently subject to the methodological constraints typical of such designs. The retrospective nature precludes any inference of causality; thus, the findings should be interpreted as associations rather than definitive causal relationships. Besides that, selection bias is another potential concern as the sample may not be fully representative of the broader obstetric population. Specific subgroups may have been underrepresented, thereby limiting the generalisability of the findings. There is also a limited generalisability since our population is predominantly Portuguese, which may further restrict the applicability of the results to other ethnic or national populations. Another limitation is the absence of data on other potentially relevant clinical or laboratory parameters, such as the presence of polycystic ovary syndrome, which could have influenced the results. Furthermore, due to anonymisation, we did not have information on the specific hospitals where the women received care. This introduces an element of heterogeneity that may have affected the results, particularly if institutional protocols or diagnostic practices varied across centres. There is, currently, no formal validation of the hypoglycaemia threshold during pregnancy, and no universal consensus exists. While the American Diabetes Association defines hypoglycaemia in pregnancy as a venous plasma glucose level below 70 mg/dL or a continuous glucose monitor reading below 63 mg/dL, these criteria are not uniformly applied across studies. The absence of a validated, standardised cut-off for hypoglycaemia in pregnancy complicates both the interpretation and comparability of findings, potentially limiting the clinical relevance of the threshold used in our analysis.
Despite its limitations, this study also possesses several notable strengths. Most notably, the large sample size of 7704 pregnant women provided sufficient statistical power, enhancing the generalisability of the findings and the robustness of our conclusions. To our knowledge, this is the first study to investigate the association between hypoglycaemia occurring during an OGTT and subsequent obstetric and neonatal outcomes in women with GDM, thereby highlighting its clinical relevance. Additionally, we adjusted for key confounding variables, such as maternal age, BMI, and pre-existing medical conditions, thereby strengthening the validity of our results.

5. Conclusions

This study represents the first to specifically investigate the association between HdOGTT and both obstetric and neonatal outcomes in women diagnosed with GDM. The prevalence of HdOGTT was 2.5%. A lower risk of HdOGTT was significantly associated with age, BMI, a previous history of miscarriage, and chronic arterial hypertension. For every one-year increase in maternal age and every one-kg/m2 increase in BMI, the risk of HdOGTT decreased by 3% and 8%, respectively. A previous miscarriage and a history of chronic arterial hypertension were associated with an 18% and 47% reduction in the likelihood of HdOGTT, respectively. Additionally, women with HdOGTT were 25% more likely to deliver an SGA newborn, while no significant associations were observed with respect to other adverse obstetric or neonatal outcomes. Our findings contribute to the existing literature concerning the relationship between HDOGTT and perinatal complications, an area where previous studies have yielded inconsistent and inconclusive results. Prospective studies are needed to further elucidate this topic.

Author Contributions

Conceptualization, M.L.M. and B.S.; methodology, F.M.C.; formal analysis, F.M.C.; investigation, M.L.M. and B.S.; resources, M.M.; data curation, M.L.M., B.S., C.C.-R., F.M., V.B.-S., V.G., C.C., C.A.P., C.M., O.F., A.M. (Anabela Melo), M.M., A.F., A.M. (Ana Morgado), M.d.C.A., A.S., M.A., and F.M.C.; writing—original draft preparation, M.L.M. and B.S.; writing—review and editing, C.C.-R., F.M., V.B.-S., V.G., C.C., C.A.P., C.M., O.F., A.M. (Anabela Melo), M.M., A.F., A.M. (Ana Morgado), M.d.C.A., A.S., M.A., and F.M.C.; supervision, F.M.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study respects the Declaration of Helsinki on medical protocol and ethics. It is a retrospective observational study using data from a well-established anonymous national GDM database. No formal approval from a Bioethics committee was needed.

Informed Consent Statement

Not applicable.

Data Availability Statement

Restrictions apply to the availability of these data. The data used in this study were obtained from a national database on gestational diabetes. Due to legal and ethical constraints, particularly to protect patient anonymity, the data are not publicly available.

Conflicts of Interest

The authors declare that they have no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Diabetology 06 00106 g001
Figure 1. Flowchart of patients’ selection. BMI: body mass index; HbA1c: glycated haemoglobin; OGTT: oral glucose tolerance test.
Figure 1. Flowchart of patients’ selection. BMI: body mass index; HbA1c: glycated haemoglobin; OGTT: oral glucose tolerance test.
Diabetology 06 00106 g001
Table 1. Population’s characteristics and comparison between women with and without hypoglycaemia during the oral glucose tolerance test.
Table 1. Population’s characteristics and comparison between women with and without hypoglycaemia during the oral glucose tolerance test.
All
n = 7704 		Without HdOGTT
n = 6880 (89.3%) 		With HdOGTT
n = 824 (10.7%) 		p
Age (years), median (IQR) 34 (30–37)34 (30–37)33 (29–36)<0.001
Age > 35 years, n (%) 2919 (37.9)2661 (38.7)258 (31.3)<0.001
BMI (kg/m2), median (IQR) 25.6 (22.6–29.7)25.9 (22.8–30.1)23.7 (21.3–28.8)<0.001
Normal weight, n (%) 3520 (45.7)3012 (43.8)508 (61.7)
Excessive weight, n (%) 2331 (30.3)2110 (30.7)221 (26.7)
Obesity, n (%) 1853 (24.0)1758 (25.6)95 (11.5)<0.001
Hight (cm), median (IQR) 162 (158–165)162 (158–165)161 (157–165)0.004
GWG, median (IQR) 10.5 (7.0–14.0)10.6 (7.0–14.0)10.0 (7.3–17.0)0.46
Adequate weight gain, n (%) 2685 (34.9)2414 (35.1)271 (32.9)
Inadequate weight gain, n (%) 2743 (35.6)2372 (34.5)371 (45.0)
Excessive weight gain, n (%) 2273 (29.5)2094 (30.4)182 (22.1)<0.001
T2D family history, n (%) 3475 (45.1)3129 (45.5)478 (42.0)0.06
Previous GDM, n (%) 870 (11.3)791 (11.6)79 (9.6)0.10
Previous abortion, n (%) 2224 (28.9)2029 (29.5)195 (23.7)<0.001
Nulliparous, n (%) 3528 (45.8)3092 (44.9)436 (52.9)0.10
Previous birth, n (%) 2999 (38.9)2713 (39.4)286 (34.7)
Multiparous, n (%) 1177(15.3)1075 (10.6)102 (12.4)<0.001
Chronic Arterial Hypertension, n (%) 376 (4.9)360 (5.2)16 (1.9)<0.001
HbA1c, median (IQR) 5.2 (5.0–5.4)5.2 (5.0–5.4)5.1 (4.9–5.3)<0.001
Insulin therapy, n (%) 1784 (23.2)1682 (24.4)10.2 (12.4)<0.001
Metformin therapy, n (%) 1274 (16.5)1194 (17.4)80 (9.7) <0.001
Pharmacological therapy, n (%) 2792 (36.2)2618 (28.1)174 (21.1)<0.001
Pre-eclampsia, n (%) 102 (1.3)95 (1.4)7 (0.8)0.26
HDP, n (%) 332 (4.3)304 (4.4)28 (3.4)0.17
Preterm delivery, n (%) 453 (5.9)404 (5.9)49 (5.9)0.93
Caesarean section n (%) 2627 (34.1)2388 (34.7)239 (29.0)0.001
AGA newborns, n (%) 6104 (79.2)5451 (79.2)653 (79.2)<0.001
SGA newborns, n (%) 783 (10.2)669 (9.7)114 (13.8)<0.001
LGA newborns, n (%) 817 (10.6)760 (11.0)57 (6.9)<0.001
Foetal male sex, n (%) 3958 (51.4)3529 (51.3)429 (52.1)0.68
Neonatal hypoglycaemia, n (%) 295 (3.8)261 (3.8)34 (4.1)0.64
RDS, n (%) 220 (2.9)199 (2.9)21 (2.5)0.58
NICUA, n (%) 478 (6.2)431 (6.3)47 (5.7)0.53
AGA: appropriate-for-gestational-age; BMI: body mass index; GDM: gestational diabetes mellitus; GWG: gestational weight gain; HDP: hypertensive disorder of pregnancy; IQR: interquartile range; LGA: large-for-gestational-age; NICUA: neonatal intensive care unit admission; OGTT: oral glucose tolerance test at 24–28th gestational week; RDS: respiratory distress syndrome; SGA: small-for-gestational-age; T2D: type 2 diabetes mellitus.
Table 2. Predictors of hypoglycaemia during the oral glucose tolerance test: multivariate logistic regression analysis.
Table 2. Predictors of hypoglycaemia during the oral glucose tolerance test: multivariate logistic regression analysis.
OR (95% CI) p
Age, per 1 year 0.97 (0.96–0.99)<0.001
BMI, per 1 kg/m20.92 (0.90–0.93)<0.001
Family history of T2D 0.97 (0.84–1.13)0.70
Previous GD history 0.97 (0.74–1.26)0.81
Previous miscarriage 0.82 (0.69–0.98)0.03
Chronic arterial hypertension 0.53 (0.22–0.87)0.02
Parity
   Previous birth (reference) 1
   Nulliparous 1.09 (0.92–1.30)0.33
   Multiparous 1.01 (0.79–1.28)0.96
BMI: body mass index; CI: confidence interval; GD: gestational diabetes; OR: odds ratio; T2D: type 2 diabetes mellitus.
Table 3. Association between the presence of hypoglycaemia during the oral glucose tolerance test and obstetric and neonatal outcomes: multivariate logistic regression analysis.
Table 3. Association between the presence of hypoglycaemia during the oral glucose tolerance test and obstetric and neonatal outcomes: multivariate logistic regression analysis.
OutcomeOR (95% CI)p
Hypertensive disease of pregnancy0.99 (0.66–1.48)0.96
Preterm labour *0.99 (0.72–1.35)0.94
Caesarean section #0.88 (0.75–1.04)0.13
Small-for-gestational-age &1.25 (1.00–1.56)0.047
Large-for-gestational-age &0.82 (0.61–1.09)0.13
Neonatal hypoglycaemia #1.13 (0.78–1.64)0.52
Respiratory distress syndrome ¥0.89 (0.56–1.44)0.64
NICU admission §0.84 (0.57–1.24)0.38
All analyses were adjusted for the variables that showed different distribution between women with and without hypoglycaemia in the oral glucose tolerance test (maternal age, body mass index—<25 kg/m2 as the reference category—maternal height, gestational weight gain—normal weight gain as the reference category—previous miscarriage, parity—1 previous birth as the reference category—chronic arterial hypertension, HbA1c, insulin treatment, and metformin treatment) and variables with known association with the outcome under analysis: * hypertensive disease of pregnancy and birth weight (with adequate-for-gestational-age as reference); # hypertensive disease of pregnancy, birth weight (with adequate-for-gestational-age as reference), and preterm labour; & hypertensive disease of pregnancy; ¥ hypertensive disease of pregnancy, birth weight (with adequate-for-gestational-age as reference), preterm labour, and neonatal hypoglycaemia; § hypertensive disease of pregnancy, birth weight (with adequate-for-gestational-age as reference), preterm labour, neonatal hypoglycaemia, and respiratory distress syndrome. CI: confidence interval; NICU: neonatal intensive care unit; OR: odds ratio for the association between hypoglycaemia < 70 mg/dL in the oral glucose tolerance test and the variable described in each row.
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Mazeda, M.L.; Silva, B.; Cidade-Rodrigues, C.; Moreira, F.; Benido-Silva, V.; Gomes, V.; Chaves, C.; Pereira, C.A.; Machado, C.; Figueiredo, O.; et al. Association Between Hypoglycaemia at the 24–28th-Week OGTT and Obstetric and Neonatal Outcomes in Women with Gestational Diabetes. Diabetology 2025, 6, 106. https://doi.org/10.3390/diabetology6100106

AMA Style

Mazeda ML, Silva B, Cidade-Rodrigues C, Moreira F, Benido-Silva V, Gomes V, Chaves C, Pereira CA, Machado C, Figueiredo O, et al. Association Between Hypoglycaemia at the 24–28th-Week OGTT and Obstetric and Neonatal Outcomes in Women with Gestational Diabetes. Diabetology. 2025; 6(10):106. https://doi.org/10.3390/diabetology6100106

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Mazeda, Maria Luís, Bruna Silva, Catarina Cidade-Rodrigues, Filipa Moreira, Vânia Benido-Silva, Vânia Gomes, Catarina Chaves, Catarina A. Pereira, Cláudia Machado, Odete Figueiredo, and et al. 2025. "Association Between Hypoglycaemia at the 24–28th-Week OGTT and Obstetric and Neonatal Outcomes in Women with Gestational Diabetes" Diabetology 6, no. 10: 106. https://doi.org/10.3390/diabetology6100106

APA Style

Mazeda, M. L., Silva, B., Cidade-Rodrigues, C., Moreira, F., Benido-Silva, V., Gomes, V., Chaves, C., Pereira, C. A., Machado, C., Figueiredo, O., Melo, A., Martinho, M., Ferreira, A., Morgado, A., Almeida, M. d. C., Saavedra, A., Almeida, M., & Cunha, F. M. (2025). Association Between Hypoglycaemia at the 24–28th-Week OGTT and Obstetric and Neonatal Outcomes in Women with Gestational Diabetes. Diabetology, 6(10), 106. https://doi.org/10.3390/diabetology6100106

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