{"id":4095,"date":"2025-12-26T08:59:17","date_gmt":"2025-12-26T08:59:17","guid":{"rendered":"https:\/\/hjog.org\/?p=4095"},"modified":"2026-01-14T09:03:02","modified_gmt":"2026-01-14T09:03:02","slug":"_research-article-12-2-19-2-48-2-2-2-2","status":"publish","type":"post","link":"https:\/\/hjog.org\/?p=4095","title":{"rendered":"Impact of fetal gender on gestational diabetes mellitus\u2019 incidence: A cohort study"},"content":{"rendered":"

Research<\/span><\/p>\n

HJOG 2026, 25 (1), 1-9| doi: 10.33574\/hjog.0610<\/p>\n

Maria-Foteini Kampeza, Antigoni Tranidou, Themistoklis Dagklis, Ioannis Kalogiannidis, Anargyros Kourtis, Apostolos Mamopoulos, Ioannis Tsakiridis<\/p>\n

\u00ad\u00ad\u00ad\u00ad\u00adThird Department of Obstetrics and Gynaecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece<\/p>\n

Correspondence:\u00a0<\/em>Ioannis Tsakiridis, Konstantinoupoleos 49, 54642, Thessaloniki Tel: +30 2313312120 and Fax: +30 2310 992950, e-mail: iotsakir@gmail.com<\/a><\/p>\n

\"\"<\/a><\/p>\n

\n
Abstract<\/strong><\/h5>\n

Introduction:<\/strong> Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder in pregnancy, associated with maternal and neonatal complications. While established risk factors are well-documented, the potential role of fetal gender on GDM development remains uncertain. The present study aimed to investigate the association between fetal gender and GDM and to assess whether fetal gender modifies the influence of maternal risk factors such as age and pre-pregnancy body mass index (BMI).
\nMaterials and methods:<\/strong> This retrospective cohort study was conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece between December 2023 and March 2025. Baseline characteristics were compared between groups. Multivariable logistic regression was used to assess independent associations with GDM, and interaction analysis was conducted to evaluate effect modification between fetal gender and maternal age or pre-pregnancy BMI.
\nResults:<\/strong> The study included 926 pregnant women, of whom 138 (14.9%) were diagnosed with GDM. Maternal age and pre-pregnancy BMI were independently associated with GDM risk. No significant association was observed between fetal gender and GDM (adjusted OR = 1.05; 95% CI: 0.72\u20131.52; p = 0.79). Additionally, fetal gender did not significantly modify the effect of maternal age, BMI, or BMI categories on GDM risk in either additive or multiplicative interaction models (all p values >0.05).
\nConclusion:<\/strong> Fetal gender was not associated with GDM in this cohort and did not appear to modify the influence of maternal risk factors. These findings suggest that fetal gender may not play a significant role in GDM risk prediction, supporting the continued emphasis on maternal characteristics in risk assessment.<\/p>\n

Keywords:<\/em> Gestational diabetes mellitus, GDM, fetal gender, glucose metabolism, insulin resistance, maternal age, BMI<\/p>\n

Introduction\u00ad<\/strong><\/h5>\n

Gestational diabetes mellitus (GDM) is currently one of the most prevalent metabolic disorders, affecting approximately 14% of pregnancies worldwide (1). Defined as glucose intolerance with first onset during pregnancy, GDM is associated with adverse short- and long- term pregnancy complications for both mothers (2\u20136) and their offspring (2). Prenatal exposure to maternal hyperglycemia, leads to hyperinsulinemia in the fetus (2), which exerts a particularly significant impact on fetal development and contributes to adverse neonatal outcomes such as macrosomia and shoulder dystocia (3,7,8). In the long term, children born to mothers with GDM are at increased risk of impaired glucose tolerance, insulin resistance, and metabolic disorders, including type 2 diabetes mellitus (T2DM) (7,9). Early identification and risk stratification are therefore critical (10).<\/p>\n

A variety of maternal risk factors have been well established; these include advanced maternal age (typically over 25 years), obesity (11), family history of diabetes (particularly T2DM), previous history of GDM or macrosomia, polycystic ovarian syndrome (PCOS) or prediabetes and certain ethnic backgrounds (6,12). In addition, a history of delivering large-for-gestational-age (LGA) neonate or a previous diagnosis of GDM further heightens the risk (5). Modifiable lifestyle factors such as diet and physical activity, as well as environmental exposures like endocrine-disrupting chemicals, are also increasingly recognized as contributors (13). Despite its common occurrence, the underlying causes and risk factors associated with GDM are not fully elucidated, prompting researchers to investigate various influences, including the potential role of fetal gender (14).<\/p>\n

In recent years, attention has turned to fetal gender as a possible factor influencing maternal metabolic adaptation during pregnancy. Several studies have reported that pregnancies with male fetuses are commonly linked to a higher prevalence of GDM and may involve more severe glucose intolerance, possibly due to increased placental demands or hormonal regulation (15\u201319). Conversely, some studies suggest that female fetuses are more often associated with maternal hypertensive disorders and pre-eclampsia (20). Despite these findings, the relationship between fetal gender and GDM remains unclear, with some studies reporting no significant association.<\/p>\n

The primary objective of this study is to investigate the impact of fetal gender on the incidence of GDM. A clearer understanding of this potential relationship could enhance risk stratification and promptly implementing preventing measures for high-risk pregnancies. Insights into the role of fetal gender, may also support the development of patient-centered approaches, improving maternal and neonatal outcomes.<\/p>\n

Material and methods<\/strong><\/h5>\n

Study design and population characteristics<\/strong><\/p>\n

This retrospective cohort study was conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece between December 2023 and March 2025. Women with pre-gestational diabetes, those aged <18 years old and those with serious medical conditions (e.g. heart failure, renal disease) were excluded from the analysis. Eligible participants had complete clinical and demographic data relevant to the study objectives. Ethical approval was not required, as the study involved anonymized, routinely collected clinical data and did not interfere with patient management. The data were handled in compliance with institutional data protection policies and relevant regulations.<\/p>\n

Diagnosis of gestational diabetes <\/strong><\/p>\n

GDM was diagnosed based on the criteria established by the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study (21). All participants underwent a 75-gram oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. The diagnosis was made when one or more of the following thresholds were met: fasting plasma glucose \u226592 mg\/dL, 1-hour glucose \u2265180 mg\/dL, or 2-hour glucose \u2265153 mg\/dL.<\/p>\n

Data collection<\/strong><\/p>\n

Data were collected from electronic medical records and included maternal demographic characteristics, anthropometric measurements, obstetric history, and fetal outcomes. Variables of interest included maternal age, height, weight, BMI before pregnancy, parity, smoking status, and use of assisted reproductive technology (ART). Pre-pregnancy BMI was calculated using self-reported pre-pregnancy weight and measured height. Fetal gender was determined by routine second-trimester ultrasound and confirmed at delivery.<\/p>\n

Statistical analysis<\/strong><\/p>\n

Regarding the population characteristics, for variables following a normal distribution, mean and SD are provided; otherwise, the median and quartiles are reported. The Shapiro\u2013Wilk (<50 samples) or Kolmogorov\u2013Smirnov test (>50 samples) tests were used to assess normality. The p-values were obtained using a t-test for normally distributed variables, Mann\u2013Whitney test for non-normally distributed variables, and chi-squared test for categorical variables. Fisher\u2019s exact test (n<5) or Chi-squared test (n>5) were applied for binary variables, contingent on the sample size.<\/p>\n

Logistic regression analyses were performed to assess the association between fetal gender (male vs. female) and the risk of GDM. Odds ratios (OR) were estimated, with adjustments made for ART, pre-pregnancy BMI, maternal age, smoking status, and parity. Interactions between fetal gender and specific maternal risk factors-including maternal age greater than 35 years and pre-pregnancy BMI categories (underweight, normal, overweight, obese), were evaluated using logistic regression models with explicit interaction terms. Biological interaction was quantified on an additive scale, calculating the Relative Excess Risk due to Interaction (RERI), Statistical significance of interaction terms was evaluated using p-values from the regression coefficients. BMI categories were defined based on standard World Health Organization (WHO) criteria: underweight (BMI <18.5 kg\/m\u00b2), normal weight (18.5\u201324.9 kg\/m\u00b2), overweight (25\u201329.9 kg\/m\u00b2), and obese (\u226530 kg\/m\u00b2). Statistical significance of interaction terms was evaluated based on p-values from the regression coefficients. All analyses were computed in R programming language.<\/p>\n

Results\u00a0 <\/strong><\/h5>\n

The study population consisted of 926 pregnant women; participants were categorized into GDM (n = 138) and non-GDM (n = 788) groups. Table 1<\/a> shows characteristics of the included population. Women with GDM were significantly older (mean maternal age 34.02\u202f\u00b1\u202f4.99 vs. 32.4\u202f\u00b1\u202f4.79 years, p\u202f<\u202f0.001) and more frequently over the age of 35 (40.58% vs. 31.09%, p\u202f=\u202f0.036) compared to those without GDM. Pre-pregnancy BMI was significantly higher among women with GDM (median 24.2 [IQR: 21.7\u201328.17] vs. 22.6 [20.67\u201326], p\u202f<0.001). The prevalence of overweight (BMI >25) and obesity (BMI >30) was also elevated in the GDM group (39.86% vs. 30.2%, p\u202f=\u202f0.032; and 19.57% vs. 10.79%, p\u202f=\u202f0.006, respectively). ART use and smoking status were not significantly different between the GDM and non-GDM groups (ART: 13.77% vs. 8.76%, p\u202f=\u202f0.09; smoking: 14.49% vs. 9.14%, p\u202f=\u202f0.074).<\/p>\n

In the multivariable logistic regression analysis (Table 2<\/a>), maternal age and pre-pregnancy BMI were significantly associated with an increased risk of GDM. Each one-year increase in maternal age was associated with a 6% increase in the odds of GDM (aOR: 1.06, 95% CI: 1.02\u20131.11, p\u202f=\u202f0.002), and each unit increase in pre-pregnancy BMI was associated with a 6% increase in GDM risk (aOR: 1.06, 95% CI: 1.03\u20131.10, p\u202f<\u202f0.001). In contrast, male fetal gender (aOR: 1.05, 95% CI: 0.72\u20131.52, p\u202f=\u202f0.79), ART use (aOR: 1.14, 95% CI: 0.60\u20132.06, p\u202f=\u202f0.67), smoking (aOR: 1.58, 95% CI: 0.90\u20132.69, p\u202f=\u202f0.097) and parity (aOR: 0.92, 95% CI: 0.70\u20131.20, p\u202f=\u202f0.56) were not significantly associated with GDM after adjusting for potential confounders.<\/p>\n

Interaction analysis was performed to evaluate whether the association between maternal pre-pregnancy BMI and the risk of GDM differed by fetal gender (Table 3<\/a>). No statistically significant interaction was observed on the multiplicative scale across any BMI category (all p\u202f>0.05). The joint effect of carrying a male fetus and being in the normal BMI range was associated with a modestly increased odds of GDM (aOR\u202f=\u202f1.62), accompanied by a small positive additive interaction (RERI\u202f=\u202f0.27), although this was not statistically significant (p\u202f=\u202f0.59). In all other BMI categories (underweight, overweight, and obese), both the joint effects and additive interaction measures (RERI) were either negative or close to null, and the interaction p-values remained non-significant (p = 0.69\u20130.82).<\/p>\n

Interaction analysis between fetal gender and advanced maternal age (>35 years) and pre-pregnancy BMI >25, revealed no statistically significant interaction on either the additive or multiplicative scales (Table 4<\/a>). The combination of male fetal gender and maternal age >35 was associated with a slightly reduced odds of GDM (aOR\u202f=\u202f0.75), alongside a small positive RERI (0.20), but this interaction was not statistically significant (p\u202f=\u202f0.50). Similarly, the joint effect of male fetal gender and BMI >25 showed no increased risk (aOR\u202f=\u202f0.61) and a negative additive interaction (RERI\u202f=\u202f\u20130.16), with a non-significant interaction p-value (p\u202f=\u202f0.63).<\/p>\n

Discussion<\/strong><\/h5>\n

The present study aimed to investigate the potential association between fetal gender and the risk of GDM, as well as whether fetal gender modifies the influence of maternal risk factors such as age and pre-pregnancy BMI. The findings of our study did not indicate a statistically significant correlation between fetal gender and the occurrence of GDM, either as a direct risk factor or as a modifier of other maternal characteristics. Consistent with existing literature, we found that maternal age and pre-pregnancy BMI were the primary factors independently associated with the risk of GDM. In contrast, fetal gender was not associated with GDM, and its inclusion in the adjusted model did not significantly alter the risk. Similarly, other maternal characteristics such as smoking, parity, and ART use did not show significant associations with GDM in this cohort.<\/p>\n

Several studies have failed to establish a definitive connection between fetal gender and GDM risk, supporting the findings of our research (22\u201324). These outcomes emphasize the stronger role of confounding maternal and environmental factors in the pathophysiology of GDM, rather than fetal gender alone. Furthermore, the inconsistencies in findings across studies may be attributed to variations in diagnostic criteria, sample size and study populations. For instance, some studies include exclusively high-risk pregnancies, whereas others analyse more heterogeneous populations with differing baseline characteristics. It is worth mentioning that the study conducted by Yamashita et al. (24) was carried out in a Japanese population, which is considered an ethnically uniform and genetically homogenous community.<\/p>\n

Conversely, several studies have reported a higher prevalence and severity of GDM in pregnancies carrying male fetuses, potentially due to increased maternal glucose levels and reduced pancreatic \u03b2-cell function associated with male fetal gender (18,25,26). Some researchers attribute this to sex-specific hormonal and placental differences, with male placentas exhibiting altered gene expression and metabolic activity that may impair maternal glucose regulation. Additionally, male fetuses have been linked to increased maternal insulin resistance, which could contribute to the heightened risk of GDM (27). Furthermore, multiple large studies have previously reported a relationship between fetal gender and GDM (23). Discrepancies between our findings and those results may be attributed to variations in diagnostic criteria and timing of GDM diagnosis. According to Di Renzo et al. (28) maternal GDM and fetal macrosomia were more commonly observed in pregnancies with male fetuses compared to those with female fetuses. Similarly, a systematic review and meta-analysis of observational studies concluded that the relative risk of GDM is 4% higher in women carrying a male fetus (29).<\/p>\n

On the other hand, the impact of female gender on GDM pregnancies has been investigated, with studies demonstrating higher levels of insulin resistance compared to those with male fetuses, even after adjusting for confounding factors (30,31). Retnakaran et al. (32), however, examined the relationship between fetal gender and the recurrence of GDM in a subsequent pregnancy, concluding that although fetal gender in the first pregnancy did not influence the recurrence risk, pregnancy with a female fetus was associated with a higher risk of developing T2DM before a future pregnancy. Comparably, Wang et al. resulted in a 6% higher relative risk of developing T2DM in the future among women with GDM pregnancies with female fetuses (30).<\/p>\n

One possible explanation for our results is the multifactorial etiology of GDM, which involves a complex interaction of genetic, metabolic, and environmental factors that may overshadow any minor effect exerted by fetal gender. Additionally, while fetal gender may modulate certain physiological parameters during pregnancy, its impact on maternal glucose metabolism appears insufficient to achieve statistical significance across diverse populations.<\/p>\n

Although fetal gender did not emerge as a significant predictor of GDM in this study, preventive measures remain crucial in mitigating GDM risk. Early intervention methods for GDM combine lifestyle interventions, medical monitoring and personal care strategies focusing on early identification of high-risk pregnancies. Adherence to appropriate gestational weight gain, healthy eating patterns, regular physical activity are key recommendations (33,34).\u00a0 Current clinical guidelines for GDM screening and management rely primarily on maternal characteristics, and our findings do not support the inclusion of fetal gender as a predictor in routine risk assessment. Nevertheless, further research into fetal-maternal interactions may help refine predictive models in the future, especially in populations with specific risk profiles.<\/p>\n

The strengths of this study lie in its utilization of a well-defined cohort from a single tertiary hospital, ensuring consistency in diagnostic criteria and clinical management. The availability of comprehensive maternal and neonatal data also enhances the validity of the findings. Additionally, the retrospective methodology facilitates the assessment of a substantial sample size, while minimizing the risk of potential biases associated with clinical decision-making processes. However, certain limitations should be acknowledged. First, the observational nature of the research inherently restricts the ability to establish causality. Furthermore, key confounding factors, including maternal dietary habits, genetic susceptibility, and socioeconomic status were not thoroughly addressed, potentially influencing the outcomes. Moreover, variability in GDM diagnostic criteria across different studies may challenge comparability. Future research incorporating multicentre approaches and advanced predictive algorithms could provide an enhanced evaluation of the association between fetal gender and GDM.<\/p>\n

Conclusion<\/strong><\/h5>\n

Fetal gender showed no significant association and did not modify the effect of maternal characteristics on GDM risk. Although not a modifiable factor, fetal gender may still offer insight into pregnancy risk assessment. Its inclusion in predictive models could contribute to early identification of at-risk pregnancies; however, current clinical guidelines continue to prioritize maternal factors in risk stratification. Further research is needed to clarify the biological mechanisms through which fetal gender may influence maternal glucose metabolism, including placental, hormonal, and genetic pathways. Large-scale, multicenter studies incorporating diverse populations and refined prediction models may help determine whether fetal gender holds any value in enhancing GDM screening and prevention strategies. While maternal characteristics remain central to GDM risk, the role of fetal gender warrants further investigation.<\/p>\n

Conflicts of Interest<\/strong><\/h5>\n

The authors declare no conflicts of interest.<\/p>\n

Funding<\/strong><\/h5>\n

No funding was received for this study.<\/p>\n

References<\/strong><\/h5>\n
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    Maria-Foteini Kampeza, Antigoni Tranidou, Themistoklis Dagklis, Ioannis Kalogiannidis, Anargyros Kourtis, Apostolos Mamopoulos, Ioannis Tsakiridis<\/p>\n

    \"\"<\/a><\/p>\n

    Introduction: Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder in pregnancy, associated with maternal and neonatal complications. While established risk factors are well-documented, the potential role of fetal gender on GDM development remains uncertain. The present study aimed to investigate the association between fetal gender and GDM and to assess whether fetal gender modifies the influence of maternal risk factors such as age and pre-pregnancy body mass index (BMI)…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1336],"tags":[1307,1337,684,784,1338,884,114],"class_list":["post-4095","post","type-post","status-publish","format-standard","hentry","category-2026-volume-25-issue-1","tag-bmi","tag-fetal-gender","tag-gdm","tag-gestational-diabetes-mellitus","tag-glucose-metabolism","tag-insulin-resistance","tag-maternal-age"],"_links":{"self":[{"href":"https:\/\/hjog.org\/index.php?rest_route=\/wp\/v2\/posts\/4095","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/hjog.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/hjog.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/hjog.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/hjog.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=4095"}],"version-history":[{"count":7,"href":"https:\/\/hjog.org\/index.php?rest_route=\/wp\/v2\/posts\/4095\/revisions"}],"predecessor-version":[{"id":4257,"href":"https:\/\/hjog.org\/index.php?rest_route=\/wp\/v2\/posts\/4095\/revisions\/4257"}],"wp:attachment":[{"href":"https:\/\/hjog.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4095"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hjog.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4095"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hjog.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4095"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}