Gestational diabetes mellitus (GDM) is a serious and common metabolic problem of pregnancy and also a important issue in maternal and neonatal care all over the world. It is a condition of hyperglycemia for the first time discovered during pregnancy, but not severe enough to be classified as pre-existing diabetes. Insulin resistance, an increase in metabolic requirements, and a failure of the pancreatic beta-cell to compensate are closely linked to the development of GDM during pregnancy. Several factors, such as previous obstetric complications, family history of diabetes, maternal age, and obesity are involved. The rise in obesity rates and alterations in maternal reproductive patterns have been associated with the rising rates of GDM. GDM has short and long-term implications on future metabolic conditions in mothers and fetuses [1-3].

Maintenance of an appropriate intrauterine environment and normal fetal development depends upon the maternal regulation of glycemia. Physiological insulin resistance in pregnancy helps to transport glucose and other nutrients to the unborn baby. But, if there is too much insulin resistance in the mother and not enough insulin production, there could be chronic hyperglycemia. Glucose enters the placenta and triggers insulin secretion in the fetus that may lead to overgrowth of tissues and fat deposition. This mechanism is associated with fetal macrosomia and large-for-gestational-age birth, and may be associated with operative delivery, birth trauma, neonatal hypoglycemia, and other perinatal complications.

The usual methods of assessing maternal glycaemia include fasting plasma glucose, postprandial glucose and glycated haemoglobin, with each of these tests needing to be interpreted in the context of the physiological changes that occur during pregnancy. Good glycemic control is thus essential in minimizing the risk of potentially harmful maternal and fetal complications [4-6].

Maternal lipid homeostasis undergoes significant changes during the course of pregnancy, aside from glucose metabolism. High triglycerides, high total cholesterol and high concentrations of other lipid fractions are helpful for supporting energy needs, placental function and fetal development. These metabolic changes are especially noticeable in the 2nd and 3rd trimesters. Hepatic lipid production, adipose tissue lipolysis, and plasma fatty acid levels are also potentially affected by the increased insulin resistance during pregnancies complicated by GDM.

 These modifications can impact the nutrients that cross the placenta and lead to variations in fetal adiposity (fat content) and fetal growth. Therefore, maternal serum triglycerides, HDL and LDL cholesterol have been gaining attention as potential markers of metabolic disturbances related to birth weight of neonates. However, their association with fetal growth is complex and can differ with gestational age, maternal nutritional status and the extent of metabolic dysfunction [5-7].

The birth weight of the newborn is a critical measurement of intrauterine growth and depends on the maternal, fetal, placental and environmental factors. A low or a high birth weight can lead to poor outcomes for the newborn. The maternal BMI, gain in weight during pregnancy, glycemic control, and blood lipid levels could affect fetal nutrient exposure, and gestational age at delivery is a key factor influencing final birth weight. In cases of GDM, levels of glucose alone may not be a complete explanation for the differences in fetal growth experienced, especially if other metabolic abnormalities are present. Maternal adiposity, insulin resistance and changes in lipid transport may also be factors in inter-individual differences in neonatal weight independent of standard glycemic markers.

A combination of these metabolic parameters may therefore be useful in the understanding of the mechanisms associated with abnormal fetal growth, and the identification of those pregnancies where more frequent antenatal surveillance is warranted [7-9].

Despite growing recognition of the metabolic changes associated with GDM, uncertainty remains regarding the relative contributions of maternal glycemic control and individual serum lipid fractions to neonatal birth weight. The influence of triglycerides, cholesterol fractions, and glycemic parameters may differ across populations because of variations in maternal BMI, dietary habits, gestational age, and clinical management. Simultaneous assessment of these parameters may provide additional information about maternal metabolic health and its relationship with fetal growth. Therefore, the present study aimed to determine the relationship between maternal glycemic status, serum lipid profile, and neonatal birth weight among women with gestational diabetes mellitus.

Study Design, Setting, and Duration This analytical observational study was conducted at Lahore General Hospital, Lahore, over six months, from January 2025 to June 2025. The study population comprised 77 pregnant women diagnosed with gestational diabetes mellitus (GDM). The primary objective was to evaluate the relationship between maternal glycemic status, serum lipid parameters, and neonatal birth weight. Maternal demographic characteristics, obstetric history, biochemical findings, and neonatal outcomes were considered for analysis. The study was designed to determine whether variations in maternal glucose and lipid concentrations were associated with neonatal birth weight and to identify potential independent predictors of fetal growth. Study Population and Eligibility Criteria The study included pregnant women with a confirmed diagnosis of GDM who received antenatal and delivery care at Lahore General Hospital during the study period. For diagnostic classification, the 2025 American Diabetes Association criteria were used as the methodological reference. Under the one-step diagnostic approach, GDM is diagnosed using a 75-g oral glucose tolerance test when at least one plasma glucose value meets or exceeds 92 mg/dL fasting, 180 mg/dL at one hour, or 153 mg/dL at two hours. Women with pre-existing type 1 or type 2 diabetes mellitus, multiple gestations, or major fetal congenital anomalies were considered for exclusion to minimize potential confounding. Maternal characteristics, including age, body mass index (BMI), gravidity, parity, family history of diabetes, previous GDM, and gestational age at delivery, were included as relevant explanatory variables. Assessment of Maternal Glycemic Status and Serum Lipid Profile Glycemic status of the mother was measured by fasting plasma glucose and postprandial glucose and glycated hemoglobin (HbA1c). Glycemic control was assessed based on the recommended targets for pregnancy which are fasting plasma glucose of <95 mg/dL, one-hour postprandial glucose of <140 mg/dL, and two-hour postprandial glucose of <120 mg/dL. The lipid parameters for the mothers were total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in mg/dL. Since the changes in lipid metabolism are physiological during the gestation, the age of the pregnancy at biochemical sampling was considered. The association between continuous variables such as glucose and lipid to the neonatal birth weight was investigated. The possibility of impact on maternal glycemic status with treatment modalities, such as dietary management, oral hypoglycemic medication or insulin therapy, was considered. Assessment of Neonatal Outcomes The birth weight of the newborn was regarded as the main outcome and was reported in grams. Birth weight was classified as low (under 2500 g), normal (2500 to 3999 g) and high (4000 g or more) weight. Other neonatal parameters included sex, gestational age at birth, preterm birth, neonatal hypoglycemia, and admission for NICU (when available). To determine whether there was a correlation between maternal metabolic parameters and neonatal birth weight, the relationship between these was explored. The following factors were also deemed to be potential confounding variables because they may affect the birth weight of a newborn: gestation period at delivery, and BMI of the mother. Statistical Analysis Data analysis was planned using IBM SPSS Statistics version 26.0. Continuous variables, including maternal age, BMI, fasting plasma glucose, HbA1c, lipid concentrations, and neonatal birth weight, were summarized as means and standard deviations or medians and interquartile ranges according to their distributions. Categorical variables were expressed as frequencies and percentages. The Shapiro–Wilk test was used to assess normality. Comparisons of neonatal birth weight between controlled and uncontrolled glycemic groups were performed using the independent-samples t-test or Mann–Whitney U test, as appropriate. Pearson's or Spearman's correlation coefficients were used to assess relationships between glycemic parameters, serum lipid concentrations, and neonatal birth weight. Multiple linear regression was used to evaluate independent associations with birth weight after adjustment for relevant maternal and obstetric characteristics. Regression coefficients, 95% confidence intervals, and p-values were reported. A p-value below 0.05 was considered statistically significant.

The mean age of the mothers at the time of the study was 28.4 ± 4.6 years and the most common age group was 26–30 years (39.0%). Mean maternal BMI was 28.2 ± 3.8 kg/m² and 33.8% of the women were obese. The average gestation period at delivery was 37.8 ± 1.3 weeks.

Table 1. Maternal demographic and clinical characteristics (n=77)

Fasting plasma glucose concentration was 102.0 ± 13.3mg/dL while the postprandial glucose concentration was 135.1 ± 21.0mg/dL. Mean HbA1c was 5.8 ± 0.5%. Nineteen (24.7%) women had controlled glycemic status and 58 (75.3%) women had uncontrolled glycemic status based on the specified glucose-control classification.

The mean levels of serum triglycerides and total cholesterol were 221.2 ± 45.4 mg/dl and 236.3 ± 29.6 mg/dl, respectively.

Table 2. Maternal glycemic parameters and serum lipid profile (n=77)

The mean neonatal birth weight was 3284.8 ± 395.6 g. The majority of the neonates (92.2%) weighed between 2500 and 3999 g and four neonates (5.2%) were considered to be macrosomic. The mean birth weight of the neonates of women with uncontrolled glycemic status was 3336.9 ± 380.7 g, which was not significantly different from women with controlled glycemic status (3125.7 ± 407.9 g; p=0.056).

Table 3. Neonatal birth characteristics and birth weight according to

maternal glycemic status (n=77)

 Low birth weight (0.05).*

Multiple linear regression (MLR) was used to determine independent predictors of neonatal birth weight. The model explained 34.3% of the variation in birth weight (R²=0.343, adjusted R²=0.297; p<0.001). Neonatal birth weight was independently related to fasting plasma glucose (B=9.42 g/mg/dl, p=0.002). Other factors that were significant were maternal BMI (B=25.84 g per kg/m², p=0.048) and gestational age at delivery (B=127.84 g per week, p<0.001). However, after adjustment, serum triglyceride was not independently associated with birth weight, nor was sex in the neonates.

Table 5. Multiple linear regression analysis of factors associated with

neonatal birth weight (n=77)

Dependent variable: neonatal birth weight (g). B represents the unstandardized regression coefficient. Model R²=0.343.

Fig. 1: Relationship between maternal fasting plasma glucose concentration and neonatal birth weight among women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) represents an important metabolic complication of pregnancy that may influence maternal health, placental function, and neonatal growth. The relationship between maternal glycemic status, serum lipid metabolism, and birth weight is particularly relevant because fetal development depends on the continuous transfer of nutrients across the placenta. Maternal insulin resistance, altered glucose utilization, and changes in lipid metabolism may contribute to variations in fetal growth. These metabolic abnormalities frequently coexist with maternal obesity, advancing maternal age, and impaired insulin sensitivity, highlighting the multifactorial nature of GDM. Moreover, metabolic disturbances during pregnancy may have consequences extending beyond delivery, including an increased susceptibility to metabolic disorders in both mothers and their offspring. Understanding these relationships is therefore essential for improving antenatal risk assessment and maternal–neonatal outcomes [2, 10, 11]. The maternal glycemic status is a key regulator of fetal growth. Glucose is easily transported across the placenta via facilitated transport, while clinically significant amounts of insulin do not cross the placenta. Thus, chronic hyperglycemia in the mother can lead to insulin production by the baby's pancreas, causing the growth and buildup of tissues and fat and eventually resulting in high birth weight. Fetal hyperinsulinemia is a significant factor in the development of macrosomia and LGA infant. However, there are some other additional factors that can affect the correlation between maternal glucose levels and neonatal birth weight, such as the duration of hyperglycemic exposure, gestational age, maternal nutritional status, and glycemic control during pregnancy. Fasting and postprandial glucose can provide clinically relevant information about maternal metabolic control and HbA1c can inform of longer term glycemic exposure, though can be influenced by physiological changes in pregnancy. Thus, thorough glycemic monitoring is still significant for the identification of pregnancies with a high risk for excessive fetal growth and related neonatal complications [12-14]. Another possibility is that changes in the woman's body lipid metabolism can also affect the growth of the fetus without affecting the glucose level. During normal pregnancy, there are progressive increases in circulating triglycerides and other lipid fractions, to meet the energy needs of the mother and the developing fetus. Insulin resistance can also be acting to alter hepatic lipid production, adipose tissue lipolysis and free fatty acid availability in women who have GDM. Triglycerides are not directly transferred across the placenta in large amounts, but rather are first hydrolysed by lipases in the placenta, and the resultant fatty acids are then available for uptake by the foetus. Therefore, elevated maternal levels of triglycerides could be associated with fetal adiposity and greater birth weight, whereas HDL-C could be indicative of differences in maternal metabolic regulation. Total cholesterol and LDL-C however have less consistent relationships with fetal growth, as the level of lipids in the blood is affected by gestational age, maternal BMI, dietary intake and placental transport mechanisms. Based on these factors, lipid parameters could be used in conjunction with glycemic parameters in assessing maternal metabolic status, but are not yet routinely used for prediction of macrosomia and require further validation for this purpose [15-17]. Birth weight at birth depends on maternal, placental, genetic and gestational factors. Maternal BMI and gestational weight gain are of special interest since excess adiposity is often linked to insulin resistance and changes in nutrient availability. Another significant factor is the gestation age at delivery, as babies' weight rises significantly in the final weeks of pregnancy. Therefore, one should take into account other factors that may affect the relationship between the maternal biochemical measurement and the weight of the newborn, such as gestational age, anthropometric characteristics of the mother, and other potential confounders. Increased fetal growth can lead to cesarean delivery, trauma, neonatal hypoglycemia, and admission to neonatal intensive care unit (NICU). On the other hand, abnormal fetal growth can be due to the reduced supply of nutrients to the fetus because of problems with the placenta or other factors. These observations highlight the importance of managing pregnancy optimally for the right fetal growth, and not just birth weight. However, the integrated antenatal monitoring, dietary counseling, physical activity, individual glucose management and fetal growth assessment have remained fundamental aspects of complete obstetric care [18-20]. Several methodological limitations need to be taken into account when interpreting associations between maternal glycemic status, lipid concentrations and birth weight in the neonate. Observational studies do not provide causality, and biochemical measurements that are taken at one point of gestation may not be representative of exposures that occur during pregnancy. The measured associations may also be affected by variations in laboratory procedures, maternal diet, gestational age at sampling and treatment adherence. In addition, small sample sizes can limit the accuracy of the statistics, especially when calculating rare events like macrosomia. The independent contribution of glucose, HbA1c, triglyceride and other lipid fractions to fetal growth may be better understood by future multicenter prospective studies, which will include repeated measurements of these factors over the course of pregnancy. The inclusion of maternal BMI, treatment characteristics, and standardization of birth weight for GA in predictive models may help to identify clinically useful metabolic markers for individualized antenatal care and improve predictive models.

Maternal glycemic control and lipid metabolism are important components of the metabolic environment influencing fetal growth in pregnancies complicated by gestational diabetes mellitus. Elevated maternal glucose concentrations may promote excessive fetal growth through increased fetal insulin secretion, while alterations in triglycerides and other lipid fractions may contribute to fetal nutrient availability and adiposity. Neonatal birth weight is also influenced by maternal BMI, gestational age, and other obstetric factors. Comprehensive maternal metabolic assessment, appropriate glycemic management, and regular fetal growth monitoring are essential for optimizing pregnancy care. Further prospective research is required to establish whether incorporating maternal lipid parameters into conventional glycemic assessment improves the prediction of neonatal birth weight and related complications.