Macrosomia is one of the most common adverse outcomes in newborns, and usually refers to a newborn with a birth weight of $\ge$4000 g, regardless of gestational age. The incidence of macrosomia is rapidly increasing worldwide [1], with an incidence among live births of 7.8% in the United States in 2018 [2]. During the same period, a British study reported the incidence of macrosomia as 12.7% [3]. The incidence of macrosomia in China has also increased recently due to significant improvements in living standards, as well as multi-faceted changes in diet and lifestyle. This has resulted in a major socioeconomic and health burden on Chinese society. Although there is no official report on the incidence of macrosomia in China, it has been reported to range from 7.23% to 15.5% in different regions [4]. In southeastern China, the incidence increased from 6.0% in 1995 to 7.8% in 2005 [5], while in northern China it increased from 6.6% in 1996 to 7.0% in 2010 [6]. A hospital-based, cross-sectional study in 14 provinces of China reported a prevalence of 7.3% [7], while a multicenter study published in 2022 reported the incidence of macrosomia in multiparous women was 7.6% [8].

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. This state of glucose intolerance occurs, or is first diagnosed, during pregnancy. A global perspective study from 2016 reported the highest prevalence of GDM in the Middle East and North African regions [9]. The prevalence of GDM in Iran was approximately 3.41%, ranging from 1.3% to 18.6%. International epidemiological data also show significant variation in the incidence of GDM between different countries, ranging from 6.6% in Japan and Nepal, to 45.3% in the United Arab Emirates [10]. The international prevalence of GDM continues to rise due to epidemiological factors such as increased rates of obesity among women of childbearing age, increased maternal age, and revisions to the criteria and diagnostic procedures for GDM by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) [11]. Between 15% and 45% of newborns born to mothers with GDM are macrosomic, compared to 12% of those born to normal mothers [12]. GDM is associated with increased short- and long-term morbidity in both neonates and mothers. Short-term maternal morbidity from GDM includes preeclampsia, gestational hypertension, hydramnios, urinary tract/vaginal infections, instrumental delivery, cesarean delivery, traumatic labor/perineal tears, postpartum hemorrhage, and difficulty initiating and/or maintaining breastfeeding. Short-term neonatal morbidity from GDM includes stillbirth, neonatal death, preterm birth, congenital malformations, macrosomia, cardiomyopathy, birth trauma (shoulder dystocia, bone fracture, brachial plexus injury), hypoglycemia, hyperbilirubinemia, and respiratory distress syndrome. Long-term maternal morbidity from GDM includes recurrence of GDM, type 2 diabetes mellitus, hypertension, ischemic heart disease, non-alcoholic fatty liver disease, dyslipidemia, and chronic kidney disease. Long-term neonatal morbidity from GDM includes metabolic syndrome, hyperinsulinemia, childhood obesity, excess abdominal adiposity, elevated blood pressure, possible early onset cardiovascular disease, possible attention-deficit hyperactivity disorder, and autism spectrum disorder [13].

Macrosomia is the most common and well-known adverse consequence of GDM. Complications of macrosomia include shoulder dystocia, cesarean section, birth trauma, asphyxia, postpartum hemorrhage, and high risk of perinatal death. In addition, macrosomic newborns are more likely to develop metabolic disorders in later life, such as obesity, type 2 diabetes, and hypertension. Brachial plexus injury caused by shoulder dystocia due to macrosomia alone can also have serious adverse consequences [14]. Medical lawsuits relating to this injury have increased annually, with medical institutions facing large compensation payments. The superposition of multiple factors has meant that GDM and adverse outcomes from macrosomia have progressively increased in China. At present, there is no official report on the incidence of macrosomia in China, with previous studies having focused mostly on the southern and northern regions. Different geographical regions of China are highly diverse, with each region having its own unique dietary culture. The factors influencing macrosomia are therefore likely to vary between regions. The present clinical epidemiological study investigated high-risk factors for macrosomia in the central region of China, which has a different dietary culture from the southern and northern regions. We also evaluated the impact of outpatient clinics for GDM, with the aim of identifying high-risk factors that could allow early intervention in future clinical work. This research provides a scientific basis for the prevention of macrosomia in China, thereby avoiding adverse perinatal outcomes and improving the quality of birth.

In Chinese tradition, giving birth to a large, fat boy is considered a blessing. However, the negative effects of macrosomia are drawing increased attention. The incidence of macrosomia in our hospital was 7.29%, the proportion of newborns weighing $>$5000 g was 1.41%, and the proportion of newborns weighing between 4500 and 5000 g was 8.27%. The overall incidence of maternal obesity in this study population was 10.12%, and 21.08% of subjects were considered to be overweight. The demographic characteristics of the macrosomia group were not significantly different from the non-macrosomia group, with the exception of maternal age. However, other characteristics such as gravidity, parity, height, pre-pregnancy weight, delivery weight, pre-pregnancy BMI, pre-pregnancy BMI distribution, weight gain during pregnancy, GDM and occupation were significantly higher in the macrosomia group. After adjusting for confounding factors, binary logistic analysis revealed OR values $>$1 for GDM and occupation, indicating they were independent risk factors for macrosomia. The other indicators did not change significantly after adjustment.

The incidence of macrosomia is increasing worldwide. According to data from the National Center for Health Statistics, the incidence of macrosomia among live births in the USA was 7.8% in 2018 [1]. China has yet to officially release national data on the incidence of macrosomia, but it has been reported to vary greatly according to region. The incidence found in this study (7.29%) was consistent with the latest literature report of 7.6%. However, there was a very high incidence (27.2%) in subsequent pregnancies in mothers with a history of macrosomia [8]. The overall prevalence of pre-pregnancy obesity and overweight in the present study population was 31.18%, of which the overweight incidence was 47.1% in the macrosomia group and 26.5% in the non-macrosomia group. Obesity is a controllable factor that has received growing attention and is currently a major public health issue. The 2010 National Survey on Nutritional Status in Colombia showed that an increasing number of women are overweight during pregnancy, with 39.9% of pregnant women of all ages being overweight (24.7% overweight, 15.2% obese). Observational studies of representative cohorts of pregnant women in other countries have shown the prevalence of overweight to be 63.8% in Peru, 47.5% in Brazil [17, 18, 19]. Excessive maternal weight can alter the intrauterine environment, leading to a higher risk of obstetric and neonatal complications. Moreover, excessive weight gain during pregnancy is the strongest variable affecting the probability of neonatal macrosomia, with obese and overweight women experiencing a higher proportion of total weight gain [20]. A 2016 expert review found that women with large increases in BMI were more likely to have fetal macrosomia, indicating the need to strictly monitor weight gain, especially in women who are overweight before pregnancy. These women require special attention to help them achieve an appropriate pre-pregnancy weight [21]. To limit the increase in overweight, Colombian women receive comprehensive interventions before, during and after pregnancy aimed at improving their sexual and reproductive health. These measures focus on prevention and timely intervention in overweight women, as well as the prevention of excessive gestational weight gain. Regardless of their pre-pregnancy BMI, such measures may help to reduce the incidence of fetal macrosomia [16, 22].

The present study found the macrosomia group had significantly higher gravidity, parity, height, pre-pregnancy weight, predelivery weight, pre-pregnancy BMI, weight gain during pregnancy, and excess weight gain compared to the non-macrosomia group. Male fetuses were found to account for $>$50% of newborns in the macrosomia group. In multivariate analysis, we found that pre-delivery weight, history of macrosomia, pre-pregnancy weight gain, BPD, AC, occupation, and GDM remained statistically significant risk factors after adjusting for confounding factors. The ORs for occupation and GDM were both $>$1. In particular, the increased risk associated with GDM should be noted by obstetricians. After excluding a history of macrosomia, multivariate analysis revealed that pre-delivery weight, BPD, AC, occupation, and weight gain during pregnancy remained important influencing factors. The OR value was 0.960 for pre-delivery weight and 0.416 for weight gain during pregnancy, implying that higher pre-delivery weight is an important independent risk factor for macrosomia. After adjusting for potential confounding factors, occupation was found to be a significant risk factor for macrosomia, regardless of whether there was a previous history of macrosomia (OR = 1.511, 95% CI: 1.117–2.043, p = 0.007). These two factors are controllable, and our results are consistent with the conclusions of a previous report [23]. A large birth cohort study showed that low maternal BMI was inversely correlated with the occurrence of macrosomia, although this was conducted in Chinese populations rather than the European and American population [24].

The classification of obesity and overweight, and recommendations for gestational weight gain, are different between China and other countries. According to the definition of the World Health Organization, European and American Caucasians are considered overweight and obese if their BMI exceeds 25.0 kg/m² and 30.0 kg/m², respectively. However, this classification is not necessarily applicable to Asians, since the upper limit of the normal range of 24.9 kg/m² is too high for Asians.

With regard to weight gain during pregnancy, the Institute of Medicine (IOM) of the United States recommends that underweight women gain 12.5–18.0 kg, normal-weight women gain 11.5–16.0 kg, overweight women gain 7.0–11.5 kg, and obese women gain 5.0–9.0 kg [25]. Weight gain guidelines for pregnant Chinese women were proposed in 2021 and are slightly different from those of the United States [15]. The incidence of macrosomia in South Korea was found to be 3.22%, and a male fetus was considered to be an independent risk factor for macrocephaly [26]. Although we also found that the proportion of male fetuses among macrosomic infants was 64.1%. However, we did not find that a male fetus was an independent risk factor for macrocephaly, with the incidence as high as 64.1%. This may be related to traditional Chinese concepts, whereby many families prefer to have boys. If the fetus is found to be female during the early and middle stages of pregnancy, parents may choose to terminate the pregnancy, further exacerbating the gender imbalance in the Chinese population. This may also be related to genetic and environmental factors. The complex interaction between the placenta and fetal sex means that from the early stages of pregnancy, male fetuses are longer than female fetuses [26, 27]. Some studies have also reported that maternal parity and height can affect the risk of macrosomia [23, 28]. This is consistent with our study, which found significantly greater height and more gravidity and parity in the macrosomia group. The maternal peritoneum and uterine wall of multiparous women are more relaxed than those of primiparous women, which may lead to an increase in uterine volume and therefore an increased risk of fetal macrosomia [29].

It is well known that GDM can affect fetal weight and increase the risk of macrosomia. However, there is currently no effective management or treatment for GDM, with medical nutritional therapy (MNT) considered the first-line treatment. In most cases, blood glucose levels can be regulated through diet alone, but up to half of all GDM patients are unable to achieve good metabolic control and require the use of insulin or other glucose-lowering drugs. MNT remains the most commonly used method worldwide for controlling blood glucose levels in women with GDM [30]. However, the efficacy of MTN is often unsatisfactory due to a lack of follow-up. In order to improve the management of pregnant women with GDM, our hospital established a gestational diabetes clinic. This comprehensive clinic provides health and nutrition guidance, dietary advice, exercise knowledge, and regular follow-up by obstetricians, endocrinologists and nutrition experts [31]. In 2019, the International Diabetes Federation estimated that 1 in 6 live births worldwide suffered from maternal diabetes. More than 90% of cases with hyperglycemia during pregnancy occur in low- and middle-income countries [32]. Obesity and GDM are known to interact with each other. A meta-analysis found the risk of GDM was 2.14-fold higher in overweight pregnant women, 3.56-fold higher in obese pregnant women, and 8.56-fold higher in severely obese pregnant women compared to normal-weight pregnant women [33]. Consistent with the results of previous studies, the incidence of GDM in the macrosomia group in the present study (33.3%) was higher than in the non-macrosomia group (24.9%).

Following intervention in the GDM outpatient clinic, the birth weight and weight gain of mothers during pregnancy were found to be significantly lower than in the control group. Moreover, the incidence of appropriate weight gain was significantly higher than in the control group, while excessive weight gain was significantly lower. No significant difference in the fasting blood sugar level was found between the two groups, but blood sugar and glycosylated hemoglobin in the GDM study group were significantly lower two hours after a meal. The use of insulin was significantly higher after intervention, consistent with the reduction in blood sugar two hours after intervention. Although not statistically significant, the incidence of macrosomia was reduced by 8% after intervention, which may still be important in actual clinical practice. No significant differences were observed in other indicators such as pregnancy, parity, age, pre-pregnancy weight, and pre-pregnancy BMI, which is consistent with the actual situation. The failure to detect a difference may be due to comparison with the same population, since a blank control group was not used. Our multivariate analysis revealed no significant difference in the occurrence of macrosomia between the intervention and control groups before adjusting for confounding factors. After adjustment, the occurrence of macrosomia was more than 5-fold higher in the control group compared to the intervention group (OR = 5.34, 95% CI: 2.51–11.34, p 0.001), while insulin use increased 3.739-fold. Differences in other indicators, such as weight gain during pregnancy, blood sugar two hours after meals, and pregnancy weight gain in specific conditions, remained significantly different. The indicators of birth weight, glycosylated hemoglobin, and pre-pregnancy BMI distribution were not significantly different between the GDM and control groups. These results demonstrate that intervention for gestational diabetes can significantly reduce the occurrence of macrosomia and improve the control of blood sugar, suggesting this measure should be promoted.

Macrosomia is caused by abnormal fetal growth and can lead to serious consequences for the mother and fetus. From a practical perspective, most of the known risk factors are not easily modifiable. Techniques for diagnosing macrosomia include ultrasound examination, clinical assessment, maternal assessment, and MRI. The ability to accurately predict birth weight is still limited, with the available techniques having an error rate of at least 15% [34]. Ultrasound examination is simple and convenient, and is therefore the most commonly used method worldwide to estimate fetal weight. Many ultrasound methods exist for predicting neonatal birth weight, including the Hadlock, MerzE, OttWJ, CombsCA, and SciosciaM formulas. The most commonly used method in China is the Hadlock formula, which is based on the four fetal biological indicators of AC, FL, BPD, and HC [35]. Studies have found that fetal AC is more predictive of large birth weight than other fetal ultrasound soft indicators. However, a weighted formula that can accurately predict macrosomia has yet to be reported [36]. Some authors have found that prenatal fetal ultrasound measurement indicators, including estimated fetal weight (EFW) and amniotic fluid index (AFI), can effectively predict macrosomia [37]. Although these two indicators are correlated and ultrasound measurement can predict the birth weight of newborns to a degree, it cannot estimate the fetal weight of macrosomic newborns with a birth weight of $>$4000 g. Excessive fetal growth and development may lead to narrowing of the intrauterine space, thus limiting the ultrasound measurement angle. The current study analyzed ultrasound-related indicators, including BPD, HC, AC, and FL. With the exception of FL, the other three indicators were significantly higher in the macrosomia group compared to the non-macrosomia group. Multivariate analysis found that BPD and AC retained important predictive value. The larger the value for these parameters, the greater the risk of macrosomia, with the differences being statistically significant. In contrast, HC and FL were less important. The predictive value of specific indicators was calculated using ROC curve analysis, which revealed AUC values of 0.703 for birth weight, 0.642 for pre-pregnancy BMI, 0.742 for BPD, and 0.866 for AC. The latter two indicators had the highest predictive value, with cutoff scores of 9.45 cm and 34.95 cm. Although the results of ultrasound can sometimes be uncertain, especially in the hands of inexperienced operators, it is currently the most economical examination in China. When BPD and AC exceed a certain value, this finding must be taken seriously by clinicians, especially if multiple risk factors are present.

Macrosomia has received increased attention thanks to China’s new fertility policy and a greater emphasis on the quality of birth. Most of the risk factors for macrosomia remain present or become even more severe in subsequent pregnancies. Therefore, it is important to prevent macrosomia during the first pregnancy in order to reduce the likelihood of its recurrence. This study found that pregnancy, parity, pre-pregnancy weight, pre-delivery weight, pre-pregnancy BMI, weight gain during pregnancy, GDM, occupation, and newborn gender are important factors in the occurrence of macrosomia. Moreover, multifactorial analysis revealed that GDM and occupation may be independent risk factors. In multiparas with a history of macrosomia, a multifactorial study found that pre-delivery weight, weight gain during pregnancy, and occupation were independent risk factors for the recurrence of macrosomia. Since GDM and weight are the most influential factors in macrosomia, our group established a GDM outpatient clinic. Multifactorial analysis showed that the risk of macrosomia in pregnant women with GDM was 2.57-fold higher in the absence of intervention. Intervention also significantly reduced weight gain and controlled blood sugar, thus demonstrating its importance in clinical practice.

The incidence and recurrence of macrosomia continue to rise, representing a major burden under China’s new fertility policy. Pre-pregnancy weight, pre-pregnancy BMI, and gestational weight gain were identified as risk factors for macrosomia, with each being amenable to intervention. Appropriate maternal weight also has potential benefits for health beyond pregnancy and childbirth. Therefore, women should maintain their pre-pregnancy BMI within the normal range before becoming pregnant. Hospitals should establish multidisciplinary outpatient clinics for gestational diabetes according to the needs of the hospital, thereby facilitating intervention for pregnant women with nutritional needs and gestational diabetes. This intervention can be simple so that it effectively changes eating habits, increases exercise, avoids excessive weight gain during pregnancy, and better controls blood sugar, thereby preventing macrosomia and improving the quality of birth. Pregnant women with a history of delivering a macrosomic newborn also have a significantly increased risk of macrosomia in subsequent pregnancies. Therefore, women with a history of macrosomia should be encouraged to undergo pre-pregnancy counseling before their next pregnancy. Obstetricians should pay attention to pre-pregnancy weight, birth weight, and weight gain during all pregnancies, and should be alert to the possibility of macrosomia in all pregnant women who gain excessive weight. Intervention through multiple measures is important for preventing macrosomia and improving the health of pregnant women and newborns.

The datasets used and analyzed during the current study are available from the first and corresponding authors upon reasonable request.

GL, JG and NZ designed the research study. LM and RZ performed the research. GL and JG analyzed the data. All authors contributed to critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study was carried out in accordance with the guidelines of the Declaration of Helsinki. The study was approved by the Ethics Committee of People’s Hospital of Fuyang (IRB No. FYPH-2024-173). As only de-identified routinely collected surveillance data were used, the need for informed consent was waived by the institutional ethical committee board.

We would like to thank the reviewer, doctors, nurses, technicians, and patients involved in their dedication to the study.

This study was supported by Youth Science Fund of the Anhui Medical University (Grant No.2022xkj085).

The authors declare no conflict of interest.