Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder impacting women of reproductive age. It is characterized by a range of symptoms, among which irregular menstrual cycles are prominent, along with high levels of androgens in the body, and the occurrence of cysts on the ovaries [1]. Many studies have highlighted that PCOS can significantly impact the development of gestational diabetes mellitus (GDM) during pregnancy. Women with PCOS face an elevated risk of developing GDM compared to those without PCOS [2, 3]. Both PCOS and GDM can impact adverse maternal and neonatal outcomes [4, 5]. Women with PCOS or GDM have a higher risk of experiencing preeclampsia, as well as an increased likelihood of preterm birth and neonatal hypoglycemia. Complications that have been explored in earlier research include a higher likelihood of preterm birth, preeclampsia, and increased Cesarean section rates among women with PCOS or GDM. Furthermore, infants born to mothers with both PCOS and GDM may face an elevated risk of experiencing neonatal complications, exhibiting a notably higher rate of admission to the neonatal intensive care unit (NICU) [6, 7].

Research gaps in this area often include the need for more comprehensive investigations into the specific mechanisms linking PCOS with GDM. Studies focusing on maternal and neonatal outcomes for women with both PCOS and GDM remain relatively limited [8, 9]. This study aims to retrospectively assess how the presence of comorbid PCOS affects pregnancy outcomes in women with GDM. We seek to explore birth complications and neonatal outcomes in this specific population. The goal of our study is to unravel the complex relationship between adverse outcomes associated with both PCOS and GDM, guide clinical practices, enhance obstetric and neonatal outcomes through these measures, and provide comprehensive healthcare in the future.

Out of the 149 women included in the study with GDM, 44 (29.5%) had PCOS. Women with PCOS and GDM have higher levels of plasma glucose level at 120 minutes (PG120) (9.17 mmol/L vs 8.59 mmol/L, p = 0.001) and are more likely to experience postpartum hemorrhage (22.7% vs 2.9%, p 0.001). On regression analysis, plasma glucose level at 60 minutes (PG60) (odds ratio (OR) 6.341, 95% confidence interval (CI) 1.69~23.76, p = 0.06) and PCOS (OR 36.105, 95% CI 3.89~335, p = 0.002) were independent risk factors for postpartum hemorrhage. Neonates born to mothers with GDM and PCOS have lower APGAR scores at 1 minute after birth (p 0.001). S positive correlation was observed between gestational age at delivery and the neonatal APGAR score at 1 minute after birth ($\beta$ = 0.193, Standard Error (SE) = 0.03, t = 2.556, p = 0.012). PCOS was identified as an independent risk factor for lower 1-minute APGAR scores in the regression analysis ($\beta$ = –0.296, t = –3.852, p 0.001).

PCOS is a prevalent gynecological endocrine disorder among women of childbearing age, with an incidence rate of 5% to 10% [11]. The typical pathophysiological features include an increase in androgens, persistent anovulation, and insulin resistance. Clinical manifestations mainly involve obesity, hirsutism, menstrual irregularities, and infertility [12]. The incidence of GDM in our country is showing a trend of increasing occurrence and affecting younger individuals each year. Additionally PCOS is identified as an independent risk factor for GDM. GDM and PCOS are both linked with adverse pregnancy and neonatal outcomes [13, 14, 15, 16]. Despite the prevalence of both conditions, there remains a paucity of research and discussion regarding the impact of GDM on the effects and results experienced by both mothers with PCOS and their newborns.

We observed that women with both GDM and PCOS had a higher blood PG120 on OGTT. Many studies have already revealed the impact of PCOS on GDM. A nationwide population-based study found a history of PCOS as a noteworthy and independent risk factor for development of GDM. PCOS is typically associated with insulin resistance, which is closely related to the occurrence of GDM during pregnancy [17]. Our study also confirms their findings. These findings underscore the additional influence of PCOS on blood glucose regulation in women with GDM. It highlights the necessity of closely monitoring both glycemic parameters throughout pregnancy. Our study reveals that a history of PCOS exacerbates postprandial blood glucose levels in women with GDM, but does not significantly impact fasting blood glucose levels. According to the collections of menstrual and reproductive histories, as well as past medical histories, most of PCOS women in our study had received treatment before pregnancy, which might be one of the possible explanations to the study results.

In our study, although the neonatal birth weight of the PCOS with GDM group was higher than that of the GDM group, there was no statistically significant difference between two groups. If the sample size were larger, further analysis could be conducted. Numerous studies have confirmed the association between high blood glucose and macrosomia. In GDM, there is an increased transfer of blood glucose across the placenta, which enters the fetal circulation. Excess glucose in the fetus circulation is stored as body fat, leading to macrosomia, also known as “large-for-gestational-age” [18]. These conclusions are also consistent with our research findings. The results of our study have found that GDM with PCOS patients had a higher incidence of postpartum hemorrhage. Additionally, PG60 $\ge$10.0 mmol/L and a history of PCOS were the independent risk factors of postpartum hemorrhage. The larger the birth weight, the more likely it is to lead to prolong labor. Along with that, the likelihood of requiring vaginal assistance during delivery increases, and there may even be a need for an emergency Cesarean section. There is a higher risk of vaginal tissue tearing. In the case of macrosomic deliveries, the likelihood of experiencing postpartum bleeding and injuries to the genital tract is approximately three to five times higher compared to deliveries with normal-sized babies. Moreover, there is a heightened risk of uterine atony, characterized by ineffective contraction of the muscles of the uterus, leading to significant bleeding and postpartum hemorrhage [19]. A retrospective cohort study indicated women with PCOS experienced a higher incidence of postpartum hemorrhage [20]. Furthermore, a meta-analysis conducted in China shows a correlation between PCOS during and elevated rates of pregnancy complications, underscoring PCOS as an important risk factor for pregnancy complications [21]. We can infer that PCOS exacerbates the high blood glucose conditions of GDM women, increasing the incident rate of postpartum hemorrhage.

GDM is linked to higher rates of adverse outcomes for newborns [22, 23], these complications include macrosomia (larger-than-average baby), respiratory distress syndrome (RDS), neonatal hypoglycemia, hospitalization in the NICU, and intrauterine growth restriction [24, 25, 26]. As widely reported in literature [27, 28], we also found an increased occurrence of negative outcomes in newborns among women with both GDM and PCOS. The APGAR score, a clinical evaluation conducted at 1 minute and 5 minutes post-birth, is a method used to gauge the well-being of a newborn. It considers factors like skin color/tone, heart rate, reflexes, muscle tone, and respiration. The APGAR scores can serve as indicators for anticipating enduring neurological challenges in infants [29, 30]. We found significant differences in the APGAR score at 1 minute. Furthermore, the percentage of newborns from mothers with both GDM and PCOS having an APGAR score below 10 at 1 minute was notably higher. Some studies have indicated that women with GDM and PCOS exhibited a greater occurrence of NICU admissions due to hypoglycemia [31]. The prognosis of the fetus is often associated with an increased incidence of admissions to the NICU, making NICU admissions a frequently used indicator for adverse pregnancy outcomes [29, 30]. However, these adverse neonatal outcomes did not reach statistical significance in our study.

Despite our efforts, there are several limitations in our study. Given the retrospective nature of our study, it is possible that cases of PCOS may have been undetected or misdiagnosed. While some patients were directly asked about their diagnosis of PCOS, for others, the diagnosis and/or history of symptoms related to PCOS may have been inferred from their general medical history. Furthermore, the scarcity of cases in our study may result in the lack of statistical power needed to identify potential influencing factors. Future studies may benefit from a larger sample size. The lack of data on pre-pregnancy PCOS management, especially the duration of metformin treatment, prevents our ability to assess the effects of metformin therapy for PCOS on maternal and fetal outcomes. Additionally, insufficient follow-up data related to postpartum OGTT prevents us to analyze the combined effects of concurrent GDM and PCOS in postpartum women.

In conclusion, our research of women with GDM revealed marked contrasts in postprandial blood glucose, postpartum hemorrhage, and neonatal APGAR scores in the presence of PCOS. Women with co-existing GDM and PCOS had worse postprandial blood glucose levels, higher rates of postpartum hemorrhage, and lower 1-minute APGAR scores in newborns. Additionally, in regression analyses, postprandial blood glucose and PCOS were independent risk factors for postpartum hemorrhage in GDM women, which demonstrates the impacts of these factors on the health of both mothers and infants. The significance of regular prenatal follow-up, vigilant monitoring of blood pressure and glycemic control in women with GDM and PCOS is underscored by our findings, aiming to optimize obstetric and health results in newborns.

APGAR, Appearance, Pulse, Grimace, Activity, and Respiration; PCOS, Polycystic Ovary Syndrome; GDM, Gestational Diabetes Mellitus; OGTT, 75 g oral glucose tolerance test; PG120, plasma glucose level at 120 minutes; PG60, plasma glucose level at 60 minutes; BMI, body mass index.

The datasets utilized in this study are not publicly accessible as they contain information that could compromise the privacy of the participants. However, they can be made available by contacting the corresponding author upon reasonable request.

JW and WH designed the research study. JW, CY and XJ performed the research. WH, JF and YL provided help and advice on data collection. JW, CY and XJ analyzed the data. JW wrote the first draft of the paper. WH and JW provided critical reviews and interpretation of the results. All authors helped improve the paper, reviewed it carefully, and agreed on the final version. Each author had an important role in the research, taking responsibility for specific parts. They all committed to ensuring the study’s accuracy. If there are questions, they’re ready to answer them. All authors contributed to editorial changes in the manuscript.

The study obtained Institutional Review Board approval from The Fourth Affiliated Hospital of Soochow University (231019). Given the retrospective nature of the study, the requirement for informed consent was waived.

Not applicable.

This study was supported by Suzhou Research on Collaborative Innovation of Medical-Engineering Integration (SZM2022008).

The authors declare no conflict of interest.