FormalPara Key Summary Points

Why carry out this study?

It has been reported that maternal height is significantly associated with increased risk of GDM and GDM-related adverse outcomes. We aim to evaluate association between maternal height and adverse outcomes stratified for gestational weight gain (GWG) and pre-pregnancy body mass index (BMI) in women with GDM.

What was learned from the study?

The association between maternal height and adverse pregnancy outcomes including low birth weight (LBW), primary CS, macrosomia, abnormal neonatal ponderal index and postpartum hemorrhage varies with prepregnancy BMI and GWG in GDM women. Our results provide evidence for prenatal management in consideration of maternal height by pre-pregnancy BMI and GWG to prevent adverse pregnancy outcomes in GDM women.

Introduction

Gestational diabetes mellitus (GDM) is glucose intolerance that occurs for the first time during pregnancy [1]. Globally, the prevalence of GDM is rising, and its deleterious consequences, including pregnancy-induced hypertension, macrosomia, preterm birth, and maternal and fetal metabolic disorders, have a serious negative impact on public health [2]. The mode of delivery and adverse pregnancy outcomes have long been related to height, weight, and other anthropometric parameters. Preterm birth, hypertension, fetal growth restriction, and cesarean delivery have all been independently associated with short height [2,3,4].

Height, weight and other anthropometric measurements have long been related to mode of delivery and pregnancy complications. Short stature was found to be an independent risk factor for cesarean delivery, preterm birth, preeclampsia and fetal growth restriction [5,6,7], whereas being taller was found to be a significant risk factor for macrosomia [8,9,10]. Maternal height has been reported to be significantly associated with increased risk of GDM and GDM-related adverse outcomes [4, 8, 9]. These findings suggest that maternal height may play an important role in predicting adverse outcomes in women with GDM.

It is also important to note that gestational weight gain (GWG) and pre-pregnancy BMI have independent effects on pregnancy outcomes in GDM [11]. GWG has been reported to have a significant relationship with large gestational age (LGA) in women with GDM [12]. Moreover, a study showed that shorter women with pre-pregnancy obese body mass index (BMI) had three times higher risk of macrosomia compared to shorter women with normal or overweight pre-pregnancy BMI [13]. Therefore, when determining the effect of maternal height on pregnancy outcomes in women with GDM, it is reasonable to consider pre-pregnancy BMI and GWG.

Given this background, the goal of our study is to evaluate the association between maternal height and adverse outcomes in different pre-pregnancy BMI and GWG groups. Findings from this study may help identify Chinese women with GDM at higher risk of adverse outcomes.

Methods

Study Design and Population

This retrospective study included 2639 women with singleton pregnancy and GDM who were diagnosed using a 75 g oral glucose tolerance test (OGTT) at 24–28 gestational weeks. Women who received prenatal care and gave birth to a livebirth singleton of > 28 gestational weeks at Women’s Hospital, Zhejiang University School of Medicine, from July 1, 2017, to June 30, 2018, in Zhejiang Province, China were included. Relevant information about pregnant women including age, height, weight before pregnancy (within 1 month before pregnancy), weight gain during pregnancy, gravidity, parity, OGTT levels, glycated hemoglobin (HbA1c), mode of delivery, gestational week of delivery, neonatal birth weight, pregnancy complications such as macrosomia, pregnancy-induced hypertension (PIH, including gestational hypertension, preeclampsia, eclampsia) and postpartum hemorrhage was obtained from medical records. Women with previous history of diabetes mellitus, overt diabetes, chronic illnesses (hypertension, diseases of the liver, kidney, heart, lung and other major organs), autoimmune conditions (Sjogren’s syndrome, anticardiolipin syndrome, myasthenia gravis), tumors or autoimmune diseases and women with missing medical records were excluded. A total of 2048 women with GDM were included in this study (Fig. 1). This study was approved by the Human Ethics Committee at Women’s Hospital, School of Medicine, Zhejiang University (IRB-20210269-R), and all participants signed the informed consent form. This study was performed in accordance with the Helsinki Declaration.

Fig. 1
figure 1

Flow chart of study population

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Diagnostic Criteria

GDM

According to International Association of Diabetes and Pregnancy Study Group (IADPSG) standards, GDM was identified using a 75 g OGTT with cutoff values of 5.1 mmol/l for fasting plasma glucose (FPG), 10.0 mmol/l for 1 h-postprandial glucose (1 h-PG) and 8.5 mmol/l for 2 h-PG. At 24–28 gestational weeks, OGTT and HbA1c tests were conducted in the morning following an overnight fast of at least 8 h.

Maternal Anthropometry

Maternal weight was measured in kilograms (kg), and maternal height was measured in centimeters (cm). Maternal height and weight were self-reported. Pre-pregnancy BMI was calculated as pre-pregnancy weight in kilograms (kg) divided by the square of height in meters(m). Pre-pregnancy BMI was categorized into underweight (< 18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obese (≥ 30.0 kg/m2). GWG was the difference between pre-delivery weight and pre-pregnancy weight. According to the standard definition of IOM guidelines in 2009 [14], appropriate GWG was 12.5–18.0 kg for underweight BMI, 11.5–16.0 kg for normal BMI, 7.0–11.5 kg for overweight and 5.0–9.0 kg for obesity, respectively. GWG below the thresholds was defined as inadequate GWG, while exceeding the thresholds was defined as excessive GWG.

Adverse Outcomes

Newborns with gestational age ≥ 28 weeks but < 37 weeks were considered preterm neonates. Newborns with birth weight ≥ 4000 g were defined as having macrosomia while those < 2500 g were defined as having low birth weight (LBW) [15]. LGA was defined as neonate birth weight > 90th percentile based on national population references for age and sex. PIH was diagnosed in women with no previous history of hypertension with systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) ≥ 90 mmHg on two occasions at least 4 h apart after 20 gestational weeks with or without proteinuria [16]. Primary cesarean section (CS) was defined as cesarean section performed on women with no previous history of cesarean delivery. Postpartum hemorrhage was defined as blood loss ≥ 500 ml after vaginal delivery or ≥ 1000 ml after cesarean section [17]. The ponderal index was determined by the ratio of birth weight to birth length (birth weight [kg] /length [m3]), and abnormal neonatal ponderal index was defined as < 10th percentile or > 90th percentile [18].

Statistical Analysis

Maternal and neonatal demographic and clinical features were reported as frequency (%) or mean (SD). Continuous variables were analyzed using one-way ANOVA while categorical variables (maternal age groups, parity, gravidity, pre-pregnancy BMI groups, GWG groups, adverse pregnancy outcomes) were analyzed using chi-square test. Maternal height was divided into three different categories by tertiles: shorter: ≤ 158.0 cm, average: (158.1–162.0 cm) and taller: > 162.0 cm [19]. The relationship between maternal height and adverse outcomes in different pre-pregnancy BMI groups and GWG groups was analyzed using logistic regression. Two-sided p values < 0.05 were considered significant. Statistical analyses were done with SPSS 26.0.

Results

General Characteristics and Incidence of Adverse Outcomes Among Maternal Height Categories

There were differences in GWG (p = 0.006), pre-pregnancy weight (p = 0.001), birthweight (p = 0.001), birth length (p < 0.001) and neonatal ponderal index (p < 0.001) among maternal height categories. We also noted no difference in pre-pregnancy BMI, maternal age, parity, HbA1c, fasting plasma glucose, 1 h-PG or 2 h-PG among maternal height categories. We found differences in the incidence of abnormal neonatal ponderal index, macrosomia, postpartum hemorrhage, primary CS and LBW among height categories. Women with shorter stature had higher rates of LBW (p = 0.003) and primary CS (p < 0.001). Taller women had higher rates of abnormal neonatal ponderal index (p < 0.001), postpartum hemorrhage (p = 0.044) and macrosomia (p < 0.001). The incidence of preterm birth did not significantly differ among maternal height categories (p = 0.136) (Table 1).

Table 1 Characteristics of study population
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Association Between Maternal Height and Adverse Outcomes Stratified for GWG

Maternal height was positively associated with the risk of macrosomia in taller women who gained excess GWG compared to average height women who gained excess GWG (aOR 1.97, 95% CI 0.95–4.10). Maternal height was negatively associated with postpartum hemorrhage in shorter women who gained excess GWG compared to average height women who had excess GWG (aOR 0.15, 95% CI 0.03–0.72). Maternal height was associated with an increased risk of LBW (aOR 2.20, 95% CI 1.13–4.29) and primary CS (aOR 2.08, 95% CI 1.38–3.12) among shorter women who gained inadequate gestational weight compared to average height women with inadequate GWG. In women who gained adequate GWG, maternal height was negatively associated with the risk of abnormal neonatal ponderal index in both shorter and taller women compared to average height women (aOR 0.68, 95% CI 0.49–0.96; aOR 0.51, 95% CI 0.37–0.71) (Table 2).

Table 2 Association between maternal height and adverse outcomes in different gestational weight gain groups
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Association Between Maternal Height and Adverse Outcomes Stratified for Pre-pregnancy BMI

In women with normal pre-pregnancy BMI, maternal height was positively associated with LBW (aOR 2.00, 95% CI 1.15–3.49) and primary CS (aOR 1.71, 95% CI 1.28–2.28) in shorter women while it was negatively associated with the risk of abnormal neonatal ponderal index in both shorter and taller women compared to average height women (aOR 0.71, 95% CI 0.55–0.92; aOR 0.66, 95% CI 0.51–0.85). However, there was no significant association between maternal height and macrosomia and postpartum hemorrhage when stratified for pre-pregnancy BMI (Table 3).

Table 3 Association between maternal height and adverse outcomes in different pre-pregnancy body mass index groups
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Discussion

This study found that the association between maternal height and adverse pregnancy outcomes (macrosomia, postpartum hemorrhage, primary CS and LBW) varied in different pre-pregnancy BMI groups and GWG groups. Taller women with excess GWG had a higher risk of macrosomia compared to average height women with excess GWG. Shorter women with inadequate GWG had more than two times the risk of LBW and primary CS compared to women with average height who had inadequate GWG. Excess GWG was a protective factor for postpartum hemorrhage in shorter women. Shorter women with normal pre-pregnancy BMI had an increased risk of low birth weight and primary CS compared to average women with average height. Our findings suggest that maternal height can be used as a reference to identify Chinese women at high risk of adverse outcomes; however, pre-pregnancy BMI and GWG should be considered.

A study showed that pre-pregnancy BMI was independently associated with neonatal birth weight in women with normal glucose tolerance [20]. Higher pre-pregnancy BMI and excess GWG were far more important in macrosomia prediction than other maternal characteristics [21]. However, the rate of women with higher BMI is lower than in western countries [22]. In fact, the prevalence of underweight women is higher in East Asian countries [23,24,25]. Taller height and GDM are two distinct risk factors that could interact to cause macrosomia. According to studies, GDM only had an impact on macrosomia in taller women [8, 9]. Thus, hyperglycemia and excess GWG can be the main contributing factors to macrosomia compared to other factors in Chinese women [22]. Therefore, taller Chinese women with GDM can benefit from strict counseling on appropriate weight gain during pregnancy to decrease the risk of macrosomia.

A study showed that shorter women have a higher risk of LBW [26]. Risk of LBW may decrease with increasing maternal height from < 160.0 cm to 160.0 cm [27]. However, what causes LBW in women of short stature is still unclear. We found that shorter women had a higher incidence of LBW in accordance with previous studies [26, 28]. Inadequate GWG has been reported as a risk factor for LBW, similar to our findings [29]. A study involving Spanish women showed that women who gain inadequate GWG in both the second and third trimesters have increased risk of LBW [30]. On the other hand, a systemic review showed that high GWG was a protective factor against LBW in singleton pregnancy [31]. Malnutrition is known cause of LBW in shorter women; however, for Chinese women, particularly in Zhejiang Province, malnutrition is not the cause of short stature. Contrarily, different studies have shown that the GWG recommendation using IOM guidelines (2009) in Chinese women may not be appropriate; thus, GWG guidelines considering Chinese women's characteristics have been emphasized [32, 33]. Studies have reported that adopting appropriate GWG following Chinese population characteristics may reduce adverse pregnancy outcomes [34, 35]. According to our findings, Chinese women with shorter stature are at increased risk of LBW, particularly those who gain inadequate GWG or with normal pre-pregnancy BMI; clinicians should counsel shorter women on increasing GWG appropriately to decrease the risk of LBW. Nevertheless, further studies are needed to evaluate GWG cutoffs according to Chinese population characteristics.

Additionally, recent studies assessed birth size by birth length, birthweight, head circumference and ponderal index rather than only birthweight, which was associated with adverse preteen cardiometabolic health [36, 37]. Therefore, we further explored the association between maternal height and neonatal ponderal index, which has been researched in few studies. A previous observational cohort study showed that maternal height had no impact on offspring's ponderal index [9]. Another study revealed a significant correlation between infant ponderal index and maternal height for nulliparas but not for the multiparas [38]. We found maternal height was negatively associated with the risk of abnormal neonatal ponderal index in both shorter and taller women with adequate GWG or normal pre-pregnancy BMI, which showed the effect of maternal height on the ponderal index was dependent on GWG and pre-pregnancy BMI. Thus, it is recommended to consider these maternal anthropometric parameters when assessing the birth size. Furthermore, our study lacked offspring’s metabolic indices, and this warrants further study.

According to a research study, increasing maternal height reduces the risk of CS [39]. Also, studies have reported that excess GWG increases risk of delivery by cesarean section [40, 41]. Therefore, it is imperative to counsel shorter women on appropriate GWG during pregnancy. A study showed that overweight and obese pre-pregnancy BMIs were the leading risk factors of primary CS in women of average height, whereas excess GWG was the leading risk factor of primary CS in women of taller stature, similar to our findings [42,43,44]. Another study showed that women with pre-pregnancy BMI > 30 kg/m2 had increased risk of primary CS compared to women with pre-pregnancy BMI < 20 kg/m2 [41]. Excess GWG and obesity increase risk of delivery by cesarean section because of increased abdominal fat, thus hindering abdominal muscle contraction. Strict health education and counseling of women with overweight/obese pre-pregnancy BMI earlier in pregnancy and strict monitoring of GWG might reduce the risk of delivery by CS [45, 46].

Maternal height was previously related to postpartum hemorrhage in singleton pregnancy [47]. In a deep machine learning prediction study model, the relationship between maternal height and postpartum hemorrhage following vaginal delivery was positive [48]. According to one study, the risk of postpartum hemorrhage increased with maternal height (160–170 cm versus 160 cm) [49]. On the other hand, a study showed that shorter stature < 151 cm was significantly associated with risk of postpartum hemorrhage [50]. Another study found that maternal and fetal genes may contribute to postpartum hemorrhage, which may help explain the inconsistency [51]. It is critical to consider the relationship between maternal height and postpartum hemorrhage; however, more extensive studies are required.

To the best of our knowledge, this is the first study to evaluate the relationship between maternal height and adverse outcomes in different pre-pregnancy BMI and GWG groups. Our findings can help clinicians prevent GDM-related adverse outcomes when different maternal heights are considered, as well as pre-pregnancy BMI and GWG.

Limitations of Our Study

Our study had several limitations. First, it is a retrospective study including a small sample from a single health center. Maternal weight and height were self-reported, which might affect the accuracy of the result. Second, data on social demographic characteristics and nutrition status information were not found. Third, the association between maternal height and risk of adverse outcomes was not adjusted for other associated clinical conditions such as cervix incompetence, maternal infections, fetal malpresentation and so on [49]. Thus, further research is needed to evaluate the association between maternal height and adverse outcomes in GDM by BMI and GWG considering relevant clinical conditions.

Conclusion

The relationship between maternal height and adverse pregnancy outcomes varies with pre-pregnancy BMI and GWG in GDM women. Comprehensive counseling and health education considering maternal height and pre-pregnancy BMI and GWG may help prevent adverse outcomes in GDM women.