In this study, we found that pregnant women with multiple metabolic risk factors had more severe reduced LA function than those with PIH or GDM. The LASr cutoff value, below which the risk of iatrogenic preterm delivery (due to severe preeclampsia, placental abruption, and fetal distress) was significantly increased, was 38.35%.
In normal pregnancy, the left atrium is remodeled to meet special hemodynamic and metabolic needs. It is well known that the total blood volume, plasma volume, and red blood cell mass increase significantly during pregnancy, resulting in the expansion of the LA volume. This is supported by findings that the LAVi for normal pregnant women in the second and third trimester is significantly higher than that for normal non-pregnant women [16, 17]. Song et al.  demonstrated that the reservoir function and the booster pump function were significantly increased while the conduit function was decreased in normal pregnant women as compared with non-pregnant women. This is a normal physiological adaptation of the LA function to the changes in volume load during pregnancy. However, in pregnant patients with metabolic diseases, the maternal cardiac diastolic function is decreased. In this study, we found that pregnant women with abnormal glucose tolerance had significant differences in the Mitral A wave and TDI mitral E’/A’ ratio compared with control group, which may be explained by the effect of insulin resistance on deteriorating cardiac diastolic function . Melchiorre et al. reported that pregnant women with preterm delivery due to preeclampsia had LV diastolic dysfunction and LA remodeling and these damages remained for one year after delivery . LA function itself is an important indicator of cardiac diastolic function. However, few studies have been performed to study LV function in pregnant women with metabolic diseases. A previous study examined the LA function in pregnant patients with PIH using 2D-STI and reported that the global LA peak strain decreased in these patients, which was associated with postpartum persistent hypertension . Consistent with their findings, we also found in this study that the LA reservoir function, expressed by the LASr value, decreased in the PIH group, furthermore the CMR group had the lowest LASr.
The LA function includes reservoir function, conduit function, and booster pump function. LASr and pLASRr, which appear during the systolic period, represent the reservoir function. LAScd and pLASRcd represent the shortening deformation and rate of atrial myocardium during the early LV diastolic period as well as the function of the LA conduit. LASct and pLASRct are the shortening rates of atrial myocardium during active LA contraction in the late LV diastolic period, representing the function of the booster pump. We found that the CMR group had decreased function in the LA reservoir, conduit, and pump compared to the control and GDM groups. However, compared to the PIH group, only the reservoir function was decreased in the CMR group. Nevertheless, the LASr has been reported to be the most valuable indicator of LV function, which is closely related to the prognosis of heart disease [20,21,−22].
During pregnancy, the physiological enlargement of the breast increases the difficulty of obtaining LV apical images due to the fact that the left ventricle is located in the near field. The left atrium is a mirror of LV systolic and diastolic function. It connects to the pulmonary veins during systole and supplies the blood to the ventricle during diastole to promote ventricular performance . Therefore, LASr is very important to the overall cardiac performance. As we reported here, LASr sensitively reflected the impaired cardiac function of the CMR patients and exhibited a worthy predictive value in the multivariable cox regression analyses. Our study further showed that impaired LA function (LASr ≤ 38.35%) also predicted the adverse outcome of iatrogenic preterm delivery, which caused by severe preeclampsia, placental abruption, and/or fetal distress. This may be because the decline of LA function represents the degree of systemic damage caused by metabolic diseases, especially the cardiovascular system. Previous studies have showed LA function to be a sensitive and reliable prognostic indicator which can be used as a marker of target organ damage in metabolic diseases [24,25,25].
The relationship between a single metabolic abnormality, such as PIH or GDM, and poor prognosis, has been reported. For instance, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study showed that an increase in blood glucose levels during pregnancy is related to a poor prognosis . Another report showed that hypertriglyceridemia is a predictor of macrosomia in non-obese women . Bakker et al.  reported that elevated blood pressure during pregnancy negatively affects fetal growth and development, and increases the risk of preterm delivery. However, pregnant women with multiple metabolic abnormalities have a higher risk of adverse pregnancy outcomes. A prospective study involving 5535 pregnant women showed that the more metabolic risk factors a pregnant woman had, the greater the risk of adverse pregnancy outcomes will be (including preterm delivery, pre-eclampsia, GDM, small/large for gestational age) . The study also found that the odds ratio for a cluster of two factors was 3.32 (95% CI 2.69–4.10) and that for a cluster of three and more factors was 10.40 (95%CI 7.37–14.69) . Consistent with the report, in our study, the CMR group had a significantly higher rate of iatrogenic preterm delivery than the other three groups.
Insulin resistance and oxidative stress, which increase inflammation and endothelial dysfunction, constitute the pathophysiological basis of various metabolic abnormalities . These factors are also the pathophysiological basis of cardiovascular disease, affecting the cardiac structure and hemodynamics. Patients with metabolic disorders may develop reduced LV systolic and diastolic reserve, leading to increased left ventricular stiffness. As a result, left atrial afterload increases . However, the damage of left atrial function caused by metabolic diseases is not only due to hemodynamic changes, but also due to myocardial damage of atrium caused by metabolic disorders. One study showed that in type 2 diabetes, subjects with normal left atrial size and left ventricular filling pressure also had left atrial strain abnormalities, which may indicate that the underlying cause is not of hemodynamic origin . Take atrial fibrillation for instance, the multiple metabolic diseases are the established risk factors for its underlying pathogenesis, namely atrial remodeling, which is the hall mark of impaired atrial function . It is worth noting that endothelial dysfunction may be the link between reduced LA function and poor pregnancy prognosis. Normal vascular endothelial functions include: 1) the exchange of substances between blood and tissues, transportation of nutrients, water and oxygen to organs, and removal of waste molecules and carbon dioxide; 2) the maintenance of normal blood pressure by regulating vasoconstriction and relaxation; and 3) the prevention of blood agglutination and maintenance of a liquid state . In patients with metabolic disorders, endothelial cells are dysfunctional and lose regulatory activity. For example, fetal placental endothelial dysfunction is one of the pathological features of GDM  and cannot be rescued by insulin replacement therapy . In patients with preeclampsia, endothelial dysfunction results in increased peripheral resistance, causing a series of maternal obstetrical complications . In addition, endothelial dysfunction persists after delivery, including higher arterial stiffness and a lower reactive hyperemia index value, and is thus associated with subsequent maternal cardiovascular disease .
A previous study emphasized the importance of the hemodynamic and morphological aspects of the maternal heart in predicting complications. The authors reported that mid-wall mechanical impairment at 24 weeks’ gestation reflects a decrease in LV diastolic function and predicts adverse pregnancy outcomes . Consistent with the study, Siegmund et al. reported that right ventricular function is altered in pregnant women with coarctation of the aortic valve and is associated with impaired placentation, which is correlated with adverse offspring outcomes . In line with these reports, our study also found that the impairment of the maternal cardiovascular function was associated with adverse outcomes such as iatrogenic preterm delivery.
The limitations of our study should be noted. Firstly, our study did not include postpartum data or the long-term effects of multiple metabolic diseases during pregnancy on maternal. Long-term follow-up study on LA function is needed. Secondly, in the present study, we only compared CMR patients with patients with either PIH or GDM; we did not explore the respective contribution of each metabolic abnormality to reduced LA function. Gestational hypertension and diabetes mellitus are common metabolic abnormalities during pregnancy that raise the concern of clinicians. However, in clinical practice, it is very common to encounter a combination of metabolic abnormalities. In a cohort of 5535 pregnant women, more than 1/4 showed an aggregation of metabolic risk factors . This study emphasizes that LA function in pregnant women with multiple metabolic abnormalities is worse, and this is worthy of attention. Finally, we did not have complete pre-pregnancy data for the participants in this study. However, When we choose our subjects, we excluded patients with hypertension and diabetes before pregnancy.