Blood pressure trajectories during pregnancy and preterm delivery: A prospective cohort study in China

Abstract Women's blood pressure (BP) changes throughout pregnancy. The effect of BP trajectories on preterm delivery is not clear. The authors aim to evaluate the association between maternal BP trajectories during pregnancy and preterm delivery. The authors studied pregnant women included in the Born in Guangzhou Cohort Study in China between February 2012 and June 2016. Maternal BP was measured at antenatal visits between 13 and 40 gestational weeks, and gestational age of delivery data was collected. The authors used linear mixed models to capture the BP trajectories of women with term, and spontaneous and iatrogenic preterm delivery. BP trajectories of women with various gestational lengths (34, 35, 36, 37, 38, 39, 40 weeks) were compared. Of the 17 426 women included in the analysis, 618 (3.55%) had spontaneous preterm delivery; 158 (.91%) had iatrogenic preterm delivery; and 16 650 (95.55%) women delivered at term. The BP trajectories were all J‐shaped curves for different delivery types. Women with iatrogenic preterm delivery had the highest mean BP from 13 weeks till delivery, followed by those with spontaneous preterm delivery and term delivery (p < .001). Trajectory analysis stratified by maternal parity showed similar results for nulliparous and multiparous women. Excluding women with pre‐eclampsia and gestational hypertension (GH) significantly attenuated the aforementioned association. Also, women with shorter gestational length tend to have higher BP trajectories during pregnancy. In conclusion, Women with spontaneous preterm delivery have a higher BP from 13 weeks till delivery than women with term delivery, while women with iatrogenic preterm delivery have the highest BP.


INTRODUCTION
Preterm delivery, defined as delivery before 37 completed weeks of gestation, is the leading cause of perinatal and neonatal morbidity and mortality. 1 Preterm delivery affected about 10.6% live births based on the worldwide estimate in 2014. 2 It contributes to various short-and long-term adverse offspring outcomes including neonatal death, respiratory distress, cerebral palsy, feeding difficulties, visual disorders and needs for prolonged and repeated hospitalization, [3][4][5] exposing family and the health system to tremendous economic burden. 6,7 So far, approximately 70% in preterm delivery are spontaneous preterm delivery and the remains are iatrogenic preterm delivery. 1 It is suggested that placenta dysfunction may partially be responsible for preterm delivery. [8][9][10][11] Improper remodeling of the uterine spiral arteries may lead to worse placenta perfusion and subsequent maternal vascular endothelium dysfunction, which may result in further preterm delivery. 8,9 In addition, Kim and colleagues 12,13 indicated that failure of physiologic transformation of spiral arteries is more frequent for preterm delivery than term delivery. All things considered, nonoptimal physiologic transformation of spiral arteries and subsequent worse placenta perfusion may result in complementary increased blood pressure (BP) to support fast-growing fetus. Thus, it is reasonable to assume that maternal BP during pregnancy is related to preterm delivery.
Women experience considerable changes of BP during pregnancy, with BP decreasing until about 18 weeks of gestation and then increasing until delivery. 14 However, the understanding of the relationship between maternal BP change during pregnancy and preterm delivery is limited. The Avon Longitudinal Study of Parents and Children showed that smaller decrease in BP before 18 weeks and greater increase between 18 and 36 weeks were associated with shorter gestation. 15 Yet it was unable to distinguish between spontaneous and iatrogenic preterm delivery. Zhang and colleagues 16 found that an excessive rise in BP from early pregnancy (12∼19 gestational week) to midthird trimester (30∼34 gestational week) was related to spontaneous preterm delivery in a dose-response manner. Nevertheless, this study focused on women with spontaneous preterm delivery without detailed investigation of the association between all preterm delivery and BP change. All in all, the few relevant studies were unable to explore the relationship between BP change and all preterm delivery subtypes. A placenta histology study indicated that both spontaneous and iatrogenic preterm delivery have maternal vascular malperfusion lesions but are different in terms of severity, 17 which suggests that these two subtypes may be similar to some extent. Therefore, it may not be appropriate to simply exclude either spontaneous or iatrogenic preterm delivery.
We aimed to determine whether trajectories of BP during pregnancy is related to spontaneous and iatrogenic preterm delivery in a Chinese population.

METHODS
The present study was part of the Born in Guangzhou Cohort Study, a prospective cohort study performed in Guangzhou Women and Chil-dren's Medical Center, China. Its recruitment procedure and study protocol have been described elsewhere. 18 (Figure 4).

Between
Since PE and GH are well-established risk factors for preterm delivery, we further did the trajectory analysis excluding women with PE and GH. Results in Figure 5 indicated that the trajectory  Figure 6).

DISCUSSION
Women with spontaneous preterm delivery have consistently higher BP from 13 weeks till delivery than those with term delivery. A novel finding of our study is that women with spontaneous preterm delivery experienced consistently higher BP during pregnancy than women with term delivery, while it has been well known that women with iatrogenic preterm delivery are exposed to higher maternal BP during pregnancy. Misra and colleagues 24 found that both uterine artery resistance index (RI) and umbilical artery RI were significantly higher for spontaneous preterm delivery than term delivery throughout pregnancy, which partially supported our findings. partially support the abovementioned vascular mechanism, which warrants further thorough examination of the placenta in future studies.
Despite substantial research directed at understanding the pathophysiology of preterm delivery and evaluating strategies for prevention, prevalence has continued to rise from 5.36% in 1990-1994-7.04% in 2015-2016. 28 Previous attempts at risk prediction of preterm delivery showed limited predictive capacity. 29 Most of these studies focused on risk factors during the second half of pregnancy, 30 which might limit the potential for early intervention. Moreover, risk factors such as cervical length and fetal fibronectin have been proved to be of high predictive utility only in high-risk population. 30 To make things worse, the majority of women who deliver prematurely have no known risk factors and over 50% of preterm delivery occurred in lowrisk population. 31  Therefore, although medication during pregnancy is not adjusted for, the observed differences among three different groups might be an underestimation of the actual differences. Sixthly, although the BP among three groups were significantly different, the causality between BP and preterm delivery still remained to be elucidated. Lastly, previous study has shown a seasonal pattern in preterm delivery. However, the change in the rate of preterm delivery in different season was quite minimal, 37 which was unlikely to change the observed association in this study. Nevertheless, we admit that there were still possibilities of residual confounding.

CONCLUSION
In summary, women with spontaneous preterm delivery experience consistently higher BP during pregnancy than women with term delivery, which also applies to iatrogenic preterm delivery. Further, higher maternal BP during pregnancy is associated with shorter gestational length.

ACKNOWLEDGMENTS
The authors gratefully acknowledge all the participants from the Born in Guangzhou Cohort Study (BIGCS). Also, our gratefulness goes to the manage team, the obstetric care providers and all the staff in the BIGCS group who assisted in the implementation of this study.

CONFLICT OF INTEREST DISCLOSURE
The authors declare that they have no conflict of interests.

PATIENT CONSENT STATEMENT
Written informed consent was obtained from all participants before participating in Born in Guangzhou Cohort Study. Mol contributed to analysis and interpretation of the data. All authors approved the manuscript and agree to be accountable for all aspects of the work.