Effect of Hypertensive Disorders of Pregnancy on Outcome and Relative Telomere Length in Preterm Infants

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Telomere, as a potential biomarker reflecting cellular aging and future health risks, its length can indirectly indicate the long-term prognosis of newborns. Although significant progress has been made in this field, the impact of gestational hypertension on the prognosis of premature infants and telomere length (TL) still requires further exploration. This article mainly conducts a preliminary exploration of the effects of hypertensive disorders of pregnancy (HDP) on preterm infant outcomes and telomere length (TL). Methods: A total of 128 preterm infants born between January 2022 and December 2023 were included.The included subjects were divided into the hypertensive disorders of pregnancy(HDP) group and the no-hypertensive disorders of pregnancy(NHDP) group based on whether the mother has gestational hypertension. Maternal and neonatal clinical data were collected and TL was measured from infant peripheral blood using quantitative PCR. Statistical analyses included chi-square tests for categorical data and t-tests for continuous variables. Results: 1 The HDP group had a significantly higher rate of cesarean delivery (100% vs. 74.7%, P < 0.001) and congenital heart malformations (12.2% vs. 2.0%, P =0.013), along with lower birth weight (1.68 ± 0.50 kg vs. 2.08 ± 0.75 kg, P = 0.001) compared with the NHDP group. 2 TL was shorter in the HDP group than in the NHDP group (1.917 ± 0.792 vs 2.249 ± 0.797, P = 0.024). Infemale neonates, the TL in the HDP group was significantly shorter than that in the NHDP group(1.930 ± 0.697 vs 2.405 ± 0.684, P = 0.023). In male neonates,there was no TL difference between the HDP group and the NHDP group. There was no TL difference between genders in the HDP group and the NHDP group. Conclusion: HDP can lead to an increase in the rate of cesarean section, an elevated risk of congenital heart defects in newborns, and a decrease in birth weight. HDP can lead to shortened TL in premature infants, especially in female infants. hypertensive disorders of pregnancy(HDP) outcome of premature Infants telomere length(TL) Figures Figure 1 1. Background Hypertensive Disorders of Pregnancy (HDP) is one of the common complications during pregnancy. Currently, it has become the main cause of maternal and perinatal deaths [ 1 ] . HDP can affect the intrauterine growth and development of the fetus, leading to adverse outcomes such as premature birth, fetal growth restriction, neonatal brain damage and neonatal asphyxia. Telomeres are heterochromatin structures located at the ends of linear chromosomes. They play a role in protecting chromosomes from degradation and the effects of DNA repair activities, thereby maintaining the stability of chromosome structure and function [ 2 ][ 3 ] . TL shortens throughout a person's lifetime, and the rate of shortening is jointly determined by genetic and environmental factors, and is closely related to various aging and age-related diseases [ 4 ] . The accumulation of telomere loss is considered to be the main molecular cause of aging and age-related diseases. TL can indirectly reflect the degree of cell aging and disease status, and is a good candidate for markers of cellular aging and future health risks [ 5 ] . The growth and development of newborns in the womb are closely related to their long-term health. Existing evidence has shown that newborns with intrauterine growth retardation or premature birth are at an increased risk of obesity, hyperlipidemia and hypertension in their later lives [ 6 ][ 7 ] . The possible mechanism of this phenomenon is related to abnormal telomere biology. The severe shortening of TL can trigger the signaling pathways of DNA damage and extracellular stress [ 8 ][ 9 ] . As a well-established marker of cellular aging, the baseline TL at birth has a certain impact on long-term health. Longitudinal studies that repeatedly measured TL in adults have found that the baseline TL, rather than the rate of telomere loss, is associated with the risk of atherosclerosis, indicating the significance of the baseline TL determined in early life [ 10 ] . The TL of newborns can be affected by maternal diseases during pregnancy. The TL of fetuses with gestational diabetes mellitus is significantly shorter than that of the normal pregnancy group [ 11 ] . This phenomenon may be related to the intrauterine environment [ 12 ] and oxidative stress [ 13 ] . Studies on animals have shown that the HDP hormone produced by the mother rat can cause a reduction in the TL of the kidney tissue in the offspring rats [ 14 ] . However, the impact of TL on newborns, especially premature infants, remains to be further explored. This is of great significance for us to comprehensively understand the possible cross-generational health effects of HDP on offspring and the underlying biological pathways. This study investigated the impact of HDP on adverse outcomes and TL in premature infants, providing clues for further understanding the role of telomeres in the course of life. 2. Methods 2.1 Study Participants. A total of 128 premature infants and their mothers from January 2022 to December 2023 in Liaocheng People’s Hosptial were selected for observation. These mothers have no bad habits and maintain harmonious social relationships. The collection of blood samples and the retrieval of their medical records were all obtained with the informed consent of the mothers. The newborn’ umbilical cord blood was collected in the labour room or operation theatre immediately after delivery by trained midwives. Patient’s particulars, pregnancy complications, birth outcomes and neonatal conditions were collected from the electronic medical record system. According to whether the mothers of preterm infants had HDP, they were divided into HDP group and NHDP group. 2.2 Measures 2.2.1 Inclusion criteria and exclusion criteria Inclusion criteria: ①Born in this hospital; ②Natural conception; ③ The HDP group criteria were based on the "Expert Consensus on Blood Pressure Management in Hypertensive Disorders of Pregnancy (2019 Edition)"[15] Exclusion criteria: ①Incomplete medical records, transfer to another hospital, and death cases; ②The mothers with gestational diabetes mellitus, hypothyroidism, hyperthyroidism, anemia, obesity, abnormal uterine structure and function (cervical insufficiency, placenta sail, placental abruption, placenta previa, uterine fibroids), heart failure. 2.2.2. General characteristics and neonatal outcomes The general characteristics of newborns (including gestational age, father's age, mother's age, number of pregnancies, number of deliveries, and gender) and the outcomes of newborns(Cesarean section rate, Brain injury, Sepsis, Heart malformations, neonatal respiratory distress syndrome (NRDS), Hypoxic-ischemic encephalopathy, Birth weight) are collected from electronic medical records. 2.2.3 TL measurement Using PrimerBank design telomeres(TEL) and internal genes(HBG) primers, the sequence is as follows: (1) telomere:telg 5'-ACACTAAGGTTTGGGTTTGGGTTTGGGTTTGGGTTAGTGT-3'; tele 5'-TGTTAGGTATCCCTATCCCTATCCCTATCCCTATCCCTAACA-3'; (2) internal gene:hbgu 5'-CGGCGGCGGGCGGCGCGGGCTGGGCGCCTTCATCCACGTTCACCTTG-3'; hbgd 5'-GCCCGGCCCGCCGCGCCCGTCCCGCCGGAGGAGAAGTCTGCCGTT-3'. Genomic DNA was isolated and extracted from the collected samples, and the purity of the DNA was evaluated using a Nanodrop 1000 spectrophotometer. The qualified standard was a ratio of A260/A280 between 1.90 and 2.10, and the qualified DNA was used for the next TL test. The relative TL was measured by real-time fluorescence quantitative PCR (RT-qPCR). Telomere repeat copy number(T) and Single-copy gene copy number(S) were detected respectively, and the ratio (T/S value) between the two was calculated. The relative length of the telomere can be obtained. The formula is as follows: ΔCt = Ct tel –Ct hbg ; ΔΔCt = Ct sample -Ct reference , T/S = 2 −ΔΔCt . where Ct Tel represents the Ct value of the telomere gene and Ct hbg represents the Ct value of the reference gene. 2.3 Statistical Analysis Using SPSS 29.0 statistical software and the count data were expressed as n(%) for χ 2 test; Measurement data that conform to the normal distribution were expressed as mean ± standard deviation (M ± SD) and t-test was performed; P < 0.05 was considered statistically significant. 3. Results 3.1 Comparison of general characteristics of neonates A total of 128 neonates were included in the study, 49 in the HDP group and 79 in the NHDP group. The comparison of general characteristics is recorded in Table 1 , and there is no significant difference between the HDP group and the NHDP group. Table 1 Comparison of general characteristics of neonates HDP group n = 49 NHDP group n = 79 χ 2 / Z value P value Gestational age (W, M ± SD) 33.38 ± 2.11 33.61 ± 3.62 -0.753 0.452 Maternal age (Y, M ± SD) 32.65 ± 7.04 30.09 ± 5.77 -1.763 0.078 Father's age (Y, M ± SD) 33.14 ± 7.18 30.71 ± 5.83 -1.776 0.076 Number of pregnancies (M ± SD) 2.59 ± 1.63 2.09 ± 1.13 -1.458 0.145 Number of deliveries (M ± SD) 1.68 ± 0.50 1.90 ± 0.89 -0.688 0.491 Neonatal gender 2.286 * 0.093 Male (n, %) 27 (55.1%) 54 (68.4%) Female (n, %) 22 (44.9%) 25 (31.6%) Note: *:χ 2 ; the residual Z value. 3.2 Comparison of outcomes between two groups of preterm infants As shown in Table 2 . The rate of cesarean section and congenital heart malformations in the HDP group of preterm infants was significantly higher than that in the NHDP group, and the difference was statistically significant ( P < 0.05); The birth weight of the HDP group was significantly lower than that of the NHDP group, and the difference was statistically significant ( P = 0.001); There was no statistically significant difference in the incidence of brain injury, sepsis, NRDS, and hypoxic-ischemic encephalopathy between the two groups of preterm infants. Table 2 Evaluation comparison of outcomes between the two groups of preterm infants [n,%] HDP group n = 49 NHDP group n = 79 t / Z value P value Cesarean section rate (n, %) 49 (100%) 59 (74.7%) 14.702 < 0.001 Brain injury (n, %) 6 (12.2%) 20 (25.3%) 3.192 0.112 Sepsis (n, %) 21 (42.9%) 33 (41.8%) 0.015 1.000 Heart malformations (n, %) 6 (12.2%) 1 (2.0%) 7.051 0.013 NRDS (n, %) 35 (74.1%) 47 (59.5%) 1.871 0.190 Hypoxic-ischemic encephalopathy (n, %) 2 (4.1%) 3 (3.8%) 0.007 1.000 Birth weight (Kg, M ± SD) 1.68 ± 0.50 2.08 ± 0.75 3.558 * 0.001 Note: *:t value; the residual Z value. 3.3 Comparison of TL in different groups As shown in Fig. 1 . The TL in the HDP group was significantly shorter than that in the NHDP group, and the difference was statistically significant (Fig. 1 A); in the HDP group and the NHDP group, no differences in TL were found between newborns of different genders(Fig. 1 B C); in male neonates, no statistically significant difference in TL between the HDP group and the NHDP group(Fig. 1 D); in female neonates, the TL in the HDP group was significantly shorter than that in the NHDP group, and the difference was statistically significant (Fig. 1 E). 4. Discussion 4.1 Chronic diseases in adulthood can be traced back to the fetal period Adult chronic diseases have become one of the main factors threatening human health, such as hypertension. According to the results of the "China Hypertension Survey" (CHS) released in 2018, approximately one quarter of adults in China suffer from hypertension, and the total number of patients has reached 244 million [ 16 ] . Adult chronic diseases can be traced back to the fetal period, which is known as the fetal origin theory of adult diseases [ 17 ] . This theory holds that: during the development process, if the fetus is exposed to harmful factors in the womb, the body will prioritize the supply of nutrients to important organs such as the brain, sacrificing the protection of general organs like the kidneys and liver, in order to facilitate short-term survival. However, such fetuses will significantly increase the risk of developing chronic metabolic diseases in adulthood after birth.If the adverse factors that occur during the fetal stage are not promptly corrected, they will cause changes in the fetal's metabolism and organ structure. Eventually, this will lead to permanent changes in the metabolic functions of various body tissues and organs, such as blood vessels, pancreas, liver and lungs. These changes will then progress to adult diseases, including coronary heart disease, typeⅡdiabetes and hypertension [ 18 ][ 19 ] . Furthermore, Victoria et al. first proposed the concept of the "first 1000 days of life" in 2008. This refers to the initial period from the formation of the fertilized egg to the age of 2 years after birth. This period is a crucial time for the maturation of the body's tissues, organs, and systems. It not only affects the early physical and brain development of children, but also can influence health during adolescence and even adulthood, and is closely related to the occurrence of long-term chronic diseases in the future [ 20 ][ 21 ] . 4.2 HDP can have adverse effects on the outcome of preterm infants HDP is a common disease specific to pregnancy, which can cause serious harm to both the mother and the fetus. HDP can cause spasm of the small arteries in the placenta, resulting in a reduction in placental blood flow, causing the fetus to be in a continuous state of hypoxia within the womb. This has an impact on the growth of the fetus and the newborn, as well as on the heart function, blood sugar levels, and nervous system of the fetus and newborn, leading to the malignant development of fetal or neonatal diseases and having long-term effects on their adulthood [ 22 ][ 23 ] . This long-term effect is manifested in several aspects, such as increased risk of cardiovascular metabolism, delayed neurodevelopment, and increased risk of allergic diseases. It even leads to a significant increase in the risk of all-cause mortality [ 24 ] . This study investigated the impact of HDP on the outcomes of premature infants. The results showed that the cesarean section rate and congenital heart malformations in the HDP group were significantly higher than those in the NHDP group, while the birth weight in the HDP group was significantly lower than that in the NHDP group.This is consistent with the previous literature reports [ 25 ][ 26 ] . It is mainly due to the small artery spasm caused by HDP, resulting in a decrease in placental blood flow perfusion and causing changes in placental hemodynamics. This not only leads to placental abruption and abnormal amniotic fluid, but also causes the fetus to be in a chronic hypoxic state, resulting in fet al growth retardation and low birth weight of the newborn [ 27 ] . During HDP, the remodeling of uterine spiral arteries is insufficient, resulting in reduced placental perfusion. The placenta is in an ischemic and hypoxic state, leading to an increase in the secretion of soluble vascular endothelial growth factor receptor-1 (sFlt-1), which antagonizes vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), inhibiting maternal vascular endothelial repair and placental angiogenesis, causing insufficient placental perfusion and resulting in intrauterine hypoxia, leading to a lower birth weight for the newborn compared to normal pregnant mothers [ 28 ] . HDP is an important risk factor for premature rupture of membranes, abnormal amniotic fluid, and placental abruption [ 29 ][ 30 ][ 31 ] . For patients with HDP combined with excessive or insufficient amniotic fluid, pregnancy should be terminated as soon as possible, and the fetus should be delivered within 6 hours after the onset of placental abruption symptoms. This will effectively protect the lives and long-term prognosis of the newborn and the pregnant mother. This is an important reason why the cesarean section rate of premature infants in the HDP group is significantly higher than that in the NHDP group.The development of the heart is a continuous and complex process. Genetic factors and maternal-related factors can all affect the development of the fetus's heart. HDP is one of the independent risk factors for congenital heart malformations in the fetus [ 32 ] . The fetus absorbs nutrients from the mother to maintain normal development. If the nutrition during pregnancy is poor, the fetus will have insufficient nutrition, which will have an adverse effect on the development of the heart and increase the risk of malformations [ 33 ] . The hypoxic state of the intrauterine environment in pregnant women with gestational hypertension leads to less nutrient absorption by the fetus compared to normal pregnant women, which can explain the higher incidence of congenital heart defects in the HDP group than in the NHDP group. 4.3 HDP can lead to shortened TL in Preterm Infants In addition to the damage to telomeres caused by normal cell division, exogenous factors can also lead to telomere damage, such as psychological factors [ 34 ] and lifestyle factors [ 35 ] . They mainly accelerate the depletion of telomeres by intensifying oxidative stress and inflammatory responses [ 36 ] . Previous studies have reported that adverse factors such as the mother's lifestyle, social psychological factors, and pregnancy-related complications during pregnancy can all affect the TL of the newborn [ 37 ][ 38 ] . This study investigated the impact of HDP on the TL of premature infants. The results showed that the TL of newborns in the HDP group was significantly shorter than that in the NHDP group. It may be due to the following three aspects: ① HDP can increase maternal oxidative stress levels, which may be passed through the placenta to the fetus, causing telomere damage to fet al cells. Zhao Qiaomian et al.'s research [ 39 ] found that the activity of δ-aminolevulinic acid dehydratase in HDP patients is inhibited, leading to an increase in the level of oxidative stress in the body. Furthermore, previous studies have reported that the TL of umbilical cord blood and placental tissue in pregnant women with preeclampsia were shorter than those of healthy pregnant women. Additionally, the total oxidative state and total antioxidant state were higher in these pregnant women compared to healthy ones. Moreover, it was concluded that oxidative stress can shorten the TLs of the placenta and umbilical cord [ 40 ] . ②The inflammatory cytokines produced during pregnancy can act on telomere DNA, causing telomere damage[41]. HDP can lead to an increase in IL-6, IL-8, IL-17, CRP and SAA levels in the pregnant woman's body. Interleukins and other substances can activate NADPH oxidase (NOX) and mitochondrial respiratory chains, generating reactive oxygen species (ROS) that directly attack telomere guanine-rich (G-rich) repeat sequences (TTAGGG), causing oxidative base damage such as 8-oxogine. Causing telomere DNA to break or shorten [ 42 ] . ③ HDP leads to chronic hypoxia of the fetus in the uterus, It can cause damage to telomere DNA [ 43 ] . In addition, placental TL is associated with placental function and pregnancy outcomes. PHILLOPPE proposed the telomere - pregnancy clock in 2015, stating that the peak of short telomeres in the placenta determines the time of trophoblast apoptosis. This affects placental function and pregnancy outcomes [ 44 ][ 45 ] . However, whether there is a definite link between neonatal TL and pregnancy outcomes remains to be further explored. 4.4 There are certain differences in TL among preterm infants of different genders In the NHDP group, there was no statistically significant difference in TL between preterm infants of different genders, but the TL of female preterm infants was longer than that of male preterm infants. Factor-Litvak P’s study [ 46 ] consistent with the results of this study, though not all studies support this conclusion [ 47 ] . A study on the TL of twins found that the results of same-sex twins showed that the TL of female infants was longer than that of male infants, while the TL of male and female infants in opposite-sex twins was similar. It may be related to the different hormones secreted by fetuses of different genders during intrauterine development [ 48 ] . A subsequent study also indicated that male newborns were born with shorter TLs than female newborns. It is speculated to be related to the activation of telomerase by intrauterine estrogen [ 49 ] . The antioxidant properties of estrogen and its ability to up-regulate telomerase may explain why telomeres in women are longer than those in men of the same age [ 50 ] . Higher levels of estrogen during intrauterine development in girls may have a role in resisting oxidative stress. In this study ,we found that in the female preterm infant group, the TL in the NHDP group was significantly longer than that in the HDP group, and the difference was statistically significant. However, in the male preterm infant group, there was no statistically significant difference in TL between the NHDP group and the HDP group. Besides the effect of gestational hypertension on TL, it cannot be ruled out that estrogen plays a certain role in protecting telomere. However, the small sample size included in this study may lead to inaccurate results, which need to be further improved in subsequent studies. 4.5 Limitations First, the sample size included in this study is relatively small. Although it can reveal the differences and correlations between variables, further large-sample studies are needed to confirm the results of this study. Second, there are numerous influencing factors for TL. Although we fully considered various factors when including the samples, potential confounding factors may still affect the results. The following research will further control confounding factors to improve the accuracy of the results. Third, this study currently lacks long-term health outcome data for newborns. Further research is needed to investigate the persistent impact of gestational hypertension on their health. 5. Conclusion HDP can lead to an increase in the rate of cesarean section, an elevated risk of congenital heart defects in newborns, and a decrease in birth weight. HDP can lead to shortened TL in premature infants, especially in female infants. Combining with TL, it can serve as a potential indicator for assessing the long-term health risks of newborns, providing clues for further elucidating the role of telomeres in the life process. Declarations Ethics approval and consent to participate The ethics committee of Liaocheng People’s Hosptial has approved the conduct of this research (ethics number: 2025066). All procedures performed in studies involving human participants were in accordance with the ethics standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethics standards. All the newborn guardians and pregnant women have been informed and have given their consent to participate in this study. Consent for publication Consent for publication was obtained from the participants. Availability of data and materials The datasets analysed during the current study are available in the Mendeley Data repository .The permanent link is as follows [https://data.mendeley.com/preview/ttjbfztw5g?a=51ded0ad-cc0a-4e5d-8369-2b281c13e05d]. Competing interests No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. Funding This study was supported by the Science and Technology Development Project of Weifang Medical College (2023FYZ110); Liaocheng key R&D project Program (2022YDSF19), and Shandong Province Traditional Chinese Medicine Technology Development Plan Project (2019-0895). Authors' contributions Lei Weikai, Ma Cuizhu, Yang Chunyan conceived and designed research; Zhang Dezhi, Shen Qinghua, Liu Fengmin collected data and conducted research; Lei Weikai, Yang Chunyan analyed and interpreted data; Lei Weikai wrote the initial paper; Yang Chunyan revised the paper; Yang Chunyan had primary responsibility for final content. All authors read and approved the final manuscript. Acknowledgements Thank all the newborns and their families for their contributions to this research. References Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013;25(2):124–32. 10.1097/GCO.0b013e32835e0ef5 . Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005;6(8):611–22. 10.1038/nrg1656 . Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34. 10.1146/annurev.genet.41.110306.130350 . Rossiello F, Jurk D, Passos JF. d'Adda di Fagagna F. 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Nutrition of neonates with congenital heart disease: existing evidence, conflicts and concerns. J Matern Fetal Neonatal Med. 2020;33(14):2487–92. 10.1080/14767058.2018.1548602 . Schutte NS, Malouff JM. The association between depression and leukocyte TL: a meta-analysis. Depress Anxiety. 2015;32(4):229–38. 10.1002/da.22351 . Astuti Y, Wardhana A, Watkins J, Wulaningsih W, PILAR Research Network. Cigarette smoking and TL: A systematic review of 84 studies and meta-analysis. Environ Res. 2017;158:480–9. 10.1016/j.envres.2017.06.038 . Kawanishi S, Oikawa S. Mechanism of telomere shortening by oxidative stress. Ann N Y Acad Sci. 2004;1019:278–84. 10.1196/annals.1297.047 . Bosquet Enlow M, Petty CR, Hacker MR, Burris HH. Maternal psychosocial functioning, obstetric health history, and newborn TL. Psychoneuroendocrinology. 2021;123:105043. 10.1016/j.psyneuen.2020.105043 . Marchetto NM, Glynn RA, Ferry ML, Ostojic M, Wolff SM, Yao R, Haussmann MF. Prenatal stress and newborn TL. Am J Obstet Gynecol. 2016;215(1):e941–8. 10.1016/j.ajog.2016.01.177 . Zhao Qiaomian L, Yang S, Shuhong, et al. Correlation Study on Oxidative Stress Markers and δ-Aminolevulinic Acid Dehydratase Activity in Pregnant Patients with Hypertension [J]. Labeled Immunoass Clin Pract. 2020;27(03):416–22. Baser E, Inandiklioglu N, Aydogan Kırmızı D, et al. Placental and Umbilical Cord Blood Oxidative Stress Level and Telomere Homeostasis in Early Onset Severe Preeclampsia. Z Geburtshilfe Neonatol. 2023;227(2):112–9. 10.1055/a-1938-0010 . Zhang J, Rane G, Dai X, et al. Ageing and the telomere connection: An intimate relationship with inflammation. Ageing Res Rev. 2016;25:55–69. 10.1016/j.arr.2015.11.006 . Lin J, Epel E. Stress and telomere shortening: Insights from cellular mechanisms. Ageing Res Rev. 2022;73:101507. 10.1016/j.arr.2021.101507 . Badran M, Abuyassin B, Ayas N, Sin DD, Laher I. Vascular and renal telomere shortening in mice exposed to chronic intermittent hypoxia. Can J Physiol Pharmacol. 2021;99(10):1112–3. 10.1139/cjpp-2021-0143 . Phillippe M, Cell-Free Fetal DNA. Telomeres, and the Spontaneous Onset of Parturition. Reprod Sci. 2015;22(10):1186–201. 10.1177/1933719115592714 . Phillippe M, Sawyer MR, Edelson PK. The telomere gestational clock: increasing short telomeres at term in the mouse. Am J Obstet Gynecol. 2019;220(5):496. 10.1016/j.ajog.2019.01.218 . .e1-496.e8 . Factor-Litvak P, Susser E, Kezios K, McKeague I, Kark JD, Hoffman M, Kimura M, Wapner R, Aviv A. Leukocyte TL in Newborns: Implications for the Role of Telomeres in Human Disease. Pediatrics. 2016;137(4):e20153927. 10.1542/peds.2015-3927 . Lee SP, Hande P, Yeo GS, Tan EC. Correlation of cord blood TL with birth weight. BMC Res Notes. 2017;10(1):469. 10.1186/s13104-017-2791-6 . Benetos A, Dalgård C, Labat C, Kark JD, Verhulst S, Christensen K, Kimura M, Horvath K, Kyvik KO, Aviv A. Sex difference in leukocyte TL is ablated in opposite-sex co-twins. Int J Epidemiol. 2014;43(6):1799–805. 10.1093/ije/dyu146 . Wojcicki JM, Olveda R, Heyman MB, Elwan D, Lin J, Blackburn E, Epel E. Cord blood TL in Latino infants: relation with maternal education and infant sex. J Perinatol. 2016;36(3):235–41. 10.1038/jp.2015.178 . Zhao Yuan L. Yuxiu. Effect of estrogen on TL of peripheral blood leukocytes[J]. Chin J Geriatric Multi-organ Dis 2021,20(05):383–7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Apr, 2026 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Revision requested 17 Feb, 2026 Reviewers agreed at journal 17 Feb, 2026 Reviews received at journal 29 Jan, 2026 Reviewers agreed at journal 27 Jan, 2026 Reviewers agreed at journal 23 Jan, 2026 Reviews received at journal 22 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers invited by journal 14 Jan, 2026 Editor assigned by journal 26 Dec, 2025 Editor invited by journal 09 Dec, 2025 Submission checks completed at journal 09 Dec, 2025 First submitted to journal 01 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8181846","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":574803832,"identity":"7bf37c5e-b0fc-4581-8cf1-5c4257a29eac","order_by":0,"name":"Lei Weikai","email":"","orcid":"","institution":"Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Weikai","suffix":""},{"id":574803833,"identity":"c14243b8-10c0-4dda-92a4-9f9dcc45e093","order_by":1,"name":"Ma Cuizhu","email":"","orcid":"","institution":"Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Ma","middleName":"","lastName":"Cuizhu","suffix":""},{"id":574803834,"identity":"7b330f56-2e54-4497-9713-dfb42a8c7396","order_by":2,"name":"Zhang Dezhi","email":"","orcid":"","institution":"Weifang Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhang","middleName":"","lastName":"Dezhi","suffix":""},{"id":574803835,"identity":"90e6ae15-db6b-4fff-950f-f9e77cb30b5b","order_by":3,"name":"Shen Qinghua","email":"","orcid":"","institution":"Liaocheng People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shen","middleName":"","lastName":"Qinghua","suffix":""},{"id":574803836,"identity":"1c72ec73-549b-494a-8a8d-3798528c11e4","order_by":4,"name":"Liu Fengmin","email":"","orcid":"","institution":"Liaocheng People's 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09:14:24","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":111726,"visible":true,"origin":"","legend":"","description":"","filename":"debd6165f9ec402788a22d96daede0f81structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8181846/v1/94f80ce881cfada4a8205e9f.xml"},{"id":100567860,"identity":"59058ed5-5da6-4bec-8147-c2749db13d4e","added_by":"auto","created_at":"2026-01-19 09:14:24","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":123577,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8181846/v1/2eca3b57928098e06f853255.html"},{"id":100567856,"identity":"f28ef38d-21db-40b8-b682-5b4780e75ced","added_by":"auto","created_at":"2026-01-19 09:14:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":219845,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of TL among different groups\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8181846/v1/901d004db0ce214090083f7b.png"},{"id":107928458,"identity":"246cb7c4-5f9c-4c76-811b-46eb3733c3c6","added_by":"auto","created_at":"2026-04-27 16:10:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":471589,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8181846/v1/32876a3c-68ea-4e70-a96d-4a3578887ead.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of Hypertensive Disorders of Pregnancy on Outcome and Relative Telomere Length in Preterm Infants","fulltext":[{"header":"1. Background","content":"\u003cp\u003eHypertensive Disorders of Pregnancy (HDP) is one of the common complications during pregnancy. Currently, it has become the main cause of maternal and perinatal deaths\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. HDP can affect the intrauterine growth and development of the fetus, leading to adverse outcomes such as premature birth, fetal growth restriction, neonatal brain damage and neonatal asphyxia.\u003c/p\u003e \u003cp\u003eTelomeres are heterochromatin structures located at the ends of linear chromosomes. They play a role in protecting chromosomes from degradation and the effects of DNA repair activities, thereby maintaining the stability of chromosome structure and function\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. TL shortens throughout a person's lifetime, and the rate of shortening is jointly determined by genetic and environmental factors, and is closely related to various aging and age-related diseases\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The accumulation of telomere loss is considered to be the main molecular cause of aging and age-related diseases. TL can indirectly reflect the degree of cell aging and disease status, and is a good candidate for markers of cellular aging and future health risks\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The growth and development of newborns in the womb are closely related to their long-term health. Existing evidence has shown that newborns with intrauterine growth retardation or premature birth are at an increased risk of obesity, hyperlipidemia and hypertension in their later lives\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e][\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. The possible mechanism of this phenomenon is related to abnormal telomere biology. The severe shortening of TL can trigger the signaling pathways of DNA damage and extracellular stress\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. As a well-established marker of cellular aging, the baseline TL at birth has a certain impact on long-term health. Longitudinal studies that repeatedly measured TL in adults have found that the baseline TL, rather than the rate of telomere loss, is associated with the risk of atherosclerosis, indicating the significance of the baseline TL determined in early life\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. The TL of newborns can be affected by maternal diseases during pregnancy. The TL of fetuses with gestational diabetes mellitus is significantly shorter than that of the normal pregnancy group\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. This phenomenon may be related to the intrauterine environment\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e and oxidative stress\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Studies on animals have shown that the HDP hormone produced by the mother rat can cause a reduction in the TL of the kidney tissue in the offspring rats\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. However, the impact of TL on newborns, especially premature infants, remains to be further explored. This is of great significance for us to comprehensively understand the possible cross-generational health effects of HDP on offspring and the underlying biological pathways.\u003c/p\u003e \u003cp\u003eThis study investigated the impact of HDP on adverse outcomes and TL in premature infants, providing clues for further understanding the role of telomeres in the course of life.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Participants.\u003c/h2\u003e \u003cp\u003eA total of 128 premature infants and their mothers from January 2022 to December 2023 in Liaocheng People\u0026rsquo;s Hosptial were selected for observation. These mothers have no bad habits and maintain harmonious social relationships. The collection of blood samples and the retrieval of their medical records were all obtained with the informed consent of the mothers. The newborn\u0026rsquo; umbilical cord blood was collected in the labour room or operation theatre immediately after delivery by trained midwives. Patient\u0026rsquo;s particulars, pregnancy complications, birth outcomes and neonatal conditions were collected from the electronic medical record system. According to whether the mothers of preterm infants had HDP, they were divided into HDP group and NHDP group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Measures\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Inclusion criteria and exclusion criteria\u003c/h2\u003e \u003cp\u003eInclusion criteria: ①Born in this hospital; ②Natural conception; ③ The HDP group criteria were based on the \"Expert Consensus on Blood Pressure Management in Hypertensive Disorders of Pregnancy (2019 Edition)\"[15]\u003c/p\u003e \u003cp\u003eExclusion criteria: ①Incomplete medical records, transfer to another hospital, and death cases; ②The mothers with gestational diabetes mellitus, hypothyroidism, hyperthyroidism, anemia, obesity, abnormal uterine structure and function (cervical insufficiency, placenta sail, placental abruption, placenta previa, uterine fibroids), heart failure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2. General characteristics and neonatal outcomes\u003c/h2\u003e \u003cp\u003eThe general characteristics of newborns (including gestational age, father's age, mother's age, number of pregnancies, number of deliveries, and gender) and the outcomes of newborns(Cesarean section rate, Brain injury, Sepsis, Heart malformations, neonatal respiratory distress syndrome (NRDS), Hypoxic-ischemic encephalopathy, Birth weight) are collected from electronic medical records.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.2.3 TL measurement\u003c/h2\u003e \u003cp\u003eUsing PrimerBank design telomeres(TEL) and internal genes(HBG) primers, the sequence is as follows: (1) telomere:telg 5'-ACACTAAGGTTTGGGTTTGGGTTTGGGTTTGGGTTAGTGT-3'; tele 5'-TGTTAGGTATCCCTATCCCTATCCCTATCCCTATCCCTAACA-3'; (2) internal gene:hbgu 5'-CGGCGGCGGGCGGCGCGGGCTGGGCGCCTTCATCCACGTTCACCTTG-3'; hbgd 5'-GCCCGGCCCGCCGCGCCCGTCCCGCCGGAGGAGAAGTCTGCCGTT-3'.\u003c/p\u003e \u003cp\u003eGenomic DNA was isolated and extracted from the collected samples, and the purity of the DNA was evaluated using a Nanodrop 1000 spectrophotometer. The qualified standard was a ratio of A260/A280 between 1.90 and 2.10, and the qualified DNA was used for the next TL test. The relative TL was measured by real-time fluorescence quantitative PCR (RT-qPCR). Telomere repeat copy number(T) and Single-copy gene copy number(S) were detected respectively, and the ratio (T/S value) between the two was calculated. The relative length of the telomere can be obtained. The formula is as follows: ΔCt\u0026thinsp;=\u0026thinsp;Ct\u003csub\u003etel\u003c/sub\u003e\u0026ndash;Ct\u003csub\u003ehbg\u003c/sub\u003e; ΔΔCt\u0026thinsp;=\u0026thinsp;Ct\u003csub\u003esample\u003c/sub\u003e-Ct\u003csub\u003ereference\u003c/sub\u003e, T/S\u0026thinsp;=\u0026thinsp;2\u003csup\u003e\u0026minus;ΔΔCt\u003c/sup\u003e. where Ct\u003csub\u003eTel\u003c/sub\u003e represents the Ct value of the telomere gene and Ct\u003csub\u003ehbg\u003c/sub\u003e represents the Ct value of the reference gene.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistical Analysis\u003c/h2\u003e \u003cp\u003eUsing SPSS 29.0 statistical software and the count data were expressed as n(%) for χ\u003csup\u003e2\u003c/sup\u003e test; Measurement data that conform to the normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) and t-test was performed; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Comparison of general characteristics of neonates\u003c/h2\u003e \u003cp\u003eA total of 128 neonates were included in the study, 49 in the HDP group and 79 in the NHDP group. The comparison of general characteristics is recorded in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and there is no significant difference between the HDP group and the NHDP group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of general characteristics of neonates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHDP group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;49\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNHDP group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;79\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e/\u003cem\u003eZ\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age (W, M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.61\u0026thinsp;\u0026plusmn;\u0026thinsp;3.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.452\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age (Y, M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.65\u0026thinsp;\u0026plusmn;\u0026thinsp;7.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.09\u0026thinsp;\u0026plusmn;\u0026thinsp;5.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.763\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFather's age (Y, M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.14\u0026thinsp;\u0026plusmn;\u0026thinsp;7.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.71\u0026thinsp;\u0026plusmn;\u0026thinsp;5.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.776\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of pregnancies (M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.458\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.145\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of deliveries\u003c/p\u003e \u003cp\u003e(M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.688\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.491\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal gender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.286 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (55.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (68.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (44.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: *:χ\u003csup\u003e2\u003c/sup\u003e; the residual Z value.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Comparison of outcomes between two groups of preterm infants\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The rate of cesarean section and congenital heart malformations in the HDP group of preterm infants was significantly higher than that in the NHDP group, and the difference was statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05); The birth weight of the HDP group was significantly lower than that of the NHDP group, and the difference was statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001); There was no statistically significant difference in the incidence of brain injury, sepsis, NRDS, and hypoxic-ischemic encephalopathy between the two groups of preterm infants.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEvaluation comparison of outcomes between the two groups of preterm infants [n,%]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHDP group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;49\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNHDP group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;79\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e/\u003cem\u003eZ\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean section rate (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59 (74.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.702\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrain injury (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (25.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33 (41.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart malformations (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRDS (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (74.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47 (59.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.871\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.190\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoxic-ischemic encephalopathy (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (Kg, M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.558 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: *:t value; the residual Z value.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Comparison of TL in different groups\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The TL in the HDP group was significantly shorter than that in the NHDP group, and the difference was statistically significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA); in the HDP group and the NHDP group, no differences in TL were found between newborns of different genders(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB C); in male neonates, no statistically significant difference in TL between the HDP group and the NHDP group(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD); in female neonates, the TL in the HDP group was significantly shorter than that in the NHDP group, and the difference was statistically significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Chronic diseases in adulthood can be traced back to the fetal period\u003c/h2\u003e \u003cp\u003eAdult chronic diseases have become one of the main factors threatening human health, such as hypertension. According to the results of the \"China Hypertension Survey\" (CHS) released in 2018, approximately one quarter of adults in China suffer from hypertension, and the total number of patients has reached 244 million\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Adult chronic diseases can be traced back to the fetal period, which is known as the fetal origin theory of adult diseases\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. This theory holds that: during the development process, if the fetus is exposed to harmful factors in the womb, the body will prioritize the supply of nutrients to important organs such as the brain, sacrificing the protection of general organs like the kidneys and liver, in order to facilitate short-term survival. However, such fetuses will significantly increase the risk of developing chronic metabolic diseases in adulthood after birth.If the adverse factors that occur during the fetal stage are not promptly corrected, they will cause changes in the fetal's metabolism and organ structure. Eventually, this will lead to permanent changes in the metabolic functions of various body tissues and organs, such as blood vessels, pancreas, liver and lungs. These changes will then progress to adult diseases, including coronary heart disease, typeⅡdiabetes and hypertension\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e][\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Furthermore, Victoria et al. first proposed the concept of the \"first 1000 days of life\" in 2008. This refers to the initial period from the formation of the fertilized egg to the age of 2 years after birth. This period is a crucial time for the maturation of the body's tissues, organs, and systems. It not only affects the early physical and brain development of children, but also can influence health during adolescence and even adulthood, and is closely related to the occurrence of long-term chronic diseases in the future\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e][\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.2 HDP can have adverse effects on the outcome of preterm infants\u003c/h2\u003e \u003cp\u003eHDP is a common disease specific to pregnancy, which can cause serious harm to both the mother and the fetus. HDP can cause spasm of the small arteries in the placenta, resulting in a reduction in placental blood flow, causing the fetus to be in a continuous state of hypoxia within the womb. This has an impact on the growth of the fetus and the newborn, as well as on the heart function, blood sugar levels, and nervous system of the fetus and newborn, leading to the malignant development of fetal or neonatal diseases and having long-term effects on their adulthood\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e][\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. This long-term effect is manifested in several aspects, such as increased risk of cardiovascular metabolism, delayed neurodevelopment, and increased risk of allergic diseases. It even leads to a significant increase in the risk of all-cause mortality\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study investigated the impact of HDP on the outcomes of premature infants. The results showed that the cesarean section rate and congenital heart malformations in the HDP group were significantly higher than those in the NHDP group, while the birth weight in the HDP group was significantly lower than that in the NHDP group.This is consistent with the previous literature reports\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e][\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. It is mainly due to the small artery spasm caused by HDP, resulting in a decrease in placental blood flow perfusion and causing changes in placental hemodynamics. This not only leads to placental abruption and abnormal amniotic fluid, but also causes the fetus to be in a chronic hypoxic state, resulting in fet al growth retardation and low birth weight of the newborn\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. During HDP, the remodeling of uterine spiral arteries is insufficient, resulting in reduced placental perfusion. The placenta is in an ischemic and hypoxic state, leading to an increase in the secretion of soluble vascular endothelial growth factor receptor-1 (sFlt-1), which antagonizes vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), inhibiting maternal vascular endothelial repair and placental angiogenesis, causing insufficient placental perfusion and resulting in intrauterine hypoxia, leading to a lower birth weight for the newborn compared to normal pregnant mothers\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. HDP is an important risk factor for premature rupture of membranes, abnormal amniotic fluid, and placental abruption\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e][\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e][\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. For patients with HDP combined with excessive or insufficient amniotic fluid, pregnancy should be terminated as soon as possible, and the fetus should be delivered within 6 hours after the onset of placental abruption symptoms. This will effectively protect the lives and long-term prognosis of the newborn and the pregnant mother. This is an important reason why the cesarean section rate of premature infants in the HDP group is significantly higher than that in the NHDP group.The development of the heart is a continuous and complex process. Genetic factors and maternal-related factors can all affect the development of the fetus's heart. HDP is one of the independent risk factors for congenital heart malformations in the fetus\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. The fetus absorbs nutrients from the mother to maintain normal development. If the nutrition during pregnancy is poor, the fetus will have insufficient nutrition, which will have an adverse effect on the development of the heart and increase the risk of malformations\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e. The hypoxic state of the intrauterine environment in pregnant women with gestational hypertension leads to less nutrient absorption by the fetus compared to normal pregnant women, which can explain the higher incidence of congenital heart defects in the HDP group than in the NHDP group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.3 HDP can lead to shortened TL in Preterm Infants\u003c/h2\u003e \u003cp\u003eIn addition to the damage to telomeres caused by normal cell division, exogenous factors can also lead to telomere damage, such as psychological factors\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e and lifestyle factors\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. They mainly accelerate the depletion of telomeres by intensifying oxidative stress and inflammatory responses\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e. Previous studies have reported that adverse factors such as the mother's lifestyle, social psychological factors, and pregnancy-related complications during pregnancy can all affect the TL of the newborn\u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e][\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study investigated the impact of HDP on the TL of premature infants. The results showed that the TL of newborns in the HDP group was significantly shorter than that in the NHDP group. It may be due to the following three aspects: ① HDP can increase maternal oxidative stress levels, which may be passed through the placenta to the fetus, causing telomere damage to fet al cells. Zhao Qiaomian et al.'s research\u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e found that the activity of δ-aminolevulinic acid dehydratase in HDP patients is inhibited, leading to an increase in the level of oxidative stress in the body. Furthermore, previous studies have reported that the TL of umbilical cord blood and placental tissue in pregnant women with preeclampsia were shorter than those of healthy pregnant women. Additionally, the total oxidative state and total antioxidant state were higher in these pregnant women compared to healthy ones. Moreover, it was concluded that oxidative stress can shorten the TLs of the placenta and umbilical cord\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e. ②The inflammatory cytokines produced during pregnancy can act on telomere DNA, causing telomere damage[41]. HDP can lead to an increase in IL-6, IL-8, IL-17, CRP and SAA levels in the pregnant woman's body. Interleukins and other substances can activate NADPH oxidase (NOX) and mitochondrial respiratory chains, generating reactive oxygen species (ROS) that directly attack telomere guanine-rich (G-rich) repeat sequences (TTAGGG), causing oxidative base damage such as 8-oxogine. Causing telomere DNA to break or shorten\u003csup\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e. ③ HDP leads to chronic hypoxia of the fetus in the uterus, It can cause damage to telomere DNA\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn addition, placental TL is associated with placental function and pregnancy outcomes. PHILLOPPE proposed the telomere - pregnancy clock in 2015, stating that the peak of short telomeres in the placenta determines the time of trophoblast apoptosis. This affects placental function and pregnancy outcomes\u003csup\u003e[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e][\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/sup\u003e. However, whether there is a definite link between neonatal TL and pregnancy outcomes remains to be further explored.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e4.4 There are certain differences in TL among preterm infants of different genders\u003c/h2\u003e \u003cp\u003eIn the NHDP group, there was no statistically significant difference in TL between preterm infants of different genders, but the TL of female preterm infants was longer than that of male preterm infants. Factor-Litvak P\u0026rsquo;s study\u003csup\u003e[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/sup\u003e consistent with the results of this study, though not all studies support this conclusion\u003csup\u003e[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/sup\u003e. A study on the TL of twins found that the results of same-sex twins showed that the TL of female infants was longer than that of male infants, while the TL of male and female infants in opposite-sex twins was similar. It may be related to the different hormones secreted by fetuses of different genders during intrauterine development\u003csup\u003e[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/sup\u003e. A subsequent study also indicated that male newborns were born with shorter TLs than female newborns. It is speculated to be related to the activation of telomerase by intrauterine estrogen\u003csup\u003e[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/sup\u003e. The antioxidant properties of estrogen and its ability to up-regulate telomerase may explain why telomeres in women are longer than those in men of the same age\u003csup\u003e[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/sup\u003e. Higher levels of estrogen during intrauterine development in girls may have a role in resisting oxidative stress.\u003c/p\u003e \u003cp\u003eIn this study ,we found that in the female preterm infant group, the TL in the NHDP group was significantly longer than that in the HDP group, and the difference was statistically significant. However, in the male preterm infant group, there was no statistically significant difference in TL between the NHDP group and the HDP group. Besides the effect of gestational hypertension on TL, it cannot be ruled out that estrogen plays a certain role in protecting telomere. However, the small sample size included in this study may lead to inaccurate results, which need to be further improved in subsequent studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.5 Limitations\u003c/h2\u003e \u003cp\u003eFirst, the sample size included in this study is relatively small. Although it can reveal the differences and correlations between variables, further large-sample studies are needed to confirm the results of this study. Second, there are numerous influencing factors for TL. Although we fully considered various factors when including the samples, potential confounding factors may still affect the results. The following research will further control confounding factors to improve the accuracy of the results. Third, this study currently lacks long-term health outcome data for newborns. Further research is needed to investigate the persistent impact of gestational hypertension on their health.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eHDP can lead to an increase in the rate of cesarean section, an elevated risk of congenital heart defects in newborns, and a decrease in birth weight. HDP can lead to shortened TL in premature infants, especially in female infants. Combining with TL, it can serve as a potential indicator for assessing the long-term health risks of newborns, providing clues for further elucidating the role of telomeres in the life process.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe ethics committee of Liaocheng People’s Hosptial has approved the conduct of this research (ethics number: 2025066). All procedures performed in studies involving human participants were in accordance with the ethics standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethics standards. All the newborn guardians and pregnant women have been informed and have given their consent to participate in this study.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained from the participants.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets analysed during the current study are available in the Mendeley Data repository .The permanent link is as follows [https://data.mendeley.com/preview/ttjbfztw5g?a=51ded0ad-cc0a-4e5d-8369-2b281c13e05d].\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eNo financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Science and Technology Development Project of Weifang Medical College (2023FYZ110); Liaocheng key R\u0026amp;D project Program (2022YDSF19), and Shandong Province Traditional Chinese Medicine Technology Development Plan Project (2019-0895).\u003c/p\u003e\n\u003cp\u003eAuthors' contributions\u003c/p\u003e\n\u003cp\u003eLei Weikai, Ma Cuizhu, \u0026nbsp;Yang Chunyan conceived and designed research;\u0026nbsp;Zhang Dezhi, Shen Qinghua,\u0026nbsp;Liu Fengmin\u0026nbsp;collected data and conducted research;\u0026nbsp;Lei Weikai, Yang Chunyan\u0026nbsp;analyed and interpreted data;\u0026nbsp;Lei Weikai\u0026nbsp;wrote the initial paper;\u0026nbsp;Yang Chunyan\u0026nbsp;revised the paper;\u0026nbsp;Yang Chunyan\u0026nbsp;had primary responsibility for final content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThank all the newborns and their families for their contributions to this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013;25(2):124\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/GCO.0b013e32835e0ef5\u003c/span\u003e\u003cspan address=\"10.1097/GCO.0b013e32835e0ef5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlasco MA. Telomeres and human disease: ageing, cancer and beyond. 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Chin J Geriatric Multi-organ Dis 2021,20(05):383\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"hypertensive disorders of pregnancy(HDP), outcome of premature Infants, telomere length(TL)","lastPublishedDoi":"10.21203/rs.3.rs-8181846/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8181846/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHypertensive disorders of pregnancy(HDP) are the most common obstetric complications and may cause severe neonatal morbidity, leading to adverse long-term outcomes. Telomere, as a potential biomarker reflecting cellular aging and future health risks, its length can indirectly indicate the long-term prognosis of newborns. Although significant progress has been made in this field, the impact of gestational hypertension on the prognosis of premature infants and telomere length (TL) still requires further exploration. This article mainly conducts a preliminary exploration of the effects of hypertensive disorders of pregnancy (HDP) on preterm infant outcomes and telomere length (TL).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 128 preterm infants born between January 2022 and December 2023 were included.The included subjects were divided into the hypertensive disorders of pregnancy(HDP) group and the no-hypertensive disorders of pregnancy(NHDP) group based on whether the mother has gestational hypertension. Maternal and neonatal clinical data were collected and TL was measured from infant peripheral blood using quantitative PCR. Statistical analyses included chi-square tests for categorical data and t-tests for continuous variables.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1 The HDP group had a significantly higher rate of cesarean delivery (100% vs. 74.7%, P \u0026lt; 0.001) and congenital heart malformations (12.2% vs. 2.0%, P =0.013), along with lower birth weight (1.68 ± 0.50 kg vs. 2.08 ± 0.75 kg, P = 0.001) compared with the NHDP group.\u003c/p\u003e\n\u003cp\u003e2 TL was shorter in the HDP group than in the NHDP group (1.917 ± 0.792 vs 2.249 ± 0.797, P = 0.024). Infemale neonates, the TL in the HDP group was significantly shorter than that in the NHDP group(1.930 ± 0.697 vs 2.405 ± 0.684, P = 0.023). In male neonates,there was no TL difference between the HDP group and the NHDP group. There was no TL difference between genders in the HDP group and the NHDP group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHDP can lead to an increase in the rate of cesarean section, an elevated risk of congenital heart defects in newborns, and a decrease in birth weight. 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