The Impact of ART on the Elevation of Offspring Blood Pressure: A Cohort Study

The Impact of ART on the Elevation of Offspring Blood Pressure: A Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Impact of ART on the Elevation of Offspring Blood Pressure: A Cohort Study Yifei Sun, Jinli Chang, Xiaoqian Zhou, Linlin Cui This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6137949/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : This study examined blood pressure disparities between assisted reproductive technology (ART)-conceived and naturally conceived (NC) offspring. It also explored the associated influencing factors and elucidated the role of ART in this process. Methods : A total of 479 pairs of children, comprising a matched group in terms of age and sex, were selected from a single reproductive center. The groups included NC children and ART children. Various indicators,such as glucose and lipid metabolism levels, birth conditions, parental health status, and infertility causes,were analyzed. The study also investigated the correlation between these indicators and children's blood pressure, as well as the role they play. Results : Multivariate analyses revealed that ART-conceived offspring had elevated systolic blood pressure (SBP) (Δz-score=0.09, p<0.001) and diastolic blood pressure (DBP) (Δz-score=0.13, p<0.001) compared to NC counterparts. Especially, while the observed blood pressure (BP) differences were statistically high, all values fell within age- and sex-adjusted normative ranges for pediatric populations. The increase in offspring blood pressure was unrelated to parental factors such as age, BMI, or infertility conditions but was rather associated with the type of ART procedure—either fresh embryo transfer (Fresh-ET) or frozen embryo transfer (FET). After controlling confounding factors, offspring from Fresh-ET pregnancies presented a greater blood pressure than those from FET and naturally conceived pregnancies. Conclusion : Compared with NC children, childrenconceived through ART havehigher SBP and DBP, despite all blood pressure values being within the physiological range. This obvious and stable difference deserves our attention. Multivariable analyses revealed that ART procedures themselves—particularly fresh embryo transfer—may exert direct influences on offspring hemodynamics. Reproductive technology assisted blood pressure children Introduction Assisted reproductive technology (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the primary methods to assist couples with infertility in conceiving offspring. Currently, over 11 million children worldwide are born through ART[ 1 ]. According to the World Health Organization, infertility and subfertility are projected to become the third most severe global health concern in the 21st century, following cancer and cardiovascular diseases[ 2 ]. As the incidence of infertility increases and the widespread application of ART continues, the immediate and long-term health and safety concerns of this substantial population, particularly those born through in vitro fertilization, have got increasing attention. With the growing utilization of ART, concerns about their long-term effects on offspring health, particularly cardiovascular outcomes, have emerged as a critical research focus. A comprehensive review[ 3 ] summarized the long-term outcomes of children conceived through ART, indicating an increased risk of cardiovascular and metabolic complications, elevated blood pressure, and suboptimal cardiac diastolic function within this population. A multicenter cohort analysis focusing on the long-term cardiovascular and metabolic health issues of offspring born through ART revealed that these children initially presented lower blood pressure in childhood but developed higher blood pressure in adulthood, along with arterial atherogenic lipid abnormalities [ 4 ]. Another study investigating the cardiovascular health of children aged 6–10 years via ART [ 5 ] revealed increased blood pressure and adverse alterations in left ventricular structure and function among ART offspring. These studies collectively suggest the potential hypertension risk of ART in children. Studies have suggested that low birth weight[ 6 ], high maternal BMI before pregnancy[ 7 ], gestational diabetes[ 8 ], and gestational hypertension[ 9 ] were related to increased BP in offspring. Additionally, the application of ART has also increased the incidence of most of these diseases[ 10 ]. The procedural interventions of ART occur during a critical period of sperm and egg maturation as well as their crucial union. This period of intervention is unavoidable and highly significant. Embedded within the Developmental Origins of Health and Disease (DOHaD) framework[ 11 , 12 ], our study posits that ART-mediated intrauterine exposures may imprint long-term cardiovascular risks. Current research reveals contradictory evidence regarding BP in ART offspring. Some evidence suggests that ART offspring have a higher risk of elevated BP[ 3 , 13 – 17 ]. Our previous study on ART offspring ages 6 to 10 years revealed elevated BP levels in this population[ 5 ]. Another muti-cohort analysis indicated a trend towards higher SBP in young adulthood among ART offspring[ 4 ]. But a meta-analysis demonstrated that ART was not associated with offspring SBP or DBP, although heterogeneity remained high (I²=76% for SBP and I²=87% for DBP)[ 18 ]. Despite the growing interest in the developmental origins of health and disease, a significant knowledge gap persists regarding the roles of ART procedures and underlying parental subfertility in shaping hypertension risk trajectories in offspring. This study aims to assess the impact of ARTs on offspring blood pressure by comparing matched cohorts of ART-conceived and naturally conceived (NC) children, identifying key differences and potential contributing factors. Method This study was a retrospective cohort investigation, and the research protocol received approval from the Structural Review Committee of the Reproductive Medicine Center at Shandong University. Written informed consent was obtained from the parents or guardians of all the participants. This report adhered to the guidelines outlined in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for cohort studies. From January 2008 to September 2023, families with naturally conceived pregnancies and those utilizing ART for conception have been followed up at our center. The inclusion criteria for the study included children under 18 years of age at the time of follow-up, and the exclusion criteria were as follows: 1. Parents diagnosed with chromosomal disorders (e.g., Down syndrome, Turner syndrome, chromosomal translocation); 2. Conception through oocyte or sperm donation; 3. Parents with autoimmune diseases (e.g., lupus, type 1 diabetes) due to their potential confounding effects on pregnancy outcomes; 4. Mothers with reproductive system developmental abnormalities. Furthermore, singleton births were exclusively included to eliminate confounding effects from multiple pregnancies. Preterm birth (< 37 weeks) and low birth weight (< 2500 g) were recorded and adjusted for in multivariate analyses. In last, the study included 1579 ART children and 1463 NC children. Using propensity score matching on the basis of age and sex, with a matching tolerance of 0.01, 479 ART children were matched with 479 NC children. All the measurement indices were standardized via established protocols and instruments. BP measurements were obtained using a validated automated device (Omron, Japan) following a standardized protocol: after 10 minutes of seated rest, three consecutive readings were taken at 5-minute intervals, with the average of the last two measurements used for analysis. Examiners were blinded to conception type throughout the process. Fasting blood glucose levels were measured using enzymatic assays (Roche Diagnostics), and birth weight data were extracted from obstetric records. Data Analysis Due to the wide age range and its significant impact on children's BP, we standardized the data by calculating Z scores for height, weight, SBP, and DBP based on age-specific mean and standard deviation values for Chinese children. Anthropometric data were further standardized to Z scores according to Chinese age- and sex-specific standards[ 19 ] to minimize age and sex effects. Statistical analyses were conducted via SPSS 25.0 software (SPSS Inc., Chicago, IL, USA). 1) Normally distributed data are presented as the mean ± standard deviation (mean ± SD), whereas nonnormally distributed data are presented as the median (interquartile range) (median (IQR)). 2) Normally distributed metric data, comparisons between the means of two groups were performed via the independent samples t test, and comparisons among multiple groups were performed via one-way analysis of variance (ANOVA). 3) Nonnormally distributed data, the Mann‒Whitney U test was used to compare means between two groups. 4) Categorical data comparisons, the chi-square test or Fisher's exact probability test was used. Pearson correlation analysis was used to determine the correlation between children's BP and continuous variables, and point-biserial correlation analysis was used to determine the correlation between children's blood pressure and binary variables. A two-sided P value < 0.05 was considered statistically significant. Results Propensity score matching was performed on the enrolled participants according to age and sex, with the match tolerance set at 0.01. Each of the ART and NC groups included 479 children. The results indicated that ART children had higher SBP Z scores (0.243 ± 0.787 vs. 0.156 ± 0.796, p < 0.001) and DBP Z scores (0.187 ± 0.876 vs. 0.061 ± 0.870, p < 0.001). Although all blood pressure values were within the physiological range, the significant and consistent differences observed warrant concern. Additionally, the ART offspring presented lower fasting blood glucose (FBG) levels (5.005 mmol/L ± 0.402 vs. 5.087 mmol/L ± 0.404, p < 0.05) and lower birth weights (3328.476 g ± 616.843 vs. 3407.912 g ± 467.3, p < 0.05), with a slightly shorter duration of pregnancy (274.748 d ± 111.749 vs. 275.873 d ± 9.362), although these differences were small and lacked significant clinical implications. We compared maternal characteristics between the two groups of children and found that mothers of ART-conceived children were elder (31.29 ± 4.29 vs. 27.77 ± 4.325 years, p < 0.001), had greater incidences of gestational hypertension (9.4% vs. 2.5%, p < 0.001) and placenta previa (2.1% vs. 0.2%, p < 0.05), with big differences, respectively. No significant difference was observed in the incidence of gestational diabetes mellitus (3.5% vs. 3.1%, p = 0.858) among mothers. Furthermore, fathers of ART children were older (31.84 ± 4.727 vs. 28.88 ± 4.988 years, p < 0.001) and had a greater BMI (25.936 kg/m²±3.613 vs. 25.483 kg/m²±3.694, p < 0.05). (Table 1 ) Table 1 Participant characteristics by conception type NC (n = 479) ART (n = 479) P Offspring Age, y 7.146 ± 3.727 7.196 ± 3.645 0.834 Male, no. (%) 233(48.6%) 245(51.1%) 0.477 Height Z score 0.204 ± 1.407 0.385 ± 1.13 0.344 Weight Z score 0.247 ± 1.179 0.376 ± 0.982 0.096 BMI, kg/m2 17.876 ± 3.409 17.985 ± 3.407 0.248 SBP, mmHg 99.777 ± 11.537 101.896 ± 11.066 < 0.05 SBP Z score 0.156 ± 0.796 0.243 ± 0.787 < 0.05 DBP, mmHg 60.351 ± 9.705 63.067 ± 10.299 < 0.001 DBP Z score 0.061 ± 0.87 0.187 ± 0.876 < 0.05 Pulse, cpm 90.804 ± 9.069 92.317 ± 10.319 0.142 TG, mmol/L 0.833 ± 0.486 0.815 ± 0.333 0.388 FBG, mmol/L 5.087 ± 0.404 5.005 ± 0.402 < 0.05 CHOL, mmol/L 4.026 ± 0.688 4.074 ± 0.744 0.401 LDL, mmol/L 2.379 ± 0.572 2.459 ± 0.601 0.064 HDL, mmol/L 1.411 ± 0.296 1.395 ± 0.298 0.372 Birth weight, g 3407.912 ± 467.3 3328.476 ± 616.683 < 0.05 Days of pregnancy, d 275.873 ± 9.362 274.748 ± 111.749 < 0.001 Maternal Maternal age, y 27.77 ± 4.325 31.29 ± 4.29 < 0.001 Maternal height, cm 162.056 ± 4.812 161.643 ± 4.481 0.733 Maternal weight, kg 61.954 ± 10.38 60.484 ± 9.17 0.141 Maternal BMI, kg/m2 23.581 ± 3.732 23.119 ± 3.275 0.177 Maternal prepregnancy diseases Hyperlipidemia, no. (%) 0(0%) 1(0.2%) 1 Hyperthyroidism, no. (%) 4(1%) 1(0.2%) 0.18 Maternal pregnant diseases GDM, no. (%) 15(3.1%) 17(3.5%) 0.858 PIH, no. (%) 12(2.5%) 45(9.4%) < 0.001 PP, no. (%) 1(0.2%) 10(2.1%) < 0.05 Paternal Paternal age, y 28.88 ± 4.988 31.84 ± 4.727 < 0.001 Paternal height, cm 174.014 ± 5.163 173.223 ± 5.421 0.063 Paternal weight, kg 77.267 ± 12.344 77.753 ± 11.577 0.343 Paternal BMI, kg/m 2 25.483 ± 3.694 25.936 ± 3.613 < 0.05 Paternal diseases Paternal mellitus, no. (%) 0(0%) 3(0.6%) 0.251 Paternal hypertension, no. (%) 1(0.2%) 4(0.8%) 0.376 Parental smoking, no. (%) 132(30.9%) 144(30.8%) 1 Alcoholism, no. (%) 7(1.6%) 12(2.6%) 0.364 NOTE: Continuous variables presented as mean ± SD; categorical data as n(%). Body mass index, BMI; Systolic blood pressure, SBP; Diastolic blood pressure, DBP; Counts per minute, cpm; Triglyceride, TG; Fasting blood glucose, FBG; Cholesterol, CHOL; Low-density lipoprotein, LDL; High-density lipoprotein HDL; Preterm birth, PTB; Gestitional diabetes mellitus, GDM; Pregnancy-induced hypertension, PIH; Placenta praevia, PP The above results indicate that offspring conceived through ART indeed have increased BP but this effect may be influenced by parental factors such as age. Therefore, we conducted correlation analyses to explore potential factors associated with BP in ART-conceived children. In addition to parental age and BMI, we analyzed the birth circumstances of the children, including premature birth and cesarean section, reasons for maternal infertility, maternal preconception and prenatal diseases, paternal habits and diseases, and ART procedures such as embryo cryopreservation and ICSI. The results revealed that SBP and DBP were associated with only whether fresh embryo transfer (Fresh-ET) or frozen embryo transfer (FET) occurred (β=-0.165, p < 0.05), and were not related to parental BMI, age, hypertension status, adverse lifestyle habits (such as smoking and alcohol consumption), maternal pregnancy complications, or infertility causes (Table 2 ). Table 2 Correlation Analysis of Blood Pressure in ART Offspring SBP DBP Point-biserial p Point-biserial p Offspring Sex 0.055 0.233 -0.02 0.668 Preterm birth 0.06 0.187 0.047 0.305 Cesarean 0.076 0.096 0.046 0.316 Maternal Age, y -0.018 0.692 -0.050 0.281 BMI, kg/m2 0.068 0.163 0.049 0.313 Paternal Age, y -0.040 0.384 -0.086 0.062 BMI, kg/m2 0.035 0.466 0.046 0.339 Etiology of infertility Tubal infertility 0.021 0.653 0.05 0.279 Endometrial polyp -0.058 0.206 -0.041 0.368 PCOS -0.045 0.328 -0.027 0.558 POI -0.043 0.345 0.025 0.593 RSA -0.043 0.345 0.025 0.593 Maternal prepregnatal diseases Hyperlipidemia 0.116 <0.05 0.021 0.645 Hyperthyroidism 0.033 0.474 0.017 0.716 Maternal pregnant diseases PIH 0.002 0.97 0.015 0.738 PP 0.026 0.563 0.012 0.796 Paternal diseases Paternal mellitus 0.041 0.379 0.011 0.811 Paternal hypertension 0.002 0.968 0.018 0.697 Parental smoking -0.009 0.841 -0.026 0.569 Embryo transfer Whether FET -0.165 <0.05 -0.235 <0.001 Whether ICSI 0.005 0.926 0.051 0.327 NOTE: Body mass index, BMI; Polycystic ovarian syndrome, PCOS; Primary ovarian insufficiency, POI; Recurrent spontaneous abortion, RSA; Gestational diabetes mellitus, GDM; Pregnancy-induced hypertension, PIH; Placenta previa, PP; Frozen-embryo transfer, FET; Intracytoplasmic sperm injection, ICSI These findings suggest that the BP of ART offspring is influenced mainly by the transplantation method during ART but is slightly attributable to parental infertility. To further substantiate this viewpoint, we divided the ART children into FET and Fresh-ET groups, which were matched on the basis of parental age and BMI via propensity scores with a tolerance of 0.01. Each group included 135 children. Comparisons of BP between these groups revealed that the Fresh-ET group had higher SBP (0.438 ± 0.832 vs. 0.073 ± 0.677, p < 0.001) and DBP (0.423 ± 0.909 vs. -0.091 ± 0.690, p < 0.001) than did the FET group. Especially, there were no differences in BP between the FET group and the NC group, whereas the Fresh-ET group presented higher SBP (0.438 ± 0.832 vs. 0.156 ± 0.796, p < 0.001) and DBP (0.423 ± 0.909 vs. 0.061 ± 0.870, p < 0.001) than the NC group did, indicating that Fresh-ET is the cause of elevated BP in ART offspring. (Table 3 ) Table 3 Comparison of blood pressure among the Fresh-ET group, frozen-embryo transfer group and natural conception group Fresh-ET (n = 135) FET (n = 135) NC (n = 479) SBP, mmHg 104.100 ± 11.513 a 98.870 ± 10.607 b 99.777 ± 11.537 b SBP Z score 0.438 ± 0.832 a 0.073 ± 0.677 b 0.156 ± 0.796 b DBP, mmHg 66.100 ± 10.631 a 59.130 ± 9.899 b 60.351 ± 9.705 b DBP Z score 0.423 ± 0.909 a -0.091 ± 0.690 b 0.061 ± 0.87 b NOTE: The fresh-embryo transfer group and the frozen-embryo transfer group were propensity score matched on the basis of parental age and BMI. Fresh-embryo transfer, Fresh-ET; Frozen-embryo transfer, FET; Systolic Blood Pressure, SBP; Diastolic Blood Pressure, DBP; Identical subscript letters indicate no significant difference, whereas different subscript letters indicate significant (P < 0.05) differences. Discussion Compared with NC children, children born through ART exhibit higher SBP and DBP, despite all BP values being within the physiological range. This significant and consistent difference warrants attention. ART, especially fresh ET, appears to have a direct impact on offspring BP. In this study, a negative correlation was observed between FET and blood pressure in ART offspring. The BP of offspring from FET was lower than that of offspring from Fresh-ET. Age and BMI of the parents were included in adjusted models, suggesting limited confounding effects. Similar findings were observed in a study on offspring of overweight/obese mothers, where offspring conceived through FET presented significantly higher BMI-Z scores, SBP-Z scores, and overall metabolic scores than offspring conceived through fresh-ET [ 20 ]. Additionally, studies[ 5 , 21 ] have shown that offspring from ART commonly exhibit atrial enlargement, ventricular wall thickening, and impaired systolic-diastolic function. This phenomenon was more pronounced in the fresh embryo transfer group, suggesting that fresh embryo transfer may have a greater impact on cardiovascular abnormalities in offspring[ 22 ]. In addition, a study based on an analysis of a large Nordic dataset revealed that singleton pregnancies conceived through frozen embryo transfer reduced the likelihood of low birth weight, preterm birth, and small for gestational age (SGA)[ 23 ]. Reducing the risk of adverse birth outcomes, such as preterm birth or SGA, may help mitigate the occurrence of these phenomena[ 24 – 27 ]. In addition, freezing and thawing may cause changes in epigenetics during embryonic stages and subsequently alter the development of FET offspring [ 28 ]. Some of these epigenetic changes may persist and be passed on to the offspring after birth[ 29 – 32 ]. However, currently, this impact is not serious. From the perspective of the intrauterine environment, the supraphysiological hormone levels of ovarian stimulation in fresh-ET cycles may influence the implantation and development of the embryo[ 33 , 34 ]. Research has shown that elevated levels of estradiol and progesterone (> 3,450 pg/mL) on the day of hCG administration during controlled ovarian hyperstimulation are associated with increased odds of developing preeclampsia and delivering small-for-gestational-age (SGA) infants in IVF cycles, resulting in singleton pregnancies[ 35 ]. In contrast, the intrauterine environment of FET cycles is more natural than that of fresh-ET cycles[ 36 ]. The lower BP in FET offspring may result from reduced exposure to supraphysiological hormone levels during ovarian stimulation, which are characteristic of fresh-ET cycles and may impair vascular development. This matched cohort study represents a comprehensive multigenerational assessment of blood pressure (BP) determinants in children conceived through assisted reproductive technology (ART) to date. By utilizing age- and sex-matched naturally conceived controls, we systematically incorporated various factors, including pediatric parameters (Anthropometric measures, glucose homeostasis, and lipid metabolism profiles) and parental exposures (Demographic characteristics, metabolic comorbidities, infertility etiologies, and lifestyle behaviors). Through rigorous multivariable regression models and propensity score matching analyses, we elucidated the association between specific ART procedures (e.g., treatment protocols, ICSI or IVF, and fresh or frozen embryo transfer) and elevated BP trajectories in offspring.. However, it is important to note that this study is retrospective, and despite strict testing during the population follow-up process, there may still be recall bias regarding parental medical history and lifestyle habits. In past designs, accurate ascertainment of these factors is inherently constrained by recall bias and the lack of standardized assessment tools. Additionally, the single-center design limits generalizability. Nevertheless, the elevated BP in children conceived through ART still warrants attention, even if the increase is within the physiological range. Declarations Data available on request The data underlying this article will be shared upon reasonable request to the corresponding author. Authors Contributions Study design: Y-FS and L-LC. Data collection: Y-FS, and J-LC. Data analysis: Y-FS, X-QZ, and J-LC. Supervision: Y-FS. Writing the original article: Y-FS. Revision: L-LC. All the authors contributed to the article and approved the submitted version. Funding This study was partly funded by the National Key R&D Program of China (2022YFC2704404), the Shandong Provincial Natural Science Foundation (ZR2022JQ33), the CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), and the National Special Support Program for High-level Talents. References Wyns C, De Geyter C. ART in Europe, 2018: results generated from European registries by ESHRE. 2022, 2022: hoac022. Qiao J, Feng HL. Assisted reproductive technology in China: compliance and non-compliance. Transl Pediatr 2014, 3: 91-7. Pinborg A, Wennerholm UB, Bergh C. Long-term outcomes for children conceived by assisted reproductive technology. Fertil Steril 2023, 120: 449-56. Elhakeem A, Taylor AE, Inskip HM. Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis. 2023, 44: 1464-73. Cui L, Zhao M, Zhang Z, Zhou W, Lv J, Hu J, et al. 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Imudia AN, Awonuga AO, Doyle JO, Kaimal AJ, Wright DL, Toth TL, et al. Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization. Fertility and Sterility 2012, 97: 1374-9. Lawrenz B, Coughlan C, Melado L, Fatemi HM. The ART of frozen embryo transfer: back to nature! Gynecol Endocrinol 2020, 36: 479-83. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-6137949","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":423335697,"identity":"4837f166-1fc1-4584-8f1f-3391b47b980d","order_by":0,"name":"Yifei Sun","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Yifei","middleName":"","lastName":"Sun","suffix":""},{"id":423335698,"identity":"2b63d8f6-b162-4fbb-8b6d-8d3855a3be08","order_by":1,"name":"Jinli Chang","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Jinli","middleName":"","lastName":"Chang","suffix":""},{"id":423335699,"identity":"82ac2527-2548-4a1b-88d9-f1d85c603a68","order_by":2,"name":"Xiaoqian Zhou","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoqian","middleName":"","lastName":"Zhou","suffix":""},{"id":423335700,"identity":"36ec2792-b2f4-46e0-8437-4811c202d40b","order_by":3,"name":"Linlin Cui","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYBAC9oYExgNA2o6fmfngA6K08BxIYABpSZZsZ0s2IEkL44bzPGYCxGlhT35w4EPNPWbjwwxmDAw1NtGEtfA8Mzg441gxn9lhhrQHDMfSchsIabGXyGE4zMOWwAzUctyAseEwYS08IC1//iUwbm5mbJMgXgtjWwLjBmZmNiK1gPzS25eQLHGYjdkggRi/AEPs4YMf3xLs+PvPf3zwocaGsBZUkECa8lEwCkbBKBgFuAAAZy4/C60RPSgAAAAASUVORK5CYII=","orcid":"","institution":"Shandong University","correspondingAuthor":true,"prefix":"","firstName":"Linlin","middleName":"","lastName":"Cui","suffix":""}],"badges":[],"createdAt":"2025-03-02 07:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6137949/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6137949/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":77874468,"identity":"a274c0d7-5943-400e-8c94-07b23de3ab8a","added_by":"auto","created_at":"2025-03-06 11:01:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":547701,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6137949/v1/9aa1e9a7-73cb-4e4d-aada-07358de64297.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Impact of ART on the Elevation of Offspring Blood Pressure: A Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAssisted reproductive technology (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the primary methods to assist couples with infertility in conceiving offspring. Currently, over 11\u0026nbsp;million children worldwide are born through ART[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. According to the World Health Organization, infertility and subfertility are projected to become the third most severe global health concern in the 21st century, following cancer and cardiovascular diseases[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. As the incidence of infertility increases and the widespread application of ART continues, the immediate and long-term health and safety concerns of this substantial population, particularly those born through in vitro fertilization, have got increasing attention. With the growing utilization of ART, concerns about their long-term effects on offspring health, particularly cardiovascular outcomes, have emerged as a critical research focus.\u003c/p\u003e \u003cp\u003eA comprehensive review[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] summarized the long-term outcomes of children conceived through ART, indicating an increased risk of cardiovascular and metabolic complications, elevated blood pressure, and suboptimal cardiac diastolic function within this population. A multicenter cohort analysis focusing on the long-term cardiovascular and metabolic health issues of offspring born through ART revealed that these children initially presented lower blood pressure in childhood but developed higher blood pressure in adulthood, along with arterial atherogenic lipid abnormalities [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Another study investigating the cardiovascular health of children aged 6\u0026ndash;10 years via ART [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] revealed increased blood pressure and adverse alterations in left ventricular structure and function among ART offspring. These studies collectively suggest the potential hypertension risk of ART in children.\u003c/p\u003e \u003cp\u003eStudies have suggested that low birth weight[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], high maternal BMI before pregnancy[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], gestational diabetes[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and gestational hypertension[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] were related to increased BP in offspring. Additionally, the application of ART has also increased the incidence of most of these diseases[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The procedural interventions of ART occur during a critical period of sperm and egg maturation as well as their crucial union. This period of intervention is unavoidable and highly significant. Embedded within the Developmental Origins of Health and Disease (DOHaD) framework[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], our study posits that ART-mediated intrauterine exposures may imprint long-term cardiovascular risks.\u003c/p\u003e \u003cp\u003eCurrent research reveals contradictory evidence regarding BP in ART offspring. Some evidence suggests that ART offspring have a higher risk of elevated BP[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Our previous study on ART offspring ages 6 to 10 years revealed elevated BP levels in this population[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Another muti-cohort analysis indicated a trend towards higher SBP in young adulthood among ART offspring[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. But a meta-analysis demonstrated that ART was not associated with offspring SBP or DBP, although heterogeneity remained high (I\u0026sup2;=76% for SBP and I\u0026sup2;=87% for DBP)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the growing interest in the developmental origins of health and disease, a significant knowledge gap persists regarding the roles of ART procedures and underlying parental subfertility in shaping hypertension risk trajectories in offspring. This study aims to assess the impact of ARTs on offspring blood pressure by comparing matched cohorts of ART-conceived and naturally conceived (NC) children, identifying key differences and potential contributing factors.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e This study was a retrospective cohort investigation, and the research protocol received approval from the Structural Review Committee of the Reproductive Medicine Center at Shandong University. Written informed consent was obtained from the parents or guardians of all the participants. This report adhered to the guidelines outlined in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for cohort studies. From January 2008 to September 2023, families with naturally conceived pregnancies and those utilizing ART for conception have been followed up at our center. The inclusion criteria for the study included children under 18 years of age at the time of follow-up, and the exclusion criteria were as follows: 1. Parents diagnosed with chromosomal disorders (e.g., Down syndrome, Turner syndrome, chromosomal translocation); 2. Conception through oocyte or sperm donation; 3. Parents with autoimmune diseases (e.g., lupus, type 1 diabetes) due to their potential confounding effects on pregnancy outcomes; 4. Mothers with reproductive system developmental abnormalities. Furthermore, singleton births were exclusively included to eliminate confounding effects from multiple pregnancies. Preterm birth (\u0026lt;\u0026thinsp;37 weeks) and low birth weight (\u0026lt;\u0026thinsp;2500 g) were recorded and adjusted for in multivariate analyses. In last, the study included 1579 ART children and 1463 NC children. Using propensity score matching on the basis of age and sex, with a matching tolerance of 0.01, 479 ART children were matched with 479 NC children. All the measurement indices were standardized via established protocols and instruments. BP measurements were obtained using a validated automated device (Omron, Japan) following a standardized protocol: after 10 minutes of seated rest, three consecutive readings were taken at 5-minute intervals, with the average of the last two measurements used for analysis. Examiners were blinded to conception type throughout the process. Fasting blood glucose levels were measured using enzymatic assays (Roche Diagnostics), and birth weight data were extracted from obstetric records.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eDue to the wide age range and its significant impact on children's BP, we standardized the data by calculating Z scores for height, weight, SBP, and DBP based on age-specific mean and standard deviation values for Chinese children. Anthropometric data were further standardized to Z scores according to Chinese age- and sex-specific standards[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] to minimize age and sex effects. Statistical analyses were conducted via SPSS 25.0 software (SPSS Inc., Chicago, IL, USA). 1) Normally distributed data are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), whereas nonnormally distributed data are presented as the median (interquartile range) (median (IQR)). 2) Normally distributed metric data, comparisons between the means of two groups were performed via the independent samples t test, and comparisons among multiple groups were performed via one-way analysis of variance (ANOVA). 3) Nonnormally distributed data, the Mann‒Whitney U test was used to compare means between two groups. 4) Categorical data comparisons, the chi-square test or Fisher's exact probability test was used. Pearson correlation analysis was used to determine the correlation between children's BP and continuous variables, and point-biserial correlation analysis was used to determine the correlation between children's blood pressure and binary variables. A two-sided P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e Propensity score matching was performed on the enrolled participants according to age and sex, with the match tolerance set at 0.01. Each of the ART and NC groups included 479 children. The results indicated that ART children had higher SBP Z scores (0.243\u0026thinsp;\u0026plusmn;\u0026thinsp;0.787 vs. 0.156\u0026thinsp;\u0026plusmn;\u0026thinsp;0.796, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DBP Z scores (0.187\u0026thinsp;\u0026plusmn;\u0026thinsp;0.876 vs. 0.061\u0026thinsp;\u0026plusmn;\u0026thinsp;0.870, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Although all blood pressure values were within the physiological range, the significant and consistent differences observed warrant concern. Additionally, the ART offspring presented lower fasting blood glucose (FBG) levels (5.005 mmol/L\u0026thinsp;\u0026plusmn;\u0026thinsp;0.402 vs. 5.087 mmol/L\u0026thinsp;\u0026plusmn;\u0026thinsp;0.404, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and lower birth weights (3328.476 g\u0026thinsp;\u0026plusmn;\u0026thinsp;616.843 vs. 3407.912 g\u0026thinsp;\u0026plusmn;\u0026thinsp;467.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with a slightly shorter duration of pregnancy (274.748 d\u0026thinsp;\u0026plusmn;\u0026thinsp;111.749 vs. 275.873 d\u0026thinsp;\u0026plusmn;\u0026thinsp;9.362), although these differences were small and lacked significant clinical implications. We compared maternal characteristics between the two groups of children and found that mothers of ART-conceived children were elder (31.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29 vs. 27.77\u0026thinsp;\u0026plusmn;\u0026thinsp;4.325 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), had greater incidences of gestational hypertension (9.4% vs. 2.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and placenta previa (2.1% vs. 0.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with big differences, respectively. No significant difference was observed in the incidence of gestational diabetes mellitus (3.5% vs. 3.1%, p\u0026thinsp;=\u0026thinsp;0.858) among mothers. Furthermore, fathers of ART children were older (31.84\u0026thinsp;\u0026plusmn;\u0026thinsp;4.727 vs. 28.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.988 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and had a greater BMI (25.936 kg/m\u0026sup2;\u0026plusmn;3.613 vs. 25.483 kg/m\u0026sup2;\u0026plusmn;3.694, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\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\u003eParticipant characteristics by conception type\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eNC\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;479)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eART\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;479)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOffspring\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.146\u0026thinsp;\u0026plusmn;\u0026thinsp;3.727\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.196\u0026thinsp;\u0026plusmn;\u0026thinsp;3.645\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.834\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233(48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e245(51.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight\u0026nbsp;Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.204\u0026thinsp;\u0026plusmn;\u0026thinsp;1.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.385\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight\u0026nbsp;Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.247\u0026thinsp;\u0026plusmn;\u0026thinsp;1.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.376\u0026thinsp;\u0026plusmn;\u0026thinsp;0.982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.876\u0026thinsp;\u0026plusmn;\u0026thinsp;3.409\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.985\u0026thinsp;\u0026plusmn;\u0026thinsp;3.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99.777\u0026thinsp;\u0026plusmn;\u0026thinsp;11.537\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101.896\u0026thinsp;\u0026plusmn;\u0026thinsp;11.066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP\u0026nbsp;Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.156\u0026thinsp;\u0026plusmn;\u0026thinsp;0.796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.243\u0026thinsp;\u0026plusmn;\u0026thinsp;0.787\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.351\u0026thinsp;\u0026plusmn;\u0026thinsp;9.705\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.067\u0026thinsp;\u0026plusmn;\u0026thinsp;10.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\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\u003eDBP\u0026nbsp;Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.061\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.187\u0026thinsp;\u0026plusmn;\u0026thinsp;0.876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse, cpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.804\u0026thinsp;\u0026plusmn;\u0026thinsp;9.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.317\u0026thinsp;\u0026plusmn;\u0026thinsp;10.319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTG, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.833\u0026thinsp;\u0026plusmn;\u0026thinsp;0.486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.815\u0026thinsp;\u0026plusmn;\u0026thinsp;0.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.388\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFBG, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.087\u0026thinsp;\u0026plusmn;\u0026thinsp;0.404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.005\u0026thinsp;\u0026plusmn;\u0026thinsp;0.402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCHOL, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.026\u0026thinsp;\u0026plusmn;\u0026thinsp;0.688\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.074\u0026thinsp;\u0026plusmn;\u0026thinsp;0.744\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.379\u0026thinsp;\u0026plusmn;\u0026thinsp;0.572\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.459\u0026thinsp;\u0026plusmn;\u0026thinsp;0.601\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.411\u0026thinsp;\u0026plusmn;\u0026thinsp;0.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.395\u0026thinsp;\u0026plusmn;\u0026thinsp;0.298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth\u0026nbsp;weight, g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3407.912\u0026thinsp;\u0026plusmn;\u0026thinsp;467.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3328.476\u0026thinsp;\u0026plusmn;\u0026thinsp;616.683\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays\u0026nbsp;of\u0026nbsp;pregnancy, d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e275.873\u0026thinsp;\u0026plusmn;\u0026thinsp;9.362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e274.748\u0026thinsp;\u0026plusmn;\u0026thinsp;111.749\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\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\u003eMaternal\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal\u0026nbsp;age, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.77\u0026thinsp;\u0026plusmn;\u0026thinsp;4.325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\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\u003eMaternal\u0026nbsp;height, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e162.056\u0026thinsp;\u0026plusmn;\u0026thinsp;4.812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e161.643\u0026thinsp;\u0026plusmn;\u0026thinsp;4.481\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal\u0026nbsp;weight, kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.954\u0026thinsp;\u0026plusmn;\u0026thinsp;10.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.484\u0026thinsp;\u0026plusmn;\u0026thinsp;9.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal\u0026nbsp;BMI, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.581\u0026thinsp;\u0026plusmn;\u0026thinsp;3.732\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.119\u0026thinsp;\u0026plusmn;\u0026thinsp;3.275\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.177\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal\u0026nbsp;prepregnancy diseases\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperthyroidism, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal\u0026nbsp;pregnant\u0026nbsp;diseases\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGDM, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.858\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIH, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45(9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\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\u003ePP, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\u0026nbsp;age, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.84\u0026thinsp;\u0026plusmn;\u0026thinsp;4.727\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\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\u003ePaternal\u0026nbsp;height, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174.014\u0026thinsp;\u0026plusmn;\u0026thinsp;5.163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e173.223\u0026thinsp;\u0026plusmn;\u0026thinsp;5.421\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\u0026nbsp;weight, kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.267\u0026thinsp;\u0026plusmn;\u0026thinsp;12.344\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.753\u0026thinsp;\u0026plusmn;\u0026thinsp;11.577\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\u0026nbsp;BMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.483\u0026thinsp;\u0026plusmn;\u0026thinsp;3.694\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.936\u0026thinsp;\u0026plusmn;\u0026thinsp;3.613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\u0026nbsp;diseases\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\u0026nbsp;mellitus, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(0.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.251\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\u0026nbsp;hypertension, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParental\u0026nbsp;smoking, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e132(30.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144(30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcoholism, no.\u0026nbsp;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNOTE: Continuous variables presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD; categorical data as n(%). Body mass index, BMI; Systolic blood pressure, SBP; Diastolic blood pressure, DBP; Counts per minute, cpm; Triglyceride, TG; Fasting blood glucose, FBG; Cholesterol, CHOL; Low-density lipoprotein, LDL; High-density lipoprotein HDL; Preterm birth, PTB; Gestitional diabetes mellitus, GDM; Pregnancy-induced hypertension, PIH; Placenta praevia, PP\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe above results indicate that offspring conceived through ART indeed have increased BP but this effect may be influenced by parental factors such as age. Therefore, we conducted correlation analyses to explore potential factors associated with BP in ART-conceived children. In addition to parental age and BMI, we analyzed the birth circumstances of the children, including premature birth and cesarean section, reasons for maternal infertility, maternal preconception and prenatal diseases, paternal habits and diseases, and ART procedures such as embryo cryopreservation and ICSI. The results revealed that SBP and DBP were associated with only whether fresh embryo transfer (Fresh-ET) or frozen embryo transfer (FET) occurred (β=-0.165, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and were not related to parental BMI, age, hypertension status, adverse lifestyle habits (such as smoking and alcohol consumption), maternal pregnancy complications, or infertility causes (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eCorrelation Analysis of Blood Pressure in ART Offspring\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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\u003eSBP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDBP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePoint-biserial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePoint-biserial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOffspring\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=\"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\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.668\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.305\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.316\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal\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=\"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\u003eAge, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.692\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.281\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.313\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal\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=\"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\u003eAge, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.339\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEtiology of infertility\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=\"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\u003eTubal infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.653\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.279\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrial polyp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal prepregnatal diseases\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=\"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\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.645\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperthyroidism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.474\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.716\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal pregnant diseases\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=\"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\u003ePIH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.738\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.563\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal diseases\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=\"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\u003ePaternal mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.379\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.968\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.697\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParental smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.569\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbryo transfer\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=\"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\u003eWhether FET\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.235\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhether ICSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.926\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.327\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNOTE: Body mass index, BMI; Polycystic ovarian syndrome, PCOS; Primary ovarian insufficiency, POI; Recurrent spontaneous abortion, RSA; Gestational diabetes mellitus, GDM; Pregnancy-induced hypertension, PIH; Placenta previa, PP; Frozen-embryo transfer, FET; Intracytoplasmic sperm injection, ICSI\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThese findings suggest that the BP of ART offspring is influenced mainly by the transplantation method during ART but is slightly attributable to parental infertility. To further substantiate this viewpoint, we divided the ART children into FET and Fresh-ET groups, which were matched on the basis of parental age and BMI via propensity scores with a tolerance of 0.01. Each group included 135 children. Comparisons of BP between these groups revealed that the Fresh-ET group had higher SBP (0.438\u0026thinsp;\u0026plusmn;\u0026thinsp;0.832 vs. 0.073\u0026thinsp;\u0026plusmn;\u0026thinsp;0.677, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DBP (0.423\u0026thinsp;\u0026plusmn;\u0026thinsp;0.909 vs. -0.091\u0026thinsp;\u0026plusmn;\u0026thinsp;0.690, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than did the FET group. Especially, there were no differences in BP between the FET group and the NC group, whereas the Fresh-ET group presented higher SBP (0.438\u0026thinsp;\u0026plusmn;\u0026thinsp;0.832 vs. 0.156\u0026thinsp;\u0026plusmn;\u0026thinsp;0.796, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DBP (0.423\u0026thinsp;\u0026plusmn;\u0026thinsp;0.909 vs. 0.061\u0026thinsp;\u0026plusmn;\u0026thinsp;0.870, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than the NC group did, indicating that Fresh-ET is the cause of elevated BP in ART offspring. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of blood pressure among the Fresh-ET group, frozen-embryo transfer group and natural conception group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eFresh-ET\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;135)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFET\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;135)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNC\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;479)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104.100\u0026thinsp;\u0026plusmn;\u0026thinsp;11.513 \u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.870\u0026thinsp;\u0026plusmn;\u0026thinsp;10.607 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e99.777\u0026thinsp;\u0026plusmn;\u0026thinsp;11.537 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP\u0026nbsp;Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.438\u0026thinsp;\u0026plusmn;\u0026thinsp;0.832 \u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.073\u0026thinsp;\u0026plusmn;\u0026thinsp;0.677 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.156\u0026thinsp;\u0026plusmn;\u0026thinsp;0.796 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.100\u0026thinsp;\u0026plusmn;\u0026thinsp;10.631 \u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.130\u0026thinsp;\u0026plusmn;\u0026thinsp;9.899 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60.351\u0026thinsp;\u0026plusmn;\u0026thinsp;9.705 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP\u0026nbsp;Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.423\u0026thinsp;\u0026plusmn;\u0026thinsp;0.909 \u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.091\u0026thinsp;\u0026plusmn;\u0026thinsp;0.690 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.061\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 \u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNOTE: The fresh-embryo transfer group and the frozen-embryo transfer group were propensity score matched on the basis of parental age and BMI. Fresh-embryo transfer, Fresh-ET; Frozen-embryo transfer, FET; Systolic Blood Pressure, SBP; Diastolic Blood Pressure, DBP; Identical subscript letters indicate no significant difference, whereas different subscript letters indicate significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) differences.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCompared with NC children, children born through ART exhibit higher SBP and DBP, despite all BP values being within the physiological range. This significant and consistent difference warrants attention. ART, especially fresh ET, appears to have a direct impact on offspring BP.\u003c/p\u003e \u003cp\u003eIn this study, a negative correlation was observed between FET and blood pressure in ART offspring. The BP of offspring from FET was lower than that of offspring from Fresh-ET. Age and BMI of the parents were included in adjusted models, suggesting limited confounding effects. Similar findings were observed in a study on offspring of overweight/obese mothers, where offspring conceived through FET presented significantly higher BMI-Z scores, SBP-Z scores, and overall metabolic scores than offspring conceived through fresh-ET [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Additionally, studies[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] have shown that offspring from ART commonly exhibit atrial enlargement, ventricular wall thickening, and impaired systolic-diastolic function. This phenomenon was more pronounced in the fresh embryo transfer group, suggesting that fresh embryo transfer may have a greater impact on cardiovascular abnormalities in offspring[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In addition, a study based on an analysis of a large Nordic dataset revealed that singleton pregnancies conceived through frozen embryo transfer reduced the likelihood of low birth weight, preterm birth, and small for gestational age (SGA)[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Reducing the risk of adverse birth outcomes, such as preterm birth or SGA, may help mitigate the occurrence of these phenomena[\u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In addition, freezing and thawing may cause changes in epigenetics during embryonic stages and subsequently alter the development of FET offspring [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Some of these epigenetic changes may persist and be passed on to the offspring after birth[\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, currently, this impact is not serious. From the perspective of the intrauterine environment, the supraphysiological hormone levels of ovarian stimulation in fresh-ET cycles may influence the implantation and development of the embryo[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Research has shown that elevated levels of estradiol and progesterone (\u0026gt;\u0026thinsp;3,450 pg/mL) on the day of hCG administration during controlled ovarian hyperstimulation are associated with increased odds of developing preeclampsia and delivering small-for-gestational-age (SGA) infants in IVF cycles, resulting in singleton pregnancies[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In contrast, the intrauterine environment of FET cycles is more natural than that of fresh-ET cycles[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The lower BP in FET offspring may result from reduced exposure to supraphysiological hormone levels during ovarian stimulation, which are characteristic of fresh-ET cycles and may impair vascular development.\u003c/p\u003e \u003cp\u003eThis matched cohort study represents a comprehensive multigenerational assessment of blood pressure (BP) determinants in children conceived through assisted reproductive technology (ART) to date. By utilizing age- and sex-matched naturally conceived controls, we systematically incorporated various factors, including pediatric parameters (Anthropometric measures, glucose homeostasis, and lipid metabolism profiles) and parental exposures (Demographic characteristics, metabolic comorbidities, infertility etiologies, and lifestyle behaviors). Through rigorous multivariable regression models and propensity score matching analyses, we elucidated the association between specific ART procedures (e.g., treatment protocols, ICSI or IVF, and fresh or frozen embryo transfer) and elevated BP trajectories in offspring.. However, it is important to note that this study is retrospective, and despite strict testing during the population follow-up process, there may still be recall bias regarding parental medical history and lifestyle habits. In past designs, accurate ascertainment of these factors is inherently constrained by recall bias and the lack of standardized assessment tools. Additionally, the single-center design limits generalizability. Nevertheless, the elevated BP in children conceived through ART still warrants attention, even if the increase is within the physiological range.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData available on request\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article will be shared upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy design: Y-FS and L-LC. Data collection: Y-FS, and\u0026nbsp;J-LC. Data analysis: Y-FS,\u0026nbsp;X-QZ, and J-LC. Supervision: Y-FS. Writing the original article: Y-FS. Revision: L-LC. All\u0026nbsp;the\u0026nbsp;authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was partly funded by the National Key R\u0026amp;D Program of China (2022YFC2704404), the Shandong Provincial Natural Science Foundation (ZR2022JQ33), the CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), and the National Special Support Program for High-level Talents.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWyns C, De Geyter C. ART in Europe, 2018: results generated from European registries by ESHRE. 2022, 2022: hoac022.\u003c/li\u003e\n\u003cli\u003eQiao J, Feng HL. Assisted reproductive technology in China: compliance and non-compliance. Transl Pediatr 2014, 3: 91-7.\u003c/li\u003e\n\u003cli\u003ePinborg A, Wennerholm UB, Bergh C. Long-term outcomes for children conceived by assisted reproductive technology. 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J Am Coll Cardiol 2018, 72: 1267-74.\u003c/li\u003e\n\u003cli\u003eRexhaj E, Pireva A, Paoloni-Giacobino A, Allemann Y, Cerny D, Dessen P, et al. Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media. Am J Physiol Heart Circ Physiol 2015, 309: H1151-6.\u003c/li\u003e\n\u003cli\u003eYeung EH, Trees IR, Clayton PK, Polinski KJ, Livinski AA, Putnick DL. Infertility treatment and offspring blood pressure-a systematic review and meta-analysis. Hum Reprod Update 2025, 31: 2-20.\u003c/li\u003e\n\u003cli\u003eZhu Futang Practical Pediatrics (8th edition)[J]. Chinese Journal of Clinicians, 2015(07):53.DOI:CNKI:SUN:ZLYS.0.2015-07-017.\u003c/li\u003e\n\u003cli\u003eZhang B, Wang Z, Dai K, Cui L, Chen ZJ. Associations of maternal obesity, frozen embryos, and offspring adverse cardiometabolic alterations. 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Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update 2018, 24: 35-58.\u003c/li\u003e\n\u003cli\u003eGullo G, Scaglione M, Cucinella G, Chiantera V, Perino A, Greco ME, et al. Neonatal Outcomes and Long-Term Follow-Up of Children Born from Frozen Embryo, a Narrative Review of Latest Research Findings. Medicina (Kaunas) 2022, 58.\u003c/li\u003e\n\u003cli\u003eRobbins CL, Hutchings Y, Dietz PM, Kuklina EV, Callaghan WM. History of preterm birth and subsequent cardiovascular disease: a systematic review. Am J Obstet Gynecol 2014, 210: 285-97.\u003c/li\u003e\n\u003cli\u003eCruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, Figueras F, Sitges M, Bijnens B, et al. Fetal cardiovascular remodeling persists at 6 months in infants with intrauterine growth restriction. Ultrasound Obstet Gynecol 2016, 48: 349-56.\u003c/li\u003e\n\u003cli\u003eGuo XY, Liu XM, Jin L, Wang TT, Ullah K, Sheng JZ, et al. 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Large for gestational age and macrosomia in singletons born after frozen/thawed embryo transfer (FET) in assisted reproductive technology (ART). Birth Defects Res 2018, 110: 630-43.\u003c/li\u003e\n\u003cli\u003eMing L, Liu P, Qiao J, Lian Y, Zheng X, Ren X, et al. Synchronization between embryo development and endometrium is a contributing factor for rescue ICSI outcome. Reprod Biomed Online 2012, 24: 527-31.\u003c/li\u003e\n\u003cli\u003eImudia AN, Awonuga AO, Doyle JO, Kaimal AJ, Wright DL, Toth TL, et al. Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization. Fertility and Sterility 2012, 97: 1374-9.\u003c/li\u003e\n\u003cli\u003eLawrenz B, Coughlan C, Melado L, Fatemi HM. The ART of frozen embryo transfer: back to nature! Gynecol Endocrinol 2020, 36: 479-83.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Reproductive technology, assisted, blood pressure, children","lastPublishedDoi":"10.21203/rs.3.rs-6137949/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6137949/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: This study examined blood pressure disparities between assisted reproductive technology (ART)-conceived and naturally conceived (NC) offspring. It also explored the associated influencing factors and elucidated the role of ART in this process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A total of 479 pairs of children, comprising a matched group in terms of age and sex, were selected from a single reproductive center. The groups included NC children and ART children. Various indicators,such as glucose and lipid metabolism levels, birth conditions, parental health status, and infertility causes,were analyzed. The study also investigated the correlation between these indicators and children's blood pressure, as well as the role they play.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Multivariate analyses revealed that ART-conceived offspring had elevated systolic blood pressure (SBP) (Δz-score=0.09, p\u0026lt;0.001) and diastolic blood pressure (DBP) (Δz-score=0.13, p\u0026lt;0.001) compared to NC counterparts. Especially, while the observed blood pressure (BP) differences were statistically high, all values fell within age- and sex-adjusted normative ranges for pediatric populations. The increase in offspring blood pressure was unrelated to parental factors such as age, BMI, or infertility conditions but was rather associated with the type of ART procedure—either fresh embryo transfer (Fresh-ET) or frozen embryo transfer (FET). After controlling confounding factors, offspring from Fresh-ET pregnancies presented a greater blood pressure than those from FET and naturally conceived pregnancies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Compared with NC children, childrenconceived through ART havehigher SBP and DBP, despite all blood pressure values being within the physiological range. This obvious and stable difference deserves our attention. Multivariable analyses revealed that ART procedures themselves—particularly fresh embryo transfer—may exert direct influences on offspring hemodynamics.\u003c/p\u003e","manuscriptTitle":"The Impact of ART on the Elevation of Offspring Blood Pressure: A Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-06 10:37:12","doi":"10.21203/rs.3.rs-6137949/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4a61a443-aae0-45c2-b700-59944e54f0d3","owner":[],"postedDate":"March 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-06T10:37:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-06 10:37:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6137949","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6137949","identity":"rs-6137949","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}