Hypertension during childhood has emerged as an early marker of future cardiovascular and renal disease, contributing to an increased lifetime morbidity and mortality risk [1]. Children born preterm or with very low birth weight (VLBW) are especially vulnerable, due to impaired nephrogenesis, altered vascular development, and heightened susceptibility to early-onset hypertension [1,2]. Hypertensive disorders in pregnancy (HDP) — including preeclampsia and gestational hypertension—are linked to elevated blood pressure (BP) and adverse vascular phenotypes in offspring, extending from childhood into adulthood [3–7].

Multiple cohort and population-based studies support the role of intrauterine exposure to HDP in shaping long-term cardiovascular risk. Children exposed to HDP exhibit higher systolic BP, increased arterial stiffness, and subclinical endothelial dysfunction [6,8,9]. Evidence from genetic and developmental studies further corroborates the concept of fetal programming of cardiovascular outcomes [10,11]. However, most investigations have prioritized term infants or combined heterogeneous gestational age groups, potentially obscuring mechanisms specific to preterm or VLBW neonates [1,5,12–14].

Despite these findings, important knowledge gaps persist regarding the BP trajectories of preterm infants exposed to HDP, particularly in the VLBW population. These infants represent a biologically distinct group with combined risks — reduced nephron number, neonatal kidney injury, and prolonged hospital exposures — that may amplify susceptibility to hypertension [1]. Moreover, few studies have examined the potential interaction between maternal cardiovascular profile and offspring outcomes across the early life course [15,16].

Given these considerations, this study aims to evaluate the association between maternal HDP and systolic BP (SBP) in preterm children with VLBW. By focusing on a high-risk neonatal cohort, this research aims to clarify the contribution of maternal HDP to early-life SBP, addressing an important gap in pediatric cardiovascular prevention.

This study examined the association between maternal HDP and longitudinal BP outcomes in 277 VLBW infants. The primary findings include modest differences in SBP and DBP trajectories across childhood, a progressive decline in SBP % and DBP % over time, and a higher frequency of SGA births among offspring of hypertensive mothers.

These findings align with a growing body of evidence suggesting that intrauterine exposure to maternal HDP is associated with modest but persistent elevations in BP across the lifespan [5,14,18–20]. Recent findings underscore the cumulative cardiometabolic influence of maternal conditions—including HDP—on offspring cardiovascular health [5]. Consistent with this, Alsnes et al. reported sustained increases in SBP and DBP during childhood and adolescence in offspring of hypertensive pregnancies [18]. Similarly, Davis et al. observed a mean increase of 2.39 mmHg in SBP and 1.35 mmHg in DBP among exposed individuals in a meta-analysis, supporting the hypothesis that even minor BP elevations in early life may contribute to lifelong cardiovascular risk [18]. The authors’ own finding of a ∼2 mmHg difference at the upper SBP quantile and a ∼3 mmHg difference at the upper DBP quantile is in line with this evidence and may reflect early manifestations of developmental programming. Although modest in magnitude, these elevations are clinically relevant, as BP in childhood tracks into adulthood and predicts future cardiovascular outcomes [21].

These results also underscore the importance of distribution-sensitive approaches — such as quantile regression — to detect risk heterogeneity across the SBP and DBP distribution, which may be masked in mean-based analyses. Importantly, all children in the studied cohort were born VLBW, a population inherently predisposed to elevated BP and cardiovascular morbidity. This uniform high-risk background may have attenuated between-group differences, potentially masking additional contributions of maternal HDP. The co-occurrence of HDP and prematurity warrants particular attention, as both are independently associated with increased cardiovascular risk in offspring. However, separating their individual and combined effects remains a challenge. Nahum Sacks et al. highlighted the importance of clarifying whether HDP amplifies the cardiovascular risk conferred by prematurity, or vice versa [22]. Similar concerns were noted in prior research, where low birth weight, adiposity, and other perinatal factors confounded associations between maternal HDP and offspring BP [3,18,23].

Moreover, most prior studies evaluated outcomes in adolescents or young adults, when cardiovascular phenotypes are more fully expressed [3,5,19]. In contrast, the present study focuses on early childhood — a critical but underexplored window when BP trajectories may still be modifiable. Supporting this, Gootjes et al. reported no significant association between maternal HDP and SBP or DBP in children under six years [16]. Data from an Indian cohort revealed elevated SBP, but not DBP, at ages 3–7 years among those exposed to HDP.⁸ A Mendelian randomization study by Wang et al. found no evidence of a causal effect of maternal BP on offspring cardiometabolic health, including BP, using data from over 29,000 mother-offspring pairs. Together, these results suggest that intrauterine effects on offspring BP may be subtle or latent in early childhood, emphasizing the importance of long-term follow-up [24].

In the studied cohort, absolute SBP and DBP values increased with age — consistent with growth and maturation. However, SBP % and DBP % declined over time, especially among individuals in the lower quantiles — highlighting a dynamic, quantile-dependent BP trajectory. These age- and distribution-sensitive trends reinforce the need to interpret childhood BP against population-based norms. Despite these nuanced patterns, the longitudinal quantile regression did not reveal a significant association between maternal HDP and either SBP or DBP across age or quantiles. This contrasts with Hovi et al., who found significantly higher BP in young adults born VLBW compared to those born at term. Among individuals exposed to maternal HDP, the elevation in BP was even greater, suggesting that the effects of prenatal HDP exposure on BP may become more apparent later in life [2].

Several factors may explain the absence of significant associations in the present study. In addition to the homogeneous VLBW profile, which itself elevates cardiovascular risk,2 advances in perinatal care may have mitigated intrauterine HDP effects. Postnatal environments also play a crucial role: Meng et al. demonstrated that BP in early life is fluid, with trajectories influenced by growth, behavior, and socioeconomic conditions [25]. These findings emphasize the need for a life-course approach, as postnatal factors may modify or delay phenotypic expression of prenatal exposures [25].

The high frequency of SGA among exposed infants aligns with established associations between HDP and impaired fetal growth [2,26–28]. However, in the present cohort, no significant differences in BP values were observed between SGA and AGA children. This finding is consistent with the results reported by Hovi et al., who found that both SGA and AGA individuals born at VLBW had similarly elevated SBP and DBP compared to term-born controls, suggesting that prematurity and VLBW themselves may be the primary contributors to altered BP, regardless of fetal growth status [2].

A major strength of this study is the longitudinal analysis of a well-characterized VLBW cohort, using quantile-specific a method that captures variations in BP distribution often missed by conventional means. However, its single-center design may limit external validity. Residual confounding cannot be fully excluded, including lifestyle, genetic, and postnatal factors, or variability in adherence. These aspects should be considered when interpreting the results.

In this high-risk VLBW cohort, maternal HDP was not significantly associated with early childhood blood pressure. These findings suggest that the cardiovascular effects of prenatal hypertensive exposure may be delayed, subtle, or overshadowed by postnatal factors. Longitudinal monitoring into adolescence and beyond is essential to fully capture the trajectory of risk and guide early preventive strategies.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data that support the findings of this study are available from the corresponding author.