Neonatal hypotension is a common condition/disorder encountered in the neonatal intensive care unit (NICU) [1]. However, its definition, diagnosis, treatment, and prognosis remain controversial, and there is a lack of consensus among clinicians regarding its influencing factors [2]. Myocardial dysfunction and abnormal peripheral vasoregulation during the transitional period are the most common causes of hypotension in neonates [3].

In the NICU, targeted echocardiography is used to detect heart disease and assess cardiac function [4]. Following technological advancements, several tools have been developed to evaluate the cardiac function in children and adults. However, portable echocardiography has limited applicability for thorough cardiac evaluation in neonates because of their small size and relatively unstable condition. Despite the limitations of echocardiographic equipment, M-mode assessment remains rapid, easily applicable, and highly reliable, making it the preferred method for evaluating the ejection fraction (EF) in critically ill neonates.

Our research was initiated to determine which treatment is most appropriate when hypotension develops in newborns. There are several causes of low blood pressure; however, in newborns, the most common treatment for hypotension involves the provision of a volume of inotropes. Therefore, we aimed to determine whether echocardiography results were helpful in determining the cause of hypotension and whether using inotropics improved EF in such patients. Furthermore, we aimed to identify the correlation between EF and blood pressure in neonates using M-mode echocardiography and investigate the factors that may influence neonatal hypotension.

Among the 1,191 echocardiograms, 55 performed after 7 days of life were excluded. The remaining 1,136 echocardiograms were used in this study. The mean±standard deviation GA of the cohort was 34.8±4.0 weeks, and the mean birth weight was 2,404.9±876.5 g. The male-to-female ratio was 53.4% to 46.6%. A total of 760 neonates (68.6 %) were delivered via cesarean section. Mechanical ventilation was required for 394 patients (34.7%). Fentanyl was administered in 195 patients (17.2%), morphine in 43 patients (3.8%), and aminophylline and/or caffeine in 219 patients (19.3%). RDS was diagnosed in 253 patients (22.3%) and PDA in 415 patients (36.5%). The mean age at which echocardiograms were obtained was 3.4±1.6 days of life.

Among the 1,191 echocardiograms, 55 performed after seven days of life were excluded. Among the 1,136 remaining echocardiograms, 86 showed low EF and 1,050 showed normal EF. Only 11 (12.8%) patients with low EF had actual hypotension, whereas 59 (5.6%) with normal EF had hypotension (Table 1).

We assessed the correlations between EF and SBP, DBP, and MBP using M-mode echocardiography and found that EF was significantly associated with SBP in both univariate and multivariate analyses but not with DBP and MBP. Multivariate analysis showed that higher GA, absence of PDA, and lack of fentanyl and aminophylline/caffeine use were significantly correlated with higher SBP, whereas higher GA, absence of PDA, and lack of fentanyl and aminophylline/caffeine use were significantly correlated with DBP. MBP, considered a sensitive indicator of hypotension, significantly correlated with higher GA, absence of PDA, and no need for fentanyl administration or aminophylline/caffeine usage (Table 2). EF was also significantly associated with HR but not with UO in both univariate and multivariate analyses. The multivariate analysis revealed that lower GA and aminophylline/caffeine use were associated with HR, whereas lower GA, absence of PDA, and lack of fentanyl and aminophylline/caffeine correlated with increased UO (Table 3). We further investigated the influence of EF on the inotropes (dopamine and dobutamine). As expected, EF showed no significant differences according to inotrope use, and this analysis included all study participants regardless of GA (Table 4).

Figure 1 shows the correlations of EF with SBP, DBP, and MBP. Only the EF and SBP were significantly correlated. There was also a correlation between the EF, HR, and UO. EF did not correlate with HR or UO.

Overall, our study found that EF was not correlated with MBP, a sensitive clinical indicator of blood pressure, although it was correlated with SBP. Additionally, inotropes did not affect the EF. Although it has been hypothesized that inotropes may influence EF, it is important to consider that they also increase peripheral vascular resistance. As both blood pressure and EF remained unchanged, we performed a statistical analysis of the collected data.

Studies in adults have shown that reduced EF is generally associated with lower SBP and MBP because these parameters are influenced by cardiac output [7,8]. In patients with heart failure, a lower EF often correlates significantly with decreased SBP and MBP owing to impaired ventricular function [9]. However, the relationship between EF and DBP is less consistent because DBP is more dependent on peripheral vascular resistance than on cardiac output [10]. In some cases, a markedly low EF has been associated with reduced DBP; however, this relationship has not been uniformly observed across studies. Overall, while EF is a critical indicator of systolic function and influences blood pressure levels, the degree of impact can vary depending on the patient’s overall cardiovascular health and the presence of conditions such as heart failure [11].

EF can be measured using M-mode echocardiography as the fraction of blood ejected from a ventricle with each heartbeat and serves as a primary indicator of left ventricular systolic function, which can be easily obtained by dividing the volume ejected by the heart (stroke volume) by the volume of the filled heart (end-diastolic volume). Studies in adults have previously shown that individuals with a low EF showed significantly lower BP than those with a normal EF [12], and that a marked reduction in EF (≤35%) is more significantly correlated with hypotension than those with a moderately reduced (35% to 55%) and/or normal-range EF (≥55%). Patients diagnosed with congestive heart failure or myocardial infarction demonstrate low cardiac output due to myocardial dysfunction; thus, EF was low in such cases, whereas hypotension was found to be associated in most studies [12-14]. Conversely, our study found no significant correlations between EF and DBP or MBP in neonates, although SBP alone showed a significant correlation with EF (P=0.046), which was statistically significant but not clinically meaningful. As shown in Table 3, EF was found to be associated with HR but showed no statistically significant relationship with UO. As shown in Figure 1, EF was weakly correlated with HR and UO. When considering a P-value threshold of <0.001 for significance in multivariate analysis, neither HR nor UO reached statistical significance. These results suggest that the EF is weakly associated with the HR and UO.

Blood pressure depends on the cardiac output and systemic vascular resistance. Cardiac output is determined by the preload, myocardial contractility, and afterload. Some researchers have previously shown that hypotensive preterm infants demonstrate normal or high ventricular output; therefore, their EF may appear to be normal [15,16]. Preterm infants with hypotension have a limited ability to increase cardiac output in response to volume infusion or the administration of inotropes. In addition, they are more sensitive to increased afterload, which frequently leads to decreased cardiac output [17,18]. A previous study reported a weak correlation between left ventricular output and blood pressure in preterm infants [19].

Myocardial dysfunction and abnormal peripheral vasoregulation are the primary causes of hypotension in neonates, including preterm infants. The neonatal myocardium comprises a large quantity of collagen (primarily type I collagen), resulting in a more rigid and less compliant myocardium [20,21]. Left ventricular relaxation and compliance improve when the collagen content reaches normal levels approximately 1 month after birth [20]. Myocardial contraction, relaxation and calcium homeostasis in preterm infants differ from those in full-term neonates because immature myocytes rely less on the release and reuptake of calcium from the sarcoplasmic reticulum. Preterm infants also exhibit reduced systolic and diastolic functions and increased sensitivity to increments in afterload, often resulting in decreased cardiac output, consequently causing hypotension in some cases [3]. Contraction and relaxation of the myocardium are both decreased in preterm infants, indicating that the EF can be normal. Term infants show higher basal contractility than older children, whereas the immature myocardium is more sensitive to changes in afterload; contractility decreases significantly with small increases in afterload. However, following the transitional period, the myocardium tends to adapt to increases in afterload as the blood pressure increases [2,3]. One study performed in Finland showed that the diastolic pressure patterns demonstrated by preterm infants represented a transition between those found in the fetus and those in term infants [22]. These changes reflect an improvement in left ventricular diastolic function, which is more marked during relaxation than during compliance. Furthermore, in prior studies, age-related changes were observed in diastolic but not systolic heart performance in term infants during the first 6 months of life [20,22].

Neonatal hypotension is associated with several other factors. Our study showed that PDA was significantly associated with low SBP and DBP, consistent with the results of previous studies. Ratner et al. [23] reported that a mean DBP <28 mm Hg on the 3rd day of life was significantly associated with PDA in 93% of patients. Some medications such as fentanyl can also affect blood pressure and are commonly used in infants receiving mechanical ventilation. A previous study reported no statistically significant differences between fentanyl and placebo groups with regard to MBP [24]. Another study reported that sufentanil and fentanyl had no effect on blood pressure [25]. However, our study also showed that fentanyl was most significantly correlated with low blood pressure.

A limitation of this study is that it did not compare differences in EF based on inotrope use before versus after cardiac evaluation, as it focused on inotrope use only at the time of cardiac assessment and did not distinguish between the types of inotropes. In addition to myocardial dysfunction, decreased peripheral resistance should also be considered an important factor in the development of neonatal hypotension. Therefore, neonatologists should exercise caution when prescribing medications that can affect the peripheral vascular resistance and potentially lead to hypotension.