Systemic Hypertension

Factors that Influence Neonatal Blood Pressure

Many studies have examined the factors that influence BP patterns in normal and premature infants. In a study of BP in over 600 infants of various birthweights (BWs) and gestational ages (GAs) admitted to 14 Philadelphia-area NICUs, Zubrow et al. made a series of observations. First, they found that BP at birth is closely correlated with GA ( Fig. 81.1 ) and BW ( Fig. 81.2 ). Then after delivery, there is a predictable increase in BP over the first 5 days of life that is independent of these factors. Thereafter, BP continues to rise gradually, with the most important determining factor being postmenstrual (postconceptual) age ( Fig. 81.3 ). A more recent study of stable NICU infants showed a similar pattern, with BPs in each GA category of premature infants increasing at a faster rate during the first week of life, with subsequent slowing ; the rate of rise was more rapid in preterm infants than in term infants ( Fig. 81.4 ). The rate of change in BP has also been shown to be slower in infants born small for GA compared to those born appropriate for GA.

Several maternal factors have emerged that also may have important influences on neonatal BP, including antenatally administered medications and maternal health conditions. Regarding antenatal steroids, while an initial case series suggested that antenatal glucocorticoid exposure led to increased BP in the first week of life, a later randomized controlled trial of corticosteroids versus placebo showed no difference in infant BPs between groups. Inadvertent exposure to agents affecting the renin-angiotensin-aldosterone system (RAAS) during pregnancy is well-known to result in neonatal hypotension, particularly when the exposure occurs in the third trimester. There is some suggestion in the literature that chorioamnionitis and HELLP (hemolysis, elevated liver enzyme levels, low platelet count) syndrome may also be associated with lower infant BPs. On the other hand, maternal preeclampsia appears to be associated with higher offspring BP during the first month of life. Higher infant BPs have been correlated with maternal body mass index greater than 30 kg/m ² and low socioeconomic status in a study of Nigerian infants and in an Australian study of premature infants born to mothers with diabetes or neonates with abnormal uteroplacental perfusion as evidenced by placental pathology. While these factors may not have caused hypotension or HTN per se, it is clear that many prenatal and postnatal processes combine to influence BP in the newborn period.

Epidemiology

Although one recent series found that 28% of very low birth weight (VLBW) infants had at least one elevated BP reading documented during their NICU stay, the actual incidence of HTN in neonates is very low, ranging from 0.2% in healthy newborns to between 0.7% and 2.5% in high-risk newborns. However, in a recent publication from the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, while the proportion of diagnosed HTN was 1.8% in infants admitted to the NICU, they found that another 3.7% had undiagnosed HTN. This was estimated based upon BP values from a literature review conducted by the AWAKEN investigators themselves, as opposed to the values recommended by the AAP CPG, again highlighting the need for more robust normative data for neonatal BP.

Certain categories of infants are at significantly higher risk, however. For example, HTN is relatively common in patients with a history of umbilical artery (UA) catheterization (3%) and those with bronchopulmonary dysplasia (BPD) (as high as 43%). In one series it was also associated with patent ductus arteriosus and intraventricular hemorrhage. On the other hand, HTN is so uncommon in otherwise healthy term infants that routine BP determination is not even recommended.

Fewer data are available on the incidence of sustained HTN in NICU graduates. In their classic study, Sheftel et al. performed BP measurement in infants followed up in a neonatal follow-up clinic and found that 8.9% were hypertensive according to criteria used at that time. A later report by some of the same authors demonstrated an incidence of 2.6%. Secondary causes such as those discussed later were found in most cases. More recently, an incidence of elevated BP of 2.9% was seen in a cohort of infants from the neonatology follow-up clinic at the University of Iowa Children’s Hospital; elevated BP was associated with the cytochrome P450 genotype ( CYP2D6 ) in that cohort. Given these data, it is recommended that BP screening be incorporated into the long-term follow-up of NICU graduates.

Pathophysiology

While the differential diagnosis of HTN in the neonate or older infant is extensive ( Box 81.1 ), the most important categories of causes of neonatal HTN include renovascular HTN, BPD, and congenital and acquired kidney disease.