Factors Affecting Blood Pressure at Birth

There are many complexities to the changing patterns of blood pressure (BP) in the newborn period. Infant characteristics such as gestational age at birth, postnatal and postmenstrual (formerly termed postconceptual [AAP 2004]) age, as well as appropriateness of size for gestational age all influence BP. Maternal illnesses such as diabetes and other prenatal factors may also affect BP levels following delivery. As in older children, BP values in neonates may vary according to the method of BP assessment (e.g., intraarterial, Doppler, oscillometric) and according to the infant’s state (e.g., sleeping, crying, feeding). All these factors need to be taken into account when reviewing the literature on BP standards as well as in clinical practice. Despite the fact that neonatal BPs have been measured for decades, we are still in the early phase of identifying the normal patterns of infant BPs, and there are still many physiologic changes that need further investigation.

Data on BP on the first day of life was published in 1995 by Zubrow and coworkers. From data on 329 infants on day 1 of life, they were able to define the mean plus upper and lower 95% confidence limits for BP; their data clearly demonstrated increases in BP with increasing gestational age and birth weight ( Fig. 16.1A and B ). A more recent study by Pejovic and coworkers, limiting their analysis to hemodynamically stable premature and term infants admitted to the neonatal intensive care unit (NICU), also showed that BPs on day 1 of life correlated with gestational age and birth weight. Healthy term infants do not seem to demonstrate this same pattern.

(A and B) Linear regression of systolic and diastolic blood pressures by birth weight (A) and gestational age (B), with 95% confidence limits (CLs; upper and lower dashed lines ).

(Reproduced from Zubrow AB, Hulman S, Kushner H, et al. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. J Perinatol. 1995;15:470-479, with permission from Nature Publishing Group.)

After the first day of life, it appears that BPs in premature newborns increase more rapidly over the first week or two of life followed by a slowing of the rate of increase. The previously mentioned Philadelphia study categorized over 600 infants in the NICU into gestational age groups and showed a similar rate of BP increase over the first 5 days of life, regardless of gestational age. The more recent study by Pejovic and colleagues on stable NICU infants showed a similar pattern with BPs in each gestational age category of premature infants increasing at a faster rate over the first week of life with subsequent slowing. In these infants, they determined that the rate of rise was more rapid in the preterm than full-term infants ( Fig. 16.2 ). As premature neonates mature, the strongest predictor of BP is postmenstrual age. Fig. 16.3 from Zubrow and coworkers shows the regression lines between postmenstrual age and systolic and diastolic BP along with the upper and lower 95th confidence limits for systolic and diastolic BP for each week of postmenstrual age.

Increase in systolic (A), diastolic (B), and mean (C) blood pressure during the first month of life in infants classified by estimated gestational age: A, ≤28 weeks; B, 29–32 weeks; C, 33–36 weeks; D, ≥37 weeks.

(Reproduced from Pejovic B, Peco-Antic A, Marinkovic-Eric J. Blood pressure in non-critically ill preterm and full-term neonates. Pediatr Nephrol. 2007; 22:249-257, with permission from Springer Science + Business Media.)

Linear regression of mean systolic (A) and diastolic (B) blood pressures by postmenstrual (postconceptual) age in weeks, with 95% confidence limits (CLs; upper and lower dashed lines ).

(Reproduced from Zubrow AB, Hulman S, Kushner H, et al. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. J Perinatol. 1995;15:470-479, with permission from Nature Publishing Group.)

In term infants, appropriateness for gestational age seems to be an important influence on BP. In an Australian study of healthy term infants, BPs were higher on day 2 of life compared to day 1 but not thereafter. In addition, a correlation between birth weight and BP on day 3 of life was recently demonstrated in a large Japanese study of term infants ; this study also showed an increase in BP from days 2 through 4 of life, which is consistent with studies mentioned previously. A Spanish study demonstrated that small for gestational age infants had the lowest BP at birth but subsequently had the fastest rate of rise, so by 1 month of age, all term infants had similar BPs. Genetic factors likely also play a role in determining BP, although only limited studies have been completed to date. One study identified the cytochrome P450 (CYP2D6) CC genotype as being associated with higher BPs in preterm infants during hospitalization and at neonatal follow-up. It is likely that additional genetic mutations with an effect on neonatal BP will be identified in the future.

Maternal factors, including medications, underlying illnesses, and adequacy of nutrition during pregnancy, can also influence a neonate’s BP. Higher infant BPs have correlated with maternal body mass index greater than 30 kg/m ² and low socioeconomic status in Nigerian infants and in an Australian study to premature infants born to mothers with diabetes or neonates with abnormal uteroplacental perfusion by placental pathology. There is some suggestion in the literature that chorioamnionitis and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome may be related to lower infant BPs. While these factors may not have caused hypotension or hypertension by definition in all infants, it is clear that many antenatal and postnatal processes combine to influence BP values in the newborn period.

Normal BPs in infants older than 1 month have not been extensively studied recently. The percentile curves reported by the Second Task Force of the National High Blood Pressure Education Program (NHBPEP) ( Fig. 16.4 ) remain the most widely available reference values. These curves allow BP to be characterized as normal or elevated not only by age and gender, but also by length (provided in the legend below the curves). Unfortunately, these BP values were determined by a single measurement on awake infants by the Doppler method, which reduced the number of diastolic BP readings by more than half. Comparison with the more recently published values for 1-year-olds in the Fourth Report from the NHBPEP reveals significant differences that further question the validity of the 1987 curves. Additionally, a recent study of 406 healthy term infants with BPs measured by the oscillometric method on day 2 of life and then at 6 and 12 months of age demonstrated BPs that are slightly higher than the Task Force values. These issues highlight that there is clearly a pressing need for new normative BP data on infants during the first year of life.

Age-specific percentiles for blood pressure in boys (A) and girls (B) from birth to 12 months of age.

(Reprinted from Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children—1987. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, January 1987.)

What Level of BP Should Be Considered Hypertensive?

In older children, the definition of hypertension is persistent systolic and/or diastolic BP equal to or greater than the 95th percentile for age, gender, and height. As can be deduced from the preceding discussion, there is considerable variation in neonatal BP, and no generally agreed upon reference values are available. For term infants and infants between 1 and 12 months of age, the best available reference data would be those from the Second Task Force Report (see Fig. 16.4 ). In this age group, the diagnosis of hypertension is made if the infant’s BP is repeatedly greater than or equal to the 95th percentile for an infant of comparable age (also note that weight and length are given below the curves, and could also be used to help determine if an infant’s BP is normal or elevated).

The major unresolved question is what BP values to use in diagnosing hypertension in preterm infants. From the limited published data, it is possible to derive systolic and diastolic BP percentiles, as well as mean arterial pressure percentiles according to postmenstrual age ( Table 16.1 ). Although not derived from a large-scale study (which is sorely needed), these values may be useful clinically. Specifically, infants with BP values persistently at or above the 95th percentile may warrant closer monitoring, and those with BP values above the 99th percentile would clearly merit investigation, and possibly initiation of antihypertensive drug therapy. Although it is tempting to use these values to diagnose hypertension in a similar manner as in older infants and children, such decisions need to be tempered by clinical circumstances and personal experience.