Hypertension Research (2015) 38, 577–587

& 2015 The Japanese Society of Hypertension All rights reserved 0916-9636/15
www.nature.com/hr

REVIEW

Strengths and limitations of current pediatric blood

pressure nomograms: a global overview with a special
emphasis on regional differences in neonates and
infants
Massimiliano Cantinotti1,2, Raffaele Giordano1, Marco Scalese2, Sabrina Molinaro2, Bruno Murzi1,
Nadia Assanta1, Maura Crocetti1, Marco Marotta1, Sergio Ghione1,2 and Giorgio Iervasi1,2

The availability of robust nomograms is essential for the correct evaluation of blood pressure (BP) values in children. A literature
search was conducted by accessing the National Library of Medicine by using the keywords BP, pediatric and reference values/
nomograms. A total of 43 studies that evaluated pediatric BP nomograms were included in this review. Despite the accuracy of
the latest studies, many numerical and methodological limitations still remain. The numerical limitations include the paucity of
data for neonates/infants and for some geographic areas (Africa/South America/East Europe/Asia) and ethnicities. Furthermore,
the data on ambulatory BP and response to exercise are extremely limited, and the criteria for stress-test interruption are
lacking. There was heterogeneity in the methodologies employed to perform the measurements, in the inclusion/exclusion criteria
(often not reported), in the data normalization and the data expression (Z-scores/percentiles/mean values). Although most studies
adjusted the measurements for age and/or height, the classification by specific age/height subgroups varied. Gender differences
were generally considered, whereas other confounders (that is, ethnicity/geographic area/environment) were seldom evaluated. As
a result, nomograms were heterogeneous, and when comparable, at times showed widely different confidence intervals. These
differences are most likely because of both methodological limitations and differences among the populations studied. Some
robust nomograms exist (particularly those from the USA); however, it has been demonstrated that if adopted in other countries/
continents, they may generate an unpredictable bias in the evaluation of BP values in children. Actual pediatric BP nomograms
present consistent limitations that affect the evaluation of BP in children. Comprehensive nomograms, which are based on a
large population of healthy children (including neonates/infants) and use standardized methodology, are warranted for every
country/region.
Hypertension Research (2015) 38, 577–587; doi:10.1038/hr.2015.45; published online 16 April 2015

Keywords: blood pressure; children; neonates; nomograms

INTRODUCTION need to be normalized according to age and somatic growth.1–46

Arterial blood pressure (BP) is a basic vital parameter that is measured Thus, the availability of robust nomograms is essential for the correct
at all ages1–48 (http://www.mercuryfreehealthcare.org). In adults, evaluation of BP values in children.49–53
elevated BP is defined as a risk-related threshold, that is, as that level For the determination of reference values, of paramount impor-
of BP above which clinical trials have shown (and international tance is the selection of reference individuals based on extensively
guidelines have agreed upon) that lowering BP reduces the likelihood documented inclusion and exclusion criteria and the use of quality-
of CV diseases and death.47,48 This threshold is usually 140/90 mm Hg, controlled procedures to collect data.49–53 When only small numbers
and although it may be lower in higher risk conditions (for example, of values are available, reference intervals (RIs) may be highly
in diabetes), it is not considered to be dependent on other factors such imprecise.49–53
as age, sex, body mass, ethnicity and so on.3,4 However, an essential From a clinical point of view, when multiple nomograms are
aspect of BP in the pediatric and adolescent populations is that it available and no clear recommendations exist regarding the use of one
changes (increases) with growth, making BP measurements mean- nomogram over another, a clinician makes an arbitrary choice and
ingful only if related to some indices of growth or body size.4–46 relies on it in the decision making process.49–51 As a result, if various
As a result, BP values in children, as well as any other parameter,49–53 nomograms present significant differences in RIs, this may generate

1
Department of Pediatric Cardiology and Cardic Surgery, Tuscany Foundation G. Monasterio, Massa, Italy and 2Department of Cardiology, Institute of Clinical Physiology, Pisa, Italy
Correspondence: Dr R Giordano, Tuscany Foundation ``G. Monasterio'', Pediatric Cardiology and Cardiac Surgery, Via Aurelia sud, Heart Hospital - Massa 54100, Italy.
E-mail: [email protected]
Received 27 June 2014; revised 13 January 2015; accepted 9 February 2015; published online 16 April 2015
 Pediatric blood pressure nomograms
M Cantinotti et al
578

confusion in the estimation of disease severity,49–51 thus affecting the On the basis of available data, a progressive increase in systolic BP
management of children with hypo/hypertension. (SBP) and diastolic BP (DBP) seems to occur during the first week of
The aim of this study was to critically review the strengths, accuracy life2,3,17,34 with the highest variations during the first days2,17,32,34 and
and limitations of available pediatric blood pressure nomograms. New with little variation thereafter up to 6–12 months of life.2,17,31,33 Weak
perspectives for research in the field are also described to convey the but significant positive correlations of SPB and DBP with birth
current knowledge gaps. weight,2,17,29,32–34 birth length,29,32 head circumference29 and gesta-
tional age17,29,34 were also found.
MATERIALS AND METHODS Naturally delivered neonates had higher mean BP values than
Search strategy neonates delivered by cesarean section29 and a more rapid rate of
Candidate studies for inclusion were identified by a systematic search of the increase was found in preterm compared with full-term infants.17,34 As
National Library of Medicine (PubMed access to MEDLINE citations, http:// expected, BP was lower when measured during the sleep state than
www.ncbi.nlm.nih.gov/PubMed/) conducted in March 2013. The period when the child was in a quietly awake state.34
searched covered 1985–2013. The search strategy included a combination of
Medical Subject Headings (MeSH) and free text terms for the key concepts Ambulatory blood pressure and response to stress test
starting with BP, pediatric and reference values/nomograms. The search was Ambulatory blood pressure monitoring is of great relevance for the
further refined by adding the keywords neonates/infants/adolescent, range and diagnosis of hypertension in children because of the white coat and
intervals. In addition, we identified other potentially relevant publications using masked hypertension phenomena.56 However, only a few studies have
a manual search of the references from all eligible studies and review articles as
tried to establish reference values for ambulatory BP in normal
well as from the Science Citation Index, expanded on Web of Science.
healthy children57–65 and in disease states.66 The only normative data
Titles and abstracts of all articles identified by the search strategy were
evaluated and assessed independently by two reviewers; articles were excluded
generated in a relatively large number of healthy children and
(1) if the studies included populations other than normal subjects or included adolescents (1141 healthy children and adolescents) are from
adults with children (N = 6), and (2) if the reports were published in languages Germany,62 and there are very limited data for infants and
other than English (N = 16). toddlers.67–70 Special considerations are required for neonates and
infants where important variations in BP values may occur depending
RESULTS on sleeping/awake state. In particular, infants frequently exhibit
A total of 67 publications were identified for potential inclusion sudden hypotensive or hypertensive events during sleep because the
in the study. Twenty-two studies were excluded on the basis of the autonomic nervous system is immature or may be altered in preterm
criteria listed above, leaving 45 publications for analysis; 36 babies.69,70 Finally, data on BP response to exercise in children are
surveys2–4,6,8–13,16,19–21,25–35,39,40,44,45,54,55 were performed with the extremely limited,71–73 and no clear BP cut-off values exist to
specific aim of providing reference BP values for children in a definite distinguish between the healthy and pathological states; in addition,
population, whereas the other surveys1,5,18,23,24,36,37,42,43,46 were for there are no criteria for the interruption of stress tests in cases of
other purposes, such as comparison with reference data, identification excessive BP increases.73
of time trends, comparison among different ethnicities and testing of
METHODOLOGICAL ISSUES
the methodological issues related to BP normalization in the pediatric
Selection criteria
age group.
Inclusion/exclusion criteria have been reported in many but not all of
the nomograms. In particular, studies involving neonates generally
NUMERICAL ISSUES
described the criteria employed to select the healthy subjects in some
Nomograms divided according to geographic area
detail3,14,17,29–32,34 with a few exceptions.2,33 In contrast, in articles
In Table 1, major pediatric BP nomograms, divided according to the
involving older children, the inclusion/exclusion criteria were often
major region of origin, are detailed. For some countries/continents
not reported.6,9,10,12,19,24,26,28 Furthermore, data from the Fourth
(North America, Europe, Middle East, part of Asia), there are one or
Report of the National Health and Nutrition Examination Surveys
more nomograms calculated over a wide sample of healthy children
and from other US studies have been utilized by various authors with
(from 2876 to 63 227 healthy children).6,9,39,45,54,55 In contrast, some
different selection criteria.5,24 The National High Blood Pressure
geographic areas, particularly Africa, East Europe, South America and Education Program Working Group on High BP in Children and
wide areas of Asia (particularly China and Russia) are poorly/not Adolescents decided to use height (rather than weight or body mass
represented. index (BMI)) in constructing the nomograms representing 63 227
American children to discourage the misinterpretation of relatively
Neonates and infants high BP as normal just because a child is overweight/obese.9 In fact,
The data on neonates and infants are extremely limited (0–12 months) overweight children tend to exhibit19,21,24,36 higher BP values com-
with only nine studies2,3,14,17,29–34 exhibiting a relatively good sample pared with normal weight children of the same age and height.
size of healthy subjects (over 400 subjects) (Table 2). Most of the However, overweight children were still included in the normative
above studies evaluated neonates at birth,2,17,29–32,34 and the majority database.7,9 To overcome this limitation, Rosner and colleagues, using
contained measurements repeated at 4 days of life.2,30,32–34 Few data the same data, rebuilt the nomograms excluding overweight
are available for days 2–3 of life,17,30,32,34 and up to 6 months;2,30,33 children,21 which produced only slightly lower nomograms.
data at 6 and 12 months2,31,33 are also limited. Some ethnicities, in
particular black, are almost absent, and some geographic areas are not Methods of BP measurement
represented at all (East Europe, Asia, South America). Premature and Various methodological issues affected the evaluation of the method of
full-term neonates have been considered separately only by a few BP measurement, including the use of different recorders, the cuff
authors,29,34 and various age intervals have been used in different sizes, operator skill and the number of measurements (Table 3).
studies. Consistent with both US,9 European44 and Asian74 guidelines, most of

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 Pediatric blood pressure nomograms
M Cantinotti et al
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Table 1 Major pediatric blood pressure nomograms dividedPl according to geographic area

Age
Author Numerosity interval W/H/BMI G (M) Groups Region/ethnicity

America
Nichols et al.19 3749 12–18 M/F 1610 1 Year groups 12–18 years Region: Trinidad and Tobago
Years BMI 20.6 ethnicity: nr
(4.2), 21.8 (5)
Paradis et al.8 3589 9–16 Years nr 9 Years (n = 1243, M 51%) Region: Quebec
13 Years (n = 1171 M 51%) ethnicity: nr
16 Years (n = 1156 M 50%)
Park et al.3 1554 2 Weeks–5 nr 747 2–3 Weeks (n = 105); White 1203; Black 106; Hispanic
years 1–5 Months (n = 232); 245
6–11 Months (n = 183);
1 Years (n = 245);
2 Years (n = 212);
3 Years (n = 193);
4 Years (n = 226);
5 Years (n = 158)
Park et al.11 7208 5–17 Years nr nr nr 58.5% Mexican-American, 28.3%
non-Hispanic White,13.2% African-
American
Rosner et al.13 49 967a 1–17 Years nr 25 651 1 Year groups 1–17 years Caucasian 55%, African-Amreican
29%, Hispanic 9%, Asian 3%,
Native America 1%, other 3%
Fourth report9 63 227 1–17 Years nr 51% 1 Year groups 1–17 years Nih 1963–1965 6–17 years
(n = 3647); Pittsburgh 1984 1–5
years (n = 3647);
Dallas 1976 13–17 years
(n = 11565);
Bogalusa 1976 1–17 years
(n = 7358);
Houston 1981 3–17 years
(n = 2834);
South Carolina 1985 4–17 years
(n = 6430);
Iowa 1970–1981 3–17 years
(n = 4092);
Providence 1985 1–3 years
(n = 461);
Minnesota 1986–1987
9–17 years (n = 19409);
NHANES 1988–1994
5–17 years (n = 5042)
NHANES 1999–2000 8–17years
(n = 2104)
Caucasian 55%, African-American
29%, Hispanic 9%, Asian 3%,
Native American 1%, Other 3%

Australia
Blake et al.12 2876 1–6 Years BMI 546 Caucasian 89.7%; Age 3 n 976 M
17.0 (1.4) Age 1 (n = 1090) 465 Caucasian 90%; Age 6 n 1178
16.2 (1.3) Age 3 (n = 976) Caucasian 88%
15.8 (1.8) Age 6 (n = 1178)

Europe
De Man et al.10 28 043 4–19 Years nr nr Berlin breman 11–17 years Region: Germany, Denmark,
n = 1302 (731 M); Cologne 15–19 France, Netherlands
years n = 2934 (1353 M); Copen- Ethnicity: nr
hagen 6–18 years n = 898 (447 M);
Essen 4–18 years n = 1471
(751 M)
Nancy 4–17 years n = 17 067
(8647 M); Zoetermeer 5–19 years
n = 4371 (2198 M)
De Swiet et al.33 1895 4 Days–10 nr nr 4 Days, 6 weeks, 6 months, 1 year Region Kent
born437 Years and yearly up to 10 year Ethnicity: nr
wg 4 days (n = 1895), 6 weeks
(n = 1797),
6 months (n = 1777), 1 year
(n = 1738), 2 years (n = 1681), 3
years (n = 1570), 4 years
(n = 1484),
5 years (n = 1403), 6 years
(n = 1339),
7 years (n = 1304), 8 years
(n = 1262),
9 years (n = 1235), 10 years
(n = 1211)

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M Cantinotti et al
580

Table 1 (Continued )

Age
Author Numerosity interval W/H/BMI G (M) Groups Region/ethnicity

Menghetti et al.16 11 519 5–17 Years nr 6258 M/F Region: Italy

5 Years (n = 195/145); 6 years Ethnicity: nr
(n = 443/393);
7 years (n = 349/344); 8 years
(n = 371/386);
9 years (n = 882/795); 10 years
(n = 979/ 881);
11 years (n = 688/511); 12 years
(n = 983/910);
13 years (n = 893/621); 14 years
(n = 301/172);
15 years (n = 126/34); 16 years
(n = 75/25);
17 years (n = 76/44)
Sanchez et al.6 34 986 1–18 Years nr M/F Madrid 1985 6–14 years
1 Years (n = 52/43); 2 years (n = 2003);
(n = 153/147); Alicante 1984 1–14 years
3 years (n = 244/183); 4 years (n = 2011);
(n = 375/330); Malaga 1985 5–14 years
5 years (n = 811/745); 6 years (n = 6922);
(n = 1739/1570); Avila 1983 4–14 years (n = 951);
7 years (n = 1730/1530); 8 years Madrid 1986 1–18 years
(n = 1679/1395); (n = 2419);
9 years (n = 1786/1517); 10 years Madrid 1984 2–18 years
(n = 1870/1692); 11 years (n = 3885);
(n = 2071/1712); 12 years Madrid 1985 4–14 years
(n = 1611/1517); 13 years (n = 2069);
(n = 1688/1277); 14 years Madrid;1984 4–18 years
(n = 1159/829); (n = 6990)
15 years (n = 821/762); 16 years Cantabria 1984 5–18 years
(n = 699/455); (n = 1140);
17 years (n = 594/362); 18 years Madrid 1984 6–18 years
(n = 236/204) (n = 2947);
Valencia 1986 5–14 years
(n = 559);
Valencia 1987 6–14 years
(n = 684);
Aragon 1984 4–14 years (n = 837);
Canarias 1984 5–14 years
(n = 439);
Canarias1985 5–15 years (n = 833)
Ethnicity: Caucasian
Tumer et al.40 5599 0–18 y.o. nr 2835 0–2 Years (n = 349/312); 2 years Region: Turkey
(n = 147/120); Ethnicity: nr
3 years (n = 170/170); 4 years
(n = 16/164);
5 years (n = 165/162); 6 years
(n = 190/156);
7 years (n = 146/136); 8 years
(n = 163/177);
9 years (n = 168/146); 10 years
(n = 158/162);
11 years (n = 159/156); 12 years
(n = 160/145);
13 years (n = 170/142); 14 years
(n = 125/ 139);
15 years (n = 133/ 131); 16 years
(n = 132/133);
17 years (n = 71/127); 18 years
(n = 68/86)
Mead East
Merhi et al.45 5710 5–15 Years b 2918 M–F Beirut 45.65%, Mount Lebanon
5 Years (n = 128/131); 6 years 11.22%, North 14.71%, Bekaa
(n = 320/315); 7 years (n = 366- 12.9% and South 15.41%.
/378); 8 years (n = 388/344); 9
years (n = 364/356); 10 years
(n = 394/359); 11 years (364/375);
12 years (n = 199/215); 13 years
(n = 193/140); 14 years (n =
164/161); 15 years (n = 38/18)

Asian
Chadha et al.26 8293 5–14 Years BMI 14.4 4623 5 Years (n = 311); 6 years Region: New Delhi
(1.5) (n = 725); Ethnicity: nr
7 years (n = 894); 8 years
(n = 958);
9 years (n = 1029); 10 years

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Table 1 (Continued )

Age
Author Numerosity interval W/H/BMI G (M) Groups Region/ethnicity

(n = 1019);
11 years (n = 917); 12 years
(n = 998);
13 years (n = 892); 14 years
(n = 550)
Jafar et al.24 5641 5–14 Years BMI 2974 Pakistan: Muhajir, Punjabi, Sindhi,
15.2 (4.3) M Pasthun, Baluchi
15.3 (4.3) Fb
Kelishadi et al.39 21 111 6–18 Years BMI 10 253 6 Years (n = 814); 7 years Persian 51%, Azeri 24%, Gilaki and
18.53 ± 3.84 (n = 1330); 8 years (n = 1499); 9 Mazandarani 8%, Kurd 7%, Arab
years (n = 1435); 10 years 3%, Lur 2%, Baloch 2%,Turkmen
(n = 1638); 11 years (n = 1755); 2% and other 1%).
12 years (n = 2116); 13 years
(n = 1939); 14 years (n = 2246);
15 years (n = 2131); 16 years
(n = 2036); 17 years (n = 1410);
18 years (n = 747)
Krishna et al.27 2278 3–18 Years nr 2500 M/F Region: Karnataka
3 Years (n = 42/56); 4 years Ethnicity: nr
(n = 97/73);
5 years (n = 43/27); 6 years
(n = 92/73);
7 years (n = 105/138); 8 years
(n = 118/134);
9 years (n = 109/147); 10 years
(n = 103/119);
11 years (n = 183/179); 12 years
(n = 253/272);
13 years (n = 318/469); 14 years
(n = 269/565);
15 years (n = 298/402); 16 years
(n = 158/178);
17 years (n = 34/60); 18 years
(n = 56/38)
Sharma et al.28 2453 7–16 Years b 159 1 Year groups 7–16 years Region: Chandigarh
Ethnicity: nr
Taghi Ayatollahi 2270 6.5–11.5 nr 1174 Age group7: 6.5–7.49 years; Age Iranian
et al.35 Years group 8: 7.5–8.49 years; age group Ethnicity: nr
9:8.5–9.49 years; age group 10:
9.5–10.49 years; age group 11:
10.5–11.5 years
Hashimotoet al.54 5316 2–6 Years b 2808 Age groups Niigata Prefecture (rural and city)
2 Years (n = 158); 3 years
(n = 553); 4 years (n = 793);
5 years (n = 856); 6 years (n = 448)
Abbreviations: A, ausculatory sphygmomanometry method; BMI, body mass index (kg m−2); D, dinamap; F, females ; G, gender; h, height; M, males; nr, not reported; W, weight.
Every year BMI 5 years 13.9(1.0) 13.8(1.0) 13.7(1.1) 13.8(1.1) 13.9(1.3) 14.1(1.2) 14.5(1.4) 14.9(1.6) 15.3(1.7) 15.8(1.7) 14 years 14.4(1.5).
Height 12,7 (17.9) M, 126,7 (17.4) F; Weight 24.9 (9.1) M; 25.2 (9.7) F.
aFrom Fourth report database subjects have been included only if their BMI percentile was less than the 85th percentile.
bMeasurements indicated for every age group.

the studies used the auscultatory manual method for BP measurement there are obvious limitations in obtaining a fixed position). Multiple
in older children, whereas the oscillometric method was employed in readings taken at a single visit were common in most studies, whereas
neonates and infants. Regarding recorders however, aneroid sphyg- in a few studies, the data were based on single readings.9,21 Only a few
momanometers should be considered the method of choice, because reports indicated the time of the day (mostly in the morning)2,8,16,54
mercury sphygmomanometers are being progressively banned world- and the seasons in which the data were collected.6,17,40,54 Table 3.
wide (http://www.mercuryfreehealthcare.org) as a result of being Finally, intra-observer and inter-observer variability were generally
poorly employed. Furthermore, only a few oscillometric devices have ignored, with only a few exceptions.27
been validated in children.1 Finally, regarding auscultatory measure-
ments, in almost all recent surveys, the disappearance of Korotkoff Statistical issues
sounds (K5) was established as the definition of DBP, whereas some Data normalization and expression. In children, BP measurements
older studies used K4.9,26,45 In the majority of the must be adjusted for body size, age and/or some other parameter
surveys,2,6,8,11,26–28,30–35,39 multiple cuff sizes were used according to to compare the values with those from a healthy pediatric
arm size, although the criteria for selection of cuff length and width population.9 Most of the studies had estimated values of BP
differed among the various studies. according to age2–6,8,11,12,14,16,17,19,28,31–33,39,40,45,54 or height35 or
A standard protocol9 (right arm, sitting position and rest period both.9,10,13,20,21,26,27,35 In the majority of the studies, significant linear
preceding the measurement) was usually observed, with few correlations with age were observed both for systolic and DBP with
exceptions.10 In particular, the position was not always widely ranging ‘r’ values3,4,6,8,9,11,13,19,21,27,28,35,45,54 (SBP r: 0.26–0.64;
indicated2,8,30,31 or it was supine,10,32,34 especially in neonates (where DPB r: 0.018–0.56); in a few instances, statistically significant

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Table 2 Major blood pressure nomograms for neonates and infants

Author Numerosity Age Gender/ race Age BW Weight (g)

Europe
De Swiet et al.33 1895 4 Days–10 81 M 4 Days (n = 1895), 6 weeks —
Born437 years Cucasian 97% (n = 1797), 6 m (n = 1777), 1 year
wg (n = 1738), 2 years (n = 1681)
Gemelli et al.2 514 0–12 Months 260 M Groups 3402 ± 451
0–12 months; 1 day (n = 260);
4 days (n = 260); 1 month
(n = 258); 3 months (n = 220); 6
months (n = 171); 9 months
(n = 132); 12 months (n = 144)
Pejovic et al.34 373 1 Day of life 178 M Age groups (WG): Groups:
292 Pre- Ao 28 (n = 62); I 600–999 (n = 44);
term 81 B = 29–32 (n = 146); II 1000–1240 (n = 78);
term C = 33–36 (n = 81); III 1250–1499 (n = 94);
D ⩾ 37 (n = 81) IV 1500–1999 (n = 76);
V ⩾ 200 (n = 100)
Salihoglu et al.29 982 At born 513 M WG 39.01 ± 1.49 range 34–43 BW group (g): Ao2500 (n = 45); B
34–43 WG 2500–4000 (n = 873),44000 g
(n = 64)

Australia
Kent et al.31 406 Term 1 Day– 218 M Median GW 40 weeks (range 37– 3535.0 (range 2425–4990
infants 12 months 42 weeks).
150 fol- 406 1 day, 6 months 150 (83 M),
lowed at 12 months 118 (65 M)
6 M, and
118 at
12 m
Kent et al.30 147 1–28 Days 81 M Median WG 31.9 (2.4) Median 1797 (620)
Premature 1, 2, 3, 4, 7.14, 21, 28 days range 850–4990
28–36 WG

America
Park et al.3 1554 2 Week–5 years 747 M 2–3 Week (n = 105); 1–5 months —
(n = 232); 6–11 months (n = 183);
1 year (n = 245); 2 year (n = 212); 3
year (n = 193); 4 year (n = 226); 5
year (n = 158)
Second Task Force on 7643 0–12 Months 3887 M o7 Days (n = 2880) —
Blood Pressure in 8 days ⩽ 1 months (n = 686)
Children14 1 ⩽ 6 months (n = 2374)
6 ⩽ 12 month (n = 1783)

Africa
Sadoh et al.32 473 Babies 1–4 Days 229 M WG 39.3±1.4 range 37–43 BW group (g): Ao2500 (n = 33); B
1, 2, 3, 4 days 2500–4000 (n = 402),44000 g
(n = 38)

Abbreviations: BW, birth weight; g, grams; WG, gestation weeks.

correlations were found for systolic but not DBP.11 An acceleration of is, o 5–6 years) were generally less well represented, and for some age
the increase in BP values during puberty was also reported.39 groups (especially neonates and infants), the data were very limited.
In some studies, linear correlations with Furthermore, the choice to rank BP according to just age and
height9,11,13,19,21,27,28,33,35,39,40,45 were demonstrated more strongly height implies, by definition, no consideration of body weight. BP,
than with age (SBP r: 0.11–0.64; DBP r: 0.13–0.65).14,35,45 The use however, was found to strongly correlate with body
of age and height to normalize data was confronted with a number of weight,2,28,33,39,40,45 BM,8,12,25,36,45 body surface area (BSA)28,31 and
potential problems. First, the age range and the height intervals used, waist circumference.39,75
as well as the number of subjects enrolled for various age/height Data expression also varied among the publications. The data
subgroups differed widely (Table 1). In particular, the lower ages (that were generally expressed by percentile table2,6,8,9,11,13,26,27,29,35,39,45

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 Table 3 Methodologies of major nomograms

Criteria for cuff

Study Sphygmomanometer lenght selection Criteria for cuff width selection Time of the day Time of the year Observer training Nr observer Place

America
Fourth Report9
NII MS 2 Cuff 9.5 and 13 mm — Trough-out day Trough-year No Multiple; all physician Special vans
Pittsburgh Doppler Multicuff At least 75% of upper circum. Trough-out day Trough-year — — Home
Dallas RZ (HawksleyTechnology, London, UK) Four cuff size Most of the circ upper arm Trough-out day October-December Yes Multiple School
Bogalusa MS 2/3 Of upper arm lenght At least 50% of upper arm Morning Trough-year Yes 3 School
Houston MS Multicuff At least 75% of upper arm Trough-out day Trough-year Yes Multiple Health Cl
South Carolina MS Four cuff size — Trough-out day Trough-year Yes Multiple School
Iowa RZ 2/3 Of upper arm lenght — Afternoon February-March Yes Multiple School
Providence Arteriosnde and RZ Five cuff size — Trough-out day Trough-year Yes Multiple Clin
Minessota MS At least 90% of upper arm Trough-out day Trough-year Yes Multiple School
Park et al.11 OD, Critikon Co, Tampa, FL Multiple 40–50% Of upper arm Trough-out day Trough-year Yes Multiple
Nichols et al.19 MS Multiple 40–50% Of upper arm Trough-out day Sept-Jan Yes Multiple School
Paradis et al.8 OD (Dinamap XL, model Multicuff At least 75% of upper arm Trough-out day Jan-May Yes Multiple School
CR9340, Critikon)

Australia
Blake et al.12 D 8100 AOD (CritiKon) Two cuff size Cuff width to arm circumference Trough-out day Trough-year Yes Multiple Clinic
ratio of 40–50

Europe
De Man et al.10
Berlin-Bremen RZ 3 Cuff size — — — — — School
Cologne LSH 1 Size — — — — — School
Copenhagen RZ 3 Size — — — — — School
Essen LSH 2 Size 2/3 Arm circumference — — — — School
Nancy MS 2 Size 2/3 Arm circumference — — — — Open
Zoetermeer RZ 2 Size — — — — — Open
De Swiet et al.33 MS Multiple — Trough-out day Trough-year Yes Multiple Home/clinical
Gemelli et al.2 OD Multiple — Morning Trough-year Yes Multiple Clinic
Critikon
Menghetti et al.16 SM 2 Cuff size — Trough-out day Trough-year Yes Multiple Clinic
Sanchez et al.6 SM 14 Multicuff 14 — Trough-out day Trough-year Yes Multple 14 School
Automatd 1 Not ment 1 1 not mentionated
M Cantinotti et al

Tumer et al.40 MS Multiple ½ Arm Trough-out day Trough-year Yes Multiple —

Asia
Sharma et al.28 MS Multiple — Trough-out day Trough-year Yes Multiple School
Merhi et al.45 MS Multiple 50% Of arm Trough-out day Trough-year Yes Multiple School
Ayatollahi et al.35 DA Model 500 C, Osaka Japan Multiple — Trough-out day Trough-year Yes Multiple School
Pediatric blood pressure nomograms

Kelishadi et al.39 MS Multiple 40% Of arm Trough-out day Trough-year Yes Multiple School
Krishna et al.27 MS Multiple 2/3 Of arm Trough-out day Trough-year Yes 4 dottor for 5° pts School
inter-observer variab
Chadha et al.26 MS Multiple 40% Trough-out day Trough-year Yes Multiple School
Hashimoto et al.54 OD Multiple — Morning Trough-year Yes Multiple Pre-school
Critikon

Neonates
Kent et al.30,31 OD Multiple 2/3 Of arm Trough-out day Trough-year Yes Multiple Clinical
Hewlett Packard Merlin Multiplanar
Monitor (Phillips, Sydney, NSW, Australia)
Pejovic et al.34 OD Multiple 85% Of arm Trough-out day Trough-year Yes Multiple Clinical
555 Corometric Medical System,
Wallingford, CT, USA
Salihoglu et al.29 OD Multiple 80% Of arm Trough-out day Trough-year Yes Multiple Clinical
Automated indirect oscillometer tecnique
(Life scope, Nhihon Kohden, Tokyo
Sadoh et al.32 OD 2 Size 80% Of arm Trough-out day Trough-year Yes Multiple Clinical
Dinamap 8100 monitor (Critikon)
Abbreviations: AOD, automated osillator device; LSH, London School of Hygiene spygmomanometer; OD, oscillometric device; MS, mercury spygmomanometer; RZ, random zero.
583

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and/or percentile charts3,10–12,28,29,35,39 and/or mean values plus this population.45 Heterogeneity within the same country between
s.d.,2–4,6,8,11,12,16,19,25,27–29,32–35,37,39,42,45,54,55,74 without parametric diverse regional areas has also been reported.20,41
normalization. Nonparametric methods do not assume that the
response variable adopts a given distribution and are therefore less Other confounders
prone to bias.49–51 However, because BP reference ranges change as Many other factors have been reported to variably influence childhood
the body grows, if one wants to define precise reference ranges across BP; they include school attendance,39 physical activity,39
growth using non-parametric methods, one must compute the breastfeeding,39 dietary habits25,39 and familiarity.25,39 In particular,
percentiles for several growth strata (from birth to adulthood) of in American children, a significant and independent association
the studied population.49 Parametric normalization (where the depen- between high sodium intake and elevated BP has been recently
dent variables were SBP and DBP) has only been performed by a few demonstrated.78 Sleep duration (that is, 48.5 h) was also positively
authors8,12,25–27,35 by using different types (and numbers) of indepen- associated with high BP in female adolescents.79 However, it is most
dent variables. The regressions were the same only in two studies,26,27 likely doubtful that all these factors should be taken into account in
but the age groups evaluated were different, making comparisons the construction of BP nomograms or reference tables.
among the studies difficult. Furthermore, quantile regressions, which
offer a greater flexibility and the best fit21 compared with polynomial/ DISCUSSION
spline models, have been seldom employed. Lastly, the issue of In the past 30 years, several surveys2,5,6,8,11–13,19–36,39,40 and a few
heteroscedasticity, a statistical term used to describe the behavior of reviews4,9,10 that provide normative data of childhood BP have been
variance of the residuals, which may create important bias especially published. Nevertheless, many numerical and methodological limita-
when using parametric normalization, has never been addressed.49–51 tions still remain. For some geographic areas (North America, Europe,
India, Japan), there are one or more robust nomograms providing
Confounders normative percentiles based on the large size of healthy children,
Other methodological limitations are represented by the different especially for children 45 years of age. The data for many other
attention to some relevant confounders including gender, geographic areas (South America, Africa, East Europe, wide areas of
Asia) and for some ethnicities however are extremely limited or even
ethnicity and geographic regions and socio-economic
absent. Furthermore, globally, there is a paucity of data for neonates
factors.2,3,8,11,27,28,30,31,34,35,39,75–79
and infants. Finally, data on ambulatory BP and BP response to
exercise in children are extremely limited,57–73 and no clear BP cut-off
Gender
values exist to distinguish between healthy and pathological states.
The data have usually been presented separately regarding gender with
Additionally, the criteria for interruption of stress tests in the presence
limited exceptions.27,30,31,34 Gender differences in BP were found in
of excessive BP increases are lacking, which could because for
some2,3,35,39 but not all studies.28 Generally higher BP values have been
concern.73
reported in boys,8,11,33 although a few authors29,35 reported higher
There are also various methodological limitations including the lack
values in girls.
of clear inclusion/exclusion criteria with a few exceptions,9,13,30–32,39,45
differences in the method employed for measuring BP (for example,
Ethnicity
manual vs. automated devices), heterogeneity in the data normal-
Controversies remain regarding the specific influence of ethnicity on
ization (according to age and/or height) and units of expression
BP values in children. A major issue is whether the higher prevalence
(percentile/mean value). The choice to express data according to age
of hypertension found in black compared with white adults in the US9
and/or height and not according to BMI was made to avoid the
and the UK42 is reflected in BP differences in the pediatric age group. assumption that being overweight may be a justification for high BP at
In some series, only slight differences between black and white subjects a given age/height.9,21 The inclusion of overweight/obese in the
have been shown, with a prevalence of BP elevation in Hispanic and database however, implies a bias in the nomograms that some authors
black male youth compared with white male youth in the USA.25 It is have tried to overcome by excluding the lowest and highest BMI
supposed, however, that ethnic differences in the prevalence rates of percentiles.21 The inclusion of data collected over multiple decades (in
pediatric BP elevation may be not entirely explained by obesity; rather, reviews), also represents another potential bias. As observed by
they may be because of genetic or environmental factors.77 Munter and colleagues7 and more recently by Rosner et al.78 an
increase in childhood BP over the past decade has occurred, which
Geographic areas: continents, countries and regions may be partially attributable to an increased prevalence of overweight
Geographic influence may be even more relevant than ethnicity. In children.
fact, several studies highlighted region specific childhood BP distribu- Interestingly, no studies reported BP values normalized for BSA,
tions. There were important differences among continents, countries which is the parameter that is commonly used to normalize some
and even within same the country among various regions.20,45 pediatric data (such as cardiac structure dimensions).50 Usually,
Therefore, for instance, studies indicate that BP may be higher in parametric normalization by percentile has been used, because it is
European and Asian children than in their American easy to understand and is very familiar to most pediatricians.
counterparts.6,16,40 Sanchez et al.6 found that SBP and DBP values However, an insufficient number of healthy subjects have been
were higher in 34 946 Spanish children than in their US counterparts. evaluated at times, especially in the case of neonates and infants.47,48
Furthermore, Tobagonian adolescents had SBP and DBP that were Furthermore, the use of percentiles in a pediatric population implies a
10 mm Hg lower and higher, respectively, than their UK counterparts, division (from 0 to 18 years) in growth strata,49 but no clear rules exist
whereas Jamaican adolescents had DBP consistently lower than on how this division should be performed. Conversely, non-
Tobagonians.19 Additionally, it has been demonstrated that in parametric methods of normalization (that is, z scores) have been
Lebanese children, normal US values were too high and neither the rarely used.21,47 Z-scores (that is, the number of s.d. from the mean)
European normal standards nor the Italian standards were suitable for however, may help in eliminating a number of the sources of variance

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Table 4A Example of blood pressure normal values for a male child of Table 4B Example of blood pressure normal values for a female child
3 y.o. according to different nomograms of 9 y.o. according to different nomograms

Author SPB (mm Hg) DPB (mm Hg) Author SPB (mm Hg) DPB (mm Hg)

America America
Fourth report9 50th height p. 50th height p. Fourth Report9 50th height p. 50th height p.
50th p. 89 50th p. 46 50th p. 100 50th p. 59
95th p. 107 95th p. 65 95th p. 117 95th p. 77
Rosner et al.13 50th height p. 50th height p. Paradis et al.8 Mean s.d. Mean s.d.
50th p. 103 50th p. 59 50th p. 102 (101–104) 50th p. 57 (56–58)
(5th p. 101–95th p. 105) (5th p. 58–95th p. 61) 95th p. 121 (118–123) 95th p- 67 (66–68)
Rosner et al.13 50th height p. 50th height p.
Australia 50th p. 111 50th p. 73
Blake et al.12 50th p. 99 (5th p. 86–95th 50th p 52 (5th p. 40–95th (5th p. 108-95th p. 114) (5th p. 71–95th p. 73)
p. 113) p. 65)
Europe
Europe De Swiet et al.33 Mean s.d. 92.3 (8.7) Mean s.d. 60.2 (7.6)
de Swiet et al.33 Mean s.d. 96.8 (9.7) Menghetti et al.16 Mean s.d. 106.6 (13.3) Mean s.d. 65.7 (12.5)
Sanchez et al.6 Mean s.d. 93.0 (7.1) Mean s.d. 53.5 (7.6) Sanchez et al.6 Mean s.d. 106.2 (10.5) Mean s.d. 59.9 (9.5)

Asia Mead East

Krishna et al.7 Mean s.d. 98 (11) Mean s.d. 63 (11) Merhiet al.45 Mean s.d. 97.0 (9.9) Mean s.d. 55.7 (6.7)
Hashimoto et al.54 Mean s.d. 97.1 (9.9) Mean s.d. 52.4 (9.6) 90th p. 110 90th p. 70

Abbreviations: p., percentile; y.o., years old.

Asia
Kelishadi et al. Mean s.d. 99.83 (12.4) Mean s.d. 62.79 (9.9)
in raw numbers, especially when there is a significant variation in body Krishna et al. Mean s.d. 105 (11) Mean s.d. 71 (9)
size, and they allow for a further simplification of data interpretation,
Abbreviations: DBP, diastolic blood pressure; p. percentile; SBP, systolic blood pressure; y.o.,
also based on the use of electronic computation.49–51 years old.
Among the confounders, the issue of ethnicity remains debatable. In
fact, differences among nomograms from various continents have
been highlighted;6,18,19,25,38 however conversely, in American children, a result, calls for the development of country/region specific nomo-
the influence of ethnicity/race did not seem to be relevant for BP grams have been made by multiple sources.20,44,45
values.46 In fact, the higher BP values encountered in black male
youths7,24,46 seem to be more attributable to the incidence of over- Limitations
weight in this subgroup rather than to ethnicity per se.37 This review is limited to results from reports written in English.
All these numerical and methodological issues are not self-limiting However, there have been several non-English publications showing
but may have a series of important consequences for clinicians.49–51 In pediatric BP nomograms especially in Japan and China where English
fact, the lack of clear recommendations regarding the nomogram that is not an official language. Review and meta-analysis of the data from
should be employed (with the exception of the USA) forces the publications written in a local language could add helpful information
clinician to arbitrarily chose one (or more nomograms) among those to define the pediatric BP ranges of normality for a given country/
available. Secondly, clinicians interpret blood pressure values and geographic area.
make decisions regarding diagnosis (hyper/hypotensive or not?) and
management (to treat or not to treat?) according to the proposed RIs, CONCLUSION
which at times may have been substantially different. In fact, actual Various pediatric BP nomograms exist, but many numerical and
nomograms are heterogeneous, difficult to compare and, when methodological limitations still persist. For some geographical areas
comparable, sometimes show considerably different confidence inter- (particularly the USA), there are nomograms of sufficiently good
vals (Tables 4A and B). For instance, according to different authors, a quality, whereas for others, data are limited/absent. Furthermore,
3-year-old boy, at the 50th percentile of SBP (mm Hg), may vary from worldwide there is a paucity of data specific to the neonatal age group.
89 (9) to 105.9 (6), whereas at the 95th percentile, the range is from Various nomograms are difficult to compare, and when comparable,
100.1 (6) to 109.2 (9). Nomograms from the Fourth Report present they sometimes show different RIs that may lead to confusion in the
various advantages: (i) a solid methodological structure despite a few interpretation of the BP values in children and in estimating disease
limitations (that is, the lack of clear inclusion/exclusion criteria, the severity. Nomograms from the Fourth Report are of good quality but
use of data obtained at more than one age vs. cross-sectional data, the are not universally applicable.
use of single readings for some studies, the employment of mercury For every country, the development of new nomograms based on a
manometers); and (ii) a good sample size (with the exception of wide range of healthy children including a sufficient number of
neonates and infants).21 As a result, data from the Fourth report have neonates and infants is recommended. New nomograms should define
been frequently adopted worldwide.20,45 The simple adoption of detailed exclusion/inclusion criteria, standardized protocols (that is,
nomograms from the USA, however, may not be suitable for other right arm, sitting position, resting period preceding the measurements
geographic areas/countries/ethnic groups20,44,45 where they may intro- and multiple readings), methods (that is, the auscultatory manual
duce an unpredictable bias in the evaluation of BP values resulting in method in older children vs. the oscillometric method in neonates and
significant over/underestimation of hypo/hypertensive values.20,44,45 As infants) and instruments (that is, aneroid sphygmomanometers and

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