Review

Primordial Prevention of High Blood Pressure in Childhood

An Opportunity Not to be Missed
Bonita Falkner, Empar Lurbe

Abstract—Hypertension is a condition with increased risk for subsequent adverse events, and treatment of hypertension is
prescribed for primary prevention of adverse events. Primordial prevention is a concept that precedes primary prevention
and focuses on risk factor prevention. Primordial prevention of hypertension consists of strategies to maintain blood
pressure in a normal range and prevent development of elevated blood pressure or hypertension. Childhood is a period
in which primordial prevention could be effective and if sustained throughout childhood could contribute to a healthier
young adulthood. Targets for primordial prevention in childhood include preventing and reducing childhood obesity,
achieving an optimal diet that includes avoiding excessive salt consumption, and removing barriers to physical activity
and healthy sleep throughout childhood. Primordial prevention also includes the prenatal period wherein some maternal
conditions and exposures are associated with higher blood pressure in child offspring.

P rimordial prevention is a term that is seldom used in hy-

pertension research or clinical care. Primordial prevention
is defined as preventing the risk factor. For the condition of
hypertension, primordial prevention would be prevention of
abnormal elevations of blood pressure (BP) among normoten-
sive individuals. Thus, primordial prevention precedes primary
prevention in which the standard of care for established hyper-
tension in children, as well as adults, is treatment to lower BP,
regardless of the cause, to prevent hypertension-related events.
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recently updated. In the American guidelines, for children age
<13 years, hypertension is defined as systolic or diastolic BP
>95th percentile of the sex, age, height distribution of normal-
weight children, and elevated BP is defined as BP >90th to
<95th percentile. For adolescents age >13 years, the updated
adult definitions for hypertension and elevated BP are now
used.7 According to the European guidelines, hypertension in
children <16 years is defined as systolic or diastolic BP per-
sistently ≥95th percentile for sex, age, and height. Children

Primordial prevention of abnormal BP in childhood, if effec-
tive, could lead to lower rates of hypertension in young adult-
hood and possibly dampen the rates of hypertension-associated
cardiovascular disease.
The prevalence of hypertension in childhood varies in dif-
ferent countries. A recent systematic review reported a pooled
worldwide prevalence of hypertension in youth estimated at
4.00% (95% CI, 3.29%–4.78%).1 In addition, the prevalence
of elevated BP is ≈12%.2 Reports on BP trajectory curves
from childhood to adulthood demonstrate that BP levels in
the higher range of the BP distribution in childhood progress
to hypertension in young adulthood. High body mass index
(BMI) and low birth weight (LBW) in childhood were among
risk factors associated with high and increasing BP trajec-
tory.3 An analysis of BP data in a community-based primary
care population demonstrated that among youth age 10 to 17
years with persistent elevated BP, progression to hypertension
occurred in 5.9% over a 2-year period.4 Therefore, the com-
bined prevalence of elevated BP and hypertension in child-
hood is not trivial and is progressive.
Clinical practice guidelines on hypertension in chil-
dren and adolescents in the United States5 and Europe6 were
with average systolic BP or diastolic BP at least 90th, but
<95th are classified as having high-normal BP. For children
≥16 years, hypertension is defined using the updated adult
European definitions.8
Hypertension in childhood can be secondary to under-
lying renal disease, endocrine abnormalities, and other con-
ditions. However, only about 1% of childhood hypertension
is secondary to an underlying disorder, and children with
secondary hypertension are usually identified in early child-
hood.9 Therefore, abnormal BP is potentially modifiable for a
substantial portion of children. Research, including epidemi-
ology, prospective cohort studies, and other clinical studies in
children, provide evidence on early life exposures that are as-
sociated with higher BP in childhood. This review will discuss
the exposures linked with higher BP in the young and will
consider the possible impact that removing these exposures
would have on mitigating the prevalence of elevated BP and
hypertension in childhood.
Risk Factors for Pediatric Hypertension
The increasing prevalence of cardiovascular risk factors
in children and adolescents has been largely, but not en-
tirely, related to the childhood obesity epidemic.10 Among

From the Departments of Medicine and Pediatrics, Thomas Jefferson University, Philadelphia, PA (B.F.); and Pediatric Department, Hospital General,
University of Valencia, Spain (E.L.).
Correspondence to Bonita Falkner, Department of Medicine/Nephrology, 833 Chestnut St. Suite 700, Philadelphia, PA 19107. Email bonita.falkner@
jefferson.edu
(Hypertension. 2020;75:1142-1150. DOI: 10.1161/HYPERTENSIONAHA.119.14059.)
© 2020 American Heart Association, Inc.
Hypertension is available at https://www.ahajournals.org/journal/hyp DOI: 10.1161/HYPERTENSIONAHA.119.14059

1142
 Falkner and Lurbe   Primordial Prevention in Childhood   1143
the obesity-associated risk factors detectable in childhood is
high BP. Emerging findings indicate that, in addition to over-
weight and obesity, diet, insufficient physical activity, exces-
sive screen time (ST), and sleep disorders are associated with
elevated BP in youth.11
Overweight and Obesity
The prevalence of overweight and obesity among children
has increased substantially worldwide since the 1990s. The
association of obesity with hypertension in children has been
well documented in both sexes, all age groups, and for every
geographic and ethnic group.12 The magnitude of the asso-
ciation was assessed by Freedman et al13 who reported that
overweight children were 4.5× as likely to have elevated
systolic BP compared with normal-weight counterparts. In
school-based screenings, hypertension was 3× more frequent
in obese than in nonobese adolescents. Excess adiposity can
also affect young infants. Therefore, prevention of childhood
obesity and its consequences should begin at the earliest
stages of human development. Several modifiable risk fac-
tors present in early life are associated with childhood over-
weight. In an observational study, Gillman et al14 reported that
in preschool-age children of mothers who did not smoke or
gain excessive weight during pregnancy, and their infant was
breastfed for 12 months, and slept 12 h/d predicted an obe-
sity prevalence of 6% at age 3 years compared with a prev-
alence of 29% among children with the opposite of these 4
mother/child behaviors. The difference in obesity prevalence
was similar (4% and 28%, respectively) when these children
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reached age 7 to 10 years.
Preventive interventions beginning in infancy could have
a substantial impact on childhood obesity and BP levels. The
STRIP (Special Tuku Coronary Risk Factor Intervention
Project), a clinical trial of dietary counseling, is a key study
that contributed evidence on the benefit of early preventive
intervention. The STRIP project started in Finland in the
early 1990s where infants were randomized to noninterven-
tion control versus an intervention of individual dietary coun-
seling, starting before their first birthday, on healthful fats,
more fruits, vegetables, and whole grains, and less sodium.
Investigators reported a lower BP measured each year until
age 15 years. BP levels were 1.0 mm Hg lower in the group
receiving the diet counseling throughout childhood com-
pared with the control group (95% CI for systolic, −1.7 to
−0.2; 95% CI for diastolic, −1.5 to −0.4).15 More recently, the
STRIP investigators reported the effect of the intervention on
the prevalence of metabolic syndrome among participants at
age 15 to 20 years. The annual prevalence of metabolic syn-
drome in the intervention group was 6% to 7% compared with
an annual prevalence of 10% to 14% in the control group.
The relative risk reduction for metabolic syndrome was 0.59
(95% CI, 0.40–0.88; P=0.009). These results were driven by
reductions in high BP in both sexes and high triglycerides in
boys.16 Other reports described modest intervention effects on
lowering adolescent BP and insulin resistance, lower lipids
in boys, and less overweight in girls.17,18 The findings from
STRIP support the benefit of primordial prevention on cardi-
ovascular risk factors when initiated in early childhood. For
obesity prevention, the best time to intervene is infancy and
early childhood, when behaviors are modifiable, but few stud-
ies include children younger than age 2 years.19 Despite the
evidence from observational studies that elevated cardiometa-
bolic risk status begins in childhood,20 long-term clinical trials
to determine if an intervention benefits extends into adulthood
are limited. Indeed, such trials might not be feasible given its
long duration and challenges of maintaining separation of in-
tervention versus control groups.
Dietary Factors
Diet pattern and quality is an important issue in development
of high BP in childhood. Dietary factors associated with high
BP in youth are high sodium intake, a low potassium diet,
and high consumption of sugar-sweetened beverages (SSBs).
Evidence for an association of sodium intake with BP in oth-
erwise healthy children is limited. Although some studies
report a positive association, others have not. A recent meta-
analysis of studies that included participants from birth to 18.9
years determined 18 of 85 reports to be high quality based on
methods for sodium intake assessment and BP measurement.
Analysis of pooled data from these reports detected a positive
association of sodium intake with BP in childhood, with a sys-
tolic BP increase of 0.8 mm Hg and a diastolic BP increase of
0.7 mm Hg with each additional gram sodium intake per day.21
Systematic reviews have also been conducted on clinical
trial studies to lower sodium intake in youth. A meta-analysis
of pooled data by He and MacGregor22 reported a reduction of
1.2 mm Hg in systolic and 1.3 mm Hg in diastolic BP follow-
ing sodium reduction intervention. In another meta-analysis,
Aburto et al23 reported an 0.8 mm Hg decrease in systolic and 0.9
mm Hg in diastolic BP following sodium reduction. Although
the strength of the association of sodium intake with BP in child-
hood is modest, it is significantly stronger among overweight
and obese children.24 Moreover, sodium intakes in children and
adolescents are well above recommended levels, largely due to
consumption of processed and prepared foods.25 In addition to
encouraging limiting high sodium foods, focused interventions
to limit sodium intake should be directed at children born pre-
mature and small for gestational age as well as overweight/obese
children.26 Recently, the National Academy of Medicine recom-
mends a sodium dietary intake ranging between 110 mg/d to 1.5
g/d from birth to 18 years, respectively (Table).27
Regarding potassium, an inverse association of potas-
sium intake with BP level has been observed in clinical stud-
ies in adults.28 Studies on effects of dietary potassium intake
on BP in children and adolescents are limited. A prospec-
tive study on girls found that higher dietary potassium in-
take was associated with lower BP throughout adolescence,
suggesting that consuming potassium-rich foods throughout
childhood would support a more favorable BP outcome.29 An
example of a potassium-rich diet is the Dietary Approaches
to Stop Hypertension diet, due to high consumption of fruits
and vegetables, and the benefits of the Dietary Approaches
to Stop Hypertension diet in lowering BP in adults are firmly
established. A small clinical trial conducted on untreated hy-
pertensive adolescents compared counseling on a Dietary
Approaches to Stop Hypertension-type diet to routine care.
Following 6 months of diet intervention, BP was lower in
the Dietary Approaches to Stop Hypertension diet group
 1144  Hypertension  May 2020
Table.  Primordial Prevention of High Blood Pressure: Scientific Statements
Factor for Intervention Scientific Statements Strength of Evidence
Under 5 y
 Physical activity, Guidelines on physical
sedentary activity, sedentary behavior,
behavior, and sleep and sleep for children under
5 y of age. WHO 201928
Children and adolescents
 Sodium diet National Academies of
Sciences, Engineering, and
Medicine. 2019. Dietary
reference intakes for
sodium and potassium.27
 Potassium diet National Academies of
Sciences, Engineering, and
Medicine. 2019. Dietary
reference intakes for
sodium and potassium.27
 Physical activity Global recommendations
on physical activity for
health. WHO 201029
Physical activity guidelines
for Americans 2018.30
 Sugar-sweetened A scientific statement
beverages from the American Heart
Association.31
 Screen time American Academy of
Pediatrics. policy statement:
children, adolescents, and
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the media.32
 Sleep disorders Consensus Statement of
the American Academy
of Sleep Medicine on the
recommended amount
of sleep for healthy
children: methodology and
discussion.33
WHO indicates World Health Organization.
*Strength of evidence derived from the statements themselves.
†Strength of evidence derived from the statements themselves targeting
adults; otherwise in healthy children and adolescents, the evidence is limited.
‡Strength of evidence derived from the statements themselves but limited to
obese and hypertensive children and adolescents.
compared with the routine care group.30 On the basis of
available findings, the National Academy of Medicine rec-
ommends a potassium dietary intake ranging between 400
mg/d to 3 g/d from birth to 18 years, respectively (Table).27
A dietary component that contributes to childhood obesity
is SSBs. In a birth cohort followed from age 2 to 17, inves-
tigators reported a significant association SSBs consumption
with increasing BMI Z scores.31 A meta-analysis of random-
ized clinical trials on reducing SSB intake determined that
reducing SSBs in children resulted in lower BMI. A sensi-
tivity analysis showed greater benefit in SSB substitution
trials compared with school-based education programs.32 A
cross-sectional analysis of data from the National Health and
Nutrition Examination Survey on adolescents aged 12 to 18
years found that higher SSB consumption was associated with
higher serum uric acid and higher BP levels. This association
did not appear to be modified by presence or absence of obe-
sity.33 Considering the high sugar intake among children and
adolescents, the American Heart Association recommends
Very low* limiting added sugar intake (including beverages) to 25 g/d
in all children.34
Physical Activity, ST, and Sleep
The most recommended approach to prevention, and treat-
ment, of childhood obesity and obesity-associated hyperten-
High†
sion consists of achieving a healthy lifestyle, characterized by
healthy eating, physical activity, avoiding sedentary behav-
iors, and sleep quality.
There is no doubt about the health benefits associated
Moderate†
with regular physical activity in children and adolescents. The
World Health Organization recommends at least 60 minutes
daily of moderate- to vigorous-intensity physical activity.35
Recent Guidelines on Physical Activity published by the US
Department of Health and Human Services were concurrent
High‡ with the World Health Organization, and emphasized vig-
orous-intensity physical activity at least 3 days a week. For
preschool children, this guideline recommended that children
High‡ should be physically active throughout the day with active
play, including all kinds of movement to optimize healthy
High*
growth and development.36 Findings from clinical studies that
examined relationships between physical activity and BP in
children have been inconsistent with some showing that an
Low*
increase in physical activity lowers BP,37-38 and others find no
association.39,40 The Identification and Prevention of Dietary
and Lifestyle-Induced Health Effects in Children and Infants
is an epidemiological multi-center European study to iden-
Low* tify nutritional-associated and lifestyle-associated factors of
childhood obesity and related morbidities. At baseline, 5221
children aged 2 to 9 years were selected for accelerometer
measurements, and 5061 were followed for 2 years to deter-
mine the association of physical activity or sedentary behavior
on BP levels. The authors reported that consistent sedentary
behaviors in childhood increase risk of developing high BP.41
Advancements in technology have contributed to more
sedentary behavior in children and adolescents. ST includes
time spent viewing television, computer use, playing elec-
tronic games, and using mobile phones. Currently, ST is the
most common sedentary behavior, starting even in infants.
Time spent on screen-based activities can replace time for
physical activity and may affect physical and mental health in
youth.42 Adverse effects of excessive ST on physical strength,
obesity, and sleep disturbances have been documented in
many studies.43 The risk for high BP associated with ST is
mainly due to the risk of obesity and sleep restriction.44 The
impact of intervention programs in school to reduce ST dem-
onstrated a reduction in television viewing, playing video
games, and computer use, but the effect was small.45 The
American Academy of Pediatrics published guidelines on ST
in 2013 that was largely based on television viewing.46 This is
now outdated because computer and cell phone use and play-
ing electronic games have become widespread. ST is leading
to more sedentary behavior in childhood. Encouraging parents
to limit ST is an important step in prevention of risk factor de-
velopment in children and adolescents.
 Falkner and Lurbe   Primordial Prevention in Childhood   1145
Sleep disturbance is a commonly overlooked risk fac-
tor associated with high BP in children and adolescents.
Lower levels of parental education, lack of regular enforce-
ment of rules about caffeine, and presence of electronics
in the child’s bedroom overnight are among the factors re-
lated to poor sleep.47 Insufficient sleep is widespread among
children but largely greater in adolescents.48 Chronic sleep
restriction,49 poor sleep quality,50 and sleep variability51
have been found to be associated with increased BP in
adolescents, although the association in younger children
is less apparent. This association may be primarily driven
by blunting the nocturnal fall in BP, but the association of
obesity-associated sleep disturbances is also implicated.52
A Consensus Statement of the American Academy of Sleep
Medicine concluded that serious gaps in knowledge about
the impact of sleep on health exist in the pediatric popula-
tion and that additional research is needed.53
A pathological sleep condition is obstructive sleep apnea,
a common condition among obese children. Some studies
have reported that obstructive sleep apnea is associated with
24-hour BP dysregulation and that, independent of obesity,
the frequency of obstructive apnea, oxygen desaturation, and
arousal contributes to abnormal BP control.54
The importance of early introduction of healthy habits, in-
cluding physical activity, sleep, and screen use, has led the
World Health Organization to publish guidelines in 2019 on
physical activity, sedentary behavior, and sleep for children
under age 5 years.55 Early childhood is a period of rapid phys-
ical and cognitive development, a time during which a child’s
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habits are formed, and family lifestyle routines are open to
changes and adaptations. World Health Organization guide-
lines recommend replacement of restrained sedentary ST
with more moderate-intensity to vigorous-intensity physical
activity while preserving sleep time. Lifestyle behaviors de-
veloped in early life can influence physical activity levels and
diet patterns throughout the life course.
Prenatal and Maternal Risk Factors
The intrauterine environment is critical for optimal fetal
growth and organ development in the prenatal period. LBW is
a hallmark of a suboptimal intrauterine environment. Maternal
conditions and exposures are also associated with heightened
risk for abnormal BP and related risk factors in childhood.
Low Birth Weight
Following original observations by Barker et al,56 epidemio-
logical studies demonstrated an association of LBW with ad-
verse cardiometabolic outcomes in adulthood. Preeclampsia
is a noted maternal condition that increases risk for premature
delivery and LBW. Other identified causes of LBW include
mechanical obstruction of uterine arteries, maternal cortico-
steroid treatment, and severe protein deficiency.57 A subop-
timal intrauterine environment can induce epigenetic changes
that promote fetal survival but can also lead to changes in
metabolic function that have adverse health consequences
later in life. Young adults (aged 18 to 27 years), born preterm
with very LBW, have significantly more impaired glucose tol-
erance and higher BP compared with age- and sex-matched
individuals born at term with normal birth weight (BW).58
In another study, healthy full-term infants of uncomplicated
pregnancies were stratified as small for gestational age (SGA),
appropriate for gestational age, or large for gestational age.
Repeated measures of growth and BP were obtained from
age 6 months to 5 years. At the 5-year exam, the cohort was
further grouped based on current weight, as small, average,
and heavy, and a blood sample was obtained for metabolic
parameters. BP level, at age 5 years, was positively associated
with current weight. Fasting insulin levels were higher in all
children who became heavy by age 5 years and were highest
among the SGA group. However, an estimate of insulin resist-
ance using the homeostatic model of assessment index was
highest in the SGA group compared with the other birthweight
groups, regardless of current weight. Even the SGA infants
who remained small at age 5 years had measures of insulin
resistance comparable to those who became heavy at age 5
years, suggesting metabolic programing in the SGA group.59
Among participants reexamined at age 10 years, children with
fasting insulin levels >15 U/L had higher office systolic BP,
plasma triglyceride and uric acid levels, and lower HDL-C
(high-density lipoprotein-cholesterol).60
Based on data from a longitudinal population in Helsinki,
Barker et al61 connected this child growth pattern with sub-
sequent cardiovascular events. A sample of adults, identified
with coronary heart disease, were found to have LBW, were
thin at age 2 years, but then gained weight rapidly and had
insulin resistance later in life. These reports describe a phe-
notype of LBW paired with developing overweight/obesity in
childhood. This growth pattern represents an increased risk
for high BP in childhood and adverse cardiometabolic out-
comes in later adulthood.62 Therefore, children with LBW
would benefit from careful BP monitoring and interventions
to prevent overweight/obesity.
Maternal Hypertension in Pregnancy
Prospective childhood studies that also include the maternal
prenatal period provide data on relationships of maternal
conditions, with offspring health measures. Reports from the
Avon Longitudinal Study of Parents and Children describe
higher BP among offspring of both preeclampsia and gesta-
tional hypertension pregnancies compared with offspring of
normotensive pregnancies.63 Avon cohort data demonstrate
that at age 10 years, there was an inverse association of BW
with systolic BP. In subsequent growth periods, all growth
parameters including weight, height, and BMI were positively
associated with systolic BP, indicating that development of ex-
cess adiposity was a modifiable determinant of later BP.64
Preeclampsia is commonly associated with premature
birth and LBW. A meta-analysis of published reports on pre-
eclampsia and offspring BP by Ferreira et al65 concluded
that nearly all studies demonstrate higher BP in offspring of
women with preeclampsia, in the range of 2 to 3 mm Hg sys-
tolic BP. Subsequent reports examined the risk of maternal
hypertension, including gestational hypertension, as well as
preeclampsia, in the absence of LBW or prematurity. Mother-
offspring pairs in the Avon study were stratified as normoten-
sive pregnancy, gestational hypertension, and preeclampsia.
At age 9 years, systolic BP was significantly higher in off-
spring of gestational hypertension pregnancy (2.04 mm Hg
 1146  Hypertension  May 2020
[95% CI, 1.42–2.67]) and in offspring of preeclampsia preg-
nancy (2.05 mm Hg [95% CI, 1.72–3.38]) compared with off-
spring of normotensive pregnancies. Following adjustment for
BW and gestational age, the association of preeclampsia preg-
nancy with offspring systolic and diastolic BP became non-
significant. However, the same adjustments did not attenuate
the significant association of gestational hypertension with
higher BP in offspring.66 Analyses of data obtained on these
offspring obtained at ages 12 years and 17 years resulted in
the same findings, suggesting genetic or familial nongenetic
risk factors were related to offspring BP.63 Other reports on
offspring of hypertensive disorders of pregnancy versus off-
spring of normotensive pregnancy describe similar findings in
adolescent offspring,67 and in young adult offspring.68 A sys-
tematic review of 18 studies, with and without BW adjust-
ment, found that offspring of preeclampsia have significantly
higher systolic BP, diastolic BP, and BMI than offspring of
normotensive pregnancies.69 Overall, the evidence is strong
that both gestational hypertension and preeclampsia increase
the risk for high BP in offspring, regardless of BW, and the
risk for elevated BP is heightened with development of over-
weight/obesity in childhood. Children with a prenatal history
of maternal hypertension would benefit from BP monitoring
and obesity prevention interventions.
Maternal Obesity
Maternal obesity before pregnancy is a risk factor for off-
spring development of obesity in childhood.70 Child offspring
of mothers with prepregnancy obesity and greater gestational
weight gain have higher BP than offspring of nonobese moth-
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ers.71 Higher BP in offspring of maternal obesity is commonly
associated with excess adiposity.72 A study conducted by the
Pregnancy and Childhood Epigenetics consortium examined
epigenetic modifications, including DNA methylation, in fetal
cord blood. In a cohort of over 10 000 mother-newborn pairs,
the association of newborn blood DNA methylation with ma-
ternal BMI was minimal.73 These findings indicate that cardio-
metabolic risk factors in child offspring of maternal obesity
are not a consequence of fetal programming and more likely
related to genetic or lifestyle factors. Infants born of obese
mothers are at high risk for childhood obesity and would ben-
efit from early childhood interventions to prevent obesity.
Maternal Diabetes Mellitus
Maternal diabetes mellitus and gestational diabetes mellitus
alter the intrauterine environment by exposing the developing
fetus to hyperglycemia. Reports from prospective studies de-
scribe increased risk for obesity and metabolic disorders in
offspring of mothers with diabetes mellitus and gestational di-
abetes mellitus.74,75 Several reports describe excess adiposity
with higher BP in child offspring exposed to intrauterine hy-
perglycemia.76–78 The Generation XXI Project, a prospective
birth cohort of 8301 mother-offspring pairs, included offspring
of mothers with type 2 diabetes mellitus. Offspring of diabetic
mothers were age- and sex-matched with offspring of nondia-
betic mothers and examined at in early childhood. There was
no difference in BP between the 2 groups at age 4 and 7 years.
There was then an accelerated increase in systolic BP among
the offspring of diabetic mothers with a significantly higher
BP by age 10 years compared with offspring of nondiabetic
mothers. This BP shift appeared to be mediated by a greater
increase in BMI.79 In a similar recent study, offspring of moth-
ers with gestational diabetes mellitus were matched with off-
spring of nongestational diabetes mellitus, all born at term,
and examined at approximate age of 5.8 years. BP, as well as
BMI and BMI Z score, were significantly higher in offspring
of gestational diabetic mothers compared with offspring of
nondiabetic mothers.80 Whether exposure to hyperglycemia
could induce epigenetic changes in the developing fetus is
currently unknown. Due to the clinical evidence of increased
risk maternal hyperglycemia for excess adiposity and higher
BP in child offspring, optimizing blood glucose control during
pregnancy could be beneficial, and offspring should be moni-
tored with preventive interventions in childhood.
Other Maternal Exposure
Maternal smoking can have an adverse effect on offspring.
Compared with offspring of maternal nonsmokers, child off-
spring of mothers who smoke during pregnancy have sig-
nificantly higher BMI Z score81 and metabolic syndrome
parameters, including higher BP.82 Although a direct effect of
maternal smoking on BP in child offspring has not been con-
firmed, there is heightened risk for obesity-associated increased
BP.
Air pollution is another maternal inhaled exposure that
has been linked with abnormal BP. Particulate matter inhala-
tion from air pollution is reported to be significantly associ-
ated with hypertensive disorders of pregnancy83 and preterm
birth,84 conditions that are associated with higher BP in child
offspring. A prospective study on a mother-offspring cohort in
Boston identified a marked increase in offspring systolic BP
percentile and elevated BP when third-trimester particulate
matter exposure (PM2.5) was ≥13 µg/m3 (highest tertial of
PM2.5).85 A significant association was reported on maternal
prenatal exposure to the air pollutant nitrogen dioxide (NO2)
with DNA methylation in offspring cord blood.86 Breton et
al87 examined prenatal exposure to NO2 and other pollutants
in cord blood samples on participants in the Children’s Health
Study. The investigators reported greater DNA methylation in
cord blood was associated with higher BP levels in 11-year-
old children. These findings are consistent with epigenetic
modification, and the BP outcomes were related to gestational
timing of the maternal exposure.
Assisted Reproductive Technology
A maternal exposure that could have an effect on BP in off-
spring is assisted reproductive technology (ART), a relatively
new, but increasingly used, fertility treatment. There are little
data on long-term outcomes of children who are conceived by
ART, followed by full-term pregnancies, and who appear to be
healthy infants. A study on vascular function in healthy off-
spring of ART at age 11.5 years was reported by Scherrer et
al.88 ART children and control offspring of normal pregnancy,
matched by age, sex, and BMI, underwent noninvasive vascular
measurements. ART children had greater endothelial dysfunc-
tion, higher pulse wave velocity, and greater carotid thickness
compared with controls. However, there was no difference
in clinic BP, and elevated BP was not detected. These find-
ings were replicated in an ART rodent model.89 In a follow-up
study, when ART participants were aged 16 years, 24-hour
 Falkner and Lurbe   Primordial Prevention in Childhood   1147
ambulatory BP monitoring was performed. Compared with
controls, ART adolescents had significantly higher 24-hour
mean systolic and diastolic BP; and 15.4% of the ART group
had ambulatory hypertension versus 2.5% of controls.90 These
findings of possible vascular dysfunction and elevated BP in
apparently healthy children conceived by ART are striking.
The sample size is small, and additional research is needed.
However, the findings are sufficiently compelling to add ART
to the list of prenatal risk factors related to later elevated BP.
Is Primordial Prevention Possible?
The prevalence of abnormal BP is over 10% in children and
adolescents. There are also racial disparities in childhood with
a higher prevalence of abnormal BP in Black and Hispanic
youth compared with whites.91 Realistically, abnormal BP
in childhood cannot be entirely eliminated due to potential
contributions of familial-genetic factors. However, efforts to
promote optimal healthy behaviors and avoid adverse expo-
sures beginning in early childhood could have a substantial
impact on preventing abnormal BP levels in youth (Figure).
Even in the prenatal period, achieving better maternal health
and avoiding known adverse exposures could have a favorable
impact on primordial prevention. Many Guidelines, cited in
this review and others, provide evidence-based recommenda-
tions on optimal diet, physical activity, and limitations in ST
for children and adolescents. However, evidence is limited on
effective methods for implementation of the recommended
guidelines for healthy lifestyles in childhood. Research is
needed on how messages from scientific-based guidelines can
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be implemented to benefit the health status of children and
adolescents. Strategies to prevent risk factor development in
childhood would include parental education, counseling, and
supportive reinforcement in addition to well childcare. An en-
vironment needs to be supportive as well with access to afford-
able healthy foods and resources for physical activities that
are safe for children and adolescents. Research areas include
clinical monitoring with focused interventions on high-risk
children, as well as public health policies, school programs,
and community services that reinforce primordial prevention.
Research is also needed on the intrauterine environment to
Figure.   Factors related to high blood pressure and the interaction among
them. OSA indicates obstructive sleep apnea; and SSB, sugar-sweetened
beverages.
determine how known exposures such as gestational hyperten-
sion, maternal diabetes mellitus, and other exposures can be
managed to optimize fetal growth and development. However,
there are known obstacles to achieve effective preventive pro-
grams, including poverty, food insecurity, cultural beliefs,
family structure, childcare availability, parent work schedules,
and difficulty in preventing the leading obstacle of childhood
obesity. The obstacles require input from multiple disciplines.
In addition to public health policies, all clinicians can have
a positive role in encouraging healthy lifestyles, not only in
their patients but also in the patient’s family, including infants,
children, and adolescents. Babies are the future.
Sources of Funding
None.
Disclosures
None.
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