• No results found

Cardiovascular Risk Factors in Children and Young Adults Born to Preeclamptic Pregnancies: A Systematic Review

N/A
N/A
Protected

Academic year: 2020

Share "Cardiovascular Risk Factors in Children and Young Adults Born to Preeclamptic Pregnancies: A Systematic Review"

Copied!
12
0
0

Loading.... (view fulltext now)

Full text

(1)

Cardiovascular Risk Factors in Children and Young

Adults Born to Preeclamptic Pregnancies: A Systematic

Review

abstract

BACKGROUND AND OBJECTIVE:Preeclampsia is an independent car-diovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardio-vascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero.

METHODS: We performed a systematic review and meta-analysis on studies reporting traditional cardiovascular risk factors in those ex-posed to preeclampsia compared to controls. Information was extracted on the classic cardiovascular risk factors, including blood pressure, lipid

profile, glucose metabolism, and BMI from articles published

be-tween 1948 and August 2011 in Medline and Embase.

RESULTS:Eighteen studies provided cumulated data on 45 249 indi-viduals. In utero exposure to preeclampsia was associated with a 2.39

mm Hg (95% confidence interval: 1.74–3.05;P,.0001) higher systolic

and a 1.35 mm Hg (95% confidence interval: 0.90–1.80; P, .00001)

higher diastolic blood pressure during childhood and young

adult-hood. BMI was increased by 0.62 kg/m2 (P, .00001). Associations

were similar in children and adolescents, for different genders, and

with variation in birth weight. There was insufficient evidence to

identify consistent variation in lipid profile or glucose metabolism.

CONCLUSIONS: Young offspring of pregnancies complicated by

pre-eclampsia already have increased blood pressure and BMI, afinding

that may need to be considered in future primary prevention strategies

for cardiovascular disease.Pediatrics2012;129:e1552–e1561

AUTHORS:Esther Frances Davis, MBBS, MBioethics,a

Merzaka Lazdam, MBChB, MRCP,aAdam James

Lewandowski, BSc (Hons),aStephanie Anne Worton,

MBChB, MRes,bBrenda Kelly, MBChB, BSc, PhD, MRCOG,b

Yvonne Kenworthy, BSc,aSatish Adwani, MBBS, MD, DM,

MRC,cAndrew R. Wilkinson, MB ChB, MA, DCH, FRCP,

FRCPCH,dKenny McCormick, MBChB, MRCP, (UK), FRCPCH,d

Ian Sargent, PhD,bChristopher Redman, MA, MB, BChir,

FRCP,band Paul Leeson, MB BChir, PhD, MRCPa

Departments ofaCardiovascular Medicine andbObstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom; and Departments ofcPaediatric Cardiology anddNeonatology, John Radcliffe Hospital, Oxford, United Kingdom

KEY WORDS

preeclampsia, offspring, cardiovascular risk, systematic review

ABBREVIATION

CI—confidence interval

All authors have read and approved the submission of the article and have made substantial intellectual contribution to this work.

Accepted for publication Jan 18, 2012

www.pediatrics.org/cgi/doi/10.1542/peds.2011-3093

doi:10.1542/peds.2011-3093

Address correspondence to Paul Leeson, PhD, MRCP, Oxford Cardiovascular Clinical Research Facility, Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom. E-mail: paul.leeson@cardiov.ox.ac.uk

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE:The authors have indicated they have nofinancial relationships relevant to this article to disclose.

(2)

Women who develop preeclampsia have an increased risk of later

cardiovas-cular disease,1,2so guidelines propose

that a history of preeclampsia is an integral part of preventive cardiology

assessments in women.3 It has now

emerged that there also may be car-diovascular health implications for offspring of affected pregnancies. Authors of a long-term follow-up study found that these offspring had almost

double the risk of stroke in adulthood,4

and subsequent meta-analysis of early studies of blood pressure variation found they had a 2.3 mm Hg higher systolic and a 1.7 mm Hg higher diastolic

blood pressure.5Because preeclampsia

affects 2% to 5% of pregnancies,6,7

thesefindings are potentially relevant

to the cardiovascular health of.300

million people worldwide. We inves-tigated whether an increased

car-diovascular risk profile was already

evident in childhood, which may war-rant early prevention advice, and the characteristic features of this risk

profile. We performed a systematic

review of all studies that reported variation in cardiovascular risk fac-tors, including blood pressure, BMI,

lipid profile, and glucose metabolism

in children and young adults exposed to preeclampsia in utero. Furthermore, we determined whether associations vary between genders, with age, or in the presence of intrauterine growth restriction.

METHODS

Search Strategy

All studies describing the effect of preeclampsia on offspring cardiovas-cular risks in childhood and young adulthood were sought by

computer-ized Ovid search of Medline (1948–

August 2011) and Embase (1980–August

2011). The search strategy is described in Supplemental Fig 6. Review was un-dertaken with reference to the PRISMA

and the MOOSE Group guidelines8,9

(Supplemental Fig 7). Case-control stud-ies, cohort studstud-ies, and clinical trials

were included. References of identified

studies were searched, and all identified

studies were sifted by abstract for rele-vance by 2 authors (E.F.D. and M.L.). Eli-gibility was assessed without reference to results, author, or journal. Discrep-ancies were resolved by discussion. Data were extracted from eligible stud-ies by 1 author (E.F.D.) and cross-checked for accuracy by a second author (A.J.L.). When required data could not be ex-tracted, authors of the relevant studies were contacted.

Inclusion Criteria

Studies were selected if they compared cardiovascular risk factors in children exposed to preeclampsia in utero with controls. In addition to diagnosis of a risk factor, outcome measures in-cluded were blood pressure, BMI, lipid levels, insulin sensitivity, and glucose or glucose metabolism. The primary summary measure for continuous outcome variables was difference in means. Studies reporting only relative risk of an outcome such as hyperten-sion, obesity, or diabetes, rather than mean values in the study population, were excluded. Preeclampsia was

de-fined by using the current International

Society for the Study of Hypertension in

Pregnancy research definition10;

how-ever, as diagnostic criteria have varied historically, studies in which preeclamp-sia was diagnosed by de novo onset of hypertension and proteinuria also were included. When the same co-hort was reported in multiple pub-lications at similar ages, the most recent publication was included. Studies in which distinction between gesta-tional hypertension and preeclampsia was impossible and studies comparing offspring to another potential risk group were excluded. All studies were published in peer-reviewed journals, undertaken in human participants, and published in English or French.

Analysis

From each included study, definition of

preeclampsia, age of offspring at follow-up, number of cases and controls, birth weight, and the gestational age of cases and controls were collected. Outcome measures were documented and, for each, the mean and SD were recorded. Funnel plots were examined for evidence of bias (Supplemental Fig 8).

Comparative review of outcome meas-ures was undertaken, and consideration was given to whether results varied be-tween genders, with age, or in the pres-ence of intrauterine growth restriction. When informative, meta-analysis was performed by using Cochrane Collabo-rations RevMan software (Review Man-ager (RevMan) Version 5.1.1, The Nordic Cochrane Centre: The Cochrane

Col-laboration, Copenhagen)11 based on an

inverse variance method. The mean dif-ference between outcome measures and

95% confidence interval (CI) was

calcu-lated by using a fixed-effect model,

which reflects only the random error

within each study and is less affected by publication bias, which is a greater issue in observational studies compared with

randomized controlled trials.12–14 To

ensure our conclusions were not unduly

influenced by choice of model, we also

repeated the analysis with a random effects model, but no differences in

out-come were identified (data not shown).

Statistical assessment of heterogeneity

was undertaken.11

RESULTS

Study Identification

Of the 2484 articles identified by the

(3)

preeclampsia (17 studies); repeat pub-lication of data (4 studies); inability to exclude hypertension before pregnancy (12 studies); and studies reporting rel-ative risk of a diagnosis rather than mean values in the study population (2 studies).

Blood Pressure

Blood pressure data on 44 293 individ-uals, 1241 of whom were exposed to preeclampsia, was available from 10

studies (Table 1).15–24Authors of 1

ad-ditional study reported only relative risk of hypertension in adult offspring 60 to 70 years after a preeclamptic pregnancy, and the study was not

in-cluded in the analysis.4 Persons who

had been included were aged from 4 to 30 years, with all but 1 study reporting

only on those aged ,20 years. Five

studies reported increased systolic blood pressure in those exposed to

preeclampsia (range: 1.8024– 6.70

mm Hg22), and 6 studies reported

in-creased diastolic blood pressure

(range: 1.719–6.0 mm Hg22).16–20,22None

reported significant decreases.

Quanti-tative summary measures obtained by meta-analysis indicated that in childhood,

offspring of preeclamptic women have

a 2.39 mm Hg (P,.0001) greater

sys-tolic (Fig 2) and a 1.35 mm Hg (P ,

.00001) greater diastolic blood pres-sure (Fig 3).

Two studies reported increased systolic blood pressure in male individuals only16,17; for diastolic blood pressure, 2 studies reported increases in female

individuals,17,19and 1 reported

increa-ses in male individuals.16Meta-analysis

of studies in which data were reported in genders separately demonstrated

a 2.41 mm Hg (P,.0001) increase in

systolic blood pressure in those who were female, similar to the 2.48 mm Hg

(P,.0001) increase in those who were

male. For diastolic blood pressure, however, female individuals had a 1.69

mm Hg (95% CI: 0.89–2.50; P, .0001)

increase, and male individuals had

a nonsignificant 0.67 mm Hg (95% CI:2

0.312 to 1.45;P= .1) difference. We then

studied whether the blood pressure difference varied with age of follow-up.

Studies of younger children, aged,10

years at the time of follow-up, had a mean increase of 2.91 mm Hg in

sys-tolic blood pressure (95% CI: 1.55–4.27;

P,.00001), similar to the 2.24 mm Hg

increase (95% CI: 1.49–2.98;P,.00001)

in those aged$10 years. Because birth

weight25and gestational age26associate

with later blood pressure, we also

ana-lyzed 4 studies that reportedfindings in

term-born offspring and in which those born to pregnancies complicated by preeclampsia had a mean birth weight

.2.5 kg, similar to the level in controls.

In these studies, preeclampsia still was associated with a 2.26 mm Hg (95% CI:

1.35–3.16; P,.00001) higher systolic

and a 1.48 mm Hg (95% CI: 0.82–2.14;

P,.0001) higher diastolic blood

pres-sure (Fig 4).

BMI

Eight studies compared BMI with data

on 39 611 participants.15,17–21,27 In 5

studies, BMI was greater in exposed

individuals, but this finding was

sig-nificant only in 2, and then only in girls

in 1 study17and boys in the other study.27

In 1 study of adolescents living at

alti-tude, BMI was reduced significantly15;

however, meta-analysis identified a

sig-nificant increase of 0.57 (P,.00001) in

the children of preeclamptic women.

Heterogeneity was significant

(hetero-geneity:x2= 23.40, degrees of freedom =

9 [P= .005]; I2= 62%), and appeared to

be driven by the study of offspring living

at altitude.15 Because the authors of

some works have suggested that living at high altitude is associated with a lower BMI, this factor was consid-ered a plausible explanation for the

observed heterogeneity.28 When this

study was removed, an increase in BMI

without significant heterogeneity was

noted (0.62; 95% CI: 0.41–0.84;P,.0001;

Fig 5). Significant increases in BMI were

seen both when female individuals were

considered alone (0.69; 95% CI: 0.35–

1.03;P,.0001) and in studies

consid-ering male individuals alone (0.83; 95%

CI: 0.48–1.18; P , .006); however, no

difference was evident in studies that

included only children aged,10 years

(0.15; 95% CI:20.34 to 0.64;P, .55),

whereas there was a significant increase

FIGURE 1

(4)
(5)

in those$10 years (0.69; 95% CI: 0.35–

1.03; P,.0001). When studies which

reported findings in term born

off-spring and in which those born to preg-nancies complicated by preeclampsia had a mean birth weight greater than

2.5 kg were considered, a significant

increase in BMI was seen (0.67; 95% CI:

0.35–0.99;P,.0001).

Cholesterol

Ten studies considered lipid levels, representing data on 6164 individuals, of whom 423 were exposed to

pre-eclampsia18,20,23,29–35 (Table 2). Uniquely,

6 of the studies, comprising 366 par-ticipants, reported levels at birth in

cord blood.30–35 Because these studies

reflect the unique postdelivery biological

situation, we considered the studies separately. Five reported changes in

lipid profile; 4 reported an increase in

triglycerides30–32,34; 2 reported an

in-crease in total cholesterol; 2 reported an

increase in low-density lipoprotein32,33;

and 3 reported a decrease in

high-density lipoprotein.30–32In studies in

later life (considering children and

young adults aged 9–30), 1 was

per-formed on nonfasted samples.23Two

of the fasting studies found increased total cholesterol, with 1 reporting an increase in low-density lipoprotein

cho-lesterol.20,29 No other differences were

demonstrated. These studies included only 208 subjects, and in view of the small number of participants, meta-analysis was not performed.

Glucose Metabolism

Only 2 studies have considered fasting glucose, representing only 174

par-ticipants.18,20At age 12, there was no

difference in serum insulin, glucose, or

glucose-to-insulin ratio.18In young

adult-hood, preterm offspring of preeclamptic mothers had increased fasting glucose

(5.04 vs 4.57 mmol/L;P= .0001).20In view

of the limited number of studies, no meta-analysis was performed.

DISCUSSION

This study generates thefirst

compre-hensive analysis of the cardiovascular phenotype of children and young adults whose mothers had preeclampsia. The results are based on published data, on

FIGURE 2

Mean difference in systolic blood pressure in mm Hg between those who were exposed to preeclampsia in utero and controls. IV, inverse variance.

FIGURE 3

(6)

multiple outcomes, on ∼45 000 indi-viduals. In childhood and early adult life, these offspring have higher blood pressure and a small increase in BMI. Differences are evident in both male individuals and female individuals and in those with normal birth weight. Based on current reports, there are

insufficient studies to allow an

appre-ciation of the long-term effects, if any, of preeclampsia on the glucose me-tabolism or lipid levels of offspring, except for probable acute changes in

perinatal lipid profiles.

If the 2.4 mm Hg difference in systolic blood pressure tracks into

adult-hood,36this difference would be

asso-ciated with an∼8% increased risk of

mortality from ischemic heart disease

and a 12% increased risk from

stroke.37The only long-term mortality

follow-up study reported so far showed a 1.9-fold increased risk of stroke mor-tality in the offspring of preeclamptic

pregnancies.4Together, these data

sug-gest that this population of children may be one in which intensive monitoring and early primary prevention advice may be warranted. Current data are limited almost exclusively to young cohorts, and it is possible the blood pressure difference increases with age to explain the greater observed stroke risk. We found no evidence that the observed increase in blood pressure varies between childhood and young

adulthood, however, and it is possible that preeclampsia exposure is asso-ciated with other biological variations that alter risk. Some studies found

gender-specific variation in associations

between preeclampsia and offspring

blood pressure38; however, our

com-bined analysis indicates gender is

un-likely to be a further significant factor,

certainly for systolic blood pressure, al-though there was some evidence for differences in diastolic pressure that may warrant investigation.

Preeclampsia is a recognized cause of

fetal growth restriction,39 which is

itself associated with increased blood pressure in adult life. We therefore performed an analysis restricted to

FIGURE 4

A, Mean difference in systolic blood pressure in term-born infants of normal birth weight. B, Mean difference in diastolic blood pressure in term-born infants of normal birth weight.

FIGURE 5

(7)

studies of individuals who were born at term, and in which the mean birth

weight of the cases was.2.5 kg. These

offspring still had a 2.26 mm Hg higher systolic and a 1.48 mm Hg higher di-astolic blood pressure and a 0.67 in-crease in BMI. Currently available data do not allow for more detailed analysis of the effects of various degrees of growth restriction. Interestingly, some evidence suggests that very low birth weight in-dividuals born preterm have higher blood pressure regardless of whether

the mother had preeclampsia17,37,38;

however, the underlying mechanistic link with later blood pressure may vary, de-pending on the blood pressure of the

mother.17More focused studies will

pro-vide interesting insight into the potential highly complex interaction of growth re-striction and exposure to preeclampsia in modulating offspring cardiovascular phenotype.

Rapid postnatal growth also may

im-pact blood pressure,25and offspring of

mothers with affected pregnancies ap-pear to have a consistently higher BMI

of∼0.6. It remains unlikely that this

in-crease alone accounts for the variation in blood pressure, because based on previous reports, at least a 1 to 2 dif-ference in BMI would be needed to

ex-plain the .2 mm Hg difference.40–42

Although some studies have shown an attenuation of the difference in blood pressure when offspring BMI was

ad-justed for,27 more recent data in

chil-dren exposed to preeclampsia in utero suggest that the increase in blood pressure remains after adjustment for

BMI43and childhood growth trajectory.44

Furthermore, the increase in BMI was most evident in early adulthood, whereas the blood pressure difference was al-ready established in childhood. Nev-ertheless, it remains possible that raised BMI contributes in part to increased blood pressure in later life or that the impact of preeclampsia exposure on body fat distribution, and thereby blood pressure, in childhood has so far been underestimated. BMI may not be the best predictor of adiposity in

chil-dren, particularly in thin individuals.45

Alternatively, because raised maternal BMI is a risk for both preeclampsia and

offspring obesity,46,47shared

environ-mental influences may be important

in this association.

The data available on lipid, glucose, and insulin levels were more limited, so the

available publications are insufficient

to allow definitive conclusions on the

ef-fect, if any, of preeclampsia on offspring glucose metabolism or lipids. There did

appear to be changes in lipid profile in

cord blood. These samples likely reflect

acute conditions at delivery in a mother with increased circulating oxidative and

inflammatory stimuli. Samples from

later in life suggest that, if preeclampsia exposure has a longer-term impact on childhood cholesterol levels, it is likely to account for up to 1 mmol/L variation in total cholesterol. Further data will be

useful to refine this estimate.

There are several potential limitations to our analysis. Our study cannot pro-vide insight into mechanisms underlying this phenotype. It seems probable that there are links with the etiology and

TABLE 2 Lipid Studies in Offspring of Preeclamptic Pregnancies

Total Cholesterol HDL LDL Triglyceride

Studies on cord blood Akcakus et al,

201030, mg/dL

No difference: 73.3 vs 80.5;P= .72

Decreased: 17.3 vs 27.6;P= .002

No difference: 48.2 vs 49.9;P= .82

Increased: 39.2 vs 14.9;

P= .039 Catarino et al,

200831, mg/dL

No difference: 73 vs 86;P= .09

Decreased: 32 vs 53;P,.001

No difference: 34 vs 32;P= .68

Increased: 49 vs 39;

P= .049 Howlander et al,

200932, mg/dL

Increased: 70.9 vs 48.2;P,.001

Decreased: 10.3 vs 13.3;P,.001

Increased: 65.6 vs 28.0;P,.001

Increased: 52.4 vs 31.6;

P,.01 Ophir et al, 200633,

mg/dL

No difference: 70.6 vs 82.0;P= NS

Not reported:— Increased: 42 vs 36.8;

P,.01

No difference: 46.5 vs 45.0;

P= NS Rodie et al, 200434,

log mmol/L

Increased: 0.36 vs 0.11;P= .003

No differencea Not reported:Increased:20.21 vs20.49; P= .02

Yavuz et al, 200635, mg/dL

No difference: 65 vs 56;P= NS

No difference: 28.3 vs 25.2;P= NS

No difference: 30.4 vs 25.5;P= NS

No difference: 30.6 vs 32.6;

P= NS Studies in children and

young adults

Kvehaugen et al, 201129, mmol/L

Increased: 5.01 vs 4.43;P= .04

No difference: 1.60 vs 1.41;P= .1

No difference: 1.81 vs 1.53;P= .3

No difference: 0.60 vs 0.58;

P= .9 Lazdam et al, 201020,

mmol/L

Increased: 4.7 vs 3.87;P= .001

No difference: 1.6 vs 1.46;P= .42

Increased: 2.65 vs 2.00;P= .0001

No difference: 0.99 vs 0.89;

P= .44 Lawlor et al, 201123,

mmol/L

Not reported No difference: 1.37 vs 1.40;P= .21

No difference: 2.87 vs 2.87;P= .76

No difference: 0.99 vs 1.03;

P= .78 Tenhola et al, 200318,

mmol/L

No difference: 4.54 vs 4.50;P= .618

No difference: 1.31 vs 1.36;P= .468

No difference: 2.82 vs 2.75;P= .342

No difference: 0.90 vs 0.86;

P= .617

HDL, high-density lipoprotein; LDL, low-density lipoprotein; NS, not significant.

(8)

pathogenesis of maternal preeclampsia. Disturbed placentation is thought to be

a key factor in preeclampsia,6with

rela-tive placental ischemia and decreased

uterine and placental flow.48 There is

extensive literature on developmental programming of offspring in response

to placental insufficiency and in utero

insults4951; however, most of these

stud-ies considered the effects of intrauterine growth restriction, and it remains un-clear as to whether this model accurately represents the situation of preeclamp-sia. More relevant may be studies that have investigated programming of vas-cular function, which appear to show

effects independent of birth weight.52

Alternatively, blood pressure program-ming may occur in response to unique biological features of preeclampsia or

reflect shared genetic factors relevant to

both preeclampsia and blood pressure

control.53 We have considered only the

effect of preeclampsia on traditional cardiovascular risk factors. Recent studies have linked preeclamptic preg-nancy to alterations in other recognized cardiovascular risk factors, such as

de-pression in the offspring.54 Other novel

cardiovascular risk factors will warrant further consideration in future studies. Furthermore, the data available in the current literature do not allow for full exploration of potential confounding

factors. It is possible that ourfindings

may, in part, reflect such factors. For

example, raised maternal BMI is a risk for both preeclampsia and offspring

obesity,46,47 and raised maternal

preg-nancy BMI is associated with higher off-spring blood pressure, although this

relationship attenuates when childhood

BMI is considered.44Conversely, some

potential confounding factors may lead to underestimation of the true effect size of in utero exposure to preeclampsia. For example, maternal smoking reduces the

risk of preeclampsia by up to 50%,55but

it increases offspring blood pressure in

adult life.56

Interpretation of our findings also

needs to take into account the fact that observational studies are more prone to publication bias than randomized

clinical trials12; however, funnel plots

for considered outcome measures were grossly symmetrical. Meta-analysis of continuous outcome variables also can

be affected significantly by heterogeneity,

and without source data, it can be diffi

-cult to explore subgroup variation. Nev-ertheless, our review did not highlight heterogeneity. It did highlight a striking paucity of end-point data in this research area. In this situation, meta-analysis of continuous variables previously has been used effectively to provide clinically

in-terpretable assessment of effects.57The

studies also had been published during

a period when preeclampsia definitions

varied, and we cannot exclude the

pos-sibility that studies misidentified cases

or included individuals who would not meet current diagnostic criteria. We did not include studies examining gesta-tional hypertension, because it may have

a different pathophysiology.58

Never-theless, offspring of hypertensive preg-nancies have been noted to have an

increased blood pressure,59–61 and this

literature warrants review. We also

identified increasing reports of variation

in other biological measures in offspring

of preeclamptic pregnancies,32,6265 but

these reports were excluded because they did not report established prog-nostic markers of cardiovascular dis-ease. Finally, nearly all studies were of infants born close to term, presumably to mothers with less severe preeclamp-sia. The one study that considered the risk of hypertension found this risk to be greater in those born to mothers with

more severe preeclampsia,4 and there

was some evidence that the blood pres-sure differences may be greater in those

born preterm.20The impact on the

off-spring of maternal disease severity needs further exploration.

CONCLUSIONS

Children and young adults born to pregnancies complicated by preeclamp-sia have adverse changes in cardio-vascular risk factors present from early life. The predominant phenotype that is now evident in multiple studies is of changes in blood pressure and BMI. Greater mechanistic understanding of these differences in blood pressure may provide useful insights into why some people are predisposed to hyper-tension and preeclampsia. From a public health perspective, children born to a pregnancy complicated by pre-eclampsia appear to have a unique,

life-time cardiovascular risk profile that is

present from early life, and so may constitute a population that may

ben-efit from risk profile monitoring and

early implementation of primary pre-vention strategies.

REFERENCES

1. Bellamy L, Casas J-P, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis.BMJ. 2007;335 (7627):974

2. McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae

of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J. 2008;156(5):918–930

3. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the

American Heart Association. Circulation. 2011;123(11):1243–1262

(9)

5. Ferreira I, Peeters LL, Stehouwer CD. Pre-eclampsia and increased blood pressure in the offspring: meta-analysis and critical review of the evidence.J Hypertens. 2009; 27(10):1955–1959

6. Steegers EAP, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia.Lancet. 2010; 376(9741):631–644

7. Wen SW, Chen XK, Rodger M, et al. Folic acid supplementation in early second trimester and the risk of preeclampsia.Am J Obstet Gynecol.2008;198(1):45.e1–7

8. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339: b2535

9. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemi-ology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.JAMA. 2000;283(15):2008– 2012

10. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin J-M. The classification and diagnosis of the hypertensive dis-orders of pregnancy: statement from the International Society for the Study of Hy-pertension in Pregnancy (ISSHP). Hyper-tens Pregnancy. 2001;20(1):IX–XIV 11. Review Manager (RevMan) [computer

pro-gram]. Version 5.1. Copenhagen, Denmark: The Nordic Cochrane Centre, The Cochrane Collaboration; 2011

12. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet. 1991;337(8746):867–872

13. Owen CG, Whincup PH, Kaye SJ, et al. Does initial breastfeeding lead to lower blood cholesterol in adult life? A quantitative re-view of the evidence.Am J Clin Nutr. 2008; 88(2):305–314

14. Owen CG, Martin RM, Whincup PH, Smith GD, Cook DG. Effect of infant feeding on the risk of obesity across the life course: a quan-titative review of published evidence. Pediat-rics. 2005;115(5):1367–1377

15. Jayet P-Y, Rimoldi SF, Stuber T, et al. Pul-monary and systemic vascular dysfunction in young offspring of mothers with pre-eclampsia.Circulation. 2010;122(5):488–494 16. Palti H, Rothschild E. Blood pressure and

growth at 6 years of age among offsprings of mothers with hypertension of preg-nancy.Early Hum Dev. 1989;19(4):263–269 17. Seidman DS, Laor A, Gale R, Stevenson DK,

Mashiach S, Danon YL. Pre-eclampsia and offspring’s blood pressure, cognitive ability and physical development at 17-years-of-age.Br J Obstet Gynaecol. 1991;98(10):1009– 1014

18. Tenhola S, Rahiala E, Martikainen A, Halonen P, Voutilainen R. Blood pressure, serum lip-ids, fasting insulin, and adrenal hormones in 12-year-old children born with maternal preeclampsia.J Clin Endocrinol Metab. 2003; 88(3):1217–1222

19. Vatten LJ, Romundstad PR, Holmen TL, Hsieh CC, Trichopoulos D, Stuver SO. In-trauterine exposure to preeclampsia and adolescent blood pressure, body size, and age at menarche in female offspring.Obstet Gynecol. 2003;101(3):529–533

20. Lazdam M, de la Horra A, Pitcher A, et al. Elevated blood pressure in offspring born premature to hypertensive pregnancy: is endothelial dysfunction the underlying vascular mechanism?Hypertension. 2010; 56(1):159–165

21. Kvehaugen AS, Andersen LF, Staff AC. An-thropometry and cardiovascular risk factors in women and offspring after pregnancies complicated by preeclampsia or diabetes mellitus.Acta Obstet Gynecol Scand. 2010;89 (11):1478–1485

22. Hiller JE, Crowther CA, Moore VA, Willson K, Robinson JS. Calcium supplementation in pregnancy and its impact on blood pres-sure in children and women: follow up of a randomised controlled trial.Aust N Z J Obstet Gynaecol. 2007;47(2):115–121 23. Lawlor DA, Macdonald-Wallis C, Fraser A,

et al. Cardiovascular biomarkers and vas-cular function during childhood in the off-spring of mothers with hypertensive disorders of pregnancy:findings from the Avon Longitudinal Study of Parents and Children.Eur Heart J. 2012;33(3):335–345 24. Øglaend B, Forman MR, Romundstad PR,

Nilsen ST, Vatten LJ. Blood pressure in early adolescence in the offspring of preeclamptic and normotensive pregnancies.J Hypertens. 2009;27(10):2051–2054

25. Huxley RR, Shiell AW, Law CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a sys-tematic review of the literature.J Hypertens. 2000;18(7):815–831

26. Norman M. Preterm birth—an emerging risk factor for adult hypertension?Semin Perinatol. 2010;34(3):183–187

27. Ogland B, Vatten LJ, Romundstad PR, Nilsen ST, Forman MR. Pubertal anthropometry in sons and daughters of women with pre-eclamptic or normotensive pregnancies. Arch Dis Child. 2009;94(11):855–859 28. Sherpa LY, Deji H, Stigum H,

Chongsuvi-vatwong V, Thelle DS, Bjertness E. Obesity in Tibetans aged 30-70 living at different alti-tudes under the north and south faces of Mt. Everest.Int J Environ Res Public Health. 2010;7(4):1670–1680

29. Kvehaugen AS, Dechend R, Ramstad HB, Troisi R, Fugelseth D, Staff AC. Endothelial function and circulating biomarkers are disturbed in women and children after preeclampsia.Hypertension. 2011;58(1):63– 69

30. Akcakus M, Koklu E, Baykan A, et al. Mac-rosomic newborns of diabetic mothers are associated with increased aortic intima-media thickness and lipid concentrations. Horm Res. 2007;67(6):277–283

31. Catarino C, Rebelo I, Belo L, et al. Fetal li-poprotein changes in pre-eclampsia. Acta Obstet Gynecol Scand. 2008;87(6):628–634 32. Howlader MZ, Parveen S, Tamanna S, Khan

TA, Begum F. Oxidative stress and antioxi-dant status in neonates born to pre-eclamptic mother. J Trop Pediatr. 2009;55 (6):363–367

33. Ophir E, Dourleshter G, Hirsh Y, Fait V, German L, Bornstein J. Newborns of pre-eclamptic women: a biochemical difference present in utero.Acta Obstet Gynecol Scand. 2006;85(10):1172–1178

34. Rodie VA, Caslake MJ, Stewart F, et al. Fetal cord plasma lipoprotein status in un-complicated human pregnancies and in pregnancies complicated by pre-eclampsia and intrauterine growth restriction. Ath-erosclerosis. 2004;176(1):181–187 35. Yavuz T, Yavuz O, Ozdemir I, Afsar Y. Cord

blood lipoprotein profile after magne-sium sulphate treatment in pre-eclamptic patients.Acta Paediatr. 2006;95(10):1224– 1227

36. Chen X, Wang Y. Tracking of blood pressure from childhood to adulthood: a systematic review and meta-regression analysis. Cir-culation. 2008;117(25):3171–3180

37. NICE. Hypertension (update). Available at: www.nice.org.uk/newsroom/pressreleases/ NewGuidelineForDiagnosingAndTreatingHigh BloodPressure.jsp. Accessed February 22, 2011

38. Langford HG, Watson RL. Prepregnant blood pressure, hypertension during pregnancy, and later blood pressure of mothers and offspring.Hypertension. 1980;2(4 pt 2):130– 133

39. Duley L. The global impact of pre-eclampsia and eclampsia.Semin Perinatol. 2009;33(3): 130–137

40. He Q, Ding ZY, Fong DY-T, Karlberg J. Blood pressure is associated with body mass index in both normal and obese children. Hypertension. 2000;36(2):165–170 41. Maximova K, O’Loughlin J, Paradis G, Hanley

(10)

42. Wright CM, Emmett PM, Ness AR, Reilly JJ, Sherriff A. Tracking of obesity and body fatness through mid-childhood. Arch Dis Child. 2010;95(8):612–617

43. Geelhoed JJM, Fraser A, Tilling K, et al. Preeclampsia and gestational hypertension are associated with childhood blood pressure independently of family adiposity measures: the Avon Longitudinal Study of Parents and Children.Circulation. 2010;122(12):1192–1199 44. Wen X, Triche EW, Hogan JW, Shenassa ED, Buka SL. Prenatal factors for childhood blood pressure mediated by intrauterine and/or childhood growth?Pediatrics. 2011; 127(3). Available at: www.pediatrics.org/ cgi/content/full/127/3/e713

45. Freedman DS, Ogden CL, Berenson GS, Horlick M. Body mass index and body fat-ness in childhood. Curr Opin Clin Nutr Metab Care. 2005;8(6):618–623

46. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: sys-tematic review of controlled studies.BMJ. 2005;330(7491):565

47. Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH. Predicting obesity in young adulthood from childhood and parental obesity.N Engl J Med. 1997;337(13):869–873 48. Kanasaki K, Kalluri R. The biology of pre-eclampsia.Kidney Int. 2009;76(8):831–837 49. Vickers MH, Breier BH, Cutfield WS, Hofman

PL, Gluckman PD. Fetal origins of hyper-phagia, obesity, and hypertension and post-natal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000;279(1): E83–E87

50. Warner MJ, Ozanne SE. Mechanisms in-volved in the developmental programming of adulthood disease.Biochem J. 2010;427 (3):333–347

51. Wang Z, Huang Z, Lu G, Lin L, Ferrari M. Hypoxia during pregnancy in rats leads to early morphological changes of athero-sclerosis in adult offspring.Am J Physiol Heart Circ Physiol. 2009;296(5):H1321–H1328 52. Torrens C, Brawley L, Barker AC, Itoh S, Poston L, Hanson MA. Maternal protein re-striction in the rat impairs resistance artery but not conduit artery function in pregnant offspring.J Physiol. 2003;547(pt 1):77–84 53. Genetics of Pre-eclampsia (GOPEC)

consor-tium. Babies, pre-eclamptic mothers and grandparents: a three-generation pheno-typing study.J Hypertens. 2007;25(4):849– 854

54. Tuovinen S, Räikkönen K, Kajantie E, et al. Depressive symptoms in adulthood and intrauterine exposure to pre-eclampsia: the Helsinki Birth Cohort Study.BJOG. 2010;117 (10):1236–1242

55. Hutcheon JA, Lisonkova S, Joseph KS. Epi-demiology of pre-eclampsia and the other hypertensive disorders of pregnancy.Best Pract Res Clin Obstet Gynaecol. 2011;25(4): 391–403

56. Power C, Atherton K, Thomas C. Maternal smoking in pregnancy, adult adiposity and other risk factors for cardiovascular dis-ease.Atherosclerosis. 2010;211(2):643–648 57. Owen CG, Whincup PH, Gilg JA, Cook DG. Effect of breast feeding in infancy on blood pressure in later life: systematic review and meta-analysis. BMJ. 2003;327(7425): 1189–1195

58. Roberts JM, Pearson G, Cutler J, Lind-heimer M; NHLBI Working Group on Re-search on Hypertension During Pregnancy. Summary of the NHLBI Working Group on Research on Hypertension During Preg-nancy.Hypertension. 2003;41(3):437–445

59. Higgins M, Keller J, Moore F, Ostrander L, Metzner H, Stock L. Studies of blood sure in Tecumseh, Michigan. I. Blood pres-sure in young people and its relationship to personal and familial characteristics and complications of pregnancy in mothers.Am J Epidemiol. 1980;111(2):142–155 60. Kotchen JM, Kotchen TA, Cottrill CM, Guthrie

GP Jr, Somes G. Blood pressures of young mothers and theirfirst children 3-6 years following hypertension during pregnancy. J Chronic Dis. 1979;32(9-10):653–659 61. Himmelmann A. Blood pressure and left

ventricular mass in children and adoles-cents: the Hypertension in Pregnancy Off-spring Study.Blood Press Suppl. 1994;3:1–46 62. Steinert JR, Wyatt AW, Poston L, Jacob R, Mann GE. Preeclampsia is associated with altered Ca2+ regulation and NO production in human fetal venous endothelial cells. FASEB J. 2002;16(7):721–723

63. Laskowska M, Laskowska K, Oleszczuk J. Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normo-tensive and preeclamptic pregnant women: a comparison between preeclamptic pa-tients with appropriate-for-gestational-age weight infants and healthy pregnant women [published online ahead of print July 27, 2011].J Matern Fetal Neonatal Med. doi: 10.3109/14767058.2011.595852 64. Davidge ST, Signorella AP, Lykins DL, Gilmour

CH, Roberts JM. Evidence of endothelial ac-tivation and endothelial activators in cord blood of infants of preeclamptic women.Am J Obstet Gynecol. 1996;175(5):1301–1306 65. Stark MJ, Clifton VL, Wright IMR. Neonates

(11)

DOI: 10.1542/peds.2011-3093 originally published online May 21, 2012;

2012;129;e1552

Pediatrics

Kenny McCormick, Ian Sargent, Christopher Redman and Paul Leeson

Worton, Brenda Kelly, Yvonne Kenworthy, Satish Adwani, Andrew R. Wilkinson,

Esther Frances Davis, Merzaka Lazdam, Adam James Lewandowski, Stephanie Anne

Preeclamptic Pregnancies: A Systematic Review

Cardiovascular Risk Factors in Children and Young Adults Born to

Services

Updated Information &

http://pediatrics.aappublications.org/content/129/6/e1552 including high resolution figures, can be found at:

References

http://pediatrics.aappublications.org/content/129/6/e1552#BIBL This article cites 61 articles, 19 of which you can access for free at:

Subspecialty Collections

http://www.aappublications.org/cgi/collection/cardiology_sub

Cardiology

following collection(s):

This article, along with others on similar topics, appears in the

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml in its entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or

Reprints

(12)

DOI: 10.1542/peds.2011-3093 originally published online May 21, 2012;

2012;129;e1552

Pediatrics

Kenny McCormick, Ian Sargent, Christopher Redman and Paul Leeson

Worton, Brenda Kelly, Yvonne Kenworthy, Satish Adwani, Andrew R. Wilkinson,

http://pediatrics.aappublications.org/content/129/6/e1552

located on the World Wide Web at:

The online version of this article, along with updated information and services, is

http://pediatrics.aappublications.org/content/suppl/2012/05/16/peds.2011-3093.DCSupplemental Data Supplement at:

by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Figure

FIGURE 1Study selection process.
TABLE 1 Characteristics of Included Studies
FIGURE 2Mean difference in systolic blood pressure in mm Hg between those who were exposed to preeclampsia in utero and controls
FIGURE 4A,Mean differenceinsystolicbloodpressure interm-born infantsofnormal birthweight
+2

References

Related documents

A special thank you is extended to all of the Departments who supplied updated information for the 2006 revised “Patterns of Government” including: Onondaga County Office of the

Although the equilibrium of the model is characterized by low inflation, episodes of high inflation and unemployment can occur when policymakers simultaneously underestimate both

Summer Internship : Stock Holding Corporation of

Research Agaskhind, Sinner , Nasik. Warane A.L.,K.K.Wagh Nasik. College of Engg., Bavada, Indapur, Pune. Sapkal College of Engineering Angeri,.. Nasik. Trust Group of Inst., Kasti

Structural Connectivity Based Parcellation Our first contribution is a parsimonious model for the long-range axonal connectivity (extrinsic connectivity), and an efficient technique

ALTHOUGH ANY INFORMATION, RECOMMENDATIONS, OR ADVICE CONTAINED HEREIN IS GIVEN IN GOOD FAITH, SUPPLIERS MAKE NO WARRANTY OR GUARANTEE, EXPRESS OR IMPLIED, (i) THAT THE

Due to which Russia is weighing its options favorable to its core interests; to counter or maintain the balance of power in the region, as Russia continue to be the

Mike DeWine (right) speaks with local farmer, Kris Swartz, at his farm along Reitz Road in Perrysburg Township..