Preterm birth and maternal smoking in pregnancy are strong risk factors for aortic narrowing in adolescence

Article (PDF Available)inActa Paediatrica 97(8):1080-5 · September 2008with9 Reads
DOI: 10.1111/j.1651-2227.2008.00890.x · Source: PubMed
Abstract
Preterm transition from foetal to neonatal circulation might permanently alter aortic growth and development. To test this hypothesis, we measured aortic dimensions in adolescents born very preterm. Eighty-six healthy 15-year-old subjects were studied; 45 born very preterm at an average gestational age of 28 weeks (birth weight < 1500 g) and 41 controls born at term. Using a pulse-gated Fiesta sequence on a 1.5T MR-scanner, 25 images were collected within the heart cycle at several levels of the descending aorta. End-diastolic cross-sectional areas were semi-automatically calculated using an active contour model. Subjects born preterm had narrower aortic lumen. The difference was 16% in the thoracic and 19% in the abdominal aorta after adjustment for body surface area and gender (p < 0.001). Maternal smoking in pregnancy was also found to be an independent risk factor for aortic narrowing in the offspring (difference 10%-13% throughout the aorta vs. offspring to nonsmoking mothers). Adolescents born preterm had higher systolic and diastolic blood pressures; however, blood pressures did not correlate with aortic size or maternal smoking during pregnancy. Very preterm birth and exposure to maternal smoking in foetal life are independent and strong risk factors for general aortic narrowing 15 years after birth.

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Acta Pædiatrica ISSN 0803–5253
REGULAR ARTICLE
Preterm birth and maternal smoking in pregnancy are strong risk factors for
aortic narrowing in adolescence
Anna-Karin Edstedt Bonamy (anna-karin.edstedt.bonamy@ki.se)1,JohanBengtsson
2, Zoltan Nagy1,2, Hans De Keyzer3, Mikael Norman3
1.Department of Woman and Child Health, Karolinska Institutet, 171 76 Stockholm, Sweden
2.Department of Medical Physics, MR-physics unit, Karolinska University Hospital, 171 76 Stockholm, Sweden
3.Department of Clinical Science, Intervention and Technology, Karolinska Insitutet, 141 86 Stockholm, Sweden
Keywords
Aorta, Blood pressure, Magnetic resonance imaging,
Paediatrics, Smoking
Correspondence
Anna-Karin Edstedt Bonamy, Q8:00, Astrid Lindgren
Children’s Hospital, 171 76 Stockholm, Sweden.
Tel: +46-709-387260 |
Fax: +46-87533713 |
Email: anna-karin.edstedt.bonamy@ki.se
Received
18 March 2008; revised 2 May 2008;
accepted 12 May 2008.
DOI:10.1111/j.1651-2227.2008.00890.x
Abstract
Aim: Preterm transition from foetal to neonatal circulation might permanently alter aortic growth and
development. To test this hypothesis, we measured aortic dimensions in adolescents born very
preterm.
Methods: Eighty-six healthy 15-year-old subjects were studied; 45 born very preterm at an average
gestational age of 28 weeks (birth weight <1500 g) and 41 controls born at term. Using a pulse-
gated Fiesta sequence on a 1.5T MR-scanner, 25 images were collected within the heart cycle at
several levels of the descending aorta. End-diastolic cross-sectional areas were semi-automatically
calculated using an active contour model.
Results: Subjects born preterm had narrower aortic lumen. The difference was 16% in the thoracic
and 19% in the abdominal aorta after adjustment for body surface area and gender (p <0.001).
Maternal smoking in pregnancy was also found to be an independent risk factor for aortic narrowing
in the offspring (difference 10%–13% throughout the aorta vs. offspring to nonsmoking mothers).
Adolescents born preterm had higher systolic and diastolic blood pressures; however, blood
pressures did not correlate with aortic size or maternal smoking during pregnancy.
Conclusion: Very preterm birth and exposure to maternal smoking in foetal life are independent and strong risk
factors for general aortic narrowing 15 years after birth.
INTRODUCTION
Preterm delivery is a common pregnancy complication.
Among young people, 5% to 12% have been born before
37 weeks of gestation. Furthermore, the number of adult
survivors of very preterm birth (<32 weeks of gestation) is
steadily increasing, mainly as a result of improved antenatal
and neonatal care (1). Although the vast majority is healthy,
recent observations indicate that people born preterm are at
an increased risk of hypertension later in life (2–6). While
the causes are still unclear, there is convincing epidemio-
logic evidence for perinatal contributions to this association,
rather than a common genetic explanation (3,7).
Supported by experimental data (8), and observations in
girls born preterm (6), we have suggested that preterm birth
has lasting adverse effects on growth and development of
the aorta. Normal aortic size and structure are important
for an effective blood circulation. During cardiac ejection,
the aorta temporarily accommodates the propelled stroke
volume. At the same time it modifies the transmission of
pressure to downstream vascular beds. These functions are
dependent on the elastic properties of the aorta, as well as
on its size (9).
To explore the hypothesis that very preterm birth per-
manently affects aortic development, we measured aortic
dimensions using magnetic resonance imaging in a prospec-
tively recruited cohort of healthy adolescents.
METHODS
The Stockholm Neonatal Project (10), a prospective
population-based study, was initiated in September 1988
and continued until March 1993. All children with a birth
weight of 1500 g or less were included if they were born
at or transferred to the neonatal intensive care unit at the
Karolinska Hospital or at an annex unit at St. G ¨
oran’s Hos-
pital in Stockholm, Sweden.
Of the 291 infants originally included, 182 were available
for follow-up at 51
/
2years of age (1994–1998), the remain-
der having either died, declined participation or moved out
of the Stockholm area. At that age, a control group of 125
term-born children was assembled from a population-based
register according to birth date, birth hospital and gender.
From the available 182 cases, we excluded all those who
were from multiple births or had a gestational age (GA) of
32 weeks or more. We invited all of the remaining 114 study
subjects and 75 of the original controls to participate in the
study in a random order. The response rate was close to 90%
in both groups. Because of metallic implants of unknown
composition (after surgical closure of a patent ductus arte-
riosus in the neonatal period), 16 children from the study
group were excluded from MRI. Another 35 adolescents in
the study group and 26 in the control group declined par-
ticipation. The MRI examinations were performed between
April 2005 and February 2006. In four examinations (one
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Bonamy et al. Risk factors for aortic narrowing in adolescence
of them a control), the data quality was suboptimal. In two
subjects, one from each group, the exams could not be fin-
ished due to claustrophobia, leaving 45 datasets for the study
group and 41 datasets for the control group. The mean ges-
tational age, birth weight and maternal age did not differ
between participants and nonparticipants in either group.
Perinatal data collection
The prospectively collected perinatal data contained infor-
mation on gestational age, birth weight and maternal ed-
ucation level according to the classification by Statistics
Sweden, and for those born preterm; mode of delivery,
patent ductus arteriosus (PDA), intraventricular hem-
orrhage (IVH), periventricular leucomalacia (PVL) and
retinopathy of prematurity (ROP). We also searched medical
records to gather further information on pre- and postnatal
steroid treatment, diagnosis or suspicion of necrotizing ente-
rocolitis (NEC), the use of umbilical artery catheter (UAC)
in the neonatal period and the cause of preterm delivery
(data shown on request). Small for gestational age (SGA)
was defined as having a birth weight less than 2 SD be-
low the mean birth weight for gestational age, according to
Swedish standards for normal foetal growth (11).
The study protocol had been approved by the regional
ethics committee and all participating adolescents and the
accompanying parent gave written informed consent to
participation.
Examination procedure
The subjects arrived at least 30 min prior to commence-
ment of the MR-examination. After 15 min of rest in the
upright sitting position, three measurements of heart rate
and brachial blood pressure (BP) were taken in the left arm
with an automated oscillometric method (Boso MedicusTM,
Bosch+Sohn GmbH u. Co., Jungingen, Germany), us-
ing an appropriately sized arm cuff. There were at least
3 min between consecutive measurements. The mean value
of the three consecutive determinations was used for further
analyses. The weight and height were measured according
to standard clinical procedure.
The subjects were asked about age at menarche (girls
only), present tobacco use and current medication. The par-
ents were interviewed about maternal smoking in the index
pregnancy and about family history of cardiovascular dis-
eases and hypertension in first- and second-degree relatives.
Subject characteristics and BP are summarized in Table 1.
Magnetic resonance imaging
Each participant underwent a single scanning session on
a 1.5 T MR scanner (GE, Milwaukee, USA). The protocol
included localizer scans along all three axes of the body
(Fig. 1). Based on these images, and depending on the height
of the subject, five to seven 5-mm thick slices were posi-
tioned along and approximately perpendicular to the de-
scending aorta. The slices were positioned 4.5 cm apart. For
reference, the first and most inferior slice was positioned just
below the iliac bifurcation. The images, which were used in
Table 1 Subject characteristics
Preterm Term controls
(n =45) (n =41) P-value
Family history
FH of hypertension, n (%) 30 (67%) 16 (39%) 0.01
Perinatal data
Maternal education level (median) 4 4 0.84
Maternal smoking in pregnancy 13 (29%) 11 (27%) 0.83
Maternal preeclampsia 10 (22%) 0
Gestational length, weeks 27.6 (2) 39.8 (1.2)
–range 24–31 37–42 —
Birth weight, g 1011 (211) 3510 (371)
Small for gestational age, n (%) 11 (24%) 0
Patent ductus arteriosus 19 (42%) 0
–surgery 4 (21%)
–indomethacin treatment 15 (79%)
Current data
Gender, female 23 (51%) 24 (57%) 0.57
Age, yrs 15.1 (1.2) 14.6 (1.2) 0.06
Weight, kg 54.3 (10.8) 56.1 (8.2) 0.39
Height, m 1.65 (0.11) 1.67(0.10) 0.45
Body mass index, kg/m219.8 (2.6) 20.2 (2.6) 0.49
Body surface area, m21.59 (0.20) 1.62 (0.15) 0.35
Menarche 19 (83%) 19 (79%) 0.91
–age at menarche 12.5 (0.9) 12.4 (0.8)
Tobacco use 2 (5%) 2 (5%) 0.92
Blood pressure and heart rate
Systolic blood pressure, mm Hg 122 (14) 115 (11) 0.01
Diastolic blood pressure, mm Hg 72 (8) 68 (9) 0.03
Heart rate, bpm 80 (13) 78 (10) 0.32
Data are mean (SD) or number of subjects (%).
P-values according to Chi-squared test or Student’s t-test shown where
appropriate.
further analysis, were acquired during breath-hold with a
retrospectively pulse-gated Fiesta sequence (12), providing
25 images within the subject’s heart-cycle for each slice. The
image acquisition parameters were as follows: field of view =
240 mm, repetition time =4.2 ms, echo time =1.8 ms, flip
angle =45, acquisition matrix =224 ×224 and then
padded with zeros to 256 ×256 before image reconstruc-
tion. The field of view was reduced to 80% in the phase
encoding directions (anterior–posterior).
The images of the aorta were segmented by an observer
blinded to subject group, using a subpixel-precision Active
Contour Model (13) implemented in Matlab, permitting
semi-automatic calculations of aortic end-diastolic cross-
sectional areas, defined as the smallest aortic area within
the heart cycle. Corresponding methods have previously
been used for aortic segmentation from MRI data (14). For
statistical analyses the second, fourth and fifth to seventh
slices were used, representing the distal abdominal aorta,
the proximal abdominal aorta and the thoracic aorta, respec-
tively (Fig. 1). For calculation of the coefficient of variation
(CV) for the aortic segmentation, we acquired five consec-
utive image series of an adult volunteer using the same MR
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Risk factors for aortic narrowing in adolescence Bonamy et al.
Figure 1 MRI slice positioning and segmentation in the descending aorta.
Part A and B depict the positioning of the MRI slices. Part C displays slice 4 in A
and B. The square indicates the area magnified in Part D. Part D illustrates the
result of the aortic segmentation (white outline).
image acquisition parameters as for the participants. The CV
varied between 0.6% and 2.3% at the different aortic levels.
In a random subset of end-diastolic images (n =90), we
also compared aortic measurements by the Active Contour
Model to those manually traced by an experienced blinded
MR-observer (Johan Bengtsson). The overall CV for the dif-
ferent aortic levels was 4.2%.
Statistical methods
The results are presented as mean and standard deviation
(SD), median (inter-quartile range) or proportions (%). Stu-
dent’s t-test, Wilcoxon rank-sum test and Chi-squared test
were used to investigate group differences. The α-level was
chosen to be 0.05. Inference about statistical significance
was made for each set of analyses after Bonferroni cor-
rection for multiple comparisons. Aortic end-diastolic areas
were log transformed before regression analyses to obtain a
better approximation of normal distribution.
The association between aortic areas and covariates, such
as group, gender, age, standard deviation score (SDS) for
birth weight in relation to gestational age, body surface
area, a family history of hypertension, maternal education
level and maternal smoking during pregnancy, were investi-
gated using simple linear regression or analysis of variance
(ANOVA). Associations with a p <0.25 were entered into
a forward stepwise multivariate regression model. In addi-
tion, associations between aortic area and neonatal charac-
teristics, such as gestational age, birth weight, SDS for birth
weight, mode of delivery, ROP, PDA, NEC and use of UAC,
were investigated within the preterm group. Group, gender,
age, height, SDS for birth weight, maternal smoking, aortic
size and heart rate were investigated as possible blood pres-
sure determinants. All data were analyzed using Intercooled
Stata 9.1 (StataCorpLP, TX, USA) and JMP 5.0.1 (SAS In-
stitute, Inc., Cary, NC, USA). The authors had full access to
the data and take responsibility for its integrity. All authors
have read and agreed to the article as written.
RESULTS
Preterm birth and aortic size
Subjects born very preterm had significantly smaller aortic
end-diastolic area at all levels. Table 2 shows unadjusted
group comparisons for four levels: the thoracic, proximal,
mid- and distal abdominal aorta. Results from univariate
regression analyses entering the other covariates are pre-
sented in Table S1 (supplementary material online). In a
multivariate analysis, preterm birth and maternal smoking
in pregnancy were found to be strong and highly significant
Table 2 Aortic end-diastolic cross-sectional area (mm2) measured by magnetic
resonance imaging in healthy adolescents born preterm or at term (total n =
86)
Preterm Term controls
(n =45) (n =41) P-value
Thoracic aorta, mm2114 (99–135) 139 (129–153) <0.001
Proximal abdominal aorta, mm2103 (84–117) 126 (104–147) <0.001
Mid-abdominal aorta, mm269 (61–86) 91 (75–107) <0.001
Distal abdominal aorta, mm273 (65–89) 96 (83–110) <0.001
Data are presented as median (inter-quartile range).
P-values according to Wilcoxon rank-sum test.
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Table 3 Change in end-diastolic aortic area in 15-year old subjects (n =86)
in relation to preterm birth, gender and exposure to maternal smoking in
pregnancy. Estimates are based on results of multivariate linear regression
analysis of log aortic area adjusted for body surface
% Change (95%CI) P-value
Thoracic aorta
Preterm 16.2 (10.2 to 21.8) <0.001
Male 9.8 (2.0 to 18.2) 0.013
Maternal smoking in pregnancy 12.4 (5.4 to 18.8) 0.001
Proximal abdominal aorta
Preterm 17.0 (10.9 to 22.6) <0.001
Male 12.5 (4.5 to 21.2) 0.002
Maternal smoking in pregnancy 13.2 (6.2 to 19.6) 0.001
Distal abdominal aorta
Preterm 19.0 (12.9 to 24.8) <0.001
Male 16.8 (8.0 to 26.3) <0.001
Maternal smoking in pregnancy 9.6 (2.0 to 16.7) 0.015
contributors to a narrower aorta, even after adjustment for
body surface area. Male sex was associated with a larger aor-
tic cross-sectional area (Table 3). Maternal education level,
a proxy variable for socioeconomic status, was not associ-
ated with aortic narrowing in uni- or multivariate analyses.
No interaction between maternal smoking in pregnancy and
preterm birth could be found, neither was there any inter-
action between maternal smoking and maternal education
level with respect to aortic narrowing.
Within the preterm group, the aortic area did not cor-
relate with perinatal covariates such as preeclampsia, SDS
for birth weight, UAC or PDA, at any of the levels of mea-
surement. Multivariate analyses, adjusted for body surface
area and gender, demonstrated that lower gestational age
and maternal smoking were independent contributors to a
narrower thoracic and distal abdominal aorta (Table S2 in
supplementary material online).
Blood pressure and heart rate
Both systolic and diastolic blood pressures were higher in
the preterm group, but there was no difference in heart rate
between groups, which is displayed in Table 1. The blood
pressures in adolescents of smoking mothers did not differ
from those without such exposure (p =0.60 for SBP and
p=0.77 for DBP). Height (regression coefficient β=0.5, p <
0.001), preterm birth (β=6.9, p =0.005) and heart rate (β=
0.4, p <0.001), but not sex, were associated with systolic BP
in the final multiple regression model (R2=0.33). Finally,
neither systolic nor diastolic blood pressure correlated with
aortic cross-sectional area.
DISCUSSION
The major findings of this study are that preterm birth and
foetal exposure to maternal smoking—two common adverse
perinatal risk factors—contribute to significant aortic nar-
rowing in adolescence.
Our results extend current knowledge on the link between
preterm birth and altered vascular outcome later in life. The
finding of marked aortic narrowing (16%–19%) despite a
higher distending pressure indicates that the reduced aortic
size in subjects born preterm has a structural basis.
Previous studies of aortic size in relation to perinatal char-
acteristics have focused on the role of foetal growth re-
striction. Both normal (15,16) and reduced aortic diameter
(17,18) have been reported. As shown in this study, very
preterm birth, and not only growth restriction at term, is
a strong predictor of later aortic narrowing. The degree of
prematurity seems to be important for this effect, as indi-
cated by the correlation between gestational age and aor-
tic area within the preterm group. Bearing the limitation of
small numbers in mind, we observed no obvious contribu-
tion to aortic narrowing from being small for gestational age
at birth.
The underlying mechanisms behind the association be-
tween preterm birth and reduced aortic size are unclear.
It is known that the birth-related termination of the pla-
cental circulation leads to a significant reduction in aortic
blood flow (8). Moreover, after birth the aortic development
will occur in face of higher systemic pressure, rather than
against the low vascular resistance of the placenta. If birth
and the subsequent changes in aortic blood flow occur two
to three months prior to term, during a period of rapid
somatic growth, we suggest that normal vascular develop-
ment may be impaired. This hypothesis is supported by ex-
perimental data, showing that reduced aortic blood flow
induces adaptive remodelling of the aorta (8). In addi-
tion to premature uncoupling of the placental circulation,
preterm infants are frequently exposed to other causes of
reduced aortic blood flow. The presence of a hemodynam-
ically significant PDA reduces the neonatal blood flow in
the descending aorta, which potentially could play a role for
aortic growth and development. We did not find a contribu-
tion from PDA to aortic size in later life. However, within
the preterm group, 16 subjects with metallic implants af-
ter neonatal surgical PDA-closure were excluded from MRI,
possibly introducing selection bias underestimating the role
of a PDA for aortic growth.
The primary aim of this investigation was not to study
long-term vascular effects of maternal smoking in preg-
nancy. However, interestingly we found a strong association
between smoking in pregnancy and aortic narrowing in the
near-adult offspring. Smoking in pregnancy induces changes
in the foetal aortic circulation (19), but foetal tobacco ex-
posure has not previously been associated with long-term
structural changes in the human vascular tree. This associa-
tion may reflect a causal relation as lasting abnormalities in
elastin structure and function—that are known to occur in
the lungs of cigarette smokers (20)-may also adversely and
irreversibly affect the growth and development of the foetal
vascular tree (21).
Experimental data indicate that not only smoke exposure,
but also reduced blood flow and undernutrition in early in
life have the potential to affect elastin deposition, size of the
aorta and aortic telomere length; a factor involved in vas-
cular senescence (22–24). In humans, a micro-deletion in
the elastin gene (William’s syndrome) causes reduced and
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Risk factors for aortic narrowing in adolescence Bonamy et al.
abnormal elastin content of the arterial wall presenting as
congenital arterial vasculopathy characterized by smaller ar-
teries and hypertension (25). These models suggest that early
adverse influences could have life-long consequences for
vessel wall composition and mechanical behaviour. Inter-
estingly, we have previously found a more elastic abdominal
aorta in healthy adolescent girls born preterm (6). Hypo-
thetically, a narrower and more pulsating aorta could lead
to premature rupture of elastin fibres, collagen replacement
and subsequent aortic stiffening. These processes could all
be part of accelerated aortic ageing (9,26) and future stud-
ies should address them if preterm birth is a risk factor for
aortic aneurysm development.
We were not able to measure the aortic wall thickness,
and can thus not exclude that the observed reduction in
aortic luminal size is due to aortic wall thickening. How-
ever, although aortic intima–media thickening is present
in term SGA-babies (27), follow-up studies in young adults
have failed to show increased intima–media thickness after
preterm birth (28).
Genetic confounding of the association between short-
ened length of gestation and smaller aortic size cannot be
excluded. We found a larger proportion of hypertension
among first- and second-degree relatives to adolescents born
preterm, as compared to term controls. A familial predis-
position for cardiovascular disease may manifest in terms
of pregnancy complications, such as preterm delivery. Al-
though speculative, such a predisposition may also include
a smaller aorta.
In line with several previous studies, we found signifi-
cantly higher BP in subjects born very preterm. There was
no correlation between blood pressure and aortic size. The
higher blood pressure found in adolescents born preterm is
accordingly more likely to reflect increased peripheral vas-
cular resistance on a functional (29) and structural basis
(30).
There are some limitations related to selections made in
the present study. The inclusion criterion in the original
preterm cohort was very low birth weight and not gesta-
tional age. This means that the proportion of children born
SGA increases with increasing gestational age in the preterm
cohort. Therefore, the lack of association between foetal
growth restriction and aortic narrowing should be inter-
preted cautiously.
In conclusion, very preterm birth and foetal exposure to
maternal smoking during pregnancy are both and indepen-
dently associated with persistent, general aortic narrowing.
Questions relating to if and how aortic narrowing affects
the future cardiovascular health in subjects born to smoking
mothers and/or very preterm remain to be clarified. Given
the central circulatory role of the aorta, such studies should
focus not only on ageing of the vessel itself, but also on
consequences for end-organs such as the heart, brain and
kidneys.
ACKNOWLEDGEMENTS
We would like to thank Jessica Schi ¨
ott, research nurse,
Jonna Karl ´
en, medical student and Birgitta B ¨
ohm for in-
valuable help with this study. This study was supported
by grants from HRH Crown Princess Lovisa’s Memorial
Foundation, Karolinska Institutet Research Foundations,
Swedish Heart Lung Foundation, S ¨
allskapet Barnav ˚
ard and
Stiftelsen Frimurare Barnhuset.
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SUPPLEMENTARY MATERIAL
The following supplementary material is available for this
article:
Table S1 Percent change (95% confidence interval) in aor-
tic cross-sectional area in relation to different covariates in
healthy adolescents (n =86). Estimates are based on re-
sults of unadjusted univariate linear regression analysis of
log aortic area
Table S2 Change in end-diastolic aortic area in 15-year-old
subjects born preterm (n =45) in relation to gestational age
and exposure to maternal smoking in pregnancy. Estimates
are based on results of multivariate linear regression analysis
of log aortic area adjusted for body surface area and gender
This material is available as part of the online
article from: http://www.blackwell-synergy.com/doi/abs/
10.1111/j.1651-2227.2008.00890.x
(This link will take you to the article abstract).
Please note: Blackwell Publishing is not responsible for the
content or functionality of any supplementary materials sup-
plied by the authors. Any queries (other than missing mate-
rial) should be directed to the corresponding author for the
article.
C
2008 The Author(s)/Journal Compilation C
2008 Foundation Acta Pædiatrica/Acta Pædiatrica 2008 97, pp. 1080–1085 1085
    • "In 2011, Crump et al. showed in a cohort of over 630,000 individuals followed to age 25 to 37 years that young adults born preterm have an increased relative rate of antihypertensive medication prescription, which increased monotonically with the degree of prematurity and was independent of foetal growth restriction [13]. Whether the macrovascular changes in aortic size are also of relevance is unclear [7,8] . We, like others, demonstrated no particular difference in aortic stiffness between preterm-born individuals and term-born controls [15,16] . "
    [Show abstract] [Hide abstract] ABSTRACT: Investigations into how perinatal growth and intrauterine environment may ‘programme’ risk of later cardiovascular disease have been ongoing for over two decades. One of the more recent outcomes of these studies is the observation that certain pregnancy-related conditions, such as preterm birth, have an unusually large impact on the long-term cardiovascular health of the offspring. In the present paper, we review the current literature of how preterm birth affects the long-term cardiovascular structure and function of the offspring, considering three major areas of investigation: firstly, outlining the long-term cardiovascular phenotypic changes in preterm-born individuals; secondly, investigating factors related to preterm birth that may be modifying cardiovascular phenotype, such as preeclampsia, perinatal interventions, and physiological disturbances; and thirdly, the expected clinical relevance of these cardiovascular changes. This review discusses the importance of continued research focused on the mechanistic understanding of these cardiovascular alterations in order to develop specific primary prevention strategies.
    Full-text · Article · Sep 2014
    • "Tonic elevation of sympathetic activity and / or parasympathetic withdrawal may precede development of clinically overt hypertension [20,21] and cardiac hypertrophy [22], alter angiogenesis and vascular [23,24], contribute to the evolution of diabetes [25,26] and underlie sudden cardiac death [27]. The altered sympatho-vagal balance that we report here may therefore underlie the association between preterm birth and these later adverse cardiovascular outcomes [2,4,5,28,29]. Gestational age and preterm corticosteroid exposure both may be implicated in early postnatal autonomic function and separation of the two factors is challenging. "
    [Show abstract] [Hide abstract] ABSTRACT: Globally, 11% of infants are born preterm. In adulthood, individuals born preterm are at increased risk of cardiovascular morbidity and mortality, but the mechanistic basis of this remains unknown. Clinically overt cardiovascular disease may be preceded by altered cardiac autonomic activity characterised by increased sympathetic activity and/or reduced parasympathetic activity. Thus, altered cardiac autonomic activity in survivors of preterm birth may underlie later cardiovascular risk. To investigate the impact of gestational age on cardiac autonomic activity in juvenile and adult sheep. Singleton-bearing ewes were randomised antenatally to spontaneous term birth (TC; n=73) or corticosteroid induced preterm birth (PT; n=60). Cardiac autonomic modulation was assessed using heart rate variability analysis in juvenile and adult offspring. Preterm birth in adult males was associated with altered sympatho-vagal modulation (LFnu: PT 64±4 vs. TC 49±4, p<0.05; LogLF/HF: PT 1.8±0.1 vs. TC 1.5±0.1, p<0.05) and reduced parasympathetic modulation (LogRMSSD: PT 2.9±0.2 vs. TC 3.4±0.1, p<0.05; LogNN50: PT 0.3±0.4 vs. TC 1.6±0.4, p<0.05). Within the range of term birth, each one-day increment in gestational age was associated with a decrement in LFnu in juvenile females and with a decrement in LFnu and LF/HF ratio, but an increment in RMSSD and NN50 in adult females. Cardiac autonomic function in adult sheep is affected in a sex-specific manner by gestational age at birth, even within the term range. Altered cardiac autonomic function may contribute to increased later cardiovascular morbidity in those born preterm.
    Full-text · Article · Dec 2013
    • "Differently from Anna-Karin et al., we have only evaluated term newborns, by considering all the parameter able to influence the relationship. At a linear analysis, smoking increased abdominal aorta intima-media thickness [24], probably through endocrine modifications, involving serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels and actions [23] or by inducing a long-lasting " reprogramming " of the blood pressure control mechanisms [25], but the evaluation was not confirmed after adjustment for confounding variables. Nevertheless, as the hypothesis of Anna-Karin et al. about a reduced flow in placental circulation due to smoke could have influenced the reduced diameter found at abdominal aortic level, the same vascular alterations induced by smoke could enlarge the aortic diameter. "
    [Show abstract] [Hide abstract] ABSTRACT: Aim. To evaluate the influence of selected maternal and neonatal characteristics on aorta walls in term, appropriately grown-for-gestational age newborns. Methods. Age, parity, previous abortions, weight, height, body mass index before and after delivery, smoking, and history of hypertension, of diabetes, of cardiovascular diseases, and of dyslipidemia were all assessed in seventy mothers. They delivered 34 males and 36 females healthy term newborns who underwent ultrasound evaluation of the anteroposterior infrarenal abdominal aorta diameter (APAO), biochemical profile (glucose, insulin, total cholesterol, HDL and LDL cholesterol, triglycerides, fibrinogen, and D-dimers homeostasis model assessment [HOMAIR]index), and biometric parameters. Results. APAO was related to newborn length (r = +0.36; P = 0.001), head circumference (r = +0.37; P = 0.001), gestational age (r = +0.40, P = 0.0005), HOMA index (r = +0.24; P = 0.04), and D-dimers (r = +0.33, P = 0.004). Smoke influenced APAO values (odds ratio: 1.80; confidence interval 95%: 1.05–3.30), as well as diabetes during pregnancy (r = +0.42, P = 0.0002). Maternal height influenced neonatal APAO (r = +0.47, P = 0.00003). Multiple regression analysis outlined neonatal D-dimers as still significantly related to neonatal APAO values. Conclusions. Many maternal and neonatal characteristics could influence aorta structures. Neonatal D-dimers are independently related to APAO.
    Full-text · Article · Jul 2013
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