Journal Reading

PRETERM DELIVERY AND

FUTURE RISK OF MATERNAL
CARDIOVASCULAR DISEASE:
A SYSTEMATIC REVIEW AND
META-ANALYSIS
PENSEE WU, MBCHB, MD(RES); MARTHA GULATI, MD, MS; CHUN SHING KWOK, MBBS,
MSC, BSC; CHUN WAI WONG; ADITYA NARAIN, MBCHB;, SHAUGHN O’BRIEN, MB BCH, MD,
DSC; CAROLYN A. CHEW-GRAHAM, MBCHB, MD; GANGA VERMA, MBCHB; UMESH T.
KADAM, MBCHB, PHD; MAMAS A. MAMAS, BM BCH, DPHIL
PUBLISHED 2018

Presented by :
dr. Khoirunnisa Novitasari

Tutor :
Dr. dr. Hermanto Tri Joewono, Sp.OG(K)
O B S T E T R I C A N D G Y N E C O L O G Y D E PA RT M E N T
FA C U LT Y O F M E D I C I N E A I R L A N G G A U N I V E R S I T Y
S O E T O M O H O S P I TA L S U R A B AYA
2020
LIKE MOTHER LIKE DOUGHTER : EPIGENETIC
THEORY

Sherf et al 2017 : Low birth weight and preeclampsia are both

independent risk factors for recurrence in the next generation.

A retrospective study with total of 1490 in F1, 1616 in F2, and 2311 in
F3 were included.
LBW in mothers was significant predictor for LBW in offspring
(OR=1.6, 95% CI 1.02-2.6, P=0.043). Preeclampsia was also noted as a
significant intergenerational factor (OR=2.9, 95% CI 1.4-5.8, P=0.004).
 Hauspurg, 2017
Adverse Pregnancy
Outcome : Preeclampsia, Future
GDM, IUGR CVD risk

women with a history of preeclampsia have a 71% increased risk of CVD

mortality, a 2.5-fold increase in risk of CAD, and a 4-fold increase in heart
failure risk (Pensee Wu, 2017)

A Canadian study with 10 years of follow-up : women with GDM who did not
develop T2DM still had 30% greater risk of CVD and 41% greater risk of CAD
(Hauspurg, 2017)

Across various cohort studies, women with IUGR infants have been found to be
twice as likely to experience future CVD (Bonamy, 2011)
NEW ISSUE …. !!!

adverse pregnancy outcomes such as

spontaneous preterm delivery
(sPTD) have been identified as a risk
factor for future maternal CVD
PREGNAN challenge to the cardiovascularsystem with a doubling of
blood volume, elevated coagulation and inflammatory

CY
factors, hyperlipidemia, and insulin resistance (Harsk,
2007).

The pregnancy response may serve

as a window into future maternal CVD risk
(Minissian, 2018).
acts as a stress test that exposes
subclinical CVD risk under the
physiologic stress of pregnancy
(Minissians, 2018)
Overdistention

Vascular disease (arterial

stiffness)
PRETERM BIRTH
Systemic inflamation

Globally, preterm birth affects 11% of all Infection

pregnancies,with an estimated 14.9 million
babies born before 37 weeks gestational age
Uteroplasental ischemic or
each year
hemorrage

Background :
evaluate and summarize the
evidence on the relationship between
preterm birth and future maternal
risk of cardiovascular diseases.
Method : Random effect meta-
analysis
Population : Twenty-one studies with over 5.8
million women, including over 338 000 women
with previous preterm deliveries, were identified.
Result : Preterm birth associated with an increased
risk 2 fold of future maternal cardiovascular disease.
Sensitivity analysis showed that the highest risks
occurred when the preterm deliveries occurred before 32
weeks gestation or were medically indicated.
Conclusion : Preterm delivery is associated with an
increase in future maternal adverse cardiovascular
outcomes, including a 1,4- 2
fold increase in deaths caused by coronary heart
disease.
6
Inclusion Pathway of
Study Literature
 Almost of
them Cohort
Studies
 Risk of CVD
Risk of CVD death
Risk of CHD
Risk of Stroke
 Cardiovascular
Preterm Birth
disease

Common Risk Factor

Catov, 2007 :
dyslipidemia in pregnancy were 2.8
times more likely to deliver befire 34
w

Inflamatory marker
(cytokines, matrix metalloproteinase, fibrinolysis,
prostaglandin)
Mudd et al, 2012 dyslipidemia : +
Low HDL Dyslipidemia
High TG
High TC
+
Atherosclerosis + endothelial dysfunction

Pensee Wu et al,
2018
Preterm Birth VS Term Birth

Arterial stiffness Khalil et al, 2012

Blood pressure

Atherogenic lipid
profile Catov et al, 2013

IMT (Carotid Intima-

Media Thickness)

C-reactive protein
levels

Minissian, 2018
 Mothers with no preeclampsia but a preterm delivery
experienced a 2.95-fold increased risk of CVD death
compared with controls over a 25-year follow-up period
Preterm delivery is associated may be an independent CVD
risk predictor after controlling some CV related risk factor
(Minissian, 2018).
 Study
No Journal Author Published Title Design Population Method Result

Preterm 70,182 parous women in

Delivery and the Nurses' Health Study
Lauren Maternal II who has history of 1. women who delivered either moderately or very preterm
Multivariable Cox
Pubmed J. Tanz, Cardiovascula having delivered an were slightly more likely to have a BMI greater than or
1 2017 Cohort proportional hazards
Central MSPH r Disease in infant preterm (37 equal to 30 kg/m2, have pre-pregnancy hypertension and
models
et al Young and weeks). aged 25–42 at hypercholesterolemia, and a family history of CVD.
Middle Aged baseline in 1989.
Adult Woman Followed until 20 years

2. Compared to a normotensive term first pregnancy,

women with a normotensive preterm first pregnancy had a
35% (HR=1.35, 95% CI: 1.06, 1.72) increased rate of
CVD, while those with both preterm delivery

3. We report that women who deliver their first child

preterm (<37 weeks) experience a 40% increased risk of
CVD, while women with a very preterm first birth (<32
weeks) have double the risk, after adjustment for pre-
pregnancy cardio-metabolic risk factors.

Preterm delivery is independently predictive of CVD and

may be useful for CVD prevention efforts.
No Journal Author Published Title Study Design Population Method Result

1. adjusted for CVD risk factors other than

smoking, compared to mothers of term
infants, AHR [95 % CI] of CVD among
2 BMC mothers with any preterm birth was 1.78
Pregnancy Preterm birth Birth records were linked to
and Anh D. 2. Compared to non-smoking mothers, both
and future risk A population-based the mothers’ subsequent
Childbirth Ngo et al crude and adjusted HRs of CVD (and CVD
of maternal record linkage study of hospitaliation or death from
subgroups) among mothers who smoked
cardiovascular 797,056 women who CVD. Preterm births were
during last pregnancy were consistently
disease – is the retrospective delivered a singleton categorised as late (35-36
2015 higher than that among mothers who smoked
association Cohort infant between 1994 weeks), moderate (33–34
during a prior pregnancy, but not during last
independent of and 2011 in New weeks), or extreme (≤32
pregnancy
smoking South Wales, weeks); and as spontaneous or
during Australia. indicated. Cox proportional the association of preterm birth and future
pregnancy hazard regression risk of maternal CVD is independent of
maternal smoking and hypertensive disorder
during pregnancy.

Association of
Spontaneous
14 cohort studies
Margo B. Preterm
about preterm
AHA Minissia Delivery and Systematic The totality of this evidence suggests that all-
3 2018 deliveries and sytematic review
Journal n, PhD et Future Review cause preterm delivery (medically indicated
association to
al Maternal and sPTD) is associated with a 1.5- to 3-fold
cardiovascular disease
Cardiovascula independent, increased risk of cardiovascular
r Disease morbidity and mortality after controlling for
some CV-related risk factors.
CONCLUSION
 This meta-analysis examined 96 341 474 women and included 338 007
women with preterm birth out of 5 813 682 study participants in 21
studies.
 Preterm delivery is associated with an increased maternal risk for future
incident cardiovascular events, cardiovascular death, coronary heart
disease events, coronary heart disease death, and stroke. The adjusted
risk ranged between 1.4- and 2-fold compared with those without a
history of preterm birth.
 This increased risk is greatest in preterm births that occur before 32
weeks in gestation or in those that are delivered for medical indications
such as fetal growth restriction or pre-eclampsia.
MESSAGE
 who experience a preterm delivery are at a higher risk of
cardiovascular events and this suggests that a formal
cardiovascular risk assessment using established risk scores
should be considered for those women, which would benefit
from early screening, prevention, and treatment.
 Clinicians have to educate women regarding their
increased cardiovascular risk and potentially motivate
women toward controlling any modifiable risk factors.
MATERNAL PROGRAMMING
 in 2011, the American Heart Association (AHA) updated its guidelines for
the prevention of CVD in women to include preeclampsia, GDM, preterm
birth as major risk factors for CVD
 American College of Obstetricians and Gynecologists recommends patient
education for women with recurrent or preterm preeclampsia outlining the
increased risk of future CVD, as well as implementation of a healthy
lifestyle with weight loss, physical activity, and smoking cessation in
addition to aspirin prophylaxis in future pregnancies.
 In women with a history of GDM, the American Diabetes Association
recommends screening for persistent diabetes 6 to 12 weeks postpartum and
every 1 to 3 years, as well as encouraging healthy eating patterns and
lifestyle interventions to support weight loss.
 (Hauspurg, 2017)
 Jyotsna Maddury1 Kumar Achukatla2 , 2018