Appropriate prenatal care system: the best way to prevent preeclampsia in Andean countries

Colombia Médica
Vol. 40 Nº 2, 2009 (Abril-Junio)
Appropriate prenatal care system:
the best way to prevent preeclampsia in Andean countries
PATRICIO LÓPEZ-JARAMILLO, MD, PHD1, RONALD GARCÍA, MD, PHD (C)2,
LAURA REYES, MD3, SILVIA RUIZ, RN2
SUMMARY
The main cause of maternal mortality in Colombia is preeclampsia; even though it is a major public health problem its etiology
and physiopathology remain unknown. However it is believed that endothelial dysfunction plays a central role in the
development of this disease. Many clinical trials have been carried out to demonstrate the effect of certain interventions to
prevent preeclampsia and improve pregnancy outcomes. Our hypothesis is that the reduction of preeclampsia risk could be
achieved through an appropriate health system that would provide an opportune and effective prenatal care to pregnant women
allowing early diagnosis and treatment of frequent nutritional and health related problems.
Keywords: Pregnancy; Preeclampsia; Prevention; Prenatal care; Endothelial dysfunction; Public health.
Control prenatal apropiado: la mejor manera de prevenir la pre-eclampsia en los países andinos
RESUMEN
La primera causa de mortalidad materna en Colombia es la pre-eclampsia; pero aunque es un problema de salud pública su
etiología y fisiopatología no se han esclarecido completamente. Sin embargo, se cree que la disfunción endotelial juega un papel
importante en el desarrollo de la enfermedad. Se han llevado a cabo múltiples ensayos clínicos para demostrar el efecto de ciertas
intervenciones a fin de prevenir la pre-eclampsia y mejorar los resultados de estos embarazos. Nuestra hipótesis consiste en
que la reducción del riesgo de desarrollar pre-eclampsia se puede obtener mediante un sistema de salud apropiado que brinde
a la madre un control prenatal efectivo y oportuno y permita el diagnóstico temprano y el tratamiento de sus problemas de salud
y nutricionales.
Palabras clave: Embarazo; Pre-eclampsia; Prevención; Control prenatal; Disfunción endotelial; Salud pública.
The main cause of maternal mortality in Colombia is
substances, especially nitric oxide (NO), prostacyclin,
preeclampsia (PE). It causes 42% of the maternal
and pro oxidizing free radicals2. Furthermore, this article
demises and increases the perinatal mortality by five
proposes that the weight of these risks factors varies
fold. It is even a bigger problem if it is considered that
depending on the level of socioeconomic development
maternal mortality in Colombia is ten times higher than
reached by a given society3.
in United States of America1. In spite of its impact on
Relevant epidemiological observations to prevent
public health PE’s aetiology and physiopathology remain
PE. PE complicates about 6% to 8% of pregnancies;
unknown. In this paper it is postulated that PE is a
however, noticeable regional differences exist in its
disorder due to multiple causes, and that nutritional,
incidence due to the greater presence of certain risk
socioeconomic, genetic and environmental factors might
factors in developing societies4. Nutritional factors like
lead to an endothelial function alteration characterized
the low intake of calcium1, antioxidizing vitamins5 and
by a modification in the production of vasoactive
essential fatty acids6 are considered elements
1. Director of Research, Fundación Cardiovascular de Colombia y de Investigaciones de la Facultad de Medicina, Univer-
sidad de Santander (UDES), Bucaramanga, Colombia. e-mail: joselopez@fcv.org
2. Coordinator of Research, Fundación Cardiovascular de Colombia, Bucaramanga, Colombia. e-mail: ronaldgarcia@fcv.org
e-mail: silviaruiz@fcv.org
3. Assistant of Research, Fundación Cardiovascular de Colombia, Bucaramanga, Colombia. e-mail: laurareyes@fcv.org
Received for publication March 8, 2009 Accepted for publication April 14, 2009
226
© 2009 Universidad del Valle, Facultad de Salud
Colomb Med. 2009; 40: 226-30

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Colombia Médica
Vol. 40 Nº 2, 2009 (Abril-Junio)
contributing to an increasing risk of developing PE. In
with a low intake of calcium (less than 600 mg per day)
addition, the findings of a large scale population study
and less than 20 weeks pregnant; of them, 4,157 received
carried out in Colombia led the present authors to
1.5 g of calcium per day and 4,168 received placebo.
propose that chronic subclinical infections are the main
This calcium supplementation was associated with a
risk factor for PE in this country7, proposal which it has
small non statistically significant reduction of PE (4.1%
been recently supported by demonstrating that
vs. 4.5%). However, severe pregnancy-induced hyper-
inflammation associated to oral, vaginal, and urinary
tension (RR 0.71, 95% CI: 0.61-0.62) and eclampsia
infections precedes the PE development8,9. These
(RR 0.68, 95% CI: 0.48-0.97) were significantly lower
observations are important since they have served as a
in the supplemented group. Besides, a reduction in the
support for the realization of studies directed to prevent
rate of complications of severe PE was observed (RR
the disease.
0.76, with a 95% CI: 0.66-0.89). Severe maternal
PE preventing strategies. The lack of an adequate
morbidity and the mortality rate (RR 0.80, 95% CI: 0.70-
knowledge of PE’s physiopathology has determined
0.91), and neonatal mortality rate (RR 0.70, 95% CI:
that many of the strategies used to prevent it are based
0.56-0.88) were also significantly lower in the calcium
on observational or anecdotic facts or in studies
supplemented group. This important clinical trial realized
performed with women at high risk of developing the
in a low calcium intake population demonstrated that
disease. Many non pharmacological strategies have
although 1.5 g of calcium supplementation per day did
been used to prevent PE, especially those related with
not statistically diminish the total incidence of PE, it
nutritional restrictions or nutritional supplements, and
significantly diminished the risk of the most serious PE
rest in bed10,11. In the next section those in which greater
complications, including maternal death, preterm birth
evidences of a beneficial effect exists will be reviewed.
and maternal and neonatal morbidity. Based on these
Calcium supplements. Three pioneer clinical trials
results, the authors analyzed the practical implications
carried out by López-Jaramillo et al.12-14 with 408
of calcium supplementation in population with a low
Andean Ecuadorian primigravid women showed that
intake of this mineral and concluded that 125 women
calcium supplement of 2 g daily in this population with
should be treated to prevent a severe complication of
history of a low intake of this mineral was useful to
PE, and 167 should be treated to prevent a very premature
prevent the development of pregnancy induced
preterm birth. These numbers are reduced to 45 and 71,
hypertension and PE. The Cochrane library most recent
respectively if the pregnant women are less than 20
metaanalysis15 which included 11 randomized, double-
years old. Finally, they assure that it would be necessary
blind placebo-controlled clinical trials reported that
to supplement 100 women to prevent severe maternal
calcium supplementation is associated with a reduction
morbidity and one death event, and that it would be
of the risk of increased arterial pressure during pregnancy
necessary that 250 pregnant women receive calcium
(11 clinical trials, 14,946 women: relative risk (RR) 0.70,
supplementation to prevent one neonatal death. The
95% CI 0.57-0.86). There also was a reduction in the
WHO group affirms that «acute and long term
risk of PE associated to calcium supplementation (12
consequences of these poor outcomes; combined with
clinical trials, 15,206 women RR 0.48, 95% CI: 0.33-
the socioeconomic limitations justified the calcium
0.69), specially in those who had a low basal intake of
supplementation».
calcium (7 clinical trials, 10,154 women: RR 0.36, 95%
Recently, Hofmeyr et al.17 proposed that the
CI: 0.18-0.70) and in those considered at high risk (5
investigation about this subject should be redirected
clinical trials, 587 women: RR 0.22, 95% CI: 0.12-0.42).
from clinical trials to communitarian interventions with
The authors of this important metaanalysis concluded
calcium supplementation. This proposal, consistent with
that calcium supplementation appears to almost halve
López-Jaramillo & de Félix’s18, considers calcium
the risk of PE, and to reduce the occurrence of a
supplementation as a preventive nutritional measure
composite outcome of death or «serious morbidity».
directed at overcoming a socioeconomic problem, which
Villar and the clinical trial group of calcium
frequently impedes the access to dairy products to poor
supplementation for the prevention of PE of the World
women in Colombian society during their pregnancy,
Health Organization (WHO)16, included 8,325 women
and that it should not be prescribed to women with an
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Vol. 40 Nº 2, 2009 (Abril-Junio)
adequate consumption of the mineral. Pregnancy is a
of 17% in the risk of PE associated with the use of
period during which women need an extra calcium
antiplatelets doses was observed [(46 clinical trials,
consumption to guarantee a positive balance of the
32,891 women, RR 0.83, 95% CI: 0.77-0.89), number
mineral to compensate the great demand of calcium
needed to treat (NNT) 72 (52,119)]. Despite the fact
necessary for fetal bone mineralization19.
that there were no statistical differences in the RR
Other dietary supplementations: Antioxidants.
based on maternal risk, a significant increase in the
There are multiple clinical trials, in which a dietary
reduction of the absolute risk of developing PE was
supplementation including either magnesium, fish oil or
observed in women at high risk compared with those at
C and E vitamins was administered, but results have
moderate risk. The authors concluded that the
been contradictory. Indeed, the most recent metaanalysis
administration of low aspirin doses has moderate benefits
of the Cochrane library20 determined that there was no
in the prevention of PE and proposed that more
significant difference between antioxidant and control
information is necessary to determine which women
groups in the RR of PE (RR 0.73, 95% CI 0.51 to 1.06;
can benefit from this intervention, when the treatment
nine trials, 5,446 women) or any other primary outcome:
should be initiated, and which dose must be used. From
severe PE (RR 1.25, 95% CI 0.89 to 1.76; two trials,
a practical point of view, the authors leave the decision
2,495 women), preterm birth (before 37 weeks) (RR
of its use to both the pregnant woman and her doctor.
1.10, 95% CI 0.99 to 1.22; five trials, 5,198 women),
Since it is a small reduction in the risk of developing PE,
small-for-gestational-age infants (RR 0.83, 95% CI
a large number of women need to be treated to prevent
0.62 to 1.11; five trials, 5,271 babies) or any baby death
only one adverse outcome, which seems little practical,
(RR 1.12, 95% CI 0.81 to 1.53; four trials, 5,144 babies).
although even this small reduction could be useful from
The authors concluded that the evidence from this
a public health perspective.
review does not support routine antioxidant supplemen-
Treatment of vaginal, periodontal and urinary
tation during pregnancy to reduce the risk of PE and/or
infections. Some studies have shown that urinary and
other serious complications in pregnancy.
vaginal infections can cause PE7,24-26. Furthermore, it is
On the other hand, the results of a clinical trial
well known that the incidence of asymptomatic
including 2,951 pregnant women were recently
bacteriuria is three times higher in women with PE, and
published21 demonstrating that multivitamins and folic
that urinary infection is a strong risk factor for PE25,26.
acid supplementation were associated with an increase
Recently Herrera et al.9 demonstrated an association
in serum folate, a decrease of plasmatic homocysteine
between PE, C-reactive protein concentration and
and a risk reduction of PE (RR 0.37, 95% CI: 0.18-0.75).
periodontitis.
More studies are necessary to confirm this persuasive
Many studies have shown that the identification and
interaction in view of the proposal that a change in the
treatment of bacterial vaginosis and urinary infection
oxidant/antioxidant balance is one of the mechanisms
reduces the presentation of preterm delivery, and
leading to an endothelial function alteration which
premature rupture of fetal membranes27,28, and Herrera
characterizes PE22. Since many serious and well
et al.7 demonstrated in Colombian women that early
designed clinical trials are being carried out, we should
detection (14-20 weeks of gestational age) and opportune
wait for their results before recommending the routine
treatment of vaginal and urinary infections reduced the
use of antioxidant vitamin supplements during pregnancy
incidence of PE by 64.7%.
to prevent PE.
Since the realization of double blind, placebo-
controlled clinical trials to evaluate the effect of the
PHARMACOLOGICAL INTERVENTIONS
treatment of subclinical infection are not ethically
acceptable, community work evaluating the impact of
Low aspirin doses. A recent review of the Cochrane
early diagnoses of subclinical infections and their
library23 examined the results of 59 clinical trials which
adequate treatment is an urgent need in countries where
included 37,560 pregnant women and that were directed
vaginal, oral, and urinary infections can affect up to 50%
to evaluate the effectiveness and safety of low aspirin
of the expectant mothers. Besides, it has been
doses to diminish the risk of developing PE. A reduction
demonstrated that low grade inflammation associated to
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Vol. 40 Nº 2, 2009 (Abril-Junio)
The specific weight of each factor differs between
developed and developing countries2. Poor women from
developing countries like Colombia and Ecuador are the
most exposed to these risk factors, which explains the
high incidence of the disease, converting it into the main
cause of maternal mortality.
We have proposed an integral model which pretends
to include and relate the different factors that could
participate in the reduction of PE incidence in our
countries (Figure 1). The right interpretation of this
model allows us to understand that the most economical,
effective and universal way to prevent PE is a social
system that guarantees an adequate nutrition of the
pregnant women and the access to an adequate system
of prenatal care which would include the administration
of prenatal tablets containing among other components
vitamins C and E and minerals such as calcium, which
Figure 1. Interventions to reduce the incidence of
would compensate for the extra demand of nutrients
PE. Integral model which pretends to include and
that are taken from the mother by the foetus for its
relate the different factors that could participate in
organic development. Moreover, an adequate prenatal
the reduction of PE incidence in our countries.
control not only allows the diagnosis and early treatment
endothelial dysfunction, precedes the clinical mani-
of subclinical urinary, oral and vaginal infections, but
festation of PE, and that the treatment of infections
also the identification and correction of bad nutritional
recovers the endothelial function8,29.
practices that are expressed in an excessive weight gain
and biochemical alterations of the lipid profile and
OTHER PHARMACOLOGICAL
carbohydrates. In populations with marked deficiencies
INTERVENTIONS
of some nutrients, as it is the case of calcium in Latin-
American women, or antioxidant vitamins in Caucasian
It has been reported that the use of diuretics does not
women, the administration of these supplements is
have any effect on PE prevention or its complications30,
necessary.
and that their use is not recommended considering the
high levels of adverse events found a recent metaanalysis
ACKNOWLEDGMENT
(1,836 women). Regarding the use of exogenous donors
of NO or of the substratum for its synthesis (L-arginine)
The authors acknowledge Colciencias (Instituto Co-
to prevent PE, the metaanalysis31 of six clinical trials that
lombiano para el Desarrollo de la Ciencia y la Tecnolo-
included 310 women showed that the data available are
gía «Francisco José de Caldas») for the financial support
insufficient to reach appropriate conclusions about
to the VILANO Group (Grant N° 6566-04-18061).
whether exogenous donors of NO or its substratum are
Laura Marcela Reyes and Silvia Liliana Ruiz received
useful to prevent PE.
a young investigator grant from Colciencias. The authors
also thank Jean Noël Guillemot for the correction of the
HYPOTHESIS
English style.
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