Funding Statement
We worked with help of “Fondo Publicalo” by Pontifical Catholic
University of Quito resources.
Introduction
Premature rupture of membranes is losing the integrity of chorioamniotic
membranes, which occurs from 20 weeks of gestation until before the
onset of labor1, it happens with a frequency of 2 to
3% before 37 weeks2 and is associated with 30 to 49%
of preterm pregnancies3.
Latency period refers to the time elapsed since the rupture of membranes
occurs until delivery occurs; and gestational age will determine the
prognosis, ideal treatment, and the way to end
pregnancy1.
It is possible that rupture of membranes in preterm pregnancies
originates activation of apoptosis mechanisms, mechanical forces, or by
the action of catabolic enzymes such as collagenase linked to both
inflammatory and infectious responses4, 5. Although
etiology is different, triggering is likely that all processes interact
with each other, reaching a common pathway that is membrane
rupture6.
An inflammatory response caused by maternal infection, whether systemic
or localized, has as a possible component, activation of cytokines such
as interleukin 1β and TNF-α7. Cytokines, also called
interleukins (IL), are soluble mediators that allow interactions between
cells of the immune system8. Cytokines’ functions are
stimulating prostaglandin synthesis and metalloproteinases production by
extracellular matrix. One of these is IL-8, which causes weakness of the
chorioamniotic membranes and the softening of the
cervix9. Cytokines also promote the apoptosis of
amniocytes and activation of complement leading to endothelial damage
with increased permeability, impaired fetal placental perfusion, and
myometrial contractions that lead to rupture of
membranes10.
It is possible that there is a sterile inflammatory response, which
stimulates the production of cytokine receptors identical to those that
would be generated secondary to an infection, but they surely follow
different processes9. In a study by Romero et al.
(2014)11 found that sterile intraamniotic inflammation
occurred in 29% of patients with premature rupture of membranes and was
more common the earlier pregnancy.
Intraamniotic infection is the main cause of preterm delivery, one of
the main problems in obstetrics10. intraamniotic
infection demonstrated by amniotic fluid study after amniocentesis shows
that microbial invasion into the amniotic cavity is present in 10 to
15%12; other authors say 20%13 of the patients with
preterm delivery and integral membranes, reaching 25% when cause
labor11, and 30 to 50% of patients with preterm
delivery and premature rupture of membranes12, 1 4.
For identification of both maternal and neonatal infection secondary to
ruptured membranes, the quantification of interleukin 6 levels may be
chosen. Reference values in maternal blood range from 0.2 to
7.8pg/ml15. In neonates, this cytokine is a good
predictor of early sepsis with a cut-off point of 40pg/ml with a
positive predictive value of 100% when is used in combination with
another marker such as C-reactive protein (CRP) as long as it is
positive16. Other markers, such as leucocytes,
neutrophils, and procalcitonin, are also used such as diagnostic
criteria, reference ranges may vary according to the laboratory performs
the analysis.
Complications secondary to this pathology increase the risk of morbidity
and mortality for both mother and neonate, among the most important are:
intraamniotic infection, premature placental abruption, cord prolapse,
maternal sepsis, neonatal respiratory distress, neonatal sepsis,
enterocolitis necrotizing, neurodevelopmental impairment,
etc17.
Management of preterm rupture of membranes varies according to
gestational age; it is a controversial issue in pregnancies of 34 to
36.6 weeks, when the fetus is considered relatively mature, without
being exempt from complications typical of prematurity, therefore that
benefits in the fetus when continuing the gestation after the PROM
(Premature Rupture of Membranes) can be considerable. Optimal expectant
management aims to maximize the benefits of fetal lung maturity after
the administration of corticosteroids, allow an increase in fetal weight
by continuing the waiting time, and avoid potential damage to the
mother-child binomial.
Corticosteroid and antibiotic therapy are part of expectant management
of preterm rupture of membranes, which includes observation of the
mother while awaiting the start of labor spontaneously in absence of
complications that increase needs for immediate preterm delivery. The
primary objective is getting as close to term as possible. Recognition
of maternal and fetal complications is imperative in terms of being able
to adequately manage them during expectant management.
The potential risk of iatrogenic prematurity associated with ending a
pregnancy so early and unplanned pregnancies with PROM is significant.
It includes complications typical of prematurity, mainly respiratory
distress, neurodevelopmental deficits, difficulty in feeding and
thermoregulation, and a prolonged neonatal hospitalization that will
depend on the gestational age at which delivery occurs.
The study by Lewis 1996 concludes that complications of prematurity are
significantly reduced when delivery occurs after 34 weeks of gestation
compared to those born before 34 weeks; however, are considered that
preterm newborns between 34 and 37 weeks still physiologically immature,
so their morbidity and mortality is significantly increased compared to
those born at term18, 19.
Therefore, evaluation of perinatal results in the study of patients with
ruptured membranes from 34 to 36.6 weeks managed expectantly could be an
alternative in the reduction of neonatal complications related to
prematurity compared to active management.
Materials and methods
A retrospective cohort that included 209 patients from 34 to 36.6 weeks
of gestation with a history of premature rupture of membranes, from
Carlos Andrade Marin Hospital in Quito between years 2016 to July 2019.
The sample was separated according to inclusion criteria for each group,
in exposed and unexposed; 103 cases were found in expectant management
and 106 cases in active management.
Definition of groups:
• Group of exposed (expectant management)
It refers to all patients with a pregnancy between 34 to 36.6 weeks with
rupture of membranes, regardless of maternal age, in which termination
of pregnancy occurs after spontaneous onset (without administration of
medication or extrinsic mechanisms) of uterine contractions; regardless
of the administration of antibiotic therapy or pulmonary maturation with
corticosteroids.
Inclusion criteria: Patients treated at the Carlos Andrade Marín
Hospital between 2016 and July 2019; with spontaneous onset of labor,
regardless of latency time of ruptured membranes, fetal presentation, or
whether or not a previous caesarean section had. Patients who had
ruptured membranes greater than 26 weeks, but delivery had not yet
occurred at 34 weeks. Patients for whom induction of labor was indicated
at 37 weeks with a history of ruptured membranes up to 36.6 weeks after
being managed expectantly.
Group of not exposed (active management)
It refers to all patients with a pregnancy of 34 to 36.6 weeks with
ruptured membranes, regardless of maternal age, in which the termination
of pregnancy occurs after administration of medication ( misoprostol,
oxytocin ) or extrinsic mechanisms (traction tube) that cause the onset
of uterine contractions or indication of termination of pregnancy by
caesarean section, immediately after hospital admission. Regardless if
we’re administrated antibiotic therapy or pulmonary maturation with
corticosteroids.
Inclusion criteria: Patients treated at the Carlos Andrade Marín
Hospital between 2016 and July 2019; patients who were inducing labor
(administered misoprostol, oxytocin) immediately after to hospital
admission; performing caesarean section without spontaneous uterine
activity.
Exclusion criteria for both groups: Criteria for clinical
chorioamnionitis on admission to hospital; fetal anomalies; stillbirth;
patients with vertically transmitted diseases such as HIV - VHS; n
preterm infants referred from other nursing homes.
The data were subjected to tabulations in explanatory tables using
Microsoft Word and Microsoft Excel programs. Data were exported to the
SPSS version 24.0 program for analysis. For descriptive variables,
percentages, average, and means will be calculated.
For associating variables such as the risk of complications and the type
of therapeutic management, contingency tables were used; the dependence
between the variables was determined by means of Chi-square. The level
of association between the variables was measured by calculating RR and
Chi-square to compare qualitative variables, with a statistically
significant p <0.05 and a confidence interval of 95%.
Results
Of 12036 deliveries attended from 2016 to July 2019 at the Carlos
Andrade Marín Hospital, 2683 were preterm, this represents 22.41%; 1728
deliveries occurred between 34 and 36.6 weeks, which represents 64.40%
of this group, the cases of deliveries with ruptured membranes between
34 and 36.6 weeks was 235 (1.95% of all births and 13.59% of the
preterm group).
209 patients met inclusion criteria: 103 for expectant management and
106 for active management. 26 patients were excluded: most cases (20
patients ‒ 8.5%) had congenital fetal malformations, 4 (1.70%) were
excluded due to lack of data, 1 case was admitted with signs of
chorioamnionitis and another with a diagnosis of stillbirth (0.42%)
each case).
Table 1 describes the clinical characteristics of patients who were
attended between January 2016 and July 2019, due to premature rupture of
the membranes. In all cases, the ruptured membranes occurred after 34
weeks of gestation.
Active management was more frequent in 73.5% of patients with the
evolution of fewer than 24 hours, while in conservative management,
delivery occurred spontaneously in 55.4% within the first 24 hours of
admission; in patients with a latency of 2 to 6 days the frequency was
22.3%, and 11.7% of patients break greater than 7 days.
Regarding the use of corticosteroids for lung maturation, it was similar
in both groups: 58.3% of expectant management versus 48.1% of patients
with active management.
There were no signs of intrauterine infection in any of the groups,
however, when taking into account of inflammatory values and
hematological biomarkers (leucocytes over 15,000
cells/mm3 and Interleukin-6, greater than 14 pg/mL),
it was established that, 8.5% of patients who were actively managed and
15.5% of patients managed expectantly presented elevation of these
markers.
Regarding the administration of antibiotics at hospital admission, in
the group of patients managed actively it was 75.5%, while in the group
of patients managed expectantly it was 70.9% without there being a
significant difference between both groups.
There were significant differences in the frequency of caesarean
delivery between groups. Patients who were managed expectantly had a
caesarean delivery frequency of 25.2%, compared to patients who were
actively managed, whose caesarean delivery frequency was 50.9%, RR:
3.075 (95% CI: 1.713‒5,522).
The main reasons for implementation caesarean, in both expectant
management group as in the active management group was: a history of
caesarean section (30.2% and 42.3% of patients respectively), breech
presentation (34% and 19.2% respectively), amniotic fluid alterations
(3.8% and 15.4% respectively) and compromise of fetal well-being
(15.1% and 7.7% respectively). Among all the causes that indicated
caesarean section, there were no statistically significant differences
between both groups.
In all cases, a leucocyte count with a differential formula was
performed, as part of the evaluative process; in addition, the
biomarkers were quantified: procalcitonin, C-reactive protein, and
interleukin 6.
Table 2 shows the means obtained in hematological parameters and in
inflammatory biomarkers, which suggest the presence or not of infection
(leucocytes more than 15,000 cells/mm3 and
Interleukin-6 more than 14 pg/mL). Significant differences were found in
each of the tests applied to patients. The mean leucocytes in patients
with infection were 14,310 cells/mm3 versus 9,230
cells/mm3, established in patients without any
infection/inflammation. In the case of the neutrophil difference, a mean
of 75.55% was calculated in patients with infection and 70.21% in
patients without infection.
The behavior of inflammatory biomarkers was notable among patients with
infection. For procalcitonin, a mean of 0.48 ng/mL was obtained in
patients with infection and 0.07 pg/mL in patients without infection.
For C-reactive protein, the mean in patients with infection was 1.47
mg/dL and 0.91 mg/dL in patients without this condition, in the same
way, an important difference was founded in the quantification of
interleukin-6 in patients with infection, whose mean was 29.53 pg/mL in
relation to 5.66 pg/mL in patients without infection.
Table 3 shows the clinical characteristics of the newborns
of mothers who were actively and expectantly treated for premature
rupture of the membranes. In each treatment group, there were no
significant differences in relation to sex, weight, or Apgar score of
newborns.
Regarding the length of hospitalization, there were no differences
between the newborns of mothers who were treated actively or
conservatively, although, a higher frequency of prolonged
hospitalizations (more than 48 hours) was evidenced in the group of
infants born to mothers under active treatment. 47 patients were
referred to other health units (24 in a group of newborns of mothers
under expectant treatment and 23 in the group of newborns of mothers
under active treatment).
The most common causes of prolonged hospitalization were rum: the study
of infection in 39.7% in patients with expectant management and
respiratory distress syndrome in 34.8% of patients with active
management, a similar proportion was found in terms of the study of
infection and hyperbilirubinemia of 25% for each cause, with no
statistically significant difference between the two groups.
Table 4 describes the complications presented in neonates
of mothers with premature rupture of the membranes according to the
treatment received. Regarding infectious complications, there were no
significant differences between each of the groups, however, a greater
number of newborns with clinical signs of infection (n=6) were detected
in the group with a history of active treatment, compared to newborns
with a history of expectant treatment (n=3).
37 blood cultures were performed in neonates of mothers who received
expectant treatment and 34 in neonates of mothers who received active
treatment, which two were positive in the expectant treatment group and
one in active treatment group.
According to this, 29.2% of neonates undergoing active treatment
received an incomplete antibiotic regimen and 31.1% in the expectant
treatment group. Such discontinuation of therapy was due to initial
suspicion of infection but with the subsequent confirmation of
biomarkers within normal parameters. The majority of neonates (58.3% in
the expectant treatment group and 64.2% in the active group) did not
receive any antibiotic treatment, and only 10.7% in the expectant
treatment group and 6.6% in the active treatment group received full
antibiotic treatment.
Regarding syndrome cases distress respiratory, 22 described cases
(20.8%) in the group of infants of mothers with active treatment, and
19 cases (18.4%) in the expectant management group, however, no
significant differences between each modality of oxygen therapy and
ventilatory support.
In other complications, there was a low prevalence of necrotizing
enterocolitis, finding 1 case in the expectant treatment group and 2
cases in the active management group, however, these differences are not
statistically significant.
The survival rate was higher than 98% in both groups, however, one case
of neonatal death was detected in the group of neonates of mothers with
active treatment.
Table 5 shows the relationship between gestational age and
the presence of neonatal complications. There were no significant
differences in the frequency of neonatal infection between each of the
gestational age groups. Nor was there any evidence of a difference in
the frequency of diagnosis of necrotizing enterocolitis.
In the case of respiratory distress syndrome, there was a greater need
for ventilatory support in newborns aged 34‒35 weeks (35.9%), compared
to newborns aged 35.1‒36 weeks (21.2%) and older than 36 weeks (7.5
%), therefore, there is a significant difference in the appearance of
this complication depending on the gestational age.
Regarding the frequency of prolonged hospitalization, it was
significantly higher in newborns with a gestational age of 34‒35 weeks
(76.5%) and 35.1‒36 weeks (67.3%), compared to neonates older than 36
weeks (p=0.001). There were no significant differences between prolonged
hospitalization causes; however, there was a greater frequency of stay
greater than 48 hours, in neonates of 34 and 35 weeks due to respiratory
distress syndrome (38.72%).
According to the differences found in the prevalence of respiratory
distress syndrome, Table 6 describes the relationship between a history
of lung maturation and the appearance of this complication in newborns
of mothers with premature rupture of membranes.
In-group of neonates of mothers with expectant management, newborns who
did not receive lung maturation had a higher frequency of respiratory
distress syndrome, compared to newborns who received said treatment
(35% versus 9.3%, p=0.003). Similarly, it happens in newborns of
mothers with active management (32.7% in those who received lung
maturation and 15.7% in newborns who did not receive lung maturation,
p=0.042).
Regarding ventilatory support, a greater need for CPAP use as evidenced
in newborns without previous lung maturation (25% in the group of
newborns of mothers with expectant management and 18.2% in newborns of
mothers with active management).
Table 7 shows an analysis of risk related to maternal and neonatal
complications, depending on the type of management applied in mothers
with premature rupture of membranes.
In women who received expectant management, an increased risk of
maternal infection was evidenced with a RR: 1,324 (95% CI:
0.972‒1.885), while active management seems to be a protective factor
against this event, with a RR: 0.683 (95% CI: 0.398‒1.172).
The risk of neonatal sepsis did not show significant differences,
depending on the type of management, in the case of newborns of mothers
under expectant management, a RR: 0.909 (95% CI: 0.608‒1.359) is
described, while, in those born of mothers under active management, have
a RR: 1.091 (95% CI: 0.773‒1.540). Nor were there any differences in
terms of management and presence of respiratory distress syndrome RR:
0.993 and RR: 1.01, respectively.
Risk of neonatal mortality and necrotizing enterocolitis is higher in
newborns of mothers under active management, with RR: 2,013 (95% CI:
1,723‒2,351) and RR: 1,321 (95% CI: 0.587‒2,973) respectively.
4. Discussion
Premature rupture of membranes in pregnancies from 34 to 36.6 weeks,
represented 1.94% of all births, a frequency similar to that reported
by Schmitz et al. (2019)2. It was associated with
preterm birth in 13.54%, which is consistent with what Mercer
(2015)3 and Van der Heyden (2014)20report in their studies.
Latency time in expectant management reached more than 7 days in 11.3%,
from 2 to 6 days in 22.3%, while in most cases it occurred within the
first 24 hours by 55.4%. These findings coincide with the results of
Sae‒Lin, and Wanitpongpan (2018)21 in which report the
average latency period was 2 days with a mean gestational age of 35
weeks.
The use of corticosteroids was similar to an average of 53.2% in each
type of management; this is because during this period their
administration in pregnancies greater than 34 weeks was under debate, so
their prescription was a medical consideration. Now the recommendation
they make in the study by Gyamfi et al. (2016)22 and
ACOG (2018)23 of a single dose of corticosteroid
between 34 and 36.6 days of gestational age, if they had not previously
received them.
Maternal inflammatory markers elevation occurred in 15.5% of expectant
management, in relation to 8.5% of active management. However, no signs
of infection were clinically expressed, which may have been favored by
the prophylactic use of antibiotics such as it is reported by Bond et
al. (2017)24 in which they find that the prophylactic
use of antibiotics is effective in reducing maternal infection. The
differences found in evaluating the leucocyte formula were statistically
significant between the two groups, finding the highest values in the
expectant group; it is explained by the longer duration of the latency
period and longer exposure to uterine activity (regular or irregular) in
expectant management25.
When evaluating the positive maternal biomarkers, it was determined that
the mean for leucocytes was 14,310cells/mm3,
neutrophils of 75.5%, procalcitonin of 0.48ng/ml, and CRP of 1.47mg/dl
with statistically significant differences in comparison with maternal
biomarkers in a normal range. According to the compartmental theory in
the study carried out by Dulay et al. (2015)26 found
no relationship between histological chorioamnionitis and serum IL-6,
CRP, or procalcitonin values and none exceeded the predictive value of
leukocytosis. According to Popowski et al. (2011)27leucocytosis has a higher specificity (95%) the higher its serum levels
are: 16‒20,000cells/mm3. Therefore, these markers by
themselves do not play a preponderant role in the prognosis and
determination of intraamniotic infection.
The majority of patients received antibiotic prophylaxis before delivery
in both groups with a frequency of 78.3 for expectant management and
70.9% for active management, which is the recommendation in these
patients according to CONGOF (2019)2, FASGO
(2018)28, AGOG (2018)23, RCGO
(2018)29, among others.
We found statistically significant differences in the frequency of
caesarean delivery in actively managed patients in 50.9% versus 25.2%
under expectant management. Previous caesarean section and breech
presentation being the most frequent causes in both groups; which is
related to the results found by Bond et al. (2017)24and Quist et al. (2018)30 in which the frequency of
caesarean sections was higher in the active management group.
No significant differences were found regarding the sex, weight, and
Apgar of the newborns in both groups, which gives homogeneity of the
population.
Prolonged hospitalization time (greater than 48 hours) was more frequent
in infants of actively treated mothers, however, these differences were
not statistically significant. In correlation with the study by Morris
et al. (2016)31 where a significant increase in the
stay in the intensive care unit was determined in neonates in the active
management group, as a consequence of low birth weight, increased risk
of respiratory distress syndrome (RR 1.6, 95% CI 1.1–2.3) and
mechanical ventilation (RR 1.4, 95% CI 1.0–1.8).
Regarding infectious complications, no significant differences were
found between both groups; findings consistent with other studies24, 30, 31, 32, 33, 34. However, there was a higher
frequency of clinical signs of sepsis in neonates after active
management, as well as the elevation of inflammatory/infectious markers,
without finding any cause other than prematurity. The administration of
antibiotics in neonates was not necessary for 58.3% with a history of
expectant management and in 64.2% of active management, and only 10.7%
after expectant management of a complete antibiotic scheme, without this
being statistically significant
Regarding the occurrence of respiratory distress syndrome and the use of
oxygen supplementation or ventilatory support, there was no statistical
difference in both cases (expectant management‒RR: 0.993 and active
management‒RR: 1.01), however in one case there was it required the use
of invasive mechanical ventilation by the hyaline membrane, after active
management.
Statistically significant differences were found regarding the
occurrence of respiratory distress syndrome and lower gestational age,
35.9% between 34 and 35 weeks, and 7.5% after 36 weeks, as well as in
newborns who did not receive lung maturation previously. These findings
are in accordance with the meta-analysis 35 where they found that the
incidence of severe respiratory distress syndrome was significantly
reduced. However, repeated doses are not
recommended36.
Necrotizing enterocolitis was not prevalent, this may be due to the fact
that it is dependent on gestational age (less than 32 weeks) and birth
weight (less than 1500gr). However, it occurred in one case after
expectant management and two cases in the group of active management.
Neonatal death occurred in the active management group, with a single
risk factor that is prematurity (values of normal biomarkers in the
mother-child binomial. neonatal weight was 1830gr, received antibiotic
prophylaxis, and lung maturation), confirming its high index of
mortality that consider it between 20 and 50%37.
In women who received expectant management, an increased risk of
maternal infection was evidenced with a RR: 1,324 (95% CI:
0.972‒1.885), while active management seems to be a protective factor
against this event, with a RR: 0.683 (95% CI: 0.398‒1.172); determined
according to the elevation of biomarkers above the reference values.
However, to determine its impact, studies have been carried out in
search of histological chorioamnionitis at the placental level. Seong et
al. (2008)25 found that in placentas from term
pregnancies, labor produced histological chorioamnionitis without
increased inflammation at the level of fetal tissue with a prevalence of
19%. According to Rodríguez et al. (2016)38,
histological sensitivity of placentas study from patients with clinical
chorioamnionitis and ruptured membranes was 81% for predicting neonatal
sepsis, however, 49% of newborns with sepsis had a histological study
of their normal placentas.
Neonatal sepsis risk did not show significant differences, between
management. In the case of newborns of mothers under expectant
management RR: 0.909 (95% CI: 0.608‒1.359) is described, while, in
those born of mothers under active management have RR: 1,091 (95% CI:
0.773‒1.540), this despite the fact that higher levels of biomarkers
were found in mothers with expectant management. What is correlated to
studies such as that of Gisslen et al. (2016)39 in
which it was determined that in moderate and late preterm infants,
despite fetal exposure to funisitis and increased cytokines in umbilical
cord blood, neonatal morbidity did not increase.
The neonatal survival rate was greater than 98% in both groups.
Neonatal mortality risk for necrotizing enterocolitis is higher in
newborns of mothers undergoing active management, with RR: 2,013 (95%
CI: 1,723‒2,351) and RR: 1,321 (95% CI: 0.587‒2,973) respectively,
findings consistent with Bond et al. (2017)24 that
found an increase in neonatal mortality risk (RR 2.55, 95% CI
1.17‒5.56) in the active management group.4.1. Study limitations
Although the estimated sample number was reached, it was not possible to
do a long-term follow-up of infants who were transferred due to the
inability to access that information.
5. Conclusions
- In the present study, it was possible to evaluate expectant management
versus active management of premature rupture of membranes and it was
determined that degree of neonatal complications will depend on the
gestational age at which delivery occurs, with slight differences but
not statistically significant between both groups.
- A neonatal survival rate greater than 98% was identified for both
groups, with a higher risk of mortality and necrotizing enterocolitis in
the active management group.
- Neonatal sepsis risk did not show significant differences, depending
on the type of management.
- Necrotizing enterocolitis was not very prevalent; however, it occurred
in one case after expectant management and two cases in the active
management group, being the reason for neonatal death in this group.
- Frequency of respiratory distress syndrome was similar in both groups,
however, there was a statistical difference with a tendency to be more
frequent in neonates who did not receive lung maturation and between 34
and 35 weeks of gestation in 35.9% in relation to age gestational age
greater than 36 weeks.
- Prevalence of caesarean section was higher in cases of active
management with 50.9%.
- Hospitalization prolonged (greater than 48 hours) was more common in
infants of mothers treated actively, more often associated with
respiratory distress syndrome, however, this result was not
statistically significant.
- Maternal infection considering positive inflammatory and infectious
markers did not increase the risk of neonatal sepsis, there were no
clinical manifestations of chorioamnionitis in either of the two groups.
Abbreviations:
PROM Premature Rupture of Membranes
HECAM Hospital de Especialidades Carlos Andrade Marín
PUCE Pontificia Universidad Católica del Ecuador
WHO World Health Organization
ACOG American College of Obstetricians and
Gynecologists
IL Interleukin
TNF - α Tumor Necrosis Factor Alpha
CONGOF French College of Gynaecologists and Obstetricians
FASGO Federación Argentina de Sociedades de Ginecología y
Obstetricia
CRP C-reactive protein
Disclosure of interest
The authors declare no have financial, personal, political, intellectual
or religious interests.
Contribution to authorship
AJ: With conception, design work, planning, recollection data. AJ and
LC: getting results. AJ, RH, and LC: carrying out, analysing,
interpretation of data, and writing up of the work. RH, LC and SC:
Critical revision of the work.
Approval of its final version: All authors read and approved the final
version of the article.
Author information
Amanda Angélica Jácome Espinoza. Specialty in Obstetrics and
Gynaecology, Pontificia Catholic University of Ecuador. Obstetrics and
Gynaecology Treating Physician, El Puyo Basic Hospital. Puyo - Ecuador.
ORCID:https://orcid.org/0000-0002-3036-3254
Luis Ramiro Hidalgo Yánez. Doctor in Medicine and Surgery, Specialty in
Obstetrics and Gynaecology Central University of Ecuador. Attending
Physician of Obstetrics and Gynaecology, Hospital Carlos Andrade
Marín. Quito -
Ecuador. ORCID: https://orcid.org/0000-0001-9736-5783María Lucila Carrasco Guerra, Doctor of Medicine and Surgery, Medical or
Clinical-Health Pathologist. Professor, Faculty of Medicine PUCE, Quito
- Ecuador. Quito, Ecuador.
ORCID: https://orcid.org/0000-0002-1552-8532Lautaro Santiago Chávez Iza, Doctor of Medicine and Surgery, Specialty
in Obstetrics and Gynaecology, Central University of Ecuador. Attending
Physician of Obstetrics and Gynaecology, Hospital Carlos Andrade
Marín. Quito,
Ecuador. ORCID: https://orcid.org/0000-0002-7506-4215
Availability of data and materials
Free and limited use of physical and virtual bibliographic resources
were used.
The database was created based on the statistics of the High Obstetric
Risk Center of the Carlos Andrade Marín Specialty Hospital, maintaining
the confidentiality of data.
Collected documents are available upon request to the main author.
Ethics committee approval and consent to participation
The study was approved in act #010 on September 19, 2019; by the Human
Research and Ethics Committee/Carlos Andrade Marín Specialty Hospital
(CEISH / HECAM).
Consent for publication
Pending12. AcknowledgmentsSpecial thanks are given to the Department of Teaching and Research of
the Carlos Andrade Marín Specialities Hospital, for providing the
necessary permits and authorizations for the execution of the study, as
well as the Maternal and Child and High Obstetric Risk Area for
facilitating the search information from records doctors and nurses.
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