medicina

Article
Retrospective Study of First Trimester Metrorrhagia: Pregnancy
Follow-Up and Relationship with the Appearance of
Gestational Complications
Laura Baños Cándenas 1,2, * , Daniel Abehsera Davó 3 , Lucía Castaño Frías 4 and Ernesto González Mesa 4,5,6

1 Medicine School, Malaga University, 29071 Málaga, Spain

2 Obstetrics and Gynecology Service, Virgen de la Victoria University Hospital, 29010 Málaga, Spain
3 Obstetrics and Gynecology Service, HM Málaga Hospital, 29010 Málaga, Spain
4 Obstetrics and Gynecology Service, Regional University Hospital of Malaga, 29011 Málaga, Spain
5 Surgical Specialties, Biochemistry and Immunology Department, Malaga University, 29071 Málaga, Spain
6 Biomedical Research Institute of Malaga (IBIMA) Research Group in Maternal-Fetal Medicine, Epigenetics,
Women’s Diseases and Reproductive Health, 29071 Málaga, Spain
* Correspondence: laurabc84@hotmail.es; Tel.: +34-616567347

Abstract: Background and Objectives: The purpose of this study was to describe and evaluate the
bleeding that occurs during the first weeks of gestation and its implications throughout pregnancy.
Secondarily, we assessed the associated complications in order to identify potential risk factors
that could be used to select women at higher risk of adverse outcomes that could benefit from an
early diagnosis and improved monitoring. Materials and Methods: We made a selection of all the
women who consulted in the Emergency Department of the Hospital QuirónSalud in Malaga on
2015 presenting with first trimester metrorrhagia. We refer to first trimester metrorrhagia as that
which occurs until week 12 + 6. Once these pregnant women were identified, we studied several
variables not related to the gestation and some others associated with it and its natural course.
Results: The average age of the patients assessed was 34.1. Associated gestational complications were
Citation: Baños Cándenas, L.; metrorrhagia in the second trimester (6.3%), threatened preterm labor (7.4%), preeclampsia (2.5%),
Abehsera Davó, D.; Castaño Frías, L.; gestational diabetes (7.4%), late abortion (1.2%), and early postpartum hemorrhage (1.8%). We sought
González Mesa, E. Retrospective associations to assess possible risk factors, establishing an increased maternal age as an aggravating
Study of First Trimester Metrorrhagia: factor for the development of complications. We also studied gestational complications, finding a
Pregnancy Follow-Up and higher prevalence of them in older women, such as prematurity (33.11 vs. 34.48 years), gestational
Relationship with the Appearance of diabetes (33.11 vs. 36.06 years), and preeclampsia (33.25 vs. 35 years). Conclusions: Maternal age is
Gestational Complications. Medicina
a risk factor for first-trimester spontaneous miscarriage and for the development of complications
2023, 59, 1370. https://doi.org/
of pregnancy. It is crucial to perform a correct screening of different pathologies throughout the
10.3390/medicina59081370
pregnancy to anticipate potential complications.
Academic Editors: Ioannis Tsakiridis
and Simone Ferrero Keywords: first trimester bleeding; metrorrhagia of the first trimester; emergency room; gestational
complications; preeclampsia; gestational diabetes; abortion; threatened preterm labor; prematurity
Received: 18 June 2023
Revised: 23 July 2023
Accepted: 25 July 2023
Published: 27 July 2023
1. Introduction
Metrorrhagia or first trimester bleeding is defined as bleeding before 20 weeks of
gestation [1,2]. Bleeding of genital origin during the initial stages of pregnancy is a frequent
Copyright: © 2023 by the authors.
problem (20–30%) and has been shown to be associated with increased risk of adverse
Licensee MDPI, Basel, Switzerland.
pregnancy outcomes, such as preeclampsia, gestational diabetes (GD), preterm delivery,
This article is an open access article
threatened preterm labor, and preterm premature rupture of the membranes (PPROM).
distributed under the terms and
Other studies also include small-for-gestational-age (SGA) fetal measurements, low birth-
conditions of the Creative Commons
weight, and fetal death, though evidence is unclear [3]. Bleeding in the early stages of
Attribution (CC BY) license (https://
pregnancy is of great concern to the patient. This is one of the most common reasons for
creativecommons.org/licenses/by/
4.0/).
consultation in emergency services [4]. The main causes of bleeding in the first trimester

Medicina 2023, 59, 1370. https://doi.org/10.3390/medicina59081370 https://www.mdpi.com/journal/medicina

Medicina 2023, 59, 1370 2 of 23

include voluntary termination of pregnancy, spontaneous abortion or miscarriage, ectopic

pregnancy, gestational trophoblastic disease, and various non-obstetric causes (cervicitis,
vaginitis, trauma, cervical cancer, polyps) [1].
The Spanish Society of Obstetrics and Gynecology (SEGO) defined pregnancy loss as
“the expulsion or removal from its mother of an embryo or foetus weighing less than 500 g
(approximately 22 completed weeks of pregnancy) or other absolutely non-viable product
of pregnancy of any weight or gestational age, whether or not there is evidence of life or
whether the abortion was spontaneous or induced” [5].
The World Health Organization (WHO) describes pregnancy loss as the expulsion
of the embryo before 20 weeks of gestation, distinguishing between early pregnancy loss,
before week 12, and late abortion, between week 12 and 20.
Early pregnancy loss is one that occurs before 12 weeks. Within early pregnancy
loss, we can describe biochemical, preimplantation or preclinical abortion. These types of
miscarriage occur prior to implantation and therefore, before the clinical and ultrasound
appearance of pregnancy is established, so for their diagnosis it is sometimes necessary to
determine the value of β-hCG [6].
We refer to late abortion as that which takes place after the 12th week of gestation [7].
There is no consensus on the terminology, so there are variations in the different
definitions used.
It can be challenging to precisely establish a diagnosis of miscarriage, because very
early pregnancy losses generally go unnoticed, being classified as simple menstrual delays
or dysfunctional metrorrhagia.
The etiology of spontaneous abortion is usually unknown in most cases. Numerous
factors, from both maternal and embryonic origin, are involved in its development, such
as infectious or environmental factors, which constitute the etiology of the majority of
spontaneous abortions [8].
Due to its high prevalence among the population, we studied visits to the emergency
room over a year and followed up these pregnancies to assess whether a relation between
first trimester vaginal bleeding and the development of further complications throughout
the pregnancy could be established. Any potential pregnancy-related complication can
be extremely distressing for both the patient and her family. For the gynecologist, it is
important to identify symptoms related to certain complications that may arise during the
first weeks of pregnancy, as well as their potential short and long-term complications, in
order to reassure, advise, and support the couple at such a difficult time. [9,10].
Despite its high prevalence, first trimester bleeding should not be considered physio-
logical, and it is advisable to carry out an adequate differential diagnosis to rule out any
possible obstetric, gynecological, or systemic underlying pathology.
The aim of the study was to review the cases of bleeding that occur in the first weeks
of gestation and their implications throughout pregnancy. Secondarily, we studied the
associated complications and tried to identify possible risk factors that could be used
to select those women at higher risk of adverse outcomes that could benefit from early
diagnosis and improved follow-up.

2. Materials and Methods

For this study, we selected women who consulted the Emergency Department of the
Hospital QuirónSalud in Málaga throughout the year 2015 for first trimester bleeding. We
refer to metrorrhagia in the first trimester as that which occurs during weeks 1 through 12.
Once the pregnant women were identified, we studied risk factors already present prior to
the gestation, and others intrinsic to the pregnancy and its natural course.
In the following table (Table 1), we can see a summary of the variables collected in
our study.
Medicina 2023, 59, 1370 3 of 23

Table 1. Variable summary.

Variable Name
Maternal age
Parity
Number of emergency room visits
Gestational age at first visit
Previous uterine surgery
History of previous miscarriages
First trimester miscarriage
Weeks of miscarriage
Risk of trisomy 21 or Down Syndrome
Risk of trisomy 18 or Edwards Syndrome
PAPP-A
BHCG
TSH
Cervical length
Second trimester bleeding
Threatened preterm labor
Preterm premature rupture of the membranes
O’Sullivan value in the second trimester
Gestational diabetes
Preeclampsia
Gestational age at delivery
Way of delivery
Newborn weight
Venous pH
Apgar 1
Apgar 5
Early postpartum hemorrhage

Among the characteristics of our pregnant women, we collected maternal age in years
during the first visit to the emergency room.
For each patient, we recorded parity, which refers to the number of times that the pa-
tient has previously given birth. We divided our patients into two subgroups: primiparous
and multiparous.
For descriptive purposes of the sample, we recorded the obstetric history of the
patients, including previous spontaneous abortions and surgeries performed on the uterus.
We also collected the number of visits to the emergency department due to first
trimester bleeding, the gestational age at the time of the first visit, and those cases that
resulted in miscarriage.
Once the gestation reaches weeks 7 + 6 and 13 + 6 of amenorrhea, the first trimester
analysis is performed, preferably between the 8th and 10th week. Within this analysis,
the value of PAPP-A and β-hCG are used as biochemical markers to perform the com-
bined screening of aneuploidies. The values obtained are expressed in multiples of the
median (MoM).
Pregnancy-associated plasma protein A (PAPP-A) is secreted by the syncytiotro-
phoblast and its concentration increases during pregnancy. There are studies that have
Medicina 2023, 59, 1370 4 of 23

shown the relationship between low values of PAPP-A and β-hCG detected in the early
stages of pregnancy and several complications of pregnancy.
The relationship between the length of the cervical canal and prematurity has been
demonstrated. Ultrasound measurement of the cervical length can be useful to predict
which pregnancies are at increased risk of preterm delivery. The shorter the cervical length,
the greater the risk. In the second trimester, this parameter is measured by ultrasound to
detect pregnant women who are more likely to give birth prematurely.
Moreover, in the second trimester, we perform the O’Sullivan test, consisting of an oral
overload with 50 g of glucose, and the subsequent measurement of blood glucose levels in
venous plasma 60 min after ingestion.
This determination is performed on every pregnant woman in the second trimester
regardless of whether or not they have any risk factors. However, it will only be performed
during the first trimester to those women with risk factors, such as maternal age over 35,
obesity (BMI > 30), a history of gestational diabetes or carbohydrate intolerance, first-degree
relatives with diabetes, and history of fetal macrosomia. It is considered pathological when
values are ≥140 mg/dL or ≥7.8 mmol/L. In these cases, a further diagnostic confirmation
test is carried out using an oral glucose overload with 100 g of glucose.
In our study, we only used the value in mg/dL obtained in the analysis of the second
trimester. Even if performed in some cases, we did not take into account results obtained
from the analysis of the first trimester.
Gestational diabetes (GD) is defined as the form of diabetes that is first detected during
pregnancy regardless of the need for insulin treatment, the degree of metabolic disorder
involved, or its persistence after the end of pregnancy. For its diagnosis, the O’Sullivan
test is used (pathological when ≥140 mg/dL) and a further confirmation test with an oral
glucose overload of 100 g. The oral glucose tolerance test (OGTT) reference values are
≥105– ≥190– ≥165– ≥145 (fasting, 1-h, 2-h, and 3-h post glucose intake, respectively). For
diagnostic confirmation, two of four abnormal values are required. We included in our
study patients diagnosed with gestational diabetes during pregnancy using these criteria.
During pregnancy, hypertensive disorder is diagnosed by elevated blood pressure (BP)
(systolic ≥ 140 and/or diastolic ≥ 90 mm Hg), in two or more measurements separated
by 6 h. We define proteinuria as the presence of ≥300 mg of protein in a 24-h urine
sample. Preeclampsia is defined as hypertension that appears after 20 weeks of gestation
accompanied by proteinuria.
Second trimester hemorrhage is defined as bleeding occurring after 12 + 6 weeks,
regardless of the amount.
Late abortion is defined as that gestational loss above week 12, we collect those above
12 + 6 weeks.
Preterm premature rupture of membranes (PPROM) refers to membrane rupture
before 37 weeks of gestation. PPROM is estimated to complicate 3% of pregnancies and ac-
counts for approximately one third (33.3%) of all preterm deliveries. Rupture of membranes
occurring near the limit of fetal viability are much less frequent (estimated 0.04%) [11].
We compiled preterm membrane ruptures and analyzed those occurring at the limit of
viability and pre-viability.
We define postpartum hemorrhage as any bleeding that occurs during the first 24 h
after birth. We reviewed the obstetric history on admission and collected all the patients
who had heavy bleeding, regardless of whether it was resolved with conservative medical
treatment or by performing a puerperal curettage.

3. Results
3.1. Population
The total number of visits to the emergency room was 9451, 1161 of which were consul-
tations about first-trimester bleeding. Our final sample of study consisted of 696 patients.
The average age of the patients studied was 34.1, the median was 34, and age ranged from
18 to 50 years of age.
Medicina 2023, 59, x FOR PEER REVIEW 5 of 24

Medicina 2023, 59, 1370 5 of 23

3.2. Parity
The rate of primiparous women was 54% and the rate of multiparous women was
46%.
3.2. Parity
The rate of primiparous women was 54% and the rate of multiparous women was 46%.
3.3. Obstetric History
Within the
3.3. Obstetric obstetric history, we collected previous miscarriages and uterine surger-
History
ies. Within the obstetric history, we collected previous miscarriages and uterine surgeries.
The average
The averagenumber
numberofofprevious
previous miscarriages
miscarriages in our
in our sample
sample population
population was with
was 0.51, 0.51,
awith a standard
standard deviation
deviation of 0.867.
of 0.867. As weAs canwe
seecan
in see
Tablein 2Table 2 and Figure
and Figure 1, in the1,sample,
in the sample,
66% of
66%women
the of the women in ourhad
in our study study had noof
no history history of previous
previous miscarriages,
miscarriages, while 44% while 44% had
had previous
previous pregnancy
pregnancy losses.
losses. Among theAmong the had
latter, 23% latter,
one23% had one
previous previous spontaneous
spontaneous abortion, whileabor-
the
tion, while the remaining 10.8%
remaining 10.8% had more than one. had more than one.

Table 2.
Table 2. Obstetric
Obstetric history,
history, number
number of
of previous
previousmiscarriages.
miscarriages.

Number
NumberofofPrevious
Previous Miscarriages
Miscarriages Rate
Rate Incidence
Incidence
0 445 66.0
0 445 66.0
11 156156 23.1
23.1
22 4545 6.7
6.7
33 1616 2.4
2.4
44 1111 1.6
1.6
5 1 0.1
5
Total 1674 0.1
100
Total 674 100

Figure
Figure 1. Distribution according
1. Distribution according to
to obstetric
obstetric history.
history.

We recorded the gestational age at which the pregnancy loss occurred by reviewing
We recorded the gestational age at which the pregnancy loss occurred by reviewing
the emergency room visits and the outpatient follow-up. As we can see in the following
the emergency room visits and the outpatient follow-up. As we can see in the following
table (Table 3), we found that 68.6% of the miscarriages occurred between 6 and 8 weeks
table (Table 3), we found that 68.6% of the miscarriages occurred between 6 and 8 weeks
of gestation, 22.4% in the 6th week, 25.6% in the 7th week, and 20.6% in the 8th week
of gestation, 22.4% in the 6th week, 25.6% in the 7th week, and 20.6% in the 8th week
(Figure 2).
(Figure 2).
Medicina 2023, 59, x FOR PEER REVIEW 6 of 24

Medicina 2023, 59, 1370 6 of 23

Table 3. Gestational age at which pregnancy loss occurs.

Gestational age
Table 3. Gestational Ageat which pregnancy lossRate
occurs. Incidence
4 Age
Gestational 4
Rate 1.4
Incidence
5 31 11.0
4 4 1.4
56 3163 22.4
11.0
67 6372 25.6
22.4
78 7258 25.6
20.6
8 58 20.6
9 27 9.6
9 27 9.6
10
10 1818 6.4
6.4
11
11 33 1.1
1.1
12
12 44 1.4
1.4
13
13 11 0.4
0.4
Total 281 100
Total 281 100

pregnancy loss
Figure 2. Distribution according to pregnancy loss gestational
gestational age.
age.

Regarding
Regarding the
theexistence
existenceofofprevious
previousuterine
uterinesurgery,
surgery,wewe
classified the the
classified patients accord-
patients ac-
ing to whether or not they had previous surgeries.
cording to whether or not they had previous surgeries.
Uterine
Uterine surgeries
surgeriesreviewed
reviewedincluded
includedpolypectomies
polypectomies bybyhysteroscopy,
hysteroscopy,cesarean section,
cesarean sec-
curettage, myomectomy,
tion, curettage, myomectomy,and conization for cervical
and conization dysplasia.
for cervical We recorded
dysplasia. data from
We recorded a
data
sample of 689 women, of whom 467 had not had uterine interventions prior to
from a sample of 689 women, of whom 467 had not had uterine interventions prior to the the current
pregnancy, corresponding
current pregnancy, to 67.8% of
corresponding to the total.
67.8% ofThe
the remaining
total. The 222 patients 222
remaining (32.2%) had
patients
undergone some type of uterine intervention.
(32.2%) had undergone some type of uterine intervention.
3.4. Number of Emergency Department Visits
3.4. Number of Emergency Department Visits
Once the study population was selected, the number of times they visited the emer-
Once the study population was selected, the number of times they visited the emer-
gency department was reviewed as well as the reason for consultation. To establish the
gency department was reviewed as well as the reason for consultation. To establish the
total number of visits to the emergency department, we recorded consultations for bleeding
total
in thenumber of visitsup
first trimester to to
theand
emergency
includingdepartment,
the 12th week we recorded consultations
of gestation (12 to 12 + for bleed-
6 weeks).
ing in the first trimester up to and including the 12th week of gestation (12
The remaining visits to the emergency department during pregnancy, as well as obstetric to 12 + 6 weeks).
The remaining
check-ups, werevisits to theinto
not taken emergency
account department
for the study. during pregnancy, as well as obstetric
check-ups, were not taken into account for the study.
In Table 4, we can see the summary of visits to the emergency room. The largest group
In Table
of patients, 4, we
who can see the
accounted forsummary
52.7% andof32.5%
visits of
to visits,
the emergency
attended room. The largest
the emergency group
room on
of patients, who accounted for 52.7% and 32.5% of visits, attended the
one and two occasions, respectively; this group totals 85.2%. The remaining 14.8% of theemergency room
patients visited the emergency department more than twice (Figure 3).
 Medicina 2023, 59, x FOR PEER REVIEW 7 of 24

Medicina 2023, 59, 1370 7 of 23

on one and two occasions, respectively; this group totals 85.2%. The remaining 14.8% of
the patients visited the emergency department more than twice (Figure 3).
Table 4. Emergency visits.
Table 4. Emergency visits.
Emergency Visits Rate Incidence
Emergency Visits Rate Incidence
1 1 367367 52.7 52.7
2 226 32.5
2 226 32.5
3 80 11.5
4 3 8016 11.5 2.3
5 4 16 6 2.3 09
8 5 61 09 0.1
Total 8 1696 0.1 100
Total 696 100

Figure 3.
Figure 3. Distribution
Distributionaccording to number
according of emergency
to number visits.visits.
of emergency

We reviewed
reviewedthe thenumber
number of times thatthat
of times patients consulted
patients for first-trimester
consulted bleedingbleeding
for first-trimester
and assessed whether or not the pregnancy resulted in miscarriage.
and assessed whether or not the pregnancy resulted in miscarriage. The averageThe average numbernumber of
of visits to the emergency room among patients who miscarried
visits to the emergency room among patients who miscarried was 1.92 ± 0.923,was 1.92 ± 0.923, com-
compared
pared
to 1.52to±1.52 ± 0.794
0.794 among
among thosewho
those who did
did not
not(p(p< <
0.0001) (Figure
0.0001) 4). This
(Figure 4). means that the that the
This means
patients who experienced pregnancy loss the most were those who had previously visited
patients who experienced pregnancy loss the most were those who had previously
Medicina 2023, 59, x FOR PEER REVIEW 8 of 24 visited
the emergency department on more occasions.
the emergency department on more occasions.

Figure 4.
Figure 4. Distribution
Distribution of of
first trimester
first miscarriages
trimester according
miscarriages to the number
according of visits to
to the number of the emer-
visits to the emer-
gency room.
gency room.
We combined the data collected on the number of visits to the emergency room before
week 12 for first-trimester bleeding in pregnancies that did not result in miscarriage with
the number of cases of threatened preterm labor. We found 21 cases of pregnancies that
consulted for first trimester bleeding that were later diagnosed with threatened preterm
labor compared to 263 who were not (Figure 5).
 Figure 4. Distribution of first trimester miscarriages according to the number of vis
gency room.
Medicina 2023, 59, 1370 8 of 23

We combined the data collected on the number of visits to the emergenc

week We12 for first-trimester
combined bleeding
the data collected in pregnancies
on the number that did room
of visits to the emergency not result
before in mi
week 12 for first-trimester
the number of casesbleeding in pregnancies
of threatened that did
preterm not result
labor. Weinfound
miscarriage with of pre
21 cases
the number of cases of threatened preterm labor. We found 21 cases of pregnancies that
consulted for first trimester bleeding that were later diagnosed with threa
consulted for first trimester bleeding that were later diagnosed with threatened preterm
laborcompared
labor compared to 263to 263were
who who notwere
(Figurenot
5). (Figure 5).

Figure 5. Distribution of threatened preterm labor according to the number of visits to the
Figure 5. Distribution of threatened preterm labor according to the number
emergency room.
of vis
gency room.
3.5. Gestational Age at the First Emergency Department Visit

3.5. The mean gestational age (number of weeks) at which the first consultation took place
Gestational Age at the First Emergency Department Visit
was 7.19 weeks, with a standard deviation of ±2.069. The highest percentage of women
The mean
who consulted gestational
for first age (number
trimester bleeding of weeks)
(23.4%) did so in the at
6thwhich
week ofthe first consultat
amenorrhea.
The most part of the consultations occurred between the 5th and 8th week of gestation,
was 7.19 weeks, with a standard deviation of ±2.069. The highest percenta
constituting 74.4% of the consultations (Table 5) (Figure 6).
who consulted for first trimester bleeding (23.4%) did so in the 6th week o
The 5.most
Table partage
Gestational ofatthe consultations
the first visit. occurred between the 5th and 8th wee
constituting 74.4%
Gestational Age of the consultations
First Visit Rate (Table 5) (Figure 6).
Incidence
3 2 0.3
4 20 2.9
5 130 18.7
6 163 23.4
7 130 18.7
8 95 13.6
9 47 6.8
10 42 6.0
11 33 4.7
12 28 4.0
13 6 0.9
Total 696 100
 9 47 6.8
10 42 6.0
11 33 4.7
12 28 4.0
Medicina 2023, 59, 1370 13 6 0.9 9 of 23

Total 696 100

Figure6.6. Distribution
Figure Distributionof
ofgestational
gestationalage
ageat
atfirst
firstvisit
visitto
tothe
theemergency
emergencyroom.
room.

3.6.
3.6. Miscarriage
Miscarriage
In
In our
our study,
study,early
earlypregnancy
pregnancy loss
loss isis defined
defined as
as that
that occurring
occurring before
before 12
12 weeks,
weeks, in-
in-
cluding 12 + 6 weeks. Of the 696 women who consulted for bleeding in the first
cluding 12 + 6 weeks. Of the 696 women who consulted for bleeding in the first trimester, trimester,
Medicina 2023, 59, x FOR PEER REVIEW 10 of 24
296
296 ended
ended inin miscarriage,
miscarriage, which
which corresponds
corresponds to to 45.3%
45.3% ofof the
the women
women whowho consulted
consulted forfor
hemorrhage
hemorrhage(Figure
(Figure7).
7).

Figure7.7.Distribution
Figure Distribution of of
miscarriages.
miscarriages.

3.7. Second Trimester Bleeding

We considered second trimester metrorrhagia as vaginal bleeding occurring after the
13th week of gestation. Of the 268 pregnancies, 17 presented with second trimester bleed-
ing, which corresponds to 6.3% of the total.

3.8. Cervical Length in Second Trimester

 Figure 7. Distribution of miscarriages.

Medicina 2023, 59, 1370 3.7. Second Trimester Bleeding 10 of 23

We considered second trimester metrorrhagia as vaginal bleeding occu

13th week of gestation. Of the 268 pregnancies, 17 presented with second tri
3.7. Second Trimester Bleeding
ing, which corresponds to 6.3% of the total.
We considered second trimester metrorrhagia as vaginal bleeding occurring after the
13th week of gestation. Of the 268 pregnancies, 17 presented with second trimester bleeding,
3.8.
whichCervical Length
corresponds in of
to 6.3% Second Trimester
the total.

The measurement
3.8. Cervical of cervical
Length in Second Trimester length during the second trimester ultra
formed to establishof acervical
The measurement higher or lower
length risk
during the of preterm
second delivery. isThe
trimester ultrasound per- shorte
formed to establish a higher or lower risk of preterm delivery. The shorter
length, the greater the likelihood of delivering before 37 weeks. The mean c the cervical
length, the greater the likelihood of delivering before 37 weeks. The mean cervical length
in oursample
in our sample waswas
39.8839.88 mm,
mm, with an with an SD
SD of 6.25 mm.of 6.25
The mm.measurement
smallest The smallest measurem
recorded
was 20mm
was 20 mm andand the largest
the largest was(Figure
was 57 mm 57 mm 8). (Figure 8).

Mean 39.88

SD 6.252

N 225

Figure 8. Distribution of cervical length.

3.9. Preeclampsia
The calculation of the combined screening of the first trimester is based on several
parameters: weeks of gestation according to the first day of the last menstrual period (LMP),
crown–rump length (CRL), maternal age, nuchal translucency measured by ultrasound,
and biochemical parameters such as PAPP-A and β-hCG expressed in multiples of the
median (MoM). In our study, we recorded the value of PAPP-A in MoM.
The mean value of the PAPP-A was 1.0717, with a standard deviation (SD) of ±0.71.
The lowest value was 0.21 and the highest was 5.89.
As previously stated, we define preeclampsia as hypertension that appears after
20 weeks of gestation accompanied by proteinuria. In our study, we recorded data from
243 pregnant women, 6 of whom were diagnosed with preeclampsia, corresponding to
2.5% of them (Figure 9).
 the median (MoM). In our study, we recorded the value of PAPP-A in MoM.
The mean value of the PAPP-A was 1.0717, with a standard deviation (SD) of ±0.71.
The lowest value was 0.21 and the highest was 5.89.
As previously stated, we define preeclampsia as hypertension that appears after 20
weeks of gestation accompanied by proteinuria. In our study, we recorded data from 243
Medicina 2023, 59, 1370
pregnant women, 6 of whom were diagnosed with preeclampsia, corresponding to112.5% of 23

of them (Figure 9).

Figure 9. Distribution
Figure 9. Distribution of
of cases
cases of
of preeclampsia.
preeclampsia.

We were able to establish a statistically significant relationship between blood levels

We were able to establish a statistically significant relationship between blood levels
of PAPP-A and the development of preeclampsia (p < 0.005). In the sample, 75% of women
of PAPP-A and the development of preeclampsia (p < 0.005). In the sample, 75% of women
with preeclampsia presented with low PAPP-A levels during the first trimester analysis
with preeclampsia presented with low PAPP-A levels during the first trimester analysis
(Table 6).
(Table 6).
Among all the women with low PAPP-A levels, only 11.1% had developed
Table 6. Relationship between preeclampsia and low PAPP-A levels.
preeclampsia.
In summary, low PAPP-A levels are not associatedPreeclampsia with an increased risk of
preeclampsia, but preeclampsia associates with low blood No PAPP-A levels. Total
Yes

Table 6. RelationshipYes Count

between preeclampsia 24
and low PAPP-A levels. 3 27
% with low PAPP-A levels 88.9% 11.1% 100.0%
Low PAPP-A Preeclampsia
Count 106 1 Total
107
No No Yes
% with low PAPP-A levels 99.1% 0.9% 100.0%
Count 24 3 27
Yes Count 130 4 134
Total % with low PAPP-A levels 88.9% 11.1% 100.0%
Low PAPP-A
% with low PAPP-A levels
Count 97.0%
106 3.0%
1 100.0%
107
No
% with low PAPP-A levels 99.1% 0.9% 100.0%
Count levels, only 11.1%
Among all the women with low PAPP-A 130 had developed
4 134
preeclampsia.
Total
In summary, low PAPP-A levels
% with lowarePAPP-A
not associated
levels with an increased
97.0% risk of preeclamp-
3.0% 100.0%
sia, but preeclampsia associates with low blood PAPP-A levels.

3.10. Prematurity
The gestational age of delivery was recorded in all pregnancies. We considered all
pregnancies over 12 + 6 weeks, so this analysis may also include those that resulted in
late abortions.
We consider late abortion to be gestational losses above week 12, up to and including
week 12 + 6. In our sample, we have a total of 7 women who had a late abortion, which
corresponds to 1.2%
Gestational age at delivery ranged from 17 weeks, which corresponded to a late
abortion, to 42 weeks, being 38.69 weeks with a SD of ±3.4 weeks mean gestational age at
delivery (Figure 10).
 abortions. abortions.
We consider Welate abortion
consider latetoabortion
be gestational losses above
to be gestational week
losses 12, up
above to and
week 12, including
up to and including
week 12 + week
6. In our
12 +sample,
6. In ourwesample,
have awe
total of 7a women
have total of who had awho
7 women late had
abortion,
a late which
abortion, which
corresponds to 1.2% to 1.2%
corresponds
GestationalGestational
age at delivery
age atranged from
delivery 17 weeks,
ranged from which corresponded
17 weeks, to a late abor-
which corresponded to a late abor-
Medicina 2023, 59, 1370 12 of 23
tion, to 42 tion,
weeks, being 38.69 weeks with a SD of ±3.4 weeks mean gestational age at de-
to 42 weeks, being 38.69 weeks with a SD of ±3.4 weeks mean gestational age at de-
livery (Figure 10).
livery (Figure 10).

Mean 38.69 Mean 38.69

SD 3.402 SD 3.402

N 228 N 228

Figure 10. Average distribution

Figure 10. according to
Average distribution the weeks
according
according toof
to termination
the
the weeks
weeks of of pregnancy.
of termination
termination of
of pregnancy.
pregnancy.

The number The

The ofnumber
womenof
number of women
who who
delivered
women delivered
who before before
week
delivered week
37 was
before 21,37
week was
was 21,
which
37 21, which
which corresponds
corresponds to
corresponds to
to
9.2%
9.2% of the9.2% of the total
totalof(Figure (Figure
11).
the total 11).
(Figure 11).

Figure 11. Distribution

Figure 11.
Figure 11. Distribution according toaccording toof
the weeks the weeks of termination
termination of
of pregnancy.
of pregnancy. pregnancy.

3.11. Preterm Premature Rupture of the Membranes (PPROM)

3.11. Preterm Premature
3.11. Preterm Rupture of Rupture
Premature the Membranes (PPROM) (PPROM)
of the Membranes
As for the cases of PPROM, considering those that occurred before 37 weeks, we
As for the As
cases
forofthe
PPROM,
cases ofconsidering those that those
PPROM, considering occurred
thatbefore 37 weeks,
occurred before we rec- we rec-
37 weeks,
recorded a rate of PPROM in our sample of 5.26%.
orded a rate of PPROM
orded a rate ofinPPROM
our sample of sample
in our 5.26%. of 5.26%.
Among our results, we recorded four pre-viable preterm premature ruptures of mem-
branes and one near the limit of fetal viability: two of them at 19 weeks, one at 17 weeks,
one at 23 + 5 weeks, and another at 24 + 6 weeks. The percentage of previable preterm
premature rupture of membranes in our study was 2.18%.

3.12. Gestational Diabetes

To screen for gestational diabetes, an oral glucose tolerance test using 50 g of glucose
is performed in the second trimester, known as the O’Sullivan test. In those women with
risk factors or history of gestational diabetes in previous pregnancies, this determination is
done during the first trimester. In our study, we collected the results obtained in the second
trimester, and considered the result pathological when glucose levels were ≥140 mg/dL.
 3.12. Gestational Diabetes
To screen for gestational diabetes, an oral glucose tolerance test using 50 g of glucose
is performed in the second trimester, known as the O’Sullivan test. In those women with
risk factors or history of gestational diabetes in previous pregnancies, this determination
Medicina 2023, 59, 1370 13 of 23
is done during the first trimester. In our study, we collected the results obtained in the
second trimester, and considered the result pathological when glucose levels were ≥140
mg/dL.
We collected
We collected data
data from
from 259
259 pregnant
pregnant women.
women. The
The mean
mean glucose
glucose value
value obtained
obtained from
from
theO’Sullivan
the O’Sullivantest
testwas
was125.67
125.67 ± 29.51
± 29.51 mg/dL.
mg/dL. The The lowest
lowest and highest
and highest recorded
recorded valuesvalues
were
were
51 and51221
and 221 mg/dL,
mg/dL, respectively
respectively (Figure(Figure
12). 12).

Figure 12. Distribution of O’Sullivan levels.

Figure 12. Distribution of O’Sullivan levels.
We only took into account cases of gestational diabetes diagnosed during pregnancy;
We only took into account cases of gestational diabetes diagnosed during pregnancy;
cases of diabetes diagnosed before were not included in the study. Among the women
cases of diabetes diagnosed before were not included in the study. Among the women
Medicina 2023, 59, x FOR PEER REVIEW
included in the study, 18 developed gestational diabetes, which corresponds to 7.4%14ofofthe
24
included in the study,
total (Figure 13). 18 developed gestational diabetes, which corresponds to 7.4% of
the total (Figure 13).

Figure 13.
Figure 13. Distribution of
of cases
cases of
of gestational
gestational diabetes.
diabetes.

3.13.
3.13. Early
Early Postpartum
Postpartum Hemorrhage
Hemorrhage
We
We consider early postpartum
consider early postpartum hemorrhage
hemorrhage to to be
be that
that which
which occurs
occurs within
within 24
24 h
h after
after
birth.
birth. Of the 228 pregnancies in which we registered deliveries, four of them had early
Of the 228 pregnancies in which we registered deliveries, four of them had early
postpartum hemorrhage, which corresponds to 1.8%.
postpartum hemorrhage, which corresponds to 1.8%.
We expanded the study by selecting the patients based on maternal age to assess
We expanded the study by selecting the patients based on maternal age to assess
whether maternal age relates to certain obstetric complications.
whether maternal age relates to certain obstetric complications.

3.14. Threatened Preterm Labor

We reviewed the cases of threatened preterm labor. We did not find a statistically
significant relationship between maternal age and threatened preterm labor (33.40 ± 4.462
vs. 33.41 ± 5.335 years) (Figure 14).
 3.13. Early Postpartum Hemorrhage
We consider early postpartum hemorrhage to be that which occurs within 24 h after
birth. Of the 228 pregnancies in which we registered deliveries, four of them had early
postpartum hemorrhage, which corresponds to 1.8%.
Medicina 2023, 59, 1370 14 of 23
We expanded the study by selecting the patients based on maternal age to assess
whether maternal age relates to certain obstetric complications.

3.14.
3.14. Threatened
Threatened Preterm
Preterm Labor
Labor
We
We reviewed
reviewed thethe cases
cases ofof threatened
threatened preterm
preterm labor.
labor. We did
did not
not find
find aa statistically
statistically
significant
significant relationship
relationshipbetween
betweenmaternal
maternalage
ageand
andthreatened
threatenedpreterm
pretermlabor (33.40±± 4.462
labor(33.40 4.462
vs. 33.41 ±
vs. 33.41 5.335 years)
± 5.335 years) (Figure
(Figure 14).
14).

Figure 14. Boxplot distribution of threatened preterm labor cases in relation to maternal age.
Figure 14. Boxplot distribution of threatened preterm labor cases in relation to maternal age.
3.15. Maternal Age
3.15.Regarding
Maternal Ageprematurity, we assessed maternal age in relation to having a preterm
delivery. The mean
Regarding maternal age
prematurity, weofassessed
women maternal
who delivered before
age in week
relation to37 was 34.48
having years,
a preterm
Medicina 2023, 59, x FOR PEER REVIEW
while it was 33.11 years for those who delivered at term (Figure 15). We found no 15 of 24
statistically
delivery. The mean maternal age of women who delivered before week 37 was 34.48 years,
significant
while it wasdifference between
33.11 years both
for those groups
who (p < 0.187).
delivered at term (Figure 15). We found no statisti-
cally significant difference between both groups (p < 0.187).

Figure 15. Boxplot distribution

Figure 15. distribution of
of cases
cases of
of prematurity
prematurity in
in relation
relation to
to maternal
maternalage.
age.

If
If we
we analyze
analyze the
the results
results of
of the
the O’Sullivan
O’Sullivantest
test(using
(using>140
>140 mg/dL
mg/dL asas the
the cut-off
cut-off value)
value)
in relation to maternal age, we conclude that the mean maternal age for those
in relation to maternal age, we conclude that the mean maternal age for those women with women
with test results
test results within
within the the normal
normal range
range waswas 33.04;
33.04; whilstthe
whilst themean
meanmaternal
maternal age
age among
among
women
women with pathological test results was 34.12 years (Figure 16). Therefore, the result
with pathological test results was 34.12 years (Figure 16). Therefore, the result
seems
seems to to be
be influenced
influenced by
by maternal
maternal age,
age, with
with higher
higher prevalence
prevalence of
of pathological
pathological test
test results
results
with
with increased
increased maternal
maternal age.
age. However,
However, statistical
statisticalsignificance
significancewas
wasnot
notfound
found(p(p<< 0.069).
0.069).
 If we analyze the results of the O’Sullivan test (using >140 mg/dL as the cut-off value)
in relation to maternal age, we conclude that the mean maternal age for those women with
test results within the normal range was 33.04; whilst the mean maternal age among
women with pathological test results was 34.12 years (Figure 16). Therefore, the result
Medicina 2023, 59, 1370
seems to be influenced by maternal age, with higher prevalence of pathological test results15 of 23
with increased maternal age. However, statistical significance was not found (p < 0.069).

O’Sullivan > 140

Figure 16. Boxplot distribution of pathological O’Sullivan cases in relation to maternal age.
Figure 16. Boxplot distribution of pathological O’Sullivan cases in relation to maternal age.
Comparing the mean maternal age in women who developed gestational diabetes
Comparing
with respecttheto mean
those maternal age in
who did not, wewomen
found awho developed
statistically gestational
significant diabetes with
difference,
with
Medicina 2023, 59, x FOR PEER REVIEWp < 0.007. The mean maternal age of those who presented with GD waswith
respect to those who did not, we found a statistically significant difference, p <years,
36.06
0.007.compared
The meanto maternal age of those who presented with GD was 36.06 years, compared
a mean age of 33.11 years of those who did not suffer from GD (Figure 17).
to a mean age ofthe
Therefore, 33.11 years ofof
prevalence those who did not
GD increased suffer
with from age.
maternal GD (Figure 17). Therefore,
the prevalence of GD increased with maternal age.

Figure 17. Boxplot distribution of cases of gestational diabetes in relation to maternal age.

Figure 17.not
We did Boxplot distribution
find a statistically of cases
significant of gestational
difference betweendiabetes in relation
the mean maternal ageto
of matern
women who developed preeclampsia and women who did not (35 and 33.25 years of age,
respectively)
We did withnot findof ap <statistically
a value 0.350 (Figure 18).
significant difference between the
mean
of women who developed preeclampsia and women who did not (35 and
age, respectively) with a value of p < 0.350 (Figure 18).
 Figure 17. Boxplot distribution of cases of gestational diabetes in relation to maternal age.

We did not find a statistically significant difference between the mean maternal age
Medicina 2023, 59, 1370 16 of 23
of women who developed preeclampsia and women who did not (35 and 33.25 years of
age, respectively) with a value of p < 0.350 (Figure 18).

Figure 18. Boxplot distribution of cases of preeclampsia in relation to maternal age.

Figure 18. Boxplot distribution of cases of preeclampsia in relation to maternal age.
4. Discussion
4. Discussion
Our study focuses mainly on the knowledge of bleeding in the first trimester and its
implications
Our study throughout pregnancy.
focuses mainly on the knowledge of bleeding in the first trimester and its
Within the data reviewed
implications throughout pregnancy. in the patients who presented with bleeding in the first
trimester, we collected different
Within the data reviewed in variables such as
the patients whomaternal age, with
presented obstetric history,
bleeding in number
the first
of previouswe
trimester, abortions,
collectedand existence
different of previous
variables gynecological
such as maternal age,surgery. Data
obstetric on gestational
history, number
follow-up
of previous and the appearance
abortions, of associated
and existence obstetric
of previous pathology were
gynecological also collected.
surgery. Data on gesta-
We selected the pregnant women who consulted for bleeding
tional follow-up and the appearance of associated obstetric pathology werein the firstalso
trimester, we
collected.
did not find a triggering cause of the bleeding.
We selected the pregnant women who consulted for bleeding in the first trimester,
In the
we did not following section,
find a triggering we describe
cause each of the variables and results obtained in
of the bleeding.
our study.

4.1. Obstetric History

In our sample, 44% of the pregnant women had a history of a previous pregnancy loss.
This history increases the risk of subsequent miscarriages, thus the chances are estimated
at approximately 16–20, 30, and 40%, depending on the history of 2, 3, or more pregnancy
losses. Other authors find similar figures, with an increase in risk of miscarriage of 30% and
33% after the second and third miscarriage, respectively. For this reason, the most important
predictor of recurrent pregnancy loss is a history of a previous pregnancy loss [12–15].
We reviewed the surgical history of the patients and found that the rate of previous
uterine surgery was 32.2%. Of the patients with uterine interventions prior to the pregnancy,
46.39% experienced first trimester pregnancy loss. There was no difference in the results
compared to those without previous surgical interventions performed on the uterus. In
terms of the route of delivery, 43.24% of mothers gave birth by vaginal birth, while 56.7%
had a cesarean section. We see that the caesarean section rate is somewhat higher than the
rate observed the global population. This can be explained by the fact that the surgical
history includes those patients with a previous cesarean section, so cesarean section is more
frequent in this group [16].
However, we did not find statistical significance for any of the associations stud-
ied. There are no major complications or increased risk of threatened preterm labor,
preeclampsia, late miscarriage, prematurity, or early postpartum hemorrhage in patients
who underwent uterine surgery before pregnancy.
Medicina 2023, 59, 1370 17 of 23

4.2. Number of Emergency Department Visits

In our study, we observed a relationship between the number of visits to the emergency
department and the subsequent occurrence of a higher number of complications.
The complications with which we could establish a relationship were first-trimester
pregnancy loss and threatened preterm labor.
Regarding the number of visits to the emergency department, a study on fetal growth
patterns in pregnant women with first trimester bleeding found that bleeding lasting more
than one day was associated with lower fetal birth weight [3].
Other studies in relation to low birth weight show similar results, with lower birth
weight in those pregnant women who presented bleeding in the first weeks [17–19].

4.3. Gestational Age at the First Emergency Department Visit

The mean gestational age of consultation for first-trimester bleeding is 7.19 weeks.
The gestational age with the most consultations was the 6th week, with 23.4% of the cases.
Results published in a study on bleeding patterns and its predictive factors in the first
trimester are in line with ours, the gestational age at which most consultations occur is
between the 5th and 8th weeks, peaking between the 6th and 7th weeks [20].
A recent mortality study in the United States in 2020 reports that 80.9% of miscarriages
occur below 9 weeks, and 93.1% before week 13 [21].
According to different studies, if the embryo develops and displays cardiac activity,
the chances of pregnancy loss decrease drastically to 3–4%. An increased gestational age at
which bleeding occurs for the first time is related to a better prognosis, thus 90 to 96% of
pregnancies between the 7th and 11th weeks in which vaginal bleeding occurs and there is
already embryonic cardiac activity will evolve. The higher the gestational age, the higher
the pregnancy success rate [7,22].
Medicina 2023, 59, x FOR PEER REVIEW 18 of 24
The following graph (Figure 19) shows how the prevalence of spontaneous abortions
is higher in the first weeks of gestation, and how it decreases as gestational age increases.

Figure
Figure 19.
19. Distribution
Distribution of
of miscarriages
miscarriages according to gestational
according to gestational age
age [23].
[23].

Therefore, it would be advisable to pay special attention to the patients who consult
for first trimester hemorrhage and who have a history of previous miscarriages.
miscarriages.
The most
most frequent
frequentgestational
gestationalage
ageatatwhich
whichgestational losses
gestational occur
losses is between
occur the the
is between 6th
andand
6th 8th week (68.6%).
8th week According
(68.6%). to the
According toliterature, approximately
the literature, 90–95%
approximately of miscarriages
90–95% of miscar-
occur in
riages the first
occur in thetrimester, most ofmost
first trimester, themofbefore
them the 8ththe
before week.
8th week.

4.4. Miscarriage
Among all the pregnant women who consulted for first trimester bleeding, the mis-
carriage rate obtained was 45.3%. Comparing this result with the miscarriage rate in the
Medicina 2023, 59, 1370 18 of 23

4.4. Miscarriage
Among all the pregnant women who consulted for first trimester bleeding, the mis-
carriage rate obtained was 45.3%. Comparing this result with the miscarriage rate in
the general obstetric population, regardless of the presence or absence of bleeding, the
miscarriage rate is approximately 12–15% [24].
Reviewing the literature on first trimester pregnancy losses and their prevalence, we
found similar results to those obtained in our study. Approximately 50% of pregnancies
that present with bleeding in the first weeks result in miscarriage.

4.5. Second Trimester Bleeding

Regarding second trimester bleeding, 6.3% of the pregnancies that reached the second
trimester also presented with bleeding then. In the publications reviewed, we found a rate
of bleeding in the second trimester of 3–4%, somewhat lower than that obtained in our
study. This may be explained by the fact that our patients already had bleeding in the first
trimester, so it may be more common for them to present with or maintain bleeding until in
the second trimester [10,15,17].

4.6. Cervical Length in Second Trimester

We also reviewed the value of cervical length in the second trimester. The average
value of our patients was 39.88 mm. According to the results obtained, therefore, it was not
decreased, the cervical length in our patients was not diminished. Measurements above
30 mm are considered normal and those below 25 mm are associated with a greater risk of
threatened preterm labor [25].
We compared the cervical length in those patients who presented APP with respect
to those who did not present it and found a statistically significant difference. We found
a relationship between the shorter cervical length and threatened preterm labor.
Multiple studies have previously demonstrated this relationship between the mea-
surement of the cervical canal and subsequent presentation of threatened preterm labor
and prematurity [25–27].

4.7. Preeclampsia
The rate of preeclampsia in our patients was 2.5%, a lower value than that estimated
globally, approximately between 5 and 10%. According to the WHO, this rate is seven
times higher in developing countries and in areas of greater prevalence of cardiovascular
disease [28–30].
In our study, we did not find an increase in cases of preeclampsia. However, we
observed that 75% of patients with preeclampsia presented low blood levels of PAPP-A in
the laboratory tests performed on the first trimester.
We found studies showing similar results, in which they also observed a greater risk
of preeclampsia, preterm labor, and low birth weight, in pregnant women with low levels
of PAPP-A [31–33].
As previously stated, low levels of PAPP-A do not relate to an increased risk of
preeclampsia, but preeclampsia is related to having low blood PAPP-A levels.
In our sample, we used a value of 0.6 MoM as a cuff-off for PAPPA-A, with values
lower than 0.6 being considered low. Other authors used values of 0.4 and 0.2 MoM
as the cuff-off, observing more striking statistically significant differences in terms of
adverse outcomes in these two groups. The most severe cases, associated with intrauterine
fetal death or placental abruption, presented for the most part values of PAPPA-A below
0.2 MoM [34].
For the above-mentioned reasons, the measurement of serum PAPP-A during the first
trimester analysis may be useful to predict future adverse outcomes in pregnancy [35].
Medicina 2023, 59, 1370 19 of 23

4.8. Prematurity
Regarding pre-term delivery, understood as that which takes place before the end of
week 37 of gestation, we found a rate of 9.2% preterm births among our patients.
According to data from the National Institute of Statistics, the prematurity rate rep-
resents 6.5–9% of all births and may increase to and reach 12.5% in reference centers. We
compared the prematurity rate obtained in our study with that published by other work
groups and found similar results, with a rate of pre-term birth around 10.24% [36,37].
We studied maternal age as a risk factor for prematurity, finding no statistically
significant differences in the rate of prematurity with increasing maternal age.
We analyzed the data published by other authors on this matter and found disparate
results. There are publications with similar results to ours, in which they did not find
an increase in prematurity [38]. However, other authors have documented an increase in
prematurity among pregnant women of advanced aged. This increase could be influenced
by the greater degree of associated maternal pathology, which in turn could result in a
premature delivery [39].
A recent study shows the same conclusions; it assessed the association between ma-
ternal age and prematurity and found no increase in maternal age among pregnancies
that terminated spontaneously, while they demonstrated a rise in prematurity with in-
creased maternal age among pregnancies that required a planned delivery due to associated
medical complications. Therefore, there was a correlation between increased maternal
age and prematurity but as a result of maternal medical conditions that required planned
delivery [36].

4.9. Threatened Preterm Labor

Regarding threatened preterm labor, as previously stated, the data we obtained were
in line with that previously published in other studies. We classified the patients according
to maternal age and did not observe a statistically significant increase in the cases of
threatened preterm labor with increasing maternal age. However, other studies found
greater risk of threatened preterm labor, which resulted in increase rates of hospitalizations
and the need for specific tocolytic treatment [38].

4.10. Gestational Diabetes

The rate of gestational diabetes in our sample (7.4%) is similar to that previously
reported by other studies. The latest studies show rates ranging from 7 to 14%, with a
significant increase in recent years [40]. However, other studies suggest rates somewhat
higher than ours; for instance, it is estimated that 15% of pregnancies are affected by DG in
Australia [12].
In line with the rest of our study, we classified women according to age in order to
assess whether there is an association between increases in maternal age and the develop-
ment of GD. In this case, we found that there is also a correlation between maternal age
and GD, with increasing maternal age being a risk factor for GD.

4.11. Preterm Premature Rupture of the Membranes (PPROM)

Premature rupture of membranes occurs before the onset of labor, with subsequent
loss of amniotic fluid. Most cases of PROMs occur at term; preterm PROM is uncommon
and complicates 2–4% of all singleton pregnancies [41].
According to other authors, preterm premature rupture of membranes complicates
approximately 3% of pregnancies [11,42].
In a study based on late pregnancy outcomes associated with first trimester vaginal
bleeding (FTVB), compared to control group, the FTVB cases had more premature rupture
of membranes (OR = 10). The incidence of premature rupture of membranes was 3.6% in
the controls and 27.1% in the cases (RR = 10, p < 0.001) [43].
Medicina 2023, 59, 1370 20 of 23

The rate of preterm premature rupture of membranes in our sample was 5.26% and
accounted for 57.14% of all preterm deliveries. This rate is higher than that published in
the general population.
Within these PPROMs, we have four pre-viable preterm premature rupture of mem-
branes and one rupture near the limit of fetal viability, which represents 2.18% of all PPROM.
This value is much higher than that reported by other studies, less than 1% [11].
As important data in the follow-up of these patients, it should be noted that all of
them presented bleeding in the second trimester.
Therefore, closer monitoring of patients with FTVB and subsequent bleeding during
the second trimester would be recommended.
The incidence in our study is somewhat higher than the global incidence in PPROM
and much higher in pre-viable preterm premature rupture of membranes, finding similar
data, even higher, than other authors.

4.12. Late Abortion

The rate of late miscarriage in pregnancies that presented bleeding in the first trimester
was 1.2%. The rate of late abortions in gestations between the 13th and 19th weeks ranges
from 1 to 5%, and the rate drops to 0.3% between weeks 20 and 27 [23]. In our study, there
were seven late abortions between weeks 17 and 24. Therefore, the rate of miscarriage in
our sample is similar to that published by other authors.
Possible causes of pregnancy loss in the second trimester due to maternal pathology
include placental problems, thrombophilia, new onset of severe acute diseases, poorly
controlled chronic disorders (diabetes, hypertension, etc.), immunological factors (lupus,
antiphospholipid syndrome, etc.), infections, cervical insufficiency, and anatomical abnor-
malities [21].

4.13. Early Postpartum Haemorrhage

Regarding the data collected on early postpartum hemorrhage, only four women in
our study developed this complication (1.8%), only one of them was older than 35 years.
Therefore, we found no relationship between maternal age and increased frequency of
early postpartum hemorrhage. We found one study whose results were in agreement with
ours, and also failed to demonstrate an increase in early postpartum hemorrhage with
increasing maternal age [44]. However, most studies do find a clear rise in the incidence of
this complication with increasing maternal age [45–52].
In addition, many authors previously studied the relationship between increased
maternal age and poor perinatal outcomes [47], and found in their analysis a statistically
significant increase in the prevalence of GD, hypertensive disorders, induction of labor,
and cesarean sections in women over 35 years of age [53].
As has been well-established, advanced maternal age increases the risk of several
pregnancy-related complications. Consequently, we must emphasize the need to screen for
GD and maintain strict control of blood pressure levels in all pregnant women, especially
among the older ones.

5. Strengths and Limitations

Our study had several strengths. First, the sample of our study was constituted by all
the patients that visited the emergency department of our hospital throughout a year, and
their reasons for consultation were analyzed. Week 12 + 6 was established as the time limit
for vaginal bleeding to be considered as first-trimester metrorrhagia, which allows us to
establish clear inclusion and exclusion criteria.
Second, we have an acceptable sample size with a total of 696 pregnant women. Third,
we carried out of a comprehensive assessment of each patient, reviewing previous medical
and obstetric-gynecological history (abortions, uterine surgeries), current gestational data
(first trimester screening and analytical values, cervical length, history of obstetric compli-
Medicina 2023, 59, 1370 21 of 23

cations), and data regarding the delivery and the newborn (weeks of gestation, mode of
delivery, newborn weight, Apgar test value, birth weight, etc.).
However, this study also has some limitations. As a first limitation, this is a retro-
spective study, therefore the data we used were limited to the information included in the
digitized clinical history. Secondly, our study is solely based on visits to the emergency
department of Hospital QuironSalud Málaga, and therefore the follow-up of the gestation
and the subsequent analysis of obstetric history was performed in this same center. In
consequence, data regarding patients with prenatal care at different centers were missing.
We were able to retrieve some of the data lost by external monitoring from the collection of
medical histories from the Andalusian Health System.
Another limitation was the absence of a control group with which to compare the
results and assess the rate of complications among women who did not present with
vaginal bleeding during the first trimester. Due to the high prevalence of first-trimester
bleeding, and its potential implications for the pregnancy, it would be interesting to further
continue the study and perform it prospectively, allowing for the establishment and control
of potential risk factors that may lead to poor gestational outcomes.

6. Conclusions
In view of the results obtained in our study, which are in line with those previously
observed by others, among the complications studied, we can establish a positive correlation
between bleeding in the first trimester and two of them, miscarriage and pre-viable preterm
premature rupture of membranes. However, we cannot establish a positive correlation between
FTVB and the increased prevalence of various comorbidities and associated complications.
Although we found no association between the increase in gestational complications
in women who presented with bleeding in the first trimester, in our study, we did observe
a relationship between the appearance of complications with increasing maternal age. The
increased risk of gestational outcomes in women with advanced age highlights the need
for close follow-up, early detection, and management of medical complications.

Author Contributions: Conceptualization, L.B.C., D.A.D. and E.G.M.; methodology, L.B.C., D.A.D.
and E.G.M.; software, L.B.C.; validation, D.A.D. and E.G.M.; formal analysis, L.B.C.; investigation,
L.B.C. and D.A.D.; data curation, L.B.C.; writing—original draft preparation, L.B.C.; writing—review
and editing, L.B.C., D.A.D., E.G.M. and L.C.F.; visualization, L.B.C., D.A.D. and E.G.M.; supervision,
D.A.D. and E.G.M.; translation, L.C.F. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments: We would like to thank all the authors included in this original paper. This
research contributes to the doctoral work of L.B.C. We would like to thank all the participants in
the study.
Conflicts of Interest: The authors declare no conflict of interest.

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