Keywords
preterm birth - prematurity - preterm labor - tocolysis - neonatal outcomes - maternal
outcomes
Palavras-chave
parto prematuro - prematuridade - trabalho de parto prematuro - tocólise - desfechos
neonatais - desfechos maternos
Introduction
Despite recognized advances in obstetrical care in the last decades, preterm birth
(PTB), defined as delivery before 37 weeks, continues to be one of the most significant
burdens worldwide, with increasing numbers in most high and middle-income countries,
including Brazil.[1]
[2]
[3] Preterm newborns represented ∼ 10% of live births in Brazil in the last decade.[4] The impact of prematurity is relevant not only for neonatal health but also for
infant health, with major long-term consequences, such as neurologic handicap, deafness,
blindness and chronic respiratory disease.[5] Furthermore, prematurity is the main cause of neonatal deaths.[6] Around 75% of PTBs follow spontaneous prematurity (preterm labor [PTL] and preterm
premature rupture of membranes), while the remaining 25% are provider-initiated PTBs
due to fetal or maternal complications.[7]
[8]
The pathogenesis of spontaneous PTBs is most likely multifactorial, which makes it
very difficult to prevent or predict this condition. The main identified causes are
related to intrauterine infection, bleeding and uterine overdistension, among others.[3]
Tocolysis is an available resource in the care of these women, aiming to prolong pregnancies.[9] The use of tocolytic medications is not clearly associated with a reduction in perinatal
or neonatal mortality; however, the potential benefits are related to inhibition of
uterine contractions, allowing the administration of antenatal glucocorticoids.[10] The antenatal corticosteroid administration is shown to reduce the risk of fetal
complications related to prematurity, such as respiratory distress syndrome, intraventricular
hemorrhage, and necrotizing enterocolitis. Another relevant goal of tocolysis is to
allow the maternal transfer, in a timely manner, to a center with neonatal intensive
care unit.[9]
[11]
Tocolytic drugs should be considered only in the absence of contraindications, such
as non-reassuring fetal status, severe fetal growth restriction, intra-amniotic infection,
lethal fetal anomalies, and complicated maternal comorbidity. There are many groups
of tocolytic drugs, and the decision as to which agent should be used for an individual
woman should be based on multiple factors, including gestational age, medical conditions,
cost, personal experience, and commercial availability.[12]
Calcium channel blockers (CCB), such as nifedipine, cause the inhibition of calcium
reuptake by myometrial cell, leading to smooth muscle relaxation. Nifedipine is usually
well tolerated and the main described mild side effects are nausea, flushing, headache,
and palpitations. However rare, more severe side effects can also present, such as
pulmonary edema, atrial fibrillation, and hypotension. The fetal side effects are
related to maternal hypotension and placental hypoperfusion. A significant reduction
in neonatal morbidity is shown with CCB use in comparison with other tocolytic drugs.[13]
Betamimetics (terbutaline) are β-adrenergic agonists that stimulate the enzyme adenyl
cyclase in the smooth muscle cell. By doing so, they decrease the availability of
intracellular calcium and suppress myometrial contractility. The most common maternal
side effects are tachycardia, pulmonary edema, and hyperglycemia. For that reason,
the woman should be constantly monitored. Furthermore, this class of medication is
contraindicated in women with poorly controlled baseline diseases, such as diabetes
or heart disease, and it should be discontinued if maternal heart rate reaches over
120 beats/minute or if the woman experiences chest pain or dyspnea. Terbutaline can
cause fetal side effects, especially hypoglycemia and tachycardia. The use of betamimetics
presented no benefits in comparison with placebo in cases of respiratory distress
syndrome as well as in cases that resulted in perinatal or neonatal deaths.[14]
Prostaglandin inhibitors, such as indomethacin, constrain the cyclooxygenase enzyme,
which synthesizes prostaglandins from arachidonic acid. The most common side effects
are nausea, vomiting, gastritis, and platelet dysfunction. Indomethacin is contraindicated
over 32 weeks of gestation because of the risk of premature closure of ductus arteriosus
and oligohydramnios. No clear benefits were shown over placebo or any other tocolytics;
however, a 2012 systematic review concluded that prostaglandin inhibitors and CCB
had the highest probability of delaying delivery and improving neonatal and maternal
outcomes.[9]
[15]
Oxytocin receptor antagonists (ORA), represented by atosiban, act on the uterine myometrial
cell and can cause fewer side effects (like nausea, vomiting, and headache) than treatment
with the CCB or betamimetics. Oxytocin receptor antagonists did not demonstrate superiority
as a tocolytic compared with placebo, betamimetics or CCB for pregnancy prolongation
or neonatal outcomes.[16] Currently, this medication is not easily available in public hospitals in Brazil
due to its high cost.
Magnesium sulfate reduces calcium in the intracellular and extracellular levels, which
decreases myometrial contractility. The administration should be monitored regularly
due to the risk of lethargy, nausea, hyporeflexia and respiratory depression. A Cochrane
systematic review (2002)[17] concluded that magnesium sulfate is ineffective at delaying birth and its use is
associated with an increased mortality for the infant.
The long-term use of tocolysis has not shown effectiveness; therefore, tocolytics
should not be continued once uterine contractions have been suppressed.[13] The benefit of using associations of tocolytics are also not clear in the literature.[18]
Given the scarce data on the actual clinical practice on tocolysis in our setting,
and the great variances among available protocols, this study aims to evaluate women
with PTB due to PTL in 20 institutions of different regions of Brazil, regarding the
prevalence of tocolytic drugs used, factors associated with this use, the most prescribed
drugs, and the maternal and perinatal outcomes, according to the drug and gestational
age considered.
Methods
This is a cross-sectional multicenter study called Brazilian Multicenter Study on
Preterm Birth (Estudo Multicêntrico de Investigação de Prematuridade [EMIP, in the Portuguese acronym]), which assessed PTB in 20 obstetric reference
hospitals in three regions of Brazil from April 2011 to July 2012. The research protocol
and main results have already been published previously elsewhere.[7]
[19]
For the current analysis, we focused on cases of PTB (gestational age at birth up
to 36 + 6 weeks) due to PTL only. Among those, we analyzed the frequency of tocolysis
and split all cases into two groups: women who underwent tocolysis, and those in which
tocolysis was not performed (expectant group). Specific analyses were performed also
considering only births before 34 weeks. Afterwards, a bivariate analysis was conducted
to estimate the odds ratios (ORs) with their respective 95% confidence intervals (CIs)
for perinatal results. Finally, a comparison of maternal complications and neonatal
outcomes between the two most prevalent classes of tocolytics, CCB and betamimetics,
was considered. For statistical analysis, the Statistical Analysis System (SAS) for
Windows version 9.4 (SAS Institute, Cary, NC, USA) was used. The Mann-Whitney test
was performed to compare the numeric variables, and the Chi-square and Fisher Exact
tests were used to evaluate the categorical variables.
This study followed all ethical principles of the Helsinki Declaration. It abides
by the guidelines and rules of the Resolution 196/96 of the National Health Council
on research involving human beings, current at the time of data collection. The study
was approved by the National Council for Ethics in Research and by the Institutional
Review Board of each participating institution. An Informed Consent Form was developed,
and each subject was enrolled in the study only after the understanding and accepting
the conditions on the form. Confidentiality of the data and medical care of these
women were assured.
Results
From April 2011 to July 2012, 1,491 women with PTBs due to PTL were enrolled. Tocolysis
was performed in 342 women, 23% of all PTBs. Out of these, 233 (68.1%) delivered before
34 weeks, and 109 (31.9%) delivered between 34 and 36 + 6 weeks. Among women with
expectant management, the majority was late preterm (73%), as shown in [Fig. 1].
Fig. 1 Flowchart of subjects and gestational age at birth in the Brazilian Multicenter Study
on Preterm Birth (EMIP, in the Portuguese acronym). Abbreviation: GA, gestational
age.
[Tables 1] and [2] present the sociodemographic characteristics, obstetric history and characteristics
of the current pregnancy in the studied population. Among the women who underwent
tocolysis, there were significantly more nulliparous, more cases with a history of
vaginal bleeding during pregnancy, cervical insufficiency, women without comorbidities,
the integrity of membrane at admission, more cases of antenatal corticosteroids prescribed
and more maternal complications. They were: 23 cases of genital hemorrhage (1.6%),
57 chorioamnionitis (3.9%), only one maternal sepsis (0.1%), 6 cases of treatment
interruption due to adverse effects, only 1 cardiac decompensation (0.1%), 14 oligoamnios
(1.0%), 34 other complications (2.3%) and 10 associations of answers (0.6%). The majority
of cases related no maternal complications (1,292 or 88.3%).
Table 1
Comparison of sociodemographic characteristics, obstetric history, and current pregnancy
conditions between women who were treated with tocolytic drugs and women who were
treated expectantly (Chi-square test) (n = 1,449)
|
Condition
|
Tocolysis
|
Expectant
|
p Value
|
|
n (%)
|
n (%)
|
|
Maternal Age
|
|
≤ 19
|
114 (33.3)
|
313 (28.2)
|
|
|
20–34
|
203 (59.3)
|
689 (62.2)
|
0.1354
|
|
≥ 35
|
25 (7.3)
|
105 (9.4)
|
|
|
Skin Color
|
|
White
|
150 (43.8)
|
483 (43.6)
|
0.9407
|
|
Other
|
192 (56.1)
|
624 (56.3)
|
|
|
Schooling (years)a
|
|
≤ 8
|
150 (44.3)
|
478 (43.8)
|
|
|
09–12
|
171 (50.5)
|
546 (50.0)
|
0.7804
|
|
≥ 13
|
17 (5.0)
|
66 (6.0)
|
|
|
Parity
|
|
Nulliparous
|
167 (48.8)
|
438 (39.5)
|
|
|
1–2 deliveries
|
116 (33.9)
|
431 (38.9)
|
0.0090
|
|
≥ 3 deliveries
|
59 (17.2)
|
238 (21.5)
|
|
|
Previous cesarean sectionb
|
|
Yes
|
54 (15.8)
|
191 (17.2)
|
0.5414
|
|
Previous preterm birthc
|
|
Yes
|
18 (5.2)
|
69 (6.3)
|
0.4966
|
|
Previous preterm labord
|
|
Yes
|
39 (11.4)
|
113 (10.2)
|
0.5164
|
|
Previous pPROMe
|
|
Yes
|
23 (6.7)
|
98 (8.8)
|
0.2126
|
|
Previous cerclagef
|
|
Yes
|
9 (2.6)
|
14 (1.2)
|
0.0750
|
|
Prenatal careg
|
|
Yes
|
319 (93.8)
|
1053 (95.2)
|
0.3110
|
|
Use of alcoholh
|
|
Yes
|
42 (12.3)
|
183 (16.6)
|
0.0556
|
|
Smoking
|
|
Yes
|
45 (13.1)
|
192 (17.3)
|
0.0673
|
|
Antenatal substance abuse
|
|
Yes or before pregnancy
|
19 (5.5)
|
73 (6.5)
|
0.4911
|
|
No
|
323 (94.4)
|
1034 (93.4)
|
|
|
Vulvovaginitisi
|
|
Yes
|
65 (32.5)
|
194 (29.6)
|
0.4376
|
|
Urinary tract infectionj
|
|
Yes
|
86 (33.4)
|
313 (36.6)
|
0.3440
|
|
Vaginal bleeding during pregnancyk
|
|
Yes
|
119 (35.0)
|
282 (25.5)
|
0.0007
|
|
Anemial
|
|
Yes
|
96 (29.0)
|
314 (29.0)
|
0.9878
|
|
Cervical insufficiency (clinical or US) m
|
|
Yes
|
12 (11.0)
|
20 (4.2)
|
0.0059
|
|
Cerclagen
|
|
Yes
|
10 (3.1)
|
19 (1.9)
|
0.1708
|
|
Maternal comorbidity
|
|
Yes
|
79 (23.1)
|
336 (30.3)
|
0.0095
|
|
Membrane integrityo
|
|
Yes
|
320 (94.9)
|
853 (81.1)
|
< 0.0001
|
|
Antenatal corticosteroidsp
|
|
Yes
|
274 (80.8)
|
138 (12.6)
|
< 0.0001
|
|
Maternal Complicationq
|
|
Yes
|
67 (19.7)
|
94 (8.6)
|
< 0.0001
|
Abbreviations: pPROM, pre-labor premature rupture of membranes; US, ultrasonography;
Note: Missing information for – a: 21; b: 1; c: 14; d: 5; e: 5; f: 3; g: 3; h: 7;
i: 594; j: 39; K: 5; l: 38; m: 874; n: 163; o: 61; p: 19; q: 19.
Table 2
Characteristics at admission and perinatal outcomes comparing women who were treated
with tocolytic drugs and women who were treated expectantly (n = 1,449)
|
Variables
|
Tocolysis
n (%)
|
Expectant
n (%)
|
p Value
|
|
Adequacy of number of prenatal care visitsa
|
< 0.0001
|
|
Adequate (≥ 6)
|
101 (35.5)
|
507 (52.7)
|
|
|
Inadequate (< 6)
|
183 (64.4)
|
455 (47.3)
|
|
|
Number of contractions in 10-minute at admissionb
|
0.0006
|
|
< 3
|
132 (57.3)
|
288 (44.3)
|
|
|
≥ 3
|
98 (42.6)
|
362 (55.6)
|
|
|
Cervical dilatation ≥ 5 cm in the current hospitalizationc
|
< 0.0001
|
|
Yes (≥ 5)
|
116 (35.6)
|
606 (58.6)
|
|
|
Cervical effacement ≥ 50% in the current hospitalizationd
|
0.9174
|
|
Yes (≥ 50%)
|
187 (87.7)
|
526 (87.5)
|
|
|
Birthweight
|
< 0.0001
|
|
≤ 1,500 g
|
120 (35.2)
|
161 (14.6)
|
|
|
1,501 to 2,500 g
|
181 (53.2)
|
535 (48.5)
|
|
|
> 2,500 g
|
39 (11.4)
|
406 (36.8)
|
|
|
Gestational age at birth (weeks)
|
< 0.0001
|
|
< 32
|
151 (44.1)
|
171 (15.4)
|
|
|
32–33
|
82 (23.9)
|
124 (11.2)
|
|
|
34–36
|
109 (31.8)
|
812 (73.3)
|
|
Missing information for: a: 203; b: 569; c: 91; d: 635.
The cases of expectant management were clearly of more advanced labor at admission
(significantly more contractions in 10 minutes and increased cervical dilation); the
mean dilation at admission for expectant management was overall 5.3 cm and 6.5 cm
under 34 weeks of gestation. Furthermore, cases submitted to tocolysis were more preterm
(mean gestational age at birth of ∼ 31 weeks versus 33 weeks for expectant management)
and more likely to have neonatal intensive care unit (NICU) admission ([Table 2]).
The most used class of tocolytic drug was the CCB (62.3%), followed by betamimetics
(33%) and prostaglandin inhibitors (1.5%) ([Fig. 2]). There was a therapeutic failure in 11.3% of the attempted inhibitions, leading
to change in the medication. Again, we considered only cases that progressed to PTB.
Fig. 2 The proportion of different tocolytic drugs used in the Brazilian Multicenter Study
on Preterm Birth (EMIP, in the Portuguese acronym) among spontaneous preterm birth
submitted to tocolysis.
[Table 3] compares betamimetics and CCB concerning neonatal and maternal outcomes. The Cesarean
section rate as well as the need for newborn admission to NICU were significantly
higher in women who used betamimetics compared with those who used CCB.
Table 3
Acute tocolysis: betamimetics compared with calcium channel blockers (n = 342)
|
Variables
|
Betamimetics
n (%)
|
Calcium channel blockers
n (%)
|
p Value
|
|
Categorical Variables*
|
|
Therapeutic failurea
|
17 (15.4)
|
21 (10.1)
|
0.1611
|
|
Antenatal corticosteroidsb
|
85 (75.2)
|
177 (83.8)
|
0.0588
|
|
Maternal complicationsc
|
21 (18.5)
|
43 (20.3)
|
0.6989
|
|
Neonatal morbidityd
|
86 (78.1)
|
179 (86.4)
|
0.0577
|
|
Delivery Variables
e**
|
|
Vaginal
|
73 (66.9)
|
161 (78.5)
|
|
|
Forceps
|
1 (0.9)
|
3 (1.4)
|
0.0493
|
|
C-section
|
35 (32.1)
|
41 (20.0)
|
|
|
(mean SD)
|
|
|
Duration of use in hoursf***
|
18.94 (20.1)
|
28.38 (28.3)
|
0.0533
|
|
Gestational age at birth in weeksg***
|
31.25 (3.5)
|
31.17 (3.4)
|
0.7252
|
|
Newborn birthweight (g)h***
|
1741.0 (651.6)
|
1753.4 (661.4)
|
0.6995
|
|
Neonatal intensive care unit (days)i***
|
21.04 (24.9)
|
14.99 (20.9)
|
0.0264
|
Abbreviation: SD, standard deviation.
Notes: Categorical variables: *Chi square test; **Fisher exact test; numeric variables;
***Mann-Whitney test. Missing information for: a- 24; b- 18; c- 18; d- 25; e- 28;
f: 40; g: 16; h: 18; i: 45.
Considering the clinically most relevant group for tocolysis, cases under 34 weeks
of gestational age and comparing those submitted to tocolysis to those with expectant
management, again it is clear that the cases of expectant management had more advanced
labor at admission (significantly more contractions, cervical dilation, and effacement)
([Table 4]).
Table 4
Comparison of characteristics at admission and birth outcomes in spontaneous preterm
birth < 34 weeks between women who were treated with tocolytic drugs and women who
were treated expectantly (Chi-square test) (n = 528)
|
Variables
|
Tocolysis
n (%)
|
Expectant
n (%)
|
p Value
|
|
Vaginal bleeding in the current hospitalizationa
|
0.8340
|
|
Yes
|
51 (23.2)
|
61 (24.1)
|
|
|
Contractions in 10 minutes (< 3)b
|
0.0106
|
|
Yes
|
97 (62.1)
|
73 (47.7)
|
|
|
Cervical dilatation ≥ 5 cm in the current hospitalizationc
|
< 0.0001
|
|
Yes
|
87 (39.5)
|
203 (74.0)
|
|
|
Cervical effacement ≥ 50% in the current hospitalizationd
|
0.0334
|
|
Yes
|
127 (87.5)
|
141 (94.6)
|
|
|
Birth weighte
|
0.9717
|
|
≤ 1,500 g
|
120 (51.7)
|
147 (50.6)
|
|
|
1,501 to 2,500 g
|
104 (44.8)
|
133 (45.8)
|
|
|
> 2,500 g
|
8 (3.4)
|
10 (3.4)
|
|
|
Gestational age at birth (weeks)
|
0.1096
|
|
< 32
|
151 (64.8)
|
171 (57.9)
|
|
|
32–33
|
82 (35.1)
|
124 (42.0)
|
|
Note: Missing information: a - 56; b - 219; c - 34; d - 234; e - 6.
On the multiple analysis, cases undergoing tocolysis presented 29 times more risk
of receiving corticosteroids, 18 times considering only cases under 34 weeks. The
rate of maternal complications was 55% higher for the cases under 34 weeks, in which
labor inhibition was attempted ([Tables 5] and [6]).
Table 5
Variables independently associated with tocolysis: multiple analyses by nonconditional
logistic regression
|
Variables
|
n
|
p Value
|
OR
|
CI 95%
|
|
Maternal complications
|
1,430
|
< 0.0001
|
2.613
|
1.85–3.67a
|
|
Neonatal morbidity
|
1,380
|
< 0.0001
|
2.742
|
2.01–3.72b
|
|
Neonatal respiratory distress
|
914
|
< 0.0001
|
2.567
|
1.73–3.79c
|
|
Newborn intubation
|
1,386
|
< 0.0001
|
2.372
|
1.77–3.17d
|
|
Necrotizing enterocolitis
|
897
|
0.0022
|
4.024
|
1.64–9.82e
|
|
Antenatal corticosteroids
|
1,430
|
< 0.0001
|
29.105
|
21.05–40.24f
|
Abbreviations: CI, confidence interval; OR, odds ratio.
Note: Missing information: a - 19; b - 69; c - 535; d - 63; e - 552; f - 19.
Table 6
Variables independently associated with tocolysis in women who delivered before 34
weeks: multiple analyses by nonconditional logistic regression
|
Variables
|
n
|
p Value
|
OR
|
CI 95%
|
|
Maternal complications
|
517
|
0.0487
|
1.551
|
1.003–2.40a
|
|
Neonatal morbidity
|
482
|
0.3690
|
1.364
|
0.69–2.68b
|
|
Neonatal respiratory distress
|
439
|
0.0753
|
1.810
|
0.94–3.48c
|
|
Newborn intubation
|
483
|
0.1624
|
1.295
|
0.90–1.86d
|
|
Necrotizing enterocolitis
|
424
|
0.1926
|
1.822
|
0.73–4.49e
|
|
Antenatal corticosteroids
|
520
|
< 0.0001
|
18.521
|
11.60–29.55f
|
Abbreviations: CI, confidence interval; OR, odds ratio.
Note: Missing information: a - 11; b - 46; c - 89; d - 45; e - 104; f - 8.
Discussion
Here we present the results of the EMIP for tocolysis in cases of PTB due to PTL.
Among the cases that delivered preterm (< 37 weeks), we studied and compared the tocolysis
and the expectant management groups. The main results show that tocolysis is favored
in cases of earlier labor at admission and also among those with less than 34 weeks
of gestation, using preferably CCB, with success in achieving increased corticosteroid
use, in spite of higher maternal and perinatal complication rates.
The use of antenatal corticosteroids and tocolysis have been previously analyzed in
the World Health Organization (WHO) Multicountry Survey on Maternal and Newborn Health,
with data from 29 different countries, including Brazil, with overall 6% of PTB and
among women who delivered at 26–34 weeks of gestation, 52% received antenatal corticosteroids.[20] In the WHO-multicountry study, the specific data on Brazil presented a low number
of subjects (288 women), with 30% coverage of corticosteroids in the considered gestational
age interval and 13% of tocolysis and antenatal corticosteroids (only 14 women). We
do not have a population-based study and need to highlight that most of the 20 considered
facilities in our study (EMIP) were tertiary care centers, which might explain the
difference in our findings, with overall 12% of preterm deliveries, 23.6% of tocolysis
among PTB due to PTL and 80% of combined corticosteroids and tocolysis. In the current
study, we only considered PTL; however, the analysis on the provider-initiated PTBs
on the same database has also shown over 70% use of corticosteroids between 28–31weeks
of gestation.[8]
Tocolysis is still a very controversial topic; Nonetheless, most clinical protocols
consider it plausible to attempt inhibition aiming the complete course of corticosteroids.[9] The use of antenatal corticosteroids, though, is key in improving the outcomes in
preterm babies with 31% reduction in neonatal deaths and a significant reduction in
morbidity as well, including a recently published additional benefit in late preterm
with a reduction in the rate of neonatal respiratory complications.[11] In the current study, it was estimated that women who underwent tocolysis had 29
times more chance of receiving corticosteroids than the ones who did not and the chances
were 18 times higher among those under 34 weeks.
In the EMIP, the mean dilation at admission for expectant management was 5.3 cm and
6.5 cm under 34 weeks of gestation. Cervical dilation over 5 cm at diagnosis of PTL
has been shown to progress to delivery in less than 24 hours in 50% of cases, and
the chance of delivery before 24 hours increases to 89% when dilation is over 6 cm
at diagnosis, according to a 2009 study.[21] Again, we have to emphasize that our study only considered cases that progressed
to PTB, which justifies the findings on dilation and effacement at admission.
As pointed previously, it is very difficult to predict PTBs; however, known risk factors
and early recognition of the signs and symptoms of PTL should always be considered.[3] We did find that among the tocolysis group, there were significantly more cases
with a history of bleeding during gestation and with cervical insufficiency, which
shows that risk factors were assessed.
An important finding in our study was that tocolytic drugs, in general, were related
to higher neonatal complication rates. We cannot ascertain causality, and this might
be a consequence of the difference in baseline gestational age at admission and not
necessarily due to tocolysis. The cases submitted to tocolysis were more preterm (mean
gestational age at birth of ∼ 31 weeks versus 33 weeks in the expectant management
group) and therefore more likely to have NICU admission. Unfortunately, we do not
have specific data on latency from the time of the initiated use of tocolytic drugs
to delivery, but we do have the information on the time of use of medications and,
in average, for all considered drugs, it was less than 30 hours (∼ 19 hours for betamimetics
and 28 hours for CCB). Given the strong association between tocolysis and corticosteroid
use, another factor to be considered for the presented worse neonatal outcomes is
the lack of optimal time for corticosteroids action in many cases. The best effect
of antenatal corticosteroids is seen after 48 hours of the initiation of treatment.[22]
Tocolytic drugs, in general, were also related to higher maternal complications rates.
It is noteworthy that detailed clinical assessment, and an infection screening at
admission and during all the in-hospital period is paramount to early diagnose possible
infection and other complications. The increase in complications must be addressed
in future studies considering all cases of tocolysis and not only those that progressed
to PTB.
The most used drug in our study was CCB (mainly Nifedipine), currently considered
first-line therapy in many countries due to how simple it is to administer, to the
low rate of severe side effects and low cost. According to the last Cochrane Systematic
review, CCB is better than betamimetics in terms of increased prolongation of pregnancy,
decreased maternal side effects and neonatal outcomes.[23] In our sample, there was a significant difference between these drugs, with increased
NICU stay and increased cesarean rates among users of betamimetics. Although known
to be less safe than CCB, the prescription rate of betamimetics was high, including
one third of the sample.
Since many important institutions worldwide have protocols that consider the restricted
or no use of tocolysis, the results of this study can also be considered as an alert
and incentive to review regional protocols and raise awareness toward the careful
use of tocolysis.[24]
[25]
[26]
Brazil is in the tenth position among the countries with the highest absolute number
of PTBs, according to the report “Born too soon,” published by the World Health Organization
in 2013.[1] Therefore, EMIP was a study with great clinical and epidemiological relevance due
to the focus on prematurity and its risk factors and management in the most populated
areas of the country.[7]
Conclusion
The original study was not designed to evaluate the efficiency of tocolysis, and we
only have the outcomes of cases that did deliver preterm. However, our findings present
a very interesting picture of management on prematurity. The EMIP was an innovative
study that enabled a broad and detailed assessment of PTL in Brazil.
