Keywords
preterm birth - tocolysis - survey - clinical practice - guideline recommendations
Schlüsselwörter
Frühgeburt - Tokolyse - Erhebung - klinische Praxis - Leitlinienempfehlungen
Abbreviations
ACOG:
American College of Obstetricians and Gynecologists
ACS:
antenatal corticosteroids
AWMF:
Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften
COX:
Cyclooxygenase
fFN:
fetal fibronectin
IGFBP-1:
insulin-like growth factor-binding protein-1
NICE:
National Institute for Health and Care Excellence
NO:
nitric oxide
OC:
obstetric clinic
PAMG-1:
placental alpha microglobulin-1
PNC:
perinatal care center
PPROM:
preterm premature rupture of membranes
PTB:
preterm birth
RCOG:
Royal College of Obstetricians and Gynaecologists
RCT:
randomized controlled trial
SOP:
standard operating procedure
Introduction
Preterm birth (PTB) accounting for five to 12% of deliveries in Europe is one of the
major causes of neonatal morbidity and mortality [1]. Its etiology is multifactorial [2]. In 2022, the rate of preterm birth in Austria was 7.2%, 1.9% of live births were
PTBs before 34 weeks of gestation [3]. Spontaneous onset of labor, preterm premature rupture of membranes (PPROM) or medically
indicated PTBs due to maternal or fetal conditions are the main contributors [4]. Gestational age is strongly associated with neonatal mortality and morbidity, in
particular, with higher rates of respiratory distress syndrome (RDS), necrotizing
enterocolitis (NEC), intraventricular hemorrhage (IVH) or neurologic
morbidities occurring especially in extreme PTBs [5].
Tocolysis is a mainstay in the prevention of PTB and recommended by all international
guidelines to prolong pregnancy by at least 48 hours to complete a full course of
antenatal corticosteroids (ACS) and to ensure in utero transfer of the pregnant woman
to a perinatal center (PNC) before 34 weeks of gestation [6]. According to meta-analyses prolongation of pregnancy can be achieved with the use
of tocolytics by 48 hours in approximately 80% of cases [7]
[8]
[9]. Tocolysis after PPROM remains a matter of debate [10]. Maintenance tocolysis, mostly defined as continuation of tocolytic treatment beyond
48 hours, is not recommended
by international guidelines due to the lack of evidence that it improves neonatal
outcomes [7]
[8]
[9].
This can be explained by a considerable heterogeneity among studies including study
design, inclusion and exclusion criteria, use of different tocolytics and doses as
well as different outcome parameters [6]. However, maintenance tocolysis is commonly used in clinical practice for numerous
reasons, hence maintenance tocolysis still remains a controversial issue.
Despite the availability of international and national guidelines, our and other groups
have covered low adherence of obstetricians in different countries to evidence-based
recommendations [11]
[12]
[13]
[14]
[15]. The aim of our cross-sectional study was to evaluate current clinical practice
in Austrian obstetric units of higher and lower perinatal care levels and to compare
the results with actual guideline recommendations.
Materials and Methods
All 78 obstetric departments in Austria were invited to participate in a nationwide
survey. Since 2017, the obstetric units are categorized to four perinatal care levels
according to specified standards of the Austrian Structural Plan for Health (Österreichischer
Strukturplan Gesundheit OESG): PNC level I or II, obstetric clinic (OC) level I with
≥ 500 and OC level II with < 500 deliveries annually. The head of each unit received
a link to a web-based questionnaire via email containing information on the purpose
of the study. The questionnaire was developed according to international guidelines.
The questionnaire was created based on the German survey conducted by our study group
[16] and was pre-tested by three experts and modified to warrant comprehensibility and
feasibility. Each participant was only allowed to complete the questionnaire once
during an 88-days study period (June 5th –
August 31st 2023). Reminders with an interval of four weeks were sent twice. The questionnaire
consisted of 20 multiple choice and open-ended questions addressing the following
items: baseline characteristics (3 questions), indications for tocolysis (2 questions),
timing of tocolysis and ACS (3 questions), choice of tocolytics (3 questions), serious
side effects (1 question), maintenance tocolysis (4 questions), tocolysis in PPROM
(1 question), monitoring of tocolysis (1 question), guidance for decision-making (1
question) and recommendations at patient’s discharge from the hospital (1 question).
The study was conducted anonymously without financial compensation. Only one participant
per department was accepted. No personal data were collected. Only complete questionnaires
were included into final statistical analysis.
Statistical analysis
Data was descriptively analyzed by performing measures of frequency. Fisher’s exact
test was used for group comparison. P < 0.05 was considered statistically significant.
Results
Baseline characteristics of responding obstetric units
78 Austrian obstetric departments were invited to take part in the survey, 54 clinics
completed the questionnaire, accounting for a response rate of 69.2%. Ten clinics
started the survey without completion. One third of responding clinics were PNC level
I or II (33.3%), two thirds were OC level I or II (66.7%). The characteristics of
responding clinics and interviewed personnel are shown in [Table 1].
Table 1
Characteristics of responding clinics.
|
|
n
|
%
|
|
Level of obstetric clinic (n = 54)
|
|
|
|
Perinatal center (PNC) Level I
|
9
|
16.7
|
|
Perinatal center (PNC) Level II
|
9
|
16.7
|
|
Obstetric clinic (OC) I (≥ 500 deliveries/year)
|
26
|
48.1
|
|
Obstetric clinic (OC) II (< 500 deliveries/year)
|
10
|
18.5
|
|
Annual delivery rate
|
|
|
|
< 1000
|
29
|
53.7
|
|
1000–2000
|
17
|
31.5
|
|
2001–3000
|
4
|
7.4
|
|
> 3000
|
4
|
7.4
|
|
Clinical position of interviewed person
|
|
|
|
Head of clinic
|
35
|
64.8
|
|
Leading senior physician
|
9
|
16.7
|
|
Senior physician
|
5
|
9.3
|
|
Attending physician
|
4
|
7.4
|
|
Resident physician
|
1
|
1.9
|
Indications for tocolysis
Indications for tocolysis were ≥ 4 contractions within 20 minutes (n = 26, 48.1%),
shortening of cervical length ≤ 25 millimeters (n = 14, 25.9%), a positive biomarker
test (n = 9, 16.7%) or subjective contractions (n = 5, 9.3%) ([Table 2]).
Table 2
Which is your most important clinical parameter for indicating tocolysis (single choice)?
|
|
PNC Level I–II (n = 18)
|
OC I–II (n = 36)
|
Total (n = 54)
|
p-value
|
|
|
n
|
%
|
n
|
%
|
n
|
%
|
|
|
fFN = fetal fibronectin; IGFBP-1 = insulin-like growth factor-binding protein-1; OC
= obstetric clinic; PAMG-1 = placental alpha microglobulin-1; PNC = perinatal care
center
|
|
Cervical length ≤ 25 mm
|
5
|
27.8
|
9
|
25.0
|
14
|
25.9
|
1.00
|
|
≥ 4 contractions within 20 min
|
6
|
33.3
|
20
|
55.6
|
26
|
48.1
|
0.16
|
|
Preterm birth/late miscarriage in patient’s history
|
0
|
0.0
|
0
|
0.0
|
0
|
0.0
|
1.00
|
|
Positive biomarker testing (PAMG-1, fFN, IGFBP-1)
|
5
|
27.8
|
4
|
11.1
|
9
|
16.7
|
0.14
|
|
Subjective contractions
|
2
|
11.1
|
3
|
8.3
|
5
|
9.3
|
1.00
|
Decision-making support
The AWMF Guideline “Prevention and Therapy of Preterm Birth” 015‑025 was the most
important decision-making support regarding tocolytic treatment (n = 33, 61.1%), followed
by hospital specific standard operating procedures (SOPs)/algorithms (n = 15, 27.8%).
Further details are shown in [Table 3].
Table 3
On which guidance do you base your decision for tocolysis (single choice)?
|
|
PNC Level I–II (n = 18)
|
OC I–II (n = 36)
|
Total (n = 54)
|
p-value
|
|
|
n
|
%
|
n
|
%
|
n
|
%
|
|
|
ACOG = American College of Obstetricians and Gynecologists; AWMF = Arbeitsgemeinschaft
der Wissenschaftlichen Medizinischen Fachgesellschaften; NICE = National Institute
for Health and Care Excellence; OC = obstetric clinic; PNC = perinatal care center;
RCOG = Royal College of Obstetricians and Gynaecologists; SOP = standard operating
procedure
|
|
Clinical intern SOP/algorithm
|
6
|
33.3
|
9
|
25.0
|
15
|
27.8
|
0.54
|
|
National guidelines (AWMF 015‑025)
|
10
|
55.6
|
23
|
63.9
|
33
|
61.1
|
0.57
|
|
Personal experience
|
1
|
5.6
|
2
|
5.6
|
3
|
5.6
|
1.00
|
|
Professional experience of supervising/more experienced colleagues
|
0
|
0.0
|
1
|
2.8
|
1
|
1.9
|
1.00
|
|
International guidelines (e.g. ACOG, RCOG, NICE)
|
1
|
5.6
|
1
|
2.8
|
2
|
3.7
|
1.00
|
Timing of tocolysis and ACS
Most of obstetric units (n = 19, 35.2% – PNC: 38.9%, OC: 33.3%) started tocolysis
earliest at gestational week 23 + 0, 29.6% (n = 16 – PNC: 38.9%, OC: 25.0%) at 22 + 0
gestational weeks, 22.2% (n = 12 – PNC: 16.7%, OC: 25.0%) at 23 + 5 gestational weeks
and 13.0% (n = 7 – PNC: 5.6%, OC: 16.7%) at 24 + 0 gestational weeks. There were no
significant differences between PNCs und OCs.
66.7% of obstetric units (n = 36 – PNC: 77.8%, OC: 61.1%) stopped tocolysis at 34 + 0
gestational weeks, 11.1% (n = 6 – PNC: 5.6%, OC: 13.9%) at 35 + 0 gestational weeks,
16.7% (n = 9 – PNC: 11.1%, OC: 19.4%) at 36 + 0 gestational weeks and even 5.6% (n = 3
– PNC: 5.6%, OC: 5.6%) at 37 + 0 weeks of gestation. There were no significant differences
between PNCs und OCs.
38.9% (n = 21 – PNC: 50.0%, OC: 33.3%) performed administration of ACS concomitantly
with tocolysis beginning at 23 + 0 weeks of gestation, 16.7% (n = 9 – PNC: 11.1%,
OC: 19.4%) at 23 + 5 gestational weeks, 14.8% (n = 8 – PNC: 16.7%, OC: 13.8%) at 22 + 0
gestational weeks, 13.0% (n = 7 – PNC: 0%, OC: 19.4%) at 24 + 0 weeks and 16.7% (n = 9
– PNC: 22.2%, OC: 13.8%) of obstetric units stated to confer with a nearby PNC before
initiating ACS. There was again no significant difference between PNCs and OCs.
Choice of tocolytics
The first line tocolytic was stated to be atosiban in 79.6% (n = 43) of the respondents,
followed by oral nifedipine in 13.0% (n = 7), and intravenous hexoprenaline as bolus
in 5.6% (n = 3) or as continuous administration in 1.9% (n = 1). Most common criteria
for the choice of a specific tocolytic agent were efficiency (n = 47, 87.0%), low
maternal side effects (n = 45, 83.3%), recommendations from guidelines (n = 41, 75.9%)
and approval (n = 34, 63.0%). There were no statistically significant differences
between PNCs and OCs, as shown in [Table 4].
Table 4
What is the first line tocolytic at your clinic (single choice)? Please state your
most important criteria for the choice of the tocolytic drug (multiple choice)!
|
|
PNC Level I–II (n = 18)
|
OC I–II (n = 36)
|
Total (n = 54)
|
p-value
|
|
|
n
|
%
|
n
|
%
|
n
|
%
|
|
|
OC = obstetric clinic; PNC = perinatal care center
|
|
First line tocolytic
|
|
|
|
|
|
|
|
|
Hexoprenaline continuously
|
0
|
0.0
|
1
|
2.8
|
1
|
1.9
|
1.00
|
|
Nifedipine
|
2
|
11.1
|
5
|
13.9
|
7
|
13.0
|
1.00
|
|
Atosiban
|
16
|
88.9
|
27
|
75.0
|
43
|
79.6
|
0.30
|
|
Hexoprenaline bolus
|
0
|
0.0
|
3
|
8.3
|
3
|
5.6
|
0.54
|
|
Indomethacin
|
0
|
0.0
|
0
|
0.0
|
0
|
0.0
|
1.00
|
|
Most important criteria
|
|
|
|
|
|
|
|
|
Approval
|
14
|
77.8
|
20
|
55.6
|
34
|
63.0
|
0.14
|
|
Efficiency
|
17
|
94.4
|
30
|
83.3
|
47
|
87.0
|
0.40
|
|
Low maternal side effects
|
16
|
88.9
|
29
|
80.6
|
45
|
83.3
|
0.70
|
|
Low fetal side effects
|
9
|
50.0
|
19
|
52.8
|
28
|
51.9
|
1.00
|
|
Practicability
|
4
|
22.2
|
13
|
36.1
|
17
|
31.5
|
0.36
|
|
Drug costs
|
1
|
5.6
|
4
|
11.1
|
5
|
9.3
|
0.65
|
|
Guideline recommendation
|
13
|
72.2
|
28
|
77.8
|
41
|
75.9
|
0.74
|
Maintenance tocolysis
49 of 54 obstetric units (90.7%) stated to perform maintenance tocolysis (16 PNCs,
33 OCs), among these 93.9% (n = 46) on special indications such as placenta previa,
fetal congenital anomalies to prolong pregnancy for further interventions or amniotic
sac prolapse; 46.9% (n = 23) conducted maintenance tocolysis in threatened preterm
birth < 29 + 0 weeks of gestation. There were no significant differences between PNCs
and OCs regarding the use of maintenance tocolysis ([Table 5]). 55.1% (n = 27) of obstetric units conducting maintenance tocolysis reported to
use atosiban, 22.4% (n = 11) oral nifedipine, 16.3% (n = 8) hexoprenaline and 6.1%
(n = 3) intravenous magnesium sulfate. Atosiban was significantly more often used
in PNCs than in OCs (81.3% vs. 42.4%; p = 0.01) and betamimetics significantly more
often in OCs than in PNCs (24.2% vs. 0.0%; p = 0.04). Bedrest during maintenance tocolysis
was recommended by
68.5% of obstetric units.
Table 5
Do you regularly perform maintenance tocolysis beyond 48 hours, and if yes for which
reason(s) (multiple choice)?
|
|
PNC Level I–II (n = 18)
|
OC I–II (n = 36)
|
Total (n = 54)
|
p-value
|
|
|
n
|
%
|
n
|
%
|
n
|
%
|
|
|
OC = obstetric clinic; PNC = perinatal care center
|
|
No
|
2
|
11.1
|
3
|
8.3
|
5
|
9.3
|
|
|
Yes
|
16
|
88.9
|
33
|
91.7
|
49
|
90.7
|
1.00
|
|
On patient’s request
|
2
|
12.5
|
1
|
3.0
|
3
|
6.1
|
0.25
|
|
On special indications (e.g. placenta previa, amniotic sac prolapse)
|
15
|
93.8
|
31
|
93.9
|
46
|
93.9
|
1.00
|
|
In early weeks of gestation (< 29 + 0)
|
8
|
50.0
|
15
|
45.5
|
23
|
46.9
|
1.00
|
|
Only in case-by-case decisions
|
5
|
31.3
|
5
|
15.2
|
10
|
20.4
|
0.26
|
Tocolysis in PPROM
52 of 54 clinics performed tocolysis in cases of PPROM, among these 34 (65.4% – PNC:
50%, OC: 73.5%) only for 48 hours to complete a full course of ACS, and 28.8% (n = 15
– PNC: 38.9%, OC: 23.5%) conducted tocolysis in patients with PPROM in a case-by-case
decision (e.g. in association with preterm labor and/or pregnancy < 29 + 0 weeks of
gestation). Three clinics (5.8% – PNC: 11.1%, OC: 2.9%) stated to generally perform
tocolysis longer than 48 hours in patients with PPROM. Regarding this issue there
were no statistically significant differences between levels of care.
Monitoring of tocolysis
Repeated transvaginal sonography of cervical length measurement was the most frequent
method to monitor tocolytic efficacy (n = 47, 87.0% – PNC: 88.9%, OC: 86.1%), followed
by tocography (n = 46, 85.2% – PNC: 77.8%, OC: 88.9%), and 37 (68.5% – PNC: 72.2%,
OC: 66.7%) of the respondents stated to ask the patients for subjective contractions.
Serious side effects of tocolytics
77.8% of the respondents (PNC: 22.2%, OC: 22.2%) reported to have experienced serious
side effects, mostly associated with the use of hexoprenaline (cardiac arrhythmia,
severe hypokalemia, pulmonary edema). Severe hypotension and/or significant tachycardia
were observed with the use of nifedipine by 5 (9.3% – PNC: 5.6%, OC: 11.1%) of the
respondents including one case of pulmonary edema. Minor side effects as headache
and dizziness, particularly, if the initial bolus was administered rapidly, were stated
to be associated with the use of atosiban (n = 17, 31.5% – PNC: 27.8%, OC: 33.3%).
Recommendations at patient’s discharge from the hospital
These recommendations are listed in [Table 6]. Activity restriction (n = 47, 87.0%), close surveillance by the patient’s health
care provider (n = 40, 74.1%) and daily administration of progesterone (n = 36, 66.7%)
were the most frequent recommendations at patient’s discharge from the hospital.
Table 6
What are your most important recommendations after tocolysis when patients are discharged
from hospital (multiple choice)?
|
|
PNC Level I–II (n = 18)
|
OC I–II (n = 36)
|
Total (n = 54)
|
p-value
|
|
|
n
|
%
|
n
|
%
|
n
|
%
|
|
|
OC = obstetric clinic; PNC = perinatal care center
|
|
Bedrest
|
2
|
11.1
|
3
|
8.3
|
5
|
9.3
|
1.00
|
|
Progesterone (oral or vaginal)
|
14
|
77.8
|
22
|
61.1
|
36
|
66.7
|
0.36
|
|
Close follow-ups at patient’s health provider
|
12
|
66.7
|
28
|
77.8
|
40
|
74.1
|
0.51
|
|
Close follow-ups in your clinic
|
10
|
55.6
|
9
|
25.0
|
19
|
35.2
|
0.04
|
|
Sick leave/employment prohibition
|
13
|
72.2
|
22
|
61.1
|
35
|
64.8
|
0.55
|
|
Oral tocolysis (e.g. nifedipine)
|
2
|
11.1
|
4
|
11.1
|
6
|
11.1
|
1.00
|
|
Activity restriction
|
15
|
83.3
|
32
|
88.9
|
47
|
87.0
|
0.67
|
Discussion
Tocolytic treatment is one of the most common procedures in obstetrics. Despite the
widespread availability of evidence-based recommendations there are considerable discrepancies
between these recommendations and clinical practice. This has been shown by numerous
surveys from different countries [11]
[13]
[14]
[15] and also by a recent German-wide survey [12]
[16] which was conducted one year after implementation of the AWMF Guideline 015‑025
“Prevention and Treatment of Preterm Birth” [7].
Indications for tocolysis vary among different international guidelines. While the
AWMF Guideline 015‑025 recommends spontaneous, regular contractions (≥ 4 within 20
minutes) in association with cervical shortening/dilatation as the leading criterion
[7], only 48.1% of the Austrian obstetric units were in accordance with this guideline
recommendation, which was similar to the 42.5% in the German survey [12]. In addition to that, cervical shortening without contractions should not be a reason
for tocolysis, but is stated to be the main indication for 25.9% of clinics. Also,
repeated transvaginal ultrasound is not recommended to monitor the tocolytic efficacy,
but is performed by 87% of units. In this context it has to be considered that 61.1%
of respondents stated to use the AWMF Guideline 015‑025 for decision-making, which
was in line
with the German survey. Interestingly, even 11.1% of PNCs state that subjective contractions
are their main indication for tocolysis. The beginning of tocolysis was in accordance
to guideline recommendations; 33.3% of the obstetric units continued tocolysis up
to 37 weeks of gestation, contrasting to the national and other guideline recommendations.
Calcium channel blockers as nifedipine are the preferred tocolytic agent in Germany
(49.1% of obstetric units) as well as in other countries [13]
[15] and recommended as first-line tocolytic drug by numerous guidelines [17]
[18]
[19]
[20], however, nifedipine was stated to be the first-line tocolytic drug by only 13.0%
of the Austrian obstetric units, while 79.6% stated atosiban to be the tocolytic of
choice.
Atosiban and nifedipine have shown to be equally effective in prolonging pregnancy
by 48 hours and no significant differences between both were found regarding perinatal
and neonatal outcomes as well as long-term infant morbidity [21]
[22]
[23]
[24]
[25]. The advantage of atosiban over nifedipine is the lower rate of maternal side effects
[23], the disadvantages are the higher purchase price and the necessity of intravenous
administration associated with immobilization thus lowering patient’s acceptance compared
to orally given nifedipine [6]. In accordance with guideline recommendations none of the obstetric units stated
to use orally applied magnesium for tocolysis [7]
[17]
[18]
[19]
[26]. Efficacy, low maternal side effects and guideline recommendation were the most
important criteria for the choice of the tocolytic agent.
Since there is insufficient evidence from qualified RCTs that maintenance tocolysis
reduces neonatal morbidity and mortality, current guidelines consistently do not recommend
maintenance tocolysis [27]
[28]. Surprisingly, 90.7% of obstetric units stated to perform maintenance tocolysis,
the majority of them only on special indications.
Independently, if maintenance tocolysis is taken into consideration, the question
which tocolytic drug may be suitable is unsolved. Briefly, due to the loss of efficacy
through tachyphylaxis and the high rate of maternal side effects betamimetics should
be omitted for maintenance tocolysis [27]. According to a meta-analysis the use of oral nifedipine beyond 48 hours compared
to placebo/no treatment has shown to be not associated with a significant prolongation
of pregnancy and a significant reduction of neonatal morbidity [29]. Cyclooxygenase (COX) inhibitors such as indomethacin should only be given for 48
hours until 32 weeks of gestation and nitric oxide (NO) donators have never been investigated
for maintenance tocolysis in randomized controlled trials (RCTs) [27]. Data on the use of atosiban for maintenance tocolysis are limited to only one RCT
in 2000 [30]. Although the interval from start of therapy to the first recurrence of labor was
prolonged, there was no difference in neonatal outcome and preterm birth rates in
this study. Also, it has to be mentioned that Atosiban was given subcutaneously, whereas
in Austria it is routinely administered intravenously. Atosiban is only approved for
tocolysis up to 48 hours. With respect to several meta-analyses [31] the use of vaginal/oral progesterone for maintenance tocolysis has shown not to
be associated with a significant prolongation of pregnancy and a significant reduction
of neonatal morbidity in “high quality studies”. Hence, progesterone is not recommended
for maintenance tocolysis by the AWMF Guideline 015‑025 [7]. 93.9% of respondents answered to perform maintenance tocolysis in patients with
symptomatic placenta previa and amniotic sac prolapse, and 46.9% in threatened preterm
birth < 29 weeks of gestation. At this point it has to be mentioned that 93.9% of
OCs stated to perform tocolysis in these cases, which would be well advised to transfer
patients with threatened preterm birth to a clinic with a higher perinatal care level.
According to two meta-analyses [32]
[33] and one RCT [34], there is no sufficient evidence that maintenance tocolysis leads to prolongation
of pregnancy and improves perinatal outcomes in women with symptomatic placenta previa.
However, in two of the analyses there is no
information about gestational age at study entry [32]
[33]. There is no RCT evaluating maintenance tocolysis in women with amniotic sac prolapse.
Finally, two meta-analyses came to the conclusion that there is no evidence for the
effectiveness of tocolytic treatment in women with threatened extremely preterm birth
[35]
[36]. Hence, maintenance tocolysis in these patients may be a case-by-case decision.
In women with PPROM the use of tocolytic agents is still a matter of debate; 96.3%
of the Austrian obstetric units stated to perform tocolysis in patients with PPROM,
among these 65.4% to complete a full course of ACS. Similar results were shown in
the German survey [16]. However, several guidelines [7]
[17]
[20] do not recommend tocolysis in patients with PPROM based on a meta-analysis in 2014
[37] and two prospective cohort studies [10]
[38]. The AWMF Guideline 015‑025 stated that
tocolysis in women with PPROM may only be an option to complete a full course of ACS
in terms of a case-by-case decision (expert opinion) [7]. In our survey we did not collect any information about the upper gestational age
limit for tocolysis in PPROM.
Betamimetics are the tocolytics with the highest rate of maternal and fetal side effects
[6]. Hence, it was not surprising that 48.1% of respondents had observed cardiac arrhythmia
and 33.3% pulmonary edema related to the use of hexoprenaline. In the German survey
70% of respondents reported on severe side effects in association with the use of
fenoterol.
Severe hypotension, significant tachycardia and pulmonary edema are dose-dependent
side effects of nifedipine and were reported in a range of 0.9% to 1.9% [39]
[40]. These severe side effects had been observed by 9.3% of the respondents which was
similar to the results of the German survey [12]. According to a recent meta-analysis, atosiban is the tocolytic agent with the lowest
rate of maternal and fetal side effects [41], minor side effects such as headache or dizziness may occur, especially if the intravenous
bolus is administered undiluted and rapidly [6].
There exist no evidence-based recommendations regarding measures after tocolysis at
patient’s discharge from the hospital. As in the German survey close surveillance
by the patient’s health care provider, followed by the daily administration of progesterone
were the most important recommendations made by the obstetric units. However, there
is no sufficient evidence that tocolysis with progesterone leads to prolongation of
pregnancy [7]. Bedrest should be omitted, since it is associated with an increased risk of venous
thromboembolism, loss of muscle mass and body weight as well as psychological sequelae
such as depression and anxiety [42]
[43]
[44]. Nevertheless, 68.5% of clinics stated to
recommend bedrest during maintenance tocolysis.
Conclusion
Our survey agrees with others from Germany and different countries demonstrating considerable
discrepancies between guideline recommendations and daily clinical practice. In this
context, it should be considered that only a minority of guideline recommendations
are based on high levels of evidence due to the lack of sufficient data from RCTs.
Nevertheless, if obstetricians decide not to adhere to national guideline recommendations,
they are at least well advised to obtain written informed consent.
It is mandatory to improve obstetrician’s low adherence to guidelines, e.g. by early
access, improved dissemination, key messages with presentation of evidence levels,
decision trees to improve applicability of the messages and regular external audits
of PNCs. However, in some special cases one will have to choose an individual approach.
Regular national surveys are also mandatory to reveal faults in obstetrician’s adherence
to national guidelines and to develop novel approaches in this issue for improving
maternal health care.
Funding
This research did not receive any specific grant from funding agencies in the public,
commercial, or not-for-profit sectors.
Availability of Data and Materials
Availability of Data and Materials
The datasets used and/or analyzed during the current study are available from the
corresponding author on reasonable request.
