I Guideline Information
Guidelines program
For information on the guidelines program, please refer to the end of the guideline.
Citation format
Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k
Level, AWMF Registry Number 015/025, February 2019) – Part 1 with Recommendations
on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm
Birth. Geburtsh Frauenheilk 2019; 79: 800–812
Guideline documents
The complete long version, a slide version of this guideline and a guideline report
on the methodological approach used, including the management of conflicts of interest,
are available in German on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-025.html
Guideline authors ([Table 1])
Table 1 The following medical societies/working groups/organizations/associations were interested
in participating in the compilation of the guideline text and in the consensus conference
and nominated representatives who attended the consensus conference.
|
Author
Mandate holder
|
DGGG working group (AG)/AWMF/
non-AWMF medical society/organization/association
|
|
Prof. Dr. Harald Abele
|
DGGG – Arbeitsgemeinschaft für Geburtshilfe und Pränatalmedizin (AGG) – Sektion Frühgeburt
|
|
Prof. Dr. Franz Bahlmann
|
Deutsche Gesellschaft für Ultraschall in der Medizin e. V. (DEGUM)
|
|
Dr. Ivonne Bedei
|
DGGG – Arbeitsgemeinschaft Kinder- und Jugendgynäkologie e. V. (AGKJ)
|
|
Prof. Dr. Richard Berger
|
Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG)
|
|
Dr. Klaus Doubek
|
Berufsverband der Frauenärzte e. V. (BVF)
|
|
Prof. Dr. Ursula Felderhoff-Müser
|
Gesellschaft für neonatale und pädiatrische Intensivmedizin (GNPI)
|
|
Prof. Dr. Herbert Fluhr
|
DGGG – Arbeitsgemeinschaft für Immunologie in Gynäkologie und Geburtshilfe (AGIM)
|
|
PD Dr. Dr. Yves Garnier
|
DGGG – Arbeitsgemeinschaft für Geburtshilfe und Pränatalmedizin (AGG) – Sektion Frühgeburt
|
|
Dr. Susanne Grylka-Baeschlin
|
Deutsche Gesellschaft für Hebammenwissenschaften (DGHWi)
|
|
Prof. Dr. Hanns Helmer
|
Österreichische Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG)
|
|
Prof. Dr. Egbert Herting
|
Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ)
|
|
Prof. Dr. Markus Hoopmann
|
DGGG – Arbeitsgemeinschaft für Ultraschalldiagnostik in Gynäkologie und Geburtshilfe
(ARGUS)
|
|
Prof. Dr. Irene Hösli
|
Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe (SGGG)
|
|
Prof. Dr. Dr. h. c. Udo Hoyme
|
DGGG – Arbeitsgemeinschaft für Infektionen und Infektionsimmunologie (AGII)
|
|
Alexandra Jendreizeck
|
Bundesverband “Das frühgeborene Kind” [Federal Association “The preterm Infant”]
|
|
Dr. Harald Krentel
|
DGGG – Arbeitsgemeinschaft für Frauengesundheit in der Entwicklungszusammenarbeit
(FIDE)
|
|
PD Dr. Ruben Kuon
|
Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG)
|
|
Dr. Wolf Lütje
|
DGGG – Deutsche Gesellschaft für psychosomatische Frauenheilkunde und Geburtshilfe
e. V. (DGPFG)
|
|
Silke Mader
|
European Foundation for the Care of the Newborn Infants (EFCNI)
|
|
PD Dr. Holger Maul
|
Deutsche Gesellschaft für Perinatale Medizin (DGPM)
|
|
Prof. Dr. Werner Mendling
|
DGGG – Arbeitsgemeinschaft für Infektionen und Infektionsimmunologie (AGII)
|
|
Barbara Mitschdörfer
|
Bundesverband “Das frühgeborene Kind” [Federal Association “The preterm Infant”]
|
|
Tatjana Nicin
|
Deutscher Hebammenverband (DHV)
|
|
Dr. Dirk Olbertz
|
Gesellschaft für neonatale und pädiatrische Intensivmedizin (GNPI)
|
|
Prof. Dr. Werner Rath
|
Deutsche Gesellschaft für Pränatal- und Geburtsmedizin (DGPGM)
|
|
Prof. Dr. Claudia Roll
|
Deutsche Gesellschaft für Perinatale Medizin (DGPM)
|
|
PD Dr. Dietmar Schlembach
|
DGGG – Arbeitsgemeinschaft für Geburtshilfe und Pränatalmedizin (AGG) – Sektion Präeklampsie
|
|
Prof. Dr. Ekkehard Schleußner
|
DGGG – Deutsche Gesellschaft für psychosomatische Frauenheilkunde und Geburtshilfe
e. V. (DGPFG)
|
|
Prof. Dr. Florian Schütz
|
DGGG – Arbeitsgemeinschaft für Immunologie in Gynäkologie und Geburtshilfe (AGIM)
|
|
Prof. Dr. Vanadin Seifert-Klauss
|
DGGG – Deutsche Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin
e. V. (DGGEF)
|
|
Susanne Steppat
|
Deutscher Hebammenverband (DHV)
|
|
Prof. Dr. Daniel Surbek
|
Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe (SGGG)
|
Abbreviations
AFP:
alpha-fetoprotein
AUC:
area under the curve
CI:
confidence interval
COX:
cyclooxygenase
CPAP:
continuous positive airway pressure
CRP:
C-reactive protein
CTG:
cardiotocography
fFN:
fetal fibronectin
FIRS:
fetal inflammatory response syndrome
GBS:
group B streptococcus
GW:
week of gestation
IGFBP-1:
insulin-like growth factor-binding protein-1
IL-6:
interleukin-6
NEC:
necrotizing enterocolitis
NICU:
neonatal intensive care unit
NNH:
number needed to harm
NNT:
number needed to treat
OR:
odds ratio
17-OHPC:
17α-hydroxyprogesterone caproate
PAMG-1:
placental alpha microgobulin-1
phIGFBP-1:
phosphorylated insulin-like growth factor-binding protein-1
PIVH:
peri-/intraventricular hemorrhage
PPROM:
preterm premature rupture of membranes
PVL:
periventricular leukomalacia
RDS:
respiratory distress syndrome
RR:
relative risk
s/p:
status post
TCO:
total cervical occlusion
TNF-α:
tumor necrosis factor alpha
Triple I:
intrauterine inflammation or infection or both
II Guideline Application
Purpose and objectives
The purpose of this guideline is to improve both the outpatient and the inpatient
care of patients at risk of imminent preterm birth in order to reduce the rate of
preterm births. If preterm birth cannot be prevented, the aim is to reduce perinatal
and neonatal morbidity and mortality. This should lead to improvements in the psychomotor
and cognitive development of children born preterm.
Targeted areas of patient care
Outpatient and/or inpatient care
Target user groups/target audience
The recommendations of the guideline are aimed at gynecologists in private practice,
gynecologists in hospitals, pediatricians in hospitals, midwives in private practice
and midwives in hospitals. Other target user groups include advocacy groups for affected
women and children, nursing staff (obstetrics/postnatal care, pediatric intensive
care), medical and scientific societies and professional associations, institutions
for quality assurance (e.g. IQTIG), healthcare policy institutions and decision-makers
at the federal and state level, funding agencies and payers.
Adoption and period of validity
The validity of this guideline was confirmed by the executive boards of the participating
medical societies, working groups, organizations and associations as well as by the
executive boards of the DGGG, the SGGG and the OEGGG and by the DGGG/OEGGG/SGGG guidelines
commission in February 2019 and was thus confirmed in its entirety. This guideline
is valid from 1 February 2019 through to 31 January 2022. Because of the contents
of this guideline, this period of validity is only an estimate. The guideline may
need to be updated earlier if urgently required. If the guideline continues to mirror
current knowledge, its period of validity may also be extended.
III Method
Basic principles
The method used to prepare this guideline was determined by the class to which this
guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective
rules and requirements for different classes of guidelines. Guidelines are differentiated
into lowest (S1), intermediate (S2) and highest (S3) class. The lowest class is defined
as a set of recommendations for action compiled by a non-representative group of experts.
In 2004, the S2 class was divided into two subclasses: a systematic evidence-based
subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class
combines both approaches. This guideline is classified as: S2k
Grading of recommendations
A grading of evidence and grading of recommendations is not envisaged for S2k-level
guidelines. The individual Statements and Recommendations are only differentiated
by syntax, not by symbols ([Table 2]).
Table 2 Grading of recommendations.
|
Level of recommendation
|
Syntax
|
|
Strong recommendation, highly binding
|
must/must not
|
|
Simple recommendation, moderately binding
|
should/should not
|
|
Open recommendation, not binding
|
may/may not
|
In addition to the level of evidence, the above listed classification of “Recommendations”
also takes account of the clinical relevance of the underlying studies and measures/factors
which were not included in the grading of evidence, such as the choice of patient
cohort, intention-to-treat or per-protocol outcome analyses, medical and ethical practice
in dealing with patients, country-specific applicability, etc.
Statements
Scientific statements given in this guideline which do not consist of any direct recommendations
for action but are simple statements of fact are referred to as “Statements”. It is
not possible to provide any information about the grading of evidence for these Statements.
Achieving consensus und strength of consensus
As part of the structured process to achieve consensus (S2k/S3 level), authorized
participants attending the session vote on draft Statements and Recommendations. This
can lead to significant changes in the wording, etc. Finally, the extent of consensus
is determined based on the number of participants ([Table 3]).
Table 3 Grading of strength of consenus.
|
Symbol
|
Strength of consensus
|
Extent of agreement in percent
|
|
+++
|
Strong consensus
|
> 95% of participants agree
|
|
++
|
Consensus
|
> 75 – 95% of participants agree
|
|
+
|
Majority agreement
|
> 50 – 75% of participants agree
|
|
–
|
No consensus
|
< 51% of participants agree
|
Expert consensus
As the name already implies, this term refers to consensus decisions taken with regard
to specific Recommendations/Statements made without a prior systematic search of the
literature (S2k) or for which evidence is lacking (S2e/S3). The term “expert consensus”
(EC) used here is synonymous with terms used in other guidelines such as “good clinical
practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation
is graded as previously described in the chapter “Grading of recommendations”, i.e.,
purely semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”)
without the use of symbols.
Addendum by the SGGG
To 1. Definition and epidemiology (and a number of other chapters: 6.9.1., 6.9.6.,
6.9.7., 8.8., 8.9.)
As regards care at the limits of viability, please refer to the Recommendations for
Switzerland which were developed together with neonatologists. Reasoning: The Recommendations for Switzerland diverge in many points from the Recommendations
for Germany. They are currently being revised [1].
To 3.2.3 Indications for measuring cervical length
In individual cases, an examination can also be carried out in asymptomatic women.
This is described in the chapter “Asymptomatic patients” below as follows: “Measurement
of cervical length using transvaginal sonography may be carried out in asymptomatic
pregnant women with no risk factors for spontaneous preterm birth.” Reasoning: Emphasizing this circumstance is important in Switzerland, because in many places
in Switzerland, transvaginal sonographic measurement is done as part of standard second
trimester screening.
IV Guideline
1 Definition
|
Consensus-based Statement 1.S1
|
|
Expert consensus
|
Strength of consensus +++
|
|
Preterm birth is defined as delivery prior to GW 37 + 0. It has a significant effect
on perinatal morbidity and mortality.
|
Preterm birth is defined as a birth which occurs before the end of the 37th week of
gestation. The consensus about what constitutes the limit of viability varies according
to country and culture. For Germany, please refer to the German-language guideline
“Frühgeborene an der Grenze der Lebensfähigkeit 024-019” [Preterm infants at the limits
of viability]. Preterm birth has a significant effect on perinatal morbidity and mortality.
Every year, approximately 965 000 preterm infants die worldwide in the neonatal period,
and a further 125 000 children die in the first 5 years of life from the effects of
preterm birth. Preterm birth is one of the main risk factors for disability-adjusted
life years (lost years due to illness, disability or early death) [2].
|
Consensus-based Statement 1.S2
|
|
Expert consensus
|
Strength of consensus +++
|
|
In 2017, the rate of preterm births in Germany was 8.36%. This means that Germany
ranks quite low compared to other European countries.
|
The preterm birth rate for infants born before 37 weeks is more than 8% and has remained
approximately the same in Germany since 2008 [3]. This means that Germany ranks quite low compared to other European countries [4]. The rate of preterm births occurring before the 37th week of gestation was 7.9%
in Austria in 2016 [5] and 7.0% in Switzerland in 2017 [6]. The highest rate of preterm births in Europe is reported for Cyprus where it stands
at 10.4%; the lowest rate of preterm births is in Iceland with a rate of 5.3% [4].
The reasons for these differences are ultimately still not clear. As already mentioned,
the lower limit of viability for extremely preterm infants is defined and recorded
very differently in different countries. It is possible that different standards of
medical care also play a role. In Portugal, for example, a structural reform carried
out in 1989 during which all departments with fewer than 1500 births were closed down
led to a significant decrease in the mortality of preterm infants. However, the rate
of preterm births increased in subsequent years. It cannot be excluded that the improvement
in healthcare led to the survival of more children, who were then recorded in the
register of preterm births and who would otherwise not have been recorded in that
way [4].
2 Etiology
|
Consensus-based Statement 2.S3
|
|
Expert consensus
|
Strength of consensus +++
|
|
Around two thirds of all preterm births occur due to premature labor with or without
premature rupture of membranes (spontaneous preterm births).
|
|
Consensus-based Statement 2.S4
|
|
Expert consensus
|
Strength of consensus +++
|
|
The etiology of preterm birth is multifactorial. Different pathophysiological mechanisms
activate a common pathway which manifests clinically as premature labor and cervical
dilation.
|
|
Consensus-based Statement 2.S5
|
|
Expert consensus
|
Strength of consensus +++
|
|
[7]
|
|
Preterm birth may be associated with bacterial inflammation, decidual bleeding, vascular
disease, decidual senescence, impaired maternofetal immune tolerance, “functional”
progesterone withdrawal or overstretching of the myometrium.
|
3 Prediction
3.1 Risk factors ([Table 4])
|
Consensus-based Recommendation 3.E1
|
|
Expert consensus
|
Strength of consensus +++
|
|
Potential risk factors must be determined prior to conception or at the start of prenatal
care at the latest. The particular focus must be on risk factors which can be controlled.
The intervals between examinations must be adjusted to take account of the individual
risk of preterm birth to implement preventive strategies.
|
Table 4 Risk factors for preterm birth.
|
Risk factor
|
OR
|
95% CI
|
|
[3], [8], [9], [10], [11], [12], [13]
|
|
s/p spontaneous preterm birth
|
3.6
|
3.2 – 4.0
|
|
s/p medically indicated preterm birth
|
1.6
|
1.3 – 2.1
|
|
s/p conization
|
1.7
|
1.24 – 2.35
|
|
Interval between pregnancies is < 12 months
|
4.2
|
3.0 – 6.0
|
|
Pregnant woman is younger < 18 years
|
1.7
|
1.02 – 3.08
|
|
Poor socioeconomic living conditions
|
1.75
|
1.65 – 1.86
|
|
Single mother
|
1.61
|
1.26 – 2.07
|
|
Bacterial vaginosis
|
1.4
|
1.1 – 1.8
|
|
Asymptomatic bacteriuria
|
1.5
|
1.2 – 1.9
|
|
Vaginal bleeding in early pregnancy
|
2.0
|
1.7 – 2.3
|
|
Vaginal bleeding in late pregnancy
|
5.9
|
5.1 – 6.9
|
|
Twin pregnancy
|
ca. 6
|
|
|
Smoking
|
1.7
|
1.3 – 2.2
|
|
Periodontitis
|
2.0
|
1.2 – 3.2
|
|
Anemia
|
1.5
|
1.1 – 2.2
|
3.2 Cervical length
3.2.1 Measurement technique
|
Consensus-based Recommendation 3.E2
|
|
Expert consensus
|
Strength of consensus +++
|
|
When using transvaginal sonography to measure cervical length to predict preterm birth,
the measurement technique must be precisely adhered to.
|
The approach used to standardize the measurement technique as far as possible has
been described previously in detail by Kagan and Sonek [14].
3.2.2 Normal and shortened uterine cervix
|
Consensus-based Statement 3.S6
|
|
Expert consensus
|
Strength of consensus +++
|
|
[15]
|
|
In singleton pregnancies, the median cervical length prior to the 22nd week of gestation
(GW) as measured by transvaginal sonography is > 40 mm; between GW 22 and 32 it is
40 mm, and after GW 32 it is approximately 35 mm.
|
|
Consensus-based Statement 3.S7
|
|
Expert consensus
|
Strength of consensus +++
|
|
[16]
|
|
A cervical length of ≤ 25 mm as measured by transvaginal sonography before GW 34 + 0
is considered to be shortened.
|
3.2.3 Indications for measuring cervical length
|
Consensus-based Recommendation 3.E3
|
|
Expert consensus
|
Strength of consensus +++
|
|
A general screening with transvaginal sonography to investigate for shortened cervical
length should not be carried out in asymptomatic pregnant women with no risk factors
for spontaneous preterm birth.
|
According to a single large cohort study, universal screening of singleton pregnancies
in women without a previous history of preterm birth is associated with a small but
significant decrease in the rates of preterm births before 37 weeks, before 34 weeks
and before 32 weeks (preterm birth < GW 37: 6.7 vs. 6.0%; adjusted odds ratio [AOR]
0.82 [95% CI: 0.76 – 0.88]; preterm birth < GW 34: 1.9 vs. 1.7%; AOR 0.74 [95% CI:
0.64 – 0.85]; preterm birth < GW 32: 1.1 vs. 1.0%; AOR 0.74 [95% CI: 0.62 – 0.90])
[17]. Whether this study will result in any changes to the Cochrane review done in 2013
which concluded that routine screening to determine cervical length in all (asymptomatic
and even symptomatic) pregnant women should not be recommended because knowledge of
the cervical length only resulted in a non-significant reduction in the rate of preterm
births before 37 weeks [18] remains to be seen, but it is highly unlikely. The fact is that there are no data
available which can confirm the impact of measuring cervical length on the parameters
considered in the perinatology literature to have a significant impact on perinatal
mortality. At all events, insofar as there were any data available, the Cochrane review
of 2013 was unable to find any differences with respect to the parameters ‘perinatal
mortality’, ‘preterm birth before the 34th or 28th week of gestation’, ‘birth weight
< 2500 g’, ‘maternal hospitalization’, ‘tocolytics’, ‘antenatal steroid administration’
[18].
|
Consensus-based Recommendation 3.E4
|
|
Expert consensus
|
Strength of consensus +++
|
|
Measurement of cervical length using transvaginal sonography should be included in
the therapeutic concept of symptomatic pregnant women (regular spontaneous premature
contractions) and/or in pregnant women with risk factors for spontaneous preterm birth.
|
|
Consensus-based Statement 3.S8
|
|
Expert consensus
|
Strength of consensus ++
|
|
[19], [20], [21], [22], [23]
|
|
The benefit of carrying out serial measurements of cervical length using transvaginal
sonography has not been sufficiently proven for either asymptomatic or symptomatic
pregnant women.
|
Asymptomatic patients
|
Consensus-based Recommendation 3.E5
|
|
Expert consensus
|
Strength of consensus ++
|
|
Measurement of cervical length using transvaginal sonography may be carried out in
asymptomatic pregnant women with no risk factors for spontaneous preterm birth.
|
|
Consensus-based Recommendation 3.E6
|
|
Expert consensus
|
Strength of consensus ++
|
|
[24], [25]
|
|
Measurement of cervical length using transvaginal sonography should be carried out
from GW 16 in asymptomatic pregnant women with a singleton pregnancy and a prior history
of spontaneous preterm birth.
|
|
Consensus-based Recommendation 3.E7
|
|
Expert consensus
|
Strength of consensus +++
|
|
[26], [27], [28], [29]
|
|
Measurement of cervical length using transvaginal sonography may be carried out from
GW 16 in asymptomatic pregnant women with a twin pregnancy.
|
Symptomatic patients
|
Consensus-based Recommendation 3.E8
|
|
Expert consensus
|
Strength of consensus +++
|
|
[30], [31], [32], [33]
|
|
Measurement of cervical length using transvaginal sonography must be carried out in
symptomatic women (contractions, start of cervical shortening or opening of the cervix
based on palpatory findings).
|
3.3 Biomarkers
|
Consensus-based Statement 3.S9
|
|
Expert consensus
|
Strength of consensus +++
|
|
[34]
|
|
None of the currently available biomarkers are suitable to predict the risk of preterm
birth in asymptomatic pregnant women with no cervical shortening as determined by
the measurement of cervical length using transvaginal ultrasonography.
|
|
Consensus-based Statement 3.S10
|
|
Expert consensus
|
Strength of consensus +++
|
|
* negative predictive value
[35], [36], [37], [38], [39], [40]
|
|
In addition to using vaginal sonography to measure cervical length, the negative predictive
value* of biomarkers obtained from cervico-vaginal secretions may be used in symptomatic
pregnant women with a cervical length of between 15 and 30 mm to evaluate the risk
of preterm birth occurring in the next 7 days.
|
|
Consensus-based Recommendation 3.E9
|
|
Expert consensus
|
Strength of consensus +++
|
|
[41]
|
|
Biomarkers should not be used to evaluate the risk of preterm birth in asymptomatic
pregnant women with risk factors for preterm birth.
|
|
Consensus-based Recommendation 3.E10
|
|
Expert consensus
|
Strength of consensus +++
|
|
[42]
|
|
Biomarkers must not be used to evaluate the risk of preterm birth in asymptomatic
pregnant women with no risk factors for preterm birth.
|
4 Primary Prevention
4.1 Progesterone
|
Consensus-based Recommendation 4.E11
|
|
Expert consensus
|
Strength of consensus ++
|
|
[43], [44], [45], [46], [47]
|
|
Progesterone may be administered to women with a singleton pregnancy and a history
of previous spontaneous preterm birth, starting in GW 16 + 0 and continuing up until
GW 36 + 0.
|
Dosage: 17-OHPC (17 α-hydroxyprogesterone caproate) with a weekly dose of 250 mg [43]. In the studies, progesterone was administered either orally (200 – 400 mg daily)
or vaginally (90 mg gel, 100 – 200 mg capsule daily) [44], [45], [48], [49], [50].
4.2 Cerclage/total cervical occlusion
|
Consensus-based Recommendation 4.E12
|
|
Expert consensus
|
Strength of consensus +++
|
|
Primary (prophylactic) cerclage may be considered for women with a singleton pregnancy
and a history of previous spontaneous preterm birth or late miscarriage(s). The procedure
should be carried out from early in the 2nd trimester of pregnancy.
|
There is no longer any doubt that secondary cerclage in women who are s/p preterm
birth and have a shortened cervical length of ≤ 25 mm before GW 24 + 0 is beneficial.
When counseling patients who are s/p preterm birth, patients often also ask whether
early placement of cerclage before the start of cervical shortening could be effective.
No disadvantages have been reported for this approach compared to secondary cerclage
in terms of either the prevalence of preterm birth or perinatal mortality [51]. However, a wait-and-see approach can reduce the number of surgical procedures by
58%.
|
Consensus-based Statement 4.S11
|
|
Expert consensus
|
Strength of consensus +++
|
|
There is some evidence that total cervical occlusion (TCO) may reduce the rate of
preterm births in women with a singleton pregnancy and a history of previous spontaneous
preterm birth or late miscarriage(s). The procedure should be carried out early in
the 2nd trimester of pregnancy.
|
An article published in 1996 discussed outcomes after TCO as reported by 11 German
hospitals [52]. These retrospective studies found a significant prolongation of pregnancy after
TCO for women who were s/p preterm birth. To date, there are no randomized, prospective
studies which confirm the benefit of TCO in women with cervical shortening and a cervical
length of less than 15 mm. The surgical technique used for TCO differs quite considerably
in the various international centers, making it difficult to compare outcomes.
4.3 Bacterial vaginosis
|
Consensus-based Statement 4.S12
|
|
Expert consensus
|
Strength of consensus +++
|
|
A vaginal flora with normal pH values and dominated by Lactobacillus species has a
protective effect on the course of pregnancy in terms of preterm birth or late miscarriage.
|
|
Consensus-based Recommendation 4.E13
|
|
Expert consensus
|
Strength of consensus +++
|
|
Pregnant women with symptomatic bacterial vaginosis should be treated with antibiotics
to deal with their symptoms.
|
|
Consensus-based Statement 4.S13
|
|
Expert consensus
|
Strength of consensus ++
|
|
A diagnostic workup (which includes investigation of surrogate parameters such as
vaginal pH values) to detect asymptomatic and symptomatic bacterial vaginosis followed
by treatment of bacterial vaginosis does not generally reduce the rate of preterm
births.
|
|
Consensus-based Statement 4.S14
|
|
Expert consensus
|
Strength of consensus +++
|
|
There is some evidence that the diagnosis and treatment of asymptomatic and symptomatic
bacterial vaginosis prior to GW 23 + 0 GW reduces the rate of preterm births which
occur before GW 37 + 0.
|
Numerous meta-analyses of case control and cohort studies have proven that there is
an association between infections of the genital tract and the occurrence of preterm
births [53], [54]. However, there is still no clear evidence that treatment of an infection, particularly
if it is still subclinical, reduces the preterm birth rate [53], [55]. To date, there is only a single study [56] in which pregnant women were screened by Gram stain for bacterial vaginosis at the
beginning of their 2nd trimester of pregnancy. The women were randomized into an intervention
group and a control group, with the test results either communicated to the womanʼs
clinician (in the intervention group) or not revealed. The women in the intervention
group were subsequently treated (with clindamycin if the test results revealed bacterial
vaginosis). In the intervention arm of the study, the preterm birth rate before 37
weeks was 3.0% compared to 5.3% in the control arm; the difference between the two
groups was thus significantly different. This study is currently the only one which
was included in the Cochrane review of this highly relevant topic, and its findings
therefore affect the outcome of the review. The revision of the review published in
2015 [57] states: “There is evidence from one trial that infection screening and treatment
programs for pregnant women before 20 weeksʼ gestation reduce preterm birth and preterm
low birthweight.”
The results of the PREMEVA trial were recently published [58]. More than 84 000 pregnant women were screened for bacterial vaginosis before the
end of their 14th week of gestation. Bacterial vaginosis, defined as a Nugent Score
of 7 – 10, was detected in 5360 pregnant women. Pregnant women with bacterial vaginosis
but a low risk of preterm birth were then randomized 2 : 1 into 3 groups as follows:
single course (n = 943) or three courses (n = 968) of 300 mg clindamycin administered
2 × daily for 4 days or placebo (n = 958). Women with a high risk of preterm birth
were randomized separately 1 : 1 into 2 groups: single course (n = 122) or three courses
(n = 114) of 300 mg clindamycin 2 × daily. The primary outcome was late miscarriage,
defined as occurring between the 16th and the 21st week of gestation, or very early
preterm birth, defined occurring as between the 22nd and the 32nd week of gestation.
In the group of 2869 pregnant women with a low risk of preterm birth, 22 women (1.2%)
in the clindamycin group and 10 women (1.0%) in the placebo group had a late miscarriage
or a very early preterm birth (RR 1.10, 95% CI: 0.53 – 2.32; p = 0.82). In the group
of 236 pregnant with a high risk of preterm birth, 5 women (4.4%) in the group treated
with 3 courses of clindamycin and 8 women (6.0%) in the group treated with one course
of clindamycin had a late miscarriage or a very early preterm birth (RR 0.67, 95%
CI: 0.23 – 2.00; p = 0.47). Side effects were noted significantly more often in the
group of pregnant women with a low risk of preterm birth in the clindamycin groups
compared to the placebo group (58/1904 [3.0%] compared to 12/956 [1.3%]; p = 0.0035).
The most common side effects were diarrhea and abdominal pain.
The authors concluded from their results that screening for bacterial vaginosis and
treatment with clindamycin, when required, does not reduce the risk of late miscarriage
or very early preterm birth in patients with a low risk of preterm birth.
4.4 Prevention programs
|
Consensus-based Statement 4.S15
|
|
Expert consensus
|
Strength of consensus +++
|
|
[59]
|
|
The efficacy of multimodal prevention programs and risk scoring systems has not been
sufficiently proven.
|
4.5 Cessation of smoking
|
Consensus-based Statement 4.S16
|
|
Expert consensus
|
Strength of consensus +++
|
|
[60], [61]
|
|
Stopping smoking reduces the preterm birth rate.
|
4.6 Asymptomatic bacteriuria
|
Consensus-based Statement 4.S17
|
|
Expert consensus
|
Strength of consensus +++
|
|
Asymptomatic bacteriuria is a significant risk factor for preterm birth. Because of
the lack of data, screening for the sole purpose of reducing the preterm birth rate
is not currently recommended.
|
|
Consensus-based Recommendation 4.E14
|
|
Expert consensus
|
Strength of consensus +++
|
|
Because of the lack of data, it is not possible to issue a recommendation that antibiotic
treatment of asymptomatic bacteriuria reduces the rate of preterm births.
|
In its final report on screening for asymptomatic bacteriuria published in 2015, the
IQWIG came to the following conclusion [62]: The patient-relevant medical benefit or harm of screening for asymptomatic bacteriuria
in pregnant women is not clear due to a lack of studies. There is no evidence that
antibiotic treatment of pregnant women for asymptomatic bacteriuria has any patient-relevant
medical benefit or harm, as the existing data is unsuitable with regard to the current
standard of care for pregnant women.
4.7 Supplementation with omega-3 polyunsaturated fatty acids
|
Consensus-based Statement 4.S18
|
|
Expert consensus
|
Strength of consensus +++
|
|
The data from studies on reducing preterm birth rates through dietary supplementation
with omega-3 polyunsaturated fatty acids (omega-3 PUFA) is inconsistent. Supplementation
with omega-3 PUFA may be considered for women with a history of spontaneous preterm
birth.
|
A Cochrane Review carried out in 2006 showed that pregnant women whose diet included
higher levels of marine oil had a mean gestation that was 2.6 days longer compared
to pregnant women without marine oil supplementation and women given placebo, and
that women with marine oil supplementation had a significantly lower risk of preterm
birth before 34 + 0 weeks of gestation (RR 0.69, 95% CI: 0.49 – 0.99) [63]. These findings were confirmed in a recently published update [64].
5 Secondary Prevention
5.1 Progesterone
|
Consensus-based Recommendation 5.E15
|
|
Expert consensus
|
Strength of consensus +++
|
|
Women with a singleton pregnancy and a sonographically measured cervical length before
24 + 0 weeks of ≤ 25 mm must be treated with daily intravaginal administration of
progesterone up until 36 + 6 weeks of gestation (200 mg capsule/day or 90 mg gel/day).
|
An individual patient data meta-analysis (IPDMA) carried out in 2018, which included
data from the OPPTIMUM trial [44], found that intravaginal administration of progesterone resulted in a significant
reduction in the rate of preterm births and improved neonatal outcomes for pregnant
women with asymptomatic cervical shortening (≤ 25 mm) before 24 + 0 weeks of gestation
[65].
5.2 Cerclage
|
Consensus-based Recommendation 5.E16
|
|
Expert consensus
|
Strength of consensus +++
|
|
Women with a singleton pregnancy following a previous spontaneous preterm birth or
late miscarriage and whose sonographically measured cervical length before 24 + 0
weeks of gestation is ≤ 25 mm, should be treated with cerclage.
|
A meta-analysis of the 5 prospective randomized studies on this topic showed that
the preterm birth rate of patients who had had a previous preterm birth and had an
incompetent cervix measuring less than 25 mm before 24 weeks of gestation was significantly
reduced by the placement of a cerclage. Moreover – and this is particularly clinically
relevant – placement of the cerclage also significantly reduced perinatal mortality
and morbidity [66].
5.3 Cervical pessary
|
Consensus-based Recommendation 5.E17
|
|
Expert consensus
|
Strength of consensus ++
|
|
Women with a singleton pregnancy whose sonographically measured cervical length before
24 + 0 weeks of gestation is ≤ 25 mm may benefit from placement of a cervical pessary.
|
A number of prospective randomized studies have been carried out to evaluate the benefit
of cervical pessary placement in women with singleton pregnancies whose cervical length
before 24 + 0 weeks of gestation was less than 25 mm as measured by transvaginal sonography.
The results of these prospective studies have differed considerably. Some studies
reported a significant reduction in the rate of preterm births following placement
of a cervical pessary [67], [68], [69], other studies did not [70], [71], [72], [73]. Cervical pessary placement is a procedure with an extremely low rate of complications.
Increased vaginal discharge following the procedure is quite common, but this has
no pathological significance. In view of the above, placement of a cervical pessary
may be considered in individual cases for women with singleton pregnancies whose cervical
length before 24 + 0 weeks of gestation is ≤ 25 mm.
5.4 Workload and physical activity
|
Consensus-based Statement 5.S19
|
|
Expert consensus
|
Strength of consensus +++
|
|
[74]
|
|
Prolonged working hours, shift work, standing every day for more than 6 hours, heavy
lifting and heavy physical labor done by working pregnant women are associated with
little, if any, significant adverse effects on preterm birth. Employers must evaluate
the individual risk for the pregnant woman according to the respective situation and
must consider whether the activities she carries out as part of her workload constitute
an unjustifiable risk. An additional individual medical consultation which takes account
of other risk factors and obstetric complications would be useful.
|
|
Consensus-based Statement 5.S20
|
|
Expert consensus
|
Strength of consensus +++
|
|
The data on whether pregnant women at risk for preterm birth and pregnant women not
at risk for preterm birth should avoid strenuous physical activities at home is insufficient
to draw reliable conclusions.
|
