Escolar Documentos
Profissional Documentos
Cultura Documentos
Kwabena Appiah-Sakyi
Justin C Konje
Abstract
Preterm labour complicates 3e4% of all pregnancies and its causes are
multifactorial. The incidence is rising and it is more common in the
economically deprived populations and communities in the rich countries.
The recurrence rate is doubled after one previous preterm delivery. Secondary preventive measures have not been shown to be as effective as
primary measures. A concerted multidisciplinary effort to eliminate risk
factors for inducing preterm labour such as early marriage, smoking,
short inter-pregnancy intervals, domestic violence and under nutrition
will significantly reduce the incidence while optimisation of medical disorders pre-pregnancy and during pregnancy will result in a reduced
incidence.
Keywords cervical length; enhanced antenatal care; oncofetal fibronectin; premature rupture of fetal membranes; preterm birth; preterm
labour; progesterone; tocolysis; ultrasound
Introduction
Preterm labour (PTL) is defined by the World Health Organisation (WHO) as the onset of labour after the gestational age of
viability and before 37 completed weeks or 257 days of pregnancy. It is clinically confirmed by demonstrable uterine contractions associated with documented cervical changes.
Threatened preterm labour is diagnosed when there are documented uterine contractions without cervical changes.
Every year about 15 million babies are born prematurely and
preterm birth (PTB) remains the biggest cause of neonatal death.
It is also one of the commonest causes of under- 5 deaths. About
50% of preterm births follow spontaneous onset of labour, 30%
after premature rupture of fetal membranes and the remaining
20%, iatrogenic due to maternal and fetal medical indications.
There is evidence that the preterm birth rate is increasing in all
countries where there are reliable data. In the UK, the rate is
about 7.9%.
Key reasons for the rise in the number of preterm deliveries
include a rise in multiple pregnancies from reproductive techniques, widespread obesity with its associated comorbidities of
hypertension and diabetes and an increased incidence of sexually
transmitted infections. Whilst an improved understanding of
some of the underlying mechanisms and advances in technologies have culminated in the introduction of new tools for both the
255
REVIEW
Decidual
bleeding
Uterine
distension
Infection
Figure 1
Infections such as bacteria vaginosis (BV), human immunodeficiency virus (HIV), syphilis, periodontal disease, subclinical
chorioamnionitis and UTI have been associated with PTB. Noninfectious causes such as vaginal bleeding, abnormal uterine
distention and pathological weakness and dilatation of the cervix
may all trigger PTL by stimulating the release of pro-inflammatory
markers.
Primary prevention
Primary prevention of PTB involves the provision of interventions before and between pregnancies which enhance the
mothers health and reduce risks of her or the baby succumbing
to preventable adverse pregnancy conditions. In the past, this
aspect of womens health received less attention but awareness is
now growing. It comprises of interventions aimed at identifying
and improving the biochemical, behavioural and social risks of
womens health or pregnancy outcomes through prevention and
management. These interventions can be grouped under preconception care, enhanced antenatal care, reducing multiple
births and infections, optimizing the management of medical
disorders and progesterone prophylaxis.
256
REVIEW
(f) Progesterone
Progesterone is an essential steroid produced by the corpus
luteum for the maintenance of early pregnancy until 7e9 weeks
of gestation when the placenta takes over this function. The
administration of the anti -progesterone, mifepristone induces
abortion in early pregnancy. Though the relevance of progesterone in late pregnancy is poorly understood, it appears to help
maintain uterine quiescence by inhibiting myometrial contraction through the modulation of cytokine production and inhibiting the expression of contraction associated protein genes
within the myometrium.
The preventative effect of progesterone on PTB has been
extensively studied but some of the results have been discordant. While a meta-analyses in 2013 concluded that progesterone was protective against the recurrence of preterm births and
improved neonatal outcomes (i.e. reducing neonatal deaths,
necrotizing enterocolitis and respiratory distress syndrome
rates), the largest RCT did not demonstrate any benefit. The
most significant benefit of progesterone for PTBs is in women
with sonographically diagnosed short cervices. In a meta-analyses
of 775 patients with cervix <25 mm, treated with vaginal
progesterone of variable doses (90 mg, 100 mg, 200 mg), there
was a significant reduction in PTBs before 28, 33, and 35 weeks
relative to placebo (relative risk 0.50, 0.58, and 0.69,
respectively). In multiple pregnancies and those complicated by
preterm premature rupture of membranes, there is no evidence
that progesterone is effective in preventing preterm delivery.
Despite the evidence of potential benefits in selected cases,
there is no consensus on the appropriate dose, route of administration, gestation to initiate treatment and long-term effects on
infants.
Secondary prevention
Diagnostic modalities
The first step in patients presenting with possible PTL is an
appropriate diagnosis. Unfortunately the diagnosis that is often
made on the basis of clinical findings is unreliable. In two systematic reviews, only 13.3% of those who fulfilled the criteria of
257
REVIEW
258
REVIEW
(c) Antibiotics
A number of reviews and meta-analyses have concluded that
there is no benefit from the use of prophylactic antibiotics
regardless of antimicrobial agents or gestational age at initiation
in cases of PTL. The ORACLE II study confirmed that while there
is no benefit with antibiotic use in the presence of intact membranes, babies exposed to antenatal augmentin had an increased
risk of cerebral palsy. In a 7-year follow-up study, combination
antibiotics seemed only to increase this risk. While the cause of
this increased incidence of cerebral palsy is unclear, there is a
suggestion that subclinical chorioamnionitis may not be fully
eliminated by prophylactic antibiotics treatment, but rather
prolong intrauterine existence in a hostile environment and thus
increase the risk of cerebral infection especially with intact
membranes.
(d) Cervical cerclage
There are three types of clinical situations requiring cerclage
insertion and these include (i) history indicated cerclage e based
on maternal factors which increase the risk of PTL, (ii) ultrasound indicated cerclage e based on ultrasound demonstration
of a short cervix and (iii) rescue/emergency cerclage e as a
salvage measure in case of premature cervical dilatation with
exposure of fetal membranes.
The large Medical Research Council trial in 1993, together
with two other randomised trials demonstrated that cerclage only
showed real benefit when performed in women with 3 previous
preterm deliveries. For women with 2 or fewer previous preterm
deliveries, cervical cerclage offered no significant benefit with 25
cerclages needed to prevent one delivery before 33 weeks. The
typical presentation associated with cervical weakness (i.e.
painless cervical dilatation, rupture of membranes before the
onset of contraction, or a history of cervical surgery are all risk
factors) has been found to be unhelpful in deciding which patients require a history-indicated cervical cerclage.
Women with a shortened cervix on transvaginal scan who
also have a previous history of miscarriage or PTB are the most
suited for ultrasound-indicated cerclage. RCOG guidance is that
those with a short cervix but no previous history should not have
a cerclage. Women with a significant past history but not enough
to warrant an elective cerclage could be offered serial sonographic surveillance and cerclage advised once the cervix is <2.5
cm. Women with multiple pregnancies, however, even in the
presence of a short cervix do not seem to benefit from cerclage
and there is evidence it may even increase perinatal mortality by
increasing preterm deliveries and miscarriage.
According to RCOG Guidelines, rescue sutures must be individualised based on clinical presentation, cervical dilatation and
uterine activity. A small study of 26 women randomized to either
a rescue suture or expectant management had an average of 4
weeks delay to delivery compared to those having just bed rest.
Suture placement before 20 weeks, is highly likely to result in
preterm birth before 28 weeks. After the age of viability, it is
259
REVIEW
Practice points
C
260