L11 Preterm Birth Flashcards
Why might reporting on later cases of preterm birth be limited?
- Lack of data on later cases since they are typically less severe
- As a result, they are lower in priority
Outline the classifications of preterm birth:
- Extreme PTB: <28 weeks
- Very PTB: 28 - 31 weeks
- Moderate PTB: 32 - 33
- Late PTB: 34 - 37
How many live births are preterm in the UK vs worldwide?
- 7.8% in UK
- 1 in 10 globally
- Results in 1 million PTB-related deaths a year
What is the data behind preterm births in twins?
- Over 50% of twin pregnancies deliver preterm
What complications are associated with prematurity?
- KEY: Largest cause of perinatal mortality for a normal fetus, and a major contributor to developmental delay
- Respiratory
- Cardiovascular
- GI
- Metabolic
- Sensory (vision and hearing)
- IVH and white matter injury
- Cerebral palsy, neurodevelopmental delay
- ADHD and behavioural problems
- Failure to thrive
- Insulin resistance, hypertension
Outline some economic pressures for delaying preterm birth:
- Cost of special care/neonatal care stays
- Associated long term costs with conditions of premature babies
- Costs NHS upwards of £2.9 billion a year
What are factors are involved in preterm parturition syndrome?
- Uterine overdistension
- Decidual haemorrhage
- Cervical insufficiency (dilation before term)
- Cervical remodelling
- Infection and inflammation (KEY)
- Other causes, known and unknown
What are the 4 key routes for intrauterine infection?
- Ascending infection (genital tract)
- Haematogenous (via placenta)
- Retrograde (seeding via fallopian tubes)
- Iatrogenic (following invasive procedures)
Evidence for a causal relationship between infection and PTL:
- Present in 25 - 40% of preterm births
- Animal studies: systemic/I-U administration of microbes can provoke PTB
- Extra-uterine infections increase risk of PTB (e.g pyelonephritis, malaria)
- Subclinical intrauterine infection also associated with PTB
- Evolutionary argument (protecting mother and preserving reproductive function)
Outline the broad pathway leading from infection to PTB:
- Microbial invasion of amniotic cavity
- -> Proinflammatory response
- -> Cervical remodelling and myometrial activity
- Preterm delivery
Fetal tissue response to choriodecidual bacterial colonisation:
- Increased CRH by fetus, placenta
- Increased cytokines and chemokines (particularly IL-1B and TNF-a)
- Leading to increased cortisol and increased PGs
- Increase in metalloproteases (degrading structures of chorioamnion and cervix)
- -> Cervical ripening, weakening/rupture of chorioamnion, myometrial contractions
- ->PTB
Maternal response to choriodecidual bacterial colonisation:
- Decidua release cytokines and chemokines
- Neutrophil infiltration and simultaneous PG release
- -> Increase in metalloproteases (degrading structures of chorioamnion and cervix)
- -> Cervical ripening, weakening/rupture of chorioamnion, myometrial contractions
- -> PTB
What 3 cytokines play a key role in infection-driven PTB?
- Proinflammatory: IL-1B and TNF-a
- Antiinflammatory: IL-10
List 4 inherent defenses against infection in the reproductive tract:
- Acid vaginal pH (secondary to lactobacilli)
- Cervical mucus
- Epithelial barriers
- Innate immune system receptors (TLRs)
- Issues with these defences lead to higher risk of infection and PTB
What is ischaemia?
- Ischemia is a less-than-normal amount of blood flow to part of your body
- This lack of blood flow means your tissues aren’t getting the oxygen they need.
Evidence for the link between ischaemia and PTB:
- Obersvational evidence linking placental vascular lesions and PTB (higher rate of vascular lesions in PTB placentas)
- Abruption commoner in PTL/PROM cases than term labour
Mechanism for ischaemia link to PTB:
- Largely unclear
- Keep in mind that under adverse conditions, the body treats the placenta as a terminal organ
When may cervical insufficiency occur?
- More likely in patients with abnormally disrupted cervices
- e.g. Post LLETZ surgery
- e.g. Congenital abnormality
- Also evidence for link between cervical insufficiency and intrauterine infection (50% acute cervical insufficiency cases)
What factors lead to uterine overdistension?
- Multiple gestation
- Polyhydramnios
- Uterine anomalies
Mechanism linking uterine distension and labour induction:
- Increased distension -> increased expression of contraction associated proteins
- This includes gap junction proteins, oxytocin receptors, proteins in PG synthetic pathway
- -> Increased PG release -> Labour induction
- (Also higher levels of collagenase and IL8 in membranes)
Why may an endocrine disorder lead to preterm birth?
- Key role of progesterone in maintaining uterine quiescence during pregnancy, and preventing untimely cervical ripening
- Endocrine control over proinflammatory cytokines and CRH levels
What techniques are currently used to predict preterm birth?
- History-based assessment (most gestational disorders more likely to repeat in mothers who’ve previously had them)
- USS (cervical length)
- Actim partus test
- Infection screening
- Clinical diagnosis
What is the actim partus test?
- Swab for placental proteins
- Particularly interested in pIGFBP1
- Looking for evidence of disruption to placenta (e.g. abruption)
- Indicator for PTB since pIGFBP1 is produced in the fetal decidua and leaks into the cervix when the decidua and chorion detach
- 1 in 6 positive actim partus -> PTB (Good negative predictive value but not very specific so only useful as a screening measure)
Outline the risk factors for PTB:
- History: Previous preterm birth, previous cervical history
- Multiple pregnancy
- Lifestyle: Smoking
- Background: Age, ethnicity
- Clinical: bacterial vaginosis, short cervix, uterine abnormalities
What is the current pathway for predicting PTB in the UK?
- Risk assessment
- Cervical length screen to high-risk women
- Treatment based on findings and history
Primary prevention of PTB (outline strategy):
- Aiming to reduce population risk
- e.g. smoking cessation, reducing multiple pregnancy
- Not yet particularly effective
Secondary prevention of PTB (outline strategy):
- Selecting those at increased risk for surveillance and prophylaxis
- e.g. cervical length screening -> cervical pessary, cervical cerclage, progesterone supplementation
Tertiary prevention of PTB (outline strategy):
- Treatment following diagnosis of preterm labour (aiming to reduce morbidity and mortality)
- e.g. tocolysis, antenatal cortico-steroids, in utero transfer
- Essentially buying time to prepare and transfer to appropriate birthing unit
What is cervical cerclage?
- Placement of a suture to prevent dilation of cervix
- Conflicting evidence base (heterogeneity in approach)
When might antibiotics be administered to prevent PTB?
- Asymptomatic baceteriuria
- Bacterial vaginosis
- Periodontal disease (evidence does not support)
- Group B strep (high mortality in minority of cases where transmitted to baby but higher chance of tranmission in PTB so issued to premature babies rather than screening)
ORACLE studies for gestational antibiotic use:
- Both large multicentre RCTs (2001)
- ORACLE 1: Antibiotics in PPROM, reduced neonatal morbidity and prolonged pregnancy (erythromycin) -> no difference in outcomes at 7-year follow up
- ORACLE 2: Antibiotics in spontaneous labour with intact membranes -> no difference for neonates in short-term, reduced maternal deaths but increased cerebral palsy rate at 7 year follow up
Outline the components of the package of medicines issued for preterm birth:
- Antenatal corticosteroid treatment to reduce neonatal death (lung maturation)
- MgSO4 -> not an effective tocolytic but reduces incidence of cerebral palsy
- Tocolytic agents (?) -> delaying delivery does not in itself improve outcomes, should be used sensibly
Give two examples of tocolytic agents:
- Nifedipine (calcium channel blocker)
- Atosiban (oxytocin receptor antagonist)
