Preterm birth Flashcards
Incidence of PTB
5-10% of births
7% in NZ, 8% in Australia
Extreme PTB <28 weeks = 0.5% in NZ
Definition of extreme preterm, very preterm, and moderate-late preterm - gestations
extremely preterm = less than 28 weeks
- combined 2% of births in Australia
very preterm = 28 to 32 weeks
- combined 2% of births in Australia
Moderate to late preterm = 32 to 37 weeks
7% of births in Australia
Broad causes of PTB - rule of thirds
1/3 = iatrogenic e.g. PET, severe IUGR
1/3 = following PPROM
1/3 = spontaneous labour
Causes of preterm birth = PICFUPS
P = previous PTB (15% with 1x PTB, 30% with 2x, 45% with 3x)
I = infection Intrauterine = ascending (BV, trich, chlamydia, gonorrhoea, GBS, gardnerella, mycoplasma, ureaplasma, kleibsiella, E coli), transplacental via maternal blood stream (bacteraemia), from abdomen via tubes (e.g. appendicitis, TOA), introduced via procedure (e.g. amniocentesis) Extrauterine = sepsis e.g. urosepsis, pneumonia, viral, peridontal disease
C=cervix
Shortened cervix - previous LLETZ >1cm, cone biopsies, previous D+Cs/STOPs, cervical trauma in previous deliveries, CS at full dilatation
F=fetal
Chromosomal or congenital abnormalities
U=uterine (OUT)
Overdistension (polyhydramnios, LGA, multiple pregnancy), uterine structural abnormalities (bicornuate/septate), trauma
P=placenta
Placental abruption, placental insufficiency
S=social Substance use (smoking, ETOH, drugs) Low SES, Maori/Pacific/Indigenous Low pre-pregnancy weight AMA Stress, IPV
History taking
PC - abdo pain, back pain, ROM, FM, localising sx of infection
Pregnancy this far
PTB risk factors
Gestation accurate?
Whether appropriate to do fFN = no bleeding, PPROM, VE, intercourse
NICE Guidance on USS Cx length vs fFN
Treat as TPTL if 29+6 or less based on clinical assessment only
If 30+0 or more
Offer TV ultrasound first line
If > 15mm - unlikely preterm labour, consider other diagnoses and offer inpatient observation vs outpatient
If 15mm or less - diagnose preterm labour
Offer FFN if TVUSS not available or acceptable
If 50ng/ml or less - unlikely preterm labour, consider other diagnoses and offer inpatient observation for outpatient
If >50ng/ml - diagnose preterm labour
Maternal and Fetal Impacts of PTB
Maternal
Increased operative birth
Increased PPH
Reduced bonding due to increased NICU admissions
Increased postpartum depression and anxiety
Morbidity related to underlying cause - infection, abruption, PET
Fetal Intrapartum hypoxia Low birth weight Hypothermia Hypoglycaemia Respiratory - TTN, RDS, surfactant deficiency, BPD, apnoeas Cardiac - PDA Gut - NEC Brain - IVH Jaundice Retinopathy Neonatal death
Counselling in event of PTL or TPTL
Discuss implications for mother and baby, short and long term consequences
Consider gestation - active management vs palliative
If active: steroids, tocolysis unless contraindications, MgSO4, benzylpenicillin, NICU availability - transfer in-utero or ex-utero
BV Definition Associated organisms Does routine treatment of BV reduce PTB? Who should we treat for BV?
Imbalance of vaginal flora - reduction in protective acids producing lactobacilli and overgrowth of BV associated organisms:
Gardnerella vaginalis,
bactericides, peptostreptococcus, mycoplasma species, atopbium species, moriluncun species
Routine treatment of BV in pregnancy is not associated with reduced PTB or PPROM
Treat those with other risk factors for preterm birth
Treat those who are symptomatic
MgSO4 for neuroprotection: dose and monitoring
Dose
4g bolus over 25-20 minutes
Then IV infusion 1g per hour until birth or for 24 hours (Which ever is sooner)
Monitoring
At least 4 hourly HR, BP, RR, deep tendon reflexes, UO
Rescue cerclage indications and contraindications
Indications
- 16+0 - 27+6
- Dilated cervix, exposed, unruptured membranes
Contraindications
- Vaginal bleeding
- Uterine contractions
- Signs of infection
- Ruptured membranes
Caesarean section - choice of uterine incision
Depends on presence of lower segment, position of fetus, multiple pregnancy, placental location, membranes ruptured
Options - classical, upper transverse, J or T
Classical facilitate atraumatic and rapid delivery of the fetus
Ventouse and forceps contraindicated before what gestation?
Ventouse contraindicated < 34 weeks
Forceps relatively contraindicated < 34 weeks - perform with caution, do not perform rotational forceps, only if certain of position
FSE and FBS contraindicated before what gestation?
34/40
Avoid FSE if <34+0/40 unless it is not possible to monitor externally
AND has been discussed with a senior obstetrician AND benefits outweigh risks
AND alternatives and inappropriate to the woman
FBS - avoid if less that 34+0/40
Cervical length measurements and risk of PTB <37 weeks
Length 30mm, 27mm, 22mm
30mm (10th centile) - RR 3.8
27mm (5th centile) - RR 5.4
22mm (2.5th centile) - RR 6.3
(Median length at 20 week is 42mm)
USS technique for cervical measurement
Consider TA scan with partially full bladder as potential firstline screening test. If >35mm do not need TV USS.
Most accurately measured using TV ultrasound
- Empty bladder
- Probe in anterior fornix, minimising pressure on cervix
- Measure from internal to external os, take smallest of three measurements over 5 minutes (As cervix is dynamic)
Transperineal not adequately studied
Cervical USS assessment - Predictive value of funnelling and shortening with fundal pressure, or presence of amniotic sludge?
Associated with PTB but don’t contribute to predictive monitoring beyond the cervical length itself
Progesterone vs cerclage in LOW RISK WOMEN? RR?
Progesterone - RR 0.66 (ie reduces risk by 34%) reduces risk of preterm delivery before 34 weeks or fetal death. NNT = 11.
Progesterone also reduces risk of RDS, composite neonatal morbidity and mortality,
birthweight <1.5kg, admission to NICU
Cervical cerclage
- RR 0.74 if low risk
- RR 0.61 if previous PTB.
No clear benefit of cerclage to progesterone, therefore progesterone is generally preferred treatment as avoids surgical risks.
Role of progesterone vs cerclage in WOMEN WITH RFS FOR PRETERM BIRTH? RR?
- Previous PTB
- benefit from progesterone or cerclage, consider cervical length surveillance to guide decision and if progressive shortening consider cerclage. - Multiple pregnancy
- Cervical length has predictive value however there
is conflicting evidence regarding therapeutic intervention. - Previous cervical excisional procedure - can help stratify risk for women and determine appropriateness of intervention
Possible interventions for shortened cervix or women with multiple RFs
- Conservative:
- If no risk factors or patient declines
- Consider cervical length monitoring - Progesterone
- CONSIDER if history of PTB <34 weeks but normal cervical length
- RECOMMEND if CL <25mm (singleton or multi) - Cervical cerclage
- CONSIDER if history of PTB, PPROM or cervical surgery AND cervix <25mm
- No significant difference between two interventions and increased risk with cerclage
- Therefore, progesterone should be firstline in these women with serial cervical length in 1-2 weeks
- If further shortening of cervix despite progesterone, consider cerclage
PV progesterone mechanism of action?
Reduces myometrial sensitivity to oxytocin
Blocks adrenergic receptors and prostaglandin synthesis
Stimulates lymphocyte associated synthesis of progesterone induced blocking
factor
Progesterone insufficiency thought to trigger uterine contractility
Second and third trimester timing of progesterone
From 16-24 weeks, until 34-36 weeks
Progesterone benefits, and safety profile
Reduced risk of PTB in meta-analysis - RR 0.66. NNT 11.
Also reduced risk of RDS, composite neonatal morbidity and mortality, birthweight <1.5kg, admission to NICU
No evidence of teratogenicity or adverse childhood outcomes (2 year follow up - OPPTIMUM trial)
Cerclage timing
From 12-14 weeks for history indicated (2 or more early PTB)
From 16-24 weeks for ultrasound indicated
Risks of cercvical cerclage
ROM, chorioamnionitis, bleeding, cervical trauma, anaesthetic risks
Average additional gestational time added - prolongs pregnancy for average of 6 weeks. Could still end up with a pre-viable or very preterm baby
Types of cervical cerclage
Transvaginal
- Shirodkar (buried, needs spinal to remove)
- McDonald
Transabdominal
- When vaginal sutures have failed
- Bladder is reflected and suture placed over the internal os
- Stays in place, delivery via CS
Contraindications to cerclage
Rupture of membranes
APH
Evidence of infection
Uterine activity
Gestation range for insertion of rescue cerclage
16-28 weeks with a dilated cervix and exposed membranes - discuss with SMO and paeds
Rescue cerclage insertion process
Trendelenburg Consider uterine relaxant Reduce prolapsed membranes with smooth surfaced device such as inflated IDC balloon Use McDonalds suture Remain in hospital for 1 night Follow up 2 weeks post insertion
Contraindications to MgSO4
myasthenia gravis
myocardial compromise/ conduction defects (anti-inotropic effects)
Caution with impaired kidney function - use 0.5g/hr
MgSO4 for neuroprotection in PTB - mechanisms of action
Exact mechanism not fully understood. Likely combination of following
Down regulation of excitatory stimuli
- blocks NMDA receptors, preventing influx of calcium causing neuronal cell death
- blocking NMDA receptors also decreases seizure threshold
Cerebral vasodilation through ca antagonism
- leading to an increase in cerebral blood flow
- minimising hypoxic ischaemic changes
Reduction of pro-inflammatory cytokines
Anti-apoptotic effect
Steroids and Cochrane review 2017 - what are the benefits to infants? What do steroids not have an impact on?
Reduced rates of:
- Neonatal Death RR 0.72
- Respiratory Distress RR 0.66
- Need for mechanical ventilation RR 0.68
- Intraventricular Haemorrhage RR 0.55
- Necrotising Enterocolitis RR 0.50
- Systemic infection in the first 48 hours of life RR 0.6
No effect on: Chronic lung disease Mean birthweight Death in childhood or adulthood Neurodevelopment Chorioamnionitis/endometritis
Steroids optimal treatment to delivery interval
> 24 hours <7 days
No confirmed benefit in infants delivered >7 days after dose (possible some small benefit up to 14 days)
Still some benefit in those delivered less than 24 hours after the first dose
Adverse effects of single course (1x pair) of steroids?
No known short term maternal or fetal adverse effects after single course
No known longer term risks of a single course in terms of cognitive/neurological effects
Insufficient evidence regarding multiple doses
Contraindications to steroids
Requirement for acute delivery - do not delay delivery for purpose of steroid effect
Contraindication in systematic infection - TB, sepsis
Consider in chorioamnionitis but do not delay delivery for purpose of steroid effect
Steroids and elective CS?
RCOG and Aus/NZ recommendations?
ASTECs study
RCOG suggest giving for elective CS up until 38+6
Aust/NZ Practice guideline suggest >34+6 if confirmed fetal lung immaturity
ASTECS study - reduced admission to SCBU with RDS (RR 0.46) but very low baseline risk at advancing gestation and no BSL measurements and long term outcomes
Indication and gestation for rescue steroids (after initial pair)
Give if at ongoing risk of preterm delivery >7 days after single course
Give up to 3 x further rescue doses 1 week apart up til 32+6 (Aus/NZ Practice Guideline)
ACTORDS study - repeat steroid doses - outcomes RR
Reduces RDS RR 0.82
reduces severe lung disease RR 0.6
reduces O2 use, mechanical ventilation, surfactant use.
Decreased birthweight, head circumference and length at birth but not at discharge.
Increased CS rate
No difference in rate of NICU admission, APGAR scores, NEC, Retinopathy of prematurity, IVH
2 year follow showed increase need for attention problems assessment but no difference in major neurosensory disability
Rescue steroids Cochrane 2015 study results
Associated with reduced RDS (RR 0.83)
Associated with reduced serious infant outcome (RR 0.84)
Associated with reduced mean birthweight -76g (no difference when adjusted for birthweight)
No significant harm or benefit at 2 and 3 years (although ACTORDS found increased risk of need for assessment for attention problems)
What is fFN?
When is it normally present in the cervicovaginal secretions?
Extracellular matrix glycoprotein present at the decidual-chorionic
interface
<16 weeks (prior to fusion of
chorion and amnion) and >37 week
Why do we use the fFN test?
To help predict likelihood of preterm labour and guide use of steroids and tocolytics
fFN cause of false positives?
Negative predictive value?
False positives: semen, blood, digital cervical examination, lubricant
99.7%
fFN positive predictive values?
10, 50, 200, 500 ng/ml?
Positive predictive value increases the higher the number 10ng/ml = 11-19% PPV 50ng/ml = 20-32% PPV 200ng/ml = 37- 61% PPV 500ng/ml = 46-75% PPV
fFN sensitivity, specificity, positive and negative predictive values
Sensitivity 65%, PPV 43%
Specificity 93%, NPV 97%
QUIPP tool for PTB
Use in two clinical settings:
- Asymptomatic women at high risk for PTB in preterm surveillance clinics (based on 1803 women)
- Symptomatic women e.g. abdominal pain, contractions, tightenings (based on 1032 women)
Relies on:
A clinical history for current risk factors and symptoms
FFN OR TV USS cervical length measurements (both is better, don’t need both)
1. Symptomatic Symptom present Y/N Previous cervical surgery Y/N Previous preterm Y/N Previous PPROM Y/N Number of fetuses Gestation of test Shortest cervical length AND/OR fFN result
2. Asymptomatic Previous cervical surgery Y/N Previous preterm Y/N Previous PPROM Y/N Previous late miscarriage 16-24/40 Y/N Number of fetuses Gestation of test Shortest cervical length fFN result
Gives results as percentage: Within 1 week Within 2 weeks Within 4 weeks Before 30/40 Before 34/40 Before 37/40
PPROM incidence and risk factors
2-3% of pregnancies
PPROM precedes 1/3 of preterm births
RFs:
Previous PPROM
Infection - vaginal, urine, systemic infection
Uterine overdistension: multiple pregnancy, LGA, polyhydramnios
Uterine trauma
Short interpregnancy interval
Smoking/substance use
Amnisure or Actim PROM tests to diagnose PPROM
Amnisure
- Measures alpha micro globulin
- Not affected by semen of small amounts of blood
- Specificity = 87-100%
- Sensitivity around 94-98%
- Can be positive in up to 1/3rd of term woman with intact membranes in labour
Actim PROM test
- Measures insulin-like growth factor binding protein
(secreted by decidual and placental cells in high concentrations in amniotic fluid)
- Not affected by infection, urine, semen or small amounts of blood
- Specificity 98%
- Sensitivity 93%
Likelihood of labouring after PPROM
- Median time to delivery in general
- Median time to deliviery for 24-28 weeks; 31 weeks
Medium time to delivery is 7 days (80% deliver within 7 days)
10 days at 24 -28 weeks
5 days at 31 weeks
25% deliver within 48 hour
Risks of PPROM - fetal
Preterm labour, complications of prematurity (hypoxia, NEC, IVH, respiratory, low birthweight)
Chorioamnionitis
Ongoing pregnancy with PPROM: fetal lung hypoplasia, limb contractures, growth restriction
Likelihood of lung hypoplasia if PPROM at 21 weeks, vs 29 weeks
If PPROM at 21 weeks - 90% have lung hypoplasia
If PPROM at 29 weeks - 10% have lung hypoplasia
ORACLE 1 trial for PPROM
Abx used?
Findings
PPROM < 37/40, randomised to erythromycin, co-amoxiclav, both or neither.
Associated with prolongation of pregnancy, reduced surfactant use, reduced oxygen use at 28 days, reduced abnormal cerebral ultrasound
Increased NEC with augmentin (RR 4)
