Pathophysiology of preterm labor

1. Dr Majaz Ahmed Khan
Fellow Neonatology
Pathophysiology of Preterm Birth

2. INTRODUCTION
 Accounts for 6% to 10% of all births.
 Two thirds of all perinatal deaths
 > 34 weeks + minor morbidities = 37 weeks.
 < 34 weeks accounts for 3-7 % of all preterm births(
75% of neonatal death and 50% of long term
neurologic impairment.)

3. Risk factors for preterm labor-
1. Race
2. Age- low maternal age
3. Socioeconomic status-inadequate nutrition,
substance abuse, psychological factors
4. Body mass index (BMI)-low BMI, poor weight gain,
excess weight gain, obesity.
5. Alcohol consumption
6. Smoking
7. Cocaine exposure
8. Maternal stress— Activates–- maternal, placental
,fetal endocrine system --- promote parturition by
way of an immune or inflammatory pathway.

4. Endocrinology and Biochemistry of Labor-
 During pregnancy-PROPREGNANCY-progesterone
and PGI2 –inhibit myometrial contraction.
 At end of pregnancy- PROLABOR- Remodeling of
cervix / uterus is stimulated to begin coordinated
contractions.
 Labor occurs due to activation of cassette of
contraction-associated proteins (CAPs) / labor
associated proteins—
1. Gap junction proteins
2. Oxytocin
3. Prostanoid receptors
4. Enzymes for prostaglandin synthesis
5. Cell signaling proteins.

5. Inflammation/Infection-
Up-regulation of proinflammatory genes in fetal
membranes/ myometrium / cervix.
Transcription factor nuclear factor kappa B
(NF-кB) is activated in uterus.
Promotes IL-6 and IL-8 and COX-2
cervical ripening Prostglandin
synthesis

6. Transcription factor nuclear factor kappa B (NF-кB)
Down regulates progesterone receptors leading to
functional progesterone withdrawal.

7. Corticotropin-Releasing Hormone-
produced by- Hypothalamus/ placenta / maternal serum.
 Rise in the second half of pregnancy
 Peak during labor
 Rapidly decline post partum.
CRH raised as early as 18 weeks of gestation in PTL.
CRH concentrations could help identify women at high risk
for preterm delivery
CRH antagonists may be useful in preventing preterm labor.

8. Progesterone-
 Inhibit labor associated gene expression and inhibit
contractions.
 PR antagonist RU486 can be used to ripen the cervix
and induce labor.
 PTL occurs if increased expression of PR-A relative to
PR-B.
Oxytocin-
 Increase in OTR mRNA concentrations in the
myometrium are associated with up-regulation of OT-
binding sites and causes onset of PTL.

9. CAUSES OF PRETERM LABOR
Causes-
1. Intrauterine infection(chorioamnionitis)
2. Placental abruption
3. Cervical incompetence
4. Premature membrane rupture
5. Multiple pregnancy
6. Intrauterine death
7. Fetal and uterine abnormalities
8. Genetic factors
9. Hypertensive disorders.

10. 1. Infection-
 Activates biochemical pathways leading to
cervical ripening and uterine contractions.
 After twin preterm delivery, chorioamnionitis is
more common and severe in the presenting twin
than in the second twin.
 Indicating ascending infection-organism identical
to that in the maternal lower genital tract.

11. organism settles in decidua of the lower segment.
leading to deciduitis, chorionitis
extension through the amnion into the amniotic cavity
To fetus from aspiration and swallowing
 Most common organisms- Ureaplasma urealyticum,
Fusobacterium, Mycoplasma hominis, Bacterial
vaginosis and Trichomonas vaginalis.

12.  chronic periodontal disease reservoir for bacterial
products or inflammatory mediators leading to
infection.
 causative pathogens include Prevotella and
Porphyromomas species.

13. 2.PLACENTAL ABRUPTION-
Placental abruption
Release thrombin
Protease activated recptors
stimulates myometrial contractions

14. 3.Cervical Incompetence-
 Normal uterus is composed of collagen arranged in fibers
and embedded in proteoglycans. Other components
include a small amount of smooth muscle (10%) and
some fibroblast cells.
 At onset of labor-Decrease in collagen associated with
an increase in cervical prostaglandins, proinflammatory
cytokines, leukocytes, cell adhesion molecules, and nitric
oxide synthase production.
 Ascending infection- increased inflammatory response
leading to cervical shortening and dilation.

15. 4.Multiple Pregnancies/ polyhydramnios-
Over distention of the uterus
up-regulation of contraction-associated proteins
Increase the expression of COX-2 and PGE2
synthesis.
Multiple pregnancy-multiple placenta increased
CRH earlier higher rates of preterm birth.

16. 5.Genetics-
 SNP of Matrix metalloproteinases (MMPs) causes
extracellular matrix degradation leading to rupture of
membranes and cervical ripening and dilatation.
• 3 fold increase if 1st delivery is a preterm birth
• 1/3rd increase if two previous deliveries are preterm
births
• Risk transmission to off springs.

17. Management of Preterm Labor
The key aspects in management are-
1. Establishment of diagnosis
2. Need to inhibit/deliver
3. Investigation about causes of labor
4. Assessment of gestational age, expected fetal
weight and associated fetal complications
5. Tocolysis/steroids in selected cases
6. Choosing of mode of delivery and place of delivery
7. Provision of necessary neonatal back up.

18. Diagnosis of Preterm Labor-
 For documenting true preterm labor the following
criteria should be met–
i. Regular uterine contractions after 20 weeks and
before 37 weeks which are 5-8 minutes apart or
less and accompanied by one or more of the
following:
ii. progressive change in cervix
iii. cervical dilatation of 2 cm or more
iv. cervical effacement 80 percent or more.

19. PREDICTION OF PRETERM LABOR
1. Fetal fibronectin-
 Location- deciduas basalis next to the placental
intervillous space.
 Function- fetal membranes to the uterine decidua.
 Mechanical/inflammatory changes- leaked into the
cervicovaginal fluid.
 Strong negative predictive value:0.5% deliver within
7 to 10 days after a negative test result.
 If > 50 ng/ml greatest odds ratio for preterm delivery
before 35 weeks gestation.

20. 2.Cervical Length Measurement-
Cervical Length-30 mm risk < 1%
Cervical Length-5 mm risk > 80%.
Inhibition of Preterm Labor
 The commonly used drugs are beta-mimetics,
calcium channel blockers, prostaglandin
synthetase inhibitors and magnesium sulfate.

21. Contraindications to Inhibition of Preterm Labor
Absolute
1. Congenital fetal malformation incompatible with life
2. Intrauterine fetal death
3. Chorioamnionitis
4. Abruptio placentae
5. Fetal distress
6. Uncontrolled diabetes and thyrotoxicosis
Relative
1. Placenta praevia
2. Intrauterine growth retardation
3. Maternal hypertension

22. PREVENTION OF PRETERM LABOR
1. Cerclage-
NNT is 25, so indication is > 3 2nd trimister losses(halved
the incidence of PTL before 33 weeks)
TRANSVAGINAL TRANSABDOMINAL
McDonald Shirodkar failed vaginal cerclage.
Suture at junction of
vagina and cervix
Suture at cervico
isthmic junction
Suture placed above
cardinal and
uterosacral ligament.
Suture removed at 37-38 weeks to allow NVD -

23. 2. Progesterone-
 100 mg of progesterone as a vaginal suppository
between 24 and 34 weeks.
 Significant reduction in preterm delivery rates before
37 weeks and before 34 weeks in high-risk
populations.
 Reduction in the incidence of birth weight less than
2500 g, necrotizing enterocolitis, intraventricular
hemorrhage, and the need for supplemental oxygen.
 No reduction in perinatal death or respiratory
distress syndrome.
 NNT is 7.

24. 3.Role of Antibiotics in Preterm Labor-
 In meta-analysis of 13 randomized studies about
efficacy of antibiotics benefit was found with regards
to chorioamnionitis, neonatal sepsis and
prolongation of pregnancy by 7 days.
 But severe neonatal morbidity in the form of
necrotizing enterocolitis, respiratory distress and
intracranial hemorrhage and neonatal survival were
not improved.

25. 4. Measures to Prevent Intraventricular Hemorrhage-
1. Corticosteroids are beneficial in reducing Periventricular
hemorrhage.
The other interventions that are considered are
i. Antenatal Vit K: Periventricular hemorrhages are shown to
be reduced by Antenatally administered Vit K.
ii. Antenatal phenobarbitone: Phenobarbitone when given to
mothers Antenatally is shown to reduce postnatal
intraventricular hemorrhages in the infant.
 However, in a recent report the combination of vitamin K and
phenobarbitone was found to cause a small and insignificant
reduction in intraventricular hemorrhage.

26.  Exact mechanism and cause of idiopathic preterm
labor is still largely unknown.
 However, the role of antenatal steroids and
antibiotics is largely established in improving
perinatal outcome
 Provided when such deliveries are conducted at a
well appointed maternal unit of a institution with
appropriate neonatal units equipped and trained for
such eventualities.

27. Thank You