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Pathohysiology

Cervical Insufficiency

Cervical insufficiency is a condition in which the cervix is weak and unable to hold a pregnancy, leading to premature delivery or miscarriage

PATHOGENESIS:

Structural abnormalities in the cervix, such as a short or weak cervix, cervical incompetence or previous cervical surgery

Hormonal changes that affect cervical function, such as progesterone deficiency or imbalance

Infection or inflammation of the cervix or uterus, such as bacterial vaginosis, cervicitis or chorioamnionitis

Genetic factors, including inherited connective tissue disorders that affect the strength and structure of the cervix

Environmental factors, such as exposure to toxins or radiation that can damage cervical tissue

Behavioral factors, such as smoking or substance abuse, which can increase the risk of cervical insufficiency.

PATHOGENESIS

Structural abnormalities

Hormonal changes

Infection or inflammation of the cervix or uterus

Genetic factors

Environmental factors

Behavioral factors

PREVALENCE

Account for approximately 10-15% of preterm births

The prevalence of cervical insufficiency in preterm labor ranged from 2.2% to 20.5%, with an overall prevalence of 7.1%

Common in women with a history of preterm birth or cervical surgery

The prevalence rates can vary depending on the population being studied and the diagnostic criteria used

INTERVENTIONS

Cervical cerclage

Progesterone supplementation

Bed rest and pelvic rest

Treatment of infections or inflammation

Tocolytic medications to suppress contractions

Rescue cerclage in cases of failed cerclage or advanced cervical dilation

Cervical pessary to support the cervix

Amniocentesis to assess fetal lung maturity in case of imminent preterm birth

Expectant management with close monitoring and follow-up

INEFFICIENT INTERVENTIONS

Delayed diagnosis and management

Inappropriate use of tocolytic medications without addressing the underlying cause

Inadequate or inappropriate cervical cerclage placement or technique

Inconsistent or inadequate use of progesterone supplementation

Failure to address co-existing conditions such as infection, inflammation, or uterine overdistension

Insufficient or inadequate monitoring and follow-up of patients with cervical insufficiency

Untimely and inappropriate use of rescue cerclage or other interventions

Failure to consider individual patient factors such as gestational age, cervical length, and obstetrical history when selecting interventions.

FUTURE INTERVENTIONS

Improved diagnostic tools: biomarkers, imaging

Advancements in cerclage techniques: minimally invasive, biodegradable materials

Personalized treatment approaches based on patient factors

Investigate new pharmacological therapies: collagen synthesis, anti-inflammatories

Non-surgical interventions: cervical pessaries, support devices

Telemedicine and remote monitoring integration

Large-scale clinical trials and registries

RESEARCH GAPS

Reliable biomarkers and imaging

Efficacy and safety of cerclage

Role of non-surgical interventions

Personalized treatment algorithms

Patient education and support

Long-term outcomes and quality of life

Underlying pathophysiology exploration

Green, E. S., & Arck, P. C. (2020, August). Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus. In Seminars in Immunopathology (Vol. 42, No. 4, pp. 413-429). Berlin/Heidelberg: Springer Berlin Heidelberg.

Robinson, J. N., & Norwitz, E. R. (2018). Preterm birth: Risk factors, interventions for risk reduction, and maternal prognosis. UpToDate.[(accessed on 20 January 2022)]. Available online: https://www. uptodate. com/contents/preterm-birth-risk-factors-interventions-for-risk-reduction-and-maternal-prognosis.

Thakur, M., & Mahajan, K. (2021). Cervical incompetence. In StatPearls [Internet]. StatPearls Publishing.

Inherited pathogenic variants

genetic mutations that increase the risk of preterm labor in a heritable manner

PATHOGENESIS

• Genetic mutations

• Altered immune response

• Cervical remodeling

• Placental dysfunction

RISK FACTORS

• Family history

• Consanguinity

• Ethnicity

• Advanced maternal age

GENETICS

• Inherited variants: autosomal dominant/recessive, X-linked

• Polymorphisms: associated with gestational duration/sPTB

• Maternal variants at EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci associated with gestational duration and at EBF1, EEFSEC, and AGTR2 loci with PTB.

• PTB susceptibility genes identified, but epigenetic and gene-environmental factors play a bigger role than maternal genotype.

RACIAL DISPARITIES

• African American pregnant people have a 50% higher rate of sPTB than non-Hispanic White pregnant people

• Multiple maternal and fetal inflammatory pathway genetic polymorphisms linked to inflammation-associated sPTB are found in greater prevalence among African American mothers and/or fetuses than among other racial groups

• African American mothers harboring both a polymorphism of the tumor necrosis factor-alpha gene and bacterial vaginosis are at significantly greater risk of PTB (odds ratio 6.1, 95% CI 1.9-21.0)

• Higher vaginal levels of the host-derived antimicrobial peptide, beta-defensin 2, are linked to a lowered risk of sPTB

• Lower levels of beta-defensin 2 were linked to spontaneous PTB only among African American pregnant people.

INTERVENTIONS

• Genetic counseling and testing

• Prenatal screening and diagnosis

• Preimplantation genetic diagnosis

• In vitro fertilization with donor eggs or sperm

• Use of assisted reproductive technologies

• Prophylactic measures during pregnancy, such as cervical cerclage or progesterone supplementation.

FUTURE INTERVENTIONS

• Comprehensive genetic testing panels

• Gene therapies for genetic variants

• Personalized medicine approaches

• Understanding genetic-environment interactions

• Medications targeting genetic pathways

• CRISPR-Cas9 for genetic modification

• Non-invasive diagnostic tools development

RESEARCH GAPS

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