Preterm Labor and Birth

Overview

Definitions

Preterm labor is defined as regular Regular Insulin uterine contractions that lead to cervical change in dilation and/or effacement prior to 37 weeks of gestation.

Preterm birth is defined as birth at a gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care of 20–37 weeks.

Epidemiology

Preterm labor:

• < 10% of women with preterm labor give birth within 7 days.
• 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship hospitalized for preterm labor will ultimately deliver at term.

Preterm birth:

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 12% of all live births
  • Spontaneous preterm birth: approximately 75%
  • Indicated preterm birth: approximately 25%
• Racial and ethnic bias Bias Epidemiological studies are designed to evaluate a hypothesized relationship between an exposure and an outcome; however, the existence and/or magnitude of these relationships may be erroneously affected by the design and execution of the study itself or by conscious or unconscious errors perpetrated by the investigators or the subjects. These systematic errors are called biases. Types of Biases: African American > Caucasians
• Impact:
  • 70% of neonatal deaths
  • 25%–50% of long-term neurological impairment

Etiology and Risk Factors

Etiology of spontaneous preterm birth

• Preterm labor
• Preterm prelabor rupture of membranes Prelabor Rupture of Membranes Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, refers to the rupture of the amniotic sac before the onset of labor. Prelabor rupture of membranes may occur in term or preterm pregnancies. Prelabor Rupture of Membranes (PPROM)
• Cervical insufficiency

Etiology of indicated preterm birth

• Maternal indications:
  • Hypertensive disorders:
    • Severe preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders
    • Poorly-controlled chronic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Severe infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Hemodynamic instability
• Obstetric indications:
  • PPROM without labor after 34 weeks
  • Intra-amniotic infection (IAI)
  • Prior classical cesarean section
• Fetal indications:
  • Intrauterine growth restriction (IUGR)
  • Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios
  • Multiple gestation
  • Congenital Congenital Chorioretinitis anomalies
• Placental indications:
  • Placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity previa ( placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity near the cervical os)
  • Placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity accreta ( placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity invading the myometrium)
  • Placental abruption Placental Abruption Premature separation of the normally implanted placenta from the uterus. Signs of varying degree of severity include uterine bleeding, uterine muscle hypertonia, and fetal distress or fetal death. Antepartum Hemorrhage (placental separation from the decidua)

Risk factors for preterm labor and birth

Because preterm labor is a major etiology of preterm birth, all risk factors for preterm labor are also risk factors for spontaneous preterm birth.

• Prior obstetric history Obstetric History Prenatal Care:
  • Prior preterm birth:
    • Most important risk factor overall
    • Includes both spontaneous and indicated preterm births
  • Prior PPROM
  • Prior uterine evacuation 
• Age, race, and genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics:
  • Nonhispanic black women
  • Extremes of maternal age (young and old)
  • Genetic polymorphisms: contribute to risk (though environmental factors are likely more important)
• Fetal factors:
  • Congenital Congenital Chorioretinitis anomalies
  • Growth restriction 
• Cervical factors:
  • History of cervical surgery (e.g., conization Conization Cervical Cancer)
  • Short cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy on ultrasound
  • Cervical dilation Cervical dilation A measurement of the diameter of the cervical canal, reported in centimeters Normal and Abnormal Labor ≥ 1 cm prior to 24 weeks
• Uterine factors:
  • Congenital Congenital Chorioretinitis uterine anomalies (e.g., uterine septum)
  • Leiomyomas ( fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility)
  • Uterine overdistension:
    • Multiple gestation
    • Polyhydramnios Polyhydramnios Polyhydramnios is a pathological excess of amniotic fluid. Common causes of polyhydramnios include fetal anomalies, gestational diabetes, multiple gestations, and congenital infections. Patients are often asymptomatic but may present with dyspnea, extremity swelling, or abdominal distention. Polyhydramnios
• Intrauterine bleeding:
  • Placental abruption Placental Abruption Premature separation of the normally implanted placenta from the uterus. Signs of varying degree of severity include uterine bleeding, uterine muscle hypertonia, and fetal distress or fetal death. Antepartum Hemorrhage
  • Decidual hemorrhage early in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • IAI ( chorioamnionitis Chorioamnionitis Chorioamnionitis, commonly referred to as intraamniotic infection (IAI), is a common obstetric complication involving infection and inflammation of the fetal membranes, amniotic fluid, placenta, or the fetus itself. Chorioamnionitis is typically caused by a polymicrobial infection that ascends from the lower genitourinary tract. Chorioamnionitis)
  • Genital tract infection:
    • Group B streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus ( GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy)
    • STD
    • Bacterial vaginosis Bacterial vaginosis Polymicrobial, nonspecific vaginitis associated with positive cultures of gardnerella vaginalis and other anaerobic organisms and a decrease in lactobacilli. It remains unclear whether the initial pathogenic event is caused by the growth of anaerobes or a primary decrease in lactobacilli. Vulvovaginitis
    • Note: Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis is not a risk factor.
  • Pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia 
  • Periodontal disease
  • Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria
• Maternal chronic medical disorders:
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus Type 1 Type 1 Spinal Muscular Atrophy
  • Renal insufficiency
  • Autoimmune disease
• Other maternal factors:
  • Pregnant as a result of assisted reproductive technology Assisted Reproductive Technology Clinical and laboratory techniques used to enhance fertility in humans and animals. Reproductive Ethical Issues
  • Abdominal surgery during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Short interval between pregnancies
  • Poor prenatal care Prenatal care Prenatal care is a systematic and periodic assessment of pregnant women during gestation to assure the best health outcome for the mother and her fetus. Prenatal care prevents and identifies maternal and fetal problems that adversely affect the pregnancy outcome. Prenatal Care
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases and substance use disorder
  • Undernutrition
  • Extremes of prepregnancy weight (low and high)
  • Occupational activity:
    • Prolonged standing and walking
    • Lifting heavy objects
    • Working night shifts
    • Working long hours
• Environmental factors:
  • Air pollution Pollution The presence of contaminants or pollutant substances in the air (air pollutants) that interfere with human health or welfare, or produce other harmful environmental effects. The substances may include gases; particulate matter; or volatile organic chemicals. Asthma (fine particulate matter, ozone)
  • High environmental temperature
  • Phthalate exposure

Pathophysiology and Clinical Presentation

Preterm labor

Common final pathway for initiating preterm labor:

• Prostaglandin secretion Secretion Coagulation Studies:
  • Alters collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology and glycosaminoglycans in cervical tissue (cervical maturation, cervical ripening)
  • ↑ Uterine contractility
• Degradation of the extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars around fetal membranes
• Oxytocin → coordinated uterine contractions

Primary pathways (4) leading to the common final pathway:

• Stress:
  • Stress → ↑ placental corticotropin-releasing hormone Corticotropin-releasing hormone A peptide of about 41 amino acids that stimulates the release of adrenocorticotropic hormone. Crh is synthesized by neurons in the paraventricular nucleus of the hypothalamus. After being released into the pituitary portal circulation, crh stimulates the release of acth from the pituitary gland. Crh can also be synthesized in other tissues, such as placenta; adrenal medulla; and testis. Hypothalamic and Pituitary Hormones (CRH) → ↑ prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids
  • Fetal stress (more common): uteroplacental vascular insufficiency Vascular insufficiency Anal Fissure
  • Maternal stress (less common): psychosocial stress
• Infection and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation:
  • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can produce:
    • Phospholipase A2 Phospholipase A2 Phospholipases that hydrolyze the Acyl group attached to the 2-position of phosphoglycerides. Nephrotic Syndrome → promote prostaglandin synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Endotoxin Endotoxin Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Proteus → stimulate uterine contractions directly
    • Protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS, collagenase, elastase Elastase A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25, 000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. Proteins and Peptides → degrade fetal membranes → PPROM
  • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology bind BIND Hyperbilirubinemia of the Newborn toll-like receptors Toll-like receptors A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the interleukin 1 receptor and the drosophila toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of signal transducing adaptor proteins. Innate Immunity: Barriers, Complement, and Cytokines (TLRs) on uterine, placental, and membrane tissue → trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation release of inflammatory mediators:
    • Interleukin (IL)-1, IL-6, and IL-8
    • Tumor necrosis factor Tumor necrosis factor Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF) ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF))
    • Matrix metalloproteinase Matrix metalloproteinase A family of zinc-dependent metalloendopeptidases that is involved in the degradation of extracellular matrix components. Pulmonary Fibrosis (MMP)
  • Effect of inflammatory mediators:
    • ↑ Prostaglandin secretion Secretion Coagulation Studies
    • ↑ Uterine contractility
    • Induce protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS → PPROM
• Decidual hemorrhage:
  • Intrauterine bleeding → activation of the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis
  • Thrombin Thrombin An enzyme formed from prothrombin that converts fibrinogen to fibrin. Hemostasis → binds protease-activated receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( PAR PAR The PAR is the attributable risk for an entire population. It represents the fraction of cases that would not occur in a population if the exposure was eliminated. Measures of Risk) 1 and 3:
    • ↑ Frequency, intensity, and tone of myometrial contractions
    • ↑ MMP 
    • ↑ IL-8 in decidual cells Decidual cells Embryoblast and Trophoblast Development 
• Uterine overdistension:
  • Common causes:
    • Multiple gestations
    • Polyhydramnios Polyhydramnios Polyhydramnios is a pathological excess of amniotic fluid. Common causes of polyhydramnios include fetal anomalies, gestational diabetes, multiple gestations, and congenital infections. Patients are often asymptomatic but may present with dyspnea, extremity swelling, or abdominal distention. Polyhydramnios
  • Stretched myometrium:
    • Upregulates oxytocin receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
    • ↑ Inflammatory cytokine, prostaglandin, and collagenase

Preterm birth

All pathways leading to preterm labor (above) can progress to preterm birth.

Preterm birth may also be caused by cervical insufficiency:

• Cervical dilation Cervical dilation A measurement of the diameter of the cervical canal, reported in centimeters Normal and Abnormal Labor without contractions (not labor)
• Due to structural weakness of the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy:
  • Prior cervical surgery 
  • Ehlers-Danlos syndrome Ehlers-Danlos syndrome Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders that are characterized by hyperextensible skin, hypermobile joints, and fragility of the skin and connective tissue. Ehlers-Danlos Syndrome
  • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation

Clinical presentation

Pregnant women < 37 weeks’ gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care who present with:

• Labor-like contractions or pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Menstrual-like cramping
• Back or lower abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Pelvic or vaginal pressure
• Vaginal discharge (mucus plug)
• Vaginal bleeding
• Leaking fluid (preterm labor associated with PPROM)

Diagnosis

The key to diagnosing preterm labor is to determine whether cervical change is occurring, and if regular Regular Insulin contractions are causing those changes. The cervical length is also important in helping to predict preterm birth regardless of contractions.

Exam and initial monitoring

• Sterile Sterile Basic Procedures speculum exam (SSE): always done 1st
  • Visually assess cervical dilation Cervical dilation A measurement of the diameter of the cervical canal, reported in centimeters Normal and Abnormal Labor: ≥ 3 cm suggests preterm labor.
  • Assess membrane status: Pooling of fluid suggests PPROM.
  • Collected swabs for testing 
• Digital cervical examination (after SSE):
  • Exclude placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity previa and PPROM prior to cervical exams.
  • Often repeated to monitor for cervical change
• Fetal monitoring Fetal monitoring The primary goals of antepartum testing and monitoring are to assess fetal well-being, identify treatable situations that may cause complications, and evaluate for chromosomal abnormalities. These tests are divided into screening tests (which include cell-free DNA testing, serum analyte testing, and nuchal translucency measurements), and diagnostic tests, which provide a definitive diagnosis of aneuploidy and include chorionic villus sampling (CVS) and amniocentesis. Antepartum Testing and Monitoring and tocometry:
  • Tocometry: records uterine contractions
  • Fetal heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology monitor: verifies fetal well-being

Tests and imaging

• Testing for urogenital tract infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Rectovaginal culture for GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy (if not already obtained)
  • Microscopy (for vaginitis)
  • Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia and gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea test (high-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship only)
  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children and urine culture Urine culture Urinary tract infections (UTIs)
• Fetal fibronectin Fibronectin Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Connective Tissue: Histology (fFN):
  • fFN: an extracellular matrix protein Matrix protein Proteins associated with the inner surface of the lipid bilayer of the viral envelope. These proteins have been implicated in control of viral transcription and may possibly serve as the ‘glue’ that binds the nucleocapsid to the appropriate membrane site during viral budding from the host cell. Parainfluenza Virus present at the interface between the decidua and chorion Chorion The outermost extraembryonic membrane surrounding the developing embryo. In reptiles and birds, it adheres to the shell and allows exchange of gases between the egg and its environment. In mammals, the chorion evolves into the fetal contribution of the placenta. Placenta, Umbilical Cord, and Amniotic Cavity
  • Disruption of the interface releases fFN into cervical secretions.
  • Predicting preterm birth:
    • Detection of fFN helps to predict delivery within the next 7 days.
    • Most useful in cases with cervical lengths 20–30 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma 
    • ↑ Negative predictive value
    • ↓ Positive predictive value Positive predictive value The positive predictive value is the percentage of people with a positive test result who actually have the disease among all people with a positive result, regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests
  • False positives can be caused by:
    • Exposure to coital ejaculate within the last 24 hours
    • Blood
    • Digital cervical examinations
• Transvaginal ultrasound Transvaginal Ultrasound Obstetric Imaging:
  • Cervical length:
    • > 30 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma has ↑ negative predictive value Negative predictive value The NPV is the percentage of people with a negative test result who are actually disease free, among all people with a negative result regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests for preterm birth.
    • < 30 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma predicts ↑ risk for preterm birth.
• Obstetric abdominal ultrasound:
  • Confirm placental location.
  • Assess fluid volume:
    • Single deepest pocket of fluid: Normal range is 2–8 cm.
    • Amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity index: Normal range is 5–25 cm.
    • Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios: single deepest pocket ≤ 2 cm or amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity index ≤ 5 cm
    • Polyhydramnios Polyhydramnios Polyhydramnios is a pathological excess of amniotic fluid. Common causes of polyhydramnios include fetal anomalies, gestational diabetes, multiple gestations, and congenital infections. Patients are often asymptomatic but may present with dyspnea, extremity swelling, or abdominal distention. Polyhydramnios: single deepest pocket ≥ 8 cm or amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity index ≥ 24 cm
  • Estimate fetal weight (helpful for the pediatrics team).

Diagnostic criteria

Diagnosing preterm labor requires uterine contractions plus cervical change:

• Uterine contractions:
  • ≥ 4 in 20 minutes, or ≥ 8 in 60 minutes
• Cervical change:
  • Dilation ≥ 3 cm
  • Cervical length < 20 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma on ultrasound
  • Cervical length 20–30 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma on ultrasound with a positive fFN

Management

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship diagnosed with preterm labor should be hospitalized for observation of progressing labor and for treatment.

• Corticosteroids Corticosteroids Chorioretinitis ( betamethasone Betamethasone A glucocorticoid given orally, parenterally, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Its lack of mineralocorticoid properties makes betamethasone particularly suitable for treating cerebral edema and congenital adrenal hyperplasia. Glucocorticoids most commonly given):
  • Benefits: ↓ neonatal morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status
    • ↑ Fetal lung maturity → ↓ risk of neonatal respiratory distress
    • ↓ Intraventricular hemorrhage Intraventricular hemorrhage Bleeding within the cerebral ventricles. It is associated with intraventricular trauma, aneurysm, vascular malformations, hypertension and in very low birth weight infants. Intracerebral Hemorrhage
    • ↓ Necrotizing enterocolitis Necrotizing enterocolitis Necrotizing enterocolitis (NEC) is an intestinal inflammatory process that can lead to mucosal injury and necrosis. The condition is multifactorial, with underlying risk factors that include prematurity and formula feeding. The clinical presentation varies in severity from feeding intolerance, acute findings on abdominal exam, and systemic symptoms. Necrotizing Enterocolitis
    • ↓ Death
  • Dosage Dosage Dosage Calculation:
    • A single course: 2 doses, 24 hours apart
    • Maximum benefit: 48 hours to 7 days after the 1st dose
  • Give to:
    • All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship < 34 weeks
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 34–37 weeks when delivery is anticipated within 7 days 
• Magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes sulfate:
  • Benefits:
    • Fetal neuroprotection → ↓ cerebral palsy Cerebral palsy Cerebral palsy (CP) refers to a group of conditions resulting in motor impairment affecting tone and posture and limiting physical activity. Cerebral palsy is the most common cause of childhood disability. It is caused by a nonprogressive CNS injury to the fetal or infant brain. Cerebral Palsy
    • Beneficial when given at the time of delivery
  • Give to patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship < 32 weeks’ gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care.
• Tocolytics:
  • Benefits:
    • Lessen contraction strength and intensity
    • Given for up to 48 hours only → allows for maximal benefit of corticosteroids Corticosteroids Chorioretinitis
  • Options:
    • Indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
    • Nifedipine Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
    • Terbutaline Terbutaline A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic. Asthma Drugs
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Intra-amniotic infection
    • PPROM
    • Nonreassuring fetal status
    • Nonviable fetus
    • Maternal instability (e.g., maternal hemorrhage, severe preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders)
• GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy prophylaxis Prophylaxis Cephalosporins:
  • IV penicillin Penicillin Rheumatic Fever or ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins
  • Treat during labor if GBS GBS An acute inflammatory autoimmune neuritis caused by t cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. Polyneuropathy status is positive or unknown.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with recent documented negative cultures do not require treatment.

Prevention

History of spontaneous preterm birth

• Progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones supplementation
• Cerclage:
  • A permanent suture placed in a purse-string fashion around the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy to keep it closed.
  • Transvaginal ultrasound Transvaginal Ultrasound Obstetric Imaging screening Screening Preoperative Care in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a history of cervical insufficiency 
  • Indicated for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship < 24 weeks with a cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy < 25 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
  • Cut in labor: Force of contractions will cause the suture to tear through the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy.
• Preconception correction of any uterine malformations:
  • Myomectomy 
  • Resection of uterine septum
• Preconception optimization of:
  • Weight
  • Nutrition
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation

History of indicated preterm birth

• Low-dose aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) → reduces the risk of recurrent preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders
• Preconception optimization of chronic medical conditions

Differential Diagnosis

• False labor/Braxton Hicks contractions: uterine contractions without cervical changes. Mild, irregular contractions are normal throughout pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care. Braxton Hicks contractions typically do not increase in intensity or duration but may occur more frequently with increased gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care. No clear test or threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction exists to identify who will progress onto true labor. Therefore, serial assessment is often required for diagnosis. Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration and extended activity have been associated with false labor.
• Preterm prelabor rupture of membrane (PPROM): the rupture of membranes ( chorion Chorion The outermost extraembryonic membrane surrounding the developing embryo. In reptiles and birds, it adheres to the shell and allows exchange of gases between the egg and its environment. In mammals, the chorion evolves into the fetal contribution of the placenta. Placenta, Umbilical Cord, and Amniotic Cavity and amnion Amnion The innermost membranous sac that surrounds and protects the developing embryo which is bathed in the amniotic fluid. Amnion cells are secretory epithelial cells and contribute to the amniotic fluid. Placenta, Umbilical Cord, and Amniotic Cavity) before the onset of labor. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually present with a “gush of fluid” from the vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy. The key difference between PPROM and preterm labor is the presence of contractions. Contractions will initially be absent in PPROM but often develop if infection is present. Preterm labor may be precipitated by PPROM. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are at high risk for ascending intra-amniotic infection once membranes have ruptured.