Preterm labor and birth

Preterm labor and birth

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Overview

Preterm birth is any birth that happens between 20 weeks of gestation and 36 6/7 weeks of gestation. In Europe it is defined after 22 weeks and before 37 weeks of gestation. The gestation can be dated using first trimester ultrasound. In the US, approximately 12% of the births are preterm, while in Europe it varies between 5-18%. The diagnosis is made based on clinical criteria which include: cervical dilation of at least 2cm and/or cervical effacement, which happens with regular uterine contractions. It may happen with or without rupture of membrane. Preterm labor and delivery is associated to many risks for the babies such as: respiratory distress syndrome, periventricular leukomalacia, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, late-onset infection, retinopathy of prematurity, cerebral palsy and other adverse neurological outcomes. (25300768)

Historical Perspective

[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].

The association between [important risk factor/cause] and [disease name] was made in/during [year/event].

In the 1930s, George Corner was the first to suggest the association between progesterone and the development of preterm labor.

In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].

There have been several outbreaks of [disease name], including -----.

In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].

Classification

Preterm labor may be classified according to the WHO into 3 subtypes/groups: extremely preterm (<28 weeks), very preterm (28 to 32 weeks), moderate to late preterm (32-37 weeks). https://www.who.int/news-room/fact-sheets/detail/preterm-birth

Pathophysiology

• It is thought that preterm labor is the is mediated by either progesterone, which promotes uterine relaxation to maintain pregnancy and inflammation of the gestational tissues, which acts as a key trigger opposing the effects of progesterone and inducing progesterone withdraw.
• The switch from a quiescent myometrium into an active one is mediated by inflammatory pathways that include IL-8, IL-1, IL-6 and proteins such as oxytocin receptor, connexin 43 and prostaglandin receptor.
• Changes in the extracellular matrix proteins leads to cervical effacement and is the result of an increase in glycosaminoglycans and loss in collagen cross-linking results in a decrease in the tensile strength of the cervix.
• Increase in inflammatory factors such as TNF-a and IL-1 lead to the activation of proteases (MMP-8) and dissolution of fibronectin which leads to withdrawal of decidual support for pregnancy. This event causes separation of the chorioamniotic membranes from the decidua and eventually membrane rupture.
• Therefore, the occurrence of preterm labor with intact membranes depends on a balance between pro-labor/pro-inflammatory factors versus pro-pregnancy effects of progesterone.
• Preterm premature rupture of membranes (PPROM) has unknown etiology and may lead to preterm labor.
• Some factors increase the risk of PPROM such as cervical shortening or intra-amniotic infection.

Causes

• Preterm labor may be caused by infection, uterine ovedistension, decidual senescence, vascular disorders, stress, cervical disease, decline in progesterone action, or breakdown in maternal-fetal tolerance.
• So far, only intra-amniotic infection has been shown to cause preterm delivery. The other factors are being associated based on reports by clinical, epidemiologic, placental pathologic, or experimental studies.
• Intra-amniotic infections can be subclinical. One in four preterm infants are born due to this cause.
  • The most frequent route is the ascending pathway, but hematogenous dissemination can occur.
  • Microorganisms are recognized by pattern recognition receptors, such as toll-like receptors (TLRs)
  • TLRs stimulate the production of chemokines such as (IL-8, and C-C motif ligand 2 (CCL2), cytokines such as IL-1b and TNF-a, prostaglandins and proteases which activate the quiescent myometrium and stimulates parturition.
  • In 30% of cases of intra-amniotic infection, bacteria can be found in the fetal circulation which causes fetal systemic inflammatory response. These fetuses are at risk for long-term complications, such as cerebral palsy and chronic lung disease, which emphasizes that these complications may not only occur due to immaturity but also inflammatory response.

Differentiating preterm labor from other Diseases

Preterm labor diagnosis is not challenging and the it must be investigated if it is caused by other diseases that also cause abdominal pain, rupture of membrane and fetal distress.

Epidemiology and Demographics

The incidence of preterm labor is approximately 12% of the births in the United States. In Europe the incidence varies between 5-18% of the births.

Risk Factors

There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

Screening

There is insufficient evidence to recommend routine screening for preterm labor.

Natural History, Complications, and Prognosis

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

OR

Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

OR

Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

Diagnosis

Diagnostic Study of Choice

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].

OR

The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

There are no established criteria for the diagnosis of [disease name].

History and Symptoms

The majority of patients with [disease name] are asymptomatic.

OR

The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].

Physical Examination

Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Laboratory Findings

An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

Electrocardiogram

There are no ECG findings associated with preterm labor.

X-ray

There are no x-ray findings associated with preterm labor.

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with [disease name].

OR

Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

CT scan

There are no CT scan findings associated with preterm labor.

MRI

There are no MRI findings associated with preterm labor.

Other Imaging Findings

There are no other imaging findings associated with preterm labor.

Other Diagnostic Studies

Uterine monitoring may be helpful in the diagnosis of preterm labor. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR   The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].