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Prelabor Rupture of Membranes

Prelabor rupture of membranes (PROM), previously known as premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother's last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis rupture of membranes, refers to the rupture of the amniotic sac before the onset of labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor. Prelabor rupture of membranes may occur in term or preterm pregnancies. The presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor includes a painless discharge of clear or pale-yellow 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 in the form of a large gush or as small, intermittent trickles. Management depends on 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. Beyond 34 weeks, the recommendation is to induce labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor and, if indicated, use antibiotics for group B streptococcus Group B Streptococcus Meningitis in Children ( 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. Prior to 34 weeks, management involves prolonging the 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 as long as possible while avoiding intra-amniotic infection (IAI), also known as 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, and minimizing risk to the fetus. The primary complications associated with PROM are related to 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 and preterm birth Preterm birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth.

Last updated: 11 Mar, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Prelabor rupture of membranes (PROM) is defined as the rupture of fetal membranes (the fused 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 Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor ( regular Regular Insulin uterine contractions causing cervical change).

Epidemiology

Prelabor rupture of membranes complicates approximately 2%–3% of pregnancies.

Risk factors:

  • Genital 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 (e.g., 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)
  • PROM or preterm delivery in previous pregnancies
  • Uterine distension:
    • 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 
    • Multiple gestation
  • Cervical incompetence
  • Trauma
  • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
Table: Epidemiology of PROM
Pre-viable PROM Preterm PROM (PPROM) Term PROM
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 < 24 weeks 24–36 weeks > 37 weeks
Frequency < 1% of pregnancies
  • ~ 3% of pregnancies overall
  • ~ 30% of preterm pregnancies
~ 8% of pregnancies
PROM: prelabor rupture of membranes

Pathophysiology and Clinical Presentation

Anatomy

The fetal membranes create the amniotic sac to surround the fetus and protect it from infection. 

  • Composed of 2 layers: 
    • 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: 
      • Innermost layer
      • Contains 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 and fetus
    • 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
      • Separates 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 from maternal decidua (innermost uterine layer)
      • Acts as a protective barrier
  • 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: 2 distinct layers with the chorionic cavity Chorionic cavity A cavity which develops within the extraembryonic mesoderm. Gastrulation and Neurulation between
  • Later 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: Layers fuse to become a single amniochorion.
  • 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:
    • Produced primarily from fetal urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat
    • Allows for:
      • Fetal movement → skeletal development
      • Fetal breathing → lung development
The fetal membranes development

Fetal membranes at 7 weeks and 4 months of development:
The membranes arise from trophoblastic and mesodermal tissue. 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, the 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 are 2 distinct layers with a cavity between. As the 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 progresses, the 2 layers fuse to form a single amniochorion in direct contact with the maternal decidua.

Image by Lecturio.

Pathophysiology

  • Poorly understood
  • Membrane strength comes from: 
    • 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
    • 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
    • Laminin Laminin Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. Connective Tissue: Histology
  • Possible mechanism for PROM is the imbalance between matrix metalloprotease (MMP) and MMP inhibitors:
    • MMP degrades 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.
    • MMP inhibitors maintain membrane integrity.
  • Potential pathologic events may disrupt membranes:
    • Infection
    • 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
    • Mechanical stress
    • Bleeding

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

  • Sudden gush of fluid without labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor contractions
  • Often copious, but also small amounts
  • Continuous or intermittent leakage
  • Color of fluid may be:
    • Clear 
    • Straw colored
    • Greenish ( meconium Meconium The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the intestinal glands; bile pigments; fatty acids; amniotic fluid; and intrauterine debris. It constitutes the first stools passed by a newborn. Prenatal and Postnatal Physiology of the Neonate stained)
    • Blood tinged (concern for associated 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)
    • Purulent (infected)

Diagnosis

Once labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor is excluded, a sterile Sterile Basic Procedures speculum exam and ultrasound should be performed to diagnose PROM.

  • Pooling
    • Visualize 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 on sterile Sterile Basic Procedures speculum exam and ask the mother to bear down ( Valsalva maneuver Valsalva maneuver Forced expiratory effort against a closed glottis. Rectal Prolapse).
    • Positive test: visualization of fluid coming from 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 (often significant)
    • Most accurate diagnostic test
  • Nitrazine test
    • Collect sample of vaginal fluid on sterile Sterile Basic Procedures speculum exam.
    • Positive test: pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance paper turns blue in presence of basic 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.
    • Low 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 → also turns blue in presence of: 
      • Semen
      • 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
      • Blood
  • Ferning
    • Obtain swab of vaginal fluid → allow to dry on a glass slide
    • Positive result: Ferning pattern appears on a slide and is visible on microscopy.
    • Cervical mucus can leave a similar ferning pattern ( false positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests).
  • Ultrasound: 
    • Suggestive of PROM: 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 (maximal vertical pocket of fluid < 2 cm) 
    • Relatively low sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques and specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays:
      • PROM often exists without 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.
      • 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 often exists without PROM.
  • Exclude labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor:
Ctg in a case of prelabor rupture of membranes

Intrapartum 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 with tocometry:
The bottom panel shows tocometry (records uterine contractions). The upper panel shows the fetal heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology (baseline of around 140/min) with moderate variability and late heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology decelerations (descent time > 60 sec with nadir after the peak of the contraction, and slow return up to baseline of 140). The tracing is from a case of fetal cord prolapse 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 (a potential complication of PROM), which compromises fetal blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure. The fetal heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology pattern is nonreassuring.

Image: “CTG in a case of prelabor rupture of membranes” by Department of Obstetrics and Gynaecology, Royal United Hospital Bath NHS Trust Trust Confidence in or reliance on a person or thing. Conflict of Interest, Bath, UK. License: CC BY 2.0

Management

Management is based on 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, group B streptococcus Group B Streptococcus Meningitis in Children ( 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, signs of labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor or contractions, and signs of IAI.

General management

  • Confirm fetal well-being:
    • Non-stress test ( 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 with tocometry)
    • Assess 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 levels with ultrasound.
  • Deliver if:
    • > 34 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
    • IAI is present (regardless of 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).
  • Monitor for development of IAI; ↑ risk in PROM, ↑↑↑ risk in preterm prelabor rupture of membranes (PPROM):
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Maternal leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus > 15,000/L
    • Maternal tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • Fetal tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children > 160/min for ≥ 10 minutes
    • Purulent 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 on exam
    • Fundal tenderness
    • Contractions/ labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor
  • Antibiotics for group B streptococcus Group B Streptococcus Meningitis in Children ( 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):
    • IV penicillin Penicillin Rheumatic Fever or ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins in labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor
    • If preterm and/or 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 unknown → collect a swab at presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor
    • Treat in labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal 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 positive
      • 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 unknown with risk factors
    • Risk factors for fetal 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 disease:
      • Preterm (< 37 weeks gestation)
      • Rupture of membranes (ROM) ≥ 18 hours
      • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever ≥ 100.4°F (≥ 38°C)
      • Prior documented 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 colonization Colonization Bacteriology in urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat
      • Prior infant with early-onset 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 disease

Management of PROM by 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

Fetal age > 34 weeks:

  • Induction of labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor
  • Antibiotics: 
    • 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 prophylaxis Prophylaxis Cephalosporins only
    • Given if patient is:
      • 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 positive 
      • Unknown with risk factors 
      • 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 34–37 weeks (risk factor)

Fetal age 24–33 weeks:

  • Antibiotics:
    • Latency antibiotics: 
      • Attempt to ↑ time to delivery by preventing IAI
      • Regimen: azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides + ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins/ amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins
    • 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: Treat when delivery is imminent and 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 is positive or unknown.
  • 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
    • Benefits:
      • ↑ Fetal lung maturity
      • 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 (IVH)
      • ↓ Necrotizing enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis
  • Magnesium sulfate Magnesium Sulfate A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Laxatives: for fetal neuroprotection against cerebral palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies
  • Tocolytics: 
    • Given only for initial 48 hours (allows time for maximum benefit of steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors)
    • Prevents contractions if not yet started
    • Do not give if contractions are already present → likely due to infection → ↑ risk of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status
  • Delivery indications:
    • Achieve 34 weeks of gestation
    • IAI
    • Spontaneous labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor
    • Fetal distress

Fetal age < 24 weeks:

  • Expectant management or induction of labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor
  • No antibiotics, corticosteroids Corticosteroids Chorioretinitis, tocolysis, or magnesium sulfate Magnesium Sulfate A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Laxatives
  • ↑↑ Risk of infection if 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 continues

Complications

Neonatal complications

Complications can be related to:

  • Infection:
    • Fetal infection
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Neurodevelopmental impairment
  • Compromised blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure:
    • Umbilical cord Umbilical cord The flexible rope-like structure that connects a developing fetus to the placenta in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus. Placenta, Umbilical Cord, and Amniotic Cavity compression Compression Blunt Chest Trauma and/or prolapse
    • 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:
      • Occurs with rapid decompression of uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy
      • Obstetric emergency 
  • 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 (with early PPROM):
  • Preterm delivery:

Maternal complications

  • 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
    • Postpartum endometritis Postpartum Endometritis Inflammation of the endometrium, usually caused by intrauterine infections. Endometritis is the most common cause of postpartum fever. Endometritis
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
  • Postpartum hemorrhage Postpartum hemorrhage Postpartum hemorrhage is one of the most common and deadly obstetric complications. Since 2017, postpartum hemorrhage has been defined as blood loss greater than 1,000 mL for both cesarean and vaginal deliveries, or excessive blood loss with signs of hemodynamic instability. Postpartum Hemorrhage (common after IAI)
  • Deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus (due to prolonged bed rest in PPROM)

Differential Diagnosis

  • Urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. Urinary Incontinence: an involuntary loss of urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat. Urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. Urinary Incontinence is common towards the end of 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 due to increased pressure on the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess from the fetus. Prelabor rupture of membranes (PROM) should always be ruled out 1st (pooling, nitrazine test, ferning, and ultrasound). 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 should also be obtained to rule out urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection ( UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs)), which can increase the risk of urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. Urinary Incontinence. Management 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 is usually reassurance Reassurance Clinician–Patient Relationship and observation since incontinence is typically minor.
  • Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection: an infection of the urinary system most commonly caused by Enterobacteriaceae Enterobacteriaceae A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock. Cephalosporins, especially Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli. Presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor typically includes suprapubic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs), and urinary urgency Urinary Urgency Normal Pressure Hydrocephalus. Diagnosis is made with 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 culture. 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 is more common 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 and is diagnosed when flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever accompany the UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs). Management is with antibiotics.
  • Vaginal infection/vaginitis: 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 of 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 can resulting in discharge, itching, and discomfort. The most common causes include 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 ( BV BV 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), candidiasis Candidiasis 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, and trichomoniasis. Sexually transmitted 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 can also cause cervicitis Cervicitis Inflammation of the uterine cervix. Gonorrhea with purulent discharge Purulent Discharge Dacryocystitis. Discharge from vaginitis (especially BV BV 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) can be confused with 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. Diagnosis is made on microscopy with KOH and wet prep of vaginal discharge. Management is with antimicrobials.
  • Semen: If the patient presents to labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor and delivery complaining of PROM, ask directly about recent sexual activity. Semen will cause nitrazine paper to turn blue ( false positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests), and sperm can be seen on microscopy. If PROM is confidently ruled out and history or exam suggest recent unprotected intercourse, the gush of fluid is commonly semen.

References

  1. Scorza, W. E. (2020). Management of prelabor rupture of the fetal membranes at term. In Barss, V. A. (Ed.), UpToDate. Retrieved February 22, 2021, from https://www.uptodate.com/contents/management-of-prelabor-rupture-of-the-fetal-membranes-at-term
  2. Duff, P. (2020). Preterm prelabor rupture of membranes: Clinical manifestations and diagnosis. In Barss, V. A. (Ed.), UpToDate. Retrieved February 22, 2021, from https://www.uptodate.com/contents/preterm-prelabor-rupture-of-membranes-clinical-manifestations-and-diagnosis
  3. Duff, P. (2020). Preterm prelabor rupture of membranes: Management and outcomes. In Barss, V. A. (Ed.), UpToDate. Retrieved February 24, 2021, from https://www.uptodate.com/contents/preterm-prelabor-rupture-of-membranes-management-and-outcome 
  4. Baker, C. J. (2020). Neonatal group B streptococcal disease: Prevention. In Barss, V. A. (Ed.), UpToDate. Retrieved February 24, 2021, from https://www.uptodate.com/contents/neonatal-group-b-streptococcal-disease-prevention
  5. American College of Obstetrics and Gynecology (2020). Practice Bulletin No. 217: Prelabor rupture of membranes. Retrieved February 22, 2021, from https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/03/prelabor-rupture-of-membranes 
  6. Cunningham, F. G., Leveno, K. J., et al. (2010). Williams Obstetrics (23rd ed. pp. 50‒54).
  7. Dayal, S. (2020). Premature rupture of membranes. In Hong, P. (Ed.) StatPearls. Retrieved February 24, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/27659/

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