Abstract
Morning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient’s chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case.
This report examines the story of a 43-year-old (gravida 3, para 2) woman who sought evaluation for leakage of vaginal fluid at 15 weeks of gestation. Using questions, physical examination, and testing, an illness script for the presentation emerges. As her clinical course progresses, the differential is refined until a final diagnosis is made.
Reason for presentation:
leakage of vaginal fluid
Part 1: The Case
History of Present Illness:
A 43-year-old (gravida 3, para 2) woman presented to the obstetrics emergency department at an urban, safety-net hospital in Texas for leakage of vaginal fluid at 15 weeks of gestation. When she stood up that morning, she felt a gush of clear fluid, which she initially thought was urine. She experienced five episodes of similar leakage of fluid throughout the day. She called the obstetrics nurse helpline and was instructed to seek evaluation in the emergency department. She did not have any headaches, vision changes, chest pain, shortness of breath, nausea/vomiting, diarrhea, or dysuria. Additional information about the patient is shown in Box 1.
Box 1: Obstetrical and Gynecologic History, Medical and Surgical History, Medications, Allergies, and Social History.
Obstetrical and Gynecologic History:
Obstetrical history: The current pregnancy and her two prior pregnancies were conceived through in vitro fertilization. Her first pregnancy was complicated by gestational hypertension, and the second pregnancy was complicated by gestational diabetes. Her current pregnancy is complicated by hypertension but had been progressing well otherwise. She has no history of miscarriage, cervical insufficiency, preterm labor, or preterm delivery.
Gynecologic history: A recent Pap smear was positive for human papillomavirus (no history of abnormal Pap smears). She had not previously had any sexually transmitted infections. She is sexually active with her husband and they are in a monogamous relationship.
Medical and Surgical History:
She received a diagnosis of chronic hypertension after her first pregnancy but is not currently requiring treatment with antihypertensive medications. She has not had any prior surgical procedures.
Medications:
Prenatal vitamins
Aspirin 81 mg for preeclampsia prevention
Allergies or Adverse Reactions:
No known drug allergies
Social History:
She lives with her husband and two children and feels safe at home. She does not use alcohol, tobacco, or other drugs. She speaks Spanish as a primary language and requests an interpreter for all medical interactions.
WHAT ADDITIONAL QUESTIONS WOULD HELP FORMULATE THE PROBLEM REPRESENTATION AND GENERATE AN INITIAL DIFFERENTIAL DIAGNOSIS?
Q1: Does the patient have any abdominal pain, pelvic pressure, or vaginal bleeding?
Rationale for question: Leakage of vaginal fluid associated with abdominopelvic pain and/or vaginal bleeding suggests a threatened or ongoing miscarriage. Miscarriage, also referred to as spontaneous abortion, is generally defined as a pregnancy loss before 20 weeks of gestation.
Answer: She has not had any abdominal pain, pelvic pressure, or vaginal bleeding associated with the leakage of vaginal fluid.
Q2: Is there any odor or color associated with the leakage of vaginal fluid, and does the patient report any fevers, chills, or malaise?
Rationale for question: Malodorous vaginal discharge, or abnormally colored discharge (anything aside from clear or white), suggests a lower genital tract infection. Fevers, chills, or malaise would raise concern for a systemic infection, which may be caused by chorioamnionitis. Chorioamnionitis, also called intraamniotic infection, is defined as infection with resultant inflammation of any combination of the amniotic fluid, placenta, fetus, fetal membranes, or decidua, and it occurs predominantly by ascending bacterial invasion from the lower genital tract.1
Answer: There is no color or odor associated with the fluid. She has not had any fevers, chills, or malaise.
Q3: Is the leakage associated with any specific activities?
Rationale for question: Leakage of clear fluid that occurs with activities that increase intraabdominal pressure, such as sneezing, jumping, or lifting heavy objects, is suggestive of stress urinary incontinence, which is not uncommon during pregnancy; however, leakage of vaginal fluid with activity can also be observed after premature rupture of membranes.
Answer: She reports that the vaginal fluid leakage occurs sporadically and is not associated with any specific activities.
Part 2: Formulating the Problem Representation and Building the Differential Diagnosis
This patient presented with leakage of vaginal fluid at 15 weeks of gestation without symptoms of miscarriage (i.e., no vaginal bleeding or abdominal pain). The differential diagnosis can be classified into infectious and noninfectious etiologies, with the latter including pregnancy-related and non–pregnancy-related causes. Box 2 expands the diagnostic possibilities within each of these categories.
Box 2: Framework for Approaching the Differential Diagnosis of Leakage of Fluid During Pregnancy.
Infectious Etiologies:
Sexually transmitted infections: gonorrhea, chlamydia, or trichomonas
Non–sexually transmitted infections: bacterial vaginosis, candida vulvovaginitis, urinary tract infection
Noninfectious Etiologies:
Pregnancy-related causes
Prelabor rupture of membranes (PROM)
Increased physiologic discharge during pregnancy
Non–pregnancy-related causes
Urinary incontinence
Perspiration
WHAT ADDITIONAL INVESTIGATIONS WOULD BE HELPFUL?
The evaluation of a pregnant person presenting with leakage of vaginal fluid centers on the history and physical examination. After obtaining a focused history, the diagnosis can usually be made after physical examination and bedside ultrasound imaging. Key elements of the physical examination include abdominal and pelvic examinations. Abdominal examination should include assessment for tenderness on palpation of the uterine fundus, which would suggest an intrauterine infectious process. A sterile speculum examination should be performed to assess for three specific findings that would be consistent with rupture of membranes: pooling, positive nitrazine test, and ferning. Pooling is the direct observation of amniotic fluid leaking from the cervical os and collecting in the vaginal vault. Nitrazine paper can be used to test the pH of this fluid. Amniotic fluid usually has a pH of 7.0 to 7.3, different from a normal vaginal pH of 3.8 to 4.2. Nitrazine paper will turn blue in the presence of amniotic fluid, but not normal vaginal fluid2; however, other alkaline substances, including blood and seminal fluid, can also cause nitrazine paper to turn blue. Ferning refers to the delicate fern-like pattern that appears when dried amniotic fluid is viewed under a microscope. The presence of at least two of these three signs supports a clinical diagnosis of rupture of membranes. Additional information can be obtained from bedside ultrasonography. Low amniotic fluid (defined as amniotic fluid index <5 cm or maximum vertical pocket <2 cm) supports the diagnosis of rupture of membranes in the appropriate clinical scenario. If the diagnosis remains unclear, several commercial tests, including those that test vaginal fluid for levels of placental alpha microglobulin-1 protein and insulin-like growth factor binding protein 1, are available to help guide the diagnosis. Saline microscopy and endocervical swabs for nucleic acid amplification testing can be used to evaluate vaginal fluid for microbial causes of cervicitis or vaginitis. Laboratory tests play a limited role when evaluating leakage of vaginal fluid in a pregnant person, although a complete blood count with differential may help assess for systemic infection.
PHYSICAL EXAMINATION
The patient’s vital signs are shown in Box 3.
Box 3: Vital Signs.
Temperature: 98.8°F (oral); heart rate: 86 beats per minute; blood pressure: 133/71 mm Hg; respiratory rate: 18 breaths per minute; and O2 saturation: 98% breathing ambient air.
The patient appeared well nourished and in no distress. Her heart rhythm was regular, with clear first and second heart sounds and a soft systolic murmur. Examination of the chest showed normal ventilatory movement; there were no adventitious sounds on auscultation. The abdomen was soft, gravid, and nontender, with no rebound or guarding. A sterile speculum examination demonstrated pooling of clear fluid in the vaginal canal. Samples were collected for nitrazine and ferning evaluations, and swabs were obtained for microbial tests. The cervix was visually closed. There was no blood in the cervical os or within the vaginal canal.
RESULTS
The results of laboratory testing are shown in Figure 1, and imaging studies are shown in Figure 2 and Box 4.
Figure 1. The Patient’s Laboratory Results.
This illustration shows the results of laboratory testing for a pregnant patient presenting with leakage of fluid in the second trimester. Reference ranges are in parentheses. HCT denotes hematocrit; Hgb, hemoglobin; PLT, platelet; NAAT, nucleic acid amplification test; and WBC, white blood cell.
Figure 2. The Patient’s Ultrasound and an Ultrasound from a Normal Pregnancy.
Representative ultrasound images are presented to demonstrate the concept of oligohydramnios (decreased amniotic fluid, defined as amniotic fluid index <5 cm or maximum vertical pocket <2 cm). Panel A shows the fetus in this case with oligohydramnios in the second trimester. Amniotic fluid appears anechoic on ultrasound imaging, and there is virtually none seen in this image. For comparison, Panel B shows a fetus with a normal volume of amniotic fluid in the second trimester (area of amniotic fluid is marked with the star). For both images, fetal anatomy is labeled, including bladder, stomach, and heart (HRT).
Box 4: Imaging Results.
Bedside transabdominal ultrasound demonstrated a single fetus in transverse position measuring 15 weeks 1 day by biometry. Limited fluid was seen around the fetus, with amniotic fluid index measuring 0.3 cm (normal amniotic fluid index is 5 to 24 cm). Fetal cardiac activity was present, with a fetal heart rate of 156 beats per minute.
Part 3: Refining the Differential Diagnosis
The patient’s history, physical examination, and ultrasound imaging results are all consistent with rupture of membranes and leakage of amniotic fluid — that is, prelabor rupture of membranes or PROM (Box 5). The earliest stage of fetal maturity when there is a chance of extrauterine survival differs on the basis of the clinical setting and the capabilities of each neonatal intensive care unit. In the United States, the limit of viability is typically considered to be 22 to 23 weeks of gestation, although neonates born at this early gestational age face substantial risks of morbidity and mortality. This patient has presented with PROM at 15 weeks of gestation, which is well before the limit of viability and therefore represents a case of previable PROM.
Box 5: Making the Diagnosis.
Infectious Etiologies:
Sexually transmitted infections: gonorrhea, chlamydia, or trichomonas
Non-sexually transmitted infections: bacterial vaginosis, candida vulvovaginitis, urinary tract infection
Noninfectious Etiologies:
Pregnancy-related causes
Prelabor rupture of membranes (PROM)
Increased physiologic discharge during pregnancy
Non–pregnancy-related causes
Urinary incontinence
Perspiration
There is no clear evidence of intrauterine or systemic infection on examination, although her elevated white blood cell (WBC) count and neutrophilic predominance may suggest a developing infection. The primary infectious consideration is chorioamnionitis. Although the patient is stable at this time, clinical vigilance is required, because systemic infection, placental abruption with resultant hemorrhage, or preterm labor can develop quickly and can lead to substantial maternal morbidity.
WHAT ARE THE NEXT STEPS IN MANAGEMENT?
Previable PROM affects less than 1% of pregnancies.3 It may occur spontaneously or in association with procedures that breach the fetal membranes. Major risk factors for spontaneous previable PROM are similar to those for preterm labor: a history of cervical insufficiency or preterm labor, a history of preterm PROM, and multifetal gestation.4 Most patients presenting with previable PROM deliver soon after presentation, with the majority delivering within 1 week and median latency to delivery ranging from 6 to 13 days.5 Pregnancy complications associated with previable PROM include preterm birth, maternal and fetal/neonatal infection, placental abruption and maternal hemorrhage, retained placenta, fetal/neonatal death, and maternal morbidity and mortality. Risk of maternal morbidity is substantial. Up to one in seven patients with previable PROM may experience severe morbidity, including sepsis, acute renal insufficiency, deep venous thrombosis, pulmonary embolus, or death.6 Interventions needed may include intensive care unit admission (and readmission), uterine curettage, hysterectomy, or blood transfusion. The current standard of care for previable PROM described by the American College of Obstetricians and Gynecologists is to offer immediate delivery (pregnancy termination) or expectant management, with the understanding that waiting poses a substantial risk to maternal health and is associated with poor neonatal outcomes. Pregnancy termination, also referred to as abortion, may entail either induction of labor or dilation and evacuation. Shared decision-making is encouraged in formulating a management plan tailored to the patient.7
At the time this patient presented for care in Texas, state-level legislation had effectively banned all abortions after 6 weeks of gestation without an immediate threat to maternal life, although what constitutes an immediate threat to maternal life is not specifically defined by the law and interpretations vary among healthcare providers and systems. Such legislation severely encroaches on access to reproductive care and disproportionately harms people from underserved communities, as in this case.8 Texas Senate Bill 8 bans abortions after cardiac activity is detected, with a novel enforcement mechanism by private plaintiffs through civil lawsuits.9 Texas Senate Bill 4 states that a physician violating the law that requires administration of medicine to end a pregnancy to be within the first 49 days of pregnancy and according to a new set of treatment protocols, informed consent procedures, and reporting requirements, has committed a felony, with punishment that includes jail time of up to 2 years and a $10,000 fine.10 Whereas the evidence demonstrates severe maternal risks and negligible fetal benefits associated with expectant management for this patient, Texas physicians are unable to provide the standard of care as outlined by American College of Obstetricians and Gynecologists: offering both pregnancy termination and expectant management. Instead, obstetricians are only legally permitted to offer expectant management. They must wait until patients deteriorate and demonstrably prove an immediate threat to maternal life. The legislation does not comment specifically on the legality of physician counseling regarding traveling to other states where abortion is permitted, but many physicians fear that such counseling may instigate litigation and hesitate to discuss options to travel out of state for abortion care.
Clinical Course 1
The patient was admitted to the obstetrics antepartum service for observation, given the concern for developing infection. She was counseled regarding the risks and benefits associated with expectant management versus pregnancy termination in the setting of previable PROM and informed that only expectant management was legally permitted in the state of Texas. The option of traveling out of state for pregnancy termination was discussed. The patient elected to pursue expectant management. On hospital day 2, she reported intermittent, mild lower abdominal pain, but remained afebrile with no other signs or symptoms of infection. Repeat WBC count decreased to 11.9 × 103/μl, and the patient’s abdominal pain resolved. On hospital day 3, she was discharged home with an expectant management plan. She was counseled to check her temperature twice daily at home and to return to the hospital immediately if she had a fever or any other infectious symptoms, such as abdominal pain or foul-smelling vaginal discharge. Close observation in the obstetrics clinic was arranged.
Clinical Course 2
The patient represented 6 days after discharge with increased leakage of vaginal fluid, vaginal bleeding, and subjective fevers. On examination, she was afebrile with no abdominal tenderness. Sterile speculum examination showed ongoing trickling of clear amniotic fluid, no bleeding, and a closed cervix. Results of repeat laboratory testing were similar to those obtained before her discharge. The patient expressed the desire to proceed with an abortion because she feared that her life was at risk. She was counseled that abortion was not permitted unless there was an immediate threat to maternal life and that she did not currently meet these criteria. The option of traveling out of state for an abortion was again discussed, but the patient did not have the financial resources to pursue this. After several hours of observation, she was discharged home with strict precautions and plans for close clinic observation.
Clinical Course 3
The patient sought repeat evaluation 3 days later for fevers, chills, muscle aches, and headaches. The gestational age was now 16 weeks and 3 days. Examination demonstrated a temperature of 100.5°F, maternal heart rate of 112 beats per minute, and marked fundal tenderness. Bedside ultrasonography showed fetal cardiac activity with fetal heart rate of 182 (normal fetal heart rate ranges from 110 to 160 beats per minute) and persistent oligohydramnios. Laboratory data showed elevated WBC count of 21.2×103/μl. The clinical picture was now consistent with chorioamnionitis. Given several maternal risks, including sepsis, organ failure, and death, the patient was now legally permitted to have an abortion in Texas because of the immediate threat to maternal life. Per hospital policy designed to adhere to state laws and minimize legal liability, she was evaluated by both the attending obstetrician on call and the maternal-fetal medicine attending physician on call. Her case was discussed with the Chief of Obstetrics and the Chief Medical Officer. All four attending physicians agreed with the diagnosis of chorioamnionitis and the recommendation for abortion as a result of the immediate threat to maternal life. The patient was counseled regarding the risks and benefits associated with medical (induction of labor) versus surgical (dilation and evacuation) abortion, and she elected to proceed with dilation and evacuation.
She was admitted to the labor and delivery department, started receiving antibiotic treatment with ampicillin and gentamicin, and monitored closely according to the hospital’s sepsis protocol. For cervical ripening, seven hygroscopic dilators (laminaria) were placed in the cervix, and she received buccal misoprostol 1 hour before the procedure. On hospital day 2, an uncomplicated dilation and evacuation was performed in the operating room. Antibiotics were discontinued after she remained afebrile with normal heart rate and normal abdominal examination for 24 hours after the procedure. She recovered well postoperatively and was provided with grief counseling. She declined contraception and desired future pregnancy as soon as physicians advised it to be safe. She was discharged on postoperative day 1. In clinic follow-up, she continued to recover well without complications. Postpartum depression screening showed elevated depressive and anxiety symptoms. The patient reported coping well with excellent support from her family and declined referral for psychotherapy or psychiatric follow-up. She again expressed a desire for future pregnancy and received preconception counseling to optimize her health before conception.
Part 4: Making the Diagnosis
FINAL DIAGNOSIS
For this patient presenting at 15 weeks of gestation with PROM, there was an extremely small likelihood that she would remain pregnant long enough to achieve a viable gestation.5,11 Expectant management in this clinical situation is associated with risks of serious maternal morbidity and even mortality. Recently, a small retrospective cohort study evaluated outcomes from expectant management of previable PROM and other severe pregnancy complications in two safety-net hospitals in Texas after passage of Senate Bills 8 and 4. The majority of patients (57%) experienced serious maternal morbidity compared with only 33% among patients choosing pregnancy termination in similar circumstances in states without restrictive legislation. Despite incurring such maternal risks, fetal outcomes were poor with the expectant management strategy; in 96% of cases, the fetus/neonate did not survive.12 In addition to the immediate risks of severe maternal morbidity, there are long-term impacts on maternal health. For example, chorioamnionitis can cause intrauterine scarring and impaired fertility.13 Complications during birth can increase the risk of psychological distress and posttraumatic stress disorder.14
In Texas and many other states, obstetricians caring for patients with previable PROM and other severe pregnancy complications are prohibited from providing the standard of care. Vague legislation written by lawmakers without medical expertise makes medical decision-making difficult and not evidence based. Medical teams often struggle with such questions as “How imminent does the threat of death need to be?” Few clinicians in the United States ever imagined asking such questions and counseling patients about how their state of residence limits their ability to access the standard of care when facing unexpected and tragic pregnancy complications.
Take-Home Points.
Previable prelabor rupture of membranes (PROM) is a clinical diagnosis that can be made on the basis of sterile speculum examination and bedside ultrasonography. Examination findings supporting this diagnosis include pooling, positive nitrazine test, and ferning, in addition to low levels of amniotic fluid (oligohydramnios).
Expectant management of previable PROM is associated with the potential for substantial maternal morbidity and even mortality. This case highlights one of the most prominent risks, that of maternal intraamniotic infection, which can lead to life-threatening sepsis.
Standard of care in the United States for previable PROM is to engage the patient in a shared decision-making process that weighs the relative risks and benefits associated with pregnancy termination versus expectant management.
In states where there are strict abortion restrictions, these limitations severely limit the ability of medical staff and patients to pursue the standard of care endorsed by the American College of Obstetricians and Gynecologists and may put the patient’s life at great risk.
Footnotes
Disclosures
Author disclosures are available at evidence.nejm.org.
References
- 1.American College of Obstetricians and Gynecologists. Committee opinion No. 712: intrapartum management of intraamniotic infection. Obstet Gynecol 2017;130:e95–e101. DOI: 10.1097/AOG.0000000000002236. [DOI] [PubMed] [Google Scholar]
- 2.Seeds AE, Hellegers AE. Acid-base determinations in human amniotic fluid throughout pregnancy. Am J Obstet Gynecol 1968;101:257–260. DOI: 10.1016/0002-9378(68)90196-8. [DOI] [PubMed] [Google Scholar]
- 3.Linehan LA, Walsh J, Morris A, et al. Neonatal and maternal outcomes following midtrimester preterm premature rupture of the membranes: a retrospective cohort study. BMC Pregnancy Childbirth 2016;16:25. DOI: 10.1186/s12884-016-0813-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.McElrath TF, Hecht JL, Dammann O, et al. Pregnancy disorders that lead to delivery before the 28th week of gestation: an epidemiologic approach to classification. Am J Epidemiol 2008;168:980–989. DOI: 10.1093/aje/kwn202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Waters TP, Mercer BM. The management of preterm premature rupture of the membranes near the limit of fetal viability. Am J Obstet Gynecol 2009;201:230–240. DOI: 10.1016/j.ajog.2009.06.049. [DOI] [PubMed] [Google Scholar]
- 6.Dotters-Katz SK, Panzer A, Grace MR, et al. Maternal morbidity after previable prelabor rupture of membranes. Obstet Gynecol 2017;129:101–106. DOI: 10.1097/AOG.0000000000001803. [DOI] [PubMed] [Google Scholar]
- 7.American College of Obstetricians and Gynecologists. Prelabor rupture of membranes: ACOG Practice Bulletin, Number 217. Obset Gynecol 2020;135:e80–e97. DOI: 10.1097/AOG.0000000000003700. [DOI] [PubMed] [Google Scholar]
- 8.Perritt J, Grossman D. The health consequences of restrictive abortion laws. JAMA Intern Med 2021;181:713–714. DOI: 10.1001/jamainternmed.2020.9279. [DOI] [PubMed] [Google Scholar]
- 9.Texas Senate Bill No. 8. 87th Legislature, 2021 Special Session (Texas 2021). May 19, 2021. (https://capitol.texas.gov/tlodocs/87R/billtext/pdf/SB00008F.pdf).
- 10.Texas Senate Bill No. 4. 87th Legislature, 2021 Special Session (Texas 2021). December 2, 2021. (https://capitol.texas.gov/tlodocs/872/billtext/pdf/SB00004F.pdf).
- 11.Falk SJ, Campbell LJ, Lee-Parritz A, et al. Expectant management in spontaneous preterm premature rupture of membranes between 14 and 24 weeks’ gestation. J Perinatol 2004;24:611–616. DOI: 10.1038/sj.jp.7211163. [DOI] [PubMed] [Google Scholar]
- 12.Nambiar A, Patel S, Santiago-Munoz P, Spong CY, Nelson DB. Maternal morbidity and fetal outcomes among pregnant women at 22 weeks’ gestation or less with complications in 2 Texas hospitals after legislation on abortion. Am J Obstet Gynecol 2022;227:648–650.e1. DOI: 10.1016/j.ajog.2022.06.060. [DOI] [PubMed] [Google Scholar]
- 13.Shai D, Orvieto R, Touval O, et al. Fertility and pregnancy complications following chorioamnionitis. Hum Fertil (Camb) 2021;2021:1–4. DOI: 10.1080/14647273.2021.1981552. [DOI] [PubMed] [Google Scholar]
- 14.Ertan D, Hingray C, Burlacu E, Sterlé A, El-Hage W. Post-traumatic stress disorder following childbirth. BMC Psychiatry 2021;21:155. DOI: 10.1186/s12888-021-03158-6. [DOI] [PMC free article] [PubMed] [Google Scholar]