12: 16-year-old female with vaginal bleeding and UCG

Question 1

Chlamydia: Epidemiology, Course of Disease, & Screening Recommendations

Answer 1

Epidemiology
Chlamydial infection is the most common sexually transmitted bacterial infection in the United States. In 2007, more than 1.1 million chlamydia cases were reported to the CDC. It is thought that another million cases of chlamydia remain unreported.

Course of disease
Chlamydia is often insidious and asymptomatic. In women, genital chlamydial infection may result in urethritis, cervicitis, pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain. Chlamydial infection during pregnancy is related to adverse pregnancy outcomes including miscarriage, premature rupture of membranes, preterm labor, low birth weight, and infant mortality.

Screening recommendations
The USPSTF found fair evidence that nucleic acid amplification tests (NAATs) can identify chlamydial infection in asymptomatic men and women, including asymptomatic pregnant women, with high test specificity. In low prevalence populations, however, a positive test is more likely to be a false positive than a true positive, even with the most accurate tests available.

Question 2

Qualities of a Good Screening Test

Answer 2

1. The condition should be an important health problem and the condition screened for must have a high prevalence in the population.
2. There should be a latent stage of the disease.

3. There should also be effective treatment for the condition being screened.

4. Facilities for diagnosis and treatment should be available.
5. There should be a test or examination for the condition.
6. The test should be acceptable to the population and the total cost of finding a case should be economically
   balanced in relation to medical expenditure as a whole. The potential benefits of early detection and treatment of a condition need to be weighed against many factors including: adverse side effects of the screening test, time and effort required (of both the patient and the healthcare system) to take the test, financial cost of the test, potential psychological and physical harm of false positive results (such as labeling and overtreatment), adverse effects of the treatment.
7. The natural history of the disease should be adequately understood.
8. There should be an agreed policy on who to treat.
9. Case-finding should be a continuous process, not just a “once and for all” project.
10. An effective screening test should have very good sensitivity (identify most or all potential cases) and specificity (label incorrectly as few as possible as potential cases). Even a test with a sensitivity of 95% will lead to many false positives when the prevalence of the condition is very low.

Question 3

United States Preventive Services Task Force Recommendations for Chlamydia Screening

Answer 3

The USPSTF recommends screening for chlamydia infection in the following B):

• -All sexually active women age 24 and younger
• -Sexually active women age 25 and older who are at increased risk

Rationale: There is direct evidence that screening reduces complications of chlamydial infection in women who are at increased risk, with a moderate magnitude of benefit. Such complications include pelvic inflammatory disease, infertility, and premature delivery (among pregnant women)

Question 4

United States Preventive Services Task Force Recommendations for Chlamydia Screening

Answer 4

The USPSTF advises against screening women age 25 and older if not at increased risk, regardless of pregnancy status.

Only the above categories are found to have a high enough pretest probability to recommend screening. Women (pregnant or non-pregnant) in general are not recommended for chlamydial screening as the overall benefit of screening would be small, given the low prevalence of infection among women not at increased risk.

Risk factors for chlamydial infection include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, inconsistent condom use, and exchanging sex for money or drugs. Risk factors for pregnant women are the same as for nonpregnant women.

Finally, the USPSTF states that there is “Insufficient” evidence for or against screening men.

Question 5

Counsel all sexually active adolescents regarding contraception.

Answer 5

Options include: oral contraceptives, medroxyprogesterone (Depo-Provera) injections, transdermal options, IUDs, and the vaginal ring (NuvaRing)

Remind patients these options do not protect against sexually transmitted infections

Discuss condoms and abstinence

Recommend folic acid supplementation to prevent neural tube defects in the event of pregnancy

Question 6

Preconception Counseling

Answer 6

Finding the opportunity to do preconception counseling in situations where the woman does not take the initiative to schedule a preconception visit can be difficult. Whether it is walk-in / urgent care visits, sports pre-participation examinations, or adolescent well-child exams, the following list should be “on your radar screen” to effectively avail yourself of often scarce opportunities to advise women in these preconception issues.

Question 7

Preconception Health Care Checklist:

Answer 7

Genetic
»Folic acid supplement (400 mcg routine):
—The USPSTF recommends that all women “planning or capable of pregnancy” take a daily supplement containing 400 - 800 mcg of folic acid.
—-The dose is increased for the following high-risk scenarios:
A. 1 mg in patients with diabetes or epilepsy
B. 4 mg in patients who bore a child with a previous neural tube defect

> > Carrier screening (ethnic background):

• —sickle cell anemia
• —thalassemia
• —Tay-Sachs disease

> > Carrier screening (family history):

• —cystic fibrosis
• —nonsyndromic hearing loss (connexin-26)

Screen for infectious diseases, treat, immunize, counsel
>HIV
>Syphilis
>Hepatitis B immunization
>Preconception immunizations (rubella, varicella)
>Toxoplasmosis-avoid cat litter, garden soil, raw meat
>Cytomegalovirus, parvovirus B19 (fifth disease)-frequent hand washing, universal precautions for child care and health care

Environmental toxins
>Occupational exposures: Material Safety Data Sheets from employer
>Household chemicals: avoid paint thinners and strippers, other solvents, pesticides >Smoking cessation: bupropion (Zyban), nicotine patches (Nicoderm)
>Screen for alcoholism and use of illegal drugs

Medical assessment
>Diabetes: optimize control, folic acid, 1 mg per day, off ACE-inhibitors
>Hypertension: avoid ACE inhibitors, angiotensin II receptor antagonists, thiazide diuretics
>Epilepsy: optimize control; folic acid, 1 mg per day
>DVT: switch from warfarin (Coumadin) to heparin
>Depression/anxiety: avoid benzodiazepines

Lifestyle
>Recommend regular moderate exercise >Avoid hyperthermia (hot tubs, overheating
>Caution against obesity and being underweight
>Screen for domestic violence
>Assess risk of nutritional deficiencies (vegan, pica, milk intolerance, calcium or iron deficiency)
>Avoid overuse of Vitamin A (recommendations are to 750 mcg (2500 IU per day) with daily upper intake limit of 3,000 mcg (10,000 IU))
>Avoid overuse of Vitamin D (recommendations are 600 IU per day, tolerable upper intake is 4000 IU) Caffeine (limit to the equivalent of two cups of coffee or six glasses of soda per day)
»Note: The sugar intake in six glasses of soda is not recommended.

Question 8

Signs and Symptoms of Pregnancy

Answer 8

Amenorrhea with fatigue, nausea, and/or vomiting as well as breast changes, including tenderness, are the classic presentations of pregnancy.

Urinary frequency can also occur. Although urinary frequency can be a normal symptom of pregnancy, the possibility of a UTI in a pregnant woman should also be considered.

Softening of the cervix is known as Goodell’s sign, while softening of the uterus is known as Hegar’s sign.

The bluish-purple hue in the cervix and vaginal walls is known as Chadwick’s sign and is caused by hyperemia.

Enlargement of the uterus can be detected by an experienced examiner as early as 8 weeks on bimanual exam. Around 12 weeks, the uterine fundus can be palpated above the symphysis pubis. Between 20 to 36 weeks of gestation, the uterine enlargement, measured in centimeters, approximates gestational age and will become a routinely elicited physical exam finding.

Fetal heart tones are typically elicited by hand-held Doppler between 10-12 weeks gestation.

Fetal movement or “quickening” is detected by the mother around 18-20 weeks of gestation.

Unfortunately, the menstrual history is not an entirely reliable indicator of pregnancy. Only 68% of pregnant adolescents report having missed a menses. Conversely, not every adolescent who misses a menses is pregnant because anovulatory cycles are normal in the early postmenarcheal years. Bleeding can occur in early pregnancy around the time of the missed menses as a result of an invasion of the trophoblast into the decidua (implantation bleed). Some adolescents mistake this bleeding for a menses, leading to a delay in diagnosis of pregnancy and potential misdating of the pregnancy. We should also remember that young women who have not yet menstruated, but are sexually active, may be at risk for pregnancy because ovulation can occasionally occur before the first menstrual period.

Question 9

Reproductive Choice Counseling

Answer 9

Continue the pregnancy…
…and raise the child.
…and create an adoption plan.

Terminate the pregnancy…
…medically
…surgically

Question 10

Calculating the Estimated Gestational Age (EGA)

Answer 10

based on the Last Normal Menstrual Period (LNMP). Calculating the EGA in this manner is not only convenient but ubiquitous in clinical practice. Keep in mind, however, that the actual embryonic age (e.g., the age of the fetus since the date of conception) will typically be approximately two weeks less than the clinically calculated EGA based upon the LNMP.

Question 11

The other calculation used in clinical practice - which patients care a great deal about - is the Estimated Due Date.

Answer 11

Calculating the estimated due date (EDD - sometimes referred to as the estimated date of confinement or EDC) from the last menstrual period is a relatively simple process that can be done with an obstetric “wheel”, with an electronic calculator (e.g., http://www.mdcalc.com/pregnancy-due-dates-calculator ) or using Naegele’s Rule.

Naegele’s Rule is commonly described as starting with the first day of the last normal menstrual period, then:
»add 1 year
»subtract 3 months
»add 1 week

For example, if a patient’s LNMP was 7/10/2009, then:

7/10/2010 (+1 yr)
4/10/2010 (-3 mo)
4/17/2010 (+1 wk)

Thus, the EDD is 4/17/2010.

Question 12

Hemodynamic Instability

Answer 12

Typically, a significant bleed will first cause the pulse to rise and then the blood pressure to drop. Despite the fact that blood pressure is normal, bleeding can continue for a while before the blood pressure reflects this. This finding really changes how urgently you need to begin to make your assessment and, in some cases, intervene.

Question 13

Rhesus immune globulin (RhoGam)

Answer 13

Rho(D) Immune Globulin is a critical part of modern obstetrics. Prior to the clinical use of this medication, Rh- negative mothers with Rh-positive first gestations were at high risk of having subsequent gestations and developing hemolytic anemia, hydrops, and/or fetal death. With every pregnancy, there is some passage of fetal red blood cells into the maternal circulation. This occurs at either miscarriage or delivery and can even occur in small but significant quantities across the otherwise placental barrier.

When a mother with an intact immune system detects enough of the fetal Rho-D antigen, she forms antibodies to this antigen. This immune response is usually not robust enough to impact the first gestation, but subsequent gestations are at significant risk of an immune response. When this occurs, the maternal antibodies attack the fetus’ red blood cells, causing hemolytic anemia, which can lead to fetal hydrops and even fetal death.

Rho(D) Immune Globulin administered at appropriate times interrupts the maternal immunologic process. You can visualize this process by imagining the RhoGAM attaching to all of the fetal Rho-D antigenic load, making it immunologically “invisible” to the maternal immune system.

Question 14

First Trimester Vaginal Bleeding

Answer 14

One in four pregnant patients experience vaginal bleeding during the first trimester.

When women have significant bleeding in the first trimester, there is a 25-50% chance of miscarriage.

Question 15

Ectropion

Answer 15

When the central part of the cervix appears red from the mucous-producing endocervical epithelium protruding through the cervical os, onto the face of the cervix. It has no clinical significance and is common in women who are taking oral contraceptive pills.

Question 16

1T measure crown-rump length…+/- 1 wk accuracy

Answer 16

If the EGA & EDD from the ultrasound measurements are within one week of the EGA / EDD estimated from the LNMP, today’s gestational age and the due date (EGA & EDD) should not change to reflect the ultrasound calculations, as in this case.

If, however, the ultrasound measurements suggest an EGA & EDD that is greater than seven days from the EGA & EDD calculated from the LNMP (or, in some cases, if the LNMP is historically inaccurate), then the estimated gestational age today, as well as the estimated due date, should be changed to reflect the ultrasound measurements and estimates.

(same for 2T)

Question 17

2T

measure:

1. biparietal diameter
2. head circumference
3. abdominal circumference
4. femur length

Answer 17

+/- 2 wks accuracy

Question 18

3T: +/- 3 wk accuracy

Answer 18

Fetal size cannot be used accurately to assess EGA or EDD and should not change a due date.

This is because of the response of the fetus to internal and external insults. During the 1st and 2nd trimester, many problems that develop result in pregnancy loss and/or teratogenensis. However, during the third trimester, many of fetal and maternal challenges manifest themselves in fetal growth. Two examples would be macrosomia due to gestational diabetes or intrauterine growth restriction as a part of the pre-eclampsia syndrome. Additionally, fetal size discrepancies can be either familial or idiopathic.

Since the ultrasound estimate of gestational age and due date is based on measurements of fetal size compared to a computerized nomogram, these third-trimester measurements should not be used for dating the EGA or EDD.

Question 19

Spontaneous Abortion: Incidence, Causes, and Recurrence

Answer 19

Incidence
Miscarriages are very common: about one-third of all pregnancies end in miscarriage.

Causes
Women who have a spontaneous abortion and their partners frequently struggle with guilt about their role in the loss. Physicians should address the issue of guilt with their patients and allay any concerns that they may have “caused” the spontaneous abortion. There is no proof that stress or physical / sexual activity causes miscarriage. About half of all miscarriages that occur in the first trimester are caused by chromosomal abnormalities.

Recurrence
Most women (87 percent) who have miscarriages have subsequent normal pregnancies and births.

Question 20

Pre-participation exams are a great opportunity for prevention and counseling, as otherwise healthy adolescents may not come in for this routinely.
HEEADSSS covers the following issues:

Answer 20

Home
Education / Employment 
Eating
Activities
Drugs
Sexuality
Suicide / Depression 
Safety / Violence

Question 21

Management of Inevitable Abortion

Answer 21

In the setting of an inevitable (or similarly, an incomplete) spontaneous abortion, the traditional choices for management are expectant management or surgical management.

Expectant management means watchful waiting with precautions regarding unusual amounts of bleeding or pain, or fever, and is effective in over 75% of cases in this setting. The disadvantage with this course of action is that it can take up to a month for the products of conception to be completely expelled. This timeframe might not normally be a problem, but a spontaneous abortion is usually complicated by sadness, grief, and even guilt. Expectant management can delay emotional closure. Nevertheless, this is a viable course of action.

Surgical options include dilitation and curettage (D&C), with or without vacuum aspiration, or manual or electric vacuum aspiration. These choices depend on a variety of factors, including primarily local resources and the surgeon’s preference and experience. The main indication for suction D&C is unusually heavy bleeding and patient preference. The main contraindication is active pelvic infection and patient refusal.

Medical management, despite being off-label, is a useful third option that is becoming more common. The most common protocol involves the vaginal administration of 800 mcg of misoprostol (Cytotec), possibly repeated on day three. Success with this method is generally around 95%, and the time to completion is generally 3-4 days (but may take up to 2 weeks), as opposed to 2-6 weeks with expectant management.
Finally, confirming the receipt of rhesus immune globulin (RhoGam) in the Rhesus negative patient is advisable. If it was not given previously, it should now be administered.

Question 22

Initial Pregnancy Laboratory Studies

Answer 22

> > CBC is important to detect various nutritional and congenital anemias, and to detect platelet disorders.
Rubella immunity should be tested by assessing the presence of IgG antibodies. If the patient isn’t immune, they should receive a postpartum immunization. The Rubella and the MMR vaccine is a live-virus vaccine and should not be used during pregnancy. (Note: This is part of the initial prenatal laboratory workup, despite the childhood immunization history.)
Hepatitis B surface antigen tests for Hepatitis B, which is a major risk to the newborn. (Note: This is part of the initial prenatal laboratory workup, despite the childhood immunization history.)
Blood type to detect rhesus antibody presence. RH(D)-negative women should receive anti (D)-immune globulin to prevent hemolytic disease of the newborn.
RPR tests for syphilis, which is of particular concern during pregnancy because of the risk of transplacental infection of the fetus. Congenital infection is associated with several adverse outcomes, including:perinatal death, premature delivery, low birth weight, congenital anomalies, and active congenital syphilis in the neonate.
HIV status should be checked as the risk of perinatal transmission can be reduced from 15-40% without treatment to less than 2% with antiretroviral therapy and avoidance of breastfeeding and labor.
It is probably not necessary to test serum hCG as well as urine hCG to confirm pregnancy, in the setting of a positive urine hCG.

However, as early pregnancy urine hCG concentrations are lower than serum hCG concentrations, it is possible to have a positive serum hCG result, even with a negative urine hCG result.

Additionally, one must specify a qualitative (positive vs. negative) vs. a quantitative serum hCG. Quantitative serum hCG levels rise at a predictable rate, so serial testing of serum hCG levels can be useful to determine viability or to diagnose an ectopic pregnancy, although one measurement alone is not sufficient to accurately estimate gestational age.
»An ultrasound would not be the best test to order at an early stage of pregnancy. For example, at five weeks estimated gestation, an embryo would typically not be seen. Furthermore, the results would be difficult to interpret without a serum quantitative beta human chorionic gonadotropin test (quantitative pregnancy test).

Question 23

Recommended Laboratory Studies to Investigate First Trimester Vaginal Bleeding

Answer 23

CBC: The main utility of the CBC is for the Hemoglobin / Hematocrit. The white blood cell (WBC) count is limited in its usefulness to detect infection (and thus a septic abortion) during pregnancy because most pregnant patients have a mild leukocytosis. Nevertheless, if significantly elevated, or associated with a bandemia, this test would need to be factored into the consideration of a septic abortion.

Wetmountpreparationfortrichomonas,aswellasPCRtestingforgonorrheaandchlamydia: All sexually transmitted infections can cause vaginal bleeding. These tests should be obtained in this clinical context, despite a previously normal recent result.

Progesterone: Laboratory testing for progesterone is most useful in extreme situations. If the result is >25, it is highly associated with a sustainable intrauterine pregnancy. If the result is <5, it is highly associated with an evolving miscarriage or ectopic pregnancy. Levels between 5 and 25 have minimal diagnostic value in distinguishing intrauterine from ectopic pregnancy. Algorithms for the diagnosis of ectopic pregnancy emphasizing progesterone measurements have been associated with a higher use of surgical management and often miss ectopic pregnancy since 85% of ectopic pregnancies will have a normal progesterone level. Nevertheless, the test remains valuable because of its positive and negative predictive value at the extremes of the reference range. In many labs, it is a common and quick test, which makes it frequently ordered.

Quantitative beta-human chorionic gonadotropin (quant. beta-hcg): This test has enormous significance, and when combined with the pelvic ultrasound, they are the definitive diagnostic modalities. However, in isolation, one beta-hCG can be challenging to interpret, especially without the ultrasound results. Human chorionic gonadotropin is secreted by the trophoblastic cells very early in embryonic life (day 7, post-ovulation). Additionally, testing for the beta-subunit is exquisitely sensitive (down to 5 mIU/mL) and specific (the placenta is the only normal tissue that excretes beta-hCG). By the expected date of menses, the beta-hCG is usually > or = 100 mIU/mL.

Furthermore, in a normal pregnancy, the beta-hCG approximately doubles every 48 hours for the first 6-7 weeks of gestation. However, an intrauterine pregnancy may not be conclusively detected until the quantitative beta-hCG reaches 1500-1800. To detect an intrauterine pregnancy by transabdominal ultrasound, the beta-hCG will typically be >5000 mIU/mL. In both ectopic gestations and spontaneous abortions, hCG levels are usually lower than normal and increase at less-than-normal rates during early gestation. Molar pregnancy and multiple gestations are both associated with higher-than-normal hCG levels.

Not recommended:
Type and screen: Knowing the Rhesus status is critical, as all Rh negative women who are pregnant need to be given RhoGam during any episode of bleeding. However, this does not need to be repeated after initial type and screen, especially in a setting that does not appear that this is a major bleed. If the bleeding is of great volume, a type and screen would be warranted both for potential transfusion and for Kleihauer-Betke testing, which helps to estimate the quantitative amount of fetal hemoglobin in the maternal circulation and with dosing RhoGam.

Question 24

Spontaneous Abortion

Answer 24

Spontaneous abortion is the loss of a pregnancy without outside intervention before 20 weeks’ gestation. Spontaneous abortions can be subdivided into:
»Threatened abortion - bleeding before 20 weeks gestation.
—-Threatened abortion is simply a pregnancy complicated by bleeding before 20 weeks gestation, and is - in some ways - a “catch-all” descriptive diagnosis.

> > Inevitable abortion - dilated cervical os.
Incomplete abortion - some but not all of the intrauterine contents (or products of conception) have been expelled.
Missed abortion - fetal demise without cervical dilitation and/or uterine activity (often found incidentally on ultrasound without a presentation of bleeding).
Septic abortion - with intrauterine infection (abdominal tenderness and fever usually present).
Complete abortion - the products of conception have been completely expelled from the uterus.

Question 25

Differential of First Trimester Vaginal Bleeding

Answer 25

There are many important causes of bleeding in early pregnancy, but the three most common are spontaneous abortion, ectopic pregnancy, and idiopathic bleeding in a viable pregnancy.

Less Likely Diagnoses:
Gestational trophoblastic disease (GTD), or molar pregnancy, is a hetergeneous constellation of conditions whereby the placenta acts like a tumor. GTDs are usually benign, but can sometimes be malignant. Typically, they have a characteristic appearance on ultrasound and are associated with markedly increased (>100,000 mIU/mL) quantitative hCG levels.

Vaginal trauma and cervical pathology are unlikely if nothing abnormal is seen on physical exam. However, these can’t be ruled out conclusively until gonorrhea and chlamydia results are obtained.

Question 26

Differential of First Trimester Vaginal Bleeding: PE Findings

Answer 26

A cervical os dilated with obvious bleeding lends support to the diagnosis of a spontaneous abortion.

A distended, acute abdomen may turn one’s attention to the immediate possibility of a ruptured ectopic pregnancy.

However, an unremarkable pelvic exam does not rule out either a spontaneous abortion, ectopic pregnancy, or a normal pregnancy.

Question 27

Differential of First Trimester Vaginal Bleeding: Quantitative beta-hCG

Answer 27

Neither transabdominal nor transvaginal ultrasound can reliably detect an intrauterine pregnancy at a beta-hCG level less than 1500 mIU/mL. A quantitative beta-hCG slightly less than 1500 mIU/ml does not argue for or against a spontaneous abortion, an ectopic pregnancy, or a normal pregnancy.

However, the quantitative beta-hCG should approximately double every 48 hours in a normal pregnancy, so the velocity of the increase or decrease is a more useful diagnostic modality than the point value in a stable patient. If the patient is stable, 1-2 serial hCG measurement(s) can prove diagnostically useful and often conclusive when combined with a repeat ultrasound.

Question 28

Differential of First Trimester Vaginal Bleeding: US

Answer 28

An ovarian cyst is not necessarily abnormal, and a report stating “cannot rule out ectopic pregnancy” is a classic reminder by the radiologist that they simply cannot rule out ectopic pregnancy.

One should be neither cavalier that such an ultrasound finding is a benign finding nor overly aggressive in “treating” for a suspected ectopic pregnancy in a stable patient. Better to make the diagnosis more certain. It would be a mistake to assume a confirmed ectopic pregnancy and to begin either medical or surgical treatment for ectopic pregnancy. This may, after all, prove in 48 hours to be the corpus luteum cyst supporting a normal intrauterine pregnancy.

Intrauterine contents (e.g., gestational sac, fetal pole, etc.) are not expected to be seen until the quantitative beta-hCG reaches > 1500 IU/L, so a serial reading (in the stable patient) is needed. In a stable patient without active bleeding, serial readings every 48-72 hours would be appropriate.

Question 29

Abortions

Answer 29

When the cervical os is open or dilated bleeding in early pregnancy is classified as an inevitable abortion.

When the cervical os is closed with bleeding before 20 weeks, the correct diagnosis is a threatened abortion.

A missed abortion is fetal demise without cervical dilation.

Complete abortion occurs when products of conception have been completely expelled from the uterus

Question 30

Quantitative serum beta-hCG

Answer 30

Quantitative serum beta-hCG levels rise at a predictable rate, making it a useful tool to help distinguish between an intrauterine pregnancy and an ectopic pregnancy.

During the first 6-7 weeks of gestation, beta-hCG levels double every 48 hours. With a beta-hCG level of 1500-1800 mIU/ml, a transvaginal ultrasound will be able to detect an intrauterine pregnancy.

A transabdominal ultrasound will be able to detect pregnancy when beta-hCG levels > 5000 mIU/ml. An ectopic pregnancy will have beta-hCG levels lower than normal and levels aren’t expected to double during early gestation.