Inherited Thrombophilias and Anticoagulation in Pregnancy

Check out PB 196 and PB 197 for the primary reading on this topic!

Remember way back when, when we talked about physiologic changes of pregnancy (Part I and Part II)? Recall that pregnant women are 4-5x more likely than non-pregnant women to experience VTE, owing in part to factors we can trace back to Virchow’s Triad: hypercoagulability, venous stasis, and endothelial injury. In pregnancy we have hypercoagulability: increased clotting potential, decreased anticoagulant activity, and decreased fibrinolysis  And we certainly have venous stasis, particularly in the lower extremities due to compression of the IVC by the uterus. Persons with inherited thrombophilias are at even higher risk of VTE owing to these factors.

Inherited Thrombophilas

There are lots of different types of inherited thrombophilias:

• Factor V Leiden: 

  1. The most common mutation is factor V leiden heterozygosity, and is responsible for about 40% of all VTEs during pregnancy.

  2. By itself, it doesn’t really put you at that much of an increased risk for VTE (only about 5-12/1000 deliveries), but if you have a personal history of VTE as well, then risk goes up to about 10%.

• Prothrombin Gene

  • Heterozygote is next most common mutation; like factor V Leiden, if you are a homozygote, you’re at higher risk of VTE than heterozygote.

• Antithrombin gene deficiency

  • Unommon (only 0.02% prevalence), but it is highly thrombotic 

    1. In non pregnant people, the risk of VTE is 25x normal.

    2. More severe deficiencies is associated with increased VTE risk; so, if you have a personal history of VTE, and you have a severe antithrombin deficiency (<60% activity), your risk of VTE in pregnancy could be as high as 40%.

Testing for Inherited Thrombophilias

Testing is generally considered in two scenarios: either a patient who has a history of VTE herself, or the patient has a family member with a known high risk inherited thrombophilia. Screening is generally not recommended for women who have experienced fetal loss or various adverse pregnancy outcomes, outside of those meant for antiphospholipid syndrome testing.

ACOG PB 196

Basis for Anticoagulation in Inherited Thrombophilias

• We can divide these mutations in to high and low risk thrombophilias: 

  1. High risk = Factor V Leiden homozygosity, prothrombin gene homozygosity, antithrombin deficiency, or factor V leiden + prothrombin gene heterozygosity (meaning one mutation of each gene) 

  2. Low risk = Factor V Leiden heterozygosity, prothrombin gene heterozygosity, protein C or protein S deficiency, and antiphospholipid antibody 

• It is important to realize that according to ACOG, there is insufficient evidence that anticoagulation use will prevent adverse pregnancy outcomes in patients with inherited thrombophilias, such as preeclampsia, FGR, or placental abruption. The indication for anticoagulation is for the purpose of preventing VTE.

Choice of Anticoagulant Agent

• Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) - neither cross the placenta and are safe, and are first line choices.

• Warfarin - we KNOW that there are harmful fetal effects, especially in first trimester, so don’t use it as first line. The only case that this is used in pregnancy is for women with mechanical heart valves because there is a higher risk of VTE even with LMWH or UFH.

  1. Usually will use LMWH or UFH from weeks 6- 13 in pregnancy and switch back to warfarin later.

• Oral direct thrombin inhibitors should be avoided in pregnancy and postpartum because insufficient data on safety.

When and How Much Anticoagulation?

In the Practice Bulletins, there is a large table of conditions with recommendation for anticoagulation. We’ve broken it down a bit for you, as the progression actually is logical once it’s written out.

For inherited thrombophilias, you’ll need to remember the high risk and low risk groupings:

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(c) CREOGS Over Coffee, 2020

The other group that should be considered for anticoagulation are patients who may have had a VTE in the past, but do not have evidence of inherited thrombophilia:

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(c) CREOGS Over Coffee, 2020

Delivery Considerations on Anticoagulation

Peri-delivery, the use of anticoagulation can be challenging if patients desire or require neuraxial analgesia. PB 196 reviews recommendations for holding anticoagulation before delivery. In general:

• Prophylactic doses of UFH or LMWH should be held 12 hours prior to anticipated delivery/admission.

• Therapeutic doses of UFH or LMWH should be held for 24 hours prior to anticipated delivery/admission.

  • UFH may be resumed 1 hour after catheter removal or neuraxial blockade, whether at prophylactic or therapeutic doses.

  • LMWH may be resumed:

    • 12 hours after neuraxial blockade and 4 hours after catheter removal, whichever is longer, at prophylactic doses.

    • 24 hours after neuraxial blockade and 4 hours after catheter removal, whichever is longer, at therapeutic doses.

Alloimmunization Part II: Management

What to do with a positive antibody screen?

• First, obtain a antibody titer: a value of dilution at which the antibody screen remains positive.

  • So a 1:32 titer is more significant than a 1:4 titer.

  • A critical titer is one that carries risk for hydrops, which is generally between 1:8 - 1:32, depending on the lab.

    • Additionally, a change in titer of more than one dilution is considered significant. 

  • For titers less than 1:8, titers should be obtained every 4 weeks to reassess.

    • Exception: anti-Kell antibodies, as these titers do not correlate with fetal status. 

• Assess paternal genotype.

  • If the infant can’t get the antigen that the mother is sensitized to (i.e., dad has no Kell antigen for mom’s anti-Kell antibodies to attack), then there’s no need for assessment.

  • If the father does carry an offending antigen, DNA testing can be utilized to determine if the father is heterozygous or homozygous. 

• Assess fetal DNA.

  • Can be employed when paternal status is unknown, or carries risk.

  • Amniocentesis is the gold-standard methodology for fetal blood typing; CVS can also be employed, but carries a higher risk of de novo alloimmunization than amniocentesis.

  • Rh (D) antigen carriage can also be determined by cell free fetal DNA assays.

Monitoring the Alloimmunized Pregnancy

• Historically: serial amniocentesis

  • The concentration of bilirubin in amniotic fluid is assessed by spectral analysis through 450 nm light (OD450)

• Currently: middle cerebral artery (MCA) Doppler ultrasonography

  • Studies have correlated the relationship between peak systolic velocity 1.5 times the median for gestational age with moderate-to-severe fetal anemia, with 100% sensitivity.

    • However, this monitoring should be done by those with experience in the technique, as even with good technique the false positive rate approaches 12%.

• For minor blood group antigen sensitization, protocols may be different.

  • Anti-Kell in particular has a less predictable course and often results in more severe fetal anemia than alloimmunization due to other blood antigens. 

• If severe anemia is suspected, periumbilical cord blood sampling (PUBS, aka cordocentesis) can be used to measure the fetal hemoglobin directly.

  • An intrauterine transfusion (IUT) can be performed to transfuse the fetus as well. 

Interventions and delivery

• Delivery timing is controversial:

  • ACOG recommends if only mild hemolysis is suspected, induction can be considered at 37-38 weeks.

  • With more severely sensitized pregnancies, the risk of repeated cord blood sampling and intrauterine transfusion has to be compared to that of early delivery, and this is often dependent on the center and their experience. 

Alloimmunization Part I: Basics, Prevention

Further Reading
PB 181 - Preventing Rh Alloimmunization
PB 192 - Management of Alloimmunization

The basics

• Over 36 blood group systems for human blood, but the most commonly used are:

  • the ABO system

  • the Rhesus (or Rh) blood group system. 

• The Rh system has over 40 blood group antigens; of these, the most important are “D,” “C,” “c,” “E,” and “e.” (There is no “d.”)

  • The D group is what we most commonly think about.

  • Someone who is Rh+ refers to having a positive Rh(D) antigen. 

  • Antibodies to Rh(D) and Rh(c) group antigens confer significant risk of hemolytic disease of the newborn.

• Rh negative status is more common amongst white persons (15%).

  • In contrast, 5-8% of black persons are Rh(D) negative.

  • 1-2% of Asians and Native Americans are Rh(D) negative.

  • In white Rh(D) positive individuals, 60% are heterozygous and 40% are homozygous at the D locus. 

• Beyond the Rh system blood antigens, there are also a number of other significant or common blood group antigens encountered in clinical practice, such as:

  • “Lewis” (‘Lea’ and ‘Leb’) antigens

  • “I” antigens

  • “Kell” antigens.

  • PB 192 has a big table of these atypical antibodies and their relationship to fetal hemolytic disease.

Alloimmunization

• Alloimmunization or isoimmunization (synonymous) is the formation of maternal antibodies against blood group antigens not possessed by the mother

  • For instance, an Rh-negative mother developing anti-Rh(D) antibodies if exposed to Rh-positive blood.

  • This can occur if a sufficient number of erythrocytes from an Rh-positive fetus gain access to the circulation of an Rh-negative mother. 

• Hemorrhage sufficient enough to cause alloimmunization most commonly occurs at delivery (15-50%)

• But only a small amount of bleeding across this interface (as little as 0.1 mL!) is sufficient to cause alloimmunization.

  • Only 1-2% Rh alloimmunization occurs as a consequence of antepartum bleeding or trauma.

  • Alloimmunization has been reported after ectopic pregnancy, threatened abortion, and spontaneous or induced abortion as well.

  • Obstetrical procedures may also predispose to fetomaternal hemorrhage, such as CVS (14% risk), amniocentesis (2-6%), cordocentesis/PUBS, or external cephalic version (2-6%). 

• Rh alloimmunization was formerly a much more common pregnancy complication that has considerably decreased in incidence in the US and other countries, from 13-16% of pregnancies pre-1970s, to 0.14-0.2% today.

  • Pregnancy complication that in the US is almost completely avoidable with good prenatal care and adherence to protocols. 

• Rh alloimmunization predisposes to Rh hemolytic disease of the newborn: 

• Generally, a sensitizing pregnancy (1st event) is unaffected as antibodies are created in maternal serum from the first exposure to Rh(+) antigen. 

• Subsequent infants with Rh(+) types will be affected by disease as antibodies in maternal serum cross and attack fetal red cells. 

• This in turn puts the fetal hematopoietic system into overdrive, causing organomegaly of the liver and spleen (due to shifting production of immature red cells to these organs). 

• This will ultimately cause portal hypertension and failure of the liver to make other products such as albumin, which then will cause a high output cardiac failure and hydrops. 

• In areas where prophylaxis and treatments are not standard/available, 14% of affected fetuses are stillborn, and up to 50% of live-born infants suffer neonatal death or brain injury from kernicterus (hyperbilirubinemia) as a result of this disease.

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Wikipedia.

Prevention of Rh(D) Alloimmunization

• Women should be tested for ABO blood group and RhD type and screened for presence of any erythrocyte antibodies at entry to care.

  • This should be repeated with each subsequent pregnancy. 

• Assuming a negative antibody screen for anti-D antibodies, Rh negative patients should be considered for anti-D immune globulin, better known as Rhogam, at 28 weeks gestation.

  • Since the 1970s, the strategy in the United States has been to prevent RhD alloimmunization by universal administration of anti-D immune globulin. 

    • Studies looking at cost-effectiveness of selective administration based on the partner’s blood type versus universal administration have shown the approaches to be cost equivalent.

    • Cell free fetal DNA testing is another approach that is actively being studied in the literature and considered to help reduce exposure to RhIg, which is a human blood product; its sensitivity is 99% and specificity 95%, though this is variable to some degree with respect to race. 

• Postpartum administration of RhIg brings the risk of alloimmunization from 16% (with no RhIg) to just over 2%.

  • RCTs that examined RhIg versus placebo administration postpartum had an astonishingly high risk reduction of 88-96%, depending on the time period after the pregnancy studied. 

• The single 300 mcg dose of RhIg at 28 weeks gestation reduces the risk of new 3rd trimester alloimmunization even further:

  • Since the introduction of universal RhIg at 28 weeks in addition to postpartum RhIg, Rh alloimmunization rates went from over 2% to less than 0.2%. 

• RhIg should also be given within 72 hours of a sensitizing event -- that is, one that causes or potentially causes bleeding at the fetal-maternal interface.

  • 1st trimester or early 2nd trimester event such as a procedure, an ectopic, a threatened or complete miscarriage or abortion, the overall risk of alloimmunization is low.

    • Fetal red cell volume is only about 1.5 cc at 12 weeks (3cc total blood volume).

    • 50 - 120 mcg RhIg before 12 weeks.

    • 300mcg dose for events after 12 weeks. 

  • Late 2nd or 3rd trimester bleeding events have a more significant risk for alloimmunization, as fetal blood volume is higher.

    • In this case, a type-and-screen should be obtained, as well as a rosette and a Kleihauer-Betke test.

      • Rosette qualitative screen that can detect greater than 2mL of fetal whole blood in circulation.

        • By incubating a maternal blood sample with Rh immunoglobulin, this will bind any present Rh-positive fetal cells, forming “rosettes” that can then be seen on microscopy.

        • If a rosette test is positive, the next step is to perform a quantitative assessment such as the KB test or flow cytometry.

      • KB test measures the amount of fetal hemoglobin in the mother’s circulation, and thus estimates the amount of RhIg needed to prevent alloimmunization.

        • Results are reported as the number of fetal erythrocytes in maternal blood per 2,000 red blood cells. This often is reported as a percentage of fetal red cells in maternal blood volume (i.e., 200/2000 = 0.1, or 10%).

        • Because KB tests utilize a stain looking for fetal hemoglobin, they are less accurate in hemoglobinopathies that increase fetal hemoglobin in maternal red cells (such as sickle-cell disease or thalassemias).

      • Flow cytometry uses monoclonal antibodies to detect hemoglobin F or RhD antigens, and is also very sensitive and accurate in detecting fetal cells in maternal blood. 

    • 300 mcg of RhIg (or one vial) is sufficient enough to cover against up to 30 mL of fetal blood; up to 8 vials can be administered every 12 hours until reaching the desired dosage -- and fortunately, there’s an IV form if you need larger quantities! 

• Other important facts to know about Rhogam:

  • RhIg has a half life of about 23 days, and thus a 300mcg dose is detectable for approximately 12 weeks. 

  • Redosing may be held if delivery or subsequent sensitizing events occur within 3 weeks (or 1 half life) of a dose; redosing should be more strongly considered after this interval. 

  • After delivery, given the window of 72 hours for effective administration, it’s reasonable to hold off on re-dosing RhIg until Rh type results are available on the infant; if it is Rh negative, there is no indication for additional dosing.

  • RhIg is a human blood product, collected from volunteer donors who have high titers of anti-Rh(D) antibodies. There are no available synthetic/recombinant forms or alternative medications currently available. 

  • Rhogam only prevents Rh(D) alloimmunization by neutralizing the antigen; it doesn’t work on those who have already been sensitized to Rh(D) antigen.

One classic CREOG question involves calculating the amount of RhIg needed to prevent alloimmunization from a KB test. 

• Often, these questions supply the volume of fetal bleed, rather than a KB, which makes life a lot easier.

• Since 300 mcg covers up to 30 cc fetal blood, if the fetal bleeding volume is known, you just need to set up a proportion:

  • 30 mL fetal blood / 300 mcg RhIg = __ mL fetal blood (in question) / x mcg RhIg.

• If the volume of fetal bleeding is not supplied and you only have the KB result, you must first calculate the fetal bleeding volume based on maternal weight. The maternal blood volume is expected to be 70 cc/kg.

  • Maternal blood volume = 70 mL / kg x __ kg (maternal weight).

  • KB % x maternal blood volume = fetal bleed volume detected.

Thyroid Disease in Pregnancy

The thyroid is obviously an important endocrine organ. As we’ve talked through many of our GYN episodes, from infertility to bleeding, the thyroid is part of our basic workup. Thyroid function is important in pregnancy as well, as uncontrolled thyroid disease is associated with adverse pregnancy outcomes. Subclinical thyroid disease, on the other hand, has unclear benefit and likely risks to therapy. Read and listen on, and check out ACOG PB 148 for further reading!

Thyroid physiology in pregnancy

• Thyroid function fluctuates in pregnancy in part due to bHCG

  • Thyroid stimulating hormone (TSH) and bHCG share an alpha subunit as hormones of the anterior pituitary. Thus, bHCG has mild thyrotropic effects.

    • In the first trimester, TSH may be lower as a reflection of this.

    • Free T4 may also be slightly elevated in the first trimester.

  • TSH values should revert to normal after 12 weeks gestation.

  • Important: TSH should not routinely be measured in women with hyperemesis gravidarum, unless other symptoms of hyperthyroidism are pregnant, for this reason. Treatment of transient hyperthyroidism associated with HG has not been shown to be beneficial. 

• Maternal T4 is transmitted transplacentally throughout the pregnancy and is important for normal fetal brain development

  • It is especially important before fetal thyroid gland begins functioning at approximately 12 weeks.

  • Thus, preconception screening and treatment for symptomatic thyroid disease is very important! 

• Nonpregnant iodine intake recommendation is 150 mcg daily.

  • 220 mcg daily in pregnancy.

  • 290 mcg daily in lactation.

    • Iodine is not always included in prenatal vitamins

    • American diet generally has enough iodine intake without supplementation, though should be a consideration for anyone with hypothyroid symptoms.

Thyroid Disease Testing

Recommendation by ACOG, Endocrine Society, Association of Clinical Endocrinologists recommend against universal screening for thyroid disease in pregnancy.

• Only screen women for those at increased risk of overt hypothyroidism, or with symptoms of overt hyper- or hypothyroidism. 

TSH and free T4 are the recommended baseline screening tests. 

• TSH is most important baseline screening test. In pregnancy, values:

  • 1st trimester: 0.1 - 2.5 mIU/L

  • 2nd trimester: 0.2 - 3.0 mIU/L

  • 3rd trimester: 0.3 - 3.0 mIU/L

• Free T4 (thyroxine) contextualizes the TSH result, and is often sent as a reflex if TSH is abnormal.

• Free T3 is generally not useful.

  • Very rare to have an abnormally high T3 causing hyperthyroidism; can be obtained if suspicious based on symptoms, with low TSH and normal T4.

• Antithyroid antibodies rarely lead to changes in management, so no evidence to routinely test for these. 

Pathophysiology of Various Thyroid Conditions in Pregnancy

Overt Hyperthyroidism:

• Occurs in 0.2% of pregnancies, with Graves’ disease (anti-thyroid antibody stimulation) accounting for 95% of cases.

• Diagnosis: low TSH (often undetectable), high free T4, and symptoms

  • tremors, tachycardia, weight loss, heat intolerance, insomnia, goiters, palpitations, hypertension (“activating symptoms”).

• Risks of Disease:

  • Maternal: hypertension, preeclampsia, heart failure

  • Fetal/Neonatal: premature delivery (medically-indicated), growth restriction/low birth weight, stillbirth, hydrops, neonatal hypothyroidism or hyperthyroidism.

    • Maternal anti-thyroid antibodies can cross placenta and can stimulate or inhibit fetal thyroid. 

    • This risk is not necessarily mitigated in neonates of mothers who have had treatment for Graves’ with surgery or radioactive iodine treatment -- antibodies can persist and still cross placenta. 

    • Thioamide treatment helps to suppress antibody production in medically-treated patients. 

Subclinical Hyperthyroidism:

• 1.7% of pregnancies.

• Diagnosis: low TSH, with normal free T4. 

• Has not been associated with adverse pregnancy outcomes.

  • Due to potential for antithyroid medication to cross placenta and cause adverse fetal effects, treatment is not recommended. 

Overt Hypothyroidism:

• 0.2 - 1% of pregnancies.

•  Diagnosis: high TSH, decreased free T4, and symptoms:

  • Fatigue, constipation, cold intolerance, weight gain, dry skin, hair loss, prolonged relaxation of DTRs, edema.

  • Challenge -- these symptoms sound a lot like early pregnancy!

    • Goiter more likely in women with Hashimoto thyroiditis -- 

      • most common cause of hypothyroidism in pregnancy (glandular destruction by thyroid autoantibodies).

• Risks of Disease:

  • Maternal: preeclampsia

  • Fetal/Neonatal: SAB/pregnancy loss, preterm birth, placental abruption

    • Untreated hypothyroidism may predispose to impaired neuropsychological development in offspring.

      • This is due to low active thyroid hormone, though; it is extremely uncommon for maternal thyroid inhibitory antibodies to cross placenta and cause fetal hypothyroidism. 

    • Prevalence of fetal hypothyroidism in offspring of women with Hashimoto is only 1 in 180k neonates. 

Subclinical Hypothyroidism

• 2-5% of pregnancies.

• Diagnosis: high TSH, normal free T4; unlikely to progress to overt hypothyroidism in pregnancy in otherwise healthy women.

• Bottom line: not associated with adverse pregnancy/neonatal outcomes.

  • Controlled Antenatal Thyroid Screening Study 2012 RCT with follow up to age 3, and additional follow up in 2018 to age 9.5.

    • Antenatal screening of thyroid function at mean GA of 12w3d.

    • No difference in neurocognitive development of offspring at both age 3 and age 9.5.

    • Secondary analyses find no definitive association with preterm birth, placental abruption, NICU admission, preeclampsia, GDM. 

• Recommendation by ACOG, Endocrine Society, Association of Clinical Endocrinologists recommend against universal screening for thyroid disease in pregnancy for this reason.

  • Thus -- as stated before, only screen women for those at increased risk of overt hypothyroidism or with symptoms of overt hypothyroidism. 

Treating Overt Thyroid Conditions in Pregnancy

Hyperthyroidism

• Mainstay of therapy is thioamide medications, either propylthiouracil or methimazole.

• PTU inhibits thyroperoxidase, an essential enzyme in creation of free T4. Also partially inhibits conversion of T4 to T3.

  • Preferentially used in1st trimester -- less readily crosses the placenta than methimazole.

  • Major side effect of note is hepatotoxicity, affecting 0.1-0.2% of women on PTU. 

  • Thus the recommendation is to switch to methimazole in the second trimester. No indication for routine LFTs.

• Methimazole also inhibits thyroperoxidase. 

  • Preferentially used in 2nd trimester due to hepatotoxicity.

  • Avoided in 1st trimester due to rare risk of embryopathy, characterized by esophageal or choanal atresia as well as aplasia cutis (congenital absence of skin, usually on the scalp).

• Rare but important side effect of both drugs: leukopenia in up to 10% of pregnant women on these drugs, which does not usually require therapy cessation.

  • However, rarely progresses to agranulocytosis in less than 1%, and this mandates discontinuing the offending agent. 

  • If women develop flu-like symptoms, they should discontinue these meds and immediately obtain CBC to assess WBC count. 

• Initial dosing for both drugs is empiric:

  • 50-150mg TID for PTU

  • 10-40mg total daily divided into 2-3 doses for MTZ.

• Goal is to use the  lowest thioamide dose to maintain free T4 in the high-normal range, regardless of TSH level. 

  • Measure free T4 concentrations q2-4 weeks after initiating therapy (not TSH levels!) and adjust thioamide dose accordingly. 

Hypothyroidism

• Levothyroxine is the mainstay for thyroid hormone replacement. 

  • Dosing should begin at 1-2 mcg/kg daily, or approximately 100mcg daily. 

  • Monitor therapy by measuring TSH levels every 4-6 weeks (not T4!)

    • Adjust dose by 25-50 mcg increments until TSH normalizes.

    • Anticipatory 25% increase in T4 replacement at pregnancy confirmation in women with known thyroid disease may reduce the risk of significant hypothyroidism in early pregnancy in higher risk women (i.e., history of thyroidectomy or radioiodine ablation).

Thyroid Storm and Thyrotoxic Heart Failure

• Thyroid storm is rare - 1-2% of pregnant patients with hyperthyroidism.

  • Cardinal symptoms include fever, tachycardia, arrhythmias, and CNS dysfunction. Develops abruptly and leads to multiorgan failure. 

• Thyrotoxic heart failure is more common, actually, and has been identified in 8% of women with uncontrolled hyperthyroidism.

  • Due to an excess of free T4 and effects on myocardium.

  • Decompensation usually precipitated by other disease, such as PEC, sepsis, anemia. 

  • Fortunately this is often reversible with treatment.

• Tenets of treatment of these conditions:

  • Evaluate TSH and T4, but if suspected -- do not withhold treatment!

  • Follow the ACOG algorithm here (read out loud):

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ACOG PB 148

Postpartum Thyroiditis

• Defined as thyroid dysfunction within 12 months of delivery that can manifest as hyperthyroidism, hypothyroidism, or both. 

  • Transient autoimmune thyroiditis present in 5-10% of women in this time period.

  • Often attributed to “the stresses of motherhood” so actually infrequently encountered clinically. 

• Often develops in two phases:

  • First, hyperthyroid state that is charactrized by simultaneous thyroid gland destruction, lasting maybe a few months at the longest.

    • Often a small, painless goiter can be found in these patients.

    • If diagnosed during this phase, thioamides are generally ineffective, but beta blockers can help with symptoms if necessary. 

  • Then, hypothyroid symptoms that begin somewhere between 4-8 months postartum, requiring thyroid replacement for 6-12 momnths.

  • Most women will have symptoms resolve sponteneously, but up to ⅓ of women will develop permanent hypothyroidism. 

Thyroid nodules in pregnancy

• Can be found in 1-2 % of reproductive-aged women.

• If pregnant, should perform H&P, TSH, and ultrasound of the neck

  • Ultrasound reliably detects nodules greater than 0.5 cm.

  • If suspicious for malignancy, next step is fine needle aspiration.

    • Radioiodine scanning is not recommended in pregnancy due to theoretical risk of fetal irradiation. 

• If cancer is detected, multidisciplinary discussion should be had regarding treatment timing. 

  • Many times surgery is delayed until after delivery due to concern for potential removal of parathyroid glands. 

Operative Vaginal Birth

So today’s episode won’t be a “how to” on operative birth; that requires some years of residency and even fellowship, but we want to help you recognize what operative births are and when to use them. For more reading, check out the new ACOG PB 219.

Operative vaginal birth is when an obstetrician or other trained birthing provider uses a device such as vacuum extractor or forceps during the second stage of labor to achieve or expedite a vaginal birth for maternal or fetal indications. The two tools generally available are forceps or vacuum extractors.

Forceps 

• Generally, metal devices with two blades that are placed around the head of the fetus to assist in birth.

• Consist of the components of blade, shank, lock or articulating portion, and handle 

• The blades have a toe (front) and a heel (back toward the provider), as well as a pelvic curve and cephalic curve:

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OBGynKey

• Some history on forceps:

  1. First developed by the Chamberlen family of surgeons in France as early as possibly 1634, though they kept them secret for about 150 years.

  2. They largely haven’t changed. Simpson forceps (split shanks), for example, were created in 1848, and Elliot forceps (overlapping shanks) in 1860.

  3. There are multiple types, but the majority of forceps in use today are in the Simpson or Elliot class. Some you may encounter:

     1. Simpson - Luikhart: split shank (Simpson type), pseudofenestrated blade.

     2. Luikhart - McLain: Elliot type with pseudofenestrated blade.

     3. Tucker McLain: Elliot type, no fenestration to blade.

Vacuum Extractor 

• A suction cup that is placed on the head of the baby approximately 2-3 cm anterior from the posterior fontanelle over the flexion point to guide the head through the birth canal.

• Some history 

  1. The first vacuum extractor was developed by James Young Simpson in 1849.

  2. Didn’t really catch on until a Swedish doc named Tage Malmstromo developed the “ventouse” or Malmstrom extractor in the 1950s.

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A Kiwi vacuum extractor

Indications and Prerequisites for Operative Vaginal Birth

1. Indications 

   1. Prolonged second stage of labor.

   2. Suspicion of immediate or potential fetal compromise.

   3. Shortening of second stage of labor for maternal benefit (ie. maternal exhaustion or maternal cardiac issues that may make it difficult for them to Valsalva for an extended amount of time).

2. Prerequisites (“checks” before attempt).

   1. Cervix is fully dilated and membranes are ruptured.

   2. Engagement of the fetal head.

   3. Position of fetal head is known (either by exam or by ultrasound).

   4. EFW has been performed and assessment that the pelvis is adequate for vaginal birth (don’t want to pull into a shoulder!).

   5. Adequate anesthesia.

   6. Maternal bladder has been emptied.

   7. Patient has agreed after being informed of risks and benefits of procedure.

   8. Willingness to abandon the attempt, with back-up place (ie. cesarean) in case of failure to deliver.

   9. We do not recommend doing a prophylactic episiotomy anymore, but if you have to, reasonable to give prophylactic antibiotics, per the ANODE trial, and also give if there is a 3rd or 4th degree laceration.

3. When should you NOT perform an operative vaginal birth: 

   1. If fetal head is unengaged or fetal head position is unknown.

   2. If fetus is suspected to have osteogensis imperfecta or other both demineralization condition.

   3. If fetus is thought to have bleeding disorder (ie. thrombophilia or von Willebrand disease).

4. Categorization of forceps deliveries (we don’t do high forceps anymore… YIKES!) 

   1. Midforceps 

      1. Station is above +2 cm, but head is engaged.

   2. Low forceps 

      1. Leading point of the fetal skull is at station +2 cm or more and not on the pelvic floor.

      2. Without rotation: rotation is 45 degrees or less (ROA, ROP, LOA, LOP).

      3. With rotation: Rotation is > 45 degrees, requires rotation with rotational forceps or Scanzoni maneuver.

   3. Outlet forceps

      1. Fetal scalp is visible at the introitus without separating the labia.

      2. Fetal skull has reached the pelvic floor.

      3. Fetal head is at or on perineum.

      4. Sagittal suture is in an AP diameter or ROA, ROP, LOA, LOP.

      5. Rotation does not exceed 45 degrees.

Counseling a Patient on Operative Vaginal Birth

• Benefits 

  1. Avoidance of cesarean delivery for the indications above.

  2. Operative vaginal delivery is undeniably faster to achieve delivery, and when indicated, helps to avoid major surgery and its recovery and potential complications.

• Maternal Complications 

  1. Higher risk of anal sphincter injury (10-20%), though it may be difficult to separate this out from other risks that are associated with operative vaginal birth like prolonged second stage, fetal size, episiotomy, etc. 

     1. One study that controlled for all these other clinical factors: forceps still associated with 6x increase in 3rd and 4th degree tears, and vacuum associated 2x increase.

     2. However, other studies do not clearly show that there is a significant difference in fecal or flatal incontinence through 1 year postpartum.

• Fetal/Newborn Complications 

  1. Very low in general! Intracranial hemorrhage occurs 1/650-850 operative vaginal births and neurologic complication 1/220-385.

  2. Vacuum: usually due to traction on fetal scalp, ie. laceration, cephalohematoma, subgaleal or ICH.

  3. Forceps: facial lacerations, facial nerve palsy, corneal abrasion, and external ocular trauma, skull fracture, ICH.

     1. Rates of ICH are similar for forceps, vacuum, and cesarean deliveries performed during labor.

  4. Compared to those delivered by cesarean, those delivered by:

     1. Forceps: higher rates of fracture, facial nerve palsy, and brachial plexus injury, but lower rates of neurologic complications (ie. seizures, IVH, subdural hemorrhage),

     2. Vacuum: higher rates of cephalohematoma, fracture, and brachial plexus injury, but not central neurologic complications.

  5. Few data assess long-term consequences of operative vaginal birth on the infant, but of the studies we have, there does not appear to be significant differences in cognitive development from those born from forceps or vacuum compared to spontaneous vaginal birth.

When should you abandon operative vaginal birth? 

1. Traditionally, it’s 3 pop-offs for the vacuum extractor, but this may depend on the type of vacuum and institutional policy.

2. With deterioration of the fetal heart tracing without progress, or just no progress in general.

3. Maternal request.

A Pros and Cons Comparison of Methods of Operative Vaginal Birth

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