An Update on Pelvic Inflammatory Disease

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We last covered PID and TOA on the podcast in February 2019 — and since then, as with our gonorrhea and chlamydia update, have some new updates to reflect the 2021 CDC Treatment Guidelines.

What is PID/TOA? 

  • PID: pelvic inflammatory disease 

    • This is a wide variety of inflammatory disorders of the upper female genital tract, including: 

      • Endometritis

      • Salpingitis

      • TOA: tubo-ovarian abscess

      • Pelvic peritonitis 

    • Caused by many infectious diseases. 

      • Most common: N. gonorrhoeae and C. trachomatis (gonorrhea and chlamydia)

        • 50% of PID diagnoses test positive for GC/CT, though this proportion is decreasing.

    • Other organisms that can be implicated:

      • Anaerobes, 

      • G. vaginalis 

      • H. influenzae

      • Enteric GNRs

      • Strep agalactiae

      • Cytomegalovirus 

      • Trichomonas (Trichomonas vaginalis)

      • Mycoplasima hominis and M. genitalium

      • Ureaplasma urealyticum

Diagnosis of PID

  • Can be difficult because of many vague symptoms, and some are asymptomatic 

  • Differential diagnosis is broad for abdominopelvic pain: 

    • Appendicitis 

    • Ectopic pregnancy

    • Ovarian torsion or ovarian cysts

    • Diverticulitis

    • Functional GI pain, IBS, IBD

    • Etc. etc. etc. 

  • A presumptive dx should be made, and treatment started,

    • In sexually active women and those at risk for STIs experiencing pelvic/lower abdominal pain, if no other cause for illness can be identified,

    • and if they have 1 or more of these minimum clinical criteria: 

    • Cervical motion tenderness 

    • Uterine tenderness 

    • Adnexal tenderness  

  • One or more of the following can be used to enhance specificity of the minimal clinical criteria: 

    • Oral temp > 101 F (38.3) 

    • Abnormal cervical mucopurulent discharge or friability 

    • Presence of abundant WBC on saline microscopy of vaginal fluid 

    • Elevated erythrocyte sedimentation rate 

    • Elevated C-reactive protein 

    • Laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis 

  • Even more specific criteria can include:

  • Endometrial biopsy with histopathologic evidence of endometritis 

  • TVUS or MRI showing thickened, fluid-filled tubes with or without free fluid or tubo-ovarian complex

  • Laparoscopic findings of PID (Fitz-Hugh-Curtis syndrome) 

What should I do if I think someone has PID?

  • Testing:

  • HIV

    • Testing recommended by CDC “in all persons seeking STI testing who do not have a known diagnosis of HIV.” 

  • GC/CT

    • 50% will test positive, so they are high yield for PID testing.

    • NAAT testing is preferred method.

      • Patient self-collected swabs are just as accurate as clinician-collected.

      • First void urine is most sensitive; decreases with later voids during the day.

        • Urine testing may miss over 400k infections per year in USA - vaginal swab testing should be offered first, and patient-collected may help improve acceptability.

  • Imaging

    • Not recommended outright by CDC in PID evaluation.

    • Will frequently be part of your evaluation in a differential diagnosis

      • TVUS - may continue to have cervical motion tenderness, can demonstrate TOA. Can also demonstrate other GYN pathologies.

      • CT/MRI - unlikely to demonstrate specific findings for PID outside of large TOAs.

  • Treatment:

    • Primary Considerations: 

  • Choice of medication:

    • Treatment is empiric, requiring broad spectrum coverage of likely pathogens

    • All treatment types should be effective against gonorrhea and chlamydia 

  • Need for hospitalization:

    • Recommended if:

      • A surgical emergency (ie. appendicitis) cannot be excluded

      • Presence of tubo-ovarian abscess 

      • Pregnancy

      • Severe illness including nausea, vomiting, or high fever,

      • Inability to tolerate or follow outpatient regimen

      • Failed outpatient therapy based on follow up

    • Parenteral treatments

      • Ceftriaxone (1g IV q24 hrs) + doxycycline (100 mg oral or IV q12hrs) + metronidazole (500mg oral or IV q12h).

      • Cefoxitin (2g IV q6hrs) + doxycycline (100mg oral or IV q12hrs) 

      • Cefotetan (2g IV q12h) + doxycycline (100mg oral or IV q12hrs)

    • Because of pain associated with IV infusion, doxycycline should be given orally whenever possible.

    • Oral and IV doxycycline and metronidazole have similar bioavailability

  • Alternative regimens pending allergies and antibiotic availability:

    • Clindamycin (900 mg IV q8hrs) + gentamicin (2mg/kg loading dose IV or IM, then maintenance of 1.5mg/kg every 8 hrs, or single daily dosing of 3-5mg/kg) 

    • Ampicillin-sulbactam (Unasyn) 3g IV q6hrs + doxycycline 100mg q12hrs  

  • Goal of parenteral therapy will be to transition to oral antibiotics within 24-48 hours if clinical improvement.

    • Those with TOA should have at least 24 hours of inpatient observation

    • IM/Oral treatment - For continuation of inpatient treatment, or start here in those with mild-to-moderate symptoms of acute PID. 

  • Clinical outcomes are similar to those treated with IV therapy, but if women don’t respond in 72 hours, should be re-evaluated and treated with IV

    • Ceftriaxone 500mg IM x1 + doxycycline 100mg BID x14 days + metronidazole 500 mg BID x14 days 

    • Cefoxitin 2g IM + Probenecid 1g orally + doxycyline 100mg BID x14 days + metronidazole 500mg BID x14 days 

    • Some other 3rd generation cephalosporin + doxy + metronidazole 

  • If starting with outpatient treatment, improvement should be documented by follow up within 72 hours.

    • If no improvement has occurred, then hospitalization, assessment of the antimicrobial regimen, and considering potential additional diagnostics (imaging, laparoscopy) are indicated.

  • Retesting should occur at 3 months after treatment, regardless of treatment of sex partners, to assess for reinfection.

    • Patients should refrain from sex until treatment is completed, symptoms resolved, and sex partners have been treated.

    • Sex partners within previous 60 days of patients with PID should also be treated presumptively for gonorrhea and chlamydia

      • This is regardless of PID etiology or pathogens isolated 

      • Consider expedited partner therapy (EPT).

Managing TOAs 

  • Surgical drainage indicated if:

    • Failure to respond to treatment within 48-72 hours 

    • Clinical decline (ie. becoming septic) 

  • Likelihood of need for surgical intervention is related to the size of TOA: 

    • 60% of those with abscess >10cm 

    • 30% in 7-9cm 

    • 15% in those of 4-6 cm

Special considerations for treatment in certain populations:

  • Pregnancy

    • Pregnant patients with PID are at high risk of morbidity, pregnancy loss, preterm delivery.

    • Hospitalization and consultation with ID are recommended.

  • Persons with HIV

    • Patients with HIV may be more likely to have TOA, though symptoms are similar overall to those without HIV.

    • No data currently to suggest more aggressive therapy is needed in patients with HIV.

  • If patient has an IUD:

    • IUD is not required to be removed with a diagnosis of PID.

    • However, if there is no clinical improvement in 48-72 hours, then should consider removing the IUD.

Systemic Lupus Erythematosus, Part II: Treatment

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So how do we manage lupus in pregnancy? 

  • Medications 

    • Hydroxychloroquine

      • Can decrease disease activity, prednisone use, and adverse pregnancy outcomes.

      • SMFM: We recommend that all patients with SLE, other than those with quiescent disease, either continue or initiate HCQ in pregnancy. 

      • ACR: conditionally recommends starting HCQ in pregnant patients with SLE who are not on it.

      • Some investigators recommend that patients with quiescent disease who have anti-SSA, anti-SSB, or APLS to consider starting HCQ because some studies suggest improved maternal and fetal outcomes in this specific population.  

    • Corticosteroids 

      • Recommended where SLE is not controlled simply with HCQ 

      • Un-fluorinated corticosteroids are largely inactivated by the placenta and preferred:

        • Prednisone, hydrocortisone, prednisolone.

      • Recent evidence suggests corticosteroids are not associated with fetal malformations 

      • However, steroids use can increase risk of gestational diabetes, preeclampsia, FGR, PPROM and PTB 

    • Other immunosuppressive agents 

      • Azathioprine - ok to use, not usually associated with fetal teratogenicity 

      • Cyclosporine - can also be used for refractory lupus flares 

      • Tacrolimus - calcineurin inhibitor - can be used, and has been reported to be more effective than cyclosporine 

    • What should I avoid? 

      • Prolonged use of NSAIDs - can lead to oligohydramnios, increased risk of NEC, premature closure of ductus arteriosus, and pulmonary hypertension 

      • Methotrexate discontinue 1-3 months prior to pregnancy due to teratogenicity 

      • Mycophenolate discontinue at least 6 weeks before attempting pregnancy 

      • Leflunomide - teratogen, and pregnancy should be delayed 2 years after use because of its long half-life and enterohepatic circulation 

    • Biologics 

      • There have been a lot used recently, including TNF-alpha inhibitors (ie. certolizumab, infliximab, adalimumab, golimumab) and other biologics 

      • Certolizumab can be safely used throughout pregnancy 

      • Decision to initiate or continue biologics should be made in collaboration with rheumatology and also be individualized for each patient

What about antenatal considerations? 

  • APLS 

    • If someone has met clinical and laboratory criteria for APLS, goal is to improve maternal, fetal, and neonatal outcomes.

    • For those who have not had previous thrombotic event: recommend prophylactic anticoagulation during pregnancy + 6 weeks postpartum 

    • For those with history of thrombotic event: recommend therapeutic anticoagulation throughout pregnancy + 6 weeks postpartum 

  • Antiphospholipid antibodies without APLS 

    • Patients with antibodies, especially lupus anticoagulant, who don’t meet clinical criteria for APLS remain at risk for preeclampsia

      • The risk of other adverse pregnancy outcomes and optimal management remains unclear 

    • Meta-analysis of those with asymptomatic APL antibodies with or without SLE found no difference in adverse pregnancy outcomes in those who had prophylactic treatment (aspirin) and those who did not 

    • SMFM recommend treatment with low-dose aspirin alone (i.e., no prophylactic anticoagulation)

  • SSA, SSB antibodies 

    • Given risk of neonatal lupus syndrome with or without SLE in those with these antibodies, recommendation is to treat 

    • Treatment with HCQ throughout pregnancy has been proposed to decrease the occurrence of congenital heart block in at-risk fetuses 

      • However, data is still lacking due to adequately powered clinical trials 

    • Another method proposed is to screen for 1st and 2nd degree heart block with echocardiograms, and then use steroids to try and prevent 3rd degree heart block 

      • However, in the PR Interval and Dexamethasone Evaluation (PRIDE) study, they showed that treatment with dexamethasone in some women did reverse first degree heart block 

        • However, some first degree heart block resolved on its own 

        • Several cases of complete heart block occurred without a graded progression through 1st and 2nd degree heart block 

      • There is some retrospective data as well to look at this, but overall, the utility of screening for or treating early heart block remains unproven 

      • Current studies ongoing = STOP BLOQ (Surveillance and Treatment to Prevent Fetal AV Block Likely to Occur Quickly)

    • Current recommendation: steroids should not be used routinely for treatment of fetal heart block due to anti-SSA/SSB antibodies given their unproven benefits nad known risks 

    • Serial fetal echos for assessment of PR interval not be routinely performed in patients with anti-SSA or SSB antibodies outside of clinical trial settings 

    • Doppler assessment of fetal heart rate during routine prenatal visits can be used to screen for fetal complete heart block 

  • Mild lupus flares 

    • Clinical and lab evaluation of possible SLE flare 

      • Physical exam, CBC, anti-dsDNA, complement levels 

      • Start HCQ 200 mg BID, if not already on it 

      • If already on it, can increase to 400 mg 2x/day 

      • If not responding, then can start 15-20 mg of prednisone a day.

  • Severe lupus flares 

    • Same clinical and lab evaluation 

    • Can also look for preeclampsia 

    • Start glucocorticoid dosage 1.0-1.5 mg/kg, then tapered per improvement 

    • Hospitalization may be needed 

    • Rheumatology consultation 

Other recommendations in pregnancy and labor

  • Pre-pregnancy counseling 

    • Patients with SLE should get prepregnancy counseling with MFM and rheumatology - discuss risks for both mom and fetus 

    • In those with severe maternal risk, pregnancy should be discouraged 

      • Active nephritis

      • Severe pulmonary, cardiac, renal, or neurologic disease

      • Recent stroke

      • Pulmonary hypertension 

  • Antenatal Testing

    • Antenatal testing and serial growth scans recommended in patients with SLE due to increased risk of FGR and stillbirth 

      • Currently no evidence to support optimal approach 

      • Usually, will start interval growths at 28 and assess every 4 weeks 

      • Fetal surveillance may start at around 32 weeks 

  • Delivery considerations 

    • Timing, mode, and management of delivery should be individualized 

    • If uncomplicated, early delivery is not recommended, but can be considered at term - ie. at 39 weeks 

    • If other complications, should manage per complication

    • Stress dose steroids in those with prolonged use of steroids 

  • Postpartum management 

    • Incidence of relapse or flare will increase in SLE - as with other autoimmune disease 

    • Can discuss with rheumatology regarding treatment postpartum - not all patients will need prophylactic treatment 

    • NSAIDs can be used for joint pain  

    • Can breastfeed if desired (NSAIDs, HCQ, and corticosteroids are considered compatible by AAP) 

  • Contraception 

    • LARCs such as IUD (with or without levonorgestrel) and etonogestrel implants are good options for patients with SLE 

    • Estrogen-containing oral contraceptives pose a theoretical risk for SLE flares 

      • Can be used in patients with SLE 

      • However, patients with history of active and severe SLE were excluded from randomized trials proving estrogen safety in those with SLE 

      • Contraindicated in those with previous thrombosis or those with APLS  

    • Progesterone only contraception is also safe

Systemic Lupus Erythematosus, Part I: Diagnosis and Risks

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Reading: SMFM Consult Series #64: SLE in Pregnancy

What is systemic lupus erythematosus?

  • Definition

    • Chronic, multisystem, inflammatory autoimmune disease characterized by relapses and remission

    • Many organs can be involved and manifestations are variable between individuals

  • Why do we care about SLE in pregnancy?

    • The prevalence of SLE is about 28-150/100,000 individuals

    • More prevalent in females than males; often affects young adults, so it is a condition that can be encountered in pregnant individuals – currently 3300 deliveries per year are in people with SLE

How do we diagnose lupus?

  • Lupus = a syndrome and diagnosis requires presence of characteristic clinical features + confirmatory laboratory studies

    • Unfortunately, there are broad clinical manifestations, lack of pathognomic features or lab tests

    • Usually, you won’t have to diagnose lupus and someone will come into pregnancy already with the diagnosis

    • However, knowing the diagnostic criteria can be helpful in recognizing individuals who may have lupus

    • Can help the patient have faster recognition + referral to rheumatology

  • Diagnostic criteria – will include 2

    • From The European Alliance of Associations for Rheumatology (EULAR) – sensitivity of 96%, specificity is 93%

    • From the Systemic Lupus International Collaborating Clinics (SLICC) – sensitivity is 97%, specificity is 84%

smfm sTATEMENT ON sle; eular cRITERIA FOR sle

smfm; slicc criteria for sle

smfm; aplas criteria

Pregnancy and lupus

  • Increased maternal morbidity and mortality

    • Complications include nephritis, hematologic complications, neurologic abnormalities

    • Several fold increased risk of thrombosis, thrombocytopenia, infection, multiorgan disease

    • Pregnancy can also increase risk of disease flare, and 15-30% of flares are severe, and some can be life-threatening  

  • Lupus nephritis

    • Active renal disease is defined as >1g/day of proteinuria or GFR <60 in non-pregnant state

    • There is increased risk of permanent renal damage if GFR going into pregnancy is <40 or creatinine is >/= 1.5 mg/dL

    • One issue: difficult to differentiate lupus nephritis from preeclampsia

      • We discussed this in our episode “Imitators of Pre-eclampsia”

      • Features more common with lupus flare and less likely to be preeclampsia: increased anti-dsDNA ab, decreased levels of complements, usually will not have thrombocytopenia or elevated LFTs

      • Also, kidney biopsy that showed glomerulendotheliosis can yield a definitive diagnosis

      • Important to differentiate because the treatment for lupus nephritis can be medical, while severe preeclampsia may require delivery à if we don’t differentiate, could deliver extremely premature infant with no need

  • Hematologic Complications

  • Central Nervous System and Neurologic Complications

    • Can include headache, seizures, neuropathy, chorea, cerebritis, and even psychosis

    • CNS vasculitis is the most serious CNS disorder  

  • Other organ manifestation:

    • Cutaneous lupus erythematousus

    • Can also affect bones, joints, lungs, heart

  • So… how does all this affect pregnancy?

    • Obstetric outcomes:

      • 3x increased risk of pregnancy loss; however, if well controlled, risk ranges from 8-32%, which may not be substantially different from rates reported in the general obstetrical population for early pregnancy loss

      • Increased risk of preeclampsia: 15-35%

        • Risk is highest in those with active disease at time of conception, renal disease, chronic hypertension, those on high-dose prednisone, or those with APLS antibodies  

        • Prevention: low dose aspirin beginning at 12 weeks of gestation until delivery to decrease risk of preeclampsia

    • Fetal outcomes:

      • Risk of fetal growth restriction is 6-35% depending on the study

      • Increased risk of preterm birth, ranging from 19%-49%

        • The risk of preterm birth is associated with increased disease activity at time of conception, nephritis, chronic hypertension, and APLS antibodies

    • Neonatal complications 

      • Occurs in 1/20,000 live births, so it is rare but it is a serious complication

      • Caused by antibodies that can cross the placenta, usually anti-SSA, though anti-SSB antibodies can also cause this

      • Manifestations include skin lesions, congenital heart block, anemia, hepatitis, and thrombocytopenia

        • Skin lesions occur in approximately 50% of affected infants

      • Recurrence risk in patients with history of neonatal lupus and positive antibodies is 15-20% 

      • Because it is due to antibodies, skin, hematologic manifestations, and hepatitis usually resolves 3-6 months after birth; however, congenital heart block will not resolve as SSA antibodies lead to fibrosis of myocardial tissue and conduction system 

Inflammatory Bowel Disease (IBD)

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We’re joined back today by Dr. David Abel, an assistant professor in OB/GYN at Oregon Health and Sciences University. Newly joining us today is Dr. Rachel Madding, who is a PGY-2 at OHSU. Together they share with us some pearls about IBD and IBD in pregnancy, specifically!

Overview of IBD 

  • Comprised of two major disorders:

    • Ulcerative Colitis (UC)

      • Affects the colon and is characterized by inflammation of the mucosal layer.

      • Key defining symptom is bloody diarrhea.

      • UC can also be associated with systemic findings including uveitis, scleritis, erythema nodosum, pyoderma gangrenosum, arthritis, lung disease, and venous thromboembolic disease.

      • Notable for rectal involvement, with a continuous pattern of inflammation.

    • Crohn’s disease.

      • Can involve any component of the gastrointestinal tract from the oral cavity to the anus.

      • Characterized by transmural inflammation often with skip lesions.

      • It may also include perianal and rectal involvement about 50% of the time. 

      • Symptoms of Crohn’s are highly vari­able and include fatigue, diarrhea, abdominal pain, weight loss, rectal bleeding, fistula, perianal abscess formation and aphthous ulcers.

Epidemiology of IBD

  • Approximately 1.6 million Americans have IBD.

    • About 70,000 new cases diagnosed in the US each year.

    • More than 50% of those with IBD are women and will carry the diagnosis during their reproductive years.

      • For every 100,000 deliveries, approximately 130 will be complicated by IBD.

      • Crohn’s disease in particularly seems to carry a slight female preponderance.

IBD and Pregnancy-Specific Risks

  • Patients with IBD appear to be at increased risk of preterm delivery, low birth weight, and cesarean delivery.

    • Active disease, particularly at the time of conception, seems to increase the risk of adverse outcomes.

  • Preterm delivery is the most consistent adverse outcome associated with IBD disease activity in pregnancy.

    • A meta-analysis of over 3900 pregnant women with IBD showed an increased rate of preterm delivery and low birth weight by approximately 2-fold, regardless of disease activity as com­pared with patients without IBD.

    • Large population-based studies have also shown that patients with IBD have a 1.5- to twofold increase in the rate of cesarean delivery.

      • The etiology of the association of IBD with adverse pregnancy outcomes remains unclear.

      • One theory is that IBD represents a generalized inflammatory state.

  • With regards to other adverse perinatal outcomes, the data is conflicting.

    • Possible increased risks of spontaneous abortion, preeclampsia, eclampsia, placental abruption, fetal distress, placenta previa, and premature rupture of membranes.

  • VTE Risk

    • Increased risk of venous thromboembolism in patients with IBD

    • The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy recommends consideration of prophylactic anticoagulation when a pregnant patient with IBD is hospitalized for an IBD flare, or after undergoing a cesarean section. 

      • The American College of Chest Physicians does not consider IBD specifically as a venous thromboembolism risk factor, however it does recommend post-cesarean prophylactic anticoagulation for those with one major or at least two minor risk factors for VTE.

Pregnancy’s Impact on IBD

  • Risk of having a flare during pregnancy in patients with quiescent disease is similar to the nonpregnant patient.

    • For those who conceive when their disease is quiescent, disease tends to remain in remission throughout the pregnancy and postpartum.

    • Among patients with Crohn’s disease who conceive while their disease is active, the disease goes into remission in one-third, remains stably active in one-third, and worsens in one-third.

    • Patients with UC in pregnancy often have more active disease compared with Crohn’s.

  • Medication Use:

    • Greatest risk to their pregnancy is active disease at the time of conception, so discontinuing their medication during this time can have adverse effects.

    • Most medications are not associated with congenital anomalies and adverse perinatal outcomes.

    • There are several classes of medications including corticosteroids, which are used to treat flares mostly, aminosalicylates, antibiotics, immunomodulators and biologics.

      • Aminosalicylates i.e., sulfasalazine and mesalamine

        • Commonly used in UC to reduce intestinal inflammation.

        • Not associated with fetal risks, but may increase nausea and gastrointesti­nal reflux in pregnancy.

        • Should be given with at least 2 mg folic acid during pregnancy because of antifolate effects.

      • Antibiotics primarily used for flares and complications such as pouchitis and perianal disease.

        • Generally avoid fluoroquinolone.

      • Immunomodulators

        • Azathioprine, cyclosporine, 6-mercaptopurine can be used.

          • Data suggests a high rate of relapse when these drugs are discontinued.

        • Methotrexate and thalidomide are contraindicated

          • For those who are taking methotrexate, the recommendation is to wait 3-6 months after discontinuation before trying to conceive.

      • Biologics / anti-TNF agents

        • Increasingly used in the treatment of both IBD and autoimmune conditions

        • Infliximab, also known as remicade, adalimumab, also known as humira, and certolizumab, also known as cimzia.

        • These agents are IgG antibodies and cross the placenta

          • Exception: certolizumab, which does not cross the placenta because it lacks the necessary Fc receptor to facilitate placental transfer.

        • Safety data from prospective trials and large nationwide cohorts of women who continued taking biologics in pregnancy have not shown an increase in adverse fetal outcomes.

          • The greatest amount of safety data is for infliximab and adalimumab, which have shown no increased rates of congenital anomalies or infections among infants up to 1 year of age who were exposed to these agents in utero.

          • PIANO study (Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes): no increase in adverse events based on drug exposure during pregnancy or placental transfer of biologics.

        • Biologics may result in B cell suppression in the infant; however, this appears to subside after 4-6 months.

Mode of Delivery Considerations with IBD

  • All patients have the option of having an elective primary cesarean section.

  • For most patients, a vaginal delivery is encouraged as the risks of a cesarean section are greater.

    • For those with Crohn’s disease and a history of perianal disease but no current active disease, a vaginal delivery is reasonable, although some may still elect to undergo cesarean section.

      • For those with active perianal disease, a cesarean section is often performed due to concerns for complicated perianal and/or sphincter injury and healing.

    • For those with UC who have undergone an ileal pouch anal anastomosis, also referred to as an IPAA or J-pouch, a cesarean delivery is often performed due to concerns for anal sphincter injury and pouch dysfunction.

      • However, a history of an IPAA is not an absolute contraindication to a vaginal delivery.

Preconception Counseling Pearls

  • Stress the importance of remaining on their medications, unless taking MTX.

  • Patients need to know that if their disease is quiescent prior to pregnancy, this portends a more favorable course during pregnancy.

    • Most patients with inactive disease do well during pregnancy.

    • It is important to watch for a flare in the postpartum period.

  • For patients who have active disease, ideally contraception until disease is controlled is important to reduce the risk of adverse perinatal outcomes.

  • Most patients should be under the care of a gastroenterologist

    • If not, it is important to reestablish care, as a multidisciplinary approach serves to optimize outcomes.

Advanced Maternal Age (AMA)

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Check out the new ACOG/SMFM Obstetric Care Consensus #11, Pregnancy at Age 35 Years or Older.

Why do we care about age in pregnancy? 

  • Maternal age 

    • CDC data (2020): continuing upward trend in the mean age of pregnant people in the US 

      • 19% of all pregnancies are currently in people 35 and older 

      • Mean age of people having their first birth in 2020 was 27.1, compared to 21.4 in 1970 

    • Pregnancies in patients that are older are associated with higher risks, even if they come into the pregnancy as healthy individuals 

  • Definition 

    • Advanced maternal age: women who are 35 years or older at estimated date of delivery.

      • Why 35?

        • Selected based on evidence of declining fertility and concern surrounding increased risk for genetic abnormalities in babies born to those who are over the age of 35 

        • This has been a historical figure that we have used – this threshold is pretty arbitrary 

    • Some risks associated with older age may not influence outcomes until even later in life (ie. 40 and older) 

      • The risk is on a continuum - there is no jump in risk just because someone hits 35 

      • More recent studies will stratify risk by age group, so for example, will divide out patients by age in 5 year increments (ie. 35-39, 40-44, etc).

Risks of AMA Status

  • Pregnancy risks

    • Compared to those of younger age, patients who are >35 at time of delivery are at higher risk of

    • Gestational diabetes,

    • Preeclampsia,

    • Labor dystocia, and

    • Cesarean delivery  

  • Fetal/neonatal risks 

    • Increased risk of preterm delivery

    • Increased risk of NICU admission, low birth weight 

  • These risks are on a continuum, with risks increasing progressively with advanced age, particularly in those older than 40 at the time of delivery 

    • When looking at cohort studies, women 45-54 were at the highest risk of overall complications 

  • Chronic medical disorders 

    • More prevalent in individuals >35 years of age 

    • Include things like obesity, hypertension, diabetes - studies show that pregnant people 35 or older are 2-4x more likely to have cHTN and nearly twice as likely to have T2DM as pregnant people 25-29 years old 

      • These are also risk factors for poor outcomes.

Considerations in pregnancy care for=patients older than age 35:

  • Prevention of Preeclampsia 

    • There is increased risk of preeclampsia in pregnancy patients older than 35 

    • In one large meta-analysis, the risk of preeclampsia progressively increased with increasing age.

      • However, the difference was only statistically significant in women aged 40 years and older 

    • In USPSTF systematic review, there was reduction in risk of preeclampsia, preterm birth, small for gestational age, and perinatal mortality in individuals at increased risk of preeclampsia who took low-dose aspirin prophylaxis. 

    • Recommendation: start low-dose aspirin (81 mg/day) ideally between 12-16 weeks of gestation, and continue daily until delivery in those at high-risk of preeclampsia 

      • Those who are 35 or older are at moderate risk of preeclampsia, so it is reasonable for those who are 35 or older with one high risk factor or at least one additional moderate risk factor to start low-dose aspirin therapy 

    • Other moderate risk factors:

      • Nulliparity

      • Obesity (BMI >30)

      • Family history of preeclampsia

      • Black race (as proxy for underlying racism)

      • Lower income

      • Personal history factors (ie. low birth weight, previous adverse pregnancy outcome)

      • IVF  

    •  High risk factors 

      • History of preeclampsia

      • Multifetal gestation

      • Chronic hypertension

      • Pregestational diabetes,

      • Chronic kidney disease

      • Autoimmune disease

  • Genetic Screening 

    • Over time, there is decrease in oocyte and oocyte quality 

      • Decline accelerates in 4th decade of life likely due to myriad of hormonal changes regulating the ovaries 

      • Individual’s fertility will decline with increasing age 

    • Frequency of aneuploidy will increase with age 

      • However, not all aneuploidies or genetic abnormalities increase with age:

        • Sex chromosome trisomies and other trisomies increase with age 

        • However, sex chromosome monosomies and copy number variants seem to be independent of maternal age at pregnancy 

    • Pregnant individuals should be aware of these risks and therefore, clinicians should be ready to discuss prenatal genetic testing (both screening and diagnostic) 

    • There is conflicting data about increased risk of major congenital anomaly affecting the fetus in patients who are 35 years of age or older.

      • However, a detailed fetal anatomic survey should be done.

ACOG/SMFM OBSTETERIC CARE CONSENSUS #11

  • Growth abnormalities 

    • Both large for gestational age and small for gestational age occurs in neonates at higher frequencies as maternal age increases.

      • Most of this data is for patients who are age 40 or above 

    • Insufficient evidence to recommend ultrasound for growth assessment in third trimester for individuals 35-39 years of age in absence of other risk factors 

    • But given the data for individuals age 40 and above, SMFM and ACOG recommend a growth ultrasound in the third trimester 

      • However, there is no data to guide timing or frequency of ultrasound assessments in individuals 40 or older 

  • Prevention of stillbirth 

    • We know there is increased risk of stillbirth with advancing age in pregnancy:

    • In 2013, the stillbirth rate in the US was 6.0/1000 pregnancies that extended beyond 20 weeks of gestation 

      • For women 40-44: 10.1/1000 births 

      • For women >45: 13.8 /1000 births 

      • Risk of stillbirth at 37-41 weeks was 1/382 pregnancies for those 35-39, 1/267 in women 40 and older 

    • However, the benefit of antenatal fetal surveillance to reduce the risk of stillbirth in this population remains unknown.

      • ACOG and SMFM have established guidance that suggests surveillance for conditions where stillbirth occurs more frequently than 0.8/1000 

      • Therefore, for those who will be 40 or older at time of delivery, antenatal surveillance is reasonable.

        • Reasonable to initiate some time between 32- 36 weeks of gestation 

      • Insufficient evidence for those 35-39 years of age

    • Regarding delivery 

      • Rate of stillbirth at 39 weeks in women 40 or older is nearly the same as rate of stillbirth of women aged 25-29 who are beyond 41 weeks gestation 

        • Therefore, delivery in well-dated pregnancies at 39 weeks of gestation or later for individuals 40 or older should be considered 

      • Evidence for elevated stillbirth risk in individuals aged 35-39 is not sufficient to support a clear recommendation regarding timing of delivery beyond routine practice 

  • Health equity 

    • There is currently inequity in terms of maternal mortality and perinatal outcomes in patients who identify as non-Hispanic Black, as well as those that identify as American Indian and Alaskan Native 

    • Maternal mortality 

      • CDC Pregnancy Mortality Surveillance System data shows that maternal mortality trends determined a pregnancy related mortality ratio of 3.2 for non-Hispanic Black women compared to non-Hispanic White women 

      • Ratio increased to 4.9 for non-Hospanic Black women between ages 35-39 

      • 3.6 for women aged 40 years and older 

    • Fetal outcomes 

      • Preterm birth, SGA, stillbirth occur more frequently in some racial and ethnic groups that are disproportionately affected by social and structural barriers to care 

      • Infant mortality rate for non-Hispanic black and American Indian/Alaska Native infants are 10.7/1000 live births and 7.9/1000 live births respectively 

      • This is double the rate of non-Hispanic white infants 

    • It is unclear the best strategy to overcome these inequities, but: 

      • Ob/Gyns and other professionals should consider systems-based and individual strategies to reduce racial and ethnic disparities in care and outcomes 

      • Systems: internal assessment of barriers and facilitators to providing equitable care, implementing unconscious bias and communication training, advocating for patient input in decision making