Anemia in Pregnancy

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Be sure to check out the new ACOG Practice Bulletin #233 on anemia — first time it’s been updated in a while! And while you’re at it, check out our old episode on sickle cell anemia.

Physiologic Changes in Pregnancy to Blood Volume 

  • Definitions

    • Remember that anemia in pregnancy is defined as: 

      • Hgb <11 g/dL in the first and third trimester 

      • Hgb <10.5 g/dL in the second trimester 

      • Previously, ACOG had discussed a lower threshold for certain people based on race, but one important study found that this lower threshold likely contributes to the perpetuation of racial disparities in medicine without a scientific reason for lower Hgb 

  • What happens in pregnancy? 

    • Physiologic

      • Plasma volume expands by 40-50%

      • Erythrocyte mass expands by 15-25% 

      • So even though there is increased red cell mass, it seems overall that HCT % goes down 

    • There is also increased iron requirement, so it is more likely for people to become iron deficient 

Causes of Anemia in Pregnancy 

  • Acquired 

    • Deficiency 

      • Iron deficiency - by far the most common 

      • B12 deficiency 

      • Folic acid deficiency 

    • Hemorrhagic 

    • Anemia of chronic disease 

    • Acquired hemolytic anemia 

    • Aplastic anemia 

  • Inherited 

    • Thalassemias 

    • Sickle cell 

    • Hemoglobinopathies 

    • Inherited hemolytic anemias 

Work-up of Anemia in Pregnancy 

  • Screening 

    • All pregnant people should be screened for anemia with CBC in the first trimester and again right before third trimester (usually 24-28 weeks) 

    • Also, should have discussion with everyone about screening for hemoglobinopathies if they have not been screened before 

  • Work up of asymptomatic with mild to moderate anemia: 

    • Anemia type: microcytic vs normocytic vs macrocytic 

      • Microcytic (MCV < 80 fl) 

        • Most commonly: iron deficiency 

        • But can also be caused by thalassemias, anemia of chronic disease, sideroblastic anemia, etc. 

      • Normocytic (MCV 80-100fL) 

        • Hemorrhagic or early iron deficiency = common 

        • Others: anemia of chronic disease, bone marrow suppression, chronic renal insufficiency, hemolytic anemia 

      • Macrocytic (MCV > 100 fL) 

        • Folic acid deficiency, B12 deficiency = most common 

        • Others: Reticulocytosis, liver disease, alcohol abuse, drug-induced hemolytic anemia 

  • Iron studies with measurement of red blood cell indices, serum iron levels, ferritin levels 

    • Some places also include a total iron-binding capacity 

    • In someone with iron deficiency, iron levels and ferritin will be low, while TIBC will be high 

  • Peripheral blood smear 

  • Can also look at vitamin B12 and folate levels if macrocytic 

  • Other work-up: 

    • If not responding to treatment with iron, folate, or B12, then further workup should be done 

    • Ie. is there a reason for malabsorption (gastric bypass?) 

    • Is there a reason for blood loss? 

Treatment of Anemia in Pregnancy 

  • Iron deficiency 

    • Can start with oral iron, unless there is a reason for malabsorption 

      • Usual requirements: 27 mg daily during pregnancy, and usual diet will live 15 mg of elemental iron/day 

      • Most oral forms of iron will exceed this 

      • If unable to tolerate oral iron or has reasons for malabsorption, can do IV iron, which can come in the form of iron dextran, ferric gluconate, or iron sucrose 

  • Folate or B12 deficiency

    •  MCV > 115 is almost exclusively seen in people with folate or B12 deficiency 

    • Give folate or B12! 

    • Folic acid: 400 mcg/day unless there are other indications for increased folate (ie. history of neural tube defect affecting child, on anti-epileptics) 

    • B12: usually only seen in people with gastric resection or Crohn disease 

      • Usually given IM every month, 1000 mcg/injection 

  • Other causes 

    • Depending on the cause, may need to work with colleagues from other specialties 

    • Or your friendly neighborhood MFM 

  • A word on transfusion 

    • Hgb <6 g/dL have been associated with abnormal fetal oxygenation 

    • Usually recommend transfusion if Hgb <7 or if symptomatic 

    • However, can consider higher threshold if other co-morbidites (ie. sickle cell anemia with known crises if Hgb <7) 

Obesity and Pregnancy

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Definition and Epidemiology

  • Obesity - classified by BMI 

    • Prevalence of obesity has increased to 34.0% in women 20-39 years in 2010  

ACOG PB 230

Effect of Obesity on Pregnancy 

  • Pregnancy Loss 

    • Increased risk of SAB (1.2 OR) and recurrent miscarriage (OR 3.5) 

    • Also have increased risk of pregnancies affected by neural tube defects, hydrocephaly, and other anomalies 

  • Pregnancy Complications 

    • Antepartum

      • Medical issues: increased risk of cardiac dysfunction, proteinuria, sleep apnea, nonalcoholic fatty liver disease 

      • Pregnancy issues: increased risk of gestational diabetes, preeclampsia, stillbirth 

        • Risk of stillbirth increases with increasing obesity

          • OR 1.71 for BMI 30-34.9

          • OR 2.0 for BMI 35.0-39.9

          • OR 2.48 for BMI >40

          • OR 3.16 for BMI > 50

        • Of note, the practice bulletin does point out that black pregnant people with obesity have a higher risk of stillbirth than white pregnant people - discusses that while this is not a biological reason, is a proxy for likely negative influence of racism on health 

    • Intrapartum

      • Increased risk of cesarean delivery, failed trial of labor, endometritis, wound rupture/dehiscence, and venous thrombosis  

      • Decreased likelihood of VBAC after TOLAC 

    • Postpartum Complications - increased risk of future metabolic dysfunction 

    • Fetal complications - increased risk of growth abnormalities 


  • How Can We Manage Obesity Before And During Pregnancy 

  • Pre-pregnancy Counseling 

    • Discussion of control of obesity with weight loss (either surgical or non-surgical) 

    • Even small weight loss can be associated with improved outcomes (even 5-10%) 

    • Can try motivational interviewing 

      • Encourage diet, exercise, and behavior modification 

    • Medications 

      • Not recommended pre-pregnancy or during pregnancy 

  • During Pregnancy 

    • Recommended weight gain 

      • Overweight: recommend 15-25 lb weight gain 

      • Obese: recommend 11-20 lb weight gain 

      • There is a lack of data regarding short-term and long-term maternal and newborn outcomes, no recommendation for lower targets for pregnant women with more severe degrees of obesity 

    • Congenital Anomalies

      • As previously discussed, increased risk of congenital anomalies, but detection of these anomalies is significantly decreased with increasing maternal BMI 

      • Cell-free DNA test failures are also more frequent in patients that are obese. This is because a minimum fetal fraction of 2-4% usually is needed. The median fetal fraction between 10-14 weeks is around 10%, but with increasing BMI, it’s associated with decreased fetal fraction. 

      • Can consider repeating screening if it’s because of early gestation, but not recommended if there are ultrasound findings of anomalies 

    • Metabolic Disorders - screen for glucose intolerance and OSA at first antenatal visit with history, exam, and labs 

      • Sleep medicine evaluation 

      • Can consider early glucose screening; if negative, repeat at usual time of 24-28 weeks 

    • Stillbirth and Antepartum fetal testing 

      • This is going to be different based on your institution 

      • Can consider weekly testing after 37 weeks for BMI 35-39.9 

      • Can consider weekly testing after 34 weeks for BMI >40 

  • Intrapartum 

    • Many studies that show an increased risk of C-section among overweight and obese women 

      • There are studies that show an increased length of time in labor; another study showed that maternal BMI was not associated with longer second stage 

      • Maybe consider allowing more time in first stage of labor before C-section in obese individuals? 

      • Remember that pregnant women with higher BMI have a higher rate of complications with elective repeat cesarean section - so not a reason to not TOLAC them! 

    • Some considerations during labor 

      • Consider anesthesia consult - especially if OSA. An epidural may be technically more difficult to place 

      • Antibiotics - may need to increase the amount of Ancef before C-section (remember usual is 2g). Increase to 3g if >120 kg 

  • Postpartum 

    • There is an increased risk of VTE in obese women, so definitely use your SCDs and encourage early mobilization  

    • In very high risk groups, discuss pharmacologic thromboprophylaxis 

      • Dose can be BMI stratified

        • BMI < 40: 40 mg Lovenox daily 

        • If BMI 40-59.9: 40 mg BID 

        • If BMI 60 or greater: 60 mg BID 

Headaches & Pregnancy

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What are the different types of headaches? 

  • Migraine 

    • Episodic disorder that is usually manifested as unilateral headaches, sometimes associated with nausea or light/sound sensitivity 

    • Common disorder that affects 12-15% of general population 

    • Can occur over several hours to several days 

    • Different phases of migraine:

      • Prodrome - can occur in up to 77% of people, usually can be symptoms like yawning, depression, irritability, food cravings, neck stiffness, etc 

      • Aura - 25% of people will experience an aura that is gradual, sometimes visual (bright lines), auditory (tinnitus, etc), somatosensory, motor, or even can be smell 

      • Headache - usually unilateral, tends to be throbbing 

      • Postdrome - sometimes can happen. Head movement may cause pain in location of the previous headache 

    • Triggers - can be different for different people. Common triggers are things like menstrual cycle, stress, etc 

  • Tension headache 

    • Usually moderate headaches with bilateral, non-throbbing quality 

    • Often described as “pressure,” sometimes may feel like a band around the head (headband area) 

    • Precipitated usually by stress

  • Cluster headache 

    • Severe headache that can be accompanied by autonomic symptom, come in “clusters”  

    • It is a type of trigeminal autonomic cephalagia (TACs) 

    • Usually characterized by severe orbital, supraorbital, or temporal pain, and also with autonomic features. Always unilateral. 

    • Different from migraines because these patients usually prefer to move around or pace, can be restless (people with migraines want to lie down in a dark room) 

    • Autonomic symptoms: ptosis, miosis, tearing, rhinorrhea, nasal congestion on the same side as the pain 

  • Secondary headaches

    • Have an underlying cause (i..e., headache is a symptom of the problem) - this is something we may need to be worried about.

      • More benign: sinusitis, URI, idiopathic intracranial hypertension (IIH) 

      • More serious: tumor, bleeding, meningitis.

Evaluating a Headache 

  • History 

    • Your usual history, but be sure to ask about age of onset of headaches (has this been going on for 20 years, or just today?), presence of aura/prodrome, frequency and intensity

    • # of headaches/month, site of headache/other symptoms associated

    • Current meds 

    • Changes in vision, association with trauma, changes in work/lifestyle, timing around menstrual cycle 

  • Physical 

    • Blood pressure and pulse - always in pregnancy — worry about preeclampsia!

    • Palpation of neck, head, and shoulder 

    • Full neuro exam 

  • Labs and Imaging 

    • CT or MRI are common modalities 

    • Consider imaging if danger signs are present (i.e., abnormal neuro exam)

    • Also consider lumbar puncture if there is concern for infection 

When should I be worried about a headache? 

  • Low Risk Features

    • Age <50

    • Features that are typical of primary headaches (see above) 

    • History of similar headaches, no change in usual headache or new symptoms 

    • No abnormal neurologic symptoms  

  • Higher Risk Characteristics

    • Fever, abrupt onset, older age, neurologic deficit (including altered mental status), history of tumors, papilledema

    • Change in previous pattern, headache with positional change, post-trauma, painful eyes (or change in vision!) 

    • And of course, pregnancy!

    • Reason for emergency eval: thunderclap headache, Horner syndrome or other neurologic deficit, concern for meningitis or encephalitis, papilledema, possible carbon monoxide exposure. 

What are typical headache treatments? 

  • Non-Pregnant 

    • Migraine Headache

      • Analgesics like NSAIDs, Tylenol; treating earlier in the course is more effective 

      • If unresponsive, can consider triptans or ergots 

      • If still severe, consider ketorolac and a dopamine receptor blocker (ie. prochorperazine and metoclopramide)  

      • Some patients may need to be on medications like triptans or beta blockers to prevent headaches 

        • Preventive first line agents are propranolol, amitriptyline, topiramate 

    • Tension Headache

      • Usually rest, hydration

      • NSAIDs, acetaminophen 

      • Then consider caffeine, metoclopramide, diphenydramine, etc. 

    • Cluster Headaches

      • Oxygen! Try it first if available - 100% oxygen inhalation 

      • If not available, then subcutaneous sumatriptan (3mg-6mg); can also use intranasal if subq not available 

        • Administer the intranasal sumatriptan to the contralateral side because patients with cluster headaches and other trigeminal autonomic cephalalgias have rhinorrhea or nasal congestion that is on same side as pain.

      • Prevention: verapamil… agent of choice for initial preventative therapy. Can also start with a short course of prednisone

        • This is because we know that cluster headaches come in… you guessed it! Clusters!  

  • In Pregnancy 

    • May need to avoid NSAIDs in certain trimesters 

    • Start with Tylenol (650-1000mg), then can ad metoclopramide 10 mg 

    • Can also try combination like butalbital-acetaminophen-caffeine 

      • Other options are things like diphenhydramine (benadryl), or prochlorperazine, as some types of headaches may be associated with n/v and can help with this 

    • Consider fluids if someone is dehydrated (again, n/v in pregnancy) 

    • Magnesium sulfate or magnesium oxide sometimes can help. If someone has frequent headaches, there is some data that magnesium can prevent headaches 

    • If still bad, consider NSAID, but usually should not be used after 32 weeks to prevent closure of the PDA; usually a one time dose is ok 

    • Third line = opioids because they can be addicting and can worsen other issues of pregnancy like nausea/vomiting/constipation 

    • Triptans - if not responding to anything else, can consider triptans. Most studies showing exposure in pregnancy have been reassuring (most studies are with sumatriptan) 

      • Long term triptan use in pregnancy - discuss individually with patient 

      • Limited data, but from registries, no increased risk of major malformation

      • If patients can use other meds, try those first, but if refractory and need sumatriptan, ok to use 

    • Other things to consider if refractory: 

      • Glucocorticoids, peripheral nerve blocks 

      • Call your neurology colleagues!

    • Meds to avoid 

      • Ergotamine - do not use because can cause tetanic uterine contractions 

Opioid Use Disorder in Pregnancy

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For more on this topic, check out ACOG Committee Opinion #711

Opioid use in pregnancy

  • It is becoming more and more common, just like opioid use in general in the US population 

    • In 2007 - 22.8% of women who were enrolled in Medicaid filled an opioid prescription

    • There has also been an increase in neonatal abstinence syndrome (1.5/1000 hospital births in 1999 → 6.0/1000 births in 2013) 

    • Substance use can be a major risk factor in pregnancy-associated deaths 

What is opioid use disorder? 

  • Pattern of opioid use characterized by tolerance, craving, inability to control use, and continued use despite adverse consequences 

    • DSM-5: 11 main symptoms of opioid use disorder and defines severity of the disorder based on # of recurring symptoms experienced within 12-months 

      • 2-3 symptoms = mild, 4-5 = moderate, 6+ = severe 

  • OUD should be handled like a disease and is treatable 

  • Is it harmful in pregnancy? 

    • Most opioids have not been shown to increase the risk of birth defects in prenatal exposure 

      • There has been some association between first trimester use of codeine with some congenital abnormalities in some studies, but not in others 

    • Untreated addiction to heroin is associated with lack of prenatal care, increased risk of fetal growth restriction, placental abruption, fetal death, and preterm labor 

      • Untreated addiction is also associated with engagement in high-risk activities (ie. prostitution, criminal activities) that can expose patients to violence, STIs, etc 

    • On other thing to be aware of is the social implications - can lead to patients being arrested and losing custody of their children 

How do we identify opioid use disorder in pregnancy? 

  • Ask about it!!!

  • ACOG states to use the SBIRT method: 

    • Screening - assess for opioid use with a validated screening method 

      • One common tool is the “5-P tool” which asks about parents, peers, partners, past, and present 

        • Basically: did your parents have a problem with substance use? Do any of your friends have a problem with substance use? Does your partner have an issue ***. Have you in the past? Have you in the past month etc. 

    • Brief Intervention - engage patient showing risky behavior in a short conversation, provide feedback and advice 

    • Referral to Treatment 

  • Quick note on urine drug screens

    • These should only be done with patient consent, and should be done in compliance with your state laws 

    • Pregnant patients should also be made aware of legal ramifications of testing positive  

    • You shouldn’t do this to “penalize” your patient or “catch” your patient. 

How do we treat opioid use disorder in pregnancy? 

  • Medication-assisted therapy (MAT)

    • Usually with opioid agonist therapy like methadone or buprenorphine 

    • Reasoning: avoid withdrawal symptoms and prevent complications of nonmedical opioid use by reducing relapse risk and its associated consequences 

      • Patients that have opioid use disorders will engage in risky behaviors to obtain opioids (ie. heroin) that can sometimes be dangerous (both behaviors and the non-medical opioid

      • Also improves adherence to prenatal care and addiction treatment programs 

    • Methadone 

      • Dispensed daily by registered treatment programs/clinics 

      • Usually have a comprehensive treatment location 

      • Methadone doses may need to be adjusted throughout pregnancy to avoid withdrawal symptoms

        • May need to go to twice daily dosing  

      • Can have interactions with other medications (ie antivirals) and can prolong QTc 

    • Buprenorphine (Subutex)

      • Acts on same mu-opioid receptors as heroin and morphine, but is a partial agonist → overdose is less likely 

      • Fewer drug interactions

        • Therefore, can be treated on an outpatient basis without need for daily visits to an opioid treatment program 

      • Can also be combined with naloxone (Suboxone) to reduce diversion because if injected, will cause severe withdrawal 

    • You should not transition from methadone to buprenorphine because of significant risk of precipitated withdrawal (remember that buprenorphine is a partial agonist) 

  • What about withdrawal as therapy? 

    • Usually not recommended because it is associated with higher relapse rates (59-90%) and poorer outcomes 

      • Relapse leads to risky behavior, no prenatal care, etc. 

    • However, if patient does not accept medication, medically supervised withdrawal is an option — often requires prolonged inpatient care and intensive outpatient behavioral health follow up 

  • Behavioral therapy - also encouraged 

Considerations in antepartum/intrapartum/postpartum care 

  • Consult with NICU, anesthesia, and pain specialists 

    • Patients may require more pain medication than average, especially if recovering from C/S 

    • Also, they should be aware of neonatal abstinence syndrome and that their baby will need to stay in the NICU for a few extra days and may not be able to go home with the immediately 

      • Can be seen in 30-80% of babies born to patients taking opioids 

      • Can manifest as disturbances in GI, autonomic, and central nervous systems → irritability, crying, poor sleep, uncoordinated sucking reflexes, and poor feeding 

      • Each NICU or nursery may have their own protocols, so check with yours to see how long they tend to observe babies after birth 

    • Breastfeeding is encouraged if patients are stable on opioid agonists 

  • Continue their medication - don’t stop methadone or buprenorphine while inpatient!

  • Possible dose reduction postpartum - work closely with their methadone clinic 

Asthma

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Asthma is a common disorder of the lung where inflammation causes the bronchi to swell and narrow the airways (ie. bronchospasm) . This leads to reversible, recurrent airway obstruction. Symptoms include wheezing, shortness of breath, or difficulty breathing, which are often associated with “triggers” → at night, during exercise, with allergens (ie. infection, animals, mold, smoking, pollen, etc).

Let’s talk through asthma and how to treat it!

  • How do I diagnose asthma? 

    • History - wheezing, cough, shortness of breath, chest tightness; temporal relationships and triggers 

    • Physical - wheezes on auscultation 

      • Should be confirmed by demonstrating airway obstruction on spirometry that is at least partially reversible 

      • Pulmonary function tests!

  • FEV1 forced expiratory volume in 1 second

    • >12% increase in FEV1 after bronchodilator = asthma

  • FVC forced vital capacity (basically all the air that you can breathe out) 

  • Normal FEV1/FVC ratio is around 75%, but predicted normal values can be calculated based on age, sex, and height

    • Asthma is an obstructive process, so FEV1/FVC ratio will be reduced

      • This is opposed to a restrictive process, where the FEV1/FVC ratio is not reduced, but both FEV1 and FVC ARE reduced about equally)

  • How does asthma change in pregnancy / why do we care about it in pregnancy? 

    • Oxygen is good for everyone!

      • Goal is adequate oxygenation of the fetus and prevent hypoxic episodes in pregnant person 

    • Poorly controlled asthma may be associated with increased prematurity, need for C/S, preeclampsia, growth restriction, other perinatal complications, and maternal morbidity/mortality 

  • How do I classify asthma?

ACOG PB 90

  • How do I treat asthma? 

    • In general: 

      • Avoid factors that precipitate attacks (ie. allergens, smoke, pollen) 

      • Get consultants on board if complex or difficult! (i.e., medicine/pulmonary)

    • Mild intermittent asthma - albuterol as needed, no daily meds 

    • Mild persistent asthma - add low dose inhaled corticosteroids 

      • Additional alternatives that could be considered are things like Cromolyn, leukotriene receptor antagonist, or theophylline 

    • Moderate persistent asthma - add long-acting beta agonist (i.e., salmeterol) alongside low dose inhaled corticosteroid / increase to medium-dose inhaled corticosteroid (if needed) / medium-dose inhaled steroid and salmeterol 

    • Severe persistent asthma - High-dose inhaled corticosteroid and salmeterol, and if needed, oral corticosteroid 

@AmbCareRx

  • Assessment of acute asthma

    • Medical history and exam (as always) 

    • Examine airway function and fetal well-being if after 24 weeks 

    • Patients with FEV1 measurements >70% for >60 minutes can usually be discharged if not in distress

    • Can order VBG if you want to get a gas, and can likely keep in ED for treatment if FEV1 <70% but >50%  

    • However, if FEV1 <50%, may need admission 

    • If patient becomes more drowsy, poor response, severe symptoms, confusion or PCO2>42mmHg, this may be a reason to admit to ICU 


  • Treatment of acute asthma (in ED or in OB triage) 

    • Oxygen for saturation >95%; measure spirometry at bedside with respiratory therapy.

    • Inhaled short-acting beta2 agonist by nebulizer or metered dose inhaler 

    • Oral systemic corticosteroid if no immediate response.

      • If patients have FEV1 that is <40%, may need high dose inhaled short-acting beta2 agonist + ipratropium by nebulizer every 20 minutes or continuously for 1 hour and oral corticosteroids 

    • If impending respiratory arrest - intubation and mechanical ventilation — get critical care, pulmonary, and/or anesthesia on board!

    • If improved / discharging: short-acting inhaler (i.e., albuterol) 2 puffs every 3-4 hours as needed and oral corticosteroids 40-60mg for 3-10 days. No need for tapering the steroid!

      • Ensure post-discharge follow up within 1 week!