Fetal Growth Restriction: An Update

Two years ago we did a podcast on fetal growth restriction with Dr. Chris Nau based on ACOG PB 204. Little did we know that soon there would be even more changes to fetal growth restriction management! We offer up today’s podcast as an overview of those changes.

More reading on these changes in the form of SMFM Consult Series #52 and the new ACOG PB #227.

Terminology to Know

• Estimated fetal weight - is… an estimated fetal weight! In utero 

• Fetal growth restriction - means “fetal” growth restriction. Again… in utero! 

• SGA = small for gestational age - refers to the baby when it is born. So:

  • A fetus cannot be SGA, but can be FGR;

  • A baby can be SGA, but not FGR.

Etiologies of FGR 

• Unchanged… review our prior episode! 

• Realize that it can result from multiple maternal, fetal, and placental disorders 

Why do we care? 

• Fetal growth restriction occurs in up to 10% of pregnancies and is a cause of infant morbidity and mortality around the world 

• Fetuses <10th%ile at any gestational age have a risk of stillbirth of 1.5%, which is 2x the rate of fetuses with normal growth 

• Infants with birthweights <10th%ile have increase risk of acidosis at birth, low 5 min Apgar scores, and need for NICU admission, as well as 2-5x rates of perinatal death 

Who is considered fetally growth restricted, and how do we figure that out? 

• The SMFM Consult Series #52 recommended the definition to be:

  • ultrasonographic EFW < 10%, OR

  • AC <10% for gestational age 

• You need to do an ultrasound - but prior to that, you probably need to have suspicion. 

  • This can be done with fundal heights at appointments.

  • Make sure you have appropriate dating!

• US uses population-based fetal growth references (such as Hadlock) in determining fetal weight percentiles:

  • Hadlock was generated from a study of 392 pregnancies in predominantly white, middle-class women at a single institution in TX

  • An NICHD study previously developed racial/ethnic standards for fetal growth 

    • It was found that Hadlock still was better at predicting SGA and composite neonatal morbidity at birth, and had a lower ultrasound-to-birthweight percentile discrepancy than the NICHD growth standard.

  • Hadlock is usually calculated by using BPD, HC, AC, and Femur length 

Classification of fetal growth restriction 

• Early vs. late fetal growth restriction

  • Again, per SMFM consult series defined as onset <32 weeks (early) or late (at or after 32 weeks) 

  • Early FGR tends to be more severe, tends to follow an established Doppler pattern of fetal deterioration, and can show more severe placental dysfunction than late-onset FGR.

    • Also, early FGR can be associated with genetic abnormalities 

    • Therefore, in early FGR, should get detailed ultrasound.

      • The SMFM consult series also recommends chromosomal microarray analysis if there is also fetal malformation or polyhydramnios is noted. 

• Severity 

  • EFW <3% has been associated with an increased risk of adverse perinatal outcome irrespective of UA or MCA Dopplers.

Management of Fetal Growth Restrictions 

Remember: The reason we care about fetal growth restriction is its association with stillbirth and perinatal mortality/morbidity. To prevent that, we try and look for signs that the baby/placenta is not doing well. We can do this with umbilical artery dopplers and antenatal testing (ie. BPPs, modified BPPs … see our recent episode!) 

• What are umbilical artery dopplers?

  • Assessment of blood flow toward the placenta in the umbilical arteries of the fetus 

  • In systole, the blood is being pumped forward, and in diastole, the blood should still move forward, but may be slower than in systole.

    • We look at the S:D ratios, or the speed of the blood flow toward the placenta in systole compared to diastole 

  • With increasing placental dysfunction comes placental resistance. Therefore, this can start to affect forward flow from the umbilical arteries.

    • In systole, the blood should always flow forward.

    • However, in diastole, without the heart as a pump, that blood flow can slow down. This is where we can begin to see elevated S:D ratios! Generally, elevated is >95%ile.

      • If there is even more resistance, blood flow during diastole stops. This is when you have “absent end diastolic flow” 

      • In very severe cases, the resistance in the placenta is so high that the blood flows backward toward the fetus. This is called “reverse end diastolic flow” 

• Why do we use them?

  • As a way to assess placental dysfunction 

  • Absent and reverse end diastolic flow are associated with high rates of perinatal mortality. ‘

    • One study shows an odds ratio for fetal death of 3.59 and 7.27 for AEDV and REDV, respectively!

• What do we do with UAs? 

  • Once fetal growth restriction is diagnosed, UAs should be serially assessed, usually 1-2 weeks depending on your institution 

  • If elevated, they should be assessed more frequently

  • The SMFM series also recommends assessment of dopplers 2-3x/week when UAs become AEDF to assess for REDF 

Management and Delivery Planning

We should mention that this can vary to some degree based on your institution! Generally speaking:

• If FGR but >/=3rd%ile with normal UA dopplers: 

  • Serial growth scans (every 3-4 weeks) 

  • Weekly or every 2 week UA dopplers 

  • Weekly or 2x/week antenatal testing 

  • Delivery by 39th week 

• If FGR but <3rd%ile with normal UA dopplers 

  • Same as above, but delivery at 37 weeks 

• If Elevated S:D ratios (meaning decrease end diastolic flow)

  • Continue weekly dopplers (some institutions will do 2x/week) 

  • Growth scans q2-4 weeks 

  • 2x/week antenatal testing 

  • Delivery at 37 weeks  

• If absent end diastolic flow 

  • Increase to 2-3x/week dopplers 

  • Discuss corticosteroids for fetal lung maturity 

  • Antenatal testing 2x/week 

  • Consider q2 week growth scans 

  • Deliver at 33-34 weeks (per SMFM). Can consider cesarean delivery. 

• If reversed end diastolic flow (highest risk for stillbirth) 

  • Inpatient admission 

  • Corticosteroids for FLM 

  • 1-2x/day antenatal testing 

  • Consider q2 week growth scans 

  • Deliver at 30-32 weeks. Can consider cesarean delivery. 

Headaches & Pregnancy

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 

Sickle Cell Disease & Pregnancy

What is sickle cell disease?

• Sickle hemoglobin (HbS) results from a point mutation in the beta hemoglobin gene. 

• Sickle hemoglobin disease results from inheritance of at least one sickle mutation, and co-inheritance of another beta-hemoglobin modifying gene.

  • Classically, this is homozygosity for HbS genes (HbSS); however, sickle disease also manifests with co-inheritance of hemoglobin C (HbSC); beta-thalassemia; and others.

• The disease causes significant pain crises and multi-system disease, thought to arise primarily from hemolytic anemia as well as vaso-occlusion.

  • Importantly from an infection perspective, splenic infarction is common early in life and thus results in a hyposplenic, immunocompromised state. 

  • Manifestations of disease can be seen in:

    • Infection, particularly a susceptibility to pneumonia and a related but indistinguishable complication known as acute chest syndrome

    • Anemia

    • Pain from vaso-occlusive crisis

    • Stroke and myocardial infarction

    • Renal disease

    • Retinopathy (particularly with HbSC disease)

    • Pregnancy complications, including growth restriction, preeclampsia, stillbirth, and maternal mortality. 

Who should be screened, and how?

• Screening for sickle trait and sickle cell disease is now part of universal newborn screening in all 50 US states. 

• Screening in adults is done via hemoglobin electrophoresis.

• Screening should be offered if:

  • A partner is known to have sickle cell disease, and the other partner does not know their carrier status, or;

  • A patient does not know their carrier status and wishes to know.

    • IMPORTANT: race/ethnicity-based screening is ineffective and problematic in identifying at-risk individuals, and thus anyone who desires testing should be offered it! 

      • ACOG PB 78 on hemoglobinopathies in pregnancy, updated in 2007, notes that “ethnicity is not always a good predictor of risk,” though focuses to a large degree on observed ethnic group differences.

      • Similarly, ACOG CO 691 endorses hemoglobinopathy screening via CBC for all women, and electrophoresis for women “suspected of hemoglobinopathy based on at risk ethnicity” 

      • Other ACOG guidance now endorses offering hemoglobinopathy screening universally, including the ACOG FAQ document for patients on carrier screening. 

    • However, there are risks to screening that your patients should be made aware of, particularly with respect to genetic discrimination. 

      • Health insurance markets and employer-based plans are prohibited from this through the Genetic Information Non-Discrimination Act (GINA).

      • These protections do not extend into: 

        • life, disability, or long-term care insurance markets,

        • employers with fewer than 15 employees

        • US military and the TRICARE health system

        • the Indian Health Service

        • the Veterans Health Administration

        • Federal employees Health Benefits Program. 

  • A quick plug here for licensed genetic counselors – they are awesome and know lots of things, as well as when your patients may benefit from different types of screening! If you have access, we totally recommend listening in on a counseling session with them! 

What should be done to optimize pregnancy in the preconception period for those with sickle cell disease?

• Most pregnancies can be managed successfully and result in live birth, with proper surveillance and preparation. 

• Partner screening is recommended if status is not known, as we previously mentioned, as the likelihood of the fetus having a hemoglobinopathy can be 0% (if partner is not a carrier) or 50% (if the partner is a carrier). 

  • This can also help to inform approach to prenatal genetic testing and subsequent decisions for the pregnancy, if desired. 

• Baseline preeclampsia screening 

  • Hypertension may be present due to renal disease in pregnant patients, and sickle nephropathy can result in significant proteinuria. 

  • Baseline 24 hour urine protein, in addition to LFTs, BUN, and creatinine, are useful. 

• Ophthalmologic screening for retinal disease, which has a tendency to worsen in pregnancy

•  Hemoglobin and iron studies 

  • Frequently, due to hemolysis, those with sickle disease are severely iron-overloaded and should potentially delay pregnancy until they receive chelation therapy (which cannot be given in pregnancy).

    • Prenatal vitamins with iron should be avoided in this particular group.

• Baseline urine culture as asymptomatic bacteriuria and UTIs are more common in sickle disease, and are often more difficult to treat due to renal disease. 

• Pulmonary function tests can be considered, as those with particularly severe sickle cell disease are at higher risk of pulmonary embolus and reactive airway disease, in addition to having a baseline to reference for acute concern for acute chest syndrome. 

  • Echocardiography may also be useful in severe cases to assess for underlying pulmonary hypertension. 

• Type and screen is often one of the most important tests:

  • Often due to a history of transfusion, multiple antibodies may be present on screening, which can be significant for alloimmunization of the fetus and hemolytic disease of the fetus/newborn (HDFN).

    • If the patient is positive for an offending antibody, this will allow for partner testing to occur to determine if a fetus may be at risk for HDFN.

• Medication Management:

  • Hydroxyurea: is generally a mainstay of sickle cell disease management in the nonpregnant patient which works by increasing Hemoglobin F production. Gamma globulin is not affected by sickling, so decreased overall concentration of HbS  

    • Regrettably in the peri-conception period, there is not much data regarding its use – but guidelines recommend discontinuing in the three months prior to conception, though the limited data that exists suggest there is no increase in major anomalies. 

  • Folic acid: due to increased red cell turnover, generally there is consensus that folate supplementation should be higher in those with sickle cell disease; 4mg daily is recommended (versus the 0.4mg – 0.8mg/day recommended universally).

  • Iron chelators: should be discontinued for conception, as they are associated with some risk of anomalies.

  • Antihypertensive medications: often patients with SCD may be taking ACE-Is or ARBs, as they are renal protective. However, these are teratogenic and should be replaced with agents that are safe in pregnancy. 

  • Pain medication: opioids are standard of care for management of severe pain in sickle cell disease. Patients who are on standing doses of opioids should be counseled with regards to risk of neonatal abstinence syndrome but should not routinely discontinue their pain medications.

    • Acetaminophen, non-medicinal strategies for pain control are also appropriate.

    • Short courses of NSAIDs may be appropriate in some circumstances, but generally are avoided in pregnancy. 

    • Aspirin in low dose should be considered in pregnancies of patients affected by sickle cell disease to help reduce preeclampsia risk.

  • Anticoagulation: patients with sickle cell disease are not typically on anticoagulants just for sickle disease; though with a history of DVT/PE, they might be, and in those cases you should treat them like other patients with that history. 

    • Absent a high-risk DVT/PE history, pharmacologic thromboprophylaxis should just be considered with any hospitalization given the high risk of clotting. 

• Immunizations: should be up to date, and also remember due to functional hyposplenism, additional vaccines should be considered: meningococcal, pneumonia, and H. influenzae type b are all recommended for patients with sickle cell disease. 

• Breastfeeding: should still be encouraged! Resumption of hydroxyurea use may be delayed with breastfeeding, as its not well studied in terms of its effects on infants. 

Pain crises in pregnancy – how to manage them?

• Avoid triggers for pain crises as best as possible – dehydration, hypoxia, acidosis, infection, and cold temperatures are all common triggers. 

  • Termination of pregnancy and delivery/postpartum are two common times for pain crisis development – so appropriate hydration and monitoring are key at those time points!

  • With crisis, one key management point is reversal/correction of the trigger – and in or out of pregnancy, hydration is often key to that.

  • Oxygen therapy is often also needed due to inadequate oxygen delivery during vaso-occlusive crisis. 

• In crisis, pain control should be aggressive!

  • Opioids are the therapy of choice, if acetaminophen is not satisfactory.

  • The patient’s experience, and their hematologist’s knowledge of the patient, are often of significant benefit in these situations! 

• Keep your diagnostician hat on!

  • Pain crises can often be part of, or proceed significant events for patients with sickle cell disease – including DVT/PE, acute chest syndrome, or stroke. 

    • Each complication of sickle cell disease could be a podcast of management on its own – so a multidisciplinary approach is often required to ensure good patient outcomes. 

    • If patient or family is telling you the pain is different – listen! This can be a clue that something else is going on than usual pain crisis.

    • Use your hematology colleagues to guide, but often management will consist of at least CBC, chemistry panel with LFTs, and a chest xray. 

Acute Chest in Pregnancy - ACS is the leading cause of death in SS disease 

• Often preceded by a vaso-occlusive pain episode, present with chest, arm, and leg pain consistent with a pain crisis, and follow a much more severe clinical course, often requiring mechanical ventilation, and sometimes resulting in death

• Dx = radiographic evidence of consolidation + one of the following: 

  • Temperature >38.5C 

  • >2% decrease in O2 sat 

  • Tachypnea 

  • Intercostal retractions, nasal flaring, or use of accessory muscles 

  • Chest pain 

  • Cough 

  • Wheezing 

  • Rales 

• Treatment: a lot of this overlaps with pain crisis:

  • Treat pain 

  • Fluids - prevent hypovolemia 

  • O2

  • Blood transfusion - discuss with heme about simple vs exchange transfusion 

  • Bronchodilators 

  • Antibiotics - usually empiric to cover things like C. trachomatis, strep, and H.flu. Usually a third gen cephalosporin with a macrolide (ie. CTX + azithromycin) 

  • Escalation of care - may need to go to the ICU! 

Antenatal Testing Modalities

Modalities of Antepartum Fetal Testing

Extra Reading:

• ACOG PB 229 (Antepartum Fetal Surveillance)

• CO 828 (Indications for Antepartum Fetal Surveillance)

What we won’t do:

• Talk about frequency / timing / specific indications for testing 

  • CO 828 provides a great overview of this as a reference, and we’ll obviously mention our own practice for testing in subject-specific episodes!

  • Various institutions may have their own policies and procedures that you should be aware of.

Rationale / Techniques of Antenatal Testing

• Testing techniques are meant to detect changes in fetal status, particularly in response to hypoxemia and acidemia.

  • Hypoxemia and resulting metabolic acidemia redirect fetal blood flow; for instance, decreasing renal perfusion and resulting on oligohydramnios.

    • Other physiologic changes such as decreased heart rate variability and decreased fetal movement or poor muscle tone can be appreciated. 

  • Progressive metabolic acidosis In these situations can result in stillbirth / fetal death – the primary outcome we are looking to avoid by employing this testing.

    • Antepartum surveillance is generally indicated for any condition which raises the risk of stillbirth.

      • In CO 828, the “cutoff” for included indications is defined as 0.8 / 1000 deliveries for a given condition, which is about twice the odds of stillbirth at term in otherwise low risk pregnancies

      • This is also the false-negative rate of a BPP, providing further justification for this cutoff.

  • Importantly, any fetus with neurologic depression/anomalies may still be at increased risk for stillbirth, but antenatal testing may not be as equipped to detect risk.

  • Similiarly, the utility and predictive value are less at earlier gestational ages.

Maternal kick counts

• A complaint of decreased in fetal movement has been demonstrated as a risk for stillbirth, which is why we ask folks to come to be assessed for it! 

• How effective are routine kick counts?

  • A meta-analysis of five RCTs and over 450,000 fetuses found no differences in stillbirth rate between groups undergoing routine kick counts, and those who did not. 

    • However, stillbirth rate in the trials overall was low – 0.54% in the kick count group, and 0.59% in the control group, with the confidence interval for the relative risk ranging from 0.85 – 1.00 – so while crossing 1 and thus being statistically non-significant, may lay more towards benefit with additional study.

      • Those in the kick count group did experience slightly higher rates of preterm delivery, labor induction, and cesarean delivery – perhaps some harm from this?

      • Likely, more studies are necessary to help make better determinations regarding the utility of kick counts.

• How should we tell people to do kick counts?

  • The practice bulletin mentions one trial instructing patients to lie on their side and count 10 movements over a 2 hour period as reassuring – we trained with this as the recommended way!

    • The bulletin also mentions another to count movements for 1 hour three times per week, and reassuring was considered to be if the movement number “equals or exceeds the previously established baseline count” – seems a bit more complicated! 

• There definitely isn’t robust evidence to do routine fetal movement assessments, or to use that as a testing technique – but again, definitely have your patients present to care for any sense of decreased movement!

Non-Stress Test (NST)

• The NST is the classic method for antenatal testing. It’s based on the notion that if the fetus is not acidotic, the heart rate variability will be appropriate, and the heart rate will accelerate with fetal movement. 

• The heart rate should be monitored for at least 20 minutes, but may require longer periods due to fetal sleep cycles.

  • Vibroacoustic stimulation (VAS) is permissible to obtain a stimulated acceleration – it won’t falsely reassure you abut acid-base status, and can decrease the amount of time you’re waiting through a sleep cycle! 

    • Per the PB, stimulus should be applied for 1-3 seconds and may be repeated up to three times for a valid NST.

• Test results are conveyed as reactive or non-reactive. 

  • Even though this is the same tech as continuous monitoring in labor, we don’t use the same terminology! So don’t call an NST “category 1” – the only results are reactive or non-reactive. 

    • Reactive means that there should be two or more accelerations in a 20-minute period. 

      • Accelerations should be 10 beats elevation over 10 seconds (10x10) at less than 32 weeks, and 15 x 15 at greater than 32 weeks.

    • Non-reactive means that over 40 minutes of monitoring, the acceleration criteria is not met.

    • So can you have decels in a “reactive” NST? – yes! Remember – “category” system in labor is different than NST description!

      • Variable decelerations that are non-repetitive and brief (< 30 sec) are not associated with fetal compromise or need for obstetric intervention. 

        • If repetitive (>3 in 20 mins), there is increased risk for cesarean delivery for non-reassuring monitoring, and so should be considered for additional testing.

      • Decelerations lasting for over 1 minute during an NST is associated with a high risk of cesarean as well as stillbirth – so additional testing or delivery should be considered if present.

  • One common question – when should an NST be reactive?

    • This is hard to answer – studies have looked at this using the original 15x15 criteria:

      • At 24-28 weeks, up to 50% of NSTs are non-reactive

      • At 28-32 weeks, up to 15% of NSTs are non-reactive

    • For this reason, the 10 x 10 criteria was proposed and deemed sufficient, but certainly the rate of non-reactive tracings are much higher at earlier gestational ages, and so some institutions adjust monitoring protocols accordingly prior to 28-32 weeks.

Contraction Stress Test (CST)

• A step-up from the NST – now, we look to interpret the fetal heart rate response to provoked uterine contractions.

  • Since contractions cause some transient fetal deoxygenation, a fetus that is compromised already will demonstrate inability to compensate physiologically – and thus show decelerations.

• There’s a lot of vocabulary regarding the CST, so let’s start with how the test is run:

  • An adequate CST requires three contractions persisting for at least 40 seconds each in a 10 minute period. If the CST is inadequate, contractions can be stimulated with IV oxytocin or nipple stimulation.  

    • In this testing, nipple stimulation actually is very useful, and can achieve adequate testing in half the time required versus IV oxytocin!

• Once the test is adequate, it should be monitored similarly to an NST over 20 minutes. The test results can be one of five options:

  • Negative: No late or significant variable decelerations elicited. A “negative” CST means the fetus is not compromised.

  • Positive: late decelerations are present after 50% or more of contractions. This is also a possible interpretation even with an inadequate CST. Thus, a “positive CST” suggests compromise of the fetus.

  • Equivocal-suspicious: Intermittent late decelerations or significant variable decelerations are present. 

  • Equivocal: FHR decelerations in the presence of contractions that are occurring more frequently than every 2 minutes, or lasting longer than 90 seconds. This suggests that tachysystole or contraction strength may be compromising the validity of the test.

  • Unsatisfactory: synonymous with an inadequate CST – that is, fewer than three contractions in 10 minutes; alternatively, if the tracing is uninterpretable. 

• CSTs are great and often overlooked tools but should not be performed, generally speaking, in conditions that are contraindications to labor or vaginal delivery – i.e., placenta previa.

Biophysical Profile (BPP) and Modified BPP

• The BPP combines an NST with up to four ultrasound criteria, which are:

  • Amniotic fluid volume: per the practice bulletin, a single deepest vertical pocket of greater than 2 cm is adequate.

    • Some practices may use the amniotic fluid index instead, or in addition to, a measurement of the deepest vertical pocket. RCTs suggest that DVP is acceptable and may even be preferred. 

  • Fetal movement: three or more discrete body or limb movements. 

  • Fetal tone: one or more episodes of extension of a fetal extremity with return to flexion, or opening and closing of a hand.

  • Fetal breathing movements: One or more episodes of fetal breathing movements of 30 seconds or more. 

    • All of the ultrasound criteria should be observed in 30 minutes or less. 

    • Each component is scored as a 0 (if criteria not met) or 2 (if criteria met), including the NST. 

      • 8-10 / 10: normal

      • 6 / 10: equivocal - generally repeat in 6-12 hours

      • 4 or less / 10: abnormal -- context dependent - deliver or repeat testing pending situation

• The modified BPP consists of just the NST in addition to assessment of amniotic fluid volume. If either of these is abnormal, the usual next step is to proceed with the remainder of the BPP. 

  • Oligohydramnios is a separate and significant risk for stillbirth – remember that delivery is recommended for this starting at 36’0 or later! Additional testing should definitely be performed if this is seen earlier than 36 weeks. 

  • If you’re seeing lots of decels – then resuscitate/deliver!

    • A BPP can’t reassure you about decels, which suggest some sort of acute decompensatory event is occurring.

Umbilical Artery Doppler Velocimetry (UAD)

• UAD is a special ultrasound technique that is generally most useful in monitoring fetuses affected by growth restriction.

  • The umbilical artery blood flow in cardiac diastole is very high in normally-growing fetuses.

  • In the growth restricted fetus, blood flow in diastole may be reduced, absent, or reversed; and with these abnormalities, perinatal mortality and stillbirth risk are significantly increased. 

    • This is particularly true in the presence of absent or reversed end-diastolic flow. 

• There is no evidence at present that UAD helps to provide more information about fetal well-being in other situations; so FGR is the only place you’ll routinely see it employed in obstetrics. 

• Listen to our FGR podcast to learn more! 

What is the comparative predictive value/efficacy of these tests?

• The evidence for antenatal testing is largely circumstantial; that is, stillbirth risk seems reduced compared to unmonitored pregnancies, which are largely historic cohorts before current technology was available.

• We can state with confidence that testing has high negative predictive value.

  • Normal test results in most cases are highly reassuring, as these tests are associated with low false-negative rates – with a false negative defined as a stillbirth within 1 week of the normal result. Fer each modality:

    • NST: 1.9 per 1,000; aka, negative predictive value of 99.8%

    • CST: 0.3 per 1,000: aka, NPV of >99.9%

    • BPP: 0.8 per 1,000: aka, NPV of >99.9%

    • Modified BPP: 0.8 per 1,000: aka, NPV of >99.9%

    • UAD: less studied, but best available evidence suggests an NPV approaching 100% as well. 

• Again, these tests can help reduce risk of stillbirth with chronic conditions; acute conditions, such as abruption or cord accident, cannot be predicted with these modalities.  

Opioid Use Disorder in Pregnancy

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