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! 

Fundamentals of Laparoscopy: Part III

Today we’re joined again by Dr. Merima Ruhotina, a minimally-invasive gynecologic surgery fellow at Yale New Haven Hospital in Connecticut. Meri has prepared for us a big series on laparoscopy in gynecology covering many of the fundamentals, particularly to help with the aptly named “Fundamentals of Laparoscopic Surgery” exam that ABOG began to require in 2020.

Here are her notes for Part III!

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