Soft Markers for Aneuploidy

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Here’s this week’s RoshReview Question of the Week!

A 38-year-old G1P0 woman at 20 weeks gestation presents to the clinic for her anatomy ultrasound examination. She underwent a first-trimester screen, which showed a borderline nuchal translucency of 3.1 mm. Which one of the following isolated ultrasound findings confers the greatest risk for trisomy 21?

Check out the links above to see if you answered correctly. Also, you can enter for a chance to win a Rosh Review Qualifying Exam (“written boards”) QBank!

Check out the SMFM Consult Series 57 for excellent companion reading!

What are the ultrasound soft markers, and why do we care? 

  • In the era of cell-free DNA, you might ask: what is the utility of soft markers? Aren’t they poor predictors of aneuploidy?

    • Originally introduced to improve the detection of Down syndrome over that of just age-based or serum-based screening 

    • While it is true that each isolated soft marker may be poor predictors, if we see multiple soft markers, that does improve sensitivity  

    • There may also be some misunderstanding of soft markers seen on ultrasound, and so the purpose here is to review some of these soft markers in the setting of cfDNA and discuss next steps 

  • Remember: patient’s baseline risk should not limit screening options, and cfDNA should be offered to all per ACOG and SMFM 

What are the first steps when you see a soft marker?

  • Make sure that the soft marker is truly isolated - look for other soft markers, fetal growth restriction, or other anomalies 

    • If you feel that your office is not equipped to do this, can refer to MFM to have a level II ultrasound performed - this is of course a discussion with the patient, and not all patients will want further evaluation 

  • Look at the patient’s history: 

    • What is their baseline risk? (age, family history, history of aneuploidy) 

    • What are their previous aneuploidy screening results? Did they have any? 

  • Ok, so I see one of the soft markers, what do I do next?

    • First of all, have they had cfDNA?

      • Most of the time, there is not much to do after that (again: ISOLATED soft marker) 

      • This is because with cfDNA, the posttest probability of a common aneuploidy (ie. Trisomy 21) of negative cfDNA is very low - it is lowered by 300x for trisomy 21

        • Per the consult series, the residual risk of a 35-yo woman, whose age related risk of Down syndrome is 1/356 is reduced to <1/50,000 after a negative cfDNA result  

    • But what if they didn’t have cfDNA? 

      • If they have had negative serum screening, also ok, no need to do further testing at this time 

        • The detection rate of serum screening test for Down is still high, about 81%-99% depending on the test 

      • If no screening at all, counsel about noninvasive aneuploidy testing - not all patients will want screening 

    • Remember: there isn’t an established cut off residual risk when there is recommendation to do diagnostic testing 

      • Many labs will establish a cutoff of 1:250 or 1:300 

    • SMFM does not recommend diagnostic testing for aneuploidy only for evaluation of isolated soft marker following negative serum or cfDNA screening result 

The Soft Markers (all photo credit to Radiopedia)

Updates in Preterm Birth Prevention

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Check out reading for this episode: PB 234

Our last podcast on preterm birth prevention was 2 years ago in November 2019, right after the PROLONG trial was published… and there have been some major guideline changes! We’ll do prevention of preterm birth redux today, going over everything once again to provide the most up-to-date summarization of ACOG’s recommendations..

Also important: we still have podcasts on assessing/managing preterm labor where nothing has really changed! Be sure to check that out as an important CREOG topic!

Why care about preterm birth?

  • Exceedingly common: 10.2% of newborns in the USA are born prematurely.

    • PTB accounts for 75% of perinatal mortality and >50% of long-term neonatal morbidity (and associated costs)

  • Preterm birth rates are actually increasing in the USA:

    • Had decreased from 2007-2014, but as of 2019 had increased back to 10.2%

      • Driven primarily by increase in late preterm birth (34-36 wks)

      • Rates of early preterm birth  (less than 34wk)  largely unchanged since 2014 (2.8%)

  • Preterm birth rates are disparate amongst racial/ethnic groups:

    • White women: 9.3% rate of PTB, vs Hispanic 10%, non-Hispanic Black 14.4%, AI/AN 11.5%, Hawaiian/PI 11.8%. 

      • Non-Hispanic Black women also have a disproportionately higher rate of < 34wk PTB (4.9% vs 2.7% overall rate)

  • Preterm birth is not just spontaneous preterm birth:

    • 50% follow preterm labor

    • 25% follow PPROM

    • 25% are intentional, medically-indicated PTB for maternal or fetal indications

Risk factors for PTB

  • Clinical

    • Prior history: prior spontaneous preterm birth <34 weeks has about a 35% recurrence risk!

      • Number of prior PTBs (more) and degree of prematurity (earlier) significantly affect this risk

      • Preterm birth followed by term birth → risk lowers

      • Twin preterm birth → still higher risk for preterm birth in subsequent singleton gestation, and as high as 40% if twins born before 30 weeks!

    • Bacterial vaginosis: 2x increased risk of spontaneous PTB, more strongly associated in early pregnancy. 

      • Treatment has not been demonstrated consistently to reduce PTB risk though.

    • UTIs in pregnancy: conflicting results based on Cochrane reviews examining risk with asymptomatic bacteriuria or symptomatic UTIs and preterm birth risk

      • However still prudent to treat - risk of pyelonephritis → sepsis, which definitely increases risk.

    • Periodontal disease: conflicting results of risk and association

    • History of prior D&C: slightly increased risk in 21-study meta-analysis of 2 million women (OR 1.29), though mechanism is uncertain. Risk slightly increased with history of multiple D&C (OR 1.74).

    • Multiple gestation: Preterm birth rate in twins of 60.3%, with 19.5% born before 34 weeks.

      • Triplets born preterm 98.3% of time, with 82.6% born before 34 weeks.

    • Short cervical length: a transvaginal short cervical length under 25mm between 16-24 weeks is associated with higher risk of PTB in a variety of screened populations.

    • History of cervical conization: inconsistent data regarding risk, though likely pronounced risk if short interval from conization-to-conception or excision greater than 15mm deep. 

  • Other modifiable risks:

    • Tobacco use: likely due to vasoconstriction, hypoxic-ischemic pathways

    • Low maternal pre-pregnancy weight: BMI < 18.5

    • Interpregnancy interval < 18 months: some association in observational studies

    • Unintended pregnancy

      • Importantly for these last two, some observational data points to increased access to LARC and family planning services is associated with lower rate of preterm birth.

  • What about race?

    • As we’ve discussed on the show before: race as a risk factor needs to be studied further -- a social, not a biological construct

    • Chronic stress related to exposure to racism is a potential explanation

    • Social and economic disadvantage are persistently associated with increased risk of preterm birth, with some factors including:

      • Lower educational attainment

      • Residence in ZIP code/region/states with economic disadvantage

      • Lack of access to prenatal care

    • More work is needed in evaluating and exploring these mechanisms, and more work is desperately needed in evaluating ways to correct inequity 

Screening Strategies: Identifying Patients who may Benefit from Interventions:

  • Lots of things that have been tried:

    • Fetal fibronectin assay: in asymptomatic patient, has not been shown to be helpful given low PPV.

    • Home uterine contraction monitors

    • Ongoing research into biomarkers, microbiome research, cervical texture, genetic associations…

  • Best and most important screening strategy we have: transvaginal cervical length screening in the 2nd trimester (16-24 weeks)

    • TVCL beyond 24 weeks is less predictive overall.

  • Recommendation for universal assessment of cervix at the time of anatomy ultrasound, with TVUS then performed if suspicious:

    • TAUS under 36mm identifies 96% of patients with TVCL under 25mm, and 100% of patients with TVCL of 20mm or less.

      • This universal assessment of length outright with TVCL is debated, though the cervix should at least be visualized to assess for previa, and a TACL is a reasonable 1st screen.

  • What cervical lengths are important to remember?

    • Compared to old guidelines, ACOG simplifies things in this document. There are two primary lengths to remember (both transvaginally assessed):

      • 25mm 

      • 10mm

    • Then, there are a few major interventions that can be considered:

      • Progesterone, either vaginal or intramuscular (17-OHP)

      • Cerclage

      • Pessary

    • The recommendations and intervention options vary by the history/clinical scenario of the patient (summarized in the table from the PB), so let’s review from there!

ACOG PB 234

Singleton Pregnancy with No Prior History of Preterm Birth:

  • Shortened cervix under 25 mm:

    • Vaginal progesterone

      • Dosing: 200mg micronized, from time of dx until 34-37 weeks gestation (Varies by trial)

      • Effects:

        • Multiple trials demonstrating lowered risk of early preterm birth (less than 34 weeks) by approximately 50%.

        • OPPTIMUM meta-analysis of progesterone demonstrated vagP reduced risk of spontaneous preterm birth prior to 34 weeks by about 40%, with an NNT of 14 patients to prevent one sPTB before 34 weeks.

    • Intramuscular progesterone

      • Dosing: 500mg weekly IM

      • Effects:

        • Very few trials on this in this population (singleton, no PTB history)

        • The few direct trials of this that exist generally have not found benefit

        • Not recommended in this population.

    • Exam-indicated cerclage

      • Identified painless cervical dilation prior to 24 weeks

      • Effects:

        • Associated with pregnancy prolongation by approximately 34 days and increased neonatal survival in a meta-analysis of multiple study types → thus recommended practice if truly painless cervical dilation.

      • Technique notes:

        • Amniocentesis to assess for infection pre-procedure: 

          • limited data, no RCT described in bulletin. Retrospective data colored by amnio-performance was tied to more severe cases. 

        • Antibiotic and tocolytic use:

          • RCT of periop abx + indomethacin demonstrated improved pregnancy lengths in rescue cerclages receiving medications, but no difference in neonatal outcomes overall (good or bad) → reasonable to consider

      • Contraindications:

        • PPROM

        • Suspected infection

        • Preterm labor or active bleeding

        • Fetal demise or anomaly incompatible with life

    • Ultrasound-indicated cerclage

      • Cervical shortening without dilation prior to 24 weeks.

      • Prior ACOG recommendation: cerclage not indicated in this population (only rescue cerclage was indicated without history of PTB)

      • NEW ACOG recommendation: possibly of benefit with extreme cervical shortening < 10mm

        • Based on a subgroup analysis of 126 patients in a meta-analysis of 5 RCTs. 

          • CL < 25mm - cerclage did not reduce risk of PTB <34wk

          • CL < 10mm - cerclage reduced risk of PTB <35 weeks (39.5% vs 58%). 

        • Importantly -- none of these patients were on vaginal progesterone, nor are there trials comparing vagP to cerclage in this population, or their combined effect.

    • Pessary

      • Cervical pessaries can compress, elevate, and posteriorly rotate the cervix.

      • Trials overall have not demonstrated effectiveness of pessary in those with short cervix without prior history of PTB, alone or in combination with vaginal progesterone.

Singleton Pregnancy in Patient with Prior Spontaneous Preterm Birth

  • Cervical Length Screening

    • In addition to the usual screen, in patients with prior PTB history, serial cervical length assessment has been studied:

      • A TVCL under 25mm before 24 weeks had a sensitivity of 65% for PTB under 35 weeks; PPV 33%, NPV 92%. However, sensitivity and PPV is similar for just risk factor of prior PTB.

      • Many studies have assessed utility of cervical length screening, without definitive data to guide frequency/schedule of assessment.

      • Most protocols will perform screening starting at 16 weeks and repeat q1-4 weeks through 24 weeks.

        • Because treatment is available for short cervix (US-indicated cerclage, we’ll get to that in a minute!), even with absence of superb data, serial screening is reasonable to perform.

  • IM Progesterone

    • We talked about this controversy on our previous podcast with the Meis trial and the PROLONG trial. 

      • Meis trial: RCT 463 patients, IM progesterone vs placebo. Reduced risk of PTB before 35 weeks by about 33% (20.6% vs 30.7%). Overall considered to be a higher risk population than the PROLONG trial, which came later.

      • PROLONG trial: RCT 1740 patients, no difference in PTB before 35 wks (11% vs 11.5%) or neonatal outcomes.

    • SQ progesterone is also available, but there is no direct evidence to support its efficacy vs IM or other formulations. 

    • In the interim, ACOG and SMFM have released statements supporting shared decision-making and patient preference in using progesterone supplementation (IM or vaginal), given the mixed evidence.

  • Vaginal Progesterone

    • Vs placebo:

      • 3 blinded RCTs demonstrate no benefit in reducing recurrent PTB.

      • 5 trial meta-analysis lookig at vagP for use in short cervix with sPTB history demonstrated a reduction of preterm birth by about 40%. 

    • Vs 17-P:

      • Meta-analysis of 3 trials comparing 17-P to vag P demonstrated patients receiving vagP had lower risk of PTB before 34 weeks, though the trials were not blinded and excluded patients with short cervix. 

      • Meta-analysis of multiple progesterone supplementation strategies suggested more robust evidence for BagP in preventing PTB prior to 34 weeks

        • Including largely heterogenous trials with a variety of risk factors present, somewhat limiting outright applicability.

  • History-Indicated Cerclage

    • Indicated in those with prior spontaneous preterm birth due to painless cervical dilation in the 2nd trimester without identified etiology (i.e., abruption), or in those who have had cerclages in prior pregnancy

    • Can be placed in early 2nd trimester with good effect.

  • Ultrasound-Indicated cerclage

    • Five-trial meta-analysis demonstrates that in those with prior sPTB and TVCL <25mm prior to 24 weeks, cerclage reduces the rate of PTB by about 35% (28% vs 41%). 

      • Unknown if progesterone supplementation may augment this effect at all, and there are no trials comparing cerclage to vaginal progesterone vs cerclage in this population.

      • There are ways to do indirect comparisons between trials, and when this is performed the effect size observed seemed to be similar between vagP and cerclage. 

        • Thus, ACOG states that cerclage or vagP are acceptable options in those with prior sPTB and short cervix, and states that cerclage may be offered in addition to continuation of progesterone.

  • Pessary

    • Evidence has not demonstrated any efficacy of pessary alone.

Multifetal Gestations

  • Cervical Length Screening

    • Multifetal pregnancies will generally have a shorter cervical length in the 2nd trimester, but the short cervix remains an effective predictor of early preterm birth:

      • TVUS < 25 mm at 20-24wks had PPV of 75.5% for delivery prior to 37 weeks, and 25.8% for delivery before 28 weeks. 

      • TVUS < 20 mm had PPV of 61.9% before 34 weeks in a separate analysis. 

    • There are not a lot of data regarding screening, and as you’ll see, less consensus regarding effectiveness of intervention in twin pregnancies; thus, serial screening is not necessarily recommended. 

    • A single screen at the anatomy scan should still be performed at minimum, as it is with singleton gestations without prior history.

  • IM Progesterone

    • Trial of 661 twin pregnancies of placebo vs 17-P demonstrated no benefit; a Cochrane review of randomized trials actually found slight increase in risk of PTB before 34 weeks with 17-P (though no difference in perinatal outcomes)

    • In those with prior sPTB and subsequent twin pregnancy, 66 patient trial showed less delivery prior to 34 weeks (20.6% vs 46.9%), but mean gestational length didn’t differ, and no significant difference in neonatal outcomes.

      • Bottom line: can consider in those with prior history of sPTB, not for use in those without sPTB history (same as singletons)

  • Vaginal Progesterone

    • Outright use - not recommended:

      • Cochrane review: no difference in rates of PTB before 34 weeks, perinatal death, NICU admission, or respiratory distress vs placebo.

      • Two other meta-analyses with similar conclusions, and an RCT subsequent to these meta-analyses demonstrated no difference.

    • Short cervix - could be considered, but insufficient data to make recommendation:

      • Six RCTs with different doses/compounds, but when analyzed together, demonstrates likely reduction in PTB risk prior to 33 weeks with vaginal progesterone.

      • Diffferent meta-analyses have not found a significant difference.

  • Cerclage

    • Prophylactic (i.e., place in a cerclage without other risk factors than multiple gestations) -- no evidence to suggest benefit.

    • Ultrasound-indicated

      • Insufficient data to recommend at this time, though trials that exist overall are small and have not found significant benefit, though at least one meta-analysis has shown potential benefit if cervical length is <15mm. 

    • Exam-indicated/”Rescue” cerclage

      • New RCT (2020) of twin gestations with asymptomatic cervical dilation between 16’0 and 23’6 demonstrated reduced risk of PTB before a variety of cut points (24/28/32/34) in patients receiving rescue cerclage vs no cerclage

      • Small trial, but based on limited data, there may be some benefit -- so could consider! Major practice change!

  • Pessary

    • Two RCTs looked at prophylactic pessary, and a third looking at pessary for short cervix, did not find benefit. 

    • Many other trials are limited by power and methodology in this space, but generally also have not found benefit.

    • Overall, pessary is not recommended in higher order gestation.

Does activity restriction reduce PTB risk?

  • Super common question, and one that this update in the PB directly addresses:

    • RCT of 165 pregnant persons found no relationship between coitus and risk for recurrent PTB

    • Secondary analysis of 17-P RCT for short cervix demonstrated PTB at less than 37 weeks was more common among pts who were placed on an activity restriction, and after controlling for confounders PTB remained more common in those placed on restrictions.

      • Thus, based on available data, activity restriction is not recommended.

Summary:

  • Singleton pregnancies without history of PTB:

    • CL screening: visualize at anatomy scan, TVUS if suspected to be short

    • 17-P: not indicated

    • Vag P: indicated if TVCL is <25mm

    • Cerclage: possibly indicated, more strong evidence if TVCL < 10mm; OR can be used for “rescue” with dilated cervix (painless)

  • Singleton pregnancies with history of sPTB:

    • CL screening: consider serial length screening from 16-24 weeks

    • 17-P: can be considered

    • Vag P: can be considered, may be of stronger benefit if short cervix identified

    • Cerclage:

      • History-indicated: if prior cerclage, or history of painless cervical dilation leading to loss in prior pregnancy 

      • US-indicated: if TVCL < 25mm, can consider this versus vaginal P

      • Rescue: still available

  • Multiples:

    • CL screening: same as singleton: at least visualize at anatomy scan

    • 17-P: Not indicated, unless prior history of sPTB

    • Vag P: not indicated, unless short cervix identified

    • Cerclage:

      • US-indicated: limited inconclusive evidence

      • Rescue: can consider → major practice change!

Alcohol Use and Fetal Alcohol Syndrome

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Here’s the RoshReview Question of the Week!

You respond to a precipitous vaginal delivery in the emergency department from a woman who has had no prenatal care. Following delivery, you notice the infant has abnormal facial features including low set ears, small eye openings, a flat nose, and an unusual-appearing upper lip. Which of the following was the fetus most likely exposed to?

Check out the link above to find out if you have the right answer!

Check out ACOG CO 496 for more on this topic!

We’ve talked before about opioid use, and also talked about some screening for substance use in primary care, but today we'll focus on alcohol use and abuse, and specific risks for pregnancy. 

Scope of the issue / definitions

  • At-risk alcohol use: 3+ drinks per occasion, or more than 7 drinks in a week for women

    • Alternatively, any alcohol use for those who are pregnant or at risk of becoming pregnant

  • Binge drinking: 3+ drinks per occasion

  • Moderate drinking: 1 drink daily

    • 50% of binge drinking occurs amongst otherwise moderate drinkers

  • Alcohol use disorder:

    • DSM-5 diagnosis of problematic alcohol use leading to clinically significant impairment or distress

  • What constitutes “one drink” ?

    • Beer or wine cooler: 12 oz

    • Table wine: 5oz

    • Malt liquor: 8-9 oz

    • 80-proof liquor (40% ABV): 1.5 oz

      • Notably, “mixed drinks” can contain 1-3 or more drinks in a single serving!

  • 28% of US adults fall into categories of unhealthy alcohol use, with 14% meeting criteria for alcohol use disorder.

  • In pregnancy, 30% of pregnant folks report any alcohol use; 8% reported binge drinking on at least 1 occasion

    • This rate has been increasing in the last 20 years despite efforts to decrease it. 

  • Alcohol use and risk for abuse in pregnancy is associated with other social risk factors, including:

    • AMA

    • Higher gravidity/parity

    • Inadequate prenatal care

    • Poor nutrition

    • Other substance use, including tobacco

    • Mental health problems

    • History of physical or sexual abuse, or IPV, or substance abuse by the partner/family

    • Social isolation, or living in rural areas during pregnancy

    • Poverty

Screening Tools to Identify at-risk drinking

Quantity based

  • Can inquire about number of drinks in a typical week, or binge drinking episodes over the past three months -- if positive on either question, then know patient is at risk.

TACE if 2 or more points, indicates positive screen

  • T - tolerance (how many drinks does it take to make you feel high?) 

  • More than 2 drinks = 2 points

  • A - annoyed (have people annoyed you by criticizing your drinking?)

    • Yes = 1 point

  • C - cut down (have you ever felt you ought to cut down on your drinking?)

    • Yes = 1 point

  • E - eye opener (have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover?)

    • Yes = 1 point

AUDIT-C if 3 or more points, positive screen.

  • How often have you had an alcoholic drink in past year?

  • How many drinks did you have on a typical day when you were drinking in the past year?

  • How often did you have six or more drinks on one occasion in the past year?

Important caveat - if someone is pregnant or considering pregnancy, any positive answer to these questions should prompt further discussion regarding patient’s attitudes towards alcohol in pregnancy.

Also important to recognize there may be a false-negative screen more likely in pregnant folks -- they may be reluctant to admit use due to fear of consequences/reprimand. There are some who argue that clinicians should always directly ask patients, as opposed to using electronic or paper-based screens.

**If screen positive -- 

  • proceed with careful, non-judgmental assessment of drinking behavior

  • Provide a brief intervention - non-judgmental counseling regarding risks and recommendation for abstinence 

    • RCTs have shown high success in reducing alcohol consumption by 33-60%, or increasing rates of abstinence from EtOH in pregnancy!

  • If concern for alcohol use disorder, should be referred for professional alcohol treatment with psychiatry and medicine.

So what are the risks of EtOH use?

  • Alcohol is a known teratogen, with effects dependent somewhat on amount, pattern of consumption, genetics, nutrition, and other maternal substance exposures (i.e., smoking, other drugs).

  • There is no known safe “lower limit” of alcohol use!

    • Contrary to popular belief, international society guidelines have actually united in stating this. 

      • US, UK, France, Australia/New Zealand, Canada all have guidelines stating no safe limit for alcohol use.

    • 1st trimester exposure associated with significant facial and other structural anomalies as well as neurobehavioral effects and miscarriage

    • 2nd and 3rd trimester exposure increases risk for stillbirth, growth, neurobehavioral effects

  • Stillbirth

    • Even after adjusting for confounders, any alcohol intake is associated with increased risk

      • 1.37 / 1000 births for <1 drink/week

      • 8.83 / 1000 births for 5+ drinks/week

  • Fetal Alcohol Spectrum Disorders

    • Umbrella term encompassing a number of conditions, such as:

      • Fetal Alcohol Syndrome

      • Partial fetal alcohol syndrome

      • Alcohol related neurodevelopmental disorder

      • Neurobehavioral disorder associated with prenatal alcohol exposure

      • Alcohol-related birth defects

    • Estimated to affect 0.75% of pregnancies globally, with high prevalence in Europe and the US (1.5% in USA).

    • While we won’t review the specific diagnostic criteria, we can review some of the common features for each of these disorders that make up the criteria.

  • Craniofacial anomalies (classic)

    • Short palpebral fissures

    • Thin vermillion border (i.e., thin upper lip)

    • Smooth philtrum (the typically indented area above upper lip)

  • Other Anomalies

    • Ears: “railroad track ears” 

    • Hands: altered palmar crease (“hockey stick” of upper palmar crease)

    • Heart: CHD risk is about 2% (1% in gen pop) and can be highly varied

  • Fetal growth restriction

    • Highly prevalent and part of most diagnostic criteria, with small growth persistent into childhood/adulthood

    • Estimates of 30-50% prevalence of FGR

  • Neurodevelopmental outcomes

    • Small head size (HC<10%, occurring in up to 45%) or microcephaly (HC <3%, occurring in about 12%)

    • Other structural brain anomalies (~20%)

    • Recurrent non-febrile seizures

    • Impairment in gross motor function such as balance, coordination

    • Cognitive or intellectual deficits - generally lower IQ 

      • prev of IQ < 70: 8% with prenatal alcohol exposure, 20% if full FAS

    • Developmental delays

    • Neurobehavioral impairments (i.e., sensory processing, self-regulating behavior)

Limiting Intervention in Labor and Birth

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Check out ACOG CO 766 for more on this subject!

Patients in labor and delivery have more information (whether accurate or inaccurate) than ever before to inform their opinions, choices, and risk tolerance.

  • One certainty - more patients are choosing birth centers and home birth as a perceived way to reduce intervention and promote physiologic labor

  • Today we review practices that are worth reviewing on your unit to limit intervention, when appropriate, in a generally low-risk patient; we are not advocating for non-intervention, to be clear! 

Coping in Labor Techniques

Continuous Emotional Support in Labor

  • Randomized trial evidence supports use! 

  • Continuous labor support:

    • Shorter labor

    • Decreased need for analgesia

    • Fewer operative deliveries

    • Fewer reports of dissatisfaction with experience 

    • Less cesarean (RR 0.75 in Cochrane review) → suggesting potential for cost-effectiveness

    • Less likely to have 5-minute Apgar <7 (RR 0.62)

  • Continuous labor support can come in the form of:

    • Doulas: individuals with some degree of training in continuous labor support

      • There are official doula certification programs, as well as those who are truly “lay doulas” if you will.

    • Friends/family: an RCT of 600 patients demonstrated teaching labor support techniques to friends/family in labor room was effective, reducing labor duration and had higher Apgar scores.

    • Tech? The pandemic has definitely increased interest in virtual or mobile doula apps… though evidence is sparse.

Nonpharmacologic Techniques for Coping

  • “Coping” -- a better and more complete way to assess labor pain, and denotes some normal, physiologic discomfort with labor. 

    • Asking the patient how they are “coping” also can provide a way to assess other factors which may influence pain or its experience, such as anxiety or support.

  • Few non-pharmacologic techniques have been well-studied to determine effectiveness or comparative effectiveness. There are trials, but with substantial heterogeneity in their techniques and application. 

    • However, some options:

      • Water immersion: has been shown in observational trials to lower pain scores without evidence of harm in 1st stage of labor

      • Intradermal sterile water injections

      • Acupuncture/massage

      • TENS (transcutaneous electrical nerve stimulation)

      • Aromatherapy

      • Audioanalgesia

      • Additional shout out to Rebcca Dekker, PhD RN, who runs the Evidence Based Birth website and has a really excellent and frequently updated series on pain management in labor. 

        • Her book, Babies Are Not Pizzas, is also a worthwhile look at our own potential biases as obstetricians / trainees from a combined patient and birth professional perspective.

Obstetrical Management of Labor and Delivery

Latent Labor: When to admit?

  • We’ve all been there: on the fence about whether and when to admit the patient in latent or early labor.

  • Observational trials associate early admission with:

    • More labor arrest

    • More oxytocin use

    • More IUPC use

    • More antibiotic use for fevers

    • More cesarean delivery in active phase

      • Importantly, these studies cannot determine whether this was directly associated with presenting to the hospital for care, or if those with a “dysfunctional” latent phase are more likely to present and thus skew these results.

  • RCTs:

    • Delayed (awaiting active phase) vs early (on presentation) admission:

      • Delayed group had lower rates of epidural use and labor augmentation

      • Delayed group had greater satisfaction

      • Delayed group spent less time in L&D

      • NO difference in operative delivery, cesarean delivery, and newborn outcomes (though too small to be powered sufficiently).

    • ARRIVE trial

      • Induction at 39 weeks versus awaiting spontaneous labor/medical induction

        • LESS cesarean delivery in 39 week IOL group (18.6 vs 22.2%)

        • NO difference in neonatal outcomes

          • Rates of spontaneous labor in the expectant management group are not reported/compared, and admission practices in this group are not reported (i.e., rate of early admission in latent labor / need for augmentation / etc)

          • So ARRIVE trial does not answer the question of whether spontaneous labor is better, but does provide a data point to suggest equipoise/potential benefit between 39 week induction and awaiting spontaneous labor, whether it comes or not. 

            • Important to keep in mind as you counsel patients re: 39 week inductions.

    • Admission may be necessary for a variety of reasons, including pain management and fatigue, and this can be used as a time to implement/supplement coping strategies (as previously discussed)

Term Prelabor Rupture of Membranes (PROM): To Induce or Not to Induce?

  • A super common scenario, in which there are a number of potential patient questions:

    • Do I need to induce right away, or can I wait for spontaneous labor?

    • If I wait, how long can I wait?

    • If I don’t wait, what is the best method to start labor?

  • Historical studies have demonstrated ~78% of patients will labor within 12 hours, and 95% in 24-28 hours after PROM.

    • TERMPROM RCT: induction vs expectant management of PROM

      • 4-armed RCT: immediate induction arms (oxytocin vs prostin gel), and expectant mgmt arms (where given up to 4 days PROM’d or clinical concern for chorio before being induced).

      • Median time to delivery for expt mgmt arms were 33 hrs, 95% delivering by 94-107 hours after rupture.

  • However, immediate induction can reduce other risks (based on systematic review, where 60% of patients were TERMPROM trial):

    • Decreased time to delivery by 10 hours

    • Chorioamnionitis / endometritis decreased (RR 0.49)

    • Early onset neonatal sepsis decreased (RR 0.73)

    • NICU admission decreased (RR 0.75)

      • Importantly, the overall quality of evidence for neonatal outcomes in particular is low, and additional RCTs in this space are welcomed! 

  • In terms of methods, TERMPROM noted that # of vaginal exams and fever risks were slightly less overall with oxytocin

    • Though the prostaglandin used here was vaginal gel, so likely increased # of exams

    • Time to delivery was similar in both groups

    • Other trials have not found significant benefits to prostaglandin vs oxytocin

    • Some other trials have evaluated balloon catheter use in PROM

      • Potentially increased infection risk, especially if used alone (9.7% vs 2.9% in oxytocin alone)

      • With respect to combining balloon with pharmacologic agent, appears to be no benefit to ballon + oxytocin vs oxytocin alone (though small numbers overall evaluating this)

  • So back to our initial questions:

    • Do I need to induce right away, or can I wait for spontaneous labor?

    • If I wait, how long can I wait?

    • If I don’t wait, what is the best method to start labor?

      • It’s reasonable to wait some time for spontaneous labor, based on TERMPROM data suggesting almost 80% of patients will labor by 12 hours after PROM. 

        • However, patients should be aware of potentially increased risk 

        • If GBS+, patients should be started on PCN to reduce neonate GBS sepsis risk.

      • Oxytocin seems to be the best agent, though evidence is somewhat limited overall.

Intermittent Auscultation of Fetal Heart Rate

  • cEFM has unfortunately not been shown to significantly affect outcomes like perinatal death or cerebral palsy rates, but has become entrenched in OB practice.

  • IA can be used in low risk patients and potentially decrease risk of cesarean:

    • Cochrane review of 13 RCTs, cEFM vs IA. cEFM:

      • Increased CD risk (RR 1.63)

      • Increased operative vaginal delivery risk (RR 1.15)

      • Decreased risk of early neonatal seizures (RR 0.50)

      • No difference in rates of CP or neonatal death, and no difference in outcomes at 4 years of age.

    • Low risk is very important to define! Inclusion criteria for IA varies by institution, but generally:

      • No meconium staining, intrapartum bleeding, or abnormal fetal testing before admission

      • No fetal conditions that may increase risk (i.e., anomalies, FGR)

      • No maternal conditions that may increase risk (i.e., TOLAC, DM, HTN)

      • No requirement for induction or augmentation of labor (i.e., spontaneous normal labor only)

  • ACNM and Association of Women’s Health, Obstetric, and Neonatal Nurses (AWHONN) have excellent guidelines and protocols for IA for nursing in particular.

Routine Amniotomy

  • Depending on where you are and practice patterns, this might be one of the most controversial things in labor management! 

  • “Routine amniotomy in spontaneous labor” 

    • Notably, this separates out when amniotomy is indicated, such as to facilitate FSE/IUPC or for slow labor progress in combination with oxytocin. 

    • This essentially is looking at just the role of amniotomy then in spontaneous labor. 

  • Amniotomy alone:

    • Doesn’t shorten duration of spontaneous labor

    • Doesn’t reduce incidence of cesarean

    • Doesn’t reduce patient satisfaction

    • Doesn’t reduce rates of 5 min Apgar score <7

    • Doesn’t increase rates of abnormal FHR pattern

    • Doesn’t increase rates of cord prolapse

  • So is there a reason?

    • Not to do routinely -- reserve in spontaneous labor to facilitate monitoring or interventions if indicated. 

  • How about within the context of labor induction?? -- that’s what you’re really wanting to know!

    • 14 trial meta-analysis:

      • When used alongside oxytocin:

        • Decreased length of first stage of labor (1.11 hrs)

        • Modest reduction in cesarean birth rate (RR 0.87 vs expectant mgmt)

    • 4 trial meta-analysis comparing “early” vs “late” amniotomy after cervical ripening:

      • Early = before active phase; late = after active phase, or awaiting SROM

        • Similar rates of cesarean (RR 1.05)

        • Early amniotomy with faster interval to delivery (5 hours)

        • SVD rates overall similar between groups, though technically reduced in early group on basis of single trial (67.5% vs 69.1%)

        • No increased risk of cord prolapse, hemorrhage, abruption, chorio, neonatal outcomes 

      • Takeaway:

        • AROM is reasonable, when indicated to facilitate monitoring, especially if oxytocin already started.

        • May reduce time to delivery without necessarily increasing other risks.

        • Very little data to guide this overall, so more study welcomed!

Immediate versus Delayed Pushing

  • The CO qualifies and speaks specifically to nulliparous patients with epidural analgesia being allowed to “passively descend” or “labor down” once identified to be 10cm.

    • The potential benefit to this is to allow the fetus to passively rotate and descend in the pelvis and conserve maternal energy.

  • Importantly, studies that have looked at risk of adverse outcomes with length of second stage (i.e., Consortium on Safe Labor data informing the ACOG/SMFM Obstetric Care Consensus about recommended length of time to push) do not take into account duration of passive descent vs active pushing, just total time in 2nd stage.

  • Data reviewed in the CO:

    • 2 meta-analyses of RCTs demonstrate delayed pushing 1-2 hours:

      • Increases length of 2nd stage by approx 1 hour

      • Decreases pushing length by approx 20 minutes

      • No difference in SVD rate

    • Recent 2018 RCT that you probably saw in JAMA, delay pushing 60 mins vs immediate pushing (again in nullips with an epidural):

      • Trial stopped before intended recruitment because of increased morbidity in the delayed group.

      • No difference in SVD rate

      • Immediate pushing resulted in:

        • Lower rates of chorio (RR 0.7)

        • Lower rates of PP hemorrhage (RR 0.6)

        • Lower risk of neonatal acidemia (RR 0.7)

  • Overall, delayed pushing in the nullipara with an epidural seems to not confer benefit, and likely increases risk for harm.

Cesarean Scar Ectopic Pregnancy

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Here’s the RoshReview Question of the Week!

A 31-year-old G2P0102 woman at 6 weeks gestation by last menstrual period presents with vaginal spotting. Her history is significant for a previous twin pregnancy where the second twin was emergently delivered by cesarean. Her vital signs are normal, hCG level is 4,440 mIU/mL, and ultrasound findings are shown above. After reviewing the treatment options, the patient indicates she prefers medical management. You further counsel her that compared to medical therapy, most interventional options have a lower risk of which of the following?

Check out the answer at the links above and get 20% off the Rosh Review question bank!

More reading: SMFM Consult Series #49

What is a Cesarean Scar Ectopic? 

  • The implantation of an early gestation in the hysterotomy incision from a previous cesarean birth. Two main types:

    • Endogenic - implantation in the scar itself  

    • Exogenic - implantation in the defect or “niche” left behind by incomplete healing of the scar 

  • Why do we care?

    • Overall very rare → 1 in 2000 pregnancies and 6% of ectopic pregnancies in total among patient with history of cesarean delivery.

    • Doesn’t seem to be related to number of prior cesareans

    • Risk factors: 

      • Not very well studied, since it is so rare 

      • There may be some increased risk associated with smoking, higher parity

    • Unrecognized C-section scar ectopics can rupture and cause hemorrhage and death! 

How do we diagnose a cesarean scar ectopic? 

  • We may suspect ectopics when there is not an appropriate rise in beta HCG (if following)

  • Signs and symptoms:

    • Early on can be asymptomatic 

    • Later on, can result in vaginal bleeding 

    • If ruptured, will lead to hemoperitoneum and hypovolemic shock 

    • Usually patients present early in first trimester 

  • Diagnosis is usually with ultrasound

    • Can be suspected if hx of C-section 

    • Gestational sac center is low (<5cm from cervical os) and anterior on ultrasound 

    • Appears to be an enlarged hysterotomy scar with embedded mass which may bulge beyond anterior contour of the uterus and toward adjacent pelvic structures 

    • Other findings that support:

      • Empty uterine cavity and endocervix  

      • Triangular gestational sac and < 8 weeks or rounded or oval sac > 8 weeks that fills the scar area 

      • Thin or absent myometrial layer between GS and bladder (1-3 mm) 

      • Prominent vascular pattern on Doppler suggestive of blood flow at the area 

  • Can also be diagnosed with surgery, where it is directly visualized 

Radiopaedia

Treatment and Management 

  • Termination of pregnancy due to risk of maternal morbidity and mortality 

  • If hemodynamically unstable

    • To OR 

    • Wedge resection or gravid hysterectomy 

      • If profusely bleeding, usually will require hysterectomy  

  • If hemodynamically stable 

    • Can consider medical or surgical treatment 

    • Medical 

      • Usually methotrexate injection 

      • Options include intrasac injection of MTX or systemic injection of MTX 1mg/kg of maternal weight up to 50 mg

        • One lit review showed that 74% of the time, no other treatment is needed.

        • Also, an additional IM or intrasac injection of MTX led to resolution up to 89% of cases 

        • However, numbers vary widely. Another review said the intrasac injection was effective 65% of the time, and UAE made it 69% effective  

    • Other surgical options 

      • Can consider UAE in addition to MTX, which seems to increase efficacy 

    • Expectant management 

      • Not recommended due to likelihood of maternal morbidity/mortality without fetal benefit 

      • May be reasonable if there is already embryonic/fetal demise and lowering bHCGs 

Follow up

  • Should have weekly HCGs drawn (like after MTX injection after other ectopics 

  • Periodic ultrasound evaluation 

  • More likely to have favorable outcome with ectopics that are diagnosed earlier vs later 

  • There have been reports of pregnancy after treatment of C-section scar ectopic, but risks include recurrence (reported at rate of 5-40%), rupture, and PAS