The APGAR Score

What is an APGAR?

  • 1952: Dr. Virginia Apgar devised scoring system to assess rapidly clinical status of a newborn to determine if prompt intervention is required to establish breathing.

  • Has subsequently stuck, and is reported at 1 minute and 5 minutes after birth for all infants

    • Continued at 5 minute intervals thereafter until 20 minutes for scores under 7.

  • The score is eponymous for Dr. Apgar as well as an acronym.

  • Each component of the score can receive 0, 1, or 2 points:

    • Appearance (color)

      • 2 points: normal over entire body

      • 1 point: normal except extremities (acrocyanosis)

      • 0 points: cyanotic/pale all over

    • Pulse

      • 2 points: HR >100

      • 1 point: HR < 100

      • 0 points: absent HR

    • Grimace (reflex irritability)

      • 2 points: sneeze, cough, or vigorous cry, active withdrawal of extremities to stimulus

      • 1 point: grimace, weak response to stimulus

      • 0 points: no response to stimulus

    • Activity (muscle tone)

      • 2 points: Active motion

      • 1 point: arms and legs flexed to some degree

      • 0 points: hypotonic, limp

    • Respirations

      • 2 points: Good effort, crying

      • 1 point: Gasping, irregular efforts, hypoventilation

      • 0 points: not breathing

  • While the Apgar score is useful for conveying information about the infant status quickly, resuscitation needs to be started before the Apgar calculator intervals.

  • The Apgar can be to some degree prognostic – an Apgar of 0 at 10 minutes have very few reports of infants surviving with normal neurologic outcomes, and it’s reasonable to consider discontinuing resuscitative efforts at that point.

  • The five minute score is generally considered more useful/prognostic:

    • A score of 7-10 is considered reassuring

    • 4-6 is moderately abnormal

    • Under 4 is abnormal, especially in term and late-preterm infants

Limitations of the Apgar Score

  • The score is one moment in time, and is subjective in some components

  • Multiple factors can influence the score and make it more “false positive” with low scores, such as:

    • Maternal sedation/anesthesia

    • Congenital malformations or genetic abnormalities

    • Gestational age

  • Biochemical disturbances such as fetal acidemia must be quite profound to affect the Apgar score

  • A low score doesn’t predict morbidity or mortality for any individual infant, and cannot be used alone to diagnose asphyxia.

    • Cord gases should be obtained to demonstrate poor gas exchange and metabolic acidemia in order to truly diagnose asphyxia.

  • Apgars are often continued to be assessed during resuscitation, but these are obviously not equivalent to scores assigned to spontaneously breathing infants

    • There is no standard for reporting Apgars after the start of postnatal resuscitation, because those interventions obviously affect the score. 

    • There are expanded Apgar score forms, where additional information regarding the infant’s resuscitation and response can be recorded to help assess the impact of interventions and the infant’s status in light of these.

      • Essentially like a “code sheet” for neonates

Outcomes after Apgar Scoring

  • 1 minute Apgar scores don’t predict outcomes well at all

  • 5 minute scores of 0-3 correlate with neonatal mortality in large populations, but are not individually good at predicting neurologic dysfunction for an infant.

    • Low Apgar scores do seem to correlate at population level with increased relative risk of cerebral palsy (20-100x higher risk with 0-3 versus 7-10 score).

    • Most infants with low Apgar scores do not go on to develop neurologic issues or CP.

  • ACOG does recommend that a cord gas be sent for any 5 minute Apgar of less than 5, and considering sending placenta to pathology as well. 

  • Apgars can also be useful to monitor for quality improvement programs to assess both obstetric and pediatric response and resuscitation.

Polyhydramnios

Reading:  SMFM Consult Series: #46: Evaluation and management of polyhydramnios 

What is polyhydramnios? 

  • Definition 

    • Abnormal increase in amniotic fluid volume 

    • Using ultrasonography, defined: 

      • Single deepest vertical pocket (DVP) of fluid >/= 8 cm or 

      • Amniotic fluid index (AFI) >/= 24 cm 

  • Prevalence: can complicate 1-2% of singleton gestations, but it is more common in twin gestations, primarily due to complications of monochorionic placentation 

  • Degree of polyhydramnios 

    • AFI of 24.0-29.9 cm or DVP 8-11 cm = mild (65-70% of cases) 

    • AFI of 30.0-34.9 cm or DVP of 12-15 cm = moderate (20% of cases) 

    • AFI of >/= 35 cm or DVP >/16 cm = severe (<15%)

What causes polyhydramnios, and how do we counsel patients? 

  • Most cases are mild and idiopathic 

  • When etiology is identified, most commonly due to fetal anomaly or maternal diabetes

    • Most anomalies have to do with swallowing issues 

      • GI obstruction: ie. duodenal atresia, TE fistula, thoracic mass, diaphragmatic hernia  

      • Neuro-muscular: Myotonic dystrophy, arthrogryposis, intracranial anatomy 

      • Craniofacial: cleft lip/palate, micrognathia, neck mass  

    •  Fewer due to excess urine production 

      • Renal/urinary - UPJ obstruction, mesoblastic nephroma, Bartter syndrome 

      • Cardiac (basically lesions that lead to high output cardiac failure as well): cardiac structural anomaly, tachyarrhythmia, sacrococcygeal teratoma, chorioangioma 

      • Osmotic diuresis/Other: maternal diabetes, hydrops, idiopathic 

  • What evaluations should be done? 

    • Fetal growth

    • Fetal cardiac anatomy 

    • Placenta for presence of large chorioangiomas 

    • Fetal movement to assess neurological function 

    • Position of hands/feet ot rule out arthrogryposis syndromes 

    • Presence and size of fetal stomach to r/o tracheoesophageal fistula or esophageal atresia 

    • Anatomy of fetal face/palate 

    • Positioning and appearance of fetal neck to r/o obstructing mass 

    • Fetal kidney to assess for UPJ obstruction 

    • Lower spine and pelvis for evidence of sacrococcygeal teratoma 

  • How worried should the patient be? 

    • Most mild polyhydramnios is idiopathic or due to T2DM, and only 6-10% risk of fetal anomaly, with 1% of neonatal abnormality 

    • However, with severe poly, there is increased risk of fetal anomaly to as high as 20-40% and even risk of neonatal abnormality of 10% 

    • Therefore, those with severe poly should deliver at tertiary care center due to possibility for fetal anomaly

Table describing outcomes of polyhydramnios based on severity

How do we manage polyhydramnios in pregnancy? 

  • Treatment 

    • If the poly is severe enough to cause maternal respiratory compromise, significant discomfort, or preterm labor → this can have underlying etiology 

    • In cases of severe poly that results in maternal respiratory compromise or other discomfort, then amnioreduction can be done 

      • However, the polyhydramnios will usually recur 

    • Indomethacin can decrease fetal urine output 

      • There have been studies looking at women who took indomethacin after amnioreduction to try and decrease reaccumulation and re-amnio 

      • However, preterm infants exposed to indomethacin in utero have decreased neonatal urine output and also elevated serum creatinines 

      • Therefore, indomethacin should not be used for sole purpose of decreasing amniotic fluid in the setting of poly 

  • Antepartum management 

    • Many studies have shown that idiopathic poly has been associated with infant birth weight >4000g in 15-30% of cases 

    • Reports of whether perinatal mortality is increased with idiopathic poly have been inconsistent 

      • Currently recommendation from SMFM is that antenatal fetal surveillance is not required for the sole indication of mild idiopathic poly 

      • Similarly, recommendation is that labor should be allowed to occur spontaneously at term for women with mild idiopathic poly, and that induction, if planned, should not occur at <39 weeks of gestation in the absence of other indications 

      • Most of delivery should be determined based on usual obstetric indications 

Monkeypox for the OB/GYN

Reading/sources:

What is monkeypox and how is it transmitted? 

  • Name and type of virus 

    • WHO is planning to rename the virus to reduce stigma and racist overtones - but this hasn’t happened yet! 

    • Orthopoxvirus (genus of Poxviridae family) and has features similar to smallpox or variola 

      • DNA genome

      • There are two different strains: the Congo basin clade and the west African clade 

        • Congo basin clade has historically caused more severe disease and is thought to be more transmissible 

        • The West African clade seems to be the dominant circulating strain → case fatality ratio of 3% to 6% 

  • Cases and outbreak 

    • First case was in 1970 in the Democratic Republic of Congo

    • First case in the US in this outbreak was on 5/17/2022 

    • Most recent reports from the CDC states (as of 8/31/2022) - there have been 18,989 total confirmed monkeypox cases in the US 

    • Demographics 

      • There is not complete demographics data for everyone

      • Most recent data from mid August from the CDC shows that only 1.5% of all cases were in women and transgender men

      • No deaths have been reported in this population  

  • Transmission 

    • Human to human transmission can occur from

      • Direct contact with infected rash, scab, or body fluid 

      • Respiratory secretions during prolonged or intimate physical contact 

      • Contact with contaminated items, such as clothing or bedding 

    • A person with monkeypox infection is considered contagious from initial viral prodrome and development of rash until lesions have full healed and new skin has formed over the scabs 

    • Unclear if transmission can also occur through vaginal or seminal fluids 

    • Perinatal infection can occur through transplacental transmission or during close contact during and after birth 

    • Zoonotic transmission can also occur following direct contact with blood, bodily fluids, or cutaneous/mucosal lesion of infected animals 

Clinical Presentation 

  • Current outbreak 

    • Many of the initial patients in this outbreak have shown painful genital and perianal lesions, oral lesions, and proctitis in the setting of mild or no prodromal symptoms 

  • Clinical course 

    • Average time between contact with monkeypox and symptoms is 5-13 days, with range of 4-17 days 

    • Classic features of infection

      • Fever, lymphadenopathy, malaise, headache, muscleaches 

      • Can have lymphadenopathy

      • Rash develops approximately 1-4 days after prodromal symptoms → deep-seated vesicular or pustular, often beginning centrally and spreading to the limbs 

      • Rash can last 2-4 weeks, progressing through stages includes macules, papules, vesicles, pustules, and even scabs and crusts 

      • Rash can leave scars

  • From the Green Journal article (not sure we can use?) 

Pregnancy Implications of Monkeypox 

  • Not very much is known: 

    • We reviewed that the monkeypox virus can be transmitted to the fetus during pregnancy or to the newborn by close contact during and after birth 

    • There has been an increased risk of maternal mortality and morbidity documented with other poxviruses, but it’s unknown if pregnant people are more susceptible to monkeypox or if disease is more severe in pregnancy 

    • One publication looked at 5 cases of documented perinatal outcomes 

      • 2 = SAB 

      • 1 = stillbirth 

      • 1 = preterm birth 

Evaluation for individual with suspected monkeypox 

  • Routine screening is not recommended for asymptomatic patients 

  • If suspicion of monkeypox virus infection:

    • Collect recent travel history, ask specifically about countries where monkeypox has been reported 

    • If rash or anogenital lesions, ask about close contact or sexual exposure to someone with monkeypox 

    • Full body skin exam, including oral mucosa, genital, and rectal areas, + evaluate lymph nodes 

    • Isolation from others

    • Consultation with infectious disease 

  • Diagnosis 

    • Two-step process requiring initial identification of an orthopoxvirus 

    • If orthopoxvirus is confirmed, specimens are sent for monkeypox virus-specific testing 

    • Multiple samples should be collected, ideally from different lesions (2-3 from different areas of the body with diff appearance) for PCR testing 

    • Please follow your own hospital’s guidelines on how to obtain these samples!

    • As there aren’t really any other orthopox viruses in the US, we shouldn’t wait for the confirmatory testing before initiating infection-control procedures and preventative strategies + treatment 

  • Healthcare provider precautions 

    • Standard precautions and wear PPE: gown, gloves, eye protection, and N95 mask 

    • Any procedure where there is aerosolization (ie. intubation/extubation), should be done in airborne infection-isolation room 

Treatment 

  • Disease is usually self-limited, but disease can progress to severe, so certain populations at risk of severe disease 

    • This includes pregnant patients, people who are breastfeeding, and those with oral, ocular, genital, or anal lesions 

  • No specific treatment for monkeypox virus infection

    • However, there are 2 antivirals +immune globulin available 

    • Tecovirimat (Tpoxx) - antiviral (limited to health department/CDC Expanded access protocol) 

      • Approved by FDA for treatment of smallpox virus infection and may prove beneficial for monkeypox 

      • Available in oral and IV formulations 

      • Works by blocking cellular transmission of the virus 

      • Both forms have been used to treat patients during the current outbreak in the US

      • No human data is available during pregnancy, but no fetal toxic effects were observed in mice studies using oral medication 

      • Not known if present in breastmilk 

    •  Cidofovir - antiviral (Off-label use, available for use in outbreak setting) 

      • Approved by the FDA for treatment of CMV retinitis in patients with AIDS 

      • Can be used for orthopoxviruses in an outbreak setting 

      • In animal studies, cidofovir has been associated with embryotoxicity and teratogenicity, but no adequate or well-controlled studies in humans 

    • Brincidofovir - antiviral (availability limited to Strategic National Stockpile distribution) 

      • Approved by FDA to treat smallpox 

      • Unfortunately, in animal studies, there have been embryo-fetal toxicity demonstrated + structural malformations

      • Therefore, alternative therapy is recommended in pregnancy  

    • IVIG - also available in outbreak setting 

      • Also no human data or animal data in pregnancy 

  • Prevention 

    • Primary prevention is from isolating from individuals with infection

      • Avoid close contact and sexual activity with people with infection 

    •  Postexposure prophylaxis 

      • CDC has tools to assess the risk of monkeypox virus infection and recommends post-exposure vaccination for specific risk exposures or risk factors 

        • Criteria

          • Within 4 days of known exposure to reduce likelihood of infection or between 4-14 days to reduce severity symptoms 

          • Known contacts of monkeypox cases ID’ed by public health via case investigation 

          • Presumed contacts who meet criteria: 

            • Know that sexual partner in the past 14 days was diagnosed with monkeypox or 

            • Had multiple sexual partners in past 14 days in a jurisdiction with known monkeypox 

      • If given within 4 days of exposure, vaccine is likely to prevent monkey pox virus infection 

      • Of note, there are two types of vaccines 

        • JYNNEOS = live-non-replicated viral vaccine - There are no studies in pregnant patients

          • Pregnancy, however, is not a contraindication to post exposure prophylaxis with vaccination if the individual is otherwise eligible 

        • ACAM2000 - repliating viral vaccine licensed for prevention of smallpox 

          • Contraindicated in pregnant or breastfeeding people due to risk of pregnancy loss, congenital defects, and vaccinia virus infection 

    • Preexposure prophylaxis 

      • Attenuated live-virus vaccine and replication-competent vaccine are available 

      • Routine immunization of all healthcare workers is not currently recommended 

      • Only recommended for those whose jobs may expose them to monkeypox (ie. lab personnel and healthcare workers who administer a replication-competent vaccinia virus vaccine or anticipate caring for many patients with monkeypox) 

Abortion: Telemedicine and Self-Management

Today we’re joined by Dr. Sarah Gutman, who is an assistant professor of OB/GYN at the University of Pennsylvania, and a recent graduate of their fellowship in complex family planning. She’s joining us today to talk about some of the most important and interesting topics trending in the weeks after the Dobbs vs Jackson Women’s Health: self-managed abortion and telemedicine abortion.

What is telemedicine abortion?

  • Provision of medication abortion care using telemedicine services, typically fully remote but can involve some degree of in-person contact for part of the process, under the supervision of a medical provider.

  • Who are the appropriate candidates for telemedicine abortion?

    • Eligibility criteria for studies evaluating telemedicine abortion have typically included:

      • Pregnancy less than 10 weeks gestation,

      • No contraindications to mifepristone or misoprostol and

      • The ability to receive mife/miso by mail

  • What are the steps of a typical telemedicine abortion visit?

    • Initial consult – confirmation of dating, review of medical history/risks factors, discussion of how medication should be used and expectations for abortion process.

    • Patients should be certain of their LMP within one week, and it should be <77days before anticipated start of mifepristone

    • Evaluate for symptoms or risk factors for ectopic pregnancy, including vaginal bleeding, pelvic pain, prior ectopic, current IUD use, prior tubal surgery

      • Interestingly, the rate of ectopic pregnancy among patients seeking abortion is lower than the general population – between 1.5 – 6 per 1,000 pregnancies compared to about 20 per 1,000 pregnancies in the general population

    • Ensure no contraindications for medication abortion

      • RH type and hemogloblin are not needed

    • Receipt of medications – due to restrictions in mifepristone accessibility, typically this has been through the mail

  • Medication abortion has been covered by the podcast in the past, but as a reminder: the two medications used for medication abortion are mifepristone and misoprostol.

    • Mifepristone is a taken orally as a one-time 200mg dose

    • Misoprostol can be used vaginally, sublingually, or buccally, 800mcg are given initially with the option to repeat a dose if needed.

      • Patients are informed to take within 48h of mifepristone administration.

      • Consider a second dose if GA >63 days or no bleeding in 24 hours.

    • Analgesics, antiemetics – many providers give ibuprofen and Zofran

  • When to seek help:

    • Heavy bleeding soaking >2 pads/hour for more than 2 hours,

    • Passing blood clots larger than a lemon, or

    • Symptoms of blood loss such as feeling dizzy/lightheaded.

  • Follow up

    • Symptoms – can be assessed at 7-14 days through a text, secure messaging, telephone all, or video.

      • Patients are counseled to expect bleeding heavier than a period, and that they may pass blood clots and see some tan/pink tissue.

    • Urine pregnancy tests – given 4 to 6 weeks following the abortion

What is the evidence behind telemedicine abortion?

  • Efficacy is very high – around 95% of abortions are completed without needing a procedure.

  • Complications are exceedingly rare.

    • Around 6% of patients visit an ER or urgent care center related to the abortion

    • The rate of adverse events is less than 1%, with hospitalization <0.5%, transfusion 0.4%, infection <0.1%

What is self-managed abortion?

  • Self-managed abortion has also been referred to as self-sourced medication abortion (SSMA)

  • Society of Family Planning definition:

    • “It refers to any action taken to end a pregnancy outside of the formal healthcare system, and includes self-sourcing mifepristone and/or misoprostol, consuming herbs or botanicals, ingesting toxic substances, and using physical methods.”

  • Historically, people fearing criminalization or unable to access abortion care often turned to unsafe or invasive methods of self-managing their abortion – think of the abortion scene in ‘Dirty Dancing’ and the use of a coat-hanger as a sign of an unsafe abortion.

    • However, increased access to the medications used for abortion, in particular misoprostol, had made self-managed abortion much safer and more effective.

    • Other reasons besides access that people may choose self-managed abortion, including privacy, discomfort with the available medical services, and person safety.

What are the components of SMA?

  • Similar to telemedicine abortion, SMA includes assessment of eligibility, administration of abortion medications, management of the abortion process, and assessment of abortion completion.

    • These actions are all taken without the formal guidance of a healthcare provider.

    • People who self-manage their medication abortions should be able to estimate their gestational age using their last menstrual period and be aware of their cycle regularity and any contraception use.

  • There are many clinical resources available online, including through the Reproductive Health Access Project, Doctors without Borders, and Aid Access.

  • The WHO recommends mifepristone followed by misoprostol.

    • However, if mifepristone is not accessible, misoprostol can be used alone, typically 800 mcg used vaginally, sublingually, or buccally repeated every 3 hours or up to 3 doses until expulsion occurs.

  • How common is SMA?

    • Recent cross-sectional data suggests 7% of individuals in the US attempt SMA at some point in their lifetime, and this is likely growing due to increased restrictions on abortion access.

  • What is the safety and efficacy of SMA?

    • Data is limited: it’s difficult to study something that is outside the healthcare system.

    • However, from the data we have available and by extrapolating data from the telemedicine abortion models with lowest amount of supervision, self-managed abortion using mifepristone and misoprostol appears to be as safe and effective as medication abortion within a clinical setting.

    • A meta-analysis of misoprostol alone regimens used <91 days gestation found a 6.8% ongoing pregnancy rate

      • Serious adverse events occur <1% of the time.

  • How can providers support patients who have chosen self-managed abortion?

    • When people are criminalized for abortion, it is often due to a healthcare provider reporting them to the police.

    • Currently, there are no mandated reporting laws for healthcare providers.

    • There is legal help available for patients concerned about their options and criminalization, such as If/When/How

      • People of color and low-income individuals are most likely to be targeted and disproportionately criminalized.

Summary

  • Telemedicine abortion is the provision of medication abortion through telehealth under a healthcare providers supervision. Self-managed abortion is actions taken outside the formal healthcare setting to end a pregnancy.

  • Both telemedicine abortion and self-managed abortion using mifepristone and misoprostol are remarkably safe and effective.

  • While protocols vary, typically patients receiving telemedicine abortion should be at or below 10 weeks gestation, should not have any risk factors or symptoms concerning for ectopic pregnancy, and should not have any contraindications to taking mifepristone or misoprostol. After taking their medications, they should be able to monitor their vaginal bleeding and cramping and take a home urine pregnancy test in 4-6 weeks to confirm completion of the abortion.

  • Importantly, there are no laws mandating that healthcare providers report patients for suspected self-managed abortion. If patients are concerned about criminalization there are legal resources available such as If/When/How.

Additional Resources

The PROLONG Trial (Progesterone for Preterm Birth, Part II)

Last week, we introduced our major progesterone trial series with a discussion of the Meis trial. We finish up this week talking about the follow up trial: the PROLONG study.

The PROLONG Trial 

Methods

  • Location

    • 93 total centers across 9 countries  

  • Eligibility criteria and exclusion criteria: pretty much the same as the earlier trial 

  • Randomization and treatment 

    • Randomized 2:1 to receive 17OHP weekly, to start between 16-20w6d 

    • Placebo was benzyl benzoate, caster oil, benzyl alcohol 

  • Outcomes 

    • Measured preterm birth <35 weeks 

    • Composite neonatal morbidity and mortality index 

    • Secondary outcomes: 

      • Neonatal death, PTB <32 weeks, PTB <37 weeks and also medical indicated preterm births 

    • Primary safety outcome: fetal/early infant death 

  • Stats 

    • Unlike previous trial, wanted it to have adequate power to identify both the primary efficacy and the primary safety analyses 

    • Therefore, needed 1665 liveborn infants to detect a reduction of 35% in the rate of the composite index 

    • Needed 1707 patients to provide 98% power to detect a reduction of approximately 30% in the rate of PTB <35w0d

Results 

  • Timeline: November 12, 2009 - October 8, 2018 

  • Total of 1740 women were consented and agreed to study 

    • 1130 allocated to 17OHP, 578 allocated to placebo 

    • 390 were randomized in the US, 1317 randomized in non-US 

  • Demographics were similar between groups 

    • 88.8% vs. 87.2% Caucasion in 17OHP vs. placebo groups 

    • Prepregnancy BMI 23 

    • Almost 90% were married, living with partner compared to just about 50% in the other study 

    • Only 7-8% smoked in pregnancy compared 20-22% in other study 

  • So… similar for each arm of this study, but very different demographic compared to the Meis trial.

  • Primary Outcome 

    • Preterm birth prior to 35 weeks: 11.0% in 17OHP vs. 11.5%

      • Spontaneous was 8.4 vs 8.9%, RR 0.93, 95% CI 0.67-1.30

    • Not a primary outcome, but PTB <37 weeks: 23.1% vs 21.9% RR 1.06, 95% CI 0.88-1.28! 

      • So different from 36 vs. 50% in Meis study 

    • Neonatal outcomes: 

      • Unsurprisingly, given no diff in preterm labor, no diff in composite neonatal morbidity and mortality 

  • Secondary Outcome 

    • Preterm birth <32 weeks - also not different 

    • Other things: cerclage, preterm labor eval, tocolysis, corticosteroids, maternal GDM, preeclampsia, chorio, abruption, CS all not different 

    • Neonatal: no difference in anything, including neonatal death, RDS, NEC, IVH, NICU admission, birth weight, TTN, PDA, ROP

Conclusions

  • Study was done in consultation with the FDA as part of approval for use of 17OHP 

  • Unlike the findings in the MFMU trial, this study had much lower event rate of PTB and did not confirm treatment efficacy 

Discussion points

  • While the Meis study was conducted in the USA, the PROLONG study was mostly not, and that was because the findings from the Meis study had changed practice 

  • Most places in the US were already prescribed 17OHP and likey didn’t want to change their practice 

  • Also, the Meis showed a large predominance of black women (60%), while there were very few in the PROLONG study 

  • Finally, there was a huge discrepancy in baseline preterm labor rates between the two studies, with the rates in PROLONG about ½ has much as that of the Meis study 

  • Why castor oil? 

    • Not that it has shown to cause preterm labor, but castor oil can cause contractions, usually due to GI distress when ingested 

  • Consequences of the Studies 

  • Follow up to the study 

    • EPPPIC - Evaluating Progesterone for Preventing Preterm birth International Collaborative - meta-analysis of individual participant data from randomized controlled trials 

      • Published in the Lancet in 2021 

      • Basically: 31 trials were included with individual participant data

        • From these studies, it seems that vaginal progesterone and 17OHP both reduce birth before 34 weeks gestation in high risk singleton pregnancies 

        • Absolute risk reduction is greater for women with short cervices 

        • The data seems a little better for vaginal progesterone in consistently decreasing preterm birth <37 weeks and <34 weeks

        • For 17OHP the data just crosses the line of no effect at <34 weeks