Prenatal Risdiplam Therapy and Potential Reversal of Spinal Muscular Atrophy

BACKGROUND AND PURPOSE:

• Risdiplam is a drug that modulates splicing of SMN2, increasing the amount of SMN protein
  • This can improve disease manifestation for people with spinal muscular atrophy (SMA)
• Finkel et al. (NEJM, 2025) present a case study in which an expectant mother carrying a fetus with no copies of SMN1 was given risdiplam pre-delivery, and report on outcomes in the exposed offspring

METHODS:

• Case study
• Participants
  • Fetus at risk of SMA (deceased older sibling with SMA)
    • Amniocentesis revealed no copies of SMN1
• Study design
  • The mother received oral risdiplam daily (5 mg) between 32 weeks 5 days and delivery at 38 weeks 6 days
  • The infant subsequently received daily risdiplam orally starting 8 days after birth, and continued to present (30 months of life)
  • Risdiplam concentration and SMN and neurofilament levels were assessed in maternal and infant blood and amniotic fluid at birth

RESULTS:

• At delivery risdiplam concentrations were
  • Maternal plasma levels: 14 ng per milliliter
  • Compared to maternal levels, amniotic fluid: 33%
  • Compared to maternal levels: cord blood: 69%
• The infant appeared normal at birth
  • A heart murmur due to ventricular septal defect was detected, but resolved
• Other infant outcomes
  • Mildly reduced visual acuity attributed to optic-nerve hypoplasia in both eyes
  • Mild hemiparesis associated with left midbrain hypoplasia
  • Global developmental delay without regression
• No other genetic disorders have been found
• No features of SMA have appeared to date
  • Muscle development and performance have been normal for age at all tests

CONCLUSION:

• In this case study, a single infant with confirmed SMN1 deletion was exposed to risdiplam in utero
• The infant was born without any features of SMA, though other effects were noted that likely occured early in development prior to maternal exposure to risdiplam
• The authors state

Results in this single case cannot be generalized but may support the consideration of prenatal risdiplam treatment for SMA identified in utero

Learn More – Primary Sources:

Risdiplam for Prenatal Therapy of Spinal Muscular Atrophy

Meta-Analysis Update: Vaginal Progesterone Reduces the Risk of Preterm Birth for Patients with Short Cervix

BACKGROUND AND PURPOSE:

• A 2018 meta-analysis found that vaginal progesterone reduced the risk of preterm birth and other adverse outcomes for women with a singleton gestation and short cervix
• Romero et al. (AJOG, 2025) provide an update to this meta-analysis, removing data from a recently retracted study included in the previous analysis

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • Randomized controlled trials
  • Studies that compared vaginal progesterone to placebo/no treatment for the prevention of preterm birth or other adverse perinatal outcomes
• Study design
  • Data were pooled and fixed- and random-effects models were used to calculate relative risk (RR)
• Primary outcome
  • Preterm birth <33 weeks

RESULTS:

• 4 trials | 966 women
• Vaginal progesterone significantly reduced the risk of preterm birth <33 weeks
  • RR 0.63 (95% CI, 0.48 to 0.82)
• Results for other adverse perinatal outcomes were similar to those of the original meta-analysis
  • Vaginal progesterone was associated with reduced risk of low birthweight | Neonatal morbidity and mortality | Admission to NICU
• There was no difference in benefit for women with a history of spontaneous preterm birth (Pinteraction=0.78)
• Sensitivity analyses performed using individual patient data confirmed vaginal progesterone was associated with a significantly reduced risk of preterm birth
  • <34 weeks: RR 0.65 (95% CI, 0.51 to 0.8)
  • <28 weeks: RR 0.67 (95% CI, 0.45 to 0.98)

CONCLUSION:

• Vaginal progesterone reduces the risk of preterm birth <33 weeks for patients with a singleton gestation and midtrimester short cervix, confirming the results of the previous meta-analysis
• Vaginal progesterone provides a benefit regardless of history of preterm birth
• The authors state

Vaginal progesterone should continue be offered to patients with a singleton gestation, with and without a history of spontaneous preterm birth, and with a midtrimester transvaginal sonographic cervical length ≤25 mm

Learn More – Primary Sources:

Vaginal progesterone reduces the risk of preterm birth and adverse perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix (≤25 mm): an updated individual patient data meta-analysis

RCT Results: Which Hereditary Cancer Risk Assessment Strategies are Most Likely to be Successful in a Primary Care Setting?

BACKGROUND AND PURPOSE:

• Many cancers are caused by heritable factors that can be readily identified with multigene test
• Swisher et al. (JAMA Network Open, 2025) compared two population-based engagement strategies for identifying primary care patients with a family or personal history of cancer and offering eligible individuals genetic testing for cancer susceptibility

METHODS:

• Clinical cluster-randomized trial
  • EDGE (Early Detection of Genetic Risk) trial
• Participants
  • English-speaking patients ≥25 years old
  • Primary care visit between April 2021 and March 2022
• Interventions
  • Point of care (POC) engagement: Cancer history assessment conducted by staff immediately preceding clinical appointments
  • Direct patient engagement (DPE): Letter and email outreach facilitated at-home completion of cancer history assessment
• Study design
  • Patients who completed risk assessment and met prespecified criteria were offered at home genetic testing at no cost
  • Logistic regression models were used to compare approaches
  • Analysis was by intention-to-treat
• Primary outcomes
  • Proportion of patients who completed risk assessment
  • Proportion of patients who completed genetic testing

RESULTS:

• 95,623 patients had a primary care visit
  • Completed risk assessment: 13,705
• Patients who completed the risk assessment were
  • Predominantly female: 64.7%
  • Predominantly 65 to 84 years: 39.6%
• The POC approach resulted in a higher proportion of patients completing risk assessment
  • POC: 19.1% | DPE: 8.7%
  • Adjusted odds ratio (aOR) 2.68 (95% CI, 1.72 to 4.17) | P<0.001
• Neither approach was better at getting patients to complete testing
  • POC: 1.5% | DPE: 1.6%
  • aOR 0.96 (95% CI, 0.64 to 1.46) | P=0.86
• Among those eligible for testing, POC test completion was approximately half of that for the DPE approach
  • POC: 24.7% | DPE: 44.7%
  • aOR 0.49 (95% CI, 0.37 to 0.64) | P<0.001
• The proportion of tested patients identified with an actionable pathogenic variant was significantly lower for the POC approach than the DPE approach
  • POC: 3.8% | DPE: 6.6%
  • aOR 0.61 (95% CI, 0.44 to 0.85) | P=0.003

CONCLUSION:

• Patients who received point of care cancer history assessment during primary care visits were more likely to complete the risk assessment than patients who received a letter or email asking them to complete the assessment
• Both approaches led to similar rates of genetic testing completion but the email group had a higher rate of pathogenic mutations
• The authors state

Relative to patients in the POC arm, those in the DPE arm who completed screening were more likely to have a personal history of cancer and 2 or more first-degree relatives with cancer, resulting in a higher proportion who were eligible for testing

Using a combination of engagement strategies may be the optimal approach for greater reach and impact

Learn More – Primary Sources:

Strategies to Assess Risk for Hereditary Cancer in Primary Care Clinics: A Cluster Randomized Clinical Trial

How Have Trends in Cervical Precancers Changed Since HPV Vaccination Began Nearly 20 Years Ago?

BACKGROUND AND PURPOSE:

• HPV vaccination began in 2008, and coverage increased steadily through 2021
  • Approximately three quarters of all adolescents are vaccinated
• Gargano et al. (CDC MMWR, 2025) describe trends in incidence of cervical precancers CIN2+ and CIN3+ lesions since vaccination began

METHODS:

• Population-based screening
  • HPV-IMPACT
  • Surveillance program in 5 sites since 2008
• Population
  • Women between 20 and 64 years
• Exposures
  • Year since vaccination began (in 2008)
• Study design
  • CIN2/3+ incidence was calculated using the estimated number of women screened as the denominator to control for changes in screening frequency
• Primary outcome
  • Annual age-specific CIN2+ and CIN3+ incidence

RESULTS:

• CIN2+ cases 2008 through 2022: 39,997
  • CIN3+: 32.6%
• For women aged 20 to 24, CIN2+ cases per 100,000 screened decreased annually by 11.0% (95% CI, 10.2 to 12.8)
• For women aged 25 to 29, CIN2+ cases per 100,000 screened remained stable over the whole period
  • Annual cases rose between 2008 and 2016: 3.1 (95% CI, 1.1 to 16.7)
  • Annual cases dropped between 2016 and 2022: −4.3 (95% CI, −14.6 to −0.7)
• Similar trends were observed for women aged 30 to 34 and women aged 35 to 29
• For women aged 40 to 49 or 50 to 64, CIN2+ incidence increased for between 2008 and 2022
  • Average annual percent change 40 to 49: 4.4% increase (95% CI, 2.2 to 7.5)
  • Average annual percent change 50 to 64: 5.2% increase (95% CI, 4.1 to 7.0)
• Trends for CIN3+ were generally similar to those for CIN2+
  • For women aged 25 to 29, the average annual percent change was negative for CIN3+ between 2008 and 2022: 3.5% decrease (95% CI, 2.1 to 5.4)

CONCLUSION:

• Among women aged 20 to 24, CIN2+ and CIN3+ incidence decreased by approximately 80% between 2008 and 2022
• For women aged 25 to 29, CIN3+ incidence decreased by 37%
• The authors state

These data are consistent with continuing impact of the U.S. HPV vaccination program on reducing cervical precancers (including CIN3+, the outcome most proximal to cervical cancer), and are consistent with both declines in vaccine-type HPV prevalence and early observations of reductions in cervical cancer among young women

The data also suggest that precancer incidence in age groups ≥25 years, which were previously observed to increase through 2015, have begun to decrease

HPV vaccination and guidelines-based cervical cancer screening are important tools for cervical cancer prevention

Learn More – Primary Sources:

Trends in Cervical Precancers Identified Through Population-Based Surveillance — Human Papillomavirus Vaccine Impact Monitoring Project

Have 2023 Cancer Screening Rates Rebounded After the COVID-19 Pandemic-Related Screening Declines?

BACKGROUND AND PURPOSE:

• Cancer screening rates declined during COVID and in the immediate aftermath, leading to increased cancer diagnoses at later stages
• Star et al. (JAMA, 2025) estimated post-pandemic cancer screening rates in 2023 relative to previously documented declines through 2021

METHODS:

• Analysis of screening trends
  • Data from National Health Interview Survey
• Population
  • Nationally representative cross-sectional cohort of noninstitutionalized US adults
• Exposures
  • Before the COVID-19 pandemic: 2019
  • During: 2021
  • After: 2023
• Study design
  • Adjustments were made for nonresponse bias
  • Screening eligibility and strategies were defined according to the USPSTF recommendations
  • Logistic regression models estimated adjusted prevalence ratios (aPRs)
    • Adjustments: was Age | Race and ethnicity | Education | Insurance | Region
• Primary outcomes
  • Self-reported breast | Cervical | Colorectal cancer screening

RESULTS:

• 2023 eligibility for screening
  • Breast cancer: 6829 | Cervical cancer: 8888 | Colorectal cancer: 13,144
• Between 2019 and 2023, reported past-year breast and colorectal cancer screening increased
  • Breast: 7% increase
    • Prevalence estimate 59.7 to 64.9%
    • aPR 1.07 (95% CI, 1.04 to 1.10)
  • Colorectal: 12%
    • Prevalence estimate: 21.2 to 24.3%
    • aPR 1.12 (95% CI, 1.06 to 1.18)
• Underlying these increases were
  • Rebounds between 2021 and 2023 in breast cancer screening
    • 56.9 to 64.9%
    • aPR 1.14 (95% CI, 1.11 to 1.18)
  • Rebounds between 2021 and 2023 in colonoscopy screening
    • 13.8 to 15.7%
    • aPR 1.13 (95% CI, 1.06 to 1.22)
  • Sustained increases in stool testing
    • 2019: 6.6%
    • 2021: 10.1%
    • 2023: 10.1%
• Reported cervical cancer screening in 2023 remained below 2019 estimates
  • 14% decrease
  • Prevalence estimate 46.8 to 40.9%
  • aPR 0.86 (95% CI, 0.82 to 0.90)
• Colorectal cancer screening increased between 2019 and 2023 for college graduates, but did not change in individuals with a high school degree or less
• Breast cancer screening met or exceeded 2019 levels across screening groups as screening rebounded between 2021 and 2023
• Cervical cancer screening rebounded between 2021 and 2023 among college graduates, but remained below 2019 levels for most education groups

CONCLUSION:

• Reported breast and colorectal cancer screening rates rebounded after pandemic-related decreases
• In 2023 screening rates were higher than pre-pandemic levels
• Cervical cancer screening remained below pre-pandemic levels
• The authors state

Cervical cancer screening rates remained below prepandemic levels, a troubling trend as early-stage diagnoses continued to decrease in 2021

The persistent decline may in part reflect longer-term declines in patient knowledge and clinician recommendation of cervical cancer screening

Learn More – Primary Sources:

Cancer Screening 3 Years After the Onset of the COVID-19 Pandemic

Are Women with “Flat” Oral Glucose Tolerance Test Curves at Higher Risk of Adverse Pregnancy Outcomes?

BACKGROUND AND PURPOSE:

• Lopian et al. (American Journal of Perinatology, 2025) analyzed whether pregnant women with “flat” oral glucose tolerance test (OGTT) curves in pregnancy are at increased risk of maternal or neonatal adverse outcomes.

METHODS:

• Retrospective cohort study
• Population
  • Pregnant women receiving 100-g OGTT test
• Exposures
  • Flat test curves
    • Defined as fasting serum glucose level <95 mg/dL and remaining values <100 mg/dL
  • Normal test curves
• Primary outcomes
  • Macrosomia
  • Small for gestational age (SGA)
• Secondary outcomes
  • Additional adverse outcomes (e.g., hypertensive disorders of pregnancy, IUFD, PPH, umbilical artery pH <7.1, Apgar score <7 at 5 min)
  • Composites of maternal and neonatal outcomes

RESULTS:

• Flat curves: 1060 patients | Control curves: 10591 patients
• Patients with flat curves tended to be
  • Younger
    • Flat: mean age 28.3 | Control: mean age 29.8 | P<0.001
  • Less likely to be >35 years old
    • Flat: 14.1% | Controls: 23.4% | P<0.001
• Patients with flat curves had a reduced risk of
  • Macrosomia
    • Flat: 11.4% | Control: 15.1%
    • Odds ratio (OR) 0.7 (95% CI, 0.58 to 0.89) | P=0.001
  • Unplanned cesarean
    • Flat: 7.5% | Control: 10.2%
    • OR 0.8 (95% CI, 0.58 to 0.96) | P=0.002
• There was no difference in the rate of the composite adverse maternal or neonatal outcome
  • Maternal adverse outcome: OR 0.9 (95% CI, 0.7 to 1.0) | P=0.1
  • Neonatal adverse outcome: OR 1.2 (95% CI, 0.9 to 1.5) | P=0.15
• Neonates born to women with flat curves had slightly lower mean birth weight, but there was no difference in the rates of SGA
  • Mean birth weight
    • Flat: 3474 g | Control: 3505 g | P=0.04
  • SGA
    • Flat: 2.5% | Control: 1.8%
    • OR 1.3 (95% CI, 0.9 to 2.0) | P=0.08

CONCLUSION:

• Women with flat OGTT curves were at lower risk of unplanned cesarean delivery and neonatal macrosomia
• Rates of adverse maternal and neonatal outcomes were not increased in this population

Learn More – Primary Sources:

The Implications of a “Flat” Oral Glucose Tolerance Test Curve in Pregnancy

Are Postmenopausal Women Who Report Intentional Weight Loss at Lower Risk of Mortality?

BACKGROUND AND PURPOSE:

• There is a well-established link between obesity and adverse health impacts
• Studies that evaluate the association between weight loss and mortality are mixed, possibly due to combining intentional and unintentional weight loss
  • Unintentional weight loss may be the result of poor health and can contribute to reverse causality
• Hendryx et al. (JAMA Network Open, 2025) evaluated associations between intentional vs unintentional weight loss and mortality reduction in postmenopausal women

METHODS:

• Prospective cohort study
  • Data from the Women’s Health Initiative Observational Study
• Participants
  • Women aged 50 to 79 across 40 centers in the US
• Exposures
  • Measured weight loss and waist circumference (WC) reduction between baseline and year 3
  • Weight loss intentionality
• Study design
  • Follow-up: 18.6 years
  • Intentional weight loss definition: ≥5 lbs loss vs stable weight)
  • Cox proportional hazards regression models were used to calculate hazard ratio (HR)
• Primary outcomes
  • All-cause | Cancer | Cardiovascular | Other mortality

RESULTS:

• 58,961 women
  • Mean age: 63.3 (SD, 7.2)
  • Mean BMI: 27.0 (SD, 5.6) | Mean WC: 84.1 (SD, 13.0) cm
  • Deaths from all causes during follow-up: 49.5%
• Intentional weight loss was associated with lower subsequent mortality rates for
  • All-cause mortality: HR 0.88 (95% CI, 0.86 to 0.90)
  • Cancer mortality: HR 0.87 (95% CI, 0.82 to 0.92)
  • Cardiovascular mortality: HR 0.87 (95% CI, 0.83 to 0.91)
  • Other mortality: HR 0.89 (95% CI, 0.86 to 0.92)
• Reported intentional weight loss coupled with actual weight reduction of 5% or more was associated only with lower cardiovascular mortality
  • HR 0.90 (95% CI, 0.81 to 0.99)
• Reported intentional weight loss coupled with measured WC loss was associated with lower rates of
  • All-cause mortality: HR 0.91 (95% CI, 0.86 to 0.95)
  • Cancer mortality: HR 0.85 (95% CI, 0.76 to 0.95)
  • Cardiovascular mortality: HR 0.79 (95% CI, 0.72 to 0.87)
• Unintentional weight loss or unintentional WC loss were each associated with increased mortality risk for all groups
• Weight gain and WC gain were also associated with increased mortality risk

CONCLUSION:

• Intentional vs unintentional weight loss in postmenopausal women was associated with lower risk of cardiovascular disease mortality
• Reducing waist circumference in older women also lowers the risk of all-cause and cancer-related mortality
• The authors state

Our findings add to the evidence base that weight may not be the preferred measure for assessing body composition among older women

Our results also suggested that older women with overweight or obesity should not be discouraged from attempting weight loss if they wish to lose weight

Learn More – Primary Sources:

Intentional Weight Loss, Waist Circumference Reduction, and Mortality Risk Among Postmenopausal Women

Can the sFLT1/PLGF Ratio Predict Need for Emergency Cesarean Among Patients with Suspected Preeclampsia?

BACKGROUND AND PURPOSE:

• The ratio between sFLT1 (soluble fms-like tyrosine kinase 1) and PLGF (placental growth factor) is a biomarker for preeclampsia
• sFLT1/PLGF ratio is also a marker for placenta dysfunction
• Dos Reis et al. (AJOG, 2025) examined the association between the sFLT1/PLGF ratio in women with suspected preeclampsia and delivery outcomes including time to delivery and need for emergency cesarean

METHODS:

• Secondary analysis of randomized interventional study
  • INSPIRE trial: sFlt-1/PlGF ratio in predicting preeclampsia in pregnant women with suspected preeclampsia
• Participants
  • Women with suspected preeclampsia
• Exposures
  • sFLT1/PLGF ratio groups
    • Category 1: sFLT1/PLGF ratio ≤38
    • Category 2: sFLT1/PLGF ratio >38 and <85
    • Category 3: sFLT1/PLGF ratio ≥85
• Study design
  • Kaplan-Meier curves were used to model time from ratio determination to delivery
    • Adjustment was for gestational age and trial arm with Cox regression
  • Multivariable logistic regression was used to assess the association between delivery outcomes
    • Adjustment was for gestational age and trial arm
  • Multiple linear regression was used to determine the association between birthweight z score and sFLT1/PLGF ratio
• Primary outcome
  • Time from ratio determination to delivery
• Secondary outcomes
  • Mode of birth
  • Fetal distress
  • Need for labor induction
  • Birthweight z score

RESULTS:

• 370 women
• Higher ratio categories were associated with a shorter latency from ratio determination to delivery
  • Cat 1: 37 days | Cat 2: 13 days | Cat 3: 10 days
  • Category 3 vs Category 1: Hazard ratio (HR) 5.64 (95% CI, 4.06 to 7.84) | P<0.001
• Category 3 ratio performance for prediction of preeclampsia indicated delivery within 2 weeks
  • Specificity: 92.7% (95% CI, 89.0 to 95.1)
  • Sensitivity: 54.72% (95% CI, 41.3 to 69.5)
• Compared to category 1, ratio category 3 was also associated with
  • Decreased odds of spontaneous vaginal delivery
    • Odds ratio (OR) 0.47 (95% CI, 0.25 to 0.89)
  • Increased odds of emergency cesarean section
    • OR 5.89 (95% CI, 3.05 to 11.21)
  • Increased odds for intrapartum fetal distress requiring operative delivery or cesarean section
    • OR 3.04 (95% CI 1.53 to 6.05)
• Higher ratio categories were also associated with
  • Higher odds of induction of labor
    • Cat 2: OR 2.20 (95% CI, 1.02 to 4.76)
    • Cat 3: OR 6.0 (95% CI, 2.01 to 17.93)
  • Lower median birthweight z score
• In subgroup analyses (no preeclampsia and spontaneous labor | with preeclampsia)
  • sFLT1/PLGF ratio was significantly higher in patients requiring intervention for fetal distress or failure to progress vs vaginal delivery without intervention
  • In the ‘no preeclampsia and spontaneous labor’ subgroup
    • Higher log ratio noted among patients requiring intervention for fetal distress or failure to progress

CONCLUSION:

• Among women with suspected preeclampsia, the sFLT1/PLGF ratio was associated with 6-fold increased risk for emergency cesarean and 3-fold risk for fetal distress
• The authors state

These data suggest that sFLT1/PLGF ratio is related to placentally mediated birth outcomes beyond preeclampsia, and could provide useful patient counseling as well as guidance for planning and monitoring of labor and delivery in these patients

Learn More – Primary Sources:

The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor predicts time to delivery and mode of birth in patients with suspected preeclampsia: a secondary analysis of the INSPIRE trial

Meta-Analysis: Does Vaginal Estrogen Increase the Risk of Recurrence for Patients with a History of Breast Cancer and GSM?

BACKGROUND AND PURPOSE:

• Vaginal estrogen is a very effective treatment for genitourinary symptoms of menopause (GSM), but the FDA currently lists a history of breast cancer as a contraindication for its use
• Beste et al. (AJOG, 2025) assessed the risk of breast cancer recurrence, breast cancer-specific mortality, and overall mortality for breast cancer survivors receiving vaginal estrogen therapy for GSM

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • Observational studies
  • Studies that examined the use of vaginal estrogen in patients with a history of breast cancer, and compared breast cancer recurrence (local and distant) with patients who did not use vaginal estrogen
• Study design
  • A random effects model was used to address clinical heterogeneity between studies and calculate pooled unadjusted odds ratios
• Primary outcome
  • Breast cancer recurrence
• Secondary outcomes
  • Breast cancer mortality
  • Overall mortality

RESULTS:

• 8 studies
• The use of vaginal estrogen in patients with a history of breast cancer was not associated with an increased risk of breast cancer recurrence
  • Odds ratio (OR) 0.48 (95% CI, 0.23 to 0.98)
  • 6 studies | 24,060 patients
• There was also no increase in the risk of breast cancer or overall mortality with vaginal estrogen
  • Breast cancer mortality
    • OR 0.60 (95% CI, 0.18 to 1.95)
    • 4 studies | 61,695 patients
  • Overall mortality
    • OR 0.46 (95% CI, 0.42 to 0.49)
    • 5 studies | 59,724 patients

CONCLUSION:

• The use of vaginal estrogen for GSM in patients with a history of breast cancer was not associated with increases in breast cancer recurrence or mortality
• Limitation of this meta-analysis: Observational studies only
• The authors state

The pooled data from these studies suggest that vaginal estrogen use is not significantly associated with an increased risk of breast cancer recurrence among survivors experiencing GSM

Learn More – Primary Sources:

Vaginal estrogen use in breast cancer survivors: a systematic review and meta-analysis of recurrence and mortality risks

Do Very Short Durations of Antenatal Corticosteroids Improve Survival for Extremely Preterm Neonates?

BACKGROUND AND PURPOSE:

• Up to a quarter of neonates born extremely premature are born after receiving only a partial course of antenatal corticosteroids
• Chawla et al. (JAMA Network Open, 2025) evaluated the link between duration of antenatal betamethasone exposure and neonatal outcomes among extremely preterm infants

METHODS:

• Retrospective cohort study
  • Data derived from the extremely preterm infant registry of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
• Population
  • Infants born at 22w0d to 27w6d 0/7 gestation
    • Exclusion: Infants who received multiple doses of antenatal betamethasone
• Exposures
  • Time in hours from antenatal betamethasone administration to birth
• Study design
  • Generalized linear models were used to calculate relative risk (RR)
  • Adjustments: Gestational age | Infant sex | Maternal race | Education | Small for gestational age | Mode of delivery | Multiple birth | Prolonged rupture of membranes | Birth center
• Primary outcome
  • Survival to discharge
• Secondary outcomes
  • Survival without major morbidity
  • Composites of individual morbidities and death

RESULTS:

• No exposures: 26.3% | Single dose of betamethasone <24 hours before birth: 73.7%
  • Median administration-to-birth interval: 3.8 (IQR, 1.4 to 9.5) hours
• The administration-to-birth interval was independently associated with
  • Survival
    • aRR per 1-hour increase: 1.01 (95% CI, 1.00 to 1.01)
    • aRR per 6-hour increase: 1.04 (95% CI, 1.01 to 1.07)
  • Survival without severe neonatal morbidity
    • aRR per 1-hour increase: 1.01 (95% CI, 1.01 to 1.02)
    • aRR per 6-hour increase: 1.09 (95% CI, 1.04 to 1.14)

CONCLUSION:

• Even when a single dose of antenatal corticosteroid was given an hour before birth, survival of extremely preterm neonates was significantly improved
• The link with survival was stronger with longer durations between administration and delivery
• The authors state

These data suggest that for individuals at risk of imminent preterm birth, even a few hours of exposure to a single dose of antenatal betamethasone has beneficial associations, and this benefit increased with greater duration of exposure

This study supports a proactive approach to administration of ANS when delivery of an extremely preterm infant is imminent, to improve survival and reduce major morbidities in this high-risk population

Learn More – Primary Sources:

Short Duration of Antenatal Corticosteroid Exposure and Outcomes in Extremely Preterm Infants

Does Induction of Labor Increase the Rate of Vaginal Delivery for Patients with a Prior History of Cesarean?

BACKGROUND AND PURPOSE:

• Ukoha et al. (AJOG, 2025) sought to determine the association between clinical outcomes and induction of labor at 39 weeks in low-risk patients with 1 prior cesarean delivery

METHODS:

• Cross-sectional study
  • Data from US Vital Statistics Birth Data
  • Between 2016 to 2021
• Population
  • Vertex, singleton pregnancies
  • 1 prior cesarean delivery
• Exposure
  • Induction of labor at 39w0d to 39w6d
  • Expectant management from 40w0d to 42w6d
• Study design
  • Regression models used to calculate risk ratio (RR) with adjustment for demographic variables
• Primary outcome
  • Vaginal delivery
• Secondary outcomes
  • Composite of maternal morbidity
    • Uterine rupture | Operative vaginal delivery | Peripartum hysterectomy | Intensive care unit admission | Transfusion
  • Composite of neonatal morbidity
    • NICU admission | Apgar score <5 at 5 minutes | Immediate ventilation | Prolonged ventilation | Seizure or serious neurological dysfunction

RESULTS:

• 198,797 pregnant women with 1 prior cesarean
  • Induction: 13.0% | Expectant management: 87.0%
• Patients who were induced were more likely to have a vaginal delivery
  • Induction: 38.0% | Expectant management: 31.8%
  • aRR 1.32 (95% CI, 1.28 to 1.36)
• Among those who had vaginal deliveries, induction of labor was associated with increased likelihood of operative vaginal delivery
  • Induction: 11.1% | Expectant management: 10.0%
  • aRR 1.15 (95% CI, 1.07 to 1.24)
• There was no difference in the rates of the maternal morbidity composite
  • Induction: 0.9% | Expectant management: 0.9%
  • aRR 0.92 (95% CI, 0.79 to 1.06)
• Rates of maternal morbidities were relatively low and were not different between induction vs expectant groups
  • Uterine rupture: 0.3% | 0.3%
  • Peripartum hysterectomy: 0.04% | 0.05%
  • ICU admission: 0.1% | 0.2%
• There was also no significant difference in the neonatal morbidity composite
  • Induction: 7.3% | Expectant management: 6.7%
  • aRR 1.04 (95% CI, 0.98 to 1.09)

CONCLUSION:

• Compared to expectant management, induction at 39 weeks for individuals with a history of 1 prior cesarean was associated with a higher rate of vaginal birth
• Maternal and neonatal morbidities did not differ between the groups
• A limitation of the study was the retrospective design, and additional research is required particularly regarding optimal protocols
• The authors state

Our results show that IOL at 39 weeks of gestation in low-risk TOLAC patients may be a method to optimize successful VBAC delivery

Learn More – Primary Sources:

Induction of labor vs expectant management among low-risk patients with 1 prior cesarean delivery