Journal Article Annotations
2025, 3rd Quarter

Women’s Health

Annotations by Diana Punko, MD, MS
September, 2025

Association of multiple indicators of pubertal timing with depressive symptoms and depression in adolescent girls.
Buprenorphine and Methadone Discontinuation During Pregnancy and the Postpartum Period: A Nationwide Cohort Study.

PUBLICATION #1 — Women’s Health

Association of multiple indicators of pubertal timing with depressive symptoms and depression in adolescent girls.

Dana Tarif, Jon Heron, Abigail Fraser, Ahmed Elhakeem, Carol Joinson.

Abstract: Br J Psychiatry. 2025 Aug 26:1-7. doi: 10.1192/bjp.2025.88. Online ahead of print.

Background:
Previous studies investigating the association between pubertal timing and depression in girls primarily use self-reported age at menarche (AAM). This study examines a range of pubertal timing indicators, including anthropometric and self-reported measures.

Aims:
Compare associations of multiple indicators of pubertal timing with depressive symptoms and depression in girls and explore whether these associations persist into early adulthood.

Method:
The sample comprised 4607 girls from UK-based Avon Longitudinal Study of Parents and Children. Seven measures of pubertal timing were assessed between ages 7 and 17 (age at: peak height velocity (aPHV); peak weight velocity; peak bone mineral content velocity; Tanner pubic hair and breast development stage 3; axillary hair; and AAM). Depressive symptoms were measured at 14, 17, 18 and 24 years using the Short Mood and Feelings Questionnaire. Depression was assessed at 15, 18 and 24 years using the Development and Well-Being Assessment and Clinical Interview Schedule-Revised. Multivariable logistic regression models were adjusted for socioeconomic status and pre-pubertal body mass index.

Results:
Later pubertal timing was associated with lower odds of depressive symptoms at age 14 across six measures, including aPHV (adjusted odds ratio (AOR): 0.82; 95% CI 0.72, 0.95) and AAM (AOR: 0.84; 95% CI 0.76, 0.92). Later AAM and Tanner breast stage 3 were associated with lower odds of depression at age 18 (AOR: 0.85; 95% CI 0.75, 0.97 and AOR: 0.83; 95% CI 0.72, 0.95, respectively). Associations attenuated by age 24.

Conclusions:
Later pubertal timing was associated with reduced odds of depressive symptoms during mid-adolescence, with associations attenuating by adulthood.

Annotation

The finding:
This longitudinal cohort study found that later pubertal timing across multiple indicators (including age at peak height velocity, age at menarche, and Tanner breast stage 3) was associated with lower odds of depressive symptoms and depression diagnosis in adolescent girls, particularly at ages 14 and 18. However, these associations attenuated by age 24, suggesting the effect is most pronounced in mid-adolescence and diminishes into early adulthood.

Strengths and weaknesses:
Strengths include the use of a large, well-characterized population-based cohort (N=4607), multiple objective and self-reported measures of pubertal timing, and repeated assessments of depressive symptoms and diagnoses into early adulthood. The study adjusted for key confounders such as socioeconomic status and pre-pubertal BMI. Limitations include potential residual confounding, reliance on self-reported pubertal milestones for some measures, different diagnostic tools for depression (Developmental and Well-Being Assessment, Short Moods and Feeling Questionnaire, and Revised Clinical Interview Schedule), and possible attrition bias over long-term follow-up.

Relevance:
For C-L psychiatrists, particularly those treating the pediatric patient population, these findings underscore the importance of considering pubertal timing as a risk factor for depression in adolescent girls, particularly those who mature earlier than peers. Awareness of this developmental vulnerability can inform risk assessment, early intervention, and psychoeducation for patients and families presenting with mood symptoms during adolescence. The attenuation of risk by early adulthood suggests that targeted support during the pubertal transition may be most impactful.

PUBLICATION #2 — Women’s Health

Buprenorphine and Methadone Discontinuation During Pregnancy and the Postpartum Period: A Nationwide Cohort Study.

Chih-Wan Grace Lin, Brian T Bateman, Loreen Straub, Sonia Hernández-Díaz, Seanna M Vine, Hendrée E Jones, Hilary S Connery, Jonathan M Davis, Kathryn J Gray, Barry Lester, Elizabeth A Suarez, Ayesha C Sujan, Mishka Terplan, Krista F Huybrechts.

Abstract: Am J Psychiatry. 2025 Aug 27:appiajp20241127. doi: 10.1176/appi.ajp.20241127. Online ahead of print.

Objective:
Treatment of pregnant patients with opioid use disorder with methadone or buprenorphine is crucial for maternal and neonatal safety. While several clinical trials have demonstrated higher treatment discontinuation rates for buprenorphine compared with methadone outside of pregnancy, evidence during pregnancy and the postpartum period is limited. The authors compared treatment discontinuation between buprenorphine and methadone during pregnancy and over follow-up through 1 year postpartum.

Methods:
This was a cohort study, using nationwide Medicaid data, of pregnant patients who initiated methadone or transmucosal buprenorphine (with or without naloxone) for opioid use disorder during the first trimester. The primary outcome was treatment discontinuation, defined as a treatment gap ≥60 days; alternative definitions for discontinuation were explored in sensitivity analyses. Hazard ratios were estimated using Cox proportional hazards regression with propensity score overlap weighting to control for confounding. Subgroup analyses were conducted, stratified by buprenorphine alone versus the buprenorphine/naloxone combination, each compared to methadone.

Results:
Overall, 696 pregnant patients were identified who initiated methadone treatment and 1,538 who initiated buprenorphine treatment in the first trimester. Compared to methadone initiators, buprenorphine initiators were more likely to discontinue treatment during pregnancy (32.8% for buprenorphine vs. 25.6% for methadone; weighted hazard ratio=1.41, 95% CI=1.15, 1.72) and through 1 year postpartum (58.8% vs. 49.0%; hazard ratio=1.37, 95% CI=1.19, 1.57). For patients initiating the buprenorphine/naloxone combination, the hazard ratio was 1.73 (95% CI=1.36, 2.19) during pregnancy and 1.56 (95% CI=1.30, 1.86) through 1 year postpartum. For patients initiating buprenorphine alone, the hazard ratios were 1.14 (95% CI=0.90, 1.46) and 1.23 (95% CI=1.04, 1.46), respectively. Varying the treatment gap used to define discontinuation in sensitivity analyses yielded consistent results.

Conclusion:
Pregnant patients initiating transmucosal buprenorphine during early pregnancy were more likely to discontinue treatment than those initiating methadone, but treatment discontinuation was high for both treatments. The study findings highlight the importance of identifying and addressing barriers to treatment retention among pregnant patients with opioid use disorder.

Annotation

The finding:
This nationwide cohort study found that pregnant patients who initiated transmucosal buprenorphine (with or without naloxone) in the first trimester for treatment of opioid use disorder (OUD) were more likely to discontinue treatment during pregnancy and through one year postpartum compared to those who initiated methadone. Discontinuation rates were high for both medications, but particularly elevated for buprenorphine/naloxone. These findings persisted across sensitivity analyses and subgroups, highlighting a significant challenge in treatment retention for both medications, but especially for buprenorphine.

Strengths and weaknesses:
Strengths include the use of a large, nationwide Medicaid dataset, robust adjustment for confounding using propensity score overlap weighting, and comprehensive sensitivity analyses. The study’s limitations include potential residual confounding, lack of granular data on reasons for discontinuation, and possible misclassification of medication exposure or discontinuation. The observational design precludes causal inference.

Relevance:
For C-L psychiatrists, these findings underscore the importance of proactive strategies to support medication retention in pregnant and postpartum patients with OUD, particularly those on buprenorphine. Given that both the American College of Obstetricians and Gynecologists and the American Society of Addiction Medicine recommend either methadone or buprenorphine as standard of care for treatment of OUD in pregnant people, but recognize differences in retention and neonatal outcomes, these data inform shared decision-making and highlight the need for enhanced postpartum support to reduce discontinuation and associated risks.