The Price of Delay and the Uncoupling of Severity: A Penalized Multivariate Analysis of Treatment Adequacy Versus Timing as Determinants of Congenital Syphilis

Authors

  • Ida Ayu Sintya Pratiwi General Practitioner, Puri Bunda Woman and Children Hospital, Denpasar, Indonesia
  • I Wayan Dharma Artana Department of Child Health, Puri Bunda Woman and Children Hospital, Denpasar, Indonesia

DOI:

https://doi.org/10.37275/bsm.v10i3.1536

Keywords:

Congenital syphilis, Firth’s penalized regression, Treatment adequacy, Treponema pallidum, Uncoupling phenomenon

Abstract

Background: Despite global elimination targets, congenital syphilis (CS) remains a critical cause of preventable neonatal morbidity. While the importance of antenatal screening is established, the relative impact of treatment adequacy (dosage/adherence) versus timing on neonatal severity—specifically the uncoupling phenomenon where severe visceral damage occurs despite normal birth biometrics—remains under-characterized in resource-limited settings.

Methods: A retrospective cross-sectional study analyzed 101 syphilis-exposed mother-infant pairs at a tertiary referral center in Indonesia (2021–2025). We evaluated maternal serologic testing time, treatment timing, and treatment adequacy (defined strictly per CDC guidelines; inadequate defined as <30 days pre-delivery, non-penicillin, or missed doses). To address sparse data bias and quasi-complete separation in the dataset, Firth’s Penalized Likelihood Logistic Regression was utilized to calculate adjusted odds ratios (aOR) for severe clinical manifestations.

Results: The prevalence of proven/possible CS was 58.4%. High-fidelity analysis revealed that inadequate maternal treatment was the dominant predictor of adverse outcomes (aOR = 85.40; 95% CI: 14.2–512.5; p<0.001), significantly outpacing delayed serologic testing (aOR = 4.8; p=0.012). A distinct uncoupling profile was identified: neonates born to inadequately treated mothers had high odds of severe visceral manifestations (hepatosplenomegaly, hematological failure) (aOR = 11.05), yet traditional biometrics (low birth weight, prematurity) showed no significant association (p>0.05).

Conclusion: Treatment adequacy is the single most critical determinant of neonatal prognosis. The dissociation between normal birth weight and severe organ damage suggests that anthropometry is a poor triage tool for syphilis. A zero-tolerance policy for therapeutic deviations is imperative.

Authors

  • Ida Ayu Sintya Pratiwi1*
  • I Wayan Dharma Artana2
  1. 1General Practitioner, Puri Bunda Woman and Children Hospital, Denpasar, Indonesia
  2. 2Department of Child Health, Puri Bunda Woman and Children Hospital, Denpasar, Indonesia

Corresponding author Ida Ayu Sintya Pratiwi — iasintya@gmail.com

Article history

  1. Submitted
  2. Accepted
  3. Published

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Published

2026-01-07

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How to Cite

1.
Ida Ayu Sintya Pratiwi, I Wayan Dharma Artana. The Price of Delay and the Uncoupling of Severity: A Penalized Multivariate Analysis of Treatment Adequacy Versus Timing as Determinants of Congenital Syphilis. Bioscmed [Internet]. 2026 Jan. 7 [cited 2026 Aug. 14];10(3):867-79. Available from: https://bioscmed.com/index.php/bsm/article/view/1536