Observational studyInternational journal of environmental research and public health2020
Warning of Immortal Time Bias When Studying Drug Safety in Pregnancy: Application to Late Use of Antibiotics and Preterm Delivery.
Observational study in International journal of environmental research and public health, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Causal Inference Approaches to Estimating the Effect of Ibrutinib Dose Modifications on Progression-Free Survival in Chronic Lymphocytic Leukemia.Clinical pharmacology and therapeutics · 2026Article
- Time-related Bias When Studying Perinatal Complications After Maternal Injuries: Application to Maternal Injuries and Preterm Birth.Epidemiology (Cambridge, Mass.) · 2025Article
- The hazard of using the Poisson model to cope with immortal time bias in the case of time-varying hazard.BMC medical research methodology · 2024Article
- Influenza Vaccination Effectiveness in Paediatric 'Healthy' Patients: A Population-Based Study in Italy.Vaccines · 2022Article
- Use of Antibiotic Treatment in Pregnancy and the Risk of Several Neonatal Outcomes: A Population-Based Study.International journal of environmental research and public health · 2021Article
- Analytical challenges in estimating the effect of exposures that are bounded by follow-up time: experiences from the Blood Stream Infection-Focus on Outcomes study.BMC medical research methodology · 2021Article
- Statistical Advances in Epidemiology and Public Health.International journal of environmental research and public health · 2021Article
- Methodological Considerations for Preterm Birth Research.Frontiers in global women's health · 2021Article
- Association between Adherence with Recommended Antenatal Care in Low-Risk, Uncomplicated Pregnancy, and Maternal and Neonatal Adverse Outcomes: Evidence from Italy.International journal of environmental research and public health · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to illustrate and account for immortal time bias in pregnancy observational investigations, using the relationship between late use of antibiotics and risk of preterm birth as an example. We conducted a population-based cohort study including 549,082 deliveries between 2007 and 2017 in Lombardy, Italy. We evaluated the risk of preterm births, low birth weight, small for gestational age, and low Apgar score associated with antibiotic dispensing during the third trimester of pregnancy. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of the outcomes, considering the use of antibiotics as time-fixed (with biased classification of exposure person-time) and time-varying (with proper classification of exposure person-time) exposure. There were 23,638 (4.3%) premature deliveries. There was no association between time-fixed exposure to antibiotics and preterm delivery (adjusted HR 0.96; 95% CI 0.92 to 1.01) but an increased risk of preterm birth when time-varying exposure to antibiotics was considered (1.27; 1.21 to 1.34). The same trend was found for low birth weight and low Apgar score. Immortal time bias is a common and sneaky trap in observational studies involving exposure in late pregnancy. This bias could be easily avoided with suitable design and analysis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.