Many perinatal and neonatal studies have incomplete data, review finds

Key takeaways:

• A review found that many recent perinatal and neonatal studies lacked complete outcome data.
• Altogether, 12% of studies did not address the missing data.

Nearly 90% of perinatal and neonatal clinical trials report incomplete primary outcome data, according to the findings of a review published in Pediatrics.

The authors noted that missing outcome data in randomized controlled trials (RCTs) may “jeopardize the comparability between the comparison groups and compromise inferences about treatment effects.” There are many reasons for missing data in perinatal and neonatal trial, the said.

“In the birth hospital or NICU, parents or guardians of participating infants may not respond to questions, fail to adhere to trial protocols, request withdrawal from protocols early, or refuse ongoing data collection,” they wrote. “Although caregivers can easily assess in-hospital outcomes for sick and preterm newborn infants admitted to the ICUs, their important longer term outcomes require ascertainment later in childhood and increase the risk of attrition.”

The researchers searched PubMed for RCTs published between Jan. 1, 2020, and Dec. 31, 2022, that enrolled newborns and parents and reported outcomes in the children. Their search was limited to high-impact general medical journals such as The Lancet, The New England Journal of Medicine and JAMA, and pediatric specialty journals such as JAMA Pediatrics, Pediatrics, and The Lancet Child and Adolescent Health.

Altogether, 87 eligible trials were included in the analysis. The researchers noted whether authors reported missing data in their results, which method they used for primary analysis and whether they performed any sensitivity analysis accounting for the missing data, and if so, what imputation methods were used.

“We did not intend to perform a systematic review of imputation practices in all recently published perinatal and neonatal trials,” they wrote. “Instead, we examined a small sample of target journals for perinatal and neonatal RCTs with high-impact factors to examine best-case scenarios of current imputation practices.”

The researchers ultimately found that 89% of the trials had incomplete primary outcome data and 12% did not address their missing outcome data at all. Within the studies, 79% restricted their main analysis to participants with complete information for the primary outcome and only 49% of the researchers performed sensitivity analyses using a variety of imputation methods.

“We conclude that the handling of missing primary outcome data was frequently inadequate in recent randomized perinatal and neonatal trials,” they wrote. “To improve future approaches to missing outcome data, we discuss the strengths and limitations of different imputation methods, the appropriate estimation of sample size, and how to deal with data withdrawal.”

In an accompanying editorial, Rachel G. Greenberg, MD, MB, MHS, and Ryan Kilpatrick, MD, MHS, called the problem of missing outcome data a “threat to the validity of neonatal and perinatal clinical trial results and therefore a threat to the health and well-being of children,” and noted that the issue is not unique to the neonatal and perinatal population.

“Clinicians, researchers, families, and policymakers must continue to advocate for the resources necessary to perform high-quality, consequential clinical trials to improve the health of children,” they wrote.

References:

Kilpatrick R, et al. Pediatrics. 2024;doi:10.1542/peds.2023-064938.

Li G, et al. Pediatrics. 2024;doi:10.1542/peds.2023-063101.