Letter to the Editor: “Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs”

We read with interest the Hanem et al. article (1), which is currently the largest follow-up study of children born to mothers with polycystic ovary syndrome and concomitant exposure to metformin in utero. While the results are profoundly noteworthy, we highlight two aspects that decrease the confidence and clinical impact of their results.

The authors concluded that metformin-exposed children had higher body mass index (BMI) and increased prevalence of overweight/obesity at 4 years of age. The authors defined and calculated overweight and obesity following the extended international (International Obesity Task Force) BMI cutoffs (2). However, according to the National Center for Health Care Statistics and the Centers for Disease Control children BMI reference standards (3), mean weights in both groups are on average under the 85th percentile and considered as normal weight. Hence, while different, this difference would be under the normal range and in consequence of uncertain clinical impact.

Also, the sample size calculation of the original PregMet study was designed to identify a 25% difference in preterm deliveries and insulin-requiring gestational diabetes mellitus (4), and not an overweight/obesity difference in children. Using the G-power software (5), and considering statistical test used by the authors, the calculated power for the study is of 66% with a confidence interval of 95%, opposed to the 80% power that is commonly recommended. When the sample size is calculated to have a power of 80%, around 110 participants per group would have been needed. This, in addition to high lost to follow-up (38%), decreases the confidence in their results.

Abbreviation:

Abbreviation:
 
• BMI

  body mass index

Acknowledgments

Disclosure Summary: The authors have nothing to disclose.

References