New risk factor identified for sudden infant death: Maternal obesity

Infants born to mothers with prepregnancy obesity are at risk of sudden unexpected infant death (SUID), with the risk increase commensurate with maternal BMI, according to a large US nationwide cohort study.

Analysis of data from Centers for Disease Control and Prevention National Center for Health Statistics showed that the odds of SUID increased by 10 percent with prepregnancy class I obesity (BMI 30.0–34.9 kg/m²; adjusted odds ratio [aOR], 1.10, 95 percent confidence interval [CI], 1.05-1.16), by 20 percent with class II obesity (BMI 35.0–39.9 kg/m²; aOR, 1.20, 95 percent CI, 1.13–1.27), and by 39 percent with  class III obesity (BMI ≥40.0 kg/m²; aOR, 1.39, 95 percent CI, 1.31–1.47) relative to normal prepregnancy BMI (18.5–24.9 kg/m²). [JAMA Pediatr 2024;doi:10.1001/jamapediatrics.2024.2455]

“Point estimates … showed a continuously increasing function across the entire BMI range; however, this increase was nonlinear,” the investigators said. “Increases were small for BMIs below approximately 25 kg/m², with an acceleration of the risk increase occurring between BMIs of approximately 25 and 30 kg/m².”

The analysis included 18,857,694 live births (median maternal age 29 years, median paternal age 31 years, median gestational age 39 weeks), with a total of 16,545 SUID cases reported, for a rate of 0.88 per 1,000 live births.

A relevant risk

Population-attributable fraction analysis showed that maternal obesity accounted for roughly 5.4 percent of SUID cases. This percentage, while lower than other modifiable risk factors such as smoking and bed-sharing, represents a substantial number of preventable deaths. [Pediatrics 2019;143:e20183325; N Z Med J 2017;130:52-64]

According to the investigators, eliminating obesity-associated risks might have reduced SUID cases by approximately 179 per year, assuming a causal relationship between maternal obesity and SUID. The escalating global prevalence of obesity suggests that this problem will only intensify in the coming years, they added.

Yet, maternal obesity has been overlooked as an SUID risk factor in previous expert reviews, in public health initiatives, and by the American Academy of Pediatrics. As such, the investigators endorsed the inclusion of maternal obesity to the list of known risk factors for SUID, based on their study findings. [Pediatr Ann 2017;46:e284-e290; Lancet 2007;370:1578-1587; Pediatrics 2022;150:e2022057990; https://safetosleep.nichd.nih.gov/about/risk-factors]

Underlying mechanisms

While the study revealed a strong association between maternal obesity and SUID, the investigators acknowledged that they were not able to establish specific mechanisms underlying such association. One possibility is that bed sharing in the presence of maternal obesity might increase the risk of suffocation for the infant, they said. [Paediatr Child Health 1994;30:198-199; Am J Forensic Med Pathol 1991;12:27-32]

“For example, the larger breast of an obese mother could occlude the infant’s airway if she fell asleep while breastfeeding, or a bed may sag more if the mother is obese, so that the infant may roll toward the mother, obstructing the infant’s soft airways,” the investigators explained, adding that future research with sufficient statistical power and a direct measure of bed sharing is needed to explore this hypothesis.

Another potential mechanism involves maternal sleep apnoea, a condition that can lead to intermittent hypoxia, which may negatively impact foetal development and contribute to the risk of infant death, the investigators pointed out. [Int J Mol Sci 2021;22:10122; Mini Rev Med Chem 2019;19:178-193; Hum Reprod Update 2021;27:531-569]

“Our work underscores the importance of understanding the nature of and casual chain between obesity as a risk factor for SUID and other causes of infant death, so that appropriate interventions to mitigate these risks can be implemented. Such mitigations could lead to substantial reductions in overall infant mortality,” they said.