Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 28:13:1523952.
doi: 10.3389/fped.2025.1523952. eCollection 2025.

Sex-differences in Mothers' own milk and neurodevelopmental outcomes in preterm infants

Tingting Zhao  1   2 , Aolan Li  3 , Xiaolin Chang  3 , Wanli Xu  4 , Tyler Quinn  1 , Jie Chen  5 , Adam P Matson  6   7 , Ming-Hui Chen  3 , Sarah N Taylor  8 , Xiaomei Cong  1
Affiliations

Sex-differences in Mothers' own milk and neurodevelopmental outcomes in preterm infants

Tingting Zhao et al. Front Pediatr. .

Abstract

Objective: To identify sex-specific feeding patterns and associations with growth and neurodevelopment in preterm infants during NICU through 2 years of corrected age (CA).

Methods: A cohort study was conducted with 216 preterm infants (gestational age 28 0/7 to 32 0/7 weeks). Daily feeding regimens, including mother's own milk (MOM), human donor milk, and formula; daily growth; acute and chronic pain/stress were documented during NICU. NICU Network Neurobehavioral Scale (NNNS) (36 to 38 postmenstrual age), and Bayley Scales of Infant and Toddler Development (Bayley) Edition III (1 and 2 years of CA) were measured.

Results: Between week 9 to 16 after birth, only females showed a positive association between growth z-score and proportion of MOM intake before week 8 (p < 0.05). Sex-differentiated associations between MOM and stress were observed (p < 0.05). MOM proportion was positively correlated with language or cognitive scores at 2 years of CA in females (p = 0.01), this correlation not evident in males.

Conclusions: We discovered a sex-specific "window of opportunity" for feeding, growth and risk predictors for neurodevelopment up to 2 years of CA. These insights may inform development of tailored feeding regimens, potentially mitigating growth and development differences observed between males and females.

Keywords: breastmilk; feeding; neurodevelopment; preterm; sex.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The weekly proportion of feeding regimen in the NICU. The weekly proportion of feeding regimens, including mother's own milk, Donor's milk, and Formula, is compared between males and females throughout their NICU stay from week 1 to 16.
Figure 2
Figure 2
Weekly mean growth trajectory by sex.
Figure 3
Figure 3
SHAP predicting risk factors for neurobehavioral and neurodevelopmental outcomes in infants. (a–c) Risk factors predicting NQMOVE, NAROUSAL, and NSTRESS. (d,e) Risk factors predicting Language and Motor skills at 8 to 12 months of corrected age (CA). (f–h) Risk factors predicting Cognitive, Language, and Motor skills at 18 to 24 months of CA.
See this image and copyright information in PMC

References

    1. Shim SY, Cho SJ, Kong KA, Park EA. Gestational age-specific sex difference in mortality and morbidities of preterm infants: a nationwide study. Sci Rep. (2017) 7(1):6161. 10.1038/s41598-017-06490-8 - DOI - PMC - PubMed
    1. Zisk JL, Genen LH, Kirkby S, Webb D, Greenspan J, Dysart K. Do premature female infants really do better than their male counterparts? Am J Perinatol. (2011) 28(3):241–6. 10.1055/s-0030-1268239 - DOI - PubMed
    1. Stevenson DK, Verter J, Fanaroff A, Oh W, Ehrenkranz R, Shankaran S, et al. Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage. Arch Dis Child Fetal Neonatal Ed. (2000) 83(3):F182–5. 10.1136/fn.83.3.f182 - DOI - PMC - PubMed
    1. Garfinkle J, Yoon EW, Alvaro R, Nwaesei C, Claveau M, Lee SK, et al. Trends in sex-specific differences in outcomes in extreme preterms: progress or natural barriers? Arch Dis Child Fetal Neonatal Ed. (2020) 105(2):158–63. 10.1136/archdischild-2018-316399 - DOI - PubMed
    1. Kent AL, Wright IM, Abdel-Latif ME, New South Wales and Australian Capital Territory Neonatal Intensive Care.... Mortality and adverse neurologic outcomes are greater in preterm male infants. Pediatrics. (2012) 129(1):124–31. 10.1542/peds.2011-1578 - DOI - PubMed

LinkOut - more resources