Research
Obstetrics
Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health?

https://doi.org/10.1016/j.ajog.2014.05.014Get rights and content

Objective

Cesarean section (CS) has been associated with a greater risk for asthma, diabetes, and cancer later in life. Although elective CS continues to rise, it is unclear whether and how it may contribute to compromised future health. Our aim was to investigate the influence of mode of delivery on the epigenetic state in neonatal hematopoietic stem cells.

Study Design

This was an observational study of 64 healthy, singleton, newborn infants (33 boys) born at term. Cord blood was sampled after elective CS (n = 27) and vaginal delivery. Global deoxyribonucleic acid (DNA) methylation in hematopoietic stem cells (CD34+) was determined by luminometric methylation assay, and genome-wide, locus-specific DNA methylation analysis was performed by Illumina Infinium 450K (Illumina, San Diego, CA), validated by bisulfite-pyrosequencing.

Results

CD34+ cells from infants delivered by CS were globally more DNA methylated (+2%) than DNA from infants delivered vaginally (P = .02). In relation to mode of delivery, a locus-specific analysis identified 343 loci with a difference in DNA methylation of 10% or greater (P < .01). A majority of the differentially methylated loci in neonatal CD34+ cells (76%) were found to be hypermethylated after vaginal delivery. In these infants, the degree of DNA methylation in 3 loci correlated to the duration of labor. The functional relevance of differentially methylated loci involved processes such as immunoglobulin biosynthetic process, regulation of glycolysis and ketone metabolism, and regulation of the response to food.

Conclusion

A possible interpretation is that mode of delivery affects the epigenetic state of neonatal hematopoietic stem cells. Given the functional relevance indicated, our findings may have important implications for health and disease in later life.

Section snippets

Participants

Pregnant women were recruited at the delivery units at Danderyd Hospital in Stockholm, Sweden. Multiple pregnancies, maternal diabetes or gestational diabetes, maternal hypertension, preeclampsia, smoking during the index pregnancy, preterm delivery (gestational age <37 weeks), small-for-gestational-age infants (birthweight ≥2 SD below the mean for a Swedish reference population,19 neonatal asphyxia (Apgar score <7 at 1 and 5 minutes), malformations, chromosomal disorders, or congenital

Global DNA methylation

In this study, isolated CD34+ hematopoietic stem cells displayed significantly more methylated DNA in cells from CS infants compared with cells from VD infants (P < .02, Figure 1). Global DNA methylation in the neonatal stem cells did not correlate with maternal characteristics (age, prepregnancy BMI, parity, duration of delivery, and duration of ruptured membranes) or infant risk factors (GA, sex, birthweight) (values of P = .13 to P = .91).

Locus/gene-specific DNA methylation

To obtain better knowledge about specific genes

Comment

Accumulating evidence suggests that early human living conditions and stress, in utero and at and immediately after birth, may affect future health.24, 25 The mechanisms for such early imprints, surviving for many years, are likely epigenetic.26 Early epigenetic modifications can poise genes for future response of a second trigger, like infection, trauma, toxicants, and aging. Thus, the limits for cellular and organ functions may be determined long before they are challenged.27

The increasing

Acknowledgments

We acknowledge the assistance of midwives and nurses of the Departments of Obstetrics at BB Stockholm and Danderyd Hospital. We also acknowledge valuable contributions in blood sampling and collection from research nurse Lena Swartling-Schlinzig and trainee Fatmire Bujupi and for valuable contribution in the validation process.

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    • Cited by (0)

    This work was supported by grants from the Swedish Order of Freemasons, from American Liver Foundation, the Samariten Foundation in Stockholm, and the Swedish Society for Medical Research (SSMF).

    The authors report no conflict of interest.

    Cite this article as: Almgren M, Schlinzig T, Gomez-Cabrero D, et al. Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health? Am J Obstet Gynecol 2014;211:502.e1-8.

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