Does the father matter? The association between the periconceptional paternal folate status and embryonic growth

In spontaneously conceived pregnancies, both low and high periconceptional paternal folate status are associated with reduced embryonic growth.

Volume 111, Issue 2, Pages 270–279


Jeffrey Hoek, M.D., Maria P.H. Koster, M.D., Ph.D., Sam Schoenmakers, M.D., Ph.D., Sten P. Willemsen, Ph.D., Anton H.J. Koning, Ph.D., Eric A.P. Steegers, M.D., Ph.D., Régine P.M. Steegers-Theunissen, M.D., Ph.D.



To study the association between periconceptional paternal folate status and embryonic growth trajectories in early pregnancy.


Prospective periconceptional cohort study.


Single tertiary hospital.


A total of 511 singleton pregnancies, with 303 conceived spontaneously and 208 after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.



Main Outcome Measure(s)

Crown–rump length (CRL) and embryonic volume (EV) at 7, 9, and 11 weeks of gestation measured offline using three-dimensional ultrasound data and a virtual reality system.


Using the third quartile of paternal red blood cell (RBC) folate levels as reference values, we found statistically significantly negative associations between RBC folate and longitudinal CRL measurements in the second quartile (beta: −0.14 √mm [95% confidence interval (CI), −0.28 to −0.006]) and fourth quartile (beta: −0.19 √mm [95% CI, −0.33 to −0.04]) in spontaneously conceived pregnancies. Comparable results were found for longitudinal EV measurements in the fourth quartile (beta: −0.12 ∛cm3 [95% CI, −0.20 to −0.05]). No statistically significant associations were observed between RBC folate levels and embryonic growth trajectories in IVF-ICSI pregnancies.


These data demonstrate for the first time that low and high periconceptional paternal RBC folate levels are associated with reduced embryonic growth trajectories in spontaneously conceived pregnancies. These data underline the importance of paternal folate status during the periconception period.

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Go to the profile of Mary Samplaski
almost 4 years ago

This is new and exciting data. Did the authors also look at semen parameters or sperm DNA fragmentation? I would be curious to see if the thread is consistent. Also, I would be curious to see if other nutritional and vitamin parameters were also low/high in men with low/high folate levels. 

Go to the profile of Marine Poulain
almost 4 years ago

What an exciting theme! Many patient are supplemented during ART procedures with commercial vitaminic complex containing high doses of folates. Authors conclude here of a potential adverse effect of high paternal folate levels. We are looking forward to further data!