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More than fetal urine: enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation

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Abstract

The purpose of our study was to investigate the importance of amniotic fluid (AF) for fetal growth during late gestation using esophageal atresia (EA) patients as a model. In this retrospective cohort study, we compared the z-scores adapted for birth weights (BW z-scores) for each of 517 European newborns with congenital pre-gastric intestinal atresia, i.e., EA, to a European reference population. To account for the influence of the intestinal atresia on fetal growth per se, we compared adapted birth weights for each of 504 European newborns with post colonic intestinal atresia (anorectal malformation (ARM) with atresia of the anus) to the same European reference population. Analysis of the complete cohort showed (i) a significantly higher rate of small for gestational age newborns among EA compared to ARM newborns (p < 0.001) and (ii) significantly lower BW z-scores among EA compared to ARM newborns (p < 0.001). BW z-scores of EA newborns were significantly lower in term compared to preterm newborns with an inverse correlation with gestational age (GA) (Spearman correlation coefficient, r = −0.185, p < 0.001).

Conclusions: Enteral uptake of AF seems to play a pivotal role in fetal growth during late gestation.

What is Known:

• Peak velocity of fetal weight gain occurs at 33 weeks of gestation and continues until birth. During this period, fetal growth is mainly characterized by cellular hypertrophy.

• Amniotic fluid (AF) comprises large amounts of hormones and growth regulators.

What is New:

• A significantly higher rate of small for gestational age and lower birth weights and z-scores are observed among newborn infants with congenital pre-gastric intestinal atresia.

• These findings suggest that enteral uptake of AF is a major predictor for fetal growth during late gestation.

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Abbreviations

AF:

Amniotic fluid

ARM:

Anorectal malformation

BW:

Birth weights

EA:

Esophageal atresia

GA:

Gestational age

SGA:

Small for gestational age

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Acknowledgments

We thank all the families and patients for their cooperation and the German self-help organizations KEKS e.V. and SoMA e.V. for their assistance with the recruitment.

Authors’ Contribution

Soyhan Bagci, Erwin Brosens, Nadine Zwink, Peter Bartmann, and Heiko Reutter conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted.

Soyhan Bagci, Erwin Brosens, Nadine Zwink, Ekkehart Jenetzky, Joerg Arand, and Heiko Reutter carried out the initial analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Dick Tibboel, Annelies De Klein, Hanneke Ijsselstijn, Charlotte H.W. Wijers, Nel Roeleveld, Ivo de Blaauw, Paul M. Broens, Iris A.L.M. van Rooij, Alice Hölscher, Thomas M. Boemers, Markus Pauly, Oliver J. Münsterer, Eberhard Schmiedeke, Mattias Schäfer, Benno E. Ure, Martin Lacher, Vera Choinitzki, Johannes Schumacher, and David Katzer designed the data collection instruments, and coordinated and supervised data collection at 11 sites, critically reviewed the manuscript, and approved the final manuscript as submitted.

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Authors and Affiliations

  1. Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, University of Bonn, Adenauerallee 119, 53113, Bonn, Germany

    Soyhan Bagci, David Katzer, Peter Bartmann & Heiko M. Reutter

  2. Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands

    Erwin Brosens & Annelies De Klein

  3. Department of Pediatric Surgery and Intensive Care, Erasmus Medical Centre—Sophia Children’s Hospital, Rotterdam, The Netherlands

    Dick Tibboel & Hanneke Ijsselstijn

  4. Department for Health Evidence, Radboud Institute for Health Sciences, Radboudumc, Nijmegen, The Netherlands

    Charlotte H. W. Wijers, Nel Roeleveld & Iris A. L. M. van Rooij

  5. Department of Surgery-Pediatric Surgery, Radboudumc Amalia Children’s Hospital, Nijmegen, The Netherlands

    Ivo de Blaauw

  6. Department of Surgery, Anorectal Physiology Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Paul M. Broens

  7. Department of Surgery, Division of Pediatric Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Paul M. Broens

  8. Department of Pediatric Surgery and Urology, University Hospital Cologne, Cologne, Germany

    Alice Hölscher & Thomas M. Boemers

  9. Department of Pediatric Surgery, Asklepios Children’s Hospital St. Augustin, St. Augustin, Germany

    Marcus Pauly

  10. Department of Pediatric Surgery, University Medicine of Mainz, Mainz, Germany

    Oliver J. Münsterer

  11. Department of Pediatric Surgery and Urology, Center for Child and Youth Health, Klinikum Bremen-Mitte, Bremen, Germany

    Eberhard Schmiedeke

  12. Department of Pediatric Surgery and Urology, Cnopf’sche Kinderklinik, Nürnberg, Germany

    Mattias Schäfer

  13. Center of Pediatric Surgery Hannover, Hannover Medical School and Bult Children’s Hospital, Hannover, Germany

    Benno E. Ure & Martin Lacher

  14. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Vera Choinitzki, Johannes Schumacher & Heiko M. Reutter

  15. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany

    Nadine Zwink & Ekkehart Jenetzky

  16. Department of Child and Adolescent Psychiatry and Psychotherapy, Johannes-Gutenberg University, Mainz, Germany

    Ekkehart Jenetzky

  17. Department of Neonatology, University Children’s Hospital of Tübingen, University of Tübingen, Tübingen, Germany

    Joerg Arand

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  1. Soyhan Bagci
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  2. Erwin Brosens
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  3. Dick Tibboel
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  11. Alice Hölscher
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  14. Oliver J. Münsterer
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  15. Eberhard Schmiedeke
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  17. Benno E. Ure
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  18. Martin Lacher
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  19. Vera Choinitzki
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  20. Johannes Schumacher
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  23. David Katzer
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  25. Peter Bartmann
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  26. Heiko M. Reutter
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Corresponding author

Correspondence to Soyhan Bagci.

Ethics declarations

The study was conducted in accordance with the Declaration of Helsinki, and ethical approval was obtained from the respective ethics committees.

Conflict of interest

The authors have no conflicts of interest to disclose. The authors have no financial relationship with the organization that sponsored the research.

Funding source

Drs. Schumacher, Zwink, Jenetzky, and Reutter are members of the “great-consortium” supported by the Else Kröner-Fresenius-Stiftung (funding code 2014_A14). Drs. Zwink, Jenetzky, and Reutter are members of “CURE-Net” supported between 2009 and 2012 by a research grant from the German Federal Ministry of Education and Research (BMBF) (funding code 01GM08107). Dr. Brosens was funded by the Sophia Foundations for Scientific Research, projects SSWO-493 and SSWO13-09.

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The authors have no financial relationships relevant to this article to disclose.

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Communicated by Patrick Van Reempts

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Bagci, S., Brosens, E., Tibboel, D. et al. More than fetal urine: enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation. Eur J Pediatr 175, 825–831 (2016). https://doi.org/10.1007/s00431-016-2713-y

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