Abstract
Background
Malformations and mental retardation in the offspring of women with Phenylketonuria (PKU) can be prevented by maintaining maternal blood Phenylalanine (PHE) within a target range (120–300 μmol/L) through a PHE-restricted diet. In a former French study, a high and unexpected proportion of intra uterine growth retardation (IUGR) has been reported. Guidelines have been proposed to all French centres caring for maternal PKU since 2002.
Objective
To confirm IUGR and investigate its causes. The other goals were to assess the follow-up of these pregnancies based on the new guidelines and the pertinence of these recommendations.
Design
Clinical, biological and ultrasound data of all pregnancies in PKU women in France, from 2002 to 2007 were retrospectively analyzed.
Results
Data from 115 pregnancies in 86 women with PKU were collected. Ninety percent of women had been informed of the risk of maternal PKU in the absence of a strict diet during pregnancy, 88 % of women had started a diet before conception, and 45 % of infants were born small for gestational age (birth length and/or weight ≤−2 SD). PHE intakes were lower in the group with IUGR from the fifth to the eighth month of pregnancy and duration of time spent at <120 μmol/L during pregnancy was associated with a higher risk of IUGR.
Conclusion
Hyperphenylalaninemia (HPA) is not the only risk factor for IUGR; PHE lower than 120 μmol/L could also be associated with the IUGR occurence. Even if the monitoring of these pregnancies has been improved since the initiation of guidelines, we would like to stress on the importance of the dietary aspect of the disease.
Similar content being viewed by others
References
Abadie V, Depondt E, Bresson JL, Vidailhet M (2001) Recommandations diététiques pour les femmes enceintes atteintes de phénylcétonurie. Arch Pediatr 8:397–406
Bhasin KK, van Nas A, Martin LJ, Davis RC, Devaskar SU, Lusis AJ (2009) Maternal low-protein diet or hypercholesterolemia reduces circulating essential amino acids and leads to intrauterine growth restriction. Diabetes 58:559–566
Carmichael S, Abrams B, Selvin S (1997) The pattern of maternal weight gain in women with good pregnancy outcomes. Am J Public Health 87(12):1984–1988
Charles MA, Basdevant A, Eschwège E, INSERM / TNS HEALYHCARE / ROCHE (2009) Enquête ObEpi 2009: 5ème enquête épidémiologique nationale sur le surpoids et l’obésité (available from: http://www.roche.fr/fmfiles/re7199006/cms2_cahiers_obesite/AttachedFile_10160.pdf. Accessed 08/30/2011)
Cho SW, Cha YS (2005) Pregnancy increases urinary loss of carnitine and reduces plasma carnitine in Korean women. Br J Nutr 93:685–691
Dubucquoi S, Caron C, Hennache B, Subtil D, Hachulla E (2005) Interprétation des examens biologiques au cours de la grossesse. Revue du Rhumatisme 72:698–706
Feillet F, Abadie V, Berthelot J, Maurin N, Ogier H, Vidailhet M et al (2004) Maternal phenylketonuria: the French survey. Eur J Pediatr 163:540–546
Godfrey KM, Barker DJ (2000) Fetal nutrition and adult disease. Am J Clin Nutr 71(5 Suppl):1344S–1352S
Hagenfeldt L, Bjerkenstedt L, Edman G, Sedvall G, Wiesel FA (1984) Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects. J Neurochem 42(3):833–837
INSEE, enquêtes Emploi 2007. Niveau général de formation selon l’âge (available from: http://www.insee.fr/fr/themes/tableau.asp?reg_id=0&ref_id=NATTEF07232. Accessed 08/30/2011)
Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines (2009) In: Rasmussen KM, Yaktine AL (eds) Weight Gain During Pregnancy: Reexamining the Guidelines. Washington (DC): National Academies Press (US)
Koch R, Friedman E, Azen C, Hanley W, Levy H, Matalon R et al (2000) The international collaborative study of maternal phenylketonuria: status report 1998. Eur J Pediatr 159:156–160
Koch R, Hanley W, Levy H, Matalon K, Matalon R, Rouse B et al (2003) The maternal phenylketonuria international study: 1984–2002. Pediatrics 112:1523–1529
Lee PA, Chernausek SD, Hokken-Koelega AC, Czernichow P, International Small for Gestational Age Advisory Board (2003) International small for gestational Age advisory board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001. Pediatrics 111:1253–1261
Lee PJ, Ridout D, Walter JH, Cockburn F (2005) Maternal phenylketonuria: report from the United Kingdom Registry 1978–97. Arch Dis Child 90:143–146
Lenke RR, Levy HL (1980) Maternal phenylketonuria and hyperphenylalaninemia. An international survey of the outcome of untreated and treated pregnancies. N Engl J Med 303:1202–1208
Levy HL, Guldberg P, Güttler F et al (2001) Congenital heart disease in maternal phenylketonuria: report from the maternal PKU collaborative study. Pediatr Res 49:636–642
Maillot F, Lilburn M, Baudin J, Morley DW, Lee PJ (2008) Factors influencing outcomes in the offspring of mothers with phenylketonuria during pregnancy: the importance of variation in maternal blood phenylalanine. Am J Clin Nutr 88:700–705
Niklasson A, Ericson A, Fryer JG, Karlberg J, Lawrence C, Karlberg P (1991) An update of the Swedish reference standards for weight, length and head circumference at birth for given gestational age (1977–1981). Acta Paediatr Scand 80:756–762
Report of Medical Research Council Working Party on Phenylketonuria (1993) Recommendations on the dietary management of phenylketonuria. Arch Dis Child 68(3):426–427
Rohr FJ, Lobbregt D, Levy HL (1998) Tyrosine supplementation in the treatment of maternal phenylketonuria. Am J Clin Nutr 67:473–476
Rouse B, Azen C, Koch R, Matalon R, Hanley W, de la Cruz F et al. (1997) Maternal Phenylketonuria Collaborative study (MPKUCS) offspring: facial anomalies, malformations, and early neurological sequelae. Am J Med Genet 69:89–95
Usher R, McLean F (1969) Intrauterine growth of live-born Caucasian infants at sea level: standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks of gestation. J Pediatr 74:901–910
Van Spronsen FJ, van Dijk T, Smit GP, van Rijn M, Reijngoud DJ, Berger R, Heymans HS (1996) Large daily fluctuations in plasma tyrosine in treated patients with phenylketonuria. Am J Clin Nutr 64(6):916–921
Van Spronsen FJ, van Rijn M, Bekhof J, Koch R, Smit PG (2001) Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Am J Clin Nutr 73(2):153–157
Waisbren SE, Hamilton BD, St James PJ, Shiloh S, Levy HL (1995) Psychosocial factors in maternal phenylketonuria: women's adherence to medical recommendations. Am J Public Health 85:1636–1641
Webster D, Wildgoose J (2010) Tyrosine supplementation for phenylketonuria. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD001507. doi: 10.1002/14651858.CD001507
Acknowledgments
We would like to thank all the doctors for their involvement in this French maternal PKU study: Angers (Dr Berthelot), Bordeaux (Dr Barat), Lille (Dr Dobbelaere, Dr Mention), Lyon (Dr Dubreuil, Dr Fouilhoux, Dr Guffon), Marseille (Dr Cano, Dr Maurin), Nancy (Dr Feillet), Paris (Dr Abadie, Dr Bilette de Villemeur, Dr De Lonlay, Dr Narcy, Dr Ogier, Dr Touati), Rennes (Dr Journel, Dr Odent, Dr Pasquier), Rouen (Dr Dumesnil), Saint-Étienne (Dr Gay), Toulouse (Dr Coustols-Valat); and the « French Association for the Diagnosis and Prevention of Child Handicap » for his support. We are indebted to the dietician. We also thank Brest University Hospital’s Medical Writer (Zarrin Alavi, MSc).
Conflict of interest
None.
Author information
Authors and Affiliations
Consortia
Corresponding author
Additional information
Communicated by: Verena Peters
Rights and permissions
About this article
Cite this article
Teissier, R., Nowak, E., Assoun, M. et al. Maternal phenylketonuria: low phenylalaninemia might increase the risk of intra uterine growth retardation. J Inherit Metab Dis 35, 993–999 (2012). https://doi.org/10.1007/s10545-012-9491-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10545-012-9491-0