Maternal PKU

• Research type

  Research Study

• Full title

  An observational study to evaluate metabolic control and dietary management in women with PKU taking PKU sphere during pre-conception and/or pregnancy.

• IRAS ID

  256857

• Contact name

  Charlotte Ellerton

• Contact email

  C.Ellerton@NHS.Net

• Sponsor organisation

  Vitaflo (International) Ltd

• Clinicaltrials.gov Identifier

  NCT04224142

• Duration of Study in the UK

  1 years, 11 months, 31 days

• Research summary

  This is an observational study evaluating the use of PKU Sphere in the dietary management of PKU during pregnancy and pre-conception.

  Patients will be aged 16 years onwards and will be recruited during either pre-conception or during their pregnancy. As this can be a stressful time for patients, the majority of data collected during the study will be from assessments, tests, procedures and visits that are standard of care. There will be some additional questionnaires related to their pregnancy and protein substitute intake. Some data will be collected via diaries completed at home but the majority will be collected by the dietitian from telephone consultations, which is standard practice, minimising hospital visits.

  The data collection will include:
  • details of the recommended dietary management plan
  • the patient’s actual intake of PKU Sphere to compare against the recommended amount
  • tolerance / GI symptoms
  • phenylalanine and tyrosine levels
  • plasma amino acid and micronutrient levels
  • 3-day food diary
  • patient acceptability assessment of the product, which may vary during pregnancy

  Phenylalanine and tyrosine monitoring will not be increased compared to standard care.

  There will be very limited, routine outcome data collected about the neonate.

  Lay summary of study results:
  • 12 participants recruited over five years from three UK sites (London, Belfast, Cardiff).
  • 10 completed
  • 2 participants withdrew due to decision to discontinue pregnancy planning following early miscarriage (< 10 weeks gestation)
  • Cohort represented 11 singleton pregnancies (8 planned), 4 used sapropterin dihydrochloride.
  • At baseline, median intake of study product was 40 g PE/day, with 8 participants using PKU sphere as their sole source of medical food.
  • Overall, good metabolic control was achieved while taking PKU sphere during pregnancy, with maternal blood spot Phe levels <360 µmol/L:
  • First trimester: 95% (n=260)
  • Second trimester: 99% (n=281)
  • Third trimester: 100% (n=192)
  • Despite a high incidence of gastrointestinal (GI) symptoms (including new-onset symptoms during pregnancy), PKU sphere was well tolerated by the majority of participants and good adherence was observed.
  • The nine term pregnancies resulted in live births.
  • Median infant birthweight (n=9) was 3.6 kg and head circumference (n=6) was 33.8 cm.
  • No adverse infant health outcomes were reported.

  Conclusion
  • The residual Phe contained in PKU sphere was not a barrier to achieving metabolic control during pregnancy, including the first trimester.
  • Infant outcomes align with those associated with good metabolic control reported in global literature in healthy term pregnancies.
  • The study demonstrated efficacy, tolerability and acceptability of PKU sphere taken during preconception and pregnancy.

• REC name

  North West - Liverpool Central Research Ethics Committee

• REC reference

  19/NW/0167

• Date of REC Opinion

  25 Apr 2019

• REC opinion

  Further Information Favourable Opinion