Maternal PKU: phenylketonuria and pregnancy

In PKU the enzyme phenylalanine hydroxylase is deficient, so the amino acid phenylalanine builds up in blood. Phenylalanine crosses the placenta, and the developing baby's brain and heart are sensitive to high levels. The harm comes from the mother's blood chemistry, not from the baby having PKU.

MedlinePlus states that babies born to mothers who have PKU and are not following a low-phenylalanine diet have a significant risk of intellectual disability because they are exposed to very high levels before birth. These infants may also have a low birth weight and grow more slowly, and may have heart defects, an abnormally small head size and behavioural problems. Women with high levels who are not on diet also have a higher risk of pregnancy loss.

The National Society for Phenylketonuria describes how metabolic control during pregnancy directly affects outcomes, and it emphasises preparing before conception. The organ systems of the baby are forming in the earliest weeks, often before a pregnancy is confirmed. Heart development and the face take shape early, while brain growth and body growth continue through the pregnancy, so each stage can be affected by high phenylalanine.

For this reason women with PKU are advised to speak to their metabolic team when they begin thinking about pregnancy, not after a positive test. The team agrees a blood phenylalanine target, adjusts the diet and protein substitute, and arranges more frequent blood spot monitoring. If a pregnancy is unplanned, the NSPKU lists an unplanned-pregnancy advice service and women should contact their metabolic team at once rather than waiting for a routine appointment.

• Contact the metabolic team before trying for a baby and again as soon as pregnancy is confirmed.

• Tell the midwife and GP about PKU at the booking appointment so that the obstetric team knows who is coordinating care.

• Avoid aspartame, the sweetener found in many diet drinks and low-calorie foods, because it contains phenylalanine.

PKU is managed with a diet that is low in phenylalanine, because phenylalanine is present in all proteins. The usual plan limits meat, dairy, nuts and other high-protein foods and relies on a phenylalanine-free protein substitute to provide protein, vitamins and minerals. The amount of phenylalanine that is safe differs for each person and is adjusted from regular blood spot results. Metabolic Support UK notes that the diet and any medicines are adjusted with age, weight and phenylalanine levels, and that blood spot tests are essential.

In pregnancy the dietitian works closely with the woman, often with more frequent contact and testing than usual. Dietary products are prescribed by the GP and obtained via a pharmacy or home delivery, and it is useful to check supplies are in date and ordered early.

Illness raises phenylalanine because protein is broken down, so the usual advice is to continue the normal diet as much as possible and tell the team if vomiting or fever stops you eating.

Reaching and keeping target levels in pregnancy is demanding. The NSPKU cites research in which many women with PKU found it hard to follow the diet during pregnancy, and notes that support from healthcare professionals and from other mothers with PKU was key for all the women studied, together with seeking knowledge and reassurance. Morning sickness, food aversions and tiredness can all interfere with the diet.

A team approach helps: metabolic dietitian, specialist nurse, obstetrician, midwife and, where needed, psychological support. Many women find that joining a PKU patient group provides practical tips on foods and routines.

If a woman with PKU conceives with a partner who does not carry the PKU gene, the baby will be a carrier but will not have PKU. If both parents carry a PKU gene, each child has a 1 in 4 chance of having PKU, and the metabolic team will write a birth plan that can include an early extra blood spot test between 48 and 72 hours after birth in addition to the routine newborn blood spot screening test. The birth plan is shared with the obstetrician and midwifery team, and the parents inform the metabolic team after the birth.

Maternal PKU syndrome affects pregnancies in which the mother has high phenylalanine. When the father has PKU, the baby is a carrier and not exposed to high phenylalanine in the womb. Genetic counselling can explain the odds if the mother also carries a PKU variant.

Contact your metabolic team the same day if you are pregnant and cannot eat or keep down your protein substitute for more than a short time. Call 999 or attend A&E for heavy bleeding, severe abdominal pain, fits or reduced baby movements in later pregnancy, as for any pregnant woman.