• Increased nutrient needs during pregnancy: Needs for most nutrients (energy, protein, amino acids, and many vitamins and minerals) are increased during pregnancy. Case reports have demonstrated appropriate fetal growth when nutrients are provided in amounts generally recommended for pregnant women without MSUD (F.78, F.102, G.30). Use of BCAA-formula is necessary to provide adequate protein, and supplemental calcium may be needed (F.102). Total protein and recommendations are summarized in TABLE #5, Protein Recommendations during Pregnancy for MSUD.

• Monitoring during pregnancy:
  There is only one study (F.102) and one expert opinion (G.50) with recommendations for monitoring during the pregnancy of a woman with MSUD:
  • Daily monitoring at home:
    • Urine ketones
    • Symptoms of dizziness, altered mental status, vomiting, or other signs of metabolic decompensation
  • Weekly to monthly:
    • Plasma amino acids
    • Plasma carnitine
  • Each trimester:
    • Urine organic acids

• Increased nutrient needs during pregnancy: All respondents agreed or completely agreed (55% of RDs and 17% of MDs completely agreed, and 46% of RDs and 83% of MDs agreed) that, guided by frequent laboratory monitoring, BCAA and protein intake should be increased to meet increased needs during pregnancy.
• Laboratory monitoring: Some disagreement was seen in the responses about type and frequency of laboratory monitoring during pregnancy; several respondents noted that they would base recommendations on clinical indicators as well:
  • Complete blood count: 29% of respondents would measure CBC monthly, 65% would measure once per trimester, and 6% would never use this indicator.
  • Comprehensive metabolic panel: Most respondents would measure this monthly (35%) or once per trimester (59%); 6% would never measure this.
  • Plasma amino acids: Respondents felt plasma amino acids should be monitored frequently: 29% would check plasma amino acids weekly, 29% biweekly, 29% monthly, 6% once per trimester, and 6% never.
  • Plasma carnitine, free, esterified and total: 6% would measure this monthly, 29% once per trimester, 24% once during pregnancy, and 41% would never measure plasma carnitine
  • Plasma transthyretin: 29% would measure transthyretin (prealbumin) monthly, 41% once per trimester, 12% once during pregnancy, and 18% would never measure transthyretin.
  • Folate (erythrocyte): 6% would measure folate monthly, 65% once per trimester, 12% once during pregnancy, and 18% would never measure folate.
  • Urine organic acids: 23% of respondents would measure urine organic acids monthly, 18% once per trimester, 18% once during pregnancy, and 41% would never measure urine organic acids.

During the second half of pregnancy, increased LEU tolerance (e.g., greater LEU intake without corresponding rise in plasma LEU) has been observed, related to protein synthesis (maternal and fetal) and BCAA metabolism by the fetus (F.78, F.102, G.50, G.30). Goal plasma BCAA levels of “as close to normal as possible” are recommended. Supplemental ILE and VAL may be required by some individuals (G.50, G.6), in addition to increases in intact protein intake. Dietary adjustments should be made based on plasma concentrations. (F.616, G.50). Possible slowed fetal growth, when plasma BCAA levels were low, was observed in one study (F.102).

83% of Delphi respondents agreed that BCAA levels should be maintained in the normal treatment ranges.

• Pregnant women with MSUD experience the same pregnancy-related problems with emesis and nausea as those without MSUD, but have the added risk of a catabolic crisis. Therefore, the general recommendations for management of the complications of pregnancy apply with the additional recommendations for MSUD management as described in these guidelines.
• Prevention of catabolism: catabolism can occur because of decreased or inadequate intake during pregnancy (e.g., related to nausea and vomiting) as well as during the postpartum period. Clinical status, protein and energy intake and BCAA blood levels should be monitored closely, and dietary adjustments may be needed (G.50). Nutrition interventions may include counseling and education, adjustment of oral intake including intact protein, supplemental VAL and ILE ,BCAA-free medical food, and tube-feeding or parenteral nutrition. Metabolic crisis can occur throughout pregnancy and the postpartum period. Nutrition intervention and medical management should focus on preventing and/or minimizing metabolic crisis.
• “Morning sickness”: nausea and vomiting can decrease appetite and intake; inadequate energy and/or protein intake can lead to elevated BCAA levels and metabolic crisis (G.50). Interventions to maintain an adequate intake despite nausea and vomiting should be implemented.
• Hyperemesis gravidarum: approximately 1-2% of pregnant women have hyperemesis gravidarum. Diagnostic criteria include intractable vomiting, weight loss, and ketosis. Weight loss and catabolism need to be aggressively treated (F.616), including hospitalization and hyperalimentation when necessary.
• Catabolism during labor and delivery and the postpartum period: see recommendation 4.5 below.
• Management during acute illness and crisis: general recommendations and procedures for medical and nutritional management during acute illness, surgery or crisis are covered in Research Question1.

100% of respondents to both the Delphi 1 and 2 agreed that poor nutrient intake due to pregnancy-related nausea and vomiting should be aggressively treated to prevent endogenous protein catabolism.

There is no published information about vitamin and mineral supplementation specifically for women with MSUD during pregnancy. Case reports have demonstrated appropriate fetal growth when nutrients are provided in amounts generally recommended for pregnant women without MSUD (F.78, F.102, G.30). Consistent with Institute of Medicine recommendations (L.8) for evaluating the intakes of individuals, the need for vitamin and mineral supplementation should include consideration of an individual’s age, current and usual intake, health status, and other factors which can affect nutrient needs. Special attention should be paid to the type of medical food consumed as they vary in degree of supplementation of vitamins and minerals.

There was 100% agreement (in both Delphi 1 and 2) among the RDs and MDs that vitamin and mineral supplementation should be evaluated individually based on specific medical food prescribed, dietary adherence and the pregnant patient’s laboratory assessment.

• Labor and delivery: Issues that may require intervention to minimize metabolic decompensation include prolonged labor (failure to progress), Caesarian section, and post-delivery hemorrhage. In one case report, IV glucose was started during labor and continued for 12 hours after delivery (F.102) and is recommended as a preemptive step to avoid catabolism (F.616).
• Postpartum Period: Three case reports noted increasing plasma LEU levels with a spike on the ninth postpartum day (F.78, F.102, G.30). A review noted tremendous catabolism during the postpartum period which lasts 6-8 weeks and results in an increased risk for metabolic decompensation (F.616). Dietary protein and BCAA restriction with high carbohydrate intake is recommended following delivery (F.616) with plasma BCAA levels carefully monitored (F.78, F.102, G.30).

• Prevention of catabolism: There was 100% agreement among Delphi survey respondents that adequate energy should be provided during labor, delivery and the post-partum period to prevent catabolism
• Laboratory monitoring in the postpartum period: There was 100% agreement among the RDs and 83% among the MDs that close monitoring of metabolic labs should continue for at least 6 weeks post-partum.
• LEU prescription: There was 91% agreement among dietitians and 67% agreement among physicians that unless breast-feeding, the MSUD mother should quickly return to her pre-pregnancy BCAA prescription.
• LEU restriction in the immediate post delivery period: There was a discrepancy between the RDs and MDs regarding complete restriction of LEU for 24-48 hours post- delivery, with 100% agreement among physicians, and 64% agreement among dietitians. Dietitians remarked on their lack of experience with pregnancy among women with MSUD.

There is no published information about management of a woman with MSUD during lactation. It is known that energy, protein, and amino acid requirements increase during lactation in women without MSUD. Because inadequate energy, protein, and/or amino acid intake can lead to catabolism, provision of an adequate intake is recommended. Because nutrient needs vary among women (and their infants), close clinical and biochemical monitoring is suggested to individualize intake recommendations. This is consistent with Institute of Medicine recommendations for evaluating the intakes of individuals (L.8)

There was 73% agreement among dietitians and 66% among physicians that nutrient (protein, BCAA, energy) requirements of lactating women with MSUD will be similar to nutrient requirements during the third trimester of pregnancy and that close clinical and biochemical monitoring will be needed to adjust for postpartum changes and increased nutrient needs of her infant.