Nutritional Support Challenges for a Cystic Fibrosis Patient with Twin Pregnancy

Michael M. Rothkopf, MD, FACN, Lisa Haverstick RD, Eleni Pellazgu, APN, Stanley Fiel, MD

Cystic Fibrosis - Overview• Autosomal recessive disease; 1 of 2,500 newborns• Cystic fibrosis transmembrane conductance

regulator (CFTR)• c-AMP regulated ion channel - Cl, Na, H2O• Apical membrane of epithelial exocrine cells• CFTR defect chromosome 7, position q3 1.2– Thickened, desiccated respiratory secretions – Pancreatic insufficiency and malabsorption– Increased RMR due to work of breathing– Diabetes and cirrhosis in older patients.

Delta F 508 CFTR Mutation• >1,900 CF mutations• delta F 508 most common

(70%)• Deletion of 3 thymine

nucleotides (TTT) spanning positions 507 and 508 of CFTR gene

• Loss of a single codon for phenylalanine (F);

• Abnormal CFTR folds improperly

• CFTR protein can not escape endoplasmic reticulum

More CF Women are Getting Pregnant• CF survival markedly

improved from 1969• U.S. median age at death

was 8.4 years of age vs 40 in 2011.

• Pregnancy among CF females has also risen steadily

• First case report in 1960• CF Foundation Patient

Registry (CFFPR) now reports 211 pregnancies/year

Fertility in Cystic Fibrosis

• CFTR - expressed in reproductive organs

• CF men – 97% infertile– vas deferens

absent/abnormal• CF females – 20% infertile

– thick cervical mucous– delayed menarche– small ovaries/uterus– aberrant cycles– decreased ovulation rates

Endocrinology. 2008 Jun; 149(6): 2790–2797.

In-Vitro Fertilization in Cystic Fibrosis

• First case report 2000• Preimplantation genetic

diagnosis (PGD) of the delta F508 deletion is possible through rapid DNA analysis

• Biopsy cleavage-stage embryo• Amplification of DNA from

single embryonic cells • Singlet pregnancy is goal • Twin pregnancy should be

avoided

Biopsy of Embryos

• Removal of one or more cells from the early preimplantation embryo

• Embryos are cultured for 3 days, or until the blastocyst stage (5th/6th day of culture)

• Removal of one or two blastomeres from each embryo

• Biopsy does not negatively affect implantation or gestational development

Pregnancy Issues in CF • Reduced FRC, FVC • Difficult Chest PT • Increased pneumonia• Chronic hypoxia• Pulmonary HTN• Cor Pulmonale• Increased nutritional

requirements • Gestational DM• Fatty Liver of Pregnancy• Bowel obstruction• Hyperemesis

Case Report - 33 year old female• ND, homozygous dF508 • In vitro twin pregnancy • Pre-pregnancy - good health, athletic, no nutritional deficiencies, weight 108,

height 61”, FVC = 2.11 (62%), FEV1 = 1.19 (42%)• No initial exacerbation for her CF• At 26 weeks, developed bilateral lower extremity edema, poor PO intake and

elevated transaminases• Dx’d with acute fatty liver of pregnancy, treated with ursodeoxycholic acid• Progressed to hyperemesis gravidarum with intractable nausea and vomiting• Started TPN - (AA) 120 grams, (150 % of req), Dext 70, no lipids 1,500 ml• Developed bowel obstruction, emergency C-section, SB resection• Successfully delivered a boy and girl at 29 weeks, 3 days• Nutritional status recovered after delivery• FVC = 2.1 (62%), FEV1 = 1.2 (42%) post discharge

Discussion – CF Twin Pregnancy

• Despite impact of twins on abdominal pressure, PFTs were stable during pregnancy

• LFT elevations – AFLP?, extrinsic hepatic compression?, intra-abdominal sepsis?

• Bowel obstruction due to meconium ileus at birth/bowel surgery

• TPN support essential but complex given pulmonary, hepatic and glycemic issues

Conclusion – CF Twin Pregnancy

• CF patients do not necessarily suffer from pulmonary or nutritional crises during pregnancy

• Twin pregnancy in CF is not preferred but can be managed with close monitoring

• Liver disease in CF pregnancy may be multifactorial

• Nutritional support is essential if PO intake is compromised

Thank You!