Placental Passage of Free and Esterified Phytosterols in Humans (PTS)

The Maternal-fetal Gradient of Free and Esterified Phytosterols in Term Human Pregnancy at Delivery

Total plasma cholesterol rises by 60 % with progressing pregnancy in humans. Because lipid-lowering drugs are contraindicated during pregnancy, natural compounds, such as phytosterols, may be a safe and effective alternative to prevent undesirable effects. Information on phytosterols in pregnancy is so far very limited. To date, to the best of our knowledge, no studies have characterized the maternal-fetal gradient of free and esterified phytosterols in full-term human pregnancy. For this purpose, maternal and cord blood cholesterol and non-cholesterol sterol (campesterol, stigmasterol, sitosterol) concentrations were measured in term pregnant women at delivery by using gas chromatography-mass spectrometry.

Study Overview

• Status: Completed
• Conditions: Mother Fetus Relations

• Study Type: Observational
• Enrollment (Actual): 68

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Pregnant women

Description

Inclusion Criteria:

• A single pregnancy
• A gestational age determined from known last maternal menstrual period higher than 37 weeks
• A normal diet without phytosterol supplementation during pregnancy
• Written informed consent available.

Exclusion Criteria:

• Major congenital anomalies
• Maternal history of cardiovascular disease
• Endocrine disorders such as diabetes, hypercholesterolemia, pre-eclampsia, thyroid or adrenal problems
• Clinical chorioamnionitis

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free and esterified phytosterol ratio	Plasma free and esterified phytosterol concentrations will be measured in mother-cord blood pairs at delivery. Plasma phytosterol concentrations will be the sum of plasma campesterol, stigmasterol and sitosterol concentrations (mg/L). Gas chromatography-mass spectrometry will be used for measurements.	the day of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total cholesterol concentrations	plasma cholesterol concentrations (mg/L) will be measured to evaluate the cholesterol metabolism in mother-cord blood pairs at delivery. Total cholesterol in pregnant women and cord blood will be calculated from plasma free and esterified cholesterol. Cholesterol concentrations will be measured by using gas chromatography-mass spectrometry.	the day of delivery
total lathosterol concentrations	plasma lathosterol concentrations (mg/L) will be measured to evaluate the cholesterol metabolism in mother-cord blood pairs at delivery. Total lathosterol in pregnant women and cord blood will be calculated from plasma free and esterified lathosterol. Lathosterol concentrations will be measured by using gas chromatography-mass spectrometry.	the day of delivery
total 7-dehydrocholesterol concentrations	plasma 7-dehydrocholesterol concentrations (mg/L) will be measured to evaluate the cholesterol metabolism in mother-cord blood pairs at delivery. Total 7-dehydrocholesterol in pregnant women and cord blood will be calculated from plasma free and esterified 7-dehydrocholesterol. 7-dehydrocholesterol concentrations will be measured by using gas chromatography-mass spectrometry.	the day of delivery
total 7-alpha-hydroxycholesterol concentrations	plasma 7-alpha-hydroxycholesterol concentrations (mg/L) will be measured to evaluate the cholesterol metabolism in mother-cord blood pairs at delivery. Total 7-alpha-hydroxycholesterol in pregnant women and cord blood will be calculated from plasma free and esterified 7-alpha-hydroxycholesterol. 7-alpha-hydroxycholesterol concentrations will be measured by using gas chromatography-mass spectrometry.	the day of delivery
fatty acid concentrations	plasma fatty acid concentrations (mg/dl) will be measured to evaluate the fat metabolism in mother-cord blood pairs at delivery. Total fatty acids will be measured by using gas chromatography with flame ionization detector will be used for the measurement of fatty acids.	the day of delivery

Collaborators and Investigators

• Sponsor: Università Politecnica delle Marche

Publications and helpful links

General Publications

• Montelongo A, Lasuncion MA, Pallardo LF, Herrera E. Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women. Diabetes. 1992 Dec;41(12):1651-9. doi: 10.2337/diab.41.12.1651.
• Rideout TC, Movsesian C, Tsai YT, Iqbal A, Raslawsky A, Patel MS. Maternal Phytosterol Supplementation during Pregnancy and Lactation Modulates Lipid and Lipoprotein Response in Offspring of apoE-Deficient Mice. J Nutr. 2015 Aug;145(8):1728-34. doi: 10.3945/jn.115.215061. Epub 2015 Jun 17.
• Berger A, Jones PJ, Abumweis SS. Plant sterols: factors affecting their efficacy and safety as functional food ingredients. Lipids Health Dis. 2004 Apr 7;3:5. doi: 10.1186/1476-511X-3-5.
• Piccoli GB, Clari R, Vigotti FN, Leone F, Attini R, Cabiddu G, Mauro G, Castelluccia N, Colombi N, Capizzi I, Pani A, Todros T, Avagnina P. Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative review. BJOG. 2015 Apr;122(5):623-33. doi: 10.1111/1471-0528.13280. Epub 2015 Jan 20.
• Gao F, Wang G, Wang L, Guo N. Phytosterol nutritional supplement improves pregnancy and neonatal complications of gestational diabetes mellitus in a double-blind and placebo-controlled clinical study. Food Funct. 2017 Jan 25;8(1):424-428. doi: 10.1039/c6fo01777k.
• Nikkila K, Riikonen S, Lindfors M, Miettinen TA. Serum squalene and noncholesterol sterols before and after delivery in normal and cholestatic pregnancy. J Lipid Res. 1996 Dec;37(12):2687-95.
• Miettinen HE, Rono K, Koivusalo S, Stach-Lempinen B, Poyhonen-Alho M, Eriksson JG, Hiltunen TP, Gylling H. Elevated serum squalene and cholesterol synthesis markers in pregnant obese women with gestational diabetes mellitus. J Lipid Res. 2014 Dec;55(12):2644-54. doi: 10.1194/jlr.P049510. Epub 2014 Oct 9.
• Vuorio AF, Miettinen TA, Turtola H, Oksanen H, Gylling H. Cholesterol metabolism in normal and heterozygous familial hypercholesterolemic newborns. J Lab Clin Med. 2002 Jul;140(1):35-42. doi: 10.1067/mlc.2002.125214.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2016
• Primary Completion (Actual): March 31, 2017
• Study Completion (Actual): October 15, 2017

Study Registration Dates

• First Submitted: November 13, 2017
• First Submitted That Met QC Criteria: October 10, 2018
• First Posted (Actual): October 15, 2018

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: PTS1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No