Maternal Serum BLyS Levels Throughout Pregnancy

Measurement of B Lymphocyte Stimulator (BLyS) in Peripheral Blood From Pregnant and Nonpregnant Women

Background and rationale: B lymphocyte stimulator (BLyS) is a potent B cell survival factor that has been found to be elevated in patients with inflammatory conditions, such as systemic lupus and rheumatoid arthritis. Because of the immunologic changes associated with pregnancy, including changes in levels of T and B lymphocytes, it is postulated that BLyS levels would be altered in pregnancy compared to the non-pregnant state.

Objectives: The primary objective of this study is to assess the levels of BLyS in each trimester of pregnancy. Secondary objectives include evaluation of an association between BLyS levels and adverse pregnancy events; comparison of BLyS levels between healthy pregnant women and pregnant women with a medical or obstetric conditions; and, assessment of APRIL levels and comparison between APRIL levels and BLyS levels in study subjects.

Study population: Pregnant and non-pregnant women receiving care in the outpatient Obstetrics and Gynecology clinics at LAC+USC Medical Center.

Study methodology: Peripheral blood samples will be drawn from pregnant women and non-pregnant controls. Pregnant women will have blood drawn each trimester, at delivery, and postpartum, and control subjects will have blood drawn once, upon enrollment in the study.

Study outcomes: BLyS and APRIL levels during each trimester, postpartum and in cord blood will be compared between healthy pregnant women, pregnant women with a medical condition, and healthy non-pregnant controls. Additionally, pregnancy outcomes will be recorded to determine whether BLyS or APRIL levels correlate with adverse events.

Statistics: Continuous data will be analyzed by Student t-test or logistic regression, where appropriate. Categorical data will be analyzed using Chi square.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Other: routine medical care, venipuncture

Detailed Description

The investigators performed a prospective observational study of pregnant women presenting for prenatal care at Los Angeles County+University of Southern California Obstetrics clinics. Subjects were recruited from October 2011 through June 2013. Pregnant women were recruited at the time of their first prenatal visit. Women under the age of 18 and women carrying a fetus with a known major congenital anomaly were excluded. A control group of premenopausal nonpregnant (NP) women without known medical or rheumatic illnesses was recruited from the Los Angeles County+University of Southern California Gynecology outpatient clinics. Informed consent was obtained from each study participant before enrollment. Approval for this study was obtained from the Los Angeles County+University of Southern California Institutional Review Board.

A participant was classified as having gestational hypertension if the participant had ≥2 episodes of new-onset HTN (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg) after 20 weeks of pregnancy. PE was defined as gestational hypertension that was accompanied by proteinuria of at least 300 mg in a 24-hour urine collection or a protein/creatinine ratio ≥0.3. HELLP syndrome was diagnosed when a woman had laboratory evidence of hemolysis, a platelet count <100,000/μL, and serum levels of aspartate aminotransferase and alanine aminotransferase that were greater than or equal to twice normal values. Superimposed preeclampsia was diagnosed in a participant with CHTN when the participant experienced an acute exacerbation of hypertension after 20 weeks of gestation. In a participant without preexisting proteinuria, new-onset proteinuria was also required for the diagnosis.

Patient characteristics were obtained through patient interviews and medical chart review. Maternal venous blood was collected by venipuncture at least once per trimester, on admission for delivery, and postpartum. The first trimester was defined as <14 gestational weeks, the second trimester as 14 0/7 to 27 6/7 gestational weeks, and the third trimester as 28 0/7 gestational weeks to delivery. Postpartum samples were collected before hospital discharge after delivery.

Blood samples were collected in sterile tubes without additives and refrigerated until processing. Sera were routinely isolated from the clotted blood samples within 12 to 24 hours and were aliquotted and stored at -80°C. Serum BAFF levels were measured in a blinded fashion using a sandwich ELISA.

Chi-squared or Fisher exact testing was used for categorical variables, and Kruskal-Wallis or signed-ranks testing was used for all continuous variables. All tests were 2-sided, with a P value <0.05 considered statistically significant. Means are expressed as ± the SD. Medians are presented for data not normally distributed.

• Study Type: Observational
• Enrollment (Actual): 222

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women seen at a single medical center

Description

Inclusion Criteria:

• Adult woman

Exclusion Criteria:

• Unable to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
pregnant; Pregnant women receiving routine medical care, including venipuncture.	Other: routine medical care, venipuncture
non-pregnant; Women not pregnant receiving routine medical care, including venipuncture.	Other: routine medical care, venipuncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
first-trimester serum blys level	maternal serum blys level during the first trimester of pregnancy	up to 13 weeks of pregnancy (first trimester)
second-trimester serum blys level	maternal serum blys level during the second trimester of pregnancy	from 14 through 26 weeks of pregnancy (second trimester)
third-trimester serum blys level	maternal serum blys level during the third trimester of pregnancy	from 27 weeks of pregnancy through delivery of baby (third trimester of pregnancy)
cord blood serum blys level	serum blys level in cord blood obtained at delivery	delivery of baby
post-partum serum blys level	maternal serum blys level post-partum	1-2 days post-partum

Collaborators and Investigators

• Sponsor: University of Southern California

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 19, 2011
• Primary Completion (ACTUAL): June 30, 2014
• Study Completion (ACTUAL): June 30, 2014

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (ACTUAL): December 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 6, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: #HS-11-00449

Drug and device information, study documents

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