Induction Versus Expectant Management With Abnormal Maternal Biochemical Markers

Induction of Labor at Term Versus Expectant Management Among Women With Abnormal Maternal Serum Biochemical Markers: A Randomized Controlled Trial

Induction of labor at term versus expectant management among women with abnormal maternal biochemical markers. A randomized controlled trial

Study Overview

• Status: Unknown
• Conditions: PREGNANCY
• Intervention / Treatment: Other: Induction of labour; Other: Expectant management

Detailed Description

Pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and inhibin A, are biochemical markers that are part of the first and second trimester screening test, for Down syndrome and neural tube defects in pregnancy. These biochemical markers have been shown also to be associated with slightly increased risk for adverse pregnancy outcomes in the absence of aneuploidy or neural tube defects, for example; preeclampsia, low birth weight, placental abruption, preterm labor, and intrauterine fetal death.

There are no guidelines regarding the management of these cases assuming a reassuring maternal and fetal status are normal, at term (38 - 39 weeks). However, adverse events may still develop between 38 to 42 weeks when calculated according to ongoing pregnancy.

Investigators aim in this randomized trial to examine the effect of induction of labor at 38 - 39 weeks compared to expectant management among women with abnormal first or second biochemical screening tests on maternal and perinatal outcomes.

Enrollment: 320 women in both groups. Interim analyses will be performed after enrolling 50% of the participants.

• Study Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel, 18101
    • Recruiting
    • Emek Medical Center
    • Principal Investigator: Manal Massalha, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• HCG, AFP or Inhibin greater than 2 multiple of median (MOM) or PAPPA less than 0.15 MOM.
• Singleton.
• Appropriate for gestational age fetus.
• Reassuring fetal status including normal amniotic fluid index.

Exclusion Criteria:

• Any hypertensive disorder.
• Indication for induction of labour at enrollment.
• Any contraindication of induction of labour.
• Prior cesarean delivery.
• Any contraindication for a trial of vaginal delivery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Induction of labour; Induction of labour at 38-39 weeks	Other: Induction of labour; Induction of labour
ACTIVE_COMPARATOR: Expectant management; Expectant management until 41 weeks.	Other: Expectant management; Expectant management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placental abruption	Clinical diagnosis. Co-primary endpoint #1.	4 weeks
Gestational hypertension	Blood pressure above 140/90 mmHg. Co-primary endpoint #2	4 weeks
Small of gestational age	Birth Weight less than the 10th percentile. Co-primary endpoint #3	4 weeks
Intra-uterine death	Fetal death. Co-primary endpoint #4	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mode of delivery	vaginal or cesarean.	4 weeks
Intrapartum fever	fever above 38C	4 weeks
Neonatal Apgar score	Apgar score	4 weeks

Collaborators and Investigators

• Sponsor: HaEmek Medical Center, Israel
• Investigators: Study Chair: Raed Salim, Emek Medical Center

Publications and helpful links

General Publications

• Yuan W, Chen L, Bernal AL. Is elevated maternal serum alpha-fetoprotein in the second trimester of pregnancy associated with increased preterm birth risk? A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2009 Jul;145(1):57-64. doi: 10.1016/j.ejogrb.2009.04.017. Epub 2009 May 19.
• Ganapathy R, Lamont RF, Bassett P. Unexplained elevated maternal serum beta-HCG concentration and adverse pregnancy outcome. Prenat Diagn. 2007 Nov;27(11):995-9. doi: 10.1002/pd.1813.
• Alkazaleh F, Chaddha V, Viero S, Malik A, Anastasiades C, Sroka H, Chitayat D, Toi A, Windrim RC, Kingdom JC. Second-trimester prediction of severe placental complications in women with combined elevations in alpha-fetoprotein and human chorionic gonadotrophin. Am J Obstet Gynecol. 2006 Mar;194(3):821-7. doi: 10.1016/j.ajog.2005.09.010.
• Gagnon A, Wilson RD; SOCIETY OF OBSTETRICIANS AND GYNAECOLOGISTS OF CANADA GENETICS COMMITTEE. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008 Oct;30(10):918-932. doi: 10.1016/S1701-2163(16)32973-5. English, French.
• Luckas MJ, Sandland R, Hawe J, Neilson JP, McFadyen IR, Meekins JW. Fetal growth retardation and second trimester maternal serum human chorionic gonadotrophin levels. Placenta. 1998 Mar-Apr;19(2-3):143-7. doi: 10.1016/s0143-4004(98)90002-9.
• Wax JR, Lopes AM, Benn PA, Lerer T, Steinfeld JD, Ingardia CJ. Unexplained elevated midtrimester maternal serum levels of alpha fetoprotein, human chorionic gonadotropin, or low unconjugated estriol: recurrence risk and association with adverse perinatal outcome. J Matern Fetal Med. 2000 May-Jun;9(3):161-4. doi: 10.1002/1520-6661(200005/06)9:33.0.CO;2-T.
• Salim R, Okopnik M, Garmi G, Nachum Z, Zafran N, Shalev E. Lack of association between unexplained elevated maternal serum alpha fetoprotein and/or human chorionic gonadotropin and the occurrence of placental thrombotic lesions. Placenta. 2010 Apr;31(4):277-81. doi: 10.1016/j.placenta.2010.01.010. Epub 2010 Feb 4.
• Saruhan Z, Ozekinci M, Simsek M, Mendilcioglu I. Association of first trimester low PAPP-A levels with adverse pregnancy outcomes. Clin Exp Obstet Gynecol. 2012;39(2):225-8.
• Dugoff L, Hobbins JC, Malone FD, Vidaver J, Sullivan L, Canick JA, Lambert-Messerlian GM, Porter TF, Luthy DA, Comstock CH, Saade G, Eddleman K, Merkatz IR, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, D'Alton ME; FASTER Trial Research Consortium. Quad screen as a predictor of adverse pregnancy outcome. Obstet Gynecol. 2005 Aug;106(2):260-7. doi: 10.1097/01.AOG.0000172419.37410.eb.
• Caughey AB, Stotland NE, Escobar GJ. What is the best measure of maternal complications of term pregnancy: ongoing pregnancies or pregnancies delivered? Am J Obstet Gynecol. 2003 Oct;189(4):1047-52. doi: 10.1067/s0002-9378(03)00897-4.
• Hossain N, Paidas MJ. Adverse pregnancy outcome, the uteroplacental interface, and preventive strategies. Semin Perinatol. 2007 Aug;31(4):208-12. doi: 10.1053/j.semperi.2007.05.002.
• Konchak PS, Bernstein IM, Capeless EL. Uterine artery Doppler velocimetry in the detection of adverse obstetric outcomes in women with unexplained elevated maternal serum alpha-fetoprotein levels. Am J Obstet Gynecol. 1995 Oct;173(4):1115-9. doi: 10.1016/0002-9378(95)91336-x.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ANTICIPATED): May 1, 2018
• Study Completion (ANTICIPATED): July 1, 2018

Study Registration Dates

• First Submitted: February 23, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (ESTIMATE): April 28, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 16, 2017
• Last Update Submitted That Met QC Criteria: August 13, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Abnormal first or second trimester biochemical markers; maternal and perinatal morbidity/mortality
• Other Study ID Numbers: 00126-15-EMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED