Maternal Serum Ferritin and Low Neonatal Birth Weight

IUGR Clinical Trial

— LBW  

Official title:

Role of Maternal Serum Ferritin in the Prediction of Low Neonatal Birth Weight

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02738463
• Other study ID #: SHMS1985
• Status: Active, not recruiting
• Phase: N/A
• First received: March 31, 2016
• Last updated: April 11, 2016
• Start date: March 2016
• Est. completion date: September 2016

Study information

• Verified date: April 2016
• Source: Ain Shams Maternity Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Health and Population
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Intrauterine growth restriction ( IUGR )is defined as fetal growth slower than the normal growth potential of a specific fetus because of genetic or environmental factors. Recently several studies have highlighted the role of many biomolecules as markers for IUGR. Measurement of maternal serum ferritin has also been used as a predictive marker for increased risk of IUGR. Iron deficiency has its known deleterious effect in pregnancy but iron loading may be associated with oxidative damage to cells and tissues. It has been shown in various studies that lower level of transferritin receptor expression in placenta is associated with preeclampsia and IUGR. This can lead to decrease extraction of iron by placenta from maternal serum leading to increase maternal serum ferritin. This fetal iron deficiency leads to increase in fetal corticotropins and fetal cortisol, causing inhibition of fetal growth

Description:

Intrauterine growth restriction (IUGR) is defined as fetal growth slower than the normal growth potential of a specific fetus because of genetic or environmental factors. IUGR is associated with a high incidence of perinatal morbidity and mortality. IUGR neonates have a greater risk of hypoxic ischemic encephalopathy, intraventricular hemorrhage and necrotizing enterocolitis with longer hospital stay and higher health care costs. Incidence of a fetus developing a small size for gestational age is about 8%. Fetal growth is regulated by the balance between fetal nutrient demand and maternal placental nutrient supply. Intrauterine growth restriction may be caused by maternal, placental, or fetal factors. Nearly one-third of IUGRs are due to genetic causes, and two-thirds are related to the fetal environment. In the developing world, IUGR is likely to be a consequence of poor maternal nutritional status prior to or during pregnancy.

There are two general patterns of growth abnormalities: symmetric and asymmetric. Symmetric growth inhibition arises during the first half of gestation, when fetal growth occurs primarily through cellular division and produces an undersized fetus with fewer cells of normal size. Asymmetric growth inhibition occurs during the second half of gestation and is usually the consequence of an inadequate availability of substrates for fetal metabolism. To prevent the previously mentioned complications of IUGR, it is important to establish markers which can identify pregnancies at risk of IUGR early enough. Recently several studies have highlighted the role of many bio-molecules as markers for IUGR like leptin, adiponectin, endothelin-1, lactate dehydrogenase, s-endoglin, pregnancy associated plasma protein, metastin. Apart from being expensive, laboratories at majority of centers are not equipped with facilities of measurement of these markers. Measurement of maternal serum ferritin has also been used as a predictive marker for increased risk of IUGR in one previous study on a limited number (seventeen) of cases. Ferritin is an intracellular protein consisting of 24 heavy and light sub-units surrounding a core that can store up to 4,500 iron atoms. The two sub-units are highly conserved during evolution, but only the heavy sub-unit has ferroxidase activity. Ferritin is released by infiltrating leukocytes, in response to acute and chronic infection. Ferritin as an acute phase reactant is well known for its intracellular iron sequestration and storage abilities during immune activation. Serum ferritin concentration is positively correlated with the amount of total body iron stores in the absence of inflammation. Serum ferritin is considered a valuable bio-marker for body iron status in healthy subjects.Iron deficiency has its known deleterious effect in pregnancy but iron loading may be associated with oxidative damage to cells and tissues. It has been shown in various studies that lower level of transferritin receptor expression in placenta is associated with preeclampsia and IUGR. This can lead to decrease extraction of iron by placenta from maternal serum leading to increase maternal serum ferritin. This fetal iron deficiency leads to increase in fetal corticotropins and fetal cortisol, causing inhibition of fetal growth.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• Older than 20 years of age

• Pregnant with singleton intrauterine pregnancy

• 30th-32nd weeks of gestation

Exclusion Criteria:

• Patients with a history of anemia due to any causes.

• Patients with history of iron supplementation, Clinical and/or laboratory evidence of hepatic, renal, hematologic, cardiovascular abnormalities.

• History of acid-peptic disorders, esophagitis, or hiatal hernia.

• Family history of thalassemia, sickle cell anemia, or malabsorption syndrome.

• Antepartum hemorrhage.

• Allergies to milk proteins / hypersensitivity to iron preparations.

• Patients with acute infection, positive CRP, raised TLC count.

• Congenital malformation and fetuses with chromosomal or genetic syndrome.

• Recent blood transfusion.

• Refusal to participate in the study.

• BMI <18.

• Placental abnormalities like velamentous insertion.

• Multiple pregnancies.

• Smoking during pregnancy

• Preterm births.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Birth Weight
• IUGR

Locations

Country	Name	City	State
Egypt	Ain Shams Maternity Hospital	Cairo
Egypt	outpatient clinics in the Obstetrics and Gynecology Department Ain Shams Maternity Hospital	Cairo

Sponsors (2)

Lead Sponsor	Collaborator
Ain Shams Maternity Hospital	Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (10)

Arosio P, Ingrassia R, Cavadini P. Ferritins: a family of molecules for iron storage, antioxidation and more. Biochim Biophys Acta. 2009 Jul;1790(7):589-99. doi: 10.1016/j.bbagen.2008.09.004. Epub 2008 Sep 26. Review. — View Citation

Bindal N, Godha Z, Kohli R, Kadam VK. Role of maternal serum ferritin as a predictive marker in intrauterine growth restriction. Int J Reprod Contracept Obstet Gynecol. 2015 Jun;4(3):804-808

Milman N. Iron Deficiency and Anaemia in Pregnant Women in Malaysia - Still a Significant and Challenging Health Problem. J Preg Child Health 2015, 2:3

Moh W, Graham JM Jr, Wadhawan I, Sanchez-Lara PA. Extrinsic factors influencing fetal deformations and intrauterine growth restriction. J Pregnancy. 2012;2012:750485. doi: 10.1155/2012/750485. Epub 2012 Jul 19. — View Citation

Muhammad T, Khattak AA, Shafiq-ur-Rehman, Khan MA, Khan A, Khan MA. Maternal factors associated with intrauterine growth restriction. J Ayub Med Coll Abbottabad. 2010 Oct-Dec;22(4):64-9. — View Citation

Murki S and Sharma D. Intrauterine Growth Retardation - A Review Article. Murki and Sharma, J Neonatal Biol 2014, 3:3

Nandini M D, Shetty HV, Rupakala BV, Usha S M R, Priyadarshini KS, Manjula HS and Victoria Ksh. Study of serum ferritin levels in preterm labor. International Journal of Recent Trends in Science and Technology, ISSN 2277-2812 E-ISSN 2249-8109, Volume 14, Issue 2, 2015 pp 477-480

Višnjevac N, Segedi LM, Curcic A, Višnjevac J, Dragan Stajic. Blood ferritin levels in pregnant women and prediction of the development of fetal intrauterine growth restriction. J Med Biochem. 2011;30:m317-22

Wang CN, Chang SD, Peng HH, Lee YS, Chang YL, Cheng PJ, Chao AS, Wang TH, Wang HS. Change in amniotic fluid levels of multiple anti-angiogenic proteins before development of preeclampsia and intrauterine growth restriction. J Clin Endocrinol Metab. 2010 Mar;95(3):1431-41. doi: 10.1210/jc.2009-1954. Epub 2010 Jan 15. — View Citation

Zhang S, Regnault TR, Barker PL, Botting KJ, McMillen IC, McMillan CM, Roberts CT, Morrison JL. Placental adaptations in growth restriction. Nutrients. 2015 Jan 8;7(1):360-89. doi: 10.3390/nu7010360. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maternal serum ferritin (microg/L)	Ferritin values will be estimated by immunometric testing for quantitative determination in human serum at Olympus analyzers using the Olympus ferritin reagent. Reference ranges from 10.00 to 30.00 microgram/L	2 months	Yes
Primary	Fetal weight (gm)	birth weight less than 10th percentile will be adjusted for small for gestational age	5 minutes	No
Secondary	Maternal hemoglobin (g/L)	estimation will be done from hemolysate of the obtained blood samples with the addition of sodium ferricyanide and sodium cyanide. Cyanmet -hemoglobin formed in the solution will be estimated by spectro photometry at the wave length of 540 nm.	2 months	Yes
Secondary	Maternal hematocrit (x10^12/L)	The level will be also estimated by spectro photometry and calculated using the following formula: Hematocrit = blood cells volume/volume of blood sample × 100.	2 months	Yes
Secondary	Apgar score	will be estimated by cardiac action, respiration of the newborn, muscle tone, skin color and reaction of the newborn will be estimated by 0, 1 or 2 summed up and compared. Apgar score can vary from 0 to 10.	5 minutes	No
Secondary	Maternal total leucocytic count (x10^9/L)	will be also estimated also by spectro photometry	2 months	Yes

External Links

•   Ross MG. Fetal growth restriction, 2008