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Indian Pediatr 2015;52: 808-809 |
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Screening
for Thalassemia Carrier Status in Pregnancy and Pre-Natal
Diagnosis
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* Vidit Gupta, Pramod Sharma,
Rakesh Jora, Minhas Amandeep and Anjani Kumar
Department of Pediatrics, Dr SN Medical College,
Jodhpur, Rajasthan, India.
*Email:
[email protected]
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This hospital-based study reports the
results of antenatal screening for thalassemia in pregnant women
visiting a hospital in Jodhpur, Rajasthan, India. Eighty-eight (5.9%) of
1500 women screened for thalassemia had thalassemia trait. Twenty
at-risk couples were identified and two fetuses were detected to be
having thalassemia major.
Keywords: Abortion, Pregnancy, Prenatal
diagnosis.
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The most effective and feasible approach to reduce the incidence of
thalassemia major is implementation of carrier screening program to test
the mothers antenatally as early as 8-12 weeks of pregnancy, offering
genetic counseling, prenatal diagnosis and selective termination of
affected fetuses. This study was planned to determine the frequency of
carrier status of thalassemia in pregnant females visiting our hospital
to identify "at-risk" couples, and to prevent birth of new cases of
thalassemia major.
This observational study was conducted over 18 months
in Departments of Pediatrics, and Obstetrics and Gynecology, Umaid
Hospital, Dr. Sampurnanand Medical College, Jodhpur, India. Pregnant
women in first trimester and early second trimester (<16 weeks), who
were willing for carrier screening, were screened by hematological
indices after an informed consent. Detailed history to ascertain the
ethnic descent, and any history of blood transfusion was obtained.
Complete blood count was done on automated cell counter (Sysmex K-100)
and hematological parameters were recorded for 1500 women. HbA 2
estimation was done in females with either of the following: (a)
MCV <77 fL (b) MCH <27 pg, (c) Mentzer Index <13, (d)
family history of thalassemia, (e) high risk ethnic groups –
Punjabis, Sindhis, Gujaratis, Bohris and Malis, (f) history of
blood transfusion, or (g) unexplained chronic anemia. Women who
attended the antenatal clinics in late second trimester and third
trimester or those who did not consent were excluded. HbA2
estimation was performed using HPLC (High Performance Liquid
Chromatography). HbA2 >3.5%
confirmed the diagnosis of b-thalassemia
trait. Those with HbA2 in
the borderline range (3.3-3.4%) were screened for thalassemia mutations
by ARMS-PCR (Amplification Refractory Mutation System - Polymerase Chain
Reaction). Chorionic villous sampling (CVS) was done if gestational age
was <12 weeks and amniocentesis was preferred for cases detected in
later weeks of pregnancy. ARMS-PCR was used for genetic analysis.
Out of 1500 pregnant women, 450 required HbA 2
estimation, and 88 (5.9%) were diagnosed as
b-thalassemia trait.
Mean (SD) age and gestational age of these women was 25.2 (4.2) y and
11.8 (1.4) wk, respectively. Forty-five (45%) had family history of
thalassemia. Husbands of 80 of these women responded for screening and
20 proved to be thalassemia trait. Seventeen out of 20 at-risk couples
agreed for prenatal diagnosis. Amniocentesis was done in thirteen and
CVS in four pregnancies. Two fetuses were detected as having thalassemia
major, and medical termination of pregnancy was done. Eleven fetuses
were detected as having thalassemia trait and 4 without any
b-globin chain
abnormality. The mutations detected are depicted in Table I.
Most common mutations were IVS 1-5 (G-C) > Fs8/9
b-globin>619bpdel=fs41/42=codon
30G-C>codon b8>Cap+1
(A-C). Five most common mutations were present in 77% of alleles. No
complication occurred in CVS/amniocentesis conducted.
TABLE I Results of Mutation Analysis in the Study Children (N=17)
Mutation |
Mother |
Father |
Fetus |
IVS 1-5 (G-C) heterozygous |
6 |
6 |
6 |
Fs 8/9 b-Globin heterozygous |
5 |
6 |
5 |
619 bp del b-Globin
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heterozygous |
1 |
1 |
- |
homozygous |
- |
- |
1 |
Codon b-8 (-AA)heterozygous |
1 |
1 |
1 |
Codon 30 G-C heterozygous |
1 |
1 |
1 |
Fs 41/42 heterozygous |
1 |
1 |
1 |
Cap+1(A-C) heterozygous |
1 |
- |
- |
Compound heterozygous ( Fs 8/9 and IVS 1-5(G-C) |
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No Mutation |
1 |
1 |
1 |
The sample size of our study was small and three
couples could not be persuaded for prenatal diagnosis despite repeated
counseling. Colah, et al. [1] conducted prenatal diagnosis on
only 15 out of 37 at-risk couples over a period of 7 years, and Xu,
et al. [2] carried prenatal diagnosis in 11 out of 12 at-risk
couples. Five common mutations were reported to be present in 89%
thalassemia patients in an earlier study [3] from India. Saxena, et
al. [3] reported abortion rate of 3.9% following prenatal diagnosis.
Antenatal screening of pregnant females is the most feasible and
effective method to reduce birth of children with thalassemia. Carrier
screening for thalassemia and hemoglobinopathies should be offered and
genetic counseling should be done to women at-risk of these disorders.
Contributors: VD: design of the study, analysis,
drafting and final approval of the manuscript; PS: data acquisition,
data analysis, revision of the manuscript for important intellectual
content and final approval; RJ: data analysis, revision of the
manuscript and final approval; MA: analysis of data, data
acquisition, drafting of the manuscript and final approval; AK: analysis
of data, data acquisition, drafting of the manuscript and final
approval.
Funding: Marwar Thalassemia society, Rajasthan;
Competing interests: None stated.
References
1. Colah R, Surve R, Wadia M. Carrier screening for
b-thalassemia
during pregnancy in India: a 7-year evaluation. Genet Test.
2008;12:181-6.
2. Xu X, Liao C, Liu Z, Huang Y, Zhang J, Li J, et
al. Antenatal screening and fetal diagnosis of
b-thalassemia in a
Chinese population: prevalence of the
b-thalassemia trait
in the Guangzhou area of China. Hum Genet. 1996;98: 199-202.
3. Saxena R, Jain PK, Thomas E, Verma IC. Prenatal
diagnosis of b-thalassemia:
Experience in a developing country. Prenat Diagn. 1998;18:1-7.
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