Genotypic distribution of thalassemia in pregnant women in Nanning, Guangxi, and its impact on pregnancy outcomes

doi:10.3969/j.issn.1674-8115.2026.05.008

Abstract

Abstract:

Objective ·To investigate the genotypic distribution of thalassemia in pregnant women in Nanning, Guangxi, and its impact on pregnancy outcomes. Methods ·A retrospective cohort study was conducted among 3 649 pregnant women enrolled from January 2021 to December 2024 at the Guangxi Zhuang Autonomous Region People′s Hospital. Participants were categorized into α-thalassemia (n=1 296), β-thalassemia (n=505), α-composite β- thalassemia (n=100), and normal controls (n=1 748) based on genetic diagnosis. Hematological parameters, including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hemoglobin (Hb), and HbA₂, as well as pregnancy outcomes such as low birth weight (LBW) and preterm birth, were compared among the groups. Multivariate Logistic regression was used to analyze the association between thalassemia genotypes and adverse outcomes. The optimal cut-off values of MCV and HbA₂ for predicting α-composite β-thalassemia were determined using receiver operating characteristic (ROC) curve analysis. Results ·The predominant genotypes were --^SEA/αα (50.62%) in α-thalassemia, βCD41-42/β^N (46.93%) in β-thalassemia, and --^SEA/αα combined with βCD17/β^N (12.00%) in α-composite β-thalassemia. The levels of MCV, MCH, and Hb in the β-thalassemia group were significantly lower than those in the other groups (all P<0.001), while the HbA₂ levels in the β-thalassemia group and the α-composite β-thalassemia group were significantly higher than those in the normal and α-thalassemia groups. The optimal cut-off values for predicting α-composite β-thalassemia were MCV ≤74.95 fL (AUC=0.788) and HbA₂ ≥3.35% (AUC=0.867). β-thalassemia was an independent risk factor for LBW in offspring (aOR=1.785, 95%CI 1.051‒3.031, P=0.032). However, before adjustment for confounding factors, the α-composite β-thalassemia group exhibited the highest risk of LBW (OR=2.592, 95%CI 1.368‒4.912, P=0.004). Conclusion ·Thalassemia genotypes in pregnant women in Nanning, Guangxi, exhibit distinct regional patterns, with β-thalassemia and α-composite β-thalassemia significantly increasing LBW risk. Combined α- and β-thalassemia genetic testing is recommended for pregnant women with MCV ≤74.95 fL and HbA₂≥3.35%, and those with β-thalassemia should be monitored as a high-risk group for LBW.

Key words: thalassemia, genotype, pregnancy outcome, cohort study

CLC Number:

R714.2

Li Jing, Liang Xuxia, Wu Hua, Zhang Chun, Lu Yanqun, Zhang Jihong. Genotypic distribution of thalassemia in pregnant women in Nanning, Guangxi, and its impact on pregnancy outcomes[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(5): 624-632.

Figures/Tables 7

TrendMD

References 27

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Item	Normal group (n=1 748)	Thalassemia group (n=1 901)	t/χ²	P value
Age/year	31.47±4.40	31.04±4.45	2.92	0.004
Age group/n(%)			2.88	0.103
≥35 years	422(24.14)	414(21.78)
<35 years	1 326(75.86)	1 487(78.22)
Ethnicity/n(%)			24.59	<0.001
Han	961(54.98)	925(48.66)
Zhuang	692(39.59)	902(47.45)
Others	95(5.43)	74(3.89)
Pre-pregnancy BMI/(kg·m^-2)	21.94±3.06	21.80±2.94	1.40	0.162
Pre-pregnancy BMI group/n(%)			6.22	0.111
<18.5 kg·m^-2	193(11.04)	208(10.94)
18.5‒23.9 kg·m^-2	1 146(65.56)	1 311(68.96)
24.0‒27.9 kg·m^-2	339(19.39)	314(16.52)
≥28.0 kg·m^-2	70(4.00)	68(3.58)
Educational attainment/n(%)			3.75	0.290
Postgraduate and above	141(8.07)	131(6.89)
University	1 310(74.94)	1 415(74.43)
High school	97(5.55)	106(5.58)
Junior high school or less	200(11.44)	249(13.10)
Marital status/n(%)			0.80	0.669
Married	1 593(91.13)	1 724(90.69)
Unmarried	138(7.89)	162(8.52)
Divorced	17(0.97)	15(0.79)
Occupation/n(%)			6.07	0.057
Service industry	814(46.57)	812(42.71)
Professional staff	575(32.89)	652(34.30)
Unemployed	359(20.54)	437(22.99)
Parity/n(%)			1.31	0.536
0	953(54.52)	1 072(56.39)
1	718(41.08)	747(39.30)
≥2	77(4.41)	82(4.31)
ART/n(%)	163(9.32)	182(9.57)	0.07	0.821
Twins/n(%)	55(3.15)	69(3.63)	0.65	0.480
Smoking and alcohol drinking/n(%)	36(2.06)	44(2.31)	0.26	0.607
Medical history/n(%)
Diabetes mellitus	10(0.57)	9(0.47)	0.17	0.821
Chronic hypertension	14(0.80)	9(0.47)	1.56	0.316
PCOS	5(0.29)	4(0.21)		0.745
Heart disease	5(0.29)	4(0.21)		0.745
Autoimmune disease	8(0.46)	10(0.53)	0.09	0.820
Thyroid function/n(%)			0.30	0.857
Hyperthyroidism	51(2.92)	53(2.79)
Hypothyroidism	31(1.77)	38(2.00)
Family history of diabetes/n(%)	97(5.55)	82(4.31)	2.98	0.103
Anemia in first trimester/n(%)	157(8.98)	304(15.99)	39.91	<0.001
Degree of anemia/n(%)			19.86	<0.001
Mild	122(6.98)	215(11.31)
Moderate	35(2.00)	89(4.68)

Item	Normal group (n=1 748)	Thalassemia group (n=1 901)	t/χ²	P value
Age/year	31.47±4.40	31.04±4.45	2.92	0.004
Age group/n(%)			2.88	0.103
≥35 years	422(24.14)	414(21.78)
<35 years	1 326(75.86)	1 487(78.22)
Ethnicity/n(%)			24.59	<0.001
Han	961(54.98)	925(48.66)
Zhuang	692(39.59)	902(47.45)
Others	95(5.43)	74(3.89)
Pre-pregnancy BMI/(kg·m^-2)	21.94±3.06	21.80±2.94	1.40	0.162
Pre-pregnancy BMI group/n(%)			6.22	0.111
<18.5 kg·m^-2	193(11.04)	208(10.94)
18.5‒23.9 kg·m^-2	1 146(65.56)	1 311(68.96)
24.0‒27.9 kg·m^-2	339(19.39)	314(16.52)
≥28.0 kg·m^-2	70(4.00)	68(3.58)
Educational attainment/n(%)			3.75	0.290
Postgraduate and above	141(8.07)	131(6.89)
University	1 310(74.94)	1 415(74.43)
High school	97(5.55)	106(5.58)
Junior high school or less	200(11.44)	249(13.10)
Marital status/n(%)			0.80	0.669
Married	1 593(91.13)	1 724(90.69)
Unmarried	138(7.89)	162(8.52)
Divorced	17(0.97)	15(0.79)
Occupation/n(%)			6.07	0.057
Service industry	814(46.57)	812(42.71)
Professional staff	575(32.89)	652(34.30)
Unemployed	359(20.54)	437(22.99)
Parity/n(%)			1.31	0.536
0	953(54.52)	1 072(56.39)
1	718(41.08)	747(39.30)
≥2	77(4.41)	82(4.31)
ART/n(%)	163(9.32)	182(9.57)	0.07	0.821
Twins/n(%)	55(3.15)	69(3.63)	0.65	0.480
Smoking and alcohol drinking/n(%)	36(2.06)	44(2.31)	0.26	0.607
Medical history/n(%)
Diabetes mellitus	10(0.57)	9(0.47)	0.17	0.821
Chronic hypertension	14(0.80)	9(0.47)	1.56	0.316
PCOS	5(0.29)	4(0.21)		0.745
Heart disease	5(0.29)	4(0.21)		0.745
Autoimmune disease	8(0.46)	10(0.53)	0.09	0.820
Thyroid function/n(%)			0.30	0.857
Hyperthyroidism	51(2.92)	53(2.79)
Hypothyroidism	31(1.77)	38(2.00)
Family history of diabetes/n(%)	97(5.55)	82(4.31)	2.98	0.103
Anemia in first trimester/n(%)	157(8.98)	304(15.99)	39.91	<0.001
Degree of anemia/n(%)			19.86	<0.001
Mild	122(6.98)	215(11.31)
Moderate	35(2.00)	89(4.68)

Type	n(%)
α-thalassemia (n=1 296)
--^SEA/αα	656(50.62)
-α^3.7/αα	258(19.91)
α^CSα/αα	117(9.03)
-α^4.2/αα	104(8.02)
α^WSα/αα	77(5.94)
α^QSα/αα	17(1.31)
--^SEA/αα^WS	12(0.93)
--^SEA/-α^3.7	10(0.77)
--^THAI/αα	9(0.69)
-α^3.7/αα^WS	6(0.46)
-α^4.2/αα^WS	6(0.46)
--^SEA/-α^4.2	5(0.39)
-α^3.7/-α^4.2	5(0.39)
--^SEA/αα^CS	4(0.31)
-α^3.7/-α^3.7	4(0.31)
-α^4.2/-α^4.2	2(0.15)
α^CSα/αα^WS	2(0.15)
-α^3.7/αα^QS	1(0.08)
-α^3.7/αα^CS	1(0.08)
β-thalassemia (n=505)
βCD41-42/β^N	237(46.93)
βCD17/β^N	119(23.56)
-β28/β^N	42(8.32)
βIVS-II-654/β^N	41(8.12)
βE/β^N	27(5.35)
βCD71-72/β^N	16(3.17)
βIVS-I-1/β^N	14(2.77)
-β29/β^N	4(0.79)
βCD43/β^N	3(0.59)
βCD27-28/β^N	1(0.20)
-β30/β^N	1(0.20)

Type	n(%)
α-thalassemia (n=1 296)
--^SEA/αα	656(50.62)
-α^3.7/αα	258(19.91)
α^CSα/αα	117(9.03)
-α^4.2/αα	104(8.02)
α^WSα/αα	77(5.94)
α^QSα/αα	17(1.31)
--^SEA/αα^WS	12(0.93)
--^SEA/-α^3.7	10(0.77)
--^THAI/αα	9(0.69)
-α^3.7/αα^WS	6(0.46)
-α^4.2/αα^WS	6(0.46)
--^SEA/-α^4.2	5(0.39)
-α^3.7/-α^4.2	5(0.39)
--^SEA/αα^CS	4(0.31)
-α^3.7/-α^3.7	4(0.31)
-α^4.2/-α^4.2	2(0.15)
α^CSα/αα^WS	2(0.15)
-α^3.7/αα^QS	1(0.08)
-α^3.7/αα^CS	1(0.08)
β-thalassemia (n=505)
βCD41-42/β^N	237(46.93)
βCD17/β^N	119(23.56)
-β28/β^N	42(8.32)
βIVS-II-654/β^N	41(8.12)
βE/β^N	27(5.35)
βCD71-72/β^N	16(3.17)
βIVS-I-1/β^N	14(2.77)
-β29/β^N	4(0.79)
βCD43/β^N	3(0.59)
βCD27-28/β^N	1(0.20)
-β30/β^N	1(0.20)

Item	Normal (n=1 748)	α-thalassemia (n=1 296)	α-composite β-thalassemia (n=100)	β-thalassemia (n=505)	H	P value
MCV/fL	87.60(83.90‒90.50)	71.85(67.40‒80.83)	67.50(64.35‒71.05)	63.60(61.50‒66.10)^①	2 218.70	<0.001
MCH/pg	29.80(28.40‒30.90)	22.80(21.20‒26.70)	21.65(20.38‒22.80)	20.20(19.50‒21.20)^①	2 226.32	<0.001
Hb/(g·L^-1)	126.00(118.00‒132.00)	117.00(110.00‒124.00)	113.00(104.75‒120.00)	106.00(99.00‒113.00)^①	1 007.41	<0.001
HbA₂/%	2.60(2.40‒2.76)	2.45(2.30‒2.76)^③	5.00(2.76‒5.40)^②	5.20(2.76‒5.50)^②	1 184.40	<0.001