Retrospective analysis of the effect of gestational hypothyroxinemia on pregnancy outcomes XIE Jun-hao 1, LIU Yu-huan 2, HUANG Qin 1*

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1 Med J Chin PLA, Vol. 42, No. 3, March 1, [ ] (TSH) (FT 4 ) 189 [ FT 4 0~5% 5%~10% 10% A(n=60) B(n=40) C(n=89) ] 752 C (P<0.05) B (P<0.05) B C A C (P<0.05) C (P<0.01) ( ) ( P<0.01) 189 (TPOAb) ( vs cm P<0.01) FT 4 FT 4 10% TPOAb [ ] [ ] R581.9 [ ] A [ ] (2017) [DOI] /j.issn Retrospective analysis of the effect of gestational hypothyroxinemia on pregnancy outcomes XIE Jun-hao 1, LIU Yu-huan 2, HUANG Qin 1* 1 Department of Endocrinology, 2 Department of Gynaecology and Obstetrics, Changhai Hospital, Second Military Medical University, Shanghai , China * Corresponding author, qxinyi1220@163.com This work was supported by the National Natural Science Foundation of China ( ), and the Special Fund of National Health and Family Planning Commission ( ) [Abstract] Objective To discuss the influence of gestational hypothyroxinemia to the pregnancy outcomes and fetus development, and find the evidence of hormone replacement therapy. Methods The clinical data of 1141 gravida admitted from Nov to Oct were retrospectively analyzed, including the data of systematic antenatal examination, all the data of pregnancy, the materials of delivery, the last ultrasound examination, production status and the thyroid stimulating hormone (TSH) of the newborn etc., to find the difference of related index. Results Of the 1141 gravida with integral data, 200 had past history of thyroid disease, 189 showed below normal of free thyroxine (FT 4 ) and 752 were normal ones. The 189 gravida with normal TSH but lower FT 4 were divided into group A (0-5% lower than the normal FT 4 value, n=60), group B (5%-10% lower than the normal FT 4 value, n=40) and group C (10% and above lower than the normal FT 4 value, n=89). The ones with both normal TSH and FT 4 value served as control group. Compared to the control group, the higher premature delivery rate, incidence of gestational diabetes mellitus and cesarean delivery rate (P<0.05) were found in group C, and more gravida in group B had a history of hypertension and dyslipidemia during pregnancy (P<0.05). The cesarean delivery rate of group B and C were higher than group A. Meanwhile, the rate of group B was higher than control group (P>0.05). At delivery, the maternal weight, BMI, diastolic pressure, and head circumference of fetus in the last ultrasound examination were higher in group C than in control group (P<0.01), but the gestational weeks of the newborn were shorter in group C ( weeks) than in control group ( weeks, P<0.01). The 189 gravida with lower FT 4 were divided into two groups according to the thyroid peroxidase antibody (TPOAb) level. The head circumference of fetus in the last ultrasound examination was higher in TPOAb(+) group than in TPOAb(-) group ( cm vs cm, P<0.01). Conclusions [ ] ( ) ( ) [ ] [ ] ( ) ( ) [ ] qxinyi1220@163.com

2 The influence of gestational hypothyroxinemia to pregnancy outcomes and fetus development cannot be ignored, especially for the pregnant women with lower FT 4 value (10% and above lower than the normal) or with positive TPOAb. It is suggested to take the thyroid function test in the early stage of pregnancy for those pregnant women mentioned above. [Key words] retrospective study; hypothyroxinemia; pregnancy outcome; thyroid autoantibody (hypothyroxinemia HT) (thyroid stimulating hormone TSH) (free thyroxine FT 4 ) 5 10 (isolated hypothyroxinemia IH) [1] HT IH [2-4] IH (L-thyroxine L-T 4 ) [5] HT IH Apgar (TSH) TSH IH (total thyroxine TT 4 ) TSH (thyroid peroxidase antibody TPOAb) 1.2 (oral glucose tolerance test OGTT) FT 4 TSH TPOAb TPOAb TSH TPOAb Cobas E 601 (total triiodothyronine TT 3 ) TT 4 TSH TPOAb (thyroglobulin antibody TGAb) Cobas E 602 (free triiodothyronine FT 3 ) FT 4 FT 4 13~23pmol/L FT 3 2.8~7.1pmol/L TSH 0.27~4.20mU/L TPOAb <34U/ml 2011 (American Throid Association ATA) 1.3 SPSS 21.0 x±s M(P 25 P 75 ) (%) χ 2 TSH TPOAb Pearson P< ( 20 ) FT 4 ( pmol/L) 1h ( mmol/L) ( g) 1141 FT ~18.38pmol/L 2.2 C ( 13.5% 32.6% 70.8%) ( 6.5% 12.9% 57.9% P<0.05 P<0.01) B ( 5.0% 7.5%) (0.3% 0.8% P<0.05 P<0.01) B (70.0%) C (70.8%) A (50.0% P<0.05 P<0.01) C (70.8%) (57.9% P<0.05) ( 1) 2.3 B C A B C (BMI) (P<0.01) B C (P<0.01)

3 Med J Chin PLA, Vol. 42, No. 3, March 1, Tab.1 The pregnancy outcomes in different groups of pregnant women Index Normal control group(n=752) Group A(n=60) Group B(n=40) Group C(n=89) Macrosomia[n(%)] 41(5.5) 4(6.7) 5(12.5) 6(6.7) Small for date infant[n(%)] 1(0.1) 0(0.0) 0(0.0) 0(0.0) Anemia[n(%)] 17(2.3) 1(1.7) 1(2.5) 2(2.3) Hyperprolactinemia[n(%)] 1(0.1) 0(0.0) 0(0.0) 0(0.0) Postpartum hemorrhage[n(%)] 16(2.13) 2(3.33) 0(0.0) 2(2.3) Preeclampsia[n(%)] 19(2.5) 0(0.0) 2(5.00) 2(2.25) Fetal distress[n(%)] 59(7.9) 7(11.7) 1(2.5) 5(5.6) Polyhydramnios[n(%)] 2(0.3) 0(0.0) 0(0.0) 1(1.1) Amniotic fluid less[n(%)] 54(7.2) 5(8.3) 0(0.0) 3(3.4) Premature labor[n(%)] 49(6.5) 5(8.3) 2(5.0) 12(13.5) (1) Neonatal anemia[n(%)] 0(0.0) 0(6.7) 0(0.0) 1(1.1) PROM[n(%)] 106(14.1) 9(0.0) 7(17.5) 12(13.5) Placental abruption[n(%)] 6(0.8) 0(0.0) 0(0.0) 0(0.0) Placenta previa[n(%)] 21(2.8) 1(1.7) 2(5.0) 3(3.4) The placenta low place[n(%)] 15(2.0) 0(0.0) 1(2.5) 3(3.4) Adherent placenta[n(%)] 12(1.6) 2(3.3) 0(0.0) 4(4.5) Pelvic adhesion[n(%)] 0(0.0) 0(0.0) 1(2.5) 0(0.0) Cord entanglement[n(%)] 194(25.8) 13(21.7) 9(22.5) 19(21.4) Gestational hypertension[n(%)] 40(5.3) 1(1.7) 5(12.5) 4(4.5) Hypertension history[n(%)] 2(0.3) 0(6.7) 2(5.0) (1) 0(0.0) GDM[n(%)] 97(12.9) 11(6.7) 9(22.5) 29(32.6) (2) Mellitus history[n(%)] 3(0.4) 0(0.0) 0(0.0) 0(0.0) Dyslipidemia[n(%)] 6(0.8) 0(0.0) 3(7.5) (2) 3(3.4) Arrhythmia[n(%)] 8(1.06) 1(1.7) 0(0.0) 1(1.1) Caesarean section[n(%)] 435(57.9) 30(50.0) 28(70.0) (3) 63(70.8) (1)(4) PROM. Premature rupture of membrane; GDM. Gestational diabetes mellitus; (1)P<0.05, (2)P<0.01 compared with normal control group; (3) P<0.05, (4)P<0.01 compared with group A (P<0.05 P<0.01) A B C (aspartate aminotransferase AST) (P<0.05) B C (alanine aminotransferase ALT) (P<0.05) C (gammaglutamyltransferase GGT) (P<0.05) FT 3 (P<0.05) FT 4 (P<0.01) C TPOAb (oral glucose tolerance test OGTT) B 1h 2h C BMI (P<0.01) (P<0.01) (P<0.01 2) 2.4 TPOAb ( ) TPOAb (glycosylated hemoglobin HbA 1c ) / ( 8.9% 5.89% ) ( 5.36% 0.99% ) FT 4 ( pmol/L) ( pmol/L P<0.05) 189 HT TPOAb ( cm) ( cm P<0.01) (low-density lipoprotein cholesterol LDL-C) BMI ( mmol/L kg/m 2 ) ( mmol/L kg/m 2 P<0.01) 752 TPOAb (125.60U/ml 29 ) (8.94U/ml 723 ) TPOAb HT Pearson TSH TPOAb

4 Tab.2 The indexes comparison in different groups of pregnant women Index Normal control group(n=752) Group A(n=60) Group B(n=40) Group C(n=89) First time pregnancy test Height (cm) Weight (kg) (1) (2)(4) BMI (kg/m 2 ) (2)(3) (2)(3)(6) SBP (mmhg) (1) (2) DBP (mmhg) Abdominal circumference (cm) Fundal height (cm) (2) Fetal heart (beat) HGB (g/l) (2)(4) (5) Gestation period ALT (U/L) (2)(3) (1) AST (U/L) (1) (1) (1) GGT (U/L) (1) TC (mmol/l) TG (mmol/l) FT 3 (pmol/l) (1) FT 4 (pmol/l) (2) (2) (2)(4)(6) TSH (mu/l) TPOAb (U/ml) (1) OGTT FBG (mmol/l) (1) 1h blood glucose (mmol/l) (2) (2) 2hPG (mmol/l) (1) (2) Ante partum Age (year) (1) (2) (2) Weight (kg) (2)(4)(5) BMI (kg/cm 2 ) (2)(4) SBP (mmhg) DBP (mmhg) (1) Last time ultrasound results Fetal heart (beat) BPD (cm) Head circumference (cm) (2)(3) Abdominal circumference (cm) Femur length (cm) Length of the humerus (cm) Thickness of the placenta (cm) Amniotic fluid index (cm) Newborn Gestational weeks (week) (2) Weight (g) TSH (mu/l) Apgar score 1min 9(9,9) 9(9,9) 9(9,9) 9(9,9) 5min 10(10,10) 10(10,10) (1) 10(10,10) 10(10,10) (1) 10min 10(10,10) 10(10,10) 10(10,10) 10(10,10) BMI. Body mass index; SBP. Systolic pressure; DBP. Diastolic blood pressure; HGB. Hemoglobin; ALT. Alanine aminotransferase; AST. Aspartate aminotransferase; GGT. Gamma-glutamyltransferase; TC. Total cholesterol; TG. Triglyceride; FT 3. Free triiodothyronine; FT 4. Freethyroxine; TPOAb. Thyroid peroxidase antibody; TSH. Thyroid stimulating hormone; OGTT. Oral glucose tolerance test; FBG. Fasting blood glucose; 2hPG. 2 hours postprandial blood glucose; BPD. Biparietal diameter. (1)P<0.05, (2)P<0.01 compared with normal control group; (3) P<0.05, (4)P<0.01 compared with group A; (5)P<0.05, (6)P<0.01 compared with group B

5 Med J Chin PLA, Vol. 42, No. 3, March 1, % [6] 15% [7] 12.3% HT [8] IH 2.0%~4.3% [9] 25%~30% [10-11] 1141 FT 4 TSH % FT 4 0~5% 5%~10% 10% 5.26%(60 ) 3.51%(40 ) 7.80%(89 ) [12-14] [13] [12] IH [4, 15-20] Cleary-Goldman [15] HT HT IH TSH FT 4 5% 10% 129 ( 11.30%) 89 ( 7.8%) HT FT 4 10% TPOAb Dosiou 2008 [21] 2012 [22] - Sarapatkova [14] FT 4 FT 4 BMI C IH Han [23] BMI IH TPOAb BMI 24kg/cm 2 (8 ) C IH OGTT FT 4 5% [15] HT TPOAb Bhattacharyya [24] TPOAb ( ) TPOAb [25] 200 TPOAb HbA 1c FT 4 TPOAb FT FT 4 TPOAb TPOAb TSH TPOAb IH IH TSH IH [26] IH 12 FT 4 TPOAb FT 4 FT 4 10% TPOAb [1] Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum[ J]. Thyroid, 2011, 21(10): [2] Modesto T, Tiemeier H, Peeters RP, et al. Maternal mild thyroid hormone insufficiency in early pregnancy and attention-deficit/ hyperactivity disorder symptoms in children[ J]. JAMA Pediatr, 2015, 169(9): [3] Ghassabian A, El Marroun H, Peeters RP, et al. Downstream

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