Thyroid hormones are critical for mammalian life, including cardiovascular, kidney, and other organs, especially the neurological system [
Autoimmune thyroid disease is the most frequent cause of hypothyroidism in women of reproductive age. The prevalence of thyroid peroxidase antibody (TPOAb) in the general population of reproductive age is 10–20% [
There still remains controversy regarding the screening strategies for thyroid functions and thyroid autoantibodies during prepregnancy, gestation, and postpartum [
Initially, 401 singleton pregnant women who underwent regular examination at Jiangsu Province Hospital between January 2013 and July 2014 were enrolled in this study, with gestational age of 24–28 weeks, with checking for thyroid functions at least 3 times antepartum, and following up until 12 months postpartum. Pregnant women with a preexisting diagnosis of thyroid dysfunction, family history of thyroid diseases, assisted reproductive technology, and recognized system autoimmune diseases were excluded from this study. Among the initially screened, 185 were excluded for history of thyroid dysfunction, 3 for family history of thyroid diseases, 3 for assisted reproductive technology, and 2 for recognized system autoimmune diseases.
Data about maternal age, parity, and history of spontaneous abortion were collected by interrogation. Gestational age was calculated according to the first day of their last menstrual cycle (LMP) (for women with regular cycles), and/or ultrasonography for those with irregular cycles. Physical exams for all participants included weight, height, and systolic and diastolic pressure. All participants had been tested for gestational diabetes mellitus at 24–28 weeks through a 2-hour, 75 g oral glucose tolerance test. Physical examination of neonate was done to determine Apgar score, weight, and height.
Thyrotropin (TSH), free thyroxine (FT4), and urine iodine concentration (UIC) were measured at baseline and checked at 4-week interval during gestation. Levothyroxine (LT4) treatments were started in women with overt and subclinical hypothyroidism to maintain euthyroid antepartum and were withdrawn postpartum. Thus, subjects were divided into two groups, according to the results of TPOAb: TPOAb-positive and TPOAb-negative groups.
3 mL of blood sample was obtained from each subject. Measurements of TSH, FT4, and TPOAb were carried out with the Cobas 6000 Centaur system (Roche Diagnostics, YZB/GEM 1815–2010, Mannheim, German), according to the instructions of the manufacturer (interassay CV <5.3%, intra-assay CV <6.4% for TSH and <7.8%, <7.1% for FT4). UICs were measured using the modified Sandell-Kolthoff reaction.
We used the ATA TSH criteria during pregnancy [
Values of TPOAb >34 IU/mL were defined as being positive.
Abnormal maternal outcomes were defined as follows. PPT is the occurrence of thyroid dysfunction in the first postpartum year in women who were euthyroid prior to pregnancy, including classical form, isolated thyrotoxicosis, and isolated hypothyroidism. In its classical form, transient thyrotoxicosis is followed by transient hypothyroidism with a return to the euthyroid state by the end of the initial postpartum year [
Abnormal neonatal outcomes were defined as follows: preterm birth: delivery occurring between 28 and 37 weeks of pregnancy; fetal distress: fetus with hypoxia during antepartum or intrapartum; LBW: fetal weight less than 2500 g; CH: neonates who had exhibited a positive screening for CH (TSH > 10 mU/L in heel blood) at birth subsequently confirmed as having a primary CH (TSH > 10 mU/L, FT4 < 12 pmol/L in venous blood). Neonatal diseases include neonatal haemorrhage, neonatal jaundice, neonatal thrombocytopenia, neonatal infections, and neonatal defects.
Statistical analysis was performed using SPSS 19.0 software. Data were expressed as means ± standard deviation or numbers and percentages. Measurement data among different groups were carried by
The study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. Written consent was obtained from the subjects individually. The purposes, the data collection procedures, and the benefits of the research were explained to them before obtaining their informed consent.
The flow diagram of the study process was described in Figure
The flow diagram of the study process. PPT: postpartum thyroiditis.
The baseline characteristics of the study population were shown in Table
Population characteristics of TPOAb-positive and TPOAb-negative women during pregnancy.
TPOAb-positive ( |
TPOAb-negative ( |
| |
---|---|---|---|
Maternal age (years) | 29.15 ± 4.10 | 29.46 ± 4.08 | 0.71 |
BMI (kg/m2) | 21.45 ± 3.45 | 21.13 ± 2.36 | 0.55 |
Gestational age (weeks) | 25.24 ± 1.26 | 24.99 ± 1.41 | 0.73 |
Parity | 0.57 | ||
Nulliparity | 21 (80.77%) | 154 (84.62%) | |
Multiparity | 5 (19.23%) | 28 (15.38%) | |
History of spontaneous abortion | 3 (11.54%) | 8 (4.40%) | 0.14 |
Blood pressure | |||
Systolic pressure (mmHg) | 118.24 ± 23.15 | 116.51 ± 12.26 | 0.62 |
Diastolic pressure (mmHg) | 74.43 ± 6.71 | 76.31 ± 7.53 | 0.37 |
FBG (mmol/L) | 4.69 ± 0.48 | 4.78 ± 0.57 | 0.56 |
PBG1h (mmol/L) | 8.17 ± 1.65 | 8.22 ± 1.93 | 0.86 |
PBG2h (mmol/L) | 7.04 ± 1.46 | 7.30 ± 1.74 | 0.53 |
MUIC ( |
188 | 202 | 0.23 |
TPOAb, thyroid peroxidase antibody; BMI, Body Mass Index; MUIC, median urine iodine concentration.
FBG, fasting blood glucose; PBG1h, 1 h plasma blood glucose; PBG2h, 2 h plasma blood glucose.
Data were presented as mean ± standard deviation (SD) or
Median urinary iodine concentration (MUIC) was 188
In TPOAb-positive group, 2 (7.69%) women were with overt hypothyroidism and 4 (15.38%) women with subclinical hypothyroidism. Six (3.30%) women with overt hypothyroidism and 13 (7.14%) women with subclinical hypothyroidism were in TPOAb-negative group. Women with overt and subclinical hypothyroidism in both groups were treated with levothyroxine to maintain euthyroid. There has been no difference in the subjects treated with thyroxine in the two groups (
TSH and FT4 were maintained in the normal range in both groups antepartum. There was no difference of thyroid functions between two groups antepartum (
Thyroid functions of women in TPOAb-positive and TPOAb-negative groups antepartum.
TPOAb-positive ( |
TPOAb-negative ( |
| |
---|---|---|---|
TSH (mIU/L) | |||
24–28 W | 4.05 (0.77–11.36) | 3.01 (0.47–12.31) | 0.07 |
28–32 W | 2.38 (0.32–10.45) | 2.34 (0.33–9.67) | 0.56 |
32–36 W | 2.24 (0.36–6.38) | 2.83 (0.31–8.62) | 0.22 |
36–40 W | 2.13 (0.21–5.04) | 2.92 (0.22–5.20) | 0.34 |
FT4 (pmol/L) | |||
24–28 W | 11.24 ± 2.37 | 11.15 ± 2.22 | 0.17 |
28–32 W | 12.02 ± 2.30 | 11.39 ± 1.68 | 0.23 |
32–36 W | 11.68 ± 1.73 | 11.62 ± 1.71 | 0.26 |
36–40 W | 12.26 ± 4.62 | 11.71 ± 1.81 | 0.18 |
TPOAb, thyroid peroxidase antibody.
TSH were presented as median with interquartile; FT4 were presented as mean ± standard deviation (SD).
As shown in Figure
Changes of TPOAb levels antepartum and postpartum in TPOAb-positive and TPOAb-negative groups. (a) Changes of TPOAb levels antepartum and postpartum in TPOAb-positive group; (b) changes of TPOAb levels antepartum and postpartum in TPOAb-negative group.
Of all women, 11.54% (24/208) had a PPT. The prevalence of PPT was significantly higher in TPOAb-positive than in TPOAb-negative group (42.31% versus 7.14%,
Onset time and presenting form of PPT in TPOAb-positive and TPOAb-negative groups.
TPOAb-positive ( |
TPOAb-negative ( | |
---|---|---|
PPT, |
11 (42.31%) |
13 (7.14%) |
Postpartum time of onset | ||
6 weeks postpartum, |
5 (45.46%) | 7 (53.85%) |
3 months postpartum, |
2 (18.18%) | 3 (23.08%) |
6 months postpartum, |
3 (27.27%) | 2 (15.38%) |
12 months postpartum, |
1 (9.09%) | 1 (7.69%) |
Presenting form | ||
Classical form, |
7 (63.64%) | 2 (15.38%) |
Isolated thyrotoxicosis, |
1 (9.09%) | 8 (61.54%) |
Isolated hypothyroidism, |
3 (27.27%) | 3 (23.08%) |
PPT, postpartum thyroiditis.
As depicted in Table
Maternal outcomes in TPOAb-positive and TPOAb-negative groups.
Pregnancy outcomes | TPOAb-positive ( |
TPOAb-negative ( |
|
---|---|---|---|
Gestational age at delivery (weeks) | 38.24 ± 1.26 | 38.99 ± 1.41 | 0.73 |
Mode of delivery | 0.54 | ||
Vaginal | 15 (57.69%) | 94 (51.65%) | |
Cesarean | 11 (42.31%) | 88 (48.35%) | |
Placenta previa | 0 (0%) | 1 (0.55%) | 1 |
Placental abruption | 0 (0%) | 1 (0.55%) | 1 |
PROM | 3 (11.54%) | 11 (6.04%) | 0.39 |
Polyhydramnios | 4 (15.38%) | 5 (2.74%) | 0.02 |
Oligohydramnios | 2 (7.69%) | 22 (12.09%) | 0.74 |
PPH | 2 (7.69%) | 10 (5.49%) | 0.21 |
PROM, premature rupture of fetal membrane; PPH, postpartum haemorrhage.
Data were presented as
The percentages of abnormal maternal outcomes between the two groups were compared by Fisher’s exact test; gestational age at delivery between the two groups was carried by
Neonatal outcomes in two groups were compared in Table
Neonatal outcomes in TPOAb-positive and TPOAb-negative groups.
Neonatal outcomes | TPOAb-positive ( |
TPOAb-negative ( |
|
---|---|---|---|
Sex of neonate (boy, %) | 12 (46.15%) | 96 (52.75%) | 0.54 |
Neonate weight (g) | 3369.05 ± 249.31 | 3404.82 ± 461.15 | 0.73 |
Neonate height (cm) | 49.89 ± 0.24 | 50.02 ± 0.90 | 0.91 |
Apgar score at 1 minute | 9.95 ± 0.22 | 9.88 ± 0.74 | 0.67 |
Apgar score at 5 minutes | 10 | 9.96 ± 0.28 | 0.55 |
Premature delivery | 2 (7.69%) | 9 (4.95%) | 0.63 |
Fetal distress | 2 (7.69%) | 9 (4.95%) | 0.63 |
LBW | 0 | 5 (2.75%) | 1 |
Neonatal diseases | 2 (7.69%) | 9 (4.95%) | 0.63 |
Congenital hypothyroidism | 1 (3.85%) | 1 (0.55%) | 1 |
LBW, low birth weight.
Data were presented as
The percentages of abnormal neonatal outcomes between the two groups were compared by Fisher’s exact test; neonate weight, height, and Apgar scores between the two groups were carried by
In the current study, we investigated the effects of TOPAb on maternal and neonatal outcomes in pregnant women in the second trimester. It was found that pregnant women who are TPOAb-positive had increased risk of PPT, which predominantly happened at 6 weeks postpartum. The presence of TPOAb was associated with increased incidence of polyhydramnios.
Prior research demonstrated a large variation in the prevalence of PPT, ranging from 1.1 to 16.7% [
The onset time of PPT has not been explicitly reported in the literature. Almost half of PPT happened at 6 weeks postpartum in both groups in our study, although it is known that the peak TPOAb in the postpartum can occur up to 6 months postpartum [
While some researches demonstrated that TPOAb results in maternal and neonatal complications such as miscarriage, preterm birth, and LBW, this had not been reported by others. In the present study, TPOAb was not found to be associated with placenta previa, placental abruption, PROM, oligohydramnios, PPH, premature delivery, fetal distress, LBW, neonatal diseases, and CH. Chen et al. reported that TPOAb was associated with PROM and LBW; no association was found with other outcomes, such as gestation diabetes, gestation hypertension, placenta previa, placental abruption, fetal distress, and preterm birth [
The adverse maternal and fetal effects linked with undiagnosed and untreated overt thyroid dysfunction in pregnant women have been clearly depicted in previous literature and guidelines [
Various reports regarding the influence of TPOAb on the impaired neuropsychological development of offspring have been published. Li et al. reported that lower motor and intellectual development of children at 25–30 months of age was associated with elevated TPOAb of women at 16–20-week gestation [
In conclusion, pregnant women who are TPOAb-positive had increased risk of PPT and polyhydramnios. We recommended that screening of thyroid function should be performed at earlier pregnancy and at approximately 6 weeks postpartum especially in TPOAb-positive women. The potential effects of TPOAb on polyhydramnios and neurodevelopment of offspring warrant further investigation.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors gratefully acknowledge the midwives and obstetricians Yueji Zhou and Wei Chen of the Jiangsu Province Maternal and Child-Care Service Center for their support in recruiting patients and collecting the samples. This work was supported by the National Natural Science Foundation of China (Project no. 81170715).