Hypothyroidism In Early Pregnancy Research Articles

Evaluation of probiotics in the treatment of hypothyroidism in early pregnancy combined with small intestinal bacterial overgrowth.

The aim of this study was to investigate the association between hypothyroidism in early pregnancy and small intestinal bacterial overgrowth (SIBO) and the effect of probiotics. Patients with hypothyroidism in early pregnancy and normal pregnant women during the same period were included in the methane-hydrogen breath test to compare the incidence of SIBO, smoothed curve fit, and differences in clinical symptoms. For those who combined with SIBO, the rate of clinical symptom conversion, thyroid hormones, and changes in associated inflammatory indexes were compared after 21 days of treatment with probiotics on top of conventional levothyroxine sodium tablets. The results are as follows: (1) The incidence of combined SIBO in patients with hypothyroidism in pregnancy was 56.0%, significantly higher than the 28.0% of normal pregnant women during the same period. (2) The highest value of hydrogen plus methane gas in 90 min in pregnancy hypothyroid patients showed a significant negative correlation with FT4 (p < .001, SD = 0.169). (3) Abdominal distension symptoms were significantly increased in both groups after combined SIBO (p = .036, p = .025), and the conversion rate after treatment was 69.2% and 75.0%, respectively. (4) In hypothyroidism, pregnancy combined with SIBO, TSH, and CRP was higher before treatment (p = .001, p = .012) and decreased significantly after treatment (p = .001, p = .008). Hypothyroidism in early pregnancy is associated with SIBO, and probiotic treatment is significantly effective.

Gut microbiome characteristics of women with hypothyroidism during early pregnancy detected by 16S rRNA amplicon sequencing and shotgun metagenomic.

This study aimed to explore the correlation between microbiota dysbiosis and hypothyroidism in early pregnancy by 16S rRNA amplicon sequencing combined with metagenomic sequencing. Sixty pregnant women (30 with hypothyroidism and 30 normal controls) were recruited for 16S rRNA amplicon sequencing, and 6 patients from each group were randomly selected for metagenomic sequencing to assess the gut microbiome profile. The 16S rRNA results showed that beta-diversity in the hypothyroidism group was decreased. The relative abundances of the Prevotella and Paraprevotella genera increased in the hypothyroidism group, and Blautia predominated in the controls. The metagenomics results revealed that Prevotella_stercorea_CAG_629, Prevotella_hominis, Prevotella_sp_AM34_19LB, etc. were enriched in the hypothyroidism group at the species level. Functional analysis revealed that the pyridoxal 5'-phosphate synthase pdxT subunit module was decreased, and the short-chain fatty acid (SCFA) transporter and phospholipase/carboxylesterase modules were strongly enriched in the hypothyroidism group. Hypothyroidism patients had increased C-reactive protein (CRP), interleukin-2 (IL-2), IL-4, IL-10, and tumor necrosis factor (TNF)-α levels. The pyridoxal 5'-phosphate synthase pdxT subunit, the SCFA transporter, and the phospholipase/carboxylesterase module were associated with different Prevotella species. In early pregnancy, women with hypothyroidism exhibit microbiota dysbiosis, and Prevotella may affect the metabolism of glutamate, SCFA, and phospholipases, which could be involved in the development of hypothyroidism during pregnancy.

Biochemical markers of renal function and maternal hypothyroidism in early pregnancy.

The physiological adaptations during a normal pregnancy affect renal and thyroid function and levels of associated biochemical markers. An association between cystatin C (CysC), creatinine, and thyroid function has been considered in nonpregnant individuals but not in pregnant women specifically. Cohort study within the North Denmark Region Pregnancy Cohort (2011-2015) with assessment of thyroid function and autoantibodies (ADVIA Centaur XPT, Siemens Healthineers) in serum residues from the early pregnancy. Consecutive samples (n = 1112) were selected for measurement of CysC and creatinine (Atellica CH 930, Siemens Healthineers), and results were linked to information in Danish nationwide registers for (i) establishment of pregnancy-specific reference intervals for CysC and creatinine and (ii) evaluation of the prevalence of maternal hypothyroidism in early pregnancy according to levels of CysC and creatinine. The established reference intervals (2.5-97.5 percentiles) differed by week of pregnancy (week 4-8, 9-11, 12-15) and were CysC: 0.58-0.92 mg/L; 0.54-0.91 mg/L; 0.52-0.86 mg/L; creatinine: 46.9-73.0 µmol/L; 42.0-68.4 µmol/L; 38.8-66.4 µmol/L. The prevalence of maternal autoimmune hypothyroidism in early pregnancy differed by the level of CysC and creatinine (<25th percentile; 25th-75th percentile; >75th percentile) and was for CysC 1.7%, 3.8%, 7.4% and for creatinine 2.5%, 4.1%, 7.1%. Reference intervals for CysC and creatinine were dynamic in early pregnancy and decreased with increasing gestational age. Furthermore, higher levels of CysC and creatinine associated with a higher prevalence of maternal autoimmune hypothyroidism. Results encourage considerations on the underlying mechanisms for the association between markers of renal and thyroid function.

Cut-offs for thyroid peroxidase and thyroglobulin antibodies in early pregnancy.

Thyroid disease in women of reproductive age is mainly of autoimmune origin, and thyroid peroxidase antibodies (TPO-Ab) as well as thyroglobulin antibodies (Tg-Ab) are key markers. Adding to this, much focus in pregnancy is on euthyroid women who are thyroid antibody positive. Evidence to substantiate the cut-offs for the definition of thyroid autoantibody positivity in early pregnant women is warranted. Stored serum samples from 14,030 Danish pregnant women were used for the measurement of TPO-Ab, Tg-Ab, TSH, and free thyroxine (ADVIA Centaur XPT, Siemens Healthineers). Among all women, a reference cohort of 10,905 individuals was identified for the establishment of antibody cut-offs. Percentile cut-offs for TPO-Ab and Tg-Ab were determined using regression on order statistics (the reference cohort). The established cut-offs were then applied (the full cohort), and frequencies of early pregnancy as well as later diagnosis of hypothyroidism were evaluated. The highest established cut-offs (95th, 97.5th, and 99th percentiles) were 59, 68, and 81 U/mL for TPO-Ab and 33, 41, and 52 U/mL for Tg-Ab. When the cut-offs were applied in the full cohort, 11.0, 10.2, and 9.7% were TPO-Ab positive, whereas 13.3, 12.3, and 11.2% were Tg-Ab positive. Antibody-positive women (TPO-Ab and/or Tg-Ab) had higher median TSH and were more likely to have hypothyroidism in early pregnancy and to be diagnosed with hypothyroidism during follow-up. This large study established and evaluated pregnancy-specific cut-offs for TPO-Ab and Tg-Ab. The findings are important regarding the classification of exposure in pregnancy and assessment of thyroid autoimmunity per se.

Postpartum Thyroid Dysfunction in Women With Known and Newly Diagnosed Hypothyroidism in Early Pregnancy.

BackgroundHypothyroidism in the first trimester of pregnancy (T1) has great adverse effects on mothers and foetuses. However, few studies have investigated the influence on postpartum thyroid dysfunction. This study aimed to evaluate their long-term effect on postpartum thyroid function within one year after delivery.MethodsIn total, 151 women were recruited from 1496 participants and were classified as newly diagnosed subclinical hypothyroidism (SCH) in T1 (ND-SCH, n=50), previously known SCH before pregnancy (PK-SCH, n=51) and previously known overt hypothyroidism (PK-OH, n=50). Their thyroid functions were dynamically monitored from pre-conception to one-year postpartum.ResultsDuring pregnancy, the first thyroid functions’ test time in T1 were 5-8 gestational weeks. After delivery, the prevalence of postpartum thyroiditis (PPT) was comparable in women with previously known and newly diagnosed hypothyroidism [ND-SCH 62.0% vs PK-SCH 64.7% vs PK-OH 64.0%, P=0.96]. For the ND-SCH group, PPT was significantly related with thyroid-stimulating hormone (TSH) >4.0 mU/L occurring at <8 gestational weeks [OR=8.06, 95% CI, 2.08-31.29] and TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.73, 95% CI, 1.04-13.41]. For patients with known hypothyroidism before pregnancy (PK-SCH and PK-OH), TSH>2.5 mU/L in T1 [OR=3.55, 95% CI, 1.43-8.81] and TPOAb≥300 μIU/mL [OR=6.58, 95% CI, 2.05-21.12] were associated with PPT. Regardless of whether SCH was diagnosed before pregnancy or in T1, the levothyroxine (LT4) treatment was discontinued at delivery. More than 50% of the patients had to face the hypothyroidism phase of postpartum and restarted LT4 treatment in the first-year follow-up. The logistic regression analysis revealed that TSH elevation occurring at <8 gestational weeks [OR=2.48, 95% CI, 1.09-5.6], TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.42, 95% CI, 1.45-8.05], and TPOAb≥300 μIU/mL [OR=6.59, 95% CI, 1.79-24.30] were the risk factors.ConclusionTSH elevation at <8 gestational weeks was associated with PPT after delivery in women with known and newly diagnosed hypothyroidism. Especially for SCH patients who stopped LT4 treatment at delivery, unsatisfactory TSH level at <8 gestational weeks and near childbirth, TPOAb≥300 μIU/mL were the risk factors for LT4 retreatment in one-year postpartum.

Impact of TPOAb-negative maternal subclinical hypothyroidism in early pregnancy on adverse pregnancy outcomes.

Purpose:To investigate the effect of subclinical hypothyroidism on pregnancy outcomes of women early in their pregnancy with different thyroid-stimulating hormone levels and thyroid peroxidase antibody–negative status and to explore reasonable thyroid-stimulating hormone levels for subclinical hypothyroidism in early pregnancy.Methods:A total of 2378 women early in their pregnancy were studied retrospectively. The baseline characteristics were collected from medical records. Pregnancy outcomes were compared between the euthyroidism and subclinical hypothyroidism groups that were diagnosed by 2011 or 2017 American Thyroid Association guidelines. In addition, the effect of different maternal thyroid-stimulating hormone levels on adverse pregnancy outcomes was analyzed using binary logistic regression.Results:According to the 2011 American Thyroid Association diagnostic criteria of subclinical hypothyroidism, the prevalence of pregnancy outcomes was not significantly higher in the subclinical hypothyroidism group than in the euthyroidism group. However, pregnant women with subclinical hypothyroidism identified by the 2017 American Thyroid Association criteria had a higher risk of premature delivery (odds ratio = 3.93; 95% confidence interval = 1.22–12.64), gestational diabetes mellitus (odds ratio = 2.69; 95% confidence interval = 1.36–5.32), and gestational anemia (odds ratio = 3.28; 95% confidence interval = 1.60–6.75). Moreover, no differences in the prevalence of adverse pregnancy outcomes were observed between the mildly elevated thyroid-stimulating hormone group (2.5 < thyroid-stimulating hormone ⩽4.0 mIU/l) and the normal thyroid-stimulating hormone group (0.27 < thyroid-stimulating hormone ⩽2.5 mIU/l). The significantly elevated thyroid-stimulating hormone group (4.0 < thyroid-stimulating hormone < 10.0 mIU/l) had a higher prevalence of premature delivery, gestational diabetes mellitus, and gestational anemia than the normal thyroid-stimulating hormone group, even after controlling for potential confounding factors.Conclusion:A mildly elevated thyroid-stimulating hormone level or maternal subclinical hypothyroidism diagnosed by 2011 American Thyroid Association guidelines during early pregnancy in thyroid peroxidase antibody–negative women was not associated with adverse pregnancy outcomes. However, maternal subclinical hypothyroidism identified by the 2017 American Thyroid Association guidelines increased the risks of several adverse pregnancy outcomes in women untreated with levothyroxine. The 2017 American Thyroid Association guidelines could be more reasonable for the diagnosis of subclinical hypothyroidism in southern China.

Effects of Maternal Subclinical Hypothyroidism in Early Pregnancy Diagnosed by Different Criteria on Adverse Perinatal Outcomes in Chinese Women With Negative TPOAb.

Aims: To compare the effects of maternal subclinical hypothyroidism (SCH) diagnosed by the 2011 or 2017 “Guidelines of the American Thyroid Association (ATA) for the diagnosis and management of thyroid disease during pregnancy and the postpartum” during the first trimester on adverse pregnancy outcomes in thyroid peroxidase antibody (TPOAb)–negative pregnant women.Methods: There were 1,556 Chinese singleton pregnant women with negative TPOAb diagnosed with either SCH or euthyroidism who were investigated, and the prevalence and risk of obstetric outcomes were compared between the two groups using 2011 and 2017 ATA standards, respectively. The effects of a mildly elevated thyroid-stimulating hormone (TSH) concentration on adverse pregnancy outcomes were evaluated by binary logistic regression.Results: Maternal SCH identified by the 2011 ATA guidelines correlated with higher rates and risks of pregnancy-induced hypertension (PIH), preeclampsia, and low-birth-weight infants, while maternal SCH diagnosed by the 2017 ATA guidelines was more likely to develop PIH, preeclampsia, cesarean delivery, preterm delivery, placenta previa, and total adverse maternal and neonatal outcomes. Moreover, a mildly elevated TSH level was significantly associated with PIH after adjustment for confounding factors.Conclusions: Compared with the 2011 ATA guidelines, the 2017 ATA guidelines could be more applicable to Chinese pregnant women to screen the effects of SCH on the majority of adverse pregnancy outcomes.

Maternal thyroid disease and adiposity in mother and child.

Thyroid hormones are crucial developmental factors, and thyroid disease in pregnant women is a concern. Overweight and obesity are also important health concerns, and we hypothesized that in utero exposure to maternal thyroid disease could programme the foetus to development of adiposity. Cohort and case-cohort studies. Pregnant women from the Danish National Birth Cohort and their 7-year-old children. Maternal thyroid disease (hyperthyroidism and hypothyroidism) was assessed from registrations of diagnoses and treatment (n=71706) or from the measurement of thyroid-stimulating hormone (TSH) in a stored blood sample from the early pregnancy (n=7624). Maternal prepregnancy body mass index (BMI) and child BMI at 7years of age were used to define overweight and obesity, and associations were evaluated using regression models adjusting for potential confounders. No association was found between maternal thyroid disease in pregnancy and child overweight (hyperthyroidism: adjusted risk ratio (aRR): 1.02 (95% confidence interval (CI): 0.58-1.82); hypothyroidism: 1.31 (0.86-1.97)) or obesity (hyperthyroidism: 0.96 (0.53-1.75); hypothyroidism: 1.25 (0.76-2.05)). On the other hand, pregnant women with hypothyroidism in early pregnancy had a higher risk of being overweight (aRR: 1.20 (95% CI: 1.03; 1.41)) and obese (1.45 (1.07; 1.96)), whereas women with hyperthyroidism had a lower risk of being overweight (0.79 (0.64; 0.98)). Results provide no evidence that maternal thyroid disease in pregnancy programmes adiposity in the child, but corroborate an association between maternal thyroid disease and adiposity in the mother.

Impact of Preconception Treatment Initiation for Hypothyroidism on Neurocognitive Function in Children.

Levothyroxine treatment for hypothyroidism in early pregnancy has inconsistent outcomes. This study evaluated children's cognitive function to ascertain the impact of preconception maternal hypothyroidism treatment on fetal neurodevelopment. This prospective, single-center cohort study was conducted at a tertiary-care hospital. Women were assigned to the before conception (BC) and after conception (AC; 8-14 gestational weeks) groups by time point of hypothyroidism diagnosis and treatment. Levothyroxine treatment was adjusted based on results of a monthly thyroid function test. The Gesell Development Diagnosis Scale (GDDS; Chinese version) was used to assess neurocognitive development of children at age 6, 12, and 24 months, with total score as the primary outcome. Of the 466 participants, 187 and 279 were in the BC and AC groups, respectively. Both groups were comparable at baseline antenatal visit, except for a higher proportion of thyroid peroxidase (TPO) antibody-positive participants in the BC group (P < .001). No significant intergroup differences were evident on the GDDS neurodevelopmental assessment at age 6, 12, and 24 months (P > .05), except for unexpected slightly lower motor ability (P = .009) and total (P = .026) scores at 12 months and adaptability at 24 months (P = .037) in the BC group. Differences for motor ability (P < .001) and total score (P = .026) persisted on subgroup analysis for subclinical hypothyroidism, without significant differences in pregnancy and neonatal outcomes by severity and TPO status (P > .05). Preconception levothyroxine treatment did not induce significantly better cognitive outcomes in children up to age 2 than treatment initiated at 8 to 14 weeks of gestation.

Association between iodine intake and thyroid autoantibodies: a cross-sectional study of 7073 early pregnant women in an iodine-adequate region.

The association between iodine intake and thyroid autoimmunity has been debated, especially in pregnant women. This study aimed to investigate thyroid autoantibodies and their association with iodine intake and hypothyroidism in early pregnancy. 7073 early pregnant women from an iodine-sufficient region participated in this study. Urinary iodine concentrations (UICs) were measured using an ammonium persulfate method. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and Tg were determined using an electrochemiluminescence immunoassay. Iodine deficiency (UIC < 100μg/L) was associated with higher risks of TPOAb positivity [adjusted odds ratio (aOR) = 1.64, 95% confidence interval [CI] (1.29-2.08)] and TgAb positivity [aOR = 1.44, 95% CI (1.16-1.80)]. Women with isolated TPOAb positivity, isolated TgAb positivity, or both TPOAb and TgAb positivity had a 14.64-fold, 7.83-fold, and 44.69-fold increased risk of overt hypothyroidism, and a 4.36-fold, 2.86-fold, and 6.26-fold increased risk of subclinical hypothyroidism, respectively. Moreover, the risks of overt and subclinical hypothyroidism in women with a high TPOAb titer were 16.99 and 4.80 times that in TPOAb-negative women, respectively. The risk of overt hypothyroidism in women with a high TgAb titer was 6.97 times that in TgAb-negative women. Our work demonstrates that iodine deficiency during early pregnancy is an independent risk factor for both TPOAb positivity and TgAb positivity. Furthermore, positivity for both autoantibodies and a high thyroid autoantibody titer are associated with significantly higher risks of overt and subclinical hypothyroidism.

Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy.

Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy. In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n = 611), one low-risk group comprising women without risk factors for thyroid disorder (n = 511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n = 88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed. The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p = 0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0 mIU/L. High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since ∼10% of women with SCH or hypothyroidism could not be diagnosed in this way.

Early Maternal Thyroid Function During Gestation Is Associated With Fetal Growth, Particularly in Male Newborns.

Intrauterine growth patterns are influenced by maternal thyroid function during gestation and by fetal sex. It is unknown, however, whether the relationships between maternal thyrotropin (TSH) and free thyroxine (fT4) levels in early pregnancy and fetal growth outcomes are modified by fetal sex. Data were obtained from a community-based cohort study of pregnant women living in Amsterdam (Amsterdam Born Children and Their Development study). TSH and fT4 levels were determined during the first prenatal screening at median 13 weeks (interquartile range, 12 to 14). Women with live-born singletons and no overt thyroid dysfunction were included (N = 3988). Associations between these maternal hormones and birth weight, small for gestational age (SGA), and large for gestational age (LGA) were analyzed separately for each sex. After adjustments, 1 pmol/L increase in maternal fT4 levels was associated with a reduction in birth weight of 33.7 g (P < 0.001) in male newborns and 16.1 g (P < 0.05) in female newborns. Increased maternal fT4 was not associated with increased odds for SGA, but was associated with a decreased odds for LGA in boys [per 1 pmol/L; odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69 to 0.90]. Maternal subclinical hypothyroidism in early pregnancy (TSH > 2.5 mU/L, 7.3%) was associated with increased odds for LGA in male newborns (OR, 1.95; 95% CI, 1.22 to 3.11). Maternal fT4 in early pregnancy was observed to be inversely associated with birth weight, with a stronger relationship in males. Male infants also had increased odds for LGA in mothers with subclinical hypothyroidism. Sexual dimorphism appears to be present in the relationship between maternal thyroid metabolism and fetal intrauterine growth, with stronger associations in male infants.

Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review.

BACKGROUND: Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy. METHODS: Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register. RESULTS: From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies. CONCLUSIONS: Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.

Диагностика субклинического гипотиреоза на ранних сроках беременности

Диагностика субклинического гипотиреоза на ранних сроках беременности

Gestational hypothyroidism: development of mild hypothyroidism in early pregnancy in previously euthyroid women

To determine the proportion of euthyroid women attending a fertility practice who develop hypothyroidism in very early pregnancy (gestational hypothyroidism [GHT]), and to examine the association of GHT with exogenous gonadotropin treatment. Retrospective cohort study. A private reproductive medicine practice. All healthy women (N = 94) with infertility or recurrent pregnancy loss, TSH level <2.5 mIU/L, negative thyroid peroxidase antibodies at initial evaluation, and not taking thyroid medication, who conceived during an 18-month period. Usual fertility care; 30 women who had received exogenous gonadotropins. Serum TSH level at the time of pregnancy detection. Gestational hypothyroidism (TSH ≥ 2.5 mIU/L) developed in 23 of 94 women (24%). The mean increase in serum TSH level from initial evaluation to early pregnancy was 0.45 ± 0.08 [SE] mIU/L. There was a trend toward the association of GHT with use of exogenous gonadotropins. Gestational hypothyroidism was positively associated with initial prepregnancy TSH level. Euthyroid women may develop mild hypothyroidism in early pregnancy, especially after exogenous gonadotropin treatment. Appropriate vigilance will allow for timely levothyroxine treatment.

Gestational Age-specific Cut-off Values Are Needed for Diagnosis of Subclinical Hypothyroidism in Early Pregnancy.

During the first trimester of pregnancy, thyroid-stimulating hormone (TSH) >2.5 mIU/L has been suggested as the universal criterion for subclinical hypothyroidism. However, TSH levels change continuously during pregnancy, even in the first trimester. Therefore the use of a fixed cut-off value for TSH may result in a different diagnosis rate of subclinical hypothyroidism according to gestational age. The objective of this study was to obtain the normal reference range of TSH during the first trimester in Korean gravida and to determine the diagnosis rate of subclinical hypothyroidism using the fixed cut-off value (TSH >2.5 mIU/L). The study population consisted of pregnant women who were measured for TSH during the first trimester of pregnancy (n=492) and nonpregnant women (n=984). Median concentration of TSH in pregnant women was lower than in non-pregnant women. There was a continuous decrease of median TSH concentration during the first trimester of pregnancy (median TSH concentration: 1.82 mIU/L for 3+0 to 6+6 weeks; 1.53 mIU/L for 7+0 to 7+6 weeks; and 1.05 mIU/L for 8+0 to 13+6 weeks). Using the fixed cut-off value of TSH >2.5 mIU/L, the diagnosis rate of subclinical hypothyroidism decreased significantly according to the gestational age (GA) at TSH (25% in 3+0 to 6+6 weeks, 13% in 7+0 to 7+6 weeks, and 9% for 8+0 to 13+6 weeks, P<0.001), whereas the diagnosis rate was 5% in all GA with the use of a GA-specific cut-off value (P=0.995). Therefore, GA-specific criteria might be more appropriate for the diagnosis of subclinical hypothyroidism.

Does the thyroid-stimulating hormone measured concurrently with first trimester biochemical screening tests predict adverse pregnancy outcomes occurring after 20 weeks gestation?

Maternal hypothyroidism in early pregnancy is associated with adverse outcomes, but not consistently across studies. First trimester screening for chromosomal anomalies is routine in many centers and provides an opportunity to test thyroid function. To determine if thyroid function tests performed with first trimester screening predicts adverse pregnancy outcomes. A cohort study of 2411 women in Western Australia with singleton pregnancies attending first trimester screening between 9 and 14 weeks gestation. We evaluated the association between TSH, free T4, free T3, thyroid antibodies, free beta human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein A (PAPP-A) with a composite of adverse pregnancy events as the primary outcome. Secondary outcomes included placenta previa, placental abruption, pre-eclampsia, pregnancy loss after 20 weeks gestation, threatened preterm labor, preterm birth, small size for gestational age, neonatal death, and birth defects. TSH exceeded the 97.5th percentile for the first trimester (2.15 mU/L) in 133 (5.5%) women, including 22 (1%) with TSH above the nonpregnant reference range (4 mU/L) and 5 (0.2%) above 10 mU/L. Adverse outcomes occurred in 327 women (15%). TSH and free T4 did not differ significantly between women with or without adverse pregnancy events. On the multivariate analysis, neither maternal TSH >2.15 mU/L nor TSH as a continuous variable predicted primary or secondary outcomes. Testing maternal TSH as part of first trimester screening does not predict adverse pregnancy outcomes. This may be because in the community setting, mainly mild abnormalities in thyroid function are detected.

Maternal Hypothyroidism in Early Pregnancy and Infant Structural Congenital Malformations

Background. The question is debated on whether maternal hypothyroidism or use of thyroxin in early pregnancy affects the risk for infant congenital malformations. Objectives. To expand the previously published study on maternal thyroxin use in early pregnancy and the risk for congenital malformations. Methods. Data from the Swedish Medical Birth Register were used for the years 1996–2011 and infant malformations were identified from national health registers. Women with preexisting diabetes or reporting the use of thyreostatics, anticonvulsants, or antihypertensives were excluded from analysis. Risk estimates were made as odds ratios (ORs) or risk ratios (RRs) after adjustment for year of delivery, maternal age, parity, smoking, and body mass index. Results. Among 23 259 infants whose mothers in early pregnancy used thyroxin, 730 had a major malformation; among all 1 567 736 infants, 48012 had such malformations. The adjusted OR was 1.06 (95% CI 0.98–1.14). For anal atresia the RR was 1.85 (95% CI 1.00–1.85) and for choanal atresia 3.14 (95% CI 1.26–6.47). The risk of some other malformations was also increased but statistical significance was not reached. Conclusions. Treated maternal hypothyroidism may be a weak risk factor for infant congenital malformations but an association with a few rare conditions is possible.

Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review

Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy. Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register. From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies. Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.

Ensuring an intelligent India: Managing hypothyroidism in pregnancy

Ensuring an intelligent India: Managing hypothyroidism in pregnancy