Preconception Thyrotropin Levels and Thyroid Function at Early Gestation in Women With Hashimoto Thyroiditis.

CONTEXT: Preconception optimization of thyroid function in women with Hashimoto thyroiditis (HT) is highly recommended to prevent/reduce the risk of thyroid insufficiency at early gestation. OBJECTIVE: This work aimed to evaluate the prevalence of first-trimester thyroid insufficiency in HT women with preconception thyrotropin (T0-TSH) values consistently less than or equal to 2.5 mIU/L with or without levothyroxine (LT4) treatment, and to calculate T0-TSH cutoffs that best preconceptionally identified HT women requiring first-trimester LT4 adjustment/prescription. METHODS: Serum TSH was obtained at 4- to 6-week intervals from 260 HT pregnant women (122 on LT4 [Hypo-HT]; 138 euthyroid without LT4 [Eu-HT]), prospectively followed from preconception up to pregnancy term. Receiver operating characteristic (ROC) curves were plotted to identify T0-TSH cutoffs best predicting first-trimester TSH levels greater than 2.5 mIU/L (diagnostic criterion [DC] 1) and greater than 4.0 mIU/L (DC 2). RESULTS: At first trimester, TSH was greater than 2.5 mIU/L in approximately 30% of both Hypo-HT and Eu-HT women, and greater than 4.0 mIU/L in 19.7% Hypo-HT and 10.1% Eu-HT women (P = .038). The optimal ROC-based T0-TSH cutoffs found were 1.24 mIU/L/1.74 mIU/L in Hypo-HT, and 1.73 mIU/L/2.07 mIU/L in Eu-HT women, for DC 1 and DC 2, respectively. T0-TSH values exceeding these cutoffs resulted in a statistically significantly increased risk of first-trimester thyroid insufficiency (odds ratio [OR] [95% CI)] 15.92 [5.06-50.15] and 16.68 [5.13-54.24] in Hypo-HT; 16.14 [6.47-40.30] and 17.36 [4.30-70.08] in Eu-HT women, for DC 1 and DC 2, respectively). CONCLUSION: The preconception TSH cutoffs that guaranteed a first-trimester TSH less than 2.5 mU/L in hypothyroid- and euthyroid-HT women were, respectively, almost 50% (1.24 mU/L) and 30% (1.73 mU/L) lower than this gestational target, and 1.74 mU/L and 2.07 mU/L in hypothyroid- and euthyroid-HT women, respectively, for a gestational target of 4.0 mU/L.

Assessment of serum thyroid hormone autoantibodies in the first trimester of gestation as predictors of postpartum thyroiditis.

BACKGROUND: Measurement of serum thyroperoxidase autoantibodies (TPOAb) during gestation as a classical marker for the risk of postpartum thyroiditis (PPT) predicts PPT in 1/3 to 1/2 of women. Very few studies have measured serum thyroid hormone Ab (THAb) during gestation, and none as a possible marker for PPT. METHODS: In 412 women who were followed up from 7 to 11 weeks of gestation through 12 months after delivery, we measured THAb (T3.IgM, T3.IgG, T4.IgM, T4.IgG), thyroglobulin autoantibodies (TgAb) and TPOAb at study entry (7-11 week of gestation). RESULTS: Sixty-three women (15.3%) developed PPT, which progressed to permanent hypothyroidism (PH) in 34/63 (54%). THAb+ve were 21/412 women (5.1%), the frequency being greater in those who then developed PPT (12/63 [19.0%] vs. 9/349 [2.6%], P = 4.6 × 10-8), and in the PH subgroup (26.5% [9/34] vs. 10.3% [10/29], P = 0.12). THAb positivity occurred in 9/76 women (11.8%) who were TgAb and/or TPOAb+ve compared to 12/336 women who were TgAb and TPOAb negative (3.6%, P = 0.0031). Of these 9 THAb+ve, TgAb and/or TPOAb+ve women, all (100%) developed PPT compared to 3/11 (27.3%, P = 0.0011) THAb+ve, TgAb and/or TPOAb negative women. Of these 9 and 3 PPT women, 8 and 1 progressed to PH (88.9% and 33.3%, respectively, P = 0.12). CONCLUSIONS: Gestational positivity of THAb enhance enormously the predictivity for PPT of gestational positivity of TPOAb/TgAb. However, their low frequency (5.1%) and their sensitivity (17.5% [21/63]) go against their application in lieu of TPOAb/TgAb.

Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. METHODS: In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (α=0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. RESULTS: From January 2011 to April 2014, 220 pregnant women at 12-13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P=.001; odds ratio 0.34, 95% confidence interval 0.17-0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, -1.0±3.1 compared with 0.1±1.8 (P=.048). CONCLUSION: Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01047982.

myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study.

OBJECTIVE: To check the hypothesis that myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) onset in pregnant women with a family history of type 2 diabetes. RESEARCH DESIGN AND METHODS: A 2-year, prospective, randomized, open-label, placebo-controlled study was carried out in pregnant outpatients with a parent with type 2 diabetes who were treated from the end of the first trimester with 2 g myo-inositol plus 200 µg folic acid twice a day (n = 110) and in the placebo group (n = 110), who were only treated with 200 µg folic acid twice a day. The main outcome measure was the incidence of GDM in both groups. Secondary outcome measures were as follows: the incidence of fetal macrosomia (>4,000 g), gestational hypertension, preterm delivery, caesarean section, shoulder dystocia, neonatal hypoglycemia, and neonatal distress respiratory syndrome. GDM diagnosis was performed according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations. RESULTS: Incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group: 6 vs. 15.3%, respectively (P = 0.04). In the myo-inositol group, a reduction of GDM risk occurrence was highlighted (odds ratio 0.35). A statistically significant reduction of fetal macrosomia in the myo-inositol group was also highlighted together with a significant reduction in mean fetal weight at delivery. In the other secondary outcome measures, there were no differences between groups. CONCLUSIONS: myo-Inositol supplementation in pregnant women with a family history of type 2 diabetes may reduce GDM incidence and the delivery of macrosomia fetuses.

A randomised trial of progesterone prophylaxis after midtrimester amniocentesis.

BACKGROUND: Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss. AIM: To test the hypothesis that progesterone prophylaxis may reduce this. STUDY DESIGN: A randomised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls. RESULTS: There were no differences in frequency of miscarriage, preterm delivery or neonatal outcome. CONCLUSION: Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome.