Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms.

Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms. We identified a missense Asn396Ser mutation (rs77960347) in the endothelial lipase (LIPG) gene, occurring with an allele frequency of 1% in the general population, which was significantly associated with depressive symptoms (P-value=5.2 × 10-08, ß=7.2). Replication in three independent data sets (N=3612) confirmed the association of Asn396Ser (P-value=7.1 × 10-03, ß=2.55) with depressive symptoms. LIPG is predicted to have enzymatic function in steroid biosynthesis, cholesterol biosynthesis and thyroid hormone metabolic processes. The Asn396Ser variant is predicted to have a damaging effect on the function of LIPG. Within the discovery population, carriers also showed an increased burden of white matter lesions (P-value=3.3 × 10-02) and a higher risk of Alzheimer's disease (odds ratio=2.01; P-value=2.8 × 10-02) compared with the non-carriers. Together, these findings implicate the Asn396Ser variant of LIPG in the pathogenesis of depressive symptoms in the general population.

The association of maternal thyroid function with placental hemodynamics.

STUDY QUESTION: What is the clinical association of maternal thyroid function with placental hemodynamic function? SUMMARY ANSWER: A higher free thyroxine (FT4) concentration in early pregnancy is associated with higher placental vascular resistance. WHAT IS KNOWN ALREADY: Suboptimal placental function is associated with preeclampsia (which, in turn, further deteriorates placental hemodynamics and impairs the fetal blood supply), fetal growth restriction and premature delivery. Studies have suggested that thyroid hormone (TH) has a role in placental development through effects on trophoblast proliferation and invasion. STUDY DESIGN, SIZE, DURATION: This study was embedded in The Generation R cohort, a population-based prospective study from early fetal life onwards in Rotterdam, the Netherlands. In total, 7069 mothers with expected delivery date between April 2002 and January 2006 were enrolled during early pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHOD: Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentrations were measured during early pregnancy (median 13.4 weeks, 95% range 9.7-17.6 weeks). Placental function was assessed by Doppler ultrasound via measurement of arterial vascular resistance, i.e. umbilical artery pulsatility index (PI) and uterine artery resistance index (RI) (both measured twice, between 18-25th and after 25th gestational weeks) and the presence of uterine artery notching (once after the 25th gestational week) in 5184 pregnant women. MAIN RESULTS AND THE ROLE OF CHANCE: FT4 was positively linearly associated with umbilical artery PI in the second and third trimesters as well as with uterine artery RI in the second trimester and the risk of uterine artery notching in the third trimester (P < 0.05 for all). The association of thyroid function with preeclampsia and birth weight was partially mediated through changes in placental function, with the percentages of mediated effects being 10.4% and 12.5%, respectively. LIMITATIONS, REASONS FOR CAUTION: A potential limitation is the availability of only a single time point for TH measurements and different numbers of missing placental ultrasound measurements for the adverse outcomes. WIDER IMPLICATIONS OF THE FINDINGS: A higher FT4 concentration in early pregnancy is associated with higher vascular resistance in the second and third trimesters in both the maternal and fetal placental compartment. These effects on placental function might explain the association of FT4 with adverse pregnancy outcomes, including preeclampsia and fetal growth restriction. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a fellowship from ERAWEB, a project funded by the European Commission (to M.B.) and by clinical fellowship from The Netherlands Organization for Health Research and Development (ZonMw), Project 90700412 (to R.P.P.). The authors have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

[What is a normal thyroid function?] / Wat is een 'normale' schildklierfunctie?

Thyroid dysfunction is currently defined by a TSH value outside of its statistically established normal range. This definition does not take patients' individual symptoms or long-term risk of disease into account. However, increasing evidence shows that certain variations in thyroid function, even within the normal range, are associated with several adverse clinical outcomes. Also, subclinical thyroid dysfunction in patients, defined by a TSH outside of the normal range and free thyroxine within the normal range, has been shown to be accompanied by more thyroid-related symptoms when compared to the general population. This raises the question whether normal ranges are truly normal, and whether a new definition of thyroid function and thyroid dysfunction should be developed.

[Influence of age at operation on the results of aortic coarctation surgery]. / Influence de l'âge opératoire sur les résultats de la chirurgie de la coarctation de l'aorte.

The aim of our study is to determine the ideal operative age of aortic coarctation. 30 patients (20 male and 10 female) have had surgery for coarctation of the aorta between 1990 and 1998. Mean operative age is 4.5 years (range 2 months and 13 years). Crafoord technique was performed in 23 cases, modified Crafoord technique in 3 cases, Waldhausen operation in 3 cases and coarctectomie with insertion of a prosthetic material in one case. A post-coarctectomy syndrome was noted in one case. There were no early deaths. The mean follow-up period is 4.5 years. 8 patients were noted to have late systemic hypertension (26.5%). It is more frequent in patients that have been operated after the age of 5 years (43%). One patient has had a recoarctation (3%). No late death was noted. 4 patients had to undergo a reoperation for cardiac associated anomalies.

[Complete repair of a corrected transposition of the great vessels by double switch. A case report]. / Réparation complete de la transposition corrigée des gros vaisseaux par double switch. A propos d'un cas.

We report the observation of a female patient with a corrected transposition of the great arteries, ventricular septal defect and complete atrio-ventricular block. This complex cardiac disease originated heart failure and was discovered at the age of 4 months. This baby has been operated at the age of 7 months, in April 1998. She had a complete repair by the double switch, closure of the ventricular septal defect and implantation of a permanent pace-maker. Short term results are favorable. Total repair of the corrected transposition of the great arteries is currently possible thanks to the recent technique of the double switch. It remains a difficult operation but with satisfactory short term results.

[Cavopulmonary shunts: apropos of 40 observations]. / Derivations cavopulmonaires: a propos de 40 observations.

Fourty patients with univentricular heart, underwent a cavopulmonary shunt procedure. The majority have an excellent hemodynamic status with ventricular end diastolic pressure > 12 mmHg and a mean pulmonary artery pressure > 15 mmHg. However, 11 patients have ventricular dysfunction, 9 have an incompetent systemic atrio-ventricular valve and 6 have mean pulmonary artery pressure > 15 mmHg. The pulmonary arteries were of a good size in all cases with a Nakata index > 100 mm2/m2. Cavopulmonary connections are satisfactory palliative procedures in the treatment of univentricular cardiac disease.

[False aneurysm of the right ventricular outflow tract due to infective endocarditis after repair of congenital heart disease]. / Faux anévrisme de la voie d'éjection du ventricule droit compliquant une endocardite infectieuse après réparation d'une cardiopathie congénitale.

A case of an enormous false aneurysm of the right ventricular outflow tract due to infective endocarditis is reported in a 12-year old girl who underwent Rastelli repair of congenital heart disease with reconstruction of the right ventricular outflow tract by bovine jugular vein graft (Contegra). The false aneurysm was associated to desinsertion of the patch of the ventricular septal defect and compresses the right ventricle leading to heart failure and shock. Surgical treatment was performed in emergency but the child died after surgery. Infectious false aneurysm of the right ventricle after surgical reconstruction of the right ventricular outflow tract is very rare. At our knowledge, only three cases have been reported in the literature. We report here another case.

Psychological causes of non-compliance with electronically monitored occlusion therapy for amblyopia.

AIM: To analyse psychological causes for low compliance with occlusion therapy for amblyopia. METHOD: In a randomised trial, the effect of an educational programme on electronically measured compliance had been assessed. 149 families who participated in this trial completed a questionnaire based on the Protection Motivation Theory after 8 months of treatment. Families with compliance less than 20% of prescribed occlusion hours were interviewed to better understand their cause for non-compliance. RESULTS: Poor compliance was most strongly associated with a high degree of distress (p<0.001), followed by low perception of vulnerability (p = 0.014), increased stigma (p = 0.017) and logistical problems with treatment (p = 0.044). Of 44 families with electronically measured compliance less than 20%, 28 could be interviewed. The interviews confirmed that lack of knowledge, distress and logistical problems resulted in non-compliance. CONCLUSION: Poor parental knowledge, distress and difficulties implementing treatment seemed to be associated with non-compliance. For the same domains, the scores were more favourable for families who had received the educational programme than for those who had not.