Iron Deficiency Is a Risk Factor for Thyroid Dysfunction During Pregnancy: A Population-Based Study in Belgium.

Background: Iron deficiency affects thyroid hormone synthesis by impairing the activity of the heme-dependent thyroid peroxidase. The prevalence of iron deficiency is elevated particularly in pregnant women. This study aimed to investigate the effects of iron status on thyroid function in a nationally representative sample of mildly iodine-deficient pregnant women. Methods: The study population comprised a sample of pregnant women in Belgium during the first and third trimesters of pregnancy (n = 1241). Women were selected according to a multistage proportional-to-size stratified and clustered sampling design. Urine and blood samples were collected, and a questionnaire was completed face to face with the study nurse. Concentrations of free thyroxine (fT4), total thyroxine (T4), free triiodothyronine, thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibodies, Tg antibodies, hemoglobin, serum ferritin (SF), soluble transferrin receptor, urinary iodine concentrations (UICs) were measured and body iron stores (BIS) were calculated. Results: Median UICs were 117 and 132 µg/L in the first and third trimesters of pregnancy, respectively (p < 0.05). The frequency of SF <15 µg/L was 6.2% in the first trimester and 39.6% in the third trimester of pregnancy (p < 0.05). UIC was a significant predictor of serum Tg concentrations (p < 0.01) but not of thyroid hormone or TSH concentrations. The frequency of fT4

Change in prevalence of gestational diabetes and obstetric complications when applying IADPSG screening criteria in a Belgian French speaking University Hospital. A retrospective cohort study.

BACKGROUND: In April 2012 our institution chose to switch from a two- step criteria for Gestational Diabetes Mellitus (GDM) screening, to the International Association of Diabetes in Pregnancy Study Group (IADSPG) criteria. This shift led to an increased prevalence of GDM in our pregnant population. We designed a study in order to estimate the magnitude of the increase in GDM prevalence before and after the switch in screening strategy. As a secondary objective we wanted to evaluate if there was a significant difference between the two periods in the percentage of maternal and neonatal complications such as gestational hypertensive disorders (GHD), primary cesarean section (pCS), preterm birth, large for gestational age (LGA) newborns, macrosomia, shoulder dystocia, 5' Apgar score less than to 7 at birth, neonatal intensive care unit (NICU) transfer and neonatal hypoglycemia. METHODS: We selected retrospectively 3496 patients who delivered between January 2009 and December 2011 who were screened with the two-step criteria (group A), and compared them to 2555 patients who delivered between January 2013 and December 2014 and who were screened with IADPSG criteria (Group B). We checked patients' electronic files to establish GDM status, baseline characteristics (age, body mass index, nationality, parity) and the presence of maternal and neonatal complications. RESULTS: GDM prevalence increased significantly from group A (3.4%; 95%CI 2.8-4.06%) to group B (16.28%; 95%CI 14.8 -17.7%). In group B there were significantly more non-Belgian and primiparous patients. There was no statistically significant difference in maternal and neonatal complications between the two groups, even after adjustment for nationality and parity. There was a non-significant reduction of the proportion of macrosomic and of LGA babies. CONCLUSIONS: In our population the introduction of IADPSG screening criteria has increased the prevalence of GDM without having a statistically significant impact on pregnancy outcomes.

Severe X-linked chondrodysplasia punctata in nine new female fetuses.

OBJECTIVES: Conradi-Hünermann-Happle [X-linked dominant chondrodysplasia punctata 2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in men while affected women show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only six antenatal presentations. METHODS: To better characterize the phenotype in female fetuses, we included nine antenatally diagnosed cases of women with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism. RESULTS: The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation. CONCLUSION: Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially because the majority of such cases involve de novo mutations.

High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta.

BACKGROUND: Imprinted genes show expression from one parental allele only and are important for development and behaviour. This extreme mode of allelic imbalance has been described for approximately 56 human genes. Imprinting status is often disrupted in cancer and dysmorphic syndromes. More subtle variation of gene expression, that is not parent-of-origin specific, termed 'allele-specific gene expression' (ASE) is more common and may give rise to milder phenotypic differences. Using two allele-specific high-throughput technologies alongside bioinformatics predictions, normal term human placenta was screened to find new imprinted genes and to ascertain the extent of ASE in this tissue. RESULTS: Twenty-three family trios of placental cDNA, placental genomic DNA (gDNA) and gDNA from both parents were tested for 130 candidate genes with the Sequenom MassArray system. Six genes were found differentially expressed but none imprinted. The Illumina ASE BeadArray platform was then used to test 1536 SNPs in 932 genes. The array was enriched for the human orthologues of 124 mouse candidate genes from bioinformatics predictions and 10 human candidate imprinted genes from EST database mining. After quality control pruning, a total of 261 informative SNPs (214 genes) remained for analysis. Imprinting with maternal expression was demonstrated for the lymphocyte imprinted gene ZNF331 in human placenta. Two potential differentially methylated regions (DMRs) were found in the vicinity of ZNF331. None of the bioinformatically predicted candidates tested showed imprinting except for a skewed allelic expression in a parent-specific manner observed for PHACTR2, a neighbour of the imprinted PLAGL1 gene. ASE was detected for two or more individuals in 39 candidate genes (18%). CONCLUSIONS: Both Sequenom and Illumina assays were sensitive enough to study imprinting and strong allelic bias. Previous bioinformatics approaches were not predictive of new imprinted genes in the human term placenta. ZNF331 is imprinted in human term placenta and might be a new ubiquitously imprinted gene, part of a primate-specific locus. Demonstration of partial imprinting of PHACTR2 calls for re-evaluation of the allelic pattern of expression for the PHACTR2-PLAGL1 locus. ASE was common in human term placenta.