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Abstract: The brain-derived neurotrophic factor (BDNF) has been shown to exert an important role during implantation, placental development, and fetal growth control in mice. Its expression is closely related to the nutritional status in several tissues such as in the nervous system. In a previous study, we demonstrated that maternal undernutrition (MU), during the perinatal life, modified both the BDNF and its functional receptor, the tyrosine kinase receptor B (TrkB) gene expression in the brain of growth-restricted rat offspring during sensitive developmental windows, suggesting that these early modifications may have long-lasting consequences. In the present study, we measured BDNF/TrkB mRNA and protein levels in rat placentas from mothers submitted to a 50% food restriction during gestation, and in human placentas from pregnancies with fetal growth restriction or fetal macrosomia. In the rat, two subtypes of placental TrkB receptors have been identified: the TrkB-FL and TrkB-T1 receptors. We found that MU induced intrauterine growth restriction (IUGR) of fetuses at term and decreased the placental BDNF mRNA and protein levels. Placentae from undernourished mothers exhibited an increased mRNA expression of TrkB-FL whereas both TrkB-FL and TrkB-T1 receptors proteins levels were not modified. In human IUGR placentas, both BDNF and TrkB receptor mRNA expressions were up-regulated. Finally, although neither BDNF nor TrkB mRNA levels were altered by fetal macrosomia alone, BDNF mRNA levels were decreased when macrosomia was associated with maternal type 1 diabetes. These results show that the placental BDNF/TrkB system is modulated in rats and humans during pregnancies with fetal growth perturbations and is affected by the maternal energetic status. These data suggest that this system may exert an important role for the feto-placental unit development and that it may also be implicated in the etiology of pathologies related to placental and fetal growth disturbances. [Copyright &y& Elsevier]

Abstract: Objectives: Fetal macrosomia is a common complication of maternal diabetes mellitus and is associated with substantial morbidity, but the precise cellular and molecular mechanisms that induce fetal macrosomia are not well understood. The imprinted genes IGF-II and H19 are crucial for placental development and fetal growth. The term placentas from diabetic pregnancies express more insulin-like growth factor II (IGF-II) than those from normal pregnancies. Deregulation of their imprinting status is observed in the macrosomia-associated syndrome, the Beckwith–Wiedemann syndrome. The aim of this study was to determine whether loss of imprinting hence biallelic expression was also a hallmark of macrosomia in diabetic pregnancies. Design and methods: IGF-II and H19 maternal and paternal expressions were studied in placentas from two groups of type 1 diabetic mothers: one with macrosomic babies and the other with babies of normal weight. Maternal or paternal allele specific expressions were defined by using DNA polymorphic markers of the IGF-II and H19 genes. RFLP analysis was performed on PCR products from genomic DNA of the father, the mother and the child, and on RT-PCR products from placental mRNA. Results: RFLP analysis showed that the IGF-II gene remains paternally expressed and the H19 gene remains maternally expressed in all placentas examined, independently of the birth weight status. Conclusions: These results suggest that, in contrast with Beckwith–Wiedemann syndrome-associated macrosomia, loss of imprinting for IGF-II or H19 is not a common feature of diabetic pregnancies associated with macrosomia. [Copyright &y& Elsevier]

Objective: To determine the relationship between pregnancy induced hypertension (PIH) and gestational glucose intolerance. Methods: A 50 g, 1 h glucose loading test was offered to all pregnant women between 24 and 28 weeks of gestation in 15 centres in northern France during 8 months in 1992. If the test was positive (≥7.2 mmol/l), the woman underwent a 3 h oral glucose tolerance test (OGTT) as soon as possible. Using the criteria of Carpenter and Coustan, gestational diabetes mellitus (GDM) was defined by two abnormal values (n=218) and gestational mild hyperglycemia (GMH) by one abnormal value (n=130). Each control group was defined by a 50 g, 1 h loading test result of <7.2 mmol/l (n=108).PIH included gestational hypertension (GH) and preeclampsia (PE). GH was defined as a diastolic pressure of more than 85 mmHg on at least two occasions arising during pregnancy. PE was defined as GH with proteinuria ≥500 mg/24 h. Results: The rate of PIH in the three groups (GDM; GMH and control group, C) was, respectively 17.0, 10.8, and 4.6%. All the six PE occured in the GDM group. Univariate analysis showed significantly higher rate of hypertension in women with a history of PE, increasing body mass index before pregnancy (BMI) and glucose intolerance. In multivariate analysis with adjustment for primiparity, independant risk factors for PIH were a history of PE, BMI>27 and GDM, contrary to GMH and maternal age. Conclusions: PIH appears to be linked to the level of glucose intolerance during pregnancy, independently of other known factors of hypertension. [Copyright &y& Elsevier]

With a review of the current literature, a clarification on screening and management of gestational diabetes is hereby set out, within the frame of a Clinical Expert Series. According to the ethnic group, the prevalence varies from 1 to 14%. The treatment is based on dietary advice, insulin. The ACHOIS study demonstrates that the treatment of gestational diabetes significantly decreases perinatal complications (4 to 1%). The place of the oral treatment (glyburide) remains to be defined. In most countries, diagnosis rests on oral glucose test tolerance: Sullivan 50 g glucose test (1 hour) and 100 g test of glucose if positive (3 hours); WHO 75 g test (2 hours). The screening can be systematic or only on risk factors (wide variations between studies). Screening of gestational diabetes is required because its management improves pregnancy outcomes. Despite this, there is no consensus on the strategy of screening and diagnosis. [Copyright &y& Elsevier]