Tuesday, February 24, 2009

Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis.

Stothard KJ, Tennant PW, Bell R, Rankin J. (2009) Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis.
JAMA. 2009 Feb 11;301(6):636-50. Review.

Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom NE2 4HH.

CONTEXT: Evidence suggests an association between maternal obesity and some congenital anomalies.

OBJECTIVE: To assess current evidence of the association between maternal overweight, maternal obesity, and congenital anomaly.

DATA SOURCES: MEDLINE, EMBASE, CINAHL, and Scopus (January 1966 through May 2008) were searched for English-language studies using a list of keywords. Reference lists from relevant review articles were also searched.

STUDY SELECTION: Observational studies with an estimate of prepregnancy or early pregnancy weight or body mass index (BMI) and data on congenital anomalies were considered. Of 1944 potential articles, 39 were included in the systematic review and 18 in the meta-analysis. Data Extraction and Synthesis Information was extracted on study design, quality, participants, congenital anomaly groups and subtypes, and risk estimates. Pooled odds ratios (ORs) comparing risk among overweight, obese, and recommended-weight mothers (defined by BMI) were determined for congenital anomaly groups and subtypes for which at least 150 cases had been reported in the literature.

RESULTS: Pooled ORs for overweight and obesity were calculated for 16 and 15 anomaly groups or subtypes, respectively. Compared with mothers of recommended BMI, obese mothers were at increased odds of pregnancies affected by neural tube defects (OR, 1.87; 95% confidence interval [CI], 1.62-2.15), spina bifida (OR, 2.24; 95% CI, 1.86-2.69), cardiovascular anomalies (OR, 1.30; 95% CI, 1.12-1.51), septal anomalies (OR, 1.20; 95% CI, 1.09-1.31), cleft palate (OR, 1.23; 95% CI, 1.03-1.47), cleft lip and palate (OR, 1.20; 95% CI, 1.03-1.40), anorectal atresia (OR, 1.48; 95% CI, 1.12-1.97), hydrocephaly (OR, 1.68; 95% CI, 1.19-2.36), and limb reduction anomalies (OR, 1.34; 95% CI, 1.03-1.73). The risk of gastroschisis among obese mothers was significantly reduced (OR, 0.17; 95% CI, 0.10-0.30).

CONCLUSIONS: Maternal obesity is associated with an increased risk of a range of structural anomalies, although the absolute increase is likely to be small. Further studies are needed to confirm whether maternal overweight is also implicated.

PMID: 19211471

Mathematical development in spina bifida

English LH, Barnes MA, Taylor HB, Landry SH. (2009) Mathematical development in spina bifida. Developmental Disabilities Research Reviews. 2009;15(1):28-34.

Department of Psychology, University of Guelph, Ontario, Canada.

Spina bifida (SB) is a neural tube defect diagnosed before or at birth that is associated with a high incidence of math disability often without co-occurring difficulties in reading. SB provides an interesting population within which to examine the development of mathematical abilities and disability across the lifespan and in relation to the deficits in visual-spatial processing that are also associated with the disorder. An overview of math and its cognitive correlates in preschoolers, school-age children and adults with SB is presented including the findings from a longitudinal study linking early executive functions in infancy to the development of later preschool and school age math skills. These findings are discussed in relation to socio-historical perspectives on math education and implications for intervention and directions for further research are presented.

PMID: 19213013

Interaction of PDGFRA promoter haplotypes and maternal environmental exposures in the risk of spina bifida

Toepoel M, Steegers-Theunissen RP, Ouborg NJ, Franke B, Ladd AM, Joosten PH, van Zoelen EJ. (2009) Interaction of PDGFRA promoter haplotypes and maternal environmental exposures in the risk of spina bifida. Birth Defects Research A: Clinical and Molecular Teratology. 2009 Feb 12.

Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, the Netherlands.

BACKGROUND: Neural tube defects are multifactorial malformations involving both environmental exposures, such as maternal nutrition, and genetic factors. Aberrant expression of the platelet-derived growth factor alpha-receptor (PDGFRA) gene has been implicated in neural-tube-defect etiology in both mice and humans.

METHODS: We investigated possible interactions between the PDGFRA promoter haplotype of mother and child, as well as maternal glucose, myo-inositol, and zinc levels, in relation to spina bifida offspring. Distributions were determined of the PDGFRA promoter haplotypes H1 and H2 in a Dutch cohort, consisting of 88 spina bifida children with 56 of their mothers, and 74 control children with 72 of their mothers, as well as maternal plasma glucose, myo-inositol, and red blood cell zinc concentrations.

RESULTS: A significantly higher frequency of H1 was observed in children with spina bifida than in controls (30.1 vs. 20.3%; OR = 1.69, 95% CI 1.02-2.83). High maternal body mass index (BMI) and glucose were significant risk factors for both H1 and H2 children, whereas low myo-inositol and zinc were risk factors for H2 but not for H1 children. Stepwise multiple logistic regression analysis showed that high maternal glucose and low myo-inositol are the main risk factors for H2 spina bifida children, whereas for H1 spina bifida children, maternal BMI was the main risk factor. Interestingly, H1 mothers (median 165.5 cm) showed a significantly lower body height than H2 mothers (median 169.1 cm; p = 0.003).

CONCLUSIONS: These data suggest that the child's PDGFRA promoter haplotype is differentially sensitive for periconceptional exposure to glucose, myo-inositol, and zinc in the risk of spina bifida. Birth Defects Research (Part A), 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19215021

Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: Identification of Tulp3 as a novel negative regulator of

Patterson VL, Damrau C, Paudyal A, Reeve B, Grimes DT, Stewart ME, Williams DJ, Siggers P, Greenfield A, Murdoch JN. (2009) Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: Identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway. Human Molecular Genetics. 2009 Feb 17.

Mammalian Genetics Unit.

The mammalian sonic hedgehog (Shh) signalling pathway is essential for embryonic development and the patterning of multiple organs. Disruption or activation of Shh signalling leads to multiple birth defects, including holoprosencephaly, neural tube defects and polydactyly, and in adults results in tumours of the skin or central nervous system. Genetic approaches with model organisms continue to identify novel components of the pathway, including key molecules that function as positive or negative regulators of Shh signalling. Data presented here define Tulp3 as a novel negative regulator of the Shh pathway. We have identified a new mouse mutant that is a strongly hypomorphic allele of Tulp3 and which exhibits expansion of ventral markers in the caudal spinal cord, as well as neural tube defects and preaxial polydactyly, consistent with increased Shh signalling. We demonstrate that Tulp3 acts genetically downstream of Shh and Smoothened (Smo) in neural tube patterning and exhibits a genetic interaction with Gli3 in limb development. We show that Tulp3 does not appear to alter expression or processing of Gli3, and we demonstrate that transcriptional regulation of other negative regulators (Rab23, Fkbp8, Thm1, Sufu and PKA) is not affected. We discuss the possible mechanism of action of Tulp3 in Shh-mediated signalling in light of these new data.

PMID: 19223390

The prevalence and predictors of anencephaly and spina bifida in Texas.

Canfield MA, Marengo L, Ramadhani TA, Suarez L, Brender JD, Scheuerle A. (2009) The prevalence and predictors of anencephaly and spina bifida in Texas. Paediatric and Perinatal Epidemiology. 2009 Jan;23(1):41-50.

Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TX, USA.

Texas shares a 1255-mile border with Mexico and encompasses a variety of ecosystems, industries and other potential environmental exposures. The Texas Birth Defects Registry is an active surveillance system which covers all pregnancy outcomes (livebirths, fetal deaths and elective pregnancy terminations). This study describes the occurrence and the predictors of neural tube defects (anencephaly and spina bifida) in Texas between 1999 and 2003. Birth prevalence, crude and adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression, for each defect, by fetal/infant sex, delivery year and maternal sociodemographic characteristics. Among approximately 1.8 million livebirths, a total of 1157 neural tube defects cases were ascertained by the Registry, resulting in an overall prevalence of 6.33 cases per 10 000 livebirths. The prevalences of anencephaly and spina bifida were 2.81 and 3.52 per 10 000 livebirths respectively. Prevalences of both defects were highest in Hispanics, among mothers living along the border with Mexico, among women of higher parity and among mothers who were 40+ years of age. In addition, the prevalence of each defect was higher among women with no record of prenatal care and among women with less than 7 years of education. Hispanic ethnicity was an important predictor for anencephaly, along with sex, maternal age, parity and border residence. However, only border residence and delivery year were significant predictors for spina bifida.

PMID: 19228313