Biomedical subjects

Gary M Shaw

Publications and source records attributed to Gary M Shaw.

79 records · Page 5Linked to original sources

PubMed2002

Apolipoprotein E and apolipoprotein B genotypes and risk for spina bifida.

BACKGROUND: Altered cholesterol metabolism and defects in cholesterol biosynthesis may influence abnormal central nervous system (CNS) development. During early stages of embryonic development, high levels of cholesterol are needed by rapidly proliferating cells that utilize cholesterol as a key cell membrane component. Alterations in cholesterol levels are influenced by variations in the apolipoprotein E (apoE) and apolipoprotein B (apoB) genes. The purpose of our study was to explore the possible association between infant genetic variations in the apoE and apoB genes and spina bifida (SB) risk. METHODS: Genomic DNA was extracted from newborn screening blood spots obtained from 26 infants with SB and 73 non-malformed control infants. ApoE and apoB genotypes were determined by restriction enzyme digestion of PCR amplification products. RESULTS: Genotype frequencies for the apoE and apoB polymorphisms were not statistically different between case and control infants. For each apoB polymorphism, however, the frequency of the wild-type allele was higher in SB infants as compared to controls. Additionally, the apoE genotype E2/E3 was observed more frequently in the controls than in SB infants [15% in controls compared to 4% in cases; OR = 0.2 (0-1.6)]. CONCLUSIONS: Results from this study suggest that genetic variations in the apoE and apoB genes, known to regulate cholesterol metabolism, do not substantially contribute to the risk of SB in infants.

Apolipoproteins B↗

PubMed2002

Timing of prenatal care initiation and risk of congenital malformations.

BACKGROUND: Although previous studies provide some evidence that timing of prenatal care initiation is associated with risks of congenital malformation, the issue has not previously been examined in depth. This study uses data from a large population-based registry to explore the association of timing of prenatal care initiation with risks of selected congenital malformation phenotypes. METHODS: Data on cases were grouped according to four-digit malformation codes of the International Classification of Diseases, Ninth Revision (ICD-9). A randomly selected group of 10,000 nonmalformed deliveries served as the comparison group. Information on month of initiation of prenatal care (categorized as during months 1-3 of gestation, months 4-7, or after month 7) and other maternal characteristics were derived from vital statistics data. RESULTS: Among the 176 four-digit ICD groupings, 67 had an adjusted odds ratio for at least one of the two prenatal care categories that was either < or = 0.67 or > or = 1.50. Later prenatal care initiation was associated with risk > or = 1.50 for most groups. Later care was associated with risk < or = 0.67 for only two groups, and the effects were imprecise. Statistical interaction between parity and prenatal care was indicated for 13 groups (P < 0.10). Risks among women with no previous pregnancy tended to increase with later prenatal care initiation; risks among parous women tended to be somewhat weaker. In general, associations applied to a wide range of malformation groups. CONCLUSIONS: This is the first large-scale study of the association of timing of prenatal care initiation and congenital malformation risks. Further defining the phenomena that surround prenatal care as a marker may help clarify the etiologies of a variety of malformations.

Congenital Abnormalities↗

PubMed2002

Physical activity and risk of neural tube defects.

OBJECTIVE: Owing to its association with known risk factors for neural tube defects (NTDs) and its impact on physiologic processes relevant to fetal development, physical activity was identified as a potential risk factor for NTD-affected pregnancy. METHODS: Using data from a population-based case-control study of deliveries occurring in California from 1989 to 1991, we estimated the potential risk of having an NTD-affected pregnancy associated with variation in maternal physical activity. In-person interviews were conducted with 538 (88% of eligible) mothers of NTD cases and with mothers of 539 (88%) nonmalformed controls on average 5 months from the term delivery date. An index reflecting reported frequency and exertion level for six activity groups (e.g., jogging and running) was used to summarize each woman's physical activity level in the periconceptional period. RESULTS: Unadjusted analyses indicated that compared to women considered inactive by this index, physically active women had 30-50% lower risk for NTD-affected pregnancies. After adjustment for several potential confounders and an evaluation of potential effect modification, results suggested that the association was restricted to women who did not take multivitamin/mineral supplements during the periconceptional period. Excluding mothers with reported medical problems did not substantially alter findings. CONCLUSIONS: This study suggests that the benefits of physical activity may extend to reduction of NTD risk among certain subgroups of women.

California↗

PubMed2002

Paternal occupational group and risk of offspring with neural tube defects.

Selected paternal occupations as well as specific occupational exposures to chemicals such as organic solvents have been suggested as possible risk factors for neural tube defects (NTD). We investigated data from a population-based, case-control study of fetuses and liveborn infants with NTDs among 1989-91 California births and fetal deaths. Interviews were conducted with mothers of 538 NTD cases and 539 non- malformed controls. Mothers were asked to report the occupations that the fathers had in the period 3 months before and 3 months after conception. Each job title and industry reported was coded in accordance with the 1990 US Census. Considering those fathers who worked in managerial and professional occupations as the reference group, elevated odds ratios (OR) for NTDs were observed for the categories: technical, sales and administrative, OR = 1.5 [95% confidence interval 1.0, 2.4]; service, OR = 2.0 [1.2, 3.1]; farming, forestry and fishing, OR = 2.1 [1.3, 3.3]; operators, fabricators and labourers, OR = 1.8 [1.2, 2.7]; and military, OR = 1.9 [0.7, 5.0]. Stratification by NTD phenotype revealed that these elevated ORs were primarily observed for spina bifida phenotypes. Analyses adjusted for maternal body mass index, maternal periconceptional use of multivitamins containing folic acid, paternal race/ethnicity, maternal race/ethnicity and maternal education revealed attenuated risk estimates for most of the occupational groups. Analyses of 182 more specific occupational groups defined by aggregating fathers on similar job titles, when compared with fathers who worked in managerial and professional occupations, revealed that four job title groups were associated with fairly precise effect estimates of >or=1.5. These groups were: cooks; janitors and cleaners; farm workers; and groundsmen/gardeners. Using occupational titles as defined in previous investigations, we did not observe an elevated OR associated with paternal occupational solvent exposures, OR = 0.8 [0.5, 1.3]. These analyses generated potential clues regarding paternal occupational exposures as NTD risk factors. Risk variation observed by spina bifida phenotype is interesting and will need to be investigated further.

Anencephaly↗

PubMed2002

Does prenatal screening for 5,10-methylenetetrahydrofolate reductase (MTHFR) mutations in high-risk neural tube defect pregnancies make sense?

Despite the fact that neural tube defects (NTDs) are the most common congenital malformations of the central nervous system, investigators have yet to identify responsible gene(s). Research efforts have been productive in the identification of environmental factors, such as periconceptional folic acid supplementation, that modulate risk for the development of NTDs. Studies of the folic acid biosynthetic pathway led to the discovery of an association between elevated levels of homocysteine and NTD risk. Researchers subsequently identified single nucleotide polymorphisms in the gene coding for the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR). Association studies suggested it was a potential risk factor for NTDs, because the thermolabile form of the enzyme led to elevated homocysteine concentrations when folic acid intake is low. Numerous studies analyzing MTHFR variants have resulted in positive associations with increased NTD risk only in certain populations, suggesting that these variants are not large contributors to the etiology of NTDs. With our limited understanding of the genes involved in regulating NTD susceptibility, the paucity of data on how folic acid protects the developing embryo, as well as the observed decrease in birth prevalence of NTDs following folic acid supplementation and food fortification, it makes little sense for prospective parents to be tested for MTHFR variants, or for variants of other known folate pathway genes.

Animals↗

PubMed2002

Maternal periconceptional vitamins: interactions with selected factors and congenital anomalies?

BACKGROUND: The mechanisms by which folic acid may contribute to reductions in risk of several congenital anomalies are unknown. The data gap includes a lack of information on possible effect modification between maternal folic acid use and other maternal exposures. We hypothesized that effects of congenital anomalies associated with maternal fever, cigarette smoking or alcohol use would be modified by intake of vitamins. METHODS: We explored case-control data that showed risk reductions among infants and fetuses whose mothers consumed vitamins. Data were from California deliveries of infants and fetuses in the period 1987-1989. Maternal telephone interviews were completed for 207 (87%) conotruncal cases, 489 (85%) orofacial cleft cases, 265 (84%) neural tube defect cases, 165 (82%) limb anomaly cases, and 734 controls (nonmalformed infants). RESULTS: Considering women who reported vitamin use and no periconceptional fever as referents, for each anomaly group we observed elevated effects for the combinations of maternal vitamin use/fever, no use/no fever and no use/fever. Effects were most elevated for the combination of no vitamin use and fever. Adjusted for maternal body mass index, education and race/ethnicity, odds ratios were 2.4 (95% confidence inter-val = 1.0-5.9) for conotruncal defects, 2.9 (1.4-5.8) for cleft lip with or without cleft palate, 1.3 (0.4-3.9) for cleft palate, 3.1 (1.4-6.8) for neural tube defects, and 2.6 (1.0-6.4) for limb-deficiency defects. These interactions were further investigated relative to maternal use of fever-reducing medications. Effects tended to be highest among those women who did not use vitamins, had fevers, and did not use fever-reducing medications. Compared with women who used vitamins and did not smoke periconceptionally, anomaly risks tended to be highest among women who did not use vitamins and smoked. No specific pattern emerged involving alcohol intake. CONCLUSIONS: These data further suggest that the underlying mechanisms of folic acid associated with congenital anomalies may be complex.

Abnormalities, Multiple↗

PubMedDate not supplied

Occurrence of low birthweight and preterm delivery among California infants before and after compulsory food fortification with folic acid.

OBJECTIVES: Studies suggest that folic acid intake influences the occurrence of low birthweight and preterm delivery. Since 1998, there has been compulsory fortification of flour and other grains with folic acid in the U.S. The objective of this study was to investigate the frequencies of low birthweight and preterm delivery after mandatory folic acid fortification among approximately six million California births. METHODS: The authors investigated prevalences of low birthweight and preterm delivery before and after compulsory fortification among 5,916,630 singleton California live births that occurred from January 1990 through December 2000. RESULTS: The unadjusted prevalences of very low birthweight, low birthweight, and preterm delivery did not substantially vary across birth years. That is, substantial decreased prevalences during the fortification period relative to the period preceding it were not observed. However, analyses that simultaneously adjusted for maternal age, parity, race/ethnicity, education, year of birth, and fortification period revealed the following relative risk ratios (RR) and 95% confidence intervals (CI): RR = 0.91, CI 0.88, 0.94 for very low birthweight, RR = 0.94; 95% CI 0.93, 0.96 for low birthweight, and RR = 0.96; 95% CI 0.94, 0.97 for preterm delivery. CONCLUSION: Findings indicate small reductions in prevalences of these outcomes associated with the timing of fortification of the U.S. food supply.

Adult↗