Gary M Shaw

Stanford University, Stanford, California, United States

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Publications (356)1077.79 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: Background: Evidence on association of maternal pre-pregnancy weight with risk of orofacial clefts is inconsistent. Methods: Six large case-control studies of orofacial clefts from Northern Europe and the USA were included in analyses pooling individual-level data. Cases included 4943 mothers of children with orofacial clefts (cleft lip only: 1135, cleft palate with cleft lip: 2081, cleft palate only: 1727) and controls included 10 592 mothers of unaffected children. Association of orofacial cleft risk with pre-pregnancy maternal weight classified by level of body mass index (BMI, kg/m(2)) was evaluated using logistic regression adjusting for multiple covariates. Results: Cleft palate, both alone and with cleft lip (CP+/-CL), was associated with maternal class II+ pre-pregnancy obesity (≥ 35)compared with normal weight [adjusted odds ratio (aOR) = 1.36; 95% confidence interval (CI) = 1.16, 1.58]. CP+/-CL was marginally associated with maternal underweight (aOR = 1.16; 95% CI = 0.98, 1.36). Cleft lip alone was not associated with BMI. Conclusions: In this largest population-based study to date, we found an increased risk of cleft palate, with or without cleft lip, in class II+ obese mothers compared with normal-weight mothers; underweight mothers may also have an increased risk, but this requires further study. These results also suggest that extremes of weight may have a specific effect on palatal development.
    No preview · Article · May 2016 · International Journal of Epidemiology
  • Wei Yang · Suzan L. Carmichael · Gary M. Shaw
    [Show abstract] [Hide abstract] ABSTRACT: Background: We examined whether prevalences of neural tube defects (NTDs), orofacial clefts, and gastroschisis changed more rapidly after than before folic acid fortification in California. Methods: This population-based study used vital statistics and birth defects registry data. The study population included all live births and stillbirths delivered in central California counties from 1989 to 2010. Cases included deliveries with NTDs, orofacial clefts, and gastroschisis. Weighted least squares regression was used to estimate slopes during prefortification (before 1997) and postfortification (after 1998), respectively. The difference of the two slopes with the 95% confidence interval (CI) was calculated. Results: For all NTDs combined, slopes indicated that NTD prevalence was decreasing by 8.7 (slope: -8.7; 95% CI, -13.5--3.9) cases per 100,000 deliveries per year before fortification and by 1.7 (slope: -1.7; 95% CI, -3.7-0.3) after fortification; thus the decline had slowed by 7.0 (95% CI, 2.7-11.3) cases per 100,000 deliveries per year. For orofacial clefts, slopes for cleft lip with/without palate as well as for cleft palate alone indicated that the postfortification slope was lower than the prefortification slope suggesting a more accelerated decrease in the postfortification time period. For gastroschisis, the slope after fortification was lower compared with prefortification, indicating a less accelerated prevalence increase in the postfortification time period. Stratification by race/ethnicity did not substantially alter results. Conclusion: We observed a slower decline in prevalence of NTDs, an emergence of a decline in orofacial clefts, and a slower increase in gastroschisis, during the postfortification period in central California, relative to the prefortification period. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.
    No preview · Article · May 2016 · Birth Defects Research Part A Clinical and Molecular Teratology
  • [Show abstract] [Hide abstract] ABSTRACT: Background: We examined risks associated with joint exposure of gene variants and pesticides. Methods: Analyses included 189 cases and 390 male controls born from 1991 to 2003 in California's San Joaquin Valley. We used logistic regression to examine risks associated with joint exposures of gene variants and pesticides that our previous work identified as associated with hypospadias. Genetic variables were based on variants in DGKK, genes involved in sex steroid synthesis/metabolism, and genes involved in genital tubercle development. Pesticide exposure was based on residential proximity to commercial agricultural pesticide applications. Results: Odds ratios (ORs) were highest among babies with joint exposures, who had two- to fourfold increased risks; for example, the OR was 3.7 (95% confidence interval [CI], 0.8-16.5) among subjects with the risk-associated DGKK haplotype and pesticide exposure; OR, 1.5 (95% CI, 0.7-3.1) among subjects with the haplotype and no pesticide exposure; and OR, 0.9 (95% CI, 0.5-1.6) among subjects without the haplotype but with pesticide exposure, relative to subjects with neither. However, results did not provide statistical evidence that these risks were significantly greater than expected on an additive scale, relative to risks associated with one exposure at a time. Conclusion: We observed elevated risks associated with joint exposures to selected pesticides and genetic variants but no statistical evidence for interaction. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.
    No preview · Article · Apr 2016 · Birth Defects Research Part A Clinical and Molecular Teratology
  • [Show abstract] [Hide abstract] ABSTRACT: This Viewpoint discusses preterm birth and the need to link and integrate epidemiologic to genetic and cellular data to look for predictive, diagnostic, and causal pathways that might be safely targeted for prevention or amelioration. Preterm birth is a ubiquitous yet mysterious phenomenon. Preterm birth, defined as birth prior to 37 weeks’ gestation, is now the primary worldwide cause of morbidity and mortality in the newborn period and the top cause of child mortality among those younger than 5 years, accounting for 1 million deaths every year.1 Nevertheless, it remains poorly understood.
    No preview · Article · Apr 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose of review: Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease in premature infants. Twin studies have shown strong heritability underlying this disease; however, the genetic architecture of BPD remains unclear. Recent findings: A number of studies employed different approaches to characterize the genetic aberrations associated with BPD, including candidate gene studies, genome-wide association studies, exome sequencing, integrative omics analysis, and pathway analysis. Candidate gene studies identified a number of genes potentially involved with the development of BPD, but the etiological contribution from each gene is not substantial. Copy number variation studies and three independent genome-wide association studies did not identify genetic variations significantly and consistently associated with BPD. A recent exome-sequencing study pointed to rare variants implicated in the disease. In this review, we summarize these studies' methodology and findings, and suggest future research directions to better understand the genetic underpinnings of this potentially life-long lung disease. Summary: Genetic factors play a significant role in the development of BPD. Recent studies suggested that rare variants in genes participating in lung development pathways could contribute to BPD susceptibility.
    No preview · Article · Mar 2016 · Current Opinion in Pediatrics
  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To identify associations between second-trimester serum inflammatory biomarkers and preterm birth among obese women.Methods: In this nested case-control study, we compared 65 serum inflammatory biomarkers in obese women whose pregnancies resulted in early spontaneous preterm birth (<32 weeks gestation, n = 34) to obese women whose pregnancies resulted in term birth (n = 34). These women were selected from a larger population-based California cohort. Random forest and classification and regression tree techniques were employed to identify biomarkers of importance, and adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using logistic regression.Results: Random forest and classification and regression tree techniques found that soluble vascular endothelial growth factor receptor-3 (sVEGFR3), soluble interleukin-2 receptor alpha-chain (sIL-2RA) and soluble tumor necrosis factor receptor-1 (sTNFR1) were related to preterm birth. Using multivariable logistic regression to compare preterm cases and term controls, decreased serum levels of sVEGFR3 and increased serum levels of sIL-2RA and sTNFR1 were associated with increased risk of preterm birth among obese women, aOR = 3.2 (95% CI: 1.0–9.9), aOR = 2.8 (95% CI: 0.9–9.0), and aOR = 4.1 (95% CI: 1.2–14.1), respectively.Conclusions: In this pilot study, we identified three serum biomarkers indicative of inflammation to be associated with spontaneous preterm birth among obese women: sVEGFR3, sIL-2RA and sTNFR1.
    No preview · Article · Dec 2015 · Journal of Maternal-Fetal and Neonatal Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background: We examined whether risks of 32 birth defects were higher than expected in the presence of overweight or obese body mass index (BMI) and low diet quality, based on estimating individual and joint effects of these factors and calculating relative excess risk due to interaction. Methods: Analyses included mothers of 20,250 cases with birth defects and 8617 population-based controls without birth defects born from 1997 to 2009 and interviewed for the National Birth Defects Prevention Study. We used logistic regression to generate adjusted odds ratios (AORs) reflecting the combined effects of BMI and diet quality. We focused analyses on 16 birth defects (n = 11,868 cases, 8617 controls) for which initial results suggested an association with BMI or diet quality. Results: Relative to the reference group (normal weight women with not low diet quality, i.e., >lowest quartile), AORs for low diet quality among normal weight women tended to be >1, and AORs for overweight and obese women tended to be stronger among women who had low diet quality than not low diet quality. For 9/16 birth defects, AORs for obese women who had low diet quality-the group we hypothesized to have highest risk-were higher than other stratum-specific AORs. Most relative excess risk due to interactions were positive but small (<0.5), with confidence intervals that included zero. Conclusion: These findings provide evidence for the hypothesis of highest birth defect risks among offspring to women who are obese and have low diet quality but insufficient evidence for an interaction of these factors in their contribution to risk. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Dec 2015 · Birth Defects Research Part A Clinical and Molecular Teratology
  • [Show abstract] [Hide abstract] ABSTRACT: Background: We examined associations of birth defects with residential proximity to commercial agricultural pesticide applications in California. Subjects included 367 cases representing five types of birth defects and 785 nonmalformed controls born 1997 to 2006. Methods: Associations with any versus no exposure to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for covariates. Overall, 46% of cases and 38% of controls were classified as exposed to pesticides within a 500 m radius of mother's address during a 3-month periconceptional window. Results: We estimated odds ratios (ORs) for 85 groups and 95 chemicals with five or more exposed cases and control mothers. Ninety-five percent confidence intervals (CI) excluded 1.0 for 11 ORs for groups and 22 ORs for chemicals, ranging from 1.9 to 3.1 for groups and 1.8 to 4.9 for chemicals except for two that were <1 (noted below). Conclusion: For groups, these ORs were for anotia/microtia (n = 95 cases) and dichlorophenoxy acids/esters and neonicotinoids; anorectal atresia/stenosis (n = 77) and alcohol/ethers and organophosphates (these ORs were < 1.0); transverse limb deficiencies (n = 59) and dichlorophenoxy acids/esters, petroleum derivatives, and triazines; and craniosynostosis (n = 79) and alcohol/ethers, avermectins, neonicotinoids, and organophosphates. For chemicals, ORs were: anotia/microtia and five pesticides from the groups dichlorophenoxy acids/esters, copper-containing compounds, neonicotinoids, organophosphates, and triazines; transverse limb deficiency and six pesticides - oxyfluorfen and pesticides from the groups copper-containing compounds, 2,6-dinitroanilines, neonicotinoids, petroleum derivatives and polyalkyloxy compounds; craniosynostosis and 10 pesticides - oxyfluorfen and pesticides from the groups alcohol/ethers, avermectins, n-methyl-carbamates, neonicotinoids, ogranophosphates (two chemicals), polyalkyloxy compounds (two chemicals), and pyrethroids; and congenital diaphragmatic hernia (n = 62) and a copper-containing compound. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Dec 2015 · Birth Defects Research Part A Clinical and Molecular Teratology
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    [Show abstract] [Hide abstract] ABSTRACT: Background We examined the association of maternal obesity with risk of stillbirth, focusing on whether the pattern of results varied by gestational age or maternal race-ethnicity or parity. Methods Analyses included 4,012 stillbirths and 1,121,234 liveborn infants delivered in California from 2007–2010. We excluded stillbirths due to congenital anomalies, women with hypertensive disorders or diabetes, and plural births, to focus on fetuses and women without these known contributing conditions. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI). Separate models were run for stillbirths delivered at 20–23, 24–27, 28–31, 32–36, 37–41 weeks, relative to liveborn deliveries at 37–41 weeks. Results For stillbirth at 20–23 weeks, RRs were elevated for all race-ethnicity and parity groups. The RR for a 20-unit change in BMI (which reflects the approximate BMI difference between a normal weight and an Obese III woman) was 3.5 (95% CI 2.2, 5.6) for nulliparous white women and ranged from 1.8 to 5.0 for other sub-groups. At 24–27 weeks, the association was significant (p<0.05) only for multiparous non-Hispanic whites; at 28–31 weeks, for multiparous whites and nulliparous whites and blacks; at 32–36 weeks, for multiparous whites and nulliparous blacks; and at 37–41 weeks, for all groups except nulliparous blacks. The pattern of results was similar when restricted to stillbirths due to unknown causes and somewhat stronger when restricted to stillbirths attributable to obstetric causes. Conclusion Increased risks were observed across all gestational ages, and some evidence of heterogeneity of the associations was observed by race-ethnicity and parity.
    Preview · Article · Oct 2015 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Importance There is a well-described association between maternal diabetes mellitus and risk of congenital heart disease (CHD) in offspring. Although the clinical diagnoses of type 2 diabetes or gestational diabetes are strong risk factors for CHD, subclinical abnormalities of glucose and insulin metabolism are common within the general population and could also confer risk for CHD. We hypothesize that continuous measures of blood analytes related to maternal diabetes are related to odds of cardiac malformations.Objective To explore the potential association of 2 different CHD phenotypes in offspring with maternal midpregnancy measures of glucose and insulin.Design, Setting, and Participants Case-control study from a population-based cohort of 277 pregnant women in southern and central California carrying infants with tetralogy of Fallot (TOF) (n = 55), dextrotransposition of the great arteries (dTGA) (n = 42), or healthy infants without CHD (n = 180). Serum samples were collected from 2003 through 2007. The analysis was conducted from March through June 2015.Main Outcomes and Measures Blood analytes related to maternal glucose metabolism were measured from random nonfasting second-trimester blood samples. We measured serum insulin levels by a validated radioimmunoassay, and we measured glucose levels. Multivariable logistic regression models estimated the association between these levels and case status.Results Serum glucose values were elevated in the maternal samples for offspring with TOF (median, 97.0 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) relative to controls (median, 91.5 mg/dL) (P = .01, Wilcoxon rank sum test), a phenomenon not observed in the maternal samples for offspring with dTGA (median, 90.0 mg/dL) relative to controls (P = .18, Wilcoxon rank sum test). Serum insulin levels were significantly different between controls (median, 18.8 μIU/mL [to convert to picomoles per liter, multiply by 6.945]) and maternal samples for offspring with dTGA (median, 13.1 μIU/mL; P = .048, Wilcoxon rank sum test) but not with TOF (median, 14.3 μIU/mL; P = .35, Wilcoxon rank sum test). Relative to maternal blood glucose levels of infants without cardiac malformations, we observed that maternal blood glucose levels in models including insulin were strongly associated with odds of TOF (adjusted odds ratio = 7.54; 95% CI, 2.30-24.69) but not with dTGA (adjusted odds ratio = 1.16; 95% CI, 0.28-4.79).Conclusions and Relevance These results represent a direct correlation of glucose as a continuous variable to odds of specific cardiac malformations. The association between serum glucose and odds of TOF indicates the need for additional epidemiological and mechanistic investigations into the risk conferred by insulin signaling and glucose metabolism during early pregnancy.
    Full-text · Article · Oct 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Environmental pollutants and neighbourhood socioeconomic factors have been associated with neural tube defects, but the potential impact of interaction between ambient air pollution and neighbourhood socioeconomic factors on the risks of neural tube defects is not well understood. Methods: We used data from the California Center of the National Birth Defects Study and the Children's Health and Air Pollution Study to investigate whether associations between air pollutant exposure in early gestation and neural tube defects were modified by neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997-2006. There were 5 pollutant exposures, 3 outcomes, and 9 neighbourhood socioeconomic factors included for a total of 135 investigated associations. Estimates were adjusted for maternal race-ethnicity, education, and multivitamin use. Results: We present below odds ratios (ORs) that exclude 1 and a chi-square test of homogeneity P-value of <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of particulate matter <10 μm (PM10 ) among those living in a neighbourhood with: (i) median household income of less than $30 000 per year [OR 5.1, 95% confidence interval (CI) 1.7, 15.3]; (ii) more than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and (iii) more than 30% with less than or equal to a high school education (OR 3.2, 95% CI 1.4, 7.4). The ORs were not statistically significant among those higher socioeconomic status (SES) neighbourhoods. Conclusions: Our results demonstrate effect modification by neighbourhood socioeconomic factors in the association of particulate matter and neural tube defects in California.
    No preview · Article · Oct 2015 · Paediatric and Perinatal Epidemiology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective To evaluate whether better diet quality in mothers is associated with lower risk for major non-syndromic congenital heart defects in their children. Design Multicentre population-based case–control study, the National Birth Defects Prevention Study. Setting Ten sites in the USA. Participants Mothers of babies with major non-syndromic congenital heart defects (n=9885) and mothers with unaffected babies (n=9468) with estimated date of delivery from 1997 to 2009. Main outcome measures Adjusted ORs for specific major congenital heart defects by quartiles of maternal diet quality in the year before pregnancy, assessed by the Diet Quality Index for pregnancy (DQI-P) and the Mediterranean Diet Score. Quartile 1 (Q1) reflecting the worst diet quality and Q4 the best diet quality. Results Better diet quality was associated with reduced risk for some conotruncal and atrial septal heart defects. For DQI-P, estimated risks reductions (Q4 vs Q1) for conotruncal defects were 37% for tetralogy of Fallot (OR 0.63, 95% CI 0.49 to 0.80) and 24% overall (OR 0.76, 95% CI 0.64 to 0.91); and for septal defects, 23% for atrial septal defects (OR 0.77, 95% CI 0.63 to 0.94) and 14% overall (OR 0.86, 95% CI 0.75 to 1.00). Risk reductions were weaker or minimal for most other major congenital heart defects. Conclusions Better diet quality is associated with a reduced occurrence of some conotruncal and septal heart defects. This finding suggests that a reduction in certain cardiac malformations may be an additional benefit of improved maternal diet quality, reinforcing current preconception care recommendations.
    No preview · Article · Aug 2015 · Archives of Disease in Childhood - Fetal and Neonatal Edition
  • [Show abstract] [Hide abstract] ABSTRACT: To study the relationship between maternal asthma and the development of bronchopulmonary dysplasia (BPD). Using a large population-based California cohort, we investigated associations between maternal asthma and preterm birth subtype, as well as maternal asthma and BPD. We used data from 2007-2010 maternal delivery discharge records of 2 009 511 pregnancies and International Classification of Diseases, Ninth Revision codes. Preterm birth was defined as <37 weeks gestational age (GA), with subgroups of <28 weeks, 28-32 weeks, and 33-37 weeks GA, as well as preterm subtype, defined as spontaneous, medically indicated, or unknown. Linkage between the 2 California-wide datasets yielded 21 944 singleton preterm infants linked to their mother's records, allowing estimation of the risk of BPD in mothers with asthma and those without asthma. Maternal asthma was associated with increased odds (OR, 1.42; 95% CI, 1.38-1.46) of preterm birth at <37 weeks GA, with the greatest risk for 28-32 GA (aOR, 1.60; 95% CI, 1.47-1.74). Among 21 944 preterm infants, we did not observe an elevated risk for BPD in infants born to mothers with asthma (aOR, 1.03; 95% CI, 0.9-1.2). Stratification by maternal treatment with antenatal steroids revealed increased odds of BPD in infants whose mothers had asthma but did not receive antenatal steroids (aOR, 1.54; 95% CI, 1.15-2.06), but not in infants whose mothers had asthma and were treated with antenatal steroids (aOR, 0.85; 95% CI, 0.67-1.07). Asthma in mothers who did not receive antenatal steroid treatment is associated with an increased risk of BPD in their preterm infants. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · The Journal of pediatrics
  • No preview · Article · Aug 2015 · Annals of epidemiology
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    Full-text · Dataset · Jul 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases. Mass cytometry (or Cytometry by Time Of Flight mass spectrometry, CyTOF) has already been employed in clinical studies to comprehensively survey patients' circulating immune system. As interest in the "bedside" application of mass cytometry is growing, the delineation of relevant methodological issues is called for. This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells (PBMCs), design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed. A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide (LPS at 0, 0.1, 1, 10, and 100 ng mL-1) to examine dose-dependent signaling responses within the toll-like receptor 4 (TLR4) pathway. Complementary analyses, grounded in traditional or unsupervised gating strategies of immune cell subsets, indicated that the prpS6 and pMAPKAPK2 responses in classical monocytes are accentuated in women with a history of preterm birth (FDR<1%). The results suggest that women predisposed to preterm birth may be prone to mount an exacerbated TLR4 response during the course of pregnancy. This important hypothesis-generating finding points to the power of single-cell mass cytometry to detect biologically important differences in a relatively small patient cohort.
    No preview · Article · Jul 2015 · Cytometry Part A

Publication Stats

10k Citations
1,077.79 Total Impact Points


  • 2016
    • Stanford University
      Stanford, California, United States
  • 2007
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 2006
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Angeles, CA, United States
  • 2005
    • Children's Hospital Oakland Research Institute
      Oakland, California, United States
    • University of California, San Francisco
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      San Francisco, California, United States
  • 2004
    • University of Nebraska at Omaha
      Omaha, Nebraska, United States
  • 2003
    • University of California, Berkeley
      Berkeley, California, United States
  • 2002
    • Texas A&M University
      College Station, Texas, United States
  • 1999
    • March of Dimes Foundation
      White Plains, New York, United States