Publications by authors named "Lydi M J W van Driel"

13 Publications

  • Page 1 of 1

Long-term yield of pancreatic cancer surveillance in high-risk individuals.

Gut 2021 Apr 5. Epub 2021 Apr 5.

Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Objective: We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.

Design: From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.

Results: 366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1-32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).

Conclusion: The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.
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http://dx.doi.org/10.1136/gutjnl-2020-323611DOI Listing
April 2021

Nationwide treatment and outcomes of perihilar cholangiocarcinoma.

Liver Int 2021 Feb 28. Epub 2021 Feb 28.

Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

Background: Perihilar cholangiocarcinoma (pCCA) is a rare tumour that requires complex multidisciplinary management. All known data are almost exclusively derived from expert centres. This study aimed to analyse the outcomes of patients with pCCA in a nationwide cohort.

Methods: Data on all patients diagnosed with pCCA in the Netherlands between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Data included type of hospital of diagnosis and the received treatment. Outcomes included the type of treatment and overall survival.

Results: A total of 2031 patients were included and the median overall survival for the overall cohort was 5.2 (95% CI 4.7-5.7) months. Three-hundred-ten (15%) patients underwent surgical resection, 271 (13%) underwent palliative systemic treatment, 21 (1%) palliative local anti-cancer treatment and 1429 (70%) underwent best supportive care. These treatments resulted in a median overall survival of 29.6 (95% CI 25.2-34.0), 12.2 (95% CI 11.0-13.3), 14.5 (95%CI 8.2-20.8) and 2.9 (95% CI 2.6-3.2) months respectively. Resection rate was 13% in patients who were diagnosed in non-academic and 32% in academic centres (P < .001), which resulted in a survival difference in favour of academic centres. Median overall survival was 9.7 (95% CI 7.7-11.7) months in academic centres compared to 4.9 (95% CI 4.3-5.4) months in non-academic centres (P < .001).

Conclusions: In patients with pCCA, resection rate and overall survival were higher for patients who were diagnosed in academic centres. These results show population-based outcomes of pCCA and highlight the importance of regional collaboration in the treatment of these patients.
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http://dx.doi.org/10.1111/liv.14856DOI Listing
February 2021

Optimization of Pancreatic Juice Collection: A First Step Toward Biomarker Discovery and Early Detection of Pancreatic Cancer.

Am J Gastroenterol 2020 12;115(12):2103-2108

Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Introduction: Imaging-based surveillance programs fail to detect pancreatic ductal adenocarcinoma at a curable stage, creating an urgent need for diagnostic biomarkers.

Methods: Secretin-stimulated pancreatic juice (PJ) was collected from the duodenal lumen during endoscopic ultrasound. The yield of biomarkers and organoids was compared for 2 collection techniques (endoscope suction channel vs catheter-based) and 3 periods (0-4 vs 4-8 vs 8-15 minutes).

Results: Collection through the endoscope suction channel was superior to collection with a catheter. Collection beyond 8 minutes reduced biomarker yield. PJ-derived organoid culture was feasible.

Discussion: The optimal protocol for secretin-stimulated PJ collection is through the endoscope suction channel for 8 minutes allowing biomarker detection and organoid culture.
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http://dx.doi.org/10.14309/ajg.0000000000000939DOI Listing
December 2020

Optimizing cytological specimens of EUS-FNA of solid pancreatic lesions: A pilot study to the effect of a smear preparation training for endoscopy personnel on sample quality and accuracy.

Diagn Cytopathol 2021 Feb 24;49(2):295-302. Epub 2020 Oct 24.

Department of Pathology, Erasmus MC University Medical Center Rotterdam, the Netherlands and Institute for Pathology, Dueren, Germany.

Background: In the absence of rapid on-side pathological evaluation, endoscopy staff generally "smears" endoscopic ultrasound guided fine needle aspiration (EUS-FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear-preparation-training for endoscopy staff.

Methods: In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS-centers in the Netherlands were invited to participate in a EUS-FNA smear-preparation-training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre-training "control" slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS-FNA of solid pancreatic lesions.

Results: Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty-eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10).

Conclusion: In this pilot EUS-FNA smear-preparation-training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities.
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http://dx.doi.org/10.1002/dc.24645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820998PMC
February 2021

Quality and performance of validated prognostic models for survival after resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

HPB (Oxford) 2021 Jan 25;23(1):25-36. Epub 2020 Aug 25.

Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands. Electronic address:

Background: The objective of this systematic review was to evaluate the performance of prognostic survival models for intrahepatic cholangiocarcinoma (iCCA) when validated in an external dataset. Furthermore, it sought to identify common prognostic factors across models, and assess methodological quality of the studies in which the models were developed.

Methods: The PRISMA guidelines were followed. External validation studies of prognostic models for patients with iCCA were searched in 5 databases. Model performance was assessed by discrimination and calibration.

Results: Thirteen external validation studies were identified, validating 18 different prognostic models. The Wang model was the sole model with good performance (C-index above 0.70) for overall survival. This model incorporated tumor size and number, lymph node metastasis, direct invasion into surrounding tissue, vascular invasion, Carbohydrate antigen (CA) 19-9, and carcinoembryonic antigen (CEA). Methodological quality was poor in 11/12 statistical models. The Wang model had the highest score with 13 out of 17 points.

Conclusion: The Wang model for prognosis after resection of iCCA has good quality and good performance at external validation, while most prognostic models for iCCA have been developed with poor methodological quality and show poor performance at external validation.
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http://dx.doi.org/10.1016/j.hpb.2020.07.007DOI Listing
January 2021

Diagnostic yield and agreement on fine-needle specimens from solid pancreatic lesions : comparing the smear technique to liquid-based cytology.

Endosc Int Open 2020 Feb 22;8(2):E155-E162. Epub 2020 Jan 22.

Department of Pathology, Erasmus MC University Medical Center Rotterdam, the Netherlands.

 The traditional "smear technique" for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71),  = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42),  = 0.56) or Cell block (62 % (39/63),  = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42),  = 0.02) or Cell block samples (40 % (25/63),  < 0.001) than smears (76 % (54/71)). Agreement on malignancy was equally good for smears and LBC (ĸ = 0.71 versus ĸ = 0.70,  = 0.98), but lower for ThinPrep (ĸ = 0.26,  = 0.01) than smears. After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE.
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http://dx.doi.org/10.1055/a-1038-4103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976322PMC
February 2020

Collaboration of community hospital endosonographers improves diagnostic yield of endoscopic ultrasonography guided tissue acquisition of solid pancreatic lesions.

Endosc Int Open 2019 Jun 12;7(6):E800-E807. Epub 2019 Jun 12.

Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.

Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) is the method of choice for establishing a pathological diagnosis of solid pancreatic lesions. Data on quality and yield of EUS-guided TA performed in community hospitals are lacking. A study was performed to determine and improve the diagnostic yield of EUS-guided TA in a group of community hospitals. Following analysis of the last 20 EUS-guided TA procedures of solid pancreatic lesions performed in each of four community hospitals, a collaborative EUS interest group was formed and a prospective registry was started. During meetings of the interest group, feedback on results per center were provided and strategies for improvement were discussed. In the BEFORE team formation cohort, 80 procedures were performed in 66 patients. In the AFTER team formation cohort, 133 procedures were performed in 125 patients. After team formation, the rate of adequate sample increased from 80 % (95 %CI [0.7 - 0.9]) to 95 % (95 %CI [0.9 - 1.0]) , diagnostic yield of malignancy improved from 28 % (95 %CI [0.2 - 0.4]) to 64 % (95 % CI [0.6 - 0.7]), and sensitivity of malignancy improved from 63 % (95 %CI [0.4 - 0.8]) to 84 % (95 %CI [0.8 - 0.9]). Multivariate regression analysis revealed team formation to be the only variable significantly associated with an increased rate of adequate sample. Formation of a regional EUS interest group with regular feedback on results per center, and discussions on methods and techniques used, significantly improved the outcome of EUS-guided TA procedures in patients with solid pancreatic lesions in community hospitals.
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http://dx.doi.org/10.1055/a-0898-3389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561772PMC
June 2019

Congenital heart defects and biomarkers of methylation in children: a case-control study.

Eur J Clin Invest 2011 Feb 27;41(2):143-50. Epub 2010 Sep 27.

Department of Obstetrics and Gynaecology/Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.

Background: Derangements in the maternal methylation pathway, expressed by global hypomethylation and hyperhomocysteinemia, are associated with the risk of having a child with a congenital heart defect (CHD). It is not known whether periconception exposure to these metabolic derangements contributes to chromosome segregation and metabolic programming of this pathway in the foetus.

Design: In a Dutch population-based case-control study of 143 children with CHD and 186 healthy children, we investigated S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), total homocysteine (tHcy), the vitamins folate and B12 and the functional single nucleotide polymorphisms in the folate gene MTHFR 677C>T and 1298A>C. Comparisons were made between cases and controls adjusting for age, medication, vitamin use and CHD family history.

Results: In the overall CHD group, the median concentrations of SAM (P = 0·011), folate in serum (P = 0·021) and RBC (P = 0·030) were significantly higher than in the controls. Subgroup analysis showed that this was mainly attributable to complex CHD with higher SAM (P < 0·001), SAH (P = 0·012) and serum folate (P = 0·010) independent of carriership of MTHFR polymorphisms. Highest concentrations of SAM, SAH and folate RBC were observed in complex syndromic CHD. The subgroup of children with Down syndrome, however, showed significantly higher SAH (P = 0·037) and significantly lower SAM:SAH ratio (P = 0·034) compared with other complex CHD, suggesting a state of global hypomethylation.

Conclusion: High concentrations of methylation biomarkers in very young children are associated with complex CHD. Down syndrome and CHD may be associated with a global hypomethylation status, which has to be confirmed in tissues and global DNA methylation in future studies.
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http://dx.doi.org/10.1111/j.1365-2362.2010.02388.xDOI Listing
February 2011

Body mass index is an important determinant of methylation biomarkers in women of reproductive ages.

J Nutr 2009 Dec 7;139(12):2315-21. Epub 2009 Oct 7.

Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.

B vitamin deficiencies lead to moderate hyperhomocysteinemia, which has been associated with health and disease. However, concomitant derangements in cellular methylation, reflected by altered plasma S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) concentrations, may be the primary cause. Therefore, we identified determinants of homocysteine, SAM, and SAH concentrations in 336 women, aged 20-48 y, as part of a large study focusing on risk factors for reproductive disorders. Blood was obtained to determine plasma SAM, SAH, and total homocysteine (tHcy), serum vitamin B-12 and folate, RBC folate concentrations, and the related single nucleotide polymorphisms 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C > T and 1298A > C, methionine synthase reductase (MTRR) 66A > G, and nicotinamide N-methyltransferase IVS1-151G > A. Questionnaires provided information on demographics, lifestyles, and nutrient intakes. Correlation coefficients were calculated and multivariable associations were assessed with a general linear model. Serum folate was positively correlated with SAM concentrations (r = 0.159; P = 0.004). Folate and vitamin B-12 were not correlated with SAH concentrations or the SAM:SAH ratio but were inversely correlated with tHcy concentrations (serum folate r = -0.324; RBC folate r = -0.294; vitamin B-12 r = -0.307; P < 0.01). From the multivariable analysis, BMI was the strongest determinant of SAM (standardized beta = 19.145; P < 0.001) and SAH concentrations (standardized beta = 3.241; P = 0.010). MTHFR 677TT (standardized beta = 0.195; P = 0.001), B vitamin supplement use (standardized beta = -0.156; P < 0.001) and dietary protein intake (standardized beta = -0.011; P < 0.001) were the strongest determinants of tHcy concentrations. Thus, the determinants of SAM and SAH differ from those of tHcy concentrations. Given that BMI was a strong determinant of SAM concentrations, it should be included in future studies on cellular methylation.
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http://dx.doi.org/10.3945/jn.109.109710DOI Listing
December 2009

Maternal global methylation status and risk of congenital heart diseases.

Obstet Gynecol 2008 Aug;112(2 Pt 1):277-83

Departments of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Pediatrics, Pediatric Cardiology CAHAL-Centre for Congenital Anomalies of the Heart Amsterdam/Leiden, the Netherlands.

Objective: To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring.

Methods: As part of a case-control study in the western part of the Netherlands, we evaluated 231 mothers of children with CHD and 315 control mothers of nonmalformed children. The total case group was analyzed and stratified into isolated (n=180) and nonisolated CHDs (n=51). The latter subgroup was further subdivided into Nonsyndromic (n=20), Down Syndrome (n=19), and Other Syndromes (n=12). A multivariable general linear model was used to test for differences between the case groups and controls. All analyses were adjusted for current B vitamin supplement use.

Results: Plasma total homocysteine was significantly different between the total case group (median, range 10.3, 4.0-43.8, P=.026) and the nonisolated cases (11.1, 5.5-43.8, P=.006) compared with the controls (10.0, 5.3-42.0). The subgroup of Down Syndrome presented significantly higher total homocysteine and S-adenosylhomocysteine levels and a lower S-adenosylmethionine/S-adenosylhomocysteine ratio than controls.

Conclusion: Maternal hyperhomocysteinemia, and not hypomethylation, is a risk factor for having a child with CHD. Maternal hypomethylation, however, seems to be associated with offspring having CHD and Down syndrome.
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http://dx.doi.org/10.1097/AOG.0b013e31817dd058DOI Listing
August 2008

Two MTHFR polymorphisms, maternal B-vitamin intake, and CHDs.

Birth Defects Res A Clin Mol Teratol 2008 Jun;82(6):474-81

Department of Obstetrics and Gynecology/Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.

Background: The methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are associated with complex congenital malformations. Whether these polymorphisms are associated with CHDs is not clear. We studied both MTHFR polymorphisms, folate and vitamin B2 by maternal food intake and supplements, and CHD risk.

Methods: A case-control family study was conducted in a European population in the Netherlands including 230 case and 251 control children with both parents. Approximately 17 months after the index pregnancy, mothers filled out standardized questionnaires on periconception use of folic acid supplements and a validated food frequency questionnaire on current dietary folate and vitamin B2 intake. All subjects were genotyped for the MTHFR C677T and A1298C polymorphisms. Data were analyzed by logistic regression analysis and ORs and 95% CIs were calculated. For the interaction analysis the dominant model was used.

Results: The risk estimates for the MTHFR 677 CT genotypes were 1.4 (0.9-2.0) in mothers, 1.1 (0.8-1.6) in fathers, and 1.2 (0.8-1.7) in children, and for the MTHFR 677 TT genotypes 0.9 (0.6-1.2), 1.4 (1.0-1.9), and 1.0 (0.7-1.3), respectively. The MTHFR 1298 CC genotype in fathers and the MTHFR 1298 AC genotype in children significantly reduced CHD risk, 0.6 (0.5-0.9) and 0.6 (0.4-0.9), respectively. Of interest is the significant interaction (p = .008) towards a nearly twofold increased risk in mothers carrying the MTHFR 1298C allele and using a periconception folic acid supplement.

Conclusions: The MTHFR C677T and A1298C polymorphisms are not strong risk factors for CHDs.
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http://dx.doi.org/10.1002/bdra.20463DOI Listing
June 2008

Eight-fold increased risk for congenital heart defects in children carrying the nicotinamide N-methyltransferase polymorphism and exposed to medicines and low nicotinamide.

Eur Heart J 2008 Jun 25;29(11):1424-31. Epub 2008 Apr 25.

Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.

Aims: Congenital heart defects (CHDs) have a multifactorial origin, in which subtle genetic factors and peri-conception exposures interact. We hypothesize that derangements in the homocysteine and detoxification pathways, due to a polymorphism in the nicotinamide N-methyltransferase (NNMT) gene, low maternal dietary nicotinamide intake, and medicine use in the peri-conception period, affect CHD risk.

Methods And Results: In 292 case and 316 control families, maternal peri-conception medicine use and low dietary intake of nicotinamide (
Conclusion: Children carrying the NNMT A allele face additional CHD risk in combination with peri-conception exposure to medicines and/or a low dietary nicotinamide intake. These findings provide a first set of data against which future studies with larger sample sizes can be compared with.
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http://dx.doi.org/10.1093/eurheartj/ehn170DOI Listing
June 2008

Genetic and lifestyle factors related to the periconception vitamin B12 status and congenital heart defects: a Dutch case-control study.

Mol Genet Metab 2008 May 15;94(1):112-9. Epub 2008 Jan 15.

Department of Obstetrics, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.

Maternal hyperhomocysteinemia is associated with congenital heart defects (CHDs) in the offspring. A low periconception vitamin B12 status is determined by genetic and lifestyle factors and causes hyperhomocysteinemia. We investigated methionine synthase reductase (MTRR) and transcobalamin II (TC) genes and maternal intake and serum concentrations of vitamin B12 in association with CHD risk. Seventeen months after the index-pregnancy, we studied 230 children with a CHD and 251 non-malformed children and their parents. Data were collected on current and periconception maternal vitamin supplement use and maternal dietary vitamin B12 intake of the month before the study moment. Blood samples were taken for the determination of MTRR A66G and TC C776G genotypes in families and maternal serum vitamin B12 concentrations. Transmission disequilibrium tests and univariate and multivariate analyses were applied. Allele transmissions were not significantly distorted. The MTRR and TC genotypes did not significantly affect CHD risk. Neither polymorphisms in mothers and/or children revealed significant interactions nor in combination with low vitamin B12 intake. Low maternal serum vitamin B12 combined with the maternal or child's MTRR 66 GG genotype resulted in odds ratios of 1.4 (95% confidence interval 0.6-3.5) and 1.3 (0.5-3.4), respectively. The TC 776 GG genotype in mothers and children revealed risk estimates of 2.2 (0.7-7.1) and 1.9 (0.5-7.4), respectively. In conclusion, MTRR 66 GG and TC 776 GG genotypes in mothers and children may contribute to the risk of CHDs, particularly when the maternal vitamin B12 status is low. The future enlargement of our sample size might demonstrate significant associations.
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http://dx.doi.org/10.1016/j.ymgme.2007.12.002DOI Listing
May 2008