The 10,000-year biocultural history of fallow deer and its implications for conservation policy.

Over the last 10,000 y, humans have manipulated fallow deer populations with varying outcomes. Persian fallow deer (Dama mesopotamica) are now endangered. European fallow deer (Dama dama) are globally widespread and are simultaneously considered wild, domestic, endangered, invasive and are even the national animal of Barbuda and Antigua. Despite their close association with people, there is no consensus regarding their natural ranges or the timing and circumstances of their human-mediated translocations and extirpations. Our mitochondrial analyses of modern and archaeological specimens revealed two distinct clades of European fallow deer present in Anatolia and the Balkans. Zooarchaeological evidence suggests these regions were their sole glacial refugia. By combining biomolecular analyses with archaeological and textual evidence, we chart the declining distribution of Persian fallow deer and demonstrate that humans repeatedly translocated European fallow deer, sourced from the most geographically distant populations. Deer taken to Neolithic Chios and Rhodes derived not from nearby Anatolia, but from the Balkans. Though fallow deer were translocated throughout the Mediterranean as part of their association with the Greco-Roman goddesses Artemis and Diana, deer taken to Roman Mallorca were not locally available Dama dama, but Dama mesopotamica. Romans also initially introduced fallow deer to Northern Europe but the species became extinct and was reintroduced in the medieval period, this time from Anatolia. European colonial powers then transported deer populations across the globe. The biocultural histories of fallow deer challenge preconceptions about the divisions between wild and domestic species and provide information that should underpin modern management strategies.

Practice guideline: joint CCMG-SOGC recommendations for the use of chromosomal microarray analysis for prenatal diagnosis and assessment of fetal loss in Canada.

BACKGROUND: The aim of this guideline is to provide updated recommendations for Canadian genetic counsellors, medical geneticists, maternal fetal medicine specialists, clinical laboratory geneticists and other practitioners regarding the use of chromosomal microarray analysis (CMA) for prenatal diagnosis. This guideline replaces the 2011 Society of Obstetricians and Gynaecologists of Canada (SOGC)-Canadian College of Medical Geneticists (CCMG) Joint Technical Update. METHODS: A multidisciplinary group consisting of medical geneticists, genetic counsellors, maternal fetal medicine specialists and clinical laboratory geneticists was assembled to review existing literature and guidelines for use of CMA in prenatal care and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the CCMG membership-at-large for feedback and, following incorporation of feedback, was approved by the CCMG Board of Directors on 5 June 2017 and the SOGC Board of Directors on 19 June 2017. RESULTS AND CONCLUSIONS: Recommendations include but are not limited to: (1) CMA should be offered following a normal rapid aneuploidy screen when multiple fetal malformations are detected (II-1A) or for nuchal translucency (NT) ≥3.5 mm (II-2B) (recommendation 1); (2) a professional with expertise in prenatal chromosomal microarray analysis should provide genetic counselling to obtain informed consent, discuss the limitations of the methodology, obtain the parental decisions for return of incidental findings (II-2A) (recommendation 4) and provide post-test counselling for reporting of test results (III-A) (recommendation 9); (3) the resolution of chromosomal microarray analysis should be similar to postnatal microarray platforms to ensure small pathogenic variants are detected. To minimise the reporting of uncertain findings, it is recommended that variants of unknown significance (VOUS) smaller than 500 Kb deletion or 1 Mb duplication not be routinely reported in the prenatal context. Additionally, VOUS above these cut-offs should only be reported if there is significant supporting evidence that deletion or duplication of the region may be pathogenic (III-B) (recommendation 5); (4) secondary findings associated with a medically actionable disorder with childhood onset should be reported, whereas variants associated with adult-onset conditions should not be reported unless requested by the parents or disclosure can prevent serious harm to family members (III-A) (recommendation 8).The working group recognises that there is variability across Canada in delivery of prenatal testing, and these recommendations were developed to promote consistency and provide a minimum standard for all provinces and territories across the country (recommendation 9).

Human exposure to environmental contaminants and congenital anomalies: a critical review.

Congenital anomalies are an important cause of infant mortality and disability. Developmental exposure to environmental contaminants is thought to increase the risk for congenital anomalies. Herein, we describe a critical review of the literature conducted between February and March 2014 yielding 3057 references from which 97 unique relevant articles published from 2003 through 2014 were evaluated. Common congenital anomalies including hypospadias, cryptorchidism, anogenital distance (AGD), congenital heart defects and oral clefts were well represented in the literature whereas other outcomes such as neural tube defects, limb deficiency defects and gastroschisis were rarely described. While definitions used for congenital anomalies and methods of ascertainment were usually consistent across studies, inconsistencies were frequently found in grouping of different congenital heart defects. Despite strong links between some congenital anomalies and parental occupation, these studies are unable to provide clear insight into the specific chemicals responsible owing to lack of direct measures of exposure. In comparison, data are mixed for contaminant exposures at concentrations representative of results from contemporary biomonitoring studies. Of the environmental contaminants studied, the association between phthalate exposures and developmental abnormalities of the male reproductive tract received the greatest attention. Important limitations of the literature studied relate to adequacy of sample size, absence of or weaknesses in exposure assessment methodologies, failure to account for biological plausibility and grouping of congenital anomalies with divergent mechanisms. We conclude that the literature is inadequate at this time to support a conclusion that exposure to environmental contaminants are or are not associated with increased risks for congenital anomalies in the general population.

A multi-isotope investigation of diet and subsistence amongst island and mainland populations from early medieval western Britain.

OBJECTIVES: This is the first investigation of dietary practices amongst multiple early medieval populations (AD 500-1000) from Wales and the Isle of Man using carbon, nitrogen, and sulphur isotope analysis. The analysis will illuminate similarities or differences between the diets and subsistence strategies of populations occupying different geographical regions, specifically those living in marginal coastal regions in comparison to inland populations well-connected to ecclesiastical centres and high-status settlements. MATERIALS AND METHODS: One hundred and two human skeletons were sampled for carbon and nitrogen isotope analysis, and 69 human skeletons were sampled for sulphur isotope analysis from nine cemetery sites from western Britain (Isle of Man = 3, southwest Wales = 4, southeast Wales = 2). Thirteen faunal skeletons from St Patrick's Chapel (southwest Wales) were sampled for carbon, nitrogen, and sulphur isotope analysis. RESULTS: Human δ13 C values range from -19.4‰ to -21.2‰ (δ13 C mean=-20.4 ±0.4‰, 1σ, n = 86), and δ15 N values range from 9.1‰ to 13.8‰ (δ15 N mean = 10.8 ± 0.9‰, 1σ, n = 86). δ34 S values range from 1.2‰ to 18.4‰ (δ34 S mean = 11.6 ± 4.5‰, 1σ, n = 66). Significant differences were noted between the mean δ13 C, δ15 N and δ34 S values according to geographic region: Isle of Man (δ13 C = -20.7 ± 0.4‰, δ15 N = 11.4 ±0.6‰, n = 13/86; δ34 S mean = 17.1 ±0.6, n = 4/66), southwest Wales (δ13 C = -20.5 ± 0.4‰, δ15 N = 11.0 ±1‰, n = 32/86; δ34 S = 16.1 ± 2.1, n = 21/66), and southeast Wales (δ13 C =-20.3 ±0.4‰, δ15 N = 10.4 ±0.7‰, n = 41/86; δ34 S= 8.8 ±3‰, n = 41/66). Faunal δ13 C values range from -23.1‰ to -21.2‰ (δ13 C mean= -22.1 ±0.5‰, 1σ, n = 13), and δ15 N values range from 6.3‰ to 9.8‰ (δ15 N mean = 7.3 ± 1.1‰, 1σ, n = 13). δ34 S values range from 4.7‰ to 18.4‰ (δ34 S mean= 16.3 ± 3.6‰, 1σ, n = 13). CONCLUSIONS: The data reveal a reliance on terrestrial protein, however differences are observed between the resource consumption of populations from southwest Wales and the Isle of Man in comparison to the populations from southeast Wales. Populations from the west coast have a marine sulphur signature that reflects their coastal proximity and may also include a reliance on seaweed as a fertiliser/food source. Populations in the southeast were connected to ecclesiastical centres and high-status settlements and had access to inland-grown produce. The data add support to the suggestion that δ34 S can be used as a mobility indicator.

Using state and provincial surveillance programs to reduce risk of recurrence of neural tube defects in the United States and Canada: A missed opportunity?

BACKGROUND: Once a woman has had a fetus or infant affected with a neural tube defect (NTD), the risk of recurrence is approximately 3%. This risk can be significantly reduced by folic acid supplement consumption during the periconceptional period; however, this requires women at risk to be adequately informed about the appropriate dosage and timing of supplement intake before planning another pregnancy. As birth defects surveillance programs are tasked with identifying and documenting NTD-affected pregnancies and births, they are in a unique position to support recurrence prevention activities. METHODS: In 2015, we surveyed state and provincial birth defects surveillance programs to assess their NTD recurrence prevention activities. The online survey was sent to programs in 52 United States (U.S.) jurisdictions and all 13 provinces and territories in Canada. Findings were compared with a similar survey conducted in 2005 among U.S. programs. RESULTS: In 2015, of the 44 U.S. and Canadian surveillance programs that responded, only 9 programs (7 U.S. and 2 Canadian) reported currently having activities specifically directed toward preventing NTD recurrence. Compared with a 2005 survey of U.S. programs, the number of U.S. programs working on NTD recurrence prevention decreased by almost 50% (from 13 to 7 programs). CONCLUSION: The number of birth defects surveillance programs with NTD recurrence prevention activities has decreased over the past decade due to a range of barriers, most notably a lack of resources. However, while some recurrence prevention activities require part-time staff, other activities could be accomplished using minimal resources. Birth Defects Research (Part A) 106:875-880, 2016.© 2016 Wiley Periodicals, Inc.

Brief report pregnancy outcome in women assigned an ICD-9/ICD-9-CM 655.0 code "central nervous system malformation in fetus affecting management of pregnancy": can these codes aid in surveillance for central nervous system defects?

BACKGROUND: The difficulty many birth defects registries have in identifying early pregnancy terminations can lead to significant underreporting of certain types of malformations. This study was designed to determine the potential benefit of using maternal ICD-9 codes relating to management of pregnancy due to fetal anomaly in surveillance of central nervous system (CNS) defects (655.0). METHODS: Women assigned the ICD-9/ICD-9-CM (henceforth termed ICD-9) code 655.0 between 1990 and 2000 were ascertained from two administrative health databases in Manitoba, Canada, one relating to maternal serum screening and one based on hospital discharges. Information was collected on the type of CNS defect identified and whether it was isolated or associated with other anomalies. The relationship of these variables to pregnancy outcome and its potential impact on surveillance for these types of defects was explored. RESULTS: Neural tube defects were the most common finding (67%) identified in the fetuses/infants of women assigned code 655.0, followed by hydrocephaly (20%) and Dandy-Walker anomaly (6%), but the proportion of neural tube defect cases declined after food fortification with folic acid. Termination of pregnancy occurred in ∼50% of neural tube defect cases, 18% before 20 weeks of gestation, but was rare for other CNS defects. CONCLUSION: The maternal ICD-9 code 655.0 had a very high (97%) positive predictive value for identifying fetuses with a CNS defect; 655.00 was particularly effective in identifying neural tube defects pregnancies terminated before 20 weeks gestation that would be difficult to ascertain, especially by passive surveillance systems using infant related data alone.

Wet feet: developing sulfur isotope provenance methods to identify wetland inhabitants.

The stable isotopes of sulfur provide a distinctive signature for marine proximity and interaction. Exploring coastal proximity has been the principal application of sulfur isotopes in archaeology and palaeoecology, but this deals only with high (greater than 14‰) isotope values, meaning little interpretation has been gained from lower values. Progress has been hindered by issues with biosphere mapping. Air pollution can impact modern landscapes, significantly lowering sulfur isotope baselines, leading to the assumption that modern vegetation-based sulfur maps are not reliable. This research explores the potential of previously undiagnostic low, and often, negative sulfur isotope values for identifying wetland dwellers. Impervious clays that support wetlands are distinctive ecosystems and this study tests the hypothesis that they will produce low isotope values owing to both the underlying substrate and to redox conditions. Primary mapping of targeted areas using modern plants highlights zones with natural negative sulfur values and demonstrates that this constitutes a distinctive wetland signature. Analysis of modern and archaeological fauna demonstrates that these distinctive isotope compositions are transferred into the food chain. These findings propel the interpretative potential of sulfur isotopes forward and add to the growing knowledge to provide means for identifying archaeological humans and animals raised in wetlands.

The oxygen isotope relationship between the phosphate and structural carbonate fractions of human bioapatite.

RATIONALE: Oxygen isotope analysis of archaeological human dental enamel is widely used as a proxy for the drinking water composition (δ(18)O(DW)) of the individual and thus can be used as an indicator of their childhood place of origin. In this paper we demonstrate the robustness of structural carbonate oxygen isotope values (δ(18)O(C)) in bioapatite to preserve the life signal of human tooth enamel by comparing it with phosphate oxygen isotope values (δ(18)O(P)) derived from the same archaeological human tooth enamel samples. METHODS: δ(18)O(C) analysis was undertaken on 51 archaeological tooth enamel samples previously analysed for δ(18)O(P) values and strontium isotopes. δ(18)O(C) values were determined on a GV IsoPrime dual inlet mass spectrometer, following a series of methodological tests to assess: (1) The reaction time needed to ensure complete release of CO(2) from structural carbonate in the enamel; (2) The effect of an early pre-treatment with dilute acetic acid to remove diagenetic carbonate; (3) Analytical error; (4) Intra-tooth variation; and (5) Diagenetic alteration. RESULTS: This study establishes a direct relationship between δ(18)O(C) and δ(18)O(P) values from human tooth enamel (δ(18)O(P) = 1.0322 × Î´(18)O(C) - 9.6849). We have combined this equation with the drinking water equation of Daux et al. (J. Hum. Evol. 2008, 55, 1138) to allow direct calculation of δ(18)O(DW) values from human bioapatite δ(18)O(C) (δ(18)O(DW) = 1.590 × Î´(18)O(C) - 48.634). CONCLUSIONS: This is the first comprehensive study of the relationship between the ionic forms of oxygen (phosphate oxygen and structural carbonate) in archaeological human dental enamel. The new equation will allow direct comparison of data produced by the different methods and allow drinking water values to be calculated from structural carbonate data with confidence.

Applying lead (Pb) isotopes to explore mobility in humans and animals.

Lead (Pb) isotopes provide a complementary method to other provenance tools for tracking the origin and movement of humans and animals. The method is founded in the geographic distribution of Pb isotope ratios. However, unlike the Sr isotope method that is closely linked to the lithology of underlying rocks, Pb more closely reflects the tectonic regimes. This makes it particularly pertinent to use in Britain as there is major tectonic boundary (the Iapetus Suture) that runs between Berwick-upon-Tweed and the Solway Firth providing a compositional boundary in Pb isotope domains that approximates to the geographic areas of Scotland versus England and Wales. Modern pollution makes it difficult to use modern floral or faunal samples to characterize biosphere variation, and so we use geological datasets to define isoscape variation and present the first Pb isotope map of Britain. We have validated the use of these data form biosphere studies using well provenanced samples. Reference fields of diagnostic compositions, are created in µ-T space and these have been used in a test case to assess the geographic origins of Neolithic animals in Great Britain.

Population-based surveillance of severe microcephaly and congenital Zika syndrome in Canada.

PURPOSE: To estimate the minimum incidence of congenital Zika syndrome (CZS) and severe microcephaly in Canada and describe key clinical, epidemiological, aetiological and outcome features of these conditions. METHODS: Two separate national surveillance studies were conducted on CZS and severe microcephaly using the well-established Canadian Paediatric Surveillance Program from 2016 to 2019. Over 2700 paediatricians across Canada were surveyed monthly and asked to report demographic details, pregnancy and travel history, infant anthropometry, clinical features and laboratory findings of newly identified cases. Reports were reviewed to assign an underlying aetiology of severe microcephaly. Incidence rates were estimated using monthly live birth denominators. RESULTS: Thirty-four infants met the case definition for severe microcephaly and <5 met the case definition for CZS. The associated minimum incidence rates were 4.5 per 100 000 live births for severe microcephaly and 0.1-0.5 per 100 000 live births for CZS. Of severe microcephaly cases, 53% were attributed to genetic causes, 15% to infectious or ischaemic causes and 32% to unknown causes. The median head circumference-for-age Z-score at birth was -3.2 (IQR -3.8 to -2.6), and catch-up growth was often not achieved. Common clinical features included intracranial abnormalities (n=23), dysmorphology (n=19) and developmental delays (n=14). Mothers of infants with non-genetic aetiologies travelled during pregnancy more often (10/16) than mothers of infants with genetic aetiologies (<5/18; p<0.01). CONCLUSION: Severe microcephaly and CZS are both rare in Canada. Minimum incidence rates can be used as a baseline against which novel or re-emergent causes of severe microcephaly or CZS can be compared.

Petrological and geochemical characterisation of the sarsen stones at Stonehenge.

Little is known of the properties of the sarsen stones (or silcretes) that comprise the main architecture of Stonehenge. The only studies of rock struck from the monument date from the 19th century, while 20th century investigations have focussed on excavated debris without demonstrating a link to specific megaliths. Here, we present the first comprehensive analysis of sarsen samples taken directly from a Stonehenge megalith (Stone 58, in the centrally placed trilithon horseshoe). We apply state-of-the-art petrographic, mineralogical and geochemical techniques to two cores drilled from the stone during conservation work in 1958. Petrographic analyses demonstrate that Stone 58 is a highly indurated, grain-supported, structureless and texturally mature groundwater silcrete, comprising fine-to-medium grained quartz sand cemented by optically-continuous syntaxial quartz overgrowths. In addition to detrital quartz, trace quantities of silica-rich rock fragments, Fe-oxides/hydroxides and other minerals are present. Cathodoluminescence analyses show that the quartz cement developed as an initial <10 µm thick zone of non-luminescing quartz followed by ~16 separate quartz cement growth zones. Late-stage Fe-oxides/hydroxides and Ti-oxides line and/or infill some pores. Automated mineralogical analyses indicate that the sarsen preserves 7.2 to 9.2 area % porosity as a moderately-connected intergranular network. Geochemical data show that the sarsen is chemically pure, comprising 99.7 wt. % SiO2. The major and trace element chemistry is highly consistent within the stone, with the only magnitude variations being observed in Fe content. Non-quartz accessory minerals within the silcrete host sediments impart a trace element signature distinct from standard sedimentary and other crustal materials. 143Nd/144Nd isotope analyses suggest that these host sediments were likely derived from eroded Mesozoic rocks, and that these Mesozoic rocks incorporated much older Mesoproterozoic material. The chemistry of Stone 58 has been identified recently as representative of 50 of the 52 remaining sarsens at Stonehenge. These results are therefore representative of the main stone type used to build what is arguably the most important Late Neolithic monument in Europe.

Reduction in neural-tube defects after folic acid fortification in Canada.

BACKGROUND: In 1998, folic acid fortification of a large variety of cereal products became mandatory in Canada, a country where the prevalence of neural-tube defects was historically higher in the eastern provinces than in the western provinces. We assessed changes in the prevalence of neural-tube defects in Canada before and after food fortification with folic acid was implemented. METHODS: The study population included live births, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces from 1993 to 2002. On the basis of published results of testing of red-cell folate levels, the study period was divided into prefortification, partial-fortification, and full-fortification periods. We evaluated the relationship between baseline rates of neural-tube defects in each province and the magnitude of the decrease after fortification was implemented. RESULTS: A total of 2446 subjects with neural-tube defects were recorded among 1.9 million births. The prevalence of neural-tube defects decreased from 1.58 per 1000 births before fortification to 0.86 per 1000 births during the full-fortification period, a 46% reduction (95% confidence interval, 40 to 51). The magnitude of the decrease was proportional to the prefortification baseline rate in each province, and geographical differences almost disappeared after fortification began. The observed reduction in rate was greater for spina bifida (a decrease of 53%) than for anencephaly and encephalocele (decreases of 38% and 31%, respectively). CONCLUSIONS: Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high.

Trans-Atlantic slavery: isotopic evidence for forced migration to Barbados.

The question of the ultimate origin of African slaves is one of the most perplexing in the history of trans-Atlantic slavery. Here we present the results of a small, preliminary isotopic study that was conducted in order to determine the geographical origin of 25 enslaved Africans who were buried at the Newton plantation, Barbados, sometime between the late 17th and early 19th century. In order to gain a more nuanced understanding of the slaves' origin, we used a combination of carbon, nitrogen, oxygen, and strontium isotope analyses. Carbon and nitrogen isotope ratios were determined in bone and dentinal collagen; oxygen and strontium isotopes were measured in tooth enamel. Results suggest that the majority of individuals were born on the island, if not the estate itself. Seven individuals, however, yielded enamel oxygen and strontium ratios that are inconsistent with a Barbadian origin, which strongly suggests that we are dealing with first-generation captives who were brought to the island with the slave trade. This idea is also supported by the fact that their carbon and nitrogen stable isotope values differ markedly between their teeth and bones. These intra-skeletal shifts reflect major dietary changes that probably coincided with their enslavement and forced migration to Barbados. While it is impossible to determine their exact origins, the results clearly demonstrate that the slaves did not all grow up in the same part of Africa. Instead, the data seem to suggest that they originated from at least three different areas, possibly including the Gold Coast and the Senegambia.

Feasting and Mobility in Iron Age Ireland: Multi-isotope analysis reveals the vast catchment of Navan Fort, Ulster.

Navan Fort is an iconic prehistoric Irish ceremonial centre and the legendary capital of Ulster. The fort has produced an exceptional pig-dominated faunal assemblage that also contained a barbary macaque skull. Dating from the 4th to 1st century BC, it is likely to be a ceremonial feasting centre that may have drawn people and their animals from across Ulster and beyond. This study uses a multi-isotope (87Sr/86Sr, δ34S, δ13C, δ15N) approach to identify non-local animals and reconstruct site catchment. New biosphere mapping means that isotope data can be more confidently interpreted and the combination of strontium and sulphur analysis has the potential to estimate origins. In the absence of human remains, fauna provide the best proxy for human movement. Results for the 35 analysed animals are wide-ranging, especially in terms of strontium (0.707-0.715), which has the largest range for an Irish site. Sulphur values are more restricted (13.1‰-17.1‰) but are high in the context of British and Irish data. Results provide clear evidence for animals (and thus people) coming from across Ulster and beyond, demonstrating the site's wide catchment. Navan Fort was clearly a major ceremonial centre with far-reaching influence and hosted feasts that drew people and animals from afar.

The association of split hand foot malformation (SHFM) and congenital heart defects.

BACKGROUND: Split hand foot malformation (SHFM) (cleft hand, central ray deficiency) is a highly variable malformation that shows genetic heterogeneity with at least five loci mapped to date. SHFM occurs as an isolated finding or in association with other anomalies, including congenital heart defects (CHDs). METHODS: In total 48 SHFM1, 52 SHFM3, 48 SHFM4, 21 SHFM5, and four chromosome 8 patients were evaluated. In addition, we performed a literature review to identify "unmapped" SHFM patients with CHD to evaluate the various etiologies of this combination of findings. The London Dysmorphology Database also served as a resource to identify syndromes with this combination of phenotypic findings. Only patients presenting with both SHFM and CHD were included in the analysis. Classification of CHD among mapped and unmapped SHFM patients was performed utilizing the revised Clark classification. A closer inspection of the types of CHD found in this patient group was performed in order to investigate possible pathogenetic mechanisms. RESULTS: CHDs were found in 10% of SHFM1 patients, 47% of SHFM5 patients, but were not reported in SHFM2, SHFM4 patients, or patients mapped to chromosome 8. Forty-two syndromic cases and 15 cases of unrecognized syndromes were identified. CONCLUSIONS: The higher frequency of heart defects seen in SHFM1 and SHFM5 of the mapped patient group raises the question as to whether common mechanisms/genetic players are involved. Candidate genes for SHFM1 and SHFM5 include members of the DLX homeobox gene family.

Impact of folic acid food fortification on the birth prevalence of lipomyelomeningocele in Canada.

BACKGROUND: Recent studies reported no reduction in the frequency of lipomeningomyelocele (LMMC) in Hawaii and Nova Scotia after the implementation of a folic acid food fortification policy in 1998, while a marked reduction in the prevalence of other NTDs was observed. This study was performed to assess the prevalence of LMMC in Canada in relation to the timing of food fortification. METHODS: The study population included livebirths, stillbirths, and terminations of pregnancies because of fetal anomaly to women residing in seven Canadian provinces, from 1993 to 2002. In each province, the ascertainment of NTD cases relied on multiple sources, and in addition all medical charts were reviewed. The study period was divided into pre-, partial, and full fortification periods, based on results of red cell folate tests published in the literature. RESULTS: A total of 86 LMMC cases were recorded among approximately 1.9 million live births. The average birth prevalence rate was 0.05/1,000, ranging from a minimum of 0.01/1,000 in 2002 to a maximum of 0.08/1,000 in 1999. There was statistical heterogeneity between years (p = .01), but no pattern compatible with a decrease following fortification. Comparing the full fortification period with the prefortification period, there was a slight but not statistically significant decrease in LMMC birth prevalence. CONCLUSIONS: LMMC seems to be pathogenically distinct from myelomeningocele and more studies are needed to understand the embryologic mechanisms leading to this condition, and the environmental and genetic factors involved in its etiology.