Ann Lambert

University of Oxford, Oxford, England, United Kingdom

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Publications (15)136.81 Total impact

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    ABSTRACT: Background In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21st Project, aimed to develop international growth and size standards for fetuses. Methods The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown–rump length in the first trimester. The five primary ultrasound measures of fetal growth—head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length—were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. Findings We screened 13 108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and −2·69 mm (3·2) for head circumference; 0·83 mm (0·9), −0·05 mm (0·8), and −0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and −1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and −4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and −0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. Interpretation We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. Funding Bill & Melinda Gates Foundation.
    The Lancet 09/2014; 384(9946):869-879. · 39.21 Impact Factor
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    ABSTRACT: Objectives There are no international standards for relating fetal crown-rump length (CRL) to gestational age (GA), and most existing charts have considerable methodological limitations. The INTERGROWTH-21st Project aimed to produce the first, international standards for early fetal size and ultrasound dating of pregnancy based on CRL measurement.Methods Urban areas in eight geographically diverse countries that met strict eligibility criteria were selected for the prospective, population-based recruitment, between 9+0 to 13+6 weeks of gestation, of healthy well-nourished women with singleton pregnancies at low risk of fetal growth impairment. GA was calculated on the basis of a certain LMP, regular menstrual cycle and lack of hormonal medication or breastfeeding in the preceding two months. CRL was measured using strict protocols and quality control measures. All women were followed up throughout pregnancy until delivery and hospital discharge. Neonatal and fetal deaths, severe pregnancy complications and congenital abnormalities were excluded.ResultsA total of 4,607 women were enrolled in the Fetal Growth Longitudinal Study (FGLS), one of the three main components of the INTERGROWTH-21st Project, of whom 4,321 women had a live singleton birth in the absence of severe maternal conditions or congenital abnormalities detected by ultrasound or at birth. The CRL was measured in 56 women at <9+0 weeks of gestation, resulting in 4,265 women who contributed data to the final analysis. The mean CRL and standard deviation (SD) increased with GA almost linearly. Their relationship to GA is defined by the two equations: Mean CRL (mm) = −50.6562 + 0.815118*GA + 0.00535302*GA2, and SD of CRL (mm) = −2.21626 + 0.0984894*GA, where GA is expressed in days. The formula for GA estimation is defined by the two equations: GA (days) = 40.9041 + 3.21585*CRL0.5 + 0.348956*CRL, and SD of GA (days) = 2.39102 + 0.0193474*CRL, where CRL is expressed in mm.Conclusions We have produced international prescriptive standards for early fetal linear size and ultrasound dating of pregnancy in the first trimester that can be used throughout the world.
    Ultrasound in Obstetrics and Gynecology 07/2014; · 3.56 Impact Factor
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    ABSTRACT: SummaryBackground In 2006, WHO published international growth standards for children younger than 5 years, which are now accepted worldwide. In the INTERGROWTH-21st Project, our aim was to complement them by developing international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants. Methods INTERGROWTH-21st is a population-based project that assessed fetal growth and newborn size in eight geographically defined urban populations. These groups were selected because most of the health and nutrition needs of mothers were met, adequate antenatal care was provided, and there were no major environmental constraints on growth. As part of the Newborn Cross-Sectional Study (NCSS), a component of INTERGROWTH-21st Project, we measured weight, length, and head circumference in all newborn infants, in addition to collecting data prospectively for pregnancy and the perinatal period. To construct the newborn standards, we selected all pregnancies in women meeting (in addition to the underlying population characteristics) strict individual eligibility criteria for a population at low risk of impaired fetal growth (labelled the NCSS prescriptive subpopulation). Women had a reliable ultrasound estimate of gestational age using crown–rump length before 14 weeks of gestation or biparietal diameter if antenatal care started between 14 weeks and 24 weeks or less of gestation. Newborn anthropometric measures were obtained within 12 h of birth by identically trained anthropometric teams using the same equipment at all sites. Fractional polynomials assuming a skewed t distribution were used to estimate the fitted centiles. Findings We identified 20 486 (35%) eligible women from the 59 137 pregnant women enrolled in NCSS between May 14, 2009, and Aug 2, 2013. We calculated sex-specific observed and smoothed centiles for weight, length, and head circumference for gestational age at birth. The observed and smoothed centiles were almost identical. We present the 3rd, 10th, 50th, 90th, and 97th centile curves according to gestational age and sex. Interpretation We have developed, for routine clinical practice, international anthropometric standards to assess newborn size that are intended to complement the WHO Child Growth Standards and allow comparisons across multiethnic populations. Funding Bill & Melinda Gates Foundation.
    The Lancet 01/2014; 384(9946):857-868. · 39.21 Impact Factor
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    ABSTRACT: Background Large differences exist in size at birth and in rates of impaired fetal growth worldwide. The relative effects of nutrition, disease, the environment, and genetics on these differences are often debated. In clinical practice, various references are often used to assess fetal growth and newborn size across populations and ethnic origins, whereas international standards for assessing growth in infants and children have been established. In the INTERGROWTH-21st Project, our aim was to assess fetal growth and newborn size in eight geographically defined urban populations in which the health and nutrition needs of mothers were met and adequate antenatal care was provided. Methods For this study, fetal growth and newborn size were measured in two INTERGROWTH-21st component studies using prespecified markers and the same methods, equipment, and selection criteria. In the Fetal Growth Longitudinal Study (FGLS), we studied educated, affluent, healthy women, with adequate nutritional status who were at low risk of intrauterine growth restriction. The primary markers of fetal growth were ultrasound measurements of fetal crown-rump length at less than 14 weeks and 0 days of gestation and fetal head circumference from 14 weeks and 0 days to 40 weeks and 0 days of gestation, and birthlength for newborn size. In the concomitant, population-based Newborn Cross-Sectional Study (NCSS), we measured birthlength in all newborn babies from the eight geographically defined urban populations with the same methods, instruments, and staff as in FGLS. From this large NCSS cohort, we selected an FGLS-like subpopulation to match FGLS with the same eligibility criteria. Findings Between May 14, 2009, and Aug 2, 2013, we enrolled 4607 women in FGLS and 59 137 women in NCSS. From NCSS, 20 486 (34·6%) women met the FGLS eligibility criteria, and constituted the FGLS-like subpopulation. With variance component analysis, only between 1·9% and 3·5% of the total variability in crown-rump length, fetal head circumference, and newborn birthlength could be attributed to between-site differences. With standardised site effect analysis in 16 gestational age windows from 9 weeks and 0 days of gestation to birth for the three measures (128 comparisons), only one was marginally higher than 0·5 SD of the standardised site difference range. Sensitivity analyses, excluding individual populations in turn from the pooling of all-site centiles across gestational ages, showed no noticeable effect on the 3rd, 50th, and 97th centiles derived from the remaining populations. Our populations were consistent at birth with those in the WHO Multicentre Growth Reference Study (MGRS). The mean birthlength for term newborn babies in that study was 49·5 cm (SD 1·9), which was very similar to that in the FGLS cohort (49·4 cm [1·9]) and the NCSS derived FGLS-like subpopulation (49·3 cm [1·8]). Interpretation Fetal growth and newborn length are similar across diverse geographical settings when mothers' nutritional and health needs are met, and environmental constraints on growth are low. The findings for birthlength are in strong agreement with those of the WHO MGRS. These results provide the conceptual frame to create international standards for growth from conception to newborn baby, which will extend the present infant to childhood WHO MGRS standards. Funding Bill & Melinda Gates Foundation.
    The Lancet Diabetes & Endocrinology. 01/2014;
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    ABSTRACT: Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH-21(st) Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocol's entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in-depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change.
    BJOG An International Journal of Obstetrics & Gynaecology 09/2013; 120 Suppl 2:129-38. · 3.76 Impact Factor
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    ABSTRACT: Please cite this paper as: Villar J, Altman D, Purwar M, Noble J, Knight H, Ruyan P, Cheikh Ismail L, Barros F, Lambert A, Papageorghiou A, Carvalho M, Jaffer Y, Bertino E, Gravett M, Bhutta Z, Kennedy S, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). The objectives, design and implementation of the INTERGROWTH-21st Project. BJOG 2013; 120 (Suppl. 2): 9–26. INTERGROWTH-21st is a multicentre, multiethnic, population-based project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care.
    BJOG An International Journal of Obstetrics & Gynaecology 09/2013; 120(s2). · 3.76 Impact Factor
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    ABSTRACT: f Programa de P os-Graduac ß~ ao em Sa ude e Comportamento, Universidade Cat olica de Pelotas, g Programa de P os-Graduac ß~ ao em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil h Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH-21 st Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocol's entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in-depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change., for the International Fetal and Newborn Growth Consortium for the 21 st Century (INTERGROWTH-21 st). A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21 st Project. BJOG 2013;120 (Suppl. 2): 129–138.
    07/2013;
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    ABSTRACT: To refine a previously reported linkage peak for endometriosis on chromosome 10q26, and conduct follow-up analyses and a fine-mapping association study across the region to identify new candidate genes for endometriosis. Case-control study. Academic research. Cases=3,223 women with surgically confirmed endometriosis; controls=1,190 women without endometriosis and 7,060 population samples. Analysis of 11,984 single nucleotide polymorphisms on chromosome 10. Allele frequency differences between cases and controls. Linkage analyses on families grouped by endometriosis symptoms (primarily subfertility) provided increased evidence for linkage (logarithm of odds score=3.62) near a previously reported linkage peak. Three independent association signals were found at 96.59 Mb (rs11592737), 105.63 Mb (rs1253130), and 124.25 Mb (rs2250804). Analyses including only samples from linkage families supported the association at all three regions. However, only rs11592737 in the cytochrome P450 subfamily C (CYP2C19) gene was replicated in an independent sample of 2,079 cases and 7,060 population controls. The role of the CYP2C19 gene in conferring risk for endometriosis warrants further investigation.
    Fertility and sterility 06/2011; 95(7):2236-40. · 3.97 Impact Factor
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    ABSTRACT: Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10⁻⁷, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10⁻⁹, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10⁻³, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10⁻⁹ (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.
    Nature Genetics 01/2011; 43(1):51-4. · 35.21 Impact Factor
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    ABSTRACT: To determine the relationship between disease severity and patient characteristics in endometriosis. Cross-sectional study of self-reported survey data. Academic research setting. One thousand women in the Oxford Endometriosis Gene (OXEGENE) study. None. Participants were assigned to one of two groups with predominantly revised AFS stage I-II (group I, n = 423) or III-IV disease (group II, n = 517). Their characteristics were compared by disease extent. Most participants were white (96%) and of reproductive age (81%). Women in group I were significantly younger on entering the study (39.9 +/- 0.5 vs. 44.5 +/- 0.4 years). Overall time to diagnosis did not differ between groups. The most common symptoms leading to a diagnosis were dysmenorrhea (79%) and pelvic pain (69%). In group II, subfertility (21.5% vs. 30.0%) and an ovarian mass (7.3% vs. 29.4%) more commonly led to a diagnosis, whereas dyspareunia (51.1% vs. 39.5%) was significantly more common in group I. Subfertility (41.5% vs. 53.4%) remained more common in group II throughout reproductive life, although birth and miscarriage rates were similar. Pelvic pain is common to all with endometriosis and those with more extensive disease report higher rates of subfertility. Remarkably, the time to diagnosis was similar among women.
    Fertility and sterility 04/2008; 89(3):538-45. · 3.97 Impact Factor
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    ABSTRACT: The aim of the International Endogene Study is to discover genes that influence susceptibility to endometriosis. The study brings together two research groups based in Australia and the United Kingdom that independently have been collecting families for linkage analysis and candidate gene studies. Both groups used similar methods to recruit families, obtain clinical notes, assign disease status based on the operative records and available histology, and collect common clinical data including age at onset of symptoms, age at diagnosis, and symptoms experienced. Recruitment has been mainly from Australia, the United Kingdom, and the United States. All affected participants have surgically confirmed disease. None. Clinical and epidemiological data. To date, >1,100 families with affected sisters have been recruited, and >1,200 triads (affected women and both parents), for case-control studies. We have created the largest resource yet assembled of clinical data and DNA for linkage and association studies in endometriosis. The increase in power to detect susceptibility genes vindicates the decision to merge the two studies and demonstrates the value of large-scale international collaboration.
    Fertility and Sterility 10/2002; 78(4):679-85. · 4.17 Impact Factor
  • Nat.Genet.
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    ABSTRACT: OBJECTIVE: To determine the relationship between disease severity and patient characteristics in endometriosis. DESIGN: Cross-sectional study of self-reported survey data. SETTING: Academic research setting. PATIENT(S): One thousand women in the Oxford Endometriosis Gene (OXEGENE) study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Participants were assigned to one of two groups with predominantly revised AFS stage I-II (group I, n = 423) or III-IV disease (group II, n = 517). Their characteristics were compared by disease extent. RESULT(S): Most participants were white (96%) and of reproductive age (81%). Women in group I were significantly younger on entering the study (39.9 +/- 0.5 vs. 44.5 +/- 0.4 years). Overall time to diagnosis did not differ between groups. The most common symptoms leading to a diagnosis were dysmenorrhea (79%) and pelvic pain (69%). In group II, subfertility (21.5% vs. 30.0%) and an ovarian mass (7.3% vs. 29.4%) more commonly led to a diagnosis, whereas dyspareunia (51.1% v
    Fertil.Steril. 89(3):538-545.
  • International Journal of Gynecology & Obstetrics. 119:S168.