S Kennedy

International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project

BACKGROUNDnIn 2006, WHO published international growth standards for children younger than 5 years, which are now accepted worldwide. In the INTERGROWTH-21(st) Project, our aim was to complement them by developing international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants.nnnMETHODSnINTERGROWTH-21(st) 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-21(st) 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.nnnFINDINGSnWe 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.nnnINTERPRETATIONnWe 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.nnnFUNDINGnBill & Melinda Gates Foundation.

International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project

BACKGROUNDnIn 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-21(st) Project, aimed to develop international growth and size standards for fetuses.nnnMETHODSnThe 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.nnnFINDINGSnWe 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.nnnINTERPRETATIONnWe recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations.nnnFUNDINGnBill & Melinda Gates Foundation.

Endometriosis in monozygotic twins

OBJECTIVEnTo describe the occurrence of endometriosis in monozygotic twins.nnnDESIGNnPostal questionnaire plus confirmation of disease status.nnnSETTINGnTwins were recruited via the American Endometriosis Association and the National Endometriosis Society of Great Britain and via British gynecologists.nnnRESULT(S)nFourteen twin pairs were concordant for endometriosis, and two were discordant. Nine pairs of twins had moderate-severe endometriosis.nnnCONCLUSION(S)nThese findings contribute to the growing body of literature that suggests endometriosis has a genetic basis.

The objectives, design and implementation of the INTERGROWTH‐21st Project

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.

The genetic basis of endometriosis.

Family studies have long suggested a role for genetic factors in the aetiology of endometriosis. The influence of genes on disease development has mainly been researched independently of environmental factors, yet their interaction must play an important role. Greater exposure to retrograde menstruation and oestrogen is likely to increase the risk of endometriosis; toxic compounds such as dioxin may increase the risk, although the only direct evidence has come from primate studies. Previous association studies implicated GALT (a gene involved in galactose metabolism), and GSTM1 and NAT2 (genes encoding for the detoxification enzymes) as possible disease susceptibility genes. Recent findings have added to the evidence for the involvement of GSTM1 and NAT2, but have cast doubt on the role of GALT. However, the design of many genetic and epidemiological studies has been inadequate with respect to sample size, consistency in phenotype definition, and the choice of control populations. These features are likely to influence results, and could partly explain the lack of consistency in the findings. Future studies should use a consistent disease definition and be of appropriate epidemiological design.

The genetics of endometriosis

There is mounting evidence that endometriosis is inherited as a complex trait, like diabetes or asthma. This implies there are environmental factors, such as dioxin, that are interacting with multiple genetic susceptibility loci to produce the phenotype. The Oxford Endometriosis Gene (OXEGENE) study, an international collaborative project, seeks to identify the susceptibility loci using linkage analysis; the aim then is to use positional cloning techniques to identify genes that predispose women to the disease. Analysis of the biochemical function of the gene products will lead to a better understanding of the pathophysiology and aetiology of endometriosis. New therapies may be designed based upon knowledge of the gene function and disease associated genetic markers may be used to identify women at high risk of developing the disease.

International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy.

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.

Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review

Neurodevelopmental disorders are increasingly believed to originate from intrauterine growth restriction (IUGR). Current reviews exploring the neurodevelopmental effects of IUGR, however, are mostly based on birthweight, an inadequate proxy.

Ultrasound evidence of early fetal growth restriction after maternal malaria infection.

Background Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation. Methodology/Principal Findings In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001–10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (nu200a=u200a336) and were not (nu200a=u200a3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; −0.57 (1.13) versus −0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (pu200a=u200a0.01) were also independently associated with a smaller BPD in multivariate analysis. Conclusions/Significance Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy.

International estimated fetal weight standards of the INTERGROWTH-21st Project.

Estimated fetal weight (EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH‐21st Fetal Growth Standards that are available for use worldwide.