), 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.

ObjectivesThere 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.MethodsUrban areas in eight geographically diverse countries that met strict eligibility criteria were selected for the prospective, population-based recruitment, between 9 + 0 and 13 + 6 weeks' 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 last menstrual period, regular menstrual cycle and lack of hormonal medication or breastfeeding in the preceding 2 months. CRL was measured using strict protocols and quality-control measures. All women were followed up throughout pregnancy until delivery and hospital discharge. Cases of neonatal and fetal death, severe pregnancy complications and congenital abnormalities were excluded from the study.ResultsA total of 4607 women were enrolled in the Fetal Growth Longitudinal Study, one of the three main components of the INTERGROWTH-21st Project, of whom 4321 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' gestation; these were excluded, resulting in 4265 women who contributed data to the final analysis. The mean CRL and SD increased with GA almost linearly, and their relationship to GA is given by the following two equations (in which GA is in days and CRL in mm): mean CRL = −50.6562 + (0.815118 × GA) + (0.00535302 × GA2); and SD of CRL = −2.21626 + (0.0984894 × GA). GA estimation is carried out according to the two equations: GA = 40.9041 + (3.21585 × CRL0.5) + (0.348956 × CRL); and SD of GA = 2.39102 + (0.0193474 × CRL).ConclusionsWe 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. © 2014 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Meticulous standardisation and ongoing monitoring of adherence to measurement protocols during data collection are essential to ensure consistency and to minimise systematic error in multicentre studies. Strict ultrasound fetal biometric measurement protocols are used in the st Project so that data of the highest quality from different centres can be compared and potentially pooled. A central Ultrasound Quality Unit (USQU) has been set up to oversee this process. After initial training and standardisation, the USQU monitors the performance of all ultrasonographers involved in the project by continuously assessing the quality of the images and the consistency of the measurements produced. Ultrasonographers are identified when they exceed preset maximum allowable differences. Corrective action is then taken in the form of retraining or simply advice regarding changes in practice. This paper describes the procedures used, which can form a model for research settings involving ultrasound measurements.

ObjectivesTo identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well‐dated pregnancies and access to antenatal care.DesignPopulation‐based, prospective, observational study.SettingEight international urban populations.PopulationPregnant women and their babies enrolled in the Newborn Cross‐Sectional Study of the INTERGROWTH‐21st Project.MethodsCox proportional hazard models were used to compare risks among antepartum stillborn and liveborn babies.Main outcome measuresAntepartum stillbirth was defined as any fetal death after 16 weeks’ gestation before the onset of labour.ResultsOf 60 121 babies, 553 were stillborn (9.2 per 1000 births), of which 445 were antepartum deaths (7.4 per 1000 births). After adjustment for site, risk factors were low socio‐economic status, hazard ratio (HR): 1.6 (95% CI, 1.2–2.1); single marital status, HR 2.0 (95% CI, 1.4–2.8); age ≥40 years, HR 2.2 (95% CI, 1.4–3.7); essential hypertension, HR 4.0 (95% CI, 2.7–5.9); HIV/AIDS, HR 4.3 (95% CI, 2.0–9.1); pre‐eclampsia, HR 1.6 (95% CI, 1.1–3.8); multiple pregnancy, HR 3.3 (95% CI, 2.0–5.6); and antepartum haemorrhage, HR 3.3 (95% CI, 2.5–4.5). Birth weight <3rd centile was associated with antepartum stillbirth [HR, 4.6 (95% CI, 3.4–6.2)]. The greatest risk was seen in babies not suspected to have been growth restricted antenatally, with an HR of 5.0 (95% CI, 3.6–7.0). The population‐attributable risk of antepartum death associated with small‐for‐gestational‐age neonates diagnosed at birth was 11%.ConclusionsAntepartum stillbirth is a complex syndrome associated with several risk factors. Although small babies are at higher risk, current growth restriction detection strategies only modestly reduced the rate of stillbirth.Tweetable abstractInternational stillbirth study finds individual risks poor predictors of death but combinations promising.

The INTERGROWTH‐21st Project data management was structured incorporating both a centralised and decentralised system for the eight study centres, which all used the same database and standardised data collection instruments, manuals and processes. Each centre was responsible for the entry and validation of their country‐specific data, which were entered onto a centralised system maintained by the Data Coordinating Unit in Oxford. A comprehensive data management system was designed to handle the very large volumes of data. It contained internal validations to prevent incorrect and inconsistent values being captured, and allowed online data entry by local Data Management Units, as well as real‐time management of recruitment and data collection by the Data Coordinating Unit in Oxford. To maintain data integrity, only the Data Coordinating Unit in Oxford had access to all the eight centres' data, which were continually monitored. All queries identified were raised with the relevant local data manager for verification and correction, if necessary. The system automatically logged an audit trail of all updates to the database with the date and name of the person who made the changes. These rigorous processes ensured that the data collected in the INTERGROWTH‐21st Project were of exceptionally high quality.

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Mid-trimester maternal plasma homocysteine concentration is not elevated in women who developed pre-eclampsia even in those at high risk defined by abnormal uterine artery Doppler velocimetry.

Although heavy alcohol use over an extended time is known to impair fetal growth, the effects, if any, of light or moderate consumption are not clear. This study examined drinking patterns on term small-for-gestational-age (SGA) births, with particular attention to binge drinking in the 3 months before pregnancy and the last 3 months of pregnancy. Data on 50,461 women who delivered singleton full-term infants (37-42 weeks gestation) were obtained from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey. Questionnaires were mailed 2 to 6 months after delivery, and nonrespondents were interviewed by phone. The study population was predominantly white, 18 to 34 years of age, had 12 or more years of education, was married, and did not smoke in late pregnancy. Light drinkers took 3 or fewer drinks in an average week, whereas moderate consumption was defined as 4 to 13 drinks and heavy drinking as 14 or more drinks per week on average. Binging was defined as taking 5 or more drinks in one sitting. Close to half the women reported drinking just before pregnancy, 94% of them at a light level. In the last trimester, fewer than 1% of all women and 18% of heavy drinkers binged. SGA births were more common in moderate or heavy prepregnancy drinkers than in light drinkers or nondrinkers. No such association was evident, however, for drinking in the last trimester. Although women who binged at either time were not significantly likelier to deliver an SGA infant, those binging in late pregnancy were 20% more likely to do so. After adjusting for confounding variables, women who were light or moderate drinkers before pregnancy were somewhat less likely to deliver an SGA infant, although the difference was not significant. Women who drank lightly or moderately in late pregnancy were not prone to have an SGA birth. At all levels of alcohol use the risk of an SGA birth was greater for bingers, but this was significant only for heavy drinkers. The lower risk of SGA birth found in some women who drink might be related to vascular effects of alcohol, or to dietary differences between women who drink before pregnancy or in late pregnancy and those who do not. A prospective study would clarify the observations made in this population of parturients. ABSTRACTVaginal bleeding in early pregnancy could be mistaken for menstruation, and it could lead to errors in estimating gestational age, especially in pregnancies that end in miscarriage. This prospective study examined patterns of vaginal bleeding in 151 healthy women whose pregnancies lasted at least 6 weeks beyond the last menstrual period (LMP). The participants collected daily urine samples that were assayed for human chorionic gonadotropin and kept a diary of vaginal bleeding as well as sexual intercourse. Early vaginal bleeding was defined as bleeding lasting a day or longer between conception and follow up, which extended through week 8 after the LMP in nearly all cases. Early vaginal bleeding was described by 9% of women. Typically, it was light and required only 1 or 2 ...