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Background: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use., Methods and Findings: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts., Conclusions: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: GP is a WHO statistical consultant and has a contract to give statistical support to the Fetal Growth Study. GP has worked with WHO for 15 years and has a relationship with WHO, both paid (contracts) and unpaid. GP is also a good friend of many of the investigators involved in this study. LDP is a Board Member of the Perinatal Quality Foundation, a nonprofit organization related to the Society for Maternal Fetal Medicine. LDP has received research support from General Electric Medical Systems unrelated to fetal growth. LDP also lectures 1 or 2 times per year at an educational meeting supported by General Electric Medical Systems unrelated to fetal growth.

Background: In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide., Methods: This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications., Discussion: The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes. While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight, no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero. Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women. Five hundred and ten healthy, primiparous pregnant Argentinean women were randomised (at <20 weeks gestation) to either placebo (n = 230) or calcium supplements (1500 mg calcium/day in 3 divided doses; n = 231). Growth parameters in utero were assessed with serial ultrasound scans. Birthweight, length, head, abdominal and thigh circumferences were recorded at delivery. No differences were found in fetal biometric measurements recorded at 20, 24, 28, 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not. Similarly, neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups. We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth.

[This corrects the article DOI: 10.1371/journal.pmed.1002220.]. [ABSTRACT FROM AUTHOR]

Objective: Preeclampsia, gestational hypertension, and unexplained intrauterine growth restriction may have similar determinants and consequences. In this study, we compared determinants and perinatal outcomes associated with these obstetric conditions. Study design: We analyzed 39,615 pregnancies (data from the WHO Antenatal Care Trial), of which 2.2% were complicated by preeclampsia, 7.0% by gestational hypertension, and 8.1% by unexplained intrauterine growth restriction (ie, not associated with maternal smoking, maternal undernutrition, preeclampsia, gestational hypertension, or congenital malformations). We compared the risk factors associated with these groups. Fetal death, preterm delivery, and severe neonatal morbidity and mortality were the primary outcomes. Logistic regression analyses were adjusted for study site, socioeconomic status, and (if appropriate) birth weight and gestational age. Results: Diabetes, renal or cardiac disease, previous preeclampsia, urinary tract infection, high maternal age, twin pregnancy, and obesity increased the risk of both hypertensive conditions. Previous large-for-age birth, reproductive tract surgery, antepartum hemorrhage and reproductive tract infection increased the risk for gestational hypertension only. Independent of maternal age, primiparity was a risk factor only for preeclampsia. Both preeclampsia and gestational hypertension were associated with increased risk for fetal death and severe neonatal morbidity and mortality. Mothers with preeclampsia compared with those with unexplained intrauterine growth restriction were more likely to have a history of diabetes, renal or cardiac disease, chronic hypertension, previous preeclampsia, body mass index more than 30 kg/cm², urinary tract infection and extremes of maternal age. Conversely, unexplained intrauterine growth restriction was associated with higher risk of low birth weight in previous pregnancies, but not with previous preeclampsia. Both conditions increased the risk for perinatal outcomes independently but preeclampsia was associated with considerable higher risk. Conclusion: Preeclampsia and gestational hypertension shared many risk factors, although there are differences that need further evaluation. Both conditions significantly increased morbidity and mortality. Conversely, preeclampsia and unexplained intrauterine growth restriction, often assumed to be related to placental insufficiency, seem to be independent biologic entities. [ABSTRACT FROM AUTHOR]

Examines the efficacy of nutritional interventions in treating impaired fetal growth. Reduction in the risk of small gestational growth; Protection against low birth weight; Presentation of a positive effects on fetal long bone growth.

[This corrects the article DOI: 10.1371/journal.pmed.1002220.]. [ABSTRACT FROM AUTHOR]