Depression and anxiety in women during pregnancy and neonatal outcome: data from the EDEN mother-child cohort.

BACKGROUND: According to the World Health Organization, mental health disorders are the leading causes of disease burden in women from 15 to 44 years. These conditions in pregnant women may affect the offspring. AIM: To analyze the relation between depression and anxiety of pregnant women and neonatal outcomes including gestational age and birthweight. STUDY DESIGN: Observational cohort study. SUBJECTS: 2002 women recruited before the 20th gestational week. OUTCOME MEASURES: Gestational age at delivery in completed weeks of amenorrhea and preterm delivery defined as birth before 37 completed weeks of gestation. Spontaneous preterm birth (PB) defined as either spontaneous preterm labor or preterm premature rupture of the membranes. Medically indicated preterm delivery defined as delivery that begins by induction or cesarean section. Birthweight as a continuous variable and centiles of the customized fetal weight norms for the French population. RESULTS: From the 1719 women included in the study, 7.9% (n=135) were classified as "anxious", 11.8% (n=203) as "depressed", 13.2% (n=227) as "depressed and anxious". After adjusting for potential confounders, depression combined with anxiety during pregnancy increased the risk of spontaneous PB (Odds Ratio: 2.46 [1.22-4.94]), but did not influence medically indicated PB nor birthweight. CONCLUSION: In this study, comorbidity of depressive and anxiety symptoms was the worst condition during pregnancy. Further studies are needed to investigate depression and anxiety together to improve the comprehension of the biological modifications involved.

Maternal exposure to air pollution before and during pregnancy related to changes in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort.

BACKGROUND: Toxicants can cross the placenta and expose the developing fetus to chemical contamination leading to possible adverse health effects, by potentially inducing alterations in immune competence. Our aim was to investigate the impacts of maternal exposure to air pollution before and during pregnancy on newborn's immune system. METHODS: Exposure to background particulate matter less than 10 µm in diameter (PM10) and nitrogen dioxide (NO2) was assessed in 370 women three months before and during pregnancy using monitoring stations. Personal exposure to four volatile organic compounds (VOCs) was measured in a subsample of 56 non-smoking women with a diffusive air sampler during the second trimester of pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to determine lymphocyte subsets. RESULTS: Among other immunophenotypic changes in cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01), 0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 µg/m3 increase in PM10 levels three months before and during the first, second and third trimester of pregnancy, respectively, were observed after adjusting for confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in association with personal exposure to benzene. A similar trend was observed between NO2 exposure and CD4+CD25+ T-cell percentage; however the association was stronger between NO2 exposure and an increased percentage of CD8+ T-cells. CONCLUSIONS: These data suggest that maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring thus increasing the child's risk of developing health conditions later in life, including asthma and allergies.

[Prophylactic use of a recombinant activated factor VII in delivery haemorrhage by caesarean in a woman with major factor VII deficiency: a case report]. / Utilisation prophylactique du facteur VII activé recombinant dans l'hémorragie de la délivrance par césarienne chez une patiente atteinte de déficit majeur en facteur VII : à propos d'un cas.

Taking in charge the delivery of pregnant women with inherited major deficiency of factor VII (FVII) is poorly reported in literature. We report here the haemorrhagic prophylaxis of delivery by recombinant activated FVII (rFVIIa) in a 27-year-old women, gravida 1, para 0, with major deficiency FVII by missense mutation (p.Arg337Cys). Her parents, first germen, presented a FVII deficiency. She has four brothers and three sisters, of which only one brother has major FVII deficiency with hemorrhagic diathesis in childhood (hematochezia). At her birth, because of dystocia, a right sterno-cleido-mastoid muscle hematoma and left clavicle fracture occurred. The FVII concentration was 0.08 U/mL. At the age of fifteen, a surgery of appendicitis was performed with substitution by FVII from plasma donors without any haemorrhagic complication. Because of anatomic specificity (bifid uterus and vagina), caesarean was planned. After reviewing of the literature, caesarean was performed at 38th week of gestation with haemorrhagic prophylaxis consisting in administration of rFVIIa (eptacog alfa) at a dose of 20 µg/kg, 30 min before surgery, then every 3 h during 48 h. No haemorrhagic complication occurred. Thrombosis prophylaxis was ensured by enoxaparin (4000 UI a day subcutaneously started 6 h after surgery for 5 days). Clinical examination of the newborn was normal. In future, modalities of taking in charge have to be evaluated by prospective studies involving a sufficiently numerous group of woman with FVII major deficiency, or by retrospective studies with the means of national or European registers.

Maternal weight change before pregnancy in relation to birthweight and risks of adverse pregnancy outcomes.

Maternal weight change before pregnancy can be considered as an indicator of maternal energy balance and nutritional status before conception, and may be involved in early life programming. We aimed to investigate the association of maternal Weight Change Before Pregnancy (WCBP) with fetal growth and adverse pregnancy outcomes. Data are from the French EDEN mother-child cohort where 1,756 mother-child pairs had information on mother's weight at 20 years, weight just before pregnancy, fetal anthropometry at second and third trimesters, infant's birthweight and pregnancy complications. The average annual WCBP between 20 years and start of pregnancy (in kg/year) was categorized as: "Weight Loss" (n = 320), "Moderate weight gain" (n = 721) and "High weight gain" (n = 715). The associations of WCBP with fetal and newborn characteristics and with adverse pregnancy outcomes were analyzed, adjusting for maternal and pregnancy characteristics, including the mother's prepregnancy BMI. Interactions between WCBP and prepregnancy BMI were tested. Birthweight and estimated fetal weight in the third trimester increased significantly with increasing WCBP in mothers with BMI <25 kg/m(2). In these mothers, weight loss before pregnancy was associated with a higher risk of newborns small for gestational age (SGA). Whatever the prepregnancy BMI, WCBP was positively associated with a maternal risk of gestational diabetes and hypertension. The ponderal history of mothers before pregnancy can impact on fetal growth and on pregnancy outcomes such as gestational diabetes or hypertension. Our analysis is the first to report that in non-overweight women, those who lost weight before pregnancy are at higher risk of having SGA newborns.

Determinants of neonatal weight loss in term-infants: specific association with pre-pregnancy maternal body mass index and infant feeding mode.

OBJECTIVE: We aimed to study the determinants of neonatal weight loss measured on the third day of life in term-infants. DESIGN: The EDEN mother-child cohort is a prospective study that recruited 2002 pregnant women before 24 weeks of gestation in two French university hospitals. Neonates were weighed every day until discharge that occurred on average 4.5 days after birth. Altogether, 1557 healthy term neonates with data on weight at day 3 and feeding mode available were included. The outcome variable was weight loss at day 3 (D3WL), expressed as a percentage of birth weight lost in the first 3 days of life. Our main explanatory variables were maternal pre-pregnancy body mass index (BMI), gestational weight gain, gestational diabetes, birth weight, gestational age and feeding mode. RESULTS: Factors associated with greater D3WL, whatever the feeding mode, were: higher birth weight, gestational diabetes and caesarean section; higher gestational age was associated with a reduced D3WL. The association between maternal pre-pregnancy BMI and D3WL differed by feeding mode (interaction p value=0.0002). In breastfed babies, mean D3WL ranged from 4.9% for neonates of underweight mothers to 5.8% for neonates of obese mothers (p trend=0.0005). In formula-fed babies, D3WL was highest for neonates of underweight mothers (4.1%) and lowest for those of obese mothers (2.6%) (p trend=0.01). CONCLUSIONS: The lower D3WL in formula-fed neonates, especially in neonates of obese mothers, suggests a relative overfeeding in the early days compared with breastfed neonates, which may potentially have consequences on later health. Overweight and obese mothers may need extra support to prevent early breastfeeding discontinuation.

A new presentation of neonatal lupus: 5 cases of isolated mild endocardial fibroelastosis associated with maternal Anti-SSA/Ro and Anti-SSB/La antibodies.

OBJECTIVE: Maternal anti-SSA/Ro or anti-SSB/La antibodies are associated with neonatal lupus erythematosus syndrome (NLES), especially congenital heart block (CHB), which may be associated with severe endocardial fibroelastosis (EFE) and dilated cardiomyopathy (DCM). A few reports have described severe EFE without CHB associated with anti-SSA/Ro antibodies, with a poor prognosis. EFE has also been observed in biopsies of DCM that had been considered idiopathic. These points, considered in association with 5 unusual cases of mild EFE, led us to consider the relationship between underrecognized cases of isolated autoantibody-associated EFE and DCM that had been considered idiopathic. METHODS: We analyzed 5 cases of EFE diagnosed in utero (n = 4) or after birth (n = 1). In 3 cases, maternal antibody status was discovered because of the EFE diagnosis. RESULTS: Endomyocardial hyperechogenicity predominated in the left atrium (n = 3) and mitral annulus (n = 3). No left-heart dysfunction was observed. Two mothers were treated with betamethasone. One mother chose to have a therapeutic abortion, and EFE was confirmed at autopsy. Electrocardiograms at birth (n = 4) did not show CHB. Other manifestations of NLES were present in all cases. One child had right ventricular hypoplasia and underwent a partial cavopulmonary anastomosis. At last followup (4-7 yrs), the other 3 children had normal heart function, and echocardiography showed a normal heart (n = 2) or mild persistent EFE (n = 1). CONCLUSION: Middle-term prognosis of isolated autoantibody-associated EFE may be better than previously reported, although the longterm prognosis remains unknown. We hypothesize that a fetal insult can lead to DCM.

Determinants of early ponderal and statural growth in full-term infants in the EDEN mother-child cohort study.

BACKGROUND: Growth velocity in the first months of postnatal life has been associated with later overweight and obesity. OBJECTIVE: We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life. DESIGN: We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex. RESULTS: Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants. CONCLUSIONS: In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations.

Prenatal mercury contamination: relationship with maternal seafood consumption during pregnancy and fetal growth in the 'EDEN mother-child' cohort.

Maternal seafood intake is of great health interest since it constitutes an important source of n-3 fatty acids, but provides also an important pathway for fetal exposure to Hg. The objective of the present study was to determine associations between Hg contamination and both maternal seafood consumption and fetal growth in French pregnant women. Pregnant women included in the 'EDEN mother-child' cohort study answered FFQ on their usual diet in the year before and during the last 3 months of pregnancy, from which frequencies of seafood intake were evaluated. Total hair-Hg level was determined for the first 691 included women. Associations between Hg level, seafood intake and several neonatal measurements were studied using linear regressions adjusted for confounding variables. The median Hg level for mothers was 0.52 µg/g. Maternal seafood intake was associated with Hg level (r 0.33; P < 0.0001). There was no association between Hg level and fetal growth in the whole sample of women, except for an early negative relationship with biparietal diameter. A positive association was found between seafood intake and fetal growth in overweight women only which remained unchanged after adjustment for Hg level (birth weight: +101 g for a difference of 1 sd in seafood consumption; P = 0.008). Although seafood intake was associated with Hg contamination in French pregnant women, the contamination level was low. There was no consistent association between Hg level and fetal growth. Taking into account Hg level did not modify associations between seafood intake and fetal growth.

Maternal blood lead levels and the risk of pregnancy-induced hypertension: the EDEN cohort study.

BACKGROUND: Prior studies revealed associations of environmental lead exposure with risks of hypertension and elevated blood pressure. OBJECTIVE: We examined the effect of blood lead levels on blood pressure and the incidence of pregnancy-induced hypertension (PIH) in the second and third trimesters of pregnancy. METHODS: One thousand seventeen pregnant women were enrolled in two French municipalities between 2003 and 2005 for the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l' Enfant) cohort study. Blood lead concentrations were measured by atomic absorption spectrometry in mothers between 24 and 28 weeks of gestation. RESULTS: PIH was diagnosed in 106 subjects (10.9%). Age, parity, weight gain, alcohol, smoking habits, and calcium supplementation were comparable between hypertensive and nonhypertensive women. Lead levels were significantly higher in PIH cases (mean +/- SD, 2.2 +/- 1.4 microg/dL) than in normotensive patients (1.9 +/- 1.2 microg/dL; p = 0.02). Adjustment for potential confounder effects slightly attenuated but did not eliminate the significant association between blood lead levels and the risk of PIH (adjusted odds ratio of PIH = 3.3; 95% confidence interval, 1.1-9.7). We also observed geographic differences in lead exposure and in the incidence of PIH and found significant correlations between blood lead levels and unadjusted as well as adjusted systolic and diastolic blood pressures after 24 weeks of gestation. CONCLUSIONS: These findings confirm the relationship between blood lead levels at mid-pregnancy and blood pressure and suggest that environmental lead exposure may play an etiologic role in PIH.

Maternal personal exposure to airborne benzene and intrauterine growth.

BACKGROUND: Studies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight. OBJECTIVE: Our aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth. METHODS: We recruited pregnant women in two French maternity hospitals in 2005-2006 as part of the EDEN mother-child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth. RESULTS: Median benzene exposure was 1.8 microg/m(3) (5th, 95th percentiles, 0.5, 7.5 microg/m(3)). Log-transformed benzene exposure was associated with a gestational age-adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), -135 to -1 g] and of 1.9 mm in mean head circumference at birth (95% CI, -3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 mm in head circumference assessed during the third trimester (95% CI, -4.0 to 0.3 mm) and of 1.5 mm in head circumference assessed at the end of the second trimester of pregnancy (95% CI, -3.1 to 0 mm). CONCLUSIONS: Our prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants.

Levofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: a preliminary study.

OBJECTIVE: Uncomplicated pelvic inflammatory disease (PID) is a common disease caused by numerous pathogens: sexually transmitted infections (such as Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium), anaerobes, and other organisms from the vaginal flora. It is currently treated by oral route and most present protocols recommend ofloxacin plus metronidazole (MET). The CDC 2006 Guidelines suggested that levofloxacin (LEV) can be a substitute for ofloxacin. This study aimed to evaluate the efficacy and safety of LEV-MET in the treatment of uncomplicated PID. STUDY DESIGN: The first 40 cases of uncomplicated PID were prospectively evaluated (June 2006 to December 2007). Diagnosis was based on the clinical signs and microbial findings. If present (N=8), IUD were removed and cultured. Treatment consisted of LEV 500mg OD+MET 500mg BID by oral route for 14 days. Visits took place at the end of therapy (EOT) and at follow-up (FU) 4-6 weeks later. The endpoints were clinical resolution (at the EOT and FU) and bacteriological eradication (at the EOT). RESULTS: 10 cases of bacterial vaginosis were found and 35 pathogens (E. coli: 12, anaerobes: 5; C. trachomatis: 5; M. hominis: 5; U. urealyticum: 3; others: 5) were isolated in the cervix. 37 patients were evaluable at the EOT: 27 were clinically cured and 10 significantly improved; all pathogens were eradicated. At FU, all 35 evaluable patients were clinically cured. Drug-related adverse events (AEs) occurred in 9 cases: 1 patient discontinued (myalgia and tendonitis) while other AEs consisted of nausea or diarrhea. CONCLUSION: This preliminary study has shown that a 14-day course of oral LEV-MET is effective and well-tolerated in the treatment of outpatients with uncomplicated PID.

Association between maternal seafood consumption before pregnancy and fetal growth: evidence for an association in overweight women. The EDEN mother-child cohort.

Studies in countries with high seafood consumption have shown a benefit on fetal growth and child development. The objective of our study was to determine the association between seafood consumption in French pregnant women and fetal growth. Pregnant women included in the EDEN mother-child cohort study completed two food frequency questionnaires on their usual diet in the year before and during the last 3 months of pregnancy (n = 1805). Fetal circumferences were measured by ultrasound and anthropometry at birth. Variables were compared across tertiles of the mother's seafood consumption using multiple linear regression to adjust for confounding variables. Analyses were stratified by maternal overweight status because of an interaction between maternal seafood consumption and her body mass index (P < 0.01). There was no association between seafood intake and fetal growth in the whole sample of women. For overweight women (n = 464), higher consumption of seafood before pregnancy was associated with higher fetal biparietal and abdominal circumferences and anthropometric measures. From the lowest to the highest tertiles, mean birthweight was 167 g higher (P = 0.002). No significant association was found with consumption at the end of pregnancy. In conclusion, high seafood consumption before pregnancy is positively associated with fetal growth in overweight women.

Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The 'EDEN mother-child' cohort (study of pre- and early postnatal determinants of the child's development and health).

Recent studies suggest a benefit of seafood and n-3 fatty acid intake on fetal growth and infant development. The objective was to study the association between fatty acid intake and fetal growth in pregnant French women. Pregnant women included in the EDEN mother-child cohort study completed FFQ on their usual diet: (1) in the year before pregnancy and (2) during the last 3 months of pregnancy (n 1439). Conversion into nutrient intakes was performed using data on portion size and a French food composition table. Associations between maternal fatty acid intakes and several neonatal anthropometric measurements were studied using linear regressions adjusted for centre, mother's age, smoking habits, height, parity, gestational age and newborn's sex. Due to significant interaction, analyses were stratified according to maternal pre-pregnancy overweight status. Neither total lipid nor SFA, MUFA or PUFA intake was significantly associated with newborn size. In overweight women only (n 366), a high pre-pregnancy n-3 fatty acid intake (% PUFA) was positively associated with the newborn's birth weight (P=0.01), head, arm and wrist circumferences and sum of skinfolds (P<0.04). A substitution of 1% of n-3 fatty acids per d before pregnancy by other PUFA was related to an average decrease in birth weight of 60 g (P=0.01). Relationships with n-3 fatty acid intake at the end of pregnancy were weaker and not significant. We concluded that a high pre-pregnancy n-3 fatty acid:PUFA ratio may sustain fetal growth in overweight women. Follow-up of the children may help determine whether this has beneficial consequences for the child's health and development.

Radiofrequency driven cord occlusion for selective termination of pregnancy: evaluation in the fetal sheep.

OBJECTIVE: This study was designed to assess the ability of an ultrasound-guided radiofrequency (RF)-driven procedure to induce complete and irreversible cord occlusion using a 90 days fetal sheep model. STUDY DESIGN: Twenty 90 days gestation sheep underwent general anesthesia. The first ten fetuses were exposed under hysterotomy, and RF electrode was inserted visually in the middle of the umbilical cord and deployed. Fetuses were then replaced into the amniotic fluid and RF procedure (average target temperature of 100 degrees C during 10 minutes) was applied. For the next ten fetuses, RF electrode was inserted into the cords under trans-parietal ultrasound guidance and the same RF procedure was applied. Cord occlusion was assessed by Doppler examination (absence of cordonal flows at the end of the procedure and until fetal heart failure occurred) and by subsequent histopathological analysis. RESULTS: Cord occlusion was always complete at Doppler examination at the end of RF procedure for the ten experiments realized under hysterotomy. No cordonal reperfusion was observed until fetal heart failure. Histopathological analysis confirmed cordonal occlusion at the site of impact. Neither cordonal rupture nor cordonal bleeding was observed for any of the ten experiments. When RF electrode was inserted under ultrasound guidance, complete occlusion could be obtained only for 6 of the ten experiments. CONCLUSION: Our results suggest that RF might be an appropriate method for selective termination of pregnancy. Yet, optimal insertion of the electrode is required to engender a complete and irreversible cord occlusion, and ultrasound-guidance training seems necessary before current human application.

Optimal standards for fetal biometry: to each measurement its fitting model.

OBJECTIVE: To determine the best mathematical model to construct charts of fetal abdominal circumference (AC) and femur length (FL). METHODS: Ultrasound measurements were made on 1,336 normal fetuses in one center. Four mathematical models were compared (a linear-quadratic model, a linear-cubic model, the Rossavik model and a new two-phase model, which has been found to best fit fetal head data). RESULTS: The best fitting of AC and FL data was obtained with the linear-quadratic model without separate computing for gender. Centile charts have been computed. CONCLUSION: Fetal growth of AC and FL is much simpler than that of the head. Therefore, a unique mathematical model should not be used to fit all measurements.

A population-based study of 518 very preterm neonates from high-risk pregnancies: prognostic value of umbilical and cerebral artery Doppler velocimetry for mortality before discharge and severe neurological morbidity.

OBJECTIVE: To evaluate in everyday practice the predictiveness of fetal umbilical artery and cerebral artery Doppler examination for mortality before discharge and for severe neurological morbidity among very preterm neonates from high-risk pregnancies. METHODS: Data came from a population-based study (EPIPAGE) of all births before 33 weeks' gestation during 1 year in nine French regions. We examined the prognostic value of Doppler findings among the liveborn singletons delivered after pregnancies with maternal hypertension or antenatal suspicion of small-for-gestational-age status. RESULTS: This study included 518 fetuses. Predischarge mortality for infants with abnormal umbilical artery Doppler findings was not significantly higher than for those with normal findings. Mortality for infants with abnormal cerebral artery Doppler findings was significantly higher in the bivariate analysis (crude OR: 3.5 (1.6-7.4)). After adjustment, the association between mortality and abnormal cerebral artery Doppler findings remained significant in the subgroup with an abnormal umbilical artery Doppler assessment (OR: 5.1 (1.1-23)). There was no significant association between neurological morbidity and Doppler findings. CONCLUSION: The prognostic value of Doppler examinations appears lower in this study than in previous hospital series. This suggests the need for quality control and improvements in these examinations.

Customized versus population-based birth weight standards for identifying growth restricted infants: a French multicenter study.

OBJECTIVE: This study was undertaken to describe the characteristics of pregnancies according to a customized definition of fetal growth restriction and to determine the association between customized standards and adverse pregnancy outcomes. STUDY DESIGN: Two definitions of growth restriction, a population and a customized standard, were applied to 56,606 births in 5 tertiary maternity hospitals in France from 1997 to 2002. The customized definition was adjusted for maternal height and weight, parity, fetal gender, and gestational age. Odds ratios and 95% CIs for neonatal morbidity and mortality were calculated to compare small for gestational age and non-small for gestational age births. RESULTS: By using customized standards, 2.7% of births were reclassified as small for gestational age. These births were to taller, heavier, multiparous women. Compared with non-small for gestational age births, these newly detected small-for-gestational-age newborn infants showed an increased risk of stillbirth (odds ratio = 4.52, 95% CI 2.47-8.14) and perinatal death (odds ratio = 2.60, 95% CI 1.62-4.15). These infants were also more likely to be born to women with hypertensive disease in pregnancy (7.0%) versus those reclassified as non-small for gestational age (2.3%) and those non-small for gestational age by both standards (5.5%). CONCLUSION: These findings highlight the interest of using customized birth weight standard adjusted for maternal and neonatal characteristics to identify fetuses at risk, particularly among apparently normal fetuses. Individual growth norms should be used to define small for gestational age.