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The article discusses the persistent issue of preterm birth rates in the United States and the role of cigarette smoking in adverse pregnancy outcomes. While overall smoking prevalence during pregnancy has decreased, disparities exist among different populations, with higher rates among American Indian/Alaska Native mothers and in certain states. The article highlights the potential benefits of smoking cessation before and during pregnancy in reducing the risk of preterm birth. However, the study faces challenges in accurately measuring the effects of smoking cessation due to limitations in data collection and confounding factors. The article suggests various strategies to support smoking cessation during pregnancy, including targeting youth and young adults, improving access to prenatal care, and conducting further research on the effects of substance use on pregnancy outcomes. [Extracted from the article]

Background: Studies evaluating the association between prenatal ultrasounds and autism spectrum disorder (ASD) have largely produced negative results. Concern remains due to the rising identification of children with ASD and ultrasound use. Objective: To evaluate the association between prenatal ultrasound use and ASD. Methods: We used data from the Study to Explore Early Development, a multisite case‐control study of preschool‐aged children with ASD implemented during 2007–2012. We recruited cases from children receiving developmental disability services and randomly selected population controls from birth records. ASD case status was based on in‐person standardised assessments. We stratified analyses by pre‐existing maternal medical conditions and pregnancy complications associated with increased ultrasound use (ultrasound indications) and used logistic regression to model case status by increasing ultrasound counts. For pregnancies with medical record data on ultrasound timing, we conducted supplementary tests to model associations by trimester of exposure. Results: Among 1524 singleton pregnancies, ultrasound indications were more common for ASD cases than controls; respectively, for each group, no indications were reported for 45.1% and 54.2% of pregnancies, while ≥2 indications were reported for 26.1% and 18.4% of pregnancies. The percentage of pregnancies with multiple ultrasounds varied by case status and the presence of ultrasound indications. However, stratified regression models showed no association between increasing ultrasound counts and case status, either for pregnancies without (aOR 1.01, 95% CI 0.92, 1.11) or with ultrasound indications (aOR 1.01, 95% CI 0.95, 1.08). Trimester‐specific analyses using medical record data showed no association in any individual trimester. Conclusions: We found no evidence that prenatal ultrasound use increases ASD risk. Study strengths included gold‐standard assessments for ASD case classification, comparison of cases with controls, and a stratified sample to account for conditions associated both with increased prenatal ultrasound use and ASD. [ABSTRACT FROM AUTHOR]

Background: Prenatal smoking cessation has substantial health benefits for mothers and offspring, but concerns about weight gain may be a barrier to quitting. We quantified gestational weight gain associated with biochemically confirmed smoking cessation. Methods: Data originated from a randomized controlled cessation trial: Smoking Cessation in Pregnancy project (1987‐1991). We calculated gestational weight gain using self‐reported prepregnancy weight and measured weight at 30‐34 weeks of gestation. We used linear regression to estimate adjusted mean differences in gain for quitters versus continuing smokers by the last trimester. The effects of quitting earlier (by 2nd trimester) versus later (by 3rd trimester) were calculated. We assessed the percentages who gained weight according to Institute of Medicine (IOM) recommendations within 2 weeks of a full‐term delivery. Results: At 30‐34 weeks, nulliparous and multiparous quitters gained an average of 3.0 pounds (95% CI 0.9‐5.1 pounds) (1.4 kg [0.4‐2.3 kg]) and 6.6 pounds (95% CI 4.3‐8.9 pounds) (3.0 kg [1.9‐4.0 kg]) more, respectively, than continuing smokers. Weight gain in early quitters did not differ significantly from that in late quitters. Quitters were more likely than continuing smokers to gain above current guidelines (60.3% vs 46.3%) and were less likely to gain below guidelines (11.5% vs 21.6%) (P = 0.002). Conclusions: Although quitters had modest additional weight gain by 30‐34 weeks compared to continuing smokers, a high proportion in both groups gained in excess of IOM recommendations. Both quitters and continuing smokers may need support to achieve optimal gestational weight gain. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the effects of nondaily smoking or low-intensity daily smoking and infant outcomes. We examined the associations between preterm delivery and small for gestational age (SGA) infants in relation to both nondaily and daily smoking.Methods: We used population-based data on women who delivered live singleton infants using the 2009-11 Pregnancy Risk Assessment Monitoring System. Women's smoking status in the last 3 months of pregnancy was categorised as nonsmokers, quitters, nondaily smokers (<1 cigarette/day), and daily smokers. Controlling for maternal age, maternal race/ethnicity, education, marital status, prepregnancy body mass index (BMI), trimester of prenatal care entry, parity, and alcohol use, we estimated adjusted prevalence ratios (PR) for the outcomes of preterm delivery (<37 weeks' gestation) and SGA.Results: Of the 88 933 women, 13.1%, 1.7%, and 9.6% of the sample were quitters, nondaily smokers, and daily smokers, respectively, in the last 3 months of pregnancy. While nondaily smoking was not associated with preterm delivery, daily smoking was. However, we found no dose-response relationship with the number of cigarettes smoked per day. Risk of delivering a SGA infant was increased for both nondaily and daily smokers (PR 1.4, 95% CI 1.1, 1.8 and PR 2.0, 95% CI 1.9, 2.2 respectively).Conclusions: Nondaily smoking in the last 3 months of pregnancy was associated with an increased risk of delivering a SGA infant. Pregnant women should be counselled that smoking, including nondaily and daily smoking, can adversely affect birth outcomes. [ABSTRACT FROM AUTHOR]

Background: Birth certificate data overestimate national preterm births because a high percentage of last menstrual period (LMP) dates have errors. Study goals were to determine: (i) To what extent errors in transfer of birthweight and LMP date from medical records to birth certificates contribute to implausibly high birthweight-for-gestational-age births; (ii) What percentage of implausible births would be resolved if the clinical estimate (CE) from birth certificates were used instead of LMP-based gestational age, and with what degree of certainty; and (iii) Of those not resolved, what percentage had a medical explanation.Methods: Medical records and birth certificates for all singleton infants with implausibly high birthweight-for-gestational-age based on LMP delivered in the Kaiser Permanente Northwest system in Oregon during 1998-2007 were examined. Percentages of implausible records resolved under various scenarios were calculated.Results: A total of 100 births with implausibly high birthweight-for-gestational age combinations were identified. When LMP date and birthweight from medical records were used instead of from birth certificates, 31% of births with implausible combinations were resolved. Substituting the CE on the birth certificate for the LMP date resolved 92%. Of the latter, the clinician's gestational age estimate in the medical record was obtained in early pregnancy in 72%. Five of the eight births with unresolved implausible combinations were to mothers with diabetes; the remaining three had no documented medical explanation.Conclusions: In this study, use of the birth certificate CE rather than the LMP resulted in a clinically reliable reclassification for the majority of implausible birthweight-for-gestational age deliveries. [ABSTRACT FROM AUTHOR]

Background Obstetric estimate ( OE) of gestational age, recently added to the standard US birth certificate, has not been validated. Using early ultrasound-based gestational age (prior to 20 weeks gestation) as the criterion standard, we estimated the prevalence of preterm delivery and the sensitivity and positive predictive value ( PPV) of gestational age estimates based on OE. Methods We analyzed 165 148 singleton livebirth records (38% of California livebirths during the study period) with linked early ultrasound information from a statewide California prenatal screening programme. OE of gestational age estimates was obtained from birth certificates. Results Prevalence of preterm delivery (<37 weeks gestation) was higher based on early ultrasound (8.1%) compared with preterm delivery based on OE (7.1%). Sensitivity for preterm birth when using OE for gestational age was 74.9% (95% confidence interval [ CI] [74.1, 75.6]), and PPV was 85.1% (95% CI [84.4, 85.7]). Incongruence, defined as a ≥ 14-day difference between early-ultrasound-derived gestational age and OE, was 3.4%. Conclusions OE reported on the birth certificate may underestimate the prevalence of preterm delivery, particularly among women of non-Hispanic non-white race and ethnicity and women with lower educational attainment, public insurance at time of delivery, and missing prepregnancy BMI. Additional validation studies in other samples of births are needed. [ABSTRACT FROM AUTHOR]

Objective To examine the potential effects of prenatal smokeless tobacco use on selected birth outcomes. Design A population-based, case-control study using a retrospective medical record review. Population Singleton deliveries 1997-2005 to Alaska Native women residing in western Alaska. Methods Hospital discharge codes were used to identify potential case deliveries and a random control sample. Data on tobacco use and confirmation of pregnancy outcomes were abstracted from medical records for 1123 deliveries. Logistic regression was used to examine associations between tobacco use and pregnancy outcomes. Adjusted odds ratios ( OR), 95% confidence intervals (95% CI), and p-values were calculated. Main outcomes measures Preterm delivery, pregnancy-associated hypertension, and placental abruption. Results In unadjusted analysis, smokeless tobacco use was not significantly associated with preterm delivery ( OR 1.44, 95% CI 0.97-2.15). After adjustment for parity, pre-pregnancy body mass index, and maternal age, the point estimate was attenuated and remained non-significant. No significant associations were observed between smokeless tobacco use and pregnancy-associated hypertension (adjusted OR 0.92, 95% CI 0.56-1.51) or placental abruption (adjusted OR 1.11, 95% CI 0.53-2.33). Conclusions Prenatal smokeless tobacco use does not appear to reduce risk of pregnancy-associated hypertension or to substantially increase risk of abruption. An association between smokeless tobacco and preterm delivery could not be ruled out. Components in tobacco other than nicotine likely play a major role in decreased pre-eclampsia risk in smokers. Nicotine adversely affects fetal neurodevelopment and our results should not be construed to mean that smokeless tobacco use is safe during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: We examined the risk of gestational diabetes mellitus (GDM) among foreign-born and U.S.-born mothers by race/ethnicity and BMI category. Design and Method: We used 2004-2007 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida to compare GDM risk among foreign-born and U.S.-born mothers by race/ethnicity and BMI category. We examined maternal BMI and controlled for maternal age, parity, and height. Results: Overall, 22.4% of the women in our study were foreign born. The relative risk (RR) of GDM among women who were overweight or obese (BMI ≥ 25.0 kg m−2) was higher than among women with normal BMI (18.5-24.9 kg m−2) regardless of nativity, ranging from 1.3 (95% confidence interval (CI) = 1.0, 1.9) to 3.8 (95% CI = 2.1, 7.2).Foreign-born women also had a higher GDM risk than U.S.-born women, with RR ranging from 1.1 (95% CI = 1.1, 1.2) to 2.1 (95% CI = 1.4, 3.1). This finding was independent of BMI, age, parity, and height for all racial/ethnicity groups. Conclusions: Although we found differences in age, parity, and height by nativity, these differences did not substantially reduce the increased risk of GDM among foreign-born mothers. Health practitioners should be aware of and have a better understanding of how race/ethnicity and nativity can affect women with a high risk of GDM. Although BMI is a major risk factor for GDM, it does not appear to be associated with race/ethnicity or nativity. [ABSTRACT FROM AUTHOR]

Objective. To examine the effects of maternal prenatal smokeless tobacco use on infant birth size. Design. A retrospective medical record review of 502 randomly selected deliveries. Population and Setting. Singleton deliveries to Alaska Native women residing in a defined geographical region in western Alaska, 1997-2005. Methods. A regional medical center's electronic records were used to identify singleton deliveries. Data on maternal tobacco exposure and pregnancy outcomes were abstracted from medical records. Logistic models were used to estimate adjusted mean birthweight, length and head circumference for deliveries to women who used no tobacco ( n=121), used smokeless tobacco ( n=237) or smoked cigarettes ( n=59). Differences in mean birthweight, length and head circumference, 95% confidence intervals and p-values were calculated using non-users as the reference group. Main Outcome Measures. Infant birthweight, crown-heel length and head circumference. Results. After adjustment for gestational age and other potential confounders, the mean birthweight of infants of smokeless tobacco users was reduced by 78g compared with that of infants of non-users ( p=0.18) and by 331g in infants of smokers ( p<0.01). No association was found between maternal smokeless tobacco use and infant length or infant head circumference. Conclusions. We found a modest but non-significant reduction in the birthweight of infants of smokeless tobacco users compared with infants of tobacco non-users. Because smokeless tobacco contains many toxic compounds that could affect other pregnancy outcomes, results of this study should not be construed to mean that smokeless tobacco use is safe during pregnancy. [ABSTRACT FROM AUTHOR]

Although cigarette smoking remains the most prevalent form of tobacco use in girls and in women of reproductive age globally, use of non-cigarette forms of tobacco is prevalent or gaining in popularity in many parts of the world, especially in low- and middle-income countries. Sparse but growing evidence suggests that the use of some non-cigarette tobacco products during pregnancy increases the risk of adverse pregnancy outcomes. In this paper we review the literature on the prevalence of non-cigarette tobacco product use in pregnant women and in women of reproductive age in high-, middle-, and low-income countries and the evidence that maternal use of these products during pregnancy has adverse health effects. In addition, we communicate findings from an international group of perinatal and tobacco experts that was convened to establish research priorities concerning the use of non-cigarette tobacco products during pregnancy. The working group concluded that attempts to develop a public health response to non-cigarette tobacco use in women are hindered by a lack of data on the epidemiology of use in many parts of the world and by our limited understanding of the type and magnitude of the health effects of these products. We highlight research gaps and provide recommendations for a global research agenda. [ABSTRACT FROM AUTHOR]

A commentary is presented that discusses tobacco use and exposure to secondhand smoke (SHS) among pregnant women residing in low- and middle-income countries. The authors enumerate some conditions caused by tobacco use in several high-income nations. They offer a chart of research priorities related to tobacco exposure during pregnancy in low- and middle-income nations. They emphasize the need to place tobacco exposure among pregnant women in the context of international challenges to women's health.

Although early ultrasound (<20 weeks' gestation) systematically underestimates the gestational age of smaller fetuses by approximately 1–2 days, this bias is relatively small compared with the large error introduced by last menstrual period (LMP) estimates of gestation, as evidenced by the number of implausible birthweight-for-gestational age. To characterise this misclassification, we compared gestational age estimates based on LMP from California birth certificates with those based on early ultrasound from a California linked Statewide Expanded Alpha-fetoprotein Screening Program (XAFP). The final sample comprised 165 908 women. Birthweight distributions were plotted by gestational age; sensitivity and positive predictive value for preterm rates according to LMP were calculated using ultrasound as the ‘gold standard’. For gestational ages 20–27 and 28–31 weeks, the LMP-based birthweight distributions were bimodal, whereas the ultrasound-based distributions were unimodal, but had long right tails. At 32–36 weeks, the LMP distribution was wider, flatter, and shifted to the right, compared with the ultrasound distribution. LMP vs. ultrasound estimates were, respectively, 8.7% vs. 7.9% preterm (<37 weeks), 81.2% vs. 91.0% term (37–41 weeks), and 10.1% vs. 1.1% post-term (≥42 weeks). The sensitivity of the LMP-based preterm birth estimate was 64.3%, and the positive predictive value was 58.7%. Overall, 17.2% of the records had estimates with an absolute difference of >14 days. The groups most likely to have inconsistent gestational age estimates included African American and Hispanic women, younger and less-educated women, and those who entered prenatal care after the second month of pregnancy. In conclusion, we found substantial misclassification of LMP-based gestational age. The 2003 revised US Standard Certificate of Live Birth includes a new gestational age item, the obstetric estimate. It will be important to assess whether this estimate addresses the problems presented by LMP-based gestational age. [ABSTRACT FROM AUTHOR]

In recent years, national vital statistics data indicate that the US preterm delivery rate has decreased among African Americans and increased among whites. These trends in preterm delivery rates may have been affected, in part, by improvements in the accuracy of gestational age reporting on birth certificates. Several data-editing methods have been developed with the intention of reducing the percentage of records with misclassified gestational age. We explored whether three data-editing methods yielded different trends in preterm delivery for years 1990–2002 among US non-Hispanic white and non-Hispanic African American singleton livebirths. Using National Center for Health Statistics (NCHS) public-use data, we assessed two published methods for editing gestational age, one by Alexander et al. and the other by Zhang and Bowes (Zhang/Bowes). We also assessed a third method that substitutes the clinical estimate (CE) of gestational age when the NCHS last menstrual period (LMP)-based estimate differs from the CE by more than 2 weeks (the LMP/CE method). The percentage of records excluded and/or reclassified by each method was calculated for years 1990, 1996 and 2002. Gestational age-specific birthweight distributions were plotted by race for each method. Preterm delivery rates were calculated and compared by method of editing over time. The percentage of records excluded or reclassified declined from 1990 to 2002 regardless of the method applied. For infants at 28–33 weeks' gestation using the NCHS edited data, birthweight distributions were bimodal, with the second (right-sided) mode showing a mean birthweight consistent with that of term infants. The second mode was less pronounced using the Alexander et al. and the Zhang/Bowes methods, and was not present when the LMP/CE method was used. From 1990 to 2002, preterm delivery rates increased for non-Hispanic whites regardless of method (range 21.3–31.3%). Preterm delivery rates increased slightly for non-Hispanic African Americans with the LMP/CE method (1.8%), and decreased with the other methods (range 6.7–10.8%). Different approaches to editing gestational age from vital records can result in variation in preterm delivery rates and trends. Uncertainty persists around the true trends in preterm delivery, especially among African Americans. Additional research is needed to identify the approach that results in the most accurate classification of gestational age. [ABSTRACT FROM AUTHOR]

Objective Children with autism are known to have larger head circumferences; whether they are above average in height and weight is less clear. Moreover, little is known about growth-related hormone levels in children with autism. We investigated whether children with autism were taller and heavier, and whether they had higher levels of growth-related hormones than control children did. Design A case-control study design was employed. Patients Boys with autism spectrum disorder (ASD) or autism ( n = 71) and age-matched control boys ( n = 59) were evaluated at Cincinnati Children's Hospital. Measurements Height, weight and head circumference were measured. Blood samples were assayed for IGF-1 and 2, IGFBP-3, growth hormone binding protein (GHBP) and for dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). Results Subjects with autism/ASD had significantly ( P = 0·03) greater head circumferences (mean z-score 1·24, SD 1·35) than controls (mean z-score 0·78, SD 0·93). Subjects with autism also had significantly ( P = 0·01) greater weights (mean z-score 0·91, SD 1·13) than controls (mean z-score 0·41, SD 1·11). Height did not differ significantly between groups ( P = 0·65); subjects with autism/ASD had significantly ( P = 0·003) higher body mass indices (BMI) (mean z-score 0·85, SD 1·19) than controls (mean z-score 0·24, SD 1·17). Levels of IGF-1, IGF-2, IGFBP-3 and GHBP in the group with autism/ASD were all significantly higher (all P ≤ 0·0001) than in controls. Conclusions Children with autism/ASD had significantly higher levels of many growth-related hormones: IGF-1, IGF-2, IGFBP-3 and GHBP. These findings could help explain the significantly larger head circumferences and higher weights and BMIs seen in these subjects. Future studies should examine the potential role of growth-related hormones in the pathophysiology of autism. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the trends in pre-pregnancy obesity among women who delivered live infants in nine states in the U.S. from 1993 to 2003. Complications associated with maternal obesity during pregnancy, including preeclampsia, are cited. According to the results, the prevalence rate of pre-pregnancy obesity rose 69.3% during the study period. It suggest a consistent contact with health care providers during pregnancy to alleviate the effects of obesity for future pregnancies.

Objective To evaluate levels of 24-hour urine insulin excretion before the onset of pre-eclampsia and gestational hypertension. Design Nested case–control study within the Calcium for Preeclampsia Prevention (CPEP) study cohort. Setting Five university medical centres in the United States. Sample Cases had developed pre-eclampsia ( n= 70) or gestational hypertension ( n= 142) in the absence of gestational diabetes. Controls ( n= 429) had remained normotensive without gestational diabetes. Methods Subjects were required to have had an adequate baseline 24-hour urine collection prior to CPEP enrolment at 13–21 weeks. Controls were matched to cases by enrolment site and specimen storage time, without regard to gestational age or CPEP treatment. Adjusted mean 24-hour urine insulin excretion was, however, calculated using analysis of covariance, with adjustment models for pre-eclampsia considering body mass index, race and smoking status; and for gestational hypertension, gestational age at specimen collection, height, body mass index and smoking. Urine insulin was measured by radio-immunoassay. Main outcome measures Twenty-four-hour urine insulin excretion. Results Adjusted 24-hour urine insulin excretion at baseline (mean 17 weeks of gestation) was greater in women who developed pre-eclampsia than in normotensive controls (mean [SE]: 15.6 [1.5] vs 13.1 [1.2] × 103μIU/24 hour, P= 0.06), but not in women who developed gestational hypertension (14.7 [0.9] vs 15.0 [0.6] × 103μIU/24 hour, P= 0.79, in cases vs controls). Among women who developed pre-eclampsia, adjusted urine insulin excretion was greater than controls only in women with mild pre-eclampsia and not in severe pre-eclampsia (mild pre-eclampsia vs controls: 17.3 [2.0] vs 13.7 [1.6] × 103μIU/24 hour, P= 0.04; severe pre-eclampsia vs controls: 12.3 [2.2] vs 11.5 [1.2], P= 0.69). Conclusion The data suggest that early hyperinsulinaemia, a marker of insulin resistance, may predispose to mild pre-eclampsia. [ABSTRACT FROM AUTHOR]

Maternal smoking reduces the risk of pre-eclampsia, but has been reported to increase the risk of adverse outcomes related to the disease. We used data from the trial of Calcium for Pre-eclampsia Prevention (CPEP) to explore whether clinical manifestations of pre-eclampsia were altered by maternal smoking. CPEP was a randomised study of 4589 nulliparous women conducted in five US medical centres. Smoking history was obtained at study enrolment and women were monitored for the development of hypertension, proteinuria, and other medical complications.Among pre-eclamptic women (n = 274), the risk of severe disease was not elevated in smokers (adjusted odds ratio 0.87[95% confidence interval (CI) 0.30, 2.51]). Compared with non-smokers, gestational age (days,±SE) at onset of pre-eclampsia was not reduced in smokers (264.8 ± 1.5, and 268.2 ± 5.5, respectively,P = 0.48). The smoking-attributable deficit in birthweight was not increased in pre-eclamptic women compared with normotensive women (97 g[95% CI−49, 244] and 185 g[95% CI 141, 229] respectively).In conclusion, among women who developed pre-eclampsia, smoking during pregnancy was not associated with disease severity. We found no evidence that pre-eclampsia and smoking act synergistically to restrict fetal growth. [ABSTRACT FROM AUTHOR]

Background: Prenatal smoking cessation has substantial health benefits for mothers and offspring, but concerns about weight gain may be a barrier to quitting. We quantified gestational weight gain associated with biochemically confirmed smoking cessation., Methods: Data originated from a randomized controlled cessation trial: Smoking Cessation in Pregnancy project (1987-1991). We calculated gestational weight gain using self-reported prepregnancy weight and measured weight at 30-34 weeks of gestation. We used linear regression to estimate adjusted mean differences in gain for quitters versus continuing smokers by the last trimester. The effects of quitting earlier (by 2nd trimester) versus later (by 3rd trimester) were calculated. We assessed the percentages who gained weight according to Institute of Medicine (IOM) recommendations within 2 weeks of a full-term delivery., Results: At 30-34 weeks, nulliparous and multiparous quitters gained an average of 3.0 pounds (95% CI 0.9-5.1 pounds) (1.4 kg [0.4-2.3 kg]) and 6.6 pounds (95% CI 4.3-8.9 pounds) (3.0 kg [1.9-4.0 kg]) more, respectively, than continuing smokers. Weight gain in early quitters did not differ significantly from that in late quitters. Quitters were more likely than continuing smokers to gain above current guidelines (60.3% vs 46.3%) and were less likely to gain below guidelines (11.5% vs 21.6%) (P = 0.002)., Conclusions: Although quitters had modest additional weight gain by 30-34 weeks compared to continuing smokers, a high proportion in both groups gained in excess of IOM recommendations. Both quitters and continuing smokers may need support to achieve optimal gestational weight gain., (© 2019 Wiley Periodicals, Inc.)

Objective: To evaluate levels of 24-hour urine insulin excretion before the onset of pre-eclampsia and gestational hypertension., Design: Nested case-control study within the Calcium for Preeclampsia Prevention (CPEP) study cohort., Setting: Five university medical centres in the United States., Sample: Cases had developed pre-eclampsia (n= 70) or gestational hypertension (n= 142) in the absence of gestational diabetes. Controls (n= 429) had remained normotensive without gestational diabetes., Methods: Subjects were required to have had an adequate baseline 24-hour urine collection prior to CPEP enrolment at 13-21 weeks. Controls were matched to cases by enrolment site and specimen storage time, without regard to gestational age or CPEP treatment. Adjusted mean 24-hour urine insulin excretion was, however, calculated using analysis of covariance, with adjustment models for pre-eclampsia considering body mass index, race and smoking status; and for gestational hypertension, gestational age at specimen collection, height, body mass index and smoking. Urine insulin was measured by radio-immunoassay., Main Outcome Measures: Twenty-four-hour urine insulin excretion., Results: Adjusted 24-hour urine insulin excretion at baseline (mean 17 weeks of gestation) was greater in women who developed pre-eclampsia than in normotensive controls (mean [SE]: 15.6 [1.5] vs 13.1 [1.2] x 10(3)microIU/24 hour, P= 0.06), but not in women who developed gestational hypertension (14.7 [0.9] vs 15.0 [0.6] x 10(3)microIU/24 hour, P= 0.79, in cases vs controls). Among women who developed pre-eclampsia, adjusted urine insulin excretion was greater than controls only in women with mild pre-eclampsia and not in severe pre-eclampsia (mild pre-eclampsia vs controls: 17.3 [2.0] vs 13.7 [1.6] x 10(3)microIU/24 hour, P= 0.04; severe pre-eclampsia vs controls: 12.3 [2.2] vs 11.5 [1.2], P= 0.69)., Conclusion: The data suggest that early hyperinsulinaemia, a marker of insulin resistance, may predispose to mild pre-eclampsia.