Comparing Fetal Ultrasound Biometric Measurements to Neonatal Anthropometry at the Extremes of Birthweight.

OBJECTIVE: Error in birthweight prediction by sonographic estimated fetal weight (EFW) has clinical implications, such as avoidable cesarean or misclassification of fetal risk in labor. We aimed to evaluate optimal timing of ultrasound and which fetal measurements contribute to error in fetal ultrasound estimations of birth size at the extremes of birthweight. STUDY DESIGN: We compared differences in head circumference (HC), abdominal circumference (AC), femur length, and EFW between ultrasound and corresponding birth measurements within 14 (n = 1,290) and 7 (n = 617) days of birth for small- (SGA, <10th percentile), appropriate- (AGA, 10th-90th), and large-for-gestational age (LGA, >90th) newborns. RESULTS: Average differences between EFW and birthweight for SGA neonates were: -40.2 g (confidence interval [CI]: -82.1, 1.6) at 14 days versus 13.6 g (CI: -52.4, 79.7) at 7 days; for AGA, -122.4 g (-139.6, -105.1) at 14 days versus -27.2 g (-50.4, -4.0) at 7 days; and for LGA, -242.8 g (-306.5, -179.1) at 14 days versus -72.1 g (-152.0, 7.9) at 7 days. Differences between fetal and neonatal HC were larger at 14 versus 7 days, and similar to patterns for EFW and birthweight, differences were the largest for LGA at both intervals. In contrast, differences between fetal and neonatal AC were larger at 7 versus 14 days, suggesting larger error in AC estimation closer to birth. CONCLUSION: Using a standardized ultrasound protocol, SGA neonates had ultrasound measurements closer to actual birth measurements compared with AGA or LGA neonates. LGA neonates had the largest differences between fetal and neonatal size, with measurements 14 days from delivery showing 3- to 4-fold greater differences from birthweight. Differences in EFW and birthweight may not be explained by a single fetal measurement; whether estimation may be improved by incorporation of other knowable factors should be evaluated in future research. KEY POINTS: · Ultrasound measurements may be inadequate to predict neonatal size at birth.. · Birthweight estimation error is higher for neonates >90th percentile.. · There is higher error in AC closer to birth..

Longitudinal changes in maternal anthropometry in relation to neonatal anthropometry.

OBJECTIVE: To characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition. DESIGN: In a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15-28 weeks) and third trimester (28-39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes. SETTING: Women were recruited from twelve US sites (2009-2013).ParticipantsNon-obese women with singleton pregnancies (n 2334). RESULTS: A higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (-0·57 to -0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (-0·05 to 0·06 mm per week). CONCLUSIONS: The rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.

Fetal growth standards: the NICHD fetal growth study approach in context with INTERGROWTH-21st and the World Health Organization Multicentre Growth Reference Study.

Three recently completed longitudinal cohort studies have developed intrauterine fetal growth charts, one in the United States and two international. This expert review compares and contrasts the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies, INTERGROWTH-21st and World Health Organization Multicentre Growth Reference Study conclusions in light of differences in aims, sampling frames, and analytical approaches. An area of controversy is whether a single growth reference is representative of growth, regardless of ethnic or country origin. The INTERGROWTH and World Health Organization Fetal studies used a similar approach as the World Health Organization Multicentre Growth Reference Study for infants and children, the aim of which was to create a single international reference for the best physiological growth for children aged 0-5 years. INTERGROWTH made the same assumption (ie, that there would be no differences internationally among countries or racial/ethnic groups in fetal growth when conditions were optimal). INTERGROWTH found differences in crown-rump length and head circumference among countries but interpreted the differences as not meaningful and presented a pooled standard. The World Health Organization Multicentre Growth Reference Study was designed to create a pooled reference, although they evaluated for and presented country differences, along with discussion of the implications. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Study was designed to assess whether racial/ethnic-specific fetal growth standards were needed, in recognition of the fact that fetal size is commonly estimated from dimensions (head circumference, abdominal circumference, and femur length) in which there are known differences in children and adults of differing racial/ethnic groups. A pooled standard would be derived if no racial/ethnic differences were found. Highly statistically significant racial/ethnic differences in fetal growth were found resulting in the publication of racial/ethnic-specific derived standards. Despite all 3 studies including low-risk status women, the percentiles for fetal dimensions and estimated fetal weight varied among the studies. Specifically, at 39 weeks, the 50th percentile for estimated fetal weight was 3502 g for whites, 3330 g for Hispanics, 3263 g for Asians, and 3256 for blacks in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study, compared with 3186 g for INTERGROWTH and 3403 g for World Health Organization Multicentre Growth Reference Study. When applying these standards to a clinical population, it is important to be aware that different percentages of small- and large-for-gestational-age fetuses will be identified. Also, it may be necessary to use more restrictive cut points, such as the 2.5th or 97.5th, for small-for-gestational-age or large-for-gestational-age fetuses, respectively. Ideally, a comparison of diagnostic accuracy, or misclassification rates, of small-for-gestational-age and large-for-gestational-age fetuses in relation to morbidity and mortality using different criteria is necessary to make recommendations and remains an important data gap. Identification of the appropriate percentile cutoffs in relation to neonatal morbidity and mortality is needed in local populations, depending on which fetal growth chart is used. On a final point, assessment of fetal growth with a one-time measurement remains standard clinical practice, despite recognition that a single measurement can indicate only size. Ultimately, it is knowledge about fetal growth in addition to other factors and clinical judgment that should trigger intervention.

Fetal growth velocity: the NICHD fetal growth studies.

BACKGROUND: Accurately identifying pregnancies with accelerated or diminished fetal growth is challenging and generally based on cross-sectional percentile estimates of fetal weight. Longitudinal growth velocity might improve identification of abnormally grown fetuses. OBJECTIVE: We sought to complement fetal size standards with fetal growth velocity, develop a model to compute fetal growth velocity percentiles for any given set of gestational week intervals, and determine association between fetal growth velocity and birthweight. STUDY DESIGN: This was a prospective cohort study with data collected at 12 US sites (2009 through 2013) from 1733 nonobese, low-risk pregnancies included in the singleton standard. Following a standardized sonogram at 10w0d-13w6d, each woman was randomized to 1 of 4 follow-up visit schedules with 5 additional study sonograms (targeted ranges: 16-22, 24-29, 30-33, 34-37, and 38-41 weeks). Study visits could occur ± 1 week from the targeted GA. Ultrasound biometric measurements included biparietal diameter, head circumference, abdominal circumference, and femur length, and estimated fetal weight was calculated. We used linear mixed models with cubic splines for the fixed effects and random effects to flexibly model ultrasound trajectories. We computed velocity percentiles in 2 ways: (1) difference between 2 consecutive weekly measurements (ie, weekly velocity), and (2) difference between any 2 ultrasounds at a clinically reasonable difference between 2 gestational ages (ie, velocity calculator). We compared correlation between fetal growth velocity percentiles and estimated fetal weight percentiles at 4-week intervals, with 32 (±1) weeks' gestation for illustration. Growth velocity was computed as estimated fetal growth rate (g/wk) between ultrasound at that gestational age and from prior visit [ie, for 28-32 weeks' gestational age: velocity = (estimated fetal weight 32-28)/(gestational age 32-28)]. We examined differences in birthweight by whether or not estimated fetal weight and estimated fetal weight velocity were <5th or ≥5th percentiles using χ2. RESULTS: Fetal growth velocity was nonmonotonic, with acceleration early in pregnancy, peaking at 13, 14, 15, and 16 weeks for biparietal diameter, head circumference, femur length, and abdominal circumference, respectively. Biparietal diameter, head circumference, and abdominal circumference had a second acceleration at 19-22, 19-21, and 27-31 weeks, respectively. Estimated fetal weight velocity peaked around 35 weeks. Fetal growth velocity varied slightly by race/ethnicity although comparisons reflected differences for parameters at various gestational ages. Estimated fetal weight velocity percentiles were not highly correlated with fetal size percentiles (Pearson r = 0.40-0.41, P < .001), suggesting that these measurements reflect different aspects of fetal growth and velocity may add additional information to a single measure of estimated fetal weight. At 32 (SD ± 1) weeks, if both estimated fetal weight velocity and size were <5th percentile, mean birthweight was 2550 g; however, even when size remained <5th percentile but velocity was ≥5th percentile, birthweight increased to 2867 g, reflecting the important contribution of higher growth velocities. For estimated fetal weight ≥5th percentile, but growth velocity <5th, birthweight was smaller (3208 vs 3357 g, respectively, P < .001). CONCLUSION: We provide fetal growth velocity data to complement our previous work on fetal growth size standards, and have developed a calculator to compute fetal growth velocity. Preliminary findings suggest that growth velocity adds additional information over knowing fetal size alone.

Maternal stress and neonatal anthropometry: the NICHD Fetal Growth Studies.

BACKGROUND: The effect of maternal mood disorders on neonatal measurements is not well-defined. The Fetal Growth Studies-Singletons provide a unique opportunity to evaluate the relationship between perceived maternal stress and neonatal growth measurements. OBJECTIVE: The purpose of this study was to determine whether perceived maternal stress during pregnancy is associated with anthropometric measurements in the neonate. STUDY DESIGN: This analysis was based on a prospective, multicenter longitudinal study of fetal growth. Women 18-40 years old with a body mass index of 19.0-29.9 kg/m2 were screened at 8+0 to 13+6 weeks gestation for low-risk status associated with optimal fetal growth (eg, healthy, nonsmoking) and underwent serial sonographic examination at 6 study visits throughout gestation. At each study visit, women completed the Cohen's Perceived Stress Survey, which could have a score that ranges from 0-40. We used a latent class trajectory model to identify distinct groupings (ie, classes) of the Perceived Stress Survey trajectories over pregnancy. Trend analysis was used to determine whether neonatal measurements including birthweight, length, head circumference, and abdominal circumference differed by Perceived Stress Survey class and whether this relationship was modified by maternal race/ethnicity, after adjustment for gestational age at delivery, maternal height, age, and parity. RESULTS: Of the 2334 women enrolled in the study, 1948 women had complete neonatal anthropometry and were included in the analysis. Latent class analysis identified 3 Perceived Stress Survey trajectory classes, with mean Perceived Stress Survey scores of 2.82 (low), 7.95 (medium), and 14.80 (high). Neonatal anthropometric measures of birthweight, length, head circumference and abdominal circumference were similar (P=.78, =.10, =.18, and =.40 respectively), regardless of the participants' Perceived Stress Survey class. There was no effect modification by maternal race/ethnicity. CONCLUSION: Neonatal measurements did not differ by levels of perceived stress among low-risk pregnant women.

Dichorionic twin trajectories: the NICHD Fetal Growth Studies.

BACKGROUND: Systematic evaluation and estimation of growth trajectories in twins require ultrasound measurements across gestation that are performed in controlled clinical settings. Currently, there are few such data for contemporary populations. There is also controversy about whether twin fetal growth should be evaluated with the use of the same benchmarks as singleton growth. OBJECTIVES: Our objective was to define the trajectory of fetal growth in dichorionic twins empirically using longitudinal 2-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard that was developed by our group for singletons. STUDY DESIGN: A prospective cohort of 171 women with twin gestations was recruited from 8 US sites from 2012-2013. After an initial sonogram at 11 weeks 0 days-13 weeks 6 days of gestation during which dichorionicity was confirmed, women were assigned randomly to 1 of 2 serial ultrasonography schedules. Growth curves and percentiles were estimated with the use of linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1731 singletons, after adjustment for maternal age, race/ethnicity, height, weight, parity, employment, marital status, insurance, income, education, and infant sex. Linear mixed models were used to test for overall differences between the twin and singleton trajectories with the use of likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables. Singleton standards were weighted to correspond to the distribution of maternal race in twins. For those ultrasound measurements in which there were significant global tests for differences between twins and singletons, we tested for week-specific differences using Wald tests that were computed at each gestational age. In a separate analysis, we evaluated the degree of reclassification in small for gestational age, which was defined as <10th percentile that would be introduced if fetal growth estimation for twins was based on an unweighted singleton standard. RESULTS: Women underwent a median of 5 ultrasound scans. The 50th percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly beginning at 32 weeks of gestation; biparietal diameter in twins was smaller from 34-36 weeks of gestation. There were no differences in head circumference or femur length. The mean head circumference/abdominal circumference ratio was progressively larger for twins compared with singletons beginning at 33 weeks of gestation, which indicated a comparatively asymmetric growth pattern. At 35 weeks of gestation, the average gestational age at delivery for twins, the estimated fetal weights for the 10th, 50th, and 90th percentiles were 1960, 2376, and 2879 g for dichorionic twins, respectively, and 2180, 2567, and 3022 g for the singletons, respectively. At 32 weeks of gestation, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age with the use of a singleton, non-Hispanic white standard. By 35 weeks of gestation, 38% of twins would be classified as small for gestational age. CONCLUSION: The comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks of gestation, is consistent with the concept that the intrauterine environment becomes constrained in its ability to sustain growth in twin fetuses. Near term, nearly 40% of twins would be classified as small for gestational age based on a singleton growth standard.

Ultrasound Quality Assurance for Singletons in the National Institute of Child Health and Human Development Fetal Growth Studies.

OBJECTIVES: To report on the ultrasound quality assurance program for the National Institute of Child Health and Human Development Fetal Growth Studies and describe both its advantages and generalizability. METHODS: After training on an ultrasound system and software, research sonographers were expected to capture blank (unmeasured) images in triplicate for crown-rump length, biparietal diameter, head circumference, abdominal circumference, and femur length. A primary expert sonographer was designated and validated. A 5% sample (n = 740 of 14,785 scans) was randomly selected in 3 distinct rounds from within strata of maternal body mass index (round 1 only), gestational age, and research site. Unmeasured images were extracted from selected scans and measured with the ultrasound software by an expert sonographer. Correlations and coefficients of variation (CVs) were calculated, and the within-measurement standard deviation (ie, technical error of the measurement), was calculated. RESULTS: The reliability between the site sonographers and the expert was high, with correlations exceeding 0.99 for all dimensions in all rounds. The CV % values showed low variability, with the percentage differences being less than 2%, except for abdominal circumference in rounds 2 and 3, in which it averaged about 3%. Correlations remained high (>0.90) with increasing fetal size; there was a monotonic increase in technical errors of the measurement but without a corresponding increase in the CV %. CONCLUSIONS: Using rigorous procedures for training sonographers, coupled with quality assurance oversight, we determined that the measurements acquired longitudinally for singletons are both accurate and reliable for establishment of an ultrasound standard for fetal growth.

Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.

OBJECTIVE: Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. STUDY DESIGN: We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. RESULTS: EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). CONCLUSION: Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.

Age at hormonal onset of puberty based on luteinizing hormone, inhibin B, and body composition in preadolescent U.S. girls.

BACKGROUND: Hormonal indicators could be useful for detecting early pubertal onset, but there is little research on how they are related to puberty in U.S. girls. We determined median age at hormonal onset of puberty based on luteinizing hormone (LH) and inhibin B (InB) and explored the extent to which body composition moderates this timing process. METHODS: We analyzed anthropometric and hormone data of 698 US peri-pubertal girls ages 6-11.99 y who had participated in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. RESULTS: Median age of hormonal onset of puberty was 10.43 y by LH and 10.08 y by InB cut-offs (1.04 mIU/ml for LH and 17.89 pg/ml for InB). Postnatal weight gain modulated onset, making it earlier by 10-11 mo among the highest (greater than +1 SD) relative to normal weight gainers. Onset occurred first in non-Hispanic black (NHB) girls, 10.08 y (95% confidence interval (CI): 10.07-10.09), followed by Mexican-American (MXAM) at 10.64 y (95% CI: 10.63-10.65), and at 10.66 y (95% CI: 10.66-10.67) for non-Hispanic white (NHW) girls using LH. With InB, onset occurred first in MXAM girls at 9.9 y, and at 10.3 y and 10.4 y for their NHB and NHW peers, respectively. CONCLUSION: Preadolescent weight gain lowers the age at hormonal onset as defined by LH concentrations. Preventing obesity in childhood may also avert the earlier initiation of the maturation process even at the hormonal level.

Methodology for establishing a population-based birth cohort focusing on couple fertility and children's development, the Upstate KIDS Study.

BACKGROUND: Critical data gaps remain regarding infertility treatment and child development. We assessed the utility of a birth certificate registry for developing a population cohort aimed at answering such questions. METHODS: We utilised the Upstate New York livebirth registry (n = 201,063) to select births conceived with (n = 4024) infertility treatment or exposed infants, who were then frequency-matched by residence to a random sample of infants conceived without (n = 14,455) treatment or unexposed infants, 2008-10. Mothers were recruited at 2-4 months postpartum and queried about their reproductive histories, including infertility treatment for comparison with birth certificate data. Overall, 1297 (32%) mothers of exposed and 3692 of unexposed (26%) infants enrolled. RESULTS: Twins represented 22% of each infant group. The percentage of infants conceived with/without infertility treatment was similar whether derived from the birth registry or maternal report: 71% none, 16% drugs or intrauterine insemination, and 14% assisted reproductive technologies (ART). Concordant reporting between the two data sources was 93% for no treatment, 88% for ART, and 83% for fertility drugs, but differed by plurality. Exposed infants had slightly (P < 0.01) earlier gestations than unexposed infants (38.3 ± 2.8 and 38.7 ± 2.7 weeks, respectively) based upon birth certificates but not maternal report (38.7 ± 2.7 and 38.7 ± 2.9, respectively). Conversely, mean birthweight was comparable using birth certificates (3157 ± 704 and 3194 ± 679 g, respectively), but differed using maternal report (3167 ± 692 and 3224 ± 661, respectively P < 0.05). CONCLUSIONS: The birth certificate registry is a suitable sampling framework as measured by concordance with maternally reported infertility treatment. Future efforts should address the impact of factors associated with discordant reporting on research findings.

Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study.

OBJECTIVE: We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN: In this prospective matched, exposure cohort design, 495 women aged 18-44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, population cohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort. RESULTS: The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3-4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3-4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57-3.76) and population (AOR, 7.91; 95% CI, 1.69-37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28-4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44-5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32-0.75), parity (AOR, 0.42; 95% CI, 0.28-0.64), and body mass index (AOR, 0.95; 95% CI, 0.93-0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor. CONCLUSION: An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized.

Perfluorochemicals and endometriosis: the ENDO study.

BACKGROUND: Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues. METHODS: We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity. RESULTS: Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively). CONCLUSIONS: Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.

Inhibin B and luteinizing hormone levels in girls aged 6-11 years from NHANES III, 1988-1994.

OBJECTIVE: To evaluate inhibin B and luteinizing hormone (LH) levels in a large, representative cross-sectional sample of US girls and characterize the relationships of these laboratory values with age, clinical signs of puberty and other correlates. DESIGN: Cross-sectional analysis of LH and inhibin B in banked serum from 720 girls aged 6-11 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III). MEASUREMENTS: Levels of inhibin B and LH, race, ethnicity and anthropometric measurements were compared for all girls. Visual assessment of pubertal stage was performed on girls aged 8 years and older. A two-part model was used to establish normative data and Tobit regression models were used to evaluate associations with participant characteristics. Receiver operating characteristic (ROC) analysis was performed to identify optimum cut points predictive of puberty onset. RESULTS: Mean hormone levels progressively increased with age. LH levels progressively increased with pubertal stage. Inhibin B levels increased gradually from breast stage I to II, then more sharply to peak at stage III, followed by a plateau at stages IV and V. ROC curves indicated that both hormones were consistent with pubertal onset as indicated by breast stage II. CONCLUSIONS: This study characterizes inhibin B and LH values in a large, representative cross-sectional sample of US girls. Inhibin B can be a useful tool in combination with other clinical and biochemical parameters to evaluate gonadal function as a reflection of pubertal progression in girls.

Urinary concentrations of benzophenone-type UV filters in U.S. women and their association with endometriosis.

Benzophenone (BP)-type UV filters are widely used in a variety of personal care products for the protection of skin and hair from UV irradiation. Despite the estrogenic potencies of BP derivatives, few studies have examined the occurrence of these compounds in human matrices. Furthermore, associations among exposure to these compounds and estrogen-dependent diseases (such as endometriosis) have not been examined previously. In this study, we determined the concentrations of five BP derivatives, 2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2'-dihydroxy-4-methoxybenzophenone (2,2'OH-4MeO-BP), 2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'OH-BP), and 4-hydroxybenzophenone (4OH-BP), in urine collected from 625 women in Utah and California, using liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The association of urinary concentrations of BP derivatives with an increase in the odds of a diagnosis of endometriosis was examined in 600 women who underwent laparoscopy/laparotomy (n = 473: operative cohort) or pelvic magnetic resonance imaging (n = 127: population cohort), during 2007-2009. 2OH-4MeO-BP, 2,4OH-BP, and 4OH-BP respectively were detected in 99.0%, 93.3%, and 83.8% of the urine samples analyzed, whereas the detection rates for 2,2',4,4'OH-BP and 2,2'OH-4MeO-BP were below 6.0%. Significant regional differences (higher concentrations in California) and monthly variations (higher concentrations in July and August) were found for urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP. In addition, urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP tended to be higher in more affluent, older, and leaner women. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the urinary concentrations of BP derivatives and the odds of an endometriosis diagnosis; ORs increased across quartiles of 2OH-4MeO-BP and 2,4OH-BP concentrations, but a significant trend was observed only between 2,4OH-BP and the odds of an endometriosis diagnosis in the operative cohort (OR = 1.19; 95% CI = 1.01, 1.41). When women in the highest quartile of 2,4OH-BP concentrations were compared with women in the first three quartiles, the OR increased considerably (OR = 1.65; 95% CI = 1.07, 2.53). Given that 2,4OH-BP possesses an estrogenic activity higher than that of 2OH-4MeO-BP, our results invite the speculation that exposure to elevated 2,4OH-BP levels may be associated with endometriosis.

Cholesterol, endocrine and metabolic disturbances in sporadic anovulatory women with regular menstruation.

BACKGROUND: Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation. METHODS: The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18-44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles. RESULTS: Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005). CONCLUSIONS: These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome.

Age at menarche and risk of type 2 diabetes: results from 2 large prospective cohort studies.

The authors investigated the association between age at menarche and risk of type 2 diabetes mellitus (T2DM) among 101,415 women from the Nurses' Health Study (NHS) aged 34-59 years (1980-2006) and 100,547 women from Nurses' Health Study II (NHS II) aged 26-46 years (1991-2005). During 2,430,274 and 1,373,875 person-years of follow-up, respectively, 7,963 and 2,739 incident cases of T2DM were documented. Young age at menarche was associated with increased risk of T2DM after adjustment for potential confounders, including body figure at age 10 years and body mass index (BMI; weight (kg)/height (m)(2)) at age 18 years. Relative risks of T2DM across age-at-menarche categories (< or =11, 12, 13, 14, and > or =15 years) were 1.18 (95% confidence interval (CI): 1.10, 1.27), 1.09 (95% CI: 1.02, 1.17), 1.00 (referent), 0.92 (95% CI: 0.83, 1.01), and 0.95 (95% CI: 0.84, 1.06), respectively, in the NHS (P for trend < 0.0001) and 1.40 (95% CI: 1.24, 1.57), 1.13 (95% CI: 1.00, 1.27), 1.00 (referent), 0.98 (95% CI: 0.82, 1.18), and 0.96 (95% CI: 0.78, 1.19), respectively, in NHS II (P for trend < 0.0001). Associations were substantially attenuated after additional control for updated time-varying BMI. These data suggest that early menarche is associated with increased risk of T2DM in adulthood. The association may be largely mediated through excessive adult adiposity. The association was stronger among younger women, supporting a role for sex hormones in younger onset of T2DM, in addition to BMI.

Influence of endogenous reproductive hormones on F2-isoprostane levels in premenopausal women: the BioCycle Study.

Endogenous reproductive hormones and oxidative stress have been independently linked to risk of chronic disease but mostly in postmenopausal women. The interplay between endogenous reproductive hormones and oxidative stress among premenopausal women, however, has yet to be clearly elucidated. The objective of this study was to investigate the association between endogenous reproductive hormones and F(2)-isoprostanes in the BioCycle Study. Women aged 18-44 years from western New York State were followed prospectively for up to 2 menstrual cycles (n = 259) during 2005-2007. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, F(2)-isoprostanes, and thiobarbituric acid-reactive substances were measured up to 8 times per cycle at clinic visits timed by using fertility monitors. F(2)-Isoprostane levels had an independent positive association with estradiol (beta = 0.02, 95% confidence interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin and follicle-stimulating hormone (beta = -0.04, 95% confidence interval: -0.07, -0.003; beta = -0.02, 95% confidence interval: -0.03, -0.002, respectively) after adjustment for age, race, age at menarche, gamma-tocopherol, beta-carotene, total cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric acid-reactive substances, a less specific marker of oxidative stress, had similar associations. If F(2)-isoprostanes are specific markers of oxidative stress, these results call into question the commonly held hypothesis that endogenous estradiol reduces oxidative stress.

Luteinizing hormone, testosterone and inhibin B levels in the peripubertal period and racial/ethnic differences among boys aged 6-11 years: analyses from NHANES III, 1988-1994.

OBJECTIVE: To determine whether the initial physical findings of puberty are accompanied by hormonal evidence of pubertal activation of the hypothalamic-pituitary-gonadal (HPG) axis and whether racial/ethnic differences exist, we have analysed hormone levels in relation to age, onset of puberty and race/ethnicity. DESIGN: Cross-sectional analysis of luteinizing hormone (LH), testosterone (T) and inhibin B from banked sera from a representative sample of US boys aged 6·0-11·99 years who participated in the National Health and Nutrition Examination Survey (NHANES) III. PATIENTS: Eight hundred and twenty-eight boys having sera including 228 non-Hispanic white (NHW), 266 non-Hispanic black (NHB), 288 Mexican-American (MA) and 46 'other'. MEASUREMENTS: Using analysis of variance and linear regression techniques, concentrations of LH, T and inhibin B were compared by race/ethnicity for all boys and pubertal status (Tanner's Staging 1, 2 and 3+) for boys aged 8 years and older. Receiver operating curves were utilized to identify cut-points predictive of pubertal HPG status. RESULTS: Mean hormones levels progressively increased with age. Receiver operating characteristic (ROC) curves indicate hormones are consistent with pubertal onset as indicated by Tanner stage 2, except for T and genital stage 2. Inhibin B and LH levels increased significantly by genital stage after adjusting for age and race/ethnicity, while LH and T concentrations increased significantly across pubic hair stages. Levels of inhibin B were significantly higher for NHB boys compared with other racial/ethnic groups. CONCLUSIONS: In these cross-sectional findings, hormone levels rise gradually as boys approach the peripubertal age, whereas an abrupt rise was not associated with the onset of physical changes of puberty.