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Fetal growth pathology score: a novel ultrasound parameter for individualized assessment of third trimester growth abnormalities.

ABSTRACT: OBJECTIVES:To study fetal growth in pregnancies at risk for growth restriction (GR) using, for the first time, the fetal growth pathology score (FGPS1). METHODS:A retrospective cohort study of GR was carried out in 184 selected SGA singletons using a novel, composite measure of growth abnormalities termed the FGPS1. Serial fetal biometry was used to establish second trimester Rossavik size models and determine FGPS1 values prior to delivery. FGPS1 data were compared to neonatal growth outcomes assessed using growth potential realization index (GPRI) values (average negative pathological GPRI (av?-?pGPRI)). Growth at the end of pregnancy was evaluated from differences in negative, individual composite prenatal growth assessment scores (-icPGAS) measured at the last two ultrasound scans. The FGPS1 and av?-?pGPRI values were used to classify fetal growth and neonatal growth outcomes, respectively, as Normal (N) or Abnormal (A). RESULTS:The risk of neonatal GR (based on birth weight (BW)) was moderate (MR: between 5th and10th percentiles (n?=?113)) or significant (SR:<5th percentile) (n?=?71)). Individual pregnancies were grouped into four categories, two representing agreement (N-N (29%), A-A (40%)) and two representing discordance (N-A (11%), A-N (20%)). In the largest and most variable subgroup (A-A,<5%tile, n?=?49), there was a statistically significant correlation (0.63, p?

SUBMITTER: Deter RL

PROVIDER: S-EPMC5813490 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Fetal growth pathology score: a novel ultrasound parameter for individualized assessment of third trimester growth abnormalities.

Deter Russell L RL Lee Wesley W Kingdom John C P JCP Romero Roberto R

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 20170320 7

<h4>Objectives</h4>To study fetal growth in pregnancies at risk for growth restriction (GR) using, for the first time, the fetal growth pathology score (FGPS1).<h4>Methods</h4>A retrospective cohort study of GR was carried out in 184 selected SGA singletons using a novel, composite measure of growth abnormalities termed the FGPS1. Serial fetal biometry was used to establish second trimester Rossavik size models and determine FGPS1 values prior to delivery. FGPS1 data were compared to neonatal gr ...[more]

PMID: 28277911

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Project description:ObjectiveTo compare third-trimester size trajectory prediction errors (average transformed percent deviations) for three individualized fetal growth assessment methods.MethodsThis study utilized longitudinal measurements of nine directly measured size parameters in 118 fetuses with normal neonatal growth outcomes. Expected value (EV) function coefficients and variance components were obtained using two-level random coefficient modeling. Growth models (IGA) or EV coefficients and variance components (PLM and CPM) were used to calculate predicted values at ∼400 third-trimester time points. Percent deviations (%Dev) calculated at these time points using all three methods were expressed as percentages of IGA MA-specific reference ranges [transformed percent deviations (T%Dev)]. Third-trimester T%Dev values were averaged (aT%Dev) for each parameter. Mean ± standard deviation's for sets of aT%Dev values derived from each method (IGA, PLM and CPM) were calculated and compared.ResultsMean aT%Dev values for nine parameters were: (i) IGA: -4.3 to 5.2% (9/9 not different from zero); (ii) PLM: -32.7 to 25.6% (4/9 not different from zero) and (iii) CPM: -20.4 to 17.4% (5/9 not different from zero). Seven of nine systematic deviations from zero were statistically significant when IGA values were compared to either PLM or CPM values. Variabilities were smaller for IGA when compared to those for PLM or CPM, with (i) 5/9 being statistically significant (IGA versus PLM), (ii) 2/9 being statistically significant (IGA versus CPM) and (iii) 5/9 being statistically significant (PLM versus CPM).ConclusionsSignificant differences in the agreement between predicted third-trimester size parameters and their measured values were found for the three methods tested. With most parameters, IGA gave smaller mean aT%Dev values and smaller variabilities. The CPM method was better than the PLM approach for most but not all parameters. These results suggest that third-trimester size trajectories are best characterized by IGA in fetuses with normal growth outcomes.

Project description:OBJECTIVES:To characterize second and third trimester fetal growth using Individualized Growth Assessment methods in a larger cohort of fetuses with normal neonatal growth outcomes. METHODS:A prospective longitudinal study of 119 pregnancies was performed from 18 weeks, MA, to delivery. Measurements of several 1D and 3D fetal size parameters were obtained from 3D volume data sets at 3-4 week intervals. Regression analyses were used to determine Start Points (SP) and Rossavik model (P?=?c {t} (k?+?st)) coefficients c. k and s for each parameter in each fetus. Second trimester growth velocity reference ranges were determined and size model specification functions re-established, the latter used to generate individual size models. Actual measurements were compared to predicted third trimester size trajectories using Percent Deviations. New age-specific reference ranges for the Percent Deviations of each parameter were defined using 2-level statistical modeling. RESULTS:Rossavik models fit the data for all parameters very well (R(2): 99%), with SP's and k values similar to those found in much smaller cohorts. The c* values were strongly related to the second trimester slope (R(2): 97%), as was predicted s* to estimated c* (R(2): 54--95%). Rossavik models predicted third trimester growth with systematic errors close to 0%; random errors (95% range) ranged between 5.7 and 10.9% and 20.0 and 24.3% for 1D and 3D parameters, respectively. CONCLUSIONS:IGA procedures for evaluating second and third trimester growth are now established based on a larger cohort (4-6 fold larger). New, more rigorously defined, age-specific standards for the evaluation of third trimester size deviations are now available for nine anatomical parameters and a weight estimation procedure that incorporates a soft tissue parameter (fractional thigh volume). These results provide a means for more reliably assessing fetal growth on an individualized basis, thus minimizing the effect of biological differences in growth.

Project description:BackgroundPregnancy associated malaria is associated with decreased birth weight, but in-utero evaluation of fetal growth alterations is rarely performed. The objective of this study was to investigate malaria induced changes in fetal growth during the 3(rd) trimester using trans-abdominal ultrasound.MethodsAn observational study of 876 pregnant women (398 primi- and secundigravidae and 478 multigravidae) was conducted in Tanzania. Fetal growth was monitored with ultrasound and screening for malaria was performed regularly. Birth weight and fetal weight were converted to z-scores, and fetal growth evaluated as fetal weight gain from the 26th week of pregnancy.ResultsMalaria infection only affected birth weight and fetal growth among primi- and secundigravid women. Forty-eight of the 398 primi- and secundigravid women had malaria during pregnancy causing a reduction in the newborns z-score of -0.50 (95% CI: -0.86, -0.13, P?=?0.008, multiple linear regression). Fifty-eight percent (28/48) of the primi- and secundigravidae had malaria in the first half of pregnancy, but an effect on fetal growth was observed in the 3(rd) trimester with an OR of 4.89 for the fetal growth rate belonging to the lowest 25% in the population (95%CI: 2.03-11.79, P<0.001, multiple logistic regression). At an individual level, among the primi- and secundigravidae, 27% experienced alterations of fetal growth immediately after exposure but only for a short interval, 27% only late in pregnancy, 16.2% persistently from exposure until the end of pregnancy, and 29.7% had no alterations of fetal growth.ConclusionsThe effect of malaria infections was observed during the 3(rd) trimester, despite infections occurring much earlier in pregnancy, and different mechanisms might operate leading to different patterns of growth alterations. This study highlights the need for protection against malaria throughout pregnancy and the recognition that observed changes in fetal growth might be a consequence of an infection much earlier in pregnancy.

Project description:ObjectivesOperators performing fetal growth scans are usually aware of the gestational age of the pregnancy, which may lead to expected-value bias when performing biometric measurements. We aimed to evaluate the incidence of expected-value bias in routine fetal growth scans and assess its impact on standard biometric measurements.MethodsWe collected prospectively full-length video recordings of routine ultrasound growth scans coupled with operator eye tracking. Expected value was defined as the gestational age at the time of the scan, based on the estimated due date that was established at the dating scan. Expected-value bias was defined as occurring when the operator looked at the measurement box on the screen during the process of caliper adjustment before saving a measurement. We studied the three standard biometric planes on which measurements of head circumference (HC), abdominal circumference (AC) and femur length (FL) are obtained. We evaluated the incidence of expected-value bias and quantified the impact of biased measurements.ResultsWe analyzed 272 third-trimester growth scans, performed by 16 operators, during which a total of 1409 measurements (354 HC, 703 AC and 352 FL; including repeat measurements) were obtained. Expected-value bias occurred in 91.4% of the saved standard biometric plane measurements (85.0% for HC, 92.9% for AC and 94.9% for FL). The operators were more likely to adjust the measurements towards the expected value than away from it (47.7% vs 19.7% of measurements; P?<?0.001). On average, measurements were corrected by 2.3?±?5.6, 2.4?±?10.4 and 3.2?±?10.4?days of gestation towards the expected gestational age for the HC, AC, and FL measurements, respectively. Additionally, we noted a statistically significant reduction in measurement variance once the operator was biased (P?=?0.026). Comparing the lowest and highest possible estimated fetal weight (using the smallest and largest biased HC, AC and FL measurements), we noted that the discordance, in percentage terms, was 10.1%?±?6.5%, and that in 17% (95%?CI, 12-21%) of the scans, the fetus could be considered as small-for-gestational age or appropriate-for-gestational age if using the smallest or largest possible measurements, respectively. Similarly, in 13% (95%?CI, 9-16%) of scans, the fetus could be considered as large-for-gestational age or appropriate-for-gestational age if using the largest or smallest possible measurements, respectively.ConclusionsDuring routine third-trimester growth scans, expected-value bias frequently occurs and significantly changes standard biometric measurements obtained. © 2019 the Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Project description:Pregnancy-induced changes in plasma pharmacokinetics of many antiretrovirals (ARV) are well-established. Current knowledge about the extent of ARV exposure in lymphoid tissues of pregnant women and within the fetal compartment is limited due to their inaccessibility. Subtherapeutic ARV concentrations in HIV reservoirs like lymphoid tissues during pregnancy may constitute a barrier to adequate virological suppression and increase the risk of mother-to-child transmission (MTCT). The present study describes the pharmacokinetics of three ARVs (efavirenz, dolutegravir, and rilpivirine) in lymphoid tissues and fetal plasma during pregnancy using materno-fetal physiologically-based pharmacokinetic models (m-f-PBPK). Lymphatic and fetal compartments were integrated into our previously validated adult PBPK model. Physiological and drug disposition processes were described using ordinary differential equations. For each drug, virtual pregnant women (n = 50 per simulation) received the standard dose during the third trimester. Essential pharmacokinetic parameters, including Cmax, Cmin, and AUC (0-24), were computed from the concentration-time data at steady state for lymph and fetal plasma. Models were qualified by comparison of predictions with published clinical data, the acceptance threshold being an absolute average fold-error (AAFE) within 2.0. AAFE for all model predictions was within 1.08-1.99 for all three drugs. Maternal lymph concentration 24 h after dose exceeded the reported minimum effective concentration (MEC) for efavirenz (11,514 vs. 800 ng/ml) and rilpivirine (118.8 vs. 50 ng/ml), but was substantially lower for dolutegravir (16.96 vs. 300 ng/ml). In addition, predicted maternal lymph-to-plasma AUC ratios vary considerably (6.431-efavirenz, 0.016-dolutegravir, 1.717-rilpivirine). Furthermore, fetal plasma-to-maternal plasma AUC ratios were 0.59 for efavirenz, 0.78 for dolutegravir, and 0.57 for rilpivirine. Compared with rilpivirine (0 h), longer dose forgiveness was observed for dolutegravir in fetal plasma (42 h), and for efavirenz in maternal lymph (12 h). The predicted low lymphoid tissue penetration of dolutegravir appears to be significantly offset by its extended dose forgiveness and adequate fetal compartment exposure. Hence, it is unlikely to be a predictor of maternal virological failure or MTCT risks. Predictions from our m-f-PBPK models align with recommendations of no dose adjustment despite moderate changes in exposure during pregnancy for these drugs. This is an important new application of PBPK modeling to evaluate the adequacy of drug exposure in otherwise inaccessible compartments.

Dataset Information

Fetal growth pathology score: a novel ultrasound parameter for individualized assessment of third trimester growth abnormalities.

Publications

Fetal growth pathology score: a novel ultrasound parameter for individualized assessment of third trimester growth abnormalities.

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