Standards for evaluating neonatal growth outcomes using individualized pathological growth potential realization indices.

OBJECTIVE: Provide standards for detecting neonatal growth abnormalities with the average pathological Growth Potential Realization Index (av. pGPRI). METHODS: Individualized Growth Assessment (IGA) evaluations of 117 neonates with normal growth outcomes were carried out using measurements of WT, HC, AC, ThC and CHL. Growth Potential Realization Index (GPRI) values for each parameter were calculated from predicted and actual birth measurements, the former obtained using Rossavik size models derived from the second-trimester growth potential estimates. Subtraction of either the upper and lower boundaries of GPRI reference ranges from these GPRI measurements gave + pGPRI and - pGPRI measurements. GPRI's within their reference ranges were assigned pGPRI values of zero. Average values for these two types of pGPRI's were calculated for the WT, HC, CHL set (n = 117) and the WT, HC, AC, ThC, CHL set (n = 112). RESULTS: The 95% reference ranges for the av. +pGPRI's and av. -pGPRI's in the WT, HC, CHL set were 0% to +0.50% and 0% to -0.40%, respectively. In the WT, HC, AC, ThC, CHL set, the comparable results were 0% to +0.50% and 0% to -0.72%. CONCLUSION: Standards are provided for classifying neonatal growth outcomes with a parameter quantifying growth pathology that was based on individualized growth potentials.

Individualized growth assessment in pregnancies complicated by fetal gastroschisis.

OBJECTIVE: Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases. STUDY DESIGN: Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements. RESULTS: Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (n = 19), there was 84% agreement between IGA and conventional methods in determining pathological growth in both the 3rd trimester and at birth. In the growth restriction and recovery group (n = 7), there was 71% agreement both in the 3rd trimester and at birth between IGA and conventional methods. In the progressive growth restriction group (n = 5), there was 100% agreement in the 3rd trimester and 60% agreement at birth between IGA and conventional methods. CONCLUSION: We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns - one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

Growth patterns and cardiovascular abnormalities in SGA fetuses: 2. Normal growth and progressive growth restriction.

OBJECTIVES: To characterize growth processes and their associated cardiovascular abnormalities in SGA fetuses with normal growth and progressive growth restriction patterns as defined by Individualized Growth Assessment (IGA). METHODS: A SGA cohort (EFW and BW < 10th percentile) was derived from the PORTO study that included 47 fetuses with normal growth outcome (SGA Normal) and 34 fetuses with progressive growth restriction (SGA Growth Restricted, Pattern 1). Composite fetal size parameters were used to quantify growth pathology at individual third trimester time points (individual composite Prenatal Growth Assessment Score {icPGAS}) and calculated cumulatively during the third trimester (Fetal Growth Pathology Score 1{FGPS1}). Paired Doppler evaluations of the umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and myocardial performance index (MPI) were used to detect cardiovascular anomalies. Outcome variables were birth age and birth weight. RESULTS: Ranking fetuses with respect to the severity of the 3rd trimester growth pathology (-FGPS1) revealed three subgroups in each of these two groups. In SGA Normal, no (51%), minimal (19%) or minor (30%) growth abnormalities were present. Although vascular flow abnormalities occurred without growth abnormalities (UA: 38%; MCA: 35%), they increased with minor growth disturbances (UA: 64%; MCA: 50%). All fetuses delivered at term and in only 7 cases (minor growth abnormalities subgroup) were the neonates abnormally small based on IGA criteria. In SGA Growth Restricted, Pattern 1, the progression of growth restriction was slow (47%), moderate (21%) and rapid (32%). Corresponding median -FGPS1 values were -1.34%, -2.67% and -4.88%, respectively. The median age of onset was 33.6, 29.7 and 29.7 weeks in these three subgroups. UA abnormalities occurred infrequently in the first two subgroups but were found in all cases of rapidly progressing pathology. Similar results were found for the MCA and DV + MPI Doppler parameters (rapid progression: MCA = 50%; DV + MPI = 50%). Premature delivery occurred less frequently with slow progression but was nearly 100% in the moderately and rapidly progressive subgroups. CONCLUSIONS: Negative FGPS1 growth restriction patterns can be used to classify SGA fetuses. Subgroups, based on ranked -FGPS1 values in both SGA Normal and SGA Growth Restricted Pattern 1 groups had marked differences in cardiovascular abnormalities and neonatal outcomes. The characteristics of these two groups are consistent with small, normally growing fetuses and fetuses with "early" growth restriction, respectively.

Growth patterns and cardiovascular abnormalities in SGA fetuses: 3. Late, adaptive and recovering growth restriction.

OBJECTIVE: To characterize abnormal growth processes and their associated cardiovascular abnormalities in SGA fetuses using Individualized Growth Assessment (IGA). METHODS: This longitudinal investigation utilized a SGA cohort [EFW and BW <10th percentile] derived from the PORTO study. Fetuses categorized by their Fetal Growth Pathology Score [FGPS1] patterns [Pattern 2 {n = 12}, Pattern 3 {n = 11}, Pattern 5 {n = 13}] were evaluated. Growth pathology was measured using the -FGPS1 and the individual composite Prenatal Growth Assessment Score {-icPGAS]. Paired cardiovascular assessments utilized measurements of the Pulsatility Index [umbilical artery {UA}, middle cerebral artery {MCA}, ductus venosus {DV}] and the myocardial performance index [MPI; heart]. Outcome variables were birth age [preterm or, term] and birth weight [small or normal (IGA criteria)]. RESULTS: Pattern 2 was usually characterized by a single, growth abnormality (67% of cases) of variable magnitude that occurred within two weeks of delivery {median onset age: 37.6 weeks}. The incidence of UA abnormalities was low (25%) while those of MCA and DV/MPI were high {60%, 42%}. Most neonates were of normal size (67%) and delivered at term (67%).Pattern 3 had an initial progressive growth restriction phase, followed by constant but abnormally low growth. Growth pathology had an early onset (median age: 31.6 weeks), was moderate but persistently abnormal. The incidences of cardiovascular abnormalities were moderate [30-50%]. Most neonates were abnormally small (80%) but delivered at term (90%).Pattern 5 had an initial progressive phase with an early onset [onset age {median}: 31.6 weeks]. However, this process was arrested and returned toward normal. Growth pathology magnitudes were minor as were the incidences of cardiovascular abnormalities. Neonatal size was usually normal and all fetuses delivered at term. CONCLUSIONS: Characteristics of SGA Growth Restricted, Patterns 2, 3 and 5 are clearly different from those found in SGA Normal or SGA Growth Restricted Pattern 1 groups. They also differed from one another, indicating that growth restriction can manifest itself in several different ways. Pattern 2 is similar to "late" growth restriction reported previously. Patterns 3 and 5 are novel and have been designated as "adaptive" and "recovering" types of growth restriction.

Growth patterns and cardiovascular abnormalities in small for gestational age fetuses: 1. Pattern characteristics.

BACKGROUND: Fetal growth restriction is being defined as either "early" or "late" depending on age of onset. A recent investigation using individualized assessment has identified five different growth restriction patterns. No previous study has related these patterns to cardiovascular abnormalities. OBJECTIVES: To determine growth patterns in small fetuses (BW < 10th percentile) using Individualized Growth Assessment (IGA) and to relate cardiovascular abnormalities found with Doppler ultrasound to these patterns. STUDY DESIGN: A secondary analysis was carried out in 126 fetuses from the PORTO data set having both estimated weights and birth weights below the 10th percentile. Only fetuses with 2nd and 3rd trimester biometry scans appropriate for IGA and cardiovascular assessments were studied. There was one-to-one matching of biometry and Doppler evaluations in the 3rd trimester. Composite growth parameters were used to quantify growth pathology at individual time points (individual composite Prenatal Growth Assessment Score (icPGAS)) and during the 3rd trimester (Fetal Growth Pathology Score {FGPS1}). Normal and growth restriction patterns were identified using plots of FGPS1 values. Doppler measurements were classified as normal or abnormal based on published cross-sectional standards. Outcome variables were birth weight and birth age. RESULTS: In these SGA cases, 38.2% showed normal fetal growth and 61.8% had growth restriction. In the latter, seven different patterns were observed. Pattern 1 was most common (43.5%), followed by Patterns 5 (16.7%), 2 (15.4%) and 3 (14.1%). The characteristics of Pattern 1 indicated progressive growth restriction while Pattern 5 demonstrated recovery from an initial growth abnormality. Cardiovascular abnormalities were quite variable, with those in the umbilical artery being most frequent in Patterns 1 and 3. Pattern 2 had the highest incidence of middle cerebral artery abnormalities. Umbilical artery abnormalities were similar in the Normal and Pattern 5 groups as were those for the middle cerebral artery. Other cardiovascular abnormalities had low frequencies except in Pattern 2 where the ductus venosus incidence was high. Abnormally small neonates, as identified with IGA, were seen primarily in Patterns 1, 3 and 6 (80-88%). Premature deliveries occurred most frequently in Pattern 1 (56%), followed by Pattern 2 (33%). CONCLUSIONS: Growth in this SGA Group was very heterogeneous with a significant proportion of these small fetuses growing normally. Growth restriction did not appear to be a single process but was manifest as seven different FGPS1 patterns. Both growth pathology and cardiovascular abnormalities differed among patterns. Further investigation will be required to determine how specific growth abnormalities are related to fetal cardiovascular changes over time.

Comparison of fetal size standards obtained with conventional methods and individualized assessment: the effect of adjusting for differences in growth potential.

Objective: Detection of fetal growth restriction depends on the biometric standard definitions of normal variability. We examined the impact of correcting for differences in fetal growth potential on the variability of third-trimester size standards.Methods: Size standards, corrected differences in growth potential using Individualized Growth Assessment [IGA], were obtained in 119 pregnancies with normal neonatal growth outcomes. Using the same cohort, a second set of size standards, without these corrections, were determined with mixed modeling [IGA Cross-sectional]. An independent set of size standards, obtained by quantile regression in a population-based sample of 1387 pregnant women [World Health Organization (WHO)], was also evaluated. The anatomical parameters studied included BPD, HC, AC, FDL, THC, HDL, ArmC and EWT whenever possible. The variability measures compared were percent deviation reference range [IGA] or twice the coefficient of variation [IGA Cross-sectional, WHO] at weekly time points between 28 and 38 weeks, menstrual age.Results: All six IGA variabilities were significantly smaller [range: 19-60%] when IGA and IGA-cross-sectional size standards were compared. Similar IGA-WHO comparisons showed that the IGA variabilities for 5 of 6 anatomical parameters were significantly smaller [range: 26-32%; exception: FDL (5.8%)]. Comparisons of cross-sectional size standards gave variable results depending on the anatomical parameter studied.Conclusions: Third-trimester variability measures, based on IGA, were consistently lower than those obtained with conventional cross-sectional methods in normal pregnancies. These results were found when the identical sample was used in both IGA and cross-sectional analyses. Decreased variability can improve the sensitivity of IGA for detecting restricted growth and may be partly responsible for its ability to identify different types of growth abnormalities earlier in pregnancy.

Second trimester growth velocities: assessment of fetal growth potential in SGA singletons.

OBJECTIVE: To evaluate the validity of second trimester growth velocities as measures of fetal growth potential in Small-for-Gestational-Age (SGA) singletons. METHODS: Second trimester growth velocities for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur diaphysis length (FDL) were determined by linear regression analysis or direct measurement in 53 SGA singletons with normal growth outcomes (SGA N Group) and 73 with growth restriction (SGA GR) based on a composite fetal growth pathology score (FGPS1). The latter were subdivided into six groups based on their growth restriction pattern (Patterns group). Similar data were available for 118 singletons with normal neonatal growth outcomes (NNGO group). Coefficients of determination (R2) and growth velocities for each anatomical parameter were compared between Patterns subgroups and the SGA N, SGA GR and NNGO groups. RESULTS: Median R2 values in the six Patterns subgroups ranged from 98.2% (Pattern 2, FDL) to 99.9% (Pattern 5, AC). Within each anatomical parameter set, no significant differences were found (Kruskal-Wallis). Patterns subgroup data were pooled to form the SGA GR group for each anatomical parameter. Mean values for the three main groups ranged from 98.4% (SGA N, FDL) to 99.6% (SGA N, HC). No significant differences between groups (ANOVA) were found for any anatomical parameter (ANOVA). Only 1.7-3.8% had R2 values <95th%. No significant differences in median second trimester growth velocities among different Patterns subgroups were found for any anatomical parameter. In the SGA N and SGA GR groups, mean BPD and HC values did not differ but were significantly smaller than the NNGO group values. No differences in mean FDL values were seen. With AC, all three means were significantly different, having the following order: NNGO > SGA N > SGA GR. Of all 504 second trimester growth rates, 92.5% were within their respective 95% reference ranges. CONCLUSION: Growth in the second trimester is linear in fetuses at risk for growth restriction. Except for FDL, growth velocities were lower than those for fetuses with NNGO. Only AC had mean velocities that differed between the SGA N and the SGA GR groups. Since most velocities (92.5%) were within normal reference ranges, they are reasonable measures of growth potential in fetuses at risk for growth restriction.

Impact of changes in maternal body composition on birth weight and neonatal fat mass in dichorionic twin pregnancies.

Background: Although the impact of gestational weight gain (GWG) on birth weight in twin pregnancies has been demonstrated, the specific components of GWG have not been delineated for twin gestations. Fetal body composition has been shown to be modifiable in singleton gestations based on nutritional intervention strategies and may prove to have similar modifications in twin gestations. Objective: We aimed to determine the relation of maternal body composition changes to birth weight, birth length, and neonatal fat mass (FM) in dichorionic-diamniotic twin pregnancies. Design: This is a prospective study of 20 women with twin gestations. Comparisons were made between body composition variables during each trimester and for the entire pregnancy and compared with the outcomes of birth weight, neonatal fat percentage, and birth length. Results: GWG within or above compared with below the IOM recommendations was associated with higher birth weights (P = 0.03, P = 0.04, respectively), but also with higher postpartum weight retention (P = 0.001). Total maternal protein gain over the pregnancy was positively associated with birth weight (P = 0.03). Changes in maternal fat-free mass (FFM), total body water (TBW), and FM from the first to the third trimester were not associated with either birth weight or neonatal FM percentage. However, maternal FM change from the second to the third trimester was significantly correlated to neonatal FM percentage (P = 0.02). Third trimester GWG and total protein gain were positively correlated with neonatal birth length (P = 0.02 and 0.03, respectively). Maternal FFM over all 3 trimesters showed a positive relation with neonatal birth length (P = 0.01). Conclusions: Significant increases in maternal protein are associated with greater birth weight and neonatal birth length. Protein accretion, in contrast to TBW and FM gains, may be the most critical component of maternal GWG in dichorionic twin gestations.

Estimated energy requirements increase across pregnancy in healthy women with dichorionic twins.

Background: Estimated energy requirement (EER) has not been defined for twin pregnancy. This study was designed to determine the EER of healthy women with dichorionic-diamniotic (DCDA) twin pregnancies. Objectives: We aimed to estimate energy deposition from changes in maternal body protein and fat; to measure resting energy expenditure (REE), physical activity level (PAL), and total energy expenditure (TEE) throughout pregnancy and postpartum; and to define the EER based on the sum of TEE and energy deposition for twin gestation. Design: This is a prospective study of 20 women with DCDA twin gestations. Maternal EER, energy deposition, REE, TEE, and PAL were obtained during the first, second, and third trimesters of pregnancy and immediately postpartum. A mixed-effects linear regression model for repeated measures with random intercept was used to test for the effects of BMI groups and time. Results: Gains in total body protein (mean ± SD: 2.1 ± 0.7 kg) and fat mass (5.9 ± 2.8 kg) resulted in total energy deposition of 67,042 ± 25,586 kcal between 0 and 30-32 weeks of gestation. REE increased 26% from 1392 ± 162 to 1752 ± 172 kcal/d across the 3 trimesters, whereas TEE increased 17% from 2141 ± 283 to 2515 ± 337 kcal/d. Physical activity decreased steadily throughout pregnancy. Reductions in physical activity did not compensate for the rise in REE and energy deposition, thus requiring an increase in dietary energy intake as pregnancy progressed. EER increased 29% from 2257 ± 325 kcal/d in the first trimester to 2941 ± 407 kcal/d in the second trimester, and stayed consistent at 2906 ± 350 kcal/d in the third trimester. Conclusion: Increased energy intake, on average ∼700 kcal/d in the second and third trimesters when compared with the first trimester, is required to support gestational weight gain and the rise in energy expenditure of DCDA twin pregnancies.

Individualized growth assessment: conceptual framework and practical implementation for the evaluation of fetal growth and neonatal growth outcome.

Fetal growth abnormalities can pose significant consequences on perinatal morbidity and mortality of nonanomalous fetuses. The most widely accepted definition of fetal growth restriction is an estimated fetal weight less than the 10th percentile for gestational age according to population-based criteria. However, these criteria do not account for the growth potential of an individual fetus, nor do they effectively separate constitutionally small fetuses from ones that are malnourished. Furthermore, conventional approaches typically evaluate estimated fetal weight at a single time point, rather than using serial scans, to evaluate growth. This article provides a conceptual framework for the individualized growth assessment of a fetus/neonate based on measuring second-trimester growth velocity of fetal size parameters to estimate growth potential. These estimates specify size models that generate individualized third-trimester size trajectories and predict birth characteristics. Comparisons of measured and predicted values are used to separate normally growing fetuses from those with growth abnormalities. This can be accomplished with individual anatomical parameters or sets of parameters. A practical and freely available software (Individualized Growth Assessment Program) has been developed to allow implementation of this approach for clinical and research purposes.

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

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 < .0001) between the FGPS1 and av - pGPRI. In N-A, all 20 cases (100%) had long last-scan-to-delivery intervals (1.9 weeks or greater), suggesting late development of the growth abnormality. For A-N, in approximately equal proportions, GR was improving, progressing or unclassifiable at the end of pregnancy. CONCLUSIONS: Significant agreement between prenatal and postnatal growth assessments was found using a novel approach for quantifying fetal growth pathology (FGPS1). Discordances appear to be due to lack of appropriate prenatal scans or an inadequate set of neonatal measurements. Evidence for a quantitative relationship between assessment methods was seen in the largest and most variable subgroup. The FGPS1 has the potential for characterizing GR in the third trimester and may provide a means for predicting the severity of corresponding abnormal neonatal growth outcomes.

Third trimester growth restriction patterns: individualized assessment using a fetal growth pathology score.

OBJECTIVE: To qualitatively and quantitatively characterize third trimester growth patterns in fetuses/neonates with growth restriction using Individualized Growth Assessment. METHODS: Serial fetal size measurements from 73 fetuses with proven growth restriction were evaluated using a novel composite parameter, the Fetal Growth Pathology Score (FGPS1). Third trimester FGPS1 measurements plotted against fetal age were examined for patterns. Identified patterns were characterized using the four components of the FGP1 [head circumference (HC), abdominal circumference (AC), femur diaphysis length (FDL), estimated weight (EWT)]. A secondary characterization using age of onset, duration and magnitude of the growth abnormality process was also performed. Frequencies and magnitudes of abnormal values in different FGPS1 patterns were compared. RESULTS: Five growth restriction patterns were found in 70/73 (95.9%) of the cases, with progressive worsening [Pattern 1 (37.0%)] and abnormal growth identified only at last scan [Pattern 2 (27.4%)] being the most common. These two patterns were usually statistically different from each other and the other three with respect to size parameter abnormalities and abnormal growth process characteristics (MANOVA). Growth abnormalities in all parameters of the FGPS1 contributed to the five abnormality patterns although AC and EWT were most important. The age of onset, duration and magnitude were similar between patterns except for Pattern 2, which had a late onset and a short duration (GLM + contrasts). CONCLUSIONS: Our study represents the first detailed evaluation of third trimester growth restriction using methods that consider the growth potential of each fetus. Five distinctive and repetitive patterns were found, suggesting that fetal growth restriction evolves in different ways. Further research is needed to determine the relationships of these patterns to physiological/biochemical changes and adverse outcomes associated with growth restriction.

Growth Patterns of Fetal Lung Volumes in Healthy Fetuses and Fetuses With Isolated Left-Sided Congenital Diaphragmatic Hernia.

OBJECTIVES: To evaluate fetal lung growth using 3-dimensional sonography in healthy fetuses and those with congenital diaphragmatic hernia (CDH). METHODS: Right and total lung volumes were serially evaluated by 3-dimensional sonography in 66 healthy fetuses and 52 fetuses with left-sided CDH between 20 and 37 weeks' menstrual age. Functions fitted to these parameters were compared for 2 groups: (1) healthy versus those with CDH; and (2) fetuses with CHD who survived versus those who died. RESULTS: Fetal right and total lung volumes as well as fetal observed-to-expected right and total lung volume ratios were significantly lower in fetuses with CDH than healthy fetuses (P< .001) and in those fetuses with CDH who died (P< .001). The observed-to-expected right and total lung volume ratios did not vary with menstrual age in healthy fetuses or in those with CDH (independent of outcome). CONCLUSIONS: Lung volume rates were lower in fetuses with left-sided CDH compared to healthy fetuses, as well as in fetuses with CDH who died compared to those who survived. The observed-to-expected right and total lung volume ratios were relatively constant throughout menstrual age in fetuses with left-sided CDH, suggesting that the origin of their lung growth abnormalities occurred before 20 weeks and did not progress. The observed-to-expected ratios may be useful in predicting the outcome in fetuses with CDH independent of menstrual age.

Classifying neonatal growth outcomes: use of birth weight, placental evaluation and individualized growth assessment.

OBJECTIVE: To compare neonatal growth outcomes determined by birth weight (BW), placental assessment (Plac Assess) and individualized growth assessment (IGA). METHODS: This retrospective analysis was carried out in 45 selected pregnancies at risk for fetal growth restriction. Serial fetal biometry was carried out in the 2nd and 3rd trimester. First and second trimester placental biomarkers, 2nd trimester uterine artery (Ut A) velocimetry and postnatal placental pathology were evaluated as indicators of placental insufficiency. At delivery, weight (WT), head circumference (HC) and crown-heel length (CHL) were measured. BWs were categorized as large-for-gestational-age (LGA), appropriate-for-gestational-age (AGA) and small-for-gestational age (SGA) (<10th, 10th-90th and >90th percentiles). In these categories, neonatal growth outcomes were classified as growth restricted (GR), normal (NORMAL) or macrosomic (MACRO) based on BW plus Plac Assess (Ut A velocimetry, biomarkers, pathology) or IGA [growth potential realization index profile (WT, HC and CHL)]. RESULTS: There were 6 LGA, 14 AGA and 25 SGA neonates in this sample. All 14 AGA neonates were considered NORMAL by both IGA and BW + Plac Assess. All six LGA neonates were classified as MACRO by BW + Plac Assess but only four by IGA (the remaining two were NORMAL and high NORMAL). The 25 SGA cases could be divided into five subgroups based on IGA and BW + Plac Assess. The largest subgroup (56%) was GR and the next largest (24%) was NORMAL by both classification methods. In the remaining 20%, there was some evidence of GR but IGA and BW + Plac Assess were not in complete agreement. CONCLUSIONS: Agreement was good for all three methods in the LGA and AGA groups. The SGA group was heterogeneous but agreement between IGA and BW + Plac Assess was 89%. These results, using more sophisticated growth assessment methods, confirm placental insufficiency as a primary cause of growth restriction. Most normal and GR SGA neonates can be identified with conventional anatomical measurements if IGA is used.

Personalized third-trimester fetal growth evaluation: comparisons of individualized growth assessment, percentile line and conditional probability methods.

OBJECTIVE: To compare third-trimester size trajectory prediction errors (average transformed percent deviations) for three individualized fetal growth assessment methods. METHODS: This 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. RESULTS: Mean 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). CONCLUSIONS: Significant 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.

A modified prenatal growth assessment score for the evaluation of fetal growth in the third trimester using single and composite biometric parameters.

OBJECTIVE: To define modified Prenatal Growth Assessment Scores (mPGAS) for single and composite biometric parameters and determine their reference ranges in normal fetuses. METHODS: Nine anatomical parameters (ap) were measured and the weight estimated (EWTa, EWTb) in a longitudinal study of 119 fetuses with normal neonatal growth outcomes. Expected third trimester size trajectories, obtained from second trimester Rossavik size models, were used in calculating Percent Deviations (% Dev's) and their age-specific reference ranges in each fetus. The components of individual % Dev's values outside their reference ranges, designated +iapPGAS, -iapPGAS, were averaged to give +apPGAS and -apPGAS values for the 3rd trimester. The +iapPGAS and -iapPGAS values for different combinations of ap (c1a (HC, AC, FDL, ThC, EWTa), c1b (HC, AC, FDL, ThC, EWTb), c2 (ThC, ArmC, AVol, TVol), c3 (HC, AC, FDL, EWTa)) were then averaged to give +icPGAS and -icPGAS values at different time points or at the end of the third trimester (+cPGAS, -cPGAS). Values for iapPGAS, ic1bPGAS, and ic2PGAS were compared to their respective apPGAS or cPGAS reference ranges. RESULTS: All mPGAS values had one 95% range boundary at 0.0%. Upper boundaries of 1D +apPGAS values ranged from 0.0% (HC) to +0.49% (ThC) and were +0.06%, +2.3% and +1.8% for EWT, AVol and TVol, respectively. Comparable values for -apPGAS were 0.0% (BPD, FDL, HDL), to -0.58% (ArmC), -0.13% (EWT), -0.8% (AVol), and 0.0% (TVol). The +cPGAS, 95% reference range upper boundaries varied from +0.36% (c1b) to +0.89% (c2). Comparable values for -cPGAS lower boundaries were -0.17% (c1b) to -0.43% (c2). CONCLUSIONS: The original PGAS concept has now been extended to individual biometric parameters and their combinations. With the standards provided, mPGAS values can now be tested to see if detection of different types of third trimester growth problems is improved.

Fetal growth cessation in late pregnancy: its impact on predicted size parameters used to classify small for gestational age neonates.

OBJECTIVE: To evaluate the impact of late 3rd trimester fetal growth cessation on anatomical birth characteristic predictions used in classifying SGA neonates. METHODS: A prospective longitudinal study was performed in 119 pregnancies with normal neonatal growth outcomes. Seven biometric parameters were measured at 3-4 weeks intervals using 3D ultrasonography. Rossavik size models were determined to predict birth characteristics at different ages. Percent Differences (% Diff) were calculated from predicted and measured birth characteristics. Growth Cessation Ages (GCA) were identified when no systematic change in % Diff values occurred after specified prediction ages. Systematic and random prediction errors were compared using different assumptions about the GCA. Predicted and measured size parameters were used to determine six new Growth Potential Realization Index (GPRI) reference ranges. Five were used to sub-classify 34 SGA neonates (weight < 10th percentile) based on the number of abnormal GPRI values. RESULTS: Growth cessation ages were 38 weeks for HC, AC, mid-thigh circumference, estimated weight and mid-arm circumference. Crown-heel length GCA was 38.5 weeks. At GCA, birth characteristics had prediction errors that varied from 0.08 ± 3.4% to 15.7 ± 9.1% and zero % Diff slopes after 38 weeks. Assuming growth to delivery gave increased systematic and random prediction errors as well as positive % Diff slopes after 38 weeks, MA. Seventeen of the SGA neonates had 0 or 1 abnormal GPRI values [Subgroup 1] and 17 others had 2 or more abnormal values [Subgroup 2]. In Subgroup 1, 4/85 (4.7%) of GPRI's were abnormal while in Subgroup 2, 43/85 (50.6%) were abnormal. Use of only one type of GPRI for SGA subclassification resulted in substantial false negative and some false positive rates when compared to subclassification based on all five GPRI values. CONCLUSIONS: Growth cessation occurred at approximately 38 weeks for all six birth characteristics studied. SGA neonates can be separated into normal and growth restricted subgroups based on the frequency of abnormal GPRI values (GPRI Profile Classification).

Reference ranges for 2-dimensional sonographic lung measurements in healthy fetuses: a longitudinal study.

OBJECTIVES: The purpose of this study was to establish reference ranges for 2-dimensional sonographic measurements of fetal lungs from longitudinal data. METHODS: A total of 214 fetal lung measurements were longitudinally evaluated in 62 healthy fetuses between 20 and 36 weeks' menstrual age. Both right and left lung areas were measured in the heart 4-chamber view using lung area tracing and axis diameter methods. Multilevel modeling was used to evaluate the expected values and variability with respect to menstrual age and to generate reference ranges for the lung area, lung-to-head ratio, quantitative lung index, and observed-to-expected lung-to-head ratio for both lungs. RESULTS: The expected values varied with menstrual age for all parameters. Variance was menstrual age dependent for all parameters except the longest diameter area measurements and their lung-to-head ratios. CONCLUSIONS: Models are presented for expected 2-dimensional sonographic lung size parameters and their variance as a function of menstrual age. These data have been used to generate age-specific reference ranges for both measurements and indices.