[Geometrical growth models of the fetal forebrain, cerebellum, brainstem and change of the cranial base angles during fetal period]. / Modèles géométriques de croissance du cerveau, cervelet, tronc cérébral et modification des angles de la base du crâne au cours de la période fœtale.

INTRODUCTION: Brain growth plays likely an important role for the skull growth. In the fetus, there exists an heterochrony for the growth of supratentorial (forebrain) and infratentorial regions (brainstem and cerebellum). The aim of the study was thus to model geometrically the growth of these two regions and to compare it with the inflection of the base of skull. MATERIAL AND METHODS: Brain growth measurements were performed from midsagittal photographs of fetal brains obtained from an Anatomical Atlas over a period from 10 to 40 amenorrhea weeks (AW). After countouring and pointing anatomical and geometrical landmarks, we have developed a linear growth model based on principal component analysis (PCA). Besides, the variation of the sphenoidal and clivo-foraminal angles was studied from anatomical midsagittal slices of fetal heads sampled over a period from 16 to 39 AW. RESULTS: The PCA model brings to light the radial expansion of the forebrain growth (first component) associated with an inferior and posterior rotation of the occipital lobe. The growth of the infratentoriel region presents an inferior and posterior expansion associated with a second component corresponding to inferior and anterior expansions. From the 17 AW, appears an heterochrony between the supra- and infratentorial growths and an inversion of the ratio between the infra- and supratentorial dimensions after 30 AW. The sphenoidal and clivo-foraminal angles decrease slightly until 25 AW, and then increase quickly until the 39 AW. CONCLUSIONS: The growth of brain is accompanied by morphological change between the compartments supra- and infratentoriel but also on the level of the base of skull. The possible interactions will be discussed.

Small and large foetuses: Identification and estimation of foetal weight at delivery from third-trimester ultrasound data.

BACKGROUND: The estimation of foetal weight (EFW) at delivery is crucial to assess the risk of foetal and neonatal morbidity and mortality, most notably when the foetus is small or large. AIM: To accurately predict the EFW at delivery of small foetuses (birth weight [BW]≤2500g) and large foetuses (BW≥4000g) identified with third-trimester ultrasound data. METHODS: We included 1309 foetuses whose age and weight at birth were known and for whom standard data were available from third-trimester ultrasound scans. Small and large foetuses were identified by extrapolation to full term of the estimated foetal weight obtained using Hadlock's equation. We built two regression models for predicting the birth weights of small and large foetuses, respectively. The results obtained with these models were compared to those obtained with Hadlock's equation. RESULTS: Third-trimester sonograms were obtained at 33.6±1.3 weeks gestational age [WGA] and birth occurred at 38.7±1.2WGA. EFW of small foetuses predicted using the regression model showed significantly less systematic bias than the Hadlock estimate (2.3% vs. 7.2%, respectively), whereas random errors were similar. EFW of large foetuses predicted using the regression model showed significantly less random error than the Hadlock estimate (6.2% vs. 10.1%, respectively), whereas systematic bias was similar. Data from an independent validation sample indicate that our regression models are accurate. CONCLUSIONS: To apply distinct models for accurately predicting the EFWs at delivery of small and large foetuses should prevent adverse events related to newborn size.

Estimation of fetal weight: accuracy of regression models versus accuracy of ultrasound data.

OBJECTIVES: To determine the respective importance of equation accuracy and variability in interexaminer measurements in estimation of fetal weight (EFW). METHODS: The study included 3 samples from three different French maternity hospitals. Sample 1 (6,508 fetuses) was used to compute a new linear regression model estimating fetal weight (FW) from ultrasound measurements. Sample 2, with 705 fetuses, was used to compare the accuracy of the new equation with Hadlock's equation. Sample 3 (1,461 fetuses) was used to assess - from our equation and from Hadlock's - the estimation errors due to the variability of ultrasound measurements recorded by 11 distinct examiners. Accuracy was determined by the signed percent difference (%Diff). Statistical analysis included the F test for correlated variances and comparisons of correlated variances. RESULTS: The random error of our model is 6.8%, significantly lower (p < 0.01) than Hadlock's which is around 7.4% (8.9% for low FW and 7.4% for high FW). The variability of ultrasound measurements among the different examiners in sample 3 generated a significant variation (p < 0.01) in the random error, ranging from 6.7 to 12.5%. This significant variation was also observed using Hadlock's equation for the same sample (from 7.2 to 12%). CONCLUSION: The accuracy of EFW depends much more on the quality of ultrasound measurements than on the choice of equation. Nevertheless, optimizing the accuracy of EFW (about 6.7-6.8%) imperatively requires standardized data collecting.

[Correlation between cranial vault size and brain size over time: preliminary MRI evaluation]. / Evolution comparative de la voûte crânienne et du parenchyme cérébral avec l'âge: étude préliminaire en IRM.

OBJECTIVES: To correlate changes of cranial vault measurements of an adult population during the aging process with brain size using the maximum width of the third ventricle in the axial AC-PC plane. MATERIALS AND METHODS: Prospective study of 126 adult subjects (range: 20 to 80 years) with normal brain MRI and without history of neuropsychiatric disorder. MEASUREMENTS INCLUDED: Cranial vault (Maximum length: Glabella-Opisthocranion, Maximum width: euryon-euryon, and maximum height: Basion-Vertex) measurements and maximum width of the third ventricle in the A C-PC plane. RESULTS: Vault measurements (length, width, high) were similar for every age group, irrespective of gender. The variability of cranial vault measurements between individuals was low (<1 cm). Cranial vault measurements were larger for men, but this was not significant when adjusted for body height Comparatively, a gradual widening of the third ventricle, with an exponential behavior, was observed with advancing age. CONCLUSION: Our results indicate that cranial vault measurements are stable over time (between 20-80 years) comparatively to brain atrophy with advancing age. The low variability of cranial vault measurements and their stability over time should be taken into account during segmentation and normalization of brain parenchymal structures.

Maternal predictors of subcutaneous fat in the term newborn.

AIM: To determine the relative influences of some maternal factors on skinfold thickness. The effects of age, parity, height, body mass index (BMI) and pregnancy weight gain (PWG) of the mother on the subscapular skinfold thickness (SST) of the newborn were estimated, and compared with their effects on birthweight (BW), crown-heel length (CHL) and head circumference (HC). METHODS: A sample of 13, 972 healthy, term singletons was selected at the Clamart Maternity Hospital (France). Stepwise regressions were used to determine the most predictive maternal factors for each parameter in the newborn. The respective effects of the mother's age and parity on each newborn dimension were tested by analysis of variance. RESULTS: The SST is a singular parameter, influenced by the mother's BMI and PWG, but not by her height. In contrast, the main predictor of BW, CHL and HC is the height of the mother, and to a lesser extent her PWG and BMI. Parity and maternal age have a smaller effect, except on SST, and essentially between the first and second pregnancies. CONCLUSION: These results clearly separate SST from other newborn dimensions. The skinfold thickness depends only on the nutritional status of the mother, while other dimensions are markedly influenced by the genetic background. This study is the first to demonstrate the singularity of skinfold thickness in newborn infants as a marker of the mother's nutritional status.

Gender differences in neonatal subcutaneous fat store in late gestation in relation to maternal weight gain.

OBJECTIVE: To study gender differences in fat store in human newborns and their relation to duration of gestation and maternal weight gain. METHODS: The ratios subscapular skinfold thickness/body weight (SST/BW) and tricipital skinfold thickness/body weight (TST/BW) were calculated in a sample of 13609 premature and term neonates from the maternity hospital of Clamart, Hauts-de-Seine, France. RESULTS: Whereas BW, SST and TST increased with gestational age, SST/BW and TST/BW ratios decreased regularly, in males as in females. This result reflects a progressive reduction of subcutaneous fat store per body weight unit as the duration of gestation increases. Males had smaller values of SST/BW and TST/BW ratios than females whatever the gestational age. Increasing maternal weight gain during the third gestational trimester did not improve the subcutaneous fatness per body weight unit of the newborn. Earlier amount of maternal weight gain had an effect on the TST/BW index exclusively in females. CONCLUSIONS: In newborns, a gender difference was observed in the ratio of subcutaneous fat per unit of body weight; this ratio is lower in males than in females. This result argues for a gender difference in mobilization of fat store to ensure normal growth in the last weeks of pregnancy: males lose more fat but gain more weight than females in this period. Late maternal weight gain does not affect the proportion of subcutaneous fatness by body weight unit in both genders.

Diagnosis of small-for-gestational-age fetuses between 24 and 32 weeks, based on standard sonographic measurements.

OBJECTIVE: To create and validate a formula using sonographic biometry measurements for the optimal diagnosis of small-for-gestational-age (SGA) fetuses between 24 and 32 weeks of gestation. METHODS: A logistic model using gestational age, femur diaphysis length, abdominal and head circumferences to diagnose SGA was set up in a first group of 64 fetuses born between 24 and 32 weeks (group I). A Receiver Operating Characteristic (ROC) curve was drawn. Our model was compared with standard single ultrasound measurements or combined into an estimated fetal weight (EFW) formula. An external validation was carried out on a second group of 183 fetuses (group II) from another maternity unit (ROC curve and comparisons). RESULTS: The area under the ROC curve was 0.91 in group I and 0.93 in group II. Using a 0.5 cut off point for our model yielded a sensitivity of 76% and specificity of 91% for group I. This model is more specific than most other measurement methods with a similar sensitivity. Using the same cut off point (0.5) in Group II, our model was more specific (98%) but less sensitive (66%) when compared with single ultrasound measurements and EFW formulae. By varying the cut off point, we were able to demonstrate that, for a similar sensitivity, our model had a higher specificity than single ultrasound measurements and had similar specificity to EFW formulae. CONCLUSION: The logistic model we set up was able to calculate an SGA risk score between 24 and 32 weeks of gestation in a population at high risk for elective delivery. The cut off point with a view to diagnosis can vary and makes it possible to give greater importance to the sensitivity or specificity depending on the clinical context.

A longitudinal study of fetal growth variability.

The aim of this study was to assess the variability in individual fetal growth rhythms in comparison to averaged standard curves obtained from cross-sectional data. Biparietal diameter (BDP), abdominal transverse diameter (ATD) and femur length (FL) were measured by ultrasonography in 24 normal subjects, and the variance in growth rates determined for four time intervals: 12-26, 26-34, 34-37 and 37-39 weeks gestation. BPD, ATD and FL growths were always linear until 26 weeks with low variances in growth rates. Growth rates decreased thereafter whereas related variances increased significantly with a great diversity in individual growth trajectories. This study questions the relevance of mathematically smoothed curves which lead to an erroneous impression of growth trajectory uniformity when ultrasonography does not seem to be able to predict accurately newborn biometrical characteristics by the end of gestation.

Sexual differences in anthropometric measurements in French newborns.

Sexual differences in anthropometric measurements have been studied in a sample of 17,787 preterm and full-term infants, born between 1980 and 1990 in the maternity of Clamart Hospital (Hauts-de-Seine, France). Body weight, body length, head and chest circumferences were found significantly larger in male newborns. Conversely, the subscapular and tricipital skinfold thicknesses had higher values in females. Such greater fatness in females could be related to the better outcome in neonates of this sex. The weight-for-height indices, however, did not show this female advantage: the body mass index (BMI) and the body weight/body length index were greater in male neonates, the ponderal index (PI) showed no sexual difference.

Growth velocity of some fetal parameters. I. Brain weight and brain dimensions.

In this study, fetal growth velocities of the brain weight (whole brain and infratentorial part) and of the right and left fronto-occipital diameters were established from 420 normal fetuses and neonates. The age of the subjects ranged from 10 to 41 gestational weeks. Growth rates were computed by time intervals, and velocity curves were plotted with their 95% confidence intervals. The whole brain displays an accelerating pattern of growth until 35 weeks; thereafter, the growth rate breaks down. The growth velocity of the infratentorial part of the brain increases throughout fetal life, without a fall at 35 weeks. Moreover, it grows faster than the whole brain after 24 weeks. The lengths of the hemispheres present a steady decreasing pattern of growth velocity throughout pregnancy.

Growth velocity of some fetal parameters. II. Body weight, body length and head circumference.

In this study, fetal growth velocities of the body weight, crown-heel length, crown-rump length and head circumference were established from 478 normal fetuses and neonates, aged 8-41 gestational weeks. The growth rates were computed by time intervals, and the velocity curves were plotted with their 95% confidence intervals. The body weight displayed an accelerating pattern of growth until 34-35 weeks and a breakdown of the growth rate afterwards, as we already observed for the brain weight in another study published in Biology of the Neonate. Decreasing patterns of growth velocity throughout pregnancy were observed for the crown-heel and the crown-rump lengths, with a marked fall at 35 weeks. The growth velocity curve of the head circumference is also decreasing, but in a more irregular way. A curious revival of growth velocity was observed in most parameters at about 38 weeks. These changes in the growth rhythm were similar to those found previously with ultrasound data.

[Increase in the pace of the growth of the human fetus towards the end of pregnancy]. / Reprise de la croissance chez le foetus humain en fin de gestation.

Growth velocity curves of 19 biometrical parameters were established from 490 normal fetuses or neonates, who died in the perinatal period, and from 4,507 ultrasound examinations. There was a velocity fall for numerous parameters during the third trimester of gestation, but growth rate started up again after 38 weeks for some of them (femur length, biparietal diameter, crown-rump length, head circumference ...). No acceleration was found for body weight and crown-heel length by the end of gestation.

Growth velocity of the biparietal diameter, abdominal transverse diameter and femur length in the fetal period.

In this study, fetal growth rates of the biparietal diameter (BPD), abdominal transverse diameter (ATD) and femur length were established from 4333 ultrasound examinations. The age of the fetuses ranged from 7 to 40 gestational weeks. The growth rates were computed by periods of 3 weeks, and the velocity curves were plotted with their 95% confidence interval. Results displayed multiphasic patterns of growth velocity for these variables, with a common peak of velocity at about 16 weeks. Between 16 and 28 weeks, growth velocity of femur length decreased, while the ATD and the BPD grew at the same constant rate. From 28 to 37 weeks, only the ATD maintained a high rate of growth. After 37 weeks, all growth rates decreased abruptly. In all cases, no sex differences in growth velocity were found.

[Speed of fetal growth: a new methodological approach]. / Vitesse de croissance foetale: une nouvelle approche méthodologique.

We suggest a new method to calculate fetal growth velocity. Fetal growth curves are divided in small linear units, and corresponding slopes calculated as growth rates. An example is detailed to set out statistical contingencies for methodological reliability. Specific interest of the method is discussed.

Differential growth between the fetal brain and its infratentorial part.

From 298 normal fetuses, we established normative curves of the development of the brain in relation to gestational age and to body weight. Means and standard deviations were calculated. There exist good curvilinear relationships, expressed by polynomial models, between brain weight--body weight and brain weight--gestational age with a wider scatter in large fetuses. These results confirm literature data. Subsequently, fresh and fixed brain weights were analysed. In addition, the development of the infratentorial part of the brain was studied with the same methods and showed close relationship with age and total brain weight. The ratios: infratentorial weight/total brain weight, brain stem/total brain weight and cerebellum/total brain weight were expressed as percentages. After 20 weeks, the cerebellar growth rate was higher than that of the brain stem.

[Estimation of fetal age from craniofacial dimensions]. / Estimation de l'âge foetal à partir des dimensions cranio-faciales.

This work gives a method for age evaluation of unknown foetus by means of skull measurements. From known foeto-skeletal specimens, twelve craniofacial growth curves were traced. Equations of regression curves, correlation and determination coefficients were calculated. Foetal skull may provide foetal age by means of these regression curves, calculating a "mean age". Sixty nine foetal skulls tested our method. Results were discussed and compared with other methods of foetal age evaluation.

[Variations as a function of time of the ossification of various bony elements of the cranial vault (experimental study in mice)]. / Variations en fonction du temps de l'ossification des différents éléments osseux de la voûte du crâne (étude expérimentale chez la souris).

Experimentally studied in the Mouse, ectocranial modeling bone processes are linked with stages of neuro-physiological development. More particularly, the weaning period is correlated with a complete change of periosteal growth processes in the cranial vault. This study details the different growth processes that model each bony unit of the cranial vault during the two distinct phases of post-natal development (before and after the weaning). Before the weaning, fast cerebral expansion involves generalised growth processes on the whole cranial vault area. A common pattern of growth is shared by several bones (or parts of bones), each bone showing particularities of growth rythm. The interparietal bone, the supraoccipital bone, and the anterior part of non-orbital frontal bone are excluded of that anatomical set of the cranial vault". After the weaning, bone modeling is dependent to muscular strengths. Local processes become more pronounced than generalised growth processes. Sutural and synchondral differential growth are playing a leading part in the craniofacial morphogenesis.

[Process of mandibular ossification in mice and evolutionary morphology (experimental study by means of vital staining)]. / Processus d'ossification de la mandibule chez la souris et morphologie évolutive (étude expérimentale par coloration vitale).

The injection in vivo of red alizarin S. in young mice during the post-natal period, enabled to show the mechanisms that were modeling the mandible during its development (by apposition-resorption). So it was possible to study : the processes of ossification involved in the eruption of the teeth, the modifications of the bony relief and the alterations of the mandibular angle. It has been attempted to find the links between these phenomena and muscular excitation, function and behaviour. The study of the osseous - muscular - mandibular anatomical set provided a good example of the principle described in Evolutionary morphology: "The comparatively free evolution of the elements in the anatomical set that they constitute (Sakka, 1973)."