Jack Fitzsimmons

Long-bone growth in fetuses with Down syndrome

Short stature is a well-recognized component of Down syndrome. The femur lengths of affected fetuses have been observed to be shorter than normal, with a ratio of actual to expected femur length of less than 0.91 indicating a high risk of trisomy. To further evaluate this finding we have determined the relationship between limb lengths and gestational age in 37 postmortem fetal specimens with trisomy 21. Control values were obtained from 174 normal fetuses. Measurements of the femur, tibia, fibula, humerus, radius, and ulna were made from roentgenograms or by direct measurement of the bone. Most measurements for each bone of the affected fetuses fell below the normal regression line for that bone, but only 3/37 femurs, 4/32 tibias, 5/32 fibulas, 9/32 humeri, 10/32 radii, and 7/32 ulnas fell more than 2 SDs below the mean. The ratios of actual to expected femur lengths were computed and six fetuses with Down syndrome (16.2%) had ratios less than 0.91. The bones of the extremities of fetuses with trisomy 21 are shorter than normal, but the differences are relatively small. The ratio of actual/expected femur lengths was a less efficient predictor of Down syndrome than were either maternal age or maternal serum alpha-fetoprotein tests. The upper extremity bones were shorter than normal more often than were the bones of the lower extremity, and this finding should be explored further in a prospective study.

Organ Weight Standards for Human Fetuses

Five hundred fifty-eight fresh human embryos and fetuses were obtained from the universities of Washington and Michigan following spontaneous loss, elective termination, or neonatal death within 2 days of delivery. The body weights ranged from 1.5 to 1500 g. Each of these autopsied specimens was morphologically normal. Specimens from diabetic or hypertensive mothers were not included. Correlations between fetal body weight and weights of adrenal, brain, kidney, liver, lung, spleen, and thymus were established. For analysis, regression curves were calculated as quadratic equations of best fit by the weighted least squares. The relation of the weights of brain, heart, and liver to body weight appeared linear. The ratios of thymus, spleen, and kidney to body weight were nonlinear and gradually increased. The ratios of lung and adrenal weights to body weight were also nonlinear and gradually decreased. Ninety-five percent prediction intervals were generated for each of the eight organs using a computerized statistical package. The results compare closely with smaller studies in the literature.

Normal Length of the Human Fetal Gastrointestinal Tract

Little information is available on the normal length of the gastrointestinal tract in fetuses or on factors that may affect its growth. To determine normal growth patterns of the fetal intestine, 58 fetuses received in the Central Laboratory for Human Embryology between January 1, 1987, and July 1, 1988, in which no abnormalities were noted on autopsy, were studied. The gastrointestinal tract was removed from the fetus en bloc from the esophagogastric junction to the pelvic floor and dissected. Measurements of stomach, small and large intestines, and appendix length were made and correlated with gestational age as determined by footlength. Overall growth of the gastrointestinal tract as well as that of each component was linear with respect to gestational age. In addition, five fetuses with omphalocele, 16 with cardiac malformations, and 20 with chromosomal abnormalities were studied. The total lengths of the gastrointestinal tracts in the first group were below the normal range in four of five fetuses. Those with cardiac defects had intestinal lengths below the mean, but the measurements were abnormal in only three. In both groups those fetuses with chromosomal abnormalities appeared to have shorter intestinal tracts than those with normal or unknown karyotypes. The gastrointestinal tracts of aneuploid fetuses fell within the normal range until approximately 20 weeks gestation, after which growth decreased. This growth failure may reflect the growth retardation seen in fetuses with chromosomal abnormalities.

Growth parameters in mid-trimester fetal Turner syndrome

Growth failure is a consistent finding at birth in infants with Turner syndrome. However, the time of onset and pattern of growth deficiency is unknown. To determine the presence of growth failure in the second trimester in fetuses with Turner syndrome, second trimester fetuses that had a complete autopsy at the Central Laboratory for Human Embryology at the University of Washington were studied. A control group of specimens with normal findings was selected and compared with a study group with Turner syndrome documented by karyotype. Footlength and crown-rump length were measured directly with a ruler and femur, tibia, fibula, humerus, ulna and radius were measured from X-rays. Crown-rump length was used as the indicator of gestational age. Statistical comparisons between the normal and study groups were performed by multiple regression. Long bone measurements were made on 105 normal and 13 Turner fetuses. Footlength and the six long bones showed evidence of statistically significant growth failure. Fetuses with 45,X/46,XX mosaic Turner syndrome may demonstrate a lesser degree of growth retardation, at least for footlength, than those with a 45,X karyotype, but small numbers limited the analysis. We conclude that the growth failure consistently demonstrated in newborns with Turner syndrome begins early in gestation and is well-established by mid-pregnancy.

Placental Weights of Normal and Aneuploid Early Human Fetuses

Placental and body weights were plotted for 252 normal human fetuses less than 600 gm and mean regressions and 95% prediction intervals were calculated. Placentas from 62 aneuploid fetuses were compared to these standards. Placenta to body weight ratios from 34 trisomy-21 fetuses were not reduced but those from 15 trisomy-18 fetuses were generally decreased. One of 5 trisomy-13 ratios was below the prediction interval. Among 7 triploid fetuses the ratios were above the normal interval in 3 and below normal in 4. Three of the triploids that were below were associated with a karyotype of 69,XXX and did not have hydatidiform degeneration. All 4 placentas with hydatidiform changes were abnormally large. All of the 7 triploids had 3-4 syndactyly and 3 had hydrocephalus.

Growth of linear parameters in trisomy 18 fetuses

Linear growth in fetuses with trisomy 18 has not been systematically described. We studied the relationship between long-bone, crown-rump, and foot length and gestational age in 17 postmortem fetal specimens with this syndrome. Long-bone and crown-rump lengths were compared with normal regression lines and foot length was compared with gestational age determined on the basis of menstrual dates. Correlation between foot length and menstrual dates was weak in trisomy 18. Gestational age predicted by crown-rump length was significantly lower than gestational age by menstrual dates. All long bones were significantly shortened and fell below normal regression lines for gestational age. The fetal femur/foot length ratio was reduced. Thus no endogenous measure of gestational age appears to exist in this aneuploidy, forcing reliance on menstrual dates. The observed pattern of growth alterations will likely preclude the development of a gestational age-dependent biometric screen for the prenatal detection of this syndrome.

WOMEN WITH CEREBRAL PALSY: OBSTETRIC EXPERIENCE AND NEONATAL OUTCOME

The aim of the study was to provide a preliminary basis for advising women with cerebral palsy (CP) who choose to initiate pregnancy regarding the course of parturition and the outcomes for their newborn infants. The authors studied 92 women with CP who had 38 pregnancies at a mean age of 26 years. Eight pregnancies were electively terminated and two resulted in miscarriage. Of the 28 viable pregnancies, one resulted in a preterm stillborn infant and two in preterm liveborn infants. Delivery was vaginal in 18 cases and by cesarean section in nine (one pregnancy was lost to followup). Pregnancy outcomes were reassuringly normal in this small, select sample of women with relatively mild CP. Possible effects of pregnancy and childbirth on general adaptive skills or specific child‐care skills of women with CP could not be assessed in this retrospective study.

Ear dysmorphism associated with cystic hygroma colli in second-trimester fetuses.

To investigate if fetuses with cystic hygroma colli have ear article dysmorphism, we studied 16 fetuses with cystic hygroma colli, all of which had 45,X karyotype, and 107 normal fetuses. All the specimens were second-trimester formalin-preserved human fetuses. The ear lengths and widths were measured and ear indices (length/width) calculated. There were no significant differences in the ear measurements of age-matched normal male and female fetuses (P > .05). Ear growth was less linear in the cystic hygroma colli group than in the normal fetuses; Pearsons coefficient .45 vs. .87 for ear length, and r = .77 vs. .88 for ear width. The mean (+/- SD) ear index of the normal fetuses was 1.56 +/- 0.22 compared to 2.10 +/- 0.36 of the cystic hygroma colli fetuses, P < .001. The ear dysmorphism (> 2 SD of gestational age norm) was observed in 6.3% (1/16) of the ear widths, 56.3% (9/16) of the ear lengths, and 62.5% (10/16) of the ear indices. We conclude that cystic hygroma colli fetuses with 45,X have unique ear auricle morphology.