Establishment of fetal biometric charts using quantile regression analysis.

OBJECTIVES: Fetal growth evaluation is an essential component of pregnancy surveillance. There have been several methods used to construct growth charts. The conventional charts used in current daily practice are based on small numbers and traditional statistical methods. The purpose of this study was to improve fetal biometric charts based on a much larger number of observations with an alternative statistical method: quantile regression analysis. A comparison between the charts is presented. METHODS: During the 12 years of study, 17,708 sonographic examinations of pregnant women from the north of Israel, between 12 and 42 weeks of pregnancy, were performed. Fetal measurements were obtained by several operators using various equipment and included head circumference, abdominal circumference, and femur length. RESULTS: Growth charts were established based on these measurements. CONCLUSIONS: In this study, we constructed biometric growth charts using a large cohort of pregnant women. These charts offer the advantages of specific estimated regression parameters for each specified percentile, thus better defining the normal range. We suggest using these new charts in routine daily obstetric practice.

Umbilical-placental blood flow gradient during the early second trimester of pregnancy.

OBJECTIVE: To characterize umbilical-placental blood flow gradient during early second trimester of pregnancy. METHODS: Forty normal pregnant women with a singleton fetus gave their informed consent to participate in this study. All scans were preformed between 12 and 20 weeks' gestation using the simultaneous multigate spectral Doppler imaging (MS-SDI) modality available on the Diasonics Synergy system. The umbilical-placental circulation was scanned at three locations: (1) umbilical artery at the cord insertion, (2) superficial placenta at a point close to the cord insertion, and (3) deep placenta branches at the area adhere to the decidua basalis. The mean value of pulsatility index (PI) and resistance index (RI) were recorded. RESULTS: PI and RI were both significantly lower in the superficial and deep placenta compared with the cord insertion area. No significant differences were found comparing between superficial and deep placenta. In 30 women we found lower values and in 10 women we found a higher value of PI and RI in the superficial and deep placenta compared with the cord insertion. Four of five cases with complicated pregnancies occurred in patients with negative placental gradient compared with only one case with positive placental gradient (p < 0.05). CONCLUSIONS: In this preliminary report the umbilical placental blood flow gradient was characterized during the early second trimester of normal pregnancy. The presence of decreasing gradient was established. Absent or opposite gradient between the umbilical artery and the placental vessels was associated with adverse pregnancy outcome.

Antenatal diagnosis of central nervous system anomalies: can we predict prognosis?

Our technical ability to diagnose fetal anomalies of the central nervous system by ultrasonography and by fetal magnetic resonance imaging far exceeds our current knowledge of their possible neurodevelopmental implications later in life. This limitation often makes obstetric and clinical decisions very difficult. We retrospectively reviewed the ultrasonographic records of 6220 women who had been followed up at two large medical centers between 1994 and 1999. One hundred and sixty (2.6%) women had abnormal fetal central nervous system findings. The neurodevelopmental outcome of these children was assessed by a telephone interview with the parents. Small cerebellar size was the most frequent anomaly, followed by isolated mild ventriculomegaly and isolated choroid plexus pathology. Suboptimal neurodevelopmental outcome was found in 24% of children with isolated ventriculomegaly and in 9% with choroid plexus pathology. In the group of children with a "small cerebellum," suboptimal neurodevelopment was found in 19%. The measurement of transcerebellar diameter in respect to its developmental implication is, to our knowledge, described here for the first time. We believe that cerebellar measurements and their possible neurocognitive implications should be an integral part of future studies.

Epidemiologic risk factors for preterm delivery.

BACKGROUND: Prematurity remains the most significant cause of neonatal morbidity and mortality. Knowing which group of women is at risk for developing preterm labor will define a target population for better prenatal care and prevention modalities. OBJECTIVE: To examine whether preterm delivery rates are associated with ethnicity, age, parity, and style of living. METHODS: We conducted a longitudinal case series examining obstetric and demographic data of 17,493 deliveries that occurred between June 1994 and May 1999. All deliveries were performed in the obstetric department of HaEmek Medical Center (Afula, Israel), which serves as a referral center. The main outcome measures were preterm delivery, as related to the women's ethnicity, age parity, and style of living--namely, town, village, or kibbutz. RESULTS: The overall preterm delivery rate was 8.5%. The preterm delivery rate in non-Jewish women (10.5%) was higher than in Jewish women (7.1%) (P < 0.00001). The preterm delivery rate in women younger than 20 or older than 40 (12.5%) was much higher than in women between the ages of 21 and 40 (8.0%) (P < 0.00001). Grand-multipara women (> 8) had a higher preterm delivery rate (13.8%) than less parous women (8.5%) (P < 0.012). Style of living was also associated with the preterm delivery rate (P < 0.00001): kibbutz 5.5%, Jewish towns 7.8%, non-Jewish towns 8.7%, Jewish villages 6.7%, and non-Jewish villages 11.0%. CONCLUSIONS: Style of living, ethnicity, age and parity are statistically significant risk factors for preterm delivery in our area. These factors provide a more definable target population for better prenatal care.

Clinical variation of Aarskog syndrome in a large family with 2189delA in the FGD1 gene.

The clinical diagnosis of ASS (Aarskog-Scott syndrome or Faciogenital Dysplasia) was made in seven individuals belonging to a large Arabic family, which was supported by molecular studies revealing a 2189delA mutation in exon 15 of the FDG1 gene. The affected individuals in this family demonstrated clinical variability particularly in their cognitive skills, raising the question whether other genetic factors might be involved in the phenotypic evolution of ASS.

The association of umbilical cord hemangioma with fetal vascular birthmarks.

OBJECTIVE: To report a rare case of umbilical cord hemangioma and to discuss its association with vascular birthmarks. METHODS: A case of umbilical cord hemangioma diagnosed by ultrasound at 28 weeks of gestation is reported. After labor induction at 38 weeks of gestation, a male infant was born. Examination of the newborn showed disseminated port wine flat skin lesions covering a significant part of his body. Reviewing the scientific literature revealed the association between umbilical cord hemangioma and fetal mortality and morbidity, in particular, vascular malformations. RESULTS: A total of 24 umbilical cord hemangioma cases were reported in detail. Of them, 37.5% were associated with perinatal mortality and 29.2% ended in the delivery of a normal healthy infant. Fetal morbidity was recognized in 33.3%. CONCLUSION: This case illustrates the importance of prenatal diagnosis of umbilical cord hemangioma for prenatal counseling.

Hydrops fetalis: an unusual prenatal presentation of hereditary congenital lymphedema.

OBJECTIVES: To report a rare case of primary congenital lymphedema (PCL) presenting as hydrops fetalis. METHODS: The patient presented at 33(+4) weeks' gestation with polyhydramnios, massive bilateral hydrothorax, skin edema, scalp edema and minimal ascites. In utero thoracocentesis was performed and delivery was induced. Follow-up at 12 months of age revealed moderate bilateral foot edema with otherwise normal development. RESULTS: The diagnosis of PCL was suspected on the basis of the family history. DNA analysis revealed a novel missense mutation, E1106K, in the tyrosine kinase domain of the vascular endothelial growth factor receptor 3 gene (VEGFR3/FLT4). CONCLUSION: PCL should be considered in the differential diagnosis of hydrops fetalis. Knowledge of the favorable course, variable clinical presentation, therapy options and genetic basis should contribute to better pregnancy counseling and management.

Graves' disease in pregnancy: prospective evaluation of a selective invasive treatment protocol.

OBJECTIVE: Graves' disease in pregnancy carries a risk of fetal thyrotoxicosis from the transplacental transfer of thyroid-stimulating antibodies or fetal hypothyroidism from transplacental transfer of antithyroid drugs and thyroid-blocking antibodies. STUDY DESIGN: From 1991 through 2002, all pregnant women with Graves' disease underwent follow-up evaluations that included serial thyroid-stimulating antibody level, thyroid function, and ultrasound examinations. Umbilical blood sampling was recommended if the thyroid-stimulating antibody level was abnormally high or if fetal tachycardia, goiter, intrauterine growth retardation, or hydrops were present. For fetal hyperthyroidism, the mother received antithyroid drugs; for fetal hypothyroidism, maternal antithyroid treatment was reduced, and thyroxine was injected into the amniotic sac. RESULTS: Of 40000 deliveries, 24 pregnancies (26 fetuses) occurred in 18 women with Graves' disease. Nine of 14 mothers with positive findings elected umbilical blood sampling. In 4 of the mothers, the results were normal. Hyperthyroidism and hypothyroidism were diagnosed in 2 and 3 fetuses, respectively. All the fetuses were treated successfully by the protocol with up to four repeated umbilical blood samplings. No complications were recorded in any of the 20 umbilical blood sampling. In the 5 patients who had only elevated thyroid-stimulating antibody levels and who did not elect umbilical blood sampling, sonographic findings remained normal up to term, and the newborn infants were normal. One of 12 children (in whose case we did not recommend umbilical blood sampling) was born with transient hypothyroidism caused by maternal propylthiouracil treatment. All children, whose cases were followed for up to 9 years, are normal. CONCLUSION: In women with Graves' disease, umbilical blood sampling in selected cases may improve the control of fetal thyroid function.

Evaluation of fetal cardiac contractility by two-dimensional ultrasonography.

OBJECTIVE: Evaluation of fetal cardiac contractility by two-dimensional ultrasonography and construction of nomograms of area shortening fraction, end-diastolic area and end-systolic area of fetal cardiac ventricles during uncomplicated pregnancy. MATERIALS AND METHODS: Fetal echocardiography was performed on 160 pregnant women between 14 and 28 weeks' gestation. Measurements were taken on the four-chamber view. The area of each ventricle was measured by tracing the endocardium at the end of systole and at the end of diastole. Area shortening fraction was calculated by the following formula: SF = (Ad - As)/Ad (SF--area shortening fraction, Ad--end-diastolic ventricular area, As--end-systolic ventricular area). RESULTS: A statistically significant increase in normal fetal area shortening fraction, end-diastolic area and end-systolic area of both ventricles with advancing gestational age was established. There were no significant differences in the area shortening fraction between right and left ventricles. CONCLUSIONS: Area shortening fraction shows good correlation with gestational age. Nomogram of area shortening fraction, end-diastolic area and end-systolic area of both ventricles can be used as the reference for evaluation of ventricle size and cardiac contractility in normal and pathological cases.

Early brain atrophy in persistent hyperinsulinemic hypoglycemia of infancy.

We present two siblings with persistent hyperinsulinemic hypoglycemia of infancy, accelerated intrauterine growth and early neonatal brain atrophy. Fetal plasma glucose and insulin levels in the second sibling revealed normoglycemia despite hyperinsulinemia. The absence of intrauterine hypoglycemia suggests that the brain damage is not secondary to hypoglycemia and other etiologies must be considered.

Prenatal diagnosis of 5p deletion syndrome following abnormally low maternal serum human chorionic gonadotrophin.

Prenatal diagnosis of 5p deletion syndrome, or cri du chat, following an abnormally low measurement of a screening of serum human chorionic gonadotrophin (hCG), is reported. Karyotyping following amniocentesis revealed a terminal deletion in the short arm of one chromosome 5. The pregnancy was electively terminated. 5p deletion syndrome has been described with abnormally high hCG levels and normal hCG levels. This is the first report of its association with abnormally low levels. The association between chromosomal abnormalities and hCG is discussed.

Evaluating the risk of tuberous sclerosis in cases with prenatal diagnosis of cardiac rhabdomyoma.

OBJECTIVE: To evaluate the prenatal parameters that increase the risk of tuberous sclerosis in prenatal management of fetal cardiac tumors suspected as rhabdomyoma. METHODS: The study was a retrospective survey of 18 documented cases in which cardiac rhabdomyoma was suspected during pregnancy. The following parameters were evaluated as possible risk factors associated with tuberous sclerosis: tumor size, isolated or multiple, and family history of tuberous sclerosis. RESULTS: Eighteen documented cases in which cardiac rhabdomyoma was found during pregnancy were evaluated. Of these cases, seven (39%) had proven tuberous sclerosis and 11 were found to be non-associated tuberous sclerosis tumors. When combining the present data with previous series, cases with diagnosis of tuberous sclerosis had equal mean tumor size to those with normal outcome. Family history of tuberous sclerosis in the presence of cardiac rhabdomyoma almost invariably ended with tuberous sclerosis (86%). All other cases with diagnosis of tuberous sclerosis and no family history had all multiple cardiac tumors. CONCLUSION: The present data suggest that 39% of in utero suspected cardiac rhabdomyoma would have tuberous sclerosis. Family history and multifocality remain the strongest predictors of tuberous sclerosis, whereas size of the cardiac tumor can not reliably be used to predict tuberous sclerosis in prenatal counseling.