Sirenomelia associated with a "vanishing twin"

A case is presented of twin gestation in which one gestational sac was completely resorbed and the remaining twin was subsequently found to be sirenomelic. First-trimester prenatal ultrasound examination demonstrated a second gestational sac that disappeared 2 weeks later. The sonographic features that led to the diagnosis of sirenomelia in the remaining fetus included severe renal dysgenesis, persistently apposed lower extremities, and absence of fibulae. Postmortem examination, including angiographic studies of the fetus, revealed caudal dysgenesis and a single umbilical artery that arose from the abdominal aorta. Sirenomelia occurs more frequently in twin gestations than in singletons. This case suggests that the association between twinning and sirenomelia may be greater than is currently recognized. Two hypotheses are given to explain this association.     

Screening for aneuploidy in twin pregnancies: maternal age- and race-specific risk assessment between 9-14 weeks.

The aim of this study was to calculate the risk for aneuploidy in twin pregnancies between 9-14 weeks utilizing maternal age, race and dizygotic twinning rates. Using previously published risks for aneuploidy in singletons and twins at the time of amniocentesis and at term, we calculated new risk estimates for twins at 9-14 weeks gestation or at the time of chorionic villus sampling. Using these tables, the risk for trisomy 21 in at least one fetus of a twin gestation in a 32-year-old at 9-14 weeks is 1/285 for Whites and for African-Americans. This is equivalent to the risk for trisomy 21 (1/265) in a 35-year-old woman with a singleton at the same gestational age. The risks for trisomies 18 and 13 also follow similar trends. In counseling women with twin pregnancies at the time of first trimester nuchal translucency screening or chorionic villus sampling, it should be noted that the maternal age-related risk for aneuploidy for a 32-year-old is equivalent to that of a 35-year-old woman with a singleton gestation.     

Total protein concentrations in human amniotic fluid from normal and twin pregnancies

Total protein concentrations (TPC) in the human amniotic fluid, during 19 to 40 weeks of gestation, from normal and twins pregnancies were compared. In the normal pregnancies the protein concentrations were found to increase with progressing gestation, but to decrease gradually to the term. TPC fluctuations also showed a similar pattern in the twin pregnancies. There was no significant difference in the total protein contents between the normal and twin pregnancies, which probably indicates that the majority of the proteins originate from maternal source.     

Cyclopia associated with triploidy and hydatidiform mole: a case report.

A live 22-week-old cyclops fetus with a 69 XYY chromosome pattern and partial hydatidiform mole of the placenta is reported. Although cyclopia and chromosomal triploidy have certain features in common they appear to be two quite distinct entities. As no other 69 XYY fetus has survived to 22 weeks gestation and no other case of cyclopia has been reported with a triploid set of chromosomes, the assumption that the two conditions occurred coincidently in this fetus will have to await the accumulation of additional case reports.     

Ultrasonographic visualization of the fetal eye

This paper describes the analysis of the fetal eye in utero using ultrasonography. Such analysis has allowed the diagnosis of two cases of cyclopia and one case of microphthalmia. Two of the three pregnancies of a woman affected by autosomal dominant aniridia were found to be normal at 17 weeks of gestation and at birth; her oldest daughter was affected. The motility of the eyes was also noted when the fetus was examined. No movement or rapid and slow movements are seen more frequently as the fetus progresses through pregnancy. The centiles for the intermalar and interethmoidal distances are described for fetuses between weeks 10 and 40 of gestation. This system should be used with caution because of the difficulties in interpreting views of the fetal eye.     

Relationship between fetal adrenal morphology and anterior pituitary function

A comparative study of adrenal morphology between normal fetuses and those with anencephaly or congenital adrenal hyperplasia (CAH) was performed in order to examine the hypothesis that fetal adrenal mass and structure are adrenocorticotrophin (ACTH)-dependent throughout gestation. Combined adrenal weight in 102 normal fetuses was used to establish a reference range for the gestational ages of 15-27 weeks. During this period, mean adrenal weight showed a 6-fold linear increase. In 38 anencephalic fetuses of similar gestation age, adrenal weight was below the normal range and did not show a rise. Three fetuses with CAH (18, 22 and 30 weeks gestation) had adrenal weights considerably above the normal range. Adrenal cortical thickness was significantly increased in CAH fetuses, largely as a consequence of cell hypertrophy, whereas decreased cortical thickness in the anencephalic group represented cellular hypoplasia. Conspicuous secretory granules in the cytoplasm was the electron-micrographic feature of the adrenal gland in the 22-week fetus with CAH. These observations are consistent with close dependency of fetal adrenal growth and development upon fetal pituitary function from an early age, mediated primarily through ACTH.     

Transabdominal chorionic villus biopsy in second and third trimesters of pregnancy to determine fetal karyotype.

Transabdominal chorionic villus biopsy is an established method of obtaining material for analysing fetal chromosomes in the first trimester of pregnancy but has not been widely used for karyotyping in the second and third trimesters, when rapid results are required. The technique was evaluated in two groups of patients, comprising 106 at risk of having a fetus with chromosomal anomalies (105) or X linked disease (one) studied between 13 and 22 weeks (median 15 weeks) of gestation (group 1) and 21 with abnormal fetal findings on ultrasonography studied between 13 and 38 weeks (median 27 weeks) (group 2). Chorionic tissue was collected at the first attempt in 109 patients and at the second attempt in a further 17 independent of the position of the placenta. In one case from group 1 sufficient material for analysis could not be obtained. Seven abnormal karyotypes (six in group 1 and one in group 2) were diagnosed. Karyotyping was unsuccessful in two cases in group 1 (at 17 and 18 weeks'' gestation) and in two in group 2 (at 29 and 38 weeks'' gestation). Follow up of group 1 four weeks after sampling showed no signs of adverse fetal development apart from one unexplained intrauterine fetal death. The findings suggest that chorionic sampling is a safe and valuable additional technique for the late detection of chromosomal defects.     

In utero paternity testing utilizing fetal blood obtained by midtrimester fetoscopy.

To evaluate paternity in a case where both rape and conjugal coitus had occurred close to the time of conception, fetoscopy with fetal blood sampling was performed at 20 weeks gestation. Detailed blood group typing of the wife, husband, and fetus, and the presence of a very long Y chromosome in the last two, indicated a 99.9% chance that the fetus was fathered by the husband and only a 0.1% chance that it was fathered by "some other male Caucasian." The couple elected to continue the pregnancy. Neonatal testing verified the prenatal findings.     

Differential transmission of parvovirus B19 in a twin gestation: a case report.

Maternal infection with parvovirus B19 during pregnancy can cause aplastic anemia in the fetus. Severe anemia may lead to nonimmune hydrops or fetal demise. In the case reported, the demise of one twin was diagnosed by ultrasonography in an asymptomatic 21-year-old para 1-0-2-1 African American at the gestational age of 25 weeks. The deceased twin (A) was grossly hydropic with anasarca, ascites, pleural and pericardial effusions, and a thickened placenta. Parvovirus B19 DNA was found in the amniotic fluid of Twin A using the polymerase chain-reaction technique. Serial scans of Twin B showed normal growth and no evidence of hydrops. The pregnancy was managed expectantly until 29 weeks when delivery was indicated by maternal disseminated intravascular coagulation. Maternal IgM antiparvovirus B19 antibodies were detected at the time of delivery. Antiparvovirus B19 IgM antibodies were not present in Twin B. These serologic studies suggest a recent acute maternal infection and refute such an infection in Twin B. We present a case of differential transmission of parvovirus B19 in a twin pregnancy with in utero death of the infected twin and subsequent maternal disseminated intravascular coagulation.     

The molecular weight of sodium hyaluronate in amniotic fluid

The molecular weight of sodium hyaluronate in human amniotic fluid was determined by gel chromatography. Pooled samples from 16 weeks of gestation exhibited a broad molecular weight distribution (Mw = 3 X 10(5); Mn = 6 X 10(4)). Samples taken at 40 weeks showed a low molecular weight fraction (M less than 10(5) presumably of fetal origin, and a high molecular weight fraction (M greater than 10(6) which varied considerably, indicating a nonfetal origin. No hyaluronate degrading activity was detected in the fluid. In a case of renal dysplasia, only minute amounts of hyaluronate were found. These findings are in accordance with a renal excretion of a low molecular weight hyaluronate from the fetus. In 12 cases with proven neural tube defects, there was no significant difference in hyaluronate level and molecular weight compared to normal controls.     

Complexities of limb anomalies: the lower extremity in the "prune belly" phenotype

The so-called "prune belly" syndrome (PBS) consists of megalocystis, cryptorchidism, and marked abdominal distension; in addition to these findings, many other abnormalities are commonly present, rarely including severe anomalies of the leg. We report two such individuals, in whom PBS coexisted with abnormal development of the lower extremity. The first, a still-born male fetus, was delivered at 21 weeks gestation; generalized hypoplasia of both legs was present, more marked distally than proximally, and more severe on the left. The second case, a liveborn male infant, was the second of dichorionic twins, delivered at 33 weeks gestation; this infant died at two hours from respiratory insufficiency due to pulmonary hypoplasia. There was severe hypoplasia of the right leg, with gangrenous necrosis of all tissues distal to the knee. Additional findings included a single right umbilical artery, and a small congenital cystic adenomatoid malformation of the right lung. The findings in these cases are compared to other similar cases in the literature, and possible mechanisms for the etiology and pathogenesis of maldevelopment of the leg in PBS are discussed.     

Quantifying the Interactions between Maternal and Fetal Heart Rates by Transfer Entropy

Evidence of the short term relationship between maternal and fetal heart rates has been found in previous studies. However there is still limited knowledge about underlying mechanisms and patterns of the coupling throughout gestation. In this study, Transfer Entropy (TE) was used to quantify directed interactions between maternal and fetal heart rates at various time delays and gestational ages. Experimental results using maternal and fetal electrocardiograms showed significant coupling for 63 out of 65 fetuses, by statistically validating against surrogate pairs. Analysis of TE showed a decrease in transfer of information from fetus to the mother with gestational age, alongside the maturation of the fetus. On the other hand, maternal to fetal TE was significantly greater in mid (26–31 weeks) and late (32–41 weeks) gestation compared to early (16–25 weeks) gestation (Mann Whitney Wilcoxon (MWW) p<0.05). TE further increased from mid to late, for the fetuses with RMSSD of fetal heart rate being larger than 4 msec in the late gestation. This difference was not observed for the fetuses with smaller RMSSD, which could be associated with the quiet sleep state. Delay in the information transfer from mother to fetus significantly decreased (p = 0.03) from mid to late gestation, implying a decrease in fetal response time. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. The effect of maternal respiratory rate derived from maternal ECG was also investigated and no significant relationship was found between breathing rate and TE at any lag. In conclusion, the application of TE with delays revealed detailed information on the fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.     

Ultrasonic prenatal diagnosis of the Jarcho-Levin syndrome

The Jarcho-Levin syndrome is an autosomal recessive disease characterized by spinal and rib malformations (spondylocostal dysplasia). The case reported concerns a fetus with a dorsal spine angulation noted at the 15th week of gestation. A more accurate ultrasound study performed at 20 weeks revealed shortness of the neck and thorax, irregular ribs and vertebrae and absence of other visceral abnormalities. The karyotype was normal. Therapeutic abortion proposed was finally accepted by both parents at 27 weeks. The diagnosis was confirmed by post mortem radiography. No parental consanguinity was noted.     

Vaginal sonography of the cervix for the prediction of "time to delivery" in ART twins gestations.

The present study aimed to determine a reliable tool to estimate the interval time to delivery in assisted conception twin pregnancies. Mid-gestation cervical length was prospectively measured using transvaginal sonography (TVS) during routine antenatal care. Fifty-seven of 101 suitable women were longitudinally followed and two TVS measurements of their cervical length were obtained, first at approximately 24 weeks gestation and then at approximately 27 weeks gestation. The mean cervical length decreased from 37 +/- 12mm at first measurement to 34 +/- 11mm at the second one. A linear regression model was found between the time interval of the first (R = 0.656, p < 0.001) and the second (R = 0.435, p < 0.001) assessments and the week of delivery. The current data confirm that the length of the preserved segment of the cervix is an important indicator of its competence. A simple equation using the cervical length (mm) divided by 3 can predict mid gestation scan-to-delivery interval in twin gestation.     

模拟急性高原低氧对妊娠大鼠及其胎儿,新生儿肝细胞与溶酶体的影响

低气压舱模拟海拔8000m24h。观察对不同期妊娠大鼠、胎儿及新生儿肝溶酶体酶血清转氨酶、肝糖原、蛋白质和总脂水平的影响。证明:22天孕鼠肝细胞及其溶酶体损伤程度比16天孕鼠和非孕鼠严重;对16天和22天胎儿鼠肝溶酶体无明显影响,显示了胎儿肝溶酶体低氧下的高稳定性和母体对胎儿的保护作用;新生儿鼠肝细胞溶酶体对低氧的耐受性明显高于孕鼠与非孕鼠。低氧使孕鼠、胎儿、和新生儿鼠肝细胞糖原含量明显降低。新生儿诞生后肝糖原贮备极度消耗,低氧加剧这种作用。随着胎儿发育,肝蛋白质含量渐增,低氧导致全肝蛋白质量减少。无论孕鼠与非孕鼠,低氧造成肝总脂水平增高。     

A prenatally ascertained,maternally inherited 14.8 Mb duplication of chromosomal bands Xq13.2–q21.31 associated with multiple congenital abnormalities in a male fetus

Duplications of the X chromosome are rare cytogenetic findings, and have been associated with an abnormal phenotype in the male offspring of apparently normal or near normal female carriers. We report on the prenatal diagnosis of a duplication on the long arm of chromosome X from chromosomal band Xq13.2 to q21.31 in a male fetus with increased nuchal translucency in the first trimester and polyhydramnios at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed additional chromosomal material in the long arm of chromosome X at position Xq13. Analysis with high resolution array CGH revealed the additional material is in fact a duplication of the region Xq13.2–q21.13. The duplication is 14.8 Mb in size and includes fourteen genes: SLC16A2, KIAA2022, ABCB7, ZDHHC15, ATRX, MAGT1, ATP7A, PGK1, TBX22, BRWD3, POU3F4, ZNF711, POF1B and CHM. Analysis of the parents revealed the mother to be a carrier of the same duplication. After elected termination of the pregnancy at 28 weeks a detailed autopsy of the fetus allowed for genotype–phenotype correlations.     

Antenatal diagnosis of thalassaemia major.

Haemoglobin synthesis was studied in fetal blood samples obtained at 17 to 20 weeks'' gestation in 22 women at risk of carrying a fetus with homozygous beta-thalassaemia. A presumptive diagnosis of homozygous beta-thalassaemia was made in four cases, and the pregnancy was terminated. An inconclusive answer was obtained in one case, and the patient also chose to have her pregnancy terminated. Two fetuses were lost as a result of the procedure. Of the remaining 15 pregnancies, 13 proceeded to term and two to 36 weeks; in each case a normal infant or one heterozygous for beta-thalassaemia was delivered. Current efforts should be directed towards improving the blood sampling technology so that fetal blood sampling can be used widely in those countries where thalassaemia is a major problem.     

Fetal proteinuria in diagnosis of congenital nephrosis detected by raised alpha-fetoprotein in maternal serum.

High concentrations of alpha-fetoprotein (alpha-FP) were found at 14, 19, and 21 weeks gestation in the serum of a woman with a history of unexplained fetal death in her previous pregnancies. The alpha-FP concentration of the liquor also was high at 21 weeks and the pregnancy was terminated. Though the fetus was macroscopically normal, measurement of albumin, alpha-FP, IgG, and alpha2-macroglobulin in the fetal urine showed a selective proteinuria, and congenital nephrosis was diagnosed after examination of the fetal kidneys by electron microscopy. Possibly some fetuses reported to be "false-positive for neural tube defect" may have had renal lesions of this nature. Examination of fetal urine may be the simplest initial diagnostic procedure in any future case.     

Comparison of final height in monozygotic twins,one with idiopathic and isolated growth hormone deficiency treated with low dose of growth hormone

OBJECTIVE: We report final heights in a pair of monozygotic twins, one unaffected and the other affected with idiopathic and isolated growth hormone (GH) deficiency treated with human GH, and discuss the effect of GH dosage on the attainment of the genetic height potential in GH deficiency. PATIENTS: Male monozygotic twins were born at 35 weeks of gestation; birth weights were 1,876 g in the unaffected and 1,510 g in the affected twin. At 4.9 years of age, the affected twin was studied for short stature (-3.38 SD) and was diagnosed as having idiopathic and isolated GH deficiency, whereas the unaffected twin was normal in height (+/- 0 SD). GH treatment was started at the age of 5.7 years and continued throughout childhood and adolescence. The average dose of GH administered during the treatment period was 0.35 IU (0.12 mg)/kg/week. The affected twin appeared to grow normally without other hormone replacement and achieved a final height of 165.6 cm (-0.86 SD) compared with that of 166.4 cm (-0.71 SD) in the unaffected twin at 17.5 years of age. CONCLUSION: Our results indicate that a relatively low dose of GH treatment started at an early age may preserve genetic height potential in patients with isolated GH deficiency.     

Clinical and molecular description of the prenatal diagnosis of a fetus with a maternally inherited microduplication 22q11.2 of 2.5 Mb

Microduplications of 22q11.2 have been recently characterized as a new genomic duplication syndrome showing an extremely variable phenotype ranging from normal or mild learning disability to multiple congenital defects and sharing some overlapping features with DiGeorge/Velocardiofacial syndrome (DGS/VCFS). We report on the prenatal diagnosis of a 22q11.2 microduplication in a fetus with normal development that was referred for chromosomal analysis at 17 weeks of gestation because of advanced maternal age. Pregnancy was the result of an IVF-ICSI attempt after 4 years of infertility, mainly due to severe oligoasthenoteratospermia of the father. Amniocentesis was undertaken and cytogenetic analysis revealed an apparently normal male karyotype. Multiple Ligation-dependent Probe Amplification (MLPA) revealed a microduplication in the 22q11.2 chromosome region. Parental analysis showed that the 22q11.2 microduplication has been inherited from the otherwise healthy mother. Analysis with high resolution array-CGH showed that the size of the microduplication is 2.5 Mb and revealed the genes that are duplicated, including the TBX1 gene. The parents elected to continue with the pregnancy and the infant is now five months old and shows normal development.