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PubMed2000

Obstetric and perinatal outcomes from the australian and new zealand twin-twin transfusion syndrome registry.

OBJECTIVE: Our purpose was to investigate the antepartum characteristics and perinatal outcomes of twin-twin transfusion syndrome cases from a multicenter national registry. STUDY DESIGN: Perinatal centers in Australia and New Zealand voluntarily notified a central evaluation registry with information on identified pregnancies with twin-twin transfusion syndrome during 1995 through 1998. RESULTS: One hundred twelve cases of twin-twin transfusion syndrome were registered. The median gestation at diagnosis was 21.5 weeks (range, 14.4-34.6 weeks). Oligohydramnios-polyhydramnios sequence was the most common presentation, with 84% of cases involving "stuck" twinning. Therapeutic amnioreduction was used in 92 cases (82.1%), with the median number of procedures per case being 2 (range, 1-23). The median gestation at delivery was 29 weeks (range, 18-38 weeks). The overall perinatal survival rate was 62.5%. Abnormal findings on cranial ultrasonography were present in 27.3% of live neonates, and periventricular leukomalacia was reported in 10.8%. Increased gestational age at delivery, the presence of umbilical artery diastolic flow, and a prolonged interval from final amnioreduction to delivery were positively associated with the delivery of live fetuses without complications. CONCLUSION: The majority of antenatally identified cases of twin-twin transfusion syndrome are managed with serial amnioreduction. Despite contemporary obstetric and neonatal management strategies, perinatal mortality and morbidity rates are high.

Australia↗
PubMed2001

Amnioreduction versus septostomy in twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to compare treatment outcomes in pregnancies affected with twin-twin transfusion syndrome. Treatment consisted of serial amnioreduction or septostomy. STUDY DESIGN: A retrospective review of patients who were diagnosed with twin-twin transfusion syndrome from June 1998 to June 2000 was conducted. Diagnosis was based on polyhydramnios (maximal vertical pocket, >8 cm) in conjunction with an enlarged fetal bladder, oligohydramnios (maximal vertical pocket, <2 cm) with nonvisualization of the fetal bladder, and documentation of a single placenta. Data evaluated were gestational age at enrollment and delivery, prolongation of gestation, and number of surviving fetuses by treatment modality. RESULTS: There were 7 patients in the amnioreduction group and 7 patients in the septostomy group. The mean gestational age at enrollment for amnioreduction was 21.0 weeks and for septostomy was 18.0 weeks (P =.01). There were 67% 2-twin survivors in the septostomy group (P = not significant), but an overall equal number of survivors (78%) in both treatment groups. The rate of no surviving twins was equal (14%) in both groups. Pregnancy was prolonged an average of 12 weeks in the septostomy group and 6.5 weeks in the amnioreduction group (P =.007). The average gestational age at delivery was 27.5 weeks for the amnioreduction group and 30.0 weeks for the septostomy group (P =.08). CONCLUSION: The prolongation of pregnancy from diagnosis to delivery was statistically significant for septostomy when compared to amnioreduction. Although not statistically significant, there appears to be a trend toward increasing gestational age at delivery with septostomy. Further randomized studies are warranted for septostomy as a treatment modality in twin-twin transfusion syndrome.

Amniocentesis↗
PubMed2002

Prolonged hypoxia upregulates vascular endothelial growth factor messenger RNA expression in ovine fetal membranes and placenta.

OBJECTIVE: In ovine fetuses, 4 days of hypoxia resulted in a large increase in urine flow, without the development of polyhydramnios, which suggests that intramembranous absorption of the amniotic fluid was enhanced. Because vascular endothelial growth factor is speculated to be a regulator of intramembranous absorption through increases of membrane vascularity and fluid transport, we hypothesized that hypoxia upregulated vascular endothelial growth factor gene expression in the fetal membranes. STUDY DESIGN: Five near-term ovine fetuses that were subjected to 4 days of hypoxia and 5 age-matched time controls were studied. On day 4, the amnion, chorion, and placenta were collected for cellular localization and quantification of vascular endothelial growth factor messenger RNA and for the determination of vascular endothelial growth factor molecular forms that were expressed. The data were analyzed statistically with the use of t tests and 2-factor analyses of variance. RESULTS: Vascular endothelial growth factor messenger RNA was expressed in the fetal membranes localized to the amniotic epithelium and chorionic cytotrophoblast, and to the villous cytotrophoblast of the placenta. In hypoxic fetuses, vascular endothelial growth factor messenger RNA levels in these cell layers were significantly increased compared with the controls. Five vascular endothelial growth factor molecular forms were identified with vascular endothelial growth factor(164) being the most abundant form expressed. The pattern of expression of the forms was not altered by hypoxia. CONCLUSION: In the near-term ovine fetus, hypoxia induced vascular endothelial growth factor messenger RNA expression in the amnion, chorion, and placenta. This was associated with an increase in intramembranous absorption of amniotic fluid. We speculate that the increased intramembranous absorption was mediated by a vascular endothelial growth factor-induced increase in the transport of amniotic fluid into the fetal membranes.

Animals↗
PubMed2003

Stage-based treatment of twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to compare the outcomes of patients with twin-twin transfusion syndrome who were treated with either serial amniocentesis or selective laser photocoagulation of communicating vessels according to disease severity (stage). STUDY DESIGN: Centers that were experienced in the treatment of twin-twin transfusion syndrome were invited to share stage-based perinatal outcome data. All patients met basic standard sonographic criteria for twin-twin transfusion syndrome (polyhydramnios maximum vertical pocket, > or =8 cm; oligohydramnios maximum vertical pocket, < or =2 cm). Gestational age at first treatment was <27 weeks of gestation. RESULTS: Three centers submitted stage-based data, for a total of 173 patients (serial amniocentesis, 78 patients from all 3 centers) and 95 selective laser photocoagulation of communicating vessels (1 center). The distribution of patients by stage was similar in the two groups. Successful pregnancy outcome (at least 1 surviving infant) was correlated inversely with stage in the serial amniocentesis but not in the selective laser photocoagulation of communicating vessels group and was significantly lower in the serial amniocentesis (66.7%) than in the selective laser photocoagulation of communicating vessels group (83.2%). Neurologic morbidity was related directly to stage in the serial amniocentesis group but not in the selective laser photocoagulation of communicating vessels group and was significantly higher in the serial amniocentesis (24.4%) than in the selective laser photocoagulation of communicating vessels (4.2%) group. Intact neurologic survival (at least 1 surviving infant without neurologic morbidity) was significantly lower in the serial amniocentesis group than in the selective laser photocoagulation of communicating vessel group (51.3% vs 78.9%), particularly in stage III and stage IV (23.5% vs 72.7% in stage IV). Patients who were treated with selective laser photocoagulation of communicating vessels were 2.4 times more likely to have at least one survivor than those treated with serial amniocentesis. CONCLUSION: Our study suggests a relationship between perinatal morbidity and mortality rates and stage in serial amniocentesis but not in selective laser photocoagulation of communicating vessel-treated twin-twin transfusion syndrome patients. These findings could be used to tailor the treatment of twin-twin transfusion syndrome. A clinical trial to confirm these results is being organized by our research groups.

Amniocentesis↗
PubMed2001

Genotype/phenotype observations in African Americans with Bartter syndrome.

BACKGROUND: Two Bartter syndrome phenotypes have been described, and molecular analyses demonstrate mutations in 1 of 3 genes encoding ascending limb of Henle transporters. We report phenotypic observations in 5 African American children with Bartter syndrome in the context of a distinct genotype. METHODS: Mutation analyses were performed in 5 unrelated African American children with Bartter syndrome. These results were correlated to clinical and laboratory data. Calcium metabolism was evaluated with a bone disk bioassay. RESULTS: Mutation analyses demonstrated homozygous deletion of the ClC-Kb gene in all children. Two children had polyhydramnios and premature birth; the others were born at term and presented with failure to thrive or dehydration. All receive indomethacin, spironolactone, and potassium chloride with improved but borderline hypokalemia. Growth has improved with therapy, but height SD scores range from -3.9- to -1.4. Urinary calcium excretion is normal, and bone disk bioassay shows no abnormal calciotropic activity. No patient had nephrocalcinosis, but renal sonograms show loss of corticomedullary differentiation. CONCLUSIONS: African Americans with Bartter syndrome genotyped to date have homozygous deletion of ClC-Kb Clinical observations in our patients include partial correction of hypokalemia and suboptimal growth despite therapy. Abnormal calciotropic activity and nephrocalcinosis are not seen, but renal ultrasounds are abnormal.

Anion Transport Proteins↗
PubMed2003

Antenatal manifestations of mitochondrial respiratory chain deficiency.

OBJECTIVE: To review the antenatal manifestations of disorders of oxidative phosphorylation. STUDY DESIGN: A total of 300 cases of proven respiratory chain enzyme deficiency were retrospectively reviewed for fetal development, based on course and duration of pregnancy, antenatal ultrasonography and birth weight, length, and head circumference. Particular attention was given to fetal movements, oligo/hydramnios, fetal cardiac rhythm, fetal heart ultrasound, and ultrasonography/echo Doppler signs of brain, facial, trunk, limb, and organ anomalies. RESULTS: Retrospective analyses detected low birth weight (<3rd percentile for gestational age) in 22.7% of cases (68/300, P<.000001). Intrauterine growth retardation was either isolated (48/300, 16%) or associated with otherwise unexplained anomalies (20/300, 6.7%, P<.0001). Antenatal anomalies were usually multiple and involved several organs sharing no common function or embryologic origin. They included polyhydramnios (6/20), oligoamnios (2/20), arthrogryposis (1/20), decreased fetal movements (1/20), ventricular septal defects (2/20), hypertrophic cardiomyopathy (4/20), cardiac rhythm anomalies (4/20), hydronephrosis (3/20), vertebral abnormalities, anal atresia, cardiac abnormalities, tracheoesophageal fistula/atresia, renal agenesis and dysplasia, and limb defects (VACTERL) association (2/20), and a complex gastrointestinal malformation (1/20). CONCLUSIONS: Although a number of metabolic diseases undergo a symptom-free period, respiratory chain deficiency may have an early antenatal expression, presumably related to the time course of the disease gene expression in the embryofetal period. The mechanism triggering malformations is unknown and may include decreased ATP formation and/or an alteration of apoptotic events controlled by the mitochondria.

Birth Weight↗
PubMed2001

Lethal prenatal onset infantile cortical hyperostosis (Caffey disease).

We describe a sporadic case of lethal prenatal onset infantile cortical hyperostosis (Caffey disease), which resulted in early postnatal death at 30 weeks gestation. The mother presented with antepartum haemorrhage and preterm labour. She was found to have polyhydramnios. The infant showed extensive symmetrical diaphyseal subperiosteal cortical thickening throughout the skeleton with short extremities. Hepatomegaly and lung hypoplasia were present. Currently, in the absence of a specific marker, diagnostic ultrasound offers the only prospect of prenatal diagnosis. This diagnosis should be considered in infants with short angulated long bones, where the diaphyses are irregular and echodense, and where there is no sign of fractures.

Fatal Outcome↗
PubMed1986

Congenital choanal atresia in North African infants.

Eleven cases of congenital choanal atresia seen over a period of 2 years are described. Its incidence in the community was 1 in 3100 births. Twenty-seven per cent of cases were missed at birth, suggesting an even higher incidence. The anomaly was significantly commoner in infants of younger mothers with less than four children (P less than or equal to 0.05). Maternal polyhydramnios was present in three cases (P less than or equal to 0.0001). The sex incidence was equivocal and three infants were of low birthweight. The atresia was bilateral in the majority of the cases, and associated congenital anomalies were present in five of the 11 infants. Five underwent surgery with no complications.

Adult↗
PubMed2003

The effect of clinical characteristics on the lecithin/sphingomyelin ratio and lamellar body count: a cross-sectional study.

OBJECTIVES: To study the changes in the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) during pregnancy and to study the effect of clinical characteristics on these measurements. METHODS: We reviewed in retrospect the amniotic fluid samples for the assessment of fetal lung maturity of consecutive women between January 1996 and December 2000. We evaluated the effect of antenatal administration of glucocorticoids, the presence of diabetes, fetal growth restriction and the amount of amniotic fluid on the L/S ratio and LBC. We then constructed normal curves, by relating the L/S ratio and LBC to gestational age in the cases without respiratory distress syndrome (RDS). Data from the literature were added to these curves. RESULTS: From the 334 included women, 64 infants (19%) developed RDS. The LBC was lower in women with polyhydramnios (p = 0.04), and similar in women with oligohydramnios. Administration of glucocorticoids, the presence of maternal diabetes or fetal growth restriction did not affect the L/S ratio or the LBC. The median L/S ratio in cases without RDS showed a constant increase from a gestational age of 28 weeks onwards. The median LBC increased slowly between a gestational age of 28 weeks and 34 weeks, to increase more steeply thereafter. CONCLUSIONS: The amount of amniotic fluid affects the LBC, but not the L/S ratio. Since the L/S ratio and the LBC increase with gestation, differences in gestational age should be taken into account in the interpretation of these fetal lung maturity tests.

Amniotic Fluid↗
PubMed1987

Hemangioma of the umbilical cord.

Tumors of the umbilical cord are extremely rare. Only two types are recognized: hemangioma and teratoma. A case of hemangioma of the cord prompted a review of the world literature that uncovered 17 other cases, bringing the total number of known cases up to 18. Our case is the first to be diagnosed by ultrasonography and was associated with polyhydramnios.

Adult↗
PubMed2003

Biological implications of bi-directional fetomaternal cell traffic: a summary of a National Institute of Child Health and Human Development-sponsored conference.

OBJECTIVE: The National Institute of Child Health and Human Development (NICHD) held a workshop on 27-28 July 2000 to bring together investigators working in the field of fetomaternal cellular and nucleic acid trafficking with the hope that this would stimulate further research into the biological implications of such phenomena. METHODS: Invited speakers from all over the world presented their latest (unpublished) data. The conference proceedings were delayed until the present time to allow independent publication of the primary data. RESULTS AND CONCLUSIONS: Bi-directional fetomaternal trafficking of cells and nucleic acids during pregnancy is now well established, through the use of molecular techniques including conventional and real-time polymerase chain reaction, as well as fluorescence in situ hybridization. In addition, human leukocyte antigen (HLA) is deposited in the skin of pregnant women. Fetomaternal trafficking is increased in some complications of pregnancy, such as pre-eclampsia, polyhydramnios, polymorphic eruption of pregnancy, preterm labor and specific fetal chromosome aneuploidies. Maternal cells and nucleic acids have been documented in umbilical cord blood and in autopsy tissue of non-transfused neonates. Fetal cells persist postpartum and may be associated with the development of disorders such as scleroderma, lichen planus, lupus and thyroid disease. The extent of fetomaternal trafficking may be affected by three generational HLA relationships. Thus, the consequences of pregnancy extend beyond gestation.

Female↗
PubMed2002

Pregnancy during chronic hemodialysis: a single dialysis-unit experience with five cases.

BACKGROUND: Pregnancy is uncommon in women with end-stage renal disease (ESRD) requiring chronic dialysis. An increasing number of successful pregnancies in women in hemodialytic treatment have been recently reported but few institutions experienced more than one or two cases of pregnancy. METHODS: Between 1988-1998 five pregnancies in patients receiving hemodialysis were observed in our center. Medical records of these patients were reviewed. RESULTS: At the conception the mean age was 27 years. One patient started dialysis after conception. All patients received bicarbonate dialysis. Three patients were dialyzed six times per week, the other two patients three-four times per week. The dry weight was increased progressively; on average of 1.2 +/- 0.5 kg in the first trimester and of 0.5 kg per week since the second trimester. The predialysis BUN was maintained between 50-100 mg/dL (17.85-35,70 mmol/L) during the pregnancy. Four patients were treated with erythropoietin to maintain hematocrit between 30-35%. Erythropoietin related-complications were not observed. Polyhydramnios was observed in all cases. All deliveries occurred before term. The mean gestational age of infants was 28.6 +/- 4 weeks. Four out of five pregnancies resulted in liveborn infants. Two infants had an Apgar score of zero. All neonates were of low birth weight (1,431 +/- 738 g) with percentile of birth weight in the normal range. No one was small for date. CONCLUSION: A successful pregnancy is possible in women on chronic dialysis. Prematurity occurs frequently as well as low weight birth leading to increased perinatal morbidity and mortality.

Adult↗
PubMed1998

Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome.

Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. We have analyzed 15 probands belonging to 13 families and have performed SSCP analysis of the coding sequence and the exon-intron boundaries of the NKCC2 gene; and we report 14 novel mutations in patients with antenatal Bartter syndrome, as well as the identification of three isoforms of human NKCC2 that arise from alternative splicing.

Amino Acid Sequence↗
PubMed2004

Haemodynamic resistance model of monochorionic twin pregnancies complicated by acardiac twinning.

An acardiac twin is a severely malformed monochorionic twin fetus that lacks most organs, particularly a heart. It grows during pregnancy, because it is perfused by its developmentally normal co-twin (called the pump twin) via a set of placental arterioarterial and venovenous anastomoses. The pump twin dies intrauterine or neonatally in about 50% of the cases due to congestive heart failure, polyhydramnios and prematurity. Because the pathophysiology of this pregnancy is currently incompletely understood, we modified our previous haemodynamic model of monochorionic twins connected by placental vascular anastomoses to include the analysis of acardiac twin pregnancies. We incorporated the fetoplacental circulation as a resistance circuit and used the fetal umbilical flow that perfuses the body to define fetal growth, rather than the placental flow as done previously. Using this modified model, we predicted that the pump twin has excess blood volume and increased mean arterial blood pressure compared to those in the acardiac twin. Placental perfusion of the acardiac twin is significantly reduced compared to normal, as a consequence of an increased venous pressure, possibly implying reduced acardiac placental growth. In conclusion, the haemodynamic analysis may contribute to an increased knowledge of the pathophysiologic consequences of an acardiac body mass for the pump twin.

Biophysics↗
PubMed2000

Impact of prenatal glucose screening on the diagnosis of gestational diabetes and on pregnancy outcomes.

The authors examined the impact of universal screening on the diagnosis of gestational diabetes and its complications. All mothers and newborns registered by the Canadian Institute for Health Information from 1984 to 1996 (even-numbered fiscal years only) were included in the analysis. Over this time period, the proportion of women with gestational diabetes increased ninefold (from 0.3% to 2.7%) while the proportion with prepregnancy diabetes fell from 0.7% to 0.4%. As rates of gestational diabetes increased, a corresponding reduction in the risks of complications (polyhydramnios, amniotic cavity infection, cesarean delivery, and preeclampsia) occurred for women with gestational diabetes. The incidence of gestational diabetes fell in Metro-Hamilton (where screening was discontinued in 1989) but remained high in the rest of Ontario (where screening continued in most areas). No related temporal trends for fetal macrosomia, cesarean delivery, or other diabetes-related complications were observed, regardless of screening policy. The authors concluded that the substantial increase in gestational diabetes in Canada is an artifact caused by universal screening, with no evidence of beneficial effects on pregnancy outcomes.

Blood Glucose↗
PubMed1998

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment.

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP-sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.

Animals↗
PubMed1997

Pregnancy with concomitant chorangioma and placental vascular malformation with mesenchymal hyperplasia.

We present two pregnancies associated with normal live births and the unusual concomitance of chorangioma and placental vascular malformation with mesenchymal hyperplasia. The enlarged placenta had the characteristic findings of chorangioma, dilated and varicose chorionic vessels and multiple vesicle-like villi containing hyaluronic acid. The vesicle-like villi showed diploid cellular DNA contents. Molecular genetic analysis using the polymerase chain reaction amplification of polymorphic microsatellite markers confirmed genetic identity among the chorangioma, the vesicle-like villi and the fetus. Both pregnancies were complicated by polyhydramnios, pre-term labour and prematurity. One neonate suffered from anaemia and thrombocytopenia. Another neonate suffered from haemangiomatosis. Our cases demonstrate that concomitant chorangioma and placental mesenchymal hyperplasia are genetically identical to the fetus and can coexist with a normal viable fetus. Since haemangiomas, chorangiomas, chorionic vessels and villi mesenchymal cells are all derived from the mesoderm, a combination of fetal haemangiomas, placental vascular malformation, chorangiomas and placental mesenchymal hyperplasia may represent a mixed form of congenital malformation of the mesoderm.

Adult↗
PubMed1999

Prenatal sonographic diagnosis of a fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo.

Here we report the first case of prenatally diagnosed fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo. A 37 year old woman, having immunological infertility, was treated by in-vitro fertilization (IVF) and embryo transfer. Following unsuccessful IVF using fresh embryos, the patient conceived after transfer of cryopreserved-thawed embryos. The chromosomal analysis identified a normal karyotype at 16 weeks' gestation when amniocentesis was performed. The pregnancy course was uneventful until 28 weeks' gestation when polyhydramnios associated with fetal renal tumour was detected using ultrasonography. A male infant weighing 2564 g was born via Caesarean section at 34 weeks' gestation. A left nephrectomy was performed 5 days after delivery and the tumour was identified histologically as a mesoblastic nephroma. The postoperative course was uncomplicated to this point.

Adult↗