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Higher order multiple pregnancies in New South Wales 1990-1999.

OBJECTIVE: To examine higher order multiple pregnancy and birth rates in NSW, and to describe trends in the characteristics and management of these births. DESIGN: Cross-sectional analytic study. SETTING: New South Wales, Australia. POPULATION: Two hundred and ninety-one women who gave birth to triplets, quadruplets or quintuplets (880 babies) from 1 January 1990 to 31 December 1999. METHODS: Data were obtained from the NSW Midwives Data Collection and rates over time were calculated. MAIN OUTCOME MEASURES: Higher order multiple birth and pregnancy rates (> or = 20 weeks), place of birth, mode of delivery, fetal death rates and Apgar scores. RESULTS: There was no significant change in the number or rate of higher order multiple births in NSW during the 1990s with an average annual rate of 10.3/10,000 births or 3.5/10,000 pregnancies > or = 20 weeks. Among women with higher order multiple pregnancies, those aged > or = 35 years increased from 19% in 1990 to 47% in 1999. There was also a trend towards delivery in a perinatal centre from 56% to 70%, and vaginal birth from 18% to 28%. There were no significant changes in infant outcomes. CONCLUSIONS: The increases in higher order multiple pregnancies observed in Australia in the 1980s, and into the 1990s in other countries, have not persisted in NSW, suggesting that guidelines for limiting the number of embryos/oocytes transferred in assisted reproductive technologies have been widely adopted.

Adult↗

Mechanosensory calcium-selective cation channels in epidermal cells.

This paper explores the properties and likely functions of an epidermal Ca(2+)-selective cation channel complex activated by tension. As many as eight or nine linked or linkable equivalent conductance units or co-channels can open together. Open time for co-channel quadruplets and quintuplets tends to be relatively long with millimolar Mg2+ (but not millimolar Ca2+) at the cytosolic face of excised plasma membrane. Sensitivity to tension is regulated by transmembrane voltage and temperature. Under some circumstances channel activity is sychronized in rhythmic pulses. Certain lanthanides and a cytoskeleton-disturbing herbicide that inhibit gravitropic reception act on the channel system at low concentrations. Specifically, ethyl-N-phenylcarbamate promotes tension-dependent activity at micromolar levels. With moderate suction, Gd3+ provided at about 0.5 micromole at the extracellular face of the membrane promotes for several seconds but may then become inhibitory. Provision at 1-2 micromoles promotes and subsequently inhibits more vigorously (often abruptly and totally), and at high levels inhibits immediately. La3+, a poor gravitropic inhibitor, acts similarly but much more gradually and only at much higher concentrations. These properties, particularly these susceptibilities to modulation, indicate that in vivo the mechanosensitive channel must be mechanosensory and mechanoregulatory. It could serve to transduce the shear forces generated in the integrated wall-membrane-cytoskeleton system during turgor changes and cell expansion as well as transducing the stresses induced by gravity, touch and flexure. In so far as such transduction is modulated by voltage and temperature, the channels would also be sensors for these modalities as long as the wall-membrane-cytoskeleton system experiences mechanical stress.

Allium↗

Multifetal pregnancy reduction: a consecutive series of 61 cases.

OBJECTIVE: The effect of selective fetocide on the course of 61 multiple pregnancies. DESIGN: An observational study. SETTING: A tertiary centre. SUBJECTS: 61 women whose pregnancies included 37 triplets, 18 quadruplets, 5 quintuplets and 1 hepatuplet; 97% followed IVF or the induction of ovulation. The aim of the procedure in most cases was to obtain twins. INTERVENTIONS: Selective reduction was performed before 13 weeks gestation under general anaesthesia, using either a transcervical (n = 26) or transabdominal approach (n = 35). Fifty-four twins, 4 singletons and 3 triplets were obtained after the procedure. MAIN OUTCOME MEASURE: Preterm labour rate. RESULTS: The rate of unplanned fetal loss was 13% and was related to the number of suppressed embryos (P < 0.05). The preterm labour rate was 56.6%, the mean gestation at delivery was 35.6 weeks. Seven deliveries were before 32 weeks and led to all neonatal deaths. A comparison with published data suggested that fetal reduction reduced the rate of preterm labour in high multiple pregnancies; in 24 twin pregnancies obtained after reduction of triplets there was probably a gain of 2 weeks gestation. Severe growth retardation occurred in 13%. The perinatal mortality rate was 10.8%. CONCLUSIONS: Selective termination reduces but does not prevent early preterm labour. The procedure is of value in pregnancies with more than 3 fetuses and should be considered carefully for triplet pregnancies.

Abortion, Induced↗

Muscle inactivation: assessment of interpolated twitch technique.

The validity, reliability, and protocol for the interpolated twitch technique (ITT) were investigated with isometric plantar flexor and leg extension contractions. Estimates of muscle inactivation were attempted by comparing a variety of superimposed with potentiated evoked torques with submaximal and maximal voluntary contraction (MVC) torques or forces. The use of nerve and surface stimulation to elicit ITT was reliable, except for problems in maintaining maximal stimulation with nerve stimulation at 20 degrees plantar flexion and during leg extension. The interpolated twitch ratio-force relationship was best described by a shallow hyperbolic curve resulting in insignificant MVC prediction errors with second-order polynomials (1.1-6.9%). The prediction error under 40% MVC was approximately double that over 60% MVC, contributing to poor estimations of MVC in non-weight-bearing postimmobilized ankle fracture patients. There was no significant difference in the ITT sensitivity when twitches, doublets, or quintuplets were used. The ITT was valid and reliable when high-intensity contractions were analyzed with a second-order polynomial.

Action Potentials↗

Multifetal pregnancy reduction: is it always justified?

In the present study we summarized the world literature on first trimester multifetal pregnancy reduction between 1985 and 1992 and added our own experience. Our aim was to reach a comprehensive view on the survival rate of reduced high multifetal pregnancies, as the data in various studies are somewhat confusing, possibly as a result of the small number of cases. The data so gathered were classified by the number of fetuses. Of 94 triplet pregnancies reduced to twins 91.6% survived. Of 108 quadruplet pregnancies reduced to twins 92.6% survived. Of 40 quintuplet pregnancies 72.5% survived, and of 93 septuplets or more 87.1% survived. The outcome of pregnancies reduced to triplets did not differ from the outcome of pregnancies reduced to twins, with a survival rate of 85.7 and 72.5%, respectively. In our opinion, in view of the infertility history of many of these patients, the risk of pregnancy loss, the high survival rate of triplets and fetal reduction in triplet pregnancies in this group of patients may be unjustified. Accordingly, our policy in cases where the patients demand or when reduction is done early in pregnancy to reduce the triplets.

Abortion, Therapeutic↗

First trimester findings in pregnancies after in vitro fertilization.

We assessed the frequency of abnormal sonographic findings and their significance with respect to outcome in pregnancies resulting from in vitro fertilization (IVF). We retrospectively reviewed first trimester sonograms of 53 consecutive IVF patients who had a positive pregnancy test and first trimester ultrasonography at least 4 weeks after embryo transfer, and we correlated the sonographic findings with pregnancy outcome. For controls, we compared the frequency of sonographic abnormalities in these study patients to that in a group of patients who became pregnant after ovulation induction only. In the 53 IVF patients, the numbers of gestational sacs identified on the initial sonogram were as follows: 34 singletons, 11 twins, two triplets, one quadruplets and one quintuplets; no sac was seen in four patients. In 32 patients, the first sonogram was normal, with a visualized yolk sac, or heartbeat, or both. In 10 patients the gestational sac appeared abnormal but sac contents were normal. In seven patients an abnormality of sac contents was identified, including four with an embryo but no heartbeat and three anembryonic sacs. Overall, 40% of IVF patients had sonographic abnormalities, in comparison to 7% in the control group of patients (P less than 0.05, Fisher's exact test). Of the 32 patients with normal sonograms, 26 (81%) delivered at least one live infant. Of the 10 patients whose gestation sacs appeared abnormal, nine (90%) gave birth to live infants. Of the seven patients with abnormal sac contents, two (29%) delivered at least one live infant. We conclude that abnormal findings are frequently present on the initial sonogram of pregnant patients after IVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryo Transfer↗

Multiple pregnancy, multiple needs.

Every year, more than 4,000 sets of twins and 80 sets of triplets are born in Canada. And those numbers are growing: Canadian women are two-and-a-half times more likely to have triplets, quadruplets or quintuplets today than 20 years ago, mainly due to increasing maternal age and the use of fertility drugs and reproductive technologies.

Adaptation, Psychological↗

Multiple gestation: reflections on epidemiology, causes, and consequences.

Multiple births (of all orders) increased in epidemic proportions in the years 1971-1997. Twins increased 53%, 32%, 31%, and 83% in white, Afro-American, Native American and Mexican American women, respectively. Triplet, quadruplet, and quintuplet+ births increased >400%, >1,100%, and >500%, respectively, in the same years. The principal causes of these changes are related to the increasing age of the maternal cohort and an increasing incidence of fertility-inhibiting diseases and conditions in association with advancing maternal age. Major immediate consequences of these changes include disproportionately large numbers of infants born at <33 weeks' gestation (1.7% for singletons vs. 41.2% for triplets) and at <1,500 g birth weight (1.1% for singletons vs. 31.9% for triplets). Additional short-term consequences include an almost 2,000% increase in infant deaths (per 1,000 live births) among triplets compared with singletons (190.4 vs. 11.2). Long-term risks include a 300% increase in the relative risk of handicap in triplets compared with singletons (2.9 vs. 1.0), and a 650% increase in the rate of cerebral palsy per 1,000 live births in triplets compared with singletons (26.6 vs. 1.6). Peripartum costs relate to prematurity rather than plurality, as do lifetime survivorship costs, which relate to morbidities and subsequent health-related problems.

Female↗

Nuchal translucency in multiple pregnancies.

AIM: To evaluate the prevalence of increased nuchal translucency (NT) in multiple pregnancies and its relation to fetal karyotype and pregnancy outcome. METHODS: We measured fetal nuchal translucency (NT) in 6,338 women pregnant from 10+3 to 13+6 weeks by ultrasound and evaluated the prevalence of NT=95th centile in 115 multiple pregnancies, including 100 pairs of twins (70 dichorionic and 30 monochorionic placentas), 9 triplets, 5 quadruplets, and one quintuplet. Chorionicity, fetal karyotype, and pregnancy outcome were also evaluated in 400 singleton pregnancies. RESULTS: NT=95th centile in a single fetus was found in 10/70 cases of dichorionic twin pregnancies (14%), in two quadruplets, in 7/30 monochorionic twin pregnancies (23.3%), and in both fetuses in one dichorionic twin pregnancy. In the control group, NT=95th centile was found in 17/400 (4.2%) cases. In multiple pregnancies, two cases of trisomy 21 and one of 47, XXY were found. NT=95th centile was found in 2/2 fetuses with trisomy 21 (one dichorionic twin pregnancy and one tetrachorionic pregnancy), but not in the 47, XXY trisomy (trichorionic triplet pregnancy). A skeletal dysplasia and a Goldenhar syndrome were found among the 10 dichorionic pregnancies with increased NT. Three intrauterine deaths of both fetuses, one congenital heart disease, and a case of twin-to-twin transfusion occurred in 7 monochorionic pregnancies with increased NT. CONCLUSION: Increased NT in multiple pregnancies indicates fetuses at risk of chromosomal abnormalities and fetal malformation, and monochorionic twin pregnancies at higher risk of adverse outcome.

Adult↗

Mechanisms of twinning. III. Placentation, calcium reduction and modified compaction.

OBJECTIVE: To elucidate phenomena contributing to the maintenance and persistence of early uniovular pregnancies. It is proposed that the decreased survival of monozygotic (MZ) multifetal gestations is related to a smaller uteroplacental junctional (UPJ) area during and following implantation when compared with dizygotic (DZ) pregnancies. STUDY DESIGN: Pertinent placental data were collected and analyzed. From this information the placental area was calculated, and an estimate of the size of the UPJ was derived. RESULTS: In the first part of the study, MZ twins, triplets, quadruplets and quintuplets displayed a decrease in mean placental area per neonate as the number of fetuses increased in each set. In the second part, as predicted, MZ twin placentas exhibited smaller placental junctional areas than DZ. This is seen as a direct result of decreased trophectoderm mass due to scission in early gestation. CONCLUSION: These data are consistent with the general impression that multifetal pregnancies, especially monozygotic, are more at risk than singletons because of diminished placental support per fetus. They also reinforce the proposal that the key to MZ twinning is depressed calcium levels.

Calcium↗

[Analysis of 55 cases of transvaginal multifetal pregnancy reduction].

OBJECTIVE: To report the outcomes of transvaginal ultrasound-guided multifetal pregnancy reduction (MFPR) in early high-order multiple gestation. METHODS: Fifty-five cases of high-order multiple pregnancy including 1 septuplet, 7 quintuplets, 16 quadruplets and 31 triplets resulted from either superovulation/intrauterine insemination or in vitro fertilization-embryo transfer, were treated by transvaginal ultrasound guided MFPR at 49 - 79 days of gestational age. Their outcomes and complications were reported. RESULTS: Multifetal reduction were successfully done in 53 cases (96%). Miscarriage occurred in 8 patients (15%). Twenty-one cases (47%) were premature delivery and 24 patients underwent term delivery resulting in 87 infants. Five preterm infants died of neonatal respiratory distress syndrome. Among them none has malformation. Of the 82 live infants, 1 had hexadactyly and another arterial septum defect occurred. No organ injury, massive hemorrhage and infection occurred after MFPR. CONCLUSIONS: MFPR during early pregnancy is a safe, effective, simple operation for the purpose of reducing perinatal and maternal complication.

Female↗

Breast-feeding and bottle-feeding of twins, triplets and higher order multiple births.

OBJECTIVE: This study was performed to determine the rates of breast-feeding and/or bottle-feeding in mothers of twins, triplets and higher order multiple births compared to those in mothers of singletons, and identify factors associated with decision as to breast-feed or bottle-feed. METHODS: The subjects were 1,529 mothers of twins aged 6 months-6 years and 258 mothers of triplets and higher order multiple births (higher multiples) aged 6 months-6 years (234 mothers of triplets, 20 mothers of quadruplets, 4 mothers of quintuplets). Also, 1,300 subjects were recruited as a control group from mothers of singletons aged 6 months-6 years. Information regarding feeding methods, including exclusive breast-feeding, mixed-feeding and bottle-feeding with formula milk only, and duration of breast-feeding (in months) was collected. RESULTS: There were significantly higher rates of bottle-feeding in mothers of twins and higher multiples than in mothers of singletons. Duration of breast-feeding in mothers who chose exclusive breast-feeding or mixed-feeding for twins and higher multiples was significantly shorter than those for the singletons. The feeding methods for the twins or higher multiples were not associated with prematurity or low birth weight. However, after adjusting for each associated factor using logistic regression analysis, the decision to bottle-feed was significantly associated with non-cooperation of the husband in childrearing and degree of anxiety that mothers felt when informed of a multiple pregnancy. The odds ratio indicated that mothers who received no cooperation from the husband for childrearing were 1.83 times more likely to choose bottle-feeding as those who received cooperation. Further, the odds ratio indicated that mothers who felt greater anxiety when informed of a multiple pregnancy were 1.73 times more likely to choose bottle-feeding as those who did not feel much anxiety. CONCLUSION: This study found that establishment and continuation of breast-feeding for twins, triplets and higher order multiple births are much more difficult than for singletons. Further, cooperation of the husband in childrearing and the degree of maternal anxiety when informed of a multiple pregnancy are significant factors affecting the decision to breast-feed or bottle-feed for twins, triplets or higher order multiple births.

Adult↗

Selective reduction in multifetal pregnancies: technical and psychological aspects.

OBJECTIVE: To evaluate efficiency and safety of a very early transvaginal selective reduction procedure in multifetal pregnancies. DESIGN: Prospective study. SETTING: Obstetric and Gynecology Department, University of Paris VI. PATIENTS: Twenty-two patients with multifetal pregnancies: 14 triplets, 8 quadruplets, and 1 quintuplet. INTERVENTION: Selective embryonic reduction was performed at 7 weeks of amenorrhea under general anesthesia by transvaginal embryo puncture and aspiration. Two embryos were left in place. MAIN OUTCOMES: Pregnancy outcome (immediate or delayed complication, term of delivery, newborns) and psychological impact. RESULTS: No complication occurred. The 22 patients now have delivered at 36.5 weeks of amenorrhea, on average giving birth to 44 neonates with no congenital malformation. If the procedure generates anxiety, it is nevertheless perceived as necessary for the successful outcome of the pregnancy. CONCLUSION: Early mechanical transvaginal embryo reduction performed at 7 weeks of amenorrhea, leaving two embryos is, in our opinion, a simple and safe procedure with no affect on remaining fetuses. It is necessary when there are four or more embryos, and it should also be proposed for triplets. In these circumstances, patients saw reduction as a necessary procedure.

Abortion, Induced↗

First-trimester transabdominal multifetal pregnancy reduction: a report of 85 cases.

Eighty-five cases of multifetal pregnancy reduction were performed transabdominally at 9.5-13 weeks' gestation. All pregnancies consisted of three or more fetuses (28 triplets, 47 quadruplets, four quintuplets, four sextuplets, one septuplet, and one nontuplet), and all except five were reduced to twins. Forty-five women have delivered viable infants and eight lost all of the fetuses; 32 pregnancies are ongoing. No temporal relationship was noted between the pregnancy losses and the procedures. The mean gestational age at delivery was 35.7 weeks; 16 women (35.5%) delivered at or after 37 weeks, 16 (35.5%) between 34.5-37 weeks, nine (20%) between 32-34.5 weeks, and four (9%) before 32 weeks. There were no perinatal deaths, and all infants are healthy except for one who developed sequelae of severe hyaline membrane disease.

Abortion, Induced↗

Transabdominal multifetal pregnancy reduction: report of 40 cases.

Forty patients with multiple gestations, all resulting from infertility treatment, underwent transabdominal multifetal pregnancy reduction at an average of 12 weeks' gestation. Twenty-three women with triplets, 13 with quadruplets, and four with quintuplets had their pregnancies reduced to twins, except for two (one reduced from five to three and one from three to one). Twenty-eight women have delivered and 12 have ongoing pregnancies; none of the 40 lost the entire pregnancy after the procedure. There was one neonatal death from prematurity, and one fetus died because of growth retardation. Ten (36%) delivered after 37 weeks' gestation, 16 (57%) between 33-36 weeks, and two (7%) before 33 weeks. No maternal complications directly related to the procedure were encountered. We conclude that selective termination is a safe procedure that may improve multifetal pregnancy outcome.

Abortion, Induced↗

[Multiple pregnancies. II. Epidemiology, clinical aspects].

It used to be rare for multiple pregnancies to occur but we have seen a spectacular rise in them in France between 1970 and 1986. Triplet deliveries increased threefold. The authors analyse a personal series of 23 pregnancies (19 triplets, 3 quadruplets and 1 quintuplet pregnancy). Sixteen of these 23 were medically induced. The main complications that have been observed were: threatened premature delivery in 86%, high blood pressure in 34.7%, anaemia in 50%, and urinary tract infections in 30.4%, 6.8% of the babies had congenital malformations. Reviewing the literature has made it possible to discern the epidemiological factors causing multi-fetal pregnancies: family history, high female fertility, maternal age, ethnic factors, hormonal contraception etc... At present it is medically assisted reproduction that is the big supplier of multi-fetal pregnancies in developed countries. We have reviews of several maternal as well as fetal complications: the ovarian hyperstimulation syndrome, extra-uterine pregnancy, hypertension, anaemia, spontaneous abortion, prematurity, intra-uterine growth retardation and malformations.

Adult↗

[Multiple pregnancies. III. Therapeutic, psychologic and social aspects].

The authors analyse a series of 23 multiple pregnancies (19 triplet pregnancies, 3 quadruplets and 1 quintuplet). The first objective is to fight prematurity. Over and above all use of drugs as tocolytics (beta-mimetic drugs and progesterone) should routinely be advised and as soon as there is any threat of premature labour hospitalisation is needed. Twenty one of the 23 patients had prophylactic cerclage (Shirodkar's stitch). In 77% of the cases respiratory distress in the newborn was avoided by using cortico-therapy. Vaginal delivery can be carried out under certain conditions in triplet pregnancies. If certain precautions are taken there does not seem to be any immediate difference in the post delivery period of these children if they are born vaginally or by caesarean. Perinatal mortality is raised (at 5.6% for triplets and 58.3% for quadruplets). The psychological implications of these pregnancies are important. Problems appear as soon as the diagnosis is made and continue for years afterwards. On the social level, help given by the social services are usually inadequate. If the couples belong to the National Association for Mutual Aid of Parents of Children of Multiple Births, a system of mutual support is available. We recommend that these pregnancies should be looked after by several disciplines. These consist not only of obstetricians, paediatricians, anaesthetists, those who resuscitate together, but also psychologists, dietitians, social workers, community workers and physiotherapists.

Clinical Protocols↗

New variant of von Willebrand disease with defective binding to factor VIII.

A new variant of von Willebrand disease (vWD) was identified by a new analytic method which characterizes the ability of plasma von Willebrand Factor (vWF) to bind to purified factor VIII (F.VIII). vWF was isolated from small amounts of plasma by immunoadsorption with a selected monoclonal antibody to vWF previously coated onto wells of microtitration plates. Plasma F.VIII was removed from immobilized vWF by washing with 0.4 mol/L CaCl2; purified F.VIII was then added to the well. The amount of bound F.VIII was estimated directly in the wells by a chromogenic assay and immobilized vWF was estimated by an immunologic a pool of normal plasma, ten control individuals, 13 with hemophilia A and five with type I vWD. In all cases, the dose-response curves were linear and the slopes of the regression lines were essentially the same. The method was then applied to investigate the binding of vWF to F.VIII in two vWD patients (sister and brother) who demonstrated significantly lower activity of F.VIII than of vWF. The first patient, with a long history of epistaxis, bruising, and hematomas, showed a slightly prolonged bleeding time (10 minutes); 15% VIII:C and 39% of vWF:Ag and vWFRCo. Her brother, who has a bleeding syndrome but no hematomas, showed similar data (bleeding time 9 minutes, 20% VIII:C, 53% vWF:Ag and vWFRCo). Similar levels of F.VIII were observed in the two propositi by four different methods (one- and two-stage clotting and chromogenic and immunologic assays). Sodium dodecyl sulfate (SDS) 1.4% agarose gel electrophoresis showed that all multimers of vWF were present in both patients. vWF binding to F.VIII was markedly decreased in the two propositi. The abnormal binding of vWF to F.VIII was not corrected during pregnancy or after infusion of 1-deamino (8-D-arginine) vasopressin despite an increase in vWF levels. The qualitative abnormality of vWF in both patients was associated with a subtle alteration of the multimeric structure by SDS 3% agarose gel electrophoresis in which the two central subbands of the quintuplet of individual oligomers were undetectable or poorly visible. SDS-polyacrylamide gel electrophoresis under reducing conditions demonstrated a single band of 275 Kd in the plasma of both patients, and there was no evidence of a second band corresponding to pro-vWF, the precursor of the mature vWF subunit, suggesting that proteolytic processing of vWF was normal.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Coagulation Tests↗