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Seventy-one quadruplet pregnancies: management and outcome.

This article reviews the epidemiology, management, and outcome of 71 quadruplet pregnancies that occurred between 1980 and 1989. A study of detailed medical questionnaires and medical records revealed that 67 (94%) of the pregnancies followed ovulation induction therapy. A majority of the pregnancies were diagnosed by 9.3 weeks' gestation and bed rest was instituted by 16.7 weeks; 14% of women had cervical cerclages. Tocolytic agents were used in 59 (83%) of the group beginning at 24.5 weeks' gestation. The mean gestational age at delivery was 31.4 weeks and the mean birth weight was 1482 gm. Cesarean sections were performed in 89% of the cases. The average maternal weight gain was 45.8 pounds. Of the 284 fetuses, there were six first-trimester losses (including one ectopic pregnancy), 10 stillbirths and 33 neonatal deaths, resulting in a stillbirth rate of 29 per 1000, and corrected neonatal and perinatal mortality rates of 37 per 1000 and 67 per 1000, respectively. Other than premature labor, the most common maternal complications were first-trimester bleeding (35%), toxemia (32%), and anemia (25%). The quadruplet fetal growth curve parallels the singleton 25th percentile until 34 weeks, when it drops below the 10th percentile. These data suggest that a majority of quadruplets are delivered after 28 weeks and a viable outcome is expected. Because of retarded growth after 34 weeks, delivery should be considered at 34 weeks in most cases.

Adult↗

Effect of advanced maternal age on early mortality among quadruplets and quintuplets.

OBJECTIVE: This study was undertaken to determine whether advanced maternal age has an impact on survival among quadruplets and quintuplets. STUDY DESIGN: A retrospective cohort study was performed on 1 448 quadruplets and 180 quintuplets delivered in the United States between 1995 and 1997. Infants of older mothers (> or =35 years old) were compared with those of younger ones (<35 years old) in terms of early mortality indices. Adjusted mortality probabilities were computed by yearly intervals of maternal age. RESULTS: The likelihood for neonatal (odds ratio [OR]=2.00, 95% CI=1.20-3.45), perinatal (OR=2.10, 95% CI=1.32-3.23), and infant mortality (OR=2.13, 95% CI=1.28-3.60) was significantly higher among younger mothers. For each unit decrease in maternal age, the odds of stillbirth, neonatal, perinatal, and infant death went up by 9%, 12%, 13%, and 12%, respectively, in a dose-dependent fashion (P for trend <.0001). CONCLUSION: We found increasing maternal age to be associated with favorable survival outcomes among quadruplets and quintuplets.

Adult↗

The origins and outcomes of triplet and quadruplet pregnancies in Nova Scotia: 1980 to 2001.

The objective of this study was to determine the rate, origin, maternal and perinatal outcomes, and the associated hospital costs of higher order multiple births in one Canadian province. All higher order multiple pregnancies (triplets and above) in Nova Scotia over a 22-year period (1980 to 2001) were reviewed, and the maternal and perinatal outcomes and hospital costs were compared with singletons and twins in the same hospital population. During the 22-year period, 116,785 infants were delivered, including 3448 twins, 99 triplets, and 16 quadruplets. Of the higher order multiple gestations, 51.4% were conceived through infertility therapy. When compared with mothers of either singletons or twins, mothers of higher order gestations were significantly older, had longer antepartum and postpartum hospital stays, were more likely to have cesarean delivery, preterm labor, preeclampsia, and require intensive care unit admission. Triplets and quadruplets had significantly higher rates of preterm delivery, major anomalies, neonatal intensive care, respiratory distress syndrome, intrauterine growth restriction, serious morbidity, 5-minute Apgar scores < or = 3, and neonatal death than twins or singletons. The estimated hospital costs for this population ranged from 6,750 US dollars for a singleton pregnancy to 278,400 US dollars for a quadruplet pregnancy. Maternal morbidity, perinatal morbidity and mortality, and hospital costs are significantly increased in higher order births compared with both twins and singletons.

Adult↗

Medical hypnosis and quadruplets: a case report.

This case report presents a new association reaction and a new treatment for quadruplet pregnancies. The hypnotic interventions can increase clinical management of quadruplet pregnancy. It illustrates new insights into the treatment of quadruplet pregnancies, and it suggests useful future research.

Adult↗

Delayed interval delivery in quadruplet pregnancy: a case report.

A case report of delayed delivery of a quadruplet pregnancy is presented. This quadruplet pregnancy resulted from in-vitro fertilization. To our knowledge, this case represents the first report of quadruplets delivered on three separate days using the technique of delayed interval delivery. All infants survived and are healthy 2 years later.

Adult↗

Umbilical artery waveforms in triplet and quadruplet pregnancies.

The incidence of abnormal umbilical waveforms in triplet and quadruplet pregnancies and its correlation with adverse pregnancy outcome was studied by a retrospective review of all our triplet and quadruplet pregnancies (1986-1993) with documented Doppler flow assessment. Obstetrical outcomes were analyzed in relation to abnormal umbilical artery waveforms. Nineteen triplet and 4 quadruplet pregnancies were studied. Of 73 fetuses, 6 had abnormal umbilical artery waveforms (8.2%). All abnormal waveforms were characterized by persistent absence of the end-diastolic velocities (AEDV). In comparing the abnormal and normal groups, significant differences were found in birth weights (910+/-433 vs. 1,724+/-434 g; p = 0.0004), small for gestational age rate [5/6 (83%) vs. 5/67 (7.5%); p = 0.0003], and perinatal mortality rate [3/6 (50%) vs. 2/67(3%); p = 0.001]. There were no differences in congenital anomalies, gestational age at birth, and neonatal intensive care admission. In conclusion, it seems that Doppler umbilical artery waveforms in multiple pregnancies were either normal or extremely abnormal (e.g. AEDV). AEDV was associated with adverse perinatal outcomes such as low birth weight, growth restriction and perinatal mortality.

Birth Weight↗

Triplet, quadruplet and quintuplet pregnancies. Management and outcome.

The management and outcome of 46 pregnancies, 37 triplets, 7 quadruplets and 2 quintuplets, were analysed. Management of pregnancies, initiated upon diagnosis of multiple pregnancy, included bed rest, beta-mimetic agents, dexamethasone late in the second trimester and selective cerclage. The mean gestational age at labor was 235 days in triplet pregnancies, 241 for quadruplets and 220 days for quintuplets. Fifty-four percent of the deliveries were by cesarean section and the remainder per vaginam. The mean weight of the neonates was 1809 g for the triplets, 1837 g for quadruplets and 1284 g for the quintuplets. The mean overall Apgar score was 8.13, total perinatal mortality 14.8% and 9.4% in cases more than 28 weeks. There was no statistically significant difference in the outcome for triplets born vaginally or by cesarean section. In recent years there has been a pronounced reduction in neonatal mortality, dropping from 17.3% during 1970-78 to 5.9% from 1979 to 1983 (p less than 0.05), probably due to the improved neonatal treatment.

Adult↗

Triplets and quadruplets born in Victoria between 1982 and 1990. The impact of IVF and GIFT on rising birthrates.

OBJECTIVES: To examine the perinatal characteristics of all higher order multiple births (133 sets of triplets and six sets of quadruplets) in the State of Victoria between 1982 and 1990. To compare the rising higher order multiple birth rates in Victoria with those in the other States of Australia, and to assess the impact of in-vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) on these rising birth rates. DESIGN: Retrospective review of all higher order multiple births registered in Victoria and other States of Australia between 1982 and 1990, and in particular those resulting from IVF and GIFT. DATA SOURCES: Victorian Perinatal Data Collection Unit, Australian Bureau of Statistics, National Perinatal Statistics Unit, data from Victorian IVF and GIFT units. MAIN OUTCOME MEASURES: Higher order multiple birth rates and perinatal mortality rates. RESULTS: The higher order multiple birth rates in Victoria rose from 3.5 per 10,000 in 1982 to 10.9 per 10,000 in 1990. The average perinatal mortality rates for the Victorian triplets and quadruplets born during this period were 10.8% and 25.0%, respectively. The rates of caesarean section were 70% and 83%; the proportions of deliveries in level III hospitals, 75% and 100%; and the mean maternal lengths of stay in hospital, 32 and 57 days, respectively. Endotracheal intubation was performed at birth in 18.5% of all infants. The proportions of triplet and quadruplet pregnancies in Victoria owing to IVF and GIFT rose during this period, reaching a peak of 42% in 1990. In the other States, the birth rates for higher order multiples increased at 1.8 times the rate observed for Victoria, with IVF and GIFT contributing to an estimated 43% of these conceptions between 1985 and 1989. CONCLUSION: Restrictions on the numbers of embryos/oocytes transferred during IVF and GIFT should reduce the frequency of higher order multiple births.

Adult↗

Quadruplet pregnancy: contemporary management and outcome.

Quadruplets are occurring more frequently as assisted-reproduction techniques improve fertility in couples previously unable to conceive. Ten quadruplet pregnancies cared for in one perinatal practice over 5 years had excellent outcome. The mean gestational age at delivery was 32.5 weeks, compared with approximately 30 weeks in the literature. There were no perinatal deaths and no long-term morbidity. Our patients were compared with a series of 57 consecutive patients with quadruplet pregnancies monitored by a home monitoring system. Parity of 1 or more appeared to improve outcome. Pregnancy-induced hypertension occurred in nine of our pregnancies and necessitated delivery in seven instances. Fetal distress was responsible for two deliveries and uncontrollable preterm labor for only one. Key points in our management protocol include prophylactic use of low-dose aspirin, home contraction monitoring, use of terbutaline pump tocolysis, and bed rest at home starting at 16 weeks.

Adult↗

Triplet and quadruplet pregnancies and management.

The rate of multiple pregnancies with more than 2 fetuses has significantly increased since the introduction of ovulation induction agents. From 1970 through 1978, there were 19 triplets and 6 quadruplets in the authors' department, incidences of 1:696 and 1:5370, respectively. Eighteen (72%) of the 25 multiple pregnancies followed treatment with ovulation induction agents and 7 were spontaneous. The diagnosis of more than 2 fetuses was made earlier in the induced than in the uninduced pregnancies. Management, initiated upon diagnosis, included bed rest, high-protein diet, beta-mimetic agents, progestins, dexamethasone late in the second trimester, and selective cerclage. The mean gestational age was 34 weeks in the triplets and 35 weeks in the quadruplets. Forty-four percent of the deliveries were by cesarean section and the remainder were by vaginal delivery. The mean weight of the neonates was 1807 g in the triplets and 1950 g in the quadruplets. The mean overall Apgar score was 8.16, and the perinatal mortality was 185 per 1000, corrected (more than 28 weeks) to 137 per 1000. The main neonatal complications resulted from prematurity, and maternal complications noted were postpartum hemorrhage necessitating hysterectomy in 2 patients. The preferable mode of delivery cannot be stated dogmatically. Fetal outcome was similar in vaginal and cesarean deliveries among the various gestational age groups.

Adult↗

Quantitative variation in sets of triplets and quadruplets: a simulation.

A computer simulation was devised to generate realistic but large samples of twins, triplets, and quadruplets in each of the possible zygosity types. To validate the simulation, I used formulas proposed by Richter and Geisser (1960) to predict the mean value of the sum of squared deviations in each of three types of triplets and five types of quadruplets and to predict the distributions of the sums of squares in pure types (e.g., monozygotic and trizygotic triplets). Use of the formulas to predict distributions in sets of mixed type or to diagnose zygosity requires more advanced mathematical methods, but the simulation readily generates standard populations of all types of sets. If large enough numbers of real triplets or quadruplets ever become available to permit useful comparison with these standards or with the formulas, developmental peculiarities of the higher-order births might be revealed.

Computer Simulation↗

Semen characteristics of genetically identical quadruplet bulls.

Modern cloning methods have become an important technology in artificial insemination which is used to create and maintain pools of genetically superior bull semen. In this study, semen from four identical quadruplet bulls (Q(1), Q(2), Q(3), and Q(4)) produced by blastomere separation was analyzed to evaluate the differences in reproductive potential, if any, that existed between the identical quadruplet siblings. Analysis of fresh semen collected from 1994 to 1996, showed lower progressive motility and lower sperm concentration for one bull (Q(3)) compared to his identical brothers (P<0.05). Semen characteristics following freezing-thawing procedures have also been tested for these quadruplet bulls. The percentage of motility, progressive motility, and mean path velocity were lower in Q(4) compared with Q(1). Moreover, intracellular calcium level and P25b level (P25b is a sperm surface protein proposed to be a potential bull fertility marker) were lower in Q(4) compared with his siblings (P<0.05). Cryodamage to Q(4)'s frozen-thawed spermatozoa were confirmed by a lower percentage of embryo development after in vitro fertilization. Thus, the higher instability of cryopreserved spermatozoa from Q(4) and the lower semen production of Q(3), compared to their siblings, indicate that differences in semen characteristics can indeed exist among genetically identical animals produced by blastomere separation.

Animals↗

Decoding of tandem quadruplets by adjacent tRNAs with eight-base anticodon loops.

To expand the genetic code for specification of multiple non-natural amino acids, unique codons for these novel amino acids are needed. As part of a study of the potential of quadruplets as codons, the decoding of tandem UAGA quadruplets by an engineered tRNA(Leu) with an eight-base anticodon loop, has been investigated. When GCC is the codon immediately 5' of the first UAGA quadruplet, and release factor 1 is partially inactivated, the tandem UAGAs specify two leucines with an overall efficiency of at least 10%. The presence of a purine at anticodon loop position 32 of the tRNA decoding the codon 5' to the first UAGA seems to influence translation of the following codon. Another finding is intraribosomal dissociation of anticodons from codons and their re-pairing to mRNA at overlapping or nearby codons. In one case where GCC is replaced by CGG, only a single Watson-Crick base pair can form upon re-pairing when decoding is resumed. This has implications for the mechanism of some cases of programmed frameshifting.

Anticodon↗

[Triplet and quadruplet pregnancy: management and perinatal outcome].

The frequency of multiple pregnancies with more than two fetuses has increased considerably since the introduction of methods of ovulation induction, in vitro fertilization, and embryo transfer. We have analyzed the evolution, complications, delivery and perinatal outcome of 23 triplet and 3 quadruplet pregnancies occurred during a four-year period in one medical center. The most frequent complication was preterm labor (62%). The mean gestational age at delivery was 32.5 weeks for the quadruplets and 31.5 weeks for the triplets and the mean birth weight was 1461 and 1526 for quadruplets and triplets, respectively. Perinatal mortality for the whole group was 148/1000.

Embryo Transfer↗

Delayed interval delivery in quadruplets.

Prolonged interdelivery periods in preterm twin and triplet gestations have resulted in a good outcome for the fetus(es) remaining in utero. This is the second reported case of delayed delivery intervals in quadruplets who were born on 3 separate days. We report on a set of quadruplets following gonadotropin induction of ovulation, in which preterm delivery of the first infant occurred at 26 weeks' gestation. Active uterine contractions ceased and ultrasonography confirmed the remaining triplets to be in separate amniotic sacs with satisfactory heart rate tracings. With bed rest and tocolysis, the delivery of the second infant did not occur until 8 days later. After a further 36-h delay, placental abruption prompted cesarean delivery of the remaining twins. The first infant died of sequelae of prematurity at 7 months, while the remaining triplets survived and are neuro-developmentally normal 1 year after delivery. This report demonstrates the feasibility of prolonging the delivery interval of the fetus(es) in higher order multiple gestations, using tocolysis and watchful expectancy, after the preterm birth of one or more fetuses.

Adult↗

Management and outcome of 21 triplet and quadruplet pregnancies.

The course of gestation and the outcome of fifteen triplet and six quadruplet pregnancies are reviewed. Twenty pregnancies followed induction of ovulation and only one was spontaneous. Bed rest, the use of beta-mimetics and betamethasone, and prolonged hospitalisation were part of the management. Elective cervical suture was not used. The most frequent antenatal complications were preterm labor, preterm rupture of membranes and pregnancy-induced hypertension. The median gestational age was 33.5 weeks in the triplets and 32 weeks in the quadruplets. The overall perinatal and neonatal mortality was 4.9%. The neonatal complications resulted from prematurity and sepsis.

Adult↗

Triplet and quadruplet pregnancies--a forthcoming challenge also for the 'general' obstetrician.

Data from 14 triplet and 2 quadruplet pregnancies (50 infants) during the period 1974-1988 were analysed. The perinatal mortality rate was only 6%, despite a preterm delivery rate of 88%. Preterm delivery was more common in young (less than or equal to 29 years) multiparous women. Perinatal complications were, as expected, strongly associated with immaturity. Respiratory problems of the infants occurred significantly more often among women delivered by elective Cesarean section than among those planned for vaginal delivery, but the mean gestational duration was 1 week longer in the latter group. Few problems arise in infants weighing 2000 g or more, or at delivery at 34 weeks or later, and under optimal conditions it would therefore seem safe to allow these women to give birth vaginally. Nor did birth order affect the outcome for infants born vaginally. It is recommended that quadruplets be delivered by Cesarean section because of the difficulty of ensuring satisfactory fetal surveillance in labor.

Adult↗

The Genain Quadruplets: psychological studies.

A series of behavioral studies is reported on the Genain Quadruplets. These monozygous women, all of whom have suffered or are suffering from schizophrenia, were studied previously at the National Institute of Mental Health (1955-1958) and were the subject of an extensive report by Rosenthal (1963). Although the Genains are genetically identical, the expression of the schizophrenic disorder is unequal among the quads, and this circumstance has led to speculation about the relative contributions of nature and nurture (or diathesis and stress in Rosenthal's terminology) in the development of this disease. Two goals were pursued in this investigation: one concerned a comparison of the status of the Genains in 1981 as compared with 1958; the other concerned whether data from the armamentarium of newer behavioral and neurobiological techniques invented and employed since 1958 might shed some light on the unequal expression of schizophrenia among the quadruplets. We conclude that the Genains are functioning about as well as they ever have in their adult lives, and scores on attentional tests show improvement as compared to 1958 measures. This is probably attributable to the medication (primarily neuroleptics) and other supportive treatments they have received over the years. With respect to the varying degrees of illness seen in the Genains, scrutiny of the biochemical, physiological, neuroradiological, immunogenetic, and behavioral test data leads to speculation that certain unique biochemical findings interacting with differing types and amounts of cerebral pathology constitute a major cause of the variable expression of the schizophrenic diathesis.

Antipsychotic Agents↗