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[Fertility treatments: possibilities for fewer multiple births and lower costs--the 'Umbrella' study].

Since the 1980s, increasingly more fertility treatments have been performed in the Netherlands. The use of ovarian hyperstimulation during in vitro fertilisation (IVF) and intrauterine insemination (IUI) has contributed to an explosive increase in the number of multiple births. To control the costs of treatment and outcomes, the Minister of Health, Welfare and Sport commissioned research on possible improvements in the performance of fertility treatments in 1999. The results of this research ('Umbrella study'), reported in 2005, suggested that costs and the incidence of multiple births could be reduced if (a) IUI is only performed if the chance of spontaneous pregnancy is less than 30%; (b) the guideline 'Intrauterine insemination' is followed more closely regarding hormonal stimulation; (c) stimulation is used less frequently during IVF; and (d) no more than 1 embryo is placed in the uterus at a time. To achieve these results, all parties involved must revise their policies. In particular, current reimbursement regulations inhibit the implementation of the research results in practice.

Costs and Cost Analysis↗

Multiple birth and cerebral palsy in Europe: a multicenter study.

BACKGROUND: A European multicenter study (Surveillance of Cerebral Palsy in Europe, SCPE) was used to describe changes over time in multiple birth rates and cerebral palsy (CP) rates among multiple born infants, to compare CP rates and clinical types between multiples and singletons, and to analyse the influence of birth order in twins. METHODS: Data were collected from 12 European population-based CP registers on 6613 children born in 1975-90, as well as demographic data. RESULTS: The rate of multiple birth in the populations increased from 1.9% in 1980 to 2.4% in 1990, and the proportion of multiples among CP infants increased from 4.6% in 1976 to 10% in 1990. Multiples have a four times higher rate of CP than singletons [7.6 vs. 1.8 per 1000 live births, relative risk (RR) 4.36; 95% confidence interval (CI) 3.76-4.97] overall. The risk is marginally higher in multiples with birthweight > 2500 g (RR 1.60; 95% CI 0.95-2.28) and born at term (RR 1.65; 95% CI 0.91-2.40), and there is no difference in the risk for the low-birthweight and preterm groups. Correcting for differences in gestational age and birthweight, the clinical type of CP was the same in multiples and singletons. Twin CP infants are more often second than first born (56% vs. 44%, p < 0.05). CONCLUSIONS: Multiple born infants have a four times higher risk of developing cerebral palsy than singletons, mainly related to the higher risk of preterm birth in multiples. As the rate of multiples doubled through the 1980s, cerebral palsy cases in multiples increased in the same period.

Birth Weight↗

The European Multiple Birth Study (EMBS).

The more that twin and other multiple pregnancies are investigated, the more it becomes mandatory that collaborative studies are set up in order to attain the critical number of cases needed to achieve meaningful and reliable results. The European Multiple Birth Study (EMBS) aims to study two aspects of twin and multiple pregnancy: 1) management of pregnancy and labour, with emphasis on the prevention of preterm delivery; 2) accurate determination of zygosity, a prerequisite for the proper use of the twin method in a variety of fields, eg, congenital malformations, genetics, clinical investigations, etc. The rationale, the methods and the organisation of the study are described and discussed.

Data Collection↗

[Higher order multiple births in the course of time].

There has been an increase of multiple births since 1980. 601 families with multiples were interviewed. The answers from 289 mothers with multiples indicate, that, nowadays, in the majority of cases treatment with fertility drugs is the cause. Most of these pregnancies end too early. Moreover, the average time of gestation and the median birth weight of the children decline from year to year. The rate of dead or disabled children is high. Nevertheless, we know many happy families with healthy multiples. Nobody can predict the result of a multiple gestation. For this very reason, selective abortions are not the solution to the problem. Extreme caution is advised in the use of hormones to avoid inducing a pregnancy with higher order multiples.

Birth Weight↗

Multiple birth rates according to different socioeconomic levels: an analysis of four hospitals from the city of Sao Paulo, Brazil.

This population based study compares the rates of multiple births in the 1990s in four hospitals of different socioeconomic levels. It is well known that women from higher socioeconomic groups have easiest access to infertility therapies because of greater financial resources. The hospital of lower socioeconomic level presented multiple birth rates of approximately 8 per thousand during the decade, which may be considered as the natural one. The other three hospitals presented increased rates that were positively correlated to socioeconomic level. This increase occurred mainly due to dizygotic twins and to triplets and was as high as 4.8 per thousand in 1999. Maternal age was also positively correlated to socioeconomic level for singletons as well as for twins. However, during the decade the mean maternal age increased only in the two hospitals with better socioeconomic levels. Gestational order decreased as socioeconomic levels increased, mainly for twins and triplets. The percentage of singletons with low birthweight and very low birthweight decreased as socioeconomic level increased. However, twins presented with an equal distribution in the four hospitals, indicating that better socioeconomic level did not affect the incidence of low birthweight and very low birthweight among twins. Fetal death rate decreased as socioeconomic level increased but twin/singleton fetal death ratio is three times greater in the hospital of higher socioeconomic level suggesting that even in ideal conditions of medical and hospital facilities, the mortality of twins continues to be much higher than that of singletons.

Adult↗

Multiple birth prevalence in The Netherlands. Impact of maternal age and assisted reproductive techniques.

OBJECTIVE: To evaluate the impact of maternal age and use of fertility drugs on multiple birth prevalence from 1970 to 1995 in the Netherlands. STUDY DESIGN: A population-based survey was carried out in which data were collected from the Centraal Bureau voor Statistiek, the Institute of Medical Statistics and from all clinics for in vitro fertilization. RESULTS: In the last two decades, the prevalence of multiple births, especially of twin and triplet births, has increased significantly. Three possible explanations for this phenomenon are: (1) introduction of assisted reproductive techniques in combination with fertility drugs; (2) increasing maternal age; and (3) decreasing fecundity with increasing maternal age, resulting in more fertility treatments. A surplus of 1,366 twins was born in 1995 as compared to 1975. The expected excess of twins was 1,368, of which 104 (7.6%) were a result of the increase in total births in 1995, 583 (42.6%) were due to maternal age > 29 years, and, respectively, 330 (24.1%) and 351 (25.7%) twins were due to in vitro fertilization treatment and intrauterine insemination. CONCLUSION: The delay in achieving pregnancy and the use of fertility-promoting therapies profoundly affect the prevalence of multiple pregnancies in a given country. The general population should be informed of this risk.

Adult↗

Meeting the educational needs of multiple birth children.

There has been a significant increase in the number of twins and higher multiples so that one child in 33 is now a multiple. It is therefore not unusual for schools to have several sets of twins, as well as triplets and even higher multiples. By being the same age and in the same school year if not class, twins and higher multiples are not like brothers and sisters born closely together. Teachers and parents need to be aware of particular issues that may affect the physical, intellectual, personal, social and emotional development of multiple birth children, and to ensure that school policy and practice include this special group of children and parents. These issues include: preterm birth catch-up and implications for starting school; the balance of competition and cooperation among multiples; separation in school and the evidence from recent longitudinal studies; legislative and other initiatives on the development of school policy; the particular needs of higher multiples.

Child↗

Infertility and the desire for multiple births.

Increased physician and patient awareness of the risks of multiple births may be an important strategy to reduce the incidence of multiple gestation associated with assisted reproductive technologies.

Female↗

The epidemiology of multiple births.

On the basis of MEDLINE and manual searches, we examined the main papers in the English literature regarding risk factors for spontaneous (i.e. not related to fertility drug use) multiple births. The constant frequency of monozygotic (MZ) pregnancies over time and in different geographical areas suggests that the determination of MZ twins is largely unchanged over time, and that a genetic mechanism may have a role. In contrast, temporal and geographical trends observed in dizygotic (DZ) pregnancies suggest that environmental factors play a role in determining this condition. At present, maternal age and hereditary components are the best-defined determinants for spontaneous multiple births.

Age Factors↗

Multiple births in Igbo women.

In a prospective study of multiple births conducted at three hospitals, a University Teaching Hospital, an urban Maternity Hospital and a Community Hospital, in Eastern Nigeria, the average incidence was found to be 35 per 1000 births. The twinning rate was found to increase progressively with both birth rank and maternal age, with an indication that parity plays the more important role.

Adult↗

Fetal death registration in multiple births: anomalies and clinical significance.

Trends in the civil registration of fetal death in multiple gestations that has occurred before, but expelled from the womb after, 24 weeks' gestation are examined using England and Wales 1993-2004 registration obtained from the Office for National Statistics. Count was made of fetal death registrations in which fetus papyraceous, fetal death before 24 weeks' gestation or fetocide before 24 weeks' gestation was recorded. There were 3700 fetal death registrations among 217,595 twin, triplet and higher order multiple births in England and Wales between 1993 and 2004. In 354 (9.6%) of these fetal deaths, death was recorded as having occurred before 24 weeks' gestation. There has been a three-fold increase in such fetal death registrations. It is a legal requirement of parents to register a fetal death. The definition of a fetal death that meets formal registration criteria is that the fetus is expelled from the womb after 24 weeks' gestation. However, if the fetal death occurs before 24 weeks, there is confusion, nationally and internationally, whether or not registration is legally required. Fetal death in a multiple gestation has serious clinical implications for a surviving co-conceptus and failure to inform parents of an early death in a multiple gestation may have important repercussions. Legal definition for the registration of fetal death requires international agreement and application.

Female↗

Management of high-order multiple births: application of lessons learned because of participation in Vermont Oxford Network collaboratives.

OBJECTIVES: The delivery and care of sextuplets is complex. Potentially better practices that were developed as part of the Vermont Oxford Network improvement collaboratives were used to prepare for a sextuplet delivery at Akron Children's Hospital. METHODS: The team used potentially better practices that were learned from the Neonatal Intensive Care Quality Improvement Collaborative 2002 using multidisciplinary teams. There was extensive media coverage of the delivery. RESULTS: The goal was to use nearly all potentially better practices that focused on the goals of reducing nosocomial infection, reducing chronic lung disease, reducing radiograph use, reducing length of stay, reducing blood gas use, promoting nutrition, reducing intraventricular hemorrhage, and enriching family-centered care. The center aimed to use these 97 potentially better practices. Of the 97 possible potential better practices as set by the Neonatal Intensive Care Quality Improvement Collaborative 2002, 96 (99%) were used. CONCLUSIONS: This is a blueprint that any center that is faced with high-order multiple births could use as a reference point to begin planning. The team created a benchmark to achieve in every birth of very low birth weight infants and not just a special situation of high-order multiple births.

Delivery, Obstetric↗

What information should the multiple birth family receive before, during and after the birth?

Advances in the management of the multiple pregnancy and delivery must be accompanied by corresponding improvements in service access outside key centres and especially in the information families receive about what may happen during or after the pregnancy. A major review of birthing services in Victoria has focussed attention on four areas where the quality of information is often inadequate. 1) Prepregnancy and the standard of counselling about the incidence of multiples as a result of fertility drugs and in vitro fertilization procedures and about problems which may accompany a multiple birth. 2) Antenatal: At what stage of the pregnancy should parents be told of the multiple pregnancy and how should monitoring of the mother and procedures such as bedrest take into account what are often conflicting demands within the family? 3) Perinatal: Families are frequently illprepared for a cesarean delivery and for the procedures for premature multiples. The problem is often compounded by separation of the mother from one or both twins. While bereavement services are improving, much still needs to be learned about handling congenital abnormalities in one or more multiples. 4) Postnatal: Irrespective of the level of prenatal advice, families greatly underestimate the workload with multiples. The resulting stress contributes to the incidence of postnatal depression, child abuse and divorce now being reported from multiple birth families. Some suggestions are made from social psychology and genetic counselling about how families can best handle risk information to achieve the goal of neither under- nor overestimating the risks at these different stages of the multiple pregnancy.

Adaptation, Psychological↗

Multivitamin supplementation and multiple births.

It is well established that maternal multivitamin supplementation reduces the risk of neural tube defects and evidence suggests that it may be associated with other reproductive outcomes. The present study was prompted by a report from a randomized trial in Hungary which showed a 40% increase in multiple births among periconceptional vitamin users. Retrospectively collected data on multivitamin supplementation were obtained on multiple and singleton births from three separate studies: Atlanta Birth Defects Case-Control Study (ABDCCS) malformed and nonmalformed infants born 1968-1980, California Birth Defects Monitoring Program (CBDMP) malformed and nonmalformed infants born 1987-1989, and Boston University Slone Epidemiology Unit Birth Defects Study (SEU-BDS) malformed infants born 1987-1994. Supplementation was divided into three mutually exclusive categories based on timing: "periconceptional" use--before through at least the third month after conception; "early" use--beginning in the first month and continuing through at least the third month after conception; and "later" use--beginning in the second or third month after conception. For periconceptional use, four of five datasets showed a 30 to 60% greater prevalence of supplementation among mothers of multiple births. In contrast, this pattern was not evident for "early" and "later" use. Overall, the study findings are tentative, due to a lack of consistency across all five datasets and they should not alter recent recommendations related to folate supplementation for the prevention of neural tube defects.

Congenital Abnormalities↗

Multiple birth resulting from ovarian stimulation for subfertility treatment.

Assisted reproductive technologies (ARTs) aim to increase a woman's chances of becoming pregnant by bringing many female and male gametes into close proximity. Techniques to achieve this objective include ovarian hyperstimulation by maturation of several oocytes, intrauterine insemination (IUI) of concentrated sperm, or in-vitro fertilisation (IVF) by bringing gametes together outside the female body. The very nature of ovarian hyperstimulation--with or without IUI--enhances the risk of multiple pregnancy (eg, two or more babies). In most IVF cycles, more than one embryo is transferred, again resulting in an increased chance of multiple pregnancy. Developed societies have witnessed a large rise in prevalence of twin, triplet, and higher order multiple births, mainly resulting from ARTs. The primary aim of this Review is to increase awareness of the many implications of the present iatrogenic epidemic of multiple births. The background of ovarian hyperstimulation, trends supporting current practice, and strategies to reduce the chance of multiple pregnancy are highlighted.

Female↗

Concordance of strabismic phenotypes in monozygotic versus multizygotic twins and other multiple births.

PURPOSE: The concordance of strabismic phenotypes was examined in monozygotic versus multizygotic twins and other multiple births to study the role of genetic background in different types of commitant strabismus. METHODS: Medical charts of 45 consecutive pairs of twins (16 monozygotic and 18 dizygotic twins, and 11 with unknown zygosity), 3 sets of triplets (one monozygotic and 2 trizygotic triplets), and one set of quadruzygotic quadruplets examined at 6 institutions between 1973 and 1999 were reviewed retrospectively. The concordance was defined as both or all members having either esotropia or exotropia in common. RESULTS: The concordance of strabismic phenotypes was noted in 33 of 49 pairs or sets (67.3%): 14 of 17 monozygotic twins or triplets (82.4%), 10 of 21 multizygotic twins, triplets, or quadruplets (47.6%), and 9 of 11 twins with unknown zygosity (81.8%). The concordance rate was significantly higher in monozygosity than in multizygosity (P =.043, Fisher exact probability test). The predominant concordant phenotypes in monozygosity were accommodative esotropia and intermittent exotropia. CONCLUSION: A high concordance rate of strabismic phenotypes, predominantly of accommodative esotropia and intermittent exotropia in monozygosity, suggests the genetic background for these types of strabismus.

Diseases in Twins↗

[Actual conditions of help and support of childcare in families with multiple birth children].

A mailed questionnaire survey was conducted on a population of 705 mothers of twins, 96 mothers of triplets, 7 mothers of quadruplets and 2 mothers of quintuplets to study the actual conditions of help and support of childcare in the families with multiple birth children. The following results were obtained. 1) In this study, 90.6% of the mothers of twins, 89.6% of the mothers of triplets, 100.0% of the mothers of quadruplets and 100.0% of the mothers of quintuplets had at least one relative and friend from whom they received practical help and regular support. However, 5.8% of the mothers of twins and 8.3% of the mothers of triplets did not have others from whom they received help and support. 2) Lack of time to take care of the other children was reported by approximately 90% of mothers with twins who did not have others from whom they received help and support for childcare. 3) Mothers who did not receive help and support from others for childcare reported severe fatigue, compared to mothers who received help and support from others: mothers of twins, especially reported severe mental fatigue and mothers of triplets or more, severe physical fatigue. 4) Mothers of twins who had no way to alleviate stress reported severe physical and mental fatigue, compared to mothers who had ways to alleviate stress. Mothers of triplets or more showed a similar tendency as mothers of twins. These mothers alleviated stress by talking with other mothers of multiple birth children, friends, their maternal mother or their husband.

Adult↗