Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.     

Contribution of twin pregnancy to perinatal mortality and fetal growth retardation; reversal of growth retardation after birth.

A survey of factors associated with perinatal mortality in 511 twins and fetal growth retardation and its reversal in 262 twins is presented. The incidence of stillbirth was almost 50% higher in twins than in singletons and the neonatal mortality was six times as high. Eighty percent of the neonatal deaths occurred in infants born prior to or at 30 weeks of gestation; 93% of the deaths were in infants weighing less than 1500 g and 75% occurred within 48 hours of birth. Fetal malnutrition was the main cause of stillbirth, and respiratory distress syndrome and asphyxia neonatorum were the main causes of neonatal death. One quarter of the twins had fetal growth retardation, a prevalence 10 times that in singletons. In almost all, the growth retardation was reversed by high-energy feedings. Although twins represented only 1% of all pregnancies and 2% of live births, they composed 12% of infants with early neonatal death and 17% of growth-retarded infants. A program is suggested for reduction of twin mortality and morbidity.     

The male genital tract and the nipples of male and female offspring of rats given the non-steroidal antiandrogens DIMP and Sch 13521, during pregnancy.

Male and female offspring of rats given antiandrogens, the steroidal BOMT or the non steroids DIMP or Sch 13521, daily during the last third of pregnancy were studied. Detailed examinations were made of the genital tract of male, and of the nipples of male and female offspring. A) Male offspring. 1) Genital tract of newborn and 31-91 day old males : Modifications of the development of accessory sexual tissues were found in all treatment groups. As indicated by the severity of deviations from normal (morphology and weight of sex accessories), the antiandrogenic effect of the preparations, in the doses given to the mother rats, increased from BOMT (50 or 75 mg/day) via Sch 13521 (30 mg/day) and DIMP (50 or 60 mg/day) to Sch 13521 (60 mg/day). 2) Nipples of 10-60 day old males : Whole mount preparations were made unilaterally of the row of 6 mammary glands with nipples. The number of intact and abnormal nipples, respectively, was recorded. The relation between intact and abnormal nipples served as indicator of the efficiency of the antiandrogenic substances studied. The result showed that the antiandrogenic effect increased from BOMT to Sch 13521, 60 mg, in the same order as that arrived at from studies of the genital tract. The combined results obtained from the male offspring indicated that the tissues of the genital region, the growth and differentiation of which was most readily impaired by antiandrogens, were the same as those known from other work to be stimulated most easily in female rat fetuses by testosterone. B) Female offspring. Nipples of 31-60 day old females were judged from whole mount preparations and recorded as in the males. The nipples of adult virginal females were examined macroscopically. The same procedure was applied to lactating females, but the results were controlled in consecutive lactational periods and at autopsy. The 3 groups of females showed uniformly that 1) offspring of rats given BOMT during pregnancy had many (about 50 per cent) malformed nipples and 2) the treatment of mother rats with DIMP or Sch 13521 did not influence the development of nipples in female offspring. The result was assumed to be due to an androgenic effect of the steroidal antiandrogen, BOMT, on the nipple anlage.     

Postfixation embryo reduction in unilateral and bilateral twins in mares

Multiple ovulations were induced with a pituitary extract in mares, and the development of multiple conceptuses was monitored daily by ultrasound on days 11 to 40. The incidence of abortion (loss of all embryos) was not significantly different between mares with multiple embryos (5 38 mares; 13%) and mares with singletons (4 36 ; 11%). Embryo reduction (elimination of excess embryos) was not detected during the embryo mobility phase (days 11-15) or on the day of fixation of embryos (day 16) in any of 38 mares with multiple embryos. The incidence of postfixation embryo reduction for mares with twins was 64% (18 28 ); however, the incidence for unilateral twins (17 19 ; 89%) was greater (P<0.01) than for bilateral twins (1 9 ; 11%). Reduction of unilateral twin embryos seemed to occur earlier (53% before day 20 and 82% before day 30) than for the set of bilateral twins (day 36). The remaining embryo in all mares in which embryo reduction occurred seemed normal in size and appearance on the last day of examination. However, in four of eighteen mares in which unilateral reduction occurred, the umbilical cord of the remaining embryo was attached in the ventral hemisphere of the all antochorion. This apparent disorientation was not seen in any of 16 bilaterally located embryos or in 16 singletons.     

Congenital malformation in twins.

Data from the population-based Metropolitan Atlanta Congenital Defects Program (MACDP) show that the overall rate of malformed infants, as well as the incidence of several specific defects, is higher for twins than for singletons. This elevated risk appears limited to same sex twins and, hence, is probably related to monozygosity. In addition to an 18-fold increase in risk of fetal death compared to singletons, twins have almost a 50% greater likelihood of congenital malformation.     

Light on the moth-eye corneal nipple array of butterflies

The outer surface of the facet lenses in the compound eyes of moths consists of an array of excessive cuticular protuberances, termed corneal nipples. We have investigated the moth-eye corneal nipple array of the facet lenses of 19 diurnal butterfly species by scanning electron microscopy, transmission electron microscopy and atomic force microscope, as well as by optical modelling. The nipples appeared to be arranged in domains with almost crystalline, hexagonal packing. The nipple distances were found to vary only slightly, ranging from about 180 to 240 nm, but the nipple heights varied between 0 (papilionids) and 230 nm (a nymphalid), in good agreement with previous work. The nipples create an interface with a gradient refractive index between that of air and the facet lens material, because their distance is distinctly smaller than the wavelength of light. The gradient in the refractive index was deduced from effective medium theory. By dividing the height of the nipple layer into 100 thin slices, an optical multilayer model could be applied to calculate the reflectance of the facet lenses as a function of height, polarization and angle of incidence. The reflectance progressively diminished with increased nipple height. Nipples with a paraboloid shape and height 250 nm, touching each other at the base, virtually completely reduced the reflectance for normally incident light. The calculated dependence of the reflectance on polarization and angle of incidence agreed well with experimental data, underscoring the validity of the modelling. The corneal nipples presumably mainly function to reduce the eye glare of moths that are inactive during the day, so to make them less visible for predators. Moths are probably ancestral to the diurnal butterflies, suggesting that the reduced size of the nipples of most butterfly species indicates a vanishing trait. This effect is extreme in papilionids, which have virtually absent nipples, in line with their highly developed status. A similar evolutionary development can be noticed for the tapetum of the ommatidia of lepidopteran eyes. It is most elaborate in moth-eyes, but strongly reduced in most diurnal butterflies and absent in papilionids.     

Gestational duration, and fetal and infant mortality for twins vs singletons.

The aim of this research was to study fetal and infant mortality in Sweden between 1973 and 1996 in twins vs singletons in relation to gestational duration. Analysis was of fetal and infant mortality based on the number of pregnancies at risk as the denominator rather than the number of deliveries each week. The analysis was based on information stored at the Medical Birth Registry (MBR), the National Board of Health and Welfare, Stockholm. The MBR keeps records on virtually all pregnancies (> 99%) regarding delivery and neonatal information, and for infant mortality up to 1 year of age. During the study period, 2,206,738 singleton and 52,658 twin births were registered. Risk evaluation was made as odds ratio (OR) with a 95% confidence interval. The material was stratified according to parity, maternal age, year of delivery, and delivery unit. Results showed the OR for twin births before 34 weeks gestation was 6 to 8-fold increased compared with singletons. The OR for fetal mortality was increased in all gestational weeks, and like-sexed twins had a consistently poorer prognosis compared to unlike-sexed. Between 1989-96, unlike-sexed twins had a fetal mortality approaching that of singletons. In conclusion, real progress in reduction of infant mortality in twins may be impossible until the high incidence of preterm births can be decreased. Hypothetically, about 100 twin labors would have to be induced to avoid one fetal death in like-sexed twin pregnancies.     

Twin entanglement revisited.

A fear of interlocking twins is one factor that has led to a high Cesarean section (C/S) rate in breech (A)/vertex (B) (Br(a)/Vtx(b)) twins. We sought to estimate the frequency of occurrence of twin entanglement, and of interlocking Br(a)/Vtx(b) twins in vaginal deliveries. 541 twins and 48,195 deliveries were retrospectively studied for the period 1987-1995. The incidence of Br(a)/Vtx(b) deliveries was noted, and the number of deliveries marked by interlocking and collision of fetuses. The mode of delivery, reason for C/S, and sources of perinatal mortality were noted. Only 43 deliveries were Br(a)/Vtx(b) (7.9% of all twins) and of these only 14 (32.6%) were delivered vaginally. One case of interlocking (2.3% of all Br(a)/Vtx(b) pairs) and five cases of collision of twins (ie competition for entry into the pelvic inlet with obstruction) were noted. All cases mentioned were delivered by C/S. No perinatal mortality resulted from these cases. In recent years the trend has been for greater use of C/S and ultrasound in managing twin deliveries. In this study 67.4% of Br(a)/Vtx(b) twins were delivered by C/S. Although there are fewer vaginal deliveries of these twins and the rate for interlocking (2.3%; 95% CI: 0.06-12.3%) for the whole group has remained about the same, we found the rate in those twins allowed vaginal delivery was 6.7% (95% CI: 0.2-31.9%). The presentation at greatest risk for entanglement was found to be Br(a)/Vtx(b).     

Twinning rate in spontaneous abortions.

An unselected series of spontaneous abortions and their mothers were karyotyped with Q-bands to obtain a frequency of twin conceptions lost during the first trimester. Among 661 spontaneous abortions, 15 twin pairs were identified including two sets of conjoined twins. Analysis of Q-band variants permitted the exclusion of cases with two cell lines that could be attributed to maternal contamination or mosaicism. The twinning rate among spontaneous abortions was 1/44 compared with 1/103 live births and stillbirths in the Ontario population. If Weinberg's differential method is applied to these data, the frequency would be as high as 1/30 under the assumption that the incidence of monozygotic twins among abortions is the same as that for live births.     

Monoamniotic twins: what should be the optimal antenatal management?

Monoamniotic twinning is a rare event with an incidence of 1% of all monozygotic twins and associated with a high fetal morbidity and mortality. Confident early diagnosis is possible, but optimal management is not yet established. This article presents the experience of a single centre in managing all monoamniotic twins diagnosed during 1994-2000. Seven pairs of monoamniotic twins were identified for analysis. All were managed in accord with a unit protocol that involved early diagnosis, serial ultrasound examination and elective early delivery. In four cases, the detection of monoamnionicity was made during a first trimester nuchal scan. Discordance for structural abnormality was found in three cases where the co-twin was normal. Cord entanglement was detected antenatally in four cases. Two pairs of twins died before 20 weeks. One of these had early onset twin-twin transfusion syndrome. In five cases, the pregnancy continued beyond 20 weeks. A live birth rate of 90% and intact survival of 70% were achieved in this group. We believe that ultrasound is reliable in diagnosing monoamniotic twins and the detection of cord entanglement. Timing of elective delivery is a balance between the risks of preterm birth at a specific gestational age in an individual centre compared with the unquantifiable risks of fetal death if an expectant policy were pursued. The decision to deliver and at which gestational age should combine input from the parents, neonatologist, fetal medicine consultant and the obstetrician.     

Multiple Endocrine Adenomatosis Type II (Sipple's Syndrome) in Twins

Medullary carcinoma of the thyroid, pheochromocytoma and multiple mucosal neuromas (MEA-II), a familial disorder of neuroectodermal tissue, is believed to be inherited in an autosomal dominant pattern. The occurrence of this syndrome in twins has not previously been reported. We have documented the presence of MEA-II in a pair of twins. The high incidence of bilaterality of pheochromocytoma is emphasized, as well as the usefulness of preoperative catecholamine fractionation, and vena cava catheterization sampling.     

The occurrence of chronic disease and other conditions in a large population-based cohort of native Californian twins.

We describe the prevalence of chronic diseases and conditions in a large cohort of twins, which has been developed to facilitate studies of the role of genetics and environment in the development of disease. The California Twin Program (CTP) comprises twins born in California between 1908 and 1982. Birth records from all multiple births (256,616 in total) were linked (multiple times between 1990 and 2001) with the California Department of Motor Vehicles (DMV) roster of licensees to obtain address information. The linkages have revealed 161,109 matches and, because of less complete DMV records in some years, were less successful in older females than in all others. To date over 51,000 of these twins have completed a detailed 16-page mailed risk factor questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, our crude response rates are as high as 63.6% (among females currently in their 50s), with an overall crude response rate of 37.9%. Similar to our previous report regarding the first 42,000 twins, the current group who have completed the questionnaire are representative of the population from which they were drawn (in terms of age, sex, race and residential distribution). Self-reported disease frequencies are provided, along with current estimates of future cancer incidence and mortality rates likely to be observed in the group. We outline our plans for cohort expansion, additional studies using the cohort, and future plans for inviting collaboration.     

Hand clasping--an overview]

The literature concerning the asymmetry clasping hands is reviewed based on 192 studies. This paper describes the incidence, sex differences, age differences and genetical problems including twinning. The incidence of left hand clasping ranges from 30% to 75% (mean 43%). The review confirms the so-called east-west-gradient and there is a predominance of the left type in Europe. Age and sex differences are only small. There is only a small relationship between hand clasping and handedness. 18 authors examined hand clasping in families and 4 in twins. The family data suggest that hand clasping may be under genetic control, yet it is clear that no simple genetic model for the inheritance can be applied. Both monozygotic and dizygotic twins show a low concordance and the R-R, R-L and L-L pairs in monozygotic and dizygotic twins are in binomial distribution.     

Comparative ultrastructure of corneal surface topography in insects with aspects on phylogenesis and function

Summary The corneas of some nocturnal Lepidoptera carry an array of surface protuberances (nipples), about 200 m high, that acts as an impedance transformer equalizing by gradual transition the refractive index of air to that of the cornea. A screening of the insect class has been carried out in the present study with respect to the variation in corneal topography seen in previous obsarvations.361 species in most insect orders were prepared for EM by thin sectioning or platinum replication. Using the amplitude of the surface protuberances as parameter, a grouping of the cornea types was made on the basis of the well-defined variation of nipple heights observed between individuals of certain species. Thus, the corneas of one extreme group were either smooth (Fig. 4A) or possessed protrusions (Fig. 4B and C) less than about 50 m high, arranged either irregularly or in a regular, hexagonal array (group I). At the other extreme, there was a group with full-sized nipples (Figs. 1 and 3) ranging in amplitude around 250 m (group III). An intermediate group of nipple heights (group II) comprised corneas with low-sized nipples (Fig. 6) between 50 and about 200 m high. Regularity in the arrangement of the various types of protuberances was observed both in groups I and II (compare Figs. 4C and 8). Irregularity tended to be associated with low amplitudes (e.g. Fig. 4B), being found only in group I corneas.Full-sized nipples (group III corneas) were found only among the anagenetically highest orders, Trichoptera and Lepidoptera (Tables 3 and 4), which, however, also had corneas with low protrusions (group I) and low-sized nipples (group II). In one of the two mecopteroid orders, Diptera (Table 2), protrusions and low-sized nipples were found (the latter only in Culicomorpha). The corneas of all other orders (Table 1) had only group I corneas with one noteworthy exception, Thysanura, the most primitive order investigated. All four thysanuran species examined had corneas with low-sized nipples (Fig. 8), thus belonging to group II.The morphological findings demonstrated in the present study can be taken to illustrate the following trends.1.a)The higher relative number of group II and III corneas (low- and full-sized nipples) in the anagenetieally highest orders and the exclusive occurrence of group III corneas in the most advanced orders, Trichoptera and Lepidoptera, may indicate a progressive development of nipples during phylogenesis. Thus, the full-sized nipples may represent an apomorphous condition. Parallelisms — leading to the appearance of low- and full-sized nipples — may have occurred several times during insect phylogenetic development, thus possibly reflecting an evolutionary potential (with or without a selective pressure for this character).b)Low-sized nipples were found in the most primitive insect order, Thysanura. This circumstance may point to regression from full-sized nipples that were present in an ancestor common to all insects. In such a case, the full-sized nipples in Trichoptera and Lepidoptera are to be considered plesiomorphous.At present nothing supports conclusively a preference for one of these two alternatives.2.Among the Lepidoptera, a greater relative number of butterflies than moths lack full-sized nipples. This may be taken to indicate a regression of nipples in the day-flying group of insects in comparison with their possible moth-like, nocturnal ancestors. That in many species there are low-sized nipples (the regression thus being incomplete) may indicate that a function of the nipples in ranges of shorter wavelengths has brought about an arrest of the regression at lower amplitudes.This investigation has been sponsored in part by the Air Force Office of Scientific Research through the European Office of Aerospace Research, OAR, United States Air Force, under grants Nos. AF EOAR 66-34 and EOOAR-68-0036, and supported by grants from the Swedish Medical Research Council and Stifteisen Gustaf och Tyra Svenssons Minne.We are grateful to Prof. L. Brundin, Department of Entomology, Swedish Museum of Natural History, Stockholm, for valuable discussion concerning the phylogenetic aspects.We also thank the William Beebe Tropical Research Station (New York Zoological Society), Arima Valley, Trinidad, West Indies.     

Retrospective determination of chorion type in twins using a simple questionnaire.

This study investigates the validity of retrospective determination of chorion type by asking the question to the mother about the number of placentas. In the "East Flanders Prospective Twin Survey" (EFPTS), accurate information on the placentation and zygosity of the multiples was collected prospectively. The mothers of 231 monozygotic (95 dichorionic and 136 monochorionic) twins and 255 dizygotic twins were asked to fill in a simple questionnaire regarding 1). the zygosity and 2). the number of placentas of their twins. The accuracy of the response to the question on "the number of placentas" was 60% for monozygotic twins and 37% for dizygotic twins. The accuracy of the response to the question on the zygosity of the twins was 93% for monozygotic and 95% for dizygotic twins. If the questionnaire was used for the determination of chorion type, a total of 31 monozygotic twins (13%) should have been assigned as dichorionic on the fact that there were two separate placentas. Of these, 10 (32%) are monochorionic and 12 (39%) were falsely reported as having two placentas. We conclude from these findings that this simple questionnaire method is unreliable for the retrospective determination of the chorion type.     

Artificial induction of twinning in cattle by means of supplemental embryo transfer

The induction of twins by surgical and nonsurgical transfer was performed 6 - 8 days after Artificial Insemination (A.I.) in a total of 142 cows. Of the 47 heifers, which received surgically transferred embryos, 32 (68%) became pregnant. Of the 95 cows, which received nonsurgically transferred embryos, 58 (61,6%) became pregnant. A total of 90 (63.5%) of the recipient animals became pregnant. Up to date 64 recipients have calved; twins have resulted in 40 and 48,2% resp, from surgical and nonsurgical inductions. Out of a total of 64 calvings 29 (45,3%) were twins, and of these 38% were males, 27% were females, and 34% were mixed births. Female - calves resulted in freemartinism. There was no increase in the incidence of either retained placenta or dystocia. The induction of twinning by means of embryo transfer can be regarded as a useful method for the increase in the reproductive performance cattle.     

Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs

BackgroundThe similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins.Methods172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables.ResultsA notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs.ConclusionsThis significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs.     

Use of the correlation of liability in twins and siblings in the study of birth defects

The epidemiologic approach to determining the etiology of disease involves identification of potential risk factors and then comparison of disease incidence among people with varying levels of exposure to the potential risk factors. This paper defines risk factors which correspond to different levels of genetic and environmental proximity to index cases of birth defects. Genetic proximity is estimated by the coefficient of relationship (R): 0.5 for siblings and dizygotic twins and 1.0 for monozygotic twins. Environmental proximity is measured by a combination of two variables: one variable for those potentially preventable risk factors common to siblings (S) and another for those common only to twins (T). Discordance in identical twins is attributed to a third type of environmental factors (U) that are unshared by twins and include random (stochastic) factors. The association between these risk factors and birth defects is estimated by using a linear model of the correlation of liability for different relatives. The coefficients derived from the model reflect the relative importance of genetic and different types of environmental risk factors as causes for the defects and can be used to identify birth defects most likely to be caused by measurable and possibly preventable risk factors. These defects could then be assigned high priority for future studies and preventive efforts.     

The risk of birth defects in dichorionic twins conceived by assisted reproductive technology.

The purpose of this study was to examine whether dichorionic twins conceived by assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI], in vitro fertilization [IVF], gamete-intrafallopian tube transfer [GIFT]) have a higher risk of birth defects compared to dichorionic twins conceived naturally. We reviewed the medical records of 406 mothers with dichorionic twin pregnancies, who received continuous antenatal care from < or = 20 weeks of gestation and gave birth to infants after > or = 24 weeks of gestation in our institute. Birth defects were diagnosed at the time of hospital discharge according to the International Classification of Diseases, 10th Revision. Occurrence of birth defects was compared between twins conceived by ART and those conceived naturally using logistic regression analysis. Overall, 51 of 812 infants (51/812 = 6.2%) had birth defects. The incidence of birth defects in ART-conceived twins was significantly higher than that of naturally conceived twins with an odds ratio of 6.9 (95% confidence interval [CI] 2.1, 22.5), 3.7 (95% CI 1.2, 12.0), and 4.3 (95% CI 1.4, 14.3) for ICSI, IVF, and GIFT, respectively. The higher frequency of birth defects in ART-conceived twins was still significant after adjusting for higher maternal age in the ART group, with an adjusted odds ratio of 6.7 (95% CI 2.1, 21.9), 3.6 (95% CI 1.1, 11.5), and 3.7 (95% CI 1.2-11.8) for ICSI, IVF, and GIFT, respectively. Dichorionic twins conceived by ART, compared to dichorionic twins conceived naturally, had a much higher risk for birth defects diagnosed at hospital discharge.     

High incidence of preterm births and early losses in pregnancy after in vitro fertilisation. Australian in vitro fertilisation collaborative group.

A fertilisation cohort of 244 pregnancies resulting from in vitro fertilisation was reported to a national register by eight units specialising in in vitro fertilisation. Early pregnancy losses were high, with 5% tubal ectopic pregnancies, 18% biochemical pregnancies, and an incidence of spontaneous abortion of 27%. Among pregnancies of at least 20 weeks'' gestation 22% were multiple, with 26 pairs of twins and four sets of triplets. The incidence of preterm births was more than three times higher than in the general population. Low birthweight rates were also higher, owing both to preterm births and to multiple pregnancies. The sex ratio and the incidence of major congenital malformations were similar to those in naturally conceived pregnancies. In this series the high fetal losses at all stages of pregnancy suggested maternal reproductive causes and should not be interpreted as being due to factors peculiar to in vitro fertilisation. Further analysis will be necessary when larger numbers are available.