Isaac Blickstein

The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study

OBJECTIVE The purpose of this study was to document pregnancy and neonatal outcome of monochorionic diamniotic twin pregnancies. STUDY DESIGN This observational study describes a prospective series included in the first trimester in 2 centers of the Eurotwin2twin project. RESULTS Of the 202 included twin pairs, 172 (85%) resulted in 2 survivors, 15 (7.5%) in 1 survivor, and 15 (7.5%) in no survivors. The mortality was 45 of 404 (11%), and 36 of 45 (80%) were fetal losses of 24 weeks or less, 5 of 45 (11%) between 24 weeks and birth, and 4 of 45 (9%) were neonatal deaths. Twin-to-twin transfusion syndrome (TTTS) occurred in 18 of 202 (9%). The mortality of TTTS was 20 of 36 (55%), which accounted for 20 of 45 (44%) of all losses. Severe discordant growth without TTTS occurred in 29 of 202 (14%). Its mortality was 5 of 58 (9%), which accounted for 5 of 45 (11%) of all losses. Major discordant congenital anomalies occurred in 12 of 202 (6%). Of the 178 pairs that continued after 24 weeks, 10 (6%) had severe hemoglobin differences at birth. After 32 weeks, the prospective risk of intrauterine demise was 2 in 161 pregnancies (1.2%; 95% confidence interval, 0.3-4.6). CONCLUSION Of the monochorionic twins recruited in the first trimester, 85% resulted in the survival of both twins, and 92.5% resulted in the survival of at least 1 twin. Most losses were at 24 weeks or less, and TTTS was the most important cause of death. After 32 weeks, the risk of intrauterine demise appears to be small.

The growth discordant twin.

The study of growth discordancy in twin gestation has gathered great momentum in recent years. Divergent intertwin growth is believed to be a direct result of the process of twinning and of the inability of the uterine environment to provide for the increased demand of multiple fetuses. The smaller twin faces increased risk of perinatal mortality and morbidity as well as reduced physical and mental development in later life. The advent of ultrasonography enabled a fairly accurate prediction of growth disparity. Although extensive investigative efforts have clarified many questions regarding divergent twin growth, the question how to manage such pregnancies remains to be answered. The present article is a review of the literature concerning the clinical aspects of growth discordant twins.

Birthweight discordance in multiple pregnancy.

This paper reviews several aspects of discordant growth in multiple pregnancies. Discordant growth is not a chance event and therefore several patterns can be discerned. About 75% of twins exhibit < 15% discordance (concordant), 20% are 15-25% (mildly) discordant, and about 5% are more than 25% (severely) discordant. Higher frequencies and increased severity are seen among triplets. Five observations regarding discordance became generally accepted: (a) not all discordant pairs are similar; (b) the larger the discordance level the greater is the risk for an adverse outcome; (c) discordant growth does not necessarily represent growth restriction; (d) a discordance level may have a different clinical implication in different gestational ages; and (e) the smaller fetuses in severely discordant pairs are at disproportionate risk for neonatal mortality. Mild discordance may represent a normal variation between sibs whereas severely discordant pairs often exhibit patterns of growth restriction. Not infrequently, discordance may represent an adaptation to the limited intrauterine space in order to increase gestational age.

Adaptive growth restriction as a pattern of birth weight discordance in twin gestations

Objective To challenge the hypothesis that discordant growth is a normal variation by relating birth weight discordance to total twin birth weight. Method Among 12,565 Israeli live-born twin pairs (1993–98), we compared total twin birth weight decile, the frequencies of three levels of discordance in the general population, over 25% discordance between like- versus unlike-sex pairs, and over 25% discordance between pairs delivered by primiparas versus multiparas. Results We found a marked change in the best-fit correlation function with increased discordance: level 15–24.9% was inversely linear whereas levels 25–34.9% and over 34.9% were inversely logarithmic (R2 = .47, .88, and .9, respectively). The best-fit correlation of frequencies of more than 25% discordance was inversely logarithmic and similar in like-and unlike-sexed twins across deciles functions (P = .7, odds ratio [OR] 1.0, 95% confidence interval [CI] 0.9, 1.2). The overall frequencies of discordance were also similar (9.3% versus 10.2%, P = .11, OR 0.9, 95% CI 0.8, 1.0). The frequencies of primiparas decreased linearly (R2 = .98) and the frequencies of more than 25% discordant pairs in multiparas and primiparas across the deciles had similar inversely logarithmic patterns (P = .55, OR 1.0, 95% CI 0.9, 1.2). Discordance over 25% was significantly more frequent among primiparas (P < .001, OR 1.45, 95% CI 1.3, 1.6). Conclusion The observed patterns of birth weight discordance did not substantiate normal variation but an adaptive growth restriction that might explain why the likelihood of discordant growth decreases as total twin birth weight increases.

Delivery of breech first twins: a multicenter retrospective study.

Objective To assess the risk of vaginal birth of breech first twins by Apgar scores and mortality. Methods We did a retrospective case-control analysis of data from 13 centers that allow vaginal birth for breech first twins. We used depressed 5-minute Apgar scores and neonatal mortality as main outcome measures between vaginal (n = 239) and cesarean (n = 374) deliveries of pairs with breech first twins, stratified by parity, birth weights of first twins, and types of cesarean. The 95% power of our sample size (α = .05) was sensitive enough to detect differences of 5% of the overall sample and 25–30% of subgroups. Results Vaginal birth was attempted in 61% of 613 pairs. There were significantly more depressed Apgar scores (P = .008, odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2, 4.7) and neonatal deaths (P < .001, OR 9.5, 95% CI 4.0, 23.4) among vaginal births of pairs in whom first twins weighed less than 1500 g but not among the higher-birth-weight cohort (for depressed Apgar scores: P = .76, OR 1.1, 95% CI 0.6, 2.1). Multiparity and elective cesarean seemed to have little influence on outcome measures. Neonatal mortality was associated with extremely preterm twins. Conclusion There was no evidence that vaginal birth is unsafe, in terms of depressed Apgar scores and neonatal mortality, for breech first twins that weighed at least 1500 g.

Depressive symptoms during late pregnancy and early parenthood following assisted reproductive technology

OBJECTIVE To evaluate the relationship between assisted reproduction technology (ART) and depressive symptoms during late pregnancy and early parenthood. DESIGN Case-control longitudinal study. SETTING The Center of Reproductive Medicine, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. PATIENT(S) Women who conceived by ART compared with men and compared with women following spontaneous conceptions. INTERVENTION(S) The sample of 87 subjects, 48 ART (25 mothers, 23 fathers; response rate of 30%) and 39 non-ART mothers were evaluated by the Edinburgh Postnatal Depression Scale (EPDS) at 30-32 weeks of gestation, and at 1 week and 3 months after delivery. MAIN OUTCOME MEASURE(S) Mean scores and prevalence of low scores. RESULT(S) The main sociodemographic and obstetric characteristics were similar between groups. Edinburgh Postnatal Depression Scale scores were higher in ART women compared with non-ART women during all assessments and higher during the third trimester of pregnancy and at 1 week postpartum compared with ART men. The prevalence of depressed subjects was significantly higher in ART women compared with non-ART women during the antenatal assessment. CONCLUSION(S) Assisted reproductive technology pregnancies are more frequently associated with depressive symptoms that may persist after delivery, suggesting a greater emotional vulnerability of these women. The risk of depression during and following ART pregnancies needs monitoring to avoid adverse effects of postpartum depression on the mother-infant relationship and infants psychologic development.

The relation between inter-twin birth weight discordance and total twin birth weight

OBJECTIVE We tested the hypothesis that the frequency of growth discordance among twins is not related to the uterine capacity for carrying twins. METHOD We counted and compared the frequencies of birth weight discordance of more than 25% in an unlike-sexed twin cohort (n = 1244) and in a population-based twin cohort (n = 7570) across the deciles of the total twin birth weight (twin A + twin B) distribution. The birth order of the heavier twin was noted. RESULTS Similar frequencies of discordant pairs were found in both cohorts (11% and 12%, respectively; Mantel-Haenszel chi2 test: P = .131, odds ratio (OR) 0.9, 99% confidence interval (CI) 0.67, 1.11; Woolf test for heterogeneity: two-tailed P = .472). In the discordant pairs, twin A was considerably more often the heavier twin in all birth weight deciles (unlike-sexed cohort: P < 10(-8), OR 5.9, 99% CI 3.0, 11.7; population-based cohort: P < 10(-8), OR 3.1, 99% CI 2.3, 4.0), and in both cohorts (inter-cohort difference: P = .109, OR 1.4, 99% CI 0.83, 2.32). Both cohorts showed a similar nonlinear trend: given that X = decile order, discordance decreased as a function of 22.0 - 6.54 ln[X] for the unlike-sexed twins cohort and 23.0 - 8.18 ln[X] for the population-based cohort, with r values of 0.967. CONCLUSION The more favorable the uterine milieu for carrying twins, the smaller the likelihood of discordant twin growth. Birth order of the heavier twin appears to be an integral part of the discordance phenomenon. The similarity of the cohorts suggests that these conclusions are valid for both like and unlike-sexed twins.

The risk of fetal loss associated with Warfarin anticoagulation

Objectives: To examine if fetal risks associated with Warfarin anticoagulation during pregnancy may have been over‐estimated at the time the drug was contraindicated during pregnancy. Methods: Seven case series with the same therapeutic objective for Warfarin anticoagulation published after 1980 were identified. The frequencies of fetal complications were calculated and compared with those of the 1980 compilation. Results: The frequencies of embryopathy, stillbirths, and neonatal deaths were similar to the 1980 database, but higher with respect to spontaneous abortions (24.1 vs. 8.6%) and premature deliveries (13.9 vs. 4.6%), and lower regarding live births (73.3 vs. 83.7%). Conclusions: Fetal risks associated with Warfarin anticoagulation during pregnancy have not been overestimated. Warfarin should not be given in cases where other anticoagulants do not increase the risk for the expecting mother.

Cerebral palsy in multifoetal pregnancies

Cerebral palsy (CP) consists of a wide range of lifetime physical disabilities caused by damage to the brain during intrauterine and early neonatal life. The risk of CP is increased among survivors of prematurity and in low-birthweight (LBW) infants. Increased prematurity and LBW rates are more common in multifoetal pregnancies, therefore, these pregnancies have also been associated with increased rates of CP. Given the world wide epidemic dimensions of multiple births, this paper discusses current concepts regarding CP in multifoetal gestations.

Why are monozygotic twins different

Abstract Although popularly designated as “identical”, monozygotic (MZ) twins are rarely identical. Much has been speculated on the origin of MZ twins and several theories have been proposed. Post-fertilization events, such as chromosomal mosaicism, skewed X-inactivation and imprinting mechanisms, as well as other epigenetic mechanisms are responsible for the differences between MZ twins. Numerous discordant MZ twins have been reported including discordance for lateral asymmetry, major malformation, growth and intrauterine death of the co-twin. This discrepancy may have long-term implications on complex diseases and their predisposition, organ transplantation and interpretation of twin-based studies. We reviewed the genotypic and phenotypic differences between MZ twins and discuss their main causes.