Perinatal outcome of pregnancy complicated by twin anemia-polycythemia sequence: systematic review and meta-analysis.

OBJECTIVE: To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively. CONCLUSIONS: The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of post-laser fetal death in selective growth restriction complicating twin-twin transfusion syndrome using standardized definitions.

OBJECTIVE: Selective fetal growth restriction (sFGR) complicating twin-twin transfusion syndrome (TTTS) is associated with a 3-6-fold increased risk of fetal demise after fetoscopic laser surgery (FLS). Identifying these patients is challenging due to varying definitions of sFGR used in the literature. The objective of this study was to determine the association of three currently used definitions for sFGR with demise of the smaller twin, typically the donor, following FLS for TTTS. METHODS: This was a retrospective cohort study of monochorionic diamniotic twin pregnancies undergoing FLS for TTTS between January 2015 and December 2018. Classification of the cohort as sFGR or non-sFGR was performed using three different definitions: (1) estimated fetal weight (EFW) of one twin < 10th centile and intertwin EFW discordance > 25%, according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) (Definition A); (2) EFW of one twin < 3rd centile, according to the solitary criterion for sFGR reported in a Delphi consensus (Definition B); and (3) presence of at least two of four of the following criteria: EFW of one twin < 10th centile, abdominal circumference of one twin < 10th centile, intertwin EFW discordance of ≥ 25% and umbilical artery pulsatility index of the smaller twin > 95th centile, according to the contributory criteria for sFGR in monochorionic diamniotic twin pregnancies reported in the Delphi consensus (Definition C). Pearson's χ2 and univariate and multivariate logistic regression analyses were performed to assess the association of classification as sFGR according to the different definitions with fetal demise within 48 h after FLS. RESULTS: A total of 124 pregnancies underwent FLS for TTTS during the study period. Of these, 46/124 (37.1%) were identified as having sFGR according to the ISUOG criteria (Definition A), 57/124 (46.0%) based on EFW < 3rd centile (Definition B) and 70/124 (56.5%) according to the Delphi contributory criteria (Definition C). There were no differences in maternal body mass index, recipient twin amniotic fluid volume, gestational age (GA) at intervention or GA at delivery between sFGR and non-sFGR cases for any of the three definitions. There were also no differences in the rates of postprocedure recipient demise or Doppler abnormalities in the recipient. Regardless of the definition used, sFGR cases showed a significantly higher rate of postprocedure donor twin demise compared with that in non-sFGR cases (Definition A: 28.3% vs 3.8%, P < 0.01; Definition B: 22.8% vs 4.5%, P = 0.02; Definition C: 22.9% vs 0%, P < 0.01). For all of the sFGR definitions, the rate of Stage-III TTTS was increased in sFGR compared to non-sFGR cases (Definition A: 65.2% vs 35.9%, P ≤ 0.01; Definition B: 59.6% vs 35.8%, P = 0.04; Definition C: 62.9% vs 25.9%, P < 0.01). All cases of donor demise met the criteria for sFGR according to Definition C. Classification as sFGR according to Definition C was associated with a significantly higher rate of post-FLS donor demise compared to Definitions A and B (χ2 , 15.32; P < 0.01). Logistic regression analysis demonstrated that sFGR cases had an increased risk of donor demise (Definition A: odds ratio (OR), 4.97 (95% CI, 1.77-13.94), P < 0.01; Definition B: OR, 4.39 (95% CI, 1.36-14.15), P = 0.01) and that staging of TTTS was also predictive of demise (OR, 2.26 (95% CI, 1.14-4.47), P = 0.02). After adjusting for GA at intervention and stage of TTTS, the results were similar (Definition A: OR, 6.48 (95% CI, 2.11-24.56), P = 0.002; Definition B: OR, 4.16 (95% CI, 1.35-15.74), P = 0.02). CONCLUSIONS: The rate of fetal demise following FLS for TTTS is increased in the presence of sFGR. Improving diagnosis of sFGR should improve counseling and may affect management. The Delphi method of defining sFGR based on the presence of at least two of four contributory criteria had the highest predictive value for donor demise following FLS for TTTS. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Growth restriction increases the risk of bronchopulmonary dysplasia, death, and sepsis in twins of 30 weeks or less of gestation. / Restricción de crecimiento aumenta el riesgo de displasia broncopulmonar, muerte y sepsis en gemelos de 30 o menos semanas de gestación.

INTRODUCTION: Multiple factors influence the risk of morbidity and mortality of premature infants with intrauterine growth restriction (IUGR). The comparison of twins with different intrauterine growth allows evaluating the effect of the restriction, excluding maternal factors and prenatal mana gement. Our objective was to assess the effect of IUGR on acute and chronic morbidity, and mortality of extreme preterm twins. PATIENTS AND METHOD: Twins weighing less than 1500 grams and gesta tion equal to or less than 30 weeks, of the Neocosur Network. Separate analyses were performed on concordant twin pairs, and on mild and severe discordant twins, evaluating the effect of IUGR on morbidity and mortality. A multivariate analysis was performed in order to establish the impact of this effect. RESULTS: 459 twin pairs, 227 concordant twins, 110 of mild discordance, and 122 of severe discordance. Among the concordant ones, there was only a difference in oxygen uptake at 36 weeks. In those of mild discordance, the smaller twin presented a lower frequency of hyaline membrane disease and required fewer doses of surfactant, but had a higher risk of bronchopulmonary dysplasia (BPD) or death. In severe discordant twins, the smaller one presented higher mortality, sepsis, use and permanence in mechanical ventilation, despite the lower frequency of hyaline membrane disease. In multiple regression analysis, the combined risk of BPD or death was higher in the smaller twin and of severe discordance. CONCLUSION: In discordant twins, the acute respiratory pathology was more frequent in the larger one, although the risk of BPD or death was higher in the one with IUGR.

Cancer Incidence and Mortality in 260,000 Nordic Twins With 30,000 Prospective Cancers.

The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.

Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

INTRODUCTION: We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. MATERIALS AND METHODS: This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. RESULTS: Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. DISCUSSION: FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option.

Restricción de crecimiento aumenta el riesgo de displasia broncopulmonar, muerte y sepsis en gemelos de 30 o menos semanas de gestación / Growth restriction increases the risk of bronchopulmonary dysplasia, death, and sepsis in twins of 30 weeks or less of gestation

INTRODUCCIÓN: Múltiples factores influyen en el riesgo de morbimortalidad del prematuro con restricción del crecimiento intrauterino (RCIU). La comparación de gemelos con crecimiento intrauterino discordante permite evaluar su efecto, excluyendo factores maternos y manejo prenatal. Nuestro objetivo fue evaluar el efecto de la RCIU sobre la morbilidad aguda, crónica y mortalidad, en parejas de recién nacidos gemelares prematuros extremos. PACIENTES Y MÉTODO: Gemelos menores de 1500 g y 30 semanas de gestación, de la Red Neocosur. Se realizaron análisis separados de pares de gemelos concordantes, discordantes leves y severos, evaluando el efecto de la RCIU sobre morbi-mortalidad. Se realizó análisis multivariado para establecer magnitud del efecto. RESULTADOS: 459 pares de gemelos, 227 concordantes, 110 discordantes leves y 122 severos. Entre los concordantes solo hubo diferencia en uso de oxígeno a las 36 semanas. En discordantes leves, el menor tuvo menos enfermedad de membrana hialina y requirió menos dosis de surfactante, pero tuvo un mayor riesgo de Displasia broncopulmonar (DBP) o muerte. En discordantes severos, el menor presentó mayor mortalidad, sepsis, utilización y permanencia en ventilación mecánica, pese a menor frecuencia de enfermedad de membrana hialina. En regresión múltiple, el riesgo combinado de DBP o muerte fue mayor en gemelo menor y discordante severo. CONCLUSIÓN: En gemelos discordantes, la patología respiratoria aguda fue más frecuente en el gemelo mayor, aunque el riesgo de DBP o muerte fue mayor en el gemelo con RCIU.

INTRODUCTION: Multiple factors influence the risk of morbidity and mortality of premature infants with intrauterine growth restriction (IUGR). The comparison of twins with different intrauterine growth allows evaluating the effect of the restriction, excluding maternal factors and prenatal mana gement. Our objective was to assess the effect of IUGR on acute and chronic morbidity, and mortality of extreme preterm twins. PATIENTS AND METHOD: Twins weighing less than 1500 grams and gesta tion equal to or less than 30 weeks, of the Neocosur Network. Separate analyses were performed on concordant twin pairs, and on mild and severe discordant twins, evaluating the effect of IUGR on morbidity and mortality. A multivariate analysis was performed in order to establish the impact of this effect. RESULTS: 459 twin pairs, 227 concordant twins, 110 of mild discordance, and 122 of severe discordance. Among the concordant ones, there was only a difference in oxygen uptake at 36 weeks. In those of mild discordance, the smaller twin presented a lower frequency of hyaline membrane disease and required fewer doses of surfactant, but had a higher risk of bronchopulmonary dysplasia (BPD) or death. In severe discordant twins, the smaller one presented higher mortality, sepsis, use and permanence in mechanical ventilation, despite the lower frequency of hyaline membrane disease. In multiple regression analysis, the combined risk of BPD or death was higher in the smaller twin and of severe discordance. CONCLUSION: In discordant twins, the acute respiratory pathology was more frequent in the larger one, although the risk of BPD or death was higher in the one with IUGR.

Mortality for Critical Congenital Heart Diseases and Associated Risk Factors in Newborns. A Cohort Study / Mortalidade para Cardiopatias Congênitas e Fatores de Risco Associados em Recém-Nascidos. Um Estudo de Coorte

Abstract Background: Congenital heart diseases are the most common type of congenital defects, and account for more deaths in the first year of life than any other condition, when infectious etiologies are ruled out. Objectives: To evaluate survival, and to identify risk factors in deaths in newborns with critical and/or complex congenital heart disease in the neonatal period. Methods: A cohort study, nested to a randomized case-control, was performed, considering the Confidence Interval of 95% (95% CI) and significance level of 5%, paired by gender of the newborn and maternal age. Case-finding, interviews, medical record analysis, clinical evaluation of pulse oximetry (heart test) and Doppler echocardiogram were performed, as well as survival analysis, and identification of death-related risk factors. Results: The risk factors found were newborns younger than 37 weeks (Relative Risk - RR: 2.89; 95% CI [1.49-5.56]; p = 0.0015), weight of less than 2,500 grams (RR: 2.33 [; 95% CI 1.26-4.29]; p = 0.0068), occurrence of twinning (RR: 11.96 [95% CI 1.43-99.85]; p = 0.022) and presence of comorbidity (RR: 2.27 [95% CI 1.58-3.26]; p < 0.0001). The incidence rate of mortality from congenital heart disease was 81 cases per 100,000 live births. The lethality attributed to critical congenital heart diseases was 64.7%, with proportional mortality of 12.0%. The survival rate at 28 days of life decreased by almost 70% in newborns with congenital heart disease. The main cause of death was cardiogenic shock. Conclusion: Preterm infants with low birth weight and comorbidities presented a higher risk of mortality related to congenital heart diseases. This cohort was extinguished very quickly, signaling the need for greater investment in assistance technology in populations with this profile.

Resumo Fundamento: As cardiopatias congênitas configuram o tipo mais comum de defeitos congênitos, sendo responsáveis por mais mortes no primeiro ano de vida do que em qualquer outra condição, quando etiologias infecciosas são excluídas. Objetivo: Avaliar a sobrevida e identificar os fatores de risco nos óbitos em recém-nascidos com cardiopatia congênita crítica e/ou complexa no período neonatal. Métodos: Realizou-se um estudo de coorte, aninhado a um caso-controle aleatorizado, considerando Intervalo de Confiança de 95% (IC95%) e nível de significância de 5%, pareado por sexo do recém-nascido e idade materna. Foram feitas buscas ativas de casos, entrevistas, análise de prontuário, avaliação clínica da oximetria de pulso (teste do coraçãozinho) e do ecoDopplercardiograma, bem como análise de sobrevida e identificação dos fatores de risco relacionados ao óbito. Resultados: Os fatores de risco encontrados foram recém-nascidos com menos de 37 semanas (Risco Relativo − RR: 2,89; IC95% 1,49-5,56; p = 0,0015), peso inferior a 2.500 g (RR: 2,33; IC95% 1,26-4,29; p = 0,0068), ocorrência de gemelaridade (RR: 11,96; IC95% 1,43-99,85; p = 0,022) e presença de comorbidade (RR: 2,27; IC95% 1,58-3,26; p < 0,0001). A taxa de incidência de mortalidade por cardiopatias congênitas foi de 81 casos por 100 mil nascidos vivos. A letalidade atribuída às cardiopatias congênitas críticas foi de 64,7%, com mortalidade proporcional de 12,0%. A taxa de sobrevida aos 28 dias de vida diminuiu em quase 70% nos recém-nascidos com cardiopatias congênitas. A principal causa de óbito foi o choque cardiogênico. Conclusão: Recém-nascidos prematuros, com baixo peso e presença de comorbidades apresentaram maior risco de mortalidade relacionada às cardiopatias congênitas. Esta coorte se extinguiu muito rapidamente, sinalizando para a necessidade de maior investimento em tecnologia assistencial em populações com este perfil.

Outcome of Twin Pregnancies Complicated by a Neural Tube Defect.

Twin pregnancies discordant for neural tube defects (NTD) is a management dilemma. Risks of preterm delivery from polyhydramnios must be balanced with the risks of selective termination (ST) of the anomalous fetus. We investigated the prevalence of twin pregnancies discordant for NTD and the rate of pregnancy complications in our institution over a 10-year period. Cases were obtained by searching the hospital ultrasound database and findings were confirmed by expert review of ultrasound images. Outcomes of ST and expectant management were assessed. Each unaffected co-twin was assigned to three consecutive twin pregnancy controls matched by chorionicity and maternal age. Primary outcome was birth before 34 weeks' gestation. Secondary outcomes were small for gestational age, mode of delivery, neonatal unit admission, and neonatal death. In total, 13 pregnancies were identified as potential cases. Of these, 11 were included in the analysis: 9 dichorionic diamniotic and 2 monochorionic diamniotic twins. Seven cases had ST and four were managed expectantly. We found 100% (4/4) of expectantly managed pregnancies delivered <34 weeks compared with 14% (1/7) of the ST group (p = .015). Polyhydramnios complicated three expectantly managed pregnancies and one pregnancy in the ST group. The birthweight SD score of all unaffected co-twins was ≥-2. The case-control analysis showed a higher rate of polyhydramnios in twin pregnancies discordant for NTD compared with controls, but little evidence for differences between groups in delivery rates <34 weeks, birthweight, neonatal unit admission, or neonatal death. ST warrants serious consideration to avoid potential complications to the unaffected co-twin.

Endoscopic Placental Laser Coagulation in Monochorionic Diamniotic Twins with Type II Selective Fetal Growth Restriction.

OBJECTIVE: To determine predictors of survival in monochorionic diamniotic twins with selective fetal growth restriction type II (sFGR-II), with or without twin-to-twin transfusion syndrome (TTTS), treated by endoscopic placental laser coagulation. METHODS: Laser surgery was performed at 20 (15-27) weeks' gestation in 405 cases of sFGR-II with and 142 without coexisting TTTS. Multivariable logistic regression analysis was performed to determine significant predictors of survival to discharge from hospital. RESULTS: There was survival of the small twin in 216 (39.5%) and of the large twin in 379 (69.3%) cases. Significant predictors of survival of both the small and larger twin were ductus venosus Doppler findings in the small twin, gestational age at laser and cervical length, but not the presence of TTTS or Doppler findings in the large twin. CONCLUSIONS: In sFGR-II, survival after laser surgery is primarily dependent on the condition of the small twin.

Optimal method and timing of intrauterine intervention in twin reversed arterial perfusion sequence: case study and meta-analysis.

INTRODUCTION: The objective of this study was to define the optimal method and timing of intervention in twin reversed arterial perfusion (TRAP) sequence. MATERIAL AND METHODS: During a period of 20 years (1993-2013), we performed endoscopic laser coagulation of umbilical cord vessels or intrafetal laser in 67 pregnancies with TRAP sequence. These data were combined with those reported in the literature to determine the survival rate of the pump twin for different methods and timing of interventions. RESULTS: A variety of techniques were used to interrupt the blood supply to the acardiac twin. Most procedures were performed at or after 16 weeks, and with most methods the survival rate of the pump twin was about 80%. Good results were also obtained for triplet pregnancies. In 18 of 30 cases (60%) diagnosed at 11-14 weeks, there was spontaneous cessation of flow in the acardiac twin before planned intervention at 16-18 weeks, and in 11 of these (61.1%) the pump twin died or suffered brain damage. In 103 pregnancies treated by intrafetal laser at 12-27 weeks, there was no correlation between gestational age at treatment and survival rate, but there was an inverse association between gestational age at treatment and gestational age at birth. DISCUSSION: In TRAP sequence, survival may be improved by elective intervention at 12-14 weeks.

Interleukin-8 predicts 60-day mortality in premature infants with necrotizing enterocolitis.

OBJECTIVE: The purpose of this study was to evaluate the predictiveness of circulating interleukin (IL)-8 for 60-day mortality in premature infants with necrotizing enterocolitis (NEC). BACKGROUND: NEC affects up to 5% of premature infants and remains a leading cause of mortality among neonates. METHODS: A total of 113 infants with surgically (n=50) or medically (n=63) treated NEC were retrospectively analyzed. Laboratory parameters including serum IL-8 were assessed at the diagnosis of NEC and during the preoperative workup. RESULTS: The 60-day mortality was 19% (22/113), 10% (6/63) in medical and 33% (16/50) in surgical NEC. IL-8 levels significantly correlated with 60-day mortality (odds ratio: 1.38; CI 1.14-1.67; p=0.001). Median IL-8 levels at diagnosis were significantly higher in neonates who were later treated surgically (median=2625 pg/ml; range: 27-7500) compared with those treated medically (median=156 pg/ml; range: 5-7500; p<0.001). The AUC to discriminate between medical and surgical NEC was 0.82 (CI, 0.74-0.90), and an exploratory IL-8 cutoff point could be established at 1783 pg/ml (sensitivity of 90.5%; specificity of 59.2%). CONCLUSIONS: Our findings that serum IL-8 (i) correlates directly with 60-day mortality and (ii) differs significantly between medically and surgically treated infants may change the process of therapeutic decision making in NEC.

Estimating heritability for cause specific mortality based on twin studies.

There has been considerable interest in studying the magnitude and type of inheritance of specific diseases. This is typically derived from family or twin studies, where the basic idea is to compare the correlation for different pairs that share different amount of genes. We here consider data from the Danish twin registry and discuss how to define heritability for cancer occurrence. The key point is that this should be done taking censoring as well as competing risks due to e.g.  death into account. We describe the dependence between twins on the probability scale and show that various models can be used to achieve sensible estimates of the dependence within monozygotic and dizygotic twin pairs that may vary over time. These dependence measures can subsequently be decomposed into a genetic and environmental component using random effects models. We here present several novel models that in essence describe the association in terms of the concordance probability, i.e., the probability that both twins experience the event, in the competing risks setting. We also discuss how to deal with the left truncation present in the Nordic twin registries, due to sampling only of twin pairs where both twins are alive at the initiation of the registries.

Invasive treatment in complicated monochorionic twin pregnancies: indications and outcome of 120 consecutively treated pregnancies.

OBJECTIVE: Monochorionic twin pregnancies are associated with increased risk of severe complications. Umbilical cord occlusion (UCO) and fetoscopic selective laser coagulation (FSLC) are used as invasive treatment. The study aim was to document treatment indications and pregnancy outcome where UCO and FSLC were used for treating fetal discrepancies and twin-to-twin transfusion syndrome (TTTS). DESIGN: Cohort study of all consecutively treated monochorionic twin pregnancies 2004-2010. SETTING: Tertiary care center. POPULATION: One hundred and twenty pregnancies treated by FSLC (55) or UCO (65). Umbilical cord occlusion was undertaken in 49 TTTS cases, in four cases with fetal abnormality and TTTS and in 12 cases because of fetal anomaly only. MAIN OUTCOME MEASURES: Overall survival per fetus, survival per pregnancy of at least one fetus and further survival according to the Quintero stages. Infant survival until at least one week after birth. RESULTS: Of the pregnancies studied, 84% had TTTS, 13% had a fetal malformation and 3% had both. Of TTTS cases, 69% were Quintero stage 3 and 4. In the UCO group with TTTS, 87% were in stage 3 and 4. Survival in the UCO group was 82%. In the laser group, the survival of at least one fetus was 85%. Overall survival per fetus was 60%. CONCLUSIONS: By far the most common indication for invasive treatment was TTTS in Quintero stage 3. Outcome by means of survival after FSLC and UCO were similar to what has been reported elsewhere. Cord occlusion was an acceptable treatment alternative to fetoscopic selective laser coagulation in severe TTTS cases.

Twinship influence on morbidity and mortality across the lifespan.

BACKGROUND: Studies in twins may be questioned with respect to their representativeness of the general population, not least considering the potential importance of the fetal environment for future health and disease. To better understand the influence twinning may have on health, we investigated long-term health outcomes of twins, their singleton siblings and singletons from the population. METHODS: Morbidity and mortality in twins was contrasted to that of their singleton siblings. These singletons from families with twins were then compared with singletons of the population to further reveal potential twin family influences on health. Familial relations were identified through the Swedish Multi-Generation Register. Among individuals born between 1932 and 1958, the number of twins and their singleton siblings identified were 49,156 and 35,277, respectively. Outcomes were incident overall cancer, cardiovascular disease (CVD) and death, identified in national registers. Standardized survival functions were estimated using Cox proportional hazards regression and the corresponding cumulative risks plotted against age. RESULTS: Cumulative risks of cancer, CVD and death in twins did not differ from singletons of families with twins, who in turn were found to be similar to singletons of families without twins. As could be expected from these findings, no differences in risks were found when twins were compared with singletons of the population. CONCLUSIONS: Despite their adverse intrauterine experience, twins do not seem to fare worse than singletons with respect to adult morbidity and mortality. The findings indicate that the unique experience of twinning does not lead to adverse long-term health outcomes.

Investigation of the factors affecting the perinatal outcome of monochorionic diamniotic twins.

PURPOSE: To investigate the factors affecting the perinatal outcome in monochorionic diamniotic (MD) twins. METHODS: We conducted a retrospective study of MD twins treated in our hospital between April 1, 2006 and February 28, 2010. The neonatal outcomes of MD twins conceived by assisted reproductive technology or ovulation induction were compared to the outcomes of those conceived naturally. RESULTS: In MD twins with twin-to-twin transfusion syndrome (TTTS), fetoscopic laser photocoagulation (FLP) resulted in the survival of at least one twin. In naturally conceived MD twins with two live births, we found that there was a higher discordance rate and the incidence of intrauterine growth retardation was higher in twins born to nulliparous women than multiparous women. CONCLUSIONS: Further FLP treatment can be performed on twins with TTTS so that prognosis may be improved. Since the risk of discordant growth is significantly greater in twins of nulliparous women, they should be monitored more carefully than multiparous women.

Cord entanglement and perinatal outcome in monoamniotic twin pregnancies.

OBJECTIVES: To assess the prevalence of cord entanglement and perinatal outcome in a large series of monoamniotic twin pregnancies and to review the recent literature on similar published large series. METHODS: Prospective observational study of all prenatally detected cases of monoamniotic twin pregnancies during an 8-year period in a tertiary fetal medicine unit. A Medline database review for publications since 2000 containing five or more cases of monoamniotic pregnancies that showed data on cord entanglement and perinatal outcome was also undertaken. RESULTS: A total of 32 monoamniotic pregnancies were diagnosed during the study period, including three conjoined twins, seven pregnancies with twin reversed arterial perfusion (TRAP) syndrome, three surgical pregnancy interruptions for discordant fetal abnormality and one miscarriage before 16 weeks' gestation. The remaining 18 monoamniotic pregnancies were included in the study analysis. All monoamniotic pregnancies were complicated with antenatal cord entanglement diagnosed by B-mode and color Doppler ultrasound. There were 34 live births and a double intrauterine death diagnosed at 19 + 2 weeks' gestation. There were two late neonatal deaths, one from congenital complete heart block and the other after surgery for transposition of the great arteries. The overall perinatal loss rate was 11.1% after 16 weeks and 5.9% after 20 weeks' gestation. The cumulative rates of cord entanglement and perinatal mortality in the reviewed literature were 74% and 21%, respectively. CONCLUSIONS: Umbilical cord entanglement is present in all monoamniotic twins when it is systematically evaluated by ultrasound and color Doppler. Perinatal mortality in monoamniotic twins is mainly a consequence of conjoined twins, TRAP, discordant anomaly and spontaneous miscarriage before 20 weeks' gestation. Expectantly managed monoamniotic twins after 20 weeks have a very good prognosis despite the finding of cord entanglement. The practice of elective very preterm delivery or other interventions to prevent cord accidents in monoamniotic twins should be re-evaluated.

Síndrome de perfusión arterial retrógrada en gemelos (trap): feto acardio: reporte de un caso / Reversal arterial perfusion syndrome in twins (trap): acardiac fetus: case report

Se presenta el caso de una paciente de 23 años de edad, procedente del Estado Barinas, II gesta, la cual presenta un embarazo gemelar monocorial, donde el primer feto tuvo desarrollo normal y falleció por dificultad respiratoria en el período neonatal y el segundo, fue un feto acardio anceps. Al examinar el feto se observó ausencia de corazón y pulmones, cerebro rudimentario y anomalías de las extremidades. La disección reveló epidermis con abundantes células vacuolizadas, dermis edematosa y ausencia del epiplón mayor. Los genitales externos femeninos estaban bien desarrollados. El examen radiológico mostró un cráneo pequeño, osificación de columna vertebral y anomalías óseas de manos y pies. Se hizo una revisión de la literatura sobre acardia en los últimos 30 años

We presente the case of a 23 year old patient, from Barinas State, II gravida, with a twin monochorial pregnancy, a normal fetus who died for respiratory distress in neonatal period and the other one, was an acardio anceps. The acardius presented absence of heart and lungs, a rudimentary brain, and anomalies of extremities. The dissection showed epidermis with numerous vacuolized cells, edematous dermis and absence of mayor epiploon. The external female genitals were well developed. Radiological screening showed a rudimentary cranium and anomalies of the hands and feet. We reviewed the last 30 years of acardia literature

Aplasia cutis congenita of the scalp: is there a better treatment strategy?

BACKGROUND: Aplasia cutis congenita (ACC) is a rare disease of unknown etiology, involving any site of the body. The scalp is the most frequent location, followed by the forearms, knees, both sides of the trunk, and neck, in decreasing order of frequency. Superficial lesions may heal spontaneously and seldom result in morbidity or mortality. However, in patients with large scalp and skull defects, there are risks of infection and bleeding. Conservative treatment has been described and advocated, but some authors have highlighted the disadvantages of this treatment modality. On the other hand, several authors claim that aggressive surgical treatment has an important role for large defects. MATERIALS AND METHODS: In this paper, we report three newborns with ACC of the scalp, two large defects and a medium one, respectively, treated conservatively and surgically. CONCLUSION: The management of ACC of the scalp is still controversial. Our series suggests that conservative treatment should be performed for initial management in newborns.

GC/MS identification of toxic pyrrolizidine alkaloids in traditional remedies given to two sets of twins.

Neo- and perinatal mortality is high in most of Africa. Twins are at particular risk of perinatal mortality. The contribution of traditional remedies is seldom addressed. The case histories of two sets of twins who were treated with traditional remedies are described. The herbal remedies were analysed using gas chromatography-mass spectrometry. In one family, both siblings survived, albeit with hepatic damage. In the other family, one twin died within 24 h and the second one month after admission with a diagnosis of veno-occlusive liver disease (VOD). In both cases, the presence of the toxic pyrrolizidine alkaloid retrorsine, which is known to lead to VOD, was identified. Health-care workers should be aware of the possibility of traditional medicine administration as a cause of illness, specifically in twin births.

Single motherhood and neonatal survival of twins among blacks and whites.

OBJECTIVE: We investigated whether an association existed between single motherhood and neonatal mortality among twins and whether such a linkage varied by race. STUDY DESIGN: Retrospective cohort analysis on 446,570 twin live births (between 24-44 gestational weeks inclusive) in the United States from 1995 through 1998. Neonatal survival was compared between twins of single and those of married mothers for blacks and whites separately using Cox proportional hazards regression that adjusted for the confounding effects of education, parity, adequacy of prenatal care and maternal smoking during pregnancy. The Robust Sandwich Estimator was employed to adjust for intracluster correlation. RESULTS: The rates for neonatal mortality among blacks were 34.9 per 1,000 among married and 43.4 per 1,000 among single mothers. Among whites, the rates were 20.6 per 1,000 for married and 28.9 per 1,000 for unmarried mothers. Neonatal mortality was significantly elevated among white twins of single mothers (Hazard Ratio (HR) = 1.23; 95% Confidence Interval (CI) = 1.14-1.31) and among black twins of single mothers (HR = 1.12; 95% CI = 1.01-1.25). However, when gestational age was adjusted for, the association between single motherhood and neonatal mortality disappeared. CONCLUSION: Single motherhood was a risk factor for neonatal mortality among twins, and the disparity in survival was more accentuated among whites. The association between single motherhood and neonatal mortality was explained by the preponderance of preterm births among twins of unmarried gravidas. Our findings reinforce the importance of future research to develop and test interventions that will decrease the incidence of preterm birth.