Quadruplet pregnancy outcome with and without fetal reduction: Danish national cohort study (2008-2018) and comparison with dichorionic twins.

To investigate the relation between first-trimester fetal growth discrepancy, as assessed by crown-rump length (CRL) at 11+0 to 13+6 weeks of gestation, and subsequent development of preeclampsia (PE) in dichorionic diamniotic (DCDA) twin pregnancies. The association between inter-twin CRL and birth weight (BW) discrepancy was also investigated. This was a retrospective, case-control study of DCDA twin pregnancies. Inter-twin CRL discrepancy was calculated as 100×(larger CRL-smaller CRL)/larger CRL. BW discordance was calculated as 100×(larger BW-smaller BW)/larger BW. The study included 299 DCDA pregnancies that remained normotensive and 35 that subsequently developed PE. There was no significant difference in the inter-twin CRL discrepancy between pregnancies complicated by PE and those that were not [3.2%, interquartile range (IQR): 0.5-4.5% vs. 3.3%, IQR: 1.4-5.5%; P=0.17]. There was a positive correlation between inter-twin CRL and BW discrepancy but only in pregnancies that remained normotensive (P<0.001). In women that subsequently developed PE, there was no association between inter-twin CRL and BW discordance (P=0.54). In unselected DCDA twins, first-trimester CRL discrepancy is not different between pregnancies that subsequently develop PE and those that remain normotensive. Furthermore, in pregnancies that are complicated by PE, the association between inter-twin CRL and BW discrepancy appears to be lost.

Background Hypertensive disorders of pregnancy (HDP) is associated with the poor prognosis of dichorionic diamniotic (DCDA) twins. The prediction value of middle cerebral artery (MCA) and umbilical artery (UA) Doppler indices requires exploration. Objective To investigate the significance of the fetal MCA and UA doppler indices in DCDA fetal outcomes and depict hemodynamic alterations. Methods DCDA twin pregnancies were classified into the normotensive control group (n = 177) and the HDP group [n = 189, with 60 gestational hypertensions (GH) and 129 preeclampsia/eclampsia (PE/EC)]. Maternal and fetal outcomes were compared, the fetal MCA and UA doppler indices were analyzed, including pulsatility index (PI), resistance index (RI), the ratio of peak systolic blood flow velocity to end-diastolic blood flow velocity (S/D), and the mean velocities (Vm), and the cerebroplacental ratio (CPR) was computed for further study. The receiver operating characteristic curve was used to predict and evaluate small for gestational age (SGA) neonates in HDP twin pregnancies. Results Significant differences were shown between the HDP group and the normotensive control group in terms of maternal age, gestational weight gain, blood pressure, post 20-week urinary protein, the use of maternal medication utilization (magnesium sulfate, labetalol, dexamethasone), inter-twin growth discordance, and SGA (p < 0.05). In DCDA twins, the fetal MCA doppler indices (PI, RI and S/D) increased initially and then declined, UA indices (PI, RI and S/D) were declining, and both the Vm of MCA and UA were going up. In late DCDA twin pregnancies with GH, UA Doppler moderately predicted SGA neonates; in those with PE/EC, CPR did the same values (p < 0.05). Conclusion In DCDA pregnancies complicated by hypertensive disorders, SGA twins exhibit distinct doppler deterioration patterns. Implementing customized monitoring strategies based on the fetal MCA and UA indices can effectively predict adverse conditions, enable timely interventions, and ensure fetal health.

Published findings on perinatal outcomes of multifetal pregnancy reduction (MPR) of dichorionic diamniotic (DCDA) twin pregnancy to singleton are controversial. We performed a meta-analysis to appraise the effects of MPR of DCDA twin pregnancy versus expectant management on perinatal outcomes. Four electronic databases were searched from their inception to June 15, 2019, to identify publications that appraised MPR before 15 weeks of gestation. Studies reporting perinatal outcomes of both MPR of DCDA twin pregnancy to singleton and expectant management were considered. The relative risks (RRs) and mean differences with 95% confidence intervals (CIs) were pooled using a random-effects model. Six studies involving 7398 participants showed that MPR of DCDA twin pregnancy to singleton was associated with a lower risk of preterm birth (5 studies with 7297 participants; RR: 0.30, 95% CI: 0.22-0.40; P < .001) and higher birth weight (4 studies with 5763 participants; mean differences: 548.10 g, 95% CI: 424.04-672.15; P < .001) than expectant management; there was no difference in the occurrence of miscarriages (5 studies with 7355 participants; RR: 1.57, 95% CI: 0.90-2.75; P = .11). Sensitivity analysis showed that all the results were stable and reliable, with the omission of 2 studies with serious risk of bias. Compared to expectant management, MPR of DCDA twin pregnancy to singleton prevents preterm birth and low birth weight, without increasing the risk of miscarriages. Regarding perinatal morbidity related to preterm birth, MPR can be reserved as a remediation measure to improve the perinatal outcomes of DCDA twin pregnancies.

BackgroundMaternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear.MethodsThis retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies.ResultsA total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB < 37 weeks was significantly higher in the dyslipidemia group compared to the group without dyslipidemia (64.5% vs. 50.4%, P = 0.003). After adjusting for confounding factors, dyslipidemia was positively associated with PTB < 37 weeks (adjusted odds ratio: 1.71; 95% confidence interval: 1.13–2.58). However, these associations varied depending on the chorionicity and mode of conception of the twins. The positive associations between early pregnancy dyslipidemia and PTB < 37 weeks remained significant only in spontaneously conceived (SC) or dichorionic diamniotic (DCDA) twin pregnancies. No statistically significant associations were observed between dyslipidemia and the other secondary outcomes.ConclusionEarly pregnancy dyslipidemia was positively associated with PTB < 37 weeks in twin pregnancies, and this association remained significant in SC or DCDA twin pregnancies. Comprehensive lipid profile assessment in the first trimester may be beneficial for patients’ monitoring and implementing interventions to mitigate adverse pregnancy outcomes.

Genetic evaluation for twin pregnancies using karyotyping and single nucleotide polymorphism array analysis

The rate of multiple pregnancies is showing a significant increase in Western countries. Twin gestations should be considered a high-risk condition because they are responsible for a disproportionate amount of overall perinatal morbidity and mortality. We used a specialised ultrasound protocol based on chorionicity to monitor 44 twin pregnancies (61% dichorionic diamniotic (DD) and 39% monochorionic diamniotic (MD)). Adverse pregnancy outcomes and pre-term deliveries were more common in MD pregnancies than in DD pregnancies; the rate of extreme pre-term delivery (< 32 weeks) was almost three-times higher in MD than in DD pregnancies (41% vs 15%) and perinatal complications were more frequent in MD than in DD pregnancies (59% vs 22%), but fetal anomalies were more frequent in DD than in MD pregnancies (30% vs 24%). Periodic ultrasound follow-up would predict the pregnancies that are at greater risk for fetal and neonatal complications and these should be monitored more closely.

To study the effect of using ursodeoxycholic acid (UDCA) to treat monochorionic and dichorionic twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP) and to examine the differences in perinatal outcomes. A total of 406 twin-carrying pregnant women who had ICP and received care at West China Second Hospital, Sichuan University between January 1, 2015 and November 1, 2018 were included in the study. The clinical data of monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twins with ICP were analyzed. Analysis was done to compare the treatment effect for lowering serum total bile acid (TBA) and the perinatal outcomes with simple UDCA medication or combination medication. There were no statistically significant differences in TBA levels, early-onset ICP, simple UDCA medication or combination medication, neonatal Apgar score, birth weight, length of hospital stay, C-section rate, and perinatal mortality between the MCDA and the DCDA twin groups with ICP. However, maternal age, BMI, scarred uterus, in vitro fertilization-embryo transfer, preeclampsia, twin comorbidity rate of the two groups showed statistical differences. Further comparison between twin pregnancies with mildly-elevated TBA and those with severely-elevated TBA showed significant difference in preterm birth rate ( P<0.05). Simple UDCA medication or combination medication may have the same therapeutic effect on MCDA and DCDA twin pregnancies with ICP. Monochorionic twin pregnancy, twin comorbidities and pregnancy complications were still important factors affecting pregnancy outcomes of twin pregnancies with ICP. Twin pregnancies with slightly elevated TBA have been managed as severe ICP, which may be associated with increased iatrogenic preterm births.

Our study compared the prospective risks of intrauterine fetal death (IUFD), neonatal death (NND), perinatal death (PND), and neonatal morbidities in monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies. This retrospective cohort study included twin pregnancies who had antenatal care and delivery in a public hospital from 2011 to 2018. Exclusion criteria included monoamnionicity, one/both twin miscarriage, twin-twin transfusion syndrome, or lethal congenital abnormalities. All twins were managed in multiple pregnancy clinic with standardized protocols. Gestational age-specific IUFD, NND, PND, and neonatal morbidity rates were compared according to chorionicity. Three hundred seventy-eight MCDA and 1282 DCDA twins were included. MCDA twins had higher risks of PND (1.9% vs. 0.7% in DCDA twins, p=0.05), composite neonatal morbidity (p=0.01), preterm delivery (p < 0.01), and low birth weight (p < 0.01). The prospective risk of IUFD was 0.6% and 0.4% for MCDA and DCDA twins, respectively after 34 weeks' gestation. No NND occurred among deliveries after 30 weeks. The risk of neonatal morbidity of MCDA twins fell from 22.7% at 34 weeks to 2.7% at 37 weeks (p < 0.01). For DCDA twins, the risk of morbidity fell insignificantly from 36 to 38 weeks (4.0% vs. 3.4%, p=0.60). Logistic regression analysis suggested that the increased risk of perinatal morbidities was related to the higher rate of preterm delivery in MCDA twins rather than chorionicity. With close fetal monitoring, the risk of late IUFD in twin pregnancies without major complications is low. Perinatal morbidity can be minimized by avoiding late preterm deliveries in twin pregnancies.

To investigate the effectiveness of low-dose aspirin (LDA) in the prevention of pre-eclampsia (PE) among otherwise low-risk twin gestations. A historical cohort study consisting of all pregnant individuals with dichorionic diamniotic (DCDA) twin pregnancy who delivered between 2014 and 2020. Patients treated with LDA were matched by a 1:4 ratio to individuals who were not treated with LDA by age, body mass index and parity. During the study period, 2271 individuals carrying DCDA pregnancies delivered at our center. Of these, 404 were excluded for one or more additional major risk factors. The remaining cohort consisted of 1867 individuals of whom 142 (7.6%) were treated with LDA and were compared with a 1:4 matched group of 568 individuals who were not treated. The rate of preterm PE did not differ significantly between the two groups (18 [12.7%] in the LDA group vs. 55 [9.7%] in the no-LDA group; P= 0.294, adjusted odds ratio 1.36, 95% confidence interval 0.77-2.40). There were no other significant between-group differences. Low-dose aspirin treatment in pregnant individuals with DCDA twin gestations without additional major risk factors was not associated with a reduction in the rate of preterm PE.

Advanced maternal age may be associated with adverse maternal and perinatal outcomes in singleton pregnancies. It is unclear whether a similar association exists for dichorionic twins. This objective of this study was to ascertain whether advanced maternal age was associated with increased perinatal morbidity and mortality in a 15 year retrospective review of dichorionic diamniotic (DCDA) twins delivered at Queen Charlotte's and Chelsea Hospital, a tertiary referral center in London, UK, between 1994 and 2008. In all, 1 174 DCDA deliveries occurred in the study period. Maternal age was not associated with neonatal unit admission or composite fetal and neonatal mortality. Advanced maternal age appeared to have no deleterious effect on the perinatal outcomes of DCDA twin pregnancies.

305: Should normally grown monochorionic diamniotic twins be routinely delivered early?

Background: Prevalence of anencephaly in dichorionic twins is higher than in singleton pregnancies. The authors report two cases with two different management strategies. Case 1: Spontaneous dichorionic diamniotic twin pregnancy with the second twin diagnosed with anencephaly at 12 weeks gestation. Selective feticide was performed at the age of 13.2 weeks. Vaginal delivery occurred at 39 weeks, and birth weight was 2,850 g. Case 2: Dichorionic diamniotic twin pregnancy discordant for anencephaly in the second twin was diagnosed at 13 weeks gestation. An expectant management was decided. Preterm delivery occurred at 35 weeks due to hydramnios of the affected fetus, delivering a healthy newborn weighing 2,300 g and an anencephalic neonate who died immediately after delivery. Conclusion: Anencephaly should be diagnosed as soon as possible, idealistically at 11-13+6 weeks ultrasound (US) scan, in order to offer the most appropriate counselling to the parents, ranging from selective feticide or expectant management. This short series suggests that selective early feticide may increase gestational age and birth weight.

Fragile X syndrome (FXS) is usually associated with a CGG repeat expansion >200 repeats within the FMR1 gene, known as a full mutation (FM). FM alleles produce abnormal methylation of the FMR1 promoter with reduction or silencing of FMR1 gene expression. Furthermore, premutation (PM: 55–199 CGGs) and full mutation alleles usually expand in size when maternally transmitted to progeny. This study describes a PM allele carried by the mother decreasing to a normal sized allele in a male from a dichorionic diamniotic (DCDA) twin pregnancy, with the female twin inheriting FM (200–790 CGGs), PM (130 CGGs) and normal-sized (39 CGGs) alleles. Further evidence of instability of the maternal PM allele was shown by a male proband (older brother) mosaic for PM (CGG 78 and 150 CGGs) and FM (200–813 CGGs), and a high level of FMR1 promoter methylation, between 50 and 70%, in multiple tissues. The fully-retracted, normal-sized allele was identified by PCR CGG sizing in the male twin, with no evidence of a FM allele identified using Southern blot analysis in multiple tissues collected postnatally and prenatally. Consistent with this, prenatal PCR sizing (35 CGGs) showed inconsistent inheritance of the maternal normal allele (30 CGGs), with single-nucleotide polymorphism (SNP) linkage analysis confirming that the abnormal FMR1 chromosome had been inherited from the mother’s PM chromosome. Importantly, the male twin showed no significant hypermethylation of the FMR1 promoter in all pre and postnatal tissues tested, as well as normal levels of FMR1 mRNA in blood. In summary, this report demonstrates the first postnatal follow up of a prenatal case in which FMR1 mRNA levels were approaching normal, with normal levels of FMR1 promoter methylation and normal CGG size in multiple pre and postnatally collected tissues.

HISTORY: After unsuccessful attempts to conceive naturally, a 31-year-old woman (height: 173 cm, body mass: 59 kg, BMI: 19.71 kg/m2), cured of non-Hodgkin's lymphoma with bilateral salpingectomy due to cancer metastasis to the right ovary, was referred to the in vitro fertilization (IVF) center. PHYSICAL EXAMINATION: The woman and her husband underwent basic laboratory testing to detect possible infertility factors. DIFFERENTIAL DIAGNOSIS: Premature ovarian failure was diagnosed as a long-term consequence of chemotherapy. TEST AND RESULTS: The woman underwent controlled ovarian stimulation using a short protocol. After oocyte collection and fertilization in the laboratory, embryo transfer with Grade II morphology was performed at 72 h post egg collection. FINAL WORKING DIAGNOSIS: Biochemical testing of circulating Beta-human Chorionic Gonadotropin (B-hCG) in the woman and later transvaginal ultrasound confirmed a dichorionic diamniotic (DCDA) twin pregnancy. One pregnancy resulted from natural conception after intercourse before egg collection. TREATMENT AND OUTCOMES: The pregnant woman joined a personalized exercise program in the 6th week of pregnancy, which was modified depending on pregnancy trimester. The exercise program consisted of 6 sessions/week, each session lasted 30-50 min. and contained moderate-intensity walking (3 times/week) and strength-training and flexibility exercises (3 times/week). The exercise intensity was continuously monitored via heart rate responses using a smart watch. In the 12th week of pregnancy and after 6 weeks of exercise training, medical examinations showed no risk of Down's syndrome or other chromosomal abnormalities and satisfactory embryo development; the nuchal translucency test showed in both fetus normal amount of amniotic fluid, imaging of fetal anatomy, heart rate, nuchal transparency, pulsatility index (PI), mean PI of the uterine artery and mean blood pressure. In the 21st week of gestation and after 15 weeks of exercise, placental maturation was Grade 0. In the 31st week of gestation and after 25 weeks of exercise, normal fetal development was shown. In the 32nd week and 4 days there was a premature rupture of the follicle in the male fetus, thus a male and a female neonate weighing 2,380 and 1,320 grams, respectively, were born by caesarean section.

Introduction: Intertwin membrane cord insertion (IMCI) is a rare variation of velamentous cord insertion (VCI) that can be seen in dichorionic twin pregnancies. This condition exposes fetal vessels to risks such as compression and rupture, which can lead to complications including fetal growth restriction (FGR) and preterm delivery. Case Presentation: A 30-year-old woman, gravida 1 para 0, was referred at 19+5 weeks for evaluation of a dichorionic diamniotic twin pregnancy due to an abdominal cyst in twin A, transposition of the great arteries in twin B, and suspected abnormal cord insertions. Ultrasound evaluation confirmed IMCI, with both umbilical cords inserting into the intertwin membrane before reaching the placenta. MRI corroborated the findings. Doppler studies remained normal until 34+2 weeks, when signs of severe FGR and abnormal umbilical artery Dopplers prompted delivery by cesarean section. The twins were delivered preterm, and postnatal evaluation confirmed VCI. Conclusion: This case highlights the importance of early identification of IMCI as it necessitates close monitoring and timely intervention to optimize perinatal outcomes.