BACKGROUND: Intraoperative blood transfer between twins during laser surgery for twin-twin transfusion syndrome can vary by surgical technique and has been proposed to explain differences in donor twin survival.
OBJECTIVE: This trial compared donor twin survival with 2 laser techniques: the sequential technique, in which the arteriovenous communications from the volume-depleted donor to the volume-overloaded recipient are laser-occluded before those from recipient to donor, and the selective technique, in which the occlusion of the vascular communications is performed in no particular order.
METHODS: A single-center, open-label, randomized controlled trial was conducted in which twin-twin transfusion syndrome patients were randomized to sequential vs selective laser surgery. Nested within the trial, a second trial randomized patients with superficial anastomoses (arterioarterial and venovenous) to ablation of these connections first (before ablating the arteriovenous anastomoses) vs last. The primary outcome measure was donor twin survival at birth.
RESULTS: A total of 642 patients were randomized. Overall donor twin survival was similar between the 2 groups (274 of 320 [85.6%] vs 271 of 322 [84.2%]; odds ratio, 1.12 [95% confidence interval, 0.73-1.73]; P=.605). Superficial anastomoses occurred in 177 of 642 cases (27.6%). Donor survival was lower in the superficial anastomosis group vs those with only arteriovenous communications (125 of 177 [70.6%] vs 420 of 465 [90.3%]; adjusted odds ratio, 0.33 [95% confidence interval, 0.20-0.54]; P<.001). In cases with superficial anastomoses, donor survival was independent of the timing of ablation or surgical technique. The postoperative mean middle cerebral artery peak systolic velocity was lower in the sequential vs selective group (1.00±0.30 vs 1.06±0.30 multiples of the median; P=.003). Post hoc analyses showed 2 factors that were associated with poor overall donor twin survival: the presence or absence of donor twin preoperative critical abnormal Doppler parameters and the presence or absence of arterioarterial anastomoses. Depending on these factors, 4 categories of patients resulted: (1) Category 1 (347 of 642 [54%]), no donor twin critical abnormal Doppler + no arterioarterial anastomoses: donor twin survival was 91.2% in the sequential and 93.8% in the selective groups; (2) Category 2 (143 of 642 [22%]), critical abnormal Doppler present + no arterioarterial anastomoses: donor survival was 89.9% vs 75.7%; (3) Category 3 (73 of 642 [11%]), no critical abnormal Doppler + arterioarterial anastomoses present: donor survival was 94.7% vs 74.3%; and (4) Category 4 (79 of 642 [12%]), critical abnormal Doppler present + arterioarterial anastomoses present: donor survival was 47.6% vs 64.9%.
CONCLUSIONS: Donor twin survival did not differ between the sequential vs selective laser techniques and did not differ if superficial anastomoses were ablated first vs last. The donor twin\'s postoperative middle cerebral artery peak systolic velocity was improved with the sequential vs the selective approach. Post hoc analyses suggest that donor twin survival may be associated with the choice of laser technique according to high-risk factors. Further study is needed to determine whether using these categories to guide the choice of surgical technique will improve outcomes.

UNASSIGNED: Triplet pregnancies carry a high risk of pregnancy-related complications. The primary aim of this study was to describe maternal, pregnancy, and neonatal outcomes in expectantly managed triplet pregnancies in Sweden. The secondary aim was to compare outcomes in expectantly managed triplet pregnancies with triplet pregnancies where fetal reduction had been performed with the only indication to reduce the number of fetuses.
UNASSIGNED: Nationwide cohort study based on linkage of data from three national Swedish registers. Triplet pregnancies with delivery at gestational age ≥ 22+0 weeks between 2014 and 2019 were included.
UNASSIGNED: In the main cohort of expectantly managed triplet pregnancies (n = 106), 98% (312/318) of infants were liveborn with a mean gestational age at birth of 32+3 weeks and a mean birthweight of 1,726 g. Nine percent (n = 29) suffered from severe neonatal morbidity, and 4% (n = 12) died during the neonatal period. In the reduced cohort (n = 13 pregnancies), all infants were liveborn (n = 22). Mean gestational age at birth (36+0 weeks) and mean birthweight (2,444 g) were higher than in the expectantly managed cohort (P < 0.01 for both comparisons). There were no cases of severe neonatal morbidity (P = 0.24) or mortality (P = 1.00).
UNASSIGNED: Overall neonatal survival from 22+0 weeks of gestation in expectantly managed triplet pregnancies in Sweden was high. Nine out of 10 infants did not suffer from severe neonatal morbidity. Fetal reduction was performed in only a very small number of cases and was associated with higher gestational age at birth and higher birth weight.

OBJECTIVE: The main aim of this study was to investigate the perinatal outcomes of dichorionic twin pregnancies complicated by selective fetal growth restriction (sFGR).
METHODS: Retrospective cohort study.
METHODS: Tertiary reference centre.
METHODS: Dichorionic twin pregnancies complicated by sFGR between 2000 and 2019 in St George\'s University Hospital.
METHODS: Regression analyses were performed using generalised linear models and mixed-effects generalised linear models where appropriate to account for pregnancy level dependency in variables. Time to event analyses were performed with mixed-effects Cox regression models.
METHODS: Stillbirth, neonatal death or neonatal unit admission with morbidity in one or both twins.
RESULTS: A total of 102 (of 2431 dichorionic twin pregnancies) pregnancies complicated by sFGR were included in the study. The Cochrane-Armitage test revealed a significant trend for increased adverse perinatal outcome rates with more severe forms of umbilical artery flow impedance, i.e. reversed, absent, positive with resistant flow and positive flow without resistance. A multivariable model including maternal and conception characteristics had poor predictive accuracy for stillbirth (area under the curve: 0.68, 95% confidence interval [CI] 0.55-0.81) and composite adverse perinatal outcomes (area under the curve: 0.58, 95% CI 0.47-0.70). When umbilical artery Doppler parameters were added to the models, the area under the curve values improved to 0.95 (95% CI 0.89-0.99) and 0.83 (95% CI 0.73-0.92) for stillbirth and composite adverse perinatal outcomes, respectively.
CONCLUSIONS: In dichorionic twin pregnancies complicated by sFGR, the umbilical artery Z-scores were associated with both intrauterine death and adverse perinatal outcomes.

BACKGROUND: Cervical insufficiency is one of the underlying causes of late miscarriage and preterm birth. Although many risk factors have been identified, the relative magnitude of their association with risk in nulliparous versus parous women has not been well demonstrated, especially for incident cervical insufficiency (ICI). The aim of this study was to investigate and compare the magnitude of the association of ICI with predictive factors in nulliparous and parous women, and to further investigate various aspects of obstetric history for parous women.
METHODS: Pregnant women with a first diagnosis of cervical insufficiency were compared to a random sample of control pregnancies from women with no diagnosis by using Swedish national health registers. Demographic, reproductive, and pregnancy-specific factors were compared in case and control pregnancies, and relative risks presented as odds ratios (OR), stratified by nulliparous/parous. Independent associations with ICI were estimated from multivariable logistic regression. Associations with obstetric history were further estimated for multiparous women.
RESULTS: A total of 759 nulliparous ICI cases and 1498 parous cases were identified during the study period. Multifetal gestation had a strong positive association with ICI in both groups, but of much larger magnitude for nulliparous women. The number of previous miscarriages was also a much stronger predictor of risk in nulliparous women, especially for multifetal pregnancies. History of preterm delivery (<37 weeks\' gestation) was an independent predictor for parous women, and for those whose most recent delivery was preterm, the association with ICI increased with each additional week of prematurity. A previous delivery with prolonged second stage of labor or delivery of a very large infant were both inversely associated with risk of ICI in the current pregnancy.
CONCLUSIONS: The differences in importance of predictive risk factors for incident cervical insufficiency in nulliparous and parous women can help resolve some of the inconsistencies in the literature to date regarding factors that are useful for risk prediction. Stratifying on parity can inform more targeted surveillance of at-risk pregnancies, enable the two groups of women to be better informed of their risks, and eventually inform screening and intervention efforts.

UNASSIGNED: Pregnancies achieved with assisted reproductive technology have an increased risk of multiple gestations, preeclampsia, and placental morphologic abnormalities. Inflammatory processes affect dichorionic twin pregnancies disproportionately more than singleton gestations and have been associated with adverse pregnancy outcomes, such as fetal growth restriction and preeclampsia. Our objective is to investigate the placental morphology of dichorionic twin pregnancies complicated by preeclampsia conceived with in vitro fertilization (IVF) versus unassisted.
UNASSIGNED: This is a retrospective analysis of placentas from dichorionic twin pregnancies affected by preeclampsia conceived with IVF versus without assistance from 2010 to 2016 at a tertiary care university hospital. Placental pathology findings were analyzed both independently and in aggregate stratified into composite outcome scores using a modified placental synoptic framework. Individual placental abnormalities were grouped into composite categories based on the site of origin: anatomic placental abnormalities; maternal vascular malperfusion; placental villous maldevelopment; fetal vascular malperfusion; chronic utero-placental separation; maternal-fetal interface disturbance; inflammation of infectious etiology; and inflammation of idiopathic etiology. Placental histopathological statistical analysis was performed using Fisher\'s exact test. Demographic variables and pregnancy outcomes were compared between groups using the Student\'s t test or Mann-Whitney U test, where appropriate. p < .05 defined statistical significance.
UNASSIGNED: Of 117 dichorionic twin pregnancies, 60 resulted from IVF (Group A) and 57 were conceived without assistance (Group B). Patients in Group A were older (36 [29-37] vs. 33 [32-38] respectively; p = .042) and less parous (18.3% vs. 38.6% percent parous in Group A and Group B, respectively p = .009) than Group B, respectively. No differences were found between groups regarding mode of delivery, gestational age at delivery, placental weight/birthweight, fetal growth restriction, and discordance of fetal growth. There were significantly more inflammatory changes of unknown etiology and composite inflammatory abnormalities in Group A versus Group B (26.7% vs. 10.5%, p = .02). The cumulative number of inflammatory abnormalities per patient had a significantly different distribution among groups (p = .005), and Composite Chronic Inflammation and Infection were found to be significantly more abundant in Group A versus Group B (p = .02). The distribution of placental composite anatomic placental abnormalities, maternal vascular malperfusion, placental villous maldevelopment, fetal vascular malperfusion, chronic utero-placental separation, or maternal-fetal interface disturbance was not statistically different between groups. The distribution of placental abnormalities was not different between groups for any individually analyzed pathological condition. Due to the relatively small sample size, adjustment for potential confounders was not performed.
UNASSIGNED: Dichorionic twin pregnancies affected by preeclampsia are associated with more placental inflammatory abnormalities if conceived with IVF versus unassisted. Further research is needed to ascertain the underlying mechanisms of these observed differences.

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Gestational diabetes in singleton pregnancies increases the risk for large for gestational age infants, hypertensive disorders of pregnancy, and neonatal morbidity. Compared with singleton gestations, twin gestations are at increased risk for fetal growth abnormalities, hypertensive disorders, and neonatal morbidity. Whether gestational diabetes further increases the risk for these outcomes is unclear.
We sought to determine the relationship between gestational diabetes and the risk for preeclampsia, fetal growth abnormalities, and neonatal intensive care unit admissions in a large cohort of women with twin pregnancies.
We used a retrospective cohort of all twin gestations that were delivered at our institution from 1998 to 2013. We excluded pregnancies delivered before 24 weeks\' gestation, monochorionic-monoamniotic twins, and patients with preexisting diabetes for a final cohort of 2573 twin deliveries. Gestational diabetes was defined as 2 abnormal values on a 100 g, 3-hour glucose challenge test as defined by the Carpenter-Coustan criteria or a 1-hour value of 200 mg/dL after a 50 g glucose test. Multivariable Poisson regression models were used to estimate the associations between gestational diabetes and preeclampsia, small for gestational age infants, large for gestational age infants, and admission to the neonatal intensive care unit after adjusting for prepregnancy body mass index, maternal race, maternal age, parity, use of in vitro fertilization, prepregnancy smoking status, and chronic hypertension as confounders.
The unadjusted incidence of gestational diabetes was 6.5% (n=167). Women with gestational diabetes were more likely to be aged 35 years or older, living with obesity, and have conceived via in vitro fertilization than women without gestational diabetes. Preeclampsia was more common among women with twin pregnancies complicated by gestational diabetes (31%) than among women with twin pregnancies without gestational diabetes (18%) (adjusted risk ratio, 1.5; 95% confidence interval, 1.1-2.1). A diagnosis of small for gestational age infant was less common among women with gestational diabetes (17%) than among women without gestational diabetes (24%), although the results were imprecise (adjusted risk ratio, 0.8; 95% confidence interval, 0.5-1.1). There was no association between gestational diabetes and the incidence of large for gestational age neonates or neonatal intensive care unit admissions. Among women with gestational diabetes who reached 35 weeks\' gestation, 62% (n=60) required medical management.
Gestational diabetes is a risk factor for preeclampsia among women with twin pregnancies. Close blood pressure monitoring and patient education are critical for this high-risk group. The association between gestational diabetes and neonatal outcomes among women with twin pregnancies is less precise, although it may reduce the incidence of small for gestational age infants. Prospective studies to determine if glycemic control decreases the risk for preeclampsia in twin pregnancies with gestational diabetes are needed.

Multifetal gestation pregnancies present a clinical challenge due to unique complications including growth issues, prematurity, maternal risk, and pathologic processes, such as selective intrauterine growth restriction (sIUGR), twin-to-twin transfusion syndrome (TTTS), and twin anemia-polycythemia sequence. If sIUGR is found, then management may involve some combination of increased surveillance, fetal procedures, and/or delivery. The combination of sIUGR with TTTS or other comorbidities increases the risk of pregnancy complications. Multifetal pregnancy reduction is an option when a problem is confined to a single fetus or when weighing the risks and benefits of a multifetal gestation in comparison to a singleton pregnancy.

OBJECTIVE: Multifetal gestation is more frequent among gestational carrier pregnancies than non-surrogacy IVF pregnancies. We aimed to evaluate the association between multifetal gestation and obstetric and neonatal morbidity among gestational carrier pregnancies.
METHODS: Pooled cross-sectional study of birth certificate data from gestational carrier pregnancies in Utah from 2009 to 2018. Our primary outcome was a composite of severe obstetric morbidity; secondary outcomes included cesarean delivery (CD), hypertensive disorders of pregnancy, preterm birth (PTB), and a neonatal morbidity composite. Logistic regression was utilized to compare odds of these outcomes between gestational carrier pregnancies with and without multifetal gestation.
RESULTS: A total of 361 gestational carrier pregnancies resulted in the delivery of 435 neonates during the study period. Of these, 284 were singleton pregnancies, and 77 were multifetal, a multifetal gestation rate of 21.3%. Baseline demographic characteristics did not differ between singleton and multifetal gestations. Multifetal gestation was not associated with higher rates of severe obstetric morbidity (odds ratio [OR] 1.87, 95% confidence interval [CI] 0.34-10.39). Multifetal gestation was associated with increased odds of neonatal morbidity (OR 9.49, 95% CI 5.35-15.83); PTB < 37, 34, and 32 weeks (OR 21.88, 95% CI 11.64-41.12; OR 11.67, 95% CI 5.25-25.91; OR 8.79, 95% CI 3.41-22.68); and CD (OR 4.82, 95% CI 2.81-8.27).
CONCLUSIONS: Severe obstetric morbidity did not differ between singleton and multifetal gestations among gestational carrier pregnancies. However, multifetal gestation was associated with increased odds of neonatal morbidity, CD, and PTB. This information may be useful when counseling prospective gestational carriers and intended parents.

In conjunction with significant cardiovascular adaptation, changes in cardioautonomic balance, specifically greater sympathetic activation and vagal withdrawal, are considered normal adaptations to healthy singleton pregnancy. Cardiovascular adaptation to twin pregnancy is more profound than that of singleton pregnancies; however, the changes in cardioautonomic control during multifetal gestation are unknown. To address this gap, beat-by-beat blood pressure (photoplethysmography) and heart rate (lead II electrocardiogram) were measured continuously in 25 twin pregnancies and 25 singleton pregnancies (matched for age, prepregnancy body mass index, and gestational age) during 10 min of rest. Data extracted from a 3- to 5-min period were used to analyze heart rate variability (HRV), blood pressure variability (BPV), cardiovagal baroreflex gain, and cardiac intervals as indicators of cardioautonomic control. Independent t tests were used to determine statistical differences between groups (α = 0.05), and the false rate discovery was determined to adjust for multiple comparisons. Resting heart rate was greater in twin compared with singleton pregnancies (91 ± 10 vs. 81 ± 10 beats/min; P = 0.001), but blood pressure was not different. Individuals with twin pregnancies had lower HRV, evidenced by lower standard deviation of R-R intervals (32 ± 11 vs. 47 ± 18 ms; P = 0.001), total power (1,035 ± 810 vs. 1,945 ± 1,570 ms2; P = 0.004), and high frequency power (224 ± 262 vs. 810 ± 806 ms2; P < 0.001) compared with singleton pregnancies. There were no differences in cardiac intervals, BPV, and cardiovagal baroreflex gain between groups. Our findings suggest that individuals with twin pregnancies have greater sympathetic and lower parasympathetic contributions to heart rate and that cardiac, but not vascular, autonomic control is impacted during twin compared with singleton pregnancy.NEW & NOTEWORTHY Individuals with healthy twin pregnancies had lower overall heart rate variability compared with those with singleton pregnancies at similar gestational ages. These results suggest a greater sympathetic and reduced parasympathetic contribution to cardiac control in twin pregnancies. Baseline heart rate was elevated, while arterial pressure and spontaneous cardiovagal baroreflex gain were not different between groups. This was result of the upward resetting of the cardiovagal baroreflex during healthy twin pregnancy, thus maintaining arterial pressure.