First-trimester serum biomarkers in twin pregnancies and adverse obstetric outcomes-a single center cohort study.

PURPOSE: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. METHODS: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. RESULTS: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. CONCLUSION: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.

First-trimester uterine artery Doppler and hypertensive disorders in twin pregnancies: Use of twin versus singleton references.

OBJECTIVE: To determine the association of first-trimester uterine artery Doppler with hypertensive disorders of pregnancy in twin pregnancies. METHODS: This was a retrospective cohort study of twin pregnancies followed at the University Hospital Center of Central Lisbon, Portugal, between January 2010 and December 2022. First-trimester uterine artery pulsatility index (UtA-PI) was determined and compared between twin pregnancies (n = 454) and singleton pregnancies (n = 908), matched to maternal and pregnancy characteristics. Maternal characteristics and mean UtA-PI were analyzed for gestational age, birth weight, gestational hypertension, early- and late-onset pre-eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and preterm birth. Univariable and multivariable logistic regression models were used. RESULTS: The mean first-trimester UtA-PI was significantly lower in dichorionic twins than in singletons (P < 0.001). To study hypertensive disorders of pregnancy in twins, 390 pregnancies were included: 311 (79.7%) dichorionic and 79 (20.3%) monochorionic twins. The observed rates of early- and late-onset pre-eclampsia, gestational hypertension, and HELLP syndrome were 1.0%, 4.4%, 7.4%, and 1.5%, respectively. We achieved a 100% detection rate for early-onset pre-eclampsia using the UtA-PI 90th centile for twins. However, when singleton references were considered, the detection rate decreased to 50%. UtA-PI at or above the 95th centile was associated with increased odds for preterm birth before 32 weeks (adjusted odds ratio 4.1, 95% confidence interval 1.0-16.7, P = 0.043). CONCLUSIONS: Unless other major risk factors for hypertensive disorders are present, women with low UtA-PI will probably not benefit from aspirin prophylaxis. Close monitoring of all twin pregnancies for hypertensive disorders is still recommended.

Higher risk of preterm twin delivery among shorter nulliparous women.

OBJECTIVE: To determine if maternal height in nulliparous women influences pregnancy results in twin pregnancies. MATERIAL AND METHODS: Retrospective cohort analysis evaluating twin pregnancies followed at Centro Hospitalar Universitário Lisboa Central, between 1995 and 2020. Of the 2900 pregnancies followed in that period, 886 nulliparous women with dichorionic twin pregnancies were selected. Two groups were considered: A - maternal height <163 cm (

Concurrence of gestational diabetes and pre-gravid obesity ("diabesity") in twin gestations.

OBJECTIVE: To assess the effect of the concurrence of gestational diabetes mellitus (GDM) and pre-gravid obesity in twin gestations ("diabesity"). METHODS: We compared perinatal outcomes of twin gestation in mothers with GDM and pre-gravid obesity (1.7%), mothers with GDM but with normal BMI (6.2%), and obese mothers without GDM (7.0%). RESULTS: Twin pregnancies with "diabesity" were associated with significantly higher incidence of stillbirth (OR = 6.4; 95%CI = 1.4, 33.4) and existing chronic hypertension (OR = 4.2; 95%CI = 1.2, 14.8) than in GDM pregnancies without obesity, and with births at 33-36 weeks as compared with the other groups. Otherwise, the comparisons showed remarkable similar results in terms of gestational age, birth weight, preeclampsia, cesarean section rate, and fetal-neonatal outcomes. CONCLUSION: It appears that diabesity has a relatively minor effect in twins. If this will be confirmed by other studies, it would be important to elucidate how twins ameliorate the adverse outcomes of diabesity.

Prediction of birth weight discordance from fetal weight estimations at 21-24 weeks' scans in monochorionic and dichorionic twins.

OBJECTIVE: To evaluate if inter-twin estimated fetal weight (EFW) differences at 21-24 weeks' scans predict birth weight discordance in monochorionic and dichorionic twins born at three gestational age periods. METHODS: We counted the number of pairs with discordant EFWs (EFWs greater than the mean + 1SD; i.e. a difference above 12% in dichorionic and 21% in monochorionic twins) derived during a 21-24 weeks' scan as compared to actual discordant birth weight (>25%) in monochorionic and dichorionic pairs born at ≤32, 33-36 and >36 weeks. RESULTS: We studied 416 dichorionic and 244 monochorionic twins. The frequency of EFWs discordance at 21-24 weeks was the same for dichorionic and monochorionic twins but the total number of birth weight discordant pairs was significantly smaller among dichorionic twins (OR 0.2, 95% CI 0.1, 0.6). Generally, the positive predictive values for birth weight discordance by using the EFWs difference were quite poor, but always better in monochorionic than in dichorionic twins. Whereas the negative predictive value and hence the sensitivity for monochorionic twins was 100% irrespective of gestational age at birth, it was much lower in the dichorionic pairs. CONCLUSION: Concordant EFWs at 21-24 weeks exclude discordant birth weight in monochorionic twins whereas discordant EFWs are poor predictors of birth weight discordance especially in dichorionic twins irrespective when the twins were born.

Prospective risk of intrauterine death of monochorionic twins: update.

OBJECTIVE: To calculate an updated prospective risk of fetal death in monochorionic-biamniotic (MCBA) twins. STUDY DESIGN: We evaluated 520 MCBA twin pregnancies that had intensive prenatal surveillance and delivered in a single Portuguese referral center. The prospective risk of fetal death was calculated as the total number of deaths at the beginning of the gestational period divided by the number of continuing pregnancies at or beyond that period. Data were compared to the 2006 previous report. RESULTS: Nearly 80% of the neonates weighed <2500 g, including 13.5% who weighed <1500 g. Half were born at <36 weeks, including 13.8% who were born at <32 weeks. The data indicate an increased IUFD rate over time - 16 fetal deaths per pregnancy (3.1%) and 22 IUFDs per fetus (2.1%). The rate of IUFD after 32-33 weeks, however, was halved (1/187 pregnancies and 1/365 fetuses, 0.5 and 0.3%, respectively). CONCLUSION: Intensive prenatal surveillance might decrease the unexpected fetal death rates after 33 week's gestation and our data do not support elective preterm birth for uncomplicated MCBA twins.

Perinatal outcome of dichorionic-triamniotic as compared to trichorionic triplets.

OBJECTIVE: To evaluate if the perinatal outcomes of dichorionic-triamniotic (DC) triplets are significantly different than that of trichorionic (TC) triplets. STUDY DESIGN: Comparison of maternal and neonatal data of 44 DC to 46 TC triplets, using univariate analysis. RESULTS: DC triplets were significantly more common after spontaneous conception but all other maternal characteristics as well complications and cesarean section rates were similar. Both groups had similar incidence of birth at <32 and <28 weeks as well as similar incidence of very low and extremely low birth weight. There was similar incidence of neonatal morbidity except for twin-twin transfusion syndrome (13.6%) in the DC group. The stillbirth rate was 45/1000 and 29/1000, the early neonatal mortality rates were 63/1000 and 45/1000, and the perinatal mortality rate was 106/1000 and 72/1000 for DC and TC triplets, respectively (all not significantly different). CONCLUSIONS: Our data indicate that DC twins are not significantly disadvantaged compared to TC triplets and the similar outcomes might be reassuring for those who consider continuing their DC triplet pregnancy.

Metabolic fingerprints in testicular biopsies from type 1 diabetic patients.

Diabetes mellitus (DM) is a metabolic disease that has grown to pandemic proportions. Recent reports have highlighted the effect of DM on male reproductive function. Here, we hypothesize that testicular metabolism is altered in type 1 diabetic (T1D) men seeking fertility treatment. We propose to determine some metabolic fingerprints in testicular biopsies of diabetic patients. For that, testicular tissue from five normal and five type 1 diabetic men was analyzed by high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy. mRNA and protein expression of glucose transporters and glycolysis-related enzymes were also evaluated. Our results show that testes from diabetic men presented decreased levels of lactate, alanine, citrate and creatine. The mRNA levels of glucose transporter 1 (GLUT1) and phosphofructokinase 1 (PFK1) were decreased in testes from diabetic men but only GLUT3 presented decreased mRNA and protein levels. Lactate dehydrogenase (LDH) and glutamate pyruvate transaminase (GPT) protein levels were also found to be decreased in testes from diabetic men. Overall, our results show that T1D alters glycolysis-related transporters and enzymes, compromising lactate content in the testes. Moreover, testicular creatine content was severely depressed in T1D men. Since lactate and creatine are essential for germ cells development and support, the data discussed here open new insights into the molecular mechanism by which DM promotes subfertility/infertility in human males.

Outcome of monochorionic twins conceived by assisted reproduction.

OBJECTIVE: To evaluate monochorionic twins conceived by assisted reproductive technology (ART). DESIGN: We compared perinatal outcomes of monochorionic twins conceived by ART with their dichorionic counterparts and with spontaneous monochorionic twins. SETTING: Referral center. PATIENT(S): Mothers to monochorionic and dichorionic twins conceived by ART and spontaneous monochorionic twins. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Maternal characteristics, pregnancy complications, and perinatal outcomes. RESULT(S): Monochorionic twin pregnancies (n = 25) comprise 7.2% of all ART twins and 4.9% of all monochorionic twins in this data set. Monochorionic pairs have a significantly worse outcome compared with dichorionic sets in terms of lower gestational age and birth weight. ART appears to increase the already high risk of monochorionicity compared with spontaneous conception: odds ratio (OR), 2.9 (1.1-7.3) for preterm birth at <32 weeks and OR, 5.9 (2.5-1.49) for birth weight <1,500 g. CONCLUSION(S): Monochorionic twins after ART are at increased risk of adverse perinatal outcomes compared with spontaneous monochorionic twins and with dichorionic twins conceived by ART.

Gestational diabetes mellitus complicating twin pregnancies.

OBJECTIVE: To compare outcomes of twin pregnancies with and without gestational diabetes mellitus (GDM). STUDY DESIGN: We compared 105 twin pregnancies with GDM (7.8% of all twin pregnancies) to 315 controls without GDM, matched for gestational age, chorionicity and year of birth. RESULTS: Pre-gravid obesity appears to predispose women to GDM during twin pregnancy [odds ratio (OR) 3.5; 95% confidence interval (CI) 1.7, 7.0]. Overweight and obese women that subsequently developed GDM during their twin gestation were less likely to conceive spontaneously (OR 0.4; 95% CI 0.3, 0.7). Twins from the GDM group had more respiratory distress syndrome (RDS, OR 2.2; 95% CI 1.3, 3.7) and had a three-fold, but not significantly increased perinatal mortality rate. Birth weight characteristics were similar in both groups. CONCLUSION: Twin pregnancies complicated by GDM might be associated with pre-pregnancy maternal obesity and are at increased risk of RDS and non-significant increased risk of perinatal death.

Abdominal circumference ratio for the diagnosis of intertwin birth weight discordance.

OBJECTIVES: We assessed the accuracy of predicting severe twin birth weight discordance (>25%) using the estimated fetal weights (EFW) and abdominal circumference (AC) ratio. METHOD: A cohort of twin gestations underwent ultrasound examinations within two weeks from birth. We focused on the accuracy of EFW and on the diagnosis of severe birth weight discordance by the difference in EFWs and the AC ratio. RESULTS: The 661 eligible twin pairs included 51 (7.7%) severely discordant pairs. The accuracy of an EFW to predict the actual birth weight was quite poor, with an acceptable specificity (96.4%), but low sensitivity (28.6-40.5%), to detect severely discordant pairs, whereas an AC ratio of 1.3 detected these discordant pairs with sensitivity and specificity of 97.3-100% and 99.6-99.7%, respectively. CONCLUSION: By comparing EFWs, 59.5-71.4% of discordant pairs >25% are missed, whereas an AC ratio >1.3 would identify almost all cases.

Perinatal outcome and change in body mass index in mothers of dichorionic twins: a longitudinal cohort study.

We used a prospective cohort to analyze the effect of change in BMI rather than change in weight, in mothers carrying dichorionic twins from a population that did not receive any dietary intervention. A total of 269 mothers (150 nulliparas and 119 multiparas) were evaluated. The average change (%) from the pre-gravid BMI was 7.2+/-6.1, 17.4+/-8.2, and 28.7+/-10.8, at 12-14, 22-25, and 30-34 weeks, respectively, without difference between nulliparas and multiparas. The comparison between maternities below or above the average change from the pregravid BMI failed to demonstrate an advantage (in terms of total twin birthweight and gestational age) of an above average change from the pregravid BMI, even when the lower versus upper quartiles were compared. Our observations reached different conclusions regarding the recommended universal dietary intervention in twin gestations. A cautious approach is advocated towards seemingly harmless excess weight gain, as normal weight women may turn overweight, or even obese, by the end of pregnancy, and be exposed to the untoward effects of obesity on future health and body image.

Puerperal complications following elective Cesarean sections for twin pregnancies.

OBJECTIVE: To estimate the maternal puerperal morbidity in elective and emergent cesareans in twins. STUDY DESIGN: We evaluated postpartum complications among patients who underwent elective cesarean birth for twin pregnancy. This group was compared to matched singletons and to emergent cesareans in twins. RESULTS: During the period September 1994-March 2006 there were 299 (47.4%) elective and 80 (12.7%) emergent cesarean sections in twin pregnancies, for a total of 379 (60.1%) cesarean births for both twins. Controls included 299 cases of elective cesareans in singletons. The comparison between elective and emergent cesareans and between elective cesareans in twins and in singletons found no significant differences in postpartum fever, scar infection, and postpartum hemorrhage. Venous thromboembolism occurred in two twin pregnancies, one in the elective and one in the emergent cesarean group. Postpartum hysterectomy was required in a singleton pregnancy following an elective cesarean birth. CONCLUSION: At present, no data exist to show a disadvantage for a planned cesarean birth for twins.

Prospective risk of intrauterine death of monochorionic-diamniotic twins.

OBJECTIVE: The purpose of this study was to calculate the prospective risk of fetal death in monochorionic-diamniotic twins. STUDY DESIGN: We evaluated 193 monochorionic diamniotic twin pregnancies that were followed and delivered after 24 weeks. Surveillance included cardiotocography and sonography performed at least once weekly. The prospective risk of fetal death was calculated as the total number of deaths at the beginning of the gestational period divided by the number of continuing pregnancies at or beyond that period. RESULTS: The fetal death rate was 5 of 193 pregnancies (2.6%; 95% CI, 1.1, 5.9); the prospective risk of stillbirth per pregnancy after 32 weeks of gestation was 1.2% (95% CI, 0.3% - 4.2%). CONCLUSION: Under intensive surveillance, the prospective risk of fetal death in monochorionic-diamniotic pregnancies after 32 weeks of gestation is much lower than reported and does not support a policy of elective preterm delivery.

Induction of labor with oral misoprostol in nulliparous mothers of twins.

The efficacy and safety of oral misoprostol for labor induction of twins is unknown. We conducted a retrospective case-control study to evaluate the use of oral misoprostol in near term (> or =35 weeks) twin pregnancies in nulliparas. Eligible cases were given 100 mcg oral misoprostol, which was repeated after 6 h if labor did not start. Either a third dose or diluted oxytocin infusion were given in intractable cases. Diluted oxytocin infusion was used for augmentation. Controls were nulliparas delivered at > or =35 weeks by elective cesarean section. The two groups were comparable in most aspects, except for fetal malpresentation, which was the major reason for avoiding induction. Of the 69 patients in whom labor was induced, 53 (76.8%) had a vaginal birth, 3 (4.3%) had a combined twin delivery, and 13 (18.8%) had a cesarean during labor. The mean length of stay of the neonates was significantly shorter among study cases, without significant difference in the frequency of delayed discharges as an overall proxy for neonatal complications. Labor induction with oral misoprostol could be offered to patients in whom near term vaginal twin delivery is unequivocally permitted and wish to deliver by the vaginal route.