Gestational diabetes in twin pregnancies-a pathology requiring treatment or a benign physiological adaptation?

There is level-1 evidence that screening for and treating gestational diabetes in singleton pregnancies reduce maternal and neonatal morbidity. However, similar data for gestational diabetes in twin pregnancies are currently lacking. Consequently, the current approach for the diagnosis and management of gestational diabetes in twin pregnancies is based on the same diagnostic criteria and glycemic targets used in singleton pregnancies. However, twin pregnancies have unique physiological characteristics, and many of the typical gestational diabetes-related complications are less relevant for twin pregnancies. These differences raise the question of whether the greater increase in insulin resistance observed in twin pregnancies (which is often diagnosed as diet-treated gestational diabetes) should be considered physiological and potentially beneficial in which case alternative criteria should be used for the diagnosis of gestational diabetes in twin pregnancies. In this review, we summarize the most up-to-date evidence on the epidemiology, pathophysiology, and clinical consequences of gestational diabetes in twin pregnancies and review the available data on twin-specific screening and diagnostic criteria for gestational diabetes. Although twin pregnancies are associated with a higher incidence of diet-treated gestational diabetes, diet-treated gestational diabetes in twin pregnancies is less likely to be associated with adverse outcomes and accelerated fetal growth than in singleton pregnancies and may reduce the risk for intrauterine growth restriction. In addition, there is currently no evidence that treatment of diet-treated gestational diabetes in twin pregnancies improves outcomes, whereas preliminary data suggest that strict glycemic control in such cases might increase the risk for intrauterine growth restriction. Overall, these findings provide support to the hypothesis that the greater transient increase in insulin resistance observed in twin pregnancies is merely a physiological exaggeration of the normal increase in insulin resistance observed in singleton pregnancies (that is meant to support 2 fetuses) rather than a pathology that requires treatment. These data illustrate the need to develop twin-specific screening and diagnostic criteria for gestational diabetes to avoid overdiagnosis of gestational diabetes and to reduce the risks associated with overtreatment of diet-treated gestational diabetes in twin pregnancies. Although data on twin-specific screening and diagnostic criteria are presently scarce, preliminary data suggest that the optimal screening and diagnostic criteria in twin pregnancies are higher than those currently used in singleton pregnancies.

Does vegan diet influence umbilical cord vitamin B12, folate, and ferritin levels?

PURPOSE: To determine the influence of maternal diets on maternal and umbilical cord blood levels of vitamin B12, folic acid, ferritin, and hemoglobin. METHODS: A prospective observational study on women who maintained the same diet for at least 3 months prior to, and throughout current pregnancy. Women were divided according to their diet. Diet questionnaires were filled in during the 3rd trimester. Blood samples for complete blood counts and levels of ferritin, vitamin B12, folate, and albumin were taken from the women prior to delivery and from the umbilical cord immediately after delivery. RESULTS: The 273 enrolled women included 112 omnivores, 37 pescatarians, 64 vegetarians, and 60 vegans. There were no significant differences in the maternal B12 levels between the study groups (P = 0.426). Vegans had lower maternal ferritin levels compared to pescatarians (27 ± 17 vs 60 ± 74 ng/ml, respectively, P = 0.034), but not compared to vegetarians (P = 0.597), or omnivores (P = 1.000). There were no significant differences in the umbilical cord B12, folate, ferritin, and hemoglobin levels between the study groups. A sub-analysis that compared women who consumed multivitamins, B12 and iron supplements during pregnancy to women who did not, revealed differences in the levels of umbilical-cord B12 (1002 ± 608 vs 442 ± 151 pg/ml, respectively, P = 0.000) and maternal blood B12 (388 ± 209 vs 219 ± 95 pg/ml, respectively, P = 0.030) only among vegans, but not among omnivores. CONCLUSION: Vegan diet does not change the umbilical cord levels of B12, folic acid, ferritin, and hemoglobin. Vegans who do not take any vitamin supplementation are at greater risk for B12 deficiency than omnivores.

Maternal cardiovascular hemodynamics in normotensive versus preeclamptic pregnancies: a prospective longitudinal study using a noninvasive cardiac system (NICaS™).

BACKGROUND: Preeclampsia is among the most common medical complications of pregnancy. The clinical utility of invasive hemodynamic monitoring in preeclampsia (e.g., Swan-Ganz catheter) is controversial. Thoracic impedance cardiography (TIC) and Doppler echocardiography are noninvasive techniques but they both have important limitations. NICaS™ (NI Medical, PetachTikva, Israel) is a noninvasive cardiac system for determining cardiac output (CO) that utilizes regional impedance cardiography (RIC) by noninvasively measuring the impedance signal in the periphery. It outperformed any other impedance cardiographic technology and was twice as accurate as TIC. METHODS: We used the NICaS™ system to compare the hemodynamic parameters of women with severe preeclampsia (PET group, n = 17) to a cohort of healthy normotensive pregnant women with a singleton pregnancy at term (control group, n = 62) (1/2015-6/2015). Heart rate (HR), stroke volume (SV), CO, total peripheral resistance (TPR) and mean arterial pressure (MAP) were measured 15-30 min before CS initiation, immediately after administering spinal anesthesia, immediately after delivery of the fetus and placenta, at the abdominal fascia closure and within 24-36 and 48-72 h postpartum. RESULTS: The COs before and during the CS were significantly higher in the control group compared to the PET group (P < .05), but reached equivalent values within 24-36 h postpartum. CO peaked at delivery of the newborn and the placenta and started to decline afterwards in both groups. The MAP and TPR values were significantly higher in the PET group at all points of assessment except at 48-72 h postpartum when it was still significantly higher for MAP while the TPR only exhibited a higher trend but not statistically significant. The NICaS™ device noninvasively demonstrated low CO and high TPR profiles in the PET group compared to controls. CONCLUSIONS: The immediate postpartum period is accompanied by the most dramatic hemodynamic changes and fluid shifts, during which the parturient should be closely monitored. The NICaS™ device may help the clinician to customize the most optimal management for individual parturients. Our findings require validation by further studies on larger samples.

Maternal hemodynamics in late gestation and immediate postpartum in singletons vs. twin pregnancies.

PURPOSE: Differences in hemodynamic changes during a cesarean section (CS) between twin and singleton pregnancies are poorly defined. The Non-Invasive Cardiac System (NICaS) is an impedance device that measures cardiac output (CO) and its derivatives. We compared maternal cardiac parameters using NICaS™ in singleton and twins before and during delivery, as well at the early puerperium in healthy women undergoing CS at term. METHODS: This prospective longitudinal study included women with twin (n = 27) or singleton pregnancies (n = 62) whose hemodynamic parameters were assessed by NICaS before an elective CS, after spinal anesthesia, immediately after delivery, after fascia closure, and within 24-36 and 48-72 h postpartum. RESULTS: By 24-36 h postpartum, the mean arterial pressure and the total peripheral resistance equaled preoperative values in both groups. The CO increased throughout the CS and peaked immediately after delivery in the singleton group (P < 0.0001), after which it abruptly began to decline until reaching a nadir 24-36 h after delivery (P < 0.0001), while it remained steady throughout the CS and then dropped until 24-36 h after delivery in the twin group (P < 0.05). None of the studied parameters differed significantly between the groups for the 24-36 and 48-72 h postpartum measurements. CONCLUSIONS: Hemodynamic parameters immediately before, during and shortly after CS in singleton and twin pregnancies are equivalent. Further evaluations of the value of NICaS™ in assessing cardiovascular-related pregnancy complications are warranted.

Twin pregnancy in women above the age of 45 years: maternal and neonatal outcomes.

Childbearing age continues to rise and, with the increasing implementation of assisted reproductive technology (ART), the number of multiple pregnancies has also risen. This is a retrospective cohort study on maternal and neonatal outcomes of the twin pregnancies of 57 women aged ≥45 years compared to 114 younger women who gave birth in our institution between January 2011 and August 2015. Data were extracted from the real-time computerized database. The rates of hypertensive complications and pre-eclampsia (PE) were much higher in the study group compared to the controls (24/57 vs. 19/114, P=0.000 and 15/57 vs. 13/114, P=0.013, respectively). The respective incidence of very low birth weight (VLBW) was also significantly higher (14/114 vs. 12/228, P=0.021). Infants in the study group required four times more intubation and had a higher admission rate to the neonatal intensive care unit (NICU) compared to control infants (14/114 vs. 6/228 P=0.000 and 42/114 vs. 57/228, P=0.023, respectively). We conclude that women older than 45 years with twin pregnancies have higher maternal and perinatal complications with worse outcomes in comparison with younger women. When pregnancy is attempted via ART, embryo transfer of only one embryo should be considered in this age group.

Clinical characteristics of preeclampsia in twin versus singleton pregnancies.

OBJECTIVE: We aimed to compare features of preeclampsia between twin and singleton pregnancies. METHODS: In this retrospective case-control study, women with twin pregnancies who were diagnosed with preeclampsia were matched to singleton pregnancies controls. RESULTS: Ninety-four women with twin gestation diagnosed with preeclampsia were compared to singleton pregnancies with preeclampsia. Twin pregnancies were diagnosed at an earlier mean gestational age (33.23 ± 7.32 vs 35.93 ± 3.52 weeks, p = .001), and had an earlier gestational age at delivery (35.05 ± 2.28 vs 36.31 ± 3.25 weeks, p = .002) in comparison to singleton pregnancies. Mean systolic blood pressure at diagnosis was lower (147.22 ± 14.62 vs 152.7 ± 15.22 mmHg, p = .013), and the rate of thrombocytopenia <100,000 platelets/microliter, (17.02% vs 7.45%, p = .045) was higher in the twin preeclampsia group. A subanalysis for diagnosis prior to 34 weeks of gestation revealed that the rate of chronic hypertension was lower (3.03% vs 26.32%, p = .020), and the gestational age at delivery was higher (32.83 ± 2.16 weeks vs 31.02 ± 2.49, p = .008) among the twin preeclampsia group. In the prior to 34 weeks gestation preeclampsia subanalysis, less women in the twin group were hospitalized due to maternal indications (hypertension, ominous signs for PE, disturbed laboratory tests and suspicion for intra-hepatic cholestasis of pregnancies) in comparison to the singleton preeclampsia group (63.64% vs 89.47%, p = .028), while non-maternal/fetal indications (active labor, premature rupture of membranes, cervical dynamics, latent phase or gastroenteritis) for hospitalization were more common in the twin preeclampsia group (30.30% vs 0.00%). CONCLUSION: Preeclampsia in women with twin pregnancies is diagnosed at an earlier gestational age with lower level of hypertension and a higher rate of thrombocytopenia in comparison to singleton pregnancies.

Twin versus singleton pregnancy in women ≥ 45 years of age: comparison of maternal and neonatal outcomes.

Objectives: The aim of the study is to compare the effect of very advanced maternal age (≥45 years) on maternal and neonatal outcomes of twin and singleton pregnancies.Materials and methods: This retrospective cohort study included women ≥ 45 years of age who gave birth to twins. Each was randomly matched to two women ≥ 45 years of age who gave birth to singletons within 7 days of the study subject. Data on maternal age, gravidity, parity, background medical information, body mass index at conception, number of fetuses, mode of conception (either spontaneous or assisted reproductive technology [ART]), mode of delivery, and gestational age at delivery were extracted from a real-time computerized database.Results: The data of 75 twin pregnancies of women aged ≥ 45 years were compared with those of 150 singleton pregnancies matched for maternal age. There were significantly more cases of hypertensive complications among the twin pregnancies compared to the singleton pregnancies (41.33 versus 14.00%, respectively, OR = 3.33, 95% CI = 2.26-8.30, p = .000) and more cases of preeclamptic toxemia (29.33 versus 12.00%, respectively, OR = 3.04, 95% CI = 1.51-6.13, p = .001). The duration of twin pregnancies was much shorter compared to singleton pregnancies, with a higher incidence of deliveries prior to 37 weeks' gestation (56.00 versus 8.00%, respectively, OR = 14.64, 95% CI = 6.94-30.85, p = .000), and deliveries prior to 34 weeks' gestation (22.67 versus 2.00%, respectively, OR = 14.36, 95% CI = 4.06-50.86, p = .000). More infants of twin pregnancies had a low birth weight (68.00 versus 10.00%, respectively, OR = 19.13, 95% CI = 10.14-36.06, p = .000), and many had a very low birth weight (10.67 versus 0.67%, respectively, OR = 17.79, 95% CI = 2.33-135.97, p = .000). The infants of twin pregnancies also included more cases of intubation (10.00 versus 0.00%, respectively, p = .000), more cases of hypoglycemia (12.67 versus 5.33%, respectively, OR = 2.57, 95% CI = 1.09-6.08, p = .026), and were admitted much more often to the neonatal intensive care unit (36.00 versus 8.00%, respectively, OR = 6.47, p = .00, CI = 3.29-12.74).Conclusions: Women ≥ 45 years of age with twin pregnancies and their neonates sustain more severe adverse outcome compared to matched pairs of singleton pregnancies. It is recommended that a single embryo transfer should be offered in preference to multiple embryos when those women are undergoing ART.

The impact of a vegan diet on pregnancy outcomes.

OBJECTIVE: To determine the effect of a maternal vegan diet on pregnancy outcome. STUDY DESIGN: This is a prospective observational study. Women with a singleton pregnancy who maintained the same diet prior to, and throughout current pregnancy were enrolled. Stratification was performed according to diet type: vegans, lacto-ovo-vegetarians, fish-eaters, and omnivores. RESULTS: Overall, 273 women were enrolled, of them, 112 omnivores, 37 fish-eaters, 64 lacto-ovo-vegetarians, and 60 vegans. The vegan diet was significantly associated with an increased risk of small-for-gestational-age newborns compared only to an omnivore diet (RR = 5.9, 95% CI, 1.2-21.8). The incidence of preterm birth was similar in all groups. Vegans had lower birthweight compared to lacto-ovo-vegetarians (3015 ± 420 g vs. 3285 ± 482 g, P = 0.004), and to omnivores (3328 ± 495 g, P < 0.001), but not to fish-eaters. Vegans also had a lower mean gestational weight gain compared only to omnivores (11.6 ± 4.2 kg vs. 14.3 ± 4.6 kg, P = 0.001). CONCLUSION: The vegan diet is associated with an increased risk for small-for-gestational-age newborns and lower birthweight.

Clinical Observation: Effect of a Second Transpositioned Variant in a Family with Autosomal Dominant Ryanodine Receptor-1-Related Disease.

Mutations in the ryanodine receptor-1 ( RYR1 ) may cause disorders inherited in an autosomal dominant/recessive fashion. Sequencing of RYR1 in an infant of Ashkenazi Jewish descent with severe hypotonia, dislocation of hip, torticollis and scoliosis, and paternal family history of autosomal dominant mild disease. The child was compound heterozygote for a missense variant c.7042G > A inherited from her father associated with autosomal dominant disease, and a missense variant of unknown significance c.5309C > T inherited from an asymptomatic mother. This case raises the possibility of a dominant disease complicated by a second variant in the other allele serving as a modifier.

Perinatal outcomes of pregnancy in the fifth decade and beyond- a comparison of very advanced maternal age groups.

To study the effect of very advanced maternal age on perinatal outcomes. A retrospective cohort study of women aged 45 years and above, who delivered ≥22 weeks of gestation in a single tertiary center between 1/ 2011 and 12/ 2018. Maternal and neonatal outcomes were compared between women ≥50 years and women of 45-49 years at delivery. Of 83,661 parturients, 593 (0.7%) were 45-49 years old and 64 (0.07%) were ≥50 years old. Obstetrical characteristics were comparable, though the rate of chronic hypertension and preeclampsia with severe features were greater in women ≥50 years (6.2% vs 1.4%, p = 0.04, 15.6% vs 7.0%, p = 0.01, 95% CI 0.19-0.86, respectively). Elective cesarean deliveries were independently associated with advanced maternal age ≥50 (OR 2.63 95% CI 1.21-5.69). Neonatal outcomes were comparable for singletons, but rates of ventilatory support and composite severe neonatal outcomes were higher in twin pregnancies of women ≥50 years (42.8% vs 13.5%, p = 0.01, and 21.4% vs 4.0%, p = 0.03, respectively). Healthy women ≥50 have higher elective cesarean rates, despite similar maternal and neonatal characteristics.

Casting doubt on the value of assessing the cardiac index in pregnancy.

OBJECTIVES: The objective of this study is to assess the reliability of the cardiac index (CI) in healthy pregnant women at term by investigating the correlation between the cardiac output (CO) and the body surface area (BSA) using a novel non-invasive cardiography technique (NICaS™). METHODS: Sixty-one healthy, normotensive women with a singleton pregnancy at term (≥37 gestational weeks) participated in this prospective observational study between 1/2015 and 6/2015 L. Each woman was assessed for CO by the NICaS™, an impedance device that non-invasively measures the CO and its derivatives. The NICaS™ demonstrated a very good correlation with the gold standard Swan-Ganz catheter. BSA was determined by the Dubois nomogram. RESULTS: The mean ± standard deviation maternal age was 34.2 ± 5.3 years, mean height 166 ± 6 cm, and mean body mass index 23.9 ± 4.9 kg/m2. The mean gestational age was 38.8 ± 0.7 weeks. The correlation between the CO and the BSA was poor (Pearson r = 0.254, p < .005). CONCLUSIONS: The current study demonstrated poor correlation between the CO and the BSA in pregnant women, therefore, making the CI a non-reliable variable for assessing CO in pregnant women. We, therefore, suggest that the CO rather than the CI is the preferred parameter for hemodynamic measurements in this population.