Insulin requirements during pregnancy in women with type 1 diabetes treated with insulin pump.

INTRODUCTION: Insulin requirement in women with Type 1 diabetes (T1DM) changes throughout pregnancy. The aim of this study was to determine the total change in insulin requirements and the effect of gestational weight gain (GWG) and pre-gestational BMI on insulin requirements during pregnancy in women with T1DM treated with continuous subcutaneous insulin infusion and continuous glucose monitoring. METHODS: This historical cohort study included all consecutive women with T1DM who were monitored during pregnancy at the high-risk pregnancy clinic at a tertiary medical center during April 2011-April 2019. One Way Repeated Measures ANOVA with Bonferroni adjustment was conducted to compare the effects of gestational age on insulin requirements and a Two Way Repeated Measures ANOVA was employed to test for the interaction between gestational age intervals and maternal BMI and GWG. RESULTS: Data regarding insulin requirements of 185 pregnancies were included in the analyses. There was a significant effect of gestational age on total insulin (Wilks' Lambda = 0.34, F(6,14) = 4.52, p = 0.009), basal insulin (Wilks' Lambda = 0.41, F(6,14) = 3.30, p = 0.031) and bolus insulin (Wilks' Lambda = 0.43, F(6,14) = 3.02, p = 0.041). Total insulin/kg requirements increased by 5.5% from 13-20 weeks to 20-26 weeks, 19% from 20-26 weeks to 26-33 weeks, and 17.4% from 26 to 33 weeks to delivery (p for trend = 0.009). Overall, insulin requirements increased by 42.1% from conception to delivery (p < 0.01). There was no significant main effect of maternal BMI or GWG on insulin requirements. CONCLUSIONS: There is a significant increase in insulin requirements per kg during pregnancy in women with T1DM who were treated with an insulin pump.

In-utero evaluation of the fetal umbilical-portal venous system among fetuses with persistent right umbilical vein: Two-and three-dimensional ultrasonographic study.

OBJECTIVE: The aim of this study was to describe the anatomy of the portal system in fetuses with persistent right umbilical vein (PRUV). METHODS: Prospective observational study of fetuses diagnosed with PRUV. All patients underwent a comprehensive portal system anatomy scan supplemented by two-dimensional (2D) and three-dimensional (3D) color doppler modalities. RESULTS: 29 fetuses with PRUV were studied. We perceived an identical anatomical pattern in 28 fetuses. The right umbilical vein drains to the portal sinus (future right portal vein, RPV), which has a configuration of a left portal vein (LPV) in the normal left portal system, with three emerging branches: inferior (RPVi), medial (RPVm) and superior (RPVs). The RPV then courses to the left, towards the stomach to the point of the bifurcation of the main portal vein (MPV) to become the left portal vein. The LPV has an RPV configuration in a normal portal system with anterior (LPVa) and posterior (RPVp) branches. This anatomical layout mimics a mirror image of the normal anatomy of left portal system. CONCLUSION: PRUV has unique umbilical portal venous anatomy, which is a mirror image of the normal left portal system. It can be demonstrated prenatally and serve as an additional tool for prenatal diagnosis of PRUV.

The relationship between neonatal hypoglycaemia and cord blood C-peptide levels in neonates of birthing individuals with type 1 diabetes.

INTRODUCTION: Neonates of individuals with type 1 diabetes (T1D) are at increased risk of neonatal hypoglycaemia. It is hypothesised that this is a result of birthing-individual hyperglycaemia and subsequent foetal hyperinsulinemia. AIMS: To test for association between clinically significant neonatal hypoglycaemia (requiring intravenous glucose treatment) and cord-blood c-peptide (CBCP) concentrations in birthing-individuals with T1D. MATERIALS AND METHODS: This is a prospective cohort study of individuals with T1D followed at a single tertiary centre. Clinical variables and glucose control during pregnancy were recorded. Cord-blood was collected and CBCP concentrations determined. The correlation between clinically significant neonatal hypoglycaemia and CBCP concentrations was determined. RESULTS: Fifty-four pregnant individuals and their newborns were included in the study. Individuals to neonates who experienced hypoglycaemia had longer diabetes duration (19 vs. 13 years, respectively, p = 0.023), higher HbA1c at conception (7.3 [6.3-8.8] vs. 6.5 [6.0-7.0], respectively, p = 0.042) and higher rates of caesarian section (73.3% vs. 28.2%, respectively, p = 0.005) than individuals to those who did not. CBCP levels were significantly higher in neonates with clinically significant neonatal hypoglycaemia as compared to those who did not experience hypoglycaemia (3.3 mcg/L vs. 1.9 mcg/L, respectively, p = 0.002). After adjustment for possible confounders, every 1 unit higher in CBCP level was associated with a 1.46 (1.02-2.09, p = 0.035)-fold greater risk for neonatal hypoglycaemia. No significant differences were observed in either birthing individual complications or glucose control indices during pregnancy between the two groups. CONCLUSIONS: In neonates of individuals with T1D, higher CBCP levels are an independent risk factor for clinically significant neonatal hypoglycaemia.

Neonatal birth weight percentile following the use of sensor-augmented pump therapy in women with pre-gestational diabetes.

AIMS: To assess the effect of using sensor-augmented pump therapy (SAP) during pregnancy on neonatal birth weight percentile and other neonatal and pregnancy outcomes. METHODS: This retrospective cohort study included consecutive women with pregestational diabetes mellitus (PGDM) treated with an insulin pump and sensor that enabled the SAP feature during pregnancy. SAP use was defined as utilization of either low-glucose suspend (LGS) or predictive LGS technology. Utilization of SAP was according to physician discretion. Differences in neonatal birth weight percentile and in other neonatal and pregnancy outcomes were compared between those who did and not use SAP. OUTCOMES: Of 142 women, 136 had type 1 diabetes, 5 type 2 diabetes and one diabetes due to pancreatectomy. 83 women used SAP and 59 did not. For the neonates of the mothers of the respective groups, the median birth weight percentiles were similar (79 and 80, pV = 0.96), as were the other neonatal outcomes assessed. The rate of cesarean section was higher in the SAP group. However, after adjusting for maternal age, BMI, and a history of severe hypoglycemic events before pregnancy, the relation between mode of delivery and the use of SAP was no longer statistically significant. CONCLUSION: In women with PGDM treated with an insulin pump and sensor, SAP use during pregnancy was not associated with higher neonatal birth weight percentile or the occurrences of other adverse neonatal or pregnancy outcomes.

Late selective termination and the occurrence of placental-related pregnancy complications: A case control study.

INTRODUCTION: Multiple pregnancies are at increased risk of placental-related complications. The aim of the study was to investigate the prevalence and cumulative incidence of placental-related complications in twin pregnancies undergoing a late selective termination, compared to matched singleton and twin controls. METHODS: A retrospective case-control study of post-selective late termination (≥20 weeks of gestation) singletons performed between 2009 and 2020 at a single tertiary center. Each post-termination pregnancy was matched to 2 singleton and 2 dichorionic twin pregnancies for: mode of conception, maternal age group and parity. The prevalence of composite placental related outcome was determined and compared. Kaplan-Meier curves were constructed, and log rank test was performed to compare the cumulative incidence of placental complications among groups. RESULTS: Included were 90 post-selective termination pregnancies and 360 matched singletons and twins. These were subdivided according to trimester at procedure: 1) late 2nd trimester (N = 43, 20-27.6 weeks); 2) 3rd trimester (N = 47, ≥28 weeks). Placental-related complications presented earlier in the 3rd trimester selective termination group compared to singletons (median 35.5 vs median 37.4 weeks of gestation, P = 0.01). The cumulative incidence of placental-related complications in twins and post-selective termination singletons rose significantly earlier compared to singletons (P < 0.0001). A late 2nd trimester selective termination resulted in a comparable gestational age and cumulative incidence of placental-related complications as singletons. DISCUSSION: Compared to singletons, the cumulative incidence of placental complications rises significantly earlier in post-third trimester selective termination singleton pregnancies. While a late 2nd trimester selective termination results in a cumulative incidence comparable to singletons.

Obstetric complications at time of delivery amongst breast cancer survivors: A population-based cohort study.

PURPOSE: Our aim was to determine whether breast cancer survivors are at increased risk of obstetric and maternal complications at time of delivery. METHODS: The USA 'National Inpatient Sample' database was queried for hospitalizations associated with deliveries, between 2015 and 2018. The incidence of maternal and fetal complications was compared between women with, and without, a personal history of breast cancer. RESULTS: Of the 2,103,216 birth related admissions, 617 (0.03%) of the women were breast cancer survivors, with the proportion increasing over time (from 0.02% in 2015 to 0.04% in 2018). Breast cancer survivors had a higher socioeconomic status (p < 0.001) and were significantly older compared to other mothers (34 vs. 28 years, p < 0.001). Additionally, they were more likely to suffer from preexisting chronic diseases including cardiopulmonary disease and diabetes mellitus, and had a higher incidence of multiple gestation (4.4% vs. 1.6%) [OR 2.7, 95% CI 1.9-4.0, p < 0.001]. The incidence of acute adverse events at time of delivery including fetal distress, preterm labor, cesarean section and maternal infection was higher amongst the breast cancer survivors. On multivariate analysis age, ethnic group, comorbidities, multiple gestations, and a previous breast cancer diagnosis, but not cancer treatment, were associated with an increased risk of an obstetric adverse event. CONCLUSION: Breast cancer survivors have more comorbidities and are at increased risk of acute obstetrical complications at time of delivery. Further studies are required to validate these findings, and evaluate the ability of interventions to improve obstetrical outcomes amongst breast cancer survivors.

The perils of true knot of the umbilical cord: antepartum, intrapartum and postpartum complications and clinical implications.

BACKGROUND: True knot of the umbilical cord (TKUC) is found in 0.3-2.1% of pregnancies and is associated with an increased risk of adverse perinatal outcomes. METHODS: A retrospective cohort study including all singleton pregnancies delivered from 2011 to 2019 was performed. Diagnosis of TKUC was made postnatally, immediately after delivery of the baby. Comparison was made between pregnancies with and without TKUC regarding maternal, fetal and neonatal adverse outcome. RESULTS: Overall, 867/85,541 (1%) pregnancies were diagnosed with TKUC. Maternal age, BMI, gravidity and parity were significantly higher in pregnancies with TKUC as well as higher rate of induction of labor, meconium-stained amniotic fluid, and delivery prior to 37 weeks. The rate of cesarean deliveries due to non-reassuring-fetal monitor was significantly higher in pregnancies with TKUC. Overall, there were 2.5% IUFD in pregnancies with TKUC vs. 1% in pregnancies without TKUC (p < 0.001). Importantly, the rate of IUFD prior to 37 weeks of gestation was not significantly higher in the group with TKUC, however, the rate of IUFD after 37 weeks of gestation was 10 folds higher in fetuses with TKUC, 0.9% vs. 0.08% (p < 0.001). Significantly, more neonates with TKUC needed phototherapy or suffered from hypoglycemia. There were no differences in the 5 min Apgar scores, admission to the NICU and number of days of hospitalization. CONCLUSION: Pregnancies complicated with TKUC are associated with a tenfold higher risk of IUFD beyond 37 weeks of gestation. To the results of this study suggest that it would be prudent to induce labor around 37 weeks of gestation in pregnancies with prenatal diagnosis of TKUC. It may be warranted to use continuous fetal monitoring during labor and delivery in those cases were antenatal diagnosis of TKUC is made.

Maternal glucose variability during pregnancy & birthweight percentile in women with pre-gestational diabetes.

INTRODUCTION: Pre-gestational diabetes mellitus (PGDM) is a major risk factor for fetal overgrowth. Interestingly, even in relatively well controlled PGDM women, as determined by average glucose indices such HbA1c, there is an increased rate of LGA (large for gestational age). Glucose variability (GV) has emerged as an important independent risk factor for several diabetes complications. The aim of this study was to determine the relationship between maternal GV indices and neonatal birth percentile. METHODS: This was a historical cohort study that included all consecutive PGDM women monitored in a single tertiary care center. Clinical and demographic variables, as well as data regarding glucose control, were prospectively recorded. Mean, standard deviation (SD) and coefficient of variance (CV) of glucose values were calculated. Pearson correlations coefficient was used to determine the correlation between glucose indices and birth percentile. The analysis was repeated after adjustment for several confounders. RESULTS: Mean birthweight and birthweight percentile were 3212 ± 532 g and 66.9%, respectively. There was a statistically significant correlation between birthweight percentile and maternal glucose SD (ß = 0.28, p = .002) and maternal glucose CV (ß = 0.21, p = .019). There was no significant correlation between birthweight percentile and mean glucose values. The association between the maternal glucose SD and birthweight percentile remained statistically significant after adjustment for maternal age, pre-pregnancy BMI and duration of diabetes. CONCLUSION: There is an association between maternal glucose variability indices (SD and CV) during pregnancy and neonatal birth percentile. Larger studies are needed to confirm these results.

Dynamic esophageal patency assessment: an effective method for prenatally diagnosing esophageal atresia.

BACKGROUND: Esophageal atresia is a major anomaly with a low prenatal detection rate. We propose a sonographic method termed dynamic esophageal patency assessment. OBJECTIVE: This study aimed to assess the feasibility and performance of the dynamic esophageal patency assessment in a high-risk population. STUDY DESIGN: A prospective study was conducted in a single tertiary fetal ultrasound unit for 12 months. The study group included pregnant women referred for a targeted scan because of one or more of the following: (1) polyhydramnios; (2) small or absent stomach; (3) vertebral, anal atresia, cardiac, tracheoesophageal fistula, renal, and limb abnormalities; (4) first-degree relative with esophageal atresia; and (5) genetic mutation associated with esophageal atresia. In addition to dynamic esophageal patency assessment, a comprehensive anomaly scan was carried out. The fetal esophagus was observed during swallowing. Cases that demonstrated uninterrupted fluid propagation through the esophagus were classified as normal. Cases that demonstrated interrupted fluid propagation, with the formation of a pouch, were classified as abnormal. Cases with unclear visualization of the esophagus or cases that failed to demonstrate either fluid propagation or a pouch were classified as undetermined. Dynamic esophageal patency assessment results were compared with postnatal findings, considered "gold standard." Test performance indices and intra- and interobserver agreements were calculated. RESULTS: For 12 months, 130 patients were recruited, and 132 fetuses were scanned. The median gestational age (interquartile range) at the time of scan was 31.4 weeks (29.0-35.3). Of 132 fetuses enrolled, 123 (93.2%) were normal, 8 (6%) were abnormal, and 1 (0.8%) was undetermined. Excluded from test performance analysis were 3 cases that were terminated without postmortem autopsy (1 was abnormal and 2 were normal), and a fourth case was excluded as it was classified as undetermined. The detection rate of esophageal atresia was 100%, with no false-positive or false-negative case. Sensitivity, specificity, and positive and negative predictive values of the dynamic esophageal patency assessment were 100%. The Kappa coefficient was 1 for both inter- and intraobserver agreements (P<.0001). The median time (interquartile range) required to complete the dynamic esophageal patency assessment was 6.00 minutes (3.00-13.25). CONCLUSION: The dynamic esophageal patency assessment is a feasible and highly effective method of ascertaining an intact esophagus and detecting esophageal atresia in suspected cases.

Risk factors for obstetric anal sphincter injury among parous women.

PURPOSE: Nulliparity and operative vaginal delivery are established risk factor for obstetric anal sphincter injury (OASI). However, risk factors for OASIS occurrence among parous women delivering vaginally are not well-established. We aimed to study the risk factors for OASI occurrence among parous women. METHODS: A retrospective study including all parous women who delivered vaginally at term during 2011-2019 at a university hospital. Deliveries of parous women with OASI were compared to deliveries without OASI. The risk factors associated with OASI were investigated. RESULTS: Overall, 35,397 women were included in the study with an OASI rate of 0.4% (n = 144). A higher rate of only one previous vaginal delivery was noted in the OASI group (78.5% vs. 46.4%, OR [95% CI] 4.20, 2.82-6.25, p < 0.001). The rate of vacuum-assisted deliveries was comparable between the study groups. The median birth weight was higher among the OASI group (3566 vs. 3300 g, p < 0.001), as was the rate of macrosomic neonates (19.4% vs. 5.5%, OR [95% CI] 4.15, 2.74-6.29, p < 0.001). On multivariate logistic regression analysis, only two factors were independently positively associated with the occurrence of OASI: a history of only one previous vaginal delivery (adjusted OR [95% CI] 4.34, 2.90-6.49, p = 0.001), and neonatal birth-weight (for each 500 g increment) (adjusted OR [95% CI] 2.51, 1.84-3.44, p < 0.001). CONCLUSIONS: Among parous women, the only factors found to be independently positively associated with OASI were the order of parity and neonatal birth-weight. Vacuum-assisted delivery was not associated with an increased risk of OASI among parous women.

Towards Implementation of the Saint Vincent Declaration: Outcomes of Women with Pregestational Diabetes.

BACKGROUND: Pregestational diabetes mellitus (PGDM) carries a significantly elevated risk of adverse maternal and fetal outcomes. There is evidence that certain interventions reduce the risk for adverse outcomes. Studies have shown that a multi-disciplinary approach improves pregnancy outcomes in women with PGDM. OBJECTIVES: To determine pregnancy outcomes in women with PGDM using a multi-disciplinary approach. METHODS: We retrospectively reviewed consecutive women with pregestational type 1 and type 2 diabetes who were monitored at a high-risk pregnancy clinic at the Sheba Medical Center. Clinical data were obtained from the medical records. All data related to maternal glucose control and insulin pump function were prospectively recorded on Medtronic CareLink® pro software (Medtronic MiniMed, Northridge, CA). RESULTS: This study comprised 121 neonates from 116 pregnancies of 94 women. In 83% of the pregnancies continuous glucose monitoring (CGM) sensors were applied during a part or all of the pregnancy. Pregnancy outcomes among women who were followed by a multi-disciplinary team before and during pregnancy, and during labor and puerperium resulted in better glucose control (hemoglobin A1c 6.4% vs. 7.8%), lower risk for pregnancy induced hypertension/preeclampsia (7.7% vs. 15.6%), lower birth weight (3212 g vs. 3684 g), and lower rate of large size for gestational age and macrosomia (23.1% vs. 54.2% and 3.3% vs. 28.4%, respectively), compared to data from European cohorts. CONCLUSIONS: The multi-disciplinary approach for treating women with PGDM practiced in the high-risk pregnancy clinic at the Sheba Medical Center resulted in lower rates of macrosomia, LGA, and pregnancy induced hypertension compared to rates reported in the literature.

The association between novel glucose indices in parturients with type 1 diabetes mellitus and clinically significant neonatal hypoglycemia.

The aim of this study was to determine the association between glucose control indices of parturient with type 1 diabetes (T1DM), treated with an insulin pump and utilizing continuous glucose monitoring (CGM), and clinically significant neonatal hypoglycemia. This was a retrospective cohort study which included 37 pregnant women with T1DM. All women were followed at a single tertiary center and had available CGM data. The association between maternal glucose indices before delivery and the risk for neonatal hypoglycemia requiring IV glucose (clinically significant hypoglycemia) was assessed using logistic regression. Mothers to neonates that experienced clinically significant hypoglycemia had a higher glucose standard deviation (SD) before delivery than did mothers to neonates who did not (25.5 ± 13 mg/dL vs. 14.7 ± 6.7 mg/dl respectively; p = .008). This association persisted after adjustment for maternal age, maternal pregestational body mass index (BMI), gestational age at delivery, neonatal birth weight, large for gestational age (LGA) and gender. This study demonstrates an association between high maternal glucose standard deviation before delivery and the risk for clinically significant neonatal hypoglycemia. Larger studies are needed to confirm these results and further explore the role of intrapartum glucose variability in the prediction and prevention of significant neonatal hypoglycemia.

Quantitative assessment of physical activity in pregnant women with sonographic short cervix and the risk for preterm delivery: A prospective pilot study.

OBJECTIVE: Bed rest or activity restriction is a common obstetrical practice, despite a paucity of data to support its efficacy. The aim of this study was to determine whether physical activity, as assessed by a smart band activity tracker, is associated with preterm birth in pregnant women at high risk for preterm delivery. METHODS: This was a pilot prospective cohort study including pregnant women at high risk for preterm delivery between 24 and 32 weeks-of-gestation. Physical activity level was assessed by smart band activity. Patients with sonographic short cervical length (≤ 20 mm) were asked to wear the smart band activity tracker continuously for at least one week, including one weekend. Both physicians and patients were blinded to the data stored in the smart band activity tracker. No specific recommendations were given to participants as to the level or intensity of physical activity. The primary outcome was the rate of preterm birth (< 37 weeks-of-gestation). Secondary outcomes included the rate of delivery before 34 weeks of gestation and neonatal outcome. Parametric and nonparametric statistics were used for analysis. RESULTS: Study population included 49 pregnant women: 37 women (75.7%) delivered preterm and 12 (24.5%) delivered at or after 37 weeks-of-gestation. The median steps per day was significantly lower in patients who delivered preterm (3576, IQR: 2478-4775 vs. 4554, IQR: 3632-6337, p = 0.02). Regression analysis revealed that the median number of steps per day was independently inversely associated with preterm birth, after adjustment for maternal age, body mass index, gestational age at recruitment, cervical length, cervical dilatation and plurality. CONCLUSION: This pilot study represents the first quantitative assessment of the association between physical activity and preterm birth. The results of this pilot study do not support the efficacy of decreased physical activity in the prevention of preterm birth in patients with sonographic short cervical length.

Risk of Aortic Dissection in Pregnant Patients With the Marfan Syndrome.

Patients with Marfan syndrome (MS) face a high risk of aortic dissection during pregnancy. A dilated aortic root (>40 to 45 mm) is considered a relative contraindication for pregnancy. We investigated the risk for aortic dissection and pregnancy outcome in patients with MS. Women with MS who attended our cardiology high-risk pregnancy clinic from 2006 to 2015 were followed clinically and with serial echocardiograms by a multidisciplinary team. Beta blockers were offered and titrated by blood pressure and heart rate. Patients with aortic root dilation ≥40 mm were considered high-risk patients with MS. A consistent increase in aortic root diameter of >1 mm during pregnancy was classified as dilation during pregnancy; 31 pregnancies in 19 patients with MS were followed. Four pregnancies were terminated early because of prenatal diagnosis of fetal MS and 4 additional babies born with MS. Eight pregnancies were in patients with a dilated aortic root (40 to 46 mm); 21 patients (68%) were treated with ß blockers. There were 2 cases of postpartum aortic dissection (6.5%): 1 type A dissection in a woman with a dilated aortic root who declined ß blockers (1 of 8, 12.5%) and 1 type B dissection. Increasing aortic root diameter (>1 mm) in pregnancy was significantly associated with later aortic dissection (2 of 6 vs 0 of 21, p = 0.04). No maternal deaths occurred. All high-risk women with MS gave birth by cesarean section, whereas in the non-high-risk group mode of delivery was by obstetric indication. Preterm delivery rate was 41% (11 of 27). One antenatal fetal death and no major neonatal morbidity or mortality were observed. In conclusion, pregnant patients with MS, especially those with a dilating aortic root, are at high risk of aortic dissection, even with tight control of blood pressure and heart rate.