Ambulatory Glucose Profile Changes During Pregnancy in Women With Type 1 Diabetes Using Intermittently Scanned Continuous Glucose Monitoring Empowered by Personalized Education.

The ambulatory glucose profile is a valuable tool in managing type 1 diabetes during pregnancy. Time in range (TIR) in the third trimester is one of the most significant parameters contributing to good pregnancy outcomes. This study aimed to evaluate the effect of intermittently scanned continuous glucose monitoring (isCGM) empowered by education on glucose dynamics and to predict third trimester TIR. Data were retrospectively analyzed from 38 pregnant patients with type 1 diabetes (mean age 30.4 ± 6.4 years, BMI 23.7 ± 3.7 kg/m2, disease duration 15.4 ± 9.5 years, preconception A1C 6.9 ± 1%) who used a first-generation FreeStyle Libre isCGM system for at least 3 months before conception and had sensor data captured >70% of the time the system was used. Patients received personalized education on diabetes and on minimizing hypoglycemia and hyperglycemia using CGM trend arrows and frequent sensor scanning. This intervention improved glycemic parameters of glucose regulation (TIR, glucose management indicator, and mean glucose), hyperglycemia (time above range), glucose variability (SD and coefficient of variation [%CV]), and scanning frequency, but did not improve parameters of hypoglycemia (time below range and a number of low glucose events). Logistic regression analysis showed that the first trimester %CV and scanning frequency contributed to the third trimester TIR (P <0.01, adjusted R2 0.40). This study suggests that the use of isCGM empowered by personalized education improves glycemic control in pregnant women with type 1 diabetes. Scanning frequency and %CV in the first trimester predicts TIR in the third trimester, which could help clinicians intervene early to improve outcomes.

Morbidly Adherent Placenta in the First Trimester with Consecutive Hysterectomy.

Background Morbidly adherent placenta (MAP) represents a risk factor for a maternal adverse outcome and its incidence continues to rise following the increasing rate of caesarean deliveries. The detection of a pathology of placental adherence in the first trimester is challenging. Transvaginal ultrasound represents (TVUS) a reliable tool for accurate and timely diagnosis. Case We report on a case of MAP in a pregnant woman at 10 weeks of gestation with two prior caesarean deliveries. She presented with abdominal pain and hematometra. The first trimester diagnosis was made with TVUS and confirmed with magnetic resonance imaging. The patient required an urgent hysterectomy. Conclusion Antenatal care in the first trimester in women with a previous cesarean delivery should include a detailed examination of the placenta with TVUS.

Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion.

Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of 60 cell-cycle-related proteins was determined in human first trimester placental tissue (gestational week 5-11) from control (n = 11) and T1DM pregnancies (n = 12). Primary trophoblasts (gestational week 7-12, n = 32) were incubated in the absence (control) or presence of hyperglycemia (25 mM D-glucose) and hyperosmolarity (5.5 mM D-glucose + 19.5 mM D-mannitol). We quantified the number of viable and dead trophoblasts (CASY Counter) and assessed cell cycle distribution (FACS) and trophoblast invasion using a transwell assay. T1DM was associated with a significant (p < 0.05) downregulation of Ki67 (-26%), chk1 (-25%), and p73 (-26%). The number of viable trophoblasts was reduced under hyperglycemia (-23%) and hyperosmolarity (-18%), whereas trophoblast invasion was increased only under hyperglycemia (+6%). Trophoblast cell death and cell cycle distribution remained unaffected. Collectively, our data demonstrate that hyperglycemia decreases trophoblast proliferation as a potential contributing factor to the reduced placental growth in T1DM in vivo.

The Impact of Hypoglycemia and EPA and DHA Supplementation on Brain-Derived Neurotrophic Factor Level in Pregnant Women with Type 1 Diabetes: A Prospective Cohort Study.

BACKGROUND: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. SUBJECTS AND METHODS: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fifteen pregnant women developed hypoglycemia episodes (≤3.9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). RESULTS: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P<0.05, in the Exposed group from 22.1 (19.8-25.9) to 18.1 (14.8-18.9), P<0.01. Pregnant patients with hypoglycemia episodes (HYPO+ subgroup) had significantly higher BDNF in the third trimester of pregnancy [22.5 (20.6-28.4)] when compared with patients who did not develop hypoglycemia [16.3 (14.3-18.8), P<0.001]. In the third trimester of pregnancy, BDNF and n-6 PUFAs were associated with hypoglycemia (OR 1.818 95 % CI 1.079-3.003, P=0.025; OR 1.103 95 % CI 1.001-1.217, P=0.048). Total F.A.s were inversely associated with hypoglycemia (OR 0.969 95% CI 0.939-0.998, P=0.048). CONCLUSION: Pregnant women with hypoglycemia (HYPO+ group) had higher concentrations of BDNF in the first and third trimesters of pregnancy compared to those without hypoglycemia. An increase in body weight during pregnancy leads to a decrease in BDNF concentration.

THE ROLE OF LOW MOLECULAR WEIGHT HEPARIN IN WOMEN WITH HEREDITARY THROMBOPHILIA FOR GOOD PERINATAL OUTCOME.

The aim of the study was to establish the importance of low molecular weight heparin (LMWH) treatment for good pregnancy outcome in patients with hereditary thrombophilia. This retrospective study included 70 patients with inherited thrombophilia who gave birth at Zagreb University Hospital Center in the period from January 2014 to January 2015. Fifty-seven women were treated and 13 women were not treated with LMWH. Perinatal outcome was significantly better in women with hereditary thrombophilia who were treated with heparin during pregnancy as compared with women without LMWH (p=0.006). Regardless of heparin therapy, patients with hereditary thrombophilia alone had a significantly better perinatal outcome as compared with women who, along with hereditary thrombophilia, had a history of habitual abortions (p=0.035) or intrauterine fetal death (p=0.033). Women treated with heparin had better perinatal outcome if they were without a history of recurrent or non-recurrent fetal loss (p=0.088). In the group without LMWH, perinatal outcome was significantly better in women with no history of habitual abortions as compared with women with recurrent miscarriages (p=0.047). Administration of LMWH is justified in women with hereditary thrombophilia and a history of adverse perinatal outcome.

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence.

BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters-pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)-and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database. RESULTS: None of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites. CONCLUSIONS: Methylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

Successful delivery of fetus with fetal inherited thrombophilia after two fetal deaths.

A pregnant woman with inherited thrombophilia (factor II mutation--20210A) had two late pregnancy losses. The first pregnancy was not well documented, but the second pregnancy was complicated by fetal thrombophilia and umbilical artery thrombosis, proven after fetal death. During the third pregnancy enoxaparine was introduced in the therapy and early amniocentesis was performed. Fetal thrombophilia was proven again. Early delivery was induced and performed with no complications, resulting in a live healthy infant. A history of miscarriages or recurrent fetal loss should raise suspicion of thrombophilia as a potential cause. It is debatable whether amniocentesis in pursuit of fetal thrombophilia should be performed and whether this will lead to a better perinatal outcome. When fetal thrombophilia is diagnosed, an earlier induction of delivery should be considered, taking into account the fetal extrauterine viability. The aforementioned approach of early delivery in cases of inherited fetal thrombophilia could be a possible solution for better perinatal outcomes.

Relationship of Glucose, C-peptide, Leptin, and BDNF in Maternal and Umbilical Vein Blood in Type-1 Diabetes.

The study aimed to determine the relationship between glucose, C-peptide, brain-derived neurotrophic factor (BDNF), and leptin between mother and fetus and neonatal weight. METHODS: In the prospective observational cohort study, we included 66 women with type-1 diabetes mellitus (T1DM). According to the z-score for neonatal weight, patients were divided into healthy-weight neonates (n = 42) and overweight neonates (n = 24). The maternal blood samples were taken during pregnancy and cesarean section when the umbilical vein blood sample was also withdrawn. The maternal vein sera were analyzed for fasting glucose, C-reactive protein (CRP), leptin, BDNF, TSH, FT3, and FT4. The umbilical vein sera were analyzed for glucose, C-peptide, leptin, TSH, thyroid-stimulating protein (FT3), free thyroxine (FT4), and BDNF concentration. The neonatologist measured the skinfold thickness on the third day of neonatal life. RESULTS: A strong correlation was confirmed between maternal and umbilical vein glucose concentration and maternal glucose and C-peptide in umbilical vein blood. A negative correlation was found between the concentration of BDNF in the umbilical vein and glucose in maternal blood. A strong correlation was seen between BMI and maternal blood leptin concentration, neonatal fat body mass, and umbilical vein blood leptin concentration. Higher BMI elevated BDNF, and TSH increase the odds for overweight neonates in the first trimester of pregnancy. Maternal higher leptin concentration in the first trimester decrease the odds of overweight neonates. CONCLUSIONS: Maternal glucose concentrations affect the fetus's glucose, C-peptide, and BDNF concentrations. Leptin levels increase in maternal blood due to increased body mass index, and in the neonate, fat body mass is responsible for increased leptin concentrations.

Awakened Beta-Cell Function Decreases the Risk of Hypoglycemia in Pregnant Women with Type 1 Diabetes Mellitus.

Diabetes in pregnancy creates many problems for both the mother and child. Pregnant women with type 1 diabetes experience more frequent hypoglycemic and hyperglycemic episodes. This study aimed to determine the risk of clinically significant biochemical hypoglycemia (CSBH) by HbA1c, fasting C-peptide, mean plasma glucose (PG), and insulin dose in pregnant women type 1 diabetes mellitus according to each trimester of the pregnancy. METHODS: We conducted a prospective observational study of 84 pregnant women with type 1 diabetes in an academic hospital. To present the hypoglycemia, we divided the participants into two groups: those who did not have clinically significant biochemical hypoglycemia (CSBH-; n = 30) and those who had clinically significant biochemical hypoglycemia (CSBH+; n = 54). RESULTS: In the first, second, and third trimesters, the duration of T1DM, fasting C-peptide, and mean glucose concentration was inversely associated with CSBH. CONCLUSIONS: Insulin overdose is the most common risk factor for hypoglycemia. In pregnant women with type 1 diabetes with elevated fasting C-peptide levels, the insulin dose should be diminished to reduce the risk of hypoglycemia.

Positive Association between Preserved C-Peptide and Cognitive Function in Pregnant Women with Type-1 Diabetes.

This study focused on the cognitive function of women with type 1 diabetes in pregnancy. We investigated risk factors for a low cognitive score such as age, duration of Diabetes, BMI, subclinical hypothyroidism, cardiovascular autonomic neuropathy, the impact of hypo-/hyperglycemia, and C-peptide preservation. Material and methods. Seventy-eight pregnant women with type 1 diabetes (age 31.1 ± 5.4 years, diabetes duration 14.3 ± 8.9 years) were included in the study. Cognitive function was assessed in different domains, such as reasoning, memory, attention, coordination, and perception. Results. The cognitive test values ≥400 were considered high scores, and values <400 were considered low. Relative risks for low scores for general cognitive function were associated with increased BMI > 25 kg/m2 2.208 (95% CI 1.116−4.370), HbA1c > 6.5% RR 0.774 (95% CI 0.366−1.638), subclinical hypothyroidism RR 3.111 (95% CI 1.140−8.491), and impaired cardiovascular autonomic neuropathy RR 2.250 (95% CI 1.000−5.062). Pregnant women with a lower score for general cognitive function had higher BMI and higher leptin levels. Preserved C-peptide reduces the risk for cognitive impairment (RR 0.297 (95% CI 0.097−0.912)) in pregnant women with type 1 diabetes Conclusion. BMI > 25 kg/m2, subclinical hypothyroidism, and cardiovascular autonomic neuropathy are associated with increased risk, and postprandial C-peptide preservation with reduced risk for cognitive impairment in pregnant women with type 1 diabetes.

Glycemic Variability in Type 1 Diabetes Mellitus Pregnancies-Novel Parameters in Predicting Large-for-Gestational-Age Neonates: A Prospective Cohort Study.

Pregnancies with type 1 diabetes mellitus (T1DM) have a high incidence of large-for-gestational-age neonates (LGA) despite optimal glycemic control. In recent years, glycemic variability (GV) has emerged as a possible risk factor for LGA, but the results of the conducted studies are unclear. This study analyzed the association between GV and LGA development in pregnancies with T1DM. This was a prospective cohort study of patients with T1DM who used continuous glucose monitoring (CGM) during pregnancy. Patients were followed from the first trimester to birth. GV parameters were calculated for every trimester using the EasyGV calculator. The main outcomes were LGA or no-LGA. Logistic regression analysis was used to assess the association between GV parameters and LGA. In total, 66 patients were included. The incidence of LGA was 36%. The analysis extracted several GV parameters that were significantly associated with the risk of LGA. The J-index was the only significant parameter in every trimester of pregnancy (odds ratios with confidence intervals were 1.33 (1.02, 1.73), 3.18 (1.12, 9.07), and 1.37 (1.03, 1.82), respectively. Increased GV is a risk factor for development of LGA. The J-index is a possible novel GV parameter that may be assessed in all three trimesters of pregnancy together with glycated hemoglobin and time-in-range.

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta.

The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (-1665, -1439, -1421, -1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

European guidelines on perinatal care- Peripartum care Episiotomy.

OF RECOMMENDATIONS1. Episiotomy should be performed by indication only, and not routinely (Moderate quality evidence +++-; Strong recommendation). Accepted indications for episiotomy are to shorten the second stage of labor when there is suspected fetal hypoxia (Low quality evidence ++-; Weak recommendation); to prevent obstetric anal sphincter injury in vaginal operative deliveries, or when obstetric sphincter injury occurred in previous deliveries (Moderate quality evidence +++-; Strong recommendation)2. Mediolateral or lateral episiotomy technique should be used (Moderate quality evidence +++-; Strong recommendation). Labor ward staff should be offered regular training in correct episiotomy techniques (Moderate quality evidence +++-; Strong recommendation).3. Pain relief needs to be considered before episiotomy is performed, and epidural analgesia may be insufficient. The perineal skin needs to be tested for pain before an episiotomy is performed, even when an epidural is in place. Local anesthetics or pudendal block need to be considered as isolated or additional pain relief methods (Low quality evidence ++-; Strong recommendation).4. After childbirth the perineum should be carefully inspected, and the anal sphincter palpated to identify possible injury (Moderate quality evidence +++-; Strong recommendation). Primary suturing immediately after childbirth should be offered and a continuous suturing technique should be used when repairing an uncomplicated episiotomy (High quality evidence ++++; Strong recommendation).

European Guidelines on Perinatal Care - Oxytocin for induction and augmentation of labor[Formula: see text].

OF RECOMMENDATIONS1. Oxytocin for induction or augmentation of labor should not be started when there is a previous scar on the body of the uterus (such as previous classical cesarean section, uterine perforation or myomectomy when uterine cavity is reached) or in any other condition where labor or vaginal delivery are contraindicated. (Moderate quality evidence +++-; Strong recommendation).2. Oxytocin should not be started before at least 1 h has elapsed since amniotomy, 6 h since the use of dinoprostone (30 min if vaginal insert) and 4 h since the use of misoprostol (Low quality evidence ++- -; Moderate recommendation).3. Cardiotocography (CTG) should be performed and a normal pattern without tachysystole should be documented for at least 30 min before oxytocin is used. Continuous CTG, with adequate monitoring of both fetal heart rate and uterine contractions, should be maintained for as long as oxytocin is used, and thereafter until delivery (Low ++- - to moderate +++- quality evidence; Strong recommendation).4. For labor induction, at least 1-h should be allowed after amniotomy before oxytocin infusion is started, to evaluate whether adequate uterine contractility has meanwhile ensued. For augmentation of labor, if the membranes are intact and there are conditions for a safe amniotomy, the latter should be considered before oxytocin is started (Very low quality evidence +- --; Weak recommendation).5. Oxytocin should be administered intravenously using the following regimen: 5 IU oxytocin diluted in 500 mL of 0.9% normal saline (NaCl) (each mL contains 10 mIU of oxytocin), in an infusion pump at increasing rates, as shown in Table 1, until a frequency of 3-4 contractions per 10 min is reached, a non-reassuring CTG pattern ensues, or maximum rates are reached (Low quality evidence ++ - -; Strong recommendation). If the frequency of contractions exceeds 5 in 10 min, the infusion rate should be reduced, even if a normal CTG pattern is present. With a non-reassuring CTG pattern, urgent clinical assessment by an obstetrician is indicated, and strong consideration should be given to reducing or stopping the oxytocin infusion. The minimal effective dose of oxytocin should always be used. (Low ++- - to Moderate +++- - quality evidence; Strong recommendation).[Table: see text]6. Use of oxytocin for induction and augmentation of labor should be regularly audited (Low quality evidence ++--; Strong recommendation).

Supplementation of EPA and DHA in pregnant women with type 1 diabetes mellitus.

BACKGROUND/OBJECTIVE: Lower proportions of n-3 PUFAs have been observed in neonates born to diabetic mothers. We aimed to investigate the association between DHA and EPA supplementation during pregnancy complicated with type 1 diabetes on concentration and proportion of fatty acids in maternal and foetal blood. SUBJECTS AND METHODS: We conducted a prospective randomized, single-blinded, placebo-controlled trial of 111 eligible pregnant women with type 1 diabetes and presented the results of 84 (intervention arm and control arm comprised 42 participants each) of them who successfully finished the trial in an academic hospital. The initiation of EPA and DHA supplementation or placebo started at randomization visit on gestational week 11-12. Blood samples were taken on the first (screening) visit to the clinic (1st trimester, between 8th and 10th gestational week, GW), then in the second trimester (19-24th GW) and third trimester (30th-33rd GW). On the delivery day, a blood sample was taken on fasting just before birth. The umbilical vein blood sample was taken shortly after the delivery. RESULTS: We found a significant increase in the intervention group when compared the first and the third trimester for n-3 PUFAs concentration, 4.3 mg/L (3.3-7.6): 10.0 mg/L (7.1-13.7), p < .001. In the intervention group, the concentration of DHA in maternal vein serum was 11.4 mg/L (7.7-17.5), and in umbilical vein serum, it was 5.1 mg/L (3.0-7.7), which was significantly higher than that in the control group, maternal vein serum: median 9.2 mg/L(6.0-12.3), p = .03 and umbilical vein serum: median 3.4 mg/L (2.1-5.6), p = .009. CONCLUSION: The increased weight gain in pregnancy and concentration and proportions of DHA, n-3 PUFAs with a decreased proportion of AA, n-6 PUFAs, and AA/DHA ratio in maternal and umbilical vein serum summarize the effect of supplementation with EPA and DHA.

N-3 PUFA and Pregnancy Preserve C-Peptide in Women with Type 1 Diabetes Mellitus.

Type 1 diabetes (T1DM) is an autoimmune disease characterized by the gradual loss of ß-cell function and insulin secretion. In pregnant women with T1DM, endogenous insulin production is absent or minimal, and exogenous insulin is required to control glycemia and prevent ketoacidosis. During pregnancy, there is a partial decrease in the activity of the immune system, and there is a suppression of autoimmune diseases. These changes in pregnant women with T1DM are reflected by Langerhans islet enlargement and improved function compared to pre-pregnancy conditions. N-3 polyunsaturated fatty acids (n-3 PUFA) have a protective effect, affect ß-cell preservation, and increase endogenous insulin production. Increased endogenous insulin production results in reduced daily insulin doses, better metabolic control, and adverse effects of insulin therapy, primarily hypoglycemia. Hypoglycemia affects most pregnant women with T1DM and is several times more common than that outside of pregnancy. Strict glycemic control improves the outcome of pregnancy but increases the risk of hypoglycemia and causes maternal complications, including coma and convulsions. The suppression of the immune system during pregnancy increases the concentration of C-peptide in women with T1DM, and n-3 PUFA supplements serve as the additional support for a rise in C-peptide levels through its anti-inflammatory action.

Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study.

OBJECTIVE: To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes. RESEARCH DESIGN AND METHODS: Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins. RESULTS: Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI -0.01, 0.04]; adjusted risk difference -0.003 [95% CI -0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (-0.032 [95% CI -0.064, 0.000]) and after (-0.036 [95% CI -0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference -0.181 [95% CI -0.300, -0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; -0.139 [95% CI -0.232, -0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference -0.030 [95% CI -0.058, -0.002]), preeclampsia (6.4% vs. 10.0%; -0.036 [95% CI -0.064, -0.007]), and stillbirth (0.4% vs. 1.8%; -0.013 [95% CI -0.024, -0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment. CONCLUSIONS: Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

[Pregnancies and deliveries in patients with Charcot-Marie-Tooth disease]. / Trudnoca i porodaj u bolesnica s hereditarnom senzomotornom polineuropatijom (Charcot-Marie-Tooth).

Hereditary motor sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth (CMT) disease, is a spectrum of disorders caused by a specific mutation in one of several myelin genes, which results in defects in myelin structure, maintenance and formation. Affected individuals show progressive distal limb atrophy and weakness, often with gait disturbance and deformity of feet and hands. There have been few studies on how CMT disease can affect pregnancy, birth and the newborn. CMT is an independent risk factor for complications during pregnancy and delivery. Patients with CMT have more operative deliveries, malpresentations and postpartum bleeding than the general obstetric population. It is not clear whether the increased prevalence of malpresentation is related to fetal disease, although the disorder typically does not present until later in childhood. Postpartum bleeding from atony may be related to the disease effect on uterine adrenergic nerves. Exacerbation of CMT disease can occur in pregnancy, an effect that may be mediated by increased plasma progesterone level. Observations in an animal model were consistent with these findings as the administration of progesterone resulted in a more progressive neuropathy, while a progesterone antagonist slowed the disease progression. We treated two patients with CMT (type 5 and type X1) at our Department. Both of them had normal course of pregnancy until delivery. Emergency cesarean section was performed in both cases; in one because of malpresentation, contracted pelvis and signs of impending fetal asphyxiation during the second stage of delivery, and in the other one based on neurologist indication. In the latter, uterine atony with profuse postpartum bleeding occurred immediately after cesarean section and emergency hysterectomy was performed according to clinical status.