Volume 44, Issue 4 - Highlight: Diabetes

Background: To evaluate the diagnostic value of the 3 rd hour plasma glucose level in the 100 g oral glucose tolerance test (OGTT). Methods: Records of all pregnant patients with abnormal 50 g glucose challenge test (GCT) between January 2005 and December 2013 were reviewed (n=1963). The 100 g OGTT results were analyzed separately for both Carpenter & Couston (CC) and National Diabetes Data Group (NDDG) criteria. Results: The number of patients diagnosed with gestational diabetes mellitus (GDM) was 297 (15.1%) according to CC criteria and 166 (8.4%) according to NDDG criteria. The 1 st hour plasma glucose level showed the highest correlation with GDM diagnosis (ρ=0.595 for CC and ρ=0.567 for NDDG). However, the 3 rd hour plasma glucose level showed the weakest correlation with GDM diagnosis (ρ=0.216 for CC and ρ=0.213 for NDDG). The 3 rd hour value of 100 g OGTT was one of the two elevated measurements in 10.8% of patients when CC criteria are used and in 13.8% of patients when NDDG criteria are used. Conclusion: Omitting 3 rd hour plasma glucose measurement in 100 g OGTT results in unacceptable rates of underdiagnosed patients.

Objective: To assess the perinatal outcomes in pregnant women with maternal hypoglycemia following a second trimester oral glucose challenge test (GCT). Materials and methods: This retrospective case control study consisted of 2091 pregnant women with hypoglycemia (glucose levels >88 mg/dL 1 h following a 50 g GCT in the second trimester of pregnancy) and a control group of 2091 pregnant women with a GCT result between 88 and 130 mg/dL. Perinatal and neonatal characteristics obtained from electronic medical records were compared between groups. Results: The rates of pregnancy complications were similar in both groups, with the exception of a lower incidence of polyhydramnios and a higher rate of deliveries before the 34 th week of gestation in patients with hypoglycemia (0.5% vs. 1.1%, P=0.016 vs. 2.6% vs. 1.7%, P=0.033); respectively. Neonates born to mothers with hypoglycemia had significantly less birth trauma (0.3% vs. 0.9%, P=0.027) and neonatal hypoglycemia. When the data for male and female infants were analyzed separately, male infants had a 1.5-fold (95% CI: 1.05–2.18) increased chance of being small for gestational age (SGA), whereas the risk for female infants did not increase (OR: 0.79, 95% CI: 0.56–1.11). Conclusion: A low maternal plasma glucose level on the GCT is associated with favorable outcomes, such as decreased rates of birth trauma and neonatal hypoglycemia. In addition, male infants have a higher risk of being SGA than female infants when maternal GCT results were <88 mg/dL.

The interplay of various nutrients provided to the developing foetus determines the growth potential of the conceptus. This study assessed the inter-relationship between these nutrients in a Mediterranean population including 1062 pregnant, previously non-diabetic women. These underwent an oral glucose tolerance test (oGTT) and were accordingly classified into gestational hyperglycaemic and normoglycaemic groups. Fasting insulin, HbA1c, and lipid profiles were further assessed, and the anthropomorphic characteristics of the mother and child at birth were measured. Lipid profiles were compared between the two groups and related to the biological characteristics of the mother and child at birth. Gestational hyperglycaemia was significantly associated with elevated triglycerides (P<0.0001) and decreased low density lipoprotein cholesterol (LDL-C) (P=0.02). There were no significant changes in total cholesterol and high density lipoprotein cholesterol (HDL-C) levels. Maternal BMI correlated positively with the various glycaemic indices (P<0.0001) and triglycerides (P<0.0001), but inversely with cholesterol (P<0.0001), HDL-C (P<0.0001) and LDL-C (P<0.0001). The infant birth weight correlated positively with maternal body weight (P<0.0001), LDL-C (P<0.0001) and the glycaemic indices (P<0.0001), but negatively with cholesterol (P<0.0001), triglycerides (P<0.0001), HDL-C (P<0.0001) and FBG (P<0.0001). This study confirms that the maternal body mass index (BMI), insulin resistance, and LDL-C levels positively contribute towards foetal growth, whereas a negative correlation was noted with cholesterol, triglycerides, and HDL-C.

Objective: To compare the results of maternal and perinatal pregnancies of obese women after bariatric surgery. Methods: A retrospective cross-sectional study was carried out on 63 women who had undergone bariatric surgery and 73 obese women (control). Demographic data, the characteristics of the bariatric surgery, and the maternal and perinatal results were evaluated. The Student’s t -test and chi-square test ( χ 2 ) were used to compare the groups. The gestational complications of the prevalence of gestational diabetes mellitus, anemia, and preeclampsia were analyzed using simple and multivariate logistical regression and odd ratios (OD) with their respective confidence intervals (CI) of 95%. Results: The average body mass index (BMI) at the 1 st prenatal appointment of the control group was 34.6±3.3 kg/m 2 and that of the post-surgical group was 26.5±4.2 kg/m 2 . The Roux-en-Y Gastric Bypass was used in 100% of cases; no complications were observed during or after the surgeries. The average weight loss in patients with a prior bariatric surgery was statistically significant (P=0.000). The average weight at birth of the control group was significantly higher than in the post-bariatric surgery group (P=0.017). The women who had a prior bariatric surgery had a higher chance of anemia (OR=3.5; CI 95%: 1.5–8.3) and a reduced chance of macrosomia (OR=0.2; CI 95%:0.1–0.5), and prematurity (OR=0.3; CI 95%:0.1–0.7). Conclusion: Those women who had been submitted to bariatric surgery presented better maternal and perinatal results when compared to obese women.

Objective: To compare the actual maternal weight gain to that recommended by the Institute of Medicine (IOM) in term singleton gestations. Methods: We used data from the Slovenian National Perinatal Information System to select singleton pregnancies born at ≥38 weeks during the period from 2003 to 2012. We calculated the frequencies of mothers who gained less than, more than, and as recommended by the IOM according to their pregravid body mass index (BMI). We also compared the fetal size parameters in under- and over-gainer to those who gained weight as recommended by the IOM. Results: We selected 173,715 patients who delivered at ≥38 weeks. Of these patients, the recommended weight gain was achieved by 56,868 (32.7%, 95% CI 32.5, 32.9) only, 82,617 (47.6%, 95% CI 47.3, 47.8) were over-gainers, and 34,230 (19.7%, 95% CI 19.5, 19.8) gained less than recommended. Neither undergaining nor overgaining were always synonymous with adverse fetal outcomes. Conclusions: Roughly two-thirds of singleton mothers did not gain weight during pregnancy according to the IOM recommendations. Inappropriate maternal weight gain, however, was not always associated with adverse fetal outcomes and this implies that a tailored approach rather than strict adherence to the IOM recommendations may be more practical.

Objective: Pregravid maternal weight and appropriate weight gain during pregnancy might be associated with increased cesarean section rate. Study design: We used data from the Slovenian National Perinatal Information System to select singleton pregnancies born at ≥38 weeks, during the period between 2003 and 2012. We calculated the frequencies of urgent and elective cesarean sections (UCS and ECS, respectively) in mothers who gained less than, more than, and as recommended by the Institute of Medicine (IOM) according to their pregravid body mass index (BMI). Results: The analysis included 170,121 women who delivered singletons ≥38 weeks. A total of 24,327 (14.3%) women underwent cesarean section: 14,692 (8.6%) UCS and 9635 (5.7%) ECS. The frequency of cesareans, both UCS and ECS, increases as BMI increases irrespective of weight gain pattern. The frequency of urgent cesareans in all women increases and that of elective cesareans among obese women decreases as the level of weight gain increases from undergainers to overgainers. Conclusion: The combination of pregravid BMI and weight gain pattern is an important determinant of cesarean section rates at term.

Background: Overweight and obesity is a serious health risk in both developed and developing nations. It is a common finding among women in their reproductive age. Half of patients entering their pregnancy in the US have a BMI >25.0 and therefore qualify as overweight or obese. Moreover, there is a tendency towards increased weight gain during pregnancy. Studies have shown that gestational overweight is associated with complications in pregnancy and birthing as well as short-term and long-term impacts on neonatal outcome in childhood and adulthood. Methods: Five hundred and ninety-one women visiting our tertiary perinatal center in 2014 were analyzed for antenatal BMI, gestational weight gain, as well as pregnancy outcome and complication together with neonatal weight and outcome. Pregnancy weight gain was assessed based on the IOM guidelines (Institute of Medicine) issued in 2009. Results: Twenty-nine percent of our population was overweight with a BMI of more than 25.0. The general weight gain was in every BMI group similar (median ranging from 12.0 to 14.0 kg). Approximately one third gained more than the appropriate amount (37%, P<0.001). Women with more gestational weight were at risk of labor induction (55.0% vs. 45.7% labor induction in total, P=0.007). Strikingly, those patients were found to have significantly higher rates of secondary cesarean section (22.4% vs. 15.4%) and decreased chances of spontaneous vaginal birth (57.5% vs. 61.4%) (P=0.008). Furthermore women with a pregnancy weight gain in excess of the guidelines gave birth to neonates with a higher birth weight (>75.centile, 28.3% vs. 21.3%, P<0.001). Conclusions: Altogether, one third of the analyzed population is already overweight or obese when entering pregnancy. A higher gestational weight gain than the recommended amount was found in 37% of cases. We found an association with pregnancy and birthing complications as well as higher infant weight. This highlights the importance of preconceptive and prenatal advice, and if necessary, intervention on BMI and weight gain.

Aims: To characterize placental glucose delivery under normoglycemic conditions, gestational and pre-gestational diabetes and to relate the clinical data to theoretical predictions. Methods: Data from 125 pregnancies: 50 normal gestations and 75 ones with various types of diabetes were collected. In parallel, we formulated a theoretical model for the transport of glucose under various diabetic conditions. Measured glucose blood levels were fed into the theoretical model that predicts glucose supply to the fetus and the results were confronted with measured fetal weights. Results: Measured fetal weight and computed glucose delivery in gestational diabetic parturients resemble the situation in normal pregnancies. However, pre-gestational diabetes has a major effect as it involves heavier fetuses and enhanced computed glucose fluxes via placental membranes. Conclusions: Fetal weight (increased in pre-gestational and unaltered in gestational diabetes) correlates with the predicted rate of glucose delivery through the placenta.

Objectives: To explore the influence of epidural analgesia on the course of the third stage of labor and on the incidence of the complete retained placenta as well as retained parts of the placenta. Study design: This is a population-based cohort study in a tertiary medical center. We collected data from all 4227 spontaneous singleton vaginal deliveries during 6 months and compared the incidence of retained placenta in deliveries with epidural analgesia with those without analgesia. Multivariable logistic regression was used to control for possible confounders. Results: More than two-thirds of the women (69.25%) used epidural analgesia during their delivery. A need for intervention due to placental disorder during the third stage of labor was noted in 4.2% of all deliveries. Epidural analgesia appeared to be significantly (P=0.028) related to placental disorders compared with no analgesia: 4.8% vs. 3%, respectively. Deliveries with manual interventions during the third stage, for either complete retained placenta or suspected retained parts of the placenta, were associated with the use of epidural analgesia (P=0.008), oxytocin (P=0.002) and older age at delivery (P=0.000), but when including all factors in a multivariable analysis, using a stepwise logistic regression, the factors that were independently associated with interventions for placental disruption during the third stage of delivery were previous cesarean section, oxytocin use and, marginally, older age. Conclusions: Complete retained placenta and retained parts of the placenta share the same risk factors. Epidural analgesia does not directly influence the incidence of complete retained placenta or retained parts, though clinically linked through increased oxytocin use. The factors that were independently associated with interventions for placental disruption during the third stage of delivery were previous cesarean section, oxytocin use and older age.

Objective: To identify risk factors among children with unknown cause intellectual disability (ID) and to estimate the population-attributable risk (PAR) associated with these factors. Methods: This was a retrospective cohort study of maternal and child pairs born between 2004 and 2010 in South Carolina, and information was obtained from Medicaid billing records, birth certificates, and other administrative data. The data included 123,922 children and logistic generalized estimating equations (GEE) regression models were used to estimate the association of maternal risk factors and ID. We estimated models with and without birth weight as a covariate, since low birth weight is known to be a mediator of the association between some risk factors and ID in children. Results: The prevalence of ID in the children was 3.85% and the associations between risk factors and ID were similar for female and male children. We found that the odds of having ID were increased if a child’s mother had a diagnosis of major depression; for male children, the odds ratio (OR) was 1.34 (95% confidence interval [CI] 1.14–1.59, PAR 2.17%); and for females, the OR was 1.59 (95% CI 1.30–1.95, PAR 4.70%). The odds of having ID were also increased for children of women with bipolar disorder (males – OR 1.95, 95% CI 1.53–2.48, PAR 2.85%; females – OR 1.63, 95% CI 1.20–2.22, PAR 2.05%). Conclusions: Major maternal depression and bipolar disorder were each significantly associated with the odds of ID in children, each accounting for approximately 2–5% of the PAR, when controlling for covariates.

Aim: To evaluate the incidence of postpartum hemorrhage (PPH) and severe PPH via routine use of a pelvic drape to objectively measure blood loss after vaginal delivery in connection with PPH management. Methods: This prospective observational study was undertaken at the obstetrical department of the Charité University Hospital from December 2011 to May 2013 and evaluated an unselected cohort of planned vaginal deliveries (n=1019 live singletons at term). A calibrated collecting drape was used to meassure blood loss in the third stage of labor. PPH and severe PPH were defined as blood loss ≥500 mL and ≥1000 mL, respectively. Maternal hemoglobin content was evaluated at admission to delivery and at the first day after childbirth. Results: During the study period, 809 vaginal deliveries were analysed. Direct measurement revealed a median blood loss of 250 mL. The incidences of PPH and severe PPH were 15% and 3%, respectively. Mean maternal hemoglobin content at admission was 11.9±1.1 g/dL, with a mean decrease of 1.0±1.1 g/dL. Blood loss measured after vaginal delivery correlated significantly with maternal hemoglobin decrease. Conclusions: This study suggests that PPH incidence may be higher than indicated by population-based data. Underbuttocks drapes are simple, objective bedside tools to diagnose PPH. Blood loss should be quantified systematically if PPH is suspected.

Aims: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a neurometabolic disease in which the degradation of γ-aminobutyric acid (GABA) is impaired. The purpose of this study was to report two novel ALDH5A1 mutations responsible for SSADH deficiency in a Chinese family and the prenatal diagnosis of an at-risk fetus with DNA sequencing. Results: Genetic analysis of ALDH5A1 , in a child with SSADH deficiency, parents, and 10 weeks’ gestation at-risk fetus and 100 healthy unrelated volunteers, was performed. The coding sequence and the intron/exon junctions of ALDH5A1 were analyzed by bidirectional DNA sequencing. The proband was identified to have a compound heterozygous mutations with c.496T>C (p.W166R) and c.589G>A (p.V197M). Each of his parents carried a deleterious mutation. DNA sequencing of chorionic villus revealed the fetus was a carrier, but not affected, and this was confirmed after birth by genetic analysis of umbilical cord blood and urine organic acid analysis. A study in 2003 described 35 mutations of ALDH5A1 in 54 unrelated families, and the current study and systematic literature review identified nine additional novel mutations in eight unrelated families bringing the total number of unique mutations of ALDH5A1 resulting in SSADH deficiency to 44, and the 44 mutations occur from exon 1 to exon 10. No mutational hotspots or prevalent mutations were observed, and all mutations appeared vital for the function of SSADH. Conclusions: Two novel ALDH5A1 mutations likely responsible for SSADH deficiency were identified, and DNA sequencing provided an accurate diagnosis for an at-risk fetus whose sibling had SSADH deficiency.

Objective: Prenatal exposure to elemental mercury may be a potential hazard for the offspring of female dental personnel working with dental amalgam. The aim of this study was to investigate whether potential in utero exposure to mercury might have affected the development of nervous system of the sons of Swedish female dental personnel leading to an increased risk of neurological disease or intellectual disability. Material and methods: We used national Swedish registers to investigate risks for diseases potentially related to adverse effects on neurodevelopment. Sons of female dentists (n=1690) and dental nurses (n=10,420) were compared with cohorts consisting of sons of other female healthcare personnel. Due to changes in mercury exposure in dentistry during the study period, analyses were stratified by decade of birth. Hazard ratios (HRs) were calculated using Cox proportional hazard models. Results: We found no elevated risk for neurological disease, epilepsy or intellectual disability among the sons of dental personnel during any of the decades studied. HRs for neurological disease among the dental nurse cohort were even below 1.00 during the 1970s and 1980s. A low number of events resulted in uncertainty regarding results in the dentist cohort. Conclusions: We did not find any support for the hypothesis that mercury exposure in Swedish dentistry during the 1960s, 1970s or 1980s had any effect on the incidence of neurological disease or intellectual disability among the sons of female dental personnel. Our results imply that current use of dental amalgam should not represent an elevated risk for neurological disease or intellectual disability among the offspring of dental personnel.

Objectives: We hypothesize that a formal simulation curriculum prepares neonatology fellows for difficult conversations better than traditional didactics. Methods: Single-center neonatology fellowship graduates from 1999 to 2013 were sent a retrospective web-based survey. Some had been exposed to a Difficult Conversations curriculum (simulation group), others had not (no simulation group). The simulation group participated in one workshop annually, consisting of lecture, simulation, and debriefing. Scenarios were customized to year of training. Epoch comparisons were made between the simulation and no simulation groups. Results: Self-rated baseline effectiveness at discussing difficult topics was not different. The simulation group reported more supervised family meetings and feedback after fellow-led meetings. Simulations were rated very positively. The simulation group reported increased comfort levels. Strategic pause and body positioning were specific communication skills more frequently acquired in the simulation group. In both groups, the highest ranked contributors to learning were mentor observation and clinical practice. In the simulation group, simulation and debriefing outranked didactics or other experiences. Conclusions: Simulation-based workshops improve communication skills in high stakes conversations. However, they do not substitute for mentor observation and experience. Establishing a structured simulation-based difficult conversations curriculum refines vital communication skills necessary for the high stakes conversations neonatologists direct in clinical practice.

Objective: Our aim was to determine whether maternal HIV infection in the current era is associated with an increased incidence of meconium aspiration syndrome (MAS) in their infants. Methods: Infants born to 149 HIV-positive women at our hospital over a 5-year period were compared with infants born to HIV-negative women in a retrospective case-control study. Charts of all 298 patients included in the study were reviewed for maternal and infant demographics, HIV treatment, vertical transmission and untoward events at delivery or during the hospital course. Results: When compared with HIV-negative women, a greater proportion of HIV-positive women had meconium-stained amniotic fluid (MSAF), 33% vs. 13%, P<0.001; and thick MSAF, 17% vs. 5%, P<0.001, respectively. Seven of 298 infants were admitted to the neonatal intensive care unit for MAS; all seven were born to HIV-positive women (P=0.015). Although in utero exposure to illicit drugs is a reported risk factor for meconium staining of the amniotic fluid and such drug exposure was more common among our HIV-positive sample, controlling for this and other possible covariates did not greatly reduce the association of HIV status with meconium-related complications of delivery. Conclusions: Infants born to HIV-positive women had significantly more MSAF and MAS than infants born to non-infected women. It is unclear whether this association results from maternal HIV infection itself or from anti-retroviral therapy. Maternal and infant care providers should be prepared for this complication when attending to the deliveries of HIV-positive women.

Objective: Transient tachypnea of the newborn (TTN) results from inadequate neonatal lung fluid clearance. Low-dose dopamine induces natriuresis in the kidneys and it has been assumed that, at this low dosage, dopamine increases renal perfusion in critically ill patients. Medium doses have positive inotropic and chronotropic effects via increased β-receptor activation. Recent studies have demonstrated that dopamine stimulates the clearance of pulmonary edema. Furthermore, β-adrenergic agonists regulate Na + channels and Na-K-ATPase activity in the pulmonary epithelium. This study investigated the effect of dopamine at different dosages on TTN treatment. Methods: A prospective controlled study examined 60 infants with TTN older than 34 weeks of gestation who required at least 24 h of O 2 and nasal continuous positive airway pressure (nCPAP) treatment. The infants were randomized into three groups of 20: controls, infants treated with low-dose dopamine (3 μg/kg/min), and infants treated with a medium dose (5 μg/kg/min). The control and study groups were compared in terms of the requirement for mechanical ventilation, and the durations of nCPAP, oxygen requirement, and hospitalization. Results: The requirement for mechanical ventilation, and durations of nCPAP, oxygen requirement, and hospitalization did not differ significantly among the three groups (P=0.54, 0.16 and 0.11, respectively). Conclusion: Dopamine treatment in low-moderate doses does not improve the outcome in TTN. Thus, further studies in this area are needed.