Volume 40, Issue 5

Objective: Oral iron substitution has shown to be insufficient for treatment of severe iron deficiency anemia in pregnancy. Ferric carboxymaltose is a new intravenous (i.v.) iron formulation promising to be more effective and as safe as iron sucrose. We aimed to assess side effects and tolerance of ferric carboxymaltose compared to i.v. iron sucrose in pregnant women. Methods: We performed a retrospective analysis of 206 pregnant women who were treated either with ferric carboxymaltose or iron sucrose for iron-deficiency anemia with intolerability to oral iron substitution, or insufficient hemoglobin increase after oral iron treatment, or need for rapid hemoglobin reconstitution. Primary endpoint was to evaluate the maternal safety and tolerability. Secondary endpoint was to assess efficacy of the treatment and exclude safety concerns for the fetus. Results: The incidence of drug-related adverse events was low and mostly mild in both groups. Mild adverse events occurred in 7.8% for ferric carboxymaltose and in 10.7% for iron sucrose. The mean rise of hemoglobin value was 15.4 g/L for ferric carboxymaltose and 11.7 g/L for iron sucrose. Conclusion: Ferric carboxymaltose administration in pregnant women is well tolerated and is not associated with any relevant clinical safety concerns. Ferric carboxymaltose has a comparable safety profile to iron sucrose but offers the advantage of a much higher iron dosage at a time reducing the need for repeated applications and increasing patients’ comfort. Ferric carboxymaltose is the drug of choice, if i.v. iron treatment becomes necessary in the second or third trimester of pregnancy.

Aims: The expression of the anti-inflammatory glycoprotein progranulin and the hypoxia-induced transcription factor 1α (HIF-1α) in the villous trophoblast was compared between placentae from patients with preeclampsia (PE), fetal growth restriction (FGR), and normal controls. Study design: Matched pairs analysis of third trimester placentae specimens (mean gestational age 36+2) was performed by semiquantitative measurements of the immunohistochemical staining intensities for progranulin and HIF-1α expression (PE n=13, FGR n=9 and controls n=11). Further, placental progranulin mRNA expression was analyzed by qRT-PCR on term placentae (n=3 for each group). Results: Compared to controls, villous trophoblast revealed a significantly higher expression of progranulin in cases of PE (P<0.05) and FGR (P<0.01). Similar results were shown for HIF-1α expression (P<0.01 for PE and <0.05 for FGR). The increase of the progranulin protein was not accompanied by an increase of the progranulin mRNA in term placentae. Conclusions: Increased expression of progranulin protein in villous trophoblast cells in cases of PE and FGR may result from disturbed placental development and, therefore, may be of pathogenetic importance. The increase was correlated to HIF-1α expression. Further evaluation of this potential mechanism of regulation is required.

Objective: To determine whether a customized standard for large for gestational age (LGA) identifies undiagnosed women at risk of operative delivery and shoulder dystocia. Methods: We previously generated customized standards from our institution. We compared the baseline maternal characteristics and neonatal outcomes between LGA and non-LGA births, which were classified by both population-based and customized standards. The risk of operative delivery (vacuum delivery or emergent cesarean section) and shoulder dystocia was compared by logistic regression analysis in LGA pregnancies that were identified by a population-based birth weight standard and a customized standard after adjusting for maternal age, parity, body mass index, and neonatal gender. Results: Multivariable analysis revealed that the pregnancies identified as LGA by a customized standard were associated with an increased risk of emergent cesarean section [odds ratio (OR), 4.09; 95% confidence interval (CI), 3.00–5.74] and shoulder dystocia (OR, 10.56; 95% CI, 5.52–20.19). However, there was no association between an increased risk of vacuum delivery (OR, 1.45; 95% CI, 0.92–2.30) and pregnancies identified as non-LGA, using both standards. In addition, customized LGA infants were at increased risk of admission to neonatal intensive care unit (OR 1.63; 95% CI, 1.09–2.43). Conclusion: A customized standard of LGA is useful in identifying previously unrecognized women at risk of emergent cesarean section and shoulder dystocia.

Objective: To examine the correlation between measurements of crown rump length (CRL), nuchal translucency (NT), and birth weight in dichorionic (DC) and monochorionic (MC) twin pregnancies. Methods: A retrospective analysis was performed on all twin term pregnancies delivered between 2001 and 2007 at the McGill University Health Center. Data collected included maternal age, CRL and NT measurement, results of glucose challenge test, birth weight and length, gestational age at delivery, and fetal gender. Results: The study population comprised 792 fetuses: 94 MC/DA and 698 DC/DA. Maternal age, gestational age at delivery, birth weight, and birth length were all significantly higher for the DC group. Male fetuses had significantly higher NT and higher birth weight than female fetuses. Discordance in CRL was found to correlate with discordance in birth weight in the entire study population (P<0.0001, R=0.25), in the DC twins (P<0.0001, R=0.275), but not in MC twins (R=0.10, P=0.33). CRL discordance above the 90 th percentile (>12%) predicted 14/40 pregnancies with birth weight discordance above the 90 th percentile (>24%) [P<0.001, LR=4.1 (2.6–6.2)]. CRL discordance above the 95 th percentile (>16%) predicted 5/21 pregnancies with birth weight discordance above the 95 th percentile (>30%) [P<0.001, LR=5.5 (2.6–10.4)]. NT discordance was correlated with CRL discordance (R=0.15, P<0.0001), but not with birth weight, regardless of chorionicity or gender. Conclusion: In twin pregnancies, CRL discordance in first trimester can predict discordance of more than 25% in neonatal birth weight.

Objectives: To examine the relationship of anxiety and quality of life and sleep variables to recurrent miscarriages (RMs) in patients during two stages of their treatment in an RM-dedicated clinic – before and after the evaluation – and determine what factors could aggravate anxiety and worsen global well-being outcomes. Study design: Thirty-nine women who had experienced two or more RMs were measured before and after their evaluation and investigation in the RM clinic. A battery of questionnaires including the STAI scale and various instruments were administered to record anxiety, mental, and physical components of quality of life and sleep quality. Several statistical tests including canonical correlation were performed. Results: All the patients revealed a mild to moderate level of anxiety, low numbers of physical and mental health but reasonably normal values of the global quality of sleep. The evaluation in the RM clinic and investigation for possible causes accounting for RM did not significantly change anxiety levels. The children-to-pregnancies ratio introduced into the analysis proved to correlate significantly with the sleep quality and mental health. Summarized anxiety in a given RM woman could be predicted based on the set of the variables, characterizing the woman’s reproductive status and her psychological health. Conclusions: This study establishes anxiety as a common response in RM patients, and suggests factors that predict it. Knowing these factors may help clinicians to identify more accurately those RM patients who would be prone to a high level of anxiety and therefore need more attention and reassurance.

Objective: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery in patients with early-stage cervical cancer is proven to be oncologically safe. After RVT, pregnancy rates vary between 40% and 80%. Outcome of infants is complicated by a preterm delivery rate of 30–50%. We investigated pregnancy and neonatal outcome after RVT. Methods: A total of 154 patients with cervical cancer underwent RVT between March 1995 and February 2008. Desire to conceive, pregnancy data, and neonatal outcome were prospectively recorded. Infants’ data were pair-matched to data of a control group according to weeks of gestation. Bayley scales of infant development scores were recorded in the group of preterm-delivered infants. Results: Fifty-five women who underwent RVT gave birth to 58 children. Twenty-five (43%) pregnancies were complicated by preterm rupture of membranes. Thirty infants (52%) were born preterm, of with 17 (29%) were <32 gestational weeks (GW) and seven (12%) were <28 GW. There were significantly more premature rupture of membranes in pregnancies after RVT. Despite a higher occurrence of postnatal infections in newborns of mothers who underwent RVT, long-term outcomes are not affected negatively. Regarding overall morbidity, a trend to fewer postnatal complications, compared with the control group, was found. Conclusion: Postnatal morbidity in infants of women who underwent RVT, based on trend, is decreased compared with controls. Intense medical observation and treatment during pregnancy, birth, and neonatal period may explain this finding. Neonates in the RVT group have a non-significantly elevated risk for postnatal infections. They do not show an additional risk due to the maternal operation. Their long-term postnatal outcome is not affected negatively.

Aims: One of the first steps in optimizing future prevention and appropriately allocating resources to future diagnosis and treatment of Gestational diabetes (GDM) is to quantify its burden. The aim of this study was therefore to conduct a systematic review of current international literature on the prevalence of GDM with a focus on advanced economies. Methods: Based on literature searches with the database “PubMed” we included studies with a publication date between 2000 and 2011. All studies were classified independently by two authors. In accordance with the PRISMA Statement we identified 27 original studies. Results: The prevalence of GDM varies substantially between populations with a range of 1.7–11.6%. Patient self-reports yield higher prevalence estimates than values that are based on medical diagnosis or clinical diagnostic tests. Prevalence seems to vary considerably within Europe with higher prevalence values being observed in Southern Europe than in Northern and Central Europe. Prevalence values from studies from Australia and North America were within this range. Conclusion: This review provides a comprehensive and sound summary of the current state of research on the prevalence of GDM in advances economies as a first step in identifying starting points for future interventions.

Aims: The present study aimed to provide normal reference ranges for decidual thickness measured ultrasonographically in healthy first-trimester pregnancies and to evaluate whether there was a relationship between decidual thickness and serum progesterone levels. Methods: Decidual thickness of 173 women with a healthy gestation between 6+0 and 9+6 weeks was measured ultrasonographically and serum progesterone concentration was determined. Distribution of decidual thickness at each gestational week and its relation with serum progesterone levels was evaluated. Results: Mean decidual thickness was 6.8, 5.7, 5.5, and 6.1 mm at 6 th , 7 th , 8 th , and 9 th gestational weeks, respectively. Decidual thickness showed a mild negative correlation with gestational week (ρ=–0.207, P=0.006) and a mild positive correlation with serum progesterone concentrations (ρ=0.191, P=0.021). Conclusion: The present study provided normal reference ranges for decidual thickness in healthy pregnancies in the first trimester. The association found between decidual thickness and progesterone levels might shed light on further studies investigating the predictive factors of pregnancy loss and might lead to changes in the management of threatened miscarriage.

Objective: Inflammatory mechanisms are thought to play an important role in the process of labor, both in preterm and spontaneous term delivery. We aimed to determine whether normal spontaneous vaginal delivery (SVD) at term was associated with an inflammatory activation compared with elective cesarean section (ECS) without previous onset of labor. Methods: Cytokine concentrations were measured in venous cord blood obtained from 60 term newborns (ECS, n=35; SVD, n=25) born to mothers with clinically uneventful pregnancy and without signs of infection. Results: Both study groups showed no differences in birth weight, umbilical artery pH, Apgar at 5 min, and gender distribution. Infants delivered by ECS had lower gestational age: mean, 38.5 weeks (range, 37.0–39.6 weeks) vs. mean, 39.8 weeks (range, 37.9–42.4 weeks) (P<0.001). Concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-17, IL-1 receptor antagonist, soluble IL-2 receptor α, granulocyte-macrophage colony-stimulating factor, interferon (IFN)-α2, IFN-γ, tumor necrosis factor (TNF)-α, TNF-β, and interferon inducible protein 10 were not different between ECS and SVD. Newborns after SVD displayed increased levels of transforming growth factor β1 (TGF-β1): mean, 8580 pg/mL (95% CI, 5554–11,606) vs. mean, 4864 pg/mL (95% CI, 2471–7257) (P<0.0012). Conclusions: Our findings suggest that, in healthy, term neonates, the exposition to normal spontaneous delivery and labor is not associated with systemic activation of different inflammatory mediators compared with ECS except for TGF-β1. Further studies are needed to evaluate the immunomodulatory role of labor-associated TGF-β1 increase in fetal cord blood.

Aim: To determine infant survival and neonatal outcome after fetoscopic laser treatment of twin-to-twin transfusion syndrome (TTTS). Results: In 53/71(75%) laser-treated TTTS cases, at least one twin was liveborn and in 42/71(59%) cases at least one twin survived infancy. Fetal survival did not differ between donors [41/71(58%)] and recipients [46/71(65%), P=0.36]. Among liveborns, infant survival was 29/41(71%) in donors and 36/46(78%) in recipients (P=0.12). Infant survival did not correlate to maternal characteristics (age, BMI, smoking or parity), gestational age at treatment or severity of TTTS (Quintero stage). No TTTS infant born before 25 weeks of gestation survived the first week. Among the 87 infant survivors, 26 (30%) had an Apgar score <7 at 5 min, 47 (54%) developed respiratory distress syndrome, 10 (11%) showed signs of severe brain damage, nine (10%) renal failure, eight (9%) bronchopulmonary dysplasia, and five (6%) infants developed retinopathy of prematurity ≥stage 3. There was no significant difference in neonatal morbidity between recipients and donors. Conclusions: Fetal survival after laser treatment was comparable to that reported by other international centers. There was no significant difference in survival or neonatal morbidity between donors and recipients. Major neonatal morbidity was common, and combined with extremely preterm delivery the prognosis of TTTS is poor.

Objectives: Infants with intrauterine growth restriction (IUGR) have increased morbidity and mortality. The decision whether to induce labor at term or to expectantly manage these pregnancies is controversial. The aim of this study was to assess the outcomes of these two management strategies in term pregnancies. Study design: This retrospective cohort study compared neonatal and maternal morbidity and mortality of IUGR fetuses (estimated fetal weight below the 10 th percentile) between induced and spontaneous labors. Results: Records of 669 IUGR newborns were reviewed; 499 were delivered through spontaneous labor and 170 were delivered through induced labor. Epidemiology and early perinatal outcomes between the two groups were similar. The cesarean section rate was significantly higher (P<0.005) in the induced group. Conclusions: Expectant management for term IUGR pregnancies seems to be safe, with lower rates of cesarean deliveries. A large, prospective, randomized controlled trial with long-term neonatal follow-up is indicated.

Objectives: The purpose of this study is to evaluate the cardiac function in anemic fetuses by tissue Doppler imaging (TDI) measuring the myocardial peak systolic strain (PS) in fetuses before and after intrauterine transfusion (IUT) of red blood cells. Methods: In our prospective clinical study in anemic fetuses, high-frame-rate TDI data files from a four-chamber view of fetal hearts pre- and post-IUT were analyzed. The biventricular PS parameters of the mid-segment of the ventricular walls [region of interest (ROI) 1 right ventricle, ROI 2 left ventricle] and the basal segment of the ventricular walls (ROI 3 tricuspid annulus, ROI 4 mitral annulus) were compared with the PS data of the normal controls. Results: We analyzed the pre-/post-data sets from the 15 hearts of anemic fetuses and from the 17 controls. The threshold of statistical significance was set to P≤0.05. Compared with the controls, in anemic fetuses the left ventricular longitudinal myocardial PS (ROI 2, P=0.001) and PS in the basal segment of the right ventricle (ROI 3 P=0.009) was significantly increased (absolute amount). Compared with pre-IUT, post-IUT PS decreased significantly in both ventricles (ROI 1 P=0.025, ROI 2 P=0.02). Compared with the controls, post-IUT left ventricular PS was still higher (absolute amount) (ROI 2, P=0.026; ROI 4, P=0.009). Conclusions: The increase in myocardial PS due to severe fetal anemia is partially normalized by IUT. In anemic fetuses, assessment of TDI fetal myocardial PS is feasible.

Objective: This study aimed to know the outcome of delayed-interval delivery for twin and triplet pregnancies at 22+0 to 25+0 weeks of gestation. Study design: A retrospective cohort of twin and triplet deliveries at the 23 rd to 26 th weeks of gestation were managed with delayed interval delivery from 2005 to 2011. Results: From 2005 until 2011, delayed delivery in five twin pregnancies and two triplet pregnancies were performed. The interval between delivery of the first fetus and the remaining twin/triplets was 1–18 days (mean, 9.7 days). In all cases, the first fetus was born vaginally. Survival of the first twin/triplet was 14.3%, whereas 57.1% of the second born twin/triplets survived. Birth weight gained due to delayed delivery was 131 g on average. No severe maternal complications were observed. When compared with a gestation age-matched group, where the delay was not possible, the delayed twin/triplet had a higher survival rate (57.1% vs. 0%, P=0.05). Conclusion: In multiple pregnancies with preterm delivery between completed 22 and completed 25 weeks of gestational age, delayed delivery seems to be a useful therapeutic option to achieve a better outcome of the remaining fetus or fetuses.

Aim: Increased neonatal weight gain has been suggested as risk factor for later overweight. Offspring of diabetic mothers (ODM) have a long-term increased overweight risk. However, the role of early postnatal weight gain for later overweight has not been addressed so far in ODM. We investigated whether increased weight gain during the first 4 months is related to later overweight in ODM. Methods: Determinants of childhood overweight and neonatal weight gain were analyzed in 152 ODM from the Kaulsdorf Cohort Study by MANOVA and regression analyses. Results: Independent of birth weight, weight gain during the first 4 months was positively related to childhood relative body weight (P=0.001). Each 100 g-increase in weight during this period increased overweight risk by 65% (95%CI: 10–247%). ODM with rapid early weight gain had a more than six-fold increased risk of later overweight (OR: 6.77; 95%CI: 1.36–33.6). Early neonatal intake of breast milk from metabolically healthy mothers protected from rapid early weight gain (P=0.03). Conclusions: Increased weight gain during the first 4 months of life is a strong, independent risk factor for childhood overweight in ODM. Preventing nutritionally-induced rapid early weight gain in ODM might be a promising strategy to lower their long-term overweight risk.

Objective: To identify factors related to the postnatal increase in superior mesenteric artery blood flow velocity (SMA BFV). Study design: SMA BFV was measured in 35 infants (birth weight 1047±246 g) on day of life (DOL) 1, 3, 5, 7 10 and 14. Latent curve modeling (LCM) was used to measure the longitudinal change in BFV for each subject, and the correlation between changes in BFV and baseline values. Non-parametric correlations were calculated between BFV and variables previously reported to be related to SMA BFV. Results: There was significant variability in SMA BFV on DOL 1, a significant increase from DOL 1–14, and significant variability in the postnatal increase. Infants with higher enteral feeding volumes had greater increases, while infants receiving positive pressure ventilation or hyperalimentation had lower increases. Conclusions: Several clinical factors affect the postnatal increase in SMA BFV. The use of LCM is useful in longitudinal studies of very low birth weight (VLBW) infants, who are clinically and demographically heterogeneous.

Aims: We assessed central-peripheral temperature gradient alteration for the diagnosis of late-onset neonatal sepsis and compared earliness detection of this sign with altered blood cell count and C-reactive protein. Method: Thirty-one preterm babies (<1500 g or <32 weeks) participated in an observational prospective study. Axillary (central) and sole (peripheral) temperatures were continuously monitored with a thermal probe (ThermoTracer; Dräger Medical AGF & Co. KgaA, Lübeck, Germany) adjusting incubator air temperature for a thermal gradient <1.5°C. Central-peripheral temperature alteration was defined as a thermal gradient >2°C that could not be corrected with protocolized air temperature modifications. Proven (positive blood culture) sepsis and probable late-onset sepsis were recorded. Results: Late-onset sepsis was diagnosed in 11 neonates (proven, 9; probable, 2). Thermal gradient alteration was present in 12 cases, in association with the onset of sepsis in 10 and concomitantly with a ductus arteriosus and stage 1 necrotizing enterocolitis in 2. Thermal gradient alteration had a sensitivity of 90.9% [95% confidence interval (CI), 62.3–98.4] and specificity of 90% (95% CI, 69.9–97.2%), and in 80% of cases, it occurred before abnormal laboratory findings. Conclusions: Central-peripheral temperature gradient monitoring is a feasible, non-invasive, and simple tool easily applicable in daily practice. An increase of >2°C showed a high-sensitivity and specificity for the diagnosis of late-onset sepsis.

Background: Retinopathy of prematurity (ROP) is a common cause of blindness in countries with rapidly developing systems of neonatal care. At present, detection and treatment programs are not widely available in many regions of middle- and low-income countries. Subject population: Case series. Methods: An analysis was undertaken to determine in which neonatal intensive care units (NICUs) in Peru babies blind from ROP had been cared for. Demographic and hospital information was gathered for children blind from ROP presenting before the age of 5 years. NICUs with a high likelihood of having ROP-blind children were offered training and equipment designed to improve neonatal care. Results: Ninety-one children with ROP blindness were identified. Twenty-six percent were <1000 g at birth, and 17% had birth weights of >1500 g. Forty-six percent came from NICUs in Lima. Interventional workshops emphasizing neonatal care and oxygen administration have been conducted thus far in six of the 13 largest NICUs in Lima. The percentage of at-risk babies being examined has generally increased, whereas the percentage of babies requiring treatment decreased in three NICUs and increased slightly in two, and no preworkshop data were available in one. Conclusion: This report represents the initial results of an evidence-based approach to decreasing blindness from ROP in Peru. Workshops emphasizing neonatal care, especially targeting oxygen administration, provide methods for improving care of at-risk babies.

Background: Neonatal resuscitation training is considered to be multifarious and includes manual ventilation as an essential competence for any health-care provider. Usually, ventilation is applied with self-inflating bags (SIBs). These devices have been shown to produce highly variable, operator-dependent peak inspiratory pressures (PIPs) and tidal volumes (V T ). Excessive PIP and V T contribute to lung injury. We studied a simple tool to improve resuscitation skills. Objective: The objectives of this study were to train health-care providers to avoid excessive PIP and V T by visualizing these values by using a respiratory function monitor (RFM) and to study the sustainability of such a training. Material and methods: Previously untrained medical professionals were educated and trained to ventilate a neonatal preterm manikin. PIP and V T were measured with an RFM. Graphical representations of the measurements were displayed during training, but the RFM was blinded during subsequent recordings. Participants were reassessed directly after training and 1 month later. Results: In total, 37 participants were trained and assessed three times during the study. Median PIPs (range) were 32.3 (4.1–44) cm H 2 O before training, 17.8 (9.6–23.6) cm H 2 O directly after training (P<0.05), and 18.7 (7.5–41.6) cm H 2 O 1 month later, and the values remained low, compared with before training (P<0.05). Median V T s were 6.7 (4.2–44) mL before training, 3.5 (1.8–7.3) mL directly after training (P<0.05), and 4.1 (1.9–9.7 mL) 1 month after training (P<0.05). Conclusion: Using a SIB, untrained staff produced excessive PIP and V T . Training with a simple RFM significantly reduced the occurrence of excessive PIP and V T . The effect was sustained for at least 1 month.

Aims: The aim of this study was to examine the applicability of the definitions of the systemic inflammatory response syndrome (SIRS) and sepsis to neonates during the first 3 days of life. Methods: This is a retrospective study of all term neonates hospitalized within the first 24 h of life from 2004 to 2010 at our neonatal intensive care unit. Results: Of 476 neonates, 30 (6%) had a diagnosis of culture-proven early-onset sepsis (EOS) and 81 (17%) had culture-negative clinical EOS or suspected EOS. SIRS and sepsis criteria were applied to 116 (24%) and 61 (13%) neonates, respectively. Of 30 neonates with culture proven, EOS 14 (53%) fulfilled SIRS and sepsis criteria. The single diagnostic criterion of SIRS applied to 20% (hypothermia or fever), 43% (white blood cell count/immature-to-total neutrophil ratio), 87% (respiratory symptoms), and 33% (cardiocirculatory symptoms) of all neonates with culture-proven EOS. Conclusions: The definitions of SIRS and sepsis did not apply to about half of all cases of culture-proven EOS. An evidence-based approach to find the appropriate criteria for defining EOS in the neonate is needed.

No Abstract available.