Band 42, Heft 1

Aims: Several studies have recently reported the detection of oncogenic human papillomaviruses (HPV) in human milk of a minority of lactating mothers. These findings raised safety concerns in the context of human donor milk banking given the potential risk of HPV transmission to recipient infants. The aim of this study was to investigate whether the Holder pasteurization, a procedure currently in use in human donor milk banks for milk pasteurization, completely inactivates high-risk and low-risk HPV. Methods: HPV pseudoviruses (PsV) were generated, spiked into cell culture medium or donor human milk and subjected to thermal inactivation. HPV PsV infectivity and morphological integrity was analyzed by cell-based assay and by electron microscopy, respectively. Results: The Holder pasteurization completely inactivated the infectivity of high-risk (types 16 and 18) and low-risk (type 6) HPV both in cell culture medium and in human milk causing PsV particle disassembly. Conclusions: The results presented here indicate that the Holder pasteurization is an efficient procedure to inactivate high-risk and low-risk HPV thus preventing the potential risk of their transmission through human donor milk.

Natural processes do not always function perfectly. In breastfeeding, problems are encountered in up to 80% of mother-infant dyads. Altogether, in Western societies, the difficulties reduce the breastfeeding rate within the first months drastically. To deal with the problems of breastfeeding efficiently requires a profound understanding of its physiology, as well as of its psychological and social determinants. This review focuses on the current knowledge of breastfeeding physiology, only touching the psychosocial factors, which are included in the promotion strategies. Subsequently, it scrutinizes definitions, incidences, prevention, and treatment of breastfeeding problems faced most frequently by nursing mothers and their consultants. Not all measures used in counseling mothers and not all treatments for the most common medical problems withstand a careful evaluation on the basis of current scientific data. However, applying proven prevention strategies will significantly improve the well being of mothers and their infants, and may contribute to an affective attitude that increases the success, frequency, and duration of breastfeeding.

Aims: The 2009 H1N1 pandemic illustrated the higher morbidity and mortality from viral infections in peripartum women. We describe clinical features of women who recently died of H1N1 in Colombia. Methods: This is a case series study that was gathered through a retrospective record review of all maternal H1N1 deaths in the country. The national mortality database of confirmed mortality from H1N1 in pregnancy and up to 42 days after delivery was reviewed during the H1N1 season in 2009. Women with H1N1 infections were confirmed by the laboratory of virology. Demographic, clinical, and laboratory data were reviewed. Statistical analyses were performed and median values of non-parametric data were reported with inter-quartile range (IQR). Results: A total of 23 H1N1 maternal deaths were identified. Eighty-three percent occurred in the third trimester. None of the mothers who died had received influenza vaccination. The median time from symptom onset to the initiation of antiviral treatment was 8.8 days (IQR 5.8–9.8). Five fatalities did not receive any anti-viral therapy. Median PaO 2 /FiO 2 on day 1 was 80 (IQR, 60–98.5). All patients required inotropic support and mechanical ventilation with barotrauma-related complications of mechanical ventilation occurring in 35% of patients. Conclusion: In Colombia, none of the women suffering H1N1-related maternal deaths had received vaccination against the disease and most had delayed or had no anti-viral therapy. Given the lack of evidence-based clinical predictors to identify women who are prone to die from H1N1 in pregnancy, following international guidelines for vaccination and initiation of antiviral therapy in suspected cases would likely improve outcomes in developing countries.

Objective: Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection for the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis. Method: A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analyses were applied. Results: A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were upregulated and 526 were downregulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction, (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression. Conclusion: This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function.

Objective: The objective of this study was to compare modified Shirodkar cerclage to bed rest for treatment of the midtrimester extremely short cervix. Methods: This study used a concurrent retrospective cohort design at two institutions over the same period, 2000–2010. Patients were included at both institutions when midtrimester endovaginal ultrasound cervical length was ≤15 mm and had modified Shirodkar cerclage (cerclage group) at New York Hospital Queens and bed rest (control group) at Weill Cornell Medical Center. Cerclage was placed as high on the cervix as possible. Indomethacin and antibiotics were used perioperatively. Results: The cerclage group included 112 patients and the control group included 55 patients. Median postoperative cervical length in the cerclage group was 3.3 cm (interquartile range 3.0–3.6). Cerclage patients were less likely to deliver preterm at 37, 35, 32, and 28 weeks (P=0.0066, 0.0004, 0.0023, and 0.03 respectively) and had longer latency (median 120 vs. 94 days P<0.0001). Kaplan-Meier survival curve showed a significant benefit in favor of cerclage (P=0.0043). Conclusions: Our data suggest that modified Shirodkar cerclage as high as possible on the cervix with perioperative indomethacin and antibiotics is superior to bed rest for treatment of the midtrimester extremely short cervix (≤15 mm). We propose a randomized trial of this specific technique.

Aims: The sFlt-1/PlGF ratio has been evaluated as a diagnostic marker for preeclampsia (PE). The aim of this study was to explore the use of the sFlt-1/PlGF ratio as an aid in prediction for PE. Methods: 150 patients with a high risk for PE were enrolled in this prospective study. Groups were compared according to the pregnancy outcome: controls (n=114), intrauterine growth restriction (IUGR) (n=14) and PE (n=22) with subclassification early PE<34 weeks (n=6). Measurements of sFlt-1 and PlGF were performed on the automated Elecsys system. Statistical comparison of the sFlt-1/PlGF ratio in different outcome groups and a mixed model analysis using random intercept models were performed. Results: The sFlt-1/PlGF ratio was significantly higher in pregnancies complicated by PE up to 4 weeks before clinical diagnosis compared to controls (106.7±47.7 vs. 21.0±4.1; P=0.02). Levels of the sFlt-1/PlGF ratio were higher throughout pregnancy in women with IUGR compared to PE/control patients (intercept 1.57 vs. 1.30/0.67; P<0.05). The slope for the sFlt-1/PlGF ratio was significantly higher in PE and IUGR pregnancies compared to controls, indicating that a steep increase of the sFlt-1/PlGF ratio correlates with pathologic pregnancy outcomes. Conclusion: The sFlt-1/PlGF ratio can identify pathologic pregnancy outcomes such as IUGR and PE before clinical diagnosis. Repeated measurements are necessary to assess the dynamics in serum values. The time-dependent slope of the sFlt-1/PlGF ratio is predictive for future pregnancy outcome and risk of developing preeclampsia.

Objective: The aim of the study was to evaluate the significance of the presence of thyroid peroxidase autoantibodies (anti-TPO Abs) in type 1 diabetes mellitus (DM1) pregnant women relative to the course of pregnancy and, especially, with regard to metabolic control, thyroid function, maternal complications and neonatal outcome. Methods: In a prospective observational study of 91 DM1 women with singleton pregnancies, anti-TPO, anti-thyroglobulin, thyroid-stimulating hormone (TSH), and free thyroxine index (T4/thyroid binding capacity) were measured in each trimester. At each visit, HbA 1c , body mass index, and units of insulin per kilogram were recorded, as were complications and pregnancy outcome. Results: Twenty-one (27%) of the 78 women who met the inclusion criteria presented with positive anti-TPO Abs. There were no differences regarding glycemic control (HbA 1c ) or insulin dose. First-trimester TSH levels were significantly higher in the anti-TPO-positive group than in the anti-TPO-negative group. Finally, no differences were observed regarding diabetic or obstetric complications and neonatal outcome. Conclusion: One fourth of DM1 pregnant women presented with positive anti-TPO Abs. However, the presence of anti-TPO Abs does not seem to be related with worse metabolic control or adverse pregnancy outcome. Further investigation is needed; meanwhile, the effort for early treatment of thyroid dysfunction and strict metabolic control in all DM1 women should be continued.

Mental health and well-being among obstetrics nurses after perinatal death are understudied. Beyond the normal strain imposed on obstetric nurses, exposure to perinatal death may add significant stress. Two studies were conducted on obstetrics nurses. In study 1, obstetrics nurses were measured longitudinally, at baseline (with no recent history of exposure to perinatal death in the past 3 months), and 3 months after (2 months after two consecutive events of perinatal death have occurred 1 month after baseline). In study 2, a cross-sectional study was conducted comparing obstetrics nurses with a history of perinatal death (nurses from study 1) to obstetrics nurses with no history of exposure to perinatal death in the past 6 months. The results of study 1 showed that obstetrics nurses showed a higher level of psychiatric symptoms [posttraumatic stress disorder (PTSD), depressive, and psychosomatic symptoms] at time 2 (after exposure to perinatal death) in comparison to time 1. The results of study 2 showed a higher level of psychiatric symptoms (PTSD, depressive, and psychosomatic symptoms) in the exposed group in comparison to the non-exposed group. The effect of exposure to perinatal death is severe and needs to be addressed by developing intervention and preparation programs to help obstetric nurses cope with this critical incident.

Maternal overnutrition and obesity are associated with fetal development and cause long-term effects in offspring. However, the effects of a high-fat diet specific to the pre-pregnancy period are not determined. The present study aimed to examine the effect of high-fat diet prior to pregnancy on the liver of mouse offspring. Female C57BL/6J mice were fed a normal chow (15.2% fat by energy) [control diet (CTR) and CTR pre-pregnancy (PP) groups] or a high-fat chow (31.2% fat by energy) [high-fat diet (HFD) and HFD-pre-pregnancy (PP) groups] for 3–4 weeks and then mated with male C57BL/6J mice fed normal chow. Some mothers continued on the same diet until pups reached 21 days of age (CTR and HFD), and others were fed the different chows from gestational day 0 (CTR-PP and HFD-PP) to determine the effects of a high-fat diet during the pre-pregnancy period in HFD-PP/CTR and HFD/CTR-PP comparisons. Liver tissues from pups were subjected to gene expression analysis by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and microarray, and histological analysis using Oil Red O staining (Sigma Chemical Co., Ltd., Balcatta, WA, USA). Lipid droplets were increased in hepatocytes of mice in HFD-PP compared to CTR and those in HFD compared to CTR-PP. Expression of stearoyl-coenzyme A desaturase 1 ( Scd1 ), acetyl-coenzyme A carboxylase beta ( Acacb ), and fatty acid binding protein 5 ( Fabp5 ) was increased by maternal high-fat diet during pre-pregnancy. The results showed that maternal high-fat diet intake prior to pregnancy uniquely affects metabolic phenotype related to health and disease in the liver of the next generation.

Objective: To describe the incidence and clinical features of twin-twin transfusion syndrome (TTTS) with third trimester onset. Methods: We performed a retrospective chart review of monochorionic diamniotic (MD) twin pregnancies delivered during a recent 4-year period. The inclusion criterion was women who received prenatal care at our center from the first trimester onward. Serial ultrasound examinations were performed at least every 2 weeks until delivery to evaluate fetal growth as well as to estimate amniotic fluid volume. The prevalence of TTTS onset after 28 weeks of gestation and clinical features, including neonatal outcomes and placental findings, were elucidated. Results: Meeting our inclusion criterion were 143 MD twin pregnancies, including 15 TTTS cases (10%). Five cases (4%) developed TTTS during the third trimester and underwent a cesarean section immediately after the diagnosis. All of these women exhibited either abdominal distension or uterine contractions. Recipient twins tended to require more intensive cardiopulmonary treatment than donors, however, neither a recipient nor a donor twin suffered neonatal death or neurological impairment. Placental arterio-arterial anastomoses were detected in three out of five cases. Arteriovenous anastomoses were present in all cases, however, venovenous anastomoses were not found in any case. Conclusions: TTTS is a relatively rare complication during the third trimester. It is imperative to be observant for the development of TTTS in MD twin pregnancies with any abdominal symptoms, even if they appear insignificant.

Objective: To evaluate short and medium term outcomes of children born of monochorionic pregnancies complicated by twin-twin transfusion syndrome treated by fetoscopic laser surgery. Methods: This was a retrospective observational study performed between May 2007 and 2012. Neonatal data was from 45 patients under 5 years of age. The prospective observational study was of the neurologic outcome of these children using the Ages and Stages Questionnaire (ASQ), 2 nd edition, French version, at up to 5 years of age. Results: Neurologic assessment at discharge from maternity unit was normal for 41 infants (93.2%). Logistic regression suggested that the risk of neurosensory sequelae was significantly related to the status of donor [odds ratio=4.62 (1.18; 18.0)] and significantly preterm birth <32 weeks of gestation [odds ratio=5.50 (1.38; 21.9)]. Eleven questionnaires were considered abnormal (31.1%). Two children presented a severe neurologic abnormality (5.7%). There was no significant correlation between any area of the questionnaire and status at birth (donor or recipient). Conclusions: The data from our cohort, particularly as regards neurologic outcome, were satisfactory and concordant with previously published results. The use of the ASQ as a screening tool for neurologic outcome in children is original, which allowed in our cohort to highlight early neurological disorders.

Aims: To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11–14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters. Methods : Prospective observational study on 240 fetuses at 11–14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided Analysis. Pearson correlation coefficient (cc) and regression analysis were used. Results : FV increased exponentially with crown rump length and was unrelated to maternal weight (cc=–0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76), smoking status ( t -test, P=0.149) and mode of conception ( t -test, P=0.8). Z-scores (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=–0.026, P=0.733), log 10 multiples of the median (MoM) free beta human chorionic gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was significantly positively correlated with log 10 MoM pregnancy associated plasma protein-A (PAPP-A; regression coefficient=1.420976, R 2 =0.0957, P<0.0001). Conclusions: FV is strongly related to PAPP-A even after adjustment for crown rump length with a mechanism unrelated to placental perfusion. FV is independent of the vast majority of first trimester parameters; hence, it is a promising marker of early fetal growth.

Aims: Compare the need for neonatal resuscitation procedures between newborn infants with and without meningomyelocele (MMC). Results: This retrospective case-control study included 94 neonates with MMC, defined as open spinal dysraphism with exposure of nervous tissue, and 94 controls without malformations, paired with MMC infants by gender, mode of delivery, gestational age and time of birth. Infants were born at a university hospital in São Paulo, Brazil, from 2001 to 2010. After adjusting for perinatal variables (prenatal care, maternal hypertension, birth during the day shift, cephalic presentation, meconium in the amniotic fluid, gestational age <37 weeks and small-for-gestational-age infants), MMC increased the chance of positive pressure ventilation at birth [odds ratio (OR) 4.55 95% confidence interval (CI) 1.82–11.41], intubation at birth (OR 3.94 95% CI 1.14–13.59) and 1-min Apgar score 95% CI 0.99–7.57). Conclusion: MMC is an independent factor associated with the need for positive pressure ventilation and intubation at birth.

Background: Newborn screening for congenital adrenal hyperplasia (CAH) based on measuring 17-hydroxyprogesterone (17-OHP) by immunoassay generates a number of false-positive results, especially in preterm neonates. We applied steroid profiling by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a second-tier test in newborns with positive CAH screening and evaluated its clinical utility in a tertiary care hospital setting. Methods: By performing a 4-year retrospective data review, we were able to test 121 dried blood spots from newborns with positive CAH screening for 17-OHP, androstenedione and cortisol levels by LC-MS/MS. We prospectively evaluated the clinical utility of steroid profiling after the implementation of steroid profiling as a second-tier test in our routine clinical practice. During the 2-year prospective study period, 104 cases with positive initial screening by FIA were tested by LC-MS/MS. Clinical and laboratory follow-up were performed for at least 6 months. Results: The preterm neonates accounted for 50.7% (76/150) and 70.4% (88/125) of screening-positive cases in retrospective and prospective cohorts, respectively. By applying steroid profiling as a second-tier test for positive CAH screening, we eliminated all false-positive results and decreased the median follow-up time from 75 to 8 days. Conclusions: Our data showed that steroid profiling reduced the burden of follow-up exams by improving the positive predictive value of the CAH screening program. The use of steroid profiling as a second-tier test for positive CAH screening will improve clinical practice particularly in a tertiary care hospital setting where positive CAH screening from preterm neonates is frequently encountered.

Aim: To investigate the influence of antenatal magnesium sulfate (MgSO 4 ) application on cord blood brain-derived neurotrophic factor (BDNF) levels – the first-line neuroprotection for preventing cerebral palsy in prematurely born infants. Subjects and methods: A randomized controlled trial was conducted by observing 72 pregnant women who were divided into three groups: group I (preterm pregnancy with MgSO 4 ), group II (preterm pregnancy without MgSO 4 ), and group III (full-term pregnancy as control group). Groups I and II were selected by block permutation randomization on subjects. Inclusion criteria consisted of preterm pregnancy at 34 weeks of gestation or less who were in labor or having planned terminations and receiving antenatal corticosteroids. Exclusion criteria consisted of previous complications caused by MgSO 4 , previous history of antenatal MgSO 4 application in the current pregnancy infant was born before 4 h administration of MgSO 4 or unborn more than 72 h after maximum course of antenatal MgSO 4 of 24 h, prolonged antenatal MgSO 4 treatment (>24 h), refusal to participate, and emergent adverse events during the study. Group I was given intravenous MgSO 4 ; initial dose was 4 g, which was maintained at 1 g/h up to maximum of 24 h. Meanwhile, groups II and III were not given any special treatment. BDNF was examined by ELISA by taking 5 mL cord blood sample shortly after birth. The result was statistically measured by ANOVA. Results: The cord blood BDNF levels in premature infants with antenatal MgSO 4 was significantly higher than in premature infants without antenatal MgSO 4 (11,568 vs. 5027 pg/mL, P=0.000). Moreover, the result was statistically comparable to full-term infants (11,568 vs. 13,300 pg/mL, P=0.085). Conclusion: The application of antenatal MgSO 4 in preterm delivery increased cord blood BDNF levels, which could have a potential role on fetal neuroprotection. Further investigation is needed.

Objective: Recent studies have implicated hepatitis C virus (HCV) in the pathogenesis of immune thrombocytopenia. In pregnancy-associated immune thrombocytopenia, multidisciplinary management is required due to a potential for bleeding complications. We performed a retrospective review of HCV-infected pregnant women and age-matched controls who were not infected with HCV. Methods: One hundred and six women with a HCV viral load were identified from 2009 to 2011. Results: Thrombocytopenia was identified in 10.3% of HCV-infected pregnant women and 1.6% of age-matched controls (P<0.001). Mean platelet count during pregnancy was 120±23×10 9 /L in HCV-infected women and at delivery was significantly lower in HCV-infected women than in controls (P=0.01). Despite the significant difference in platelet counts, there was no significant difference in estimated blood loss (EBL) at delivery. Regional anaesthesia was performed in 73% of thrombocytopenic HCV-infected women and no complications were recorded. There were no fetal bleeding complications. Conclusion: In the first study to date to investigate the impact of HCV on maternal platelet count we demonstrated a significantly higher frequency of thrombocytopenia and a significantly lower platelet count in HCV-infected pregnant women compared with controls. Interestingly, thrombocytopenia had no detectable impact on EBL at delivery.