Volume 41, Issue 3

Aim: The aim of this study was to compare the performance of tests based on the detection of insulin-like growth factor binding protein 1 (IGFBP-1) and placental α-microglobulin-1 (PAMG-1) in diagnosing rupture of fetal membranes (ROM) across different patient populations. Methods: A meta-analysis was conducted on prospective observational or cohort studies investigating ROM tests based on the detection of IGFBP-1 and PAMG-1 meeting the following criteria: (1) performance metrics calculated by comparing results to an adequate reference method; (2) sensitivity thresholds of the investigated tests matching those of the currently available tests; (3) study population, as a minimum, included patients between 25 and 37 weeks of gestation. Sensitivities, specificities, and diagnostic odds ratios were calculated. Results: Across all patient populations, the analyzed performance measures of the PAMG-1 test were significantly superior compared with those of the IGFBP-1 test. Of particular clinical relevance, PAMG-1 outperformed IGFBP-1 in the equivocal group, which comprised patients with uncertain rupture of membranes (sensitivity, 96.0% vs. 73.9%; specificity, 98.9% vs. 77.8%; PAMG-1 vs. IGFBP-1 tests, respectively). Conclusions: Compared with its performance in women with known membrane status, the accuracy of the IGFBP-1 test decreases significantly when used on patients whose membrane status is unknown. In this latter clinically relevant population, the PAMG-1 test has higher accuracy than the IGFBP-1 test.

The insulin-like growth factors and their binding proteins are important for placental and foetal growth. In this study, we have investigated the presence of proteolytic activity directed against insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy. In addition, the effect of protease activity on IGFBP-1 immunoreactivity and IGF binding was characterised. 125 I-IGFBP-1 was incubated with maternal and foetal serum, amniotic fluid and placental extracts. Breakdown of 125 I-IGFBP-1 was determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and autoradiography. The size distribution of endogenous IGFBP-1 was determined by Western immunoblotting. Protease inhibitor studies characterised the proteolytic activity, and Western ligand blotting with 125 I-IGF-I was used to determine IGF binding capacity of proteolysed IGFBP-1. Amniotic fluid samples collected after labour onset contained proteolytic activity that generated 12- and 19-kDa IGFBP-1 fragments that did not bind to 125 I-IGF-I. This activity was not detected in amniotic fluid collected prior to labour onset or in other tissues. Activity was blocked by aprotinin, leupeptin, phenyl methyl sulphonyl fluoride, and Kunitz soybean trypsin inhibitor but not by ethylene diamine tetraacetic acid or pepstatin. Incubation of IGFBP-1 with trypsin generated fragments of a similar size to the amniotic fluid protease. In conclusion, we have demonstrated the presence in vivo of a trypsin-like proteolytic activity that alters the IGF-binding function of IGFBP-1 in pregnancy.

Background: Oxygen supplementation is still part of international resuscitation protocols for premature children. Mechanisms for tissue damage by hypoxia/ischemia in the extreme premature involve inflammation. Aim and method: To study cerebral inflammation after hypoxia/ischemia and oxygen treatment in the premature, we measured NF-κB activity in 5-day-old transgenic reporter mice in response to experimental hypoxia/ischemia. Results were correlated to cerebral histological evaluation and plasma cytokine levels. A treatment strategy with the antioxidant tempol was tested. Results: One day after hypoxia/ischemia NF-κB activation was increased compared to controls [mean difference: 10.6±4.6% (P=0.03)]. Exposure to 100% oxygen after hypoxia/ischemia further increased NF-κB activation compared to hypoxia/ischemia alone [mean difference: 15.0±5.5% (P=0.01)]. Histological changes in the brain were positively correlated with NF-κB activity (P<0.001), but we found no significant difference in tissue damage between resuscitation with air and resuscitation with pure oxygen. Administration of tempol reduced NF-κB activation [mean difference: 14.6±5.0% (P=0.01)] and the plasma level of cytokines; however, the histological damage score was not affected. Conclusion: Cerebral inflammatory response after hypoxia/ischemia in a mouse model with immature brain development corresponding to human prematurity prior to 32 weeks’ gestation was influenced by administration of oxygen. Tempol treatment attenuated inflammation but did not reduce the extent of histological cerebral damage.

Aim: To examine the relationship between maternal stress in early pregnancy and cord-blood ferritin concentration. Methods: The sample consisted of 140 pregnant women who lived in a region that was under rocket attack during a military operation (December 2008 to January 2009). Mothers in the stress group (n=63) were in their first trimester during this period. Mothers in the control group (n=77) became pregnant 4–5 months after the attacks ended. Maternal subjective stress was reported retrospectively. Cord-blood ferritin concentration was compared between stress and control groups, and was the dependent variable in a hierarchical multiple regression analysis. Results: The mean cord-blood ferritin concentration was lower in the stress group compared to the control group (145.7±62.0 vs. 169.3±85.4 ng/mL, P<0.05). The cumulative distribution of cord-blood ferritin showed a shift to the left for the stress group. Hierarchical multiple regression analysis revealed that maternal subjective stress was a predictor for cord-blood ferritin concentration (hierarchical regression: β=–0.18, P<0.05), especially in the stress group (simple slope analysis: β=–0.32, P<0.01). Conclusion: Maternal stress during the first trimester of pregnancy is associated with lower cord-blood ferritin concentration.

Objective: To analyze the clinical situations that leads us to carry out curettage after cesarean section, the ultrasound prior surgery, intraoperative, and pathological findings. Methods: A retrospective study of all cases of postpartum curettage after cesarean section in a level 3 maternity unit. Results: There were 42 curettages to women with cesarean sections (1.6% of all cesarean sections). The indications for curettage were: fever: 21, methrorraghia: 11, and residual trophoblastic tissue: 10. In the previous ultrasound, all indicated curettages for retained trophoblastic tissue showed it, and in a lower proportion those indicated for fever (66.6%) or methrorraghia (22.2%). A total of fourteen curettages (35%) were performed without suspect image of retained tissue, and in all cases the surgeon described to obtain small amount of tissue. From material submitted to pathologic evaluation trophoblastic tissue was found in 64.7%, and there were no differences as curettage indication. Conclusions: When the previous ultrasound do not showed retained tissue, the surgeon did not remove retained material. When extracted there were always in small amounts. Therefore, it could be concluded that after cesarean section the curettage should be indicated only in the presence of evident ultrasound image of retained products.

Aims: To assess the women’s retrospective perception of fetal magnetic resonance imaging (MRI). Methods: Thirty-six women were investigated 1 year after fetal MRI. Data was acquired by telephone interviews and standardised rating scales (i.e., Postscan Imaging Distress Questionnaire, mood and anxiety scales). Results: In retrospect, most women felt that fetal MRI was associated with marked psychological distress, notably with significant greater distress than at the time of the actual investigation. In total, 55.6% of the women rated at least one aspect of fetal MRI as “not tolerable” at follow-up. These findings were irrespective of the affective status and of the outcome of the pregnancy. Yet, MRI was rated as “the most important” investigation during the prenatal period by 69.4% of subjects, and 80.6% felt that they had sufficiently been informed about the MRI findings. Conclusions: The acceptance of fetal MRI was found to be very high; however, fetal MRI is linked with marked psychological distress, which was still present – and in many cases even stronger – 1 year after the investigation. These data highlight the importance of sufficient information about fetal MRI and the necessity of adequate emotional support in this emotional vulnerable patient sample.

Aims: To document racial disparity in an immune modulator, hyaluronan (HA), an antimicrobial, histone H2B (H2B), and an antioxidant, superoxide dismutase (SOD) in amniotic fluid (AF) from African-American (AA) and Caucasian (C) subjects with spontaneous preterm birth (PTB). Methods: In a case (PTB) control (term) study, AF samples were analyzed for HA, H2B and SOD by ELISA. Differences in analyte concentrations between races were documented and a secondary analysis based on histologic chorioamnionitis (HC) was also performed. Results: No differences in the median HA, H2B and SOD were seen between cases and controls. AA cases had lower HA but higher H2B and SOD than controls. Analyte concentrations were not different between C cases and controls. AA samples at term had lower H2B and SOD compared to C samples at term. Cases with HC showed higher H2B and SOD. Conclusion: We report ethnic disparity in AF antimicrobial, immune mediator and antioxidant factors. Dysregulated AF production of HA, H2B and SOD was associated with PTB in AA, not in C, suggesting an overwhelming inflammatory response in AA PTB, whereas inflammation is likely a secondary phenomenon in C PTB.

Objective: To assess mode of subsequent delivery in women with previous instrumental vaginal delivery. Study design: In this retrospective longitudinal study we followed women who underwent instrumental delivery. The study group included all consecutive parturient women who underwent an instrumental vaginal delivery during a 24-month period (1996–1999). We then identified women who had a subsequent delivery in our center until the end of the year 2010. The control group included women who had a spontaneous vaginal delivery from the same time. Results: During the index period we had 349 consecutive successful instrumental vaginal deliveries. Of those, 125 women had a subsequent delivery in our center (35.8%). In subsequent pregnancies, the spontaneous vaginal delivery rate was 76.8% and 90.4%; the instrumental delivery rate was 8.8% and 1.6%; and the cesarean rate was 14.4% and 8.0%, in the instrumental delivery, and spontaneous vaginal delivery groups, respectively (P<0.05). The odds ratio for a woman to undergo either an instrumental delivery or a cesarean after having an instrumental delivery in a previous pregnancy was 2.8 (95% confidence interval 1.4–5.9, P<0.05). Conclusion: Women with a previous instrumental delivery are at an increased risk of requiring either an instrumental delivery or a cesarean section in a subsequent pregnancy compared with women with a previous spontaneous vaginal delivery.

Aim: To identify the significance of associated antenatal ultrasound findings on long-term prognosis following the antenatal diagnosis of cleft lip/palate [CL(P)]. Patients and methods: Retrospective case note analysis of patients seen at a single tertiary referral centre with a diagnosis of CL(P). The patients were classified as those with unilateral or bilateral clefts and then further subdivided according to the presence of associated anomalies, and these were related to pregnancy and neonatal outcome. Results: A total of 125 singleton pregnancies were seen at the antenatal diagnostic unit, 14 of which were subsequently lost to follow-up. Eighty-two (65.6%) had a diagnosis of unilateral CL(P) and 43 (34.4%) a bilateral CL(P). Seventy-five foetuses (67.5%) had no other anomalies detected on antenatal ultrasound. Seventeen patients (15%) underwent a termination of pregnancy. A normal postnatal outcome was seen in 79% of liveborn infants overall. Only 50% of foetuses diagnosed with a single minor anomaly and 4% of the foetuses in whom more than two minor anomalies or one major anomaly had been detected on ultrasound had a normal postnatal outcome. Infants with bilateral CL(P) had a significantly reduced incidence of a normal postnatal course (60% vs. 87.5%, P<0.01). Conclusion: In cases of CL(P), there is a high incidence of associated anomalies detected on antenatal ultrasound and these significantly increase the risk of poor neonatal outcome.

Aims : The study set out to investigate whether the osteopontin (OPN)-CD44-integrin-receptor-system is differently regulated during nephrogenesis in inborn nephron deficit, a major determinant of human primary hypertension and cardiovascular disease in adult life. Methods : We compared a genetic rat model with an inherited nephron deficit, the Munich-Wistar-Froemter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postpartal day 7 (D7). Results : Renal OPN mRNA (–75%, P<0.05) and protein expression (–38%, P<0.05) were strongly decreased at E19 in MWF compared to Wistar. Renal mRNA-expression of CD44 was increased at E19 in MWF (+271%, P<0.05). At D7, renal OPN protein expression was increased (+115%, P<0.05) and renal mRNA-expression of CD44 remained elevated compared to Wistar control (+127%, P<0.05). Conclusions : Altered fetal expression of the OPN-CD44-integrin-receptor-system in the MWF model points to a possible role in low nephron number hypertension and cardiovascular disease.

Objective: To provide the first update on drug safety profiles and adverse drug reactions (ADRs) associated with fetal disorders from the Swiss national ADR database. Methods: We conducted a retrospective study using data from 202 pharmacovigilance reports on drug-associated fetal disorders from the Swiss national ADR database from 1990 to 2009. Evaluated aspects included administrative information on the report, drug exposure, and disorders. Results: The ADR reporting frequency on the topic of fetal disorders has increased during the last 20 years, from only 1 report in 1991 to a maximum of 31 reports in 2008. Nervous system drugs were the most frequently reported drug group (40.2%) above all antidepressants and antiepileptics. The highest level of overall drug intake could be observed for the 1 st trimester (85.4%), especially for the first 6 weeks of pregnancy. The most frequently reported types of fetal disorders were malformations (68.8%), especially those of the musculoskeletal and circulatory systems. A positive association was discovered between antiepileptics and malformations in general and in particular of the circulatory system and the eye, ear, face, and neck. Conclusions: The results suggest that the nervous system drug group bears an especially high risk for malformations. The most commonly identified drug exposures can help focus pharmacoepidemiologic efforts in drug-induced birth defects.

Objective: To assess perinatal outcome in type II monochorionic (MC) diamniotic twin pregnancies (DA) affected by selective intrauterine growth restriction (sIUGR) and abnormal cord insertion managed expectantly. Methods: A prospective longitudinal study from June 2008 and July 2011 on 24 MCDA sIUGR twins. sIUGR was defined as estimated fetal weight below the 10 th percentile in one twin and was classified into three groups based on umbilical artery (UA) Doppler diastolic flow (I: presence; II: constantly absent/reverse (AEDF/ARED); III: intermittently absent or reverse). Marginal cord insertion was defined as insertion within 2 cm of the placental disc edge, and velamentous insertion as a cord insertion into the fetal membranes. Expectant management was chosen in these twins, and absent or reverse A wave in the ductus venosus (DV) was a criterion for delivery. Neonatal outcome was available for all twins delivered. Pathological examination and vascular cast of placentas were performed in all cases. Results: Fourteen twin pregnancies were type II sIUGR, and ten presented an abnormal umbilical cord insertion. Median gestational age (GA) at diagnosis of sIUGR was 18 weeks’ gestation (range 16–20 weeks), and all sIUGR co-twins showed AEDF of UA at a median gestational age of 20 weeks (range 18–22 weeks). Median gestational age at delivery was 30 weeks (range 28–34 weeks) with a median birth weight of 1285 g (range 307–1725 g). pH at birth and base excess (BE) were normal in all IUGR co-twin (pH>7.10, median BE 5.5); Apgar score at 5 min was >7. Perinatal outcome was favorable in all cases. Placental pathological examination confirmed the marginal insertion of the umbilical cord and the absence of anastomosis between the two portions of umbilical insertion. Conclusions: This study highlights that expectant management for sIUGR type II twins with or without an abnormal cord insertion should be a valid option to time delivery for these fetuses as shown by the favorable neonatal outcome.

Aims: To evaluate the prevalence of congenital heart defects (CHDs) in live-born infants with Down syndrome (DS) and to investigate whether these CHDs might be detected during routine second trimester ultrasound screening performed at the primary level. Methods: A retrospective analysis of 66 cases of DS in live-born infants. The infants with DS underwent a detailed echocardiographic examination to evaluate cardiac morphological characteristics and function. Results: Thirty-six live-born DS infants (54.5%) had associated CHDs. According to the apical four-chamber view at the first postnatal echocardiographic examination, we estimated that 20 (55.6%) of the 36 patients with associated CHDs should have been identified during the routine second-trimester prenatal scan [17 infants with complete atrioventricular septal defect (AVSD), two with partial AVSD, and one with non-restrictive perimembranous ventricular septal defect] if the results had been correctly interpreted. An additional seven patients with associated CHDs should have been identified if the evaluation of both outflow tracts had been included into the screening protocol. Conclusion: Our data suggest that the prenatal DS detection rate can be significantly increased by improving obstetricians’ skills of performing adequate foetal cardiac examination as part of the routine 18- to 23-week ultrasound examination at the primary level.

Objective: To prospectively ascertain Qatar’s national perinatal mortality rate (PMR) during 2011, compare it with recent data from selected high-income countries, and analyze trends in Qatar’s PMR between 1990 and 2011 using historical data. Study design: A national prospective cohort study. Methods: National data on live births, stillbirths, and early neonatal mortality (day 0–6) were collected from all public and private maternity units in Qatar (1 st January–December 31 st 2011) and compared with historical perinatal mortality data (1990–2010) ascertained from the database of maternity and neonatal units of Women’s Hospital and annual reports of Hamad Medical Corporation (HMC). For inter-country comparison, country data were extracted from the World Health Statistics published by WHO in 2011 and from the European Perinatal Health Report published by the Europeristat project in 2008. Results: A total of 20,725 births (20,583 live births plus 142 stillbirths) were recorded during the study period. Qatar’s national PMR during 2011 was 9.55 [early neonatal mortality rate (ENMR) 2.7 and stillbirth rate (SBR) 6.85], which was a significant improvement from a PMR of 13.2 in 1990 [risk ratio (RR) 0.72, 95% confidence interval 0.58–0.89, P=0.002]. This improvement in PMR was more significant in ENMR (P<0.001) than in SBR (P=0.019). The stillbirths constituted 55% of PMR in 1990, which increased to 71.72% of PMR during 2011. The RR of PMR had a significant downwards trend between 1990 and 2011 (P=0.016). Qatar’s 2011 PMR, SBR, and ENMR are comparable to those of selected high-income counties. Conclusions: Qatar’s PMR, ENMR, and SBR have significantly improved between 1990 and 2011, and are currently comparable to those of selected high-income countries. An in-depth research to assess the correlates and determinants of stillbirth and perinatal mortality in Qatar is indicated.

Aims: Breastfeeding significantly benefits mothers and infants. We aimed to identify the determinants of its successful initiation. Methods: A retrospective study of 1893 mothers delivering healthy term singletons at a Swiss university hospital from 1/2008 to 3/2009 determined the associations between multiple breastfeeding and early postpartum parameters by univariate and multiple regression analysis. Results: Multiparity was associated with nursing exclusively at the breast at discharge (P<0.001), less use of maltodextrin supplement (P<0.05), bottle/cup (both P<0.001), but more pacifier use (P<0.05). Among obese mothers, nursing exclusively at the breast at discharge was less frequent, and use of all feeding aids more frequent, than among normal-weight women (both P<0.001). Neuraxial anesthesia was associated with use of maltodextrin and bottle (both P<0.05) compared to no anesthesia. Delayed first skin-to-skin contact and rooming-in for <24 h/day were each associated with maltodextrin and cup (P<0.05). Nursing exclusively at the breast at discharge was less frequent (P<0.001), and bottle use more frequent (P<0.05), in women with sore nipples than in those without. Conclusions: Obesity is a potent inhibitor of breastfeeding initiation. Delivery without anesthesia by a multiparous normal-weight mother, followed by immediate skin-to-skin contact, rooming-in for 24 h/day, and dedicated nipple care, provides the best conditions for successful early postpartum breastfeeding without the need for feeding aids or nutritional supplements.