Volume 40, Issue 3

Background: In utero insults that result in low-birth-weight (LBW) infants are now recognized risk factors for the development of vascular-related diseases in adulthood. Microcirculatory pathologies are believed to form a mechanistic link between fetal insult and the manifestation of illness in adulthood. Objectives: The challenge has been to investigate microcirculatory changes in vivo . The objective of this review is to determine whether LBW infants and individuals undergo abnormal microvascular changes and, if so, whether these changes can be objectively identified and measured by investigating retinal vessels. Methods: An online publication search was carried out using the following keywords to identify and review relevant articles: retinal microvasculature, retinal vessels, small for gestation age, growth restriction, and intrauterine growth restriction. Articles published from 1980 to 2011 were considered. Conclusions: The ability of retinal imaging technology to assess and measure retinal microvasculature makes it a valuable assessment tool. The current tool is, however, unsuitable for non-invasive assessment in infants and young children. Once this hurdle has been overcome, a longitudinal study of LBW individuals from infancy to adulthood, with regular retinal microvascular assessments, would help prove the mechanistic link between LBW and cardiovascular disease in adulthood.

Objective: To investigate the outcome of pregnancy after detection of chromosomal mosaicism and to determine the correlation between human chorionic gonadotropin (free β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) levels from first-trimester-screening with pregnancy outcome. Methods: In a single-center, retrospective survey of the results of prenatal diagnostics performed between January 2000 and March 2011, we identified a total of 40 pregnancies with chromosomal mosaicism. Clinical characteristics and results of first-trimester screening, as well as the outcome of these cases, are described. Results: Out of 40 cases, 21 were defined as confined placental mosaicism, 10 classified as true mosaicism and nine were not classifiable cases. Nuchal translucency (NT) was ≥2.5 mm in 8/30 cases with respective measurements. PAPP-A levels were ≤0.4 MoM in 9/26 cases, with respective measurements, two of them being newborns with growth restriction. Remarkably, in pregnancies of all four children born with severe growth retardation, <3 rd percentile PAPP-A levels were below 0.52 MoM. Conclusions: Our observations show mosaic pregnancy outcomes to be very heterogeneous. Nevertheless, a combination of low PAPP-A and interpretation of chromosomal mosaicism might identify pregnancies at particular risk for fetal growth restriction.

Objective: To evaluate the perinatal impact of metformin and glyburide in the treatment of gestational diabetes mellitus (GDM). Methods: A randomized clinical trial conducted from July 2008 until September 2010 studied 200 pregnant women with GDM who required adjunctive therapy to diet and physical activity. Patients were randomized to use metformin (n=104) or glyburide (n=96). The drugs were replaced by insulin when they reached the maximum dose without glycemic control. Assessed outcomes: weight and neonatal blood glucose. Results: : No difference was found (P>0.05) between the groups regarding maternal age, gestational age at inclusion, body mass index, glucose levels in oral glucose tolerance test (OGTT) 75 g and glycemic control. Difference was found in the number of previous pregnancies (2.84 vs. 2.47, P=0.04) and weight gain during pregnancy (7.78 vs. 9.84, P=0.04) in the metformin group and glyburide respectively. The perinatal results showed no difference (P>0.05) in the percentage of cesarean deliveries, gestational age at delivery, number of newborns large for gestational age (LGA), neonatal hypoglycemia, admission to intensive care unit and perinatal death. We found differences in weight (3193 g vs. 3387 g, P=0.01) and ponderal index (2.87 vs. 2.96, P=0.05) of newborns, and in neonatal blood glucose levels at the 1 st (59.78 vs. 54.08, P=0.01) and 3 rd h (61.53 vs. 55.89, P=0.01) after birth between the metformin and glyburide groups respectively. Conclusions: Weight and ponderal index were lower in the newborns of the metformin group; glucose levels (1 st and 3 rd h after birth) were lower in the glyburide group.

Objective: To determine the incidence, clinical significance and causes of maternal thrombocytopenia in triplet gestations. Study design: The study population consisted of 150 patients with triplet gestation that delivered at our department between 1990 and 2008. Thrombocytopenia was defined as a platelet count <150,000/μL. Patients were classified on the basis of the lowest recorded platelet count observed during pregnancy. Results: A low platelet count was observed during the triplet gestation in 36 cases (24.0%), and after delivery in another 19 cases (12.7%). Thrombocytopenia was mild, moderate, and severe in 75% (27/36), 16.7% (6/36), and 8.3% (3/36) of the cases, respectively. During pregnancy, thrombocytopenia was associated with pregnancy-induced hypertension in 25.0% (9/36) of patients, while gestational thrombocytopenia was diagnosed in 72.2% of the cases (26/36). The mean platelet count showed a strong negative correlation with gestational age (r=–0.953, P<0.001), and at 36 weeks approached the limit of thrombocytopenia. Conclusions: Thrombocytopenia occurs more frequently in triplet gestations than in the general pregnant population, and the rate of moderate and severe forms is higher. The distribution of causes is comparable to that of the general pregnant population. The average platelet count in triplet gestations decreases with gestational age.

Aims: To determine the effects of increasing maternal age and related maternal and possibly paternal factors. Methods: A US database of more than 8 million births was analyzed to determine the relationships between maternal age, maternal ethnicity, marital status, maternal smoking and paternal age on twinning rates. Results: Twinning rates increased proportionally with maternal age. African American women had a higher twinning rate than Caucasian women. Hispanic, Asian and Native American women had comparatively lower rates than Caucasians. After controlling for ethnicity and other maternal factors, increasing maternal age was still related to increased twinning rates. Increased paternal age had a small but significant independent association with an increased rate of twinning. Conclusions: Both increasing maternal and paternal age are related to increased rates of twinning. This age effect is independent of other factors also associated with twinning.

Objective: To examine the population-based trend for cesarean births in twin pregnancies for the last 13 years in Slovenia, and to find correlates for this trend. Methods: We evaluated data from the Slovenian national perinatal information system (NPIS) of all twin pairs born at ≥24 weeks during the period 1997–2009 (n=3916 pairs). Results: We noted a significant and steady increase of about 1.1% cesarean births/year, concomitant with significant increased birth rates at 34–36 weeks, but with a significant decrease over time in neonatal mortality. These trends were neither associated with any particular maternal characteristic nor with increased neonatal morbidity. Conclusions: An association exists between an increased cesarean birth rate, increased preterm births at 33–36 weeks and concomitant significantly reduced neonatal mortality in twins.

Aims: To determine reliably the risk of stillbirth among twin pregnancies. Methods: A data analysis of 3241 and 6581 women with monochorionic diamniotic (MD) and dichorionic (DD) twins, respectively, who gave birth at ≥22 weeks of gestation. Results: The prospective risk (per 1000 women) of stillbirth, 25.3 and 11.5 at gestational week 22, decreased to <10.0 at gestational weeks 31 and 28 among the MD and DD twins, respectively. After single intrauterine fetal death, the co-twin died in utero or within 7 days of life more frequently among MD twins than among DD twins [42.7% (35/82) vs. 2.6% (2/76); relative risk, 16.2; 95% confidence interval, 4.0–65.1]. Conclusion: Women with MD twins were 2.2-fold more likely to experience stillbirth than women with DD twins. The prospective risks of stillbirth were <1.0% for both groups of women at ≥32 weeks of gestation.

Aims: To investigate the association between increased yolk sac diameter and abnormal karyotype. Methods: Retrospective analysis of 42 patients with no history of diabetes between 6 and 12 weeks of gestation with increased yolk sac diameter measuring ≥6mm was evaluated by transvaginal ultrasound. Sonographic findings were correlated with karyotype. The Fisher’s exact test and exact conditional logistic regression analysis were used for statistical analysis. Results: Chromosome abnormalities were found in 76.2% of chorionic villi samples. A statistically significant relationship between karyotype and missed abortion was detected (P=0.001). None of the patients with a yolk size diameter ≥8mm and viable pregnancy had a normal karyotype. Trisomy 15 or 16 was strongly associated with missed abortion (unadjusted odds ratio=14.97, P=0.01). Nine patients with viable pregnancy had a yolk sac ≥6mm (six patients with normal karyotype, one patient with monosomy X, one patient with trisomy 16, and one patient with trisomy 21). Conclusion: Our data indicate that enlarged yolk sac may also be visualized in viable pregnancies. Patients with an enlarged yolk sac and normal karyotype require detailed ultrasound evaluation in the second and third trimester.

Objective: To test the hypothesis that the presence of a male affects birth weight of its female co-twin. Patients and methods: We evaluated a large population dataset of bichorionic twins after exclusion of potential confounders and after controlling for parity and gestational age. We tested the hypotheses that males (M) are heavier than females (F) irrespective of gender mix, parity and gestational age, and the hypothesis that birth weight of twins might be influenced by the gender of the co-twin. Results : There were 819 MM pairs, 777 FF pairs and 1097 MF sets, for a total of 2735 males and 2651 female twins. Male twins were heavier than female twins, irrespective of parity or gestational age; twins born to multiparas were heavier than twins born to nulliparas, except for very preterm births (≤32 weeks); males from MF pairs were heavier than males from MM pairs, but the mean birth weight of females from MF was not different from that of females from FF sets suggesting no “masculinization” effect of the male on birth weight of its female co-twin, irrespective of parity and gestational age. Conclusions: After exclusion of potential confounders and controlling for chorionicity, parity, and gestational age, our data do not support the presence of a “masculinization” effect on birth weight.

In the Netherlands, both the LifeCycle Elipse (LC) and the Astraia software package are used to calculate the risk of having a child with Down syndrome. Therefore, pregnant women can be presented with dissimilar risks. In this study the conformity between these risks before and after harmonization of the screening program and its influence on the performance indicators of the first trimester screening were evaluated. The agreement between combined risks (based on the biochemical parameters PAPP-A and fβ-hCG and a nuchal translucency measurement) was expressed as intraclass correlation coefficient (ICC)=0.99. Conformity between combined risks was better after harmonization (Cohen’s κ=0.75) than before harmonization (Cohen’s κ=0.63). For both risk calculation software packages the area under the ROC-curve was 0.84. The database contained 42 Down syndrome cases; based on the odds of being affected given a positive result (OAPR), LC performed slightly better than Astraia before harmonization (17.9 vs. 21.5, respectively). It has been acknowledged that using different software packages could lead to dissimilar risk calculations. In this study the screening performance indicators of two software packages were quite similar. The agreement of the screening performance after harmonization remains to be seen, but is expected to be even higher.

Objective: Placenta increta or percreta is an uncommon pathology, sometimes associated with high maternal morbidity. Its prevalence increases proportionally to the number of cesarean sections. This study analyzed the changes of our management strategy to devise treatment guidelines for this uncommon disorder. Materials and methodology: Between 2005 and 2011, 10 cases of placenta increta or percreta were managed at our university hospital maternity department. Results: Among the 10 cases, seven were diagnosed prenatally. Two patients were diagnosed early, at 14 and 17 weeks of gestational age, and their pregnancies were terminated. Five had hysterectomies during the intrapartum period, and despite attempted conservative treatment for the two others, hysterectomy proved necessary 2 months postpartum because of intrauterine infections. Seven of the 10 women had hysterectomies. Conclusion: Prenatal diagnosis of placenta increta or percreta is essential to plan the delivery in a competent tertiary care center. The decision to perform a cesarean hysterectomy or leave the placenta in situ for spontaneous delivery is based on the extent of infiltration, the patient’s hemodynamic status, and her desire to remain fertile. The high-risk of infection and severe hemorrhage must not be overlooked should conservative treatment be chosen. This situation requires prolonged close monitoring.

Objective: To evaluate the relationship of fetal sex with obstetric risk factors and perinatal outcomes. Material and methods: Retrospective study of deliveries during 2003–2009 at a tertiary hospital based on the analysis of obstetric and neonatal risk variables according to neonatal sex. Results: Of the 29,530 deliveries studied, the neonate was a boy in 15,038 (50.92%) and a girl in 14,492 (49.08%). The rates of gestational diabetes, prematurity, true umbilical cord knot and nuchal cord were higher for male newborns, whereas the rate of echographic diagnosis of intrauterine fetal growth retardation was higher for female newborns. Mothers of male fetuses had higher rates of cesarean delivery and instrumental vaginal delivery. The indication for ending labor due to the non-reassuring fetal heart rate was also more frequent among male newborns. This group had higher rates of acidemia, although there were no significant differences between sexes in other short-term neonatal outcomes. In all subgroups analyzed here, fetal weight was higher in male newborns. Conclusions: Male sex is an independent risk factor for unfavorable outcomes of pregnancy and delivery.

Cardiotocography and echocardiography are currently standard for fetal heart monitoring. However, both do not provide adequate temporal resolution to measure fetal cardiac time intervals and detect arrhythmias, which can occur during normal sinus rhythm. Fetal magnetocardiography (fMCG) is a non-invasive technique measuring magnetic signals generated by fetal heart activity. Most fMCG devices are installed in research institutions limiting the implementation of this method in a clinical setting. Several institutions made a step forward by installing devices, in particular for fetal investigations, in hospital sites to evaluate the clinical benefit. Based on instrumentation differences which can affect signal quality, there is still no established reference database for fetal cardiac time intervals. A new magnetograph dedicated to fetal recordings was implemented with improved patient comfort. The setting was optimized to establish a standard. A total of 103 healthy fetuses starting as early as possible after the first trimester were recorded and fMCG values of cardiac time intervals were compared to former studies. Data allowed high and reliable detection for all fMCG components starting at 17 weeks. The data were comparable to fMCG multicenter studies, fetal electrocardiography and neonatal ECG results and could serve as a database of norm values for further investigation of fetal arrhythmias.

Aim: Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses. Methods: Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery. Results: Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P<0.001, TC: P<0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P<0.001). Conclusion: Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.

Objective: Tissue-tracking echocardiography (TTE) is a method for quantitative assessment of myocardial contraction and relaxation. The purpose of this study was to assess the feasibility of TTE in fetuses and investigate fetal myocardial properties in normal pregnancies. Methods: Two hundred thirty pregnant women participated in the study. Fetal four-chamber-view cineloops were saved for off-line analysis. Reference values for the global longitudinal peak velocity (V), strain (S), strain rate (SR), and displacement (D) in the fetal heart were established using data from 62 right ventricles (RV) and 68 left ventricles (LV). Furthermore, the change of the motion (V and D) and deformation (S and SR) in the course of the pregnancy was analyzed. Intraobserver variability was assessed in a total of 137 cases. The remaining 93 cases were excluded, as there was no tracking possible. Results: Normal fetuses exhibit a statistically significant increase in all motion parameters in both ventricles with increasing gestational age (GA). In contrast, the deformation parameters with advancing GA decrease. RV has a higher diastolic V and SR than LV. Conclusions: The increase in motion is attributable to fetal cardiac growth, whereas the decrease in deformation para\xadmeters indicates an intrauterine adaptation mechanism. RV appears to have a different relaxation pattern than LV. This study establishes a base for further utilization of TTE in fetal medicine and emphasizes a distinct diastolic difference between RV and LV function.

Background: Staphylococcus aureus is among the most important pathogens of bacteremia in hospitals. Colonizing strains may spread to other patients. Methods: Ninety-two mothers visiting delivery rooms were included in this study. From the mothers, specimens were obtained from the nares and vagina for the detection of S. aureus . From the babies, specimens were obtained from the nares and umbilicus within 24 h in the nursery. Results: The carriage rates of S. aureus were 25% in the parturient mothers and 30.9% in their babies. The majority (55 isolates, 94.8%) of the isolates were methicillin-sensitive S. aureus (MSSA). Of the 55 MSSA isolates, 11 genotypes were identified for isolates from the mothers and five geno-types for isolates from the infants. A major clone was identified and accounted for 82% of 34 isolates from the babies. Nine pairs of mothers and babies were colonized with MSSA; by molecular methods, the paired isolates were indistinguishable in two pairs. Conclusion: Newborn babies acquire S. aureus colonization soon after birth, partly from their mothers. Once S. aureus is introduced into a nursery, spread of the strain may occur if health-care workers do not execute infection control measures strictly.

Aims: Peripheral cannulas in newborns are commonly used for intravenous treatment. However sustained maintenance of cannula patency is often difficult to achieve in this age group. This study compares the duration for which cannula patency can be maintained in newborns under continuous infusion, or an intermittent flushing regimen, with normal saline. Methods: A prospective observational study was conducted during a 12-month period. All newborns admitted to the 16-bed intermediate care unit, who required intravenous treatment, received either continuous peripheral infusion with 0.9% saline at an infusion rate of 2 mL/h or an intravenous cannula, which was flushed with 1 mL of 0.9% saline at least once every 24 h. Results: A total of 53 patients with 86 cannulas were included. Twenty-five (47%) patients received 41 continuous infusions. The intermittent flushing group consisted of 28 (53%) patients with 45 cannulas administered. The cannula patency was significantly longer in the intermittent flushing group (mean 62.1 vs. 92.8 h, P=0.01). The patient’s underlying disease and the cannula insertion site were not related with the duration of the cannula patency. Conclusions: Our study shows that intermittent cannula flushing is associated with improved cannula patency for peripherally inserted venous catheters in newborns.

Neonatology is a relatively new subspeciality of paediatrics, and before this, newborn babies were often managed by obstetricians. The two fields are closely related in the continuity of care that is being provided, and both specialities involve difficult and critical decisions. From personal experience, training in both specialities, even at a junior level, allows a greater understanding of the complexities surrounding these choices and their implications. As such, I propose a short period of mandatory training in both specialities for anyone considering a career in either.

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