Volume 35, Issue 5

Aims: Intrauterine growth restriction (IUGR) has been demonstrated to have serious consequences for health in adult age. These include an increased risk for metabolic syndrome, pulmonary and cardiovascular disorders. These disorders are in part secondary to the development of arterial hypertension, which has been demonstrated to be more frequent in individuals subjected to restricted intrauterine growth. Methods: A review on publications on pathogenesis and epidemiology of hypertension associated to IUGR. Results: Current concepts for this association include a reduced nephrogenesis and increased arterial stiffness, impaired sympathetic regulation and steroid metabolism secondary to IUGR. Early postnatal risk-modifying factors include among others catch-up growth leading to childhood overweight. Conclusion: IUGR increases the risk of hypertension in adult life. Identifying relevant risk factors for arterial hypertension will be the basis for the development of preventive concepts to be applied for predisposed individuals.

Premature infants are more vulnerable to bone fractures than term infants for numerous reasons, directly or indirectly related to prematurity. Although the reported incidence of fractures in this vulnerable population is somewhat inconsistent, the increased risk is clear. Metabolic disorders, genetic disease, accidental trauma, and non-accidental injury can all account for fractures in premature infants, so that determining the etiology is of importance. This increased risk does not appear to continue into childhood. Thus, most of these fractures would be found in children <3 years of age, often within the first year of life. Unfortunately, this is the same age group in which the majority of non-accidental injury (NAI) cases, frequently presenting with fractures, are seen. Further confounding the diagnosis is the possibility of previously undiagnosed fractures from trauma during delivery, and fractures due to bone weakening by metabolic diseases. A multi-dimensional approach using a combination of diagnostic procedures is necessary to properly identify the location of the fractures, the bone structure and characteristics, and the history with regards to family situation and medical treatment. This paper reviews the potential factors related to fractures in premature infants and the differential diagnoses of child abuse fractures.

In this paper we show that the question, “When does human life begin?”, is not one question, but three. The first question is, “When does human biological life begin?”, and is a scientific question. A brief review of embryology is provided to answer this question. The second question is, “When do obligations to protect human life begin?”, and is a question of general theological and philosophical ethics. A brief review of major world religions and philosophy is provided to answer this question but has no settled answer and therefore involves irresolvable controversy. The third question is, “How should physicians respond to disagreement about when obligations to protect human life begin?” and is a question for professional medical ethics. A review of the ethical concept of the fetus as a patient is provided to answer this question. Physicians should manage the irresolvable controversy surrounding the second question by appealing to the ethical concept of the fetus as a patient. It is philosophically sound, respectful of all religious traditions and the personal convictions of patients and physicians alike, and clinically applicable.

Objective: S100B is produced by glia of the central and peripheral nervous systems and is considered a marker of neurologic injury in the perinatal period. Indeed, increased neonatal urine S100B concentration is associated with adverse neurological outcomes including intraventricular hemorrhage and hypoxic-ischemic encephalopathy, while elevated adult serum concentrations are associated with infectious diseases/sepsis. The objective of this study was to determine whether amniotic fluid (AF) S100B concentrations change with advancing gestational age and intra-amniotic infection (IAI). Study design: S100B concentration was measured in the AF of women in midtrimester, at term, and in pregnancies with preterm labor and intact membranes (PTL) or preterm premature rupture of membranes (PPROM), with and without IAI. Placental pathology was performed and neonatal outcomes were analyzed. Results: (1) AF S100B concentration did not change during gestation; (2) patients with IAI had significantly higher AF S100B concentration than those without IAI following an episode of PTL or PPROM and; (3) neonates who had morbidity/mortality had had an elevated AF S100B concentration; however, this could be explained by the association with intra-amniotic infection/inflammation. Thus, AF S100B concentration was not an independent predictor of neonatal morbidity or fetal/neonatal death. Conclusions: An elevated concentration of AF S100B may reflect intra-amniotic infection/inflammation and not necessarily fetal neurologic damage.

Background : Preterm premature rupture of membranes (pPROM) complicates up to one-third of preterm deliveries. We studied the Amniotic Fluid Index (AFI) in order to ascertain its validity as a predictive variable of maternal-fetal outcome in pregnancies complicated by pPROM. Study design : One hundred and fourteen pregnant women with gestational age between 24 and 34 weeks' gestation at the time of pPROM. Patients were categorized into two groups on the basis of AFI value (AFI <5 cm=63 or AFI ≥5 cm=51) performed at the time of admission. Results : AFI numeric values were significantly related to the following maternal-neonatal variables: high maternal body temperature (P≤0.001), maternal high white blood cells (WBC) count (P≤0.001) and to Apgar score >7 at 5 min (P≤0.001). No other significant correlation between the AFI score and others variables (i.e., maternal heart rate, neonatal WBC count or neonatal C-reactive protein [CRP]) were found. Latency in days from pPROM was significantly lower in the group with AFI <5 cm (P<0.05). Interestingly, AFI <5 cm was present in 66% of pregnancies complicated by chorioamnionitis (8/12), and in 70% of neonates affected by RDS at birth (19/27). Conclusion : An AFI score <5 cm at admission may be a useful prognostic variable in the management of third trimester pregnancies affected by pPROM.

Objective: To establish the adenosine deaminase (ADA) activity in women who had been pregnant with a child suffering from central nervous system (CNS) anomaly. Methods: The study group comprised 68 women who had been pregnant with an affected child, and 68 controls matched for age, gestational age and body mass index. Maternal venous blood was collected for measurement of ADA levels. We defined the diagnostic sensitivity, specificity and area under receiver-operating characteristic curve for ADA. Results: Plasma ADA activity was significantly higher in the study group (12.3 U/L, range 1.7–33.3) compared to the median value of 3.3 U/L (range 1.1–34.4) in normal pregnancies (P<0.05). The cut-off point of ADA >5.9U/L was associated with the highest combination of specificity (58.8%) and sensitivity (86.8%). Conclusion: ADA activity in women who have conceived a fetus with CNS malformations was significantly higher than that in normal pregnant women.

Objectives: To assess ductus venosus (DV) indices during the first stage of labor and the effect of ruptured membranes, meconium stained liquor and epidural analgesia (EDA). Methods: Prospective cross-sectional study. Eighty-one women with low-risk singleton term pregnancies participated, 51 had normal labor (Group 1), and 30 experienced ruptured membranes and/or stained liquor (Group 2). Of the latter group 14 received EDA. The effect of various interventions and application of EDA on the ductus venosus index (DVI) and pulsatility index for veins (DV PIV) were tested. Results: The feasibility rate was 94%. A significant increase of DV indices (DVI, DV PIV) was found in group 2 (P<0.001 and P<0.0005, respectively). The A-velocity was also significantly lower in group 2 (P<0.02). A markedly significant increase of DV indices (P<0.0001) among participants receiving EDA was observed in group 2. The mean±SD indices were: 0.53±0.10 for the DVI and 0.68±0.14 for the DV PIV in those women. There was a significant positive correlation of DV indices with the duration of amniorrhea in group 2 (PIV: r=0.66; P<0.002; DVI: r=0.68; P<0.001). Conclusions: Long-term amniorrhea seems to affect the fetal venous circulation reflected in increased DV waveform indices.

Objective: To assess the relationship between scalp pH (FBS) and ST analysis in situations of acidosis with special emphasis on the timing of cardiotocography (CTG), FBS and ST changes during labor. Study design: From a European Union multicenter study on clinical implementation of the STAN methodology, 911 cases were identified where a scalp-pH had been obtained. In 53 cases, marked cord artery acidosis was found (cord artery pH<7.06) and 44 cases showed moderate acidemia at birth (pH 7.06–7.09). Comparisons were made with 97 control cases (pH≥7.20). Results: Of those cases with FHR+ST events recorded within 16 min of delivery, 61% (17/28) had a cord artery pH≥7.20. The corresponding figure for cases where STAN indications occurred for more than 16 min was 19% (13/69) (OR 6.66, 2.53–17.55, P<0.001). Out of the 121 cases with an abnormal CTG, 84 (69%) showed a cord artery pH of <7.10. STAN indicated abnormality in 83% (70 out of 84). The corresponding figure for scalp pH<7.20 was 43% (36/84). In the case of CTG changes at the start of an adequate recording STAN guidelines provided information on developing acidosis in all cases but one (16 out of 17) in the marked acidosis group. STAN guidelines indicated abnormality prior to an abnormal FBS in 14 out of 17 cases. The median duration between STAN indications to intervention and an abnormal FBS was 29 (95% CI 11–74) min. Conclusions: ST analysis, as an adjunct to CTG, identifies adverse fetal conditions during labor similar to that of FBS but on a more consistent basis. The timing of CTG+ST changes relates to the level of acidosis at birth.

Aim: The purpose of this study was to compare the two- and three-dimensional methods for measuring fetal lung volume of normal fetuses. Methods: A cross-sectional study was performed with 51 normal pregnant women between 20 and 35 weeks. The ellipsoid formula (X*Y*Z*0.52) was used for volume calculation with the two-dimensional (2D) method. With the VOCAL TM (Virtual Organ Computer-aided Analysis) method, a rotation angle of 30° was used. Intraclass correlation coefficient (ICC), paired Student's t -test and Bland-Altman plots were used to compare the techniques. To calculate the intraobserver variability we used the ICC and compared the means between the two measures using the paired Student's p -test. Results: VOCAL TM and 2D methods were highly correlated (ICC=0.919 and 0.873 for the right and left lungs, respectively), however, there was a disagreement. The fetal lung volume means calculated by the 2D method were always overestimated in relation to the means obtained by the VOCAL TM , for the right lung (24.02 mL×19.15 mL; P<0.001), as well as for the left (16.03 mL×13.77 mL; P=0.002). As for the intraobserver variability, a good reproducibility was observed for the volume measurement of the left lung by the 2D technique (mean=0.40 mL; P=0.57) and by the VOCAL TM (mean=−0.22 mL; P=0.63). The 2D method, however, presented low reproducibility for the right lung (mean=1.73 mL; P=0.31). Conclusion: The two-dimensional method had low agreement and low reproducibility in relation to the three-dimensional method for measurement of fetal lung volume in normal fetuses.

Our aim was to compare the diagnostic capabilities of the multiplanar mode of 3D ultrasound (3D US) and MRI in the assessment of a fetal enlarged cisterna magna. Two fetuses showing an enlarged posterior fossa by conventional two-dimensional ultrasound at 24 and 29 weeks of pregnancy were assessed using both diagnostic methods. One fetus was found to have Dandy-Walker syndrome malformation. In the other, the syndrome was ruled out using both methods. Our results suggest that multiplanar 3D US is able to achieve similar results as does MRI when observing the fetal brain.

Aims: To review the course of monochorionic (MC) twin gestations in which one or both fetuses were diagnosed with congenital heart disease (CHD) and to identify clinical characteristics regarding the related intrauterine environmental factors particularly associated with non-twin-twin transfusion syndrome (TTTS). Methods: This study is a review of a two-center experience of MC twin pregnancies with CHD born between 2000 and 2006. Results: There were 87 MC twin pregnancies of which 11 were associated with fetal heart disease. We found concordance of CHD in 2 of the 11 twin sets. Among all of the discordant cases, the size of the affected twin was smaller. TTTS was observed in one case associated with CHD; in this case the donor twin had a coarctation of the aorta. Abnormal cord insertion was observed in 9 (69%) out of the 13 affected infants, and a significant relation was found between the presence of CHD and abnormal cord insertion. Conclusions: Of the MC twins, the smaller seemed more likely to be affected by primary structural cardiac anomalies. CHD in MC twins is possibly related to an abnormal cord insertion. Further studies are warranted to determine whether a causal relationship exists.

Aim: To initiate a longitudinal pilot study comparing the effect of nutrient-enriched post-discharge formula (PDF) with standard term formula (TF) on bone strength of very low birth weight (VLBW) infants in the first six months post-term. Methods: Two matched groups of VLBW infants were randomly assigned to enriched PDF (n=10) or TF (n=10) at corrected age of 40 weeks. Anthropometric measurements of growth and measurements of bone speed of sound (SOS) indicating bone strength and bone turnover markers (bone-specific alkaline phosphatase and cross-linked carboxy terminal telopeptide of type I collagen) were taken at term and at three and six months corrected age. Results: The anthropometric measurements of infants fed PDF and TF were comparable at three and six months corrected age. Bone SOS of the PDF group increased from 2760±113 m/s at term to 2877±90 m/s and 3032±60 m/s at three and six months corrected age, respectively (P<0.001). Likewise, bone SOS of the TF group increased from 2695±116 m/s at term to 2846±72 and 2978±83 m/s at three and six months, respectively (P<0.001). No statistically significant difference was found between the groups in terms of growth and bone SOS measurements. The levels of both bone turnover markers decreased significantly during the study period (P<0.001 for both groups). Conclusion: Feeding with PDF after term had no short-term beneficial effect on bone strength and bone turn-over of VLBW infants.

Objective: Parents of preterm infants require information on morbidity and duration of common interventions performed in the NICU. Since locally achieved data are often not available, information is mainly based on educated guesses of health care professionals. The present study compares estimates of neonatal nurses or medical doctors (MDs) in two separate NICUs with local data. Methods: Health care professionals were asked to estimate morbidity and duration of medical interventions of two groups of very low birth weight infants. For comparison, local data were obtained from infant charts and the Vermont Oxford Neonatal Network data base. Results: Incidence of BPD was underestimated by MDs and overestimated by nurses for low birth weight group (500–750 g) and overestimated by nurses for 1250– 1500 g infants. Incidence of IVH was significantly overestimated by nurses for both groups. Duration of ventilatory support was underestimated for infants of a gestational age of 24–27 weeks and overestimated for the age group of 31–32 weeks. Length of stay in NICU was underestimated for infants at gestational age of 24–27  weeks, but not for the 32–33 weeks group. Conclusions: Information based on estimates made by health care professionals may be misleading. Data differ significantly among different NICUs, thus, local data should be obtained by each NICU and used to inform parents appropriately.

Aim: Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. The role of cytokines and growth factors in the pathophysiology of NEC is not yet clearly defined. Among these factors, the intestinal trefoil factor (ITF) is known as cytoprotective to the gut. We studied the cytoprotective effect of trefoil factor in the 1-day-old Wistar rat pup model following hypoxic-ischemic cold stress. Materials and methods: In the present study, thirty 1-day-old Wistar rat pups were randomly divided into three groups: Group 1, normal controls: Group 2, NEC; Group 3, NEC+ITF. Experimental NEC was induced by exposure to hypoxia for 60 s followed by cold stress at 4°C for 10 min. The animals were euthanized at development of NEC, and at 96 h the intestinal tissue was processed and examined for histological changes of NEC. Results: The pathological lesions indicated severe separation of the submucosa and lamina propria and tissue necrosis in Group 2, and slight submucosal and lamina propria separation in Group 3. There were no histopathological changes in the controls. The mean of histological grade of group 2 was 2.8 (range 2–4), and 1.2 (range 0–2) in group 3. A difference was found when the two groups were compared (P<0.05). Conclusion: ITF may provide a new way for the therapy of NEC in rats.

Aim: To evaluate factors affecting survival and long-term outcome of extremely premature infants and to determine whether small for gestational age (SGA) status is an additional risk factor. Methods: Survival was analyzed in 193 infants born between 23 and 27 weeks of gestational age (GA) and compared between SGA (n=43) and appropriate for gestational age (AGA) infants. Long-term outcome was assessed in 123 infants at six years of chronological age by neurological evaluation and cognitive tests. Results: The long-term survival rates were 72.1% for SGA and 84.0% for AGA infants. Significant independent factors affecting survival were GA (OR 1.79 for one week advance, 95% CI 1.36–2.34) and SGA (OR 0.42, 95% CI 0.18–0.997) in comparison with AGA. There were no significant differences in rates of cerebral palsy or mental retardation, 12.0% and 24.0% in SGA, 14.3% and 17.3% in AGA, respectively. Fifty-two percent of SGA and 70% of AGA infants had intact long-term outcome. The perinatal factor found to affect the intact long-term outcome was RDS with surfactant therapy (OR 0.17, 95% CI 0.07–0.45). Conclusion: SGA status as well as short gestation had significant effects on survival. Respiratory complications after birth had a larger detrimental effect on long-term outcome than whether the infant was SGA or AGA.