Volume 32, Issue 5

Inflammatory cytokines are involved in both preterm labor and preterm premature of the membranes pathways; however, the interaction between TNF-α and its receptors may dictate the clinical outcome of pregnancy.

Background: Impaired trophoblast invasion is suggested as the main cause of reduced placental perfusion, which results in fetal growth restriction and preeclampsia. Immunological response against the invading tissue has been given as the explanation. Preeclampsia frequently recurs during the next pregnancy. Doppler ultrasound can predict increased vascular impedance in the uteroplacental circulation. Whether signs of increased vascular resistance in pregnancies complicated by preeclampsia are predictive of recurrence during the next pregnancy is unknown. Methods and material: Uterine artery Doppler was performed in 570 pregnant women with preeclampsia. Of these, 139 became pregnant again. The uterine artery Doppler results during the first pregnancy were related to symptoms of preeclampsia in the succeeding pregnancy. Results: Preeclampsia developed again in 43 of the 139 women. Pregnancies with signs of increased uterine artery vascular impedance during the first pregnancy were 3.4 times more likely to develop preeclampsia again (CI 1.58–7.6). Similar results for a small for gestational age newborn were 9.7 (CI 1.1–90). Conclusion: Increased uterine artery vascular impedance in pregnancies complicated by preeclampsia increases the likelihood of recurrence and growth restriction during the next pregnancy. The Doppler information gathered during the first pregnancy might thus select cases for special surveillance and possibly prophylactic anti-platelet treatment in the next pregnancy.

A nested PCR was used to detect TTV DNA in serum from 490 mother-infant pairs to determine the rate of vertical transmission of TTV in Guangzhou City, P.R. China. TTV DNA was positive in 87 mothers and 12 of their babies, giving a prevalence of 17.8% in pregnant women and a mother-to-child transmission rate of 13.8%. In eight mother-infant pairs, TTV DNA nucleotide sequences from the mothers and their corresponding infants were identical. The homology of Guangzhou TTV and Japanese TTV ranged from 85.3%–98.2% at nucleotide level. TTV infection is common in pregnant women in South China and vertical transmission can occur. Guangzhou’s and Japanese TTV isolates belong to the same genotype.

Aims: Risk estimation for Down’s syndrome in antenatal serum screening with maternal age and multiple serum biomarkers is usually complicated and computationally intensive. We have developed a simple scoring system using the Spiegelhalter-Knill-Jones approach, which was based on Bayesian theorem and the logistic regression model. Methods: A prospective data set with 3842 singleton pregnancies including 6 affected pregnancies served as “trained data”. Maternal age, maternal serum alpha-fetoprotein and human chorionic gonadotrophin levels of each pregnant woman were adopted as the predictors to establish the scoring model using the S-KJ approach. Model validation was undertaken using a receiver operating characteristics (ROC) curve with another 3050 singleton pregnancies including 4 affected pregnancies (“validated data”). Results: For the trained data the sensitivity and specificity of the scoring system at cut-off value of 1:250 was 66.7% and 92.6%, respectively. For the validated data the sensitivity and specificity at the same cut-off point was 75% and 92.2%, respectively. The area under the ROC curve of the trained and validated data was 76.96% (95% CI: 51.80–100%), and 94.07% (95% CI: 84.47–100%), respectively. Conclusions: The S-KJ scoring system has been demonstrated to be a simple, and efficient method for the risk estimation of Down’s syndrome. This system can be applied to other antenatal serum screening systems.

Aims: The association between alleles at two loci of the polymorphic β2-adrenergic receptor (β2AR) gene and pregnancy outcome was determined. Methods: In a case-control study, buccal swabs obtained from 159 mother-infant pairs after a preterm or term birth were analyzed by gene amplification and endonuclease digestion for polymorphisms at codons 16 and 27 of the β2AR gene. Results: Homozygosity for allele A at codon 16 (Arg-16) occurred in 26 (20.5%) of 127 mothers with a term birth and in none of the mothers who had a spontaneous preterm birth (p = 0.002). Conversely, 24 of 32 (75.0%) mothers with a spontaneous preterm birth, as compared to 58 of 127 (45.7%) mothers with term births, were Arg-16/allele G (Gly-16) heterozygotes (p = 0.003). There was no relation between pregnancy outcome and infant genotype at codon 16 or maternal or infant genotypes at codon 27. The alleles at codon 16 and 27 were in linkage disequilibrium and the combinations of Arg-16-Gln-27 homozygosity (p = 0.04) and Arg-16/Gly-16-Gln homozygous (p = 0.01) were associated with a decreased and increased rate of spontaneous preterm birth, respectively. Conclusion: At codon 16 of the β2-AR gene, maternal Arg-16 homozygosity protects against, and Gly-16 predisposes to spontaneous preterm birth.

Objective: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and in fetal cord blood at delivery. Methods: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, Illinois, USA), with p < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking and in fetal blood by cord blood analysis at delivery. Cord pH was also recorded. Results: There was no significant correlation between maternal IGF-1, IGF-2, or IGFBP-3 levels and fetal acidosis. However, a significant correlation does exist between cord IGF-1 levels and fetal acidosis. Conclusion: Fetal cord IGF-1 has a significant correlation with fetal acidosis at delivery.

Objective: To determine which intrapartum fetal heart rate parameters in the presence of severe neonatal acidosis (pH < 7.0) appropriately predicts the development of neonatal seizures in the context of hypoxic ischemic encephalopathy (HIE). Methods: The intrapartum fetal heart rate tracings of 25 neonates who developed neonatal seizures secondary to HIE were compared with 25 matched neonates with similar pH and gestational age who did not develop seizures. All patients had at least 2 hours of intrapartum fetal heart rate patterns available for review. We compared the fetal heart rate parameters of prolonged deceleration, variable and late decelerations, variability, accelerations, fetal heart rate baseline and duration of the fetal heart rate abnormality. Comparison between the groups was done using chi-square for nominal data and student t-tests for continuous data. Results: Neonates with seizures 2° HIE had a significantly longer duration of abnormal fetal heart rate patterns (72 ± 12 minutes vs 48 ± 12 minutes, p < 0.001). Discussion: This study demonstrated that in the setting of neonatal acidosis the development of seizures is related to the period of stress (duration of the abnormal fetal heart rate pattern).

Aim: To evaluate whether computerized CTG (cCTG) is a reliable method of predicting neonatal outcome in pregnancies complicated by pregestational diabetes at term. Patients and methods: We considered 27 pregnant women affected by pregestational diabetes and 46 normal pregnancies as controls that fulfilled the following criteria: singleton, Caucasian, euglycemic pregnancies at term (>37 weeks gestational age). All women delivered by cesarean section (CS), with an antepartum cCTG performed within one hour before the CS and an UBGA available at birth. No patient was in labor during FHR monitoring. Results: Among cCTG parameters, accelerations 15 bpm, HV min, HV ms and STV were significantly lower in comparison to controls. We observed that in the diabetic pregnant women the parameter STV was not able to predict or to linearly regress with the most important UBGA parameters: pH and pCO 2 . Contrarily, in normal pregnancies, the STV linearly regressed with both the pH (p < 0.03) and pCO 2 (p < 0.04). Conclusions: Computerized FHR criteria may not be applicable to fetuses in pregestational diabetic pregnancies at term. Therefore some criteria should perhaps be modified for a correct interpretation of cCTG in these pregnancies.

Recovery of nucleated cord blood cells after storage in liquid nitrogen was evaluated. Red cells were depleted using Ficoll-Paque™ or Puregene ® red cell lyses. Freeze Medium contained 10% dimethylsulfoxide and 20% serum for cryoprotection. Recovery of the original cell population remaining serviceable for fluorescence activated cell sorting (FACS) was 12 ± 10% (average ± standard deviation), with a range of 1% to 55%. Viability measured by FACS analysis after freezing was significantly lower than that of the same specimens prior to freezing, 62 ± 20% compared to 91 ± 11% (p < 0.001). Percentage CD45+34+ cells were the same for fresh and frozen cells. Gestational age at which specimens were collected had no effect on the percent cells carrying the CD45+34+ markers. We conclude that better cryoprotective supplements are needed to insure consistent high recovery of viable nucleated umbilical cord blood cells after preservation in liquid nitrogen.

Aims: To register the prevalence of cerebral palsy (CP) and determine etiological factors for the condition. Methods: Population based study with registration of CP-cases in children born during the 30-year period 1970–99. Cases with postneonatal etiology were excluded. Results: 166 CP-cases were registered among 70 824 children, a prevalence of 2.3 per 1000 live born infants. The prevalence did not change significantly during the period. 66 (40%) were low birthweight infants (LBWIs; <2500 g), and 100 (60%) normal birthweight infants (NBWIs; ≥2500 g). The origin was classified as prenatal in 37 (22%), perinatal/neonatal in 78 (47%) and unclassifiable in 51 (31%). In LBWIs 39/66 (59%) had a perinatal/neonatal etiology, most frequently intra- or periventricular hemorrhages (IVH/PVH) and/or periventricular leukomalacia (PVL) or cerebral infarctions (CI) (17; 44%). In NBWIs 39/100 (39%) had a perinatal etiology, most frequently hypoxic-ischemic encephalopathy (HIE) (31; 79%). Conclusions: In a substantial percentage of CP-cases perinatal/neonatal brain injury was classified as the cause. Among these IVH/PVH/PVL/CI dominated in LBWIs, while HIE dominated in NBWIs. Our data may point to preventability of a larger part of CP than earlier suggested.

Objective: Abnormal inflammatory responses are implicated in the pathogenesis of neonatal disease. This study aimed to describe the neonatal cytokine response using an in vitro model of stimulated cord blood. Methods: Cord blood samples (n = 12) were incubated in RPMI 1640 medium with and without lipopolysaccharide. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, interferon (IFN)-γ and IL-10 were determined by multiplex immunoassay at 0, 1, 3, 6 and 24 hours of incubation. The difference between stimulated and control response was defined as the potential secretory capacity (mean ± S.E.M.; pg/million white cells). Analysis included a Kruskal-Wallis test and post-hoc Mann-Whitney U test. Results: All cytokine capacities increased rapidly by 1 hour (p < 0.001), except IL-10 (p = 0.04). TNF-α peaked between 3–6 hours (1581 ± 377 pg/million WC), declining by 24 hours. Similarly, IFN-γ peaked at 3 hours. Capacity ascended throughout the incubation period for IL-6, IL-8 (631 ± 75 pg/million WC) and IL-10 (311 ± 37 pg/million WC). Overall, IFN-γ capacity was lowest (72 ± 10 pg/million WC) and IL-6 capacity was greatest (61489 ± 7059 pg/million WC). Conclusion: The neonatal inflammatory response is chronologically similar to that determined in adults. Immature neonatal T-cell function may account for the lower IFN-γ production. These results may expand our knowledge of neonatal disease, etiology and management.

Aims: To evaluate the potential benefit of amniotic fluid and amniotic/placental membrane cultures for the management of early-onset sepsis in preterm infants. Methods: The results of amniotic cavity cultures obtained during cesarean section and of peripheral blood cultures and surface swabs obtained from the preterm infant at the time of admission were analyzed with respect to the diagnosis of clinical sepsis in 221 preterm infants <34 weeks of gestation. Results: 136 (61.5%) patients had negative amniotic cavity culture results or growth of contaminants, 56 (25.3%) had growth of Ureaplasma urealyticum , and 29 (13.1%) of other pathogens. The corresponding numbers for surface swabs were 82.8%, 11.6%, and 5.6%. A positive blood culture was found in only two neonates. Fifty-four patients (24.4%) had clinical early-onset sepsis. Patients with amniotic cavity culture results that were positive for other pathogens were significantly more likely to experience clinical sepsis than patients with negative culture results (51.7% vs 15.1%, OR 6.1, p < 0.0001). Regarding surface swabs, this correlation did not reach statistical significance. Conclusion: The strong association between positive amniotic cavity culture results and clinical early-onset sepsis supports the existence of a causal relation and provides evidence for the potential value of amniotic and/or placental membrane sampling in the management of early-onset sepsis in preterm infants. Surface swabs add no additional information and hence should not be performed routinely.

Massive hepatic infarction associated with pregnancy is extremely rare, but is potentially fatal. A 35-year-old primigravida with mild preeclampsia developed acute right upper quadrant pain and marked elevation of liver enzymes at 26 weeks’ gestation. After emergent cesarean section, her condition was complicated by oliguric renal failure and pulmonary edema with further deterioration of hepatic function (aspartate transaminase 4339 IU/L; alanine transaminase 3489 IU/L; lactate dehydrogenase 10780 IU/L). The contrast-enhanced computed tomography revealed non-enhancing low attenuation throughout the right lobe of liver, compatible with infarction. Continuous hemodiafiltration was initiated as renal support on postpartum day one. However, excessive fluid accumulation persisted, and she developed severe edema formation in both lung and systemic body surface. To ameliorate microvascular endothelial injury, corticosteroid therapy was begun on postpartum day five. Following treatment initiation, her renal and hepatic function showed steady improvement, accompanied by drastic resolution of edema formation. She was discharged five weeks postpartum with no additional treatment, and is without sequelae six months later. Massive hepatic infarction should be considered in preeclamptic patients who present acute abdominal pain and severe hepatic dysfunction, and continuous hemodiafiltration with corticosteroid therapy may improve the maternal outcome.

Glanzmann’s thrombasthenia is an inherited hemorrhagic disorder characterized by a severe reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists due to qualitative or quantitative abnormalities of platelet glycoprotein IIb-IIIa. Glanzmann’s thrombasthenia is characterized by potentially major mucocutaneous bleeding and prolonged bleeding time. Platelet counts, platelet morphology, prothrombin, and activated thromboplastin times are all within normal ranges in patients with Glanzmann’s thrombasthenia. Pregnancy and delivery are rare in Glanzmann thrombasthenia patients and have been associated with immediate postpartum hemorrhage. We describe the peripartum management of a 31-year-old primipara with Glanzmann’s thrombasthenia who underwent spontaneous vaginal delivery. Four units of single-donor platelets, two units of packed red blood cells, 36 µg/kg recombinant human coagulation Factor VIIa (rFVIIa) were given during peripartum management.