Volume 32, Issue 1

Dilatation of the fetal cerebral ventricles (ventriculomegaly) is a generic sonographic sign common to several pathological entities carrying different prognoses. The main causes of fetal ventriculomegaly are aqueductal stenosis, Chiari II malformation, Dandy-Walker complex and agenesis of the corpus callosum. Ventriculomegaly is easily recognized by ultrasound by measuring the atrial width. This simple measure allows the recognition of mild forms of ventricular dilatation and is used as a screening method for ventriculomegaly. However, although the diagnosis of ventriculomegaly is easy, the prenatal identification of the cause of ventricular dilatation is a more difficult task. To this end, the evaluation of the posterior fossa in association with the visualization of the corpus callosum is a useful landmark. Research into the cause of ventriculomegaly is clinically useful, since the prognosis mainly depends on the etiology and on the presence of associated anomalies. In this article the role of prenatal sonography in recognizing the cause of ventriculomegaly and the prognostic value of the prenatal sonographic findings are discussed.

Interest for maternal fetal movement counting as a method of screening for fetal well-being boomed during the 1970s and 1980s. Several reports demonstrated that the introduction of counting charts significantly reduced stillbirth rates. However, in 1989, a large study appeared in The Lancet that annihilated research in this field by deeming charts ineffective. In retrospect, it seems evidence was lacking. This review revisits the subject of the significance of fetal movement counting in predicting outcome and reducing stillbirth rates. A structured search was performed to identify studies relating to pregnancy outcome and its association with maternal perception of fetal movements. Suspected preliminary or redundant material was excluded. Only publications from Western countries dating from after 1970 were included. Twenty-four studies were identified. Available data demonstrate that reduced fetal movements are associated with adverse pregnancy outcome, both in high and low risk pregnancies. Increased vigilance towards maternal perception of movements (e.g. by performing movement counting studies) reduces stillbirth rates, in particular stillbirths deemed avoidable. While screening for fetal well-being by maternal fetal movement counting can reduce fetal mortality rates, a resurrection in research activity is urgently needed to optimize its benefits.

Aims: To investigate the expression of apoptosis-related genes in preeclamptic placentas and the possible mechanism of the regulation process. Methods: Complementary DNA microarrays were employed to compare gene expression profiles of five preeclamptic and five normal placentas. Results: Among the 368 genes detected over 35% showed an over 2-fold difference of expression between preeclamptic placentas and normal placentas. Many genes involved in cell cycle or apoptosis were more highly expressed in preeclamptic placentas than in normal placentas. The expression of many immune-activation genes in preeclamptic placentas was also higher than that in normal placentas. Additionally, many cytokine receptor/ kinase genes were also induced in preeclamptic placentas. Conclusions: The change in expression of cell apoptosis related genes in placentas might be involved in the pathogenesis of preeclampsia, while the activation of the immune system might be one cause of this change.

Aims: To evaluate the impact of induction of labor with vaginal tablets of prostaglandin E2 on the rate of cesarean section (CS), and to identify possible predictors of successful vaginal delivery. Methods: 1541 consecutive women admitted for induction of labor with vaginal tablets of PGE2 were retrospectively compared with 574 consecutive women with spontaneous onset of labor. Results: Maternal age, nulliparity, previous CS, gestational age, and birth weight were similar in the study and control groups. The CS rate was twofold higher in the study group (20.7% vs 10.6%). CS rates in the study and control groups were 26.9% and 12.8% for the nulliparous women, and 11.2% and 5.1% for the multiparous women with no previous CS. Neither group had major maternal or fetal complications. A logistic regression model and stepwise analysis showed that nulliparity, previous CS, maternal age, number of PGE2 applications, birth weight, and the induction of labor by itself were independent significant risk factors for increased CS rate. Conclusions: Induction of labor with vaginal PGE2 tablets results in a vaginal delivery rate of 79.3%, with apparently no serious maternal or fetal complications. Nulliparity, and previous CS are the most significant risk factors for increased CS rate. However, even after these risk factors are excluded and controlling for possible predictors for CS, PGE2 induction is independently associated with a twofold increase in CS rate, most often because of labor dystocia.

The aim of our study was to investigate the cervical immunoglobulin A concentration in women with threatened preterm delivery. Immunoglobulin A concentration in the cervical mucus of 80 women with symptoms of preterm delivery was measured using radial immunodiffusion. The results were compared with those of 60 healthy pregnant women. Concentrations of immunoglobulins in maternal serum were also measured. There was no significant difference of cervical immunoglobulin A (IgA) concentration between women with threatened preterm delivery and controls: 53.98 (0.0-189.7) mg/l vs. 61.7 (1.4-400.9; p<0.4) mg/l (median, range). The median of cervical IgA levels in the group of threatened preterm delivery did not differ significantly between patients delivered preterm (n=34) or at term (n=46): 38.3 (0.0-187.9) vs. 65.7 (1.4-189.7; p<0.2) mg/l. Women with a normal vaginal flora showed a significantly higher cervical IgA concentration than those with a pathological colonization: 72.7 (0.0-187.9) vs. 42.5 (0.0-189.7) mg/l. Patients with a pathological vaginal smear and preterm delivery had the lowest IgA levels (35.0; 0.0-187.9 mg/l). Measurement of cervical IgA concentration does not differentiate between women who deliver before or at term.

Objective: This study was performed to determine the benefits and risks of multiple courses of corticosteroids in patients with preterm premature rupture of membranes (PPROM). Method: We retrospectively evaluated the pregnancy and neonatal outcomes of women with singleton pregnancies, who were admitted at 24-32 weeks of gestation due to PPROM. Patients were categorized into 3 groups according to antenatal corticosteoid exposure: (1) a nonuser group, (2) a single-course group, and (3) a multiple-course group. Result: A total of 170 patients were included in the study, with 50 in the non-use group, 76 in the single-course group, and 44 in the multiple-course group. Univariate analyses showed that clinical chorioamnionitis occurred with highest incidence in multiplecourse group (X[2]=6.20, p<0.05) and the incidence of neonatal respiratory distress syndrome (RDS) was lowest in the multiple course group (X[2]=10.0, p<0.01). Multiple logistic regression analyses showed that multiple courses of corticosteroids were independently associated with clinical chorioamnionitis (odds ratios=13.15, p<0.05) whereas no significant association was found between RDS and multiplecourse corticosteroids after adjusting for confounding variables (odds ratios=0.28, p=0.06). Conclusion: Multiple courses of antenatal corticosteroid therapy were found to be associated with an increased risk of clinical chorioamnionitis and seemed not to reduce the incidence of RDS and other neonatal morbidities in patients with PPROM.

Although maternal amniotic and vaginocervical cytokines are known to play a role in triggering preterm delivery, the effects of activating fetal phagocytes and platelets are not clear. In an attempt to clarify this issue, we measured levels of myeloperoxidase (MPO), a phagocyte activation marker, and soluble p-selectin (sCD62p), a platelet activation marker, in umbilical cord blood samples from 2200 consecutive cord blood collections, 106 of which were from preterm infants. MPO and sCD62p levels were correlated to gestational age and preterm delivery. It was found that MPO levels were significantly higher in preterm infants and were not significantly correlated to gestational age. In contrast, sCD62p levels were lower in preterm infants and were negatively correlated to gestational age. In summary, we showed that fetal phagocyte activation as demonstrated by higher cord blood MPO levels is associated with preterm delivery, but platelet activation as shown by lower sCD62p levels is not. This suggests that fetal phagocyte activation may be implicated in preterm delivery, and subsequently in prematurity related inflammatory insults.

Aim: To evaluate whether fetal magnetic resonance imaging (MRI) could replace early postnatal MRI in fetuses with central nervous system (CNS) anomalies. Methods: Thirteen pregnancies presenting with fetal CNS anomalies were investigated using MRI. Indications included ventriculomegaly combined with additional CNS anomaly (n=5), isolated ventriculomegaly (n=2), arachnoid cyst (n=2), holoprosencephaly (n=1), complex malformation syndrome (ns1), Dandy walker malformation (n=1) and midline cyst (n=1). Early postnatal MRI followed within the first six weeks of life. Results: Investigation with early postnatal MRI confirmed the fetal MRI diagnosis in all cases. Investigation with postnatal MRI presented additional information in two cases. However, there was no change in patient care. Conclusions: Fetal MRI should replace early postnatal MRI in infants with CNS anomalies.

Objective: To determine the association between changes in bone turnover markers and bone strength of very low birth weight infants during the first eight postnatal weeks. Study design: Twelve very low birth weight premature infants [mean gestational age: 28.4+-0.6 weeks, mean birth weight: 1131+-62 grams] participated in the study. Bone strength was evaluated weekly by quantitative ultrasound measurements of tibial bone speed of sound (SOS, Sunlight Omnisense™). Bone specific alkaline phosphatase (BSAP), a marker of bone formation, and carboxy terminal cross-links telopeptide of type-I collagen (ICTP), a marker of bone resorption, were collected at the ages of one, four and eight weeks. Results: BSAP increased significantly (from 119.9+-16.2 U/L to 132.1+-11.9 U/L and 152.1+-15.7 U/L at one, four and eight weeks of life, respectively, p<0.05). ICTP decreased significantly during the study period (from 122.3+-8.7 ng/ml to 96.0+-4.8 ng/ml and 92.3+-5.4 ng/ml at one, four and eight weeks of life, respectively; p<0.05). There was a significant decrease in bone SOS (from 2886+-29 m/sec to 2792+-30 m/sec and 2753+-30 m/sec at birth, four weeks and eight weeks of life, respectively; p<0.02). There was no correlation between the levels of bone markers and bone SOS. Conclusion: In VLBW premature infants, there is a significant decrease in bone strength concomitant with biochemical evidence for new bone formation (increase in BSAP and a decrease in ICTP) during the first eight postnatal weeks. Changes in the biochemical markers could not predict the changes in bone strength.

The aim of the study was to examine the ponderal index in small for gestational age (SGA) triplets. Prospectively collected data from a cohort of triplets born at 28 to 37 weeks were analyzed. A low neonatal ponderal index (birth weight / [length] [3]) was defined as less than 1 SD below the mean (2.0), and SGA was considered as birth weight below the 10th percentile by triplet standards. We studied 2181 sets of triplets. Triplets delivered at <=33 weeks have a lower mean ponderal index compared with those delivered at >33 weeks. About 70% of SGA triplets do not have a low ponderal index, whereas 79.2% of infants with a low ponderal index are not SGA by triplet standards. Both the frequency of a low ponderal index and the frequency of infants with a low ponderal index who are not SGA decrease with increasing gestational age. We conclude that the majority of triplets with a low ponderal index might not be considered growth restricted, supporting the concept that reduced fetal weight of triplets is more likely a physiological rather than a pathological phenomenon.

In order to evaluate the determinants of high and low ponderal indices in triplets, we analyzed prospectively collected data from a cohort of 2181 triplet births. Low and high neonatal ponderal indices (birth weight/ [length] [3]) were defined as below or above 1 SD from the mean. The mean ponderal index was of 2.4+=0.4. At 30-31 weeks, there were significantly more infants with a low ponderal index; after 33 weeks, more infants were born with a high index. Birth weights of infants with a high index were significantly higher throughout the entire range of gestational ages, whereas their lengths were significantly smaller. Both birth weights and infant length had significant correlations with gestational ages for infants with a low (R[2]=0.97 and R[2]=0.94, respectively) as well as with high ponderal indices (R[2]=0.95 and R[2]=0.94, respectively). The regression analyses suggest, however, different patterns for infants with low or high ponderal indices.

Our objective was to determine the association of the ponderal index with birth weight discordance in triplets. We analyzed data from triplets delivered at 28-37 weeks for birth weight discordance (>25% difference between the heaviest and lightest triplet). Three categories of discordance (low skew, symmetrical, and high skew) were classified according to the relative position of the middle triplet. Birth weights and the ponderal index (birth weight/ [length] [3]) of all concordant and discordant triplet groups were compared. Of 752 triplet sets included, 184 (24.5%) were discordant. Total triplet birth weight was higher in the concordant compared to all discordant categories. As opposed to birth weight, where only the middle triplet differed according to discordance pattern, the ponderal index for the largest triplet was significantly higher in the low skew discordant group compared to the concordant and other discordant triplet groups. In contrast, the ponderal index for the smallest and middle triplets were similar among the discordant groups. We concluded that discordance in triplet pregnancies exhibits different patterns of mass (birth weight) versus size (ponderal index). Our findings suggest that it may be the size of largest triplet that determines the presence or absence or discordance in triplet gestations.

The purpose of the study was to further evaluate the relationship between maternal height and neonatal ponderal index and length. A total of 774 triplet sets with matched maternal stature was available for analyses. We found a significant correlation between maternal height and infant length for both nulliparas (R[2]=0.70, p=0.04) and multiparas (R[2]=0.99, p=0.00005). The slopes of the regressions were different than zero, but the difference between the respective regressions was not significant (p=0.83). The analysis revealed a significant correlation between infant ponderal index and maternal stature for nulliparas (R[2]=0.68, p=0.04) but not for the multiparas (R[2]=0.08, p=0.6). The slope of the regression for nulliparas was different than zero, but that for the nulliparas was not. The difference between the respective regressions was significant (p=0.03). We conclude that taller mothers deliver longer infants, irrespective of parity, whereas the effect of maternal height on the ponderal index is parity-dependent.

Meconium aspiration induces pulmonary inflammation and reduces surfactant function. We hypothesized that albumin mixed with meconium attenuates pulmonary inflammation and improves surfactant function after meconium aspiration. We measured the concentration of free fatty acids (FFA) in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA:albumin ratio of 1:1. Newborn piglets, 0-2 day of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O[2], were randomized to group A receiving meconium (n=12), or group B receiving meconium + albumin (n=12), 3 ml/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean arterial blood pressure was <20 mm Hg or base excess was <-20 mmol/L. During 8 h of reoxygenation the interleukin-8 concentrations in tracheobronchial aspirates increased 5-fold more in the meconium vs. the meconium + albumin groups (93+-56 vs. 18+-4 pg/mL, p<0.005). There were no differences between the groups for tumor necrosis factor α in tracheobronchial aspirates, recruitment of inflammatory cells in the airspaces or surfactant function in bronchoalveolar lavage fluid. In conclusion, albumin significantly decreased interleukin-8 concentrations in tracheobronchial aspirates after meconium aspiration.

Aims: To document, and explain, the pulmonary paradox whereby despite relative lung immaturity, preterm infants exposed to amniotic infection (AI) have better postnatal pulmonary function than those exposed to preeclampsia (PE). Methods: Lung maturation was characterized in 65 preterm perinatal deaths [AI (n=40) and PE (n=25)] and postnatal respiratory function in 100 preterm survivors [AI (n=50) and PE (n=50)]. Results: At autopsy, lung architecture was in advance of gestational age in 5% of AI infants versus 40% of PE infants (P<0.001). In survivors, the groups were similar in age and Apgar scores. At birth, 40% of the AI group required continuous positive airway pressure or mechanical ventilation versus 24% of the PE group (NS). However, 24 hours later, only 1 AI infant had deteriorated compared to 40% of PE infants (P<0.05). Conclusions: Accelerated morphologic lung maturation in preterm PE infants does not translate into improved postnatal respiratory function. Most likely, this is due to a relative lack of surfactant, ascribable to low stimulant cytokine and high TNF-α levels. An intrauterine history supplemented by an antenatal cytokine profile could identify an increased exogeneous surfactant need in preterm infants exposed to PE.

Three preterm newborns affected by congenital syphilis, born to mothers not adequately treated during pregnancy, are described. The clinical picture is characterized by a severe cholestatic hepatopathy and, in the two surviving patients, by an unusually wide ischemic-hemorrhagic lesion of the cerebral parenchyma. This lesion is probably due to a syphilitic endarteritis, and has rarely been described before in preterm infants.

Twin-to-twin-transfusion syndrome (TTS) is a serious complication in about 15% of monochorionic twin pregnancies. In severe TTS, the anemic pump twin (donor) develops anhydramnios and the hypervolemic recipient tense polyhydramnios, which often first calls attention to the condition. The most common problems of TTS are fetal complications such as single or double intrauterine demise, spontaneous abortion, prematurity due to uterine distension leading to contractions, preterm rupture of membranes and ultimately neurological impairment. We report a pregnancy with TTS in which rapid development of polyhydramnios led to rupture of a scarred uterus at 19 weeks gestation. To the best of our knowledge, this is the first report of a potentially lethal maternal complication of TTS.

Premature constriction of the fetal ductus arteriosus has been described with long-term indomethacin therapy, but not in fetuses who have been exposed to the drug for less than 72 hours. The sensitivity of the ductus to extended indomethacin tocolysis increases with advancing gestational age. For this reason, it is recommended that indomethacin not be used beyond 31 weeks of gestation. In the present case the gestational age of the patient was 27 weeks and the period of indomethacin exposure was only 16 hours. Our observations of pulmonary hypertension in this case suggest that administration of indomethacin even hours before delivery can significantly affect the ductus arteriosus and the pulmonary vasculature.