Perfusion abnormalities in hemimegalencephaly.

INTRODUCTION: Cerebrovascular changes are rarely discussed in patients with hemimegalencephaly. These alterations have previously been associated with epileptical activity. CASE: We report the case of a 36-week gestation neonate presenting with total right hemimegalencephaly, as demonstrated by a magnetic resonance imaging (MRI) performed in the first days of life. Perfusion-weighted imaging displayed a clear hypervascularization of the right hemisphere. Diffusion-tensor imaging showed an arrangement of white matter fibers concentrically around the ventricle on the right hemisphere. AngioMRI showed an obvious asymmetry in the size of the middle cerebral arteries, with the right middle cerebral artery being prominent. The baby was free of clinical seizures during his first week of life. An electroencephalogram at that time displayed an asymmetric background activity, but no electrical seizures. CONCLUSION: Perfusion anomalies in hemimegalencephaly may not necessarily be related to epileptical activity, but may be related to vessel alterations.

Brain development (sulci and gyri) as assessed by early postnatal MR imaging in preterm and term newborn infants.

OBJECTIVE: To investigate fetal brain development in vivo using early postnatal cranial MRI in term and preterm newborn infants. STUDY DESIGN: 51 infants, 1.5-T whole-body system, extremity coil, spin-echo images obtained in all three planes (T1- and T2-weighted). Independent review by two neuroradiologists (blinded for gestational age and medical history) regarding the development of 12 sulci and 10 gyri using a modified scoring system. Gestational age was obtained either by ultrasound or from the first day of the last menstrual period. EXCLUSION CRITERIA: head circumference <10th or >90th percentile, cerebral malformation, chromosomal/metabolic disorder. RESULTS AND CONCLUSION: Age at study ranged from 23 5/7-43 0/7 postmenstrual weeks. Brain maturation starts in the central area and proceeds towards the parieto-occipital cortex. The frontal cortex develops last. Transition to degrees 1, degrees 2 and, degrees 3 starts at week 25, 32 and 35 in the central cortex and is completed at week 34, 36 and 39, respectively. Our data compare favourably with the two previously published reports about brain maturation. Early MR imaging seems therefore to be suited to study maturation of the fetal brain. This may be of pathophysiological relevance in neonatal intensive care and neurological follow-up studies.

Perinatal ultrasonography and magnetic resonance imaging findings in congenital hydrocephalus associated with fetal intraventricular hemorrhage.

OBJECTIVE: We present the case histories of three premature infants with congenital posthemorrhagic hydrocephalus. STUDY DESIGN: The timing of the lesion was monitored in utero in two of the three cases. Magnetic resonance imaging studies (prenatal in one case, within 24 hours of birth in all three cases) established the duration of the lesions and thereby added to the ultrasonographic findings. RESULTS: All three patients demonstrated a similar pattern of lesions, consisting of (1) unilateral germinal matrix hemorrhage with cystic resorption, (2) residual blood in the cerebrospinal fluid with a "granular" ependymal reaction, (3) asymmetric ventriculomegaly predominating on the side of the hemorrhage with mild atrophy and periventricular cysts, and (4) partial hypoplasia of the ipsilateral thalamus. On the basis of two cases in which information about the pregnancy was available and in which fetal oligohydramnios without ruptured membranes was detected, we assume that this pattern of lesions may have resulted from a hypoxic-ischemic episode followed by intraventricular hemorrhage. CONCLUSIONS: Because these three infants with congenital hydrocephalus were born during a period of only 18 months in a perinatal center serving a region with 16,000 live births per year, we speculate that a posthemorrhagic cause for congenital hydrocephalus underestimated.

Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants.

UNLABELLED: Nasal continuous positive airway pressure (CPAP) applied shortly after birth is said to be an effective treatment of respiratory distress in very low birth weight infants (VLBW). We tested the hypothesis that the use of early nasal CPAP (applied as soon as signs of respiratory distress occurred, usually within 15 min after birth) reduces the need for intubation, the duration of intermittent mandatory ventilation and the incidence of bronchopulmonary dysplasia. All liveborn VLBW infants (birth weight < 1500 g) admitted to our tertiary neonatal intensive care unit in 1990 (historical controls) and in 1993 (early nasal CPAP group) entered the study. The intubation rate was significantly lower after introduction of nasal CPAP (30% vs 53%, P = 0.016). Median duration of intubation was 4.5 days (interquartile range 3-7 days) before versus 6.0 days (2.8-9 days) after nasal CPAP was introduced (P = 0.73). The incidence of bronchopulmonary dysplasia was not reduced significantly (32% vs 30%, P = 0.94). Survival until discharge was 89.5%, before versus 92.9% after introduction of nasal CPAP (P = 0.54). CONCLUSION: Early nasal CPAP is an effective treatment of respiratory distress in VLBW infants, significantly reducing the need for intubation and intermittent mandatory ventilation, without worsening other standard measures of neonatal outcome. We found no significant decrease in the incidence of bronchopulmonary dysplasia.

Vasopressin in oligohydramnios-induced lung hypoplasia.

Experimentally-induced oligohydramnios (oligo) produces lung hypoplasia. To determine if arginine vasopressin (AVP), a hormone known to decrease fetal lung fluid production, contributes to the pathogenesis of oligo-induced lung hypoplasia, the following experiment was performed. Brattleboro rats were mated to produce litters either with AVP [heterozygotes (HZ)] or without AVP [homozygotes (HO)]. On d 15 of gestation, half of each litter underwent amniocentesis to create persistent oligo. Littermates with intact membranes served as controls. Four groups of fetuses, i.e. 10 HO litters divided into control (44 fetuses) and oligo (25 fetuses), and eight HZ litters divided into control (35 fetuses) and oligo (18 fetuses), were killed at term for measurement of organ weights and biochemical determination of lung development. Significant differences between control and oligo groups were observed for body weight (HO, p = 0.008; HZ, p = 0.03), lung weight (less than 0.001 for both crossings), lung/body weight ratio (less than 0.001 for both), DNA per lung (HO, p = 0.02; HZ, p less than 0.001), and lung dry/wet ratio (HO, p less than 0.001; HZ, p = 0.001). Oligo groups with and without AVP were not found to be different for lung weight (p = 0.217), lung/body weight ratio (p = 0.209), and DNA per lung (p = 0.822). An analysis of variance confirmed the lack of any significant difference of the impact of oligo in the presence or absence of AVP. We conclude that AVP plays no role in the development of oligo-induced lung hypoplasia.

Role of lung fluid volume in growth and maturation of the fetal sheep lung.

We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control.

Time-trends in necropsy prevalence and birth prevalence of lung hypoplasia.

Congenital lung hypoplasia (LH) has been identified with increasing frequency in perinatal and neonatal necropsy reviews. The available prevalence figures have been derived using various diagnostic criteria in different populations and at various times. We therefore reviewed our experience in 15 years of consecutive early neonatal necropsies using one constant set of diagnostic criteria for LH and looked for a time-trend. We determined the necropsy prevalence (no. of cases of LH/no. of necropsies) and the birth prevalence (no. of cases of LH documented at necropsy per 1000 livebirths for inborn patients, and per 1000 referrals for outborn patients) between 1971 and 1985. We then divided this 15-year period into five consecutive 3-year periods to determine if a time-trend was discernible. Whereas early neonatal mortality for neonatal intensive care unit (NICU) admissions progressively decreased from 11.4% to 4.0% between the first and the last 3-year periods, the number of cases of LH per 3-year period did not vary appreciably. As a result, the prevalence of LH at necropsy showed a slight upward trend with time. The overall prevalence was 18%; it was 13% during the first and 23% during the last 3-year period. We found no time-trend in birth or referral prevalence for this lesion, which averaged 1.1 per 1000 livebirths and 9.8 per 1000 referrals. We conclude that lung hypoplasia appears to be emerging as an increasingly prevalent necropsy finding as a result of a shift in proportionate mortality, with the number of patients dying of other causes (denominator) decreasing, and the number of patients dying with lung hypoplasia remaining constant.

Mothers who smoke and the lungs of their offspring.

Maternal smoking is associated with an increased prevalence of respiratory morbidity in children. It had been widely assumed in the past that this effect was the result of postnatal environment tobacco smoke exposure (passive smoking). There is mounting evidence, based on studies in humans and in animal models to suggest that maternal smoking during pregnancy adversely affects fetal lung development. The pathogenesis for this lesion is unclear and it is not known if the insult is the same in the human and the animal model.

Fetal breathing movements are not a reliable predictor of continued lung development in pregnancies complicated by oligohydramnios.

Fetal breathing activity was monitored by ultrasonography in 14 patients with oligohydramnios (4 with fetal anuria and 10 with premature rupture of the membranes). 45 patients with intact membranes, with normal amniotic fluid volume, and matched for gestational age were the controls. Fetal breathing movements were seen in all 8 patients who died in the perinatal period with a necropsy diagnosis of lung hypoplasia. While patients with premature rupture of the membranes (irrespective of outcome) spent the same or less time breathing than controls, fetuses with renal anomalies, oligohydramnios, and lung hypoplasia spent more time breathing than controls. The observation of fetal breathing activity is not helpful in identifying patients with oligohydramnios at risk of lung hypoplasia.

The effect of prolonged oligohydramnios on fetal lung development, maturation and ventilatory patterns in the newborn guinea pig.

We drained the amniotic fluid surrounding guinea pig fetuses between days 45 and 65 of gestation (term is 67 days). The fetuses were delivered by Cesarean section and the impact of prolonged oligohydramnios on lung growth, maturation and postnatal ventilatory pattern was measured. Untouched littermate fetuses served as controls. Neither fetal body, liver nor brain weights were significantly affected by the experimental situation. When expressed in percent of control values, lung weight (63%), lung/body weight ratio (70%), lung volume (67%), total lung DNA content (63%) and lung DNA per gram of fetal weight (71%) were all significantly less following amniotic fluid drainage, confirming the diagnosis of lung hypoplasia. Disaturated phosphatidylcholine content per gram of lung tissue and total lung glycogen content were not affected by the procedure, indicating that the maturity of the hypoplastic lungs was not delayed. When measured 4 to 6 hours after birth, tidal volume was significantly less (62%) and respiratory frequency was significantly more (137%); however, minute ventilation per unit of body weight was not significantly changed. This animal model of sublethal lung hypoplasia could become useful to study the potential for, and the kinetics of, postnatal catch-up lung growth about which little is known.

Umbilical cord length in Down's syndrome.

Fetal motor activity is believed to influence umbilical cord growth. As Down's syndrome is associated with hypotonicity and reduced fetal activity, we hypothesized that newborn infants with this syndrome have short umbilical cords. We identified 21 infants with Down's syndrome and compared each individual cord length to mean standard values derived from the same population and matched for sex, race, and gestational age. Infants with Down's syndrome were found to have significantly shorter umbilical cords (mean of 45.1 cm compared with 57.3 cm for matched standards). It is not clear whether their cords are shorter on the basis of decreased fetal activity, genetics, or both. If it is on the basis of decreased fetal activity, it would be interesting to see if those with the shortest cords (presumed to have been the most hypoactive in utero) could be predicted to have worse neurodevelopmental outcomes.

Fetal lung growth in experimental utero-abdominal pregnancy.

We removed rat fetuses from the uterus without disturbing the placental implantation site, placing the fetuses in the peritoneal cavity either within intact membranes (with or without amniotic fluid) or outside of the fetal membranes. Untouched littermate fetuses served as controls. The surgery was performed on day 17 of gestation and the outcome was analyzed at term, 4 days later. The utero-abdominal pregnancies with intact membranes and amniotic fluid yielded fetuses in all respects indistinguishable from littermate controls. Extrauterine fetuses maintained within their membranes but without amniotic fluid as well as extrauterine and extramembranous fetuses displayed identical features: body weight was slightly reduced; after correction for body weight, only their lungs weighed significantly less and contained less deoxyribonucleic acid. In addition, fetuses in these two groups had multiple joint contractures and occasional webbing of the skin. These experimental findings in rats indicate an important role of amniotic fluid in fetal development, especially of the lung.

Morphometric analysis of the growth of the normal fetal guinea pig lung.

The structural development of the fetal guinea pig lung is described and quantified morphometrically in this report. At 35 days gestation the lung is in the pseudoglandular phase of growth, by 40 days it is in the canalicular phase, and at 50 days the saccular growth phase has begun. At term (67 days), the fetal guinea pig lung appears mature. From the beginning of the canalicular to the end of the saccular phases, the correlation coefficient between lung volume and gestational age is +.98, between internal surface area and gestational age is +.94 and between total number of saccules and gestational age is +.97. Internal surface area (ISA) correlates closely with lung volume (r = +.99) and the correlation coefficient between total number of saccules and lung volume is +.98. At term, lung volume is 4.22 ml. ISA is 0.5 M2, and total number of saccules is 253 million. Parenchymal growth is achieved by increases in both number and size of airspaces in the canalicular phase, primarily by increases in number during the early saccular phase and largely by increases in airspace size near term. The total length of parenchymal elastic tissue increases from 223 M at 45 days gestation to 5,253 M at term. Elastic tissue fibers first appear in the parenchyma of the fetal guinea pig lung during the canalicular phase, when the rate of saccule formation is high. The quantitative increase in elastic tissue correlates closely with the increase in the total number of saccules from day 45 to day 60 of gestation (r = +.99). The rate of elastic tissue growth increases sharply in the late saccular phase, coinciding with the period of greatest saccular expansion. These data suggest an interdependent relationship between saccular growth, i.e., proliferation and expansion, and the development of lung parenchymal elastic tissue.

Oligohydramnios-induced lung hypoplasia: the influence of timing and duration in gestation.

We drained amniotic fluid for periods of 5 and 10 days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). We analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only 5 days of oligohydramnios and the percent change did not vary between the two consecutive 5-day periods studied (period A, days 40 to 45, delta of -0.047 mg, p = 0.004; period B, days 45 to 50, delta of -0.042 mg, p = 0.002). The impact of the same duration of oligohydramnios on lung growth later in gestation, during the terminal sac stage of lung development, was less (period C, days 50 to 55, delta of -0.027 mg, p = 0.097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one-way analysis of variance. Two overlapping 10-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, delta of -0.072 mg, p = 0.001; period E, days 45 to 55, delta of -0.047 mg, p = 0.001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level).(ABSTRACT TRUNCATED AT 250 WORDS)

Morphometry of hypoplastic fetal guinea pig lungs following amniotic fluid leak.

Deficient quantity of amniotic fluid causes fetal guinea pig lung hypoplasia. Oligohydramnios that lasts only 5 days in early gestation is sufficient to reduce fetal lung growth significantly. We quantitated lung structural alterations at 50 days gestation (term is 67 days) of fetal guinea pigs whose amniotic fluid was drained on day 45 gestation. The study period spans the late canalicular-early saccular phases of guinea pig lung growth. Compared to littermate controls (n = 4), experimental fetuses (n = 5) have reduced lung:body weight ratio (2.81 +/- 0.16 versus 3.21 +/- 0.20 X 10(-2), p less than 0.01), indicating lung hypoplasia. Lung volume is significantly decreased in the experimental fetuses (1.17 +/- 0.15 versus 1.34 +/- 0.07 ml, p less than 0.05). The proportion of lung containing parenchyma (i.e. developing alveoli and alveolar ducts) is reduced following oligohydramnios (0.83 +/- 0.04 versus 0.90 +/- 0.02, p less than 0.025). The hypoplastic lungs contain fewer saccules (fetal "alveoli") (46 +/- 20 versus 69 +/- 23 X 10(6), p less than 0.1) and the surface area that would be available for gas exchange is decreased (698 +/- 234 versus 974 +/- 80 cm2, p less than 0.05). Lung volume and volume proportion of parenchyma are reduced in the experimental lung and therefore diminished parenchymal elastic tissue is anticipated. However, the total length of parenchymal elastic tissue in the experimental lungs is decreased to a surprising degree and is little more than half the length in control lungs (504 +/- 222 versus 974 +/- 70 m, p less than 0.0025). Such marked reduction in total length suggests that factors other than smaller lung size have contributed to the decrease of elastic tissue in the experimental group. In fact, elastic tissue length per unit volume is significantly reduced (509 +/- 189 versus 809 +/- 115 m/cm3, p less than 0.025) indicating an absolute decrease in parenchymal elastic tissue in the hypoplastic lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal lung hypoplasia associated with maternal smoking: a morphometric analysis.

Our recently reported animal (rat) model of maternal cigarette smoke exposure during pregnancy is characterized by fetal growth retardation and lung hypoplasia. We have further defined the fetal lungs using quantitative histologic techniques. Compared to controls, lung volume at term is reduced in the experimental animals (0.28 versus 0.33 ml, p less than 0.005). Saccules (fetal "alveoli") are reduced in number (3 X 10(6) versus 5.5 X 10(6), p less than 0.005) and increased in size (average saccular volume: 35 X 10(-9) versus 21 X 10(-9) ml, p less than 0.025). These changes in size and number are consequences of reduced formation of saccule partitions (septal crests) in the experimental lungs (volume density: 0.013 versus 0.018, p less than 0.025). Internal surface area is decreased in the hypoplastic lungs (161 versus 198 cm2, p less than 0.001). The total length of parenchymal elastic tissue is diminished (224 versus 354 M, p less than 0.05). In short the hypoplastic lungs contain fewer, larger saccules and the surface potentially available for gas exchange is reduced. These results show that maternal smoking in rats adversely modifies fetal lung growth. If these observations are applicable to humans, then reduced lung growth in children of smoking mothers may begin antenatally.

Fetal breathing movements and lung hypoplasia: preliminary human observations.

Hypoplasia of the fetal lung is found in association with long-standing oligohydramnios. In animal models, interference with fetal breathing activity has led to lung hypoplasia. It has been suggested that lung hypoplasia associated with oligohydramnios is due to inhibition of fetal breathing. Observations of seven patients with prolonged oligohydramnios, three of whom had lung hypoplasia, indicate that fetal breathing does occur in these cases and that is unlikely that lung hypoplasia is merely the result of absent fetal breathing activity. In fact, when compared to the four patients with oligohydramnios and presumably normal lungs, the three patients with oligohydramnios and lung hypoplasia spent more time breathing and did so at higher rates.

Fetal growth retardation due to maternal tobacco smoke exposure in the rat.

Smoking during pregnancy results in offspring with an average birth weight 200 g less than those of non-smoking mothers. The pathogenesis of this effect is still unknown and there is no general agreement about the causal relationship between maternal smoking and subsequent fetal growth retardation. In the present study, a model of maternal smoking during pregnancy in the rat was established using the P & I Walton Exposure Machine. The study consisted of three groups: control, pair-fed, and smoke-exposed. Smoke-exposed animals were exposed continuously to tobacco smoke for cycles of 7 min, 16 times a day from d 5 to d 20 of gestation. On d 21 of gestation, fetuses from all groups were removed by cesarean section, weighed, and dissected. The fetal brain, liver, and lungs as well as the placentas were weighed and analyzed for nucleic acid content. Fetal weight was found to be significantly reduced in both pair-fed and smoke-exposed groups compared with the control group. There was also a significant reduction in fetal body weight of the animals in the smoke-exposed group in comparison to those in the pair-fed group. Exposing the mother to smoke affected neither fetal brain weight nor nucleic acid content whereas fetal liver and lungs showed a significant decrease in both weight and nucleic acid content. These results indicate that the fetal growth retardation associated with maternal exposure to tobacco smoke in the rat corresponds to a disproportionate type.(ABSTRACT TRUNCATED AT 250 WORDS)