Walker-Warburg syndrome with microtia and absent auditory canals.

Walker-Warburg syndrome is a lethal, autosomal recessive disorder characterized by anomalies of the central nervous system and eye. Typical findings include hydrocephalus, agyria, retinal dysplasia, cerebellar dysgenesis, anterior chamber dysgenesis, and encephalocele. Recently, the phenotypic spectrum has been expanded to include congenital muscular dystrophy. Two sibs with Walker-Warburg syndrome are reported. One sib had congenital glaucoma and hydrocephalus. The other sib had hydrocephalus, microtia, absent auditory canals, and pale retinas, barely within the phenotypic spectrum of the disorder. Elevation of muscle enzymes was consistent with the diagnosis of Walker-Warburg syndrome.

Cerebro-oculo-facio-skeletal syndrome: further delineation.

We report on a newborn infant with cerebro-oculo-facio-skeletal (COFS) syndrome. Congenital muscular dystrophy-like changes were present in this patient. It is debated whether the clinical spectrum of the COFS phenotype should be expanded to include congenital muscular dystrophy:

Caudal dysplasia sequence with penile enlargement: case report and a potential pathogenic hypothesis.

The clinical spectrum of caudal dysplasia sequence (CDS) is noted for its diversity. The origin of CDS remains unknown, though poorly controlled gestational diabetes has been implicated in some cases. Here we describe the case of a newborn with CDS associated with penile enlargement (PE). The main anomalies included anal atresia, agenesis of the kidneys and of the sacrococcygeal vertebrae, dysgenesis of lumbar vertebrae, and bilateral cryptorchidism. Penile enlargement (7 cm), a rather unusual finding, has so far not been reported in association with CDS. Chromosomal analysis failed, and the neonate died 30 min after birth. Comparative genomic hybridization analysis using stored DNA showed a balanced normal male DNA content, which negates chromosomal losses or gains as a cause of CDS and/or PE. PE due to virilizing-type adrenal hyperplasia, caused by common mutations in the genes encoding for the adrenal enzymes 21-hydroxylase and 11-hydroxylase, was ruled out. We report on a previously unpublished case of the coexistence of PE and severe CDS and propose a possible pathogenetic hypothesis of this association.

Anticardiolipin antibodies in patients with recurrent pregnancy wastage: treatment and uterine blood flow.

The interest in autoimmune pregnancy loss has increased recently with the discovery of the association between the presence of antibodies to phospholipids and cardiolipin and habitual abortion. To evaluate the prevalence of anticardiolipin antibodies in patients with recurrent fetal loss and the effect of low-dose aspirin and corticosteroid treatment, we examined 67 women for anticardiolipin antibodies with an enzyme-linked immunosorbent assay. Increased levels of anticardiolipin antibodies were found in 34 of these women (50.7%) and in none of 12 normal pregnant controls. Seventeen of these 34 patients conceived and were treated with aspirin, 100 mg/day, and fluocortolone, 10 mg/day. Twelve gravidas reached term, all delivering live infants with good Apgar scores and normal birth weights. Three others delivered prematurely, two of them because of premature rupture of membranes and the other because of severe fetal growth retardation. This latter woman delivered at 31 weeks, and the 1000-g infant died neonatally. The neonatal survival rate was 82% in the treated patients, versus 18% in the same group of subjects in their previous, untreated gestations. The umbilical artery resistance index of the treated subjects was not different from that of anticardiolipin-negative hypertensive women who did not receive aspirin and corticosteroid therapy. However, the uterine artery resistance index was significantly lower in the hypertensive treated group than in the untreated group. Whether this difference reflected a beneficial effect of low-dose aspirin and corticosteroid therapy on pregnancy outcome and survival rate remains to be evaluated.

Insulin in human milk: postpartum changes and effect of gestational age.

OBJECTIVE: To determine if human milk insulin (HMI) concentrations are affected by gestational age and postnatal age. DESIGN AND SETTING: An observational study carried out in a level III neonatal intensive care unit. Insulin concentrations were determined in human milk of 90 parturient mothers who delivered between 30 and 41 weeks gestation. Samples were collected on days 3 and 10 after delivery. RESULTS: HMI concentrations for mothers of preterm infants were not significantly different from those of full term infants, on either day 3 or 10 post partum. When results for all 90 mothers were pooled, regardless of gestational age, HMI concentration fell significantly from day 3 to day 10 (50.1 (34.6) v 41.1 (28.5) microU/ml; p = 0.01; mean (SD)). However, this decrease was only significant for mothers delivering at term (37-41 weeks). CONCLUSIONS: HMI concentrations were not influenced by gestational age at delivery. They decreased post partum, mainly in mothers of term infants. The postnatal changes in HMI concentrations and the effects of oral insulin on the immature intestinal mucosa warrant further investigation.

Neonatal lenticulostriate vasculopathy: further characterisation.

BACKGROUND: Lenticulostriate vasculopathy (LSV) is sometimes detected on routine brain ultrasonography in neonates, and is often associated with various perinatal and neonatal abnormalities. However, most reports on LSV are retrospective with no controls. OBJECTIVES: To compare the perinatal and neonatal clinical characteristics of neonates with LSV with matched controls and to summarise all published reports of LSV. DESIGN: A prospective study that summarises the clinical, laboratory, and neurosonographic data of neonates with LSV. METHODS: Of 1184 neonates admitted to the neonatal intensive care unit (NICU) during a three year period, 857 had a routine head ultrasound examination. Twenty one had LSV, and were compared with 42 matched controls with regard to gestational, perinatal, neonatal, laboratory, and neurosonographic characteristics. RESULTS: LSV was detected in 21 of the 857 (2.45%) neonates. It was bilateral in 10 of the 21 cases and located in the thalamus (n = 14) and basal ganglia (n = 7). Infants with LSV were not significantly different from matched controls in most tested variables. However, compared with the control group, the LSV group included significantly more multiple births and more disturbances in amniotic fluid volume, but less meconial amniotic fluid. In addition, the patients with LSV required fewer blood transfusions and less phototherapy. CONCLUSIONS: Except for more multiple births, neonates with LSV did not display more adverse findings than their matched controls.

Critical ages in brainstem development revealed by neonatal 3-channel Lissajous' trajectory of auditory brainstem evoked potentials.

Auditory brainstem evoked potentials (ABEPs) were recorded from 91 newborns from 7 age groups between 26 to 43 weeks of gestation. In addition to the widely used vertex-mastoid derivation, potentials were recorded from three orthogonal electrode configurations, and represented in 3 dimensional voltage-space as three-channel Lissajous' trajectories (3CLTs). ABEPs were evoked by alternating polarity, monaural 75 dBnHL clicks presented at rates of 10/s, 55/s and 80/s. Potentials were also recorded to 45 dBnHL and 15 dBnHL clicks presented at 10/s. 3CLT point by point (apex latencies, amplitudes and orientation) as well as planar segment (planar segment position and duration) descriptors, along with peak latencies of the vertex-mastoid peaks, were followed for effects of age, stimulus intensity and rate. ABEPs began to appear consistently at 29 weeks of gestation to high stimulus intensities, with a rapid decrease of ABEP thresholds up to 34 weeks. At 35 weeks, thresholds stabilized approximately at adult values. The results indicate a significant effect of stimulus rate and intensity as well as of gestational age group on apex latencies. The findings also showed changes in apex orientations associated with stimulus rate and intensity interacting with gestational age. 3CLT descriptors enhanced the understanding of these results in relation to developmental and maturational aspects of the auditory system. The results may be explained by maturational change in relative contributions of constituents of the complex ABEP generators.

Intra- and extra-uterine development of neonatal 3-channel Lissajous' trajectory of auditory brainstem evoked potentials.

This study compared intra- and extra-uterine maturation of the auditory pathway, using auditory brainstem evoked potentials (ABEPs), recorded with three orthogonal differential electrode configurations. From the three records of each subject, 3-channel Lissajous' trajectories (3CLTs) were derived and analyzed. 107 newborns were compared at the same gestational and post-conceptional (gestational+postnatal) age, from 29 weeks (wks) up to 43 wks. In addition, we explored the effects and neurophysiological consequences of early exposure to extra-uterine life, on the peripheral and central portions of the auditory pathway. Our findings indicate that exposure of premature infants to the extra-uterine environment is associated with advanced peripheral development, but slower central conduction compared to intra-uterine development.

Urgent delivery, the treatment of choice in term pregnant women with extended burn injury.

Two pregnant patients at term, suffering from major burn wounds, were treated in our burn unit during the year 1995, both were delivered immediately after admission by caesarean section. One of them had smoke inhalation injury which needed mechanical ventilation, both mothers and newborns survived. In spite of low maternal carboxyhaemoglobin the fetal cord blood carboxyhaemaglobin was high, supporting an objective physiological basis for the previous empirical conclusion of early delivery in pregnant patients at term with extensive burn injury (50 per cent TBSA and more). This obvious favourable outcome highlights the importance of urgent delivery in term pregnant women suffering a major burn injury.

Intratracheal pulmonary ventilation in premature infants and children with intractable hypercapnia.

The feasibility of intratracheal pulmonary ventilation (ITPV) was tested in five ventilated moribund neonatal and pediatric patients with uncontrollable hypercapnia: a 2-year-old child, a 52-day-old infant, and three premature infants (29, 29, and 26 weeks gestation; 1300 g, 1100 g and 890 g birth weight, respectively). ITPV was applied for 9.5, 8, 25, 58.5, and 47.5 hr, respectively. An intratracheal catheter (Cook Critical Care, Inc., Bloomington, IN) with a reversed continuous flow of gas at its tip (away from the lungs) allowed flushing of CO2 from the proximal dead space. Marked reductions in Paco2, ranging from 37% to 71% and improvement in pH were achieved within 4-6 hr of applying ITPV. During ITPV, the mean lowest Paco2 was significantly less than the pre-ITPV Paco2 (p < 0.0017), and the mean best pH was significantly higher than the pre-ITPV pH (p < 0.015). In four patients, despite significant reductions in Paco2, there was no substantial improvement in their baseline condition (shock and severe metabolic acidosis or coma) and they were switched back to conventional ventilation. This led to worsening hypercapnia to pre-ITPV values. These four patients subsequently died. It is possible that these patients were already too ill to derive significant benefit from the technique. One premature infant survived, was successfully weaned to conventional ventilation and was eventually discharged home. ITPV can alleviate uncontrollable hypercapnia in ventilated neonatal and pediatric patients.

Congenital subependymal pseudocysts: own data and meta-analysis of the literature.

BACKGROUND: Congenital subependymal pseudocysts are incidental findings that are found in 0.5-5.2% of neonates during postmortem examination or head ultrasonography. In our institution we detected 10 neonates with CSEPC. OBJECTIVE: To investigate associated etiological factors, morphologic characteristics and outcome of CSEPC. METHODS: We performed a meta-analysis of the literature on CSEPC (1967-98), including our 10 cases. RESULTS: A total of 256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC; 48.8% were bilateral and 53.4% were located in the caudothalamic groove or head of caudate nucleus. Altogether, 93.5% resolved during 1-12 months of ultrasonographic follow-up. Compared to the general neonatal population, the following features were more prevalent in the CSEPC population: prematurity, maternal vaginal bleeding, preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal cytomegalovirus and rubella infections, congenital malformations, chromosomal aberrations, infant mortality, and neurodevelopmental handicap. The risk for neurodevelopmental handicap was significantly higher when CSEPC were associated with fetal infections, IUGR, malformations and chromosomal aberrations, or persistence of CSEPC during follow-up. CSEPC infants without any of these four conditions had a low risk for neurodevelopmental handicap. CONCLUSIONS: CSEPC are morphologic features of various underlying conditions encountered in the fetus. Association of CSEPC with IUGR, fetal infections, malformations and chromosomal aberrations or persistence of CSEPC indicates a higher risk for future neurodevelopmental handicaps, probably because of the deleterious effects on the fetal brain that are inherent in these conditions. A favorable outcome is expected in the absence of these risk factors.

In vitro fertilisation and use of ovulation enhancers may both influence childhood height in very low birthweight infants.

CONTEXT: Term-born children conceived by in vitro fertilisation (IVF) are reportedly taller than naturally conceived (NC) children. High levels of growth promoting hormones and epigenetic imprinting have been suggested as pathogenetic mechanisms. HYPOTHESIS: Tall stature in prematurely born IVF-conceived (IVF-C) children suggests pre- or early implantation imprinting rather than a postnatal effect. METHODS: We studied 334 very low birthweight (VLBW: birth weight <1500 g) children born prematurely during 1995-1999 and obtained their anthropometric measures at 6-10 years of age. Perinatal and neonatal data were obtained from the Israeli VLBW database. We compared IVF-C, ovulating agents conceived (OA-C) and naturally conceived (NC) groups of children with respect to their and their parents' anthropometry and their perinatal/neonatal variables. RESULTS: Childhood height standard deviation scores (SDSs) were greatest in IVF-C (-0.12 (SD 1.25); p<0.022) and insignificantly greater in OA-C (-0.37 (SD 1.02)) as compared to NC (-0.58 (SD 1.36)) children. The IVF-C and NC groups were significantly different regarding 17 parental and perinatal variables; however, multiple regression analysis including these variables showed that, as compared with NC, IVF-C children had significantly older mothers at birth with earlier follow-up during pregnancy and more multi-fetal pregnancies. CONCLUSIONS: IVF-C and to a lesser extent OA-C prematurely born children are taller than otherwise NC children. After ruling out postnatal and parental causes, we speculate that pre- or early implantation factors might have contributed to the taller stature of IVF-C children.

Normal plasma-urine osmolality relationship in preterm infants on positive pressure mechanical ventilation.

Mechanical ventilation with positive pressure has been implicated in the inappropriate release of vasopressin. To examine whether such a phenomenon occurs in infancy, 26 preterm neonates with Respiratory Distress Syndrome were studied. Simultaneous urine and plasma were collected for osmolality determination during mechanical ventilation with positive end expiratory pressure of 4-8 cmH2O. Results were plotted onto our previously described nomogram. The data show normal distribution of plasma to urine osmolality ratio in 25 out of 26 infants. These results do not support the common belief that positive pressure mechanical ventilation in the newborn with RDS provokes inappropriate secretion of vasopressin.

Meconium peritonitis: a benign course in a premature infant.

A case of a premature infant with meconium peritonitis and intraperitoneal calcifications is described. The course of illness was mild and recovery complete. No evidence of congenital intestinal obstruction or cystic fibrosis was found.

Markedly elevated alpha-fetoprotein and positive acetylcholinesterase in amniotic fluid from a pregnancy affected with dystrophic epidermolysis bullosa.

Prenatal diagnosis of dystrophic epidermolysis bullosa (DEB) has been achieved in the past by fetal skin sampling. However, this invasive procedure is associated with a relatively high rate of pregnancy loss. We present a consanguineous Arab family ascertained by 2 affected offspring to be at risk for DEB. In a previous gestation, fetoscopic skin sampling for prenatal diagnosis yielded a false-positive result. In the index pregnancy, abnormally elevated amniotic fluid alpha-fetoprotein (13.7 MOM) and positive acetylcholinesterase were highly suggestive of an affected fetus. Fetal skin biopsy was declined. At term, the patient delivered a male infant with DEB that expired on the 3rd day of life. It is apparent from our experience and from review of the literature that in some genodermatoses, markedly elevated alpha-fetoprotein and positive acetylcholinesterase in amniotic fluid are highly suggestive of an affected fetus and may obviate the need for fetal skin sampling in the prenatal diagnosis of these disorders.