Value of the comparative enzyme-linked immunofiltration assay for early neonatal diagnosis of congenital Toxoplasma infection.

BACKGROUND: The transplacental transfer of specific maternal IgG antibodies makes the diagnosis of congenital Toxoplasma infection quite difficult in the neonate. The enzyme-linked immunofiltration assay (ELIFA), comparing at delivery the immunologic profile of the mother's antibody response and that of her child, allows discrimination between IgG antibodies of maternal origin and IgGs synthesized by the fetus. OBJECTIVE: To evaluate the diagnostic reliability of the comparative ELIFA for diagnosing congenital Toxoplasma infection as well as the reliability of testing for IgM- and IgA-specific antibodies in cord blood. METHODS: From November, 1991, to December, 1995, an ELIFA was prospectively performed at delivery on blood samples obtained from 227 women with primary Toxoplasma infection during pregnancy and from their infants. For each child the ELIFA result was evaluated in relation to the serologic follow-up: disappearance of specific anti-Toxoplasma gondii IgG antibodies in the absence of treatment before 12 months of age indicating an uninfected child, as opposed to persistence beyond 12 months of age indicative of a congenital infection. RESULTS: Of 227 children 139 were lost to follow-up. Among the 88 children available for follow up, the ELIFA was negative in 70 infants, 69 of whom were confirmed to be uninfected. Thirteen of these 69 cord blood ELIFA-negative samples were positive for anti-T. gondii IgM and/or IgA detected by means of a conventional immunosorbent agglutination assay. Of the remaining 18 children (representing 75% of all new cases of congenital toxoplasmosis diagnosed during the study period at our institution), the ELIFA was positive in 16, negative in 1 and inconclusive in 1. CONCLUSIONS: The ELIFA test is a valuable tool for diagnosing congenital T. gondii infection and in differentiating between true neonatal infection and cord blood contamination. In our experience the diagnostic sensitivity of the ELIFA test was 94.1% and the specificity was 98.6%. The cord blood was contaminated by specific maternal anti-T. gondii IgA and/or IgM in as many as 20% of the cases.

Enrollment of a population-based cohort of newborns at higher risk of developing a chronic condition: the EDEN study. Etude du Developpement des Nouveau-nés Study.

OBJECTIVE: To describe the methods used at birth to recruit a population-based cohort of newborns of all birthweights at higher risk of having a chronic condition, and to present baseline results. METHODS: Screening of all newborns at hospital discharge for five non-exclusive criteria: (1) low birthweight (LBW), (2) congenital anomalies or genetic disease, (3) specified conditions associated with a high probability of chronicity, (4) referral to a neonatal intensive care unit (NICU), (5) or defined social problems. Calculation of Hobel risk scores for children satisfying > or = 1 criterion. SUBJECTS: All 6477 live births delivered in the 19 maternity hospitals of a geographically defined region (Vaud, Switzerland) to resident mothers in 1993-1994. RESULTS: Twelve per cent (n = 760) of newborns met > or = 1 criterion: 6.3% of all newborns had an LBW (criterion 1), 2.4% had a birth defect, 0.9% met criterion (3), 4.4% stayed in an NICU and 1.6% had serious social problems. Hobel prenatal score was high (> or = 10 points) for 41% of children with > or = 1 criterion, the intrapartum score for 87% and the neonatal score for 68%. CONCLUSIONS: Most newborns identified by the above simple criteria also had elevated perinatal risks. The validity of the criteria will later be tested against the results of the examinations of children with > or = 1 criterion at 18 months and 4 years of age, but the assessment at birth already shows that normal birthweight (NBW) children, in agreement with previous studies, contribute half the children at high risk perinatally.

Cytomegalovirus fetal infection: prenatal diagnosis.

We report the results of prenatal diagnosis in 15 cases of primary cytomegalovirus infection during pregnancy. Sixteen fetuses (one twin pregnancy) were examined by ultrasonography, amniocentesis, and fetal blood sampling. Prenatal diagnosis was positive in eight cases as evidenced by positive amniotic fluid cultures in eight, positive immunoglobulin M (IgM) in six, and abnormal ultrasound in two. Among infected fetuses, abnormal laboratory findings included anemia, thrombocytopenia, and elevated liver function tests. Three pregnancies were terminated because of ultrasound abnormality or abnormal laboratory indices. In cases of fetal infection with normal ultrasound and normal laboratory findings, the pregnancies were allowed to proceed, leading to the birth of four infants (three with subclinical infections, one with bilateral hearing loss). The relation between anemia, thrombocytopenia, altered liver function tests, and subsequent handicap remains unknown, but the abnormalities observed in utero correspond to those described at birth in cases of cytomegalic inclusion disease. Amniocentesis alone allowed the diagnosis of infection in all cases, but fetal blood sampling provided additional information about the fetal condition.

Prenatal diagnosis of congenital cytomegalovirus infection.

OBJECTIVE: To assess prospectively the diagnostic reliability and prognostic significance of prenatal diagnosis of cytomegalovirus (CMV) infection. METHODS: One hundred ten pregnant women (four with twin pregnancies) with a risk of congenital CMV infection were investigated. Prenatal diagnosis was carried out by amniocentesis and fetal blood sampling (n = 75) or amniocentesis alone (n = 35). Serial ultrasonographic examinations were performed from time of referral until pregnancy end. All infected neonates were given long-term follow-up. Autopsy was performed in all cases of termination of pregnancy. RESULTS: Nearly 23% (26 of 114) of fetuses were infected and prenatal diagnosis was positive in 20 cases. Sensitivity of prenatal diagnosis was 77% and specificity 100%. In eight cases, parents requested termination of pregnancy on the basis of abnormal ultrasonographic findings and/or biologic abnormalities in fetal blood. In 12 cases, parents decided to proceed with the pregnancy. In this group, one intrauterine and one neonatal death were observed. In one case, prenatal diagnosis revealed an abnormal cerebral sonography and the infant had bilateral hearing loss at birth. In 15 cases (nine positive and six false-negative prenatal diagnoses), no apparent lesion was present at birth, nor did it develop during the follow-up period (mean 31 months). In 88 (77.2%) of 114 infants, no evidence of vertical transmission was found during the pre- or postnatal period. CONCLUSION: Prenatal diagnosis provides the optimal means for both diagnosing fetal infection (amniocentesis) and identifying fetuses at risk of severe sequelae (ultrasound examination, fetal blood sampling), thus allowing proper counseling.

Impact of infertility treatments on the health of newborns.

OBJECTIVE: To measure the use of infertility treatments in the general population and their association with neonatal health. DESIGN: Cross-sectional, population-based study. SETTING: Canton of Vaud, Switzerland; Etude du Developpement des Nouveau-nés (EDEN), a prospective study of chronic childhood conditions. PATIENT(S): Six thousand four hundred seventy-seven live newborns (6,379 pregnancies) delivered of residents of Vaud in the 19 maternity hospitals between 1993 and 1994. MAIN OUTCOME MEASURE(S): Neonatal morbidity, multiplicity, low birth weight, prematurity, intrauterine growth retardation, transfer to intensive care, and length of hospital stay. RESULT(S): Infertility treatments were reported for 2.1% of pregnancies (129 women, 148 newborns) and were associated significantly with adverse outcomes. Population-attributable risks varied from 3%-20%. The outcomes of twins did not differ regardless of whether their mother was treated for infertility. Among singletons, only low birth weight was significantly more frequent when infertility treatments were used. Unadjusted odds ratios for neonatal morbidity were significant only for multiple births (2.56; 95% confidence interval 1.21-5.42). This association was not influenced by maternal characteristics and it disappeared after controlling for sex, gestational age, and birth weight. CONCLUSIONS(S): An independent effect of infertility treatments on neonatal morbidity cannot be ruled out, but most of their impact appeared to be mediated by multiplicity and prematurity. Reducing the number of medically induced multiple pregnancies is the most effective prevention of neonatal morbidity related to infertility treatments. Follow-up studies are needed.

Haemodynamic changes during high frequency oscillation for respiratory distress syndrome.

In a crossover trial left ventricular output (LVO), cerebral blood flow velocity (CBFV), and resistance index (RI) of the anterior cerebral artery were compared using Doppler ultrasonography, in eight preterm infants with respiratory distress syndrome (RDS) during conventional mechanical ventilation and high frequency oscillation. LVO was 14% to 18% lower with high frequency oscillation. There were no significant changes in CBFV. On the first day of life there was a trend towards lower RI on high frequency oscillation; the fall in LVO on high frequency oscillation was not related to lung hyperinflation. Changes in ventilation type (from conventional mechanical ventilation to high frequency oscillation, or vice versa) can induce significant LVO changes in preterm infants with RDS.

Neurodevelopmental outcome at 12 months of age related to cerebral ultrasound appearances of high risk preterm infants.

A prospective neurological and developmental assessment at 12 months of age corrected for prematurity was performed on 54 surviving preterm infants of 34 weeks' gestation or less. The babies were allocated into three groups according to their ultrasound (US) appearances: Group I (n = 29), normal scan; Group II (n = 10), isolated periventricular-intraventricular haemorrhage (PVH); Group III (n = 15), association of PVH, periventricular leukomalacia (PVL) and ventricular dilatation. The developmental outcome evaluated with the Griffiths' development quotient (DQ) was good and similar in Groups I and II, while it was worse and variable in Group III. There was also a higher incidence of neurological abnormalities in Group III, as 47% of children only were found to be normal compared to 86% and 80% in Groups I and II, respectively. A major handicap was diagnosed in 5 children of Group III. Infants with small lesions of PVH or PVL or with ventricular dilatation developed as well as children with normal US scan, whereas more diffuse or extensive US changes of PVL had a poorer prognosis. The outcome of a cerebral injury seems to depend on the type, the size and localisation of the lesion, and to some extent, on the neuroplasticity of the developing brain.

Influence of perinatal, developmental and environmental factors on cognitive abilities of preterm children without major impairments at 5 years.

The relative role of perinatal factors (birthweight, gestational age, gender, asphyxia, mechanical ventilation and cerebral lesions), developmental factors (neuromotor development during the first 18 months of life) and environmental factors (socio-economic status and bilingualism) on cognitive abilities was evaluated in a cohort of preterm children who had been prospectively examined for haemorrhage (PVH) and periventricular leucomalacia (PVL) and followed-up to 5 years of age. Standardized neurological examinations and development assessment including tests of cognitive function were carried out. Major impairments could be ascribed to the presence of large PVL changes. Among the 226 children without major impairment, the overall incidence of neuropsychological anomalies (neuromotor, language, visual, auditory and behaviour anomalies) was 46.5% and did not differ within ultrasound groups (normal scans, PVH and small PVL). However, children with small changes of PVL presented more abnormal neuromotor development within the first 18 months of life and had more complex neuropsychological anomalies at 5 years. The multiple regression analysis (General Intellectual Index (GII) predicted = 113.7 - coefficient x social class - 8.5 x bilingualism - 5.5 x dystonia + 1.4 x gestational age + 8 x mechanical ventilation) showed that socioeconomic status was the most important factor affecting the General Intellectual Index (GII). The contribution of sex and cerebral lesions was not significant. As children grew-up, environmental factors seemed to overcome perinatal factors.

Significance of ultrasound appearances in the neurological development and cognitive abilities of preterm infants at 5 years.

The developmental outcome at 5 years of age was studied in 93 preterm infants who had been prospectively examined for peri-ventricular leucomalacia (PVL). Standardised neurological examination and developmental assessment, including tests of cognitive function, were carried out. Major sequelae (n = 10) could be ascribed in most cases to the presence of large PVL lesions. Children with normal scans (n = 51), with isolated haemorrhage (n = 15) and with post-haemorrhagic ventricular dilatation (n = 3) had a favourable prognosis. Patients with small focal PVL changes (n = 16) had lower cognitive abilities on the McCarthy scale and presented more abnormal neuromotor signs and more attention deficits when compared to children with normal scans and isolated haemorrhage. Small focal PVL changes seem therefore to interfere with development at 5 years of age and might represent a morphological marker of a more diffuse brain injury. This study demonstrated also the effect of socioeconomic status on outcome at the age of 5 years.

Auditory brain stem response in neurologically normal preterm and full-term newborn infants.

A study has been completed on auditory brain stem responses (ABR) in preterm and full-term newborn infants. We have drawn up a regression score for latencies of waves I and V and the I-V interval both at 80 dB and 60 dB stimulation in infants considered neurologically optimal using stringent criteria on both clinical and sequential ultrasound assessment. The 80 dB stimulus gave more consistent results with a narrower standard deviation. Hearing thresholds were difficult to establish with consistency in this population. A parallel study of a neurologically suboptimal population with transient neurological abnormality showed deviations in the ABRs from those of the optimal population. This data should provide a baseline for assessment of abnormal infants.

Elusive blood clots and fluctuating ventricular dilatation after neonatal intraventricular haemorrhage.

Two cases are described of a previously unrecognised sequel of posthaemorrhagic ventricular dilatation. The first case documents freely mobile blood clots within the lateral ventricular system, the second variable asymmetry in the size of the dilated lateral ventricle. The unilateral ventricular dilatation depended on which side the infant was lying, the dependent ventricle being considerably larger than the upper one within 4 hours of head turning. Each of these conditions spontaneously resolved with no specific treatment.

[Extremely premature infants: what is their future? Lausanne experience 1982-1992]. / Prématurés extrêmes: quel devenir? Expérience lausannoise 1982-1992.

This study describes neonatal mortality and morbidity as well as the neuropsychological outcome of extremely-low-birth-weight infants (less than 1000 grams) born between 1/1/1982 and 12/31/1992. The number of preterm infants admitted to the neonatal unit has increased over the last ten years. If neonatal mortality remains high, the prognosis of these immature children is favourable and depends on close collaboration between obstetricians and neonatologists and on the quality of perinatal care.

Periventricular leucomalacia and neurodevelopmental outcome in preterm infants.

During an 18 month period, 120 preterm infants of 34 weeks' gestation or less were prospectively examined for periventricular leucomalacia (PVL) by cerebral ultrasound. Neurological and developmental assessment was carried out at 18 months of age corrected for prematurity in 82 surviving neonates. The developmental outcome (Griffiths development quotient) was above 80 and similar in infants with normal scans (n = 41), isolated periventricular-intraventricular haemorrhage (n = 13), and post-haemorrhagic hydrocephalus (n = 4), and no major handicap was diagnosed in these groups. By contrast, the prognosis was variable and poorer in infants with PVL (n = 24) and depended on the extent and site of the lesion. Infants with frontal PVL (n = 13) developed normally. Major sequelae (n = 8) were closely related to frontal-parietal PVL and frontal-parietal-occipital PVL and could be ascribed to the presence of cysts as well as to a persistent hyperechogenic ultrasonographic PVL appearance. A relation between size and site of the lesion and type and severity of the handicap was established.