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.

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.

Long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in small-for-gestational-age preterm infants.

OBJECTIVE: To investigate the effects of neonatal hypoglycemia on physical growth and neurocognitive function. STUDY DESIGN: A systematic detection of hypoglycemia (<2.6 mmol/L or 47 mg/dL) was carried out in 85 small-for-gestational-age preterm neonates. Prospective serial evaluations of physical growth and psychomotor development were performed. Retrospectively, infants were grouped according to their glycemic status. RESULTS: The incidence of hypoglycemia was 72.9%. Infants with repeated episodes of hypoglycemia had significantly reduced head circumferences and lower scores in specific psychometric tests at 3.5 years of age. Hypoglycemia also caused reduced head circumferences at 18 months and lower psychometric scores at 5 years of age. Infants with moderate recurrent hypoglycemia had lower scores at 3.5 and 5 years of age compared with the group of infants who had 1 single severe hypoglycemic episode. CONCLUSION: Recurrent episodes of hypoglycemia were strongly correlated with persistent neurodevelopmental and physical growth deficits until 5 years of age. Recurrent hypoglycemia also was a more predictable factor for long-term effects than the severity of a single hypoglycemic episode. Therefore repetitive blood glucose monitoring and rapid treatment even for mild hypoglycemia are recommended for small-for-gestational-age infants in the neonatal period.

[Intrauterine and postnatal transfer of high risk newborn infants. Swiss Society of Neonatology]. / Intrauteriner und postnataler Transfer von Risikoneugeborenen. Schweiz. Gesellschaft für Neonatologie.

UNLABELLED: The centralisation of high risk deliveries in perinatal centres has become standard practice in most developed countries over the last 20 years. The goal of this study was to assess to which extent this practice has been implemented in Switzerland as well. In addition, we compared standard morbidity outcome measurements between outborn and inborn infants, as well as the frequencies of postnatal interhospital transfers. METHODS: All infants born alive either below the 32nd week of gestation, weighing less than 1500 g, or who required assisted ventilation before the 44th week of corrected gestational age were entered in a prospective epidemiological survey (Swiss minimal neonatal data set) if they had been admitted to a neonatal intensive or intermediate care unit. We analysed the data derived from infants born between 1 January and 31 December 1996. RESULTS: 86% of the 720 infants of less than 32 weeks gestation and/or less than 1500 g (group 1) were born in a perinatal centre, whereas only 27% of the 508 infants > or = 32 weeks gestation and > or = 1500 g who required assisted ventilation (group 2) were inborn. In group 1 outborn infants had a higher risk for pulmonary hypertension (odds ratio 3.7, 95% confidence interval 1.4 to 10.0), for hyperechogenic leucomalacia (odds ratio 2.7, CI 1.3-5.4), for necrotising enterocolitis (odds ratio 2.5, CI 1.1-5.7). The frequencies of postnatal interhospital transfer were the following for group 1 and 2: once 35% vs. 52%, twice or more 10% vs. 31%. CONCLUSION: 720 infants below 32 weeks gestation and/or < 1500 g were admitted to neonatal units in 1996 which corresponds to 0.86% of all liveborn infants in Switzerland. Fourteen percent of these infants were outborn with a high morbidity. Of the 508 larger and older new-born infants who required assisted ventilation (0.62% of all liveborn infants in Switzerland), 73% were outborn. It is speculated that improved prenatal identification of risk factors and prenatal transfer could further reduce the morbidity of these two populations of new-born infants.

[The prognosis of premature infants: from the viewpoint of gynecologists-obstetricians and results from Lausanne]. / Le pronostic des nouveau-nés prématurés: appréciation des gynécologues-obstétriciens et résultats à Lausanne.

AIM OF THE STUDY: To assess the views of obstetricians concerning the survival rate in neonates on the basis of gestational age and birth-weight, rate of severe handicap, and minimum gestational age for preventive and curative measures (steroids for foetal lung maturation and caesarean section in the event of acute foetal distress). Then, to compare these results with the outcomes observed in the referral centre for these obstetricians. METHOD: We circulated an anonymous questionnaire (two mailings between October 1995 and February 1996) to obstetricians in the Lausanne area. The replies were compared with prospective data from the Lausanne obstetric unit (1989-1995) and neonatal intensive care unit (1982-1993) backed by the neurodevelopmental outcome assessed by regular follow-up until the age of 8 1/2 years. RESULTS: We obtained 116 replies from the 270 specialists questioned (43% participation). The mortality rates in Lausanne are described by gestational age and birthweight, as is the rate of severe handicap. We observed significant overestimation of the mortality rate for premature infants between 25 and 31 weeks and for birthweights over 600 grams. The rate of severe handicap was widely overestimated for a gestational age below 28 weeks at delivery or a birthweight below 1500 g (prognosis 31.2% and 21.5% respectively, compared with actual figures of 7.4% and 6.8%). Moreover, distribution of replies showed marked heterogeneity between 26 and 29 weeks and between 600 and 1000 grams. The estimated minimum gestational age was 26 weeks (mean) for starting steroid therapy and 27 weeks for caesarean section for acute foetal distress. CONCLUSION: Assessment of prognosis by obstetricians did not correlate with our results and reflected the disparity of data found in the literature. Nevertheless, the implications of this discrepancy may be slight. The study stresses the efficacy of the regionalisation of perinatal care in the Lausanne area, where we observed only 6% of outborn weighting less than 1500 grams in the 18 maternity departments covered. The rate of completed antenatal steroid therapy (41% for infants below 1500 grams) appears to be favourable in our population compared with the literature. We advocate permanent information on local results regarding perinatal outcome, to enable individual obstetricians to consider the desirability of treating, transferring or even counselling or reassuring their patients.

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.

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.

Risk factors of sensorineural hearing loss in preterm infants.

Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.

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.

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.

[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.