Validation of a commercially available SARS-CoV-2 serological immunoassay.

OBJECTIVES: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19. METHODS: In this unmatched (1:2) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 326 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. RESULTS: COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.990 (95% Confidence Interval [95%CI]: 0.983-0.996) and 0.978 (95%CI: 0.967-0.989), respectively. IgG assays outperformed IgA assays (p=0.01). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 2.5 displayed a 100% specificity (95%CI: 99-100) and a 100% positive predictive value (95%CI: 96-100). A 0.8 cut-off displayed a 94% sensitivity (95%CI: 88-97) and a 97% negative predictive value (95%CI: 95-99). Substituting the upper threshold for the manufacturer's, improved assay performance, leaving 8.9% of IgG ratios indeterminate between 0.8-2.5. CONCLUSIONS: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.

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.

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.

Energy-nitrogen balances and protein turnover in small and appropriate for gestational age low birthweight infants.

The aim of the present study was to compare, under the same nursing conditions, the energy-nitrogen balance and the protein turnover in small for gestational age (SGA) and appropriate for gestational age (AGA) low birthweight infants. We compared 8 SGA's (mean +/- s.d.: gestational age 35 +/- 2 weeks, birthweight 1520 +/- 330 g) to 11 AGA premature infants (32 +/- 2 weeks, birthweight 1560 +/- 240 g). When their rate of weight gain was above 15 g/kg/d (17.6 +/- 3.0 and 18.2 +/- 2.6 g/kg/d, mean postnatal age 18 +/- 10 and 20 +/- 9 d respectively) they were studied with respect to their metabolizable energy intake, their energy expenditure, their energy and protein gain and their protein turnover. Energy balance was assessed by the difference between metabolizable energy and energy expenditure as measured by indirect calorimetry. Protein gain was calculated from the amount of retained nitrogen. Protein turnover was estimated by a stable isotope enrichment technique using repeated nasogastric administration of 15N-glycine for 72 h. Although there was no difference in their metabolizable energy intakes (110 +/- 12 versus 108 +/- 11 kcal/kg/d), SGA's had a higher rate of resting energy expenditure (64 +/- 8 versus 57 +/- 8 kcal/kg/d, P less than 0.05). Protein gain and composition of weight gain was very similar in both groups (2.0 +/- 0.4 versus 2.1 +/- 0.4 g protein/kg/d; 3.5 +/- 1.1 versus 3.3 +/- 1.4 g fat/kg/d in SGA's and AGA's respectively). However, the rate of protein synthesis was significantly lower in SGA's (7.7 +/- 1.6 g/kg/d) as compared to AGA's (9.7 +/- 2.8 g/kg/d; P less than 0.05). It is concluded that SGA's have a more efficient protein gain/protein synthesis ratio since for the same weight and protein gains, SGA's show a 20 per cent slower protein turnover. They might therefore tolerate slightly higher protein intakes. Postconceptional age seems to be an important factor in the regulation of protein turnover.

Magnesium sulphate as an alternative and safe treatment for severe persistent pulmonary hypertension of the newborn.

Eleven newborns admitted consecutively to the neonatal unit with respiratory failure and severe persistent pulmonary hypertension (PPHN) were included in a clinical trial to assess the efficacy of magnesium sulphate (MgSO4) in the treatment of PPHN. A loading dose of 200 mg/kg MgSO4 was given over 20 minutes, followed by a continuous infusion of 20-150 mg/kg/hour to obtain a magnesium blood concentration between 3.5 and 5.5 mmol/l. Mean (SD) duration of treatment was 75.5 (19.8) hours. No other vasodilatory drug was administered before or during the treatment and patients were not hyperventilated. Mean (SEM) PaO2 values significantly increased from 42.6 (8.8) before treatment to 70.3 (24.1) mm Hg after 24 hours, with no change in pH or PCO2. Oxygen index and alveolar-arterial oxygen gradient (A-aDO2) were significantly lower after 24 hours; respectively, 46.8 (15.2) to 28.0 (9.0) and 624.3 (11.3) to 590 (58) mm Hg. Mean airway pressure could be significantly reduced from 19.5 (3.1) to 13.9 (3.9) cm H2O after 72 hours. Mean ventilatory time support was 131 hours and mean total oxygen dependency 10 days. No systemic hypotension nor any other adverse effect were noted. All infants survived and the neurodevelopmental assessment was normal at 6 and 12 months of age. It is concluded that magnesium sulphate is a non-aggressive and low-cost treatment of short duration which is easy to apply. It may have a role in the various treatment of PPHN.

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.

[Cardiac rhabdomyomatosis and Bourneville's tuberous sclerosis in the fetus. Apropos of 2 cases]. / Rhabdomyomatose cardiaque et sclérose tubéreuse de Bourneville chez le foetus. A propos de 2 cas.

Two cases of cardiac rhabdomyoma discovered fortuitously at foetal ultrasonography gave rise to no obstructive cardiac signs or arrhythmias either in the antenatal or postnatal periods. These multiple tumours often observed in Bourneville's tuberous sclerosis orientated the clinical investigations to the diagnosis of this disease from the outset. MRI demonstrated cortical tubers and subependymal nodules in both cases. A retinal hamartoma was present in one case. No renal involvement could be detected by ultrasonic examination. No neurological or cardiovascular symptoms appeared during follow-up (20 and 4 months after birth). Investigations in the parents were negative, these two cases being sporadic forms of Bourneville's tuberous sclerosis. The functional prognosis is related to the neurological outcome. Doppler echocardiography would appear to be the best method of following up cardiac rhabdomyomas, and enabled the demonstration of partial regression of the largest tumour in one of these two cases. Cardiac MRI is also an excellent diagnostic tool. As it is usually performed at the same time as cerebral MRI, essential in the follow-up of Bourneville's tuberous sclerosis, it does not represent additional discomfort to the patient.

Outcome of infants of very low birthweight treated in neonatal intensive care unit.

The neonatal survival rate of 500 VLBW (less than or equal to 1 500 g) treated in the neonatal unit of the Departement of Paediatrics in Lausanne (C.H.U.V.) was studied according to changing patterns of nursing and medical care occurring in four successive periods (1961 IX-1963, X-1963 - 1965, 1966-1968, IV-1971-1973). The survival rate at 28 days increased from 35.5% to 47.7% between 1961 and 1965. Earlier start of feeding, intravenous fluid therapy, better control of ambient temperature and better oxygenotherapy are the main changes during this period. Further improvement in neonatal care did not affect the 28-day survival rate. 213 VLBW out of 500 (42.6%) survived at 28 days, 13 (6.1%) out of these died within the first two years of life, 36 (16.9%) were lost for the follow-up. The remaining 164 VLBW were followed until ages between 18 months and 8 years. The improvement in neonatal care was associated with a decrease in the incidence of major neurological sequels from 21.1% to 12.2% between 1961 and 1973. Cerebral palsy and epilepsy are responsible for this decrease. The incidence of mental retardation (DQ or IQ less than 80) also decreased from 17.5% to 4.9% during the same period. However, the incidence of retrolental fibroplasia remained stable. The outlook for VLBW infants is now much more encouraging. Further improvement in perinatal care is likely to further reduce the incidence of major handicaps. but it is not clear whether they will affect the incidence of minor problems such as learning difficulties or poor school performances. More prospective studies are necessary to clarify these points and to ensure early detection of these developmental problems.

Water, energy and early postnatal growth in preterm infants.

Non-invasive methods, including stable isotope techniques, indirect calorimetry, nutritional balance and skinfold thickness, have given a new insight into early postnatal growth in neonates. Neonates and premature infants in particular, create an unusual opportunity to study the fluid and metabolic adaptation to extrauterine life because their physical environment can be controlled, fluid and energy balance can be measured and the link between metabolism and the energetics of their postnatal growth can be assessed accurately. Thus the postnatal time course of total body water, heat production, energy cost of growth and composition of weight gain have been quantified in a series of "healthy" low-birth-weight premature infants. These results show that total body water is remarkably stable between postnatal days 3-21. Energy expenditure and heat production rates increase postnatally from mean values of 40 kcal/kg/day during the first week to 60 kcal/kg/day in the third week. An apparent energy balance deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein metabolism is the highest energy demanding process related to growth. The fact that nitrogen balance becomes positive within 72 h after birth places the newborn in a transitional situation of dissociated balance between energy and protein metabolism during early postnatal growth: skinfold thickness, dry body mass and fat decrease, while there is a gain in protein and increase in supine length. This particular situation ends during the second postnatal week and soon thereafter the rate of weight gain matches statural growth. The goals of the following review are to summarize data on total body water and energy metabolism in premature infants and to discuss how they correlate with physiological aspects of early postnatal growth.