Virological and clinical features of acute respiratory failure associated with COVID-19 in pregnancy: a case-control study.

Objective: Pregnancy is a risk factor for acute respiratory failure (ARF) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We hypothesised that SARS-CoV-2 viral load in the respiratory tract might be higher in pregnant intensive care unit (ICU) patients with ARF than in non-pregnant ICU patients with ARF as a consequence of immunological adaptation during pregnancy. Design: Single-centre, retrospective observational case-control study. Setting: Adult level 3 ICU in a French university hospital. Participants: Eligible participants were adults with ARF associated with coronavirus disease 2019 (COVID-19) pneumonia. Main outcome measure: The primary endpoint of the study was viral load in pregnant and non-pregnant patients. Results: 251 patients were included in the study, including 17 pregnant patients. Median gestational age at ICU admission amounted to 28 + 3/7 weeks (interquartile range [IQR], 26 + 1/7 to 31 + 5/7 weeks). Twelve patients (71%) had an emergency caesarean delivery due to maternal respiratory failure. Pregnancy was independently associated with higher viral load (-4.6 ± 1.9 cycle threshold; P < 0.05). No clustering or over-represented mutations were noted regarding SARS-CoV-2 sequences of pregnant women. Emergency caesarean delivery was independently associated with a modest but significant improvement in arterial oxygenation, amounting to 32 ± 12 mmHg in patients needing invasive mechanical ventilation. ICU mortality was significantly lower in pregnant patients (0 v 35%; P < 0.05). Age, Simplified Acute Physiology Score (SAPS) II score, and acute respiratory distress syndrome were independent risk factors for ICU mortality, while pregnancy status and virological variables were not. Conclusions: Viral load was substantially higher in pregnant ICU patients with COVID-19 and ARF compared with non-pregnant ICU patients with COVID-19 and ARF. Pregnancy was not independently associated with ICU mortality after adjustment for age and disease severity.

Effect of dietary protein on plasma insulin-like growth factor-1, growth, and body composition in healthy term infants: a randomised, double-blind, controlled trial (Early Protein and Obesity in Childhood (EPOCH) study).

The effect of protein intake on growth velocity in infancy may be mediated by insulin-like growth factor-1 (IGF-1). This study aimed to determine the effects of formulae containing 1·8 (F1·8) or 2·7 g (F2·7) protein/418·4 kJ (100 kcal) on IGF-1 concentrations and growth. Healthy term infants were randomly assigned to receive F1·8 (n 74) or F2·7 (n 80) exclusively for the first 4 months of life. A group of breast-fed infants (n 84) was followed-up simultaneously (reference). Growth and body composition were measured at 0·5, 4, 6, 12, 36, 48 and 60 months of life. The IGF-1 concentrations at 4 months (primary outcome) were similar in the F1·8 (67·1 (sd 20·8) ng/l; n 70) and F2·7 (71·2 (sd 27·5) ng/l; n 73) groups (P=0·52). Both formula groups had higher IGF-1 concentrations than the breast-fed group at 4 and 9 months of age (P≤0·0001). During the first 60 months of life, anthropometric parameters in the F1·8 group were lower compared with the F2·7 group, and the differences were significant for head circumference from 2 to 60 months, body weight at 4 and 6 months and length at 9, 12 and 36 months of age. There were no significant differences in body composition between these two groups at any age. We conclude that, in formula-fed infants, although increased protein intake did not affect the IGF-1 concentration during the first 12 months of life, it did affect length and head circumference growth, suggesting that factors other than IGF-1 could play roles in determining growth velocity.

Severe X-linked chondrodysplasia punctata in nine new female fetuses.

OBJECTIVES: Conradi-Hünermann-Happle [X-linked dominant chondrodysplasia punctata 2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in men while affected women show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only six antenatal presentations. METHODS: To better characterize the phenotype in female fetuses, we included nine antenatally diagnosed cases of women with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism. RESULTS: The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation. CONCLUSION: Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially because the majority of such cases involve de novo mutations.

In situ simulation training for neonatal resuscitation: an RCT.

OBJECTIVES: High-fidelity simulation is an effective tool in teaching neonatal resuscitation skills to professionals. We aimed to determine whether in situ simulation training (for ∼80% of the delivery room staff) improved neonatal resuscitation performed by the staff at maternities. METHODS: A baseline evaluation of 12 maternities was performed: a random sample of 10 professionals in each unit was presented with 2 standardized scenarios played on a neonatal high-fidelity simulator. The medical procedures were video recorded for later assessments. The 12 maternities were then randomly assigned to receive the intervention (a 4-hour simulation training session delivered in situ for multidisciplinary groups of 6 professionals) or not receive it. All maternities were evaluated again at 3 months after the intervention. The videos were assessed by 2 neonatologists blinded to the pre-/postintervention as well as to the intervention/control groups. The performance was assessed using a technical score and a team score. RESULTS: After intervention, the median technical score was significantly higher for scenarios 1 and 2 for the intervention group compared with the control group (P = .01 and 0.004, respectively), the median team score was significantly higher (P < .001) for both scenarios. In the intervention group, the frequency of achieving a heart rate >90 per minute at 3 minutes improved significantly (P = .003), and the number of hazardous events decreased significantly (P < .001). CONCLUSIONS: In situ simulation training with multidisciplinary teams can effectively improve technical skills and teamwork in neonatal resuscitation.

Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country.

BACKGROUND: Morbidity and mortality are higher among human immunodeficiency virus (HIV) exposed but uninfected (HEU) infants than unexposed infants, particularly if the mother had a low CD4 count. We investigated the possible association between maternal immune depression during pregnancy and the risk of infection in HEU infants in the national French Perinatal Cohort (EPF). METHODS: All neonates, born alive, to HIV-1-infected women enrolled in the EPF between 2002 and 2010 were included. The primary outcome was the first serious (hospitalization or death) infection during the first year of life. The main exposure variable was maternal CD4 cell count near delivery. The Kaplan-Meier method and multivariate Cox models were applied, with the different types of infections managed as competing events. RESULTS: Among 7638 HEU neonates, 699 had at least 1 serious infection (of which 159 were bacterial) with a Kaplan-Meier probability of 9.3% (95% confidence interval, 8.7-10.0) at 1 year. The risk of serious bacterial infection during the first year of life significantly increased with lower maternal CD4 cell count, before and after adjustment for maternal CD4 cell count <350 and 350-499 CD4/mm(3) (adjusted hazard ratio = 1.7 [1.2-2.6] and 1.2 [0.8-1.9], respectively; P = .03). This association mainly concerned infections involving encapsulated bacteria (P = .03). The risk of serious viral infection was, by contrast, independent of the mother's CD4 cell count. CONCLUSIONS: Maternal CD4 count is significantly and specifically associated with the risk of serious infections with encapsulated bacteria in HEU infants.

Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled trial.

BACKGROUND: Probiotics and prebiotics are considered to be beneficial to the gastrointestinal health of infants. OBJECTIVE: The objective was to evaluate infant formulas containing probiotics and synbiotics (combinations of probiotics and prebiotics) for safety and tolerance. DESIGN: In a prospective, controlled, double-blind, randomized trial, healthy full-term infants were exclusively fed a control formula or study formulas containing Bifidobacterium longum BL999 (BL999) + Lactobacillus rhamnosus LPR (LPR), BL999 + LPR + 4 g/L of 90% galactooligosaccharide/10% short-chain fructooligosaccharide (GOS/SCFOS), or BL999 + Lactobacillus paracasei ST11 (ST11) + 4 g/L GOS/SCFOS from < or = 2 to 16 wk of age (treatment period). Safety and tolerance were assessed based on weight gain during the treatment period (primary outcome) as well as recumbent length, head circumference, digestive tolerance, and adverse events (secondary outcomes), which were evaluated at 2, 4, 8, 12, 16, and 52 wk of age. RESULTS: Two hundred eighty-four infants were enrolled. During the treatment period, difference in mean weight gain between control and study formula groups in both the intention-to-treat and per-protocol populations were within the predefined equivalence boundaries of +/-3.9 g/d, indicating equivalent weight gain. Secondary outcomes did not show significant differences between groups during the treatment period. CONCLUSION: Infants fed formulas containing probiotics or synbiotics show a similar rate in weight gain compared with those fed a control formula and tolerate these formulas well.

Age-related modulation of dopamine d1 receptor mRNA level by hypoxia in rabbit adrenal gland.

In the perinatal period, the fetus and the neonate may be exposed to hypoxic conditions. The adrenal gland responds to systemic hypoxia by releasing catecholamines. Dopamine and dopamine D1 receptor are present in the adrenal medulla and are liable to be affected by exposure to hypoxia. We used a rabbit model to determine whether hypoxia modulates the dopamine D1 receptor (DA D1-R) mRNA expression in adrenal glands during development. Rabbits were investigated according to four different hypoxic conditions: 15% O2 for 6 h, 15% O2 for 24 h, 8% O2 for 6 h, and 8% O2 for 24 h. Control groups were maintained in normoxic conditions (21% O2). For each O2 condition, animals were studied at three different ages: 1-day old newborns, 25-day-old pups, and 6-month-old adults. We compared the hypoxic groups to their respective age normoxic group. We have shown that hypoxia decreases DA D1-R mRNA expression level, evaluated using Northern blot analysis, in newborn rabbits, whatever the duration and severity of hypoxia. This downmodulation was not observed in 25-day-old and in adult rabbits. This age-related modulation of adrenal DA D1-R mRNA could be linked to the age-related transition from the non-neurogenic to the neurogenic regulation of the adrenal function.

Effect of betamethasone on the expression of dopamine D1 receptor mRNA in the developing rabbit adrenal gland.

BACKGROUND: Antenatal corticotherapy is widely used to enhance pulmonary fetal maturation in cases in which premature birth is likely. The adrenal gland, which has a key role in controlling fetal and neonatal adaptation, appears to be a target organ of glucocorticoids. OBJECTIVES: The aim of this study was first to determine the ontogenic profile of dopamine D1 receptor (DA D1-R) messenger RNA (mRNA) in the rabbit. The effects of antenatal exposure to exogenous corticoids on levels of adrenal DA D1-R mRNA expression were examined. METHODS: Pregnant rabbits free of any treatment or handling before delivery were chosen for the study of DA D1-R mRNA ontogenic profile. For the study of the antenatal exposure to exogenous corticoids, pregnant rabbits were given 2 injections of either betamethasone 0.1 mg/kg or saline 0.1 mL/kg. DA D1-R mRNA expression was determined using northern blot analysis at 4 developmental ages: fetus (at 27 days of gestation), 1 day of age, 25 days of age, and adulthood. Rabbits were allocated to their respective group (treated or untreated) depending on maternal treatment (betamethasone or saline, respectively). RESULTS: Four pregnant rabbits were used for the ontogenic-profile group, which comprised 11 fetuses, seven 1-day-old rabbits, four 25-day-old rabbits, and 2 adults. Six other pregnant rabbits received betamethasone; 6 saline. The treated group comprised 12 fetuses, twelve 1-day-old rabbits, four 25-day-old rabbits, and 3 adults. The untreated group comprised 12 fetuses, fifteen 1-day-old rabbits, five 25-day-old rabbits, and 3 adults. DA D1-R mRNA was expressed in rabbit adrenal glands from the fetal period to adulthood and this expression was not age dependent. Moreover, antenatal corticotherapy induced a significant increase in respective DA D1-R mRNA levels of 20%, 15%, and 8% in treated fetuses, 1-day-old rabbits, and 25-day-old rabbits compared with the untreated groups (P <0.003, 0.003, and 0.005, respectively). This increase was not observed in adulthood. CONCLUSIONS: In the rabbits in this study, DA D1-R mRNA expression in the adrenal gland began during gestation. Its expression was not age dependent but was rapidly modified by antenatal exposure to betamethasone. These corticoid-induced changes, observed until late infancy, did not occur in adulthood.

McKusik-Kaufman syndrome: prenatal diagnosis, genetics and follow up.

McKusick-Kaufman syndrome (MKKS) is a rare autosomal recessive genetic disease with classical hexadactyly and hydrocolpos in females and sometimes cardiac abnormality. We report such a case diagnosed just before birth with a favourable outcome. From this case we describe and discuss all the prenatal sonographic signs which are not always present. On the genetic side, the gene has recently been localized together with the mutation responsible for MKKS. The phenotypic relationship between MKKS which has a good prognosis and Bardet-Biedl syndrome (BBS) with a worse prognosis requires great caution before diagnosing MKKS and a long follow-up is necessary to recognize obesity, growth retardation and pigmentary retinitis.