R. F. Kornelisse

Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants

OBJECTIVEnThe objective of the study was to study the effects of histologic chorioamnionitis (HC) with or without fetal involvement and antenatal steroid (AS) exposure on neonatal outcome in a prospective cohort of preterm infants.nnnSTUDY DESIGNnThe clinical characteristics and placental histology were prospectively collected in 301 infants born at a gestational age 32.0 weeks or less in the Erasmus University Medical Center.nnnRESULTSnIn univariable analyses, HC without fetal involvement (n=53) was associated with decreased severe respiratory distress syndrome (RDS) (11% vs 28%; P<.05), whereas HC with fetal involvement infants (n=68) had more necrotizing enterocolitis (9% vs 2%; P<.05), intraventricular hemorrhage (IVH) (25% vs 12%; P<.05), and neonatal mortality (19% vs 9%; P<.05). In HC without fetal involvement infants, AS reduced the incidences of RDS (43% vs 85%; P<.05) and IVH (5% vs 39%; P<.01). In multivariable analyses, HC without fetal involvement was associated with decreased severe RDS (odds ratio, 0.22; 95% confidence interval, 0.05-0.93; P<.05) and increased early-onset sepsis (odds ratio, 2.22; 95% confidence interval, 1.02-4.83; P<.05).nnnCONCLUSIONnIn a prospective cohort of preterm infants, multivariable analyses reveal only a modest association between histologic chorioamnionitis and neonatal outcome.

Chorioamnionitis Alters the Response to Surfactant in Preterm Infants

OBJECTIVEnTo study the association between antenatal exposure to chorioamnionitis and the neonatal response to surfactant.nnnSTUDY DESIGNnProspective observational cohort of 301 preterm infants of gestational age < or = 32.0 weeks, 146 of whom received surfactant according to standardized criteria. Fraction of inspired oxygen (FiO(2)) requirement (using analysis of variance) and time to extubation (using Kaplan-Meier and Cox regression analyses) were compared between groups based on the presence of histological chorioamnionitis (HC) with or without fetal involvement (HC-, n = 88; HC + F-, n = 25; HC + F+, n = 33) and between infants who developed bronchopulmonary dysplasia (BPD) or died (n = 57) and BPD-free survivors (n = 89). Multiple logistic regression was performed to investigate the association between HC and BPD.nnnRESULTSnCompared with HC- infants, HC + F+ infants had significantly greater FiO(2) requirement and prolonged time to extubation postsurfactant, not accounted for by differences in gestational age and birth weight. Infants with BPD/death had a strikingly similar pattern of increased FiO(2) requirement postsurfactant. Moreover, in infants who received surfactant, HC + F+ status was associated with increased risk for BPD (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.02-11.3; P = .047) and for BPD/death (OR = 2.72; 95% CI = 1.00-7.42; P = .049).nnnCONCLUSIONSnAn impaired surfactant response was observed in preterm infants with severe chorioamnionitis and may be involved in the association between chorioamnionitis, mechanical ventilation, and the development of BPD.

Early life intervention with glucocorticoids has negative effects on motor development and neuropsychological function in 14-17 year-old adolescents.

OBJECTIVEnTo reduce the risk of bronchopulmonary dysplasia, preterm infants receive neonatal treatment with glucocorticoids, mostly dexamethasone (DEX). Compared to current protocols, treatment regimens of the late 1980s - early 1990s prescribed high doses of DEX for an extensive period up to 6 weeks. Worldwide at least one million children have been treated with this dose regimen. Previous studies have shown adverse effects of neonatal treatment with the glucocorticoid dexamethasone (DEX) on outcome in children aged 7-10 years. On the other hand, treatment with another glucocorticoid, hydrocortisone (HC), was not related to adverse effects in childhood. In the current study we determined the consequences of early life intervention with DEX or HC in adolescents (age 14-17 years). Besides motor function and intellectual capacities, we also examined fundamental neuropsychological functions which have so far received little attention.nnnMETHODSnIn an observational cohort study we compared 14-17 year-old adolescents who received DEX (.5 mg/kg/day tapering off to .1 mg/kg/day over 21 days, n=63), or HC (5 mg/kg/day tapering off to 1 mg/kg/day over 22 days, n=67), or did not receive neonatal glucocorticoids (untreated, n=71) after premature birth (gestational age<32 weeks). Because gestational age was shorter and duration of ventilation was longer in the DEX-treated group, all analyses were corrected for these potential confounders. Motor function, IQ, and neuropsychological functions were assessed.nnnRESULTSnDEX-treated group participants scored lower on gross motor skill tasks than their HC-treated and untreated counterparts. A higher proportion of DEX-treated girls needed special education compared to the other groups. DEX-treated adolescents performed poorer on neuropsychological tasks measuring alertness, visuomotor coordination, and emotion recognition. The HC-treated group did not differ from the untreated group.nnnCONCLUSIONSnEven after 14-17 years, neonatal treatment with .5 mg/kg/day DEX was associated with adverse effects on motor function, school level, and neuropsychological functions, whereas treatment with the clinically equally effective dose of 5 mg/kg/day HC was not. Potential physiological mechanisms underlying the differences in dexamethasone and hydrocortisone effects are discussed. Based on the current findings, we recommend early identification of neuropsychological deficits after DEX treatment in order to specify extra educational needs.

Neonatal glucocorticoid treatment: Long-term effects on the hypothalamus-pituitary-adrenal axis, immune system, and problem behavior in 14-17 year old adolescents

Neonatal glucocorticoid (GC) treatment is used to prevent bronchopulmonary dysplasia (BPD) in prematurely born babies. In the 1990s, treatment regimens with relatively high doses of dexamethasone (DEX) were common. As an alternative, hydrocortisone (HC) was used. Earlier, we compared long-term effects of both GCs in children aged 7-10 and detected adverse effects of neonatal DEX treatment, but not of HC, on a range of outcomes. The aim of the current cohort study was to investigate whether long-term effects of neonatal DEX were maintained and whether effects of HC remained absent at adolescent age (14-17years). We compared 71 DEX-treated and 67 HC-treated adolescents. In addition, 71 adolescents who were not neonatally treated with GCs participated. All were born <32weeks of gestation. DEX-treated girls showed increased adrenocorticotropic hormone (ACTH) and cortisol responses in the Trier Social Stress Test. The cortisol awakening response was lower in HC-treated participants compared to untreated participants. Negative feedback function of the HPA-axis in the dexamethasone suppression test did not differ between groups. In contrast to our observations at the age of 7-10years, we did not observe group differences in mitogen-induced cytokine production at the age of 14-17years. DEX-treated girls showed more social problems and anxious/depressed behavior than HC-treated girls. Untreated girls showed more problem behavior as well. In conclusion, our results suggest that, especially in girls, neonatal DEX has a programming effect on the HPA-axis and on the ability to adjust to the environment. The loss of group differences on immune system measures indicate that potentially negative effects detected at a younger age subsided.

Colonization Dynamics of Antibiotic-Resistant Coagulase-Negative Staphylococci in Neonates

ABSTRACT Coagulase-negative staphylococci (CoNS) isolated in neonatal late-onset sepsis are often antibiotic resistant. We analyzed CoNS from skin and feces of neonates during hospitalization. Antibiotic resistance of skin isolates increased during hospitalization, especially in Staphylococcus haemolyticus. Staphylococcus warneri showed low antibiotic resistance. Our data suggest that different CoNS species may play distinct roles in colonization.

Early postnatal blood pressure in preterm infants: effects of chorioamnionitis and timing of antenatal steroids.

Previous studies suggest postnatal blood pressure in preterm infants to be decreased by chorioamnionitis and increased by antenatal steroids (AS). We examined the adjusted effects of both antenatal modulators on postnatal blood pressure (BP), with separate effects reported for histologic chorioamnionitis with or without fetal involvement and timing of AS. General characteristics, BP, and heart rate values during the first 72 h after birth were obtained from 271 infants with gestational age ≤32.0 wk. In unadjusted analyses, chorioamnionitis was associated with lower BP, most prominently so in infants with fetal involvement, without an effect on hypotension incidence. AS increased BP and decreased the incidence of hypotension when administered within 7 d before birth. In a multivariable mixed model analysis, the AS effect remained significant, whereas chorioamnionitis was not independently predictive of postnatal BP. Other variables associated with increased postnatal BP were gestational age and umbilical artery pH, whereas hemolysis, elevated liver enzymes, low platelets syndrome was associated with decreased BP. In conclusion, AS seem to increase postnatal BP and decrease hypotension in preterm infants when given within 7 d before birth. Conversely, chorioamnionitis did not significantly affect postnatal BP after multivariable adjustment.

Prenatal and postnatal findings in small for gestational age fetuses without structural ultrasound anomalies at 18-24 weeks.

To assess phenotypic and genotypic characteristics of small‐for‐gestational‐age (SGA) fetuses without structural anomalies at 18–24 weeks gestation.

Maternal and neonatal outcomes in women with severe early onset pre-eclampsia before 26 weeks of gestation, a case series.

To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre‐eclampsia before 26 weeks of gestation.

451 A Clinical Prediction Model for Histological Chorioamnionitis at Birth

Background: Antenatal exposure to histological chorioamnionitis affects neonatal outcome. Early identification of affected infants could potentiate early intervention. However, in clinical practice the final results of placental pathology may take weeks. Methods: Placental pathology and relevant clinical data were obtained from consecutively born singleton infants (gestational age < 32 wks) in the Erasmus MC. Prediction models for histological chorioamnionitis (HC) and for HC with fetal involvement (FI) were constructed using clinical variables known at birth, in a backward logistic regression model. ROC curves were computed using model-derived predictives. Results: Of the 216 included infants 84 had HC, of whom 51 had FI. HC+FI was best predicted by a combination of low gestational age, clinical chorioamnionitis, PPROM, absence of preeclampsia and not being small for gestational age (Table 1; AUC(95%CI)=0.93(0.89-0.96), p<.001). HC was best predicted by the same model with addition of placental weight (Table 2; AUC(95%CI)=0.95(0.93-0.98); p<.001). At a set specificity of 90%, sensitivity of the model is 82% for HC+FI and 85% for HC. Conclusion: HC and HC+FI can be predicted fairly accurately by a simple set of clinical variables available at birth. External validation is required to confirm the usefulness of these models. This may potentiate early intervention to improve future outcome in affected infants.

Survival at a Gestational Age of 24 Weeks in the Netherlands

violence. Although previous studies have noted gender norms that promote male dominance and control as key factors, it must be acknowledged that these studies (including the recently published multicountry study2) only include men in their measures of perpetrators. We lack similar theories for females because they have largely been excluded from the perpetration research. As noted by Righthand and Welch,3 research on females who have committed sex offenses is rare. They suggest that “[t]he incidence of sex offending may be underestimated for female juveniles even more than for males, perhaps because of a societal reluctance (and even a reluctance among professionals) to acknowledge that girls are capable of committing such offenses.”3(p14) Thus, societal norms do encourage female perpetration, just in different ways than male perpetration. Until we acknowledge that women can be violent, we will not be able to develop gender-appropriate prevention programs that reduce rates of perpetration for men and women. We appreciate Dr Goodson’s observation that it is unlikely that all teenage perpetrators of sexual violence are making a conscious decision to commit a felony. Motivations certainly vary considerably. Future research could focus on illuminating this aspect of the perpetration. At the same time, sexual violence is sexual violence, regardless of motivation. Prevention programs that address this behavior are critical. Whether the motivation behind the violence was insidious or not, the data suggest that perpetrators often do not take responsibility for their actions and that many blame the victim to some extent. Taking responsibility for one’s actions may very well be related to the motivation behind the violence, and this combination could be a useful focus within prevention programs. The research on programs that focus on rethinking scripts for acceptable behavior is encouraging.4,5 And, as suggested in the implications of our study,1 we agree that bystander intervention could play a crucial role in both helping victims and identifying perpetrators.