Predictive value of fetal growth trajectory from 20 weeks of gestation onwards for severe adverse perinatal outcome in low-risk population: secondary analysis of IRIS study.

OBJECTIVES: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. METHODS: This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. RESULTS: Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. CONCLUSIONS: In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Implication of third-trimester screening accuracy for small-for-gestational age and additive value of third-trimester growth-trajectory indicators in predicting severe adverse perinatal outcome in low-risk population: pragmatic secondary analysis of IRIS study.

OBJECTIVES: To examine the implications of third-trimester small-for-gestational-age (SGA) screening accuracy on severe adverse perinatal outcome (SAPO) and obstetric intervention in a low-risk population. Furthermore, we aimed to explore the additive value of third-trimester sonographic growth-trajectory measurements in predicting SAPO and obstetric intervention. METHODS: This was a secondary analysis of a Dutch national multicenter stepped-wedge-cluster randomized trial among 11 820 low-risk pregnant women. Using multilevel multivariable logistic regression analysis, we compared SAPO and obstetric interventions in SGA neonates with and without SGA suspected prenatally (true positives and false negatives) and non-SGA neonates with and without SGA suspected prenatally (false positives and true negatives). In a subsample (n = 7989), we analyzed the associations of abdominal circumference (AC) and estimated fetal weight (EFW) < 10th centile (p10) and third-trimester growth-trajectory indicators AC and EFW crossing > 20 and AC crossing > 50 centiles and the lowest decile of AC growth-velocity Z-scores (ACGV < 10%) with SAPO and obstetric interventions. RESULTS: SGA infants, i.e. the true-positive and false-negative cases, had an increased risk of SAPO (adjusted odds ratio (aOR), 4.46 (95% CI, 2.28-8.75) and aOR 2.61 (95% CI, 1.74-3.89), respectively), and obstetric intervention (aOR for: induction of labor, 2.99 (95% CI, 2.15-4.17) and 1.38 (95% CI, 1.14-1.66); Cesarean section, 1.82 (95% CI, 1.25-2.66) and 1.27 (95% CI, 1.05-1.54); medically indicated preterm delivery, 2.67 (95% CI, 1.97-3.62) and 1.20 (95% CI, 1.03-1.40)). The false-positive cases did not differ from the true negatives for all outcomes, including obstetric intervention. Of the third-trimester growth-trajectory indicators, only ACGV < 10% was associated moderately with SAPO (aOR, 2.15 (95% CI, 1.17-3.97)), while AC and EFW crossing > 20 and AC crossing > 50 centiles were not. Both EFW < p10 alone (aOR, 1.95 (95% CI, 1.13-3.38)) and EFW < p10 combined with ACGV < 10% (aOR, 4.69 (95% CI, 1.99-11.07)) were associated with SAPO, and they performed equally well in predicting SAPO (area under the receiver-operating-characteristics curve, 0.71 (95% CI, 0.65-0.76) vs 0.72 (95% CI, 0.67-0.77), P = 0.51). CONCLUSION: Neonates who had been suspected falsely of being SGA during pregnancy had no higher rates of obstetric intervention than did those without suspicion of SGA prenatally. Our results do not support that third-trimester low fetal growth velocity (ACGV < 10%) may be of additive value for the identification of fetuses at risk of SAPO in populations remaining at low risk throughout pregnancy. AC and EFW crossing > 20 and AC crossing > 50 centiles performed poorly in identifying abnormal fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Experiencing discrimination mediates the relationship between victimization and social withdrawal in patients suffering from a severe mental illness: A cross-sectional study.

Psychiatric patients are often victims of crime and discrimination and are often socially withdrawn. This has negative consequences for their health and recovery. We examined whether such discrimination mediates the association between victimization and social withdrawal, and whether these associations differ between men and women. We also determined the prevalence of social withdrawal and the discrimination experienced by patients suffering from a severe mental illness. This study is embedded in the Victimization in Psychiatric Patients study. Information on discrimination, social withdrawal and victimization was obtained using structured self-report questionnaires (N = 949). We reported the 12-month prevalence of these phenomena and used path analysis to estimate the direct path between personal and property victimization and social withdrawal, and the indirect path through the discrimination experienced. The impact of gender was assessed by testing interaction terms. Social withdrawal was reported by 20.6% (95%CI 18.1-23.2) of participants, and being discriminated against in the past 12 months by 75.3% (95%CI: 72.6-78.0%). While crime victimization had no direct effects on social withdrawal, personal crime victimization (B = 0.47; 95%CI 0.25-0.72; p < 0.001) and property crime victimization (B = 0.65; 95%CI 0.42-0.93; p < 0.001) had significant indirect effects on social withdrawal, which were mediated by the discrimination experienced. In men we found a direct negative effect of property crime on social withdrawal (B = -0.68; 95%CI: -1.21to -0.11, p = 0.014). We conclude that personal and property victimization, for both men and women, was associated with higher levels of social withdrawal, and this was fully mediated by the discrimination experienced.

The oxytocinergic system in PTSD following traumatic childbirth: endogenous and exogenous oxytocin in the peripartum period.

Birth experiences can be traumatic and may give rise to PTSD following childbirth (PTSD-FC). Peripartum neurobiological alterations in the oxytocinergic system are highly relevant for postpartum maternal behavioral and affective adaptions like bonding and lactation but are also implicated in the response to traumatic events. Animal models demonstrated that peripartum stress impairs beneficial maternal postpartum behavior. Early postpartum activation of the oxytocinergic system may, however, reverse these effects and thereby prevent adverse long-term consequences for both mother and infant. In this narrative review, we discuss the impact of trauma and PTSD-FC on normal endogenous oxytocinergic system fluctuations in the peripartum period. We also specifically focus on the potential of exogenous oxytocin (OT) to prevent and treat PTSD-FC. No trials of exogenous OT after traumatic childbirth and PTSD-FC were available. Evidence from non-obstetric PTSD samples and from postpartum healthy or depressed samples implies restorative functional neuroanatomic and psychological effects of exogenous OT such as improved PTSD symptoms and better mother-to-infant bonding, decreased limbic activation, and restored responsiveness in dopaminergic reward regions. Adverse effects of intranasal OT on mood and the increased fear processing and reduced top-down control over amygdala activation in women with acute trauma exposure or postpartum depression, however, warrant cautionary use of intranasal OT. Observational and experimental studies into the role of the endogenous and exogenous oxytocinergic system in PTSD-FC are needed and should explore individual and situational circumstances, including level of acute distress, intrapartum exogenous OT exposure, or history of childhood trauma.

Hours in non-parental child care are related to language development in a longitudinal cohort study.

BACKGROUND: The effects of child care services on several domains of child development have been extensively investigated, but evidence regarding the effects of child care on language development remains inconclusive. METHODS: Within a large-scale population-based study, we examined the longitudinal associations between non-parental child care and language development from 1 to 6 years (n = 5375). RESULTS: Results showed that more hours in non-parental child care were associated with better language abilities. However, more hours in care in the first year of life were associated with less language proficiency at ages 1 to 1.5. At later ages, this effect disappeared and language proficiency increased. Furthermore, children who spent more hours in centre-based care had better language scores than children in home-based care. Ethnicity, socio-economic status, gender or parity did not change these results. CONCLUSIONS: This large, multi-ethnic study demonstrates beneficial effects of non-parental child care, particularly centre-based care, on language proficiency later in childhood.

Maternal mindfulness during pregnancy and infant socio-emotional development and temperament: the mediating role of maternal anxiety.

BACKGROUND: Accumulating evidence shows that maternal anxiety during pregnancy adversely affects child outcomes. The positive effects of maternal psychosocial factors during pregnancy on child outcomes are not yet studied. This prospective study addresses the association between maternal mindfulness during pregnancy and socio-emotional development and temperament in 10months-old infants. We also investigated whether this association was mediated by maternal anxiety. METHOD: Mothers (N=90) provided information about mindfulness and anxiety at the beginning of the second trimester of pregnancy. Infant socio-emotional development (Ages and Stages Questionnaire: Social Emotional; ASQ:SE) and temperament (Infant Behaviour Questionnaire-Revised; IBQ-R) were assessed at age 10months. RESULTS: Higher maternal mindfulness during pregnancy was associated with less infant self-regulation problems and less infant negative affectivity. Mediation analysis showed that maternal anxiety mediated the association between infant self-regulation problems and maternal mindfulness. CONCLUSION: These results suggest that maternal mindfulness during pregnancy may have positive effects on infant development. This association may be mediated by reduced anxiety symptoms in pregnant women who score high on mindfulness. Additional replication studies are needed using objective measures of infant behavioural/emotional outcomes and mindfulness of the mother during child development.

Parental depressive and anxiety symptoms during pregnancy and attention problems in children: a cross-cohort consistency study.

BACKGROUND: Maternal depression and anxiety during pregnancy have been associated with offspring-attention deficit problems. AIM: We explored possible intrauterine effects by comparing maternal and paternal symptoms during pregnancy, by investigating cross-cohort consistency, and by investigating whether parental symptoms in early childhood may explain any observed intrauterine effect. METHODS: This study was conducted in two cohorts (Generation R, n = 2,280 and ALSPAC, n = 3,442). Pregnant women and their partners completed questionnaires to assess symptoms of depression and anxiety. Child attention problems were measured in Generation R at age 3 with the Child Behavior Checklist, and in ALSPAC at age 4 with the Strengths and Difficulties Questionnaire. RESULTS: In both cohorts, antenatal maternal symptoms of depression (Generation R: OR 1.23, 95% CI 1.05-1.43; ALSPAC: OR 1.33, 95% CI 1.19-1.48) and anxiety (Generation R: OR 1.24, 95% CI 1.06-1.46; ALSPAC: OR 1.32, 95% CI 1.19-1.47) were associated with a higher risk of child attention problems. In ALSPAC, paternal depression was also associated with a higher risk of child attention problems (OR 1.11, 95% CI 1.00-1.24). After adjusting for maternal symptoms after giving birth, antenatal maternal depression and anxiety were no longer associated with child attention problems in Generation R. Moreover, there was little statistical evidence that antenatal maternal and paternal depression and anxiety had a substantially different effect on attention problems of the child. CONCLUSIONS: The apparent intrauterine effect of maternal depression and anxiety on offspring-behavioural problems may be partly explained by residual confounding. There was little evidence of a difference between the strength of associations of maternal and paternal symptoms during pregnancy with offspring-attention problems. That maternal symptoms after childbirth were also associated with offspring-behavioural problems may indicate a contribution of genetic influences to the association.

Maternal psychological distress and fetal growth trajectories: the Generation R Study.

BACKGROUND: Previous research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth. METHOD: Pregnant women (n=6313) reported levels of psychological distress using the Brief Symptom Inventory (anxious and depressive symptoms) and the Family Assessment Device (family stress) at 20.6 weeks pregnancy and had fetal ultrasound measurements in mid- and late pregnancy. Estimated fetal weight was calculated using head circumference, abdominal circumference and femur length. RESULTS: In mid-pregnancy, maternal distress was not linked to fetal size. In late pregnancy, however, anxious symptoms were related to fetal size after controlling for potential confounders. Anxious symptoms were also associated with a 37.73 g [95% confidence interval (CI) -69.22 to -6.25, p=0.019] lower birth weight. When we related maternal distress to fetal growth curves using multilevel models, more consistent results emerged. Maternal symptoms of anxiety or depression were associated with impaired fetal weight gain and impaired fetal head and abdominal growth. For example, depressive symptoms reduced fetal weight gain by 2.86 g (95% CI -4.48 to -1.23, p<0.001) per week. CONCLUSIONS: The study suggests that, starting in mid-pregnancy, fetal growth can be affected by different aspects of maternal distress. In particular, children of prenatally anxious mothers seem to display impaired fetal growth patterns during pregnancy. Future work should address the biological mechanisms underlying the association of maternal distress with fetal development and focus on the effects of reducing psychological distress in pregnancy.

Prospective longitudinal analysis of viral load and surrogate markers in relation to clinical progression in HIV type 1-infected persons.

The temporal relationship between viral and surrogate markers and clinical status was analyzed prospectively every 8 weeks in 34 asymptomatic HIV-1-infected persons. After 3 years, 25 persons remained clinically healthy whereas 9 persons showed clinical progression. In accordance with other reports we found that at study entry HIV-RNA load was predictive of clinical progression. All markers tested evolved significantly in time in both progressors and nonprogressors. The HIV RNA load in plasma and HIV DNA load in T cells were linearly related only in nonprogressors. In addition, the RNA/DNA ratio during follow-up was significantly higher in progressors, indicating a higher replication rate in progressors. The HIV DNA load correlated inversely with CD4+ T cell counts and positively with p24 antigenemia in both nonprogressors and progressors. A significant correlation of HIV DNA load with SI phenotype occurred in progressors only. HIV RNA levels correlated with beta 2-microglobulin level and with p24 antigenemia but not with SI phenotype. These three markers can all routinely be measured in plasma; however, only the HIV RNA levels appear to be informative for clinical progression. Six to 8 months before clinical progression, an SI phenotype switch, increased HIV RNA in plasma, and decreased CD4+ T cell counts were all indicative of an impending clinical event.

Cotrimoxazole is effective as primary prophylaxis for toxoplasmic encephalitis in HIV-infected patients: a case control study.

In a case-control study, prophylaxis with cotrimoxazole for toxoplasmic encephalitis (TE) in HIV-infected patients was evaluated. Cotrimoxazole had been given as PCP prophylaxis. 20 patients with TE were identified and 72 matching control cases were found. All patients had IgG-antibodies to Toxoplasma gondii and CD4+ T-cell counts < or = 100/microliter. The use and duration of cotrimoxazole prophylaxis were recorded. It was found that among the patients with TE, none had used cotrimoxazole for > 70% of the observation time, and that the 1-y incidence was 0% in the control group vs. 41% in those patients without sufficient cotrimoxazole use. The conclusion is that cotrimoxazole is effective as primary prophylaxis for TE, even in a dose of 480 mg daily.

Substitution of didanosine sachets by chewable tablets: a pharmacokinetic study in patients with AIDS.

We have conducted a pharmacokinetic study of didanosine (ddI), formulated in sachets and in tablets, in patients with acquired immune deficiency syndrome (AIDS). Fifteen subjects received 250 or 167 mg of ddI twice daily as the sachet formulation and used this for at least 1 month. Subsequently, the patients were converted to receive ddI chewable/dispersible tablets (250-mg sachets to 200-mg tablets; 167-mg sachets to 125-mg tablets). Four subjects withdrew because of clinical deterioration or adverse effects. Serial blood samples were collected for pharmacokinetic monitoring during the use of the sachets and after 1 month of use of the tablets. No statistically significant differences were found in the maximum plasma concentration (Cmax), the time to reach Cmax (tmax), the area under the plasma concentration-time curve (AUC), or the terminal elimination half-life (t1/2) between the two formulations. Patients who received low-dose ddI (sachets, 167 mg; tablets, 125 mg) displayed lower plasma concentrations than did the patients receiving high-dose ddI (sachets, 250 mg; tablets, 200 mg), despite an equal weight-normalized dose of ddI in these two groups.

[Characterization and comparison of the clinical and morphological changes in adriamycin cardiomyopathy]. / Charakterisierung und Vergleich der klinischen und morphologischen Veränderungen bei der Adriamycin-Kardiomyopathie.

Through comparative clinical and pathological findings a dose-response relationship for the cardiotoxic effect of adriamycine could be proved. A myocardial damage without clinical relation could already be seen at a dose of 125 mg/m2 body surface by patho-histological examination. Therefore, all patients being treated with adriamycine should be regularly and carefully cardiologically supervised in order to avoid an irreversible cardiomyopathy.