Cristina Maggioni

PTSD, risk factors, and expectations among women having a baby: a two-wave longitudinal study.

Introduction. The aim of the study was to evaluate the incidence of chronic post-traumatic stress disorder (PTSD) after childbirth in relation to pre-partum variables (personality characteristics, anamnestic risk factors) and intra-partum obstetrical and neonatal variables. Since expectations before an event could modify the perceptions, reactions, and satisfaction afterward, the representations of the idealized delivery were carefully analyzed. Moreover, the real and desired help perception from physicians and family members were separately considered during pregnancy and after delivery in relation to PTSD. Method. The study was carried out submitting a questionnaire to pregnant women twice: firstly when women were in their 38 ≪ 42 gestational week (Time 1) and secondly after 3–6 months from childbirth (Time 2). 93 women were recruited at a University City Hospital in Milan, Italy. PTSD subscales, depression, and anxiety levels were also assessed. Results. 2.4% of women had a complete PTSD, while 32.1% of them resulted in having one or two positive subscales of symptoms: 15.5% (N = 13) had a positive intrusion subscale, 25.0% (N = 21) had a positive arousal subscale, while only 3.6% (N = 3) had a positive avoidance subscale. Pre-delivery depression influences PTSD, but only for the intrusion subscale. Pre-delivery physical risk factors are linked to PTSD on the avoidance subscale. At Time 2 depression and PTSD are often present simultaneously. Given the high percentage of healthy newborns, intra-partum obstetrical variables do not seem to influence PTSD. High trait anxiety distinctively coexists with a specific expected delivery and a ‘deception’ in desired and real support from professionals. Conclusions. Childbirth is a risk condition for PTSD, depression during pregnancy influences the intrusion subscale, while having physical problems influences the arousal subscale. Expectations and support are modulated by the anxiety levels and they are not directly related to chronic PTSD.

Cardiac autonomic adjustments to normal human pregnancy: insight from spectral analysis of R-R interval and systolic arterial pressure variability.

OBJECTIVE To assess the adaptation in autonomic control mechanisms that accompanies the marked haemodynamic changes, such as increases in cardiac size and output, that occur in the course of normal human pregnancy. DESIGN We studied 14 healthy pregnant women (aged 30+/-1 years) before the 6th week (early stage) and within weeks 32-34 (late stage) of pregnancy, while they were at rest or in a state of active orthostatism (standing), which enhances sympathetic activity. METHODS We used echocardiography to assess cardiac volumes and mass, and spectral analysis of the R-R interval and systolic arterial pressure variability to obtain indices of autonomic regulation of the circulation. This non-invasive methodology, recently validated with direct recordings of muscle sympathetic nerve activity, furnishes quantitative markers of sympathetic modulation of the sino-atrial node (low frequency component, LF in normalized units, nu), vagal modulation (high frequency component, HF in normalized units, nu) and the overall arterial pressure-heart rate baroreflex gain (alpha index). RESULTS Late pregnancy was characterized by an increase in cardiac size and volumes and by a reduction of R-R interval, R-R interval variance and the alpha index, together with an increase in the LF/HF ratio (from 1.4+/-0.4 to 5.6+/-1.9). Changes in markers of autonomic modulation of the sino-atrial node normally induced by the standing position were blunted. CONCLUSIONS The late stage of normal human pregnancy appears to be characterized by alterations in the autonomic control of the circulation and by attenuated responsiveness to active standing, possibly as a consequence of the accompanying increase in cardiac size.

The Pineal Gland and Chronobiologic History: Mind and Spirit as Feedsidewards in Time Structures for Prehabilitation

Not only circadian rhythms — recurring patterns with a period of about 24 h (in the range of 20-28 h) — but also ultradian and infradian rhythms (with periods shorter than 20 h and longer than 28 h, respectively), characterize melatonin in humans, whether it is measured in blood, saliva, or urine. Among infradians, the about-yearly (circannual) and half-yearly (circasemiannual) components are noteworthy. At mid-latitude, circannuals may predominate in circulating melatonin during the daytime, whereas circasemiannuals may become more prominent during the nighttime. A stable half-yearly component also prominently characterizes the geomagnetic disturbance index Kp. Support for the hypothesis that Kp may influence human melatonin is provided by the fact that closer to tine pole, at 65 °N in Oulu, Finland, geomagnetic effects are stronger. There, circulating melatonin, measured around noon, exhibits a clear circasemiannual variation. Circaseptans and circasemiseptans, with periods of about a week and half a week, are found ubiquitously in relation to the pineal gland. In the case of melatonin secreted into the superfusion fluid by the pike pineal in vitro, kept at constant temperature in continuous darkness, the circaseptan component has an amplitude larger than that of the circadian rhythm. Circaseptans are also observed in the mouse pineal gland in vivo, wherein the presence of melatonin has been questioned, yet established by three independent groups of investigators who all documented a circadian variation peaking during the dark (rest) span.

Feedsidewards: Intermodulation (Strictly) among Time Structures, Chronomes, in and around Us, and Cosmo‐vasculo‐neuroimmunity: About Ten‐yearly Changes: What Galileo Missed and Schwabe Found

Abstract: The spectrum of biological rhythms is extended far beyond circadians, circannuals, and ultradians, such as 1.5‐hourly melatonin and 8‐hourly endothelin‐1 (ET‐1) rhythms by statistics of natality, growth, morbidity, and mortality, some covering decades or centuries on millions of individuals. These reveal infradian cycles to be aligned with half‐weekly rhythms in ET‐1, weekly and half‐yearly ones in melatonin, and even longer‐about 50‐, about 20‐, and about 10‐year cycles found in birth statistics. About daily, weekly, yearly, and ten‐yearly patterns are also found in mortality from myocardial infarctions; the 10‐yearly ones are also in heart rate and its variability; in steroid excretion, an aspect of resistance, for example, to bacteria; and in the genetic changes of the bacteria themselves. Automatic physiological measurements cover years and, in one case, cover a decade; the latter reveal an about 10‐year (circadecennial) cycle. ECGs, covering months beat‐to‐beat, reveal circaseptans, gaining prominence in response to magnetic storms or after coronary artery bypass grafting. A spectrum including cycles from fractions of 1 Hz to circasemicentennians is just one element in biological time structures, chronomes. Chaos, trends, and any unresolved variability are the second to fourth elements of chronomes. Intermodulations, feedsidewards, account for rhythmically and thus predictably recurring quantitative differences and even for opposite treatment effects of the same total dose(s) of (1) immunomodulators inhibiting or stimulating DNA labeling of bone in health or speeding up versus slowing down a malignant growth and thus shortening or lengthening survival time, or (2) raising or lowering blood pressure or heart rate in the vascular aspect of the bodys defense. Latitude‐dependent competing photic and nonphotic solar effects upon the pineal are gauged by alternating yearly (by daylight) and half‐yearly (by night) signatures of circulating melatonin at middle latitudes and by half‐yearly signatures at noon near the pole. These many (including novel near 10‐yearly) changes, for example, in 17‐ketosteroid excretion, heart rate, heart rate variability, and myocardial infarction in us and those galactic, solar, and geophysical ones around us have their own special signatures and contribute to a cosmo‐vasculo‐immunity and, if that fails, to a cosmo(immuno?) pathology.

Effects Lasting into Adolescence of Exposure to Betamimetics In Utero

SummaryThe range of the predictable within-day change in blood pressure, assessed as the circadian blood pressure amplitude, is greater in newborns who have been exposed in utero to betamimetics than in those not exposed. A larger circadian blood pressure amplitude is also found in infants and children with a positive versus those with a negative family history of high blood pressure. In adulthood, an excessive circadian blood pressure amplitude is associated with a 6-fold increase in risk of ischaemic stroke. To determine whether the large circadian blood pressure amplitude associated with intrauterine exposure to betamimetics in newborns persists later in life, the progeny of mothers who had had similar obstetric situations but had been treated either with spasmolytics (not including betamimetics) or with betamimetics to prevent premature labour was assessed. The blood pressure of 43 adolescents aged between 11 and 14 years was measured at 15-minute intervals for 2 days with an ambulatory monitor; an echocardiogram was also taken. A multiple regression analysis accounting for gender- and age-related changes revealed a dose-dependent effect of betamimetic exposure on the circadian blood pressure amplitude of the offspring. Exposed children also tended to have a larger left ventricular mass index. Thus, in utero exposure to betamimetic drugs may have cardiovascular effects lasting into adolescence.

Melatonin Involvement in Cancer: Methodological Considerations

On the one hand, melatonin has been determined in different body fluids to seek markers of a heightened risk of cancer development. On the other hand, it has been used as an oncostatic drug in the treatment plan of cancer patients. For both applications, timing has proved to be critical, not only along the circadian scale but in relation to a number of other multifrequency rhythms as well. Like other immunomodulators, melatonin has been shown in the experimental laboratory to inhibit cancer growth when administered at one circadian stage but to enhance it when given at another. Such circadian stage-dependence of melatonin effects was observed in a mouse leukemia model, in a mouse sarcoma model, and in spontaneous mammary carcinogenesis. In the latter model, circannual and/or other secular changes were also noted. “First do no harm” is hence a particularly restrictive possibility in the clinical use of immunomodulators such as melatonin. Marker rhythmometry is a useful tool offered by chronobiology to guide treatment timing while, if specific, it can also serve for the assessment of the patienfs response to treatment.

Circadian rhythm of ANP, aldosterone and PRA in normotensive IUGR

Objective Atrial natriuretic peptide (ANP) increases are reported during normal pregnancy, but the relation to arterial pressure and the renin-angiotensin system is debatable. We assessed whether normotensive pregnancies with intrauterine growth retardation (IUGR) present an alteration of maternal ANP levels. Design A total of 11 pregnant women with IUGR, in the absence of any other maternal or fetal pathology, entered the study during the third trimester. They were compared with 12 healthy pregnant women of similar age and characteristics. We monitored all subjects for blood pressure (BP), ANP, aldosterone and plasma renin activity (PRA), under the same conditions for 24 h. All subjects were submitted to the same regimen of life; with homogenous dark : light periods, salt intake and meal times. Methods BP was monitored at 20 min intervals for 24 h and blood tests performed at six time points during the 24 h. EDTA plasma samples were immediately centrifuged. Hormone assays were performed by radioimmunoassay. Kochs nonparametric two-way analysis of variance (ANOVA) was used to compare the hormone time-dependent profiles in the two groups. Circadian rhythms were assessed by cosinor analysis. Results The IUGR group was characterized by higher ANP values compared to normal pregnancy, (205 ± 24 versus 146 ± 21 pg/ml:P < 0.05) but not significant differences were shown for PRA, aldosterone and BP circadian rhythms. Conclusions This study shows higher ANP values in human pregnancy complicated by IUGR, with presence of normal BP, aldosterone and PRA profiles.

Cardiovascular rhythmometry during pregnancy and early extrauterine life

The broad rhythmic structure of blood pressure and heart rate in clinically healthy newborns and in their mothers before and after delivery is investigated. A room-restricted automatic monitor manufactured by Nippon Colin is used to measure, oscillometrically, the systolic, mean arterial, and diastolic blood pressure and the heart rate of pregnant women before and after delivery. A neonatal instrument also manufactured by Nippon Colin is used to monitor newborns. Each data series is plotted as a function of time for identification of outliers values outside the range of the mean +or-3 standard deviations. Each series is analyzed by a single cosinor using all data (raw data series) and after elimination of outliers (edited data series). The results of this study are further compared to results from other collaborative international studies of pregnant women and newborns.<<ETX>>

Placental circadian pathway methylation and in utero exposure to fine particle air pollution

In mammals, a central clock maintains the daily rhythm in accordance with the external environment. At the molecular level, the circadian rhythm is maintained by epigenetic regulation of the Circadian pathway. Here, we tested the role of particulate matter with an aerodynamic diameter ≤ 2.5 μm (PM2.5) exposure during gestational life on human placental Circadian pathway methylation, as an important molecular target for healthy development. In 407 newborns, we quantified placental methylation of CpG sites within the promoter regions of the following genes: CLOCK, BMAL1, NPAS2, CRY1-2 and PER1-3 using bisulfite-PCR-pyrosequencing. Daily PM2.5 exposure levels were estimated for each mothers residence, using a spatiotemporal interpolation model. We applied mixed-effects models to study the methylation status of the Circadian pathway genes and in utero PM2.5 exposure, while adjusting for a priori chosen covariates. In a multi-gene model, placental Circadian pathway methylation was positively and significantly (p < 0.0001) associated with 3rd trimester PM2.5 exposure. Consequently, the single-gene models showed relative methylation differences [Log(fold change)] in placental NPAS2 (+0.16; p = 0.001), CRY1 (+0.59; p = 0.0023), PER2 (+0.36; p = 0.0005), and PER3 (+0.42; p = 0.0008) for an IQR increase (8.9 μg/m3) in 3rd trimester PM2.5 exposure. PM2.5 air pollution, an environmental risk factor leading to a pro-inflammatory state of the mother and foetus, is associated with the methylation pattern of genes in the Circadian pathway. The observed alterations in the placental CLOCK epigenetic signature might form a relevant molecular mechanism through which fine particle air pollution exposure might affect placental processes and foetal development.

CHAPTER 213 – Peptide Chronomics

Chronomics, the mapping of broad time structures (chronomes), provides the indispensable control whether studies aim at examining the effect of a given intervention such as dietary restriction, at optimizing the timing of administration of treatment, or at assessing an elevated risk of developing a disease such as cancer. An increase in circadian amplitude exceeding any effect on the mean is likely to yield controversial results from single spot checks. An analog of the adrenocorticotropic hormone (ACTH 1–17), administered in the evening may help patients with rheumatoid arthritis, but may be ineffective when given around awakening. A daytime single sample of prolactin may not be discriminatory in assessing breast cancer risk when large differences are found during the rest span. The merits of assessing peptide chronomics are perhaps best illustrated by the facts that a peptide drug may have a major effect at one circadian stage but not at another, that a major effect on a polypeptide may be exerted again at one circadian stage but not at another, and that, by the design and the software of chronomics, relatively small numbers of patients are needed to validate such effects by inferential statistics.