Health economic evaluation of a randomized controlled trial (EMBLA study), an internet-based treatment for provoked vulvodynia.

Internet-based treatment (IBT) for provoked vulvodynia (PVD) may reduce pain during intercourse and increases pain acceptance. However, a there is still a knowledge gap regarding the cost-effectiveness of IBT for PVD. The aim of this study was to perform a health economic evaluation of guided internet-based intervention for PVD as an addition to standard treatment. The sample consisted of 99 women with a PVD diagnosis. Healthcare related costs, health-related quality of life, and quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were analyzed. After the IBT, the intervention group had fewer visits to a midwife than the control group (p = 0.03), but no between-group differences were found for visits to other professionals, treatment length, health-related quality of life, QALYs, and costs for treatment. It was estimated a cost of 260.77 € for a clinical meaningful change in pain acceptance. Internet-based treatment as add-on to clinical treatment may lower number of visits to a healthcare.

Important research outcomes for treatment studies of perinatal depression: systematic overview and development of a core outcome set.

OBJECTIVE: To develop a Core Outcome Set (COS) for treatment of perinatal depression. DESIGN: Systematic overview of outcomes reported in the literature and consensus development study. SETTING: International. POPULATION: Two hundred and twenty-two participants, mainly patients, healthcare professionals and researchers, representing 13 countries. METHODS: A systematic overview of outcomes reported in recently published research, a two-round Delphi survey and a consensus meeting at which the final COS was decided using modified nominal group technique. MAIN RESULTS: In the literature search, 1772 abstracts were identified and evaluated, and 165 studies were finally included in the review. In all, 106 outcomes were identified and included in the Delphi survey. In all, 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. Thirteen participants attended the consensus meeting, where the following nine outcomes were agreed upon for inclusion in the final COS: self-assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self-assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events. CONCLUSIONS: The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We expect that this COS will contribute to the consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression. TWEETABLE ABSTRACT: Development of a core outcome set regarding treatment for perinatal depression by @SBU_en.

Association of maternal attention deficit hyperactivity disorder and preterm birth: a cohort study.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) affects 3-7% of women of childbearing age. Whether ADHD is associated with an increased risk of preterm birth is unclear. DESIGN: National register-based cohort study. SETTING: Sweden. POPULATION: Nulliparous women giving birth to singleton infants 2007-2014 (n = 377 381). METHODS: Women were considered to have ADHD if they had been dispensed at least one prescription for ADHD medication, i.e. a central nervous system stimulant or non-stimulant drugs for ADHD, prior to, during or after pregnancy (2005-2014). Women with ADHD were compared with women without ADHD in regard to prevalence, severity and mode of onset of preterm birth. Logistic regression models were used, estimating adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age and country of birth (model 1), and in addition for body mass index (BMI), education, alcohol or substance use disorders, and pre-gestational medical and psychiatric co-morbidity (model 2). MAIN OUTCOME MEASURES: Preterm birth (<37 weeks). RESULTS: During the study period, 6327 (1.7%) women gave birth and had ADHD according to our definition. These women had a higher rate of preterm birth compared with women without ADHD (7.3 versus 5.8%, aOR model 2: 1.17; 95% CI 1.05-1.30). ADHD was particularly associated with very (<32 weeks) preterm births, and associations were seen with both spontaneous and medically indicated onsets. CONCLUSIONS: Women with ADHD (i.e. who had been dispensed ADHD medication at any time in 2005-2014) had an increased risk of preterm birth. TWEETABLE ABSTRACT: Women with ADHD have a higher risk of preterm birth but most of it is due to modifiable risk factors.

Severe obstetric lacerations associated with postpartum depression among women with low resilience - a Swedish birth cohort study.

OBJECTIVE: Women's levels of resilience and attitudes towards perineal lacerations vary greatly. Some women see them as part of the birthing process, while others react with anger, depressed mood or even thoughts of self-harm. A previous study has reported increased risk of postpartum depressive (PPD) symptoms in women with severe perineal lacerations. The aim of this study was to assess the association between severe obstetric perineal lacerations and PPD. A secondary objective was to assess this association among women with low resilience. DESIGN: Nested cohort study. SETTING: Uppsala, Sweden. SAMPLE: Vaginally delivered women with singleton pregnancies (n = 2990). METHODS: The main exposure was obstetric perineal lacerations. Resilience was assessed in gestational week 32 using the Swedish version of the Sense of Coherence Scale. A digital acyclic graph was used to identify possible confounders and mediators. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). A sub-analysis was run after excluding women with normal or high resilience. MAIN OUTCOME MEASURES: Postpartum depression, assessed with the Depression Self-Reporting Scale, completed at 6 weeks postpartum. RESULTS: There was no significant association between severe obstetric perineal lacerations and PPD at 6 weeks postpartum. However, a significant association was found between severe lacerations and PPD in women with low resilience (OR = 4.8, 95% CI 1.2-20), persisting even after adjusting for confounding factors. CONCLUSION: Healthcare professionals might need to identify women with low resilience, as they are at increased risk for PPD after a severe perineal laceration. TWEETABLE ABSTRACT: Severe perineal lacerations associated with postpartum depression in women with low resilience in a Swedish cohort.

SSRI use during pregnancy and risk for postpartum haemorrhage: a national register-based cohort study in Sweden.

OBJECTIVE: Evaluate whether selective serotonin reuptake inhibitor (SSRI) use during pregnancy, as well as prior or current untreated psychiatric illness is associated with postpartum haemorrhage (PPH). DESIGN: National register-based cohort study based on data from the Swedish Pregnancy Register. SETTING: Sweden, nationwide coverage. POPULATION: A total of 31 159 pregnant women with singleton deliveries after gestational week 22+0 between January 2013 and July 2017. METHODS: Pregnant women with self-reported SSRI use at any time point during pregnancy were compared with non-SSRI-treated women with prior or current psychiatric illness, as well as wiith healthy women with no psychiatric illness or reporting SSRI use. MAIN OUTCOME MEASURES: Postpartum haemorrhage defined as blood loss >1000 ml during the first 2 hours postpartum reported by the delivering midwife or obstetrician. RESULTS: Postpartum haemorrhage prevalence was 7.0% among healthy women, 7.6% among women with prior or current psychiatric illness and 9.1% among women treated with SSRI. The unadjusted odds for PPH among women with prior or current psychiatric illness and women on SSRI treatment were increased by 9 and 34%, respectively, compared with healthy unmedicated women without a history of psychiatric illness (odds ratio [OR] 1.09, 95% CI 1.04-1.14 and OR 1.34, 95% CI 1.24-1.44, respectively). The estimates remained unchanged after adjustment for several confounders (such as maternal age, body mass index [BMI], parity, prior caesarean section, smoking, occupation and country of birth) and potential covariates (such as delivery mode, polyhydramnion, preterm delivery, labour dystocia and infant birthweight >4000 g). CONCLUSIONS: Higher risk for PPH was observed both among women treated with SSRI during pregnancy and among women with prior or current psychiatric illness. TWEETABLE ABSTRACT: SSRI use at any point during pregnancy and prior or current history of psychiatric illness was associated with an increased likelihood for PPH.

Anxiety and depression symptoms among sub-fertile women, women pregnant after infertility treatment, and naturally pregnant women.

BACKGROUND: Infertility has been associated with psychological distress, but whether these symptoms persist after achieving pregnancy via assisted reproductive technology (ART) remains unclear. We compared the prevalence of anxiety and depressive symptoms between women seeking for infertility treatment and women who conceived after ART or naturally. METHODS: Four hundred and sixty-eight sub-fertile non-pregnant women, 2972 naturally pregnant women and 143 women pregnant after ART completed a questionnaire in this cross-sectional study. The Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A≥8) and Edinburgh Postnatal Depression Scale (EPDS≥12) were used for assessing anxiety and depressive symptoms, respectively. Multivariate Poisson regression models with robust variance were applied to explore associations with anxiety and depressive symptoms. RESULTS: The prevalence of anxiety and depressive symptoms among sub-fertile, non-pregnant women (57.6% and 15.7%, respectively) were significantly higher compared to women pregnant after ART (21.1% and 8.5%, respectively) and naturally pregnant women (18.8% and 10.3%, respectively). History of psychiatric diagnosis was identified as an independent risk factor for both anxiety and depressive symptoms. The presence of at least one unhealthy lifestyle behavior (daily tobacco smoking, weekly alcohol consumption, BMI≥25, and regular physical exercise<2h/week) was also associated with anxiety (Prevalence Ratio, PR: 1.24; 95%CI: 1.09-1.40) and depressive symptoms (PR: 1.25; 95%CI: 1.04-1.49). CONCLUSIONS: Women pregnant after ART showed no difference in anxiety and depressive symptoms compared to naturally pregnant women. However, early psychological counseling and management of unhealthy lifestyle behaviors for sub-fertile women may be advisable, particularly for women with a previous history of psychiatric diagnosis.

Seasonal patterns in self-reported peripartum depressive symptoms.

BACKGROUND: In the peripartum period, the literature on seasonality in depression is still scarce and studies present varying findings. The aims of this study were to investigate whether seasonal patterns in postpartum depressive symptoms previously identified in a Swedish study could be replicated in a larger study, as well as to assess seasonal patterns in depressive symptoms during pregnancy. METHODS: This was a nested case-control study comprised of 4129 women who participated in the BASIC project and gave birth at Uppsala University Hospital, Uppsala, Sweden, between February 2010 and December 2015. RESULTS: Women who gave birth in October-December 2011 had an increased odds of depressive symptoms at 6 weeks postpartum, when compared with women giving birth in April-June 2011 (aOR=2.42; 95% CI: 1.12-5.26). The same pattern was found among women with a history of depression. No other seasonal patterns for depressive symptoms during pregnancy or at 6 weeks postpartum were identified. CONCLUSIONS: In general, no consistent seasonal patterns were found in peripartum depressive symptoms. Whether the seasonal patterns found in some studies during certain years may be due to other factors relating to specific years and seasons, such as extreme climatic conditions or other particular events, warrants further investigation.

Maternal fetal loss history and increased acute leukemia subtype risk in subsequent offspring: a systematic review and meta-analysis.

PURPOSE: History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted. METHODS: Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken. RESULTS: Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60). CONCLUSIONS: In this meta-analysis involving >50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.

Correlates of postpartum depression in first time mothers without previous psychiatric contact.

BACKGROUND: Postpartum depression (PPD) is a common disorder after childbirth. The strongest known predictors are a history of depression and/or a history of PPD. However, for a significant proportion of women, PPD constitutes their first depressive episode. This study aimed to gain further insight into the risk factors for PPD in first time mothers without previous psychiatric contact. METHODS: Women delivering in Uppsala University Hospital, Sweden, from May 2006 to June 2007, were asked to participate and filled out questionnaires five days and six weeks postpartum, containing inter alia the Edinburgh Postnatal Depression Scale (EPDS). Univariate logistic regression models, as well as a path analysis, were performed to unveil the complex interplay between the study variables. RESULTS: Of the 653 participating primiparas, 10.3% and 6.4% reported depressive symptoms (EPDS≥12 points) five days and six weeks postpartum, respectively. In the path analysis, a positive association between anxiety proneness and depressive symptoms at five days and six weeks postpartum was identified. For depressive symptoms six weeks after delivery, additional risk factors were detected, namely depressive symptoms five days postpartum and subjective experience of problems with the baby. Caesarean section and assisted vaginal delivery were associated with fewer depressive symptoms at 6 six weeks postpartum. CONCLUSIONS: Identification of anxiety proneness, delivery mode and problems with the baby as risk factors for self-reported depressive symptoms postpartum in this group of primiparas can be important in helping health care professionals identify women at increased risk of affective disorders in the perinatal period, and provide a base for early intervention.

Associations between a polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene, neuroticism and postpartum depression.

BACKGROUND: This study examined the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and neuroticism, as well as the possible mediatory role of neuroticism in the association between the polymorphism and postpartum depressive symptoms. METHODS: 769 women received questionnaires containing the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum and demographic data at pregnancy week 17 and 32 and at six weeks postpartum, as well as the Swedish universities Scales of Personality at pregnancy week 32. RESULTS: Linear regression models showed an association between the GG genotype and depressive symptoms. When neuroticism was introduced in the model, it was associated with EPDS score, whereas the association between the GG genotype and EPDS became borderline significant. A path analysis showed that neuroticism had a mediatory role in the association between the polymorphism and EPDS score. LIMITATIONS: The use of the EPDS, which is a self-reporting instrument. CONCLUSIONS: Neuroticism was associated with the polymorphism and had a mediatory role in the association between the polymorphism and postpartum depression. This finding elucidates the genetic background of neuroticism and postpartum depression.

History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype.

BACKGROUND: Despite the putative intrauterine origins of childhood (0-14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B-cell and T-cell ALL), as contrasted to acute myeloid leukaemia (AML). METHODS: One thousand ninety-nine ALL incidents (957 B-ALL) and 131 AML cases along with 1:1 age and gender-matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996-2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B-, T-ALL) and AML, controlling for potential confounders. RESULTS: Statistically significant exposure and disease subtype-specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B-ALL particularly, emerged. CONCLUSION: Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B-ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes.

Treatment with serotonin reuptake inhibitors during pregnancy is associated with elevated corticotropin-releasing hormone levels.

Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an increased risk of preterm birth, but causality remains unclear. While placental CRH production is correlated with gestational length and preterm birth, it has been difficult to establish if psychological stress or mental health problems are associated with increased CRH levels. This study compared second trimester CRH serum concentrations in pregnant women on SSRI treatment (n=207) with untreated depressed women (n=56) and controls (n=609). A secondary aim was to investigate the combined effect of SSRI treatment and CRH levels on gestational length and risk for preterm birth. Women on SSRI treatment had significantly higher second trimester CRH levels than controls, and untreated depressed women. CRH levels and SSRI treatment were independently associated with shorter gestational length. The combined effect of SSRI treatment and high CRH levels yielded the highest risk estimate for preterm birth. SSRI treatment during pregnancy is associated with increased CRH levels. However, the elevated risk for preterm birth in SSRI users appear not to be mediated by increased placental CRH production, instead CRH appear as an independent risk factor for shorter gestational length and preterm birth.

Personality and risk for postpartum depressive symptoms.

Postpartum depression (PPD) is a common childbirth complication, affecting 10-15 % of newly delivered mothers. This study aims to assess the association between personality factors and PPD. All pregnant women during the period September 2009 to September 2010, undergoing a routine ultrasound at Uppsala University Hospital, were invited to participate in the BASIC study, a prospective study designed to investigate maternal well-being. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) while the Depression Self-Rating Scale (DSRS) was used as a diagnostic tool for major depression. Personality traits were evaluated using the Swedish Universities Scale of Personality (SSP). One thousand thirty-seven non-depressed pregnant women were included in the study. Non-depressed women reporting high levels of neuroticism in late pregnancy were at high risk of developing postpartum depressive symptoms (PPDSs) at 6 weeks and 6 months after delivery, even after adjustment for confounders (adjusted odds ratio (aOR) = 3.4, 95 % confidence interval (CI) 1.8-6.5 and adjusted odds ratio (aOR) = 3.9, 95 % CI 1.9-7.9). The same was true for a DSRS-based diagnosis of major depression at 6 months postpartum. Somatic trait anxiety and psychic trait anxiety were associated with increased risk for PPDS at 6 weeks (aOR = 2.1, 95 % CI 1.2-3.5 and aOR = 1.9, 95 % CI 1.1-3.1), while high scores of mistrust were associated with a twofold increased risk for PPDS at 6 months postpartum (aOR 1.9, 95 % CI 1.1-3.4). Non-depressed pregnant women with high neuroticism scores have an almost fourfold increased risk to develop depressive symptoms postpartum, and the association remains robust even after controlling for most known confounders. Clinically, this could be of importance for health care professionals working with pregnant and newly delivered women.

Socioeconomic disparities in survival from childhood leukemia in the United States and globally: a meta-analysis.

BACKGROUND: Despite advancements in the treatment of childhood leukemia, socioeconomic status (SES) may potentially affect disease prognosis. This study aims to evaluate whether SES is associated with survival from childhood leukemia. METHODS: The US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) 1973-2010 data were analyzed; thereafter, results were meta-analyzed along with those from survival (cohort) studies examining the association between SES indices and survival from childhood leukemia (end-of-search date: 31 March 2014). Random-effects models were used to calculate pooled effect estimates (relative risks, RRs); meta-regression was also used. RESULTS: We included 29 studies yielding 28 804 acute lymphoblastic leukemia (ALL), 3208 acute myeloblastic leukemia (AML) and 27 650 'any' leukemia (denoting joint reporting of all subtypes) cases. According to individual-level composite SES indices, children from low SES suffered from nearly twofold higher death rates from ALL (pooled RR: 1.83, 95% confidence interval 1.00-3.34, based on four study arms); likewise, death RRs derived from an array of lower area-level SES indices ranged between 1.17 and 1.33 (based on 11 study arms). Importantly, the survival gap between higher and lower SES seemed wider in the United States, with considerably (by 20%-82%) increased RRs for death from ALL in lower SES. Regarding AML, poorer survival was evident only when area-level SES indices were used. Lastly, remoteness indices were not associated with survival from childhood leukemia. CONCLUSION: Children with lower SES suffering childhood leukemia do not seem to equally enjoy the impressive recent survival gains. Special health policy strategies and increased awareness of health providers might minimize the effects of socioeconomic disparities.

The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring.

It has been estimated that 20% of pregnant women suffer from depression and it is well-documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs) which are used by 2-3% of pregnant women in the Nordic countries and by up to 10% of pregnant women in the United States. Antidepressants cross the placenta and are transferred to the fetus, thus, the question arises as to whether children of women taking antidepressants are at risk for altered neurodevelopmental outcomes and, if so, whether the risks are due to SSRI medication exposure or to the underlying maternal depression. This review considers the effects of maternal depression and SSRI exposure on offspring development in both clinical and preclinical populations. As it is impossible in humans to study the effects of SSRIs without taking into account the possible underlying effects of maternal depression (healthy pregnant women do not take SSRIs), animal models are of great value. For example, rodents can be used to determine the effects of maternal depression and/or perinatal SSRI exposure on offspring outcomes. Unraveling the joint (or separate) effects of maternal depression and SSRI exposure will provide more insights into the risks or benefits of SSRI exposure during gestation and will help women make informed decisions about using SSRIs during pregnancy.

Growth velocity during the first postnatal week of life is linked to a spurt of IGF-I effect.

There is adequate evidence that growth during the perinatal period is linked to the risk of several adult onset diseases, and recent findings indicate that the insulin-like growth factor (IGF) system is involved in prenatal growth, as reflected in birthweight. However, whether major components of the IGF system are involved in the immediate post-natal growth has not been studied. Maternal questionnaires were completed, and laboratory measurements of several variables, including IGF-I, IGF-II and IGF-binding protein-3 (IGFBP-3), were made for a total of 331 apparently healthy full-term newborns, from whom routine blood samples were taken during the first 5 days of their life. Birthweight and weight at the time of bleeding were among the recorded variables, and the difference divided by the age in days of the newborn was considered as reflecting immediate postnatal growth velocity. Immediate postnatal growth velocity was strongly positively associated with IGF-I. The squared adjusted correlation coefficient was 0.29 when IGF-I was incorporated in the model predicting postnatal growth velocity but was only 0.08 when IGF-I was excluded. In contrast, IGF-II and IGFBP-3 had no effect on postnatal growth velocity. It thus appears that IGF-I underlies growth during the immediate postnatal period. To the extent that perinatal growth may affect adult onset diseases, the findings of this study suggest that the action of IGF-I during the immediate postnatal period may represent a process of major importance.

Birth size and neonatal levels of major components of the IGF system: implications for later risk of cancer.

Pre- and perinatal conditions and processes may affect the risk for some forms of cancer in later life, while the insulin-like growth factor (IGF) system may play a role in both early somatic growth and later carcinogenesis. Birth weight and length, and the variation of major components of the IGF system immediately after birth, were analyzed in relation to selected physiological and pathological variables. The study comprised 331 healthy full-term newborns from whom blood samples were taken during routine phlebotomy no later than the fifth day of life. Measurements of IGF-I, IGF-II and IGF-binding protein-3 concentrations were performed. Birth length and weight were measured and information on socio-economic and medical variables was recorded. The concentrations of all three proteins were lower when blood bilirubin levels were high, possibly as a result of compromised liver function and/or as a component of an activated acute phase reaction. Birth weight was significantly higher by about 46 g among children whose IGF-I was higher by one SD, while the associations of birth weight and length with other components of the IGF system were in the predicted directions, albeit only in trend. We conclude that in early life, growth is related to the IGF system, mostly IGF-I. The latter is lower in children with jaundice, possibly because of hepatic dysfunction and/or as part of an acute phase reaction. We speculate that elevations of IGF-I in early life might explain the increased risk of cancer in individuals born with a higher birth weight.

Evidence on the infectious etiology of childhood leukemia: the role of low herd immunity (Greece).

OBJECTIVE: Acute lymphoblastic leukemia (ALL) among children may be a rare outcome of a delayed non-specific infection in situations of overall low herd immunity. We evaluated the hypothesis as to whether newly diagnosed ALL cases, compared to their controls, are characterized by lower herd immunity, as reflected in a more seronegative spectrum to several agents, with the exception of a strongly positive response to a single infectious agent, assumed to trigger ALL. METHODS: The study included 94 incident cases of ALL, from all pediatric hematology-oncology units of Greece, and 94, matched for age and gender, controls hospitalized with minor non-infectious conditions. The past exposure to common infections was assessed using 10 serological markers. RESULTS: There was little evidence for an association of ALL with the serology of any of the studied infectious agents among the very young children. In contrast, among children aged 5 years or older, leukemia was inversely associated with seropositivity to Epstein-Barr virus, human herpes virus-6, Mycoplasma pneumoniae and parvovirus B19. CONCLUSIONS: Among children aged 5 years or older the risk of leukemia may be higher when the low herd immunity for several agents is challenged by late infection from an agent that, as a rule, would attack children at a younger age.