Adverse birth outcomes related to concentrations of per- and polyfluoroalkyl substances (PFAS) in maternal blood collected from pregnant women in 1960-1966.

BACKGROUND: Prior animal and epidemiological studies suggest that per- and polyfluoroalkyl substances (PFAS) exposure may be associated with reduced birth weight. However, results from prior studies evaluated a relatively small set of PFAS. OBJECTIVES: Determine associations of gestational PFAS concentrations in maternal serum samples banked for 60 years with birth outcomes. METHODS: We used data from 97 pregnant women from Boston and Providence that enrolled in the Collaborative Perinatal Project (CPP) study (1960-1966). We quantified concentrations of 27 PFAS in maternal serum in pregnancy and measured infant weight, height and ponderal index at birth. Covariate-adjusted associations between 11 PFAS concentrations (>75% detection limits) and birth outcomes were estimated using linear regression methods. RESULTS: Median concentrations of PFOA, PFNA, PFHxS, and PFOS were 6.189, 0.330, 14.432, and 38.170 ng/mL, respectively. We found that elevated PFAS concentrations during pregnancy were significantly associated with lower birth weight and ponderal index at birth, but no significant associations were found with birth length. Specifically, infants born to women with PFAS concentrations ≥ median levels had significantly lower birth weight (PFOS: ß = -0.323, P = 0.006; PFHxS: ß = -0.292, P = 0.015; PFOA: ß = -0.233, P = 0.03; PFHpS: ß = -0.239, P = 0.023; PFNA: ß = -0.239, P = 0.017). Similarly, women with PFAS concentrations ≥ median levels had significantly lower ponderal index (PFHxS: ß = -0.168, P = 0.020; PFHxA: ß = -0.148, P = 0.018). CONCLUSIONS: Using data from this US-based cohort study, we found that 1) maternal PFAS levels from the 1960s exceeded values in contemporaneous populations and 2) that gestational concentrations of certain PFAS were associated with lower birth weight and infant ponderal index. Additional studies with larger sample size are needed to further examine the associations of gestational exposure to individual PFAS and their mixtures with adverse birth outcomes.

Sex-dependent associations of maternal androgen levels with offspring BMI and weight trajectory from birth to early childhood.

CONTEXT: In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. DESIGN: We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. RESULTS: Higher maternal androgen levels associated with lower BMIz at birth (ß = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (ß = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). CONCLUSION: Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.

Prenatal maternal immune disruption and sex-dependent risk for psychoses.

BACKGROUND: Previous studies suggest that abnormalities in maternal immune activity during pregnancy alter the offspring's brain development and are associated with increased risk for schizophrenia (SCZ) dependent on sex. METHOD: Using a nested case-control design and prospectively collected prenatal maternal sera from which interleukin (IL)-1ß, IL-8, IL-6, tumor necrosis factor (TNF)-α and IL-10 were assayed, we investigated sex-dependent associations between these cytokines and 88 psychotic cases [SCZ = 44; affective psychoses (AP) = 44] and 100 healthy controls from a pregnancy cohort followed for > 40 years. Analyses included sex-stratified non-parametric tests adjusted for multiple comparisons to screen cytokines associated with SCZ risk, followed by deviant subgroup analyses using generalized estimating equation (GEE) models. RESULTS: There were higher prenatal IL-6 levels among male SCZ than male controls, and lower TNF-α levels among female SCZ than female controls. The results were supported by deviant subgroup analyses with significantly more SCZ males with high IL-6 levels (>highest quartile) compared with controls [odd ratio (OR)75 = 3.33, 95% confidence interval (CI) 1.13-9.82], and greater prevalence of low TNF-α levels (

MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Neuropsychological performance and family history in children at age 7 who develop adult schizophrenia or bipolar psychosis in the New England Family Studies.

BACKGROUND: Persons developing schizophrenia (SCZ) manifest various pre-morbid neuropsychological deficits, studied most often by measures of IQ. Far less is known about pre-morbid neuropsychological functioning in individuals who later develop bipolar psychoses (BP). We evaluated the specificity and impact of family history (FH) of psychosis on pre-morbid neuropsychological functioning. METHOD: We conducted a nested case-control study investigating the associations of neuropsychological data collected systematically at age 7 years for 99 adults with psychotic diagnoses (including 45 SCZ and 35 BP) and 101 controls, drawn from the New England cohort of the Collaborative Perinatal Project (CPP). A mixed-model approach evaluated full-scale IQ, four neuropsychological factors derived from principal components analysis (PCA), and the profile of 10 intelligence and achievement tests, controlling for maternal education, race and intra-familial correlation. We used a deviant responder approach (<10th percentile) to calculate rates of impairment. RESULTS: There was a significant linear trend, with the SCZ group performing worst. The profile of childhood deficits for persons with SCZ did not differ significantly from BP. Neuropsychological impairment was identified in 42.2% of SCZ, 22.9% of BP and 7% of controls. The presence of psychosis in first-degree relatives (FH+) significantly increased the severity of childhood impairment for SCZ but not for BP. CONCLUSIONS: Pre-morbid neuropsychological deficits are found in a substantial proportion of children who later develop SCZ, especially in the SCZ FH+ subgroup, but less so in BP, suggesting especially impaired neurodevelopment underlying cognition in pre-SCZ children. Future work should assess genetic and environmental factors that explain this FH effect.

Religious service attendance and spiritual well-being are differentially associated with risk of major depression.

BACKGROUND: The complex relationships between religiosity, spirituality and the risk of DSM-IV depression are not well understood. METHOD: We investigated the independent influence of religious service attendance and two dimensions of spiritual well-being (religious and existential) on the lifetime risk of major depression. Data came from the New England Family Study (NEFS) cohort (n=918, mean age=39 years). Depression according to DSM-IV criteria was ascertained using structured diagnostic interviews. Odds ratios (ORs) for the associations between high, medium and low tertiles of spiritual well-being and for religious service attendance and the lifetime risk of depression were estimated using multiple logistic regression. RESULTS: Religious service attendance was associated with 30% lower odds of depression. In addition, individuals in the top tertile of existential well-being had a 70% lower odds of depression compared to individuals in the bottom tertile. Contrary to our original hypotheses, however, higher levels of religious well-being were associated with 1.5 times higher odds of depression. CONCLUSIONS: Religious and existential well-being may be differentially associated with likelihood of depression. Given the complex interactions between religiosity and spirituality dimensions in relation to risk of major depression, the reliance on a single domain measure of religiosity or spirituality (e.g. religious service attendance) in research or clinical settings is discouraged.

Lifetime characteristics of participants and non-participants in a smoking cessation trial: implications for external validity and public health impact.

BACKGROUND: Detailed information about the characteristics of smokers who do and do not participate in smoking cessation treatment is needed to improve efforts to reach, motivate, and treat smokers. PURPOSE: The aim of this study is to explore a broad range of characteristics related to participation in a smoking cessation trial. METHODS: Eligible smokers were recruited from a longitudinal birth cohort. Participants and non-participants were compared on a broad range of sociodemographics, smoking, psychiatric and substance abuse disorders, personality, and prospective measures from early childhood. Eligible smokers were compared to a matched regional subsample of the Behavioral Risk Factor Surveillance System (BRFSS). RESULTS: Few differences were observed, most of which were statistically significant but not clinically meaningful. Compared to non-participants, participants were more likely to be single, have lower income, be more nicotine-dependent, be more motivated to quit, and have higher levels of depressed mood and stress even after covariance of gender, income, and marital status. Sociodemographic differences between participants and the BRFSS sample reflect the skew toward lower socioeconomic status in the original birth cohort. CONCLUSIONS: The encouraging conclusion is that smokers who enroll in cessation trials may not differ much from non-participants. Information about treatment participants can inform the development of recruitment strategies, improve the tailoring of treatment to individual smoker profiles, help to estimate potential selection bias, and improve estimates of population impact.

Fetal growth restriction and the development of major depression.

OBJECTIVE: To test the association between fetal growth restriction and the lifetime risk of major depression and the number of recurrent episodes. METHOD: Study subjects (n = 1101) were offspring of participants in the Providence, RI, site of the National Collaborative Perinatal Project. Cox regression was used to investigate the relation between measures of birth size and the lifetime risk of depression and the mean number of depressive episodes was compared across categories of birth size. RESULTS: There was no association between low birth weight, gestational age, ponderal index and small for gestational age and the lifetime risk of major depression, or the number of recurrent episodes. CONCLUSION: Fetal growth restriction, as reflected by multiple measures of birth size, is not associated with the risk of a major depression or the subsequent recurrence of depressive episodes. Results of this study do not support a 'fetal programming' effect in depression.

Differences in maternal smoking across successive pregnancies - dose-dependent relation to BMI z-score in the offspring: an individual patient data (IPD) meta-analysis.

INTRODUCTION: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. METHODS: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. RESULTS: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses ≥25 cigarettes per day. CONCLUSIONS: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.

Neural - hormonal responses to negative affective stimuli: Impact of dysphoric mood and sex.

BACKGROUND: Maladaptive responses to negative affective stimuli are pervasive, including clinically ill and healthy people, and men and women respond differently at neural and hormonal levels. Inspired by the Research Domain Criteria initiative, we used a transdiagnostic approach to investigate the impact of sex and dysphoric mood on neural-hormonal responses to negative affective stimuli. METHODS: Participants included 99 individuals with major depressive disorder, psychosis and healthy controls. Functional magnetic resonance imaging (fMRI) was complemented with real-time acquisition of hypothalamo-pituitary-adrenal (HPA) and -gonadal (HPG) hormones. fMRI data were analyzed in SPM8 and task-related connectivity was assessed using generalized psychophysiological interaction. RESULTS: Across all participants, elevated cortisol response predicted lower brain activity in orbitofrontal cortex and hypothalamus-amygdala connectivity. In those with worse dysphoric mood, elevated cortisol response predicted lower activity in hypothalamus and hippocampus. In women, elevated cortisol response was associated with lower activity in medial prefrontal cortex and low hypothalamo-hippocampal connectivity. In women with high dysphoric mood, elevated cortisol response was associated with low hypothalamo-hippocampal connectivity. There were no interactions with diagnosis or medication. LIMITATIONS: There was limited power to correct for multiple comparisons across total number of ROIs and connectivity targets; cortisol responses were relatively low. CONCLUSIONS: We conclude that the pathophysiology in neural-hormonal responses to negative affective stimuli is shared across healthy and clinical populations and varies as a function of sex and dysphoric mood. Our findings may contribute to the development of hormonal adjunctive therapeutics that are sex-dependent, underscoring the importance of one's sex to precision medicine.

Prenatal immune programming of the sex-dependent risk for major depression.

Maternal immune functioning during pregnancy contributes to sex-dependent deficits in neurodevelopment and to behaviors associated with affective traits in preclinical studies, and has been indirectly associated with offspring depression in epidemiologic studies. We therefore investigated the association between immune activity during pregnancy and the risk of depression among male and female offspring. We conducted a case-control study of depression (n=484 cases and n=774 controls) using data from the New England Family Study, a pregnancy cohort enrolled between 1959 and 1966 that assessed psychiatric outcomes in adult offspring (mean age=39.7 years). We assayed concentrations of three pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokine, IL-10, in maternal serum collected at the end of the second and beginning of the third trimesters. High maternal TNF-α was associated with reduced odds of depression among both male and female offspring (odds ratio (OR)=0.68; confidence interval (CI)=0.48, 0.98). However, when considering the TNF-α to IL-10 ratio, a measure of the ratio of pro- to anti-inflammatory loading, maternal immune effects on offspring depression differed significantly by sex (χ(2)=13.9, degrees of freedom=4, P=0.008). Among females, higher maternal TNF-α:IL-10 was associated with reduced odds of depression (OR=0.51; CI=0.32, 0.81), whereas, among males, high maternal TNF-α:IL-10 was associated with elevated odds of depression (OR=1.86; CI=1.02, 3.39). Thus, the balance between TNF-α and IL-10 in maternal prenatal serum was associated with depression in a sex-dependent manner. These findings are consistent with the role of TNF-α in the maturation of the sexually dimorphic fetal brain circuitry that regulates stress and affective responses, and support a prenatal stress-immune model of depression pathogenesis.

Pregnancy/delivery complications and psychiatric diagnosis. A prospective study.

We examined the hypothesis that pregnancy and delivery complications result in increased risk for the development of psychiatric disorders. The study sample included 1068 pregnancies classified as chronic fetal hypoxia, other complications, preterm birth, or normal pregnancy/delivery that had initially been studied prospectively from the prenatal period through age 7 years. Subjects were recontacted (ages 18 to 27 years) and lifetime psychiatric diagnoses made with the Diagnostic Interview Schedule. Preterm subjects had significantly higher rates of cognitive impairment. Subjects with chronic fetal hypoxia had higher rates of both cognitive impairment and psychotic disorders, although these differences failed to reach statistical significance due to the small number of cases. With these exceptions, the data did not support the hypothesis that rates of psychiatric disorders are higher among subjects born with complications of pregnancy and delivery than among normal controls born without complications.

Maternal infections and subsequent psychosis among offspring.

BACKGROUND: We tested the hypothesis that maternal infections during pregnancy are associated with the subsequent development of schizophrenia and other psychoses in adulthood. METHODS: We conducted a nested case-control study of 27 adults with schizophrenia and other psychotic illnesses and 54 matched unaffected control subjects (matched for sex, ethnicity, and date of birth) from the Providence, RI, cohort of the Collaborative Perinatal Project. We retrieved stored blood samples that had been obtained from these mothers at the end of pregnancy. These samples were analyzed for total class-specific immunoglobulins and for specific antibodies directed at recognized perinatal pathogens capable of affecting brain development. RESULTS: Maternal levels of IgG and IgM class immunoglobulins before the mothers were delivered of their neonates were significantly elevated among the case series (t = 3.06, P =.003; t = 2.93, P =.004, respectively, for IgG and IgM immunoglobulin-albumin ratios). Secondary analyses indicated a significant association between maternal antibodies to herpes simplex virus type 2 glycoprotein gG2 and subsequent psychotic illness (matched t test = 2.43, P =.02). We did not find significant differences between case and control mothers in the serum levels of IgA class immunoglobulins, or in specific IgG antibodies to herpes simplex virus type 1, cytomegalovirus, Toxoplasma gondii, rubella virus, human parvovirus B19, Chlamydia trachomatis, or human papillomavirus type 16. CONCLUSIONS: The offspring of mothers with elevated levels of total IgG and IgM immunoglobulins and antibodies to herpes simplex virus type 2 are at increased risk for the development of schizophrenia and other psychotic illnesses in adulthood.

Prevalence and risk factors for posttraumatic stress disorder among chemically dependent adolescents.

OBJECTIVE: This study ascertained the prevalence of posttraumatic stress disorder (PTSD) among chemically dependent adolescents and identified factors that influence the risk of PTSD after a qualifying trauma. METHOD: The study group consisted of 297 adolescents aged 15-19 years who met the DSM-III-R criteria for dependence on alcohol or other drugs and who were receiving treatment in seven publicly funded Massachusetts facilities. PTSD and other axis I diagnoses were assessed by the Diagnostic Interview Schedule. Data on risk factors were collected by a specially constructed interview schedule. RESULTS: The lifetime prevalence of PTSD was 29.6% (24.3% for males and 45.3% for females), and the current prevalence was 19.2% (12.2% for males and 40.0% for females). These prevalences reflect a high occurrence of traumatic exposures and a high case rate among those who experienced trauma. The risk of PTSD varied with the nature of the trauma, the number of traumas experienced, psychiatric comorbidity, and familial characteristics. The higher rate of PTSD among females was due to a greater frequency of rape, which carries a high risk of PTSD development, and to a high rate of comorbid conditions. CONCLUSIONS: The lifetime prevalence of PTSD among these chemically dependent adolescents is five times that reported for a community sample of adolescents. This extremely high rate provides new understanding of the etiologic connection between PTSD and chemical dependence and has implications for their treatment.

Depressive illness among chemically dependent adolescents.

OBJECTIVE: The purpose of this study was to investigate the prevalence and correlates of depression among adolescents being treated for chemical dependence. METHOD: Using the National Institute of Mental Health Diagnostic Interview Schedule, the authors interviewed 223 adolescents, aged 15-19 years, who were in residential treatment for alcohol or drug dependence diagnosed according to DSM-III-R criteria. Data on sociodemographic characteristics, school and social performance, past history, family composition, familial alcohol and drug abuse, and previous victimization of the subjects were also gathered. RESULTS: Fifty-four (24.7%) of the subjects met the DSM-III-R criteria for depression. Very few of the traditional correlates of depression discriminated depressed from nondepressed subjects, suggesting that the presence of chemical dependence overrides other predictors of depression. Only female gender, paternal psychopathology, and victimization (physical abuse, sexual abuse) emerged as important variables associated with depression. However, subjects whose onset of depression preceded their chemical dependence had different characteristics from those whose depression began after their chemical dependence. CONCLUSIONS: The prevalence of depressive illness in these chemically dependent adolescents was approximately three times that reported for nonreferred groups of similar age. This high rate of depression reflects the contributions of two distinct groups--those with primary depression and those with depression subsequent to chemical dependence--whose characteristics differed, suggesting the possibility of two pathologic processes, similar in manifestation but with different associated features and possibly with distinct etiologies. Confirmation of these findings in further research could indicate that the two forms of depression may require different treatment approaches.

Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study.

OBJECTIVE: Epidemiologic evidence linking obstetric complications to schizophrenia has been positive but inconclusive. One reason for the lack of conclusive evidence may be the inconsistency in measuring disturbances of fetal/neonatal brain development based on general obstetric markers of maternal health. The authors used data from the National Collaborative Perinatal Project to examine the relationship between schizophrenia and other nonaffective psychoses and a theoretically derived measure of hypoxic-ischemia-related fetal/neonatal complications. METHOD: Six hundred ninety-three men and women (average age 23) born to a community sample of women between 1959 and 1966 were followed up an average of 19 years after early childhood assessments. Subjects with DSM-IV schizophrenia and other nonaffective psychoses were identified using the Diagnostic Interview Schedule and best-estimate consensus diagnoses. RESULTS: Hypoxic-ischemia-related fetal/neonatal complications were associated with a doubling of the risk of developing a psychotic disorder, compared with no relevant complications (6.9% versus 1.4%). When mood disorders were excluded from the group of psychotic diagnoses, the risk of schizophrenia and other nonaffective psychoses associated with hypoxic-ischemia-related fetal/neonatal complications was strikingly elevated, compared with no relevant complications (5.75% versus 0.39%). Nonpsychotic mood disorders were unrelated to these fetal/neonatal complications. Schizophrenia and other nonaffective psychoses were most strongly associated with hypoxic-ischemia-related fetal/neonatal complications of disordered growth and development. CONCLUSIONS: The data show a strikingly elevated, graded, independent risk of schizophrenia and other nonaffective psychoses associated with this classification of antecedent hypoxic-ischemia-related fetal/neonatal complications.

IQ decline during childhood and adult psychotic symptoms in a community sample: a 19-year longitudinal study.

OBJECTIVE: The goal of this study was to examine cognitive antecedents of psychosis by determining whether variability in IQ during childhood was predictive of psychotic symptoms in adulthood. METHOD: Deviant responder analyses were used to examine prospectively the relationship of IQ at ages 4 and 7 to psychotic symptoms at age 23 in 547 offspring from a community sample (National Collaborative Perinatal Project) that was unselected for psychiatric illness. The authors compared three hypotheses: that 1) low IQ, 2) large IQ fluctuations regardless of direction, or 3) large IQ declines would predict the presence of adult psychotic symptoms. RESULTS: The 10% of individuals with substantially larger than expected IQ declines from age 4 to 7 had a rate of psychotic, but not other psychiatric, symptoms at age 23 that was nearly seven times as high as the rate for other persons. Parental socioeconomic status and IQ at age 7 also predicted adult psychotic symptoms. However, when IQ at age 7, IQ decline between ages 4 and 7, and socioeconomic status were all included in a logistic regression analysis, only IQ decline remained significant. CONCLUSIONS: There is an increased likelihood of developing psychotic symptoms in adulthood for a subgroup of individuals with substantially greater than expected IQ declines during childhood. IQ decline is specific for psychotic symptoms, but follow-up assessment when the study participants are further into the age of risk will be necessary to determine specificity for schizophrenia. The authors discuss the implications of this early cognitive downturn for a neurodevelopmental view of schizophrenia.

Advance care planning for children with special health care needs: a survey of parental attitudes.

OBJECTIVES: This study explored parental attitudes about their interactions with their children's providers when decision making involved critical life situations. We evaluated parents' attitudes regarding the following questions: What was the parents' understanding of their children's health care issues, and what was the parental perception of the professionals' understanding of their children and of themselves? Who should be the principal decision makers for the children? What was the parents' knowledge about advance directives? Did parents want to participate in a process of advance planning to assist with critical life decision making for their children? METHODS: We surveyed all parents attending a conference sponsored by the Massachusetts Department of Public Health for parents of children with special needs. The questionnaire was provided to all parents attending the conference. An announcement was made at the conference requesting parental participation. The 76 respondents constitute a convenience sample of parents of children with special needs sufficient for this preliminary stage of investigation. RESULTS: Of 177 parents attending the conference, 76 (43%) completed the questionnaire. Eighty-eight percent of the participants strongly agreed that they understood their children's conditions. Twenty-one percent stated that they had sufficient understanding of their children's future medical needs, and 21% thought that they had a sufficient understanding of their children's developmental potential. Ninety-nine percent of parents strongly agreed that physicians should share information with parents no matter how serious or potentially upsetting. Ninety-four percent of those parents who thought that their children's physicians understood their own needs also thought that the physicians understood their children's needs. In contrast, only half (55%) of those parents who thought the physicians did not understand their needs thought the physicians understood their children's needs. Ninety-two percent of parents who thought that the physicians understood their needs agreed that the physicians would make the best decisions in crises versus 60% of those who did not think the physicians understood their needs. Seventy-four percent stated that they would consider written guidelines for their children that dealt with critical life situations. All parents who thought their children's conditions were not understood wanted written guidelines. Of those parents who had thought their children would not survive (15 parents), 94% wanted written guidelines. All seven parents who had been told their children would not survive wanted written guidelines. CONCLUSIONS: Parents in this study were generally satisfied with care being provided to their children. Nevertheless, the results clearly suggest goals that could lead to improved capacity for parents and providers to make critical life decisions for and with children. First, physicians must understand the needs of parents to be able to make decisions that would be in the children's best interests. Second, parents should participate fully in critical life decisions for their children and should use written guidelines to assist with the process of these critical life decisions. Our findings strongly support the development of a longitudinal process, initiated early after the onset or discovery of illness and maintained longitudinally throughout the course of a child's illness, to help parents and providers work together in this vital area of health care to children.

Relationship between birthweight and blood pressure in childhood.

Studies have shown an inverse relationship between birthweight and blood pressure in later life. The objective of this study is to analyze the relationship between birthweight and blood pressure in childhood in a North American-based population. Data on 2,958 births with follow-up at 7 years of age from the Providence, RI, cohort of the Collaborative Perinatal Project of the National Institute of Neurological Diseases and Stroke were retrospectively analyzed using univariate and multivariate analytic methods. Bivariate analysis of the total cohort showed a direct relationship between follow-up weight at age 7 years and birthweight (r = 0.24; P < 0.001) and follow-up weight with systolic (SBP) and diastolic blood pressure (DBP; r = 0.33; P < 0.001 and r = 0.22; P < 0.001, respectively). On multivariate analysis, follow-up weight and height were the strongest predictors of SBP and DBP. There was also a significant inverse relationship between birthweight and SBP. A cohort of term infants (n = 2,561) was subdivided into birthweight-for-gestational-age groupings to further evaluate the effects of birthweight on blood pressure. Small-for-gestational-age (SGA) infants were markedly smaller at age 7 years than those large-for-gestational-age (LGA; 21 +/- 4 kg v 26 +/- 4 kg; P < 0.01). Despite the direct association between follow-up weight and blood pressure, the mean blood pressure did not differ between SGA (103/58 mm Hg) and LGA patients (103/59 mm Hg). To assess whether birthweight was an independent predictor of blood pressure, blood pressures were predicted using linear regression equations. For every 1-kg decrease in birthweight in term infants, SBP at 7 years increased by 1.3 mm Hg and DBP by 0.6 mm Hg. In conclusion, controlling for weight and height in term infants at 7 years of age has an inverse linear effect on blood pressure. This suggests that birthweight in relation to gestation may be a contributor to the multifactorial cause of essential hypertension.

Association of prenatal and perinatal complications with subsequent bipolar disorder and schizophrenia.

This paper presents an overview of the recent literature on the association between prenatal and perinatal complications (PPCs) and schizophrenia, then systematically reviews papers published later than 1965 examining the association of PPCs and bipolar disorder. Three of the four studies comparing bipolar cases with normal controls indicated a positive association of PPCs with the development of bipolar disorder in adult life; the four odds ratios ranged from 1.0 to 12.0. The proportion of PPCs among the bipolar samples without comparison subjects ranged from 3.8% to 50.0%. Issues of study design, measurement and severity of exposure, and outcome are addressed. This review suggests that further investigation of genetic interactions, gender differences, and the specificity of effects in the association between PPCs and mental disorders other than schizophrenia is warranted.