Maternal personality traits and risk of preterm birth and fetal growth restriction

Background/AimsMaternal personality may increase vulnerability to stress, which could lead to an unfavourable intrauterine environment to the fetus. We sought to investigate the impact of maternal personality traits on adverse birth outcomes such as preterm birth, and fetal growth restriction in the mother-child cohort study (RHEA Study) in Crete, Greece 2007–2009.MethodsFive hundred and eighty pregnant women participating in “Rhea” cohort study completed the Eysenck Personality Questionnaire-Revised (EPQ-R) at 28–32 weeks of gestation. Information on anthropometric measures at birth was obtained from the hospital delivery logs and medical records. Fetal growth restriction was based on a customized model, and multivariate logistic regression models were used adjusting for confounders.ResultsA per unit increase in the EPQ Neuroticism scale increased the risk for fetal weight growth restriction by 9% [Odds Ratio (OR) = 1.09, 95 percent CI: 1.01, 1.19)], and for fetal head circumference growth restriction by 6% [OR = 1.06, 95 percent CI: 1.01, 1.18] after adjusting for maternal age, education, origin, marital status, working status, pre-pregnancy BMI, delivery type, parity, smoking, and alcohol intake during pregnancy.ConclusionsMaternal neuroticism, which predisposes to negative mood, may be a risk factor for fetal growth restriction.     

Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero.     

The effect of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

Previous studies have suggested that prenatal exposure to nicotine is associated with abnormal development in fetuses, including fetal brain damage. The present study determined the effect of maternal administration of nicotine during different gestational periods on brain nicotine receptor subunits in fetal rats. Subcutaneous injections of nicotine in maternal rats from the early and middle gestation decreased fetal blood PO2, increased fetal blood PCO2 and hemoglobin, and decreased fetal brain weight. The nicotinic acetylcholine receptor (nAChRs) mRNA abundance in the fetal brain was significantly changed by prenatal treatment with nicotine during pregnancy. Fetal alpha2, alpha4, alpha7, and beta2 units were significantly increased in the brain by prenatal exposure to nicotine in rat fetuses. However, the expression of mRNA of fetal brain alpha3, alpha5, beta3, and beta4 units were not changed. The results showed that prenatal nicotine can change the development of both alpha and beta subunits of nAChRs in the fetal brain at gene level in association with restriction of fetal brain growth and in utero hypoxia.     

Maternal Substance Abuse and the Later Risk of Fractures in Offspring: L’abus maternel de substances et le risque ultérieur de fractures chez les enfants

Objective:To assess the association of maternal illicit drug abuse before or during pregnancy with future fractures in offspring.Methods:We performed a longitudinal cohort study of 792,022 infants born in hospitals of Quebec, Canada, between 2006 and 2016, with 5,457,634 person-years of follow-up. The main exposure was maternal substance abuse before or during pregnancy, including cocaine, opioid, cannabis, and other illicit drugs. The main outcome measure was hospitalization for traumatic fracture in offspring up to 12 years of age. We used adjusted Cox regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal drug abuse with the subsequent risk of fracture in children.Results:The incidence of child fractures was higher for maternal illicit drug abuse than no drug abuse (21.2 vs. 15.4 per 10,000 person-years). Maternal drug abuse before or during pregnancy was associated with 2.35 times the risk of assault-related fractures (95% CI, 1.29 to 4.27) and 2.21 times the risk of transport accident-related fractures (95% CI, 1.34 to 3.66), compared with no drug abuse. Associations were strongest before 6 months of age for assault-related fractures (HR = 2.14; 95% CI, 0.97 to 4.72) and after 6 years for transport-related fractures (HR = 2.86; 95% CI, 1.35 to 6.05). Compared with no drug abuse, associations with assault and transport-related fractures were elevated for all drugs including cocaine, opioids, and cannabis.Conclusions:Maternal illicit drug abuse is associated with future child fractures due to assault and transport accidents.     

Depression During Pregnancy and Postpartum

Depression is a common complication of pregnancy and the postpartum period. There are multiple risk factors for peripartum mood disorders, most important of which is a prior history of depression. Both depression and antidepressant medications confer risk upon the infant. Maternal depression has been associated with preterm birth, low birth weight, fetal growth restriction, and postnatal cognitive and emotional complications. Antidepressant exposure has been associated with preterm birth, reductions in birth weight, persistent pulmonary hypertension, and postnatal adaptation syndrome (PNAS) as well as a possible connection with autism spectrum disorder. Paroxetine has been associated with cardiac malformations. Most antidepressant medications are excreted in low levels in breast milk and are generally compatible with breastfeeding. The use of antidepressants during pregnancy and postpartum must be weighed against the risk of untreated depression in the mother.     

Decreased Birth Weight in Psychosis: Influence of Prenatal Exposure to Serologically Determined Influenza and Hypoxia

Background: Decreased birth weight (BW) is associated with later psychosis, but the sources of decreased BW for those at risk for psychosis remain unclear. Aim: To determine whether fetal exposure to influenza and/or hypoxia accounts for BW decreases among psychotic cases and controls. Method: Subjects were 111 cases diagnosed with schizophrenia or affective psychosis and 333 matched controls from the Collaborative Perinatal Project. Psychiatric diagnoses were ascertained from medical records. Influenza and hypoxia were determined from maternal and cord sera collected at birth. Results: Cases exposed to severe fetal hypoxia or influenza had significantly lower BW compared with unexposed cases and controls, regardless of exposure status. No significant differences in BW were observed among controls based on exposure status. Conclusions: Decreased BW appears to be a risk factor for psychosis only in the presence of other teratogens. Liability to psychosis likely renders fetuses vulnerable to decreased fetal growth in response to hypoxia and influenza.Key words: obstetric complications, pregnancy, schizophrenia     

Effect of maternal sleep in late pregnancy on leptin and lipid levels in umbilical cord blood

ObjectivesTo study the impact of maternal sleep in late pregnancy on birth weight (BW) and leptin and lipid levels in umbilical cord blood.Study designA total of 277 healthy and singleton pregnancy women were recruited for participation in the Shanghai Sleep Birth Cohort Study (SSBC) during their 36–38 weeks of pregnancy, from May 2012 to July 2013. Maternal night sleep time (NST), sleep efficiency (SE), sleep onset latency (SOL) and the percentage of wake after sleep onset (WASO) in NST and midpoint of sleep (MSF) were measured by actigraphy for seven consecutive days. The leptin and lipid levels were determined in cord blood samples collected from the umbilical vein immediately after delivery. Birth information (birth weight, gender, delivery type, etc.) was extracted from medical records. A multivariable linear regression model was applied to examine the effect of maternal sleep in late pregnancy on newborn leptin and lipid levels in umbilical cord blood.ResultsA total of 177 women and their infants were included in the analysis. Maternal mean NST was 7.03 ± 1.10 h in late pregnancy, and 48% had a shorter sleep time (NST < 7 h). The average maternal SE was 72.54% ± 9.66%. The mean percentage WASO/NST was 21.62% ± 9.98%; the average MSF was about 3:34 (0:53); and the SOL was 46.78 ± 36.00 min. After adjustment for confounders, both maternal NST and SE were found to be significantly associated with triglyceride levels (β = −0.219, p = 0.006; β = −0.224, p = 0.006) in umbilical cord blood; and maternal NST was also observed to have positive association with newborn leptin levels (β = 0.146, p = 0.047). However, we did not find significant association between other maternal sleep parameters in late pregnancy and leptin and lipid levels and birth weight.ConclusionsShort sleep duration and poor sleep quality during late pregnancy were associated with newborn leptin and lipid levels, and efforts on improving maternal sleep during late pregnancy should be advocated for children's health.     

Lower birth weight of Dutch neonates who were in utero at the time of the 9/11 attacks

OBJECTIVE: Maternal stress during pregnancy has been reported to have an adverse influence on fetal growth. The terrorist attacks of September 11, 2001, on the United States have provoked feelings of insecurity and stress worldwide. Our aim was to test the hypothesis that maternal exposure to these acts of terrorism via the media had an unfavorable influence on mean birth weight in the Netherlands. METHODS: We compared birth weights of 1885 Dutch neonates who were in utero during the attacks with those of 1258 neonates who were in utero exactly 1 year later. RESULTS: In the exposed group, birth weight was lower than in the nonexposed group (difference, 48 g; 95% confidence interval=13.6, 82.9; P=.006). The difference in birth weight could not be explained by tobacco use, maternal age, parity, or other potential confounders or by shorter pregnancy durations. CONCLUSION: These results provide evidence supporting the hypothesis that exposure of Dutch pregnant women to the 9/11 events via the media has had an adverse effect on the birth weight of their offspring.     

Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986

Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036–0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96–1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07–1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis.     

Fetal cells in maternal blood: a six-fold increase in women who have undergone amniocentesis and carry a fetus with Down syndrome: a multicenter study

Fetal nucleated red blood cells (FNRBCs) circulate in the maternal blood throughout pregnancy. Even if the frequency of fetal cells in the maternal circulation remains to be ascertained, complications of pregnancy such as fetal cells aneuploidies, preeclampsia, abnormal Doppler of the uterine artery without symptoms of preeclampsia, fetal growth restriction and polyhydramnios are associated with an increased feto-maternal trafficking. Based on these observations, previous studies have suggested that determination of the fetal nucleated red blood cell count (FNRBCC) might be a useful non-invasive screening test, either alone or in combination with existing maternal tests, for the non-invasive assessment of aneuploidies, in particular Down syndrome (DS). In this paper we have evaluated the distribution of FNRBCC in a set of 18 normal pregnancies and 18 pregnancies with a trisomy 21-affected fetus, matching for gestational age, maternal age, and, when possible, fetal gender, in order to quantify the difference in the number of fetal cells between the two populations. Maternal blood was collected from each pregnant woman two to three weeks after amniocentesis after knowing the cytogenetic results. Correlation of FNRBCC with the gestational week and clinical status (affected vs. non affected) by multiple regression analysis provided significant results (p < 0.001). Adjusted values of FNRBCC were 48 +/- 10.2 in controls and 301 +/- 17.01 in DS cases, corresponding to a 6.27 fold increase. These retrospective results prompt a prospective evaluation of the use of FNRBCC for screening purposes.     

Adverse effect of maternal caffeine ingestion on fetal cerebrum in rat

This study was undertaken to determine whether maternal caffeine ingestion is or is not a risk factor in fetal cerebral development using experimental rat models. Pregnant rats of the Wistar strain were given 0.04% caffeine in drinking water before and/or during pregnancy for various numbers of days. Control rats received water for the same periods. There was no reduction of maternal body weight, fetal body weight or fetal total brain weight. Low fetal cerebral weight and placental weight were observed when dams were given caffeine before mating for long times and/or throughout pregnancy. DNA, RNA and protein contents per cerebrum were also reduced in fetuses from dams given caffeine throughout pregnancy or for the last 6 gestational days. Cerebral DNA and protein contents as expressed per wet weight were higher and significantly lower respectively in the fetuses from dams given caffeine throughout pregnancy when compared to controls. Activity of thymidine kinase was not significantly decreased in caffeine-treated fetuses. There was a positive correlation between maternal serum and fetal cerebral caffeine levels. Additionally a negative correlation between maternal caffeine levels and fetal survival rates which decreased in litters from dams given caffeine throughout pregnancy was demonstrated. Our rat model indicates maternal caffeine ingestion during pregnancy is associated with reduction of fetal cerebral weight and protein content without reduction of body weight.     

Diurnal rhythm of cortisol during late pregnancy: associations with maternal psychological well-being and fetal growth

Maternal psychological functioning during pregnancy affects both maternal and fetal well-being. The hypothalamic-pituitary-adrenal (HPA) axis provides one mechanism through which maternal psychosocial factors may be transduced to the fetus. However, few studies have examined maternal psychological factors or birth outcomes in relation to the diurnal pattern of cortisol across the day. The current study examined maternal psychological well-being, parity status, and birth weight in relation to the maternal cortisol diurnal rhythm in a group of 98 low-risk pregnant women (51 primiparae). At 36 weeks gestation, participants completed both pregnancy-specific and general self-report measures of psychological functioning and provided saliva samples at 8:00, 12:00, and 16:00h on 2 consecutive working days for the assay of cortisol. The expected diurnal decline in salivary cortisol was observed. Higher trait anxiety was associated with a flatter afternoon decline for all mothers. For primiparae, steeper morning cortisol declines were associated with lower infant birth weight. The findings suggest that regulation of the HPA axis may differ by parity status with downstream implications for fetal growth and development.     

Physiological reactivity of pregnant women to evoked fetal startle

Objective

The bidirectional nature of mother–child interaction is widely acknowledged during infancy and childhood. Prevailing models during pregnancy focus on unidirectional influences exerted by the pregnant woman on the developing fetus. Prior work has indicated that the fetus also affects the pregnant woman. Our objective was to determine whether a maternal psychophysiological response to stimulation of the fetus could be isolated.

Methods

Using a longitudinal design, an airborne auditory stimulus was used to elicit a fetal heart rate and motor response at 24 (n = 47) and 36 weeks (n = 45) of gestation. Women were blind to condition (stimulus versus sham). Maternal parameters included cardiac (heart rate) and electrodermal (skin conductance) responses. Multilevel modeling of repeated measures with 5 data points per second was used to examine fetal and maternal responses.

Results

As expected, compared to a sham condition, the stimulus generated a fetal motor response at both gestational ages, consistent with a mild fetal startle. Fetal stimulation was associated with significant, transient slowing of maternal heart rate coupled with increased skin conductance within 10 s of the stimulus at both gestational ages. Nulliparous women showed greater electrodermal responsiveness. The magnitude of the fetal motor response significantly corresponded to the maternal skin conductance response at 5, 10, 15, and 30 s following stimulation.

Conclusion

Elicited fetal movement exerts an independent influence on the maternal autonomic nervous system. This finding contributes to current models of the dyadic relationship during pregnancy between fetus and pregnant woman.     

Maternal Cortisol Concentrations During Pregnancy and Sex-Specific Associations With Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors

Background

Maternal cortisol during pregnancy has the potential to influence rapidly developing fetal brain systems that are commonly altered in neurodevelopmental and psychiatric disorders. Research examining maternal cortisol concentrations across pregnancy and offspring neurodevelopment proximal to birth is needed to advance understanding in this area and lead to insight into the etiology of these disorders.

Maternal obesity leads to increased proliferation and numbers of astrocytes in the developing fetal and neonatal mouse hypothalamus

Maternal obesity during pregnancy is associated with chronic maternal, placental, and fetal inflammation; and it elevates the risk for offspring obesity. Changes in the development of the hypothalamus, a brain region that regulates body weight and energy balance, are emerging as important determinants of offspring risk, but such changes are only beginning to be defined. Here we focused on the hypothesis that the pathological exposure of developing hypothalamic astrocytes to cytokines would alter their development.A maternal high-fat diet (mHFD) mouse model was used to investigate changes in hypothalamic astrocytes in the fetus during late gestation and in early neonates by using immunochemistry, confocal microscopy, and qPCR.The number of astrocytes and the proportion of proliferating astrocytes was significantly higher in the arcuate nucleus (ARC) and the supraoptic nucleus (SON) of the hypothalamus at both ages compared to control offspring from normal weight pregnancies. Supplemental to this we found that cultured fetal hypothalamic astrocytes proliferated significantly in response to IL6 (10 ng/ml), one of the cytokines significantly elevated in fetuses of obese dams, via the JAK/STAT3 signaling pathway.Thus, maternal obesity during pregnancy stimulated the proliferation and thereby increased numbers of astrocytes in the fetal as well as early neonatal hypothalamus, which may be driven, during fetal life, by IL6.     

Birth weight and attention-deficit/hyperactivity symptoms in childhood and early adolescence: a prospective Swedish twin study

ObjectiveTo determine whether low birth weight increases the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and early adolescence.MethodIn a population-based sample of 1,480 twin pairs born in the period 1985-1986 ascertained from the Swedish Twin Registry, birth weight was collected prospectively through the Medical Birth Registry. ADHD symptoms were measured with a 14-item checklist covering DSM-III-R criteria (parental rating) at age 8 to 9 years and 13 to 14 years. We used both a dichotomous approach for birth weight (>400 g or 15% weight difference) and ADHD (eight or more symptoms) and continuous measures to investigate between- and within-twin pair effects.ResultsOur results showed that low birth weight was a risk factor for symptoms of ADHD and the associations did not diminish when we controlled for genetic influence. The lighter twin in birth weight-discordant pairs had on average 13% higher ADHD symptom score at age 8 to 9 years (p = .006) and 12% higher ADHD score at age 13 to 14 years (p = .018) compared with the heavier twin. The genetic correlations suggest modest or no genetic overlap between birth weight and ADHD.ConclusionsThe hypothesis that low birth weight is associated with the development of ADHD symptoms was supported in this prospective twin study. Fetal growth restriction seems to represent a modest but fairly consistent environmental influence on the development of ADHD symptoms.     

Birth weight and obstetric complications determine age at onset in first episode of psychosis

BackgroundEarlier age at onset of psychosis (AOP) has been associated with poor social adjustment and clinical outcome. Genetic and environmental factors such as obstetric complications, parental history of psychosis, advanced paternal age at time of birth, low birth weight and gestational age, and use of drugs have been described as bringing AOP forward. This study aims to evaluate the relationship between AOP and these factors in a sample of first episode of psychosis (FEP) patients.MethodsClinical and sociodemographic data, age at FEP, age of parents at birth, parental history of psychosis, drug-use habits of the mother during pregnancy and of the patient before psychotic onset, and Lewis and Murray obstetric complication scale were obtained from 90 patients with FEP. Statistical analysis was performed by means of Pearson correlations, Chi-square tests, Student T-test analyses and a linear regression model using SPSS version 22.ResultsPre-eclampsia, need for incubator at birth, use of forceps, parental history of psychosis, and low birth weight were associated with an earlier AOP. Use of forceps and birth weight are the variables which best predict AOP in FEP. Stimulant drugs, which were mostly used together with cannabis and cocaine, were the only substances associated with an earlier AOP.ConclusionsOur findings are consistent with previous study results and underline the role of the prenatal period in the development of psychosis and the importance of careful monitoring of pregnancy and delivery, especially in cases with familial history.     

Fetal heart rate reactivity differs by women's psychiatric status: an early marker for developmental risk?

OBJECTIVE: To determine whether there are differences in fetal heart rate (FHR) reactivity associated with women's psychiatric status. METHOD: In 57 women in their 36th to 38th week of pregnancy (mean age 27 +/- 6 years), electrocardiogram, blood pressure (BP), respiration (RSP), and FHR were measured during baseline and a psychological challenge (a Stroop color-word matching task). Subjects underwent the Structured Clinical Interview for DSM-IV (SCID) and completed the Spielberger State-Trait Anxiety Inventory prior to testing. RESULTS: There was a significant main effect of maternal diagnostic group on FHR reactivity during the Stroop task even after controlling for birth weight and women's BP reactivity (F4,44 = 2.68, p =.04). Fetuses of depressed women had greater heart rate increases compared to fetuses of women with anxiety disorders and those of healthy, low-anxiety women (post hoc comparisons using the Fisher protected least significant difference test; t = 4.12, p <.05; t = 4.72, p <.01, respectively). There was a similar pattern comparing fetuses of healthy, high-anxiety women to the same two groups (t = 3.29, p <.05; t = 3.99, p <.05, respectively). There were no group differences in FHR during a resting baseline period (F4,52 = 1.2, p =.35). CONCLUSIONS: Maternal mood disturbance is associated with alterations in children's physiological reactivity prior to birth.     

Maternal caloric restriction spares fetal brain polyunsaturated fatty acids in Wistar rats

There is increasing interest in the role of developmental programming; however, the impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. Recent reports have shown that caloric restriction regimens in adult animals reduce the occurrence of chronic diseases by reducing the oxidative stress and altering the long chain polyunsaturated fatty acids (LCPUFA). The present study examined whether caloric restriction during pregnancy alters oxidative stress and essential fatty acid metabolism in mother and offspring at birth. Pregnant female rats were fed either a standard chow (C, n = 7) or were calorie restricted (CR, n = 7) by feeding 60% of the intake of the control. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in brain and liver were analyzed in both dams and offspring. Total weight gain during pregnancy was lower (p < 0.01) in the CR group as compared to the control group but did not affect the litter size and weight. Brain malondialdehyde levels were lower (p < 0.05) in dams from the CR group. There was no change in brain and liver LCPUFA levels in both male and female offspring in the CR group. Most of the polyunsaturated fatty acids were reduced (p < 0.05) in plasma and brain in the CR dams. Caloric restriction during pregnancy did not alter LCPUFA metabolism in the offspring suggesting that during maternal caloric restriction mothers own stores are mobilized to provide docosahexaenoic acid and arachidonic acid for fetal brain development.     

Maternal hypothalamic-pituitary-adrenal disregulation during the third trimester influences human fetal responses

Maternal peptides from the hypothalamic-pituitary-adrenal (HPA) axis rise during human pregnancy. The effects of circulating maternal adrenocorticotropin (ACTH) and beta-endorphin (BE) on human fetal behavior was determined in 135 women during their 32nd week of gestation. Fetal behavior was measured by assessing heart rate habituation to a series of repeated vibroacoustic stimuli. Individual differences in habituation were determined by computing the number of consecutive responses above the standard deviation during a control period. There was no significant relation between levels of ACTH, BE and the rate of fetal heart rate habituation. However, an index of HPA disregulation (uncoupling of ACTH and BE) was related significantly to fetal behavior. Fetal exposure to high levels of maternal BE relative to ACTH was associated with significantly lower rates of habituation. Results indicate that maternal stress and stress-related peptides influence fetal response patterns. It is possible that this influence persists over the life span.