Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes.

PURPOSE: Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3-8% of all pregnancies in the US are complicated by preeclampsia and another 5-7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring. METHOD: Pub Med and Web of Science databases were searched using the terms "preeclampsia," "gestational hypertension," "imprinting genes," "imprinting dysregulation," and "epigenetic modification," in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism. RESULTS: The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development. CONCLUSION: Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

Sites of Circadian Clock Neuron Plasticity Mediate Sensory Integration and Entrainment.

Networks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons. Rather, their loss reduces sites of glutamatergic sensory neurotransmission that normally encodes naturalistic time cues from the environment. These results support an alternative model: structural plasticity in critical clock neurons is the basis for proper integration of light and temperature and gates sensory inputs into circadian clock neuron networks.

The risk for impaired learning-related abilities in childhood and educational attainment among adults born near-term.

OBJECTIVE: To examine whether near-term births (NTB) and small-for-gestational-age (SGA) infants are at high risk for childhood learning-related problems and poor adult educational attainment, and whether poverty amplifies the adverse effects of NTB and SGA on those outcomes. METHODS: A randomly selected birth cohort (n = 1,619) was followed into adulthood. IQ and learning abilities were measured in childhood and educational attainment was measured in adulthood. RESULTS: NTB (n = 226) and SGA (n = 154) were associated with lower educational attainment mediated through learning-related abilities at age 7. Childhood poverty moderated the impact of NTB on educational attainment both directly and mediated through lower learning-related abilities. Poverty did not moderate the effect of SGA. CONCLUSIONS: Poorer learning-related outcomes and educational attainment were not limited to children born very (<32 weeks) or extremely (<28 weeks) preterm, especially among those living in poverty. Targeted interventions such as remedial learning during childhood among NTB in poor families may yield higher educational attainment.

The role of perinatal problems in risk of co-morbid psychiatric and medical disorders in adulthood.

BACKGROUND: Perinatal problems may be associated with an increased risk for psychological and physical health problems in adulthood, although it is unclear which perinatal problems (low birthweight, preterm birth, low Apgar scores, and small head circumference), or what clusters of problems, are more likely to be associated with later health problems. It is also not known whether perinatal problems (singly or together) are associated with co-morbidity between psychological and physical health problems. METHOD: A regional random sample (from Baltimore) of mothers and their children (n=1525) was followed from birth to adulthood (mean age 29 years). Perinatal conditions were measured at delivery. Psychological problems (depression and suicidal ideation) were measured with the General Health Questionnaire-28 (GHQ-28) and physical problems (asthma and hypertension) with the RAND-36 Health Status Inventory. RESULTS: Children with perinatal problems were generally at increased risk for depression, suicidal ideation and hypertension, and co-morbid depression and hypertension even after controlling for confounders. One possible underlying condition, preterm low birthweight (LBW), extracted by cluster analysis, considering all of the four perinatal problems, was associated with increased risk for psychological and physical health outcomes as well as co-morbidity of the two. CONCLUSIONS: LBW, preterm birth and small head circumference singly increased the risk for both psychological and physical health problems, as well as co-morbid depression and hypertension, while low Apgar scores were only associated with psychological problems. Delineating different etiological processes, such as preterm LBW, considering various perinatal problems simultaneously, might be of benefit to understanding the fetal origin of adult illness and co-morbidity.

Low birth weight and risk of affective disorders and selected medical illness in offspring at high and low risk for depression.

Numerous studies have demonstrated that low birth weight (LBW) is associated with the development of medical conditions, such as hypertension and diabetes, and psychiatric disorders, such as depression. One possible mechanism through which LBW might increase risk for both medical and psychiatric disorders is by altering the biologic systems (such as the hypothalamic-pituitary-adrenal [HPA] axis function) that govern emotion regulation and physical reactivity. In this study, we conducted secondary data analyses in a longitudinal study originally designed to understand the intergenerational transmission of major depressive disorder (MDD). We examined the risk for both medical and psychiatric illnesses known to be influenced by HPA axis dysregulation in the context of parental depression. The study had 2 primary objectives: (1) to examine whether LBW increases the risk of selected adult illness that may be influenced by the HPA axis and (2) to examine whether the increased risk of illness varies by parental depression status. We conducted longitudinal assessments of 244 offspring of depressed and nondepressed parents for more than 20 years. Psychopathology and medical illness were assessed by direct interview conducted by clinicians blind to risk status and previous diagnosis. We examined the effect of BW in 3 categories: less than 2.5 kg (LBW), 2.5-3.5 kg, and more than 3.5 kg (reference group). Offspring with LBW had a significantly increased risk of MDD, anxiety disorders, phobia, suicidal ideation, impaired functioning, allergies, and hypertension compared to those with BW exceeding 3.5 kg. The association between LBW and depression was stronger among children of depressed parents than among children of nondepressed parents, with an interaction term (BW and parental depression status) significant for MDD (P = .05), suggesting that parental depression may augment the impact of LBW on offspring depression: