Maternal Childhood Adversity Associated with Low Infant Birth Weight
In a study of the effect on infant health of a mother’s experience of adversity in childhood by researcher Deborah Kim and colleagues, both adversity in childhood (such as physical abuse or the loss of a parent) and stress during pregnancy were associated with low infant birth weight and lower gestational age at birth.
Among 146 women enrolled in the study, 58.2% percent scored a 0 on the Adverse Childhood Experience Questionnaire (ACE), 24% scored a 1, and 17.8% scored a 2. Those who scored higher on the ACE also scored higher on a scale measuring perceived stress. A score of 2 or higher on the ACE was associated with lower gestational age at birth, indicating infants born prematurely. Greater stress during pregnancy was associated with lower gestational age at birth and lower infant birth weight. When potential confounding demographic factors were removed from the analyses, ACE scores of 2 or higher were still associated with lower infant birth weight, while perceived stress was no longer associated with either low birth weight or gestational age.
Childhood adversity is associated with increases in inflammation and multiple adverse medical consequences in adults. The researchers called childhood adversity a “significant predictor of poor delivery outcomes” for women.
Editor’s Note: This research shows that a mother’s health and earlier life stressors could have an adverse effect on her child.
Childhood adversity leaves behind a residue of neuroendocrine and neuroclinical alterations that can persist into adulthood. Many are mediated by epigenetic changes, consisting of small chemical marks that attach to DNA and the histones around which it is wrapped.
In addition to these neurobiological alterations mediated by epigenetic effects, there is new evidence that some epigenetic marks can be passed on to the next generation via a mother’s egg or a father’s sperm. Thus, either directly or indirectly, parents’ adverse life experiences can influence the health of their offspring.
Maternal Anxiety Affects Information Filtering in the Infant Brain, Choline Could Help
Sensory gating is a process by which the brain filters out unimportant information, to avoid flooding higher cortical centers with irrelevant stimuli. New research from Randal Ross and colleagues shows that infants of mothers with anxiety have deficits in the way their brains inhibit response to this type of irrelevant information.
Mothers who were rated higher on the trait of anxiety had paradoxically lower levels of the inflammatory cytokine interleukin 6 at week 16 of their pregnancy, and their one-month-old infants showed more deficits in sensory gating. The reasons for these relationships requires further investigation.
Choline is a nutrient found in liver, muscle meats, fish, nuts, and eggs, and it may help. In a 2013 article in the American Journal of Psychiatry, Ross and colleagues showed that the supplement phosphatidylcholine (which converts to choline), taken during the second and third trimesters of pregnancy (at doses of 6300 mg/day, the equivalent of about three eggs) and followed up with 700 mg/day in the infant, led to improvements in sensory gating in the infants. These infants went on to have fewer behavioral problems as toddlers.
Ross and colleagues suggest that pre- and post-natal choline supplementation may be able to reverse the effects of maternal anxiety on infants. The researchers believe it could be helpful in the prevention of schizophrenia, as insufficient cerebral inhibition (decreased sensory gating) is a characteristic of that illness as well.
Reminder: Multiple Risks for Fetus in Mothers Treated with Valproate
In pregnant women, exposure of the fetus to the anticonvulsant valproate (VPA or Depakote) is associated with a variety of serious problems that include congenital malformations, developmental delay, and autism.
The major congenital malformations that can result from valproate exposure include spina bifida, which results in lifelong paralysis of the child’s lower limbs.
Developmental delay resulting from valproate exposure can cause an average loss of 9 IQ points compared to children exposed to other anticonvulsant drugs in utero. The effects appear to be in part dose-related and dependent on the intensity of combination treatment with other agents. These deficits were originally seen in children at 3 years of age and were shown to persist in six-year-olds according to an article by Meador et al. this year in Lancet Neurology.
Now in addition, fetal exposure to valproate has been liked to autism and related disorders in an 11-year longitudinal study published this year in the Journal of Neurology, Neurosurgery and Psychiatry. A diagnosis of a developmental disorder occurred in 17% of children whose mothers were on valproate as opposed to 2% whose mothers were on carbamazepine and 7% whose mothers were on lamotrigine.
Neurologists are increasingly recommending that all women of childbearing age who are on a treatment regimen including valproate be treated with folic acid and vitamins B6 and B12, in the hopes that these might mitigate valproate’s effects on the fetus in the case of an unplanned pregnancy. The effectiveness of these vitamins has not been directly demonstrated. However, the study by Meador et al. did show that children of mothers who took prenatal folic acid supplements had IQs on average 7 point higher than children whose mothers did not. The benefit was seen only when mothers were already taking folic acid when they became pregnant and was not observed in children of mothers who began taking it after the first trimester.
Women of childbearing age should avoid valproate and if this is not possible, they should carefully protect themselves against an unwanted pregnancy. Women with bipolar disorder are 3.9 times more likely to have unplanned pregnancies than women of similar age in the general population. These data suggest the importance of careful education about birth control in patients with bipolar illness so that pregnancies can be planned for periods of good health and so that appropriate pharmacological measures can be taken.
Preterm Birth Is a Risk Factor for Bipolar Disorder
A study published in the Archives of General Psychiatry in 2012 sampled over one million births in Sweden and suggested that preterm birth (from 32 to 36 weeks) doubled the risk that a child would develop bipolar disorder later in life. Those born even earlier had a sevenfold increased risk for bipolar disorder.
Editor’s Note: A robust research literature indicates that schizophrenia is related to obstetrical and other pre- and perinatal medical problems. Now it seems bipolar disorder may be as well, with some caveats. Low Apgar score (which indicates difficulties at birth) and delayed growth were not found to relate to bipolar risk. Thus something about the shortened preterm development seems to convey the risk. The authors suggest that there may be different types of factors that predispose a person to develop bipolar disorder, and that in some people the illness may have development origins.
These data also fit with observations that only about 50% of patients with bipolar disorder have a positive family history of the illness. Thus, while bipolar disorder does run in families and has a strong genetic basis in many instances, there are many people who develop the illness without having this genetic/familial risk. Very preterm birth appears to be one other contributing risk factor, presumably among many others. Understanding the neurobiological mechanisms occurring before birth that mediate this risk may lead to direct preventive measures to lessen the risk. In the meantime, traditional measures supporting good maternal and fetal health are a good place to start. These include regular prenatal checkups, good nutrition, and prenatal vitamins that include high doses of folic acid.
