SSRI antidepressant use during pregnancy may increase the risk of autism

Posted on December 17, 2011 by Dr. Jonathan

Summary: The use of selective serotonin reuptake inhibitors (SSRIs, such as Prozac®, Celexa®, Lexapro®, Luvox® and Paxil®) taken during pregnancy—especially the first trimester—appears to increase the risk of autism spectrum disorders. There are evidence-based alternatives to SSRIs that support brain health without putting the fetus at risk.

A study recently published in the journal Archives of General Psychiatry draws attention to a risk of autism spectrum disorders (ASDs) born to mothers who took SSRI antidepressants during their pregnancy. The authors observe:

“The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.”

Therefore they set out to…

“…systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.”

In order to do so they compared the data for 298 children with ASD to 1507 randomly selected control children, along with the data for both their mothers. Their findings support a cautionary approach to the prenatal use of SSRIs:

“Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8).”

In other words, the increase in risk for the whole year before delivery was 220%, but limiting the investigation to the first trimester it was 380%. Interestingly…

“No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.”

Meaning that it wasn’t a history of mental health treatment the year before delivery but specifically the use of SSRIs that accounted for the increased risk of ASDs. The authors conclude:

“Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders.”

This would be a troubling dilemma were it not for the fact that therapies supporting brain health are available to treat depression. Serotonin production and signaling, when indicated, can be supported in a physiological and sustainable manner that promotes the brain health of mother and fetus. A categorization and description of key resources that applies to adults as well as children is available in the Parents’ Guide To Brain Health.

The use of any non-aspirin NSAIDs during pregnancy increases the risk of spontaneous abortion

Posted on November 30, 2011 by Dr. Jonathan

Summary: any type of non-aspirin NSAID must be used only with great caution during pregnancy because they may significantly increase the risk of spontaneous abortion.

Research recently published in the Canadian Medical Association Journal alerts practitioners and pregnant women to the risk for spontaneous abortions caused by the gestational use of any non-aspirin non-steroidal anti-inflammatory drug (NSAID). The authors state:

“We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women.”

They examined data for 4705 women who had a spontaneous abortion compared to ten times as many matched controls, and correlated associations between different types and dosages of non-aspirin NSAIDs with having the spontaneous abortion. Their data raises some serious alarm:

“Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43). Specifically, use of diclofenac (OR 3.09), naproxen (OR 2.64), celecoxib (OR 2.21), ibuprofen (OR 2.19) and rofecoxib (OR 1.83) alone, and combinations thereof (OR 2.64), were all associated with increased risk of spontaneous abortion. No dose–response effect was seen.”

In other words, there as an overall 243% increase in the risk for spontaneous abortion. The increase was over 300% for diclofenac (Voltaren®) and more than 200% for ibuprofen. The authors express the gravity of their concern supported by the data in their conclusion:

“Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy.”

Sleeping position associated with late pregnancy stillbirth

Posted on July 10, 2011 by Dr. Jonathan

A research paper recently published in the British Medical Journal reports a strong association between sleep practices and stillbirth late in pregnancy. The authors set out to…

“…determine whether snoring, sleep position, and other sleep practices in pregnant women are associated with risk of late stillbirth.”

The compared date for 155 women with a singleton stillbirth after 28 weeks of pregnancy (and without congenital abnormality) with 310 women with pregnancies and gestation matched to those in which stillbirth occurred as controls. They examined maternal snoring, daytime sleepiness, and sleep position at the time of going to sleep and on waking. Their data were striking for the association with sleep position in particular:

“No relation was found between snoring or daytime sleepiness and risk of late stillbirth. However, women who slept on their back or on their right side on the previous night…were more likely to experience a late stillbirth compared with women who slept on their left side… Women who got up to go to the toilet once or less on the last night were more likely to experience a late stillbirth compared with women who got up more frequently. Women who regularly slept during the day in the previous month were also more likely to experience a late stillbirth than those who did not.”

Sleeping on the back or right side conferred a 250% increase of stillbirth late in pregnancy than sleeping on the right side. The results for sleep position and frequency of rising for the toilet during the night make sense considering the vascular dynamics. Daytime sleepiness is frequently associated with decreased oxygenation due to apneas or hypopneas during the night. The authors’ conclusion is a call to action to prevent the devastating heartbreak of late pregnancy stillbirth by better advice based on more science:

“This is the first study to report maternal sleep related practices as risk factors for stillbirth, and these findings require urgent confirmation in further studies.”

Meanwhile, it seems prudent to prefer a right side sleeping position while awaiting further confirmation. Also, clinicians, pregnant patients and their partners should be alert to signs of sleep disordered breathing.

The autoimmune aspect of preterm labor

Posted on February 11, 2011 by Dr. Jonathan

A paper just published in PLoS ONE (Public Library of Science) presents findings that expand our understanding of the inflammatory aspect of preterm labor. The authors state:

“Preterm parturition is characterized by innate immune activation and increased proinflammatory cytokine levels. This well established association leads us to hypothesize that preterm delivery is also associated with neonatal T lymphocyte activation and maturation.”

For our lay readership, innate immune activation refers to the cell-mediated ‘first phase’ Th1 immune response versus the ‘second phase’ Th2 antibody aspect mediated by T lymphocyte activation. The authors obtained cord blood samples following normal and preterm deliveries, and deliveries complicated by clinical chorioamnionitis (inflammation of the fetal membranes). What did they find?

“Infants born following preterm delivery demonstrated enhanced CD4+ T lymphocyte activation… Neonates delivered following clinical chorioamnionitis also demonstrated increased T cell activation. Preterm neonates had an increased frequency of CD45RO+ T cells.”

Autoimmune cross-reactions to environmental stimuli fuels a wide range of disorders. Consider the role of gluten sensitivity in a variety of female reproductive disorders. The authors conclude:

“Preterm parturition is associated with neonatal CD4+ T cell activation, and an increased frequency of CD45RO+ T cells. These findings support the concept that activation of the fetal adaptive immune system in utero is closely associated with preterm labor.“

The obvious practical implication is that screening for preterm labor can be accomplished by testing for antibodies to the fetal membranes. In positive cases rational therapy can be applied on a functional basis to address the underlying causes of immune overactivation.

Caffeine consumption during pregnancy is not associated with pre-term birth

Posted on November 4, 2010 by Dr. Jonathan

The notion that caffeine consumption during pregnancy is a risk factor for pre-term birth does not hold up in an extensive meta-analysis published in the American Journal of Clinical Nutrition. The authors state:

“The effect of caffeine intake during pregnancy on the risk of preterm delivery has been studied for the past 3 decades with inconsistent results…We performed a meta-analysis examining the association between caffeine consumption during pregnancy and risk of preterm birth.”

They identified 15 cohort and 7 case-control studies that met inclusion criteria among MEDLINE and EMBASE articles published between 1966 and July 2010. What did the data show?

“The combined odds ratios (ORs) obtained by using fixed-effects models for cohort studies were 1.11, 1.10, and 1.08 for risk of preterm birth comparing the highest with the lowest level of caffeine intake (or no intake)during the first, second, and third trimesters, respectively. Results for the case-control studies yielded no associations for the first, second, or third trimesters.”

In other words, as they state in their conclusion, no statistically significant risk from caffeine consumption emerged from the data:

“In this meta-analysis, we observed no important association between caffeine intake during pregnancy and the risk of preterm birth for cohort and case-control studies.”

Early pregnancy folate associated with child hyperactivity

Posted on May 17, 2010 by Dr. Jonathan

The authors of this paper recently published in the Journal of Child Psychology and Psychiatry being by noting:

“Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring.”

They correlated maternal red blood cell folate (RCF) at 14 weeks of pregnancy and total folate intake (TFI) from food and supplements with their childrens’ behavioral difficulties. What did the data show?

“Lower maternal RCF and TFI in early pregnancy were associated with higher childhood hyperactivity and peer problems scores in the offspring….analyses showed significant inverse indirect associations of RCF with hyperactivity/inattention and peer problems via fetal brain growth.”

Their conclusion:

“…our data provide preliminary support for the hypothesis that lower folate status in early pregnancy might impair fetal brain development and affect hyperactivity/inattention and peer problems in childhood.”

Here we have another compelling reason to ascertain good folate status in early pregnancy, or (even better) before becoming pregnant. Although conventional blood tests for serum folate are not dependable, a convenient and reliable way to do determine folate adequacy is by measuring the organic acid formiminoglutamate in the urine.

Female reproductive disorders and gluten sensitivity

Posted on April 30, 2010 by Dr. Jonathan

Minverva Ginecologica As the authors of this paper published in the journal Minerva Ginecologica state:

“In the past coeliac disease, or intolerance to gluten, has been considered a rare disease in infancy, whose most important signs were chronic diarrhea with malabsorption and reduced growth. However, besides this classical form, there are a number of other clinical and subclinical forms which may appear even in the adult life and without any overt intestinal sign.”

The authors defined their objective:

“The aim of the present paper is to describe and evaluate the effects of coeliac disease on female reproduction. Such effects include delayed menarche, amenorrhea, infertility and early menopause.”

In addition, they noted that…

“Epidemiological studies show that besides reduced fertility, affected women are at higher risk of reproductive problems such as pregnancy loss, low birthweight of offspring and reduced duration of breastfeeding…the possible prevention or treatment of the reproductive effects is only the lifelong maintenance of a gluten-free diet.”

Another paper published in the Journal of Reproductive Medicine reports on a case that highlights the link between gluten sensitivity and amenorrhea. The authors’ conclusion:

“Celiac disease should be considered in patients presenting with malnutrition and primary amenorrhea.”

This was followed by a much more extensive study published recently in the same journal. The authors summarize an extensive body of literature on the subject:

“In women, this disease (celiac, gluten sensitivity) may have implications on menstrual and reproductive health. The symptom complex includes delayed menarche, early menopause, secondary amenorrhea, infertility, recurrent miscarriages and intrauterine growth restriction. These women benefit from early diagnosis and treatment. Therefore, celiac disease should be considered and screening tests performed on women presenting with menstrual and reproductive problems and treated accordingly.”

They offer an exhortation to doctors in their conclusion:

“Evidence in the literature suggests that celiac disease should be suspected in females with menstrual abnormalities, infertility and adverse pregnancy outcome. All health care providers should be aware of these diverse manifestations of the disease. Treating the disease has a benefit and may lead to prevention of symptoms and improvement in the quality of life…It is challenging to identify women with silent celiac disease and treat them with a gluten-free diet and nutrient supplements, which may lead to prevention of menstrual and other reproductive dysfunction.”

Another paper published in the journal Gynecologic and Obstetric Investigation focuses on the impact of gluten sensitivity on the reproductive cycle, fertility, pregnancy, and menopause. The authors explain that…

“Celiac disease (gluten-sensitive enteropathy) may manifest clinically with an array of nongastrointestinal symptoms among which are: dermatitis herpetiformis; dementia; depression; various neurological symptoms; osteoporosis; osteomalacia; dental enamel defects, and anemia of various types. Important data have accumulated in recent years regarding the association between celiac disease, fertility and pregnancy. Many primary care obstetricians and gynecologists and perinatologists are not aware of these important relationships.”

What does the scientific evidence establish?

“Review of the literature reveals that patients with untreated celiac disease sustain a significantly delayed menarche, earlier menopause, and an increased prevalence of secondary amenorrhea. Patients with untreated celiac disease incur higher miscarriage rates, increased fetal growth restriction, and lower birth weights.”

An interesting paper that dramatically shows the difference between adhering and not adhering to a gluten free diet for female reproductive health was published in the Journal of Clinical Gastroenterology:

“This study shows a broad analysis of gynaecological and obstetrical disturbances in patients with celiac disease in relation to their nutritional status and adherence to a gluten-free diet.”

In their investigation the authors analyzed data on adults and children/adolescents with gluten sensitivity, taking into consideration nutritional status and gluten-free diet adherence, and compared them to adults and adolescents with irritable bowel syndrome (not due to gluten) as a control group. What did the data show?

“…adult celiac patients, irrespective of the nutritional status…presented delayed menarche, secondary amenorrhea, a higher percentage of spontaneous abortions, anemia and hypoalbuminemia…After treatment, patients presented with normal pregnancies and one patient presented spontaneous abortion. The adolescents who were not adherent to gluten-free diet presented delayed menarche and secondary amenorrhea.”

They state what should by now be obvious in their conclusion:

“Therefore, celiac disease should be included in the screening of reproductive disorders.”

Important: gluten sensitivity without celiac manifestations (1) must be treated the same way as celiac disease and (2) cannot be diagnosed by the usual celiac tests for tissue transglutaminase antibodies, etc. Antibody levels, including anti-gliadin (gluten) antibodies, can fluctuate for a number of reasons resulting in false negatives. The gluten gene sensitivity test can be relied on for a dependable result. This post could go on at great length but the message is clear: for female reproductive disorders gluten sensitivity must be considered as a possible contributing cause.

Men: you are not immune. I am finding gluten sensitivity to be a common cause of low testosterone levels (hypogonadia).

Chronic infections like periodontitis promote global inflammation

Posted on April 21, 2010 by Dr. Jonathan

Annals of the New York Academy of Sciences In our practice we pay a lot of attention to chronic low grade infections because the inflammation associated with them contributes to a broad range of diseases including autoimmune disorders, diabetes, cardiovascular disease, etc. The gastrointestinal tract is a frequent site of chronic infection, and this paper published in the Annals of the New York Academy of Sciences investigates the link between infection in the upper end of the GI tract—periodontitis—and inflammation:

“Increasing evidence implicates periodontitis, a chronic inflammatory disease of the tooth-supporting structures, as a potential risk factor for increased morbidity or mortality for several systemic conditions including cardiovascular disease (atherosclerosis, heart attack, and stroke), pregnancy complications (spontaneous preterm birth [SPB]), and diabetes mellitus.”

Their survey identifies a ‘smoking gun’ of inflammation:

“Consistent with this hypothesis clinical studies demonstrate that periodontitis patients have elevated markers of systemic inflammation, such as C-reactive protein (CRP), interleukin 6 (IL-6), haptoglobin, and fibrinogen. These are higher in periodontal patients with acute myocardial infarction (AMI) than in patients with AMI alone, supporting the notion that periodontal disease is an independent contributor to systemic inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord blood from SBP babies indicate a strong in utero IgM antibody response specific to several oral periodontal pathogens, which induces an inflammatory response at the fetal–placental unit, leading to prematurity.”

A very good reason to take care of your teeth and gums:

“The importance of periodontal infections to systemic health is further strengthened by pilot intervention trials indicating that periodontal therapy may improve surrogate cardiovascular outcomes…and may reduce four- to fivefold the incidence of premature birth.”

Undernutrition during pregnancy and obesity, type 2 diabetes in your child

Posted on December 1, 2009 by Dr. Jonathan

This paper in Current Diabetes Reports discusses how the so-called ‘thrifty gene’ effect (the tendency to conserve calories in the form of fat during times of famine, established through gene selection over thousands of years) occurs not only through this selection process, but can also manifest as a ‘thrifty phenotype’ when eating too little during gestation is followed later by overnutrition. This means that eating too little during your pregnancy can promote obesity and type 2 diabetes in your child if they consume excess calories later. Like with most everything else, moderation is key.

Antibiotics during pregnancy and risk of birth defects

Posted on November 21, 2009 by Dr. Jonathan

Ladies, if you absolutely have to take an antibiotic during pregnancy note the results of this study just published in the Archives of Pediatrics & Adolescent Medicine. Avoid sulfonamides and nitrofurantoins (quinolones are generally not recommended while pregnant). Penicillins, erythromycins, and cephalosporins were associated with less birth defects.