A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

It is known that progesterone is an essential hormone for maintaining a pregnancy. Naturally, progesterone is secreted by the corpus luteum in the second half of the menstrual cycle. It is also secreted from the corpus luteum during early pregnancy. It prepares the endometrium for implantation. This study evaluated the effect of progesterone supplementation during the first trimester in women with a history of recurrent miscarriages.

Participants in the trial were recruited at 36 different hospitals across the U.K and the Netherlands. Eligible women were ages 18-39 years of age actively trying to conceive after receiving a diagnosis of unexplained recurrent miscarriage. This is defined as three or more pregnancy losses during the first trimester. A total of 1568 participants received 400 mg of progesterone twice daily or a matching placebo after testing positive for pregnancy. The primary outcome measure was birth. Overall, the trial demonstrated that vaginal progesterone supplementation did not significantly increase the rate of live births for women with a history of recurrent miscarriages. I am curious whether the outcomes would have changed if the progesterone was administered orally. Further studies should be conducted to evaluate various routes of administration.

Coomarasamy A, Williams H, Truchanowicz E, et al. A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med. 2015;373:2141-8.

Uncomplicated Pregnancies and Ultrasounds for Fetal Growth Restriction: A Pilot Randomized Clinical Trial

This study was a randomized control trial to see if we should continue to give women ultrasonographic exams in their third trimester if their pregnancies are deemed uncomplicated.  These ultrasounds can be expensive, and this study was designed to see if they are beneficial at that point in the pregnancy.  Specifically, they wanted to see if having a third trimester ultrasound in an uncomplicated pregnancy would have any effect on detection of “small for gestational age” (SGA) when the birth weight of the baby less than 10% for the baby’s gestational age.

From a study done in 2012, approximately 10% of babies were born with SGA, and these pregnancies did not improve with the routine prenatal care  (bed rest, nutritional care, supplements).  These pregnancies did improve when abnormal growth is discovered before birth so that it may be evaluated and techniques to improve growth could be implemented.  The thinking is that these ultrasonographic exams can provide this information as to prevent the prevalence of SGA.

Of the women who were approached and gave consent, the detection of SGA was much higher (67%) when women had an ultrasonographic exam than the control (9%).  The evidence is overwhelming that receiving an ultrasound–even in the third trimester of an uncomplicated pregnancy–can still be beneficial and worth the time and money.  It was noted in the study that this may not be reflective of the entire population, as it had a small sample size.  The women they studied were very easy to find and only came from three sites.


Hammad IA, Chauhan SP, Mlynarczyk M, et al. Uncomplicated pregnancies and ultrasounds for fetal growth restriction: a pilot randomized clinical trial. AJP Rep. 2016; 6(1):83-90.

Quality care in epilepsy: Women’s counseling and its association with folic acid prescription or recommendation

       This study focused on women of child-bearing age who are being treated for epilepsy with antiepileptic drugs (AEDs). Taking folic acid during the pre-conceptual period has been found to decrease the risk for congenital malformations in babies born to women with epilepsy who take AEDs. The purpose of this study was to determine if annual counseling about contraception and pregnancy in a treatment setting for women with epilepsy is associated with increased recommendations or prescriptions for folic acid.

        This was a retrospective cohort study that collected the data by abstracting medical records from the subjects. 77 women of childbearing age were included in this study who had two or more visits for epilepsy at a neurology clinic. The assessment included a review of documentation from the first three visits for epilepsy within a 24-month follow-up window. The women in this study were placed into 2 groups based on the type of counseling they received about pregnancy and contraception in relation to their epilepsy treatment: one group received something called DFCW (N=28) while the other group did not receive DFCW (N=49). DFCW was defined as the health care provider perfectly adhering to annual counseling about the impact of epilepsy treatment on contraception or pregnancy during their sessions with the patients. A recommendation from the provider that the patient take over-the-counter (OTC) folic acid or a prescription for folic acid was independently abstracted from the chart at each visit.

       The group of subjects who received DFCW and the group who did not receive DFCW had no significant differences in respect to age, disease duration, baseline history of drug-resistant epilepsy (DRE), presence of concurrent psychiatric disease, epileptologist involvement, number of AEDs prescribed, types of seizures experienced, and etiology. The results were that 71.4% of subjects (20 women) in the DFCW group and 85.7% of subjects (42 women) in the non-DFCW group were NOT recommended or prescribed folic acid by their health care provider. These results show that providers are missing a big area of counseling for their female patients with epilepsy who are of child-bearing age. Even though many of the providers counsel their female epilepsy patients about how epilepsy treatment may affect contraception and pregnancy, they often times do not mention or actively recommend their patients to take folic acid if they are thinking about trying to conceive.

     I think the results of this study are interesting and very eye-opening. It is concerning to me that many health care providers are not mentioning the benefits of taking folic acid to their female epilepsy patients of child-bearing age because previous studies have proved that folic acid can prevent congenital malformations in babies born to women with epilepsy who took AEDs during their pregnancies. I am wondering if this finding about folic acid is relatively new in the treatment of women with epilepsy and that many providers, especially those who have been practicing for many years, are simply not aware of this finding. Whatever the reason is, I hope this study has been reviewed in the world of epilepsy treatment and that more providers start recommending the use of folic acid in their female epilepsy patients of child-bearing age in order to prevent more congenital malfunctions from the use of AEDs during pregnancy from occurring.

My question posed to colleagues: How can pharmacists play a role in making female epilepsy patients of child-bearing age taking antiepileptic drugs aware of the fact that taking folic acid could decrease the risk for their children having congenital malfunctions?

Moura, LMVR, Mendez, DY, De Jesus, J, et al. Quality care in epilepsy: Women’s counseling and its association with folic acid prescription or recommendation. Epilepsy Behav. 2015;44:151-154.  

Use of Antidepressants During Pregnancy and Risk of Autism Spectrum Disorder

To determine the correlation between the use of antidepressants during pregnancy and the child being born with autism spectrum disorder, a group of researchers looked at infant and mother data in Quebec from 1998 to 2009. From looking at his data, they collected 145,546 infants born to mothers who were covered by Regie de l’assurance maladie du Quebec for at least a year prior to and throughout their entire pregnancy. They determined that use of an antidepressant was established by the filling of at least one prescription throughout their pregnancy. By the end of their study, with the children having a mean age of six, 1,054 children had been diagnosed with autism spectrum disorder. The women who had used antidepressants, specifically those using selective serotonin reuptake inhibitors in the second or third trimester, had a much higher frequency of giving birth to a child whom would be diagnosed with at least one diagnosis of autism spectrum disorder.

Identifying a potential cause or contributor to the autism spectrum disorder can create a great sense of caution among future mothers. When making people aware of the concern and issue of using antidepressants, it becomes a much stronger argument when you have data and research to back up the claim. Hopefully in the future, mothers will become more aware of their impact on children with the prescription medications they take and will be able to plan accordingly.

As medical professionals should we be able to restrict the access that pregnant women have to antidepressants as it poses a risk to their unborn child?

JAMA Pediatr. 2016;170(2):117-124.

Is Routine Iron Supplementation Necessary in Pregnant Women With High Hemoglobin?

Iron supplementation during pregnancy is an important component in prenatal care to prevent anemia. During pregnancy increased plasma volume exceeded increase in red cell volume which causes dilution, and reduction in the concentration of hemoglobin. It has been found that hemoglobin levels can fall from the average of 12.5-13.0 g/dL to about 11.0-11.5 g/dL. According to the WHO, more than 40% of pregnant women suffer from anemia that is caused by iron deficiency about half the time, thus 30-60 mg of elemental iron supplementation is recommended for pregnant women. However, extremely high iron levels in pregnant women can adversely affect the birth outcome. Because of this it seems logical to say that iron supplementation is unnecessary in women who have high hemoglobin levels. This study examined the effects of iron supplementation on iron status markers in pregnant women with high hemoglobin.

The trial was randomized, double-blind, and placebo controlled. The population contained 86 pregnant women with Hemoglobin > 13.2 g/dL and ferritin > 15 μg/l in the 16th – 20th week of pregnancy. From their 20th week of pregnancy to the end, the experimental group were given 1 ferrous sulfate tablet with 50 mg of elemental iron daily, and the control group received a placebo. Hemoglobin and ferritin levels were evaluated at 37 to 39 weeks of pregnancy and after delivery the baby’s birth weight was measured. However 22 women ended up dropping out of the trial due to various reasons, so the date for 64 women were used in conclusions.

The mean hemoglobin concentration was 12.05 g/dL in the experimental group, and 11.94 g/dL in the placebo group which meant a significant difference in hemoglobin levels between the two groups. Though in comparing the birth weight of the babies, there was no significant difference between the two groups. By the end of pregnancy four women in both groups were anemic, however none had a hemoglobin level of less than 10 g/dL and the difference wasn’t significant between the supplement and placebo group. The researchers concluded that since not using iron supplementation didnt cause of anemia in women with hemoglobin concentrations greater than 13.2 g/dL during pregnancy the current recommendations made by WHO for women regarding iron supplementation during pregnancy should be followed. 

The researchers had the right idea in approach this study since it was very logical to think that since high iron levels affect birth outcomes negatively it made sense not to supply those women in their third trimester of pregnancy with high hemoglobin levels with additional iron supplements. There might be more evidence had the population of the overall study been larger, but given what it was those women who were given a placebo did end up having their hemoglobin levels drop to an average of 11.94 g/dL so maybe for those women who have high hemoglobin levels during pregnancy they should take iron supplements, but either towards the lower dosage end or just not take the supplements daily

Alizadeh L, Salehi L. Is Routine Iron Supplementation Necessary in Pregnant Women with High Hemoglobin? Iran Red Crescent Med J.  doi: 10.5812/ircmj.22761 (published 27 January 2016)


Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports

The focus of this study was to reanalyze previous studies using Bayesian analysis to determine which SSRIs, if any, were associated with different types of birth defects.

The study took place across 10 centers in the U.S., with almost 18,000 mothers of infants who did not experience birth defects and almost 10,000 mothers of infants who did experience birth defects. The study then looked to see if these mothers had used citalopram, escitalopram, fluoxetine, paroxetine, or sertraline in the month before pregnancy through the third month of pregnancy. The study was adjusted to take into accound race/ethnicity, education level, smoking, and obesity of the mother.

The study concluded that the most commonly used SSRI was sertraline, but no birth defects could be correlated to the use of this drug. There were also no defects strongly correlated with citalopram or escitalopram. The researchers concluded that some birth defects did occur 2-3.5 times more frequently in the infants of women using paroxetine or fluoxetine early in pregnancy.

This study is interesting to me, as it gives us a better guideline of which SSRIs are safer to use in pregnant women. If the switch from one type of SSRI can dramatically reduce the risk of birth defect, I think most mothers would be happy to know this and would be very likely to switch medications.

Link to Article

Does thyroxine treatment improve emotional well being among women with subclinical hypothyroidism?

The main goal of this study was to determine if treatment of subclinical hypothyroidism during pregnancy improves the maternal emotional well being of the patient. Subclinical hypothyroidism is usually referred to as milk thyroid failure. It is diagnosed when the patient’s peripheral thyroid hormones are normal but their serum thyroid-stimulating hormones are mildly elevated. Only about 3-5% of the general population experiences this.

Women carrying health, normal, single pregnancies and that were diagnosed with SCH were randomized in the trial. The women could not have already been taking antidepressants or be diagnosed with depression. During the study, each patient was assessed for depressive symptoms using the CES-D scale for grading depression. The test was done prior to the third trimester of their pregnancy and then one year after giving birth.

Treatment with thyroxine or the placebo gave similar positive scores that were at baseline during the first testing. Treatment was not associated with improvements in median CES-D scores during the first testing before the third trimester. At one year postpartum, the frequency of positive screenings was higher for the placebo group but the difference was not significant. Treatment was overall not associated with improved emotional states in pregnant women. This treatment study is interesting because of the amount of women that experience post-partum depression. I have read about different homeopathic preventative measures that some women have tried but never knew if drugs were studied. I think it’s important to continue studying this disease state in pregnant women post birth because it has a big impact on the infants health and care. Should more money in the antidepressant field be going to preventative measures of post-birth depression in women?

Am J Obstet Gynecol. 2016;214(1):201-202.



Fish Intake in Pregnancy and Child Growth

Fish are commonly exposed to persistent organic pollutants, which may have endocrine-disrupting properties that contribute to obesity development. Fish intake of pregnant mothers has been shown to increase fetal growth, but this study set out to see if increased fish consumption affects child obesity as well.

Over 26,000 woman through the span on 15 years were studied through childbirth and followed up with every two years until the child was 6 years old. The results were that woman who consumed fish more than 3 times/ week gave birth to children with higher BMIs compared to those children whose mothers consumed fish less than 3 times/ week. The high fish intake mothers had children who had increased risk of rapid infant growth as well as increased risk for obesity at 4 years and 6 years old.

FDA advice on fish consumption in woman who are pregnant, breast feeding, or thinking about becoming pregnant changed in June of 2104 to match the data found in this trial. FDA now recommends for pregnant woman to consume more fish due to its cognitive benefits for their offspring, but to consume no more than 3 meals of fish/ week.

As pharmacists, we deal with a variety of factors that impact our patients health. Fish oil supplements as well as diet is something that we need to consider when counseling maternal populations.

Link to Article

Stratakis N, Roumeliotaki T, Oken E, Barros H, et al. Fish intake in pregnancy and child growth. JAMA Pediatr. 2015. doi:10.1001

In utero Exposure to β-2-Adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) have received much media attention regarding supposed links between them and childhood vaccines. While this association is false, there may be evidence to support an association between maternal use of B-2-adrenergic receptor (B2AR) agonists and child development of ASD. Previous studies support a correlation between the two, but they do not show whether the drug or the mother’s condition is causal. Evidence on the mechanism of B2AR agonists also supports the association between their use and ASD.

Researchers from Drexel University sought to further research a possible link between B2AR agonist drugs and ASD by performing a case-control study on children born in Denmark between 1997 and 2006. Cases were considered to be any children diagnosed with childhood autism, atypical autism, Asperger syndrome, and pervasive developmental disorder- unspecified, while controls were considered anyone without these diagnoses. Ten controls were matched with each case based on birth month and year, so in total there were 5,200 cases and 52,000 controls. Children were considered exposed to B2AR agonists if there was maternal use any time between 90 days before the estimated conception date and the delivery date.

The study found that 3.7% of cases were exposed to B2AR agonists and 2.9% of controls were exposed to B2AR agonists during pregnancy. Thus, the researchers concluded that exposure to B2AR agonists during pregnancy was associated with an increased risk for ASD and that the risk was similar for exposure in the first, second, and third trimesters. However, less than 1% of cases of ASD could be attributed to the exposure to B2AR agonists, if their use is in fact a cause of ASD.

This study interested me because it looked into a potential correlation between autism and medications that I have not heard of previously. I am curious to see whether articles like this one will have as large of an impact on media portrayals of autism and its causes as the false article on the causal relationship between autism and vaccines has had. I am also interested in seeing if this research has any effect on the use of B2AR agonists in pregnant women or if the benefits of the medication always outweigh the risks to the child.

 Pediatrics. 2016; 137 (2): 1-8.

Safety of artemisinins in first trimester of prospectively followed pregnancies: an observational study

This study was designed to yield the safety and efficacy of the most rapid-acting antiparasitic drug class, artemisinin derivatives, during the first trimester of human pregnancies.  Previously, it administered as a preventative intervention only during the second and third trimesters successfully. However, when these same drugs were tested on animals during their first trimester, their pregnancies either ended in a miscarriage or serious congenital malformations.   It is to be noted that the drug quinine, an antiparasitic, had been given to women in their first three months of pregnancy up to this point. This research would hopefully find out if artemisinins can safely and effectively be given to mother in the first trimester.  It is also of interest to see if it is more successful in preventing the spread of Malaria from mother to child–and ultimately miscarriages–than quinine.

This study was conducted near the border of Thailand and Myanmar between January 1994 and December 2013. They documented 55,636 pregnancies, but only 25,485 were further analyzed for Malaria and miscarriages. After ruling out many of the pregnancy cases, 183 were given the artemisinin treatment. They noticed no significant decrease or increase in the miscarriage rate as compared to treatment with quinine. They also could not draw firm conclusions on artemisinin’s effect on malformations, as the number of actual participants in the treatment ended up being too small.

Overall, they were able to determine that artemisinin derivatives are not as harmful to humans as they were in the animal trials. First-line artemisinin treatment is not deemed more effective after this research, but the miscarriage rate when receiving first-line artemisinin is lower than receiving quinine first and artemisinins secondarily. Artemisinin safety in the first trimester is still to be determined, but this sheds light to the severity of Malaria during pregnancies and how hard it can be to treat it successfully.


Moore KA, Simpson JA, Paw MK, et al. Safety of artemisinins in first trimester of prospectively followed pregnancies: an observational study. Lancet Infect Dis. 2016.