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Research Articles and Papers on:

Pregnancy, Fertility & Children

 

Thyroid dysfunction and reproductive health

Jefferys A, Vanderpump M, Yasmin E. Thyroid dysfunction and reproductive health.
The Obstetrician & Gynaecologist 2015;17:39–45.

Abstract
Key content

  • Thyroid disease is a common condition in the reproductive medicine setting due to the complex interplay between the hypothalamo-pituitary axis and the thyoid gland.

  • Abnormalities in thyroid function, including hyperthyroidism and hypothyroidism, can have an adverse effect on reproductive health and result in reduced rates of conception, increased early pregnancy loss, and adverse pregnancy and neonatal outcomes.

  • There is increasing evidence for the role of autoantibodies in subfertility and early pregnancy loss, even in euthyroid women.

  • Evidence suggests that treating thyroid disorders and keeping thyroid-stimulating hormone levels at the lower end of normal in euthyroid women may improve conception rates in subfertile women and reduce early pregnancy loss.

    Learning objectives
  • To gain an overview of the effect of thyroid disorders on reproductive health.

  • To review the evidence on how to optimise thyroid function to improve reproductive outcomes.

    Ethical issues
  • Screening for thyroid disease should be considered in women presenting with subfertility and recurrent early pregnancy loss.

The full paper is available to read online here: http://onlinelibrary.wiley.com/enhanced/doi/10.1111/tog.12161/

Or download the PDF from here: http://onlinelibrary.wiley.com/doi/10.1111/tog.12161/pdf


 

Controversies in endocrinology: On the need for universal thyroid screening in pregnant women.

Eur J Endocrinol. 2013 Nov 29;170(1):R17-30. doi: 10.1530/EJE-13-0561. Print 2014 Jan.

Vila L1, Velasco I, González S, Morales F, Sánchez E, Torrejón S, Soldevila B, Stagnaro-Green A, Puig-Domingo M.


Abstract
There is a well-known controversy among scientific societies regarding the recommendation to screen for thyroid dysfunction (TD) during pregnancy. Although several studies have shown an association between maternal subclinical hypothyroidism and/or hypothyroxinemia with obstetric problems and/or neurocognitive impairment in the offspring, there is only limited evidence on the possible positive effects of thyroxine (T4) treatment in such cases.

Despite the scarcity of this evidence, there is a widespread agreement among clinicians on the need for treatment of clinical hypothyroidism during pregnancy and the risks that could arise due to therapeutic abstention. As maternal TD is a quite prevalent condition, easily diagnosed and for which an effective and safe treatment is available, some scientific societies have proposed to assess thyroid function during the first trimester of pregnancy and ideally before week 10 of gestational age.

Given the physiologic changes of thyroid function during pregnancy, hormone assessment should be performed using trimester-specific reference values ideally based on locally generated data as geographic variations have been detected. Screening of TD should be based on an initial determination of TSH performed early during the first trimester and only if abnormal should it be followed by either a free or total T4 measurement. Furthermore, adequate iodine supplementation during pregnancy is critical and if feasible it should be initiated before the woman attempts to conceive.

Link to above abstract in PubMed http://www.ncbi.nlm.nih.gov/pubmed/24128429

The full paper is available here: http://eje-online.org/content/170/1/R17.long


 

Effect of levo-thyroxine treatment on weight and body mass index in children with acquired hypothyroidism

Abstract taken from PubMed.gov
J Pediatr.2008 Jan;152(1):96-100. Lomenick JP, El-Sayyid MD, Smith WJ.
Division of Pediatric Endocrinology, University of Kentucky, Lexington, KY, USA.

Background: To determine whether normalization of thyroid-stimulating hormone (TSH) in children with acquired hypothyroidism is associated with a decrease in weight or body mass index (BMI).

Study Design: We retrospectively identified 68 subjects with acquired hypothyroidism who were seen at least once in our center in follow-up between 1995 and 2006.

Results: Treatment with levo-thyroxine decreased the mean TSH level from 147 microU/mL initially to 5.0 microU/mL at the second visit 4.4 months later. This was not associated with a significant change in weight or BMI. Of the 68 subjects, 31% lost weight by the second visit (mean 2.3 kg). The mean initial TSH level of this group was 349 microU/mL. Thirty of the 68 children had at least 2 years of follow-up, and 19/68 had at least 4 years of follow-up. Over those intervals, weight and BMI percentiles and z scores did not change significantly from baseline values.

Conclusions: Most children treated for acquired hypothyroidism exhibited little short-term or long-term change in weight or BMI despite near-normalization of TSH. Those children who lost weight tended to have severe hypothyroidism and to have only a small weight loss. Consequently, practitioners should not expect significant decreases in weight after treatment in most children with hypothyroidism.

Donna Hurlock, MD, who has a special interest in treating hypothyroidism,  comments on this study, “The problem which caused the lack of weight loss of course is that they gave enough med to "normalize the children's thyroid levels". That amount is usually way less than the amount that makes the symptoms go away.  Thus it's only partial replacement. I also find weight gain if I don't give enough thyroid to make the hands warm, for example.”

 


 

Prenatal and Postnatal Exposure to Cell Phone Use and Behavioral Problems in Children

Abstract taken from:
Epidemiology - July 2008 - Volume 19 - Issue 4 - pp 523-529
Divan, Hozefa A.; Kheifets, Leeka; Obel, Carsten; Olsen, Jørn

Background: The World Health Organization has emphasized the need for research into the possible effects of radiofrequency fields in children. We examined the association between prenatal and postnatal exposure to cell phones and behavioral problems in young children.
Methods: Mothers were recruited to the Danish National Birth Cohort early in pregnancy. When the children of those pregnancies reached 7 years of age in 2005 and 2006, mothers were asked to complete a questionnaire regarding the current health and behavioral status of children, as well as past exposure to cell phone use. Mothers evaluated the child's behavior problems using the Strength and Difficulties Questionnaire.
Results: Mothers of 13,159 children completed the follow-up questionnaire reporting their use of cell phones during pregnancy as well as current cell phone use by the child. Greater odds ratios for behavioral problems were observed for children who had possible prenatal or postnatal exposure to cell phone use. After adjustment for potential confounders, the odds ratio for a higher overall behavioral problems score was 1.80 (95% confidence interval = 1.45-2.23) in children with both prenatal and postnatal exposure to cell phones.
Conclusions: Exposure to cell phones prenatally-and, to a lesser degree, postnatally-was associated with behavioral difficulties such as emotional and hyperactivity problems around the age of school entry. These associations may be noncausal and may be due to unmeasured confounding. If real, they would be of public health concern given the widespread use of this technology.

 


 

Locomotor Deficiencies and Aberrant Development of Subtype-Specific GABAergic Interneurons Caused by an Unliganded Thyroid Hormone Receptor α1

Karin Wallis; Maria Sjögren; Max van Hogerlinden; Gilad Silberberg; André Fisahn; Kristina Nordström; Lars Larsson; Håkan Westerblad;  Gabriela Morreale de Escobar;  Oleg Shupliakov and Björn Vennström
The Journal of Neuroscience, 20 February 2008, 28(8): 1904-1915;

Researchers at the Karolinska Insitutet in Sweden have shown in experiments on mice, that thyroid hormone is necessary for proper locomotor development (body movements) and that it is possible that children born with thyroid hormone deficiencies may have locomotor problems.

Professor Bjorn Vennstrom, leading the study, states, “The results provide fresh support for those who advocate the more thorough monitoring of pregnant women.”

The scientists were able to show that the cause of the locomotor disorders was due to abnormal development of specific nerve cells in the motor cortex and cerebellum in the brain.

Mice with modified genes were used for the study - genes with changed receptors for thyroid hormone - and this could mean that patients with those particular gene mutations of the same receptors can be identified and treated


 

Therapeutic Administration of 131I for Differentiated Thyroid Cancer: Radiation Dose to Ovaries and Outcome of Pregnancies

Jérôme-Philippe Garsi, Martin Schlumberger, Carole Rubino, Marcel Ricard, Martine Labbé, Claudia Ceccarelli, Claire Schvartz, Michel Henri-Amar, Stéphane Bardet and Florent de Vathaire
Journal of Nuclear Medicine 2008;18:854-52

This study looked at pregnancy outcome and the health of children of women previously exposed to radioiodine (131I) (RAI) during thyroid cancer treatment. 

Female patients who were treated for thyroid cancer but had not received significant external radiation to the ovaries  were interviewed and data on 2,673 pregnancies was obtained.

The results showed that the incidence of miscarriages was 10% before any treatment for thyroid cancer; but increased after surgery for thyroid cancer, both before (20%) and after (19%) 131I treatment.

In contrast to previously reported data, miscarriages were not significantly more frequent in women treated with RAI during the year before conception, not even in women who had received more than 370 MBq during that year. The incidences of stillbirths, preterm births, low birth weight, congenital malformations, and death during the first year of life were not significantly different before and after RAI therapy and thyroid and nonthyroid cancers were similar in children born either before or after the mother's exposure to radioiodine.

The researchers found no evidence that exposure to radioiodine affects the outcomes of subsequent pregnancies and children. However, they felt that the value of 1 Gy as the dose in humans should be re-evaluated.

 


 

Maternal Thyroid Autoantibodies during the Third Trimester and Hearing Deficits in Children: An Epidemiologic Assessment

Ellen E. Wasserman; Kenrad Nelson1;
;Noel R. Rose; William Eaton; Joseph P. Pillion; Eric Seaberg; Monica V. Talor; Lynne Burek; Anne Duggan; Robert H. Yolken
American Journal of Epidemiology 2008;167:701-710

Researchers in Baltimore, MD found that elevated maternal thyroid autoantibodies - thyroid peroxidase (TPO) during pregnancy are linked to infertility, miscarriage, and neurodevelopmental deficits such as in cognitive function.

The researchers tested blood samples from the mothers of 1,736 children taken from them during their third trimester for TPO. 

The children of these mothers were given an audiology examination at the age of 8 years to check for  Sensorineural Hearing Loss (SNHL).    

Compared with 4.3% of the other children, 22.7% of the children whose mothers had high TPO levels, had SNHL.

The researchers concluded that their data suggested that antenatal exposure to maternal TPOaAb during the third trimester of pregnancy is associated with impaired auditory development.

 


 

Maternal Thyroid Hormone Concentration
During Late Gestation is Associated With Foetal Position at Birth

Hennie A. Wijnen; Libbe Kooistra; Huib L. Vader; Gerard G. Essed; Ben W. Mol; Victor J. Pop
Clinical Endocrinology 2009; 71: 746-751

These researchers wanted to find out if there was an association between maternal thyroid hormone and foetal head position at birth.  Low-normal range thyroid hormone concentrations in pregnant women with normal thyroid function constitutes a risk of locomotor abnormality and the researchers hypothesized that low normal maternal thyroid hormone levels are associated with increased risk of abnormal foetal position at delivery. 

960 healthy Dutch women who had full term pregnancies and normal head presentations, had FT4, TSH and thyroid peroxidase antibody tests done at 36 weeks of gestation, and these test results were  compared with foetal head position (anterior cephalic vs. abnormal cephalic) and delivery mode (spontaneous vs. assisted delivery).

The researchers found that women who had babies with abnormal positioning of the head had significantly higher FT4 levels at 36 weeks than those with abnormal cephalic presentation (n = 69).

There were no between-group differences for TSH. The researchers concluded that the lower the maternal FT4 concentration at 36 weeks of gestation, the higher the risk of abnormal cephalic foetal presentation and assisted delivery.

 


 

Thyroid Disease Raises Risk For Birth Defects

Women with thyroid disease are more likely to give birth to babies with heart, brain and kidney defects even if the thyroid function tests are normal during the pregnancy, according to new research from Johns Hopkins.

Results of the study, to be presented Jan. 17 at the annual meeting of the Society for Maternal-Fetal Medicine in New Orleans, showed that babies born to women with overactive or underactive thyroid also were at increased risk of a variety of other anomalies, including cleft lip or palate, or extra fingers. In addition, infants born to women with underactive thyroid were at increased risk of cardiac problems even if the mothers were on medication.

The research contradicts some earlier studies indicating thyroid disease did not pose fetal risks, but those studies were conducted using less sophisticated technology for detecting birth defects, says David A. Nagey, M.D., Ph.D., study co-author and associate professor of gynecology and obstetrics.

"We already knew that there was an increased risk of problems, mostly intellectual or developmental, in children as a result of hypothyroid (underactive thyroid) pregnancies, but the link with birth defects is new and unexpected," Nagey says. "If these results are confirmed, it could lead to routine testing of women for thyroid disease prior to pregnancy and for cardiac anomalies in the fetuses of women with hypothyroidism."

Nagey recommends that doctors consider thyroid testing during a woman's pre-pregnancy consult or add it to the routine prenatal diagnostic tests. If the test indicates the woman has hypothyroidism, a fetal echocardiogram during the 20th week of pregnancy might be warranted.

The researchers studied 101 women (64 with hypothyroidism and 50 with the overactive version, hyperthyroidism) who gave birth at The Johns Hopkins Hospital between December 1994 and June 1999.

The women's average age was 31; very few admitted to smoking, drinking alcohol or using illegal drugs. Overall, there were 108 pregnancies with 114 fetuses. The research team studied the charts for all children born from these pregnancies and recorded any medical problems during the neonatal period or subsequent years.

Twenty-one babies (18 percent) had birth defects, including problems in the cardiac, renal and central nervous systems and other disorders such as sunken chest, extra fingers, cleft lip and palate, and ear deformities. Two fetuses died before being delivered.

Among a subset of 86 women who had a test of their thyroid function performed during the first trimester of pregnancy (52 with hypothyroidism and 34 with hyperthyroidism), 17 babies (20 percent) had medical problems similar to those seen among the larger group.

The women with hypothyroidism were more likely than those with hyperthyroidism to have babies with defects. Nagey says it's possible the same antibodies that cause the underactive thyroid also could be responsible for the birth defects.

Adam J. Wolfberg, M.D., M.P.H., of Brigham and Women's Hospital, Boston, was principal author of the study. He was a medical student at Hopkins when the research was conducted.

Abstract # 274: Wolfberg, Adam J. and David A. Nagey, "Thyroid Disease During Pregnancy and Subsequent Congenital Anomalies."

 


 

Antepartum Dental Radiography and Infant Low Birth Weight

Philippe P. Hujoel, PhD; Anne-Marie Bollen, PhD; Carolyn J. Noonan, MS; Michael A. del Aguila, PhD
JAMA. 2004;291:1987-1993.

Researchers investigated whether dental radiography is associated with low-birth-weight babies.

They studied 1117 women with low-birth-weight infants of whom 336 were term low-birth-weight infants. Four control pregnancies resulting in normal-birth-weight were randomly selected for each case.  They concluded that dental radiography during pregnancy is associated with low birth weight, specifically with term low birth weight.

 


 

Thyroid Autoimmunity Increases Risk of Miscarriage In Women Who Receive Fertility Treatment

Women who test positive for thyroid antibodies prior to receiving fertility treatment may be at an increased risk for miscarriage, according to new research published this month in The Journal of Clinical Endocrinology & Metabolism (JCEM) September 2003. The new study emphasizes the importance of testing thyroid autoimmunity prior to assisted reproduction therapies in women.

Thyroid dysfunction is a condition known to reduce the likelihood of pregnancy. It can also adversely affect a pregnancy. Positive thyroid antibodies, even in the presence of normal thyroid function, increase the risk of miscarriage two or three times, even in spontaneous pregnancies. Research has shown that women who suffer from infertility are at an increased risk for associated thyroid autoimmunity compared with age-matched fertile women.

While most infertile couples use assisted reproduction technologies, such as in vitro fertilization, to become pregnant, 20 to 30 percent of these pregnancies are complicated by miscarriage. Dr. Kris Poppe and researchers at the Vrije Universiteit Brussel in Belgium sought to determine whether the presence of positive thyroid antibodies influences the rate of miscarriage in infertile women.

Dr. Poppe and his colleagues conducted a prospective analysis on 234 infertile women between the ages of 20 and 50 years who visited at the Center for Reproductive Medicine in Belgium. The women were screened for thyroid peroxidase antibodies (TPO-Ab), thyroid stimulating hormone (TSH) and free T4 before undergoing assisted reproduction. The endpoints of the assisted reproduction were pregnancy, miscarriage or delivery.

The researchers found positive thyroid antibodies in about 14 percent of the subjects. Approximately 53 percent of these women became pregnant. Yet, the miscarriage rate for these women was more than 50 percent, compared with only 23 percent in the women negative for thyroid antibodies, despite comparable thyroid function prior to the procedure. The women in both groups were age-matched.

"These findings help conclude that thyroid antibodies could be assessed in women before they undergo assisted reproduction therapies," notes Dr. Poppe, the first author on the study. "This test could help determine the risk for miscarriage. Larger studies are now needed to confirm these findings.

 


 

Prenatal and Postnatal Exposure to Cell Phone Use and Behavioral Problems in Children

Abstract taken from:
Epidemiology - July 2008 - Volume 19 - Issue 4 - pp 523-529
Divan, Hozefa A.; Kheifets, Leeka; Obel, Carsten; Olsen, Jørn

Background: The World Health Organization has emphasized the need for research into the possible effects of radiofrequency fields in children. We examined the association between prenatal and postnatal exposure to cell phones and behavioral problems in young children.
Methods: Mothers were recruited to the Danish National Birth Cohort early in pregnancy. When the children of those pregnancies reached 7 years of age in 2005 and 2006, mothers were asked to complete a questionnaire regarding the current health and behavioral status of children, as well as past exposure to cell phone use. Mothers evaluated the child's behavior problems using the Strength and Difficulties Questionnaire.
Results: Mothers of 13,159 children completed the follow-up questionnaire reporting their use of cell phones during pregnancy as well as current cell phone use by the child. Greater odds ratios for behavioral problems were observed for children who had possible prenatal or postnatal exposure to cell phone use. After adjustment for potential confounders, the odds ratio for a higher overall behavioral problems score was 1.80 (95% confidence interval = 1.45-2.23) in children with both prenatal and postnatal exposure to cell phones.
Conclusions: Exposure to cell phones prenatally-and, to a lesser degree, postnatally-was associated with behavioral difficulties such as emotional and hyperactivity problems around the age of school entry. These associations may be noncausal and may be due to unmeasured confounding. If real, they would be of public health concern given the widespread use of this technology.

 


 

Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study.

Pedersen LH, Henriksen TB, Vestergaard M,  Olsen J, Bech BH.
Department of Epidemiology, Institute of Public Health, Aarhus University, Bartolin Allé 2, DK-8000 Aarhus, Denmark. LHP@dadlnet.dk

Abstract:

To investigate any association between selective serotonin reuptake inhibitors (SSRIs) taken during pregnancy and congenital major malformations.

The researchers studied 493,113 children born in Denmark between 1996 and 2003.

The outcome of the study was to see if there were any major malformations with particular interest in heart defects. Nationwide registers on prescriptions, births and hospital diagnosis provided information on mothers and newborns. Follow-up data was available up to December 2005.

The researchers found that prescriptions for SSRIs were not associated with major malformations overall but were associated with heart defects in the dividing wall of the heart ventricles (septal).

For individual SSRIs, the odds ratio for septal heart defects was 3.25 (1.21 to 8.75) for sertraline, 2.52 (1.04 to 6.10) for citalopram, and 1.34 (0.33 to 5.41) for fluoxetine.

Prescriptions for more than one type of SSRI were associated with septal heart defects 4.70 (1.74 to 12.7). The prevalence of septal heart defects was 0.5% among unexposed children, 0.9%  among children whose mothers were prescribed any SSRI, and 2.1% among children whose mothers were prescribed more than one type of SSRI.

The researchers concluded that here is an increased prevalence of septal heart defects among children whose mothers were prescribed an SSRI in early pregnancy, particularly sertraline and citalopram.

The largest association was found for children of women who redeemed prescriptions for more than one type of SSRI.