Frequent, loud snoring increases the risk of preterm delivery: News from the sleep conference

Another interesting paper presented at the annual meeting of the Associated Professional Sleep Societies linking obstructive sleep apnea and preterm and early preterm delivery. Women who are frequent, loud snorers during pregnancy and also before they were pregnant have a definite higher risk of preterm delivery as compared to their counterpart who sleep soundly throughout night.

The paper was presented at the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS), Boston. by Galit Levi Dunietz, PhD, MPH, of the University of Michigan.

It is already known that women with Sleep disordered breathing (SDB) do not fare well in pregnancy and many particularly have maternal hypertension and diabetes and possibly fetal growth restriction.

The study looked at 904 non-hypertensive, non-diabetic women, pregnant women in their third trimester, attending a prenatal clinic at a large medical center.

The women were divided into 4 groups based on their snoring pattern: non-snorers, infrequent-quiet, frequent-quiet, or frequent-loud snorers.

Only 6% of women were frequent loud-snorers and about 50% did not snore at all. 

About 25% of women in the pre-pregnancy frequent, loud- snoring category had a preterm delivery.

After adjusting for all pre-pregnancy and pregnancy confounders, those women who were frequent loud-snorers had an 81% increased risk of preterm delivery.  

The mean time to delivery in frequent loud snoring group was 37.1 weeks as compared to 38.6 weeks in controls.

Non-loud, infrequent, or pregnancy-onset snorers did not face the risk for preterm delivery.

Galit Levi Dunietz, PhD, MPH, of the University of Michigan said, “The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes.”

She further added that “The combination of snoring frequency and intensity may be a clinically useful marker to identify otherwise low-risk women who are likely to deliver earlier.”

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Adverse pregnancy and neonatal outcome in subclinical hypothyroidism: A Systematic Review and Meta-Analysis

Clinical Pearls:

• Subclinical hypothyroidism (SCH) is defined as elevated TSH levels with normal serum levels of thyroxine (T4). Recently ATA redefined the upper limit of TSH during pregnancy to 2.5 mIU/L during the first trimester and 3.0 mIU/L during the second and third trimesters
• The review confirms the association of SCH during pregnancy with multiple adverse maternal and neonatal outcomes, but there is not sufficient evidence to support the use of levothyroxine therapy to mitigate this association.
• Decision to start levothyroxine in such patients should be taken after an open and well informed discussion between patients and physicians.

  

Routine screening of all pregnant women for hypothyroidism is debatable because of conflicting data from previous studies. ACOG and American Thyroid Association (ATA) recommends against universal first trimester screening of pregnant women.

Subclinical hypothyroidism (SCH) is defined as elevated TSH levels with normal serum levels of thyroxine (T4). Recently ATA redefined the upper limit of TSH during pregnancy to 2.5 mIU/L during the first trimester and 3.0 mIU/L during the second and third trimesters.[1]

When screened according to the updated criteria’s, nearly 15% pregnant women in United states have SCH, which is almost 5 times the previous prevalence.

Many studies have reported adverse maternal and neonatal outcomes in pregnancy with SCH that includes an array of problems like including recurrent pregnancy loss, preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, placental abruption, premature rupture of membranes, intrauterine growth restriction, low birth weight, small for gestational age, low Apgar score, and neonatal death.

Some studies also report increased risk of cognitive deficits with rising TSH levels.

Other studies have not found any statistically significant association between SCH and adverse pregnancy outcomes.

This systemic review and meta-analysis estimates the effect of SCH on pregnancy outcome with patients who are euthyroid and the effect of levothyroxine on preventing the adverse pregnancy outcomes.

The study was published in the April issue of Journal Thyroid.[2]

The main outcome measures were pregnancy loss (miscarriage, IUD and fetal loss). Other outcome measure included various other complications of pregnancy.

Comprehensive search of data base from inception to January 2015, identified 1108 potentially eligible studies, of which 18 cohort studies comprising of total 3995 pregnant women with SCH were eligible. 

After meta-analysis and sensitivity analysis, it was seen that women with SCH were at higher risk for pregnancy loss, placental abruption, PROM, and neonatal death compared with euthyroid pregnant women.

The study also showed the prevalence of inconsistencies in defining SCH in different studies, absence of trimester specific range and cutoff that is used to start treatment with levothyroxine.

The ATA guidelines recommend treatment of pregnant women with SCH and positive TPO antibodies (Level B, fair evidence—USPSTF), but found insufficient evidence to recommend for or against universal levothyroxine treatment in pregnant women with SCH and negative TPO antibodies (Level I—USPSTF).[3]

The Endocrine Society panel recommends levothyroxine replacement in all pregnant women with SCH (weak recommendation, low-quality evidence).[4]although this will result in treating nearly 15% of pregnant women with levothyroxine, the guidelines panel opine that it will gain the benefits of replacing levothyroxine and reducing adverse effects as iatrogenic hyperthyroidism is unknown. 

The review stresses the importance and need of a large randomized trial to study the effects of levothyroxine supplementation on patients with SCH.  

To conclude, the review confirms the association of SCH during pregnancy with multiple adverse maternal and neonatal outcomes, but there is not sufficient evidence   to support the use of levothyroxine therapy to mitigate this association.

Clinicians and patients must have a frank and informed discussion with the patients on use of levothyroxine in patients with SCH, while we wait for larger trials to be conducted on patients with SCH and use and benefits of levothyroxine.

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[1]A Stagnaro-Green, M Abalovich, E Alexander, F Azizi, J Mestman, R Negro, A Nixon, EN Pearce, OP Soldin, S Sullivan, W Wiersinga 2011 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21:1081–1125.

[2] Maraka Spyridoula, Ospina Naykky M. Singh, O'Keeffe Derek T., Espinosa De Ycaza Ana E., Gionfriddo Michael R., Erwin Patricia J., Coddington Charles C. III, Stan Marius N., Murad M. Hassan, and Montori Victor M.. Thyroid. April 2016, 26(4): 580-590. doi:10.1089/thy.2015.0418.

[3] A Stagnaro-Green, M Abalovich, E Alexander, F Azizi, J Mestman, R Negro, A Nixon, EN Pearce, OP Soldin, S Sullivan, W Wiersinga 2011 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21:1081–1125.

[4] L De Groot, M Abalovich, EK Alexander, N Amino, L Barbour, RH Cobin, CJ Eastman, JH Lazarus, D Luton, SJ Mandel, J Mestman, J Rovet, S Sullivan 2012 Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97:2543–2565.