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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Antenatal Corticosteroids administration just few hours before preterm delivery improves survival and health gains for the infants.

Genesis Research Trust.

Imminent preterm labor, with no time to give antenatal corticosteroids? Still give it says the result of a large population based study.

Antenatal corticosteroids given few hours before an imminent delivery is effective in improving survival says results of a large population-based study of 4594 European infants born before 32 weeks’ gestation. This study was published on line today in JAMA Pediatrics.

The interval between steroids administration and birth varies, and so does the benefits achieved by the preterm infant. When women at risk for preterm delivery receive antenatal corticosteroids(ANS) 1 to 7 days before delivery, it reduces respiratory distress syndrome by 34%, necrotizing enterocolitis by 54%, intraventricular hemorrhage by 46%, and reduces Infant mortality by nearly 30%.

According to recent Cochrane Review “a single course of a corticosteroids, given to the mother in preterm labor and before the baby is born, helps to develop the baby's lungs and reduces complications such as breathing problems.”

Use of corticosteroid within the 24 hours’ window before delivery has been labelled as ‘partial’ or’ suboptimal’ according to Mikael Norman, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and the lead investigator of this study.

In fact, the latest timing of corticosteroids administration has never been investigated till now.

But this study “challenge current thinking about the optimal timing” of antenatal corticosteroids and encourage “a more proactive management of women at risk for imminent preterm birth, which may help reduce infant mortality and severe neonatal brain injury,” said Mikael Norman.

The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS.

The study also evaluated the effects of  3 other evidence based practices: delivery in a maternity unit with appropriate level of neonatal care; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure.

Nearly 55% were boys and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g.

The cohort was divided into 4 categories depending upon the timing of corticosteroids given: no injections (662 infants, or 14.4% of the study population), first injection at less than 24 hours before birth (1,111 infants, or 24.2%), first injection at the recommended 1-7 days before birth (1,871 infants, or 40.7%), and first injection more than 7 days before birth (950 infants, or 20.7%).

The study results show that:

Receiving ANS at any time before delivery is associated with significant reduction in neonatal morbidity as compared to receiving no steroids.

The largest benefit (> 50%) was achieved in group which received them at the recommended interval of 1-7 days before delivery.

Nearly 20% of the infants in the study received ANS more than 7 days before and showed an increased mortality by 40% as compared to women who received them in the recommended window of period.

Using this information on timing of administration and benefits derived, the investigators created a simulation model for 661 infants who did not received any corticosteroids. The model predicts that if these infants had received treatment at least 3 hours before delivery, overall mortality would have decreased by 26%; 3-5 hours before delivery, mortality would have decreased by 37%; and if received treatment at 6-12 hours before delivery it would have decreased by 51%.

The authors concluded that “Encouraging administration of antenatal corticosteroids when delivery is very imminent could result in substantial survival and health gains for very preterm infants.”

A current project Screening to Improve Health in Very Preterm Infants in Europe (SHIPS) is about follow-up programmes for children born preterm. The project builds on the EPICE cohort to follow them to pick up any early problem and is currently ongoing in all the 11 countries.

Migraine linked to increase in pregnancy, labor and neonatal complications!

The occurrence and frequency of migraine attacks in women is influenced by hormonal changes throughout the lifecycle. More than 50% of women report an improvement in attacks, especially during the second and third trimester irrespective of the type of migraine.

If migraines do occur, they do so most often during the first three months of pregnancy due to the rise in estrogen level. The other triggers for attacks in pregnancy are possibly from lack of sleep, additional stresses, or other headache causes.

Women who have migraine during pregnancy end up having higher rates of preeclampsia, preterm delivery, and low-birthweight babies that far exceed national statistics, a new study suggests.  In Women older than 35years of age, it is an independent risk factor for adverse pregnancy outcome.

The study was presented on April 17, 2016 at the American Academy of Neurology (AAN) 68th Annual Meeting in Vancouver, Canada.

"Over half the patients experienced some type of adverse birth outcome, which suggests that pregnancies in such patients should be considered high risk, especially in older women," said lead author Matthew S. Robbins, MD, associate professor, clinical neurology, Albert Einstein College of Medicine, chief of neurology, Jack D. Weiler Hospital, Montefiore Medical Center, and director of inpatient services, Montefiore Headache Center, Bronx, New York.

Researchers at Montefiore Medical Center reviewed 5 years of data between July 1, 2009, to June 30, 2014 and identified 90 women, who had severe attack during pregnancy.

The findings included:

• About 38.8% of women were African American, 76.7% were obese with body mass index of 30 kg/m² or more and a third of the group (30%) was nulliparous.
• More than half of these women (54 percent) had at least one complication.  
• About 30 percent of the women had a preterm delivery, as compared to nearly 10 percent in general population.
• About 20 percent of the women with migraine had preeclampsia, compared to between 5 and 8 percent in the general population.
• 19 percent of the women with migraine delivered babies with low birthweight, compared to 8 percent in the general population.
• Researchers do not know the cause for these increased incidences of co-morbidities, but is possibly linked to increased cardiovascular complications in these women, or changes in   the endothelium leading to preecclampsia.

Dr. Robbins caution against generalizing these findings to other population, as the study involved a small inner city population but does suggest a close follow up of women with migraine and treating them as high risk.

The study had many limitations, notable lack of control group of women who had migraine but did not report to physician for care. Also, Sixty-two percent of the women in the study received treatment for their migraine, which also could have played a part in the pregnancy and birth complications.

David J. Dickoff, MD, a general community neurologist in Yonkers, New York summed it well saying "The importance of the migraine study is to alert all doctors, especially obstetricians, that history of migraine headaches is a risk factor for pre-eclampsia," Dr Dickoff said. "These patients may need to be considered high risk and followed more closely for BP [blood pressure] elevations and proteinuria."

References :

http://www.prnewswire.com/news-releases/pregnant-women-with-severe-migraine-may-be-at-increased-risk-for-labor-and-delivery-complications-300230520.html

http://www.ncbi.nlm.nih.gov/pubmed/9825951

Prior First Trimester Uterine evacuation augments the risk for preterm birth in subsequent pregnancies!

Many studies have shown that a history of evacuation in women is associated with increased risk of preterm birth in subsequent pregnancy as compared to women with  no such history. But, many studies have failed to prove a direct cause and effect relationship. Other studies have linked D&C as a cause of subsequent pre term birth (PTB), but no distinction was made between surgical and medical modality of evacuation.

2 systemic reviews and meta-analysis were recently published in 2 separate journals. The first was in January, 2016 issue of Human Reproduction published on behalf of The European Society of Human Reproduction and Embryology  and the second is still in press in the forthcoming issue of  American Journal of Obstetric and Gynecology.

The Primary source of this article is the systemic review and meta-analysis in the journal of Human Reproduction, although both the analysis has concluded that Prior surgical uterine evacuation is a risk factor for subsequent pre term birth (PTB).

This is the first systematic review and meta-analysis addressing the association between D&C and preterm birth.

Since no Randomized Control Trials (RCT) were available, only cohort and case–control studies were included. A total of 21 studies reporting on 1,853,017 women were included out of that 71,231 had a history of at least one D&C in the first trimester of pregnancy. In 66,003 women, D&C had been performed for termination of pregnancy.

The control group consisted of 1,781,786 women, out of which 24. 977 women had received a medical treatment for either miscarriage or termination of pregnancy, while 1189 had had a spontaneous miscarriage and the rest were without a history of miscarriage or termination of pregnancy.

The primary outcome was a preterm delivery subsequent to an H/O curettage. The outcome of PTB was divided into 3 categories <37 weeks, <32 weeks and <28 weeks. The study also investigated a dose –response relationship by comparing women with a history of multiple D&Cs to women without a history of D&C. Many other sub-group analysis comparing   women with a D&C for miscarriage or termination of pregnancy to women with medical treatment for miscarriage or termination of pregnancy on the risk of subsequent preterm birth <37 weeks were also performed. 

The important findings of the study were:

• It was seen that that women with a previous D&C, for miscarriage or termination of pregnancy in the first trimester, are at increased risk for preterm and especially very preterm birth, in comparison to women without a previous D&C procedure.
• The increase in risk was statistically significant when it was only run against women who had medical management of pregnancy.
• The risk of preterm birth increases with number of D&C performed, indicating a dose response relationship.
• Reasonably, these findings suggest that it is the surgical management, rather than the actual miscarriage or termination, is the deciding factor about the time of delivery in the following pregnancy.

The studies included had many limitations and bias, but the strict inclusion and exclusion criteria, sensitivity and robust analysis, multiple control groups, sub-group  analysis and including prospective cohort studies  helped to limit it to certain extent. 

The mechanism by which the surgical procedure increases the risk for preterm birth remains speculative. Multiple hypotheses have been put forward such as cervical incompetence. Another theory propose a damage to  the endometrial lining which might cause abnormal placentation in a later pregnancy, thus increasing the risk of placental abruption, pre-eclampsia, placenta praevia and intrauterine growth restriction.

It is also postulated that cervical damage might impair the anti-microbial defence mechanism thereby facilitating ascending microbial colonization, a known cause of preterm births.

The clinical implications of this study are:

Frequent follow up and increase obstetrical care for women with h/o D&C, including monitoring of early signs and symptoms of threatened preterm birth.

Avoiding unneeded D&C and going more for non-invasive management options when possible i.e. expectant management or medical management in case of miscarriage, and medical management in case of termination of pregnancy.

No data is yet available on the effect of cervical priming before the D&C and subsequent risk of preterm labor. 

References:

Wieringa-de Waard M, Vos J, Bonsel GJ, Bindels PJ, Ankum WM. Management of miscarriage: a randomized controlled trial of expectant management versus surgical evacuation. Hum Reprod 2002;17:2445–2450

M. Lemmers M, Verschoor MAC, Hooker AB, Opmeer BC, Limpens J., Huirne JAF, Ankum WM, Mol BWM. Dilatation and curettage increases the risk of subsequent preterm birth: a systematic review and meta-analysis. Hum. Reprod. (2016) 31 (1): 34-

http://www.ajog.org/article/S0002-9378%2815%2902596-X/abstract

History of induced abortion as a risk factor for preterm birth in European countries: results of the EUROPOP survey Hum. Reprod. (2004) 19 (3): 734-740 first published online January 29, 200

You JH, Chung TK. Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis. Hum Reprod 2005;20:2873–2878

Pregnancy loss managed by cervical dilatation and curettage increases the risk of spontaneous preterm birth Hum. Reprod. (2013) 28 (12): 3197-3206 first published online September 19, 2013 doi:10.1093/humrep/det332

Shah PS, Zao J. Induced termination of pregnancy and low birthweight and preterm birth: a systematic review and meta-analyses. BJOG 2009;116:1425–1442.