Francesca Facco

Sleep Disturbances in Pregnancy

OBJECTIVE: To estimate the prevalence and patterns of sleep disturbances during pregnancy among healthy nulliparous women. METHODS: This was a prospective, cohort study of healthy nulliparous women, recruited between 6 and 20 weeks of gestation, who completed a baseline sleep survey at enrollment with follow-up in the third trimester. The survey was composed of the following validated sleep questionnaires: Berlin Questionnaire for Sleep Disordered Breathing, Epworth Sleepiness Scale, National Institutes of Health/International Restless Legs Syndrome Question Set, Women’s Health Initiative Insomnia Rating Scale, and the Pittsburgh Sleep Quality Index. Differences in sleep characteristics between the baseline and third trimester were compared using the paired t test or McNemar test for continuous or categorical data, respectively. RESULTS: One hundred eighty-nine women completed both baseline and follow-up sleep surveys. The mean gestational age was 13.8 (±3.8) and 30.0 (±2.2) weeks at the first and second surveys, respectively. Compared with the baseline assessment, mean sleep duration was significantly shorter (7.4 [±1.2] hours compared with 7.0 [±1.3] hours, P<.001), and the proportion of patients who reported frequent snoring (at least three nights per week) was significantly greater (11% compared with 16.4%, P=.03) in the third trimester. The percentage of patients who met diagnostic criteria for restless leg syndrome increased from 17.5% at recruitment to 31.2% in the third trimester (P=.001). Overall poor sleep quality, as defined by a Pittsburgh Sleep Quality Index score greater than 5, became significantly more common as pregnancy progressed (39.0% compared with 53.5%, P=.001). CONCLUSION: Sleep disturbances are prevalent among healthy nulliparous women and increase significantly during pregnancy. LEVEL OF EVIDENCE: II

Self-reported short sleep duration and frequent snoring in pregnancy: impact on glucose metabolism.

OBJECTIVE We sought to evaluate the impact of short sleep duration (SSD) and frequent snoring (FS) on glucose metabolism during pregnancy. STUDY DESIGN We conducted a prospective cohort study of healthy nulliparas who participated in a sleep survey study. SSD was defined as <7 hours of sleep per night and FS, as snoring >or=3 nights per week. Outcomes included 1-hour oral glucose tolerance results and the presence of gestational diabetes mellitus (GDM). Univariate and multivariate analyses were performed. RESULTS A total of 189 women participated; 48% reported an SSD and 18.5% reported FS. SSD and FS were associated with higher oral glucose tolerance values: SSD (116 +/- 31 vs 105 +/- 23; P = .008) and FS (118 +/- 34 vs 108 +/- 25; P = .04). Both SSD (10.2% vs 1.1%; P = .008) and FS (14.3% vs 3.3%; P = .009) were associated with a higher incidence of GDM. Even after controlling for potential confounders, SSD and FS remained associated with GDM. CONCLUSION SSD and FS are associated with glucose intolerance in pregnancy.

Genetic thrombophilias and intrauterine growth restriction: a meta-analysis.

OBJECTIVE: To estimate the relationship between inherited thrombophilias and intrauterine growth restriction (IUGR) using meta-analytic techniques. METHODS: A literature review identified case–control and cohort studies evaluating the relationship between IUGR and the following thrombophilias: homozygous or heterozygous factor V Leiden or prothrombin (PT) G20210A mutations and homozygous methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Using mixed effects and random-effects models, the association between thrombophilias and IUGR was explored. Publication bias was assessed with funnel plots and corrected for with Duval and Tweedie’s trim-and-fill method. RESULTS: The following number of related studies were found: studies evaluating relationships between factor V Leiden mutation and IUGR, 12 case–control and four cohort; between PT mutation and IUGR, 11 case–control and 0 cohort; and between MTHFR C677T homozygosity and IUGR, 10 case–control and two cohort. The overall summary odds ratio (OR) for the association between factor V Leiden and IUGR was significant (OR 1.23, 95% confidence interval [CI] 1.04–1.44); however, this was mainly driven by the positive association seen in the case–control studies (OR 1.91, 95% CI 1.17–3.12). The association between PT and IUGR was only explored in case–control studies yielding a summary OR that was not significant (OR 1.52, 95% CI 0.98–2.35). The overall summary OR for the association between MTHFR and IUGR was not significant (OR 1.01, 95% CI 0.88–1.17), but was significant for the case–control studies alone (OR 1.35, 95% CI 1.04–1.75). For both factor V Leiden and MTHFR mutations, a funnel-plot analysis of the case–control studies suggests publication bias. When the trim-and fill-method was used to correct for the publication bias, these summary estimates were no longer significant. CONCLUSION: The association between inherited thrombophilias and IUGR can only be discerned in case–control studies and seems to be largely because of publication bias. LEVEL OF EVIDENCE: III

Development of a pregnancy-specific screening tool for sleep apnea.

STUDY OBJECTIVE The Berlin Questionnaire and Epworth Sleepiness Scale (ESS) are commonly used to screen for sleep apnea in non-pregnant populations. We sought to evaluate the Berlin and ESS in pregnancy and to determine whether an alternative screening approach could better detect sleep apnea in pregnant women. METHODS Pregnant women at high risk for sleep apnea (women with chronic hypertension, pre-gestational diabetes, obesity, and/or a prior history of preeclampsia) completed a sleep survey composed of the Berlin and ESS, and participated in an overnight sleep evaluation with the Watch-PAT100 (WP100), a wrist-mounted device designed to diagnose sleep apnea, defined as an apnea hypopnea index ≥ 5. Using multivariable statistics, demographic, clinical, and subjective symptoms that were independently associated with sleep apnea were determined and a prediction rule for the presence of sleep apnea was developed. The predictive capacity of this newly developed system was compared to that of the Berlin and ESS using receiver-operating curve (ROC) statistics. RESULTS Of the 114 women who participated and had a valid WP100 study, 100 completed the Berlin and 96 the ESS. The Berlin and ESS did not accurately predict sleep apnea in this high-risk pregnancy cohort, with ROC area under the curves (AUC) of 0.54 (p = 0.6) and 0.57 (p = 0.3), respectively. Conversely, a model incorporating frequent snoring, chronic hypertension, age, and body mass index performed significantly better (AUC 0.86, p > 0.001). CONCLUSION The Berlin and ESS are not appropriate tools to screen for sleep apnea in high-risk pregnant women. Conversely, our four-variable model more accurately predicts sleep apnea in pregnancy.

Sleep-disordered breathing: A risk factor for adverse pregnancy outcomes?

In nonpregnant populations, sleep-disordered breathing (SDB) has been associated with cardiovascular and metabolic disease. Few studies have examined the relationship between SDB and adverse pregnancy outcomes (APO). The objective of this study was to examine the association between SDB and APO. Women who had a delivery as well as an in-laboratory polysomnogram (PSG) were identified. Demographics, PSG results, and pregnancy outcomes were abstracted from the medical record. Absence of SDB was defined as an apnea hypopnea index (AHI) of <5, mild SDB as an AHI of 5 to 14.9, and moderate to severe SDB as an AHI of ≥15. The primary outcome was a composite measure of APO: pregnancy-related hypertension, gestational diabetes, or preterm birth ≤34 weeks. We identified 143 women who had undergone a PSG and a delivery. Increasing severity of SDB was associated with an increasing risk of the composite APO: AHI <5, 18.1%; AHI 5 to 14.9, 23.5%; AHI ≥15, 38.5% (p = 0.038). Obese women (body mass index ≥30) with moderate to severe SDB had the highest rate of APO, 41.7%. SDB, especially moderate to severe disease, may be associated with APO. However, it is unclear if SDB is a risk factor for APO independent of obesity.

Association between Sleep-Disordered Breathing and Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus

OBJECTIVE To estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM). METHODS In this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models. RESULTS Three thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM. CONCLUSION There is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM.

Short ultrasonographic cervical length in women with low-risk obstetric history.

OBJECTIVE: To understand the relationship between cervical length and the risk of prematurity in parous women without a history of preterm delivery. METHODS: Data from 2,998 singleton pregnancies enrolled in a multicenter, observational cohort study were analyzed. We subgrouped the population into the following categories: those with history of at least one spontaneous preterm birth (n=467); nulliparous (n=1,237); and parous with a history of at least one term birth and no previous preterm birth (low-risk history group, n=1,284). The relationship between cervical length (measured between 22 and 22 6/7 weeks of gestation) and preterm birth was examined using logistic regression. Assuming a 40% risk reduction with the use of vaginal progesterone, we calculated the number needed to screen to prevent one preterm birth. RESULTS: An inverse relationship between cervical length and risk of preterm birth was demonstrated for each subgroup. A short cervix (15 mm or less) was identified in only 0.93% of the low-risk group participants compared with 3.4% of the previous preterm birth group participants and 2.1% of nulliparous women. The overall rate of preterm birth was lowest (10.5%) in the low-risk history group; however, the rate of preterm birth for these women with a short cervix was 25%. For a cervical length cutoff of 15 mm or less, preventing one spontaneous delivery before 34 weeks of gestation would require screening 167 (95% confidence interval [CI] 112–317) women with a previous preterm birth, 344 (95% CI 249–555) nulliparous women, and 1,075 (95% CI 667–2,500) women at low risk. CONCLUSIONS: Although ultrasonographic short cervix is a risk factor for preterm birth among parous women with exclusively term births, the incidence of a short cervix is very low. The number needed to screen to prevent one preterm birth is considerably greater for women who have a low-risk obstetric history. LEVEL OF EVIDENCE: II

Are women who have had a preterm singleton delivery at increased risk of preterm birth in a subsequent twin pregnancy

Our objective was to determine whether preterm birth of a singleton is associated with an increased risk of preterm birth of twins in a subsequent pregnancy. We identified all women who delivered a singleton followed by twins at Northwestern Memorial Hospital during a 10-year period. Using a cohort study design, we compared women with preterm singleton deliveries to women with term singleton deliveries with regard to their subsequent twin pregnancy outcomes. Two hundred ninety-three were identified who delivered a singleton followed by twins. Women who delivered a preterm singleton were significantly more likely to deliver subsequent preterm twins (73.9% versus 44.4%, odds ratio 3.5, 95% confidence interval 1.4 to 9.3). This significant difference persisted in multivariable analysis after controlling for ethnicity (adjusted odds ratio 3.3, 95% confidence interval 1.3 to 8.7). We concluded that preterm birth of a singleton is associated with an increased risk of preterm delivery in a subsequent twin gestation.

Sleep Duration and Blood Glucose Control in Women With Gestational Diabetes Mellitus.

OBJECTIVE: To describe the relationship between objectively assessed sleep and blood glucose in a prospective cohort of women recently diagnosed with gestational diabetes mellitus (GDM). METHODS: Women with GDM were enrolled immediately after attending a GDM education class. All patients were recruited during their first week of attempted dietary management of GDM. They were instructed on the use of a glucometer and on the principles of a GDM diet. Women wore an actigraph and completed a sleep log for 7 consecutive days. Glucose records were compared against the objective sleep data. Linear mixed model analysis was used to estimate the association of sleep duration on morning fasting and 1-hour postprandial blood glucose concentrations. RESULTS: Thirty-seven participants provided data for 213 sleep intervals that corresponded to at least one glucose reading. Sleep duration was negatively associated with fasting and 1-hour postprandial blood glucose concentrations In analyses adjusted for age, gestational age, and body mass index, a 1-hour increase in sleep time was associated with statistically significant reductions in fasting glucose (−2.09 mg/dL, 95% confidence interval [CI] −3.98 to −0.20) as well as postprandial glucose concentrations (lunch −4.62 mg/dL, 95% CI −8.75 to −0.50; dinner −6.07 mg/dL, 95% CI −9.40 to −2.73). CONCLUSION: Short sleep durations are associated with worsened glucose control in women with gestational diabetes. Educating women on healthy sleep and screening for and treating sleep disorders during pregnancy may have a role in optimizing blood glucose control in gestational diabetes. LEVEL OF EVIDENCE: II

Sleep-Disordered Breathing and Pregnancy

Sleep-disordered breathing (SDB) refers to a group of disorders characterized by abnormal respiratory patterns or abnormal gas exchange during sleep. The most common type of SDB, especially among young obese women, is obstructive sleep apnea. SDB has clearly been linked to poor sleep and impaired daytime function, but there are also data linking SDB to other health outcomes, principally cardiovascular and metabolic disease. SDB symptoms are common in pregnancy, and pregnancy itself has been associated with an increase in the prevalence of SDB symptoms. Although a link between SDB and adverse pregnancy outcomes appears to be biologically plausible, data exploring this relationship are only now emerging, and large prospective studies in which the authors use objective measures of sleep are lacking. Until we know more about the epidemiology and the impact of SDB in pregnancy, screening efforts for SDB in pregnancy should be focused on identifying very symptomatic patients because treatment of these individuals often leads to improved sleep quality and daytime functioning.