Background
Both short and prolonged sleep duration have been linked to impaired glucose metabolism. Sleep patterns change during pregnancy, but prospective data are limited on their relation to gestational diabetes.
Objective
We sought to prospectively examine the trimester-specific (first and second trimester) association between typical sleep duration in pregnancy and subsequent risk of gestational diabetes, as well as the influence of compensatory daytime napping on this association.
Study Design
In the prospective, multiracial Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort, 2581 pregnant women reported their typical sleep duration and napping frequency in the first and second trimesters. Diagnosis of gestational diabetes (n = 107; 4.1%) was based on medical records review. Adjusted relative risks with 95% confidence intervals for gestational diabetes were estimated with Poisson regression, adjusting for demographics, prepregnancy body mass index, and other risk factors.
Results
From the first and second trimester, sleep duration and napping frequency declined. Sleeping duration in the second but not first trimester was significantly related to risk of gestational diabetes. The association between second-trimester sleep and gestational diabetes differed by prepregnancy obesity status ( P for interaction = .04). Among nonobese but not obese women, both sleeping >8-9 hours or <8-9 hours were significantly related to risk of gestational diabetes: 5-6 hours (adjusted relative risk, 2.52; 95% confidence interval, 1.27–4.99); 7 hours (adjusted relative risk, 2.01; 95% confidence interval, 1.09–3.68); or ≥10 hours (adjusted relative risk, 2.17; 95% confidence interval, 1.01–4.67). Significant effect modification by napping frequency was also observed in the second trimester ( P for interaction = .03). Significant and positive association between reduced sleep (5-7 hours) and gestational diabetes was observed among women napping rarely/never (adjusted relative risk, 2.48; 95% confidence interval, 1.20–5.13), whereas no comparable associations were observed among women napping most/sometimes.
Conclusion
Our data suggest a U-shaped association between sleep duration and gestational diabetes, and that napping and prepregnancy obesity status may modify this association.
Introduction
Gestational diabetes mellitus (GDM), a common pregnancy complication affecting up to 13% of all pregnancies, is linked to several adverse health outcomes in both women and their children. Identifying modifiable risk factors of GDM is hence critical to prevent the growing burden of GDM and its long-term adverse health sequelae.
Evidence from experimental and observational studies suggests that both reduced and prolonged sleep duration are linked to impaired insulin sensitivity and glucose metabolism. Several underlying mechanisms have been proposed, including elevated oxidative stress, increased systemic inflammation, dysregulation of energy homeostasis, and chronic activation of the hypothalamic-pituitary-adrenal axis. Pregnant women are particularly vulnerable to sleep disturbances, owing to hormonal changes, physical discomfort, or anxiety surrounding childbirth. Whether sleep duration during pregnancy contributes to GDM risk is not clear as existing studies have been limited and conflicting. Prospective studies are particularly scarce, with only 1 study to date examining sleep duration in early pregnancy in relation to subsequent GDM risk.
In pregnancy, sleep patterns change across gestation. In the first trimester, sleep duration tends to increase, with this trend reversing in the second trimester. Compared to midpregnancy, napping is also more common toward the beginning and end of pregnancy, which may affect the total sleep exposure in a 24-hour period. Longitudinal assessments of sleeping and napping habits during pregnancy are hence needed to investigate the influence of sleep duration on GDM risk. The trimester-specific association between typical sleep duration and GDM risk, and the influence of compensatory daytime napping on this association has not yet been evaluated. In addition, although obesity is a risk factor for excessive sleepiness, its influence on the association between sleep duration and GDM during pregnancy is unknown.
In this study, our objective was to prospectively examine the trimester-specific association between self-reported sleep duration and subsequent GDM risk in a multiracial cohort of pregnant women. As a secondary objective, we examined whether daytime napping modifies the relation between sleep duration and GDM.
Materials and Methods
Study population
This prospective study was conducted on the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (2009 through 2013), consisting of 2334 nonobese pregnant women and 468 obese pregnant women between the ages of 18-40 years. Sample selection and eligibility criteria have been described in detail previously. Briefly, women with a history of chronic diseases such as hypertension, diabetes, or cancer were excluded. Eligible women were recruited between 8-13 weeks of gestation from 12 participating clinical sites across the United States and followed up throughout pregnancy. Institutional review board approval was obtained from all participating sites including NICHD. All participants provided informed consent.
The analytical population was composed of 2581 women (92.1%) with available medical records and sleep data at enrollment (8-13 weeks); 2% of the analytical sample (n = 51) were lost to follow-up at 16-22 weeks.
Exposure assessment
Structured questionnaires assessed sleep duration and napping frequency during the first (8-13 weeks) and second (16-22 weeks) trimesters. At both visits, participants were asked to indicate their typical sleep duration with possible responses including: ≤5, 6, 7, 8, 9, or ≥10 hours. Participants were also asked: “how often do you get so sleepy during the day or evening that you have to take a nap?” with possible responses including “most of the time,” “sometimes,” or “rarely or never.”
Outcome assessment
GDM diagnosis was abstracted from medical records (n = 107). The diagnosis was based on either the oral glucose tolerance test, using the Carpenter and Coustan diagnostic criteria or indication of medication-treated GDM on the hospital charge diagnosis (n = 12).
Covariates
Several covariates were examined, including sociodemographic variables such as age, race-ethnicity, education, and marital status; gestational age at interview; parity; and known risk factors of GDM including family history of diabetes, prior GDM, and prepregnancy body mass index (BMI) (calculated from self-reported weight and measured height at enrollment, kg/m 2 ). Participants also reported consumption of caffeinated beverages (coffee/tea/soda/energy drinks) during each trimester (cups) and consumption of alcoholic beverages before pregnancy. Smoking status in the 6 months prior to pregnancy was asked of the obese women; nonobese women who smoked before pregnancy were not eligible for this study.
Statistical analysis
Participant characteristics across sleep duration categories were compared using the χ 2 test for categorical data and 1-way analysis of variance for continuous variables. Poisson regression models (using log-link) with robust variance estimates were used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CI) for the association between typical sleep duration prior to GDM diagnosis and subsequent risk of GDM. Separate models were fitted for sleep duration in the first and second trimester. Typical sleep duration was categorized as 5-6, 7, 8-9, and ≥10 hours, with 8-9 hours as the reference group, to be comparable to prior studies. In the multivariable model, analyses were adjusted for a priori selected covariates including age, gestational age at interview, race-ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, Asian/Pacific Islander), nulliparity (yes, no), education (less, equal to or more than high-school), prepregnancy BMI, marital status (married/living with a partner or not), and family history of diabetes (yes, no). A second model further adjusted for napping frequency (most times, sometimes, rarely/never) at the corresponding trimester.
Caffeine consumption during pregnancy and alcohol consumption before pregnancy were not associated with GDM and hence were not considered in the multivariable models. Due to the small number of women (n = 17) who smoked before pregnancy, smoking status was not included in the multivariable models. In sensitivity analyses we excluded women who smoked before pregnancy (n = 17) and women with prior GDM (n = 32). Additionally, we assessed for effect modification by prepregnancy obesity status (BMI <30.0 vs ≥30.0 kg/m 2 ), race-ethnicity, family history of diabetes (yes vs no), napping frequency (most/sometimes vs rarely/never), and clinical site.
In sensitivity analyses, missing data (9.7%) were imputed with multiple imputation method, the majority of which stemmed from lack of medical chart abstraction. A total of 100 imputed datasets were created. There were no significant differences in age, race-ethnicity, education, parity, prepregnancy BMI, or family history of diabetes between women who were missing or not missing the medical chart. Women who were non-Hispanic white were more likely to be lost to follow-up at 16-22 weeks; none of the other key variables differed between those who were retained or lost to follow-up.
All tests were 2-tailed and P values < .05 were considered statistically significant for main effects and <.15 for interactions. Statistical analyses were completed using Software (SAS, Version 9.4; SAS Institute Inc Cary, NC).
Materials and Methods
Study population
This prospective study was conducted on the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (2009 through 2013), consisting of 2334 nonobese pregnant women and 468 obese pregnant women between the ages of 18-40 years. Sample selection and eligibility criteria have been described in detail previously. Briefly, women with a history of chronic diseases such as hypertension, diabetes, or cancer were excluded. Eligible women were recruited between 8-13 weeks of gestation from 12 participating clinical sites across the United States and followed up throughout pregnancy. Institutional review board approval was obtained from all participating sites including NICHD. All participants provided informed consent.
The analytical population was composed of 2581 women (92.1%) with available medical records and sleep data at enrollment (8-13 weeks); 2% of the analytical sample (n = 51) were lost to follow-up at 16-22 weeks.
Exposure assessment
Structured questionnaires assessed sleep duration and napping frequency during the first (8-13 weeks) and second (16-22 weeks) trimesters. At both visits, participants were asked to indicate their typical sleep duration with possible responses including: ≤5, 6, 7, 8, 9, or ≥10 hours. Participants were also asked: “how often do you get so sleepy during the day or evening that you have to take a nap?” with possible responses including “most of the time,” “sometimes,” or “rarely or never.”
Outcome assessment
GDM diagnosis was abstracted from medical records (n = 107). The diagnosis was based on either the oral glucose tolerance test, using the Carpenter and Coustan diagnostic criteria or indication of medication-treated GDM on the hospital charge diagnosis (n = 12).
Covariates
Several covariates were examined, including sociodemographic variables such as age, race-ethnicity, education, and marital status; gestational age at interview; parity; and known risk factors of GDM including family history of diabetes, prior GDM, and prepregnancy body mass index (BMI) (calculated from self-reported weight and measured height at enrollment, kg/m 2 ). Participants also reported consumption of caffeinated beverages (coffee/tea/soda/energy drinks) during each trimester (cups) and consumption of alcoholic beverages before pregnancy. Smoking status in the 6 months prior to pregnancy was asked of the obese women; nonobese women who smoked before pregnancy were not eligible for this study.
Statistical analysis
Participant characteristics across sleep duration categories were compared using the χ 2 test for categorical data and 1-way analysis of variance for continuous variables. Poisson regression models (using log-link) with robust variance estimates were used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CI) for the association between typical sleep duration prior to GDM diagnosis and subsequent risk of GDM. Separate models were fitted for sleep duration in the first and second trimester. Typical sleep duration was categorized as 5-6, 7, 8-9, and ≥10 hours, with 8-9 hours as the reference group, to be comparable to prior studies. In the multivariable model, analyses were adjusted for a priori selected covariates including age, gestational age at interview, race-ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, Asian/Pacific Islander), nulliparity (yes, no), education (less, equal to or more than high-school), prepregnancy BMI, marital status (married/living with a partner or not), and family history of diabetes (yes, no). A second model further adjusted for napping frequency (most times, sometimes, rarely/never) at the corresponding trimester.
Caffeine consumption during pregnancy and alcohol consumption before pregnancy were not associated with GDM and hence were not considered in the multivariable models. Due to the small number of women (n = 17) who smoked before pregnancy, smoking status was not included in the multivariable models. In sensitivity analyses we excluded women who smoked before pregnancy (n = 17) and women with prior GDM (n = 32). Additionally, we assessed for effect modification by prepregnancy obesity status (BMI <30.0 vs ≥30.0 kg/m 2 ), race-ethnicity, family history of diabetes (yes vs no), napping frequency (most/sometimes vs rarely/never), and clinical site.
In sensitivity analyses, missing data (9.7%) were imputed with multiple imputation method, the majority of which stemmed from lack of medical chart abstraction. A total of 100 imputed datasets were created. There were no significant differences in age, race-ethnicity, education, parity, prepregnancy BMI, or family history of diabetes between women who were missing or not missing the medical chart. Women who were non-Hispanic white were more likely to be lost to follow-up at 16-22 weeks; none of the other key variables differed between those who were retained or lost to follow-up.
All tests were 2-tailed and P values < .05 were considered statistically significant for main effects and <.15 for interactions. Statistical analyses were completed using Software (SAS, Version 9.4; SAS Institute Inc Cary, NC).
Results
From the first to second trimester, the proportion of women sleeping ≤7 hours increased (30.7% vs 36.2%), whereas the proportion of women sleeping ≥10 hours declined (24.4% vs 14.7%) considerably. Compared to the first trimester, fewer women napped most/sometimes (80.4% vs 54.4%) in the second trimester. Sleep duration in the first trimester varied significantly across several sociodemographic and lifestyle characteristics ( Table 1 ). For example, women who were younger, Hispanic, or nulliparous were more likely to sleep ≥10 hours, whereas those who were non-Hispanic white, married, or had greater education level were less likely to sleep ≥10 hours. Interestingly, women who reported napping most frequently in the first trimester were also most likely to sleep the most (≥10 hours) in a typical day. Similar sociodemographic and lifestyle patterns were observed with sleep duration in the second trimester, except for family history of diabetes, which was only associated with sleep duration in the first trimester.
| Characteristics | Sleep duration at 8–13 gestational wk | Sleep duration at 16–22 gestational wk | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall | 5–6 h | 7 h | 8–9 h | ≥10 h | P a | Overall | 5–6 h | 7 h | 8–9 h | ≥10 h | P a | |
| 2581 | 16% | 14.7% | 44.8% | 24.4% | 2530 | 15.4% | 20.8% | 49.1% | 14.7% | |||
| Age, y | 28.1 (5.5) | 28.5 (5.5) | 29.4 (5.3) | 28.5 (5.3) | 26.5 (5.6) | <.0001 | 28.2 (5.5) | 28.8 (5.5) | 29.5 (5.2) | 28.2 (5.4) | 25.5 (5.4) | <.0001 |
| Race/ethnicity | <.0001 | <.0001 | ||||||||||
| Non-Hispanic white | 27.2 | 22.5 | 31.3 | 34.0 | 15.4 | 27.7 | 19.7 | 36.5 | 31.2 | 11.6 | ||
| Non-Hispanic black | 27.7 | 38.0 | 23.9 | 19.4 | 28.5 | 27.6 | 40.3 | 20.2 | 22 | 43.3 | ||
| Hispanic | 28.7 | 27.4 | 25.0 | 28.5 | 32.3 | 28.6 | 27.4 | 23.2 | 29.7 | 33.6 | ||
| Asian/Pacific Islander | 16.3 | 12.1 | 19.7 | 17.9 | 13.8 | 16.2 | 12.6 | 20.2 | 17.1 | 11.6 | ||
| Education | <.0001 | <.0001 | ||||||||||
| <High school | 11.4 | 11.1 | 8.2 | 9.9 | 16.2 | 11.3 | 11.3 | 5.3 | 10.5 | 22.3 | ||
| High-school graduate or equivalent | 18.4 | 21.6 | 10.8 | 16.7 | 24.1 | 18.3 | 18.5 | 11.2 | 18.4 | 28.0 | ||
| >High school | 70.2 | 67.3 | 81.1 | 73.4 | 59.8 | 70.4 | 70.3 | 83.5 | 71.2 | 49.7 | ||
| Married/living with partner | 74.4 | 69.0 | 79.5 | 79.6 | 65.2 | <.0001 | 74.4 | 68.6 | 80.8 | 78.3 | 58.1 | <.0001 |
| Nulliparity | 46.8 | 35.3 | 39.5 | 48.3 | 55.9 | <.0001 | 47.0 | 35.1 | 46.6 | 50.0 | 49.7 | <.0001 |
| Smoking before pregnancy | 0.7 | 0.2 | 0.8 | 0.9 | 0.5 | .52 | 0.6 | 1.3 | 0.8 | 0.5 | 0.3 | .26 |
| Family history of diabetes | 21.8 | 28.7 | 22.9 | 19.7 | 20.5 | .002 | 21.8 | 23.4 | 20.4 | 21.8 | 21.9 | .75 |
| Alcoholic beverage consumption before pregnancy | 64.6 | 62.2 | 71 | 66 | 59.8 | .002 | 64.8 | 62.1 | 73.2 | 64.5 | 57.0 | <.0001 |
| Prepregnancy BMI, kg/m 2 | 25.5 (5.2) | 26.3 (5.8) | 25.1 (5.0) | 25.2 (5.0) | 25.5 (5.2) | .001 | 25.5 (5.2) | 26.1 (5.5) | 25.2 (5.3) | 25.3 (5.1) | 25.8 (5.4) | .016 |
| Prepregnancy BMI categories | .03 | .02 | ||||||||||
| 17.87–24.99 kg/m 2 | 56.4 | 51.0 | 59.4 | 57.6 | 56.0 | 56.5 | 51.2 | 60.8 | 57.2 | 53.5 | ||
| 25.0–29.99 kg/m 2 | 26.5 | 27.1 | 26.8 | 26.7 | 25.4 | 26.3 | 27.9 | 23.7 | 27.2 | 25.5 | ||
| 30.00–48.83 kg/m 2 | 17.1 | 21.9 | 13.8 | 15.7 | 18.7 | 17.2 | 20.9 | 15.5 | 15.6 | 20.9 | ||
| Need day nap during corresponding wk | ||||||||||||
| Most of time | 42.9 | 41.0 | 34.0 | 35.4 | 63.4 | <.0001 | 20.8 | 27.2 | 13.9 | 15.0 | 43.7 | <.0001 |
| Sometimes | 37.6 | 39.1 | 38.7 | 42.0 | 27.7 | 35.6 | 31 | 33.5 | 38.2 | 35 | ||
| Rarely or never | 19.5 | 19.9 | 27.4 | 22.6 | 8.9 | 43.5 | 41.8 | 52.7 | 46.9 | 21.3 | ||
| Gestational age during interview, wk | 12.7 (1.0) | 12.7 (0.9) | 12.8 (0.9) | 12.7 (1.0) | 12.6 (1.0) | .03 | 19.7 (2.4) | 19.7 (2.4) | 20.1 (2.5) | 19.7 (2.4) | 19.4 (2.4) | .001 |
| Caffeinated beverages consumed, cups | 0.41 (0.8) | 0.46 (0.9) | 0.33 (0.7) | 0.36 (0.7) | 0.37 (0.9) | .08 | 0.41 (0.8) | 0.43 (0.8) | 0.40 (0.7) | 0.40 (0.8) | 0.44 (0.9) | .8 |
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