Objective
We sought to examine the effect of maternal sleep-disordered breathing (SDB) on infant general movements (GMs) and neurodevelopment.
Study Design
Pregnant women with uncomplicated full-term pregnancies and their offspring were prospectively recruited from a community and hospital low-risk obstetric surveillance. All participants completed a sleep questionnaire on second trimester and underwent ambulatory sleep evaluation (WatchPAT; Itamar Medical, Caesarea, Israel). They were categorized as SDB (apnea hypopnea index >5) and controls. Infant GMs were assessed in the first 48 hours and at 8-11 and 14-16 weeks of age. At 12 months of age the Infant Developmental Inventory and the Brief Infant Sleep Questionnaire were administered.
Results
In all, 74 women and their full-term infants were studied. Eighteen (24%) women had SDB. Mean birthweight was 3347.1 ± 423.9 g. Median Apgar score at 5 minutes was 10 (range, 8–10). In adjusted comparisons, no differences were found between infants born to mothers with SDB and controls in GM scores in all 3 evaluations. Low social developmental score was detected at 12 months in 64% of infants born to SDB mothers compared to 25% of infants born to controls (adjusted P = .036; odds ratio, 16.7). Infant snoring was reported by 41.7% of mothers with SDB compared to 7.5% of controls ( P = .004).
Conclusion
Our preliminary results suggest that maternal SDB during pregnancy has no adverse effect on neonatal and infant neuromotor development but may affect social development at 1 year.
Pregnancy is associated with significant changes in sleep with a large proportion of pregnant women experiencing some form of sleep disruption. Physiologic and hormonal changes that occur during pregnancy, particularly during the third trimester, place women at risk for developing sleep-disordered breathing (SDB). Indeed, SDB is common during pregnancy and self-reported snoring has been observed in up to 46% of pregnant women. The term “sleep-disordered breathing” refers to a spectrum of abnormal respiration during sleep that ranges from primary (habitual) snoring to obstructive sleep apnea syndrome. It is characterized by episodic complete or partial obstruction of the airway during sleep, disruption of normal ventilation, intermittent hypoxemia, and sleep fragmentation.
It has been suggested that SDB during pregnancy may adversely influence the maternal and fetal well-being. Specifically, associations between SDB during pregnancy and gestational diabetes, hypertension and preeclampsia, fetal growth restriction, prematurity, cesarean delivery, and low Apgar scores have been reported. However, these observations have thus far been inconclusive, one of the reasons being that most of the published literature is based on subjective assessment of sleep and lacks objective sleep measures.
Despite this inconsistency, in a recent study we found that maternal snoring was associated with enhanced fetal erythropoiesis and elevated cord interleukin 6. We therefore hypothesized that maternal SDB with the resultant subtle intermittent hypoxia could influence the developing fetal brain.
To our knowledge, there are no reports on the effect of maternal SDB on infant neurodevelopmental status despite the ostensibly large body of data regarding the association of pediatric SDB with attention deficit, hyperactivity, and emotional and behavioral disturbances. For all these reasons, we designed a prospective study using an objective sleep study measure to investigate the effects of maternal SDB on their infants. We hypothesized that infants born to mothers with SDB will exhibit lower developmental scores.
Our aims were to determine the effect of maternal SDB on neonatal and infant spontaneous general movements (GMs) and developmental outcome at 1 year.
Materials and Methods
Women in the third trimester of a singleton, uncomplicated pregnancy who attended low-risk obstetric surveillance from March 2009 through March 2012 were recruited. All participants completed a sleep questionnaire during the second trimester and underwent a sleep study during the third trimester of pregnancy. Infant GMs were assessed during the first 4 months of life. Development and sleep questionnaires were administered at 12 months. The study design and recruitment flowchart are presented in the Figure .
The study was approved by the institutional review board. The study was registered at ClinicalTrials.gov (NCT00931099). Informed consent was obtained from all participants.
Maternal and infant data
All women completed a sleep questionnaire (gestational week 25-27) regarding the presence of habitual snoring before and during pregnancy. Habitual snoring was defined as snoring at least 3 nights per week. Pregnancy-onset snoring was considered present when habitual snoring began during pregnancy. All participants underwent an ambulatory overnight sleep study between 33-36 weeks of gestation using a validated ambulatory sleep technology (WatchPAT 200; Itamar Medical, Caesarea, Israel). Apnea hypopnea index, respiratory disturbance index, oxygen desaturation index, mean oxygen saturation (SpO2) and SpO2 nadirs were retrieved as previously described. Women with an apnea hypopnea index >5 per hour of sleep were considered to have SDB. We used the standard adult criteria for SDB, since there is no distinctive threshold for SDB in pregnancy. Medical records review was conducted by one of the researchers blinded to the sleep study results. Pertinent demographic (sex, gestational age, birthweight) and clinical (mode of delivery, Apgar scores at 1 and 5 minutes, and any perinatal complications) information were collected.
Outcome data
Spontaneous GMs assessment of infants
GMs were videotaped (15 minutes in length) for offline assessment in the first 48 hours of life, between 8-11 weeks of age, and between 14-16 weeks of age postterm. All infants were dressed in a diaper only, and were in the supine position. During off-time replay of the 3 periods videotaped, the GM quality was analyzed and assessed by an independent trained observer and the data scored. GMs were scored when infants were in active wakefulness. Periods of crying, fussing, and sucking were excluded from analysis. The observer was unaware of the infant’s group assignment (maternal SDB yes/no) as well as of other test results and clinical data.
Sleep evaluation at the age of 1 year
Sleep was evaluated at 1 year of age using the Brief Infant Sleep Questionnaire (BISQ). The BISQ is a validated sleep questionnaire assessing the infant’s typical sleep patterns based on parental reports. A yes/no question regarding snoring at the age of 1 year was added to the BISQ.
Socioeconomic status
The modified, 2-factor index Hollingshead scale was used for determining the infant’s socioeconomic status. The maternal and paternal scores were averaged.
Developmental questionnaire at the age of 1 year
At 1 year of age the developmental level was evaluated using the Infant Developmental Inventory questionnaire. This screening instrument is a parental report of the infant’s developmental skills in 5 areas (gross motor, fine motor, social, self-help, and language). The instrument shows age-appropriate standards from which an estimated developmental age was recorded for each subdomain. An estimated developmental age, divided by the infant’s chronological age, and multiplied by 100, yielded the subdomain developmental quotient. Averaging all 5 subdomains yields a total score for general developmental function, also expressed as developmental quotient.
Statistical analysis
The statistical analyses were performed with software (SPSS, version 19.0; IBM Corp, Armonk, NY). Comparisons of variables were conducted between infants born to women with SDB (study group) and infants born to non-SDB mothers (controls). Comparisons of variables according to group assignment were performed with independent t tests for continuous variables, and the χ 2 analyses for categorical variables. Linear and logistic regression analyses were performed for several dependent variables and were adjusted for the following confounders: gestational age, birthweight, sex, 5-minute Apgar score, and socioeconomic status. All reported P values are 2-tailed with statistical significance set at P < .05.
Results
In all, 74 healthy women completed a sleep questionnaire and underwent ambulatory sleep evaluation. Infant spontaneous GMs and 1-year developmental inventory were administered to 62 and 51 subjects, respectively ( Figure ). We were unable to obtain complete outcome data in all infants due to unavailability of parents or investigators. The demographic characteristics of the 23 children with a missing 1-year developmental inventory were similar to those with a complete developmental questionnaire (mean gestational age: 39.4 ± 1.3 vs 38.9 ± 1.3, P = .14, and mean birthweight: 3391.3 ± 393.4 vs 3284.8 ± 464.4 g, P = .35). No participants had maternal or pregnancy-related complications such as hypertension, gestational diabetes, infection, or fetal growth restriction. Twenty-nine (39%) women reported habitual snoring. Ten (13%) were habitual snorers before and during pregnancy and 19 (26%) were pregnancy-onset snorers. Eighteen (24%) women met our criteria for SDB and 56 served as a control group. Of the 18 women with SDB, 5 did not report snoring, 4 reported snoring before and during pregnancy, and 9 reported pregnancy-onset snoring by questionnaire. Except for 2 premature deliveries at 36 weeks of gestation, all infants were born at term. In all, 45 (61%) newborns were male. Comparison of maternal and newborn characteristics as well as maternal sleep measures between the study group (SDB) and the controls are presented in Table 1 .
| Characteristic | SDB (n = 18) | Controls (n = 56) | P value |
|---|---|---|---|
| Maternal | |||
| Age, y | 33.1 ± 3.7 | 32.7 ± 4.6 | .78 |
| BMI prepregnancy | 25.3 ± 4.3 | 21.9 ± 2.5 | .005 |
| Delivery | |||
| Normal | 14 (78%) | 42 (75%) | .95 |
| Cesarean | 3 (17%) | 11 (20%) | |
| Instrumental | 1 (6 %) | 3 (5%) | |
| Gravida, median (range) | 2.0 (1.0–7.0) | 2.0 (1.0–5.0) | .84 |
| Para, median (range) | 2.0 (1.0–3.0) | 1.0 (1.0–3.0) | .13 |
| Total sleep time, min | 334.4 ± 58.0 | 344.0 ± 83.0 | .60 |
| Respiratory disturbance index | 14.4 ± 5.7 | 6.1 ± 3.2 | < .0001 |
| Apnea hypopnea index | 11.2 ± 5.1 | 1.3 ± 1.4 | < .0001 |
| Oxygen desaturation index | 3.1 ± 1.9 | 0.3 ± 0.4 | < .0001 |
| Mean SpO2 | 94.7 ± 0.9 | 96.1 ± 0.9 | < .0001 |
| SpO2 nadir | 89.6 ± 2.3 | 93.1 ± 2.2 | < .0001 |
| Newborn | |||
| Male sex | 10 (56%) | 35 (63%) | .64 |
| Apgar 1, median (range) | 9 (4–9) | 9 (3–9) | .14 |
| Apgar 5, median (range) | 10 (8–10) | 10 (9–10) | .85 |
| Gestational age, wk | 39.3 ± 1.4 | 39.2 ± 1.4 | .13 |
| Birthweight, g | 3371.0 ± 454.6 | 3356.7 ± 419.9 | .9 |
| Cord PH | 7.28 ± 0.08 | 7.29 ± 0.09 | .81 |
General movements
The 3 sequential assessments of GMs were administered to 62 infants. No significant differences were found between the 2 groups before and after adjustment ( Table 2 ).
| GM | Maternal SDB (n = 17) | Controls (n = 45) | P value | P value a |
|---|---|---|---|---|
| First 48 h | 14.2 ± 3.9 | 15.0 ± 3.7 | .47 | .27 |
| 8-11 wk | 22.5 ± 7.8 | 22.8 ± 7.3 | .99 | .98 |
| 14-16 wk | 22.9 ± 8.1 | 23.8 ± 6.4 | .66 | .37 |
| Total score | 19.1 ± 7.3 | 20.5 ± 5.5 | .56 | .19 |
a Derived from linear regression analysis adjusted for gestational age, birthweight, sex, and Apgar score at 5 min.
Outcome at 12 months
The Infant Developmental Inventory questionnaire was administered at 1 year of age to 51 subjects (11 from the SDB group and 40 from the control group). As shown in Table 3 , no significant differences were found in the gross and fine motor, language, and self-help developmental scores between the 2 groups. Of note, the mean social developmental scores were lower in the study group when compared to the controls and almost reached statistical significance (97.8 ± 19.7 vs 114.9 ± 28.3, P = .067). A social developmental score <100 was detected in 7 (64%) infants born to SDB mothers compared to 10 (25%) controls (adjusted P = .036; odds ratio, 16.7).
| Variable | SDB (n = 11) | Controls (n = 40) | P value | P value a | OR |
|---|---|---|---|---|---|
| Age, mo | 12.9 ± 1.6 | 13.0 ± 1.4 | .88 | ||
| Male sex | 5 (45%) | 24 (60%) | .34 | ||
| Parental socioeconomic status | 24.2 ± 2.8 | 26.9 ± 7.5 | .36 | ||
| Social score | 97.8 ± 19.7 | 114.9 ± 28.3 | .067 | .13 | |
| Social score <100, n (%) | 7 (64) | 10 (25) | .029 | .036 | 16.7 |
| Self-help score | 115.3 ± 9.7 | 115.2 ± 21.0 | .93 | .63 | |
| Self-help score <100, n (%) | 2 (18) | 0 (0) | .13 | .99 | |
| Gross motor score | 114.7 ± 31.7 | 115.2 ± 21.0 | .95 | .43 | |
| Gross motor score <100, n (%) | 4 (36) | 8 (20) | .28 | .11 | 4.5 |
| Fine motor score | 115.6 ± 21.2 | 115.2 ± 21.1 | .95 | .59 | |
| Fine motor score <100, n (%) | 1 (9) | 7 (18) | .46 | .54 | 0.47 |
| Language score | 114.7 ± 21.6 | 117.0 ± 19.2 | .74 | .57 | |
| Language score <100, n (%) | 3 (27) | 5 (13) | .27 | .15 | 6.2 |
| Total developmental score | 111.6 ± 17.4 | 114.3 ± 18.2 | .66 | .34 | |
| Total score <100, n (%) | 3 (27) | 6 (15) | .39 | .13 | 6.3 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
