Longitudinal and prospective assessment of prenatal maternal sleep quality and associations with newborn hippocampal and amygdala volume.

BACKGROUND: The rapid maturation of the fetal brain renders the fetus susceptible to prenatal environmental signals. Prenatal maternal sleep quality is known to have important health implications for newborns including risk for preterm birth, however, the effect on the fetal brain is poorly understood. METHOD: Participants included 94 pregnant participants and their newborns (53% female). Pregnant participants (Mage = 30; SDage= 5.29) reported on sleep quality three times throughout pregnancy. Newborn hippocampal and amygdala volumes were assessed using structural magnetic resonance imaging. Multilevel modeling was used to test the associations between trajectories of prenatal maternal sleep quality and newborn hippocampal and amygdala volume. RESULTS: The overall trajectory of prenatal maternal sleep quality was associated with hippocampal volume (left: b = 0.00003, p = 0.013; right: b = 0.00003, p = .008). Follow up analyses assessing timing of exposure indicate that poor sleep quality early in pregnancy was associated with larger hippocampal volume bilaterally (e.g., late gestation left: b = 0.002, p = 0.24; right: b = 0.004, p = .11). Prenatal sleep quality was not associated with amygdala volume. CONCLUSION: These findings highlight the implications of poor prenatal maternal sleep quality and its role in contributing to newborn hippocampal development.

Distinct mortality patterns at 0-2 days versus the remaining neonatal period: results from population-based assessment in the Indian state of Bihar.

BACKGROUND: The objectives of this study were to understand the differences in mortality rate, risk factors for mortality, and cause of death distribution in three neonatal age sub-groups (0-2, 3-7, and 8-27 days) and assess the change in mortality rate with previous assessments to inform programmatic decision-making in the Indian state of Bihar, a large state with a high burden of newborn deaths. METHODS: Detailed interviews were conducted in a representative sample of 23,602 live births between January and December 2016 (96.2% participation) in Bihar state. We estimated the neonatal mortality rate (NMR) for the three age sub-groups and explored the association of these deaths with a variety of risk factors using a hierarchical logistic regression model approach. Verbal autopsies were conducted using the PHMRC questionnaire and the cause of death assigned using the SmartVA automated algorithm. Change in NMR from 2011 to 2016 was estimated by comparing it with a previous assessment. RESULTS: The NMR 0-2-day, 3-7-day, and 8-27-day mortality estimates in 2016 were 24.7 (95% CI 21.8-28.0), 13.2 (11.1 to 15.7), 5.8 (4.4 to 7.5), and 5.8 (4.5 to 7.5) per 1000 live births, respectively. A statistically significant reduction of 23.3% (95% CI 9.2% to 37.3) was seen in NMR from 2011 to 2016, driven by a reduction of 35.3% (95% CI 18.4% to 52.2) in 0-2-day mortality. In the final regression model, the highest odds for mortality in 0-2 days were related to the gestation period of ≤ 8 months (OR 16.5, 95% CI 11.9-22.9) followed by obstetric complications, no antiseptic cord care, and delivery at a private health facility or home. The 3-7- and 8-27-day mortality was driven by illness in the neonatal period (OR 10.33, 95% CI 6.31-16.90, and OR 4.88, 95% CI 3.13-7.61, respectively) and pregnancy with multiple foetuses (OR 5.15, 95% CI 2.39-11.10, and OR 11.77, 95% CI 6.43-21.53, respectively). Birth asphyxia (61.1%) and preterm delivery (22.1%) accounted for most of 0-2-day deaths; pneumonia (34.5%), preterm delivery (33.7%), and meningitis/sepsis (20.1%) accounted for the majority of 3-7-day deaths; meningitis/sepsis (30.6%), pneumonia (29.1%), and preterm delivery (26.2%) were the leading causes of death at 8-27 days. CONCLUSIONS: To our knowledge, this is the first study to report a detailed neonatal epidemiology by age sub-groups for a major Indian state, which has highlighted the distinctly different mortality rate, risk factors, and causes of death at 0-2 days versus the rest of the neonatal period. Monitoring mortality at 0-2 and 3-7 days separately in the traditional early neonatal period of 0-7 days would enable more effective programming to reduce neonatal mortality.

Cervical pathways for racial disparities in preterm births: the Preterm Prediction Study.

Purpose: Racial disparities in preterm birth have been long recognized, but the social and biological mechanisms for these differences are unclear. Our analysis had three goals: (1) to determine the relation between race and other social risk factors and cervical structure; (2) to determine whether social factors mediate the relation between race and cervical structure; and (3) to determine whether racial disparities in preterm birth (PTB) are mediated through changes in cervical structure observed earlier in pregnancy. Materials and methods: Data from the Maternal Fetal Medicine Unit network Preterm Prediction Study were used to examine the relation between race and other social factors and cervical properties throughout pregnancy in 2920 black and white women. Outcomes included cervical length and dilation; cervical score (cervical length-internal dilation); and whether membranes protruded at 22-24 and 26-29 weeks. Race, education, income, insurance type, and marital status were examined as predictors of the outcomes using linear and logistic regression, adjusting for age, BMI, parity, and smoking. Mediation analysis was used to examine whether (a) any social factors explained racial differences in cervical properties, and (b) whether cervical properties mediated racial differences in risk for preterm birth. Results: Shorter cervical length, especially at a subject's first visit, was associated with black race (adjusted beta -1.56 mm, p < .01) and lower income (adjusted beta -1.48, p =.05). External dilation was not associated with social factors, while internal dilation was associated with black race and lower education. Black race and marital status were associated with lower cervical score. There was no evidence of mediation of the racial effect on cervical properties by any social factor. Shorter cervical length, dilation, and score were all associated with preterm birth (p < .01). Mediation analysis indicated that each of these mediated the effect of race, but explained a small proportion of the total effect (15-25%). Conclusions: Race, and, to a lesser extent, other social factors are correlated with adverse cervical properties. This pathway could explain a proportion of the racial disparity in preterm birth.

Reproducibility of Retinal Microvascular Traits Decoded by the Singapore I Vessel Assessment Software Across the Human Age Range.

BACKGROUND: Retinal microvascular traits predict adverse health outcomes. The Singapore I Vessel Assessment (SIVA) software improved automated postprocessing of retinal photographs. In addition to microvessel caliber, it generates measures of arteriolar and venular geometry. Few studies addressed the reproducibility of SIVA measurements across a wide age range. METHODS: In the current study, 2 blinded graders read images obtained by nonmydriatic retinal photography twice in 20 11-year-old children, born prematurely (n = 10) or at term (n = 10) and in 60 adults (age range, 18.9-86.1 years). RESULTS: Former preterm compared with term children had lower microvessel diameter and disorganized vessel geometry with no differences in intraobserver and interobserver variability. Among adults, microvessel caliber decreased with age and blood pressure and arteriolar geometry was inversely correlated with female sex and age. Intraobserver differences estimated by the Bland-Altman method did not reach significance for any measurement. Across measurements, median reproducibility (RM) expressed as percent of the average trait value was 8.8% in children (median intraclass correlation coefficient [ICC], 0.94) and 8.0% (0.97) in adults. Likewise, interobserver differences did not reach significance with RM (ICC) of 10.6% (0.85) in children and 10.4% (0.93) in adults. Reproducibility was best for microvessel caliber (intraobserver/interobserver RM, 4.7%/6.0%; ICC, 0.98/0.96), worst for venular geometry (17.0%/18.8%; 0.93/0.84), and intermediate for arteriolar geometry (10.9%/14.9%; 0.95/0.86). CONCLUSIONS: SIVA produces repeatable measures of the retinal microvasculature in former preterm and term children and in adults, thereby proving its usability from childhood to old age.

Assessment of Uterocervical Angle Width as a Predictive Factor of Preterm Birth: A Systematic Review of the Literature.

BACKGROUND: Uterocervical angle (UCA) has been recently proposed as a potential marker that could accurately predict preterm birth (PTB). The purpose of the present systematic review is to accumulate current evidence and provide directions for future research. MATERIALS AND METHODS: We used the Medline (1966-2018), Scopus (2004-2018), Clinicaltrials.gov (2008-2018), EMBASE (1980-2018), Cochrane Central Register of Controlled Trials CENTRAL (1999-2018), and Google Scholar (2004-2018) databases in our search. RESULTS: Eleven studies were finally included in the present systematic review that evaluated data from 3,018 women. The significant heterogeneity in terms of outcome reporting and outcome reporting measures (use of optimal cut-off values) precluded meta-analysis. However, existing data support that second trimester UCA measurement might be used as a predictive factor of PTB <34 weeks, as at least two studies in unselected singleton pregnancies and two studies in pregnancies with an ultrasonographically shortened cervix seem to support this hypothesis. The most commonly reported cut-off values were 105° and 95°. CONCLUSIONS: UCA measurement during the second trimester of pregnancy may be a useful method of determining women at risk of delivering preterm. However, more studies are needed to assess the reproducibility of these findings and reach conclusive evidence.

Body mass index and weight-for-length ratio references for infants born at 33-42 weeks gestation: a new tool for anthropometric assessment.

BACKGROUND & AIMS: The risk of childhood obesity, an increasingly prevalent problem worldwide, might be predictable by early body mass index measurements. This study sought to develop body mass index and weight-for-length ratio references for infants born at 33-42 weeks gestation and to validate these data against the growth curves of the World Health Organization Multicenter Growth Reference Study. METHODS: Data were collected from the Neonatal Registry of Rabin Medical Center for all healthy singleton babies born live at 33-42 weeks gestation. Crude and smoothed reference tables and graphs for body mass index and weight-for-length ratio by gestational age were created for males and females, separately. RESULTS: Birth weight, length, and body mass index percentiles for full-term neonates were similar to the World Health Organization study, reinforcing the generalizability of our reference charts for infants born at 33-42 weeks. Cutoff values for small for date (<5th, <10th percentile) and large for date (>85th, >95th percentile) infants differed across gestational ages in both pre-term and full-term infants. CONCLUSIONS: As body proportionality indexes provide an assessment of body mass and fatness relative to length, we suggest that BMI and Wt/L ratio percentiles be added to weight and length growth curves as a routine intrauterine growth assessment at birth.

Proteomics of the amniotic fluid in assessment of the placenta. Relevance for preterm birth.

Proteomics is the study of expressed proteins and has emerged as a complement to genomic research. The major advantage of proteomics over DNA-RNA based technologies is that it more closely relates to phenotypes and not the source code. Proteomics thus holds the promise of providing a direct insight into the true mechanisms of human diseases. Historically, examination of the placenta has been the first modality to subclassify pathogenetic entities responsible for preterm birth. Because placenta is a key pathophysiological participant in several major obstetrical syndromes (preterm birth, pre-eclampsia, intrauterine growth restriction) identification of relevant biomarkers of placental function can profoundly impact on the prediction of fetal outcome and treatment efficacy. Since proteomics is a young science and studies that associate proteomic patterns with long-term outcome require follow-up of children up to school age, using placental pathological footprints of cellular injury as intermediate outcomes can be useful in the interim. Furthermore, knowledge on the identity of the dysregulated proteins may provide the needed breakthrough insight into novel pathophysiological pathways and unravel possible targets for therapeutical intervention that could not have been envisioned through hypothesis-driven approaches.

Is sonographic assessment of cervical length better than digital examination in screening for preterm delivery in a low-risk population?

BACKGROUND: This randomized controlled trial compared the diagnostic accuracy of the sonographic assessment of cervical length and clinical digital examination of the cervix in the second trimester regarding the prediction of preterm delivery in a low-risk population. METHODS: In total, 282 unselected, asymptomatic women with singleton pregnancy randomly underwent sonographic cervical length measurement (study group, n=138) or clinical digital examination (control group, n=144) in the second trimester. In the study group cervical length or=95th percentile (>or=4) for our population was defined as high. The primary outcome measure was the diagnostic accuracy of both tests regarding the prediction of preterm delivery (<37 weeks). RESULTS: Shortened cervical length was found in 6/138 (4.3%) women whereas the high Bishop score was found in 17/144 (11.8%) (p=0.038, Fisher's exact test). The incidence of preterm delivery was 5.7% (16/282). Regarding the prediction of preterm delivery, shortened cervical length and high Bishop score had sensitivity 57.1% versus 33.3% and positive predictive value 66.7% versus 17.6%. Shortened cervical length in comparison with high Bishop score had 12-fold higher positive likelihood ratio for preterm delivery in a low-risk population (37.4; 95%CI [8.2-170.7] versus 3.2; 95%CI [1.1-9.2]). CONCLUSION: Sonographic assessment of cervical length has better diagnostic accuracy in the prediction of preterm delivery compared to digital examination in a low-risk population.