Characterization of METTL16 as a cytoplasmic RNA binding protein.

mRNA modification by N6-methyladenosine (m6A) is involved in many post-transcriptional regulation processes including mRNA stability, splicing and promotion of translation. Accordingly, the recently identified mRNA methylation complex containing METTL3, METTL14, and WTAP has been the subject of intense study. However, METTL16 (METT10D) has also been identified as an RNA m6A methyltransferase that can methylate both coding and noncoding RNAs, but its biological role remains unclear. While global studies have identified many potential RNA targets of METTL16, only a handful, including the long noncoding RNA MALAT1, the snRNA U6, as well as the mRNA MAT2A have been verified and/or studied to any great extent. In this study we identified/verified METTL16 targets by immunoprecipitation of both endogenous as well as exogenous FLAG-tagged protein. Interestingly, exogenously overexpressed METTL16 differed from the endogenous protein in its relative affinity for RNA targets which prompted us to investigate METTL16's localization within the cell. Surprisingly, biochemical fractionation revealed that a majority of METTL16 protein resides in the cytoplasm of a number of cells. Furthermore, siRNA knockdown of METTL16 resulted in expression changes of a few mRNA targets suggesting that METTL16 may play a role in regulating gene expression. Thus, while METTL16 has been reported to be a nuclear protein, our findings suggest that METTL16 is also a cytoplasmic methyltransferase that may alter its RNA binding preferences depending on its cellular localization. Future studies will seek to confirm differences between cytoplasmic and nuclear RNA targets in addition to exploring the physiological role of METTL16 through long-term knockdown.

African American and Latino patient versus provider perceptions of determinants of prenatal care initiation.

Few studies have compared provider and patient perceptions of barriers, motivators and facilitators of prenatal care (PNC) initiation. The current study compared these perceptions in providers and patients in Washington, DC, a city characterized by infant mortality and low birth weight rates that are among the highest in the nation, and poor utilization of PNC, particularly among minority groups. The results reported here were part of a larger study of barriers, motivators and facilitators influencing PNC utilization in Washington, DC. A convenience sample of 331 African American and Latino patients and 61 providers were interviewed to identify which of 63 motivators, facilitators, and barriers significantly influenced PNC initiation. Both sample groups were recruited at 14 PNC facilities, selected to represent all sites in DC known to serve high-risk, low-income minority women, including hospital-based clinics, community-based clinics, and private practices. Data were analyzed using Fisher exact tests and Kendall's concordance tests. Results indicated that there was good agreement between patients and providers about the relative importance of the various barriers (especially psychosocial), motivators, and facilitators. However, differences were found between patients and providers in the response frequencies. Providers were more likely to report barriers while patients were more likely to report certain motivators (especially learning better health habits and how to protect health). These results indicate that despite widespread agreement on most issues, especially psychosocial barriers, patients rated health education higher than providers.

Relationships of Pubertal Development Among Early Adolescents to Sexual and Nonsexual Risk Behaviors and Caregivers' Parenting Behaviors.

Using a school-based sample of Washington, DC, fifth graders (mean age 10.38, SD = 0.66) and their parents (N = 408), we examined associations of pubertal development with early adolescents' sexual and nonsexual risk behaviors and their caregivers' parenting behaviors; and of these risk behaviors with parenting behaviors. Youths reporting signs of pubertal development were more likely to engage in these risk behaviors than students reporting no signs. Pubertal development was not related to parenting behaviors; however, parents of youths who reported multiple nonsexual risk behaviors reported more parent-child communication about sexual topics. These results highlight the need to begin risk prevention efforts early, prior to pubertal development. Research is needed to understand how parents can help youths better cope with pubertal development to avoid involvement in sexual and nonsexual risk behaviors.

Patterns of alcohol consumption among pregnant African-American women in Washington, DC, USA.

The objective of this paper is to describe the patterns and associated behaviours related to alcohol consumption among a selected sample of pregnant women seeking prenatal care in inner city Washington DC. Women receiving prenatal care at one of nine sites completed an anonymous alcohol-screening questionnaire. Questions concerned the amount, type and pattern of alcohol consumption. Women were categorised as at no, low, moderate or high risk for alcohol consumption during pregnancy. For comparisons of risk levels of drinking, bivariate associations were examined using Fisher's exact test. Odds ratios (ORs) and 95% confidence intervals (CIs) were also computed. Although 31% of current/recent drinkers stated that they continued to drink during pregnancy, responses to quantity/frequency questions revealed that 42% continued to do so. Women who were at high compared with moderate risk acknowledged that others were worried about their consumption [OR=4.0, 95% CI 1.5, 10.6], that they drank upon rising [OR=6.7, 95% CI 1.8, 26.9], had a need to reduce drinking [OR=3.2, 95% CI 1.3, 8.1] and in the past 5 years had had fractures [OR=4.2, 95% CI 1.0, 17.8] or a road traffic injury [OR=3.4, 95% CI 1.0, 12.2]. Women in the high/moderate compared with low-risk group were more likely to have been injured in a fight or assault [OR=2.7, 95% CI 1.3, 5.6]. This study validated the usefulness of our questionnaire in identifying women who were at risk for alcohol consumption during pregnancy across a range of consumption levels. Using our screening tool, women were willing to disclose their drinking habits. This low-cost method identifies women appropriate for targeting of interventions.

Clinical data predict neurodevelopmental outcome better than head ultrasound in extremely low birth weight infants.

OBJECTIVE: To determine the relative contribution of clinical data versus head ultrasound scanning (HUS) in predicting neurodevelopmental impairment (NDI) in extremely low birth weight infants. STUDY DESIGN: A total of 2103 extremely low birth weight infants (<1000 g) admitted to a National Institute of Child Health and Human Development Neonatal Research Network center who underwent HUS within the first 28 days, a repeat one around 36 weeks' postmenstrual age, and neurodevelopmental assessment at 18 to 22 months corrected age were selected. Multivariate logistic regression models were developed with clinical or HUS variables. The primary outcome was the predictive abilities of the HUS performed before 28 days after birth and closer to 36 weeks postmenstrual age, either alone or in combination with "Early" and "Late" clinical variables. RESULTS: Models with clinical variables alone predicted NDI better than models with only HUS variables at both 28 days and 36 weeks (both P < .001), and the addition of the HUS data did not improve prediction. NDI was absent in 30% and 28% of the infants with grade IV intracranial hemorrhage or periventricular leukomalacia, respectively, but was present in 39% of the infants with a normal HUS result. CONCLUSIONS: Clinical models were better than HUS models in predicting neurodevelopment.

Determinants of inadequate prenatal care utilization by African American women.

A convenience sample of city-dwelling African American women (n=246) was interviewed during each woman's postpartum stay at one of five hospitals in Washington, D.C. to determine their perceptions of factors influencing their prenatal care utilization. The Kotelchuck Adequacy of Prenatal Care Utilization Index was used to classify prenatal care utilization as either adequate (Adequate Plus and Adequate groups combined) or inadequate (Intermediate and Inadequate groups combined). Of the 246 women studied, 40% (99) had adequate prenatal care utilization. Using Classification and Regression Trees analysis, the following risk groups for inadequate prenatal care utilization were identified: women who reported psychosocial problems as barriers and who were not participants in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) (percent adequate=8.8); women who reported psychosocial problems as barriers, were participants of the WIC program, and reported substance use (percent adequate=13.8); and women who reported psychosocial problems as barriers, were participants of the WIC program, denied substance use, and reported childcare problems as barriers (percent adequate=20.0).

Admission temperature of low birth weight infants: predictors and associated morbidities.

BACKGROUND: There is a paucity of information on the maintenance of body temperature at birth for low birth weight infants. OBJECTIVES: We examined the distribution of temperatures in low birth weight infants on admission to the NICUs in the Neonatal Research Network centers and determined whether admission temperature was associated with antepartum and birth variables and selected morbidities and mortality. METHODS: Infants without major congenital anomalies born during 2002 and 2003 with birth weights of 401 to 1499 g who were admitted directly from the delivery room to the NICU were included. Bivariate associations between antepartum/birth variables and admission temperature and selected morbidities/mortality and admission temperature were examined, followed by multivariable linear or logistic regressions to detect independent associations. RESULTS: There were 5277 study infants and the mean (+/-SD) birth weight and gestational age were 1036 +/- 286 g and 28 +/- 3 weeks, respectively. The distribution of admission temperatures was 14.3% at < 35 degrees C, 32.6% between 35 and 35.9 degrees C, 42.3% between 36 and 36.9 degrees C, and 10.8% at > or = 37 degrees C. The estimate of birth weight on admission temperature with and without intubation was +0.13 degrees C and +0.04 degrees C per 100-g increase in birth weight, respectively. The mean admission temperature for each center varied from 1.5 degrees C below to 0.3 degrees C above a reference center. On adjusted analyses, admission temperature was inversely related to mortality (28% increase per 1 degrees C decrease) and late-onset sepsis (11% increase per 1 degrees C decrease) but not to intraventricular hemorrhage, necrotizing enterocolitis, or duration of conventional ventilation. CONCLUSIONS: Preventing decreases in temperature at birth among low birth weight infants remains a challenge. Associations with intubation and center of birth suggest that assessment of temperature control for infants intubated in the delivery room may be beneficial. Whether the admission temperature is part of the casual path or a marker of mortality needs additional study.

The influence of primary caregivers on the sexual behavior of early adolescents.

PURPOSE: To describe rates of sexual intercourse initiation, anticipated level of sexual activity in the next 12 months, and other risk behaviors among fifth graders and to examine parental factors associated with such behaviors. METHODS: This study is based on a cross-sectional, self-administered survey conducted with a nonrandom sample of 408 fifth graders and their caregivers. Children answered questions regarding sexual intercourse initiation, anticipated sexual activity in the next 12 months, and involvement in other risk behaviors. Caregivers answered questions about parenting factors such as monitoring behaviors, parent-child relationship quality, and parent-child communication. Bivariate and multivariable analyses examined the association of these variables with the adolescents' behaviors. RESULTS: Almost 5% of girls and 17% of boys reported they had engaged in sexual intercourse. Only 34% of girls and 13% of boys said they did not expect to engage in any type of sexual contact in the next 12 months if they were going with someone they "liked a lot." Parental factors associated with fewer risk behaviors and expected sexual behaviors included higher levels of monitoring, fewer communication barriers, less permissive attitudes regarding adolescent sexual behavior, higher relationship quality with child, having fewer than five children in the household, higher levels of education, and being employed. Significant gender interactions were found for several variables. CONCLUSIONS: Adolescents are initiating sexual intercourse at extremely young ages. To delay early sexual activity and prevent adolescent pregnancy, prevention efforts must begin during the elementary school years and include those who raise and care for the adolescent.

Adverse neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: prevalence and antecedents.

OBJECTIVE: Severe abnormalities of the head ultrasound (HUS) are important predictors of cerebral palsy (CP) and mental retardation, and a normal HUS usually ensures the absence of major impairments. With the increasing survival of extremely low birth weight (ELBW) infants (birth weight <1000 g), the prognostic significance of a normal HUS may differ. This study examined the prevalence of and risk factors for CP and impaired mental development among ELBW infants with a normal HUS. METHODS: Study infants were ELBW infants who were cared for in Neonatal Research Network centers in the years 1995-1999, had a normal early and late HUS, survived to discharge, and returned for follow-up assessments at 18 to 22 months' corrected age. The outcomes of interest were a score <70 on the Bayley Scales of Infant Development-II Mental Developmental Index (MDI) and CP. Risk factors included maternal demographics; infant characteristics; and interventions or morbidities related to the lung, infection, and nutrition. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A time-oriented approach was used to select variables for inclusion in logistic models. RESULTS: Of 1749 infants with a normal early and late HUS (performed at a mean age of 6 and 47 days, respectively), 1473 (84%) returned for follow-up assessment. Infants had a birth weight of 792 +/- 134 g (mean +/- SD) and gestational age of 26 +/- 2 weeks. Rates of CP and MDI <70 were 9.4% and 25.3%, respectively, and 29.2% of infants had either CP or MDI <70. In multivariate analyses, factors associated with CP were male gender (OR: 1.8; 95% CI: 1.2-2.6), multiple birth, (OR: 1.6; 95% CI: 1.1-2.5), decreasing birth weight (OR: 1.3 for each 100-g decrease; 95% CI: 1.1-1.5), pneumothorax (OR: 2.3; 95% CI: 1.2-4.4), and days of conventional ventilation (OR: 1.2 for each additional 10 days; 95% CI: 1.1-1.3). With the exception of pneumothorax, these same factors were associated with MDI <70, in addition to less maternal education (OR: 1.4; 95% CI: 1.0-1.9) and Medicaid or lack of coverage for maternal insurance (OR: 1.7; 95% CI: 1.2-2.4). CONCLUSIONS: Nearly 30% of ELBW infants with a normal HUS had either CP or a low MDI. Risk factors that are associated with this high rate of adverse outcomes include pneumothorax, prolonged exposure to mechanical ventilation, and educational and economic disadvantage. Improvements in pulmonary care to reduce duration of ventilation and avoid air leaks might improve neurodevelopmental outcome for ELBW infants.

Breastfeeding practices in a cohort of inner-city women: the role of contraindications.

BACKGROUND: Little is known about the role of breastfeeding contraindications in breastfeeding practices. Our objectives were to 1) identify predictors of breastfeeding initiation and duration among a cohort of predominantly low-income, inner-city women, and 2) evaluate the contribution of breastfeeding contraindications to breastfeeding practices. METHODS: Mother-infant dyads were systematically selected from 3 District of Columbia hospitals between 1995 and 1996. Breastfeeding contraindications and potential predictors of breastfeeding practices were identified through medical record reviews and interviews conducted after delivery (baseline). Interviews were conducted at 3-7 months postpartum and again at 7-12 months postpartum to determine breastfeeding initiation rates and duration. Multivariable logistic regression analysis was used to identify baseline factors associated with initiation of breastfeeding. Cox proportional hazards models were generated to identify baseline factors associated with duration of breastfeeding. RESULTS: Of 393 study participants, 201 (51%) initiated breastfeeding. A total of 61 women (16%) had at lease one documented contraindication to breastfeeding; 94% of these had a history of HIV infection and/or cocaine use. Of the 332 women with no documented contraindications, 58% initiated breastfeeding, vs. 13% of women with a contraindication. In adjusted analysis, factors most strongly associated with breastfeeding initiation were presence of a contraindication (adjusted odds ratio [AOR], 0.19; 95% confidence interval [CI], 0.08-0.47), and mother foreign-born (AOR, 4.90; 95% CI, 2.38-10.10). Twenty-five percent of study participants who did not initiate breastfeeding cited concern about passing dangerous things to their infants through breast milk. Factors associated with discontinuation of breastfeeding (all protective) included mother foreign-born (hazard ratio [HR], 0.55; 95% CI 0.39-0.77) increasing maternal age (HR for 5-year increments, 0.80; 95% CI, 0.69-0.92), and infant birth weight > or = 2500 grams (HR, 0.45; 95% CI, 0.26-0.80). CONCLUSIONS: Breastfeeding initiation rates and duration were suboptimal in this inner-city population. Many women who did not breastfeed had contraindications and/or were concerned about passing dangerous things to their infants through breast milk. It is important to consider the prevalence of contraindications to breastfeeding when evaluating breastfeeding practices in high-risk communities.

Infant-parent bed sharing in an inner-city population.

BACKGROUND: In the United States, infant-parent bed sharing is a controversial and poorly understood practice. Proponents site potential advantages such as increases in bonding and facilitation of breastfeeding, whereas opponents site potential increases in risks of suffocation and sudden infant death syndrome, particularly among mothers who smoke. Few studies have examined normative practices in low-income populations. OBJECTIVES: To describe sleep practices in a cohort of infants born to predominantly low-income, inner-city mothers, to examine stability in sleep practices during the first 7 to 12 months of life, and to identify factors associated with bed sharing. DESIGN AND SETTING: Prospective birth cohort study in the District of Columbia, with recruitment taking place between August 1995 and September 1996 and follow-up from November 1995 to September 1997. PARTICIPANTS: Maternal-infant pairs were systematically selected from 3 hospitals. We interviewed 394 mothers shortly after delivery and at 3 to 7 months post partum. Of these, 369 were interviewed again at 7 to 12 months post partum. MAIN OUTCOME MEASURE: Usual bed sharing. RESULTS: At age 3 to 7 months (mean age, 129 days), 201 infants (51%) usually slept alone and 191 (48%) usually slept in a bed with a parent or other adult. Similarly, at age 7 to 12 months (mean age, 262 days), 190 infants (51%) usually slept alone and 175 (47%) usually slept in a bed with a parent or other adult. Of the infants who slept with a parent or other adult at age 3 to 7 months, 75% continued to do so at age 7 to 12 months. Similarly, of infants who usually slept alone at age 3 to 7 months, only 22% were reported to be usual bed sharers at age 7 to 12 months. In multivariate analyses, factors associated with bed sharing at both follow-up interviews included single marital status of the mother (first interview: odds ratio [OR] = 1.90; 95% confidence interval [CI], 1.11-3.27; second interview: OR = 1.81; 95% CI, 1.02-3.25) and 1 or more moves since the birth of the infant (first interview: OR = 1.82; 95% CI, 1.10-3.01; second interview: OR = 1.73; 95% CI, 1.05-2.86). Breastfeeding and household crowding were not significantly associated with bed sharing. CONCLUSIONS: Bed sharing was common in this inner-city population, and sleep practices were relatively stable during the first 7 to 12 months of life. These findings underscore the need for additional research clarifying the benefits and risks of bed sharing.

Audio computerized self-report interview use in prenatal clinics: audio computer-assisted self interview with touch screen to detect alcohol consumption in pregnant women: application of a new technology to an old problem.

Computer interviewing to obtain sensitive information is not a new concept. However, concerns about the acceptance of computers in disadvantaged populations with potentially low literacy led us to combine audio- and touch-screen technologies with an audio computerized self-report interview to obtain information about alcohol use. This study evaluated acceptance and ease of use by a disadvantaged population of pregnant women in the District of Columbia. Patients attending an initial visit at prenatal clinics answered questions anonymously about their consumption of alcoholic beverages and other personal information. The questionnaire was programmed on a laptop computer. The computer administered the recorded questions via earphones, as well as displayed them on the screen, and patients answered by touching the computer screen. Results were immediately available. A total of 507 women were interviewed, who were primarily African American, non-Hispanic, and never married. Nearly 24% did not complete a high school education, 43% were unemployed, and 30% received public assistance. Most of the women (59%) used computers occasionally (a few days a month) or never. Nearly all patients (96%) reported that the computer was not difficult to use, and approximately 90% liked answering the questions by computer. The study demonstrates that using computers to screen for alcohol use in disadvantaged pregnant populations is feasible and acceptable to the patients.