Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.

The manifestation of mitochondrial DNA (mtDNA) diseases depends on the frequency of heteroplasmy (the presence of several alleles in an individual), yet its transmission across generations cannot be readily predicted owing to a lack of data on the size of the mtDNA bottleneck during oogenesis. For deleterious heteroplasmies, a severe bottleneck may abruptly transform a benign (low) frequency in a mother into a disease-causing (high) frequency in her child. Here we present a high-resolution study of heteroplasmy transmission conducted on blood and buccal mtDNA of 39 healthy mother-child pairs of European ancestry (a total of 156 samples, each sequenced at ∼20,000× per site). On average, each individual carried one heteroplasmy, and one in eight individuals carried a disease-associated heteroplasmy, with minor allele frequency ≥1%. We observed frequent drastic heteroplasmy frequency shifts between generations and estimated the effective size of the germline mtDNA bottleneck at only ∼30-35 (interquartile range from 9 to 141). Accounting for heteroplasmies, we estimated the mtDNA germ-line mutation rate at 1.3 × 10 −8 (interquartile range from 4.2 × 10 −9 to 4.1 × 10) mutations per site per year, an order of magnitude higher than for nuclear DNA. Notably, we found a positive association between the number of heteroplasmies in a child and maternal age at fertilization, likely attributable to oocyte aging. This study also took advantage of droplet digital PCR (ddPCR) to validate heteroplasmies and confirm a de novo mutation. Our results can be used to predict the transmission of disease-causing mtDNA variants and illuminate evolutionary dynamics of the mitochondrial genome. mitochondria | heteroplasmy

More than 20% of US children between ages 2 and 5 years are overweight suggesting efforts to prevent obesity must begin earlier. This study tested the independent and combined effects of two behavioral interventions delivered to parents, designed to promote healthy infant growth in the first year. Mother–newborn dyads intending to breastfeed were recruited from a maternity ward. With a 2 × 2 design, 160 dyads were randomized into one of four treatment cells to receive both, one, or no interventions delivered at two nurse home visits. The first intervention (“Soothe/Sleep”) instructed parents on discriminating between hunger and other sources of infant distress. Soothing strategies were taught to minimize feeding for non-hunger-related fussiness and to prolong sleep duration, particularly at night. The second intervention (“Introduction of Solids”) taught parents about hunger and satiety cues, the timing for the introduction of solid foods, and how to overcome infants’ initial rejection of healthy foods through repeated exposure. A total of 110 mother–infant dyads completed the year-long study. At 1 year, infants who received both interventions had lower weight-for-length percentiles (P = 0.009). Participants receiving both interventions had a mean weight-for-length in the 33rd percentile; in contrast, those in other study groups were higher first intervention only—50th percentile; second intervention only—56th percentile; control group—50th percentile).This suggests that multicomponent behavioral interventions may have potential for long-term obesity prevention (ClinicalTrials.gov number, NCT00359242).

IMPORTANCE Rapid infant weight gain is associated with later obesity, but interventions to prevent rapid infant growth and reduce risk for overweight status in infancy are lacking.OBJECTIVE To examine the effect of a responsive parenting (RP) intervention on infant weight gain between birth and 28 weeks and overweight status at age 1 year. DESIGN, SETTING, AND PARTICIPANTS The Intervention Nurses Start Infants Growing onHealthy Trajectories (INSIGHT) study is an ongoing randomized clinical trial comparing an RP intervention designed to prevent childhood obesity with a safety control. The study includes primiparous mother-newborn dyads (n = 291) and was conducted at the Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, in addition to home visits. Enrollment was initiated in January 2012, and evaluable population analyses for this study were conducted between April 2015 and November 2015.INTERVENTIONS At 2 weeks post partum, initial intervention materials appropriate to the assigned treatment group were mailed to the participant's home. Research nurses conducted home visits at 3 weeks, 16 weeks, 28 weeks, and 40 weeks, and a research center visit occurred at 1 year. The Intervention Nurses Start Infants Growing on Healthy Trajectories curriculum included messages about infant feeding, sleep hygiene, active social play, emotion regulation, and growth record education. The control group received a developmentally appropriate home safety intervention also delivered by nurse home visitors. MAIN OUTCOMES AND MEASURESConditional weight gain from birth to 28 weeks was calculated. General linear models examined intervention effect on conditional weight gain. The intervention's effect on infant weight-for-length percentiles was tested using analysis of variance. Logistic regression compared the odds of overweight status (weight for length Ն95th percentile) at 1 year as a function of conditional weight gain. RESULTSOf the mothers included in the study, 246 were white (88%), 260 were non-Hispanic (93%), 210 were married (75%), and 201 were working full time (72%) at time of enrollment. The mean conditional weight gain score was lower among infants in the RP group compared with the control group (−0.18; 95% CI, −0.36 to −0.001), reflecting that the RP infants gained weight more slowly than control group infants (0.18; 95% CI, 0.02-0.34); this effect did not differ by feeding mode (predominantly fed breast milk or not). Infants in the RP group also had lower mean weight-for-length percentiles at 1 year than infants in the control group (57.5%; 95% CI, 52.56%-62.37% vs 64.4%; 95% CI, 59.94%-69.26%; P = .04) and were less likely to be overweight at age 1 year (5.5% vs 12.7%; P = .05). CONCLUSIONS AND RELEVANCEAn RP intervention is associated with reduced rapid weight gain during the first 6 months after birth and overweight status at age 1 year. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01167270.