Small-for-Gestational-Age and Vocabulary and Achievement Test Scores at Age 9 Among Children Born at Term in a Contemporary U.S. Sample.

INTRODUCTION: Children that are small-for-gestational-age (SGA) at birth are at an increased risk for cognitive impairment, even if born at term (37-41 weeks). This study examined associations between sex-specific SGA and vocabulary and achievement tests in 9 year old children born at term using a contemporary population-based US sample. METHODS: A secondary data analysis was conducted on a sample of 2144 children born at term in 1998-2000 who participated in a US birth cohort study that oversampled non-marital births, which in the U.S. are associated with socioeconomic disadvantage and racial minority status. Vocabulary and achievement tests were administered to participants at age 9. Unadjusted and adjusted Ordinary Least Squares and logistic regression models of associations between SGA and test scores were estimated. RESULTS: Sex-specific SGA was associated with 2-5 point lower test scores and 1-2 times the odds of scores less than 85 (> 1 SD below the national mean) across most outcomes. In adjusted models, measures of SGA were associated with low scores on the Woodcock-Johnson Applied Problems test (OR 2.257; 95% CI 1.434, 3.551) and the Woodcock-Johnson Passage Comprehension test (OR 1.554; 95% CI 1.132, 2.134). CONCLUSION: The findings validate previous studies of SGA at term and cognitive outcomes and provide further evidence using a contemporary high-risk population-based US sample. The findings suggest that SGA children born at term should be recruited for early interventions to promote improved cognitive functioning in school.

This study expands and updates the relatively small literature on SGA and developmental outcomes among children born at term. This was done by estimating associations between sex-specific SGA status and vocabulary and achievement tests of 9-year-old children born at term who were part of a national US birth cohort study. The cohort study over-sampled non-marital births, which in the United States are associated with socioeconomic disadvantage and racial minority status.

Secondhand Smoke Risk Communication: Effects on Parent Smokers' Perceptions and Intentions.

This study examined effective strategies to communicate with parent smokers about the risks of secondhand smoke (SHS) exposure to children. An online, between-subjects experimental survey was administered via TurkPrime Panels to recruit participants (N = 623) comprising adult smokers living with children (aged 0-15). Participants were assigned to messages conditions that differed by message recommendation (cessation; cessation+exposure reduction) and format (video; text-only) or to a no-message control. Participants in a message condition viewed a message, and all participants responded to questions about their perceptions and intentions. Parent smokers who viewed either message recommendation reported greater harm perceptions (p <.001), self-efficacy (p <.001), and help-seeking intentions (p <.05) than the no-message control group. Cessation+exposure reduction recommendations elicited greater quit intentions than the no-message control (p <.05). Compared to text-only, videos elicited greater reduce-exposure intentions (p <.05) and interpersonal communication intentions (p <.05). Only videos elicited greater quit intentions (p <.01) and help-seeking intentions (p <.01) than the no-message control. Communication about this topic can be optimized by recommending both cessation and exposure-reduction behaviors (versus cessation only), and by using videos (versus traditional print/text-based materials).

Unbound bilirubin levels in phototherapy-treated preterm infants receiving soy-based lipid emulsion.

BACKGROUND: Phototherapy is an effective treatment for neonatal jaundice. Treatment indication uses total serum bilirubin (TSB), although unbound bilirubin (Bf) more accurately predicts disability risk. The goals of this investigation were to examine the response of Bf and TSB to phototherapy in preterm infants, and we hypothesized that (i) TSB and Bf respond differently; (ii) the relationship between TSB and Bf is altered; and (iii) unexpected Bf elevations are found. METHODS: One hundred and seventeen preterm infants <2 kg at birth and receiving (IL) were enrolled; and measurements of TSB and Bf were obtained. TSB was measured by the diazo method and Bf with a fluorescent Bf sensor BL22P1B11-Rh. RESULTS: Initial mean (± SD) TSB and Bf levels (41.4 ± 6.9 h) were 8.0 ± 9.0 mg/dL and 16.9 ± 12.4 nmol/L (P < 0.05). The rates of rise (ROR) were 0.21 ± 0.10 mg/dL/h for TSB and 0.38 ± 0.33 nmol/L/h for Bf. Phototherapy reduced TSB from 8.0 ± 9.0 to 5.8 ± 9.4 mg/dL (P = 0.068) but Bf did not change (16.9 ± 12.4 to 14.1 ± 9.4 nmol/L P = n.s.). Bf levels were >11 nmol/L in 64, >17 nmol/L in 18, and >22 nmol/L in 7 infants. CONCLUSIONS: Bf and TSB responded differently. While TSB and Bf correlated well before phototherapy, they did not correlate during phototherapy. TSB showed a trend toward a reduction with treatment, Bf did not. While TSB ROR information is not helpful, ROR Bf data can be utilized to anticipate treatment. Potentially high Bf levels existed before and after phototherapy and the mean Bf level at phototherapy termination remained elevated in a significant proportion of infants.

Elective Deliveries and Neonatal Outcomes in Full-Term Pregnancies.

Cesarean and induced delivery rates have risen substantially in recent decades and currently account for over one-third and one-fourth of US births, respectively. Initiatives to encourage delaying deliveries until a gestational age of 39 weeks appear to have slowed the increases but have not led to declines. The rates are at historic highs and the consequences of these interventions when not medically necessary have not been systematically explored at the population level. In this study, we used population-level data on births in New Jersey (1997-2011) to document trends in elective deliveries (induced vaginal delivery, cesarean delivery with no labor trial, and cesarean delivery after induction) and estimate logistic and linear regression models of associations between delivery method and neonatal morbidities and cost-related outcomes in low-risk pregnancies. We found that elective deliveries more than doubled during the observation period and were associated with neonatal morbidities and cost-related outcomes even at gestational ages of 39 and 40 weeks. Findings suggest that delaying beyond 39 weeks and avoiding delivery interventions when not medically necessary would improve infant health and reduce health-care costs.

Effects of Soybean Lipid Infusion on Unbound Free Fatty Acids and Unbound Bilirubin in Preterm Infants.

OBJECTIVE: To assess the effects of a soybean lipid emulsion infusions on levels of unbound (free) bilirubin (Bf) and unbound free fatty acids (FFAu) as well as changes in Bf and total serum bilirubin (TSB) during phototherapy in infants born preterm. STUDY DESIGN: Ninety-seven infants born preterm (birth weight: 500-2000 g; gestational age: 23-34 weeks) were enrolled to investigate the effect of 0, 1, 2, and 3 g/kg/d of intralipid infusion on Bf and FFAu. Pre- and postphototherapy TSB, FFAu, and Bf also were analyzed in 91 infants to assess the effects of phototherapy. FFAu levels were measured with the fluorescent probe ADIFAB2 and Bf by the fluorescent Bf sensor BL22P1B11-Rh during intralipid infusion and at start and end of phototherapy. TSB and plasma albumin were measured by the diazo and bromcresol green techniques, respectively. Bilirubin-albumin dissociation constants were calculated based on Bf and plasma albumin. RESULTS: Bf and FFAu increased with increasing intralipid dosage across all gestational ages. TSB and Bf were correlated significantly when infants received 0 or 1 g/kg/d of intralipid but not at greater doses of intralipid (2 and 3 g/kg/d). Although phototherapy effectively reduced both TSB and Bf in the total phototherapy group (by 32% and 12%, respectively), it reduced TSB, but not Bf, in infants less than 28 weeks of gestation. CONCLUSIONS: Increasing intralipid doses result in increasing FFAu levels, which are associated with increased Bf independent of TSB. In infants born extremely preterm (<28 weeks of gestation), phototherapy effectively reduces TSB but not Bf.

Inherited disorders of bilirubin clearance.

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.

Neonatal Abstinence Syndrome in Infants with Prenatal Exposure to Methadone versus Buprenorphine.

Neonatal abstinence syndrome (NAS) has been of increasing concern. Studies suggest that prenatal exposure to buprenorphine may be preferred to methadone in regard to neonatal withdrawal. Our aim was to determine whether the incidence and severity of NAS are different between babies prenatally exposed to methadone or buprenorphine in pregnancy. This retrospective analysis of infants ≥ 35-weeks-old exposed to methadone/buprenorphine alone or in conjunction with other substances in utero. They were divided into four groups: 1-methadone alone (Met), 2-buprenorphine alone (Bup), 3 and 4-those exposed to methadone and buprenorphine, respectively, in conjunction with other drugs (Met+ and Bup+). The frequency of NAS treatment, duration of treatment (LOT) and length of stay (LOS) were compared between groups. Of the 290 mothers, 59% were in the Met group, 18% in the Bup group, 14% in the Met or Bup and another opiate group, and 9% took methadone or buprenorphine plus various other substances. Infants born to Met/Met+ mothers had a four-times higher likelihood of developing NAS (p < 0.001). There was no difference in the LOS (p = 0.08) or LOT (p = 0.11) between groups. The buprenorphine treatment in pregnancy decreased the risk of babies developing NAS. However, once the NAS required pharmacological treatment, the type of maternal prenatal exposure did not affect the LOS or LOT.

Racial differences in the impact of maternal smoking on sudden unexpected infant death.

BACKGROUND: Prenatal smoking increases the risk of Sudden Unexpected Infant Death (SUID). Whether exposure patterns and associations differ by race requires further study. OBJECTIVES: Determine if patterns of exposure and associations between SUID and maternal smoking before and during pregnancy differ by race. METHODS: Using U.S. National Center for Health Statistics linked birth/infant death files 2012-2013, we documented SUID by smoking duration and race. Maternal smoking history: never, pre-pregnancy only, and pre-pregnancy plus first, first, second, or all trimesters. RESULTS: Smoking was more common in non-Hispanic White (NHW) than non-Hispanic Black (NHB) mothers and more evident for both in SUID cases. The most common exposure duration is from before and throughout pregnancy (SUID: 78.3% NHW, 66.9% NHB; Survivors: 60.22% and 53.96%, respectively). NHB vs. NHW SUID rates per 1000 live births were 1.07 vs. 0.34 for non-smokers and 3.06 and 1.79 for smokers, ORs trended upward for both with increasing smoking duration. CONCLUSION: Fewer NHB mothers smoked, but both NHB and NHW groups exhibited a dose-response relationship between smoking duration and SUID. The most common duration was from before to the end of pregnancy, suggesting difficulty in quitting and a need for effective interventions.

Prevention of Chronic Morbidities in Extremely Premature Newborns with LISA-nCPAP Respiratory Therapy and Adjuvant Perinatal Strategies.

Less invasive surfactant administration techniques, together with nasal continuous airway pressure (LISA-nCPAP) ventilation, an emerging noninvasive ventilation (NIV) technique in neonatology, are gaining more significance, even in extremely premature newborns (ELBW), under 27 weeks of gestational age. In this review, studies on LISA-nCPAP are compiled with an emphasis on short- and long-term morbidities associated with prematurity. Several perinatal preventative and therapeutic investigations are also discussed in order to start integrated therapies as numerous organ-saving techniques in addition to lung-protective ventilations. Two thirds of immature newborns can start their lives on NIV, and one third of them never need mechanical ventilation. With adjuvant intervention, these ratios are expected to be increased, resulting in better outcomes. Optimized cardiopulmonary transition, especially physiologic cord clamping, could have an additively beneficial effect on patient outcomes gained from NIV. Organ development and angiogenesis are strictly linked not only in the immature lung and retina, but also possibly in the kidney, and optimized interventions using angiogenic growth factors could lead to better morbidity-free survival. Corticosteroids, caffeine, insulin, thyroid hormones, antioxidants, N-acetylcysteine, and, moreover, the immunomodulatory components of mother's milk are also discussed as adjuvant treatments, since immature newborns deserve more complex neonatal interventions.

Fluorescence sensor for the quantification of unbound bilirubin concentrations.

BACKGROUND: Hyperbilirubinemia in jaundiced neonates is routinely assessed by use of total serum bilirubin. However, the unbound or free form (B(f)), not total bilirubin, crosses the blood-brain barrier and can be neurotoxic. Although the peroxidase-mediated oxidation of bilirubin can be used to measure plasma concentrations of B(f), this measurement is relatively complex and the assay is not routinely used. We describe a fluorescence sensor for quantifying B(f) in plasma. METHODS: Our method uses a mutated fatty acid binding protein labeled with the fluorescent molecule acrylodan (BL22P1B11), whose fluorescence is quenched upon binding bilirubin. Another configuration (BL22P1B11-Rh) was developed that uses BL22P1B11 together with the fluorophore rhodamine B, which responds by a change in the ratio of its fluorescence. RESULTS: The "B(f) probes" were calibrated with aqueous solutions of bilirubin and yielded similar bilirubin dissociation constants [K(d) = 16 (1.5) nmol/L]. We used the probes to determine B(f) concentrations in equilibrium with human serum albumin (HSA) and in human plasma samples supplemented with bilirubin. We obtained equivalent B(f) values in both systems, and the B(f) probe results were in agreement with the peroxidase assay. B(f) measurements revealed that bilirubin-HSA binding was well described by 2 sites with K(d) values of 15.4 (1) nmol/L and 748 (14) nmol/L. We measured B(f) concentrations in the range expected in jaundiced neonates with a mean CV of approximately 3%. CONCLUSIONS: The BL22P1B11-Rh probe provides accurate plasma sample B(f) concentrations with a single measurement, in 1 min with either a handheld B(f) meter or a laboratory fluorometer.

Developmental outcomes of late-preterm infants at 2 and 4 years.

This study compared healthy late-preterm (34-36 week) and healthy full-term (37-41 week) singleton infants on a range of cognitive, motor, and behavioral outcomes at 2 and 4 years. Eighteen developmental outcomes were analyzed using the Early Childhood Longitudinal Survey-Birth Cohort, a nationally representative panel study. Ordinary Least Squares and logistic regressions were performed to estimate unadjusted and adjusted differences in developmental outcomes between late-preterm and full-term children. In unadjusted models, late-preterm children scored more poorly than full-term children on most assessments of cognitive ability at 2 and 4 years. After adjusting for demographic, economic, and obstetrical factors, late-preterm children continued to score lower than full-term children on language use at 2 years and on literacy, language, and math at 4 years, but scored at least one standard deviation below the mean on only one of the eighteen outcomes. Late-preterm birth is associated with subtle deficits in cognitive functioning as early as age 2 years. Although the effects may be too small to have clinical relevance, they suggest a trend toward poorer outcomes that have been documented at older ages and suggest that early testing and intervention may enhance the cognitive development of late-preterm children.

Neonatal hyperbilirubinemia and the role of unbound bilirubin.

BACKGROUND: Neonatal jaundice occurs in more than 80% of newborn infants. Although mild jaundice is physiologic and possibly neuroprotective, severe hyperbilirubinemia can lead to neurologic dysfunction and death. Hyperbilirubinemia is due to an imbalance between bilirubin production and the developing excretory capacity in the first days of life. Management utilizes total serum bilirubin (TSB) levels, although recent advances suggest a role for unbound bilirubin. GOALS: The goal of this review is to examine bilirubin biology, toxicology, and clinical effects, discuss preventive and therapeutic measures, describe neurodevelopmental consequences, and propose that, with the advent of new technology, unbound bilirubin is the optimal measurement for the management. METHODS: Comprehensive review on neonatal hyperbilirubinemia. RESULTS: Neonatal hyperbilirubinemia can be prevented by tin mesoporphyrin to limit heme oxygenase activity, a key enzyme in bilirubin production, or restricting bilirubin's absorption from the gastrointestinal tract. Treatment modalities include removing bilirubin from the body by exchange transfusion, binding to immunoglobulin, or converting it to a water-soluble isomer with phototherapy. While these approaches have evolved during the past decades, the diagnosis, intervention indications, and prognosis have consistently relied on TSB concentration despite its poor ability to predict an outcome. CONCLUSIONS: Total serum bilirubin is inadequate to optimize care of the term and preterm infant with hyperbilirubinemia. A rapid, accurate, and more effective indicator of bilirubin neurotoxicity is needed to manage jaundiced infants and for the universal screening of newborn infants. Future measurements of free bilirubin unattached to albumin will improve the management of neonatal hyperbilirubinemia.

Sudden unexpected infant death risk profiles in the first month of life.

BACKGROUND: Limited improvement in current SUID rates requires further identification of its characteristics, including age-specific risk patterns. OBJECTIVE: Compare SUID risk factors in the first week versus the remainder in the first month of life. DESIGN/METHODS: We compared maternal and infant data from New Jersey databases for SUID from 2000 to 2015 in infants ≥ 34 weeks GA in the two groups. RESULTS: In the period studied, 123 died in the first 27 days, 24 before seven. Deaths in the first week had a higher percentage of mothers with post-High School education (OR 3.50, CI: 1.38-8.87) and a primary Cesarean section delivery (OR 4.0, CI: 1.39-11.49), and a smaller percentage with inadequate prenatal care (OR 0.36, CI: 0.14, 0.94). A smaller percentage of first-week deaths had mothers who smoked during pregnancy or identified as Black, non-Hispanic, but these findings did not reach significance (p < .08 and p < .09, respectively). CONCLUSIONS: SUID in the first week and the first month of life is rare. However, despite a limited sample size, data suggest that even within the first month of life, there are differences in risk patterns for SUID based on age at death. Age-specific profiles may lead to new hypotheses regarding causality and more refined risk-reduction guidelines and warrant further study.

Vascular endothelial growth factor levels and bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) regulate both vasculogenesis, the development of blood vessels from precursor cells, and angiogenesis, the formation of blood vessels from preexisting vessels. In the fetal lung, high-affinity receptors for VEGF are expressed mainly in alveolar epithelial cells and myocytes, suggesting a paracrine role for VEGF in modulating activities in adjacent vascular endothelium. Previous studies have shown that vascular growth is impaired in bronchopulmonary dysplasia (BPD). OBJECTIVE: The goal of this study was to examine tracheal (T-VEGF) and gastric (G-VEGF) levels in premature infants in the first and third day of life and examine if these levels were associated with the development of BPD. DESIGN/METHODS: Tracheal aspirates from intubated infants and gastric samples from others were obtained on postnatal days 1 (D1) and 3 (D3) from 43 preterm infants (<2000 g birth weight, ≤34 wks gestation). VEGF was quantified by a VEGF Elisa Kit. Demographic, clinical, and pulmonary outcome data were collected including information on respiratory support (oxygenation index (OI) and ventilatory index (VI)) and on the development of BPD, determined at 36 weeks PMA using NICHD criteria. RESULTS: The mean birth weight was 1060 ± 379 g and gestational age 27.5 ± 2.8 wks. BPD was diagnosed in 26 infants who were less mature than the 17 controls without BPD. Day 1 and day 3T-VEGF concentrations did not correlate, but day 3 levels correlated with gestational age (r = 0.75, p < .05). BPD infants, characterized by longer ventilator, CPAP and oxygen days, had day 1T-VEGF levels similar to control infants (126.6 ± 194.7 vs. 149.7 ± 333.2 pg/ml) but day 3 levels were significantly lower (168.9 ± 218.8 vs. 1041.6 ± 676.7 pg/ml). Day 1G-VEGF levels reflected tracheal samples, trending lower in BPD infants. Mode of delivery, race, sex, antenatal steroid administration, chorioamnionitis, sepsis, or growth restriction did not impact VEGF levels. However, lower VEGF levels were associated with a lower VI and lower OI: Day 3 OI correlated with day 3T-VEGF (r = 0.72, p > .05), albeit not significantly. T-VEGF increased from day 1 to day 3 in controls and decreased in BPD infants. There was no relationship between oxygen, CPAP and ventilator days and day 1 or day 3T-VEGF levels. CONCLUSIONS: BPD may be associated with low-serum VEGF levels during the first week of life. This finding is likely related to decreased expression in the lungs of the less mature infants, who are at the highest risk for BPD.

Unbound bilirubin measurements in term and late-preterm infants.

BACKGROUND: Hyperbilirubinemia occurs in over 80% of newborns, and severe bilirubin toxicity can lead to neurological dysfunction and death. Unbound bilirubin (Bf) levels predict the risk of neurodevelopmental handicap, although total serum bilirubin (TSB) is used to manage care. OBJECTIVE: To measure Bf levels in healthy infants, its relationship to TSB, and its response to phototherapy. We hypothesize unexpectedly high Bf levels, poor correlation with TSB and unpredictable response to phototherapy. DESIGN/METHODS: Healthy infants were studied with simultaneous TSB and Bf measurements. The clinical data recorded included ethnicity, gender, birth weight, gestational age, and mode of delivery, Apgar scores, breast/formula feeds, and phototherapy. RESULTS: One hundred thirty-two infants (3248.9 ± 509.2g, GA 38.7 ± 1.4 weeks), at mean age of the initial sample of 28.5 ± 15.6 h, had a TSB of 7.9 ± 2.7 mg/dl, and a Bf of 5.2 ± 3.2 nM. The correlation between Bf and TSB was significant but not between Bf and TSB for TSB >12 mg/dl. Bf >11nm were in 22.7% and >17 nM in 3.8% of infants. Post-phototherapy TSB and Bf levels were similar to those before treatment. CONCLUSIONS: The relationship between TSB and Bf in healthy infants is complex, with the inability of one to predict the other's level in infants with elevated TSB. The mechanism of bilirubin-related neurotoxicity suggests that the management of jaundice in healthy infants requires Bf measurements. Management of jaundice with TSB may result in more infants exposed to phototherapy. However, unexpected elevations of Bf occur in an apparently healthy population.

Effects of lipid emulsions on unbound bilirubin and response to phototherapy in preterm infants.

OBJECTIVE: Bilirubin-induced neurotoxicity is mediated by the fraction of total serum bilirubin (TSB) not bound to albumin (Bf). Unbound free fatty acids (FFAu) generated from lipid emulsions compete with bilirubin for albumin binding, increasing Bf. Soy-based (IL) and soy-MCT-olive-fish oil-based (SMOF) lipid emulsions contain different fatty acids with distinct albumin binding affinities. IL increases Bf in preterm infants, but the effects of SMOF on Bf are not known. Our objective was to compare changes in TSB, Bf, FFAu, and response to phototherapy in preterm infants receiving SMOF and IL. We hypothesized that SMOF would be associated with lower Bf and better response to phototherapy than IL. METHODS: Very preterm and low birth weight infants (<1500 g, <32 weeks) were infused with IL (n = 20) or SMOF (n = 20) as prescribed by providers. Phototherapy was prescribed using the standard care practice. FFAu profiles and levels, TSB, and Bf were measured on 0, 1, 2, and 3 g/kg/day of lipid infusion and at the initiation and termination of phototherapy. TSB was analyzed in the clinical laboratory using the diazo technique. FFAu and Bf were measured using fluorescent probes. RESULTS: Escalating doses of IL and SMOF increased FFAu levels and Bf, but not TSB. Phototherapy did not significantly decrease Bf for infants receiving either lipid. IL-treated infants had higher levels of unbound linoleic acid, and SMOF-treated infants had higher unbound arachidonic, oleic, and docosahexaenoic acids. CONCLUSIONS: IL and SMOF both increase Bf similarly, and phototherapy does not significantly affect Bf for infants receiving them.

Elective Deliveries and the Risk of Autism.

INTRODUCTION: Cesarean section and induced deliveries have increased substantially in the U.S., coinciding with increases in autism spectrum disorder. Studies have documented associations between cesarean section deliveries and autism spectrum disorder but have not comprehensively accounted for medical risks. This study evaluates the extent to which cesarean section and induced deliveries are associated with autism spectrum disorder in low-risk births. METHODS: In this retrospective cohort study, California's birth records (1992-2012) were linked to hospital discharge records to identify low-risk births using a stringent algorithm based on Joint Commission guidelines. Autism spectrum disorder status was based on California Department of Developmental Service data. Logistic regression models were used to estimate associations between autism spectrum disorder and induced vaginal deliveries, cesarean section deliveries not following induction, and cesarean section deliveries following induction, with noninduced vaginal deliveries as the reference category. RESULTS: A total of 1,488,425 low-risk births took place in California from 1992 to 2012. The adjusted odds of autism spectrum disorder were 7% higher for induced vaginal deliveries (AOR=1.07, 95% CI=1.01, 1.14), 26% higher for cesarean section deliveries not following induction (AOR=1.26, 95% CI=1.19, 1.33), and 31% higher for cesarean section deliveries following induction (AOR=1.31, 95% CI=1.18, 1.45) than for noninduced vaginal deliveries. Lower gestational age and neonatal morbidities did not appear to be important underlying pathways. The associations were insensitive to alternative model specifications and across subpopulations. These results suggest that, in low-risk pregnancies, up to 10% of autism spectrum disorder cases are potentially preventable by avoiding cesarean section deliveries. CONCLUSIONS: After accounting for medical risks, elective deliveries-particularly cesarean section deliveries-were associated with a substantially increased risk of autism spectrum disorder.

Suppression of Bile Acid Synthesis in a Preterm Infant Receiving Prolonged Parenteral Nutrition.

Bile acid metabolism is altered in neonates on parenteral nutrition (PN), predisposing them to parenteral nutrition-associated liver disease. Cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the bile acid synthesis pathway, is repressed by fibroblast growth factor 19 (FGF19) and phytosterols (PS). We describe a case of a preterm infant who developed necrotizing enterocolitis (NEC) and received exclusive PN for over 2 months. Our objective was to serially assess CYP7A1 activity and plasma FGF19 and PS concentrations in this infant case compared to five healthy preterm infants. We found that CYP7A1 activity increased during the first 2 weeks of life in control infants but was undetectable in the infant case. FGF19 concentrations were high at birth in all infants and subsequently declined and did not differ between the case and control infants. As expected, PS concentrations were elevated in the infant case and continued to increase despite lipid minimization. In conclusion, CYP7A1 activity was gradually upregulated in healthy preterm infants but remained suppressed in the infant requiring prolonged PN. Preterm infants also had elevated FGF19 concentrations at birth, which decreased with advancing postnatal age.

Plasma unbound free fatty acid profiles in premature infants before and after intralipid infusion.

Background: Unbound free fatty acids (FFAu) are the bioactive fraction of plasma free fatty acids (FFA). Most plasma FFA are bound to albumin. Only when FFA dissociate from albumin, do they become biologically active.Objective: To measure the first FFAu profiles in human infants and to measure these profiles before and during intravenous administration of the soybean lipid, intralipid (IL).Study design: The study population was 16 premature infants, from a parent study of 130 infants with birth weights 500-2000 g and gestational age 23-34 weeks. The infants chosen had plasma samples of ≥120 µL (volume needed for each FFAu profile measurement) in the first day of life. Infants received IL infusions starting in the second day of life at 1 g/kg/day, increasing by 1-g/kg/day daily up to 3 g/kg/day. FFAu profiles were determined during IL infusion when plasma was available. Profiles are the concentrations of the nine most abundant long-chain FFAu and were determined using novel fluorescent probes.Results: Before intralipid infusion unbound myristic acid was the dominant FFAu, as high as 78% of the total FFAu (sum of the 9 FFAu). In contrast, unbound linoleic acid was 0% in all infants. With increasing infusion of IL to 3 g/kg/day, unbound linoleic increased to 26% of the total FFAu, with unbound oleic, myristic, and linolenic acid the second, third and fourth most abundant. The average total FFAu concentration also increased from 4 nM before intralipid to 53 nM at 3 g/kg/day. During IL infusion the FFAu profiles approached the fatty acid composition of intralipid at 3 g/kg/day.Conclusions: This first study of FFAu profiles in neonates revealed that before IL infusion unbound linoleic acid was zero in all 16 infants and levels of myristic acid were exceptionally large, as much as 78% of the total FFAu profile. These results suggest important and previously unrecognized roles of lipid metabolism in early development. Zero unbound linoleic acid before IL infusion may help promote closure of the ductus arteriosus but after IL infusion, synthesis of arachidonic from linoleic acid may tend to promote patency. The high levels of unbound myristate may be needed for immediate neonatal energy needs.

Obstetricians' and Gynecologists' Communication Practices around Smoking Cessation in Pregnancy, Secondhand Smoke and Sudden Infant Death Syndrome (SIDS): A Survey.

Secondhand smoke (SHS) is a potential direct cause of Sudden Infant Death Syndrome (SIDS) among infants. Disparities in SHS exposure and SIDS deaths may be due to inconsistent communication among practitioners about SHS/SIDS risks. In order to assess current SHS/SIDS risks and communication practices and to identify areas of improvement, we conducted a survey of 316 obstetricians and gynecologists (ob/gyns) about the length of time spent having discussions, supplemental materials used, risks covered, cessation, and frequency of discussions. Most (55.3%) reported spending 1-4 min discussing risks/cessation. Nearly a third reported not using any supplemental materials; few used apps (4.4%) or videos (1.9%). Assisting patients with steps toward cessation was infrequent. Few ob/gyns had discussions with patients immediately postpartum. Only 51.9% strongly agreed that they felt sufficiently informed about SHS/SIDS risks to educate their patients. The communication by ob/gyns of SHS/SIDS risk varies greatly and presents opportunities for improvement. Each additional minute spent having discussions and the use of supplemental materials, such as apps, may improve communication effectiveness. The discussion of smoking behaviors immediately postpartum may help to prevent smoker relapse. An increased awareness of statewide cessation resources by ob/gyns is needed to assist patients with cessation. The development of standardized risk messaging may reduce the variation in communication practices among ob/gyns.