Neonatal Frequency-Following Responses: A Methodological Framework for Clinical Applications.

The frequency-following response (FFR) to periodic complex sounds is a noninvasive scalp-recorded auditory evoked potential that reflects synchronous phase-locked neural activity to the spectrotemporal components of the acoustic signal along the ascending auditory hierarchy. The FFR has gained recent interest in the fields of audiology and auditory cognitive neuroscience, as it has great potential to answer both basic and applied questions about processes involved in sound encoding, language development, and communication. Specifically, it has become a promising tool in neonates, as its study may allow both early identification of future language disorders and the opportunity to leverage brain plasticity during the first 2 years of life, as well as enable early interventions to prevent and/or ameliorate sound and language encoding disorders. Throughout the present review, we summarize the state of the art of the neonatal FFR and, based on our own extensive experience, present methodological approaches to record it in a clinical environment. Overall, the present review is the first one that comprehensively focuses on the neonatal FFRs applications, thus supporting the feasibility to record the FFR during the first days of life and the predictive potential of the neonatal FFR on detecting short- and long-term language abilities and disruptions.

Environmental Exposure during Pregnancy: Influence on Prenatal Development and Early Life: A Comprehensive Review.

Preconception and prenatal exposure to environmental contaminants may affect future health. Pregnancy and early life are critical sensitive windows of susceptibility. The aim of this review was to summarize current evidence on the toxic effects of environment exposure during pregnancy, the neonatal period, and childhood. Alcohol use is related to foetal alcohol spectrum disorders, foetal alcohol syndrome being its most extreme form. Smoking is associated with placental abnormalities, preterm birth, stillbirth, or impaired growth and development, as well as with intellectual impairment, obesity, and cardiovascular diseases later in life. Negative birth outcomes have been linked to the use of drugs of abuse. Pregnant and lactating women are exposed to endocrine-disrupting chemicals and heavy metals present in foodstuffs, which may alter hormones in the body. Prenatal exposure to these compounds has been associated with pre-eclampsia and intrauterine growth restriction, preterm birth, and thyroid function. Metals can accumulate in the placenta, causing foetal growth restriction. Evidence on the effects of air pollutants on pregnancy is constantly growing, for example, preterm birth, foetal growth restriction, increased uterine vascular resistance, impaired placental vascularization, increased gestational diabetes, and reduced telomere length. The advantages of breastfeeding outweigh any risks from contaminants. However, it is important to assess health outcomes of toxic exposures via breastfeeding. Initial studies suggest an association between pre-eclampsia and environmental noise, particularly with early-onset pre-eclampsia. There is rising evidence of the negative effects of environmental contaminants following exposure during pregnancy and breastfeeding, which should be considered a major public health issue.

Effectiveness and Safety of Acupuncture and Moxibustion in Pregnant Women with Noncephalic Presentation: An Overview of Systematic Reviews.

BACKGROUND: Breech presentation at the time of delivery is 3.8-4%. Fetuses that maintain a noncephalic presentation beyond 32 weeks will have a lower probability of spontaneous version before labor. Given the increasing interest in exploring the use of complementary medicine during pregnancy and childbirth, the moxibustion technique, a type of traditional Chinese medicine, could be another option to try turning a breech baby into a cephalic presentation. OBJECTIVES: To review the evidence from systematic reviews (SR) on the efficacy and safety of acupuncture and moxibustion in pregnant women with noncephalic presentation. MAIN RESULTS: Our SR synthesizes the results from five clinical trials on pregnant women with a singleton noncephalic presentation. There is evidence that moxibustion reduces the number of noncephalic presentations at the time of birth compared with no treatment. The adverse effects that acupuncture and moxibustion can cause seem to be irrelevant. Most SRs agree that there are no adverse effects directly related to acupuncture and moxibustion. CONCLUSIONS: Even though the results obtained are positive and the five reviews conclude that moxibustion reduces the number of noncephalic presentations at birth (alone or combined with postural techniques or acupuncture), there is considerable heterogeneity between them. Better methodologically designed studies are required in the future to reaffirm this conclusion.

The frequency-following response (FFR) to speech stimuli: A normative dataset in healthy newborns.

The Frequency-Following Response (FFR) is a neurophonic auditory evoked potential that reflects the efficient encoding of speech sounds and is disrupted in a range of speech and language disorders. This raises the possibility to use it as a potential biomarker for literacy impairment. However, reference values for comparison with the normal population are not yet established. The present study pursues the collection of a normative database depicting the standard variability of the newborn FFR. FFRs were recorded to /da/ and /ga/ syllables in 46 neonates born at term. Seven parameters were retrieved in the time and frequency domains, and analyzed for normality and differences between stimuli. A comprehensive normative database of the newborn FFR is offered, with most parameters showing normal distributions and similar robust responses for /da/ and /ga/ stimuli. This is the first normative database of the FFR to characterize normal speech sound processing during the immediate postnatal days, and corroborates the possibility to record the FFRs in neonates at the maternity hospital room. This normative database constitutes the first step towards the detection of early FFR abnormalities in newborns that would announce later language impairment, allowing early preventive measures from the first days of life.

Placental 11B-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Intrauterine Growth Restriction versus Small-for-Gestational-Age Fetuses.

INTRODUCTION: The objective of this study was to evaluate placental 11B-hydroxysteroid dehydrogenase type 2 (11B-HSD-2) mRNA levels in intrauterine growth-restricted fetuses (IUGR) as compared with small-for-gestational-age (SGA) fetuses according to clinical criteria. MATERIAL AND METHODS: Placental levels of 11B-HSD-2 mRNA levels were measured in SGA (birth weight <10th centile) and gestational-age-matched, appropriate-for-gestational-age (AGA) births. SGA was classified as IUGR (birth weight <3rd centile or <10th percentile with abnormal uterine artery Doppler or cerebroplacental ratio) or non-IUGR SGA. After RNA extraction, mRNA levels were determined by reverse transcription and quantitative PCR. RESULTS: A total of 38 placentas were analyzed (20 AGA and 18 SGA). Among the SGA pregnancies, 13 qualified as IUGR. The activity of 11B-HSD-2 in IUGR pregnancies [0.105 (SD 0.328)] was significantly reduced compared to non-IUGR SGA [0.304 (SD 0.261); p = 0.018] and AGA [0.294 (SD 0.328); p = 0.001]. These differences remained significant after adjusting for potential confounders (such as smoking or maternal cortisol levels). Activity levels did not significantly differ between non-IUGR SGA and AGA. DISCUSSION: IUGR fetuses had reduced 11B-HSD-2 activity in comparison with SGA and normally grown fetuses. This finding provides opportunities to develop new placental biomarkers for the phenotypic characterization of fetal smallness.

Aortic intima-media thickness and aortic diameter in small for gestational age and growth restricted fetuses.

OBJECTIVE: The objective of this study is to measure aortic intima-media thickness (aIMT) and aortic diameter (AD) in appropriate for gestational age (AGA) fetuses, small for gestational age (SGA) fetuses, and intrauterine growth restricted (IUGR) fetuses. METHODS: Case-control study performed between June 2011 and June 2012. Forty-nine AGA fetuses, 40 SGA fetuses, and 35 IUGR fetuses underwent concomitant measurement of aIMT and AD at a mean gestational age of 34.4 weeks. RESULTS: Median aIMT was higher in fetuses with IUGR (0.504 mm [95%CI: 0.477-0.530 mm]), than in SGA fetuses (0.466 mm [95% CI: 0.447-0.485 mm]), and AGA fetuses (0.471 mm [95% CI: 0.454-0.488 mm]) (p = 0.023). Mean AD was significantly lower in fetuses with IUGR (4.451 mm [95% CI: 4.258-4.655 mm]), than in AGA fetuses (4.74 mm [95% CI: 4.63-4.843 mm]) (p = 0.028). CONCLUSIONS: Growth restricted fetuses have a thicker aortic wall than AGA and SGA fetuses, which possibly represents preclinical atherosclerosis and a predisposition to later cardiovascular disease.

Use of placental growth factor and uterine artery doppler pulsatility index in pregnancies involving intrauterine fetal growth restriction or preeclampsia to predict perinatal outcomes.

AIM: The potential of uterine artery (UA) Doppler pulsatility index (PI) and maternal serum placental growth factor (PlGF) level to predict perinatal outcome was explored in pregnancies complicated by intrauterine fetal growth restriction (IUGR) or preeclampsia (PE). METHODS: This longitudinal, prospective, and case-controlled study was conducted over a period of 24 months. At-risk pregnancies involving small-for-gestational-age (SGA) fetuses, IUGR, gestational hypertension (GH), or PE were investigated, analyzing UA Doppler PI findings and maternal PlGF levels determined at the time of diagnosis (third trimester). RESULTS: UA Doppler PI and maternal serum PlGF values differed significantly in pregnancies complicated by IUGR and/or PE (vs. SGA or GH, p < 0.01). In the context of IUGR or PE, both parameters also differed significantly by perinatal outcome (adverse vs. normal, p < 0.01), although no predictive advantage over UA Doppler PI alone was conferred by adding a PlGF assay. CONCLUSION: UA Doppler PI and maternal serum PlGF determinations in the third trimester help identify pregnancies at the highest risk of adverse perinatal outcomes due to IUGR and/or PE. Although joint testing confers no predictive benefit over UA Doppler PI alone, the two diagnostics are interchangeable for this purpose.

Relationship between Foetal Growth Restriction and Maternal Nutrition Status Measured by Dual-Energy X-Ray Absorptiometry, Leptin, and Insulin-Like Growth Factor.

AIMS: The aim of this study was to determine if maternal nutritional status, as defined by body composition, leptin, and insulin-like growth factor (IGF)-I levels, relates to foetal growth. METHODS: In this prospective study, mothers of foetuses with foetal growth restriction (FGR; cases; n = 46) and mothers of appropriate-for-gestational-age (AGA) foetuses (controls; n = 81) were consecutively recruited over a 14- month period. A maternal blood sample was obtained during the third trimester (between 32 and 34 weeks of gestation) for the assessment of IGF-I and leptin. Body composition was assessed by dual-energy X-ray absorptiometry within the first 15 days after delivery. The study used the SPSS-PC statistical package, version 19.0, and p < 0.05 was considered statistically significant. RESULTS: Mean serum IGF-I levels were lower in the cases than in the controls (p < 0.05), whereas leptin concentrations were higher in the cases after adjusting for age, body mass index and cigarette consumption (p < 0.05). Cases had less lean and fat tissue than controls (p < 0.05) but a relatively higher fat percentage. CONCLUSIONS: The mothers of foetuses with FGR have a body composition pattern characterized by a slightly increased fraction of fat mass, lower IGF-I concentrations, and increased serum leptin levels. Optimization of maternal nutritional status should be considered, as the nutritional status may be involved in the pathogenesis of FGR.