First Month Of Postnatal Life Research Articles

Neonatal neurobehavior effects following buprenorphine versus methadone exposure.

To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior. Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy. Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria. Thirty-nine full-term infants. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14-15 and 28-30. While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over-aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self-regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03). While neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.

Evaluating the neurotoxic effects of lactational exposure to persistent organic pollutants (POPs) in Spanish children

Although the brain continues developing in the postnatal period, epidemiological studies on the effects of postnatal exposure to neurotoxic POPs through breast-feeding remain mostly inconclusive. Failure to detect associations between postnatal exposure and health outcomes may stem from the limitations of commonly employed approaches to assess lactational exposure. The aim of the present study was to assess whether lactational exposure to polychlorinated biphenyl-153 (PCB-153), dichlorodiphenyldichloroethylene (DDE), or hexachlorobenzene (HCB) as estimated with a physiologically based pharmacokinetic (PBPK) model, is associated with decrements in mental and psychomotor development scores of the Bayley Scales of Infant Development (BSID) test in children aged around 14-months of a subsample (N=1175) of the Spanish INMA birth cohort, and to compare this with the effects of prenatal exposure. Although in the present study population PCB-153, DDE and HCB exposure increased within the first months of postnatal life, no associations were found between different periods of postnatal exposure to these compounds and mental or psychomotor scores. Increasing prenatal PCB-153 concentrations were associated with worse mental and psychomotor scores, although significance was only reached for psychomotor development (β [95%CI]=−1.36 [−2.61, −0.11]). Indeed, the association between exposure and effects observed during prenatal life weakened gradually across periods of postnatal life. Results of the present study suggest that, although breastfeeding increases children's blood persistent organic pollutants (POPs) levels during postnatal life, deleterious effects of PCB-153 on neuropsychological development are mainly attributable to prenatal exposure.

RUMINANT NUTRITION SYMPOSIUM: OPTIMIZING PERFORMANCE OF THE OFFSPRING: Nourishing and managing the dam and postnatal calf for optimal lactation, reproduction, and immunity1,2

For several mammalian species, it has been shown that fetal and early postnatal nutrition has a role in long-term lipid and glucose metabolism of the offspring, and it thus also may have consequences on milk yield in the dairy cow. For instance, high-energy diets during the last weeks of pregnancy may result in increased glycemia, which in turn, may alter fetal adipose tissue development. However, most research efforts on management and nutrition of dry cows have focused on minimizing metabolic disorders of the postpartum cow without devoting much attention to potential consequences for the offspring. Similarly, nutritional needs for proper placental development and early fetal growth have received little attention, despite the fact that alterations in placental and fetal development may alter expression of genes participating in homeorhesis of the offspring. Therefore, nutrition of the pregnant cow, both while lactating and dry, should also consider aspects of placental and fetal development that may affect health and performance of the progeny. Similarly, newborn calves and young heifers are fed to ensure a particular growth target without compromising mammary development, although data linking postnatal growth targets with future milk yield are scarce. However, milk yield not only depends on mammary development, but also on nutrient partitioning, which is regulated by the endocrine milieu. There are some periods of time during development where nutrition may have long-lasting effects on metabolic function and milk production. For instance, the first months of postnatal life seem to be critical because recent data from both retrospective and controlled studies indicate that increased growth rate or plane of nutrition during this phase is positively associated with future milk production. Postnatal growth rate depends on nutrition (a necessary but not sufficient condition) and management (i.e., grouping strategies and housing systems), and thus optimal rearing programs should be designed considering long-term consequences on milk yield.

Olfactory Marker Protein Is Critical for Functional Maturation of Olfactory Sensory Neurons and Development of Mother Preference

Survival of many altricial animals critically depends on the sense of smell. Curiously, the olfactory system is rather immature at birth and undergoes a maturation process, which is poorly understood. Using patch-clamp technique on mouse olfactory sensory neurons (OSNs) with a defined odorant receptor, we demonstrate that OSNs exhibit functional maturation during the first month of postnatal life by developing faster response kinetics, higher sensitivity, and most intriguingly, higher selectivity. OSNs expressing mouse odorant receptor 23 (MOR23) are relatively broadly tuned in neonates and become selective detectors for the cognate odorant within 2 weeks. Remarkably, these changes are prevented by genetic ablation of olfactory marker protein (OMP), which is exclusively expressed in mature OSNs. Biochemical and pharmacological evidence suggests that alteration in odorant-induced phosphorylation of signaling proteins underlie some of the OMP(-/-) phenotypes. Furthermore, in a novel behavioral assay in which the mouse pups are given a choice between the biological mother and another unfamiliar lactating female, wild-type pups prefer the biological mother, while OMP knock-out pups fail to show preference. These results reveal that OSNs undergo an OMP-dependent functional maturation process that coincides with early development of the smell function, which is essential for pups to form preference for their mother.

Posterior neonatal teeth

Teeth which are present in the oral cavity of newborn infant at the time of birth are called "natal teeth" and which erupts in first month of postnatal life are called as "neonatal teeth." The incidence of these teeth is 1 in 2000 to 1 in 3500 live birth. The most common natal teeth reported are mandibular central incisors followed by maxillary incisors and mandibular canine. The natal or neonatal tooth in maxillary molar region is a rare occurrence. This article represents a rare case of bilateral neonatal maxillary molar teeth.

Determinants of early ponderal and statural growth in full-term infants in the EDEN mother-child cohort study

Growth velocity in the first months of postnatal life has been associated with later overweight and obesity. We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life. We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex. Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants. In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations.

Growth rate of the cell populations of the rat sublingual gland during the early postnatal period

The development of the rat sublingual gland during the first month of postnatal life was analyzed by morphometry. The absolute number of cells in the various morphological glandular compartments - mixed acini with serous demilunes, intercalated ducts, striated ducts and stroma - was determined by the Aherne II morphometric method for particle counting. The data of fresh glandular volume and the number of cells were analyzed by linear, exponential and parabolic regression, with the best fits being obtained with the linear equation. Based on these equations, the growth rate of glandular volume and of each cell population was calculated. Glandular volume increased about 12-fold during the period from 2 to 30 days of postnatal life, corresponding to a rate of 1.34 mm3/day. This volumetric growth of the gland was mainly due to significant 16-, 10-, 4-, 7- and 8-fold increases in the absolute number of mucous acinar, serous demilune, intercalated duct, striated duct and stromal cells, corresponding to a growth rate of 301 x 103, 228 x 103, 19 x 103, 54 x 103 and 247 x 103 cells/day, respectively. Based on the present results, we conclude that the mucous and serous cell populations of the mixed acini grew at a rate close to that of stromal cells, but considerably higher than that obtained for the intercalated duct and striated duct populations, with the lowest growth rate being observed for the ntercalated duct cell population.

Fatty Acid Supply to the Human Fetus

Deposition of fat in the fetus increases exponentially with gestational age, reaching its maximal rate-around 7 g/day or 90% of energy deposition-at term. In late pregnancy, many women consuming contemporary Western diets may not be able to meet the fetal demand for n-3 long chain polyunsaturated fatty acids (LCPUFAs) from the diet alone. Numerous mechanisms have evolved to protect human offspring from extreme variation or deficiency in the maternal diet during pregnancy. Maternal adipose tissue is an important source of LCPUFA. Temporal changes in placental function are synchronized with maternal metabolic and physiological changes to ensure a continuous supply of n-3 and n-6 LCPUFA-enriched fat to the fetus. LCPUFA storage in fetal adipose tissue provides an important source of LCPUFA during the critical first months of postnatal life. An appreciation of these adaptations is important in any nutritional strategy designed to improve the availability of fatty acids to the fetus.

Postnatal development of GABA‐immunoreactive neurons and terminals in rat periaqueductal gray matter: A light and electron microscopic study

The development of intrinsic gamma-aminobutyric acid (GABA)-ergic neurons was studied in the first month of postnatal life in the rat periaqueductal gray matter (PAG) by light and electron microscopy using an anti-GABA serum. At birth (postnatal day 0: P0) GABA-immunopositive (GABA(IP)) neurons were detected only on the outer edge of dorsolateral PAG (PAG-DL) and were rare in the other PAG subdivisions. Their distribution did not change from P0 to P5, while they increased progressively from P5 to P10 in PAG-DL and began to be detected in ventrolateral PAG (PAG-VL). At the end of the second postnatal week the immunostaining pattern was nearly adult-like, and between P20 and P30 the adult pattern of GABA immunoreactivity was established. Quantitative light microscopic examination indicated that in the first postnatal month the cross-sectional area of GABA(IP) neurons gradually increased from 67.63 and 78.69 microm(2) at P0 to 122.15 and 119.16 microm(2) at P30 in PAG-DL and PAG-VL, respectively. Electron microscopic observations disclosed GABA labeling from P0 in cell bodies, dendrites, growth cones, and axon terminals. GABA(IP) terminals were few in neonatal rats and became more numerous and morphologically mature around the second week. Synapse development and maturation were examined by quantitative ultrastructural analysis. Synaptic vesicle number and size of GABA(IP) axon terminals progressively grew in the first postnatal month. In conclusion, the number and size of GABA(IP) cells progressively increase in postnatal PAG, with two populations of intrinsic neurons expressing their GABAergic nature in two different periods.

Dynamics of changes in iron concentration and total iron binding capacity in blood plasma of goat kids during their first month of life (Short Communication)

Abstract. The experiment was carried out on 14 kids of Polish Improved White breed during the first 30 days of life. The aim of this study was to show changes in the concentration of blood plasma iron and total iron binding capacity (TIBC) during the neonatal period. The statistically confirmed differences (P≥0.01) in blood serum iron concentration was show in the kids between 5th (20.57 μmol/l) and 14th (9.97 μmol/l) day of life, and between 3rd and 4th week with the peak in 23rd day (27.50 μmol/l). We have also shown statisticly confirmed increase in TIBC (P≥0.01) between 1st and 4th day of life (+20.13 μmol/l), and between 14th and 23rd day of life (+15.59 μmol/l). Statistically confirmed decrease of TIBC was observed between 6th (52.30 μmol/l) and 14th (31.78 μmol/l) day of life. Conclusion: The studies have revealed dynamic changes in the concentration and total binding capacity of blood plasma iron concentration during the first month of postnatal life. The pattern of such changes does not depend on the gender or litter size. It was observed a significant decrease in the concentration of this trace element in blood plasma toward the end of the second week, which may indicate a relative iron deficiency, particularly in twin-born kids.

Measurement of the Great Vessels in the Mediastinum Could Help Distinguish True From False-Positive Coarctation of the Aorta in the Third Trimester

We investigated the utility of analyzing prenatal mediastinal measures of the great arteries in distinguishing true coarctation of the aorta (CoA) from false-positive CoA. All fetuses in this study had suspicion of CoA based on the presence of right-left heart disproportion. We defined 3 study groups: group 1, true fetal CoA; group 2, false-positive fetal CoA with a narrow aortic arch; and group 3, false-positive fetal CoA without a narrow aortic arch. In group 1, the mean mediastinal pulmonary artery (PA) to ascending aorta (Ao) diameter ratio +/- SD was 2.03 +/- 0.48, and in group 2, the ratio was 1.60 +/- 0.23. The difference was statistically significant (P = .0018, t test). In group 3, the mean PA:Ao ratio was 1.35 +/- 0.14. The difference between groups 1 and 3 was statistically significant (P = .0002, t test). In our study group, for a PA:Ao ratio of 1.60, sensitivity was 83.0%; specificity, 85.0%; positive predictive value, 62.5%; and negative predictive value, 94.0%. In the third trimester, the main PA:Ao ratio as measured in the fetal mediastinum can be a helpful tool in distinguishing true CoA requiring neonatal cardiac surgery from false-positive CoA and simple disproportion requiring medical attention but no surgery in the first month of postnatal life.

Olfactory guidance of nipple attachment and suckling in kittens of the domestic cat: Inborn and learned responses

In 60 kittens (11 litters) from free-ranging domestic cats we investigated the role of chemical cues in facilitating nipple attachment and suckling during the first month of postnatal life when kittens are totally dependent on the mother's milk. Kittens were tested both together and individually on sedated females in different reproductive states. We found (1) that newborn kittens with no suckling experience responded to the ventrum of lactating but not to the ventrum of nonlactating females with search behavior and attached to nipples within minutes; (2) that even in older kittens, nipple attachment depended on females' reproductive state, with virtually no attachments on nonreproducing females, some on pregnant females, the greatest number on early-lactating females, followed by a decline on late-lactating females; and (3) that kittens could locate their particular, most used nipple on their mother but not on a female of similar lactational age, even after eye opening. We suggest that kittens respond from birth with efficient nipple-search behavior to inborn olfactory cues on the mother's ventrum, that emission of these is under hormonal control, but that kittens also quickly learn olfactory cues specific to their own mother and to their own particular nipples.

Exploring Objects With Feet Advances Movement in Infants Born Preterm: A Randomized Controlled Trial

Previous work has shown that full-term infants who were healthy contacted a toy with their feet several weeks before they did so with their hands and that movement training advanced feet reaching. Certain populations of preterm infants are delayed in hand reaching; however, feet reaching has not been investigated in any preterm population. The primary purpose of this study was to determine whether preterm infants born at less than 33 weeks of gestational age contacted a toy with their feet at 2 months of corrected age, before doing so with their hands, and whether movement training advanced feet reaching. This study was a randomized controlled trial. Twenty-six infants born preterm were randomly assigned to receive daily movement training or daily social training. During the 8-week training period, the infants were videotaped in a testing session every other week from 2 to 4 months of age. Both groups contacted the toy with their feet at 2 months of age during the first testing session prior to training, at an age when no infants consistently contacted the toy with their hands. After 8 weeks of training, the movement training group displayed a greater number and longer duration of foot-toy contacts compared with the social training group. These results suggest that movement experiences advance feet reaching as they do for hand reaching. For clinicians, feet-oriented play may provide an early intervention strategy to encourage object interaction for movement impairments within the first months of postnatal life. Future studies can build on these results to test the long-term benefit of encouraging early purposeful leg movements.

α-Tocopherol Protects Against Oxidative Stress in the Fragile X Knockout Mouse: an Experimental Therapeutic Approach for the Fmr1 Deficiency

Fragile X syndrome is the most common genetic cause of mental disability. The mechanisms underlying the pathogenesis remain unclear and specific treatments are still under development. Previous studies have proposed an abnormal hypothalamic-pituitary-adrenal axis and high cortisol levels are demonstrated in the fragile X patients. Additionally, we have previously described that NADPH-oxidase activation leads to oxidative stress in the brain, representing a pathological mechanism in the fragile X mouse model. Fmr1-knockout mice develop an altered free radical production, abnormal glutathione homeostasis, high lipid and protein oxidation, accompanied by stress-dependent behavioral abnormalities and pathological changes in the first months of postnatal life. Chronic pharmacological treatment with alpha-tocopherol reversed pathophysiological hallmarks including free radical overproduction, oxidative stress, Rac1 and alpha-PKC activation, macroorchidism, and also behavior and learning deficits. The restoration of the oxidative status in the fragile X mouse emerges as a new and promising approach for further therapeutic research in fragile X syndrome.

Intrauterine programming of the cardiovascular system

Intrauterine programming of the cardiovascular system

Is it time to add aortic isthmus evaluation to the repertoire of Doppler investigations for placental insufficiency?

Is it time to add aortic isthmus evaluation to the repertoire of Doppler investigations for placental insufficiency?

Pulmonary artery/aorta ratio in simple screening for fetal outflow tract abnormalities during the second trimester

Congenital heart disease is associated with high mortality and morbidity rates, being the most life-threatening defect in the first month of postnatal life and accounting for approximately half of all childhood mortality from birth defects. Despite this, the prenatal detection rate for congenital outflow tract anomalies by ultrasound imaging is relatively low. The aim of this study was to establish a nomogram for the pulmonary artery/aorta (PA/AO) ratio measured in the three-vessel view plane. This ratio was investigated as a simple screening tool for congenital cardiac outflow tract abnormalities. The study was a prospective evaluation of 966 singleton fetuses at 16-24 weeks of gestation and 46 fetuses with congenital cardiac outflow tract abnormalities. The diameters of the pulmonary artery and aorta were measured in the three-vessel view. The PA/AO ratio was calculated and a nomogram was constructed. The mean and 95% CI for the ratio were defined and the PA/AO ratios of cases with outflow tract abnormalities were plotted against the values for normal fetuses. The gestational age of the normal group ranged from 16 to 24 weeks, with a median of 19 weeks. The pulmonary artery diameter measured between 2.1 and 4.93 mm (mean, 3.3 mm) and the aorta measured between 2.1 and 5.2 mm (mean, 2.93 mm). The mean (SD) PA/AO ratio was 1.16 (0.18) (95% CI, 0.87-1.58; range 0.61-1.86; median, 1.14). For fetuses with outflow tract abnormalities, the median gestation was 19 weeks and 37/43 (86%) had a PA/AO ratio outside the 95% CI. The PA/AO ratio derived from measurements in the three-vessel view plane can be used as an initial screening tool for outflow tract anomalies and may have a sensitivity of up to 86%, with a 5% false-positive rate.

Renal Drug Clearance in Preterm Neonates: Relation to Prenatal Growth

Aminoglycosides and glycopeptides are almost exclusively eliminated by renal excretion. Postmenstrual age (PMA) is the best predictor of their clearance, presumably because it predicts the time course of development of the glomerular filtration rate (GFR). Intrauterine growth restriction has an impact on the normalized weight of the kidney, on the number of nephrons, on GFR, and on tubular function in human perinatal life. We investigated whether prenatal growth also affects clearance of drugs such as aminoglycosides or glycopeptides that are eliminated through the kidney. Observations collected in two population pharmacokinetic studies involving preterm neonates and investigating amikacin and vancomycin in the first month of postnatal life were used to estimate the impact of prenatal growth (as judged by birth weight for gestational age) on the clearance of these drugs. Data from 1212 drug measurements (vancomycin, 648; amikacin, 564) in 531 subjects (vancomycin, 249; amikacin, 282) were available for study. Neonates born small for gestational age (SGA) were found to have a 16.2% (coefficient of variation, 12.2%) reduction in drug clearance. This effect was present from birth up to the postnatal age of 4 weeks. The covariate size (weight 0.75) explained 47.3% of drug clearance; PMA, 25.2%; coadministration of a nonselective cyclo-oxygenase inhibitor, 3.5%; renal function, 7.6%; and SGA, 1.7%. Renal drug clearance is significantly lower in preterm neonates born SGA than in appropriate-for-gestational-age (AGA) controls. This reduced clearance was observed not only at birth but also up to the postnatal age of 4 weeks.

Postnatal exposure to cocaine in rats housed in an enriched environment: effects on social interactions

This study was undertaken to evaluate the effects of environmental enrichment (EE) in rats exposed to cocaine during the first month of postnatal life by examining several categories of social behaviour (play fighting, social investigation, comfort behaviours and invitation to play). Wistar rats were divided in four groups: pups exposed to cocaine hydrochloride (15 mg/kg body weight/day), sc, in two daily doses, from postnatal day (PND) 1 to 28 and reared in EE; exposed to cocaine as previously described and reared in standard environment (SE); saline-exposed and reared in EE; pups saline-exposed and reared in SE. On PND 21, 24 and 28, social interactions were examined for 10 min. Results show that cocaine animals reared in SE decreased the frequency of play solicitation. Control animals reared in EE exhibited decreased play fighting and social investigation behaviours compared to SE-reared rats. Animals postnatally exposed to cocaine when reared in EE displayed more comfort and invitation to play behaviours and decreased social investigation compared with SE-reared animals. The results suggest that in rats postnatally exposed to cocaine, EE rearing elicited differences in both processing of environmental stimuli and a response to social challenges.

Developmental increase in the amount of rapsyn per acetylcholine receptor promotes postsynaptic receptor packing and stability

Neuromuscular synaptic transmission depends upon tight packing of acetylcholine receptors (AChRs) into postsynaptic AChR aggregates, but not all postsynaptic AChRs are aggregated. Here we describe a new confocal Fluorescence Resonance Energy Transfer (FRET) assay for semi-quantitative comparison of the degree to which AChRs are aggregated at synapses. During the first month of postnatal life the mouse tibialis anterior muscle showed increases both in the number of postsynaptic AChRs and the efficiency with which AChR was aggregated (by FRET). There was a concurrent two-fold increase in immunofluorescent labeling for the AChR-associated cytoplasmic protein, rapsyn. When 1-month old muscle was denervated, postsynaptic rapsyn immunostaining was reduced, as was the efficiency of AChR aggregation. In vivo electroporation of rapsyn-EGFP into muscle fibers increased postsynaptic rapsyn levels. Those synapses with higher ratios of rapsyn-EGFP to AChR displayed a slower metabolic turnover of AChR. Conversely, the reduction of postsynaptic rapsyn after denervation was accompanied by an acceleration of AChR turnover. Thus, a developmental increase in the amount of rapsyn targeted to the postsynaptic membrane may drive enhanced postsynaptic AChRs aggregation and AChR stability within the postsynaptic membrane.