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PubMed2004

Clinical utilization of atypical antipsychotics in pregnancy and lactation.

OBJECTIVE: To analyze the available literature regarding the safety of atypical antipsychotics in pregnancy and lactation in order to recommend evidence-based strategies for pharmacologic management of psychosis in these conditions. DATA SOURCES: We summarized the results from articles identified via MEDLINE/PubMed/TOXNET (1993-January 31, 2004), using the key terms pregnancy, lactation, breast-feeding, human milk, psychotropic drugs, atypical antipsychotics, olanzapine, quetiapine, risperidone, clozapine, ziprasidone, and aripiprazole. STUDY SELECTION AND DATA EXTRACTION: Retrospective studies, clinical observations, and case reports regarding the 6 atypical antipsychotics mentioned above were selected and analyzed. Extensive manual review of pertinent journals and textbooks was also performed. DATA SYNTHESIS: Reviewed studies show that olanzapine and clozapine apparently do not increase the teratogenic risk if administered to pregnant women, while evidence on quetiapine, risperidone, aripiprazole, and ziprasidone is still limited. In contrast, available information is not able to exclude unwanted serious effects associated with the use of all atypical antipsychotics on mother-infant dyads. Furthermore, more than a few studies suggest increased hyperglycemic risk for pregnant women related to atypical antipsychotic therapy during gestation. Finally, published evidence about the effects on long-term infant neurodevelopment of drug exposure through both placenta and breast milk is represented only by sporadic case reports. CONCLUSIONS: It is well known that potential consequences of an untreated psychotic episode may be severe and may lead to the mother attempting suicide and/or infanticide. For these reasons, clinicians need to help mothers weigh both fetal and neonatal risks of exposure to drugs against the potential risk they and their infant may incur if the psychiatric illness is not treated. On the other hand, atypical antipsychotics in pregnancy and breast-feeding do not show evident advantages in safety when compared with typical neuroleptic agents. Therefore, we suggest that the most relevant parameters for selecting the best clinical option for pregnant and breast-feeding women with schizophrenia and related disorders remain strongly related to 3 main points: (1). cautious evaluation of the risk/benefit ratio of fetal and neonatal drug exposure, (2). degree of severity of maternal psychiatric illness, and (3). careful preliminary choice of drugs characterized by a balanced safety/efficacy profile.

Breast Feeding↗

PubMed2003

Prevalence of fatty acid ethyl esters in meconium specimens.

BACKGROUND: Fetal alcohol syndrome (FAS), alcohol-related birth defects (ARBDs), and alcohol-related neurodevelopment disorders (ARNDs) in neonates are often the result of maternal alcohol consumption during pregnancy. Facial characteristics are associated with FAS, but ARBDs and ARNDs are more difficult to diagnose. Fetal exposure to alcohol can cause central nervous system dysfunction, pre- and postnatal growth problems, cardiac defects in neonates, and attention deficit disorders and mental retardation in older children. To date, diagnosis of fetal alcohol effect has depended largely on maternal interview, although clinical tests are becoming more widely used. Fatty acid ethyl esters (FAEEs) are formed in the body by esterification of ethanol with free fatty acids and trans-esterification of glycerides and have been detected in the meconium of newborns. This report estimates the prevalence of fetal alcohol exposure in two populations by detecting FAEEs in meconium. METHODS: We analyzed the prevalence of FAEEs in the meconium of two separate groups of neonates by use of solid-phase extraction and analysis by gas chromatography-mass spectrometry in the chemical ionization mode. In the first study, meconium samples were taken anonymously from babies born in a large, regional perinatal center in Hawaii. In the second study, specimens were obtained from infants admitted to six different newborn intensive care units within the state of Utah. RESULTS: In the first study, 73 of 436 (16.7%) meconium specimens tested were considered positive for FAEEs. When broken down into quartiles, the mean total FAEEs measured were 1,059, 3,133, 6,628, and 62,115 ng/g. In the second study, 35 of 289 (12.1%) specimens were considered positive. When broken into quartiles, the mean total FAEEs were 1,139, 3,067, 7,674, and 50,143 ng/g. The overall FAEE profiles of the two study sets were remarkably similar. CONCLUSION: In an adequate meconium specimen, a total FAEE concentration >10,000 ng/g may indicate that the newborn has been exposed to significant amounts of alcohol during pregnancy.

Biomarkers↗

PubMed2001

Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.

Child Development↗

PubMed2002

A review of gene expression patterns in the malformed brain.

Major advances in the identification of genes expressed in malformation-associated epileptic disorders have been made. Some of these changes reflect the complex gene interactions necessary for proper neurodevelopment, whereas others suggest specific synaptic aberrations that could result in a hyperexcitable, and ultimately, epileptic condition. Here we review reported changes in gene expression associated with a malformed brain, with particular emphasis on how these changes provide clues to seizure genesis.

Animals↗

PubMed2001

The effect of postnatal steroids on growth and development.

Single courses of prenatal corticosteroids have many beneficial effects including reduction in respiratory distress syndrome, intraventricular hemorrhage and neonatal mortality. Postnatal corticosteroids, however, have both beneficial and harmful effects. The beneficial effects include shortened time on the ventilator and a reduction in chronic lung disease. Dexamethasone treatment started within the first 4 days of life is associated with an increased risk of abnormal neurodevelopment including cerebral palsy. Other adverse effects include metabolic disturbances, cardiac hypertrophy, reduced growth and gastrointestinal perforation. The risks of early dexamethasone treatment in currently used doses outweigh the benefits. Further research is needed to determine the optimal corticosteroid drug, its dose and timing of administration to maximize benefit and reduce risk to a minimum. Other non-drug interventions should be used to minimize the risk of chronic lung disease in very preterm infants.

Adrenal Cortex Hormones↗

PubMed2006

Impact of breast-feeding on psychomotor and neuropsychological development in children of diabetic mothers: role of the late neonatal period.

AIM: Previous data from our Kaulsdorf Cohort Study (KCS) suggest that early neonatal ingestion (1st week) of breast milk from diabetic mothers (diabetic breast milk, DBM) may increase the risk of being overweight and delay speech development in offspring of diabetic mothers (ODM). Late neonatal DBM ingestion (2nd-4th week), however, not independently influenced the risk of overweight. We investigated whether late neonatal DBM ingestion might independently influence neuro-development. METHODS: Achievement of developmental milestones according to late neonatal DBM intake was analyzed in 242 ODM. RESULTS: No impact of DBM ingestion on psychomotor parameters was observed. In contrast, it negatively influenced onset of speaking (no DBM: median 44.0 weeks, range 31.0-72.0; some DBM: 48.0, 24.0-100.0; DBM only: 52.0, 28.0-84.0; P=0.037) and halved the probability of reaching this milestone at any time point (hazard ratio: 0.53, 95% confidence interval: 0.31-0.91). However, adjustment for DBM volume ingested during the early neonatal period weakened the hazard ratio towards non-significance. In the fully adjusted model, the hazard ratio was halved, but insignificant. CONCLUSIONS: Our results underscore that neonatal DBM ingestion, particularly during the first week of life, may delay speech development, an important indicator of cognitive development. Further studies are urgently recommended on consequences of breast-feeding for neurodevelopment in ODM.

Adult↗

PubMed1996

Neurodevelopmental outcome of infants exposed to indomethacin antenatally.

The use of indomethacin as a tocolytic agent has been limited because of potential fetal and neonatal complications. We investigated the neonatal and neurodevelopmental outcome of preterm infants exposed antenatally to this drug. The records of 779 women admitted in premature labor during a five year period were reviewed. Nineteen women who received indomethacin (initial dose of 50-100 mg followed by 50-100 mg/day) and their 25 infants were identified. Delivery was delayed for a week or longer in 86.6% of the mothers. There were two deaths: a stillborn with multiple congenital anomalies and a neonate with congenital listeriosis. Seven infants were born at term without complications. Fifteen infants born prematurely were compared to 15 control infants not exposed to indomethacin antenatally. There were no statistically significant differences between the two groups in the prevalence or severity of thrombocytopenia, hyperbilirubinemia, intraventricular hemorrhages, patent ductus arteriosus, persistent pulmonary hypertension, bronchopulmonary dysplasia, and necrotizing enterocolitis. Mean BUN, creatine, and urine output for the first three days of life were similar in the two groups. No differences were found at the 6-12 month neurodevelopment assessment. We found no neonatal complications attributable to the antenatal use of indomethacin.

Adult↗

PubMed2004

Neural stem cells show bidirectional experience-dependent plasticity in the perinatal mammalian brain.

Many of the effects of prenatal stress on the endocrine function, brain morphology, and behavior in mammals can be reversed by brief sessions of postnatal separation and handling. We have tested the hypothesis that the effects of both the prenatal and postnatal experiences are mediated by negative and positive regulation of neural stem cell (NSC) number during critical stages in neurodevelopment. We used the in vitro clonal neurosphere assay to quantify NSCs in hamsters that had experienced prenatal stress (maternal restraint stress for 2 hr per day, for the last 7 d of gestation), postnatal handling (maternal-offspring separation for 15 min per day during postnatal days 1-21), orboth. Prenatal stress reduced the number of NSCs derived from the subependyma of the lateral ventricle. The effect was already present at postnatal day 1 and persisted into adulthood (at least 14 months of age). Similarly, prenatal stress reduced in vivo proliferation in the adult subependyma of the lateral ventricle. Conversely, postnatal handling increased NSC number and reversed the effect of prenatal stress. The effects of prenatal stress on NSCs and proliferation and the effect of postnatal handling on NSCs did not differ between male and females. The findings demonstrate that environmental factors can produce changes in NSC number that are present at birth and endure into late adulthood. These changes may underlie some of the behavioral effects produced by prenatal stress and postnatal handling.

Animals↗

PubMed2006

Behavioral and neurochemical alterations in mice lacking the RNA-binding protein translin.

Synapse-specific local protein synthesis is thought to be important for neurodevelopment and plasticity and involves neuronal RNA-binding proteins that regulate the transport and translation of dendritically localized transcripts. The best characterized of these RNA-binding proteins is the fragile X mental retardation protein (FMRP). Mutations affecting the expression or function of FMRP cause fragile X syndrome in humans, and targeted deletion of the gene encoding FMRP results in developmental and behavioral alterations in mice. Translin is an RNA-binding protein that regulates mRNA transport and translation in mouse male germ cells and is proposed to play a similar role in neurons. Like FMRP, translin is present in neuronal dendrites, binds dendritically localized RNA, and associates with microtubules and motor proteins. We reported previously the production of viable homozygous translin knock-out mice, which demonstrate altered expression of multiple mRNA transcripts in the brain and mild motor impairments. Here, we report that translin knock-out mice also exhibit sex-specific differences in tests of learning and memory, locomotor activity, anxiety-related behavior, and sensorimotor gating, as well as handling-induced seizures and alterations in monoamine neurotransmitter levels in several forebrain regions. Similar behavioral and neurochemical alterations have been observed in mice lacking FMRP, suggesting that both proteins may act within the same neuronal systems and signaling pathways. Our results in mice indicate that mutations in translin may contribute to fragile X-like syndromes, mental retardation, attention deficit hyperactivity disorder, epilepsy, and autism spectrum disorders in humans.

Animals↗

PubMed2004

Role of thyroid hormone during early brain development.

The present comments are restricted to the role of maternal thyroid hormone on early brain development, and are based mostly on information presently available for the human fetal brain. It emphasizes that maternal hypothyroxinemia - defined as thyroxine (T4) concentrations that are low for the stage of pregnancy - is potentially damaging for neurodevelopment of the fetus throughout pregnancy, but especially so before midgestation, as the mother is then the only source of T4 for the developing brain. Despite a highly efficient uterine-placental 'barrier' to their transfer, very small amounts of T4 and triiodothyronine (T3) of maternal origin are present in the fetal compartment by 4 weeks after conception, with T4 increasing steadily thereafter. A major proportion of T4 in fetal fluids is not protein-bound: the 'free' T4 (FT4) available to fetal tissues is determined by the maternal serum T4, and reaches concentrations known to be of biological significance in adults. Despite very low T3 and 'free' T3 (FT3) in fetal fluids, the T3 generated locally from T4 in the cerebral cortex reaches adult concentrations by midgestation, and is partly bound to its nuclear receptor. Experimental results in the rat strongly support the conclusion that thyroid hormone is already required for normal corticogenesis very early in pregnancy. The first trimester surge of maternal FT4 is proposed as a biologically relevant event controlled by the conceptus to ensure its developing cerebral cortex is provided with the necessary amounts of substrate for the local generation of adequate amounts of T3 for binding to its nuclear receptor. Women unable to increase their production of T4 early in pregnancy would constitute a population at risk for neurological disabilities in their children. As mild-moderate iodine deficiency is still the most widespread cause of maternal hypothyroxinemia in Western societies, the birth of many children with learning disabilities may already be preventable by advising women to take iodine supplements as soon as pregnancy starts, or earlier if possible.

Animals↗

PubMed1997

Elective high-frequency oscillatory ventilation versus conventional ventilation in preterm infants with pulmonary dysfunction: systematic review and meta-analyses.

OBJECTIVES: To systematically review the evidence to determine whether the routine use of high-frequency oscillatory ventilation (HFOV) as compared with conventional ventilation (CV) is beneficial or harmful in preterm infants requiring mechanical ventilation for pulmonary failure principally due to respiratory distress syndrome. METHODS: All randomized controlled trials of elective HFOV versus CV in preterm infants <36 weeks' gestation with respiratory failure mainly attributable to respiratory distress syndrome were identified from the literature through a search of MEDLINE, EMBASE, Oxford database of Perinatal trials, and previous reviews including cross-references and abstracts. Meta-analyses using event rate ratios (ERR), event rate difference, and if significant, number needed-to-treat were calculated (95% confidence limits were used for all analyses). Two prespecified subgroup analyses were performed. RESULTS: Four published trials were included. Meta-analyses revealed the following ERR (95% confidence intervals) for HFOV versus CV: mortality at 28 to 30 days, 1.02 (0.76, 1.39); chronic lung disease (CLD) at 28 days, 0.86 (0.73, 1.01); mortality or CLD, 0.9 (0.80, 1. 01); air-leak syndromes, 1.13 (0.97, 1.33); mechanical ventilation at 28 days, 1.06 (0.84, 1.33); supplemental oxygen at discharge, 0. 59 (0.37, 0.92); intraventricular hemorrhage (IVH) all grades, 1.11 (0.95, 1.29); IVH (grades 3 or 4), 1.32 (1.01, 1.72); and periventricular leukomalacia, 1.39 (0.91, 2.13). In the subgroup of trials in which a high volume strategy (HVS) was used the ERR for CLD was 0.53 (0.36, 0.78); mortality or CLD, 0.56 (0.40, 0.77); supplemental oxygen at discharge, 0.57 (0.36, 0.92); IVH (all grades), 0.90 (0.61, 1.33); and IVH (grades 3 or 4), 0.84 (0.39, 1. 84). Results were similar to these for the trials using surfactant. One recent trial suggests that HFOV may reduce the cost of in-hospital care. CONCLUSIONS: The overall meta-analysis is dominated by the HIFI study, which was criticized for its methodology and surfactant was not used. Subsequent studies, most of which used HVS and/or surfactant, have shown benefits in measures of CLD without an increase in rates of IVH. Caution is warranted in interpreting these results because: 1) the treatment is not blinded and this could affect some outcomes; 2) except for one small trial postneonatal survival, lung function, and neurodevelopment have not been reported from HVS trials; and 3) the benefits and disadvantages have not been reported in infants born at different gestational ages or different birth weights. Importantly, results from groups experienced in the use of HFOV may not be readily generalizable.

Barotrauma↗

PubMed1999

Breastfeeding effects on intelligence quotient in 4- and 11-year-old children.

OBJECTIVE: A study of preterm children found an IQ advantage among those who were breastfed as infants after controlling for maternal social class and educational status. However, this advantage needs to be examined in light of other maternal characteristics, such as maternal IQ and parenting skills, which were not measured in that study and which have been found to be related to breastfeeding. METHODOLOGY: IQ was assessed in 323 children at 4 years of age on the McCarthy Scales of Children's Abilities and the Peabody Picture Vocabulary Test-Revised and in 280 children on the Wechsler Intelligence Test for Children-Revised at 11 years of age. RESULTS: Children who were breastfed in infancy had significantly higher scores on IQ tests at both ages, even after adjusting for social class and education, confirming the earlier findings and extending them to a predominantly full-term sample. However, the effect of breastfeeding was no longer significant after adjusting for maternal IQ assessed on the Peabody Picture Vocabulary Test-Revised and for parenting skills assessed on the Home Observation for Measurement of the Environment. Significant relations between breastfeeding and Woodcock Reading Achievement scores at 11 years were also reduced to nonsignificant levels after the inclusion of maternal IQ and the Home Observation for Measurement of the Environment. CONCLUSIONS: These findings suggest that the observed advantage of breastfeeding on IQ is related to genetic and socioenvironmental factors rather than to the nutritional benefits of breastfeeding on neurodevelopment. They should not be interpreted as detracting from the medical benefits associated with breastfeeding.

Bottle Feeding↗

PubMed2001

Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 Weeks' postconceptional Age.

BACKGROUND: Management of pain in very low birth weight infants is limited by a lack of empiric knowledge about the multiple determinants of biobehavioral reactivity in infants receiving neonatal intensive care. OBJECTIVE: To examine relationship of early neonatal factors and previous medication exposure to subsequent biobehavioral reactivity to acute pain of blood collection. DESIGN: Prospective cohort study. Methods. One hundred thirty-six very low birth weight (</=1500 g) infants who underwent heel lance for blood collection at 32 weeks' postconceptional age formed the study sample, after excluding those with significant cerebral lesions (periventricular leukomalacia or cerebral parenchymal infarction [grade 4 intraventricular hemorrhage]) on cranial ultrasound. Pain reactions were assessed using the Neonatal Facial Coding System, infant state, and spectral analysis of change in heart rate variability from baseline to reaction to invasive stimulation. Factor analysis was used to provide an empirical basis for deriving summary pain scores, one factor was primarily behavioral and the other primarily autonomic. RESULTS: A normal reaction to procedural pain is characterized by facial grimacing and heightened cardiac sympathetic activity. The most significant factors associated with altered behavioral and autonomic pain reactivity at 32 weeks' postconceptional age were a greater number of previous invasive procedures since birth and gestational age (GA) at birth, both of which were related to a dampened response. After controlling for these variables, exogenous steroid exposure made an independent contribution to both the behavioral and autonomic pain scores, also in the direction of dampening the response. Conversely, previous exposure to morphine was associated with "normalized" (ie, increased) rather than diminished responses. In addition, higher mean heart rate at baseline was associated with lower GA at birth and longer time on mechanical ventilation. CONCLUSION: Early pain exposure at very low GA may alter the autonomic substrate, resulting in infants who are in a perpetual state of stress. The results of this study suggest that the judicious use of analgesia may ameliorate these effects on later pain reactivity. However, although early morphine exposure may "normalize" subsequent pain reaction, this study did not examine its effects on neurodevelopment.

Blood Specimen Collection↗

PubMed2001

Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy.

OBJECTIVE: The electroencephalogram (EEG) is widely used in full-term infants with acute neonatal encephalopathy, and its prognostic value has been confirmed by several studies. Magnetic resonance imaging (MRI) of the brain has also been applied in these patients, and increasing numbers of reports affirm its prognostic reliability. The aim of this study has been to investigate the correlation between an early EEG and MRI findings in infants with acute neonatal encephalopathy and to assess the prognostic value of a combination of EEG and MRI findings. PARTICIPANTS AND METHODS: Twenty-five full-term infants had an EEG recorded within the first 72 hours after birth and a neonatal brain MRI scan after the end of the first week. RESULTS: Both EEG and MRI were predictive of outcome. A normal MRI was always associated with normal EEG background activity and normal outcome and severe abnormalities on MRI with marked EEG abnormalities and an abnormal outcome. When the MRI showed moderate abnormalities, the EEG in all cases but one identified patients with normal and abnormal outcome.EEG, MRI, HIE, neurodevelopment.

Brain↗

PubMed2001

Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants.

OBJECTIVES: Preterm infants are frequently discharged from the hospital growth retarded and show reduced growth throughout childhood. In a large efficacy and safety trial, we tested the hypothesis that nutritional intervention in the first 9 months postterm would reverse postdischarge growth deficits and improve neurodevelopment without adverse safety outcomes. PARTICIPANTS AND INTERVENTION: Two hundred eighty-four infants (mean gestation: 30.9 weeks) were studied; 229 were randomly assigned a protein, energy, mineral, and micronutrient-enriched postdischarge formula (PDF; N = 113) or standard term formula (TF; N = 116) from discharge (mean 36.5 weeks' postmenstrual age). A reference group (N = 65) was breastfed until at least 6 weeks' postterm. Outcome measures. Anthropometry was performed at 6 weeks and 3, 6, 9, and 18 months. Development was measured at 9 months (Knobloch, Passamanick, and Sherrard's developmental screening inventory) and 18 months (Bayley Scales of Infant Development II; primary outcome) postterm. RESULTS: At 9 months, compared with the TF group, those fed PDF were heavier (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (difference 1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 months (difference 0.82 cm; 95% CI: -0.04-1.7). There was no effect on head circumference. The effect of diet was greatest in males; at 9 months length deficit with TF was 1.5cm (95% CI: 0.3-2.7), and this remained at 18 months (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in developmental scores at 9 or 18 months, although PDF infants had a 2.8 (-1.3-6.8) point advantage in Bayley motor score scales. At 6 weeks' postterm, exclusively breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6cm (95% CI: 0.8-2.3) shorter than the PDF group, and they remained smaller up to 9 months' postterm. CONCLUSIONS: 1) Improving postdischarge nutrition in the first 9 months may "reset" subsequent growth-at least until 18 months for body length. We intend to follow-up the children at older ages. The observed efficacy of PDF was not associated with adverse safety outcomes. 2) We cannot reject the hypothesis that postdischarge nutrition benefits motor development and this requires additional study. 3) Our data raise the possibility that breastfed postdischarge preterm infants may require nutritional supplementation, currently under investigation.

Anthropometry↗

PubMed2002

Maternal bone lead as an independent risk factor for fetal neurotoxicity: a prospective study.

OBJECTIVE: A number of prospective studies have examined lead levels in umbilical cord blood at birth as predictors of infant mental development. Although several have found significant inverse associations, others have not. Measurement of lead levels in maternal bone, now recognized as the source of much fetal exposure, has the potential to serve as a better or complementary predictor of lead's effect on the fetus. Our objective was to compare lead levels in umbilical cord blood and maternal bone as independent predictors of infant mental development using a prospective design. METHODS: We recruited women who were giving birth at 3 maternity hospitals in Mexico City that serve a homogeneous middle-class community. Umbilical cord blood lead levels were measured by graphite furnace atomic absorption spectroscopy, and maternal lead levels in cortical (tibial) and trabecular (patellar) bone were measured within 4 weeks of giving birth using a 109-Cd K-x-ray fluorescence instrument. At 24 months of age, each infant was assessed using the Bayley Scales of Infant Development-II (Spanish Version). RESULTS: A total of 197 mother-infant pairs completed this portion of the study and had data on all variables of interest. After adjustment for other well-known determinants of infant neurodevelopment, including maternal age, IQ, and education; paternal education; marital status; breastfeeding duration; infant gender; and infant illness, lead levels in umbilical cord blood and trabecular bone were significantly, independently, and inversely associated with the Mental Development Index (MDI) scores of the Bayley Scale. In relation to the lowest quartile of trabecular bone lead, the second, third, and fourth quartiles were associated with 5.4-, 7.2-, and 6.5-point decrements in adjusted MDI scores. A 2-fold increase in cord blood lead level (eg, from 5 to 10 micro g/dL) was associated with a 3.1-point decrement in MDI score, which is comparable to the magnitude of effect seen in previous studies. CONCLUSION: Higher maternal trabecular bone lead levels constitute an independent risk factor for impaired mental development in infants at 24 months of age. This effect is probably attributable to mobilization of maternal bone lead stores, a phenomenon that may constitute a significant public health problem in view of the long residence time of lead in bone.

Bone and Bones↗

PubMed2002

Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants.

OBJECTIVE: We tested the hypothesis that balanced addition of long-chain polyunsaturated fatty acid (LCPUFA) to preterm formula during the first weeks of life would confer long-term neurodevelopmental advantage in a double-blind, randomized, controlled trial of preterm formula with and without preformed LCPUFA. METHODS: The participants were 195 formula-fed preterm infants (birth weight <1750 g, gestation <37 weeks) from 2 UK neonatal units and 88 breast milk-fed infants. Main outcome measures were Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 18 months and Knobloch, Passamanick and Sherrard's Developmental Screening Inventory at 9 months' corrected age. Safety outcome measures were anthropometry at 9 and 18 months, tolerance, infection, necrotizing enterocolitis, and death. RESULTS: There were no significant differences in developmental scores between randomized groups, although infants who were fed LCPUFA-supplemented formula showed a nonsignificant 2.6-point (0.25 standard deviation) advantage in MDI and PDI at 18 months, with a greater (nonsignificant) advantage (MDI: 4.5 points; PDI: 5.8 points) in infants below 30 weeks' gestation. LCPUFA-supplemented infants were shorter than control infants at 18 months (difference in length standard deviation score: 0.44; 95% confidence interval: 0.08-0.8). No other significant short- or long-term differences in safety outcomes were observed. Breastfed infants had significantly higher developmental scores at 9 and 18 months than both formula groups and were significantly heavier and longer at 18 months than LCPUFA-supplemented but not control infants. CONCLUSIONS: With the dose, duration, and preparation of LCPUFA used, efficacy was not demonstrated, although an advantage in later neurodevelopment cannot be excluded by global tests of development up to 18 months, particularly in infants below 30 weeks' gestation. The surprising effect of LCPUFA-supplemented formula on growth 18 months beyond the intervention period needs to be confirmed in other studies using similar supplementation strategies. Additional follow-up of this cohort is critical at an age when more specific tests of cognitive function are possible.

Age Factors↗

PubMed2004

Bias in reported neurodevelopmental outcomes among extremely low birth weight survivors.

OBJECTIVES: The purpose of this study was to investigate possible bias in the evaluation of neurodevelopment and somatic growth at 18 to 22 months' postmenstrual age among extremely low birth weight (ELBW) survivors (401-1000 g at birth). METHODS: Data from a cohort of 1483 ELBW infant survivors who were born January 1993 through December 1994 and cared for at centers in the Neonatal Research Network of the National Institute of Child Health and Human Development were examined retrospectively. Children who were compliant with an 18- to 22-month follow-up visit, who visited but were not measured, or who made no visit were compared regarding 4 outcomes: 1) Bayley Scales of Infant Development, 2nd edition, Mental Developmental Index (MDI) <70 and 2) Psychomotor Developmental Index (PDI) <70, 3) presence or absence of cerebral palsy, and 4) weight <10th percentile for age. Logistic regression models were used to predict likelihood of these outcomes for children with no follow-up evaluation, and predicted probability distributions were compared across the groups. RESULTS: Compared with children who were lost to follow-up, those who were compliant with follow-up were more likely to have been 1 of a multiple birth, to have received postnatal glucocorticoids, and to have had chronic lung disease. These factors were significantly associated with MDI and PDI <70 in the compliant group. Chronic lung disease was associated with increased risk of cerebral palsy (CP). MDI and PDI scores <70 were found in 37% and 29% of children who were evaluated at follow-up, respectively. Prediction models revealed that 34% and 26% of infants in the no-visit group would have had MDI and PDI scores <70. Compliant children tended to have greater incidence of MDI <70 compared with those predicted in the no-visit group but not PDI <70. CP was identified in 17% of the compliant group and predicted for 18% of the no-visit group. Predicted probabilities of having CP were marginally higher among the no-visit infants compared with those who were compliant with follow-up. There were no statistically significant somatic growth differences among the compliant, visit but not measured, and no-visit groups. CONCLUSION: ELBW infant survivors who weighed 401 to 1000 g at birth and who are compliant with follow-up evaluations may have worse Bayley Scales of Infant Development, 2nd edition, MDI scores than infants with no visit. Thus, follow-up studies based on infants who are compliant with follow-up care may lead to an overestimation of adverse outcomes in ELBW survivors.

Bias↗