Incidence Of Neonatal Mortality Research Articles

Analysis of Gga null mice demonstrates a non-redundant role for mammalian GGA2 during development.

Numerous studies using cultured mammalian cells have shown that the three GGAs (Golgi-localized, gamma-ear containing, ADP-ribosylation factor- binding proteins) function in the transport of cargo proteins between the trans- Golgi network and endosomes. However, the in vivo role(s) of these adaptor proteins and their possible functional redundancy has not been analyzed. In this study, the genes encoding GGAs1-3 were disrupted in mice by insertional mutagenesis. Loss of GGA1 or GGA3 alone was well tolerated whereas the absence of GGA2 resulted in embryonic or neonatal lethality, depending on the genetic background of the mice. Thus, GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3. The combined loss of GGA1 and GGA3 also resulted in a high incidence of neonatal mortality but in this case the expression level of GGA2 may be inadequate to compensate for the loss of the other two GGAs. We conclude that the three mammalian GGAs are essential proteins that are not fully redundant.

A systematic review of severe morbidity in infants born late preterm

Late-preterm infants (34 weeks 0/7 days-36 weeks 6/7 days' gestation) represent the largest proportion of singleton preterm births. A systematic review was performed to access the short- and/or long-term morbidity of late-preterm infants. An electronic search was conducted for cohort studies published from January 2000 through July 2010. We identified 22 studies studying 29,375,675 infants. Compared with infants born at term, infants born late preterm were more likely to suffer poorer short-term outcomes such as respiratory distress syndrome (relative risk [RR], 17.3), intraventricular hemorrhage (RR, 4.9), and death <28 days (RR, 5.9). Beyond the neonatal period, late-preterm infants were more likely to die in the first year (RR, 3.7) and to suffer from cerebral palsy (RR, 3.1). Although the absolute incidence of neonatal mortality and morbidity in infants born late preterm is low, its incidence is significantly increased as compared with infants born at term.

450: A systematic review for severe morbidity in infants born late preterm

Late preterm infants (34 0/7 to 36 6/7 weeks gestation) are the largest proportion of singleton preterm births. They are usually considered to be functionally and developmentally as mature as term newborns, and therefore of little concern for medical research. As a consequence, the morbidity among late preterm infants has not been assessed systematically. We therefore performed a systematic review on the subject. We performed an electronic search of PubMed, Medline, Embase and Cochrane trials databases (from January 2000 to June 2010) for cohort studies that reported on short-term and/or long-term outcomes of infants born late preterm. When the study also reported on the outcome of infants born at term (≥ 37 weeks), we compared outcomes by calculating odds ratios (OR) with 95% confidence intervals (95% CI). We identified 33 articles. Compared to infants born at term, infants born late preterm were more likely to have a 5 minute Apgar score <7 (OR 4.1, 95% CI 3.8 to 4.4), more likely to need mechanical ventilation (OR 2.8, 95% CI 2.6 to 3.1), to suffer from transient tachypnea (OR 6.7, 95% CI 6 to 7.4), respiratory distress syndrome (OR 4.7, 95% CI 4.2 to 5.3), hypothermia (OR 13, 95% CI 5.6 to 31), hypoglycaemia (OR 6.5, 95% CI 5.6 to 7.5), jaundice requiring phototherapy (OR 3.8, 95% 3.5 to 4.1), sepsis work-up (OR 1.9, 95% CI 1.8 to 2.0), convulsions (OR 1.5, 95% CI 0.94 to 2.4), intraventricular haemorrhages (OR 3.6, 95% CI 2.8 to 4.7), necrotizing enterocolitis (OR 9.2, 95% CI 3.9 to 21) or death before 28 days (OR 9.3, 95% CI 8.8 to 9.4). Regarding long-term outcomes, late preterm infants were more likely to die in the first year (OR 3.3, 95% CI 3.2 to 3.3), to suffer from cerebral palsy (OR 3.0, 95% CI 2.5 to 3.5), and less likely to complete high school (OR 0.83, 95% CI 0.81 to 0.84). Although the absolute incidence of neonatal mortality and morbidity in infants born late preterm is low, its incidence is significantly increased as compared to term delivery.

From Paradox to Disparity: Trends in Neonatal Death in Very Low Birth Weight non-Hispanic Black and White Infants, 1989-2004

To examine temporal trends in race-specific neonatal death in California to determine whether the overall decline in mortality attenuated the paradoxical survival advantage of very low birth weight (VLBW; birth weight < 1500 g) non-Hispanic black infants relative to VLBW non-Hispanic white infants. The data set comprised the California birth cohort file on non-Hispanic black and non-Hispanic white VLBW neonatal mortality for 1989-2004. Logistic regression methods were used to control for potentially confounding maternal characteristics. In 1989 and 1990, non-Hispanic black VLBW infants demonstrated a paradox of lower neonatal mortality (adjusted odds ratio [aOR] = 0.84; 95% confidence interval [CI] = 0.75-0.94). This survival advantage disappeared after 1991, however. In 2003 and 2004, the incidence of neonatal mortality increased in non-Hispanic black VLBW infants but decreased in non-Hispanic white VLBW infants, resulting in a racial disparity (aOR = 1.34; 95% CI = 1.14-1.56). An initial survival paradox transformed into a disparity. The magnitude of this non-Hispanic black/non-Hispanic white VLBW disparity rose to its highest levels in the last 2 years of the study period. Moreover, the steady mortality increase in VLBW non-Hispanic black VLBW infants since 2001 reversed the secular decline in neonatal mortality in this population. Our findings underscore the need to augment strategies to improve the health trajectory of gestation in non-Hispanic black women.

Carrier Screening for Gaucher Disease

IT WAS A WARM SUMMER DAY MORE THAN 30 YEARS AGO when my laboratory assistant and collaborator, Wanda Kuhl, showed me some unusual results. Our laboratory had devised a facile method for measuring white blood cell glucocerebrosidase activity and was performing family studies to determine the efficiency of this technique for the detection of heterozygotes for Gaucher disease. But here was a sample from an obligate heterozygote, the mother of a patient with Gaucher disease, in which the range of enzyme activity was as low as in the patient. Bone marrow examination in this 72-year-old asymptomatic parent confirmed that she also had Gaucher disease. Discovery of Gaucher disease in an older, asymptomatic individual was by no means unique—the disease had previously been detected in such persons, including one person who was aged 86 years. However, many persons homozygous for the N370S mutation associated with Gaucher disease are never diagnosed; based on the discrepancy between the heterozygote frequency and the number of patients diagnosed, an estimated 60% of such homozygous patients may go undiagnosed. Herein lies the dilemma faced by Zuckerman and colleagues in their evaluation of prenatal screening for Gaucher disease reported in this issue of JAMA. Among an estimated 28 893 individuals screened at Israeli genetic centers, 82 couples were at risk for offspring with type 1 Gaucher disease, including 70 (85%) at risk for asymptomatic or mildly affected offspring and 12 (15%) at risk for moderately affected offspring. Following prenatal diagnosis in 68 pregnancies, 16 fetuses with Gaucher disease were detected. Of these pregnancies, 2 of 13 (15%) involving N370S homozygote fetuses and 2 of 3 (67%) involving compound heterozygote fetuses were terminated. Had the mother of my patient with Gaucher disease been conceived in Israel in this century, rather than in the early 1900s, she might never have been born. Her parents would have been informed that the fetus carried by the mother had Gaucher disease, and they might have elected to terminate the pregnancy. The clinical expression of Gaucher disease, like that of virtually all single-gene diseases, varies enormously. Physicians remember their patients with severe clinical manifestations—the patients who seek care. Often forgotten are those patients never diagnosed because they have no symptoms of the disorder. In the majority of single-gene genetic diseases, clinicians and genetics researchers have no clue as to the cause of the phenotypic variability, and therefore have no means by which to inform prospective parents whether their child will be severely affected by the disease or will have an asymptomatic life. Screening of newborns began more than 45 years ago with the introduction of the microbial inhibition test for phenylalanine for detecting possible phenyketonuria. Providing children with a phenylalanine-free diet in a timely fashion greatly ameliorated the mental retardation that is the clinical hallmark of phenylketonuria. This was soon followed by screening of newborns for galactosemia, allowing early treatment and prevention of the high incidence of neonatal mortality of infants with galactosemia. Before implementation of screening, infants who survived because they were treated were usually treated too late to avert the development of cataracts, cirrhosis, and mental retardation. Subsequently another approach to screening was introduced, the examination of parents for the carrier state, such as for Tay-Sachs disease, giving them the option after prenatal diagnosis to terminate a pregnancy. Although there is phenotypic variation in these severe genetic diseases, it is from bad to worse, rather than from bad to normal as with Gaucher disease. For example, galactosemia and phenylketonuria in adults who have never been treated are rare and are associated with mental retardation. Tay-Sachs disease, once known by the grim name of “amaurotic family idiocy,” is currently untreatable and leads to death after the first few years of life. Even these relatively straightforward screening programs have not been without some difficulties. One problem came to light with the discovery that some normal adults lacked serum hexosaminidase activity. Although this phenotype was rare, had these individuals been detected during fetal life as a con-

145 Evaluation of Surfactant Therapy in HMD and Reduction of Mortality

HMD Occurs Primarily in premature infants, and its incidence is inversely proportional to gestational age and birth weight. HMD is a Major cause of morbidity and mortality in preterm neonates. (about 30%) Surfactant deficiency is the primary cause of HMD in Previous studies, surfactant therapy has reduced mortality from HMD approximately 40% the aim of this research was determined the incidence of mortality in neonates with HMD after treatment with surfactant.Methods & materials: In this study that was a descriptive analytic study, we evaluated 450 neonates with HMD, who were admitted to NICU in Beheshti Hospital Isfahan Iran, between Mar 2003 to Aug 2004. After diagnosis of HMD by clinical signs of Respiratory distress, and radiological findings of the chest, 89 Patients received surfactant (Males 58 and females 31)Results: A group of 34 (38.2%) out of 89 neonates who received surfactant survived HMD, on the other hand, in this study surfactant therapy has reduced mortality from HMD (38.2%), 42% were females and 36.2% were males. The most efficacy of surfactant therapy and low mortality were observed on gestational age more than 32 weeks, and therapy in the Ist 24 hr of life (47.5%and 43.3% respectively). Also the most efficacy of surfactant were showed in APGAR score at 1, 5 min more than 7/10 and in birth weight more than 1500 Gr (48% and 52.5% respectively). In this study, mothers who received steroid before delivery and their neonates who took surfactant after birth, had the most efficacy and reduction of mortality (41.7% with steroid and 34.15% without steroid).CONCLUSIONS: The purpose of this study was detection the prevalence rate of reduction of mortality after surfactant therapy in HMD, our study was showed reduction of mortality and also was concluded the most efficacy of surfactant therapy on some condition which associate with HMD.

Unusual antibody titer in a severe case of rhesus incompatibility

Unusual antibody titer in a severe case of rhesus incompatibility

Treatment of preterm labor.

The ultimate goal of treating preterm labor is to prolong the pregnancy long enough to decrease the incidence of neonatal mortality and morbidity associated with prematurity, while minimizing maternal and fetal risks. There are many controversies in treating preterm labor. Much of this controversy stems from the difficulty in establishing efficacy and safety of interventions and uncertainty of the diagnosis of preterm labor. This article outlines conventional measures and tocolytic therapy directed at prolonging the pregnancy. A review of the effect of tocolytic agents, administration, side effects, and nursing interventions is included. Key words: preterm labor treatment,

Effect of mode of delivery on neonatal outcome of twins with birthweight under 1500 g.

The purpose of this retrospective study was to evaluate. The mode of delivery on neonatal outcome of twins weighing <1500 g. We reviewed the effect of birth order, presentation, and method of delivery on neonatal outcome in twin gestation under 1500 g at Princess Badeea' Teaching Hospital in North Jordan over the 6-years from 1994 to 1999. During the study period, there were 51475 deliveries of which 695 were twin gestations. One hundred and eight (108) sets of twins weighing <1500 g were included in the study (15.5%), of which 41 were in vertex-vertex presentation, 40 in vertex-nonvertex, and 27 with first twin in nonvertex presentation. The second twin pregnancies characterized by a higher incidence of respiratory distress syndrome (82 vs. 70%; p=0.02) more neonatal mortality (23 vs. 17.6%), and lower Apgar score at 1 and 5 min. Cesarean delivery for vertex-vertex presentation did not improve the neonatal outcome. Rather, the incidence of RDS was significantly greater in this group delivered by cesarean section (65.6 vs. 42%, p=0.012). For nonvertex presentation, those delivered by cesarean section had a lower incidence of neonatal mortality. We concluded there was no advantage for cesarean delivery that could be demonstrated after multivariate analysis to correct the differences in birthweight between the groups. Therefore, the differences in the neonatal outcome of non vertex twins presentation accounted for the differences in birthweight, rather than in mode of delivery.

Preterm labour

Spontaneous preterm labour remains a major obstetric problem because of the high incidence of neonatal mortality or long-term handicap associated with it. The drugs available for the management of preterm labour are poorly effective and have potentially serious side-effects for the mother or fetus. In recent years, there has been a remarkable increase in the knowledge of the biochemical mechanism underlying uterine quiescence and contractility. Many of the G protein-coupled receptors that participate in the regulation of myometrial activity have been cloned and characterized, and their intracellular signalling pathways have been elucidated. The role of G protein receptor kinases in uterine tachyphylaxis is better understood. New developments in our understanding of the cellular mechanisms involved in uterine contractions in idiopathic and infection-associated preterm labour are expected, which will lead to better, more selective therapy for this problem. However, much research remains to be done before the mechanism of human parturition is fully understood.

Nutrient partitioning during pregnancy: adverse gestational outcome in overnourished adolescent dams.

Appropriate nutrient partitioning between the maternal body and gravid uterus is essential for optimum fetal growth and neonatal survival, and in adult sheep nutrient partitioning during pregnancy generally favours the conceptus at the expense of the dam. However, recent studies using an overnourished adolescent sheep model demonstrate that the hierarchy of nutrient partitioning during pregnancy can be dramatically altered in young growing females. Overnourishing the adolescent dams to promote rapid maternal growth throughout pregnancy results in a major restriction in placental mass and leads to a significant decrease in birth weight relative to moderately-fed adolescents of equivalent gynaecological age. High maternal feed intakes are also associated with an increased incidence of non-infectious spontaneous abortion, a reduction in gestation length and colostrum production, and a higher incidence of neonatal mortality. The present paper examines the putative role of a variety of endocrine regulators of nutrient partitioning in this unusual model system, where the dam is overnourished while the stunted placenta restricts nutrient supply to the fetus. The central role of nutritionally-mediated alterations in placental growth and development in setting the subsequent pattern of nutrient partitioning between the maternal body, placenta and fetus is examined, and critical periods of sensitivity to alterations in maternal nutritional status are defined. Finally, the consequences of this form of inappropriate nutrient partitioning on the growth and development of the fetus and neonate are described with particular emphasis on the reproductive axis.

The effect of mode of delivery on neonatal outcome of twins with birthweight under 1500 grams

The purpose of this retrospective study was to evaluate the mode of delivery on neonatal outcome of twins weighing <1500 grams. We reviewed the effect of birth order, presentation, and method of delivery on neonatal outcome in twin gestation under 1500 grams at Princess Badeea' Teaching Hospital in North Jordan over the 6 years from 1994 to 1999. During the study period, there were 51 475 deliveries of which 695 were twin. One hundred and eight (108) sets of twins weighing <1500 grams were included in the study (15.5%), of which 41 were in vertex-vertex presentation, 40 in vertex-nonvertex, and 27 with first twin in nonvertex presentation. The second twin was characterised by a higher incidence of respiratory distress syndrome (82% vs. 70%; P = 0.02), more neonatal mortality (23% vs. 17.6%), and lower Apgar scores at 1 and 5 minutes. Cesarean delivery for vertex-vertex presentation did not improve the neonatal outcome. Rather, the incidence of RDS was significantly greater in this group delivered by caesarean section (65.6% vs. 42%; P = 0.012). For nonvertex presentation, those delivered by caesarean section had a lower incidence of neonatal mortality. We conclude that there was no advantage in caesarean delivery after multivariate analysis to correct for differences in birthweight between the groups. The differences in the neonatal outcome of nonvertex twin presentation was accounted for by the differences in birthweight, rather than in mode of delivery.

Elective high frequency jet ventilation versus conventional ventilation for respiratory distress syndrome in preterm infants.

This section is under preparation and will be included in the next issue. The objective of this review was to determine whether the elective (commencing soon after initiation of mechanical ventilation) use of high frequency jet ventilation (HFJV), as compared to conventional ventilation (CV) in preterm infants with respiratory distress syndrome (RDS), would decrease the incidence of chronic lung disease (CLD) without adverse effects. Randomized trials from MEDLINE were identified by means of MeSH and text words 'high frequency ventilation', 'high frequency jet ventilation', 'jet ventilation' from the years 1980 to 1997. The EMBASE database, the Oxford Database of Perinatal Trials, the Neonatal Trials Register of the Neonatal Review Group of the Cochrane Collaboration and the Cochrane library were also accessed. Proceedings of recent SPR/APS meetings were hand searched. Information was obtained from experts in the field, and cross references were checked. All randomized controlled trials of elective high frequency jet ventilation versus conventional ventilation in preterm infants born at less than 35 weeks GA or with a birth weight less than 2000 gms with respiratory distress were included in the systematic review. Trials which used HFJV to 'rescue' preterm infants due to severe respiratory distress usually beyond 24 hours, and trials that used HFJV for a mandatory time period and then switched back to CV, were not included in this review. The standard methods of the Neonatal Cochrane Review Group were used, including independent trial assessment and data extraction. Data were analysed using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits and number needed to harm (NNH) for adverse outcomes were calculated. Overall analysis of the three trials showed that HFJV is associated with a reduction in CLD at 36 weeks postmenstrual age in survivors [RR 0.58 (0.34, 0. 98), RD -0.138 (-0.268, -0.007), NNT 7 (4, 90)]. The use of home oxygen therapy was evaluated in only one study (Keszler 1997) and a lower rate was found in the HFJV group [RR 0.24 (0.07, 0.79), RD -0. 176 (-0.306, -0.047), NNT 5 (3, 21)]. Overall there was a trend towards an increase in the risk of PVL in the HFJV group, which was not significant. Subgroup analyses shows a significant increase in risk of PVL in the trial by Wiswell 1996 [RR 5.0 (1.19, 21.04), RD 0.250 (0.069, 0.431), NNH 4.0 (2.3,14.5)] where a 'low volume strategy' was the standard protocol for HFJV. In the other trial by Keszler 1997, where the intention was to use a 'high volume strategy', there was no significant difference in the incidence of PVL, RR 0.42 (0.14, 1.30). In the overall analysis, there were no significant differences in the incidence of neonatal mortality, IVH all grades or in grades 3 or 4 IVH. In the subgroup where 'low volume strategy' was used there was a non-significant trend toward an increase in risk of IVH all grades and grades 3 or 4 IVH. The overall analysis shows a benefit in pulmonary outcomes in the group electively ventilated with HFJV. Of concern is the significant increase in acute brain injury in one trial which used lower mean airway pressures when ventilating with HFJV. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to routinely ventilate premature infants with HFJV safely, ventilation with HFJV cannot be recommended for preterm infants with RDS.

Neonatal Outcome in Pregnancies Associated With Renal Replacement Therapy

Pregnancy in women receiving renal replacement therapy is not without risk to the mother and fetus. This article reviews the information on fetal outcome in pregnancies associated with renal transplantation and dialysis. The incidence of neonatal mortality, prematurity, and small-for-gestational-age infants is increased in pregnancies associated with maternal renal replacement therapy. Conversely, there does not appear to be a significant increase in the rate of congenital malformations. Whereas the fetal risk for inheritable renal disease is clearly defined in most cases, the risk associated with a host of new immunosuppressive medications is poorly understood. In addition, the newborn may be at risk for abnormalities in water homeostasis caused by the large solute load transferred from the mother receiving dialysis and requires close observation. Continued accumulation of clinical data will permit women receiving dialysis or with a kidney transplant to make informed decisions about current or future pregnancies.

A deficit of functional GABA A receptors in neurons of β3 subunit knockout mice

Mice whose γ-aminobutyric acid type A (GABA A) β 3 subunit gene is inactivated (` β 3 knockout mice') have been previously shown to have epilepsy, hypersensitive behavior, cleft palate, and a high incidence of neonatal mortality. In this study, we analyze whole-cell responses to GABA in neurons from β 3 +/+, β 3 +/− and β 3 −/− mice. We demonstrate markedly decreased responses to GABA in both hippocampal and dorsal root ganglion neurons isolated from β 3 −/− mice without major differences in the GABA concentration-response curves. We also utilize the subunit selective pharmacology of Zn 2+ and the anticonvulsant drug loreclezole to help infer the presence of β 2 and γ subunits in the GABA A receptors remaining in neurons from β 3 −/− mice.

Inhibition of retinoid signaling in transgenic mice alters lipid processing and disrupts epidermal barrier function.

To explore the role of retinoids in epidermal development, we recently targeted expression of a dominant-negative, retinoic acid receptor mutant (RAR alpha403) in the epidermis of transgenic mice and observed an unexpected loss of barrier function. In this paper, we demonstrate that transgenic mice expressing the RAR alpha403 transgene show attenuated responsiveness to topical application of all-trans retinoic acid, in agreement with our previous in vitro data. We also show that the vitamin D3 receptor is unaffected in its ability to transactivate in the presence of the dominant-negative RAR alpha403 transgene, indicating that the RAR alpha403 is unlikely to be functioning through a global sequestration of retinoid X receptors. Additionally, we show that the disruption of epidermal barrier function results in a dramatic 4 C drop in mean body surface temperature, probably accounting for the extremely high incidence of neonatal mortality in severely phenotypic pups. Some severely affected pups do survive and show a pronounced hyperkeratosis at postpartum day 4, consistent with previously documented effects of vitamin A deficiency. Biochemical analysis of the severely phenotypic neonates indicates elevated phospholipids and glycosylceramides in the stratum comeum, which results from altered lipid processing. Taken together with previous studies, these data provide strong evidence linking the retinoid-signaling pathway with modulation of lipid processing required for formation of epidermal barrier function.

Intraventricular hemorrhage in the preterm neonate: Timing and cerebral blood flow changes

Serial cranial ultrasound studies, 133xenon inhalation cerebral blood flow determinations, and risk factor analyses were performed in 31 preterm neonates. Contrast echocardiographic studies were additionally performed in 16 of these 31 infants. Sixty-one percent were found to have germinal matrix or intraventricular hemorrhage. Seventy-four percent of all hemorrhages were detected by the thirtieth postnatal hour. The patients were divided into three groups: early GMH/IVH by the sixth postnatal hour (eight infants) interval GMH/IVH from 6 hours through 5 days (10), and no GMH/IVH (12). Cerebral blood flow values at 6 postnatal hours were significantly lower for the early GMH/IVH group than for the no GMH/IVH group (P less than 0.01). Progression of GMH/IVH was observed only in those infants with early hemorrhage, and these infants had a significantly higher incidence of neonatal mortality. Ventriculomegaly as determined by ultrasound studies was noted equally in infants with and without GMH/IVH (50%) and was not found to correlate with low cerebral blood flow. The patients with early hemorrhage were distinguishable by their need for more vigorous resuscitation at the time of birth and significantly higher ventilator settings during the first 36 postnatal hours, during which time they also had higher values of PCO2. An equal incidence of patent ductus arteriosus was found across all of the groups. We propose that early GMH/IVH may be related to perinatal events and that the significant decrease in cerebral blood flow found in infants with early GMH/IVH is secondary to the presence of the hemorrhage itself. Progression of early GMH/IVH and new interval GMH/IVH may be related to later neonatal events known to alter cerebral blood flow.

Neonatal toxicity in mice associated with the Ahb allele following transplacental exposure to 3-methylcholanthrene

This study was conducted to determine if the Ah genotype in mice could influence the incidence of neonatal mortality following maternal exposure to 3-methylcholanthrene (3-MC). Male F 1 hybrids ( Ah b Ah d ) produced from a cross of C57BL 6J and DBA 2J were backcrossed to DBA 2J females. This backcross mating resulted in noninducible pregnant mice ( Ah d Ah d ) containing litters with a 1:1 ratio of AHH-inducible ( Ah b Ah d ) and noninducible ( Ah d Ah d ) fetuses. Dams were exposed by the oral route to 3-MC in corn oil at doses of 7, 21, or 63 mg/kg/day on Days 15, 16, and 17 of pregnancy, or to the positive control agent urethane at 1 mg/g ip on Day 17. The phenotype of surviving offspring was determined by zoxazolamine paralysis time and hepatic aryl hydrocarbon hydroxylase (AHH) activity measurements. Dose-related responses in all 3-MC treatment groups were obtained in measures of neonatal toxicity, i.e., number of litters surviving to term, litter size at birth, survival to weaning, and weight gain to 13 weeks of age. Correlation of the Ah phenotype with the neonatal toxicity data indicated that genetically responsive offspring had higher levels of neonatal toxicity than nonresponsive offspring within the same exposure groups. Thus, when fetuses are exposed in the same maternal environment to 3-MC, genetic differences in Ah genotype may influence the susceptibility to neonatal toxicity.

Postnatal abstinence or acute toxicity can account for morbidity in developmental studies with opiates

The incidence of neonatal morbidity and mortality in rats exposed to opiates in utero is generally high. To determine the extent to which neonatal opioid intoxication and/or withdrawal contribute to this effect, addicted pups from dams treated chronically with the long-acting opioid levo-alpha-acetylmethadol (LAAM) and appropriate controls were injected within 12 h of birth with saline, an opioid agonist (LAAM and metabolites) or an antagonist (naloxone). The incidence of neonatal mortality for pups born to dams maintained on a high dose of LAAM was 52%. A single injection of agonist on the first day of life reduced mortality in this group to 29% while a single injection of the antagonist increased mortality to 88%. In contrast, administration of the agonist to control pups and pups born to dams maintained on lower doses of LAAM resulted in increased mortality. Naloxone was apparently innocuous in non-dependent neonates. These data show that, despite LAAM's long duration of action in the mature rat, newborn rats experience withdrawal soon after drug exposure is terminated. These data also indicate that continued opioid exposure is a highly effective means of treating/preventing severe spontaneous withdrawal in the newborn.