Alteraciones neuropsiquiátricas en menores de 18 años expuestos a opioides en el periodo prenatal: Revisión Narrativa

El consumo de opioides ha venido incrementando en los últimos años, generando una crisis de salud pública que afecta a todo tipo de población. El uso de sustancias opiáceas ilegales en embarazadas también está en incremento, por lo que, en la práctica clínica se evidencian con mayor frecuencia resultados neonatales adversos como el síndrome de abstinencia neonatal (NAS). Adicionalmente, los niños expuestos prenatalmente a estas sustancias pueden sufrir alteraciones cognitivas, motoras o psiquiátricas durante el transcurso de su vida. Este artículo tiene como objetivo proporcionar una revisión de la literatura actualizada acerca del uso de opioides durante el embarazo y las consecuencias para los niños expuestos a estas sustancias.

Opioid consumption has increased greatly in recent years, creating a public health crisis that affects all types of population. The use of illegal opiates amongst pregnant women has also risen, causing a surge in the frequency in which adverse neonatal outcomes, such as Neonatal Abstinence Syndrome (NAS), are seen in clinical practice. Furthermore, children exposed prenatally to these substances have cognitive, motor and psychiatric adverse outcomes throughout their lifetime. This article's objective is to provide an updated literature review about opioid use during pregnancy and its consequences on children exposed in-utero.

Effects of antenatal corticosteroids exposure on multiple systems of preterm infants: a review / 中华围产医学杂志

Administration of antenatal corticosteroids (ACS) to pregnant women at risk of preterm delivery can significantly reduce the incidence of preterm-related complications, such as respiratory distress syndrome and necrotizing enterocolitis. However, ACS may have adverse effects on multiple systems including nervous system, cardiovascular system and carbohydrate metabolism in preterm infants. Whether ACS could influence neonatal development is still controversial. On this account, this review, focusing on short- and long-term effects of ACS therapy on nervous, cardiovascular, endocrine and other systems of infants born prematurely, will help clinical management and scientific research.

Progress on association of obesity with common congenital heart diseases and its underlying mechanisms / 中华围产医学杂志

Maternal obesity is associated with an increased risk of a range of congenital malformations in offspring, including neurological malformations, congenital heart disease, congenital kidney and urinary system abnormalities, cleft lip and palate, anorectal atresia, etc. This may be related to existing metabolic abnormalities, including increased insulin resistance, chronic inflammation, and oxidative stress caused by excessive accumulation of fat, as well as the relative deficiency of nutrients such as folic acid in obese pregnant women. Therefore, it is recommended that obese women have a planned pregnancy, address folate and micronutrient supplementation and optimize their health status prior to conception.

Role of microRNA in complications of offspring born to mothers with gestational diabetes mellitus / 中华围产医学杂志

Gestational diabetes mellitus (GDM) can lead to adverse pregnancy outcomes and epigenetic changes in offspring due to exposure to a high-glucose intrauterine environment, resulting in related short- and long-term complications. MicroRNA (miRNA)-mediated post-transcriptional regulation, a gene expression regulation mechanism that has gained much attention in recent years, may play a role in morbidity in offspring born to mothers with GDM, such as macrosomia, heart development, neurodevelopment, and long-term metabolic diseases. This article reviews the progress of miRNA in GDM and associated complications in the offspring.

Effects of early-life exposure to angiotensinⅡ type 1 receptor autoantibody on lipid metabolism in offspring rats / 中华围产医学杂志

Objective:To investigate the effects of early-life (intrauterine and breastfeeding period) exposure to angiotensin Ⅱ type 1 receptor autoantibody (AT 1-AA) on lipid metabolism in offspring rats. Methods:Thirty-two AT 1-AA negative healthy nonpregnant specific pathogen free female Sprague Dawley rats weighing 150-170 g were randomly divided into two groups. Those in the immune group ( n=16) were subcutaneously injected with the mixture of an equal volume of Freund's adjuvant and the second extracellular loop of human-derived angiotensin Ⅱ receptor type 1 (AT1R-ECⅡ) repeatedly to establish the AT 1-AA-positive rat model by active immunization and those in the control group ( n=16) with normal saline solution. Before each immunization, blood samples were collected from the tail of rats to detect serum AT 1-AA levels of those rats in both groups, and the AT 1-AA-positive rat model was successfully established when the serum AT 1-AA was positive and its level reached a plateau. After eight weeks of immunization, the female rats in the two groups were mated with healthy AT 1-AA-negative male rats to conceive. Serum samples were collected from the maternal and offspring rats at the gestation of 18 days (G18), postnatal 21 days (P21), and from the normally fed offspring rats from the time of weaning to 12 weeks old (W12). Active immunization was not performed on the offspring throughout the experiment. The serum AT 1-AA levels of maternal and offspring rats were determined by enzyme-linked immunosorbent assay, and serum AT1-AA was positive when the ratio of AT1-AA level of the immune group over the control group ≥2.1. The blood lipid levels of maternal and offspring rats were measured by an automatic biochemical analyzer. Serum AT 1-AA levels, total cholesterol (TC), high-density lipoprotein-cholesterol [instead of high-density lipoprotein (HDL)], low-density lipoprotein-cholesterol, and free fatty acid levels of the offspring and maternal rats were determined for correlation analysis. Two independent sample t-test, linear regression analysis, and analysis of variance were adopted for statistical analysis. Results:(1) The serum levels of AT 1-AA in maternal rats at G18 and P21 in the immune group were significantly higher than those in the control group (G18: 1.170±0.190 vs 0.114±0.016, t=14.64; P21: 0.988±0.283 vs 0.084±0.006, t=9.57; both P<0.001). (2) The serum levels of AT 1-AA in the offspring at G18 and P21 in the immune group were significantly higher than those in the control group (offspring at G18: 0.948±0.220 vs 0.105±0.010, t=10.10; male offspring at P21: 0.758±0.273 vs 0.080±0.002, t=7.46; female offspring at P21: 0.774±0.274 vs 0.084±0.005, t=7.55; all P<0.001), which showed a positive correlation with those in maternal rats at the same period (offspring at G18: R=0.78; male offspring at P21: R=0.82; female offspring at P21: R=0.82; all P<0.05). However, there was no significant difference in the serum AT 1-AA level in offspring at W12 between the immune and control group ( P>0.05). (3) The serum levels of TC at G18 and P21, and HDL at P21 in maternal rats in the immune group were all higher than those in the control group [TC at G18: (2.36±0.32) vs (1.95±0.24) mmol/L, t=2.70; P21: (2.82±0.50) vs (2.18±0.26) mmol/L, t=3.41; HDL at P21: (1.94±0.33) vs (1.57±0.23) mmol/L, t=2.80; all P<0.05]. (4) Compared with the offspring in the control group, there was no significant change in lipid metabolism at G18 and W12 in the offspring in the immune group (both P>0.05). The serum levels of TC and HDL in male and female offspring at P21 in the immune group were higher than their counterparts in the control[TC in male offspring: (2.38±0.52) vs (1.83±0.30) mmol/L, t=2.73; HDL in male offspring: (1.44±0.32) vs (1.07±0.18) mmol/L, t=2.98; TC in female offspring: (2.50±0.72) vs (1.70±0.26) mmol/L, t=3.16; HDL in female offspring: (1.41±0.33) vs (1.00±0.14) mmol/L, t=3.41; all P<0.05]. (5) The serum levels of TC and HDL in male and female offspring at P21 in the immune group showed no correlation with those in maternal rats at P21 (all R<0.5, all P>0.05). The serum levels of HDL in male and female offspring at P21 in the immune group had a positive correlation with their own serum TC levels (male offspring: R=0.98; female offspring: R=0.97; both P<0.001) and also with their own serum AT 1-AA levels (male offspring: R=0.74, P=0.023; female offspring: R=0.91, P=0.001). The serum levels of TC in male and female offspring at P21 in the immune group had a positive correlation with their serum AT 1-AA levels (male offspring: R=0.72, P=0.030; female offspring: R=0.90, P=0.001). Conclusion:The early-life exposure to AT 1-AA may cause abnormal expression of TC and HDL in offspring rats.

Research progress in influence of intrauterine hyper androgen on offspring health and mechanisms / 中华围产医学杂志

Maternal adverse endocrine environment severely affects the growth and development of offspring. This article reviews relevant cohort studies and animal experiments on the influence of intrauterine hyper androgen on offspring health and the mechanisms, aiming to provide a new perspective for further research, mechanism exploration, and early interventions in this field.

Long-term effects of intrauterine exposure to metformin on offspring / 中华围产医学杂志

As an oral antidiabetic drugs,metformin has been widely used to treat various diseases such as gestational diabetes mellitus,polycystic ovary syndrome and obesity in pregnant women.Current literature suggests that intrauterine metformin exposure has no significant impact on perinatal outcomes of the offspring,such as neonatal hypoglycemia,neonatal respiratory distress syndrome,premature delivery and others.However,considering the possible transfer of metformin across the placental barrier,intrauterine metformin exposure may potentially influence the development of placenta and the fetus,cell metabolism,and hormone levels.According to the "Developmental Origins of Health and Diseases" theory,the long-term effect of intrauterine metformin exposure on the growth,metabolism,reproductive function and neuropsychological development of offspring reviewed here still need continuous attention.

Timing of pubertal development in boys born with cryptorchidism and hypospadias: A nationwide cohort study / 亚洲男科学杂志(英文版)

Pubertal development may be altered in boys with cryptorchidism and hypospadias, but existing knowledge is inconsistent. Therefore, we investigated the association between cryptorchidism and hypospadias and pubertal development in a large cohort study. Boys in the Puberty Cohort, a cohort nested within the Danish National Birth Cohort, were included in this study. Information on cryptorchidism and hypospadias was retrieved from the Danish National Patient Register. From 11 years until 18 years or full pubertal development, information on physical markers of pubertal development was provided biannually, including Tanner stages, axillary hair, acne, voice break, and first ejaculation. In multivariate regression models for interval censored data, the mean (95% confidence intervals [CIs]) differences in months in obtaining the pubertal markers between boys with and without the anomalies were estimated. Among 7698 boys, 196 (2.5%) had cryptorchidism and 60 (0.8%) had hypospadias. Boys with hypospadias experienced first ejaculation and voice break 7.7 (95% CI: 2.5-13.0) months and 4.5 (95% CI: 0.3-8.7) months later than boys without hypospadias. The age at attaining the Tanner stages for gonadal and pubic hair growth was also higher, though not statistically significant. Pubertal development seemed unaffected in boys with mild as well as severe cryptorchidism. In conclusion, hypospadias may be associated with delayed pubertal development, but pubertal development seems unaffected by cryptorchidism. The relation between hypospadias and later pubertal development may be due to the underlying shared in utero risk or genetic factors.

Long-term prenatal stress increases susceptibility of N-methyl-D-aspartic acid-induced spasms in infant rats / 소아과

PURPOSE: Infantile spasms, also known as West syndrome, is an age-specific epileptic seizure. Most patients with this condition also exhibit delayed development. This study aimed to determine the effect of long-term prenatal stress on susceptibility to infantile spasms. METHODS: We subjected pregnant rats to acute or chronic immobilization stress. Resulting offspring received N-methyl-D-aspartic acid (15 mg/kg, intraperitoneally) on postnatal day 15, and their behaviors were observed 75 minutes after injection. The expression of KCC2 and GAD67 was also determined using immunohistochemistry. RESULTS: Exposure to long-term prenatal stress increased the frequency of spasms and decreased the latency to onset of spasms compared with offspring exposed to short-term prenatal stress. Expression of KCC2 and GAD67 also decreased in the group exposed to long-term prenatal stress compared with the group exposed to short-term prenatal stress. CONCLUSION: Our study suggests that exposure to long-term prenatal stress results in increased susceptibility to seizures.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation / 대한배뇨장애요실금학회지

PURPOSE: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. METHODS: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2'-deoxyuridine and doublecortin (DCX) in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT(1A)) in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in the hippocampus were evaluated by western blot analysis. RESULTS: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT(1A) expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. CONCLUSIONS: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT(1A) activation in offspring rats.

Prenatal tobacco exposure is related to neurobehavioral modifications in infants of adolescent mothers

INTRODUCTION: Prenatal tobacco exposure interferes with neonatal outcomes. OBJECTIVE: To determine the neonatal neurobehavioral effects of in utero tobacco exposure. METHODS: This prospective cross-sectional study included healthy, term, with birth weight appropriate for gestacional age neonates without exposure to alcohol, drugs, or infections, born to adolescent mothers without psychiatric disorders or post-traumatic stress. Infants were classified according to in utero tobacco exposure, as identified by the Composite International Diagnostic Interview administered to mothers. Neurobehavior was assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Both tools were administered between 24 and 72 hours after birth. Neurobehavioral outcomes were compared between exposed and nonexposed infants by ANOVA. The associations between neurobehavioral scores and number of cigarettes smoked were studied by linear correlation. RESULTS: During the study, 928 newborns of adolescent mothers were born, and 388 were included in the study. Of these, 23 were exposed to tobacco, and 365 neonates were not exposed. There were no differences between the groups in gestational age, birth weight, post-natal age at the exam, or time between last feeding and exam. Exposed neonates showed higher scores on arousal (p = 0.004), excitability (p = 0.003), and stress/abstinence signals (p = 0.019) and a lower score on regulation (p = 0.025). After adjusting for the type of anesthesia, mode of delivery, gender, age at neurologic exam, exam duration and time between last feeding and exam, differences in arousal and excitability remained significant. The mean number of cigarettes consumed daily was positively correlated with lethargy (p = 0.013) and inversely with attention (p = 0.043). CONCLUSIONS: Neonates exposed in utero to tobacco showed worse neurobehavioral performance between 24 and 48 hours of life.

Determinantes precoces da pressão arterial em adultos da coorte de nascimentos de 1982, Pelotas, RS / Determinantes precoces de la presión arterial en adultos de la cohorte de nacimientos de 1982, Pelotas, Sur de Brasil / Early determinants of blood pressure among adults of the 1982 birth cohort, Pelotas, Southern Brazil

OBJETIVO: Avaliar os efeitos de exposições ocorridas na gestação ou nos primeiros anos de vida sobre a pressão arterial. MÉTODOS: Estudo de coorte com todas as crianças nascidas em 1982 nas maternidades da cidade de Pelotas, RS. As mães residentes em área urbana foram entrevistadas e as crianças, acompanhadas em diferentes ocasiões. Em 2004-5, buscou-se acompanhar todos os indivíduos da coorte. A pressão arterial foi medida duas vezes, no início e no final da entrevista, com esfigmomanômetro digital de pulso. Foi avaliada a associação entre pressão arterial e as seguintes variáveis: cor da pele; escolaridade materna; renda familiar ao nascer; mudança de renda entre o nascimento e os 23 anos de idade; peso ao nascer e duração da amamentação. A análise de variância foi utilizada para a comparação de médias e os modelos lineares generalizados na análise ajustada. RESULTADOS: Obteve-se a medida da pressão arterial para 4.291 indivíduos, 2.208 do sexo masculino e 2.083 do sexo feminino...

OBJECTIVE: To evaluate the effects of exposure occurring during pregnancy or the first years of life on blood pressure. METHODS: Cohort study on all children born in 1982 in maternity hospitals in the city of Pelotas, Southern Brazil. The mothers living in the urban area were interviewed and the children were followed up on different occasions. In 2004-5, all the individuals in the cohort were sought for monitoring. Their blood pressure was measured twice, at the start and end of the interview, using a digital wrist sphygmomanometer. Associations between blood pressure and the following variables were evaluated: skin color; maternal schooling level; family income at birth; change in income between birth and 23 years of age; birth weight; and duration of breastfeeding. Analysis of variance was used to compare the means and a generalized linear model was used in the adjusted analysis. RESULTS: Blood pressure measurements were obtained from 4,291 individuals: 2,208 males and 2,083 females...

OBJETIVO: Evaluar los efectos de exposiciones ocurridas en la gestación o en los primeros años de vida sobre la presión arterial. MÉTODOS: Estudio de cohorte con todos los niños nacidos en 1982 en las maternidades de la ciudad de Pelotas (Sur de Brasil). Las madres residentes en área urbana fueron entrevistadas y los niños, acompañados en diferentes ocasiones. En 2004-5, se buscó acompañar todos los individuos de la cohorte. La presión arterial fue medida dos veces, en el inicio y al final de la entrevista, con esfigmomanómetro digital de pulso. Fue evaluada la asociación entre presión arterial y las siguientes variables: color de la piel, escolaridad materna, renta familiar al nacer, cambio de renta entre el nacimiento y los 23 años de edad, peso al nacer y duración del amamantamiento. El análisis de varianza fue utilizado para la comparación de promedio y los modelos lineares generalizados en el análisis ajustado. RESULTADOS: Se obtuvo la medida de presión arterial para 4.291 individuos, 2.208 del sexo masculino y 2.083 del sexo femenino...

Resistência à insulina durante a gestação e lactação de ratas wistar: influências sobre o metabolismo da glicose e da insulina na prole adulta / Insulin resistance during pregnancy and lactation in wistar rats: influence on glucose and insulin metabolism in the adult offspring

Diversos estudos observaram uma correlação entre doenças na idade adulta e o ambiente durante a vida fetal. O estudo realizado por Barker e colaboradores foi um dos primeiros a relatar a hipótese de um possível envolvimento do ambiente intra-uterino com o desenvolvimento de doenças cardiovasculares, mas os mecanismos responsáveis por esta associação ainda não são totalmente conhecidos. Estudos demonstraram uma associação entre baixo peso ao nascimento com resistência à insulina e intolerância à glicose na vida adulta. Recentemente, verificamos que o consumo de dieta hipossódica, conhecido modelo de resistência à insulina, durante a gestação e lactação está vinculado a menor sensibilidade à insulina na prole adulta. Visto que a presença de resistência à insulina durante a gestação leva a diversas alterações metabólicas na prole adulta, pode-se supor que a sobrecarga de sacarose, um modelo de resistência à insulina, durante a gestação e lactação influencie no desenvolvimento da prole. Assim, o objetivo do presente estudo foi verificar a repercussão da resistência à insulina, durante a gestação sobre a prole adulta. Para tanto, ratas Wistar foram alimentadas com dieta hipo (HO) ou normossódica (NR) suplementadas ou não com sacarose (NR+SAC - 20g/dL) ou maltodextrina (NR+MALTO - 20g/dL) desde a oitava semana de vida até o final da gestação e amamentação. Na prole resultante destes animais foi observado menor peso ao nascimento nos grupos HO, NR+SAC e NR+MALTO. Esta alteração resultou no desenvolvimento de maior insulinemia, pressão arterial e maior captação de glicose na prole de fêmeas das mães do grupo NR+SAC. Os machos apresentaram menor índice de adiposidade e maior expressão gênica renal dos componentes do sistema renina-angiotensina. Tais resultados nos permitem concluir que a sobrecarga de carboidratos durante a gestação e lactação está associada a alterações no peso ao nascimento e no metabolismo da insulina na idade adulta...

Many studies observed a correlation between diseases in adult subjects and the environment during the fetal life. Barker and coworkers hypothesized that there is a possible intrauterine enviroment association with cardiovascular diseases in adulthood. The mechanisms responsible for this association are still not very well known. Recently, we have verified that low-salt diet consumption, a well-known model of insulin resistance, during pregnancy and lactation is associated with a lower insulin sensitivity in the adult offspring. Since insulin resistance during pregnancy leads to many metabolic alterations in the adult offspring, we suppose that sucrose overload during pregnancy and lactation could influence the offspring development. The aim of this study was to verify the effects on adult offspring of insulin resistance during pregnancy and lactation. Female Wistar rats were fed low (LSD) and normal-salt diet (NSD) supplemented or not with sucrose (SUC - 20 g/dL) or maltodextrin (MALTO - 20 g/dL) until the end of pregnancy and lactation. Lower birth weight was observed in offspring of LSD, SUC and MALTO groups. Higher plasma insulin level, blood pressure and glucose uptake was detected in the adult SUC female offspring. SUC male offspring had lower adiposity index and higher gene expression of the renal renin-angiotensin components. These results show that carbohydrate overload during pregnancy and lactation is associated with alterations in birth weight and in insulin metabolism at adult life. It is possible that the maternal renin-angiotensin system activation by the carbohydrate overload is associated with alterations in the same system observed in the adult offspring.

The protective effect of prenatal hypoxia adaptation on the brain of newborn rat / 中华麻醉学杂志

Objective To examine whether the prenatal hypoxia adaptation has any protective effect on the brain of the newborn rat Methods 12 22 day pregnant Wistar rats were randomly divided into 2 groups: the control group and the treated group In the treated group the pregnant rats were placed in a tightly closed hypoxia adaptation chamber When the O 2% in the chamber dropped to 15%, the rat was taken out to breathe fresh air for 5 min then put back in the chamber This process was repeated until its natural delivery In control the chamber was not tightly closed (O 2%=21%) 40 newborn rats weighing 6 8g were selected and subjected to brain ischemia and hypoxia, Left common carotid artrey was ligated under ether anesthesia 2h after recovery from surgery the newborn rats were placed in hypoxia chamber (T=36℃?1℃,O 2%=9%)for 1 5h 24h later they were sacrificed and brain was removed for microscopic examination (optical and electron) and flow cytometry measurement Results In the treated group most newborns were normal There were a few apoptosis cells in early stage The rate of apoptosis was 2 9%, necrosis cells could hardly be seen In the control group, although most neurons were also normal but there were apoptosis cells in early, middle and late stage and even necrosis cells The rate of apoptosis was 9 51%, which was significantly different from that in the treated group Conclusions Prenatal hypoxia adaptation has protective effect on the brain of newborn rat

The expression of apoptosis-related gene bcl-2 and bax mRNA in the brain cells of fetal and newborn rat after prenatal hypoxic adaptation / 中华麻醉学杂志

Objective To investigate the mechanism involved in the brain protection afforded by prenatal hypoxic adaptation by determining the quantitative variation in bcl-2 and bax mRNA expression.Methods Twenty-four Wistar pregnant (22d pregnant) rat were randomly divided into two groups: group I (hypoxia group) and group *** ( control group) . In group Ⅰ the pregnant rats were placed in an airtight cabin specially designed for hypoxic adaptation. When O2 % in the cabin decreased to 15%, the animals were taken out breathing fresh air for 5min and then placed back in the cabin and underwent another episode of hypoxia. In group Ⅱ the animals were placed in the cabin which was not tightly closed and underwent no hypoxia. 7 fetal or newborn rats were taken at 1st, 3rd, 24th, 48th, 72nd, 120th, and 168th h after prenatal hypoxic adaptation from each group and their brains removed for determination of bcl-2 mRNA and bax mRNA. Results In control group the expression of bcl-2 and bax were observed in the brain tissue of normal fetal or newborn rats from the 22nd day in the uterus to the 7th day postpartum during which there were no significant changes in bcl-2 gene expression while bax gene expression gradually decreased with time ( the decrease was of no statistical significance) . In hypoxia group bax gene expression decreased at 8th h after hypoxic adaptation and reached the bottom at 24th h which persisted until 120th h; while bcl-2 gene expression started increasing at 24th h after hypoxic adaptation and persisted until 72nd h. The bcl-2/bax ratio also started increasing at 8th h after hypoxic adaptation and peaked at 24th h and persisted until 72nd h. Conclusions In the brain tissue of fetal and newborn rats which have undergone prenatal hypoxic adaptation, bcl-2 gene expression is elevated, bax gene expression decreases and bcl-2/bax ratio increases. These changes are time -dependent.