Amniotic Fluid Infection Research Articles

Causes of fetal and neonatal mortality by race in a selected U.S. population.

In a large prospective study (1959--1966), the perinatal mortality rate for U.S. Whites was 34 deaths per 1000 total births, for Blacks 51/1000, for Puerto Ricans 41/1000, and for Orientals 23/1000. A number of disorders were responsible for these differences. Premature rupture of the fetal membranes occurred 92 per cent more often in Blacks than in Whites, marked placental growth retardation 56 per cent more often, amniotic fluid infections 45 per cent more often, and major congenital malformations 15 per cent more often. Most other disorders were less common in Blacks than in Whites. Stratifying the data by selected factors, such as prepregnancy body weight and antenatal medical care, eliminated or greatly reduced almost all of these interracial differences. The only major unexplained differences remaining were an excess of amniotic fluid infections and major congenital malformations in Blacks, and an excess of abruptio placentae and large placental infarcts in Whites.

Amniotic Fluid Infections, Neonatal Hyperbilirubinemia, and Psychomotor Impairment

A large prospective study found that infants born with evidence of recent amniotic fluid infections subsequently had an increased frequency of mental, motor, visual, and hearing impairment. These infections also potentiated the neurotoxicity of neonatla hyperbilirubinemia. This potentiation of bilirubin neurotoxicity of neonatal hyperbilirubinemia. This potentiation of bilirububin neurotoxicity increases with the severity of the amniotic fluid infections. With or without such infections, an increased frequency of long-term mild mental retardation started at peak neonatal bilirubin levels of only 7 mg/dl in both term and preterm infants. Significant neurologic abnormalities began at peak bilirubin levels of 12 to 13 mg/dl.

Underlying Disorders Responsible for the Neonatal Deaths Associated with Low Apgar Scores

Data from a large study were used to determine the frequency of fatal disorders associated with low Apgar scores. 5-min scores had the best correlation with mortality rates. Death rates were more than ten times greater with abnormal than with normal 5-min scores. This difference was only 3-fold for 1-min values. Amniotic fluid infections were responsible for nearly half of the deaths in preterm and 24% of the deaths in term neonates with 5-min Apgar scores 0--6. The respective values for disorders that cause antenatal hypoxia were 25 and 24% and for major congenital anomalies, 7 and 28%.

Neonatal Apnea: Underlying Disorders

Data from a prospective study of 50,826 neonates were used to determine the frequency and significance of disorders related to apnea in newborns. Such apnea proved to be a significant prognosticator for neonatal death. Fifty-eight percent of preterm neonates with multiple apneic episodes and 18% with a single episode died, whereas only 6% of those without recorded apnea died. The rates were 44%, 5%, and 1% for full-term infants. Amniotic fluid infection was the underlying disorder in 35% of the preterm and 25% of the term neonates who had multiple episodes of apnea. A third of the preterm and 25% of the term infants who had such apneic episodes had antecedent hypoxia-related disorders, i.e., abruptio placentae, erythromblastosis fetalis, placenta previa, large placental infarcts, and umbilical cord compression. Among the apneic neonates, those who were infected were twice as apt to die as were those who had hypoxia-related disorders. Hypoplasia of the lungs and easily recognized central nervous system malformations were responsible for most of the apnea-related deaths associated with congenital malformations.

Causes of perinatal mortality excess in prolonged gestations.

The study sought to determine what proportion of the perinatal mortality excess associated with prolonged gestations was due to placental insufficiency. Using data from a large prospective study of pregnancy, the perinatal mortality rate was 20.9/1000 births for post-term and 11.7/1000 for term infants. Only a quarter of the perinatal mortality rate excess in the post-term pregnancies was due to disorders related to inadequate uteroplacental perfusion, i.e., abruptio placentae, large placental infarcts and marked placental growth retardation. Twenty-six per cent of the mortality excess was due to congenital malformations, 19% to amniotic fluid infections, 8% to Rh erythroblastosis fetalis and the remaining 22% to a variety of other disorders. The post-term mortality excess due to congenital malformations was in infants who had hypoplastic adrenal glands, a well-known cause of prolonged gestation. The 4205 placentas of the post-term infants did not show any significant increases in those microscopic lesions that are characteristic of uteroplacental under-perfusion.

Amniotic Fluid Infections, Neonatal Hyperbilirubinemia, and Psychomotor Impairment

A large prospective study found that infants born with evidence of recent amniotic fluid infections subsequently had an increased frequency of mental, motor, visual, and hearing impairment. These infections also potentiated the neurotoxicity of neonatla hyperbilirubinemia. This potentiation of bilirubin neurotoxicity of neonatal hyperbilirubinemia. This potentiation of bilirububin neurotoxicity increases with the severity of the amniotic fluid infections. With or without such infections, an increased frequency of long-term mild mental retardation started at peak neonatal bilirubin levels of only 7 mg/dl in both term and preterm infants. Significant neurologic abnormalities began at peak bilirubin levels of 12 to 13 mg/dl.

Effects of maternal cigarette smoking on the fetus and placenta.

In a large, prospective study, mothers who smoked during one pregnancy but not another had smaller infants in the pregnancy in which they smoked, irrespective of birth order and many other factors that affect fetal growth. Light cigarette smokers gained an average 90 g less at term than non-smokers, entirely due to the smaller size of the light smokers' newborn infants. Heavy smokers gained 533 g less than non-smokers, only one-third of which was due to the smaller size of the heavy smokers' newborn infants. As smoking increased, placentas enlarged and developed microscopic lesions characteristic of underperfusion from the uterus. This underperfusion was probably periodic rather than continuous because the smokers' decidua had few of the arterial lesions that are characteristic of chronic low blood flow. Pregnancies were a mean 1.5 days shorter in smokers than in non-smokers, due to more frequent amniotic fluid infections in the smokers.

Twins: Causes of perinatal death in 12 United States cities and one African city

The perinatal mortality rate in a large U. S. study was 139 per 1,000 births for twins and 33 per 1,000 for singletons. Sixteen per cent of the twin deaths were due to amniotic fluid infections, 11 per cent to premature rupture of the membranes, 8 per cent to the monovular twin transfusion syndrome, 8 per cent to large placental infarcts, 7 per cent to congenital anomalies, and the rest to over 20 other disorders. The perinatal mortality rate for monozygotic twins was 2.7 times that for dizygotic twins, mainly due to more amniotic fluid infections, congenital anomalies, and the twin transfusion syndrome in the monozygotic pairs. To study the role of poor maternal nutrition on twins, a similar study of perinatal mortality rates was undertaken in Addis Ababa, Ethiopia. Addis Ababa twins had 2.5 times the mortality rate of U. S. twins, mainly due to a higher frequency of amniotic fluid infections, abruptio placentae, cord accidents, obstructed labors, congenital syphilis, and the twin transfusion syndrome in the Ethiopians.

1142 AMNIOTIC FLUID INFECTIONS, HYPERBILIRUBINEMIA & BRAIN DAMAGE

The study analyzed acute amniotic fluid infections as a possible cause of brain damage using data from a prospective study of 53,518 pregnancies in which the offspring were followed to eight years of age. Acute inflammation of the subchorionic plate of the placenta, a marker for amniotic fluid infections was associated with increasing neurotoxicity as serum bilirubin levels rose in the neonatal period. The frequency of the retardation increased as the chorionitis became more severe. Significant neurologic abnormalities began at peak neonatal bilirubin levels of 13-16 mg/dl in the infected and at 17 mg/dl in the noninfected. 24 different medical, social and demographic factors that can affect psychomotor development were found not responsible for the impairment associated with the chorionitis and hyperbilirubinemia. The proportion of cases who were infected increased as neonatal bilirubin levels increased so the brain damage may have been due either to the infections or an interaction of the infections with hyperbilirubinemia.

372 CAUSES OF THE EXCESSIVE PERINATAL MORTALITY ASSOCIATED WITH PROLONGED GESTATIONS

The study analyzed placental structure and the causes of excessive perinatal mortality associated with prolonged gestations using data from a prospective study of 53,518 pregnancies. Post-term infants had a 30% greater frequency of acute inflammation in the subchorionic plate of the placenta than did term infants (P<.02). Such inflammation is a marker for amniotic fluid bacterial infections. The postterm placentas did not show any significant increase in those lesions that are characteristic of “aging” or reduced uteroplacental perfusion, i.e. fibrotic villi, excessive syncytial knots, infarcts and decidual necrosis at the margin of the placenta. The perinatal mortality rate was 20.9/1000 births for infants born after 42 weeks of gestation and 11.7/1000 for those born be tween 38-42 weeks. The perinatal mortality rate due to congenital malformations was 113% greater, amniotic fluid infections 160% greater, abruptio placentae 100% greater, placental growth retardation 280% greater, placental infarcts 81% greater and umbilical cord knots 88% greater in the postterm than in the term infants. The excess mortality due to congenital malformations was entirely in infants with hypoplastic adrenal glands. Thus, only about one quarter of the excess perinatal mortality associated with pro-longed gestations was due to placental disorders that lead to placental insufficiency. The clinical indications for inducing delivery in postterm gestations may need revision.

Amniotic Fluid Infections With Intact Membranes Leading to Perinatal Death: A Prospective Study

The pathogenesis of fatal amniotic fluid infections was analyzed in a large prospective study that included more than 1,000 medical, demographic, hereditary, and postmortem variables. The disorder was the most frequent cause of death in the study, with an overall perinatal mortality of 6.17 per 1,000 births. The mortality progressively declined after mid-gestation when antimicrobial activity normally appears in the amniotic fluid. A second peak of the fatal infections, after 37 weeks' gestation, was found mainly in the poor and undernourished. Maternal gestational weight gains were suboptimal and the involved neonates had a pattern of growth retardation characteristic of undernutrition. Maternal pregnancy weight gains were positively correlated with the number of prenatal clinic visits. Mother's race, socioeconomic status, age, short stature, and number of prior unsuccessful pregnancies lost their positive association with the fatal infections when mothers made more than nine clinic visits.

Causes of Perinatal Mortality in the US Collaborative Perinatal Project

The underlying causes of 80% of perinatal deaths were identified in a study of 53,518 pregnacies in the United States: 17% of the deaths were due to amniotic fluid infections, 11% to abruptio placentae, 10% to premature rupture of the membranes, 9% to congenital anomalies, 6% to large placental infarcts, and the rest to more than 20 other specific disorders.

Amniotic fluid infections in an african city

Amniotic fluid infections were the most common cause of perinatal death in Addis Ababa, Ethiopia (21.8/1,000 live births). Most such infections appear to originate in the fetal membranes near the cervical os. The high rate of spread of these local infections into the amniotic fluid in Addis Ababa appears related to a lack of antimicrobial activity in amniotic fluids. Factors that adversely affected nutrition in the gravid woman, lack of prenatal medical care, and low water usage were associated with the high rate of fatal infections.

AMNIOTIC FLUID INFECTIONS, A PROSPECTIVE STUDY

Fatal amniotic fluid infections were studied in a prospective analysis of 59,379 pregnancies. 31,494 well preserved placentas and approximately 60,000,000 pieces of medical, demographic, hereditary, social and postmortem data were analyzed using a log-linear model analysis of contingency tables to determine the significance of data. 386 cases were classified as amniotic fluid infections with intact membranes when acute chorioamnionitis, funisitis and inflammation of the chorionic plate were associated with acute congenital pneumonia. The fatal disorder had a frequency of 6.3/1000 live births making it the most common cause of perinatal death in the study. The disorder decreased after 27 wks gestation correlating with the appearance of antimicrobial activity in the amniotic fluid. It increased again after 37 wks when more bacteria gain access to the amniotic fluid. It was most common when gravida made few prenatal clinic visits. Many factors lost their association with the disorder when gravida made clinic visits, i.e. race, socioeconomic status, maternal age and numbers of prior pregnancies, abortions, fetal deaths and preterm deliveries. The disorder was strongly associated with gravida suboptimal weight gain suggesting that undernutrition may have a role in its genesis. The neonates had a pattern of growth retardation characteristic of undernutrition. Gravida who made few clinic visits had smaller weight gains than those who made more visits. Polyhydramnios was also correlated with the fatal disorder. (Supported by USPHS contract N01-NS-3-2311).

FAILURE OF BACTERIAL GROWTH INHIBITION BY AMNIOTIC FLUID

The bactericidal properties of amniotic fluid normally protect fetuses from late gestational infections by bacteria of low virulence. Recently mycoplasma T-strains, an organism of low virulence was found responsible for 23 fatal infections of late gestational fetuses in Addis Ababa, Ethiopia. This prompted analyses of amniotic fluid antimicrobial activity in that city. The antimicrobial activity of 53 fluids collected at term was measured by a semiquantitative plate-count technique. In the U.S. most term fluids are bactericidal but in Addis Ababa, only one fluid was bactericidal, 12 were bacteriostatic and 40 did not inhibit bacterial growth. Underprivileged gravida had about 60% of WHO recommended calorie intake, 75% protein, 35% calcium, 15% vitamin A, 50% riboflavin and niacin, 40% ascorbic acid and >100% of iron and thiamine. Their amniotic fluids had a mean 1.9 log increase in bacterial titer in the test system. Privileged gravida had near recommended intake levels of nutrients. Their fluids had a mean 0.8 log increase in bacterial titer. In vitro increasing amniotic fluid zinc levels >2 μg/ml restored antimicrobial activity. The amniotic fluid infection syndrome is the most common cause of preterm delivery and perinatal death wherever it has been studied, including the U.S. and various sites in Africa. Nutrition of the gravida may play a role in the genesis of the disorder.

Congenital Tuberculosis: Report of a Case

This report describes an infant with congenital tuberculosis. The rarity of congenital acquisition of tuberculosis makes this case unusual. The infant presented with a problem of pulmonary infiltrates unresponsive to antibiotics. Only after the patient died at 8 weeks of age was the diagnosis confirmed by isolation of M. tuberculosis. The mother was febrile at delivery and in the postpartum period. She had a negative PPD skin test reaction and chest x-ray after delivery but left the hospital before the etiology of her febrile illness was determined. She died 3½ months after delivery despite eight weeks of chemotherapy for tuberculosis. Postmortem examination of the mother revealed miliary tuberculosis with marked involvement of the pelvic organs. Progressive primary tuberculous infection of the mother appears likely. The mode of fetal infection could not be determined, but hematogenous transmission via the umbilical vein or through fetal aspiration of infected amniotic fluid is likely.

Unfavorable outcome of pregnancy: Repeated losses

Studies of repeated unsuccessful pregnancies have almost always focused on maternal rather than fetal factors because adequate autopsy data on the neonates have usually been lacking. The current study analyzed such autopsy data from 783 consecutive fetal and perinatal deaths in a New York City Hospital. Elements of the amniotic fluid infection syndrome were identified in 30.5 per cent of offspring of first pregnancies, 22.9 per cent of neonates when all previous pregnancies were successful, and in 54.5 per cent of pregnancies when 2 or more previous pregnancies were unsuccessful. In an analysis of other common fetal, neonatal, and maternal disorders, only Rh erythroblastosis fetalis had a significant association with previous premature deliveries and perinatal losses.

Relation of poverty and race to antenatal infection.

Perinatal infant mortality rates in poor families in the United States are far higher than rates in the non-poor. Analysis of 1044 consecutive autopsies on stillborn and newborn infants in New York City demonstrated congenital pneumonia or sepsis (or both), primarily related to the aspiration of infected amniotic fluid, in 27 per cent. The poorest families had about twice the rate of infections as the most prosperous, and blacks about double the rate of whites and Puerto Ricans. Adrenal glands were 19 per cent heavier in infected than in noninfected infants, owing to increased cytoplasmic mass of individual cells in the permanent zone of the gland. Hyperfunction of these adrenal cells offers a possible mechanism by which infection may initiate labor.

NEONATAL DEFECTS ASSOCIATED WITH ABNORMALITIES OF THE AMNION AND AMNIOTIC FLUID

A discussion of some of the more common fetal abnormalities associated with abnormal amniotic fluid, both in quantity and quality, is presented. Several theories of production and removal of amniotic fluid are mentioned, with fetal micturition and deglutition playing a very important role. The most important function of these two intrauterine fetal processes, however, may be in regulation of fluid volume during the middle and later stages of pregnancy. As yet, the theories presented have not been proved. The more common fetal defects associated with abnormal quantities of fluid are discussed with the radiographic findings, and it may be noted that fetal anatomic deficiencies which prevent either urination or deglutition are present in the majority of these infants. Amniogenic band defects are discussed and several theories of their formation are reviewed. Aspiration of meconium and infected amniotic fluid produce characteristic chest radiographs in the neonatal period, and examples of each are shown.

CONGENITAL TUBERCULOSIS

Four patients with congenital tuberculosis, all prematurely born infants, are described. Three infants born of mothers with acute miliary tuberculosis apparently contracted the disease by aspiration of infected amniotic fluid in utero. The fourth infant, who was born to a mother with acute pelvic tuberculosis and tuberculous peritonitis, seems to have been infected during passage through the birth canal. Two of the infants were treated by intramuscular injections of streptomycin. In both instances the tuberculous infection appears to have been arrested; the infants are in good condition at the ages of 18 and 24 months, respectively. It is recommended that all infants born to mothers with acute miliary or pelvic tuberculosis be followed with frequently repeated tuberculin tests to insure an early diagnosis and adequate treatment.