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PubMed2004

The impact of multiple pregnancies and malformations on perinatal mortality.

AIM: To evaluate the impact of the rate of multiple pregnancies and congenital malformations on perinatal mortality. METHODS: The study is based on data from the perinatal audit in Vejle County Denmark. Fetal deaths with gestational age > or = 22 weeks and deaths in livebirths within the first 28 days after birth were included in the calculated perinatal mortality. Total number of births was 30,181 and 252 pregnancies and 268 fetuses/infants were evaluated. The study period was 1995-2000. There was no routine ultrasound screening for congenital malformations in the county, though midtrimester ultrasound was used to assess gestational age. RESULTS: Perinatal mortality was 8.9 per 1000 births with no significant change over time. Rate of multiple pregnancies was 1.94% ranging from 1.81% during the first 3 years to 2.06% for the last 3 years (not significant). Fetuses and infants from multiple pregnancies contributed 18% of all deaths. Perinatal mortality for single births was 7.6 per 1000 births and for multiple births 42.2/1000 (P<0.0001). The distribution of gestational age for single and multiple births was highly significant (P<0.0001) with 67% of multiple pregnancies with GA < 28 weeks compared to 26% of single pregnancies. Nineteen percent of all deaths were caused by congenital malformations and the majority of these were potentially detectable by ultrasound investigation. CONCLUSIONS: The increasing rate of multiple pregnancies makes it difficult to see improvements in perinatal mortality. Calculated from the perinatal mortality in single and multiple pregnancies in Vejle County assisted conceptions contribute with an an excess of 45 perinatal deaths per year in Denmark. The difference between countries in rate of multiple pregnancies and in prenatal ultrasound screening recommendations for malformations makes it difficult to compare perinatal mortality.

Abnormalities, Multiple↗
PubMed2002

Is the BPD epidemic diminishing?

In a previous study of very low birth weight neonates, < or = 1500 g, admitted to the Vanderbilt University Neonatal Intensive Care Unit (NICU) from 1976-1990, improvements in survival were accompanied by a corresponding increase in the incidence of bronchopulmonary dysplasia (BPD). Since then, certain neonatal and perinatal interventions have been introduced and may influence neonatal outcomes. In this study, we have continued the analysis of the incidence of 3 outcomes: 1) Neonatal death (NEOD), 2) BPD, and 3) NEOD or BPD (NEOD/BPD) for an additional 7 years, 1991-1997. A retrospective study was performed of 3,837 patients with birth weight < or = 1500 g and admitted to the Vanderbilt NICU within 24 hours of birth from 1976 through 1997. The outcomes NEOD, BPD, or NEOD/BPD were modeled by using multiple logistic regression with the following risk factors included as covariates: birth weight, gestational age, Apgar scores at 1 and 5 minutes, gender, race, birth location, diagnosis of hyaline membrane disease, maternal age, maternal diabetes, delivery method, multiple births, duration of ruptured membranes, and biologically relevant interactions among these covariates. To assess time trends in the risk factors and outcomes, patients were divided into time periods (1 = 1976-80, 2 = 1981-85, 3 = 1986-90, 4 = 1991-95, and 5 = 1996-97). For each outcome, only covariates or interactions among covariates found to be significant were retained in the final model. Adjusted odds ratios and 95% confidence intervals were calculated to measure the risk associated with a given time period in comparison to the preceding period. There was a progressive decline in NEOD across all time periods. The previously described increase in BPD from period 1 through period 3 is followed by a decrease in periods 4 and 5. The risk of NEOD/BPD remained fairly constant from period 1 to period 3, but then showed a significant decrease over the two most recent periods. Prior to 1991, the cost of improved survival among very low birth weight infants in this large NICU was an increased incidence of BPD. Since 1991, the risk of BPD has been decreasing even though survival continues to improve. If these findings are also representative of other NICUs, they signify an important reduction in the impact of BPD as one of the costly sequelae of prematurity.

Apgar Score↗
PubMed1995

A triplet maternity in a reduced population with excessive twinning.

In 1991 a triplet maternity of same-sex (FFF) occurred in a depopulated community of Argyll, Scotland, with a history of excessive, same-sex twinning. Due to a stillbirth and its confidentiality, the maternity was recorded as a twin birth. Using public registers may result in underestimation of rates for higher multiple conceptions and births in local districts.

Adult↗
PubMed1991

Relationship of follicle number, serum estradiol, and other factors to birth rate and multiparity in human menopausal gonadotropin-induced intrauterine insemination cycles.

OBJECTIVE: To determine the characteristics associated with pregnancy and multiple gestation after human menopausal gonadotropin intrauterine insemination (hMG-IUI). DESIGN: Prospective study of all patients undergoing hMG-IUI between January 1, 1984 and December 31, 1989. SETTING: University affiliated private clinic. PATIENTS: Four hundred twenty-four infertility patients undergoing 779 cycles of hMG-IUI. MAIN OUTCOME MEASURES: The relationship between estradiol (E2), number and size of follicles, age, and initial semen quality on pregnancy and multiple gestations in hMG-IUI cycles. RESULTS: The number of follicles greater than or equal to 12 mm was correlated with births and predicted all multiple births (r = 0.140, P less than 0.001). The corrected birth rate was 25.8% for age less than 35 and 14.0% for age greater than or equal to 35 when four or more follicles were greater than or equal to 12 mm. The uncorrected clinical pregnancy rate (PR) and birth rate were 12.8% and 10.5%, respectively. Decreased births were associated with tubal adhesions alone (P less than 0.03) or with endometriosis (P less than 0.002), more than four cycles of treatment (P = 0.01), initial sperm count less than 5 x 10(6) per mL (P less than 0.01), initial sperm motility less than 30% (P less than 0.002), and age greater than or equal to 35 (P less than 0.01). Estradiol was correlated with birth rate (r = 0.160, P less than 0.001), which increased from 3.6% when E2 was less than 500 pg/mL to 19.6% when E2 was greater than or equal to 2,500 pg/mL. CONCLUSIONS: The outcome of hMG-IUI is related to the number of follicles greater than or equal to 12 mm, to E2, and to age. Optimal PRs from hMG-IUI require mild ovarian hyperstimulation.

Adult↗
PubMed2002

A chromosomal translocation causing multiple abnormalities including open eyelids at birth and glomerulonephritis.

We have characterized the phenotype of a mouse with a t(2;13) reciprocal translocation induced by chlorambucil. It results in abnormal eyelid formation as well as a series of neurological, physiological, and immunological abnormalities. This mutant has been termed T(2;13)1Fla/+. T(2;13)1Fla/+ mice exhibit open eyelids at birth, a dilute coat color, hyperactivity, and occasional circling and stargazing activity. At 1-6 months, T(2;13)1Fla/+ mice show signs of immune complex-mediated glomerulonephritis and die prematurely. Additionally, double-stranded DNA autoantibodies have been found in sera of T(2;13)1Fla/+ mice. Cytogenetic analysis situated the translocation breakpoint at the proximal end of Chromosome (chr) 2 at band A2, and on Chr 13 at band A4. The mutant phenotype completely correlated with the presence of the translocation. Additional genetic studies have mapped the mutation and translocation breakpoint to Chr 13 between D13Mit16 and D13Mit64, and to Chr 2 proximal to D2Mit5. By fluorescent in situ hybridization (FISH), the position of this mutation/translocation on Chr 13 has been mapped to a region less than 1cM from D13Mit61.

Abnormalities, Multiple↗
PubMed2006

Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy.

OBJECTIVE: The purpose of this study was to determine if weekly corticosteroids improve neonatal outcome without undue harm. STUDY DESIGN: Women 23 to 32 weeks receiving 1 course of corticosteroids 7 to 10 days prior were randomized to weekly betamethasone or placebo. RESULTS: The study was terminated by the independent data and safety monitoring committee with 495 of the anticipated 2400 patients enrolled. There was no significant reduction in the composite primary morbidity outcome (8.0% vs 9.1%, P = .67). Repeated courses significantly reduced neonatal surfactant administration (P = .02), mechanical ventilation (P = .004), CPAP (P = .05), pneumothoraces (P = .03). There was no significant difference in mean birth weight or head circumference. The repeat group had a reduction in multiples of the birth weight median by gestational age (0.88 vs 0.91) (P = .01) and more neonates weighing less than the 10th percentile (23.7 vs 15.3%, P = .02). Significant weight reductions occurred for the group receiving > or = 4 courses. CONCLUSION: Repeat antenatal corticosteroids significantly reduce specific neonatal morbidities but do not improve composite neonatal outcome. This is accompanied by reduction in birth weight and increase in small for gestational age infants.

Adult↗
PubMed2005

Gas mixing efficiency from birth to adulthood measured by multiple-breath washout.

Efficient mixing of inspired gas with the resident gas of the lung is an essential requirement of effective respiration. This review focuses on one method for quantifying ventilation inhomogeneity: the multiple-breath inert gas washout (MBW). MBW has been employed as a research tool in adults and school age children for more than 50 years. Modifications allowing data collection in infants and preschoolers have been described recently. Indices of overall ventilation inhomogeneity, such as the lung clearance index and moment ratios, are raised in many infants with lung disease of prematurity, and in young children with cystic fibrosis. These indices may be more sensitive than other lung function measures for the early detection of airway disease. We describe, for the first time, a development of the MBW analysis that allows calculation of acinar and conductive zone inhomogeneity indices in spontaneously breathing children. Although methodological and analytical issues remain, the future clinical and research applications of MBW justify accelerated research in this field.

Age Factors↗
PubMed1965

THE MECHANISM OF TOLERANCE PRODUCED IN RATS TO SHEEP ERYTHROCYTES. II. THE PLAQUE-FORMING CELL AND ANTIBODY RESPONSE TO MULTIPLE INJECTIONS OF ANTIGEN BEGUN AT BIRTH.

An active immune response to sheep erythrocytes was demonstrated in rats made "tolerant" to sheep erythrocytes by twice-weekly antigen injections beginning on the day of birth. Groups of tolerant rats were sacrificed 4 days after they had received 5 to 42 antigen injections; spleens were sampled for plaque-forming (antibody-releasing) cells and sera were titrated for antibody to sheep erythrocytes using a sensitive "plate hemolysin" technique. During the 3rd week of life and after the 5th antigen injection, the tolerant rats had an immune response equivalent to that of rats of similar age which had received a single antigen injection, but spleens contained only about one-tenth as many plaque-forming cells as adults animals receiving similar antigen injections. Continued antigen injections produced a marked decline and stabilization of this relatively small population of antibody-forming cells; however, the number of plaque-forming cells in the tolerant rats remained considerably elevated above the numbers of plaque-forming cells present in the spleens of non-immunized animals. The sera from all but 1 tolerant rat had demonstrable antibody to sheep erythrocytes in low titer. A progressive recovery of the plaque-forming cell response and rise in antibody titers occurred in adult tolerant rats when the interval between the last 2 antigen injections was increased from 3 days to 14 or 28 days. The decline and stabilization of numbers of plaque-forming cells occurring with continued injections after the 3rd week of life paralleled a similar decline and stabilization in rats receiving similar antigen injections as adults. Also, the recovery of the plaque-forming cell and antibody response of tolerant animals paralleled the recovery observed when the interval between injections was increased in rats receiving similar antigen injections as adults. These findings suggested that the same mechanism controlled numbers of antibody-forming cells in tolerant and normally responsive adult animals. Repeated closely spaced antigen injections presumably interfered with either cell division or maturation of antibody-forming cells. As the interval between injections was increased, additional antibody-forming cells matured or were formed through cell division. Relatively constant antigenic stimulation provided a mechanism for controlling or limiting the response of antibody-forming cells. The mechanism controlling or limiting the response of antibody-forming cells would not account for the stabilization of numbers of antibody-forming cells at high levels for normal animals and at low levels for the tolerant animals. Passive immunization of growing rats with homologous anti-sheep erythrocyte serum markedly inhibited the plaque-forming cell response of growing rats. It was proposed that antibody produced by the small population of antibody-forming cells in the tolerant rats provided a feedback or homeostatic mechanism which inhibited transformation of potential antibody-forming cells to antibody-forming cells. Thus, tolerance to sheep erythrocytes was induced and maintained by two mechanisms. One mechanism, dependent on relatively constant antigenic stimulation, limited or controlled the numbers of antibody-forming cells. The other, dependent on the production of small quantities of antibody by a few antibody-forming cells, limited or controlled the transformation of potential antibody-forming cells to antibody-forming cells.

Animals↗
PubMed1995

Reduced birthweight and length in the offspring of females exposed to PCDFs, PCP, and lindane.

The objective of this study was to investigate a broad range of adverse health outcomes and their potential association to wood preservative used in daycare centers. This article focuses on reproductive effects. A sample of 221 exposed teachers was provided by the employer's liability insurers. A comparison group (n = 189) insured by the same two organizations was recruited from nonexposed daycare centers. In a face-to-face interview, job history and reproductive history of 398 female teachers were ascertained. Data on exposure were provided, including measurements on concentration of pentachlorophenol (PCP) and lindane in wood panels, and of PCP, lindane, polychlorinated dibenzo-p-dioxins and dibenzofurans in indoor air. An exposure matrix based on individual job history, independent exposure information from each center, and reproductive history was set up with regard to the vulnerable time windows for each pregnancy. Using this approach, 49 exposed and 507 nonexposed pregnancies were identified, including 32 exposed and 386 nonexposed live births. For subgroup analyses the observations were restricted to independent pregnancies, excluding multiple and consecutive births. The data were analyzed with linear regression techniques, taking confounders into account. The crude median difference between exposed and nonexposed was 175 g in birthweight and 2 cm in length. Controlling for confounders, the results show a significantly reduced but weight (p = 0.04) and length (p = 0.02) in exposed pregnancies, even after restricting the data to independent pregnancies and pregnancies for which data could be validated from the mother's health cards. These differences were not explained by differences in gestational age indicating that a toxic effect, which could cause small-for date newborns, might have affected the fetus.

Adult↗
PubMed1995

Epidemiology of sudden infant death syndrome (SIDS) for Kentucky infants born in 1990: maternal, prenatal, and perinatal risk factors.

Using state vital statistics data for infants born to Kentucky residents in 1990, a nonconcurrent prospective study design was used to evaluate various risk factors for infant mortality from Sudden Infant Death Syndrome (SIDS). For comparison, an identical analysis was performed for infant mortality from all causes combined, including SIDS. The following factors were considered as potential risks: infant low birthweight, maternal age at delivery, maternal education, maternal cigarette and alcohol use during pregnancy, prenatal care, maternal race, method of delivery, premature birth, sex of the child, and multiple (twin or more) birth. A categorical analysis was used to calculate an adjusted relative risk for each potentially significant (p < 0.10) risk factor. Potentially significant adjusted relative risks for SIDS are maternal age under 20 (1.73, p < or = 0.08), maternal years of education (0.80 for one year, p < 0.01), maternal cigarette use (1.92 for one pack per day, p < 0.01), Cesarean delivery (2.09, p < or = 0.01), and premature birth (1.76, p < or = 0.08). Potentially significant adjusted relative risks for infant death from all causes are low birthweight (5.93, p < 0.01), maternal age over 35 (1.54, p < or = 0.05), maternal years of education (0.94 for one year, p < or = 0.02), marginal prenatal care (1.47, p < or = 0.01), premature birth (1.47, p < 0.01), and female sex (0.82, p < or = 0.05). Given this data, there may be unique risk factors for SIDS. The implications of these findings are discussed.

Adult↗
PubMed2004

Trends in embryo-transfer practice and in outcomes of the use of assisted reproductive technology in the United States.

BACKGROUND: During the past decade in the United States, increasing attention has been paid to lowering the incidence of multiple gestations resulting from the use of assisted reproductive technology. To determine whether such efforts have been successful, we assessed national trends in embryo-transfer practice patterns and in outcomes after the use of assisted reproductive technology. METHODS: We analyzed data on outcomes of assisted reproductive technology procedures as reported to the Centers for Disease Control and Prevention from 1995 to 2001 by fertility clinics in the United States. We also analyzed data from the National Center for Health Statistics on the rates of twin births and triplet or higher-order multiple births. RESULTS: From 1995 to 2001 in the United States, the number of infertility clinics, the number of fresh-embryo cycles initiated, and the number of fresh-embryo transfers increased steadily. The average number of embryos transferred per cycle began decreasing in 1997, with the steepest decline (an 11.1 percent decrease) between 1998 and 1999. In contrast, the number of pregnancies and live births per cycle during the period from 1995 to 2001 steadily increased. Even though the percentage of pregnancies with twins did not change significantly between 1997 and 2001, the percentage of pregnancies with three or more fetuses significantly decreased every year, with the steepest decline (a 20.8 percent decrease) between 1998 and 1999, after the publication in 1998 of the American Society for Reproductive Medicine guidelines for embryo transfer. CONCLUSIONS: Since 1997 in the United States, there have been consistent decreases in both the number of embryos transferred per cycle and the percentage of pregnancies with three or more fetuses, as well as a consistent increase in the percentage of live births per cycle.

Adult↗
PubMedDate not supplied

Impact of prenatal diagnosis on livebirth prevalence of children with congenital anomalies.

The objectives of this study were to describe the impact of prenatal diagnosis on the birth prevalence of congenital anomalies over 21 years (1979-1999) in a well defined population in northeastern France (13,500 births per year). The material for this study came from the analysis of data from multiple sources on births and terminations of pregnancy after prenatal diagnosis of congenital anomalies in 279,642 consecutive pregnancies of known outcome. The study period was divided into three subgroups 1979-1988, 1989-1993 and 1994-1999. Between 1979-1988, 1989-1993 and 1994-1999, prenatal detection of congenital anomalies increased, respectively, from 12.0% to 25.5% and to 31.7%. Termination of pregnancy (TOP) increased in the same proportions during the three time periods. However, the increase of TOP was much higher for chromosomal anomalies than for nonchromosomal congenital anomalies. The birth prevalence of Down's syndrome fell by 80% from 1979-1988 to 1994-1999. Sensitivity of prenatal detection of congenital anomalies and TOPs were lower for isolated cases (only one malformation present in the fetus) than for multiple malformations in the same fetus. Sensitivity varied with the type of malformations: it was high for neural tube defect (79.7%) and urinary anomalies (50.7%) and low for congenital heart defects (16.4%). In conclusion, the introduction of routine prenatal diagnosis has resulted in a significant fall in the birth prevalence of children with congenital anomalies. However, this fall varied with the types of congenital anomalies.

Chromosome Aberrations↗
PubMed1993

Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

BACKGROUND: There exists no reliable information that allows the ophthalmologist to predict with any degree of certainty a particular infant's chances of requiring surgical treatment for retinopathy of prematurity (ROP) or of reaching an unfavorable outcome on the basis of the retinal findings at the time of the nursery examination. METHODS: In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP), 4099 infants weighing less than 1251 g at birth underwent eye examinations that began at 4 to 6 weeks after birth and subsequently continued at 2-week intervals. Independent variables in the population were studied using multiple logistic regressions. RESULTS: An increased risk of reaching threshold ROP was found associated with lower birth weights, younger gestational age, white race, multiple birth, and being born outside a study center nursery. For infants who developed ROP (66%), corresponding probabilities are presented for developing severe ("threshold") ROP or of having an unfavorable macular outcome. The risk of an unfavorable macular outcome was increased with zone 1 ROP, "plus" disease, the severity of the stage, and the amount of circumferential involvement. A higher risk also was associated with a rapid rate of progression of ROP to prethreshold disease but not with the postconceptional age at which ROP was first noted. CONCLUSION: The findings indicate that the ocular characteristics of ROP, along with some easily identifiable and available basic systemic and demographic information about an infant, can assist the ophthalmologist in understanding variations in an individual baby's chance for a good or poor macular outcome.

Child, Preschool↗