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Fetal programming: the perspective of single and twin pregnancies.

Multiple pregnancy is associated with increased risk of adverse consequences for both mother and fetus(es), including increased rates of maternal hypertension and pre-eclampsia, spontaneous abortion, Caesarean delivery, low birthweight, birth prematurity, perinatal mortality, admission to neonatal intensive care and extended length of care, respiratory distress, cerebral palsy, developmental delay, contact with disability services and mortality to age 5 years. Premature birth, which affects 97% of triplets and 53.3% of twins in Australia, is not the sole factor involved. The rate of multiple pregnancy in Australia is 1.7%. This compares to 22.1% for pregnancies resulting from assisted reproduction technology (ART). As a result, 21.8% of babies born from ART are from a multiple pregnancy, in comparison to the USA where the majority of babies born from ART are from a multiple pregnancy. Additionally, the population rate of multiple births is rising due to the more frequent use of ART and continued multi-embryo transfers, which is operating against a background of rising implantation rates within ART clinics. Twins have been of interest from a programming perspective. However, analysis of associations between crude birthweight and subsequent metabolic risk factors or mortality in adulthood from chronic disease indicate that adaptations in pregnancy to support multi-fetal growth are not identical to fetal growth restriction in singleton pregnancies. Indeed, the process of 'maternal constraint' is incompletely understood and confounds such comparisons. From a programming perspective, it is a challenge to identify in twin pregnancies the transition from physiological adaptation to pathological growth restriction. Growth disparity between twins has been more illuminating of subtle adverse effects for the smaller of twin pairs in both blood pressure and insulin resistance in adulthood. Interestingly, these effects can be observed in both dizygotic and to a lesser degree in monozygotic twins, which indicates a role for both genetic and environmental factors in these measures. This suggests that, consistent with experimental studies in other species, the relationship between impaired growth in utero and chronic disease in later life is not simply mediated by a common genetic pathway.

Australia↗

Outcome-based management of retinopathy of prematurity. Multicenter Trial of Cryotherapy for Retinopathy of prematurity Cooperative Group.

PURPOSE: A system is presented for sequentially computing the risk of progression of retinopathy of prematurity (ROP) for infants born weighing not more than 1250 gm. A personal computer program is used to monitor infants' risk of threshold ROP from first appearance of ROP, and the progression in severity is tracked with multiple logistic risk models developed from data in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. METHODS: After entry of the infant's birth weight, gestational age, ethnicity, birth in the current hospital or elsewhere, single or multiple birth, and maturity zone of retinal vessels, risk of progression to threshold severity is calculated. New estimates of risk are computed at onset of ROP and prethreshold ROP (any zone I ROP, zone II stage 2+ or 3) according to the extent of retinal vascularization when ROP first appears, how rapidly ROP progresses, and how severe it is. When threshold ROP (8 total or 5 contiguous clock hours of stage 3+ in zone I or II) is reached,the system provides separate estimates of risk that the eye will have an unfavorable 3-month outcome if treated or not. RESULTS: Estimates of risk of progression to threshold disease among the 4099 patients in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history study varied from less than 1% to more than 70%. For eyes with threshold disease, the risk of an unfavorable outcome at 3 months without treatment varied from less than 10% to more than 90%. CONCLUSION: This method of tracking identifies infants at high risk for severe ROP and poor structural outcome. It provides information about prognosis with a specificity heretofore impossible.

Algorithms↗

Risk factors for preterm births in São Luís, Maranhão, Brazil.

Preterm birth continues to be one of the main causes of neonatal morbidity and mortality. The objective of the present study was to identify risk factors for preterm birth in São Luís, Maranhão, Brazil. The sample consisted of hospital births at 10 public and private hospitals from March 1, 1997 to February 28, 1998. A total of 2,443 live births were randomly selected, excluding multiple deliveries and stillbirths. Preterm birth rate in São Luís was 12.7%. Risk factors for preterm delivery were maternal age below 18 years, family income equal to or less than one minimum wage/ month, primiparity, vaginal delivery at a public hospital, single mothers (or living without a partner), and absence of prenatal care. The following factors remained associated with preterm birth after multivariate analysis to control for confounding: maternal age below 18 years (OR=1.9), primiparity (OR=1.5), and failure to appear for scheduled prenatal care visits (OR=1.5).

Adolescent↗

Maffucci's syndrome: amesenchymal dysplasia and multiple tumour syndrome.

A case of Maffucci's syndrome with cutaneous, bony and neurological complications is reported. The patient had lymphangiomatosis at birth and developed multiple cutaneous haemangiomas and osteochondromas during childhood. She also developed multiple neurological defects, including cranial nerve palsies due to an intracranial osteochondroma. The occurence of mesodermal dysplasias and neoplasias in the Maffucci syndrome is emphasized, and it is suggested that there is a close relationship between this disorder and Ollier's disease (multiple enchondromatosis).

Adolescent↗

Congenital heart disease: a 10 year cohort.

In order to describe the epidemiology of congenital heart disease in Western Australia, a retrospective, population-based cohort study was conducted using data collected from multiple sources of ascertainment by the Western Australian Birth Defects Registry. The prevalence of congenital heart disease was 7.65 per 1000 total births. Nine per cent of all cases had a chromosomal disorder, another 17% had extracardiac defects in addition to congenital heart disease, and 75% had isolated congenital heart disease. Congenital heart disease was more common in Aboriginal compared with non-Aboriginal infants, and in multiple births compared with singletons. Compared with infants weighing 3000 to 3499 g, infants of lower birthweight were more likely to have congenital heart disease, and infants in the heaviest category (> or = 3500 g) were less likely to have congenital heart disease. Three per cent of all stillbirths were known to have a cardiac defect, as were 15.2% of neonatal deaths and 10.8% of post-neonatal deaths.

Birth Weight↗

The prevalence at birth of cogenital malformations at a maternity hospital in Osaka City, 1948-1990.

The frequencies of congenital malformations at St. Barnabas' Hospital, Osaka were studied during the period 1948-1990. There were 1,418 malformed infants diagnosed during the first week of life among a total number of 131,996 births during the period. Of the 1.07% of malformed children, 0.90% had single and 0.17% had multiple malformations. The birth prevalence was 1.07% in singletons and 1.20% in twins. There was significant difference in prevalence between males (1.15%) and females (0.97%). The prevalence was 0.88% for the period 1948-1958 and increased with each year cohort up to the recent period when the value was 1.38%. Varus deformities of feet was the most common defect (23.4 per 10,000 births), followed by polydactyly (finger) (7.8), anencephaly (7.1), cleft lip and palate (6.5), syndactyly (toe) (6.5), cleft lip (6.3), and Down's syndrome (6.1). The prevalence of conjoined twins was 1 in 65,551 deliveries. Significant differences occurred between males and females for cleft palate, cleft lip and palate, syndactyly (finger), oligodactyly (finger), and hypoplastic auricle. The prevalences for valgus deformities of feet, syndactyly (toe) and atresia ani increased significantly with the year cohort, whereas the prevalence of cleft palate decreased significantly with the year cohort. Overall prevalence was significantly higher in 1970-1990 (1.28% than in 1948-1969 (0.88%). Similar results were examined for cleft lip and palate, syndactyly (finger), syndactyly (toe), hypospadias, hydrocele testis, and Down's syndrome.

Congenital Abnormalities↗

Birth weight and musculoskeletal health in 36-year-old men and women: results from the Amsterdam Growth and Health Longitudinal Study.

The results of recent epidemiological studies suggest that birth weight is related to adult bone mineral status. Since birth weight might also be related to muscle strength and fat-free mass, which are important determinants of bone health, the aim of this study was to investigate the following: is birth weight related to bone mineral content (BMC) and bone mineral density (BMD) at the lumbar level, at the hip and of the total body, and to structural properties of the heel bone, to fat-free mass (FFM) and to muscle strength, at the age of 36 years? Two hundred and eighty-two subjects (162 women) underwent dual X-ray absorptiometry (DEXA) measurement for the assessment of BMC and BMD at different sites and the FFM and/or measurement of the structural properties of the heel bone, which were estimated with speed of sound (H-SOS) and broadband ultrasound attenuation. Muscle strength was assessed with two fitness tests (static arm-pull, and high jump). Information on birth weight was gathered by means of a questionnaire. The data were analyzed by application of multiple linear regression. Birth weight was positively related to FFM. In a crude model, birth weight was found to be positively associated with BMC, but not after adjustment for adult body weight. No significant associations were found between birth weight and muscle strength or birth weight and BMD. Furthermore, birth weight was inversely related to H-SOS. No other relationships were observed. Results support the fetal origins hypothesis that lower birth weight is related to lower BMC and FFM, but not that birth weight is associated with BMD and muscle strength. Furthermore, FFM was not identified as a link between birth weight and musculoskeletal health.

Absorptiometry, Photon↗

Cord serum insulin-like growth factor binding protein-1 and -3: effect of maternal diabetes and relationships to fetal growth.

OBJECTIVES: Insulin-like growth factor binding protein-1 and -3 (IGFBP-1 and -3) are the main insulin-like growth factor (IGF) carriers in fetal blood whose concentrations are regulated by hormonal factors such as insulin. IGFBPs may regulate fetal growth by altering the biological activity of IGF-I and IGF-II. We studied the effect of maternal diabetes on cord serum IGFBP-1 and IGFBP-3 levels, and the usability of IGFBP-1 and IGFBP-3 in the detection of birth weight variations. METHODS: Cord serum IGFBP-1 and IGFBP-3 concentrations were measured at birth by immunofluorometric assays in 67 pregnancies with type 1 diabetes and in 62 normal pregnancies. RESULTS: Concentrations of IGFBP-1 in cord serum were lower in diabetic pregnancies than in normal pregnancies (156 +/- 28 microg/l vs 266 +/- 29 microg/l, P = 0.007), whereas those of IGFBP-3 did not differ significantly (3327 +/- 158 microg/l vs 2982 +/- 105 microg/l, P = 0.076). IGFBP-1 correlated negatively and IGFBP-3 positively with birth weight z-score in diabetic pregnancies. The trend was similar in normal pregnancies. In multiple regression models, birth weight z-score was significantly associated with IGFBP-1 in diabetic and normal pregnancies, and with IGFBP-3 in diabetic pregnancies. CONCLUSION: Maternal diabetes is associated with suppressed levels of IGFBP-1 in cord serum, whereas those of IGFBP-3 do not change markedly. In diabetic pregnancies, both cord serum IGFBP-1 and IGFBP-3 correlate with fetal growth.

Adult↗

Are children born after assisted reproductive technology at increased risk for adverse health outcomes?

As assisted reproductive technologies (ARTs) are increasingly used to overcome infertility, there is concern about the health of the children conceived. The empirical evidence for associations with outcomes related to child health is variable and should be evaluated with consideration of methodological shortcomings. Currently, there is convincing evidence that ART treatment may increase the risk of a few outcomes. Experimental laboratory studies document that various constituents in culture media affect various embryo characteristics both positively and negatively. Multiple-gestation pregnancy and birth are increased with ART, both because of multiple embryo transfer and embryo splitting. There is evidence of an increase in chromosomal abnormalities among pregnancies conceived using intracytoplasmic sperm injection and low birth weight and preterm delivery among singletons conceived with all types of ART; however, there remains uncertainty about whether these risks stem from the treatment or the parental infertility. For some outcomes, data of an increased risk with ART are suggestive at best largely because of lack of purposeful study of sufficient size and scope. These include specific perinatal morbidities, birth defects, developmental disabilities, and retinoblastoma. The evidence for an association between ART and spontaneous abortion is inconsistent and weak. There is inconclusive evidence that ART may be associated with genetic imprinting disorders. For childhood cancer, chronic conditions, learning and behavioral disorders, and reproductive effects there is insufficient empirical research to date, but given the data for more proximal outcomes, these outcomes merit further study. Future research needs to address the unique methodological challenges underlying study in this area.

Abortion, Spontaneous↗

Characteristics of preterm delivery and low birthweight among 113,994 infants in Alberta: 1994-1996.

This study examined the impact of infant and maternal factors on preterm delivery and low birthweight (LBW) in Alberta between January 1, 1994 and December 31, 1996. Data on 113,994 births were collected from vital statistics registration birth data. Logistic regression models for preterm and LBW delivery suggested the key risk factors were multiple and still birth (odds ratios > 22.0). Other characteristics included female gender, birth defects, nulliparous women, maternal age 35 and greater, unmarried, history of abortion, maternal smoking, maternal street drug use, and having less than 4 prenatal visits (odds ratios 0.86-2.54). Interactions between smoking and alcohol, and smoking and parity were noted. Efforts to improve the currently low rates (8.2%) of smoking cessation during pregnancy are required. Social, economic and medical factors associated with delayed childbearing and birth outcomes should be investigated.

Adolescent↗

Failed vaginal birth after a cesarean section: how risky is it? I. Maternal morbidity.

OBJECTIVE: Our purpose was to determine the maternal risks associated with failed attempt at vaginal birth after cesarean compared with elective repeat cesarean delivery or successful vaginal birth after cesarean. STUDY DESIGN: From 1989 to 1998 all patients attempting vaginal birth after cesarean and all patients undergoing repeat cesarean deliveries were reviewed. Data were extracted from a computerized obstetric database and from medical charts. The following three groups were defined: women who had successful vaginal birth after cesarean, women who had failed vaginal birth after cesarean, and women who underwent elective repeat cesarean. Criteria for the elective repeat cesarean group included no more than two previous low transverse or vertical incisions, fetus in cephalic or breech presentation, no previous uterine surgery, no active herpes, and adequate pelvis. Predictor variables included age, parity, type and number of previous incisions, reasons for repeat cesarean delivery, gestational age, and infant weight. Outcome variables included uterine rupture or dehiscence, hemorrhage >1000 mL, hemorrhage >2000 mL, need for transfusion, chorioamnionitis, endometritis, and length of hospital stay. The Student t test and the chi(2) test were used to compare categoric variables and means; maternal complications and factors associated with successful vaginal birth after cesarean were analyzed with multivariate logistic regression, allowing odds ratios, adjusted odds ratios, 95% confidence intervals, and P values to be calculated. RESULTS: A total of 29,255 patients were delivered during the study period, with 2450 having previously had cesarean delivery. Repeat cesarean deliveries were performed in 1461 women (5.0%), and 989 successful vaginal births after cesarean delivery occurred (3.4%). Charts were reviewed for 97.6% of all women who underwent repeat cesarean delivery and for 93% of all women who had vaginal birth after cesarean. Vaginal birth after cesarean was attempted by 1344 patients or 75% of all appropriate candidates. Vaginal birth after cesarean was successful in 921 women (69%) and unsuccessful in 424 women. Four hundred fifty-one patients undergoing cesarean delivery were deemed appropriate for vaginal birth after cesarean. Multiple gestations were excluded from analysis. Final groups included 431 repeat cesarean deliveries and 1324 attempted vaginal births after cesarean; in the latter group 908 were successful and 416 failed. The overall rate of uterine disruption was 1.1% of all women attempting labor; the rate of true rupture was 0.8%; and the rate of hysterectomy was 0.5%. Blood loss was lower (odds ratio, 0.5%; 95% confidence interval, 0.3-0.9) and chorioamnionitis was higher (odds ratio, 3.8%; 95% confidence interval, 2.3-6.4) in women who attempted vaginal births after cesarean. Compared with women who had successful vaginal births after cesarean, women who experienced failed vaginal births after cesarean had a rate of uterine rupture that was 8.9% (95% confidence interval, 1.9-42) higher, a rate of transfusion that was 3.9% (95% confidence interval, 1.1-13.3) higher, a rate of chorioamnionitis that was 1.5% (95% confidence interval, 1.1-2.1) higher, and a rate of endometritis that was 6.4% (95% confidence interval, 4.1-9.8) higher. CONCLUSION: Patients who experience failed vaginal birth after cesarean have higher risks of uterine disruption and infectious morbidity compared with patients who have successful vaginal birth after cesarean or elective repeat cesarean delivery. Because actual numbers of morbid events are small, caution should be exercised in interpreting results and counseling patients. More accurate prediction for safe, successful vaginal birth after cesarean delivery is needed.

Adult↗

Plurality-dependent risk of severe intraventricular hemorrhage among very low birth weight infants and antepartum corticosteroid treatment.

OBJECTIVE: This study was undertaken to compare the effect of antenatal corticosteroid therapy on the risk for severe intraventricular hemorrhage (IVH grade III-IV) in preterm singleton and multiple very low birth weight (VLBW) infants. STUDY DESIGN: The occurrence of severe IVH was recorded in 5022 singleton, 2032 twin, and 582 triplet infants, delivered at 24 to 32 weeks' gestation, registered in the Israeli National VLBW infant database. Antenatal corticosteroid therapy was defined as complete, partial, or none. RESULTS: The incidence of IVH grade III-IV ranged from 6.8% among singletons receiving complete course to 29.3% in triplets without antenatal corticosteroid treatment. Complete treatment significantly reduced the incidence of IVH in all plurality groups. The adjusted risk for IVH among multiple infants who received a complete course compared with singletons was not significantly different, odds ratio (OR) 1.3, 95% CI 1.0-1.7 for twins and OR 1.5, 95% CI 0.9-2.3 for triplets. CONCLUSION: Complete course of antenatal corticosteroid therapy was independently associated with decreased risk for severe IVH in singleton and in multiple preterm VLBW infants.

Betamethasone↗

Can cardiovascular risk be predicted by newborn, childhood, and adolescent body size? An examination of longitudinal data in urban African Americans.

OBJECTIVE: Recent retrospective studies of older adults have demonstrated a correlation between lower birth weight and hypertension and insulin resistance. We tested this finding in our sample of urban African Americans with prospective data on growth and blood pressure and also tested other variables (in addition to birth weight) for their relationship to adult cardiovascular risk. STUDY DESIGN: A prospective study of birth weight, growth, and blood pressure (Philadelphia Perinatal Collaborative Project) followed a sample of 137 African Americans, with nine examinations from birth through 28.0 +/- 2.7 years. Metabolic measurements (oral glucose tolerance testing, euglycemic hyperinsulinemic clamp, and plasma lipid concentration) were performed on the subjects as adults. Bivariate correlations among parameters were computed using the Pearson r. The chi-squared statistic was used to determine associations of outcomes with birth weight. Stepwise multiple linear regressions were computed using newborn, early childhood, adolescent, and young adult parameters to predict adult outcomes. RESULTS: Birth weight and blood pressure at age 28 years are not correlated (Pearson r = 0.06). Birth weight is also unrelated to adult obesity. However, weight at 0.3 years and after and body mass index at 7 years and after are correlated with adult weight. Furthermore, weight at age 14 years is significantly negatively correlated with measures of insulin-stimulated glucose use, indicating that obese adolescents may be at greater risk than nonobese adolescents for development of non-insulin dependent diabetes in adulthood. CONCLUSIONS: We found no relationship between birth weight and adult outcomes pertaining to cardiovascular risk in this sample of adult African Americans. However, we did find evidence that somatic growth (body weight and body mass index) is significantly related to obesity and attenuated insulin-stimulated glucose utilization in adulthood. These findings indicate that the origins of adult cardiovascular disease are related to somatic growth, but not intrauterine growth, and are evident during childhood.

Adolescent↗

Maternal risk factors for preterm birth and low birthweight in Cape Verde.

BACKGROUND: Fifteen years after the implementation of an antenatal risk screening program in Cape Verde, the first assessment of an association between maternal obstetric characteristics and preterm birth or low birthweight (LBW) infants was undertaken. METHODS: A cohort of 353 systematically selected antenatal clinic attenders in the county of Praia, Cape Verde, was studied prospectively during the period October 1991 through December 1992. The cohort was followed past the perinatal period and information was obtained according to a pretested structured questionnaire. In the analysis of preterm birth and LBW, multiple logistic regression was listed to estimate the relative risks of ll background variables. RESULTS: The prevalence of preterm birth (<37 gestational weeks) was 12%, and the prevalence of LBW infants was 8%. Low birthweight (<2500 grams) was significantly associated with low maternal age (< or = 19 years, RR=3.7); nulliparity (RR=5.2) and obstetric history of previous LBW infant (RR-6.5). The risk of preterm birth was significantly increased if the woman had an obstetric history of hypertension or convulsions (RR=2.6). CONCLUSIONS: In the setting studied, teenage women and women with previous pregnancy hypertension should be given selective attention in antenatal care to achieve improved pregnancy outcome. Primary prevention is needed to lower the prevalence of teenage pregnancies.

Adolescent↗

Birth-weight-adjusted infant mortality in evaluations of perinatal care: towards a useful summary measure.

Since birth-weight-specific infant mortality rates are widely considered to be measures of the effects of perinatal medical care, birth-weight-adjusted and birth-weight-specific infant mortality rates have often been used in comparisons across hospitals and geographic areas. Wilcox and Russell have provided a model which leads to the conclusion that birth weight adjustment is biased against populations with heavier birth weights and that birth-weight-specific infant mortality rates can yield misleading results. Nevertheless, evaluators and health planners still need a summary measure of the infant mortality rate in which some sort of birth weight adjustment is used to generate an (appropriately) weighted mean of birth-weight-specific relative risks. We used the 1983-85 national linked files of live births and infant deaths to investigate two new methods that extend the Wilcox-Russell approach, 'mean adjustment' and 'Z-adjustment', to compare birth-weight-specific infant mortality rates among the white populations of the states. Colorado was used as the reference population in logistic regression analyses. Statistical interactions between state and birth weight on the conventional kilogram scale, the mean-adjusted scale, and the Z scale were examined. There were substantial interactions with birth weight on all three scales. In addition, when Colorado was used as the reference population, mean adjustment shifted the odds ratios downward to implausibly low values, especially at lower weights. The Z-adjustment method incorporating the Wilcox-Russell approach appears to be a useful alternative to birth weight adjustment. However, because birth-weight-specific mortality rates do not differ uniformly across all birth weight groups, multiple summary measures are needed.

Alabama↗

Childbearing beyond maternal age 50 and fetal outcomes in the United States.

OBJECTIVE: To estimate whether achieving pregnancy beyond maternal age of 50 years compromises fetal well-being and survival. METHODS: This was a retrospective study on all deliveries in the United States from 1997 to 1999. Four maternal age groups of 20-29 (young), 30-39 (mature), 40-49 (very mature), and 50 or more years (older) were constructed to assess risk gradients for fetal morbidity and mortality. RESULTS: A total of 539 deliveries among older mothers (aged 50 and above) were documented (four per 100,000). Among singleton gestations, the risks for low birth weight, preterm, and very preterm were tripled among older mothers, whereas the occurrence of very low birth weight, small size for gestational age, and fetal mortality were approximately doubled compared with those for young mothers. Older mothers also had greater risks for fetal morbidity and mortality than their immediate younger counterparts (40-49 year olds) except for very low birth weight. Among multiple gestations, the differences in risk between older and young mothers were lower than those noted among singletons. Still, compared with young mothers, older mothers had significantly higher risks of low birth weight, very low birth weight, very preterm, and small size for gestational age. Older mothers also had higher risk estimates for multiples than 40-49-year-old gravidas in terms of all fetal morbidity and mortality indices. CONCLUSION: Pregnancy beyond age 50 was associated with increased risks for the fetus. Our findings suggest that this age group is a distinct obstetric high-risk entity that requires special counseling before and after conception.

Adult↗