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How low birthweight and gestational age contribute to increased inpatient costs for multiple births.

The dramatic rise in the number of multiple gestation births has led to concerns about heavy resource use by these newborns and the design of cost-effective interventions. This study uses medical records data to compare single and multiple births in terms of hospital charges by cost center, length of stay, neonatal intensive care unit (NICU) days, and discharge status. Potential mediators examined were gestational age and birthweight. These factors, respectively, accounted for 50% and 40% of the increase in total charges due to multiple gestation. The remaining "direct effect" was due primarily to longer hospital stays among twins and higher daily charges among higher-order multiples. Room and board charges were higher for multiples, while charges in other categories were actually lower, after controlling for birthweight and gestational age. Birthweight and gestational age accounted fully for the increased use of NICU services among multiples. These results show that while prevention of multiple gestation, where possible, is of paramount importance, strategies that decrease preterm delivery and/or increase birthweight should attenuate the adverse economic impact of multiple gestation pregnancies.

Boston↗

[The focus in neonatology].

During the last years, neonatology has greatly improved. In the last decade, mortality and morbidity have decreased: mortality from respiratory failure of prematurity has decreased from 22% to 12%, mortality of the very low birthweight infants under 1000 g fell from 56% to 35% and mortalities related to asphyxia have diminished from 21% to 12% and to malformations from 33% to 28%. Prematurity is now the first cause of neonatal mortality. During this period, the number of babies under 1000 g has increased 4-fold and the number of multiple births increased more than 2-fold from 3% to 7% of the live births of our hospital. Attitudes towards the premature infant have changed, especially towards the extremely small (called the micropremies). The number of disabled children has increased in parallel with the better survival of the very immature newborns who till recently were not resuscitated.

Asphyxia Neonatorum↗

[Multiples births: a continuing problem with assisted reproductive techniques].

Assisted reproductive techniques (ART) such as in vitro fertilisation (IVF), ovulation induction and superovulation followed by insemination have caused a sharp increase in multiple birth prevalence rates. The perinatal morbidity of multiple birth infants is high because of the high incidence of premature birth. The social and psychological problems of multiple birth families are also considerable. In 1990 high-order multiple births were mainly the result of IVF. Although the number of IVF treatments has increased more than the number of other ART treatments, nowadays high-order multiple births are predominantly caused by superovulation. Since 1990 the number of high-order multiple births has stabilised, but the recent sharp increase in ART twins results in a further rise in births of severely preterm ART infants. More restraint should be practised in superovulation treatments to bring down the number of (high-order) multiple births.

Adult↗

Effect of prenatal exposure to ethanol on intestinal development of rat fetuses.

BACKGROUND: Chronic alcoholism in pregnant animals and humans lead to general growth impairment in their offspring, which show multiple birth defects and delayed grown (fetal alcohol syndrome). Here we study the maturation of the intestine under the effect of chronic exposure to ethanol in utero together with associated malnutrition. METHODS: Lactase, acid beta-galactosidase, maltase, and alkaline phosphatase activity profiles were monitored in 18-, 19-, 20-, and 21-day-old fetuses from rats kept under three nutritional treatments before and during gestation: alcohol-treated (25% ethanol in drinking water), fiber-treated (50% cellulose-diluted diet) as a control of the malnutrition associated with chronic alcoholism, and control or normal diet. Serum corticosterone determination and lactase immunolocalization were carried out. To detect possible direct effects of ethanol during the period of mucosa development, intestinal explants from 18-, 19-, and 20-day-old control fetuses were cultured either in the basal medium alone or in a medium containing 25 mM ethanol for 72, 48, and 24 h of incubation, respectively. RESULTS: Following chronic ethanol exposure in utero, intestinal weight and brush-border protein content and the specific activities of lactase, acid beta-galactosidase, maltase, and alkaline phosphatase were significantly lower than those of nutritional controls. Organ culture results, under the assay conditions stated, did not show a direct effect of ethanol 25 mM on prenatal mucosal functionality. CONCLUSIONS: All these results suggest that maternal malnutrition is not primarily responsible for the impaired intestinal maturation in rat fetuses from alcohol-treated mothers; indirect effects of ethanol and/or its derivatives throughout embryo-fetal development could be necessary to promote this intestinal delay.

Alcoholism↗

Folic acid supplements during early pregnancy and likelihood of multiple births: a population-based cohort study.

BACKGROUND: Folic acid supplements are recommended for women of childbearing age to prevent neural tube defects in their offspring. Results of some studies, however, suggest an increase in multiple births associated with use of vitamin supplements that contain folic acid during pregnancy. Our aim was to assess this association. METHODS: We used data from a population-based cohort study from which we assessed the occurrence of multiple births in women (n=242015) who had participated in a campaign to prevent neural tube defects with folic acid supplements (400 microg per day) in China. Folic acid use was ascertained before pregnancy outcome was known. We studied the relation between multiple births and any use of folic acid pills before or during early pregnancy; additionally, we investigated mechanisms by which folic acid could potentially affect the occurrence of multiple births by examining pill-taking at three time periods: before ovulation, around the time of fertilisation, and after conception. FINDINGS: 1496 (0.62%) multiple births occurred in a cohort of 242015 women who had registered with the study between October, 1993, and September, 1995, and who had a pregnancy not affected by a birth defect; the rate of multiple births in women who did and did not take folic acid before or during early pregnancy was 0.59% and 0.65%, respectively (rate ratio 0.91; 95% CI 0.82-1.00). INTERPRETATION: Our findings suggest that consumption of folic acid supplements during pregnancy is not associated with an increased occurrence of multiple births.

Adult↗

Less is more: the risks of multiple births. The Institute for Science, Law, and Technology Working Group on Reproductive Technology.

OBJECTIVE: To review the medical, social, and financial risks caused by the birth of multiples that need to be addressed in policy and practice. RESULT(S): Many risks of multiple births are described in the literature. The medical risks to the offspring include death, low birth weight, deformational plagiocephaly, and other physical and mental disabilities. Risks to the women include premature labor, premature delivery, pregnancy-induced hypertension, toxemia, gestational diabetes, and vaginal-uterine hemorrhage. Children born in multiples face difficulty socializing, developmental delays, and behavioral problems, whereas their parents risk exhaustion, depression, and anxiety. In addition to personal costs faced by families, society often bears the financial costs of overburdened hospitals, caps on insurance and/or inability of parents to cover expenses. CONCLUSION(S): Multiple births present potential acute and long-term medical risks to the pregnant woman and her children. However, more long-term follow-up research and more research on outcomes with higher-order multiples are needed. In designing practices and policies to improve the success of IVF while reducing the risk of multiples, it is important to balance the many interests involved. At a minimum, providers and patients need to be educated about the risks of multiple gestation so that steps can be taken to prevent adverse outcomes.

Female↗

Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes.

It is suggested that the maternal transmission of islet autoantibodies increases the risk of autoimmune diabetes in mice. The aim of this study was to determine whether fetal exposure to islet autoantibodies modified the risk of type 1 diabetes in humans. Islet autoantibodies were measured at birth in 720 offspring of mothers with type 1 diabetes. Offspring were prospectively followed for the development of multiple islet autoantibodies and diabetes. Offspring who were GAD or IA-2 autoantibody positive at birth (n = 678) had significantly lower risks for developing multiple islet autoantibodies (5-year risk 1.3%) and diabetes (8-year risk 1.1%) than offspring who were islet autoantibody negative at birth (5.3%, P = 0.008; and 3%, P = 0.04, respectively). Risk remained reduced after adjustment for birth weight, gestational age, or maternal diabetes duration (adjusted hazards ratio 0.25, P = 0.007 for multiple islet autoantibodies; 0.25, P = 0.04 for diabetes). Protection in offspring with islet autoantibodies at birth was most striking in offspring without the HLA DRB1*03/DRB1*04-DQB1*0302 genotype. Maternal transmission of antibodies to exogenous insulin did not affect diabetes risk in offspring. These findings suggest that fetal exposure to islet autoantibodies in children born to mothers with type 1 diabetes may be protective against future islet autoimmunity and diabetes.

Aging↗

Reproductive fitness in maternal homocystinuria due to cystathionine beta-synthase deficiency.

Early diagnosis and improved treatment are leading to the potential for increased reproductive capability in homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency, but information about reproductive outcome and risk of thromboembolism in pregnancy is limited. To provide further information, clinical and biochemical information was obtained on women with maternal homocystinuria, on their pregnancies and on the offspring. This information included blood sulphur amino acids and total homocysteine, CbetaS gene mutations and developmental and cognitive scores in the offspring. The study involved 15 pregnancies in 11 women, of whom 5 were pyridoxine-nonresponsive and 6 were pyridoxine-responsive. Complications of pregnancy included pre-eclampsia at term in two pregnancies and superficial venous thrombosis of the leg in a third pregnancy. One pregnancy was terminated and two pregnancies resulted in first-trimester spontaneous abortions. The remaining 12 pregnancies produced live-born infants with normal or above-normal birth measurements. One offspring has multiple congenital anomalies that include colobomas of the iris and choroid, neural tube defect and undescended testes. He is also mentally retarded and autistic. A second offspring has Beckwith-Wiedemann syndrome. The remaining 10 offspring were normal at birth and have remained normal. There was no relationship between the severity of the biochemical abnormalities or the therapies during pregnancy to either the pregnancy complications or the offspring outcomes. The infrequent occurrences of pregnancy complications, offspring abnormalities and maternal thromboembolic events in this series suggest that pregnancy and outcome in maternal homocystinuria are usually normal. Nevertheless, a cautious approach would include careful monitoring of these pregnancies with attention to metabolic therapy and possibly anticoagulation.

Adolescent↗

Season of birth and reproductive performance: an analysis of family reconstitutions of 800 women born in The Netherlands at the end of the 19th century.

BACKGROUND: Several studies have reported associations between season of birth and reproductive characteristics such as menarcheal age, fecundability, and twinning, but the results are inconsistent with respect to the location of high- and low-risk seasons. To assess whether this disagreement could be due to the use of populations from different geographic areas and time frames instead of different etiologic pathways, we investigated the season-of-birth dependency of a variety of reproductive outcomes within one time- and area-limited population. METHODS: In a historic follow-up study, the reconstituted families of 800 women born between 1873 and 1887 in or near Rotterdam, The Netherlands, were used to determine eight types of reproductive outcome: childlessness, interval to first pregnancy, pregnancy interval, stillbirth, neonatal death, postneonatal death, multiple birth, and gender of offspring. The relation of these outcomes with season of birth was modeled using cosinor functions with periods of 1 year or a half year. Data were analyzed by use of logistic regression or general estimation equations (GEE), dependent on whether outcomes could occur more than once per woman. RESULTS: Peaks in the model-based risks of reproductive failure were found within two small temporal ranges, January 1 to February 11 and July 1 to August 11 for all outcomes except gender. The picture did not change after controlling for known and possible risk factors, including age, offspring's birth cohort, and some social variables. CONCLUSIONS: This study reconfirms the idea that seasonal factors around conception or birth influence later reproductive characteristics. Observing the consistency of the location of high-risk seasons across a variety of outcomes, the explanation of season-of-birth dependency of different reproductive outcomes need not involve multiple etiological pathways.

Female↗

Effect of prenatal exposure to ethanol on postnatal development of intestinal transport functions in rats.

BACKGROUND: Alcohol consumption by pregnant animals and humans leads to general growth impairment in their offspring, delayed growth and multiple birth defects collectively called "Fetal Alcohol Syndrome". In utero exposure of ethanol to rat pups causes damage to their developing intestinal epithelium which leads to impairment of nutrient assimilation and growth retardation during postnatal development. AIM: To determine the effect of prenatal exposure of ethanol on the postnatal development of rat intestinal Na(+)-dependent and independent D-glucose transporter along with the amino acids (glycine and Lleucine) transporter activity at 4, 8, 14, 20 and 30 days of postnatal age. The changes in the expression levels of Na(+)-dependent glucose transporter (SGLT1) mRNA was assessed at different days of postnatal age in rat pups. METHODS: Wistar strain albino female rats were fed ethanol at a dose of 2 g/kg body weight/day orally by Ryle's tube for one month before mating and during the entire period of gestation while the control females received isocaloric glucose. Transport studies were performed using the everted intestine of 4, 8, 14, 20 and 30 day-old control and ethanol-exposed pups employing the tissue accumulation method. The expression of SGLT1 mRNA at different days of postnatal age in control and ethanol-exposed rat pups was determined using a Northern Blot analysis. RESULTS: Prenatal exposure of ethanol to rat pups leads to a decrease in their body weight, intestinal length and weight and reduces the uptake capacities of SGLT1 as well as energy dependent glycine and L-leucine transporters with respect to their age-matched controls. However, the mRNA levels of SGLT1 remained unaltered in the ethanol-exposed pups at all ages of postnatal development compared to their controls. CONCLUSION: These findings suggest that in utero exposure to ethanol leads to a general delay in the postnatal development of the intestine of ethanol-exposed rat pups affecting mainly the development of intestinal energy dependent D-glucose and amino acid (glycine and L-leucine) transporters.

Animals↗

[Maternal partiality in attachment with multiple birth children and the related factors].

UNLABELLED: Multiple births are associated with an increased risk of child abuse and neglect. It is reported that only one child is abused in almost cases, and most abusers are the mothers. Maternal partiality regarding attachment has been suggested as the reason for this tendency. This study investigated the prevalence of this phenomenon in families with multiple birth children and identified factors associated with increased risk. The subjects were 231 mothers of multiple birth children. The following results were obtained. 1. Overall, 10.0% of mothers with multiple birth children reported that they didn't equally attach themselves to all their offspring. 2. Mothers who didn't equally attach themselves exhibited significantly poor health conditions and a higher frequency of upper respiratory infections, compared with mothers who demonstrated no partiality. Moreover, they were more likely to complain of severe fatigue (physical and mental) and poor sleeping conditions. 3. The mothers who didn't equally attach themselves to all their multiple birth children had a higher rate of handicapped children. CONCLUSION: Mothers who do not equally attach themselves to all their multiple birth children show poor health conditions and a higher frequency of upper respiratory infections, and complain of severe fatigue and poor sleeping conditions. They also have a higher rate of handicapped children.

Adult↗

Maternal testosterone levels during pregnancy are associated with offspring size at birth.

OBJECTIVE: Animal studies have indicated that maternal androgen levels influence the intrauterine environment and development of the offspring. Human data are missing. We therefore investigated the possible association between maternal androgens and offspring size at birth in humans. DESIGN: A random sample of parous Caucasian women (n=147) was followed prospectively through pregnancy. METHODS: Maternal serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone and sex hormone-binding globulin (SHBG) were measured at gestational weeks 17 and 33. The main outcome measures were weight and length at birth. Associations between maternal androgen levels and offspring birth weight and length were investigated using multiple linear regression modeling adjusted for potential confounding by maternal height, pre-pregnancy body mass index, smoking, parity, offspring gender and gestational age at birth. RESULTS: Elevated maternal testosterone levels at week 17 and 33 were both associated with lower birth weights and lengths. Accordingly, at week 17, an increase in maternal testosterone levels from the 25th to the 75th percentile was associated with a decrease in birth weight by 160 g (95% confidence interval (CI); 29-290 g), while at week 33 that estimate was 115 g (95% CI; 21-207 g). No similar associations were observed for DHEAS, androstenedione or SHBG. CONCLUSIONS: Elevated maternal testosterone levels during human pregnancy are associated with growth restriction in utero. Our results support animal studies, which have indicated that maternal androgen levels influence intrauterine offspring environment and development.

Adolescent↗

Obstetric care and proneness of offspring to suicide as adults: case-control study.

OBJECTIVE: To investigate any long term effects of traumatic birth and obstetric procedures in relation to suicide by violent means in offspring as adults. DESIGN: Prospective case-control study. SETTING: Stockholm, Sweden. SUBJECTS: 242 adults who committed suicide by violent means from 1978 to 1995, and who were born in one of seven hospitals in Stockholm during 1945-80, matched with 403 biological siblings born during the same period and at the same group of hospitals. MAIN OUTCOME MEASURES: Adverse and beneficial perinatal factors expressed as relative risks (odds ratios) and 95% confidence intervals, derived from logistic regression of cases matched with their siblings. RESULTS: For multiple birth trauma the estimated relative risks of offspring subsequently committing suicide by violent means were 4.9 (95% confidence interval 1.8 to 13) for men and 1.04 (0.2 to 4.6) for women. In mothers who received multiple opiate treatment during delivery, the estimated relative risk of offspring subsequently committing suicide was equal for both sexes (0.26, 0.09 to 0.69). CONCLUSION: Minimising pain and discomfort to the infant during birth seems to be of importance in reducing the risk of committing suicide by violent means as an adult.

Adult↗

Increased susceptibility to stress at a psychological assessment of stress tolerance is associated with impaired fetal growth.

BACKGROUND: This study aims to investigate the relationship between birthweight and psychological function, as evaluated by the results of a psychological conscript interview and assessment in young males, including an evaluation of stress susceptibility. METHODS: We performed a retrospective cohort study based on linked birth registry data and data from an assessment of psychological function during evaluation for military service. In all, 90 651 young males born 1973-1975, for whom birth record data were obtained from the Swedish Medical Birth Register, were investigated in addition to psychological stress susceptibility during their conscript evaluation in 1991-1994. The assessment of psychological functioning score, including the assessment of stress susceptibility, was used as the dependent variable in a multiple regression analysis in combination with the following independent variables: birthweight, adult weight, head circumference at birth, month of birth, gestational age, maternal parity, and maternal age. RESULTS: The mean value was 5.1 (SD 1.9) on the psychological assessment scale (range 1-9) of psychological level of functioning including evaluation of stress susceptibility, and 5.3 (1.6) on the general psychological performance (leadership) profile. A positive association was seen between birthweight and better assessment results up to a level of about 4000 g birthweight, but above that an inverse association was seen. Positive correlations (P < 0.001) were seen between psychological assessment score results and birthweight (r = 0.07), gestational age (0.03), head circumference (0.05), and maternal age (0.11), but inverse correlations with maternal parity (-0.11) and birth month of the offspring (-0.04). In multiple regression analyses, the strongest independent correlations were seen between increasing assessment scores and maternal age and birthweight (positive), as well as with maternal parity and offspring adult weight (negative). CONCLUSION: Young males at conscript testing show a better general psychological functioning score derived from psychological assessment, including evaluation of stress susceptibility, with increasing birthweight up to 4200 g. Above that birthweight an inverse association is noticed. Impaired fetal growth is predictive of suboptimal psychological functioning and increased stress susceptibility in males during early adult life.

Birth Weight↗

Parenthood in survivors after adulthood cancer and perinatal health in their offspring: a preliminary report.

Cancer survivors may fear infertility, obstetric problems, and genetic alterations in their offspring. After linkage of three registries the probability of post-treatment parenthood and the risk of obstetric and perinatal problems were estimated in cancer survivors compared to individuals without a cancer diagnosis. A total of 1531 of 13,817 patients had 2307 children after one parent's cancer diagnosis: 972 males had 1479 children and 559 females had 828. A total of 1217 patients (784 males and 433 females) became parents > or =9 months after the diagnosis (1899 births: 1221 to male cancer patients and 678 to female patients). The post-diagnosis parenthood probability was 8% at 5 years, and 14% at 10 years without further increase. Female cancer survivors gave birth to post-diagnosis infants with on average 130 grams lower birth weight and 6 days shorter gestations compared with infants in the non-cancer population. Infants fathered by male cancer survivors did not differ from control infants with respect to birth weight or gestational age. There was no increase in the prevalence of major congenital malformations in the offspring of cancer survivors as compared with the offspring of the non-cancer population. Multiple births and deliveries by cesarean sections were increased. Parenthood after cancer is possible in a significant number of patients, more so for males than females. The risk of major congenital malformations was not increased relative to the non-cancer population, nor was perinatal mortality increased. However, female cancer survivors delivered more preterm births and low-birth-weight infants than what was found in the non-cancer population.

Adult↗

Acute ethanol exposure during pregnancy in rats: effects upon a multiple learning task.

Pregnant rats received 4.8 g/kg of 20% (v/v) ethanol IP or identical volume of saline during gestational Day 8. No signs of gross physical teratogenesis were evident in the offspring as expressed by litter size, weight and external malformations at birth. However, when offspring were subjected to a multiple fixed ratio-4/differential reinforcement of low rate of responding 10-sec ( FR 4/DRL 10 sec) schedule of reinforcement at 60 days of age, significant differences were observed in the performance of DRL 10-sec schedule that required visual discrimination and response inhibition, but not in the FR 4 schedule that required a relatively simple nondiscrimination task of active-response. Bar press rates were unaffected by prenatal treatment since no differences between groups were found in the number of total responses performed on either component of the multiple schedule. Present results are discussed in terms of either response perseveration or a lower aptitude to deal with low rates of responding-discrimination learning tasks on the animals prenatally exposed to alcohol.

Analysis of Variance↗