Self-cleaving peptides for expression of multiple genes in Dictyostelium discoideum.

The social amoeba Dictyostelium discoideum is a model for a wide range of biological processes including chemotaxis, cell-cell communication, phagocytosis, and development. Interrogating these processes with modern genetic tools often requires the expression of multiple transgenes. While it is possible to transfect multiple transcriptional units, the use of separate promoters and terminators for each gene leads to large plasmid sizes and possible interference between units. In many eukaryotic systems this challenge has been addressed through polycistronic expression mediated by 2A viral peptides, permitting efficient, co-regulated gene expression. Here, we screen the most commonly used 2A peptides, porcine teschovirus-1 2A (P2A), Thosea asigna virus 2A (T2A), equine rhinitis A virus 2A (E2A), and foot-and-mouth disease virus 2A (F2A), for activity in D. discoideum and find that all the screened 2A sequences are effective. However, combining the coding sequences of two proteins into a single transcript leads to notable strain-dependent decreases in expression level, suggesting additional factors regulate gene expression in D. discoideum that merit further investigation. Our results show that P2A is the optimal sequence for polycistronic expression in D. discoideum, opening up new possibilities for genetic engineering in this model system.

Births: Final Data for 2019.

Objectives-This report presents 2019 data on U.S. births according to a wide variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Methods-Descriptive tabulations of data reported on the birth certificates of the 3.75 million births that occurred in 2019 are presented. Data are presented for maternal age, livebirth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates by age are also shown. Trend data for 2010 through 2019 are presented for selected items. Trend data by race and Hispanic origin are shown for 2016-2019. Results-A total of 3,747,540 births were registered in the United States in 2019, down 1% from 2018. The general fertility rate declined from 2018 to 58.3 births per 1,000 women aged 15-44 in 2019. The birth rate for females aged 15-19 fell 4% between 2018 and 2019. Birth rates declined for women aged 20-34 and increased for women aged 35-44 for 2018-2019. The total fertility rate declined to 1,706.0 births per 1,000 women in 2019. Birth rates declined for both married and unmarried women from 2018 to 2019. The percentage of women who began prenatal care in the first trimester of pregnancy rose to 77.6% in 2019; the percentage of all women who smoked during pregnancy declined to 6.0%. The cesarean delivery rate decreased to 31.7% in 2019 (Figure 1). Medicaid was the source of payment for 42.1% of all births in 2019. The preterm birth rate rose for the fifth straight year to 10.23% in 2019; the rate of low birthweight was essentially unchanged from 2018 at 8.31%. Twin and triplet and higher-order multiple birth rates both declined in 2019 compared with 2018.

Birth characteristics and childhood leukemia in Switzerland: a register-based case-control study.

PURPOSE: Initial genetic alterations in the development of childhood leukemia occur in utero or before conception; both genetic and environmental factors are suspected to play a role. We aimed to investigate the associations between childhood leukemia and perinatal characteristics including birth order, birth interval to older siblings, parental age, birth weight, and multiple birth. METHODS: We identified cases diagnosed between 1981 and 2015 and born in Switzerland between 1969 and 2015 from the Swiss Childhood Cancer Registry and randomly sampled five controls per case from national birth records matched on date of birth, sex, and municipality of residence at birth. We used conditional logistic regression to investigate associations between perinatal characteristics and leukemia at ages 0-15 and 0-4 years, and the subtypes acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS: The study included 1,403 cases of leukemia. We observed increased risks associated with high birth weight (adjusted OR 1.37, 95% CI 1.12-1.69) and multiple birth (1.89, 1.24-2.86). These associations were similar for ALL and stronger for leukemia at ages 0-4 years. For AML, we observed an increased risk for higher birth order (3.08, 0.43-22.03 for fourth or later born children). We found no associations with other perinatal characteristics. CONCLUSION: This register-based case-control study adds to the existing evidence of a positive association between high birth weight and risk of childhood leukemia. Furthermore, it suggests children from multiple births are at an increased risk of leukemia.

Survival and early complications of preterm infants with birthweight less than 500 grams during a 10-year period in Hungary.

BACKGROUND: There are limited data available on the survival and early complications of preterm infants with less than 500 g birthweight. To estimate the outcomes for these infants, it is important for caregivers to be aware of perinatal factors that may affect survival. OBJECTIVES: We assessed the mortality and certain early complications of preterm infants born with less than 500 g in Hungary between 2006 and 2015. METHODS: We reviewed data of 486 infants from the database of the Hungarian Central Statistical Office and in parallel of 407 infants from the "NICU database." The study period was divided into two epochs: 2006-2010 and 2011-2015. RESULTS: The survival was 27.1% in the first epoch and 39.1% in the second epoch, and the incidence of early complications was slightly higher in the second epoch. In the surviving group (first and second epoch combined), gestational age (25.1 vs 23.7 weeks), birthweight (458 vs 447 g) antenatal steroid treatment (66.3% vs 52.3%), surfactant therapy (95.1% vs 84.3%), median Apgar scores (6 vs 3 and 8 vs 5 at 1 and 5 minutes, respectively) and proportion of caesarean delivery (89.3% versus 68.5%) were higher than in the non-surviving group (first and second epoch combined). The proportion of multiple births was lower in the surviving group (15.7% vs 33.4%). CONCLUSIONS: Survival of infants with less than 500 g improved between 2006-2010 and 2011-2015 in Hungary. The slightly higher occurrence of early complications might be associated with improving survival.

Births: Final Data for 2018.

Objectives-This report presents 2018 data on U.S. births according to a wide variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Methods-Descriptive tabulations of data reported on the birth certificates of the 3.79 million births that occurred in 2018 are presented. Data are presented for maternal age, live-birth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates by age also are shown. Trend data for 2010 through 2018 are presented for selected items. Trend data by race and Hispanic origin are shown for 2016-2018. Results-3,791,712 births were registered in the United States in 2018, down 2% from 2017. Compared with rates in 2017, the general fertility rate declined to 59.1 births per 1,000 women aged 15-44. The birth rate for females aged 15-19 fell 7% in 2018. Birth rates declined for women aged 20-34 and increased for women aged 35-44. The total fertility rate declined to 1,729.5 births per 1,000 women in 2018. Birth rates for both married and unmarried women declined from 2017 to 2018. The percentage of women who began prenatal care in the first trimester of pregnancy rose to 77.5% in 2018; the percentage of all women who smoked during pregnancy declined to 6.5%. The cesarean delivery rate decreased to 31.9% in 2018 following an increase in 2017. Medicaid was the source of payment for 42.3% of all 2018 births, down 2% from 2017. The preterm birth rate rose for the fourth straight year to 10.02% in 2018; the rate of low birthweight was unchanged at 8.28%. Twin and triplet and higher-order multiple birth rates declined in 2018 (Figure 1).

Low breastfeeding continuation to 6 months for very preterm infants: A European multiregional cohort study.

Breastfeeding confers multiple benefits for the health and development of very preterm infants, but there is scarce information on the duration of breastfeeding after discharge from the neonatal intensive care unit (NICU). We used data from the Effective Perinatal Intensive Care in Europe population-based cohort of births below 32 weeks of gestation in 11 European countries in 2011-2012 to investigate breastfeeding continuation until 6 months. Clinical and sociodemographic characteristics were collected from obstetric and neonatal medical records as well as parental questionnaires at 2 years of corrected age. Among 3,217 ever-breastfed infants, 34% were breastfeeding at 6 months of age (range across countries from 25% to 56%); younger and less educated mothers were more likely to stop before 6 months (adjusted relative risk [aRR] <25 years: 0.68, 95% CI [0.53, 0.88], vs. 25-34 years; lower secondary: 0.58, 95% CI [0.45, 0.76] vs. postgraduate education). Multiple birth, bronchopulmonary dysplasia (BPD), and several neonatal transfers reduced the probability of continuation but not low gestational age, fetal growth restriction, congenital anomalies, or severe neonatal morbidities. Among infants breastfeeding at discharge, mixed versus exclusive breast milk feeding at discharge was associated with stopping before 6 months: aRR = 0.60, 95% CI [0.48, 0.74]. Low breastfeeding continuation rates in this high-risk population call for more support to breastfeeding mothers during and after the neonatal hospitalization, especially for families with low socio-economic status, multiples, and infants with BPD. Promotion of exclusive breastfeeding in the NICU may constitute a lever for improving breastfeeding continuation after discharge.

Postnatal changes in the development of rat submandibular glands in offspring of diabetic mothers: Biochemical, histological and ultrastructural study.

Development and maturation of submandibular salivary glands are influenced by intrauterine diabetic environment. Several studies investigated the effects of diabetes on the salivary glands. However, the effects of maternal diabetes on the submandibular glands of the offspring was not properly examined. Therefore, the present study was designed to describe the changes in the development of the submandibular glands of the offspring of diabetic mothers. The submandibular glands of the offspring of Streptozotocin (STZ)-induced diabetic female rats were examined at two and four weeks after birth. Detection of mRNA demonstrated that maternal diabetes affects the level of different indicators. The reduction of expression of epidermal growth factor (EGF); a protein mitogen, cytokeratin 5 (CK5); an epithelial cell progenitor, CK7 and aquaporin 5 (AQP5); differentiation markers and B cell lymphoma 2 (Bcl2); an antiapoptotic marker were found. Increase in Bcl2-associated X protein (Bax); an apoptotic marker was detected. These changes indicate their effects on saliva secretion, glands tumorigenesis, growth of normal oral flora and oral microbes, with decreased protein synthesis and production of xerostomia and dental caries. Loss of normal glandular architecture, significant increase in fibrosis, by the detection of collagen fibers, and stagnation of secretory granules were found with atrophic changes in the acinar cells. Marked defect of polysaccharides in the acinar cells, denoting functional changes, was manifested by significant reduction of the intensity of periodic acid-Schiff (PAS) reaction. The positive immunoreactivity of caspase-3, denoting cellular apoptosis, and minimal reaction of alpha-smooth muscle actin (α SMA) and proliferating cell nuclear antigen (PCNA) were evident in the offspring of diabetic mothers. We conclude that maternal diabetes produces degenerative effects in the structure and function of the submandibular salivary glands of the offspring, reflecting possible influences on their secretory activity affecting oral and digestive health.

Being a mother of preterm multiples in the context of socioeconomic disadvantage: perceived stress and psychological symptoms / Ser mãe de múltiplos prematuros no contexto de desvantagem socioeconômica: estresse percebido e sintomas psicológicos

Abstract Objective: This study aimed to examine the differences between mothers of preterm multiples and mothers of preterm singletons regarding perceived stress and maternal psychological symptoms, and to explore the putative adverse amplified effect of socioeconomic disadvantage. Method: Ninety-five mothers of 1-year-olds born preterm participated in this cross-sectional study. Data collection was carried out in two public hospitals from Northern Portugal. To assess maternal perceived daily stress and psychological symptoms, mothers completed two questionnaires. Mothers reported on socioeconomic factors, including family poverty, parent unemployment, and low education, and two groups of family socioeconomic disadvantage were created. A child medical risk index was calculated. Results: Results indicated that mothers of preterm multiples reported higher levels of stress than mothers of preterm singletons. Moreover, and specifically regarding psychological functioning, mothers of preterm multiples reported more symptoms than mothers of preterm singletons, but only when living in a context of socioeconomic adversity. Conclusions: The results of the present study have important implications for practice. Mothers of preterm multiples are at higher risk to present mental health difficulties, in comparison to mothers of singletons, especially when exposed to socioeconomic adversities. The development of psychosocial intervention programs and public policies are of decisive importance in helping mothers of multiples adjust to parenthood.

Resumo Objetivo: Examinar as diferenças entre mães de múltiplos prematuros e mães de filhos únicos prematuros a respeito de estresse percebido e sintomas psicológicos maternos e explorar o efeito adverso amplificado putativo da desvantagem socioeconômica. Método: Participaram deste estudo transversal 95 mães de crianças de um ano nascidas prematuras. A coleta de dados foi feita em dois hospitais públicos do norte de Portugal. Para avaliar o estresse diário percebido e os sintomas psicológicos maternos, as mães responderam dois questionários. As mães relataram fatores socioeconômicos, incluindo pobreza familiar, desemprego dos pais e baixo nível de escolaridade, e foram criados dois grupos de desvantagem socioeconômica familiar. Foi calculado um índice de risco médico infantil. Resultados: Os resultados indicaram que as mães de múltiplos prematuros relataram maiores níveis de estresse do que as mães de filhos únicos prematuros. Além disso e especificamente com relação ao funcionamento psicológico, as mães de múltiplos prematuros relataram mais sintomas do que as mães de filhos únicos prematuros, porém apenas quando moravam em um contexto de adversidade socioeconômica. Conclusões: Os resultados deste estudo possuem importantes implicações para a prática. As mães de múltiplos prematuros apresentam maior risco de dificuldades de saúde mental, em comparação a mães de filhos únicos, principalmente quando expostas a adversidades socioeconômicas. O desenvolvimento de programas de intervenção psicossocial e políticas públicas é de importância decisiva ao ajudar as mães de filhos múltiplos a se ajustarem à maternidade.

Umbilical Cord Hepcidin Concentrations Are Positively Associated with the Variance in Iron Status among Multiple Birth Neonates.

Background: Hepcidin is a systemic regulator of iron homeostasis. Little is known about the relative role of maternal compared with cord hepcidin on neonatal iron homeostasis. Objective: This study was undertaken to evaluate inter- and intrauterine variance in neonatal iron status, vitamin B-12, folate, and inflammatory markers in a cohort of twins (n = 50), triplets (n = 14), and quadruplets (n = 1) born to 65 women. Methods: Umbilical cord blood was obtained from 144 neonates born at 34.8 ± 2.7 wk of gestation with a mean birth weight of 2236 ± 551 g (means ± SDs). Cord hemoglobin and cord serum measures of ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, erythropoietin (EPO), iron, vitamin B-12, folate, interleukin 6, and C-reactive protein were evaluated. Results: Intraclass correlation coefficient (ICC) analyses were used to examine inter- and intrauterine variance in neonatal iron indicators. A greater variability in cord hepcidin (ICC = 0.39) was found between siblings. Cord hepcidin had the greatest association with cord iron indicators because cord hepcidin alone captured 63.8%, 48.4%, 44.4%, and 31.3% of the intrauterine variance in cord hemoglobin, SF, sTfR, and EPO, respectively, whereas maternal hepcidin had no effect on cord iron indicators. Significantly greater differences in cord SF (P = 0.03), sTfR (P = 0.03), hepcidin (P = 0.0003), and EPO (P = 0.03) were found between di- and trichorionic siblings than between monochorionic siblings. In contrast, cord folate (ICC = 0.79) and vitamin B-12 (ICC = 0.74) exhibited a greater variability between unrelated neonates. Conclusions: In summary, fetally derived hepcidin might have more control on intrauterine variance in iron indicators than maternal hepcidin and appears to be capable of regulating fetal iron status independently of maternal hepcidin. The use of a multiple-birth model provides a unique way to identify factors that may contribute to placental nutrient transport and iron stores at birth.

Births: Final Data for 2016.

This report presents 2016 data on U.S. births according to a wide variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.Descriptive tabulations of data reported on the birth certificates of the 3.95 million births that occurred in 2016 are presented. Data are presented for maternal age, live-birth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates by age also are shown. Trend data for 2010-2016 are presented for selected items. A total of 3,945,875 births were registered in the United States in 2016, down 1% from 2015. Compared with rates in 2015, the general fertility rate declined to 62.0 per 1,000 women aged 15-44. The birth rate for females aged 15-19 fell 9% in 2016. Birth rates declined for women in their 20s but increased for women intheir 30s and early 40s. The total fertility rate declined to 1,820.5 births per 1,000 women in 2016. The birth rate for unmarried women declined, while the rate for married women increased. More than three-quarters of women began prenatal care in the firsttrimester of pregnancy (77.1%) in 2016, while 7.2% of all women smoked during pregnancy. The cesarean delivery rate declined for the fourth year in a row. Medicaid was the source of payment for 42.6% of all 2016 births. The preterm birth rate rose for the second straight year, and the rate of low birthweight increased 1%. Twin and triplet and higher-order multiple birth rates declined, although the changes were not statistically significant.

Births: Final Data for 2017.

Objectives-This report presents 2017 data on U.S. births according to a wide variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Methods-Descriptive tabulations of data reported on the birth certificates of the 3.86 million births that occurred in 2017 are presented. Data are presented for maternal age, livebirth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates by age also are shown. Trend data for 2010 to 2017 are presented for selected items. Trend data by race and Hispanic origin are shown for 2016 and 2017. Results- A total of 3,855,500 births were registered in the United States in 2017, down 2% from 2016. Compared with rates in 2016, the general fertility rate declined to 60.3 births per 1,000 women aged 15-44. The birth rate for females aged 15-19 fell 7% in 2017. Birth rates declined for women in their 20s and 30s but increased for women in their early 40s. The total fertility rate declined to 1,765.5 births per 1,000 women in 2017. Birth rates for both married and unmarried women declined from 2016 to 2017. The percentage of women who began prenatal care in the first trimester of pregnancy rose to 77.3% in 2017; the percentage of all women who smoked during pregnancy declined to 6.9%. The cesarean delivery rate increased to 32.0% following 4 years of declines. Medicaid was the source of payment for 43.0% of all births in 2017, up 1% from 2016. The preterm birth rate rose for the third straight year, as did the rate of low birthweight. Twin and triplet and higher-order multiple birth rates were essentially stable in 2017.

Effect of congenital heart disease on 4-year neurodevelopment within multiple-gestation births.

OBJECTIVES: We sought to assess the effect of congenital heart disease requiring infant surgery with cardiopulmonary bypass on neurodevelopmental outcomes and growth at 4 years of age, while matching for gestational age, socioeconomic status, maternal gestational conditions, home environment, and parental intelligence by studying multiple-gestation births. METHODS: We performed within-family comparison of 14 multiple-gestation births in which 1 child had congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age. Between 4 and 5 years of age, a comprehensive neurodevelopmental assessment was performed. Paired comparisons were conducted between siblings with and without heart defects using a series of nonparametric tests. RESULTS: On average, the children qualified as late preterm (mean gestational age 35.4 ± 2.6 weeks). At an average age of 4.8 ± 0.1 years, children with congenital heart disease weighed less than their siblings (median weight for age z score -0.4 vs 0.1, P = .02) and had worse performance for cognition (median full-scale IQ 99 vs 109, P = .02) and fine motor skills (median Wide Range Assessment of Visual Motor Ability, Fine Motor score 94.5 vs 107.5, P < .01). CONCLUSIONS: After controlling for socioeconomic status, home environment, parental intelligence, and gestational factors by using multiple-gestation births, congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age is associated with lower weight, cognitive abilities and fine motor skills at 4 years of age.

Breastfeeding education and support for women with twins or higher order multiples.

BACKGROUND: There are rising rates of multiple births worldwide with associated higher rates of complications and more hospital care, often due to prematurity. While there is strong evidence about the risks of not breastfeeding, rates of breastfeeding in women who have given birth to more than one infant are lower than with singleton births. Breastfeeding more than one infant can be more challenging because of difficulties associated with the birth or prematurity. The extra demands on the mother of frequent suckling, coordinating the needs of more than one infant or admission to the neonatal intensive care unit can lead to delayed initiation or early cessation. Additional options such as breast milk expression, the use of donor milk or different methods of supplementary feeding may be considered. Support and education about breastfeeding has been found to improve the duration of any breastfeeding for healthy term infants and their mothers, however evidence is lacking about interventions that are effective to support women with twins or higher order multiples. OBJECTIVES: To assess effectiveness of breastfeeding education and support for women with twins or higher order multiples. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2016), ClinicalTrials.gov (30 June 2016), the WHO International Clinical Trials Registry Platform (ICTRP) (1 July 2016), the excluded studies list from the equivalent Cochrane review of singletons, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing extra education or support for women with twins or higher order multiples were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We planned to assess the quality of evidence using the GRADE approach, but were unable to analyse any data. MAIN RESULTS: We found 10 trials (23 reports) of education and support for breastfeeding that included women with twins or higher order multiples. The quality of evidence was mixed, and the risk of bias was mostly high or unclear. It is difficult to blind women or staff to group allocation for this intervention, so in all studies there was high risk of performance and high or unclear risk of detection bias. Trials recruited 5787 women (this included 512 women interviewed as part of a cluster randomised trial); of these, data were available from two studies for 42 women with twins or higher order multiples. None of the interventions were specifically designed for women with more than one infant, and the outcomes for multiples were not reported separately for each infant. Due to the scarcity of evidence and the format in which data were reported, a narrative description of the data is presented, no analyses are presented in this review, and we were unable to GRADE the evidence.The two trials with data for women with multiple births compared home nurse visits versus usual care (15 women), and telephone peer counselling versus usual care (27 women). The number of women who initiated breastfeeding was reported (all 15 women in one study, 25 out of 27 women in one study). Stopping any breastfeeding before four to six weeks postpartum, stopping exclusive breastfeeding before four to six weeks postpartum, stopping any breastfeeding before six months postpartum andstopping exclusive breastfeeding before six months postpartum were not explicitly reported, and there were insufficient data to draw any meaningful conclusions from survival data. Stopping breast milk expression before four to six weeks postpartum, andstopping breast milk expression before six months postpartum were not reported. Measures ofmaternal satisfaction were reported in one study of 15 women, but there were insufficient data to draw any conclusions; no other secondary outcomes were reported for women with multiple births in either study. No adverse events were reported. AUTHORS' CONCLUSIONS: We found no evidence from randomised controlled trials about the effectiveness of breastfeeding education and support for women with twins or higher order multiples, or the most effective way to provide education and support . There was no evidence about the best way to deliver the intervention, the timing of care, or the best person to deliver the care. There is a need for well-designed, adequately powered studies of interventions designed for women with twins or higher order multiples to find out what types of education and support are effective in helping these mothers to breastfeed their babies.

Association of Clomiphene and Assisted Reproductive Technologies With the Risk of Neural Tube Defects.

Clomiphene and assisted reproductive technologies (ART) are methods used to help subfertile couples become pregnant. ART has been reported to be associated with neural tube defects (NTDs) in offspring. To evaluate these associations, we studied mothers of 219 cases and 4,262 controls from the Slone Epidemiology Center Birth Defects Study (1993-2012) who were interviewed within 6 months after delivery about pregnancy events, including use of fertility treatments. We considered exposures to clomiphene (without ART) and ART during the periconceptional period. Logistic regression models were used to calculate adjusted odds ratios and 95% confidence intervals, controlling for education and study center. We observed elevated adjusted odds ratios of 2.1 (95% confidence interval: 0.9, 4.8) and 2.0 (95% confidence interval: 1.1, 3.6) for clomiphene and ART exposure, respectively. We performed a mediation analysis to assess whether the observed elevated NTD risk was mediated through multiple births. For clomiphene exposure without ART use, the direct effect estimate of the adjusted odds ratio (aORDE) was 1.7 and the indirect effect estimate (aORIE) was 1.4. Conversely, for ART exposure, the aORDE was 0.9 and the aORIE was 2.5. Our findings suggest that relatively little of the clomiphene-NTD association is mediated through the pathway of multiple births, while the ART-NTD association was explained by the multiple-births pathway.

Birth weight and adult cardiovascular risk factors using multiple birth status as an instrumental variable in the 1958 British Birth Cohort.

BACKGROUND: Birth weight is classified as a risk factor for cardiovascular disease by the World Health Organization, but appropriate preventive interventions remain unclear because the observations have not been confirmed in experiments and appear to be contextually specific. METHODS: Using 9452 participants of the 1958 British Birth Cohort at age 42years in 2000 (58% follow-up), we examined the credibility of multiple birth status as an instrumental variable (IV) for birth weight and, if appropriate, use it to obtain less confounded estimates of the associations of birth weight with cardiovascular disease risk factors including self-reported height, body mass index and hypertension than conventional regression in 2014. RESULTS: Multiple birth (203 twins and 6 triplets) was associated with older maternal age, but not with paternal occupation or maternal smoking. Multiple births had lower birth weight-for-gestational age z-score. Multiple birth status was not directly associated with height, BMI or hypertension. Using IV estimates birth weight-for-gestational age z-score was not clearly associated with height (0.99cm, 95% confidence interval (CI) -0.27, 2.25), body mass index (BMI) (0.42kg/m(2), 95% CI -0.17, 1.01) or hypertension (risk ratio 0.82, 95% CI 0.54, 1.23) adjusted for maternal age, with a first-stage F statistic of 145.3 from IV analysis. CONCLUSIONS: Multiple birth status is a credible IV for obtaining a less confounded estimate of the association of birth weight with height, BMI and blood pressure. Such analysis suggests that birth weight may be spuriously related to height, BMI and blood pressure, and thus not an effective target for intervention.

Do induced twin pregnancies influence the obstetric and neonatal results of multiple births born before 32 weeks? Comparison to spontaneous gestation / Gestações gemelares induzidas modificam o resultado obstétrico e perinatal de partos antes da 32ª semana? Comparação com gestações espontâneas

PURPOSE: To compare obstetric outcomes of induced preterm twin births (under 32 weeks gestation) with those spontaneously conceived. METHODS: Prospective study of twin pregnancies (25 induced and 157 spontaneously conceived) developed over a period of 16 years in a tertiary obstetric center. Demographic factors, obstetric complications, gestational age at delivery, mode of delivery, birth weight and immediate newborn outcome were compared. RESULTS: The analysis of obstetrical complications concerning urinary or other infections, hypertensive disorders of pregnancy, gestational diabetes, fetal malformations, intrauterine fetal death, intrauterine growth restriction and intrauterine discordant growth reveal no significant statistical differences between the two groups. First trimester bleeding was higher in the induced group (24 versus 8.3%, p=0.029). The cesarean delivery rate was 52.2% in spontaneous gestations and 64% in induced gestations. Gestational age at delivery, birth weight, Apgar scores at first and fifth minutes, admissions to Neonatal Intensive Care Unit and puerperal complications show no statistically significant differences between the two groups. These results were independent of chorionicity and induction method. CONCLUSION: The mode of conception did not influence obstetric and neonatal outcomes. Although induced pregnancies have higher risk of first trimester bleeding, significant differences were not observed regarding other obstetric and puerperal complications and neonatal results. .

OBJETIVO: Comparar os resultados obstétricos de gestações gemelares induzidas com as concebidas espontaneamente, em partos ocorridos antes da 32ª semana de idade gestacional. MÉTODOS: Estudo prospectivo de gestações gemelares (25 induzidas e 157 concebidas espontaneamente) desenvolvido durante um período de 16 anos num centro terciário de Obstetrícia. Foram comparados fatores demográficos, complicações obstétricas, idade gestacional no parto, tipo de parto, peso ao nascer e o outcome imediato do recém-nascido. RESULTADOS: A análise das seguintes complicações obstétricas: infecções urinárias ou outras, distúrbios hipertensivos da gravidez, diabetes gestacional, malformações fetais, morte fetal intrauterina, restrição de crescimento intrauterino e crescimento intrauterino discordante não revelou diferenças estatísticas significativas entre os dois grupos. No grupo das gestações induzidas, observou-se maior taxa de metrorragias do 1º trimestre (24 versus 8,3%, p=0,029). A taxa de cesariana foi de 52,2% nas gestações espontâneas e 64% nas gestações induzidas. Idade gestacional no parto, peso ao nascer, índice de Apgar no primeiro e quinto minutos, internamento em unidade de cuidados intensivos neonatal e complicações puerperais não apresentam diferenças estatisticamente significantes entre os dois grupos. Esses resultados foram independentes do tipo de placentação e método de indução. CONCLUSÃO: O modo de concepção não influenciou os resultados obstétricos e neonatais. Embora as gestações induzidas tenham maior risco de metrorragias do primeiro trimestre, não foram observadas diferenças significativas em relação a outras complicações obstétricas, complicações puerperais e em relação aos resultados neonatais. .

Hospital variation and risk factors for bronchopulmonary dysplasia in a population-based cohort.

IMPORTANCE: Bronchopulmonary dysplasia (BPD) remains a serious morbidity in very low-birth-weight (VLBW) infants (<1500 g). Deregionalization of neonatal care has resulted in an increasing number of VLBW infants treated in community hospitals with unknown impact on the development of BPD. OBJECTIVE: To identify individual risk factors for BPD development and hospital variation of BPD rates across all levels of neonatal intensive care units (NICUs) within the California Perinatal Quality Care Collaborative. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study (January 2007 to December 2011) from the California Perinatal Quality Care Collaborative including more than 90% of California's NICUs. Eligible VLBW infants born between 22 to 29 weeks' gestational age. EXPOSURES: Varying levels of intensive care. MAIN OUTCOMES AND MEASURES: Bronchopulmonary dysplasia was defined as continuous supplemental oxygen use at 36 weeks' postmenstrual age. A combined outcome of BPD or mortality prior to 36 weeks was used. Multivariable logistic regression accounting for hospital as a random effect and gestational age as a risk factor was used to assess individual risk factors for BPD. This model was applied to determine risk-adjusted rates of BPD across hospitals and assess associations between levels of care and BPD rates. RESULTS: The study cohort included 15,779 infants, of which 1534 infants died prior to 36 weeks' postmenstrual age. A total of 7081 infants, or 44.8%, met the primary outcome of BPD or death prior to 36 weeks. Combined BPD or death rates across 116 NICUs varied from 17.7% to 73.4% (interquartile range, 38.7%-54.1%). Compared with level IV NICUs, the risk for developing BPD was higher for level II NICUs (odds ratio, 1.23; 95% CI, 1.02-1.49) and similar for level III NICUs (odds ratio, 1.04; 95% CI, 0.95-1.14). CONCLUSIONS AND RELEVANCE: Bronchopulmonary dysplasia or death prior to 36 weeks' postmenstrual age affects approximately 45% of VLBW infants across California. The wide variability in BPD occurrence across hospitals could offer insights into potential risk or preventive factors. Additionally, our findings suggest that increased regionalization of NICU care may reduce BPD among VLBW infants.

Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases.

BACKGROUND: High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. METHODS: We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. RESULTS: Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. CONCLUSIONS: Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.

First reported case of sextuplets conceived via letrozole for ovulation induction.

OBJECTIVE: To report the first case of sextuplets conceived via letrozole during ovulation induction. DESIGN: Case report. SETTING: Private fertility clinic. PATIENT(S): A 32-year-old female with a history of secondary infertility and polycystic ovary syndrome. INTERVENTION(S): Letrozole, 7.5 mg, on cycle days 3-7 after a progesterone-induced menses. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Sexchorionic-sexamniotic pregnancy. CONCLUSION(S): High-order multiple gestations are possible with letrozole ovulation induction, so patients should be counseled appropriately and follicle monitoring considered.

Severe bronchopulmonary dysplasia is associated with higher fluid intake in very low-birth-weight infants: a retrospective study.

OBJECTIVE: This study aims to investigate the association between fluid intake in the first 4 days of life and the subsequent severity of bronchopulmonary dysplasia (BPD) in very low-birth-weight infants (VLBWI). STUDY DESIGN: A retrospective chart review of 75 infants with a gestational age of less than 32 weeks and a birth weight of < 1,500 g was performed. Demographic, clinical data, associated maternal risk factors, and amount of fluid received in the first 4 days of life were analyzed. RESULTS: Severe BPD was associated with a lower gestational age (27.04 ± 2.073 wks vs. 28.70 ± 1.706 wks, p=0.001), lower birth weight (981.44 ± 244.54 vs. 1,199.63 ± 165.39 g, p < 0.001), use of surfactant (91.7 vs. 63%, p=0.002), patent ductus arteriousus (PDA) (70.8 vs. 37%, p=0.004), pulmonary hemorrhage (14.6 vs. 0%, p=0.045), and more fluids received from the 2nd to 4th days of life (346.44 ± 42.38 mL/kg vs. 323.91 ± 27.62 mL/kg, p=0.007). A cut off point of 345 mL/kg of fluids from the 2nd to 4th days of life was selected using receiver operating characteristic curve analysis, and remained a significant risk factor even after multiple logistic regression analysis. CONCLUSION: Our findings demonstrate that VLBWI who received higher fluid intake from the 2nd to 4th days of life are at an increased risk of developing severe BPD.