Maternal and fetal cord blood lipids in intrauterine growth restriction

Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses.

Salt sensitivity of children with low birth weight

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.

[Arterial-adaptive dilatation and Doppler velocimetry in normal fetuses with a single umbilical artery]

PURPOSE: In this study we examined the arterial-adaptive dilatation and Doppler velocimetry, especially RI values, in normal fetuses with a single umbilical artery (SUA). MATERIALS AND METHODS: We studied 195 fetuses from 18 to 39 weeks of gestational age with a prenatally identified SUA retrospectively. They were enrolled in this study if the following information applied: > 18 weeks of gestational age, no structural or chromosomal abnormalities, and histopathological confirmation of SUA. Sonographic examination included evaluation of the umbilical artery resistance and the cross-sectional area of the umbilical cord, and its vessels were measured in all cases. Small for gestational age (SGA) was diagnosed when the birth weight was below the 10th percentile for gestational age. Fetuses with intrauterine growth restriction were defined as those with biometric data below the 5th percentile. RESULTS: There were 119 cases of prenatally identified SUA which met the inclusion criteria. RI values were below the 10th percentile in 33/119 (27.33) and below the 50th percentile in 73/119 (61.33). RI values below the 10th percentile were significantly more likely to be in the normal collective than in the growth restricted collective [31/87 (35.63%) vs. 2/32 (6.25%); p = 0.001]. Even more significant differences became apparent when comparing the RI values below the 50th percentile of both groups. An umbilical artery diameter over the 90th percentile was found in 49 (41.9%) of cases and was significantly more likely to be present in normal growing fetuses than in the growth restricted group. CONCLUSION: Normal fetuses with SUA are at higher risk to be born as SGA. With our study results we can confirm the hypothesis that Doppler flow measurements and arterial diameter in SUA are different from those found in normal fetal umbilical arteries. RI values over the 50th percentile or a cross-sectional area of the artery below 95th percentile after 26th week of gestation significantly increases the risk of SGA.

Verhalten der Gewichtsdifferenz von selektiv wachstumsretardierten, monochorialen Zwillingen

Problemstellung: Monochoriale Zwillinge (MZ) machen nur ca. 1/3 aller Mehrlinge aus. Im Vergleich zu dichorialen weisen sie jedoch eine höhere Morbidität und Mortalität auf bedingt durch das Transfusionssyndrom, mehr Fehlbildungen und Frühgeburten. In letzter Zeit kristallisiert sich eine weitere Entität heraus, die selektive intrauterine Wachstumsretardierung (sIUWR). Ziel der Studie war es, das Verhalten dieses diskordanten Wachstums im Verlaufe der Schwangerschaft zu untersuchen. Patienten und Methode: Die Diagnose einer monochorialen Situation basiert auf der Darstellung nur einer Plazenta, dem T-Sign sowie gleichgeschlechtiger Feten. Es wurden nur biamniote MZ eingeschlossen. Von einer sIUWR spricht man, wenn folgende Kriterien erfüllt sind: 1) ein Fetus wachstumsretardiert (Abdomenumfang <5. Perzentile) und 2) Gewichtsdifferenz beider Feten >20%. Letztere berechnet sich aus der Differenz der geschätzten fetalen Gewichte dividiert durch das Gewicht des Größeren in% (Delta%). Es wurden die Delta%-Werte bei Diagnosestellung und die letzten Werte vor Geburt verglichen. Ergebnisse: Retrospektiv wurden 23 Fälle mit sIUWR eingeschlossen, davon wurden 13 Fälle longitudinal beurteilt. Das mediane Gestationsalter bei Geburt lag bei 31,4 (16,7–38,6) Wochen. Die Frühgeburtsrate betrug 85,7%, die perinatale Mortalität 11,9%. Der initiale Delta%-Wert lag bei 28±10% und stieg signifikant auf 36,4±9,9%. In allen Fällen nahm der Delta%-Wert zu. Von den Co-Zwillingen waren postnatal 20% auch small for gestational age. Schlussfolgerungen: Bei MZ mit sIUWR ist nach unseren Erfahrungen damit zu rechnen, dass die Gewichtsdifferenz mit zunehmendem Gestationsalter steigt. Diese Zunahme erklärt sich durch eine progressive Verlangsamung der Wachstumsgeschwindigkeit des kleineren Feten. Leider lässt sich anhand der kleinen Fallzahl nicht eruieren, ob dieser D%-Wert und der Grad des Anstieges eine prognostische Bedeutung aufweist.

Salt intake in children and its consequences on blood pressure.

Sodium is the most abundant extracellular cation and therefore pivotal in determining fluid balance. At the beginning of life, a positive sodium balance is needed to grow. Newborns and preterm infants tend to lose sodium via their kidneys and therefore need adequate sodium intake. Among older children and adults, however, excessive salt intake leads to volume expansion and arterial hypertension. Children who are overweight, born preterm, or small for gestational age and African American children are at increased risk of developing high blood pressure due to a high salt intake because they are more likely to be salt sensitive. In the developed world, salt intake is generally above the recommended intake also among children. Although a positive sodium balance is needed for growth during the first year of life, in older children, a sodium-poor diet seems to have the same cardiovascular protective effects as among adults. This is relevant, since: (1) a blood pressure tracking phenomenon was recognized; (2) the development of taste preferences is important during childhood; and (3) salt intake is often associated with the consumption of sugar-sweetened beverages (predisposing children to weight gain).

Hypertension in pregnancy

PURPOSE OF REVIEW Hypertension in pregnancy contributes substantially to perinatal mortality and morbidity of both the mother and her child. High blood pressure is mainly responsible for this adverse outcome, in particular when associated with preeclampsia. Although preeclampsia is nowadays a well-known clinical-obstetrical entity, and screening for this complication has been part of routine care during pregnancy for nearly 100 years, its cause is still enigmatic. RECENT FINDINGS Profound changes of the demographic development of our society, the worldwide rising prevalence of obesity and metabolic disorders, and progress in reproductive medicine will inevitably modify the prevalence of many medical problems in pregnancy. Complications such as gestational diabetes mellitus, chronic hypertension, and preeclampsia will rise and an interdisciplinary approach is necessary to handle these women during pregnancy and also after delivery. Indeed, it is now well established that these women and their offspring born large or small-for-gestational age are at increased risk for severe cardiovascular and metabolic complications later in life. SUMMARY Knowledge of the pregnancy course is not only important for an obstetrician but also increasingly inevitable for the general practitioner. Recognition, classification, and adequate management of hypertensive pregnancy disorders and associated complications may considerably reduce perinatal death and morbidity.

Early life risk factors and puberty implications for cancer prevention

Earlier age at puberty is a known risk factor for breast cancer and suspected to influence prostate cancer; yet few studies have assessed early life risk factors for puberty. The overall objectives was to determine the relationship between birth-weight-for-gestational-age (BWGA), weight gain in infancy and pubertal status in girls and boys at 10.8 and 11.8 years and who were born of preeclamptic (PE) and normotensive (NT) mothers. Data for this study were collected from hospital and public health medical records and at a follow-up visit at 10.8 and 11.8 years for girls and boys, respectively. We used stratified analysis and multivariable logistic regression modeling to assess effect measure modifier and to determine the relationship between BWGA, weight gain in infancy and childhood and pubertal status, respectively. ^ There was no difference in the relationship between BWGA and pubertal status by maternal PE status for girls and boys; however, there was a non-significant increase in the odds of having been born small-for-gestational-age (SGA) in girls who were pubertal for breast or pubic hair Tanner stage 2+ compared to those who B1 or PH1. In contrast, boys who were pubertal for genital and pubic hair Tanner stage 2+ had lower odds of having been born SGA than those who were prepubertal for G1 or PH1. ^ In girls who were pubertal for breast development, the odds of having gained one additional unit SD for weight was highest between 3 to 6 months and 6-12 months for those who were B2+ vs. B1. For pubic hair development, weight gain between 6-12 months had the greatest effect for girls of PE mothers only. In boys, there were no statistically significant associations between weight gain and genital Tanner stage at any of the intervals; however, weight gain between 3-6 months did affect pubic hair tanner stage in boys of NT mothers. This study provide important evidence regarding the role of SGA and weight gain at specific age intervals on puberty; however, larger studies need to shed light on modifiable exposures for behavioral interventions in pregnancy, postpartum and in childhood.^

Use of umbilical artery Doppler velocimetry in the monitoring of pregnancy in women with pre-existing diabetes

Background: The usefulness of umbilical artery Doppler velocimetry for the monitoring of diabetic pregnancies is controversial. The aim of the present study was to assess whether umbilical artery Doppler velocity waveform analysis can predict adverse perinatal outcomes for pregnancies complicated by pre-existing diabetes mellitus. Methods: All diabetic pregnancies (type 1 and 2) delivered at Mater Mothers' Hospital, Queensland, between 1 January 1995 and 31 December 1999 were included. All pregnant diabetic women were monitored with umbilical artery Doppler velocimetry at 28, 32, 36, and 38 weeks' gestation. Adverse perinatal outcome was defined as pregnancies with one or more of the following: small-for-gestational age, Caesarean section for non-reassuring cardiotocography, fetal acidaemia at delivery, 1-min Apgar of 3 or less, 5-min Apgar of less than 7, hypoxic ischaemic encephalopathy or perinatal death. Abnormal umbilical artery Doppler velocimetry was defined as a pulsatility index of 95th centile or higher for gestation. Results: One hundred and four pregnancies in women with pre-existing diabetes had umbilical arterial Doppler studies carried out during the study period. Twenty-three pregnancies (22.1%) had an elevated pulsatility index. If the scans were carried out within 2 weeks of delivery, 71% of pregnancies with abnormal umbilical Doppler had adverse outcomes (P < 0.01; likelihood ratio, 4.2). However, the sensitivity was 35%; specificity was 94%; positive predictive value was 80%; and negative predictive value was 68%. Only 30% of women with adverse perinatal outcomes had abnormal umbilical arterial Doppler flow. Conclusion: Umbilical artery Doppler velocimetry is not a good predictor of adverse perinatal outcomes in diabetic pregnancies.

Hospital-based case-control study of bronchiectasis in indigenous children in central Australia

Background: Childhood pneumonia has been reported to be associated with the development of bronchiectasis but there are no case-control studies that have examined this. This study examined the relationship between hospital admission for episode(s) of pneumonia and the risk of radiologically proven bronchiectasis. Methods: A medical record-based case-control study of bronchiectasis in Indigenous children was conducted in Central Australia. Controls (183), matched to cases (61) by gender, age and year of diagnosis, were Indigenous children hospitalized with other conditions. Results: There was a strong association between a history of hospitalized pneumonia and bronchiectasis [odds ratio (OR), 15.2; 95% confidence interval (95% CI) 4.4-52.7]. This was particularly evident in recurrent hospitalized pneumonia (P for trend < 0.01), severe pneumonia episodes with longer hospital stay (P for trend < 0.01), presence of atelectasis (OR 11.9; 95% CI 3.1-45.9) and requirement for oxygen (P for trend < 0.01). The overall number of pneumonia episodes, rather than its site, was associated with bronchiectasis. Although the total number of pneumonia episodes in the first year of life did not increase the risk of bronchiectasis, more severe episodes early in life did. Malnutrition, premature birth and being small for gestational age were more common findings among cases. Breast-feeding appeared to be a protective factor (OR 0.2; 95% CI 0.1-0.7). Conclusions: Although we cannot fully answer the question of why bronchiectasis is much more common in Indigenous children, we have provided strong evidence of an association between bronchiectasis and severe and recurrent pneumonia episodes in infancy and childhood.

Breastfeeding and obesity at 14 years: A cohort study

Aim: To determine the influence of breastfeeding on overweight and obesity in early adolescence. Methods: Data about breastfeeding duration, BMI of children at 14 years, and confounding variables, were collected from an ongoing longitudinal study of a birth cohort of 7776 children in Brisbane. Prevalence of overweight and obesity at 14 years was assessed according to duration of breastfeeding, with logistic regression being used to adjust for the influence of confounders. Results: Data were available for 3698 children, and those not included were significantly different in age, educational level, income, race, birthweight, and small-for-gestational-age status. Breastfeeding for longer than six months was protective of obesity (OR 0.6, 95% CI 0.4, 0.96) though not of overweight. When confounding variables were considered the effect size diminished and lost statistical significance OR 0.8 (95% CI 0.5, 1.3). Breastfeeding for less than 6 months had no effect on either obesity or overweight though a trend was found for increased prevalence of overweight at 14 years with shorter periods of breastfeeding. Conclusion: This investigation contributes to the gathering body of evidence that breastfeeding for longer than 6 months has a modest protective effect against obesity in adolescence.

Iron status in early life and associations with developmental outcomes

Infants and young children are at particular risk of iron deficiency and its associated consequences for growth and development. The main objectives of this thesis were to quantify iron intakes, status and determinants of status in two year olds; explore determinants of neonatal iron stores; investigate associations between iron status at birth and two years with neurodevelopmental outcomes at two years and explore the influence of growth on iron status in early childhood, using data from the Cork BASELINE (Babies after SCOPE: Evaluating Longitudinal Impact using Neurological and Nutritional Endpoints) Birth Cohort Study (n=2137). Participants were followed prospectively with interviewer-led questionnaires and clinical assessments at day 2 and at 2, 6, 12 and 24 months. At two years, there was a low prevalence of iron deficiency and iron deficiency anaemia in this cohort, representing the largest study of iron status in toddlers in Europe, to date. The increased consumption of iron-fortified products and compliance with recommendations to limit unmodified cows’ milk intakes in toddlers has contributed to the observed improvements in status. Low serum ferritin concentrations at birth, which reflect neonatal iron stores, were shown to track through to two years of age; delivery by Caesarean section, being born small-for-gestational age and maternal obesity and smoking in pregnancy were all associated with significantly lower neonatal iron stores. Despite a low prevalence of iron deficiency in this cohort, both a mean corpuscular volume <74fl and ferritin concentrations <20μg/l were associated with lower neurodevelopmental outcomes at two years. An inverse association between growth in the second year of life and iron status at two years was also observed. This thesis has presented data from one of the largest, extensively-characterised cohorts of young children, to date, to explore iron and its associations with growth and development.

Structural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia

RATIONALE: As more preterm infants recover from severe bronchopulmonary dysplasia (BPD), it is critical to understand the clinical consequences of this condition on the lung health of adult survivors.

OBJECTIVES: To assess structural and functional lung parameters in young adult BPD survivors and preterm and term controls Methods: Young adult survivors of BPD (mean age 24) underwent spirometry, lung volumes, transfer factor, lung clearance index and fractional exhaled nitric oxide measurements together with high-resolution chest tomographic (CT) imaging and cardiopulmonary exercise testing.

MEASUREMENTS AND MAIN RESULTS: 25 adult BPD survivors, (mean ± SD gestational age 26.8 ± 2.3 weeks; birth weight 866 ± 255 g), 24 adult prematurely born non-BPD controls (gestational age 30.6 ± 1.9 weeks; birth weight 1234 ± 207 g) and 25 adult term birth control subjects (gestational age 38.5 ± 0.9 weeks; and birth weight 3569 ± 2979 g) were studied. BPD subjects were more likely to be wakened by cough (OR 9.7, 95% CI: 1.8 to 52.6), p<0.01), wheeze and breathlessness (OR 12.2, 95%CI: 1.3 to 112), p<0.05) than term controls after adjusting for sex and current smoking. Preterm subjects had greater airways obstruction than term subjects. BPD subjects had significantly lower values for FEV1 and FEF25-75 (% predicted and z scores) than term controls (both p<0.001). Although non-BPD subjects also had lower spirometric values than term controls, none of the differences reached statistical significance. More BPD subjects (25%) had fixed airflow obstruction than non-BPD (12.5%) and term (0%) subjects (p=0.004). Both BPD and non-BPD subjects had significantly greater impairment in gas transfer (KCO % predicted) than term subjects (both p<0.05). Eighteen (37%) preterm participants were classified as small for gestational age (birth weight < 10th percentile for gestational age). These subjects had significantly greater impairment in FEV1 (% predicted and z scores) than those born appropriate for gestational age. BPD survivors had significantly more severe radiographic structural lung impairment than non-BPD subjects. Both preterm groups had impaired exercise capacity compared to term controls. There was a trend for greater limitation and leg discomfort in BPD survivors.

CONCLUSIONS: Adult preterm birth survivors, especially those who developed BPD, continue to experience respiratory symptoms and exhibit clinically important levels of pulmonary impairment.

EULAR Recommendations for Women's Health and the Management of Family Planning, Assisted Reproduction, Pregnancy and Menopause in Patients with Systemic Lupus Erythematosus and/or Antiphospholipid Syndrome

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Anthropometric indicators of nutritional status and growth in very low birth-weight premature infants hospitalized in a neonatal intensive care unit

Background: Anthropometric indicators are difficult to interpret in very low birth weight (VLBW) premature infants, including both appropriate for gestational age (AGA) and small for gestational age (SGA) infants. Therefore, the purpose was to describe the anthropometric indicators of growth and nutritional status in VLBW premature infants AGA and SGA, hospitalized in a neonatal intensive care unit (NICU). Study design: The descriptive and prospective study design included 114 preterm infants, adequate for gestational age/small for gestational age hospitalized in the intensive care unit. Head, thigh, mid upper arm circumference, skin-fold measurements and weight/age, length/ age, and weight/length indices were obtained. Correlations were made among the anthropometric indices, and a multivariate regression analysis with weight/age as dependent variable was performed. Results: Weight/age in AGA premature infants had high number of significant anthropometric correlations. The SGA premature infants had few and weak correlations. The regression analysis showed that anthropometric indices better explain changes in the weight/age index in adequate for gestational age premature infants. Conclusion: Weight/age in the VLBW/AGA premature infants could reflect growth, nutritional status and energy stored as fat, but in the VLBW/SGA premature infants, thigh circumference and mid arm circumference would be better indicators just of nutritional status.

Drinking water disinfection by-products, genetic polymorphisms, and birth outcomes in a european mother-child cohort study

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