[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.

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.^

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.

The relationship between 25-hydroxyvitamin D concentration in early pregnancy and pregnancy outcomes in a large, prospective cohort

Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations <75 nmol/l at 15 weeks of gestation were more likely to develop gestational diabetes mellitus than those with concentrations >75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.

Fetal volume and crown-rump length from 7 to 10 weeks of gestational age in singletons and twins

Objective(s): We intend to verify if fetal volume and crown-rump length were different between singletons and twins in pregnancies aged from 7 to 10 weeks and to evaluate if fetal volume is more accurate to determine the gestational age than crown-rump length at this gestational age. Study design: From 52 days (7 weeks and 3 days) to 73 days (10 weeks and 3 days) weekly three-dimensional Ultrasonography was per-formed in 20 twin fetuses and 20 singletons. Crown-rump length and fetal volume using VOCAL were assessed in all examinations. The `true` gestational age was based on oocyte retrieval. Results: At the age of 52 days, the crown-rump length was 11.74 +/- 0.27 mm (mean +/- S.D.) and 11.48 +/- 0.22 mm (singletons and twins, respectively), while the fetal volume was 0.354 +/- 0.015 cm(3) and 0.324 +/- 0.012 cm(3). At the gestational age of 73 days, the crown-rump length was 36.19 +/- 0.90 mm and 35.87 +/- 0.54 mm and the fetal volume was 6.204 +/- 0.090 cm(3) and 6.083 +/- 0.081 cm(3). The total relative increase observed was much higher for fetal volume than for CRL: 1705 +/- 301% vs. 210 +/- 33% in singletons and 1827 +/- 305% vs. 214 +/- 25% in twins. The 95% limits of agreement (+/- 2.3 days vs. +/- 3.2 days, fetal volume vs. crown-rump length) and the intraclass correlation coefficients (0.989 vs. 0.978) between the ""true"" gestational age and that predicted by fetal volume were better than those predicted by crown-rump length. No significant difference was identified between singletons and twins for both fetal volume and crown-rump length. Conclusion(s): Twins and singletons had similar fetal volume and crown-rump length between the 7th and 10th week of gestational age. Additionally, fetal volume assessed by VOCAL was better than crown-rump length to estimate the gestational age at the evaluated period. However, the improvement was small and probably without clinical significance. Condensation: Fetal volume and crown-rump length were similar between singletons and twins. Fetal volume relative increase was higher and the predicted gestational age was better. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Gestational diabetes mellitus: From consensus to action on screening and treatment

The 1998 consensus guidelines on the management of gestational diabetes mellitus from the Australasian Diabetes in Pregnancy Society emphasised that, “due to a lack of good quality randomised controlled clinical trials in the area of [gestational diabetes mellitus], these guidelines are based on what is a reasonable consensus of informed opinion in Australasia”.1 The clear benefits of treating women with gestational diabetes according to these guidelines have now been demonstrated by the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS).2 This study randomised 1000 women with gestational diabetes to either routine antenatal care or to an intervention that comprised home glucose monitoring, review by a diabetes educator, dietitian and physician, and insulin therapy if glycaemic targets were not met. Serious adverse perinatal outcomes occurred in 1% of the intervention group versus 4% of the routine-care group (adjusted relative risk, 0.33 [95% CI, 0.14–0.75]). The percentage of infants who were large for gestational age was lower in the intervention group (13% v 22%), with no increase in those who were small for gestational age. Although induction of labour was more common in the intervention group (39% v 29%), rates of caesarean delivery were similar (around 31%). Measures of maternal quality of life were more favourable in the intervention group. To prevent one serious perinatal outcome, 34 women needed to be treated. The 1998 guidelines were equivocal in regard to screening for gestational diabetes, allowing either for universal screening or for selective screening based on clinical risk factors in relatively lowrisk populations. In the light of the findings of ACHOIS, we believe that universal screening should now be accepted and implemented.

Postnatal growth and cardiometabolic profile in young adults born large for gestational age

Context The association between large for gestational age (LGA) phenotype, postnatal growth and cardiometabolic risk (CMR) in adult life remains unclear. The role of IGF1 genotype on LGA-related outcomes in adult life is unknown. Aim To assess the postnatal growth, IGF-I levels, CMR and the influence of the 737.738 IGF1 in adults born LGA. Subjects Case-control study (n = 515) nested in a population-based prospective cohort (n = 2063); 117 LGA and 398 gender-matched controls appropriate for gestational age (AGA) subjects. Methods Anthropometry was evaluated at birth, at 9-10 and at 23-25 years old. At the age of 23-25 years, blood pressure (BP), glycaemia, insulinaemia, homeostasis model assessment - insulin resistance, lipids, fibrinogen, and plasma IGF-I and 737.738 IGF1 polymorphism were assessed. Results Large for gestational age subjects remained heavier and taller than AGA at 9-10 and 23-25 years (P < 0.05); at 23-25 years, LGA had greater waist circumference (WC; P < 0.05) and higher BP (P < 0.05) than controls. Body proportionality at birth did not predict metabolic outcome. LGA subjects presenting catch-down of weight in childhood had lower body mass index (BMI; P = 0.001), lower WC (P < 0.05) and lower BP (P < 0.05) at 2325 years. 737.738 IGF-I genotype differed between groups (P < 0.001). Homozygosis for polymorphic alleles was associated with increased odds of LGA (OR: 3.2; 95% CI: 1.5-6.9), higher IGF-I (56.9 +/- 16.4 vs 37.7 +/- 16.0 nm; P < 0.01) and lower BP (114/68 vs 121/73 mmHg; P < 0.05). Conclusions Young adults born LGA presented higher BMI, WC and BP and appear to be at higher CMR risk than AGA subjects. The 737.738 IGF1 polymorphism appears to play a role on birth size and LGA-related metabolic outcomes.

Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age

Objective: To assess whether the -11391G > A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life. Design: Case-control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date. Methods: ADIPOQ -11391G > A genotype-phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8-10 years (catch-down growth), and at 23-25 years of age (cardiometabolic profile). Results: The -11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16-16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23-25 years, the -11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7 +/- 6.2 versus GA: 12.2 +/- 6.5 versus AA: 14.2 +/- 6.8 mu g/ml; P < 0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P < 0.001) at 23-25 years. Conclusions: The -11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.

PRETERM BIRTH AND FETAL GROWTH RESTRICTION IN HIV-INFECTED BRAZILIAN PREGNANT WOMEN

Introduction: Maternal HIV infection and related co-morbidities may have two outstanding consequences to fetal health: mother-to-child transmission (MTCT) and adverse perinatal outcomes. After Brazilian success in reducing MTCT, the attention must now be diverted to the potentially increased risk for preterm birth (PTB) and intrauterine fetal growth restriction (IUGR). Objective: To determine the prevalence of PTB and IUGR in low income, antiretroviral users, publicly assisted, HIV-infected women and to verify its relation to the HIV infection stage. Patients and Methods: Out of 250 deliveries from HIV-infected mothers that delivered at a tertiary public university hospital in the city of Vitória, state of Espírito Santo, Southeastern Brazil, from November 2001 to May 2012, 74 single pregnancies were selected for study, with ultrasound validated gestational age (GA) and data on birth dimensions: fetal weight (FW), birth length (BL), head and abdominal circumferences (HC, AC). The data were extracted from clinical and pathological records, and the outcomes summarized as proportions of preterm birth (PTB, < 37 weeks), low birth weight (LBW, < 2500g) and small (SGA), adequate (AGA) and large (LGA) for GA, defined as having a value below, between or beyond the ±1.28 z/GA score, the usual clinical cut-off to demarcate the 10th and 90th percentiles. Results: PTB was observed in 17.5%, LBW in 20.2% and SGA FW, BL, HC and AC in 16.2%, 19.1%, 13.8%, and 17.4% respectively. The proportions in HIV-only and AIDS cases were: PTB: 5.9 versus 27.5%, LBW: 14.7% versus 25.0%, SGA BW: 17.6% versus 15.0%, BL: 6.0% versus 30.0%, HC: 9.0% versus 17.9%, and AC: 13.3% versus 21.2%; only SGA BL attained a significant difference. Out of 15 cases of LBW, eight (53.3%) were preterm only, four (26.7%) were SGA only, and three (20.0%) were both PTB and SGA cases. A concomitant presence of, at least, two SGA dimensions in the same fetus was frequent. Conclusions: The proportions of preterm birth and low birth weight were higher than the local and Brazilian prevalence and a trend was observed for higher proportions of SGA fetal dimensions than the expected population distribution in this small casuistry of newborn from the HIV-infected, low income, antiretroviral users, and publicly assisted pregnant women. A trend for higher prevalence of PTB, LBW and SGA fetal dimensions was also observed in infants born to mothers with AIDS compared to HIV-infected mothers without AIDS.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth.

OBJECTIVE: To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. METHODS: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. RESULTS: Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. CONCLUSION: Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. LEVEL OF EVIDENCE: II.

Gastrointestinal malformations: impact of prenatal diagnosis on gestational age at birth.

The aim of the study was to analyse the degree to which gestational age (GA) has been shortened due to prenatal diagnosis of gastrointestinal malformations (GIM). The data source for the study was 14 population-based registries of congenital malformations (EUROCAT). All liveborn infants with GIMs and without chromosomal anomalies, born 1997-2002, were included. The 14 registries identified 1047 liveborn infants with one or more GIMs (oesophageal atresia, duodenal atresia, omphalocele, gastroschisis and diaphragmatic hernia). Median GA at birth was lower in prenatally diagnosed cases for all five malformations, although not statistically significant for gastroschisis. There was little difference in median birthweight by GA for the pre- and postnatally diagnosed infants. The difference in GA at birth between prenatally and postnatally diagnosed infants with GIMs is enough to increase the risk of mortality for the prenatally diagnosed infants. Clinicians need to balance the risk of early delivery against the benefits of clinical convenience when making case management decisions after prenatal diagnosis. Very few studies have been able to show benefits of prenatal diagnosis of congenital malformations for liveborn infants. This may be because the benefits of prenatal diagnosis are outweighed by the problems arising from a lower GA at birth.

Fetoscopic laser therapy for twin-twin transfusion syndrome: beyond current gestational age limits.

Both "early" (< 16 weeks' gestation) and "late" (> 26 weeks' gestation) presentations of twin-twin transfusion syndrome (TTTS) are rare and challenging complications of monochorionic/diamniotic twin pregnancies. Growing evidence suggests that fetoscopic laser therapy for both "early" and "late" TTTS is feasible, safe, and yields similar outcomes to cases treated between 16 and 26 weeks' gestation. We suggest reevaluation of conventional gestational age guidelines for laser therapy for TTTS.

Body size and early growth in appropriate- and large-for-gestational-age infants.

AIMS: To study weight, length, body composition, sleeping energy expenditure (SEE), and respiratory quotient (RQ) at birth and at 5 mo of age in both adequate-for-gestational-age (AGA) and large-for-gestational-age (LGA) subjects; to compare the changes in body weight and body composition adjusting for gender, age, SEE, RQ and several maternal factors; to investigate the contribution of initial SEE and RQ to changes in body weight and body composition. METHODS: Sixty-nine neonates were recruited among term infants in the University Hospital of Verona, Italy. Forty-nine subjects participated until follow-up. At birth and follow-up, weight and length were measured and arm-fat area and arm-muscle area were calculated from triceps and subscapular skinfolds. SEE and RQ were measured by indirect calorimetry. RESULTS: At birth, weight, length, arm-muscle and arm-fat areas were significantly higher in LGA subjects than in AGA subjects. Weight status, SEE and RQ at birth did not explain the relative weight change after adjusting for gestational weight, placental weight, age at follow-up and gender. Arm-fat area and weight/length ratio at birth were negatively associated with relative changes in body weight after adjusting for the above variables (p < 0.05). CONCLUSION: Early growth from birth to 5 mo of life is significantly affected by body size and adiposity at birth. Fatter newborns had a slower growth rate than thinner newborns.

Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age.

AIM: This study quantified the impact of perinatal predictors and medical centre on the outcome of very low-gestational-age neonates (VLGANs) born at <32 completed weeks in Switzerland. METHODS: Using prospectively collected data from a 10-year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three). RESULTS: From 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live-born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors. CONCLUSION: After adjusting for perinatal factors, the survival of Swiss VLGANs without severe neonatal morbidity was strongly influenced by the medical centre that treated them.

Body mass index values for newborns according to gestational age

Objective: The combination of twho anthropometric parameters has been more appropriate to assess body composition and proportions in children, with special attention to the Body Mass Index (BMI), as it relates weight and length. However the BMI values for the neonatal period have not been determined yet. This study shows the BMI for newborns at different gestational ages represented in a normal smoothed percentile curve. Methods: Retrospective study including 2,406 appropriate for gestational age newborns following the Alexander et al curve (1996) from 29 to 42 weeks of gestational age. Weight and lenght were measured following standard procedures. For the construction aof a normal smoothed percentile curve, the 3(rd) 5(th), 10(th), 25(th), 5(th), 75(th), 90(th) and 95(th) percentiles were determined and a statistical procedure based on the mathematical model ""sinosuoidal fit"" was applied to establish a curve that estimates biological growth parameters. Results: The Body Mass Index values for gestational age in all percentiles shows a steady increase up to 38 weeks, levels off up to the 40(th) week, followed by a slight decrease to the 42(nd) week in both genders. Conclusion: The results show a direct correlation between gestational age and Body Mass Index for both genders in the nine percentiles, and can provide a useful reference to assess intra-uterine proportional growth.