Maternal arterial elasticity in the first trimester as a predictor of birthweight.

The early detection of foetal growth restriction and macrosomia is an important goal of modern obstetric care. Aberrant foetal growth is an important cause of perinatal morbidity and mortality. Current modalities for detecting the abnormal foetal growth are often inadequate. Pulse wave analysis using applanation tonometry is a simple and non-invasive test that provides information about the cardiovascular system. Arterial elasticity has previously been implicated in the pathophysiology of pre-eclampsia and cardiovascular disease. Our study examined the relationship between maternal arterial elasticity and birthweight by using pulse wave analysis. We discovered that increased large artery elasticity predicted a larger baby at birth. Large artery elasticity therefore has the potential to act as a useful screening tool which may help in the prediction of women who are at risk of aberrant foetal growth.

Birth weight and neonatal adiposity prediction using fractional limb volume obtained with 3D ultrasound.

INTRODUCTION: The objective of this investigation was to study fetal thigh volume throughout gestation and explore its correlation with birth weight and neonatal body composition. This novel technique may improve birth weight prediction and lead to improved detection rates for fetal growth restriction. MATERIALS AND METHODS: Fractional thigh volume (TVol) using 3D ultrasound, fetal biometry and soft tissue thickness were studied longitudinally in 42 mother-infant pairs. The percentages of neonatal body fat, fat mass and fat-free mass were determined using air displacement plethysmography. Correlation and linear regression analyses were performed. RESULTS: Linear regression analysis showed an association between TVol and birth weight. TVol at 33 weeks was also associated with neonatal fat-free mass. There was no correlation between TVol and neonatal fat mass. Abdominal circumference, estimated fetal weight (EFW) and EFW centile showed consistent correlations with birth weight. Thigh volume demonstrated an additional independent contribution to birth weight prediction when added to the EFW centile from the 38-week scan (p = 0.03). CONCLUSION: Fractional TVol performed at 33 weeks gestation is correlated with birth weight and neonatal lean body mass. This screening test may highlight those at risk of fetal growth restriction or macrosomia.

Fetal subcutaneous tissue measurements in pregnancy as a predictor of neonatal total body composition.

OBJECTIVE: The purpose of this study was to examine the relationship between prenatal measures of subcutaneous tissue as surrogate markers of fetal nutritional status and correlate them with neonatal total body composition. METHODS: This prospective longitudinal study of 62 singleton pregnancies obtained serial biometry and subcutaneous tissue measurements at 28, 33 and 38 weeks gestation. These measurements were then correlated with neonatal body composition, which was analysed using the PEAPOD™ Infant Body Composition System (Cosmed USA, Concord, CA, USA). RESULTS: At 38 weeks gestation, fetal abdominal subcutaneous tissue (FAST) in millimetres was significantly associated with infant fat mass at delivery (+64 g per mm of FAST, p < 0.001). Thigh fat (TF) at 28 weeks gestation was associated with infant fat mass at delivery (+79 g/mm TF, p = 0.023). TF at 38 weeks gestation was associated with infant fat mass (+63/mm TF, p = 0.004). TF and FAST at 38 weeks were also predictive of both birth weight and increased abdominal circumference (AC) (p = 0.001) with FAST measurement predicting an additional 5.7 mm in AC per millimetre of FAST (p = 0.002) and TF predicting an additional 6.9 mm per mm of TF (p = 0.002). CONCLUSION: We believe that this study further validates the use of prenatal measures of subcutaneous tissue and may help to highlight fetuses at risk of newborn adiposity and metabolic syndrome.

Longitudinal measurement of fetal thigh soft tissue parameters and its role in the prediction of birth weight.

OBJECTIVE: The aim of this study was to profile longitudinal changes in thigh muscle and fat with gestation and to determine whether thigh measurements can improve the prediction of birth weight (BW). METHODS: A prospective longitudinal study of subcutaneous soft tissue measurements was conducted in 328 singleton fetuses at 28 and 37 weeks gestation. Estimated fetal weight (EFW) was calculated using abdominal circumference, femur length, biparietal diameter, and head circumference. RESULTS: The fetal abdominal subcutaneous tissue (FAST) and thigh muscle and fat show an increase with gestation. At 28 weeks gestation, the abdominal circumference, thigh fat, FAST, and EFW percentile were found to be significant predictors of BW. A combination of EFW percentile and thigh fat were found to be the optimal multivariate model at 28 weeks for predicting BW. At 37 weeks, BW prediction using EFW percentile, FAST, and thigh fat was the most accurate. The results revealed acceptable reproducibility for fetal thigh muscle and fat. CONCLUSION: This study provides reference ranges for thigh fat and muscle at 28 and 37 weeks gestation. The inclusion of fetal thigh fat in the algorithm improves the predictive power for birth weight. This information is important to explore the role of fetal thigh in the detection of aberrant growth.

Ultrasound assessment of placental function: the effectiveness of placental biometry in a low-risk population as a predictor of a small for gestational age neonate.

OBJECTIVE: The aims of the study were to establish reference ranges for placental length and thickness in a low-risk obstetric population and to assess the likelihood of a small for gestational age (SGA) neonate on the basis of placental length at 18-24 weeks' gestation. METHODS: Placental length and thickness were measured by two sonographers in 520 singleton pregnancies. Uterine artery Doppler studies and a placental morphological assessment were also performed. Placental size was correlated with the birthweight centiles at delivery. RESULTS: A placental length <10th centile between the gestational age of 18 and 24 weeks is a significant factor associated with SGA neonate [odds ratio (OR) = 2.8, 95% CL, 1.1-6.9]. An abnormal uterine artery Doppler is a significant factor for SGA neonate (OR = 3.4, 95% CL, 1.6-7.4). There was a weak relationship between cord insertion <2 cm from the placental margin and an SGA neonate (OR = 1.8, 95% CL, 0.4-8.2). CONCLUSION: We have provided reference ranges for placental length and thickness from 18 to 24 weeks' gestation. A single measurement of placental length incorporated into the anatomy scan may assist in the early detection of a group at risk of delivering an SGA neonate.

Prospective risk of fetal death in uncomplicated monochorionic twins.

A retrospective cohort study was carried out in a university teaching hospital to determine the prospective risk of unexpected fetal death in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins delivered at or after 24 weeks' gestation from July 1999 to July 2007 were included. Pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence were excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of intrauterine death was 4.9%. The prospective risk of unexpected intrauterine death was 1 in 43 after 32 weeks' gestation and 1 in 37 after 34 weeks' gestation. Our results demonstrate that despite close surveillance, the unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is high. This rate seems to increase after 34 weeks' gestation, suggesting that a policy of elective preterm delivery warrants evaluation.

Influence of maternal glycemia on intrauterine fetal adiposity distribution after a normal oral glucose tolerance test at 28 weeks gestation.

OBJECTIVE: To examine the relationship between maternal glucose levels and intrauterine fetal adiposity distribution in women with a normal oral glucose tolerance test (OGTT) at 28 weeks gestation. STUDY DESIGN: We recruited 231 women with a singleton pregnancy. At 28 and 37 weeks gestation, sonographic measurements of fetal body composition were performed. Multiple regression analysis was used to study the influence of different maternal variables on fetal adiposity distribution. RESULTS: Maternal glucose levels correlated with the fetal abdominal subcutaneous tissue measurements (r = 0.2; P = 0.014) and with birth weight (r = 0.1; P = 0.04). Maternal glucose levels did not correlate with the fetal mid-thigh muscle thickness and mid-thigh subcutaneous tissue measurements. CONCLUSION: We found that in nondiabetic women maternal glucose levels not only influence fetal adiposity and birth weight, but also influence the distribution of fetal adiposity. This supports previous evidence that maternal glycemia is a key determinant of intrauterine fetal programming.

The role of thromboxane A(2) in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy.

BACKGROUND: To examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction. METHODS: Prospective case control study enrolled smoking and non-smoking women at ≤14 weeks gestation. Maternal urine samples were obtained at ≤14, 28 and 36 weeks. High performance liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to quantify 11-dehydrothromboxane B(2) (TX-M) and 2,3 dinor-6-ketoprostaglandin F1α (PG-M), stable urinary metabolites of thromboxane A(2) and prostacyclin I2. Confirmation of the smoking status was performed by quantitation of urinary nicotine metabolites. Data was analysed using SPSS and Stata(®). RESULTS: Thirty five were enrolled in the smoking group and 32 in the non-smoking group. Smoking resulted higher levels of TX-M at ≤14, 28 and 36 weeks gestation. There was no difference in PG-M at any gestational time point between the two groups. The median customised birthweight centile in the smoking group was 17.0 (0-78) compared to 55.5 (4-100) in the non-smoking group (P<0.001). A causal relationship between elevated TX-M and IUGR could not be established. CONCLUSIONS: Maternal smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A(2) which occurs early in the first trimester.

A comparison of maternal and paternal body mass index in early pregnancy.

AIM: To determine the body mass index (BMI) and the body composition of fathers-to-be and to compare the findings with those of mothers-to-be during early pregnancy. METHODS: This was a descriptive and comparative study based at a large university teaching hospital. We enrolled men whose partner booked for antenatal care in the first trimester of pregnancy during July 2009. The height and weight of both parents-to-be were measured digitally, and BMI was calculated. The body compositions of the couple were analysed using bioelectrical impedance. RESULTS: Of 167 fathers-to-be, 14% were obese (BMI > 29.9 kg/m2 ) compared with 16% of mothers-to-be (NS). However, 50% were overweight (BMI 25.0-29.9 kg/m(2) ) compared with 26% of mothers-to-be (P < 0.001). This may be explained, in part, because the men were on average two years older than the women, and in the men, BMI increased with age. The men had a lower overall fat percentage (P < 0.001), but their visceral fat was higher than in the women (P < 0.001). CONCLUSION: Our findings show a high level of obesity in fathers-to-be, which has implications not only for the men themselves but also their families. We suggest that public health interventions directed at obesity during pregnancy should include both parents-to-be.

The influence of maternal body composition on birth weight.

OBJECTIVE: To identify the maternal body composition parameters that independently influence birth weight. STUDY DESIGN: A longitudinal prospective observational study in a large university teaching hospital. One hundred and eighty-four non-diabetic caucasian women with a singleton pregnancy were studied. In early pregnancy maternal weight and height were measured digitally in a standardised way and the body mass index (BMI) was calculated. At 28 and 37 weeks' gestation maternal body composition was assessed using segmental multifrequency bioelectrical impedance analysis. At delivery the baby was weighed and the clinical details were recorded. RESULTS: Of the women studied, 29.2% were overweight and 34.8% were obese. Birth weight did not correlate with maternal weight or BMI in early pregnancy. Birth weight correlated with gestational weight gain (GWG) before the third trimester (r=0.163, p=0.027), but not with GWG in the third trimester. Birth weight correlated with maternal fat-free mass, and not fat mass at 28 and 37 weeks gestation. Birth weight did not correlate with increases in maternal fat and fat-free masses between 28 and 37 weeks. CONCLUSIONS: Contrary to previous reports, we found that early pregnancy maternal BMI in a non-diabetic population does not influence birth weight. Interestingly, it was the GWG before the third trimester and not the GWG in the third trimester that influenced birth weight. Our findings have implications for the design of future intervention studies aimed at optimising gestational weight gain and birth weight. CONDENSATION: Maternal fat-free mass and gestational weight gain both influence birth weight.

Maternal leptin and body composition in the first trimester of pregnancy.

BACKGROUND: Leptin is produced mainly by adipocytes. Levels are increased in women with obesity and during pregnancy. Increased levels are also associated with pregnancy complications such as, pre-eclampsia and gestational diabetes mellitus. OBJECTIVE: We studied what component of body composition correlated best with maternal leptin in the first trimester of pregnancy and, whether maternal leptin correlated better with visceral fat rather than fat distributed elsewhere. SUBJECTS AND METHODS: Women were recruited in the first trimester. Maternal adiposity was measured using body mass index and advanced bioelectrical impedance analysis. Maternal leptin was measured using an enzyme-linked immunosorbent assay technique. RESULTS: Of the 100 subjects studied, the mean leptin concentration was 37.7 ng/ml (range: 2.1-132.8). Leptin levels did not correlate with gestational age in the first trimester, maternal age, parity or birth weight. Serum leptin correlated positively with maternal weight and body mass index, and with the different parameters of body composition. On multiple regression analysis, serum leptin correlated with visceral fat but not fat distributed elsewhere. CONCLUSIONS: Visceral fat is the main determinant of circulating maternal leptin in the first trimester of pregnancy. This raises the possibility that maternal leptin in early pregnancy may be a marker for the development of metabolic syndrome, including diabetes mellitus.

Body mass index and blood pressure measurement during pregnancy.

OBJECTIVE: The accurate measurement of blood pressure requires the use of a large cuff in subjects with a high mid-arm circumference (MAC). This prospective study examined the need for a large cuff during pregnancy and its correlation with maternal obesity. METHODS: Maternal body mass index (BMI), fat mass, and MAC were measured. RESULTS: Of 179 women studied, 15.6% were obese. With a BMI of level 1 obesity, 44% needed a large cuff and with a BMI of level 2 obesity 100% needed a large cuff. CONCLUSION: All women booking for antenatal care should have their MAC measured to avoid the overdiagnosis of pregnancy hypertension.

Body Mass Index and spontaneous miscarriage.

OBJECTIVE: We compared the incidence of spontaneous miscarriage in women categorised as obese, based on a Body Mass Index (BMI) >29.9 kg/m(2), with women in other BMI categories. STUDY DESIGN: In a prospective observational study conducted in a university teaching hospital, women were enrolled at their convenience in the first trimester after a sonogram confirmed an ongoing singleton pregnancy with fetal heart activity present. Maternal height and weight were measured digitally and BMI calculated. Maternal body composition was measured by advanced bioelectrical impedance analysis. RESULTS: In 1200 women, the overall miscarriage rate was 2.8% (n=33). The mean gestational age at enrolment was 9.9 weeks. In the obese category (n=217), the miscarriage rate was 2.3% compared with 3.3% in the overweight category (n=329), and 2.3% in the normal BMI group (n=621). There was no difference in the mean body composition parameters, particularly fat mass parameters, between those women who miscarried and those who did not. CONCLUSIONS: In women with sonographic evidence of fetal heart activity in the first trimester, the rate of spontaneous miscarriage is low and is not increased in women with BMI>29.9 kg/m(2) compared to women in the normal BMI category.

Maternal weight and body composition in the first trimester of pregnancy.

OBJECTIVE: Previous studies on weight gain in pregnancy suggested that maternal weight on average increased by 0.5-2.0 kg in the first trimester of pregnancy. This study examined whether mean maternal weight or body composition changes in the first trimester of pregnancy. DESIGN: Prospective observational study. POPULATION: We studied 1,000 Caucasian women booking for antenatal care in the first trimester of pregnancy. SETTING: Large university teaching hospital. METHODS: Maternal height and weight were measured digitally in a standardized way and Body Mass Index (BMI) was calculated. Maternal body composition was measured using segmental multifrequency Bioelectrical Impedance Analysis (BIA). Sonographic examination confirmed the gestational age and a normal ongoing singleton pregnancy in all subjects. MAIN OUTCOME MEASURES: Maternal weight, maternal body composition. RESULTS: The mean BMI was 25.7 kg/m(2) and 19.0% of the women were in the obese category (> or =30.0 kg/m(2)). Cross-sectional analysis by gestational age showed that there was no change in mean maternal weight, BMI, total body water, fat mass, fat-free mass or bone mass before 14 weeks gestation. CONCLUSIONS: Contrary to previous reports, mean maternal weight and mean body composition values remain unchanged in the first trimester of pregnancy. This has implications for guidelines on maternal weight gain during pregnancy. We also recommend that calculation of BMI in pregnancy and gestational weight gain should be based on accurate early pregnancy measurements, and not on self-reported or prepregnancy measurements.

Are there sex differences in Fetal Abdominal Subcutaneous Tissue (FAST) measurements?

OBJECTIVE: To determine if Fetal Abdominal Subcutaneous Tissue (FAST) measurements using antenatal ultrasound differ between male and female fetuses. STUDY DESIGN: Women who had an ultrasound examination for fetal growth between 20 and 40 weeks gestation were studied. Women with diabetes mellitus were excluded. The fetal anterior abdominal subcutaneous tissue was measured on the anterior abdominal wall in millimetres anterior to the margins of the ribs, using magnification at the level of the abdominal circumference. The fetal sex was recorded after delivery. RESULTS: A total of 557 fetuses were measured, 290 male and 267 female. The FAST measurements increased with gestational age. The FAST increased at the same rate for both male and female fetuses and at any given week there was no sex difference. CONCLUSIONS: The increased fat composition in females reported after birth was not found in abdominal wall subcutaneous fat measurements using ultrasound during pregnancy. Antenatal centile charts for FAST do not need to be based on sex.

Body Mass Index (BMI) in women booking for antenatal care: comparison between selfreported and digital measurements.

OBJECTIVE: We set out to compare measurement of Body Mass Index (BMI) with selfreporting in women early in pregnancy. STUDY DESIGN: We studied 100 women booking for antenatal care in the first trimester with a normal ongoing pregnancy. Selfreported maternal weight and height were recorded and the Body Mass Index was calculated. Afterwards maternal weight and height were digitally measured and actual BMI was calculated. RESULTS: If selfreporting is used for BMI classification, we found that 22% of women were classified incorrectly when BMI was measured. 12% of the women who were classified as having a normal selfreported BMI were overweight and 5% classified as overweight were obese. Similar findings have been reported outside pregnancy. CONCLUSIONS: These findings have implications for clinical practice, and for research studies exploring the relationship between maternal adiposity and pregnancy complications.

Maternal morbid obesity and obstetric outcomes.

OBJECTIVE: The purpose of this retrospective cohort study was to review pregnancy outcomes in morbidly obese women who delivered a baby weighing 500 g or more in a large tertiary referral university hospital in Europe. METHODS: Morbid obesity was defined as a BMI > or =40.0 kg/m2 (WHO). Only women whose BMI was calculated at their first antenatal visit were included. The obstetric out-comes were obtained from the hospital's computerised database. RESULTS: The incidence of morbid obesity was 0.6% in 5,824 women. Morbidly obese women were older and were more likely to be multigravidas than women with a normal BMI. The pregnancy was complicated by hypertension in 35.8% and diabetes mellitus in 20.0% of women. Obstetric interventions were high, with an induction rate of 42.1% and a caesarean section rate of 45.3%. CONCLUSIONS: Our findings show that maternal morbid obesity is associated with an alarmingly high incidence of medical complications and an increased level of obstetric interventions. Consideration should be given to developing specialised antenatal services for morbidly obese women. The results also highlight the need to evaluate the effectiveness of prepregnancy interventions in morbidly obese women.

CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders.

Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MTS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Loken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.