Customised Birthweight Centiles Research Articles

Impact of bariatric surgery on maternal gestational weight gain and pregnancy outcomes in women with obesity: A population-based cohort study from Qatar.

Bariatric surgery is performed in obese women of reproductive age to help achieve a healthy prepregnancy weight to reduce the complications associated with obesity in pregnancy. However, these procedures can impact maternal nutrition and gestational weight gain (GWG). This study evaluates the maternal and neonatal outcomes in women with prepregnancy bariatric surgery and determines the impact on GWG. This study included 24 weeks gestation or more pregnancies, with a maternal BMI at delivery of 30 kg/m2 or more. It was categorized into two groups based on whether they had prepregnancy bariatric surgery (exposed) or not (unexposed). The outcomes included gestational diabetes (GDM), gestational hypertension (GHT), mode of delivery, preterm birth (PTB), GWG, birthweight (BW) and customized BW centiles, low birthweight (LBW), congenital anomalies, and admission to the neonatal intensive unit (NICU). Categorization was also done based on the adequacy of GWG (low, adequate, and excess). A total of 8,323 women were included in the study, 194 of whom had prepregnancy bariatric surgery. After adjusting for confounders, the exposed group had a mean GWG 1.33 kg higher than the unexposed group (95% CI 0.55-2.13, p=0.001). The exposed group had higher odds of PTB (aOR 1.78, 95% CI 1.16-2.74, p=0.008), CD (aOR 6.52, 95% CI 4.28-9.93, p<0.001), LBW in term babies (aOR 2.60, 95% CI 1.34-5.03, p=0.005), congenital anomalies (aOR 2.64, 95% CI 1.21-5.77, p=0.015), low APGAR score (aOR 3.75, 95% CI 1.12-12.5, p=0.032) and 80.4g lesser birthweight (95% CI -153.0, -5.8; p=0.034). More women in the low GWG category had LBW babies (28.6% versus 6.7% in the high GWG group, p=0.033), lowest mean BW and median BW centiles (2775 grams versus 3289 grams in the high GWG group, p=0.004 and 57.5% versus 74.5% in the high GWG group, p=0.040, respectively). The findings of this study highlight differences in perinatal outcomes such as preterm birth, low birth weight, congenital anomalies, cesarean deliveries, and gestational weight gain between post-bariatric women and controls. These insights can help inform the planning and provision of appropriate maternity care to enhance patient safety and outcomes. The results of this study can also guide the counseling of reproductive age-group women who are planning to undergo bariatric surgery.

Maternal positional therapy for fetal growth and customised birth weight centile benefit in a Bayesian reanalysis of a double-blind, sham-controlled, randomised clinical trial

ObjectivesTo update the Ghana PrenaBelt Trial’s (GPT) primary outcome data with the latest fetal growth standard and reanalyse it. To estimate the posterior probability, under various clinically relevant prior probabilities,...

Improved estimation of the relationship between fetal growth and late stillbirth in the United States, 2014–15

In the United States the rate of stillbirth after 28 weeks’ gestation (late stillbirth) is 2.7/1000 births. Fetuses that are small for gestational age (SGA) or large for gestational age (LGA) are at increased risk of stillbirth. SGA and LGA are often categorized as growth or birthweight ≤ 10th and ≥ 90th centile, respectively; however, these cut-offs are arbitrary. We sought to characterize the relationship between birthweight and stillbirth risk in greater detail. Data on singleton births between 28- and 44-weeks’ gestation from 2014 to 2015 were extracted from the US Centers for Disease Control and Prevention live birth and fetal death files. Growth was assessed using customized birthweight centiles (Gestation Related Optimal Weight; GROW). The analyses included logistic regression using SGA/LGA categories and a generalized additive model (GAM) using birthweight centile as a continuous exposure. Although the SGA and LGA categories identified infants at risk of stillbirth, categorical models provided poor fits to the data within the high-risk bins, and in particular markedly underestimated the risk for the extreme centiles. For example, for fetuses in the lowest GROW centile, the observed rate was 39.8/1000 births compared with a predicted rate of 11.7/1000 from the category-based analysis. In contrast, the model-predicted risk from the GAM tracked closely with the observed risk, with the GAM providing an accurate characterization of stillbirth risk across the entire birthweight continuum. This study provides stillbirth risk estimates for each GROW centile, which clinicians can use in conjunction with other clinical details to guide obstetric management.

Does fetal size affect maternal perception of fetal movements? Evidence from an individual participant data meta-analysis.

Maternal perception of fetal movements during pregnancy are reassuring; however, the perception of a reduction in movements are concerning to women and known to be associated with increased odds of late stillbirth. Prior to full term, little evidence exists to provide guidelines on how to proceed unless there is an immediate risk to the fetus. Increased strength of movement is the most commonly reported perception of women through to full term, but perception of movement is also hypothesized to be influenced by fetal size. The study aimed to assess the pattern of maternal perception of strength and frequency of fetal movement by gestation and customized birthweight quartile in ongoing pregnancies. A further aim was to assess the association of stillbirth to perception of fetal movements stratified by customized birthweight quartile. This analysis was an individual participant data meta-analyses of five case-control studies investigating factors associated with stillbirth. The dataset included 851 cases of women with late stillbirth (>28 weeks' gestation) and 2257 women with ongoing pregnancies who then had a liveborn infant. The frequency of prioritized fetal movement from 28 weeks' gestation showed a similar pattern for each quartile of birthweight with increased strength being the predominant perception of fetal movement through to full term. The odds of stillbirth associated with reduced fetal movements was increased in all quartiles of customized birthweight centiles but was notably greater in babies in the lowest two quartiles (Q1: adjusted OR: 9.34, 95% CI: 5.43, 16.06 and Q2: adjusted OR: 6.11, 95% CI: 3.11, 11.99). The decreased odds associated with increased strength of movement was present for all customized birthweight quartiles (adjusted OR range: 0.25-0.56). Increased strength of fetal movements in late pregnancy is a positive finding irrespective of fetal size. However, reduced fetal movements are associated with stillbirth, and more so when the fetus is small.

MAGIC (maternal glucose in pregnancy) understanding the glycemic profile of pregnancy, intensive CGM glucose profiling and its relationship to fetal growth: an observational study protocol

BackgroundContinuous glucose monitoring (CGM) provides the most objective method of assessing glucose in daily life. Although there have been small, short-term physiologic studies of glucose metabolism in ‘healthy’ pregnant women a comprehensive, longitudinal description of changes in glucose over the course of pregnancy and how glucose dysregulation earlier in pregnancy relates to traditional third trimester screening for gestational diabetes, fetal growth and pregnancy outcomes is lacking. This study aims to characterise longitudinal changes in glycemia across gestation using CGM, in order to understand the evolution of dysglycemia and its relationship to fetal growth.Method/designA multi-centre, prospective, observational, cohort study of 500 healthy pregnant women, recruited in the first trimester of pregnancy. Masked CGM will be performed for a 14-day period on five occasions across pregnancy at ~ 10–12, 18–20, 26–28, 34–36 weeks gestation and postnatally. Routinely collected anthropometric and sociodemographic information will be recorded at each visit including: weight, height, blood pressure, current medication. Age, parity, ethnicity, smoking will be recorded. Blood samples will be taken at each visit for HbA1c and a sample stored. Details on fetal growth from ultrasound scans and the OGTT results will be recorded. Maternal and neonatal outcomes will be collected. CGM glucose profiling is the exposure of interest, and will be performed using standard summary statistics, functional data analysis and glucotyping. The primary maternal outcome is clinical diagnosis of GDM. The primary neonatal outcome is large for gestational age (LGA) (> 90th centile defined by customised birthweight centile). The relationship of glucose to key secondary maternal and neonatal outcomes will be explored.DiscussionThis study will ascertain the relationship of maternal dysglycemia to fetal growth and outcomes. It will explore whether CGM glucose profiling can detect GDM before the OGTT; or indeed whether CGM glucose profiling may be more useful than the OGTT at detecting LGA and other perinatal outcomes.Trial registrationISRCTN 15,706,303 https://www.isrctn.com/ISRCTN15706303 Registration date: 13th March 2023.

Accuracy of ultrasound in the estimation of customised birth weight in a public hospital service.

Studies have shown that ultrasound estimated foetal weight (EFW) in small for gestational age (SGA) babies tends to be less-accurate when compared to appropriate (AGA) and large (LGA) for gestational age babies. We aimed to analyse the accuracy of ultrasound EFW overall, and by customised birth weight centile category (severe SGA, SGA, AGA, LGA). Also, the accuracy of estimating the centile category using calculated customised EFW centiles. We performed a retrospective study of pregnant women between 20-43 weeks gestation who underwent ultrasound within 7 days of delivery at a large tertiary maternity unit between January 2018 and December 2020. Stillbirths, major foetal anomalies and multiple pregnancies were excluded. The EFW and birth weight were compared, and an accurate estimate defined as ≤15% difference. The customised EFW and birth weight centiles were calculated and used to analyse the accuracy of category prediction. Of 2061 foetuses included, 92% (n = 1902) were born weighing within 15% of their EFW. Accuracy was not affected by maternal BMI, ethnicity, parity or gestation. 87% of SGA babies were within 15% of their EFW. Ultrasound sensitivity for SGA was 51% (95% CI: 46-55%). The specificity and positive predictive values were 97% (95% CI: 96-98%) and 87% (95% CI: 82-90%) respectively. The accuracy of Ultrasound EFW overall is good, however, is reduced in SGA babies whose EFW and birth weight centile categories tended to be overestimated. The high specificity for SGA supports monitoring with a lowered threshold to intervene in pregnancies identified by ultrasound as SGA.

Case-control study of prolactin and placental lactogen in SGA pregnancies.

Prolactin and placental lactogens increase during pregnancy and are involved with many aspects of maternal metabolic adaptation to pregnancy, likely to impact on fetal growth. The aim of this study was to determine whether maternal plasma prolactin or placental lactogen concentrations at 20 weeks of gestation were associated with later birth of small-for-gestational-age babies (SGA). In a nested case–control study, prolactin and placental lactogen in plasma samples obtained at 20 weeks of gestation were compared between 40 women who gave birth to SGA babies and 40 women with uncomplicated pregnancies and size appropriate-for-gestation-age (AGA) babies. Samples were collected as part of the 'screening of pregnancy endpoints' (SCOPE) prospective cohort study. SGA was defined as birthweight <10th customized birthweight centile (adjusted for maternal weight, height, ethnicity, parity, infant sex, and gestation age) in mothers who remained normotensive. No significant differences were observed in concentrations of prolactin or placental lactogen from women who gave birth to SGA babies compared with women with uncomplicated pregnancies. However, a sex-specific association was observed in SGA pregnancies, whereby lower maternal prolactin concentration at 20 weeks of gestation was observed in SGA pregnancies that were carrying a male fetus (132.0 ± 46.7 ng/mL vs 103.5 ± 38.3 ng/mL, mean ± s.d., P = 0.036 Student’s t-test) compared to control pregnancies carrying a male fetus. Despite the implications of these lactogenic hormones in maternal metabolism, single measurements of either prolactin or placental lactogen at 20 weeks of gestation are unlikely to be useful biomarkers for SGA pregnancies.Lay summaryEarly identification during pregnancy of small for gestational age (SGA) babies would enable interventions to lower risk of complications around birth (perinatal), but current detection rates of these at risk babies is low. Pregnancy hormones, prolactin and placental lactogen, are involved in metabolic changes that are required for the mother to support optimal growth and development of her offspring during pregnancy. The levels of these hormones may provide a measurable indicator (biomarker) to help identify these at risk pregnancies. Levels of these hormones were measured in samples from week 20 of gestation from women who went on to have SGA babies and control pregnancies where babies were born at a size appropriate for gestation age. Despite the implications of prolactin and placental lactogen in maternal metabolism, no significant differences were detected suggesting that single measures of either prolactin or placental lactogen at 20 weeks gestation are unlikely to be useful biomarker to help detect SGA pregnancies.

Customized birth-weight centiles and placenta-related fetal growth restriction.

The value of using customized birth-weight centiles to improve the diagnostic accuracy for fetal growth restriction (FGR), in comparison with using population-based charts, remains a matter of debate. One potential explanation for the conflicting data is that most studies used measures of perinatal mortality and morbidity as proxies for placenta-mediated FGR, many of which are not specific and may be confounded by other factors such as prematurity. The aim of this study was to compare the diagnostic accuracy of small-for-gestational age (SGA) at birth, defined according to customized vs population-based charts, for associated abnormal placental pathology. This was a secondary analysis of data from a prospective cohort study on risk factors for placenta-mediated complications and abnormal placental pathology in low-risk nulliparous women. All placentae were sent for detailed histopathological examination by two perinatal pathologists. The primary exposure was SGA, defined as birth weight < 10th centile for gestational age using either a customized (SGAcust ) or a population-based (SGApop ) birth-weight reference. The outcomes of interest were one of three types of abnormal placental pathology associated with FGR: maternal vascular malperfusion (MVM), chronic villitis and fetal vascular malperfusion (FVM). Adjusted relative risks (aRR) with 95% CIs were estimated using modified Poisson regression analysis, with adjustment for smoking, body mass index and aspirin treatment. A total of 857 nulliparous women met the study criteria. The proportions of infants identified as SGA based on the customized and population-based charts were 12.6% (108/857) and 11.4% (98/857), respectively. A diagnosis of SGA using either customized or population-based charts was associated with an increased risk of any placental pathology (aRR, 3.04 (95% CI, 2.29-4.04) and 1.60 (95% CI, 1.10-2.31), respectively) and MVM pathology (aRR, 12.33 (95% CI, 6.60-23.03) and 5.29 (95% CI, 2.87-9.76), respectively). SGAcust , but not SGApop , was also associated with an increased risk for chronic villitis (aRR, 1.85 (95% CI, 1.07-3.18)) and FVM pathology (aRR, 2.48 (95% CI, 1.25-4.93)). SGAcust had a higher detection rate for any placental pathology (30.3% vs 17.1%; P < 0.001), MVM pathology (63.2% vs 39.5%; P = 0.003) and chronic villitis (20.8% vs 8.3%; P = 0.007) than did SGApop , for a similar false-positive rate. This was mainly the result of a higher detection rate for abnormal pathology in the white and East-Asian subgroups and a lower false-positive rate for abnormal pathology in the South-Asian subgroup by SGAcust than by SGApop . In addition, pregnancies in the SGAcust group, but not those in the SGApop group, were more likely to be complicated by preterm birth and a low 5-min Apgar score than were the corresponding non-SGA group. These findings suggest that customized birth-weight centiles may be superior to population-based birth-weight centiles in detecting FGR that is due to underlying placental disease. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Reduction in perinatal mortality among small for gestational age babies in New Zealand.

A significant reduction in perinatal mortality among births ≥1000g has been observed in New Zealand. To determine, in a national cohort, if perinatal mortality has reduced in small for gestational age (SGA) and non-SGA babies. Retrospective cohort, 2008-2016, of singleton non-anomalous births and perinatal deaths from 26+0weeks gestation at birth in New Zealand. Perinatal deaths from the Perinatal and Maternal Mortality Review Committee data set were merged with the Ministry of Health national maternity data set. SGA was defined as less than the 10th customised birthweight centile using New Zealand coefficients. Perinatal mortality was defined as stillbirth from 26weeks gestation and neonatal death up to the 27th day of life. There was a 30% reduction in perinatal mortality among SGA singleton non-anomalous babies at 26weeks or more from 10.38/1000 births in 2008 to 7.28/1000 in 2016 (P=0.046) but no significant change in mortality among appropriate and large for gestational age babies. There has been a significant reduction in perinatal mortality among SGA babies in New Zealand. The mechanism for this reduction is unclear.

Placental Inositol Reduced in Gestational Diabetes as Glucose Alters Inositol Transporters and IMPA1 Enzyme Expression.

Perturbed inositol physiology in insulin-resistant conditions has led to proposals of inositol supplementation for gestational diabetes (GDM) prevention, but placental inositol biology is poorly understood. Investigate associations of maternal glycemia with placental inositol content, determine glucose effects on placental expression of inositol enzymes and transporters, and examine relations with birthweight. Case-control study of placentae from term singleton pregnancies (GDM n = 24, non-GDM n = 26), and culture of another 9 placentae in different concentrations of glucose and myo-inositol for 48 hours. Placental inositol was quantified by the Megazyme assay. Relative expression of enzymes involved in myo-inositol metabolism and plasma membrane inositol transport was determined by quantitative RT-PCR and immunoblotting. Linear regression analyses were adjusted for maternal age, body mass index, ethnicity, gestational age, and sex. Placental inositol content was 17% lower in GDM compared with non-GDM. Higher maternal mid-gestation glycemia were associated with lower placental inositol. Increasing fasting glycemia was associated with lower protein levels of the myo-inositol synthesis enzyme, IMPA1, and the inositol transporters, SLC5A11 and SLC2A13, the expression of which also correlated with placental inositol content. In vitro, higher glucose concentrations reduced IMPA1 and SLC5A11 mRNA expression. Increasing fasting glycemia positively associated with customized birthweight percentile as expected in cases with low placental inositol, but this association was attenuated with high placental inositol. Glycemia-induced dysregulation of placental inositol synthesis and transport may be implicated in reduced placental inositol content in GDM, and this may in turn be permissive to accelerated fetal growth.

Folic acid supplementation is associated with size at birth in the Screening for Pregnancy Endpoints (SCOPE) international prospective cohort study

BackgroundSmall-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. AimThe aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters. Study designWomen were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 ± 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors. SubjectsNulliparous women with singleton pregnancies. Outcome measuresSGA (<10th customised birthweight centile). Results5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67–01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (β 2.56 (95% CI: 0.87–4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference. ConclusionsIn this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.

Sex- and growth-specific characteristics of small for gestational age infants: a prospective cohort study

BackgroundAsymmetric fetal growth and male sex are both associated with adverse neonatal outcome. However, less is known about the influence of asymmetric growth and fetal sex within SGA neonates, a group of infants already at increased risk for adverse neonatal outcomes. The aim of the present study was to provide insight into variance in risk factors for SGA in a fetal sex- and growth symmetry-specific way.MethodsFor this prospective, multicenter cohort study, data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 (11.3%) pregnancies were complicated with SGA and 3376 (60.0%) women had uncomplicated pregnancies. Association between risk factors for SGA, SGA subgroups, and uncomplicated pregnancies were assessed with multivariable analyses.ResultsPrevalence of asymmetric growth varied from 45.8% of SGA infants to 5.5% of infants with a customized birthweight > 90th percentile (p < 0.001). Significantly more SGA males had asymmetric growth compared to SGA female infants (51.2% vs 40.4%, p = 0.009). Maternal pre-pregnancy diet and BMI < 20 and ≥ 30 were significantly associated with symmetric SGA but not with asymmetric SGA. Asymmetric SGA infants had not only lower customized birthweight percentile (4.4 (SD 2.8) vs 5.0 (SD 3.0), p < 0.001), but also lower rates of stillbirth (p = 0.041) and less often Apgar scores < 7 (p = 0.060).ConclusionsAmong SGA infants, low customized birthweight percentiles and male sex are associated with asymmetric growth. Only symmetric SGA is significantly associated with maternal risk factors in early pregnancy. There is a substantial variance in risk factors and neonatal outcomes for SGA based on growth symmetry, implying a different pathogenesis.Trial registrationACTRN12607000551493

EP20.11: Cohort comparison study using INTERGROWTH‐21st versus GROW customised birthweight centiles in a homogenous Caucasian population

EP20.11: Cohort comparison study using INTERGROWTH‐21st versus GROW customised birthweight centiles in a homogenous Caucasian population

Birth weight centiles and small for gestational age by sex and ethnicity for England and Wales

ObjectivesTo construct UK ethnicity birth weight centiles (UK-EBWC) for gestational age and cut-offs for small for gestational age (SGA) for England and Wales and to evaluate the SGA misclassification using...

The Ghana PrenaBelt trial: a double-blind, sham-controlled, randomised clinical trial to evaluate the effect of maternal positional therapy during third-trimester sleep on birth weight

ObjectiveTo evaluate the effect, on birth weight and birth weight centile, of use of the PrenaBelt, a maternal positional therapy device, during sleep in the home setting throughout the third...

The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age (SGA) infant.

ObjectivesMaternal lifestyles, including diet, have been linked to infant birthweight. However, customised birthweight centiles (CBWC), which more accurately identify small babies that have increased fetal growth restriction and are at higher risk of newborn morbidity and later life health complications, are rarely considered when studying maternal diet. This study investigated maternal dietary patterns and their impact on infant CBWC within a cohort of women living in South Wales.MethodsThis study utilised cross-sectional data from the longitudinal Grown in Wales (GiW) cohort. Women 18–45 years old were recruited the morning prior to an elective caesarean section (ELCS). Women completed a food frequency questionnaire (FFQ). Additional data on pregnancy and birth outcomes was extracted from medical notes. Data from 303 participants was analysed.Results‘Western’ and ‘Health conscious dietary patterns were identified. The ‘Health Conscious’ dietary pattern was significantly associated with maternal BMI, age, education, income and exercise. Adjusted regression analyses indicated that greater adherence to a ‘Health Conscious’ dietary pattern was significantly associated with increased CBWC (AOR = 4.75 [95% CI: 1.17, 8.33] p = .010) and reduced risk of delivering a small-for-gestational age (SGA) infant (AOR = .51 [95% CI: .26, .99] p = .046).ConclusionA healthier diet was significantly associated with higher birthweight using CBWC and a reduced risk of delivering an SGA infant suggesting that birthweight will be improved in areas of Wales by focused support encouraging healthier dietary habits.

Influence of maternal adiposity, preterm birth and birth weight centiles on early childhood obesity in an Indigenous Australian pregnancy-through-to-early-childhood cohort study.

Childhood obesity rates are higher among Indigenous compared with non-Indigenous Australian children. It has been hypothesized that early-life influences beginning with the intrauterine environment predict the development of obesity in the offspring. The aim of this paper was to assess, in 227 mother-child dyads from the Gomeroi gaaynggal cohort, associations between prematurity, Gestation Related-Optimal Weight (GROW) centiles, maternal adiposity (percentage body fat, visceral fat area), maternal non-fasting plasma glucose levels (measured at mean gestational age of 23.1 weeks) and offspring BMI and adiposity (abdominal circumference, subscapular skinfold thickness) in early childhood (mean age 23.4 months). Maternal non-fasting plasma glucose concentrations were positively associated with infant birth weight (P=0.005) and GROW customized birth weight centiles (P=0.008). There was a significant association between maternal percentage body fat (P=0.02) and visceral fat area (P=0.00) with infant body weight in early childhood. Body mass index (BMI) in early childhood was significantly higher in offspring born preterm compared with those born at term (P=0.03). GROW customized birth weight centiles was significantly associated with body weight (P=0.01), BMI (P=0.007) and abdominal circumference (P=0.039) at early childhood. Our findings suggest that being born preterm, large for gestational age or exposed to an obesogenic intrauterine environment and higher maternal non-fasting plasma glucose concentrations are associated with increased obesity risk in early childhood. Future strategies should aim to reduce the prevalence of overweight/obesity in women of child-bearing age and emphasize the importance of optimal glycemia during pregnancy, particularly in Indigenous women.

Fractional fetal thigh volume in the prediction of normal and abnormal fetal growth during the third trimester of pregnancy

BackgroundCurrently, 2-dimensional ultrasound estimation of fetal size rather than fetal growth is used to define fetal growth restriction, but single estimates in late pregnancy lack sensitivity and may identify small for gestational age rather than growth restriction. Single or longitudinal measures of 3-dimensional fractional thigh volume may address this problem.ObjectiveWe sought to derive normal values for 3-dimensional fractional thigh volume in the third trimester, determine if fractional thigh volume is superior to 2-dimensional ultrasound biometry alone for detecting fetal growth restriction, and determine whether individualized growth assessment parameters have the potential to identify fetal growth restriction remote from term delivery.Study DesignThis was a longitudinal prospective cohort study of 115 unselected pregnancies in a tertiary referral unit (St Mary’s Hospital, Manchester, United Kingdom). Standard 2-dimensional ultrasound biometry measurements were obtained, along with fractional thigh volume measurements (based on 50% of the femoral diaphysis length). Measurements were used to calculate estimated fetal weight (Hadlock). Individualized growth assessment parameters and percentage deviations in longitudinally measured biometrics were determined using a Web-based system (iGAP; http://iGAP.research.bcm.edu). Small for gestational age was defined <10th and fetal growth restriction <3rd customized birthweight centile. Logistic regression was used to compare estimated fetal weight (Hadlock), estimated fetal weight (biparietal diameter–abdominal circumference–fractional thigh volume), fractional thigh volume, and abdominal circumference for the prediction of small for gestational age or fetal growth restriction at birth. Screening performance was assessed using area under the receiver operating characteristic curve.ResultsThere was a better correlation between fractional thigh volume and estimated fetal weight ((biparietal diameter–abdominal circumference–fractional thigh volume) obtained at 34-36 weeks with birthweight than between 2-dimensional biometry measures such as abdominal circumference and estimated fetal weight (Hadlock). There was also a modest improvement in the detection of both small for gestational age and fetal growth restriction using fractional thigh volume–derived measures compared to standard 2-dimensional measurements (area under receiver operating characteristic curve, 0.86; 95% confidence interval, 0.79–0.94, and area under receiver operating characteristic curve, 0.92; 95% confidence interval, 0.85–0.99, respectively).ConclusionFractional thigh volume measurements offer some improvement over 2-dimensional biometry for the detection of late-onset fetal growth restriction at 34-36 weeks.

Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history: a randomized trial

Preeclampsia and small-for-gestational-age pregnancy are major causes of maternal and perinatal morbidity and mortality. Women with a previous pregnancy affected by these conditions are at an increased risk of recurrence in a future pregnancy. Past trials evaluating the effect of low-molecular-weight heparin for the prevention of recurrence of preeclampsia and small-for-gestational-age pregnancy have shown conflicting results with high levels of heterogeneity displayed when trials were compared. We sought to assess the effectiveness of enoxaparin in addition to high-risk care for the prevention of preeclampsia and small-for-gestational-age pregnancy in women with a history of these conditions. This was an open-label randomized controlled trial in 5 tertiary care centers in 3 countries. Women with a viable singleton pregnancy were invited to participate between >6+0 and <16+0 weeks if deemed to be at high risk of preeclampsia and/or small for gestational age based on their obstetric history. Eligible participants were randomly assigned in a 1-to-1 ratio to standard high-risk care or standard high-risk care plus enoxaparin 40 mg (4000 IU) by subcutaneous injection daily from recruitment until 36+0 weeks or delivery, whichever occurred sooner. Standard high-risk care was defined as care coordinated by a high-risk antenatal clinic service, aspirin 100 mg daily until 36+0 weeks, and-for women with prior preeclampsia-calcium 1000-1500 mg daily until 36+0 weeks. In a subgroup of participants serum samples were taken at recruitment and at 20 and 30 weeks' gestation and later analyzed for soluble fms-like tyrosine kinase-1, soluble endoglin, endothelin-1, placental growth factor, and soluble vascular cell adhesion molecule 1. The primary outcome was a composite of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile. Alldata were analyzed on an intention-to-treat basis. The trial is registeredwith the Australian New Zealand Clinical Trials Registry (ACTRN12609000699268). Between July 26, 2010, and Oct. 28, 2015, a total of 156 participants were enrolled and included in the analysis. In all, 149 participants were included in the outcome analysis (72 receiving standard high-risk care plus enoxaparin and 77 receiving standard high-risk care only). Seven women who miscarried <16 weeks' gestation were excluded. The majority of participants (151/156, 97%) received aspirin. The addition of enoxaparin had no effect on the rate of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile: enoxaparin 18/72 (25%) vs no enoxaparin 17/77 (22.1%) (odds ratio, 1.19; 95% confidence interval, 0.53-2.64). There was also no difference in any of the secondary outcome measures. Levels of soluble fms-like tyrosine kinase-1 and soluble endoglin increased among those who developed preeclampsia, but there was no difference in levels of these antiangiogenic factors (nor any of the other serum analytes measured) among those treated with enoxaparin compared to those receiving standard high-risk care only. The use of enoxaparin in addition to standard high-risk care does not reduce the risk of recurrence of preeclampsia and small-for-gestational-age infants in a subsequent pregnancy.

Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology.

ObjectiveTo investigate the proportion of stillbirths at term associated with abnormal growth using customized birth weight percentiles and to compare histological placental findings both in underweight stillborn fetuses and in live births.MethodsA retrospective case-control study of 150 singleton term stillbirths. The livebirth control groups included 586 cases of low-risk pregnancies and 153 late fetal growth restriction fetuses. Stillbirths and livebirths from low-risk pregnancies were classified using customized standards for fetal weight at birth, as adequate for gestational age (AGA; 10-90th percentile), small (SGA; <10th percentile) or large for gestational age (LGA; >90th percentile). Placental characteristics in stillbirth were compared with those from livebirths using four categories: inflammation, disruptive, obstructive and adaptive lesions.ResultsThere was a higher rate of SGA (26% vs 6%, p<0.001) and LGA fetuses (10.6% vs 5.6%, p<0.05) in the stillbirth group. Among stillbirth fetuses, almost half of the SGA were very low birthweight (≤3°percentile) (12% vs 0.3%, p<0.001). The disruptive (7.3% vs 0.17%;p<0.001), obstructive (54.6% vs 7.5%;p<0.001) and adaptive (46.6% vs 35.8%;p<0.001) findings were significantly more common in than in livebirth-low risk. Placental characteristics of AGA and SGA stillbirth were compared with those of AGA and FGR livebirth. In stillbirths-SGA we found a higher number of disruptive (12.8% vs 0%; p<0.001), obstructive (58.9% vs 23.5%;p<0.001) and adaptive lesions (56.4% vs 49%; p 0.47) than in livebirth-FGR.ConclusionThe assessment of fetal weight with customized curves can identify fetuses which have not reached their genetically determined growth potential and are therefore at risk for adverse outcomes. Placental evaluation in stillbirths can reveal chronic histological signs that might be useful to clinical assessment, especially in underweight fetuses.