Low maternal circulating levels of vitamin D as potential determinant in the development of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM), defined as any glucose intolerance with the onset or first recognition during pregnancy, is characterized by rising incidence, fostered by the worldwide increase of pathological nutritional status from young age. Clinical research has intended to identify potential risk factors, suggested improvements in screening strategies, and recommended the combination between promotion of an appropriate lifestyle before and during pregnancy and selected therapeutic approaches. Preventing pathological hyperglycemia could have several benefits, ranging from clinical side (reduction in the risk of adverse perinatal and long-term sequelae) to financial side (cost reduction to healthcare systems). Among risk factors recognized, deficiency in 25-hydroxyvitamin D [25(OH)D], already acknowledged as involved in calcium homeostasis, pathogenesis of cardiovascular, oncological, infective and immunity diseases, could predispose to the development of both type 1 and 2 diabetes, modifying the activity of pancreatic ß-cells vitamin D (VD) receptor. In pregnant women, lower 25(OH)D concentrations have been suggested to present an inverse association with maternal glycaemia, insulin resistance, and increased risk of GDM. In spite of growing body of evidence, there is not full agreement on the therapeutic association between GDM based on VD deficiency and 25(OH)D supplementation. In the attempt to bring up-to-date the role of low VD levels on subsequent development of GDM, this narrative review, based on medium-high-quality randomized clinical trials, systematic reviews, and meta-analysis published in last decade, has a twofold purpose: firstly, to elucidate the relationship between maternal VD status and GDM; and secondly, to illuminate the impact of VD supplementation on GDM onset.

Differential performance of first-trimester screening in predicting small-for-gestational-age neonate or fetal growth restriction.

OBJECTIVE: To assess the ability of integrated first-trimester screening, combining maternal characteristics and biophysical and biochemical markers, to predict delivery of a small-for-gestational-age (SGA) neonate, and compare this with its ability to predict fetal growth restriction (FGR). METHODS: This was a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening. SGA was defined as birth weight (BW) < 10th percentile and FGR was defined as an ultrasound estimated fetal weight < 10th percentile plus Doppler abnormalities, or BW < 3rd percentile. Logistic regression-based predictive models were developed for predicting SGA and FGR. Models incorporated the a-priori risk from maternal characteristics, and mean arterial pressure, uterine artery Doppler, placental growth factor and soluble fms-like tyrosine kinase-1. RESULTS: In total, 9150 births were included. Of these, 979 (10.7%) qualified for a postnatal diagnosis of SGA and 462 (5.0%) for a prenatal diagnosis of FGR. For predicting SGA, the model achieved a detection rate of 35% for a false-positive rate (FPR) of 5% and 42% for a 10% FPR. The model's performance was significantly higher for predicting FGR (P < 0.001), with detection rates of 59% and 67%, for a FPR of 5% and 10%, respectively. CONCLUSION: The predictive performance of first-trimester screening for cases with growth impairment by a combination of maternal characteristics and biophysical and biochemical markers is improved significantly when a prenatal and strict definition of FGR is used rather than a postnatal definition based on BW. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of fetal growth restriction using estimated fetal weight vs a combined screening model in the third trimester.

OBJECTIVES: To compare the performance of third-trimester screening, based on estimated fetal weight centile (EFWc) vs a combined model including maternal baseline characteristics, fetoplacental ultrasound and maternal biochemical markers, for the prediction of small-for-gestational-age (SGA) neonates and late-onset fetal growth restriction (FGR). METHODS: This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester (32 + 0 to 36 + 6 weeks' gestation) evaluation. Maternal baseline characteristics, mean arterial pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently delivered a SGA neonate (n = 175), defined as birth weight < 10th centile according to customized standards, and in a control group (n = 875). Among SGA cases, those with birth weight < 3rd centile and/or abnormal uterine artery pulsatility index (UtA-PI) and/or abnormal cerebroplacental ratio (CPR) were classified as FGR. Logistic regression predictive models were developed for SGA and FGR, and their performance was compared with that obtained using EFWc alone. RESULTS: In SGA cases, EFWc, CPR Z-score and maternal serum concentrations of unconjugated estriol and PlGF were significantly lower, while mean UtA-PI Z-score and lipocalin-2 and inhibin A concentrations were significantly higher, compared with controls. Using EFWc alone, 52% (area under receiver-operating characteristics curve (AUC), 0.82 (95% CI, 0.77-0.85)) of SGA and 64% (AUC, 0.86 (95% CI, 0.81-0.91)) of FGR cases were predicted at a 10% false-positive rate. A combined screening model including a-priori risk (maternal characteristics), EFWc, UtA-PI, PlGF and estriol (with lipocalin-2 for SGA) achieved a detection rate of 61% (AUC, 0.86 (95% CI, 0.83-0.89)) for SGA cases and 77% (AUC, 0.92 (95% CI, 0.88-0.95)) for FGR. The combined model for the prediction of SGA and FGR performed significantly better than did using EFWc alone (P < 0.001 and P = 0.002, respectively). CONCLUSIONS: A multivariable integrative model of maternal characteristics, fetoplacental ultrasound and maternal biochemical markers modestly improved the detection of SGA and FGR cases at 32-36 weeks' gestation when compared with screening based on EFWc alone. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Performance of third-trimester combined screening model for prediction of adverse perinatal outcome.

OBJECTIVE: To explore the potential value of third-trimester combined screening for the prediction of adverse perinatal outcome (APO) in the general population and among small-for-gestational-age (SGA) fetuses. METHODS: This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester evaluation (32 + 0 to 36 + 6 weeks' gestation). Maternal baseline characteristics, mean arterial blood pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently had an APO (n = 148) and in a control group without perinatal complications (n = 902). APO was defined as the occurrence of stillbirth, umbilical artery cord blood pH < 7.15, 5-min Apgar score < 7 or emergency operative delivery for fetal distress. Logistic regression models were developed for the prediction of APO in the general population and among SGA cases (defined as customized birth weight < 10th centile). RESULTS: The prevalence of APO was 9.3% in the general population and 27.4% among SGA cases. In the general population, a combined screening model including a-priori risk (maternal characteristics), estimated fetal weight (EFW) centile, umbilical artery pulsatility index (UA-PI), estriol and PlGF achieved a detection rate for APO of 26% (area under receiver-operating characteristics curve (AUC), 0.59 (95% CI, 0.54-0.65)), at a 10% false-positive rate (FPR). Among SGA cases, a model including a-priori risk, EFW centile, UA-PI, cerebroplacental ratio, estriol and PlGF predicted 62% of APO (AUC, 0.86 (95% CI, 0.80-0.92)) at a FPR of 10%. CONCLUSIONS: The use of fetal ultrasound and maternal biochemical markers at 32-36 weeks provides a poor prediction of APO in the general population. Although it remains limited, the performance of the screening model is improved when applied to fetuses with suboptimal fetal growth. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Changes in uterine artery Doppler velocimetry and circulating angiogenic factors in the first half of pregnancies delivering a small-for-gestational-age neonate.

OBJECTIVE: To assess the relationship between longitudinal changes in placental Doppler indices and maternal circulating angiogenic factors in the first half of pregnancy and delivery of a small-for-gestational-age (SGA) neonate, and ascertain whether longitudinal evaluation of these variables improves the prediction achieved by second-trimester cross-sectional evaluation. METHODS: From a prospective cohort of unselected singleton pregnancies undergoing first-trimester screening for aneuploidy, 138 were included in this study. Of these, 46 were complicated by SGA (delivering after 34 weeks' gestation with a birth weight < 10th centile) and 92 were appropriate-for-gestational-age (AGA) pregnancies, which were included as controls (ratio 1:2). First-to-second trimester longitudinal changes in uterine artery (UtA) Doppler indices and maternal circulating levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed. RESULTS: Compared with the AGA group, SGA pregnancies had significantly higher UtA impedance in the first (Z-score: 0.46 vs -0.57; P < 0.001) and second (Z-score: 1.71 vs -0.75; P < 0.001) trimesters. Likewise, the sFlt-1/PlGF ratio was significantly higher in SGA than in AGA pregnancies in the first (98.0 vs 67.9; P = 0.01) and early second (22.4 vs 8.8; P < 0.001) trimesters. The predictive performance of the longitudinal changes in UtA Doppler indices for SGA was significantly lower than that of second-trimester cross-sectional values (area under receiver-operating characteristics curve (AUC), 60.8% vs 84.3%; P = 0.0035). The detection rate of SGA, at a 10% false-positive rate (FPR), was 17.7% by longitudinal changes in UtA Doppler and 56.2% by second-trimester cross-sectional UtA Doppler values. Similarly, the predictive performance of the longitudinal changes in PlGF was significantly lower than that of early second-trimester cross-sectional values (AUC, 71.4% vs 76.5%; P = 0.008). The detection rate of SGA at a 10% FPR was 40.6% when screening by longitudinal changes in PlGF and 52.1% when screening by early second-trimester cross-sectional values. CONCLUSIONS: First- and second-trimester UtA Doppler velocimetry and maternal circulating angiogenic markers have clinical utility as a cross-sectional assessment for the identification of pregnancies at high risk of delivering a SGA neonate, however, they do not improve prediction when their longitudinal changes are used. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of delivery of small-for-gestational-age neonates and adverse perinatal outcome by fetoplacental Doppler at 37 weeks' gestation.

OBJECTIVE: To explore the predictive capacity of fetoplacental Doppler at 37 weeks' gestation in identifying small-for-gestational-age (SGA) neonates, fetal growth restriction (FGR) and adverse perinatal outcome. METHODS: This was a prospective cohort study of low-risk singleton pregnancies undergoing ultrasound assessment at 37 weeks. At study inclusion, biometry for estimated fetal weight (EFW), and fetoplacental Doppler variables (uterine artery pulsatility index (UtA-PI), cerebroplacental ratio (CPR) and umbilical vein blood flow (UVBF) normalized by EFW) were measured. SGA was defined as a customized birth weight between the 3rd and 10th centiles, and FGR was defined as a birth weight < 3rd centile, according to local standards. Adverse perinatal outcomes included emergency Cesarean section for non-reassuring fetal status, 5-min Apgar score < 7 and neonatal acidosis at birth. RESULTS: A total of 946 pregnancies were included in the study. Of these, 89 (9.4%) were classified as SGA and 40 (4.2%) as FGR, with an overall rate of adverse perinatal outcome of 4.9%. At a fixed 10% false-positive rate (FPR), the detection rate of SGA by EFW, UtA-PI, CPR, UVBF and by a combination of Doppler variables (UtA-PI and CPR) and EFW was 59.2%, 10.5%, 13.7%, 3.2% and 61.0%, respectively. At a fixed 10% FPR, the detection rate of FGR by EFW, UtA-PI, CPR, UVBF and a combination of CPR and EFW centile was 83.3%, 13.9%, 27.8%, 13.9% and 88.6%, respectively. At a fixed 10% FPR, the detection rate of adverse perinatal outcome by EFW, UtA-PI, CPR and UVBF was 19.2%, 9.2%, 23.1% and 16.9%, respectively, while combining EFW with Doppler variables (including CPR and UVBF normalized by EFW) improved the detection rate to nearly 30%. CONCLUSION: In low-risk pregnancies, Doppler evaluation at 37 weeks' gestation did not improve the prediction of SGA and FGR compared with that given by EFW alone, however, combining Doppler variables with EFW improved the prediction of adverse perinatal outcomes given by these parameters alone, although not markedly. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Validation of a first-trimester screening model for pre-eclampsia in an unselected population.

OBJECTIVE: To validate the performance of a previously constructed first-trimester predictive model for pre-eclampsia (PE) in routine care of an unselected population. METHODS: A validation cohort of 4621 consecutive women attending their routine first-trimester ultrasound examination was used to test a prediction model for PE that had been developed previously in 5170 women. The prediction model included maternal factors, uterine artery Doppler, blood pressure and pregnancy-associated plasma protein-A. Model performance was evaluated using receiver-operating characteristics (ROC) curve analysis and ROC curves from both cohorts were compared unpaired. RESULTS: Among the 4203 women included in the final analysis, 169 (4.0%) developed PE, including 141 (3.4%) cases of late-onset PE and 28 (0.7%) cases of early-onset PE. For early-onset PE, the model showed an area under the ROC curve of 0.94 (95% CI, 0.88-0.99), which did not differ significantly (P = 0.37) from that obtained in the construction cohort (0.88 (95% CI, 0.78-0.99)). For late-onset PE, the final model showed an area under the ROC curve of 0.72 (95% CI, 0.66-0.77), which did not differ significantly (P = 0.49) from that obtained in the construction cohort (0.75 (95% CI, 0.67-0.82)). CONCLUSION: The prediction model for PE achieved a similar performance to that obtained in the construction cohort when tested on a subsequent cohort of women, confirming its validity as a predictive model for PE. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester screening with specific algorithms for early- and late-onset fetal growth restriction.

OBJECTIVE: To develop optimal first-trimester algorithms for the prediction of early and late fetal growth restriction (FGR). METHODS: This was a prospective cohort study of singleton pregnancies undergoing first-trimester screening. FGR was defined as an ultrasound estimated fetal weight < 10(th) percentile plus Doppler abnormalities or a birth weight < 3(rd) percentile. Logistic regression-based predictive models were developed for predicting early and late FGR (cut-off: delivery at 34 weeks). The model included the a-priori risk (maternal characteristics), mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). RESULTS: Of the 9150 pregnancies included, 462 (5%) fetuses were growth restricted: 59 (0.6%) early and 403 (4.4%) late. Significant contributions to the prediction of early FGR were provided by black ethnicity, chronic hypertension, previous FGR, MAP, UtA-PI, PlGF and sFlt-1. The model achieved an overall detection rate (DR) of 86.4% for a 10% false-positive rate (area under the receiver-operating characteristics curve (AUC): 0.93 (95% CI, 0.87-0.98)). The DR was 94.7% for FGR with pre-eclampsia (PE) (64% of cases) and 71.4% for FGR without PE (36% of cases). For late FGR, significant contributions were provided by chronic hypertension, autoimmune disease, previous FGR, smoking status, nulliparity, MAP, UtA-PI, PlGF and sFlt-1. The model achieved a DR of 65.8% for a 10% false-positive rate (AUC: 0.76 (95% CI, 0.73-0.80)). The DR was 70.2% for FGR with PE (12% of cases) and 63.5% for FGR without PE (88% of cases). CONCLUSIONS: The optimal screening algorithm was different for early vs late FGR, supporting the concept that screening for FGR is better performed separately for the two clinical forms. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Contingent versus routine third-trimester screening for late fetal growth restriction.

OBJECTIVE: To evaluate the use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population. METHODS: Maternal characteristics, fetal biometry and second-trimester uterine artery (UtA) Doppler were included in logistic regression analysis to estimate risk for late FGR (birth weight < 3(rd) percentile, or 3(rd) -10(th) percentile plus abnormal cerebroplacental ratio or UtA Doppler, with delivery ≥ 34 weeks). Based on the second-trimester risk, strategies for performing contingent third-trimester ultrasound examinations in 10%, 25% or 50% of the cohort were tested against a strategy of routine ultrasound scanning in the entire population at 32 + 0 to 33 + 6 weeks. RESULTS: Models were constructed based on 1393 patients and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At the second-trimester scan, the a-posteriori second-trimester risk (a-posteriori first-trimester risk (baseline a-priori risk and mean arterial blood pressure) combined with second-trimester abdominal circumference and UtA Doppler) yielded an area under the receiver-operating characteristics curve (AUC) of 0.81 (95% CI, 0.74-0.87) (detection rate (DR), 43.1% for a 10% false-positive rate (FPR)). The combination of a-posteriori second-trimester risk plus third-trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI, 0.88-0.96) (DR, 74% for a 10% FPR). Subjecting 10%, 25% or 50% of the study population to third-trimester ultrasound, based on a-posteriori second-trimester risk, gave AUCs of 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.78-0.91) and 0.89 (95% CI, 0.84-0.94), respectively. Only the 50% contingent model proved statistically equivalent to performing routine third-trimester ultrasound scans (AUC, 0.92 (95% CI, 0.88-0.96), P = 0.11). CONCLUSION: A strategy of selecting 50% of the study population to undergo third-trimester ultrasound examination, based on accrued risk in the second trimester, proved equivalent to routine third-trimester ultrasound scanning in predicting late FGR.

Potential impact of maternal vitamin D status on obstetric well-being.

Despite its discovery 100 years ago, vitamin D (VD) has emerged as one of the most controversial nutrients and prohormones of the 21st century. In the past few years, a growing interest in VD has been observed in the biomedical literature due to evidences demonstrating a relevant relationship not only between regulation of calcium and phosphorus homeostasis, but also multiple disease states and low VD status in the population. Indeed, several studies carried out to decipher its role in the body in almost every cell, tissue, and different organs. Recent findings suggested a significant implication of VD in different physiologic processes , such as vascular health, immune function, metabolism, and placental function. In the attempt to focus the attention on effect of VD on female reproductive health, there has been a paucity of data from randomized controlled trials to establish clear beneficial. Human and animal data suggest that low VD status is associated with impaired fertility, endometriosis, and polycystic ovary syndrome. Findings from observational studies show higher rates of preeclampsia, gestational diabetes, preterm birth, and bacterial vaginosis in women with low VD levels. By recent evidences, this review explored the association between maternal VD status and selected effects on maternal, perinatal, and infant health, and the impact of VD supplementation during pregnancy on obstetric well-being.

An integrated model with classification criteria to predict small-for-gestational-age fetuses at risk of adverse perinatal outcome.

OBJECTIVE: To develop an integrated model with the best performing criteria for predicting adverse outcome in small-for-gestational-age (SGA) pregnancies. METHODS: A cohort of 509 pregnancies with a suspected SGA fetus, eligible for trial of labor, was recruited prospectively and data on perinatal outcome were recorded. A predictive model for emergency Cesarean delivery because of non-reassuring fetal status or neonatal acidosis was constructed using a decision tree analysis algorithm, with predictors: maternal age, body mass index, smoking, nulliparity, gestational age at delivery, onset of labor (induced vs spontaneous), estimated fetal weight (EFW), umbilical artery pulsatility index (PI), mean uterine artery (UtA) PI, fetal middle cerebral artery PI and cerebroplacental ratio (CPR). RESULTS: An adverse outcome occurred in 134 (26.3%) cases. The best performing predictors for defining a high risk for adverse outcome in SGA fetuses was the presence of a CPR < 10th centile, a mean UtA-PI > 95th centile or an EFW < 3rd centile. The algorithm showed a sensitivity, specificity and positive and negative predictive values for adverse outcome of 82.8% (95% CI, 75.1-88.6%), 47.7% (95% CI, 42.6-52.9%), 36.2% (95% CI, 30.8-41.8%) and 88.6% (95% CI, 83.2-92.5%), respectively. Positive and negative likelihood ratios were 1.58 and 0.36. CONCLUSIONS: Our model could be used as a diagnostic tool for discriminating SGA pregnancies at risk of adverse perinatal outcome.

Correlation between histological signs of placental underperfusion and perinatal morbidity in late-onset small-for-gestational-age fetuses.

OBJECTIVE: To investigate whether signs of placental underperfusion (PUP), defined as any maternal and/or fetal vascular pathology, confer an increased risk of neonatal morbidity in late-onset small-for-gestational-age (SGA) fetuses with normal umbilical artery (UA) Doppler indices. METHODS: A cohort of 126 SGA singleton fetuses with normal UA Doppler indices that were delivered after 34 weeks' gestation was studied. For each case, the placenta was evaluated histologically for signs of PUP using a hierarchical and standardized classification system. Neonatal morbidity was assessed according to the score calculated from the morbidity assessment index for newborns (MAIN), a validated outcome scale. The independent association between PUP and neonatal morbidity was evaluated using multivariable median regression analysis. RESULTS: In 84 (66.7%) placentae, 97 placental histological findings that qualified as signs of PUP were observed. These PUP cases had a significantly higher incidence of emergency Cesarean section for non-reassuring fetal status (44.1% vs 21.4%, respectively; P = 0.013) and neonatal metabolic acidosis at birth (33.3% vs 14.3%, respectively; P = 0.023), than did those without PUP. The median MAIN score differed significantly between those with PUP and those without (89 vs 0, respectively; P = 0.025). This difference remained significant after adjustment for potential confounders. The proportion of cases with scores indicative of mild to severe morbidity was also significantly higher in the PUP group (31% vs 14.3%, respectively; P = 0.043). CONCLUSION: In late-onset SGA fetuses with normal UA Doppler indices, signs of PUP imply a higher neonatal morbidity. These findings allow the phenotypic profiling of fetal growth restriction among the general population of late-onset SGA.

Impact of maternal under nutrition on obstetric outcomes.

Maternal malnutrition, ranging from under nutrition to over dietary intake before and in the pregnant state, is worldwide problem with significant consequences, not only for survival and increased risk for acute and chronic diseases both in mother and child, but also for economic productivity of individuals in the societies and additional costs on health system. Inter alia, pre-pregnancy underweight and insufficient gestational weight gain are considered as individual risk factors for the occurrence of spontaneous interruption, preterm birth, fetal growth restriction, and hypertensive disorders, strongly associated with poorer perinatal outcome. In a portion of this population, major eating disorders (anorexia and bulimia nervosa), once thought to be rare, but nowadays enlarged due to cultural pressure on the drive for thinness, have been identified as the etiology of an abnormal nutritional condition in developed countries, in contrast to long standing food deprivation in developing countries. Actually, even if without a complete weight management guidance for these selected pregnant women, an appropriate weight gain is recommended during pregnancy. Mainly, therapeutic approach is prevention using specific programs of improving weight before pregnant status. In this article, a review of the literature on selected obstetrical risks associated with maternal underweight has been performed and both the target prevention and management strategies have been described.

Cancer in pregnancy: diagnosis, treatment and neonatal outcome.

The estimated incidence of cancer diagnosed in pregnant women in developed societies is 1:1000 pregnancies. The most common cancers associated with pregnancy are gynecological, breast, hematological, and skin. A multidisciplinary care team is required. Various treatment modalities are used, including surgical intervention, chemotherapy and radiological. The management of the malignant condition should be standardized, similarly to management offered without pregnancy. Hormone therapy and chemotherapy in the first trimester, and radiotherapy are most contra-indicated. The delivery term depends on the date of discovery of cancer, but is beyond 35 weeks of gestation in the majority of cases, to minimize fetal or obstetrical risks. Pregnancy does not have a deleterious effect on the prognosis of cancers generally, but it is often associated with a delay in diagnosis. Malignant disease management and feto-maternal outcome are described in the present review and particular attention is focused on the treatment effects.

[Screening of obesity, overweight and thinness in a children population in Rome, Italy]. / Screening per obesità, sovrappeso e sottopeso in una popolazione in età scolare a Roma, Italia.

AIM: Objective of the study was to estimate the prevalence of obesity, overweight and thinness in a children population in Rome, Italy. METHODS: The study sample was created, after informed consent, in a school in Rome, available to the study project. A total of 595 children (289 males, 306 females), aged between 6 to 19 years, underwent following measurements: height and weight, evaluation of body mass index. RESULTS: A normal BMI was recorded in 73.6% of cases. Morbid obesity, obesity, overweight, and thinness grade 1 and 2 prevalence was 1.2%, 4%, 15.3%, 9.2% and 3.8%, respectively, without statistical differences in both genders, except the prevalence of overweight that resulted statistically significant (11.4% females vs. 19.3% males, P<0.05). Differences in the age groups have been found. About 17.2% and 18.7% of children between 7 to 11 years were overweight and obese and about 33.3% and 26.6% between 6 to 8 years thin grade 1 and 2, respectively. CONCLUSION: The study suggests a prevalence of overweight and obesity in our sample lower than that reported in a recent epidemiological survey carried out on Italy. Attention must be taken to underweight, particularly with regard to the most severe form, as a public health problem for all possible risks correlated. In addition, our study shows the involvement of specific age groups. This finding, if confirmed in a larger population, should be associated with a major attention on specific age groups at risk, in order to plan an appropriate treatment program.

Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion.

OBJECTIVE: This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP). METHODS: In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters. RESULTS: A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p = 0.008). DISCUSSION: Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates. CONCLUSIONS: Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.

Association of Doppler parameters with placental signs of underperfusion in late-onset small-for-gestational-age pregnancies.

OBJECTIVE: To elucidate the association between Doppler parameters and histological signs of placental underperfusion in late-onset small-for-gestational-age (SGA) babies. METHODS: Umbilical, fetal middle cerebral and uterine artery pulsatility indices and umbilical vein blood flow (UVBF), which had been recorded within 7 days prior to delivery, were analyzed from a cohort of SGA singleton pregnancies delivered after 34 weeks' gestation and confirmed as having a birth weight < 10(th) percentile by local standards. In each case, the placenta was histologically evaluated for signs of placental underperfusion using a hierarchical and standardized classification system. The independent association of the Doppler parameters with placental underperfusion was evaluated using logistic regression and decision tree analysis. RESULTS: In 51 cases (53.7%), there were 61 placental histological findings indicative of placental underperfusion. These cases had a significantly higher incidence of Cesarean section for non-reassuring fetal status (52.1% vs 11.9%; P < 0.001) and neonatal metabolic acidosis at birth (21.6% vs 0%; P = 0.001). Significant and independent contributions to the presence of placental underperfusion lesions were provided by increased mean UtA pulsatility index (PI) (P = 0.018; odds ratio (OR) 2 (95% CI, 1.1-3.7)) and decreased UVBF normalized to estimated fetal weight (P = 0.027; OR 0.97 (95% CI, 0.95-0.99)). The combination of both parameters revealed three groups with differing risks for placental underperfusion: normalized UVBF > 82 mL/min/kg (risk 31.3%), normalized UVBF ≤ 82 mL/min/kg and mean UtA-PI ≤ 95(th) percentile (risk 65.5%), and normalized UVBF ≤ 82 mL/min/kg and UtA-PI > 95(th) percentile (risk 94.4%). CONCLUSIONS: In late-onset SGA pregnancies, uterine Doppler and UVBF are surrogates for placental underperfusion. These findings facilitate phenotypic profiling of cases of fetal growth restriction among the general population of late-onset SGA babies.

Impact of overweight and obesity on obstetric outcomes.

Abnormal nutritional status is an increasingly common complication in developed countries and, as reproductive age women are a part of this trend, the effect of maternal obesity on the pregnancy and neonate must be investigated. Pregestational obesity or overweight condition or an excessive gestational weight gain can be an independent risk factor for feto-maternal complications and long-term risks in adult life for the fetus. The selected risks include infertility, miscarriage, congenital anomalies, hypertensive disorders, gestational diabetes, intrauterine fetal death, macrosomia, and delivery complications. From an etiological point of view, the causes of the adverse outcomes include maternal body habitus, proinflammatory state of obesity, and metabolic dysfunction. Actually, a weight management guidance for obese pregnant women is limited, recommending a gain between 5 and 9 kg during the pregnancy period, while weight loss is discouraged. Mainly, therapeutic approach is prevention using specific programs of reducing weight before pregnant status. In addition, mechanistic studies, in animal models especially, have identified potential areas for intervention which might limit adverse risk factors for obesity from mothers to infants during pregnancy. In this article, a review of the literature on selected obstetrical risks associated with maternal overweight and obesity has been performed and both the target prevention and management strategies have been assessed.

Placental findings in late-onset SGA births without Doppler signs of placental insufficiency.

OBJECTIVES: To describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. METHODS: A series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation. RESULTS: A total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161). DISCUSSION: In most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease. CONCLUSIONS: A significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency.