Twin twin transfusion syndrome with and without selective fetal growth restriction: Predictors of donor demise.

OBJECTIVE: Evaluate survival in twin twin transfusion syndrome (TTTS) with and without selective fetal growth restriction (sFGR) after fetoscopic laser surgery (FLS). METHODS: Retrospective study of monochorionic diamniotic twins undergoing FLS. The cohort was classified as TTTS and TTTS with sFGR. Baseline, intra-operative and postoperative variables were analyzed. Mann-Whitney U, Pearson chi-square, Fisher's exact, t-test and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Four hundred and ninety-two pregnancies were included, 304 (61.78%) TTTS and 188 (38.22%) TTTS with sFGR. No difference in donor outcomes. TTTS group had higher donor estimated fetal weight (EFW%) percentile (19.7 ± 18.8 vs. 2.2 ± 2.1, p < 0.001). Significant predictors for demise at 30 days were 37% intertwin weight discordance (IWD) with donor EFW% < first (area under ROC curve [AUC] = 0.85, p = 0.001) or IWD >25% and intertwin umbilical artery pulsatility index discordance (DUAPI) ≥0.4 (AUC = 0.71, p = 0.001). CONCLUSION: Combination of IWD of 37% and donor EFW%

The relationship between placental characteristics and birthweight discordance in different types of selective intrauterine growth restriction in monochorionic diamniotic twins: A single-center 7 year cohort study.

OBJECTIVE: To clarify the relationships between placental characteristics and birthweight discordance in three types of selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic twins. METHODS: A retrospective cohort study was conducted between april 2013 and april 2020. Associations between placental characteristics and birthweight discordance were evaluated through multiple linear regression analyses with two models for each sIUGR type. Model A was adjusted for gestational age, Model B additionally adjusted for the impact of placental characteristics interacted. RESULTS: In cases of type I sIUGR, birthweight discordance ratio was positively associated with placental territory discordance ratio [(ß = 0.181,95%CI(0.072,0.290), p < 0.05), (ß = 0.239,95%CI(0.125, 0.353), p < 0.05)] under both Model A and Model B. In-type II sIUGR [(ß = -0.012,95%CI(-0.020, -0.004), p < 0.05) (ß = -0.010,95%CI (-0.018, -0.002), p < 0.05)] and type III sIUGR [(ß = -0.011,95%CI (-0.021, -0.001), p < 0.05), (ß = -0.012,95%CI(-0.022, -0.003), p < 0.05)], birthweight discordance ratio was negatively associated with the total diameter of all the anastomoses as calculated with both Model A and Model B. CONCLUSION: Birthweight discordance is primarily related to placental territory discordance in type I sIUGR, whereas vascular anastomoses play important roles for growth-restricted fetal compensation in type II and III sIUGR.

[Unadjusted and customized fetal growth curves: a comparative study in a sub-Saharan population]. / Courbes de croissance fœtale non ajustées et personnalisées: une étude comparative dans une population du Sud du Sahara.

The purpose of this study was to compare the unadjusted EPOPé M0 curve with the customized Gardosi curve in the diagnosis of small-for-gestational-age (SGA) fetuses in a sub-Saharan population. We compared the Gardosi et al. and EPOPé M0 classifications. Classification differences were analyzed according to patient characteristics and obstetric conditions. Data collected from FileMaker software were analyzed using SPSS 20.0 and R Studio software. The statistical tests were carried out according to applicability conditions. Alpha risk was set at 0.05. The Gardosi curve showed that the rate of SGA newborns was higher (31.4% versus 28.9%) and did not differ between overweight and normal-weight women. The rate of severe SGA in preterm infants was also higher (23.6 versus 19.7%). Diseases were more frequent in newborns classified as severe SGA by the customized growth curve. The customized curve is recommended for the sub-Saharan Africa population.

Intrauterine growth retardation (IUGR) as determinant and environment as modulator of infant mortality and morbidity: the Tanjungsari Cohort Study in Indonesia.

BACKGROUND AND OBJECTIVES: Intrauterine growth retardation (IUGR) is related to mortality and morbidity. However, defining IUGR by suitable field methods remains a challenge. A maternal-child Risk-Approach- Strategy (during 1988-1989) and follow-on Tanjungsari Cohort Study (TCS) (1989-1990), aimed to generate a practical classification of IUGR and explore its usage in predicting growth, mortality and morbidity of infants in the cohort. STUDY DESIGN: Some 3892 singleton live-birth infants were followed. IUGR was defined by birth weight (BW) and length (BL) classified as: acute, chronic, non-IUGR or 'probably preterm'. Growth, mortality, and survival curve were calculated to prove that the classification identified the most vulnerable infants. Fever >3 days and diarrhoea were assessed based on IUGR classification, sex, exclusive breastfeeding, and environmental factors. RESULTS: IUGR infant weight and length did not catch-up with the non-IUGR in the first year. Infant mortality rate was 44.7 per 1000 where some 61% died within 90 days. Using age specific mortality by BW, 23.6% of all deaths occurred when it was <2500 g compared to 66.2% from IUGR and preterm groups. Fever and diarrhoea rates increased over 12 months. Diarrhoea was associated with poor source-of-drinking-water and latrine. CONCLUSION: The IUGR classification predicted one-year growth curves and survival, besides age and sex. IUGR based on BW and BL identified a larger group of at-risk infants than did low BW. High morbidity rates were partly explained by poor environmental conditions. IUGR inclusive of BL has value in optimizing nutritional status in the first 1000 days of life.

Prediction of adverse pregnancy outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction.

OBJECTIVE: To identify key factors associated with adverse perinatal outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction (sFGR). METHODS: This was a retrospective cohort study of all monochorionic diamniotic twin pregnancies diagnosed with sFGR at ≥ 16 weeks' gestation, in a single tertiary referral center between March 2000 and May 2015. The presence of coexisting twin-twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including those of the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow in the UA of the smaller twin. DV pulsatility indices for veins (DV-PIV) were converted to Z-scores and estimated fetal weight values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome, which was defined according to survival and included both intrauterine fetal demise and neonatal death of the FGR twin. RESULTS: We analyzed 104 pregnancies, of which 66 (63.5%) were diagnosed with Type-I and 38 (36.5%) with Type-II sFGR at initial presentation. In pregnancies complicated by Type-II sFGR, the diagnosis of sFGR was made earlier than in those complicated by Type-I sFGR (mediam GA, 19.6 vs 21.5 weeks; P = 0.012), and Type-II sFGR was associated with increased risk of adverse perinatal outcome (intrauterine demise of the smaller twin, 34.2% vs 10.6%; P = 0.004). Twin pregnancies complicated by sFGR resulting in perinatal demise had a significantly earlier diagnosis (P = 0.002) and lower birth-weight centile of the smaller twin (P < 0.01), those with Type-I sFGR had earlier GA at delivery (P = 0.007) and those with Type-II sFGR had higher DV-PIV Z-score of the smaller twin (P = 0.003), when compared with pregnancies resulting in live birth. Coexisting TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR (P > 0.05 for both). Earlier GA at diagnosis (hazard ratio (HR), 0.70 (95% CI, 0.56-0.88); P = 0.002), Type-II sFGR (HR, 3.53 (95% CI, 1.37-9.07); P = 0.008) and higher DV-PIV Z-score (HR, 1.36 (95% CI, 1.12-1.65); P = 0.001) were significantly associated with increased risk of adverse perinatal outcome of the smaller twin. CONCLUSIONS: Pregnancies complicated by Type-II sFGR are diagnosed significantly earlier and are associated with increased risk of adverse perinatal outcome compared with those with Type-I sFGR. Coexisting TTTS has no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR. Earlier GA at diagnosis, Type-II sFGR and higher DV-PIV Z-score are associated significantly with increased risk of adverse perinatal outcome of the smaller twin. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

[Preeclampsia: New Classifications]. / Präeklampsie: neue Definitionen.

Preeclampsia: New Classifications Abstract. Preeclampsia is a multisystem disease leading to systemic impairment of the maternal endothelial function. A dysbalance of pro- and antiangiogenic factors appears to be significantly involved. The vascular disease leads to the manifestation of symptoms such as arterial hypertension and involvement of end organs such as kidney, liver and brain. The classical diagnostic criterion for arterial hypertension, 'proteinuria' has been downgraded and is no longer obligatory for diagnosis, if other criteria, as maternal organ dysfunction or intrauterine growth retardation, are present. In addition, white-coat hypertension has been included in the classification of hypertension in pregnancy. To classify preeclampsia as 'mild' is being discouraged in the clinical setting to account for the possibility of rapid worsening with significant danger for mother and foetus.

Fetal growth restriction in twins.

Twin pregnancies are more likely to be affected by fetal growth restriction (FGR), preterm birth and perinatal loss. The management of fetal growth restriction in multiple pregnancy, particularly where only one fetus is affected is complicated by the need to consider the interests of both twins. Selective growth restriction in monochorionic (MC) twins is a pathophysiological process distinct from FGR in dichorionic (DC) pregnancies and management demands an understanding of the monochorionic placental structure and interdependent fetal circulations. The introduction of fetal therapy has introduced a range of potential interventions for the antenatal management of sFGR including selective fetal reduction and laser photocoagulation of the placental communicating vessels. This review summarizes up to date evidence on diagnosis, classification and management of sFGR and considers research directions likely to be of benefit in the future.

Variation in the definition of intrauterine growth restriction in routine antenatal care: a physician survey among gynecologists in Northwest Germany.

OBJECTIVE: To assess how intrauterine growth restriction (IUGR) is defined by gynecologists in routine practice. MATERIALS AND METHODS: We surveyed primary care gynecologists in Bremen and Lower Saxony, Northwest Germany, between January and July 2014. Descriptive statistics were used to analyze the data; consensus was considered as 90% agreement among the respondents. Multiple logistic regression models were performed for the associations between respondents' background characteristics and choice of the small for gestational age (SGA) cutoff values. RESULTS: Overall, 185 primary care gynecologists participated in the survey. Consensus was only observed in two items: (1) an accurate determination of gestational age (91%) and (2) repeated measurement of the abdominal circumference (91%). Umbilical artery Doppler (76%) and repeated ultrasonography (76%) were the most frequently used methods to confirm suspected IUGR diagnoses, but different responses prevailed. Notably, only 46% of the respondents opted for the 10th percentile of estimated fetal weight as a cutoff for SGA classification, which is the internationally recommended value. CONCLUSIONS: The results of this survey indicate considerable practice variation regarding detection and management of IUGR pregnancies. There is a need for better agreement in terminology and definition of core aspects of IUGR in antenatal care.

Caracterización de las embarazadas con restricción del crecimiento intrauterino en el servicio de ginecología y obstetricia del hospital central del instituto de previsión social, 2017 / Characterization of pregnant women with intrauterine growth restriction in the gynecology and obstetrics service of the central hospital of the social security institute, 2017

Introducción: Se considera restricción de crecimiento intrauterino al crecimiento fetal menor que el esperado para la edad gestacional. Asociado con un aumento de 6-10 veces de riesgo de muerte perinatal. Cada año nacen en el mundo más de 20 millones de niños con peso inferior a 2.500 gramos; de ellos, más del 96 % en países en desarrollo, lo cual demuestra que esta situación se asocia a condiciones socioeconómicas de pobreza. La prevalencia en Latinoamérica oscila entre el 10 a 17% de los nacidos vivos. Objetivo: Caracterizar a las embarazadas con restricción del crecimiento intrauterino en el Servicio de Ginecología y Obstetricia del Hospital Central del Instituto de Previsión Social, del año 2017. Materiales y métodos: Estudio observacional descriptivo de corte transversal. Fueron incluidas todas las embarazadas con restricción de crecimiento intrauterino que acudieron al Servicio de Ginecología y Obstetricia del Hospital Central de Instituto de Previsión Social del año 2017. Resultados: Fueron 42 embarazadas con restricción de crecimiento intrauterino. Con rango etario de 20 a 42 años, la mediana de 28 años, el 54,76% casadas, el 84,10% proceden del área urbana, y el 52,38% con estudio superior, la mitad eran multigestas, nulíparas sin antecedentes de aborto previo, el 59,62% realizaron más de 5 controles prenatales. El antecedente patológico materno más frecuente fue anemia en el 66,67%. En su mayoría con un índice de masa corporal normal, y moderada ganancia de peso materno durante el embarazo. El 81,25% son de tipo asimétrico, con diámetro biparietal y circunferencia abdominal disminuidos. Conclusión: Este estudio realizado en un centro de referencia nacional de cuarto nivel, similar a resultados de trabajos anteriores, aporta datos actuales sobre las características de las embarazadas con restricción de crecimiento intrauterino.

IMAGe and Related Undergrowth Syndromes: The Complex Spectrum of Gain-of-Function CDKN1C Mutations.

CDKN1C is a cyclin-dependent kinase Inhibitor and negative regulator of cellular proliferation. Recently, gain-of-function mutations in the PCNA domain of CDKN1C have been reported as the genetic basis of various growth-retarded syndromes including IMAGe syndrome, Russell Silver syndrome as well as a novel undergrowth syndrome that additionally exhibited early adulthood onset diabetes. This review summarizes the key clinical features and the molecular advances that have contributed to our understanding of this complex phenotypic spectrum.

Maternal serum ferritin as a clinical tool at 34-36 weeks' gestation for distinguishing subgroups of fetal growth restriction.

OBJECTIVE: To compare maternal ferritin levels across pregnancies with fetal growth restriction including SGA and IUGR compared to appropriate for gestational age (AGA). METHODS: Three groups were enrolled: AGA, SGA (birth weight below 10th percentile for gestational age with no placental insufficiency findings), and IUGR (birth weight below 5th percentile for gestational age accompanied by abnormal umbilical artery Doppler waveforms and/or oligohydramnios). Maternal serum ferritin samples were obtained at gestational weeks 34 through 36, and delivery occurred at or beyond 36 weeks. RESULTS: A total of 126 pregnancies with AGA (36%), SGA (40%), and IUGR (24%) were enrolled. The mean maternal serum ferritin level was higher in the IUGR group than in the AGA group (59 µg/l versus 32.5 µg/l, p < 0.001). A maternal serum ferritin cutoff of 48 µg/l was found to be optimal for distinguishing between IUGR and AGA with a sensitivity of 67.7%, specificity of 92%, PPV of 84%, NPV of 82%, diagnostic accuracy of 82.7%, LR + of 8 and LR- of 0.3, respectively. CONCLUSION: Maternal serum ferritin levels differ in pregnancies with IUGR. The role of maternal serum ferritin measurements as a clinical tool for distinguishing different forms of fetal growth restriction warrants further investigation.

Clustering and classical analysis of clinical and placental phenotypes in fetal growth restriction and constitutional fetal smallness.

This study aims to determine whether placental examination can be used to distinguish between pathologic fetal growth restriction (FGR) and constitutional fetal smallness. Data were extracted from a clinicoplacental database of high risk pregnancies during the period 1994-2013. These data were used to compare the 590 consecutive cases having birth weights below the 10th percentile with the 5201 remaining cases having gestational ages ≥20 weeks. The authors analyzed 20 clinical and 46 placental phenotypes using classical statistics, clustering analysis, and multidimensional scaling. Of the low-birth-weight babies, the following types of cases were compared: Four categories of placental phenotypes (those with features of poor uteroplacental perfusion, postuterine placental pathology, chronic inflammation, and a mixed category) better defined the presumably true FGR than did the clinical phenotypes. Maternal smoking and oligohydramnios were associated with fewer abnormal placental phenotypes than were maternal hypertensive diseases and abnormal Dopplers. Early-onset cases of fetal smallness clustered with placental features of poor uteroplacental perfusion, whereas late onset cases did not. Placental examination helps to retrospectively distinguish constitutionally small fetuses from those that are pathologically growth restricted. The latter correlate best with the clinical risk for FGR and with early-onset FGR. This correlation may have prognostic significance for the child and for future pregnancies, since hypoxic placental lesions can occur without clinical risk factors but with a tendency to recur in future pregnancies.

Consensus definition of fetal growth restriction: a Delphi procedure.

OBJECTIVE: To determine, by expert consensus, a definition for early and late fetal growth restriction (FGR) through a Delphi procedure. METHOD: A Delphi survey was conducted among an international panel of experts on FGR. Panel members were provided with 18 literature-based parameters for defining FGR and were asked to rate the importance of these parameters for the diagnosis of both early and late FGR on a 5-point Likert scale. Parameters were described as solitary parameters (parameters that are sufficient to diagnose FGR, even if all other parameters are normal) and contributory parameters (parameters that require other abnormal parameter(s) to be present for the diagnosis of FGR). Consensus was sought to determine the cut-off values for accepted parameters. RESULTS: A total of 106 experts were approached, of whom 56 agreed to participate and entered the first round, and 45 (80%) completed all four rounds. For early FGR (< 32 weeks), three solitary parameters (abdominal circumference (AC) < 3(rd) centile, estimated fetal weight (EFW) < 3(rd) centile and absent end-diastolic flow in the umbilical artery (UA)) and four contributory parameters (AC or EFW < 10(th) centile combined with a pulsatility index (PI) > 95(th) centile in either the UA or uterine artery) were agreed upon. For late FGR (≥ 32 weeks), two solitary parameters (AC or EFW < 3(rd) centile) and four contributory parameters (EFW or AC < 10(th) centile, AC or EFW crossing centiles by > two quartiles on growth charts and cerebroplacental ratio < 5(th) centile or UA-PI > 95(th) centile) were defined. CONCLUSION: Consensus-based definitions for early and late FGR, as well as cut-off values for parameters involved, were agreed upon by a panel of experts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Restricción del crecimiento intrauterino: una aproximación al diagnóstico, seguimiento y manejo / Intrauterine growth restriction: an approach to diagnosis, monitoring and management

ANTECEDENTES: La restricción del crecimiento intrauterino (RCIU) es una entidad de origen multifactorial que puede ser causada por una gran variedad de patologías a nivel materno, fetal o placentario, y que representa altas tasas de morbimortalidad materna y perinatal. Es importante realizar un diagnóstico certero de esta patología con el fin de llevar a cabo un enfoque de seguimiento y de manejo que pueda disminuir todas las complicaciones asociadas a la enfermedad. OBJETIVO: Realizar una revisión detallada y actualizada de la etiopatogenia, criterios diagnósticos, seguimiento con ecografía Doppler y manejo de la restricción del crecimiento intrauterino. MÉTODO: Se realizó una búsqueda de literatura publicada en inglés y español en bases de datos como PubMed/MEDLINE, Ovid, MDconsult utilizando las palabras clave: restricción del crecimiento intrauterino, feto pequeño para la edad gestacional, circulación fetal, ecografía Doppler, además de la búsqueda de estadísticas relacionadas con RCIU, de los resultados obtenidos se seleccionaron 61 artículos. La información obtenida fue clasificada y utilizada como soporte para la realización de esta revisión. RESULTADOS: Se presentan los estudios disponibles, las revisiones y artículos recomendados para la evaluación de pacientes con RCIU, adicionalmente aquellos que brindan nueva información con respecto al diagnóstico, evaluación de circulación fetal, seguimiento y manejo de esta entidad clínica. CONCLUSIÓN: La restricción del crecimiento intrauterino es una patología que presenta altas tasas de morbimortalidad perinatal. La identificación temprana de estos fetos y el seguimiento adecuado mediante la evalución Doppler permiten disminuir los resultados adversos y las secuelas a corto y largo plazo.

BACKGROUND: Intrauterine growth restriction has a multifactorial origin and can be caused by a variety of pathologies in the mother, fetus or placenta, representing high rates of maternal and perinatal morbidity and mortality. Therefore, it is important to accurately diagnose this condition in order to focus in the follow and management, which can reduce the complications associated with the disease. OBJECTIVE: To perform a detailed and up to date review of the etiology, diagnostic criteria, follow up with Doppler ultrasonography and management of intrauterine growth restriction. METHODS: A literature search was done in English and Spanish in databases such us PubMed/MEDLINE, Ovid, MDconsult using the following key words: intrauterine growth restriction, small for gestational age fetus, fetal circulation, Doppler ultrasonography. Also national statistics for intrauterine growth restriction were used, obtaining 61 documents. The information obtained was classified and used in the development of this review. RESULTS: The available studies are presented, and recommended revisions to the evaluation of patients with IUGR, additionally those that provide new information regarding the diagnosis, evaluation of fetal circulation, monitoring and management of this clinical entity. CONCLUSION: Intrauterine growth restriction is a pathology with a frequent diagnosis an represents high rates of perinatal morbidity and mortality. Early identification of these fetuses and adequate monitoring by Doppler evaluation allow reducing adverse outcomes and consequences in the short and long term.

Gestational age and fetal growth assessment among obstetricians.

OBJECTIVE: We aimed to characterize gestational age assessment and fetal growth evaluation among obstetricians. METHODS: Observational, cross-sectional study. We applied a questionnaire to obstetrics specialists and residents, during a national congress on obstetrics. RESULTS: Almost all 179 respondents correct gestational age in the first trimester by ultrasound, but 63% only if there is a difference of 2-9 days. Ultrasound at 11-13 weeks was considered more accurate than at 8-10 weeks by 81%, with a higher proportion of specialists choosing correctly the last answer (p = 0.05). One-third of the respondents did not correctly point the error associated with the ultrasound estimation of fetal weight (EFW). Of the 88% who use a growth table, only 32% were able to identify it by publication/author. Ninety-eight percent identify fetal growth restriction risk (FGR) with centiles (10th in 76%) and 73% of doctors diagnose FGR without other pathological findings (10th in 49%). 44% finds that a low EFW centile maintenance (4th to 3rd) is more worrisome than the crossing of two quartiles (75th to 24th). CONCLUSIONS: The role of ultrasound in gestational age assessment and use of EFW use for FGR classification was disparate among participants. EFW and respective centiles may be over relied upon.

Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol.

Small fetuses are defined as those with an ultrasound estimated weight below a threshold, most commonly the 10th centile. The first clinically relevant step is the distinction of 'true' fetal growth restriction (FGR), associated with signs of abnormal fetoplacental function and poorer perinatal outcome, from constitutional small-for-gestational age, with a near-normal perinatal outcome. Nowadays such a distinction should not be based solely on umbilical artery Doppler, since this index detects only early-onset severe forms. FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio, uterine artery Doppler, a growth centile below the 3rd centile, and, possibly in the near future, maternal angiogenic factors. Once the diagnosis is established, differentiating into early- and late-onset FGR is useful mainly for research purposes, because it distinguishes two clear phenotypes with differences in severity, association with preeclampsia, and the natural history of fetal deterioration. As a second clinically relevant step, management of FGR and the decision to deliver aims at an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. We propose a protocol that integrates current evidence to classify stages of fetal deterioration and establishes follow-up intervals and optimal delivery timings, which may facilitate decisions and reduce practice variability in this complex clinical condition.

[Systemic production of cytokines and growth factors in various forms of syndrome of delayed fetal growth].

The syndrome of delayed fetal growth (SDFG) is one of the most wide-spread pathological conditions while course of pregnancy; it is characterized by disorder of the feto-placental system function. Its incidence is from 3 to 8%. The studying of peculiarities of the system and local immune disorders, coinciding with SDFG, would permit to establish the immune mechanisms of its formation. Revealing of immunoregulation disorders on systemic and local levels would promote the creation of a concept, depicting participation of the immune system in formation of asymmetrical and symmetrical forms of SDFG, to elaborate new approaches for prognosis and diagnosis.