FIGO (International Federation of Gynecology and Obstetrics) initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction

Fetal growth restriction (FGR) is defined as the failure of fetus to meet its potential due a pathological factor, most commonly placental dysfunction. Worldwide, FGR leading cause stillbirth, neonatal mortality, and short- long-term morbidity. Ongoing advances in clinical care, especially definitions, diagnosis, management FGR, require efforts effectively translate these changes wide range obstetric care providers. This article highlights agreements based on current research diagnosis areas that need more provide further clarification recommendations. The purpose this comprehensive summary available evidence along with practical recommendations concerning pregnancies at risk or complicated by overall goal decrease stillbirth mortality morbidity associated condition. To achieve goals, FIGO (the International Federation Gynecology Obstetrics) brought together international experts review summarize knowledge FGR. directed multiple stakeholders, including healthcare providers, delivery organizations member societies, professional organizations. Recognizing variation resources expertise for different countries regions, attempts take into consideration unique aspects antenatal low-resource settings (labelled “LRS” recommendations). was achieved collaboration authors societies from such India, Sub-Saharan Africa, Middle East, Latin America. Aspects addressed include prediction, investigation, management, postpartum counselling. main are given below summarized Table 1 (section 8) algorithms high-resource (Figure 1a) 1b) 4). stakeholders intention bringing attention assessment fetal growth, particular focus screening, which proposes standardize guidance prevention, intended target audience includes: Healthcare providers: all those qualified pregnant women (obstetricians, maternal-fetal medicine specialists, general practitioners, midwives, nurses, advance practice clinicians, radiologists, sonographers, pediatricians, neonatologists). governments, federal state legislators, organizations, health insurance development agencies, nongovernmental Professional organizations: international, regional, national obstetricians gynecologists, ultrasound, family neonatologists, worldwide dedicated their offspring. In assessing quality grading strength recommendations, follows terminology proposed Grading Recommendations, Assessment, Development Evaluation (GRADE) Working Group.5 system uses consistent language graphical descriptions they based. Recommendations classified strong conditional (weak) (Table S1).6 recommendation dependent not only evidence, but also factors risk–benefit, cost, resource allocation, values, preferences. Thus, some may be low-quality still represent benefit outweighs risks burdens, therefore strongly recommended. assessed each expressed using four levels quality: very low, moderate, high S2).7 Considerations primarily study design methodology. As such, randomized controlled trials considered high-quality observational studies moderate low others low. However, other parameters must while level evidence: bias, limitations, consistency results, precision, publication indirectness scarcity evidence. For cross-filled circles used: ???? denotes evidence; ???? quality; ???? ???? common pregnancy complication morbidity.8-15 definition, optimal have generated controversy clinicians strive harmonized care. regarding early prediction monitoring, timing complication. Given monitoring we included, addition standard “best” specific settings, marked tables. Management Figure 1a,b, respectively. Clinically, reflected drop size percentiles over course gestation. difficult determine, serial assessments detect weight percentile usually available. Instead, providers “snapshot” estimation point time. Therefore, practice, small gestational age (SGA), estimated (EFW) abdominal circumference certain threshold 10th 3rd percentile, used suspect use SGA proxy has several limitations recognized. First, fetuses constitutionally healthy fetuses, whose smallness merely result predetermined (i.e. false-positive FGR). Second, growth-restricted depending original insult, remain above described thus false-negative Third, limited accuracy sonographic estimation, an error up ±15%–20%. Finally, highly chart being used, can considerable effect proportion infants flagged population. It should noted there inconsistency literature above, where term describe infant birth age. article, indicate EFW age, refer failed because pathologic process. major follow definition means diagnosing fetus, then leads testing, assessment, follow-up. There proposals address validity reduction adverse outcomes needs tested. example, attempt overcome consensus-based placenta-mediated been via Delphi procedure.1 likelihood consensus combination measures (fetal circumference) abnormal Doppler findings umbilical, uterine, middle cerebral arteries, Box 1. implementation lack define circumference. addition, needed correlate perinatal outcomes. Early-onset (<32 weeks) Late-onset (?32 Abbreviations: AC, circumference; AREDV, absent reversed end-diastolic velocity; CPR, cerebroplacental ratio; EFW, weight; PI, pulsatility index; UA, umbilical artery; UtA, uterine artery. Adapted Gordijn et al.1 suggested broadly classified, time early-onset late-onset weeks). rationale underlying classification differences between two phenotypes severity, natural history, findings, association hypertensive complications, management.16-18 prevalence 0.5%–1%, severe, likely artery than pathology frequently similar observed cases pre-eclampsia (maternal vascular malperfusion), explains pre-eclampsia. easier detect, history tends predictable sequence ductus venosus. challenge delivery), attempting determine balance opposing prematurity.19 5%–10%. contrast it milder, less pre-eclampsia, normal Doppler. regard delivery) relatively simple made during late-preterm periods, small. mainly relies adaptive circulation (“redistribution” “brain-sparing effect”), resistance flow thereby generating ratio, section 8.1.7. venosus sudden decompensation stillbirth.16, 19 often one maternal, placental, disorders interfere mechanisms regulating growth.20, 21 etiologies listed 2. important note confusion “etiologies” (or pathogenetic pathways) “risk factors” although maternal conditions chronic hypertension, kidney disease, systemic lupus erythematosus, long-standing diabetes “maternal etiologies” probably viewed instead placentation nutrition closely related,22, 23 undernutrition worldwide.24-26 impact depends severity.20 date, interventions dietary advice modifications lacked significant success preventing While anemia contribute unclear, both impaired nutrient transport 27 adaptation hemoglobin 28 mechanisms. Abnormal 29 diagnosed ultrasound 30 typical histopathological findings.31-33 Chromosomal abnormalities 5% cases; triploidy trisomy 13 18 considerations many aneuploidies higher presence structural anomalies.34-36 1%–6% karyotype, submicroscopic (micro) duplications/deletions found chromosomal microarray analysis,35 even when apparently isolated finding.37 prevalent malformations, increases anomalies present.38 related intrauterine infection cases.20, 39 Viral agents rubella, cytomegalovirus, HIV, Zika causes infection-related FGR.40-44 Protozoan infections like toxoplasmosis malaria another cause, endemic areas.45, 46 mechanism involved pathogenesis decline cell population.20 exposure teratogens radiation,47 illicit drugs,48, 49 alcohol50 etiology 3. complications. devastating stillbirth,51-53 well-established inverse relationship stillbirth,54-57 pronounced preterm period term.58 iatrogenic birth,59 remains perhaps strategy prevention severe FGR.16, 60 independent factor spontaneous birth.61 Other complications abruption, pathophysiology related.29, 30, 62-66 Despite ongoing improvements increased short-term reported five- 10-fold appropriately grown neonates.57, 61, 67 severity abnormalities, prematurity predictors complications.68 Among infants, co-presence prematurity-related respiratory morbidity, intraventricular hemorrhage, necrotizing enterocolitis, metabolic disorders.57 cord pH,69 Apgar score,69 hypoglycemia, hypothermia, jaundice.70-72 Growth-restricted neurodevelopmental impairment 11, 73-78 noncommunicable diseases.15, 79-82 discussed greater detail 9.1 (Infant follow-up). Early identify who preventive close pregnancy. 4 lists predictive value individual models combinations outlined considerably improve One limitation gold postnatal among predicted, either (birth percentile) (but to) healthy, differentiating critically important. rule, better restriction; PlGF, factor; PAPP-A, pregnancy-associated plasma protein-A; AFP, alpha-fetoprotein. aRefers dimension (short-based thick placenta) texture (calcifications, echogenic cystic lesions). Several influence FGR: advanced racial/ethnic origin (e.g. South Asian), consanguinity, body mass index, nulliparity, recreational drugs alcohol, assisted reproductive technology, medical mellitus, autoimmune (Box 4).83-89 Cigarette smoking reduces average 200 g dose–response manner.90 cohort 33 602 pregnancies, characteristics predicted 37% subsequently delivered neonates <5th rate 10%.83 Some relevant countries. recent were nutritional status, HIV infection, malaria, diseases. Based concluded large extent Africa preventable through established undernutrition.42 lactation toxic environmental chemicals heavy metals become growing problem, countries.91 At no role routine screening serum biomarkers biochemical markers part prenatal genetic 21, reasonable information stratification placenta releases stages pregnancy, first-trimester shown subsequent complications.92, 93 Low protein-A (PAPP-A), glycoprotein produced syncytiotrophoblast layer, SGA. A meta-analysis 32 175 240 PAPP-A 5th had (OR 2.08, positive 18%), stronger 1st 3.4; 28%).94 majority will outcome, biomarker women. indication closer growth.95 Elevated second-trimester alpha-fetoprotein thought reflect permeability stillbirth.96, 97 first trimester second particularly FGR.98 human chorionic gonadotropin (hCG) 2.5 MoM trimester, alone combined levels, SGA.99 Angiogenic play key regulation development.100 Placental (PlGF) proangiogenic endothelium. Impaired reduced production protein. PlGF outcome SGA.101-104 case–control 296 609 controls, detection 10% 15% 21%, 19% 27%, respectively.103 multicenter factors, biometry, 19–24 weeks 32, 32–36, equal 37 gestation 100%, 76%, 38%, respectively, 10%.96 Findings soluble fms-like tyrosine kinase-1 (sFlt-1), antiangiogenic released results endothelial dysfunction characteristic pre-eclampsia.105 Although sFlt-1 known elevated pre-eclamptic demonstrated 10–14 actually slightly 0.92; 95% CI, 0.88–0.96).101 sFlt-1:PlGF ratio test diagnose FGR.106 ultrasound-based Doppler, morphology, volumes. modest accuracy, cannot recommended universal Increased largely reflects extravillous cytotrophoblast invasion transformation spiral arteries malperfusion placenta.107 First- waveforms, mean index 95th FGR.108-110 prospective 4610 nulliparous women, 11+0 13+6 60% 17% 10%.111 shows promise, does support low- high-risk pregnancies.112 Sonographic evaluation examination. method systematic two-dimensional (2D) examination described, 113, 114 morphology dimensions, shape, texture, insertion. shape thickness cm 50% length. homogenous, heterogeneous contains lesions jelly-like appearance turbulent uteroplacental flow.115, 116 insertion central (>2 disc margin), marginal (within 2 velamentous (inserting surrounding membranes).114 19–23 odds 4.7) shape.108 2D imaging difficulty nonanterior placentas variability placentas. Furthermore, large-scale validating modality FGR.114 Improvements ultrasonographic tool estimating volume three- four-dimensional scanning techniques. marker various defective function, FGR.117, 118 3D 24.7% rate.119 Another parameter quotient, crown–rump quotient negative useful low-risk population, sensitivity 27.1%.120 discriminatory ability appears modest, integrated multivariable model. proper equipment training required obtain measurements reproducible manner. Currently single sufficiently recommend use. Investigations underway combine tests, validated terms investigative protocols 4970 beta hCG, blood pressure, performed 73% (<34 32% late (?34 weeks).19 model included characteristics, evaluated larger 9150 86% 66% 10%.19, 121 SCOPE consortium examined 5606 singleton 15-week (53 used), 20-week biometry arteries) 91%.122 Ideally, plan adopting lifestyle optimizing any index. preconception provides opportunity promotion aim reducing accepted FGR.123 Insufficient gain (BMI, calculated kilograms divided height meters squared).124 associations data, believe would informing range, 2009 Institute Medicine guidelines.125 These guidelines total 12.5–18 kg (28–40 lb) underweight (BMI <18.5); 11.5–16 (25–35 group 18.5–24.9); 7–11.5 (15–25 overweight 25.0–29.9); 5–9 (11–20 obese ?30).126 Substance use, smoking, drugs, mortality.90 Interventions promote cessation (RR 0.81) increase (+33 g).127 Women advised benefit, greatest before 15 pregnancy.128 alcohol intake little drink per day.129 Most focused extrapolated pathophysiology. modifications, prevent clearly established. 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