NFOG - The Nordic Federation of Obstetrics and Gynecology



Intrauterine growth restrictionUltrasonographic measurement of the fetal head, abdomen and femur length should be used to estimate fetal weight and growth where there are identified risk factors for, or suspected growth restriction (strong recommendation). Doppler examination of the umbilical artery flow velocity waveform should be used to diagnose placental cause of intrauterine growth restriction and to guide of clinical management (strong recommendation). An overall assessment where the maternal condition, fetal age, weight and growth, amniotic fluid volume, CTG with short variability (STV) and Doppler evaluation included should be done (strong recommendation) Delivery should be considered when absent (34 weeks) or reversed (32 weeks) end diastolic blood flow in the umbilical artery (ARED) (strong recommendation).Give maternal corticosteroids betamethasone (Celestone Chronodose?) where delivery is planned ≤ week 33 + 6 (strong recommendation)Consider giving magnesium sulfate by preterm birth ≤ 31 weeks + 6? (suggestion)Low dose aspirin (75mg) should be given as prophylactic treatment from early pregnancy (12 weeks gestation) where there is moderate or high risk of preeclampsia (recommendation)Litterature:Pyramidesearch, UpToDate, The Cochrane Library, National Guideline Clearinghouse, Clinical guidelines (US), Royal College of Obstetricians and Gynaecologists (British guidelines), Clinical Guidelines (Canadian), Danish guidelines (dsog.dk), Pubmed.DefinitionsAGA (Appropriate for gestational age) estimated fetal weight (EFW) by ultrasound biometry between 10-90 percentile. SGA (small for gestational age): EFW less than expected in relation to gestational age (EFW <10 percentile or weight deviation> ÷ 14%). IUGR (intrauterine growth restriction, intrauterine growth retardation) involves slow growth by serial measurements. A fetus can be both AGA and have IUGR. Where IUGR is suspected or confirmed Doppler examination of the umbilical artery (UA) can be applied to assess placental insufficiency as the cause of slow growth(1). Approximately ?- ? of fetuses who are SGA are constitutionally small and are not IUGR. It is essential to apply adequate reference values for biometrics and EFW in the assessment of fetal size and growth(2-5), and be aware of the methods strengths and limitations in estimating fetal weight and growth. A precise assessment of the gestational age is a prerequisite for later assessment of weight and growth.OccurrenceCa. 10-15% of all pregnancies evaluated for slow fetal growth.Etiology and risk factors IUGRBoth genetic and environmental factors are decisive for fetal growth. Causes may be divided into fetal, placental, maternal, in one case several factors may be involved.Fetal causes: Multiple births, chromosome abnormalities, deformities, infections (toxoplasmosis, rubella, CMV herpes simplex, syphilis).Placental: Abnormal placentation, infarcts, abnormal umbilical cord attachment, bleeding in pregnancy.Maternal: Preeclampsia, previously given birth to neonate with IUGR or intrauterine death, chronic illness in the mother (hypertension, chronic obstructive pulmonary disease, collagenosis, diabetes mellitus, thrombophilia, kidney disease, anemia), drugs (cytostatics, steroids), high maternal age (> 40 years)(6), mother born with low birthweight (7) nutritional deficiencies, uterine malformations, smoking, substance abuse.Distinguish between early (<34 weeks) and late plicationsGrowth restriction is associated with increased risk of perinatal morbidity and mortality, and may have long term health implications. Also neurological development seems to be influenced by growth restriction(15).Diagnosis, monitoring, treatment and prophylaxisDiagnosticsGoalsClarify whether there are maternal conditions that can be treated, clarify whether the fetus is a healthy SGA fetus or an IUGR fetus,schedule monitoring of pregnancy, consider intervention measures before (preterm) birth (betamethasone (Celeston?)).IndicationIdentified risk factor (s), low symphysis-fundus (SF) measurements, or that mother feel less fetal movements , or is of the opinion that her uterus is small. Suspected small fetus at ultrasound examination.Low SF measurement refers to that one SF measurement after week 24 is below the green field at the reference curve (helsekort for gravide). By non- or stunted growth by the SF measurement, the woman should be referred for an ultrasound examination (recommendation). The SF measurement method has a substantial intra- and inter-observer variability and low sensitivity (but better specificity) to identify SGA fetuses. The threshold for referring to ultrasound should be low (8).With less fetal movements we mean that mother feels less fetal movements than she has done earlier in pregnancy. If substantial and sustained reduction in fetal movements despite adequate time and concentration, we suggest that the next maternity or out clinic should offer examination of the woman(9 10). There is insufficient evidence to recommend routine counting of fetal movements to avoid intrauterine death in an unselected population(11 12).Examinations? Medical history, blood pressure and urine examination and control of gestational age determination? Fetal biometry and assessment of growth:Biometry: head size (HC), abdominal circumference (AC) and femur length (FL) and estimation of fetal weight (EFW) using formulas (13-15). Another approach is to measure biparietal diameter (BPD) and middle abdominal diameter (MAD), and calculate weight deviation percentage (10 percentile = -14% weight deviation, 5 percentile: -20% weight deviation 2.5 percentile = -22% weight deviation).Assessment of growth: both a former and current weight estimate are included in the assessment of growth(16).If risk factors are identified: we suggest Doppler examination of the uterine arteries (UTA) at approximately gestation 22-24. If UTA Doppler normal is normal we suggest estimation of growth in the 3rd trimester, If the UTA Doppler is pathological we suggest monitoring of growth and Doppler examinations every 4 weeks or more frequent.? Evaluation of amniotic fluid volume (amniotic fluid index (AFI) or deepest vertical pocket (DVP)), fetal movements and fetal anatomy is recommended. Oligohydramnios when AFI <5 cm or DPV <2cm (17). By anatomical abnormalities, severe early IUGR, or polyhydramnios fetal karyotype and infection serological examination may be appropriate(18).Doppler examination of the umbililcal artery (UA) is recommended. This improves precision in the diagnosis of IUGR(19) and clinical management guided by UA Doppler reduces the number of interventions (induction or cesarean) and the risk of perinatal death(1).? In early severe IUGR we suggest monitoring with extended feto-maternal Doppler Evaluation (inkl.UA, middle cerebral artery (MCA), ductus venosus (DV), vena umbilicalis(20-21) (UV)) and CTG with short variability (CTG STV) (22). In order to find the optimal time of delivery the MCA Doppler has limited predictive value ( severe early IUGR), while changes in the MCA Doppler in to a more pathological pattern may be a sign of worsening the fetal condition and suggests shorter monitoring intervals. In severe early IUGR DV Doppler and CTG with STV should guide the clinician in timing the delivery.? Late IUGR less pronounced changes are seen in the UA and DV Doppler, while MCA Doppler and cerebro-placental ratio (MCA PI / UA PI), UTA Doppler, amniotic fluid volume and CTG with STV are useful in timing of delivery (23-27).Suggested follow-up and treatment depend on gestational ageAn individual assessment where all information about maternal comorbidities, risk factors, previous findings, gestational age and development over time is recommended. Current understanding suggests delivery if testing indicates that the risk of fetal death exceeds the risk of neonatal death (death resulting from prematurity). Between gestational week 26-29, each day intrauterine improve neonatal survival by 1-2% (20). By preterm birth before 33 weeks+ 6 days betamethasone (Celeston?) 12 mg intramuscularly in two days is recommended to promote lung maturation and reduce neonatal death and morbidity(28). Magnesium sulphate given before preterm birth is shown to have neuroprotective effect; fewer children getting cerebral palsy. There is still lack of evidence about the optimal treatment regimen (dose and therapeutic window), and the effect on fetuses with IUGR has not been studied (29).The table below is a suggestion for the handling of IUGR pregnancies by gestational age, but individual adaptation must always be done. In early and severe IUGR, the care should be given by an obstetrician with fetal medicine expertise and in a department with neonatal intensive care unit service.Gestational week 24+0-33+6Week 34-36+6Week >37AU PI og MCA PI normal:Growth and Doppler assessment after 2 weeks.In severe IUGR with normal Doppler: specialist fetal medicine examination is suggested.AU PI og MCA PI normal: Growth and Doppler assessment after 2 weeks.AU PI normal: MCA-Doppler, amniotic fluid amount, CTG with STV.Hvis MCA PI<5 percentile, CPR<1 and/or anomalous CTG consider delivery.Delivery should be considered if EFW <5 percentile (induction before GA 40+2PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlBpbGxpb2Q8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA 24;26), or oligohydramnios or reduced growth (<10-percentile, or increased growth deviation). If observation is chosen; intensive monitoring is indicated(11).AU PI >95 percentile:We suggest to discuss the case with a fetal medicine specialist.Extended feto-maternal Doppler evaluation including amniotic fluid, and CTG with STV.If STV ≤3,0 ms consider delivery.AU PI >95 percentile: Add MCA-Doppler, amniotic fluid amount and CTG: If normal, reassess in 1 week.If MCA PI<5 percentile or CPR <1.0 and/or oligohydramnios: extended feto-maternal Doppler evaluation, CTG with STV 2 times/week. Consider delivery if extended Doppler assessment or CTG abnormal. AU PI >95 percentile: MCA-Doppler, amniotic fluid amount, and CTG. Delivery should be considered if MCA PI <5 percentile or CPR <1 and/or oligohydramnios or abnormal CTG.AU ARED: Extended feto-maternal Doppler evaluation every 2.-3. Day. CTG with STV dailyMaternal Betametason 12 mg intra-musckul?rt in 2 days. In DV absent/reversed A-wave, UV pulsations, or STV ≤3.0 ms consider delivery. AU ARED: CTG and delivery. AED (no positive diastolic flow), CTG and consider delivery.AU ARED (rare at GA> 37 weeks): CTG and delivery is recommended.Absolute delivery indications in IUGR? CTG changes: pre-terminal pattern, complex variable or uniform decelerations, STV ≤ 3.0 ms(22)? Pathological DV Doppler (reversed or no positive blood flow in the A-wave) Gestational age> 26-28 weeks (30)? UA Doppler with reversed blood flow in diastole (ARED) by week 32, no positive diastolic blood flow in the UA (AED) by week 34 (31,32)? When EFW ≤400 and gestational age <26 weeks, the clinician should in consultation with the woman, her partner and neonatologists discuss further conservative management and vaginal delivery? Estimated fetal weight <5 percentile and (certain) gestational age ≥40+ 2 weeksDelivery method? From week 34-36 weeks may fetuses with abnormal UA PI, but positive diastolic blood flow try vaginal delivery with adequate monitoring, if maternal history and fetal condition allows it. Oligohydramnios and changes in MCA, CPR or pathological UTA involve greater risk for asphyxia and acute cesarean delivery (23,27,33)? When UA ARED before 34 weeks delivery is usually done by cesareanRecurrence risk and prophylaxisBy IUGR we suggest pathological examination of the placenta. There is an increased risk of recurrence of IUGR in a subsequent pregnancy (34). Planning of the next pregnancy is recommended, with investigation of the woman, and early dating of a new pregnancy with ultrasound is suggested (35; 36). Monitoring with ultrasound which includes evaluation of growth and Doppler every 4 weeks or more frequent is suggested. At high or moderate risk of preeclampsia development a low-dose aspirin (75 mg orally daily) from 12 weeks gestation is suggested, as this reduces the risk of developing preeclampsia and IUGR (37).ReferencesAlfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev 2010;(1):CD007529.Ioannou C, Talbot K, Ohuma E, Sarris I, Villar J, Conde-Agudelo A et al. Systematic review of methodology used in ultrasound studies aimed at creating charts of fetal size. BJOG 2012; 119(12):1425-1439.Hutcheon JA, Zhang X, Cnattingius S, Kramer MS, Platt RW. Customised birthweight percentiles: does adjusting for maternal characteristics matter? BJOG 2008; 115(11):1397-1404.De Jong CL, Francis A, Van Geijn HP, Gardosi J. Customized fetal weight limits for antenatal detection of fetal growth restriction. Ultrasound Obstet Gynecol 2000; 15(1):36-40.Mongelli M, Gardosi J. Reduction of false-positive diagnosis of fetal growth restriction by application of customized fetal growth standards. Obstet Gynecol 1996; 88(5):844-848.Odibo AO, Nelson D, Stamilio DM, Sehdev HM, Macones GA. Advanced maternal age is an independent risk factor for intrauterine growth restriction. Am J Perinatol 2006; 23(5):325-328.Magnus P, Bakketeig LS, Skjaerven R. Correlations of birth weight and gestational age across generations. Ann Hum Biol 1993; 20(3):231-238.Robert PJ, Ho JJ, Valliapan J, Sivasangari S. Symphysial fundal height (SFH) measurement in pregnancy for detecting abnormal fetal growth. Cochrane Database Syst Rev 2012; 7:CD008136.Froen JF, Heazell AE, Tveit JV, Saastad E, Fretts RC, Flenady V. Fetal movement assessment. Semin Perinatol 2008; 32(4):243-246.Flenady V, MacPhail J, Gardener G, Chadha Y, Mahomed K, Heazell A et al. Detection and management of decreased fetal movements in Australia and New Zealand: a survey of obstetric practice. Aust N Z J Obstet Gynaecol 2009; 49(4):358-363.Saastad E, Winje BA, Stray PB, Froen JF. Fetal movement counting improved identification of fetal growth restriction and perinatal outcomes--a multi-centre, randomized, controlled trial. PLoS One 2011; 6(12):e28482.Mangesi L, Hofmeyr GJ. Fetal movement counting for assessment of fetal wellbeing. Cochrane Database Syst Rev 2007;(1):CD004909.Johnsen SL, Rasmussen S, Wilsgaard T, Sollien R, Kiserud T. Longitudinal reference ranges for estimated fetal weight. Acta Obstet Gynecol Scand 2006; 85(3):286-297.Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study. Am J Obstet Gynecol 1985; 151(3):333-bs CA, Jaekle RK, Rosenn B, Pope M, Miodovnik M, Siddiqi TA. Sonographic Estimation of Fetal Weight Based on A Model of Fetal Volume. Obstet Gynecol 1993; 82(3):365-370.Johnsen SL, Wilsgaard T, Rasmussen S, Sollien R, Kiserud T. Longitudinal reference charts for growth of the fetal head, abdomen and femur. Eur J Obstet Gynecol Reprod Biol 2006; 127(2):172-185.Chauhan SP, Sanderson M, Hendrix NW, Magann EF, Devoe LD. Perinatal outcome and amniotic fluid index in the antepartum and intrapartum periods: A meta-analysis. Am J Obstet Gynecol 1999; 181(6):1473-1478.Snijders RJ, Sherrod C, Gosden CM, Nicolaides KH. Fetal growth retardation: associated malformations and chromosomal abnormalities. Am J Obstet Gynecol 1993; 168(2):547-555.Divon MY. Diagnosis of fetal growth restriction. www uptodate com [ 2012 [cited 2012 Oct. 1]; Available from: URL: Baschat AA, Cosmi E, Bilardo CM, Wolf H, Berg C, Rigano S et al. Predictors of neonatal outcome in early-onset placental dysfunction. Obstet Gynecol 2007; 109(2 Pt 1):253-261.Morris RK, Selman TJ, Verma M, Robson SC, Kleijnen J, Khan KS. Systematic review and meta-analysis of the test accuracy of ductus venosus Doppler to predict compromise of fetal/neonatal wellbeing in high risk pregnancies with placental insufficiency. Eur J Obstet Gynecol Reprod Biol 2010; 152(1):3-12.Serra V, Moulden M, Bellver J, Redman CW. The value of the short-term fetal heart rate variation for timing the delivery of growth-retarded fetuses. BJOG 2008; 115(9):1101-1107.Hershkovitz R, Kingdom JC, Geary M, Rodeck CH. Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2000; 15(3):209-212.Boers KE, Vijgen SM, Bijlenga D, van der Post JA, Bekedam DJ, Kwee A et al. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BMJ 2010; 341:c7087.Oros D, Figueras F, Cruz-Martinez R, Meler E, Munmany M, Gratacos E. Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in late-onset small-for-gestational age fetuses. Ultrasound Obstet Gynecol 2011; 37(2):191-195.Pilliod RA, Cheng YW, Snowden JM, Doss AE, Caughey AB. The risk of intrauterine fetal death in the small-for-gestational-age fetus. Am J Obstet Gynecol 2012; 207(4):318-6.Severi FM, Bocchi C, Visentin A, Falco P, Cobellis L, Florio P et al. Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2002; 19(3):225-228.Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006;(3):CD004454.Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009;(1):CD004661.Bilardo CM, Wolf H, Stigter RH, Ville Y, Baez E, Visser GHA et al. Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction. Ultrasound Obstet Gynecol 2004; 23(2):119-125.Resnik R. Fetal growth restriction: evaluation and management. www uptodate com [ 2012 [cited 2012 Nov. 2]; Available from: URL: Arcangeli T, Thilaganathan B, Hooper R, Khan KS, Bhide A. Neurodevelopmental delay in small babies at term: a systematic review. Ultrasound Obstet Gynecol 2012; 40(3):267-275.Prior T, Mullins E, Bennett P, Kumar S. Prediction of intrapartum fetal compromise using the cerebroumbilical ratio: a prospective observational study. Am J Obstet Gynecol 2013; 208(2):124-126.Bakketeig LS, Hoffman HJ, Harley EE. The tendency to repeat gestational age and birth weight in successive births. Am J Obstet Gynecol 1979; 135(8):1086-1103.Kirkegaard I, Henriksen TB, Uldbjerg N. Early fetal growth, PAPP-A and free beta-hCG in relation to risk of delivering a small-for-gestational age infant. Ultrasound Obstet Gynecol 2011; 37(3):341-347.Shah PS, Shah V. Influence of the maternal birth status on offspring: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 2009; 88(12):1307-1318.Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010; 116(2 Pt 1):402-414. ................
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