Fetal growth restriction and small for gestational age

• Antenatal SGA is defined as an estimated fetal weight (EFW) <10^th centile.
• Isolated antenatal SGA is defined as an EFW 3^rd-9^th centile with normal uterine and umbilical artery Doppler waveforms.
• EFW centiles should be calculated using customised centile standards. Customised centiles for Aotearoa are available at GROW-App NZ and are incorporated into the BadgerNet platform where these tools are available.

• FGR is defined using a combination of fetal size, fetal growth and Doppler assessment.

• Early-onset FGR is diagnosed <32⁺⁰ weeks gestation with:

  - Abdominal circumference (AC) or customised EFW <3^rd centile OR

  - Umbilical artery Doppler waveform with absent or reversed end-diastolic flow (EDF) OR
  - AC or customised EFW 3^rd-9^th centile and one or more of: umbilical artery Doppler Pulsatility Index (PI) >95^th centile, mean uterine artery Doppler PI >95^th centile or bilateral notching (uterine artery Doppler to be performed only once at time of diagnosis).

• Late-onset FGR is diagnosed ≥32⁺⁰ weeks gestation with:

  - AC or customised EFW <3^rd centile OR

  - Two or more of: AC or customised EFW 3rd-9th centile, slowing fetal growth (see below) or, any abnormal Doppler waveform (umbilical artery Doppler PI >95^th centile, cerebroplacental ratio (CPR) <5^th centile or uterine artery mean PI >95^th centile or bilateral notching (uterine artery Doppler to be performed only once at time of diagnosis).

• Severe FGR is diagnosed when customised EFW <3^rd centile.

• Slowing of fetal growth is defined as a decline in AC or customised EFW trajectory >30 centiles from 28⁺⁰ weeks gestation.

• Follow the Preterm risk assessment and antenatal surveillance Algorithm adapted from Te Whatu Ora SGA and FGR In Aotearoa New Zealand clinical practice guideline.

• A health history for all wāhine/people in early pregnancy (<12 weeks) should include a clinical risk assessment for FGR.

  • Risk factors for early-onset FGR (<32 weeks gestation) are:

  - Previous FGR with birth <32 weeks gestation

  - Previous hypertensive disorder of pregnancy with birth <34 weeks gestation

  - Chronic hypertension

  - Renal impairment

  - Antiphospholipid syndrome

  - Diabetes with vascular disease

  - Previous stillbirth.

• Major risk factors (≥2 fold increased) for FGR are:

  - Previous FGR

  - Previous hypertensive disorder of pregnancy

  - Chronic hypertension

  - Renal impairment

  - Antiphospholipid syndrome

  - Diabetes with vascular disease

  - Previous stillbirth

  - Wahine/person age ≥40 years (nulliparous)

  - Continued smoking ≥16 weeks gestation and >10 cigarettes per day

  - Drug use

  - Heavy bleeding in current pregnancy <20 weeks.

• Minor risk factors (<2 fold increased) for FGR are:

  - Nulliparity

  - Wahine/person age ≥40 years (multiparous)

  - Continued smoking ≥16 weeks gestation and 1-10 cigarettes per day

  - Pregnancy interval <6 months

  - Pregnancy interval >5 years

  - Conception through assisted reproduction

  - BMI ≥30 kg/m²

  - BMI <18.5 kg/m²

• Biomarkers such as placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), pregnancy-associated plasma protein-A (PAPP-A) are not recommended as screening tools.

• Uterine artery Doppler is not recommended as a screening tool for the general population.

• Integrated risk assessments (combinations of clinical risk factors, biomarkers and early pregnancy ultrasound parameters) are not recommended as screening tools for FGR.

• Uterine artery Doppler should be performed at 20-24 weeks gestation for wāhine/people with risk factors for early onset FGR.
• Uterine artery Doppler assessment should include mean pulsatility index (PI) and presence/absence of diastolic notching.
• The Obstetric Doppler for preterm SGA/FGR and preeclampsia assessment Standard Operating Procedure has adapted the Wāhi Rua New Zealand Maternal Fetal Medicine Network Obstetric Doppler Guideline 2014⁸ to provide information on how to perform uterine artery Doppler assessment and includes gestational age specific reference table for the 95^th centile.

• Pregnancy periconception lifestyle advice should include information on healthy diet, regular moderate activity, and entering pregnancy with a healthy BMI (18.5 – 24.9 kg/m²).

• Wāhine/people considering pregnancy should be advised to supplement their preconception diet with daily folic acid 800 mcg.

• Wāhine/people should be encouraged and enabled to book with a Lead Maternity Carer early in pregnancy (<12 weeks gestation) to allow timely risk assessment and referral.

• Referral for an obstetric consultation should be recommended and made for wāhine/people with major risk factors for FGR (Consultation referral code 3023).¹⁷
• Where possible referral should be prior to <16⁺⁰ weeks for wāhine/people with previous FGR pregnancy and previous hypertensive disorder of pregnancy requiring birth <34 weeks gestation.¹⁷
• Obstetric consultation should include advice on lifestyle changes, aspirin (and calcium) use and ultrasound surveillance plan.

• Wāhine/people who smoke cigarettes in early pregnancy should be advised to become smokefree by 15⁺⁰ weeks gestation to reduce their FGR risk to non-smoking status, and that smoking cessation at any gestation is beneficial.
• Wāhine/people who smoke cigarettes in pregnancy should be offered referral to local smoking cessation programmes.
• Smoking cessation resources and programmes should focus on engaging young wāhine/people and wāhine Māori.
• Incentive-based smoking cessation programmes are most likely to be successful.
• Nicotine replacement therapy (patches, lozenges or gum) should be considered to support smoking cessation in pregnancy as part of an overall programme including an incentive-based approach.
• Electronic nicotine delivery systems (e-cigarettes and vaping) may be considered as an aid to stop cigarette smoking. Vaping is likely to be less harmful than cigarette smoking but it is not harmless.²⁰ Less is known about the effects of vaping on FGR (and other pregnancy outcomes). The goal should be for complete cessation of all nicotine-containing products.

• Wāhine/people using drugs including cannabis, cocaine and metamphetamine should be advised and supported to become drug free as early as possible in pregnancy.
• Wāhine/people using drugs in pregnancy should be offered referral to local drug support programmes and provided with resources explaining the impact of non-prescribed drug use on pregnancy.

• Wāhine/people with the following risk factors for FGR should be recommended and prescribed aspirin:

  - Previous FGR

  - Previous hypertensive disorder of pregnancy

  - Chronic hypertension

  - Diabetes with vascular disease

  - Renal impairment

  - Antiphospholipid syndrome.

• Aspirin should be prescribed as 100 mg dose taken at night/evening.

• Aspirin should be commenced between 12⁺⁰ to 16⁺⁶ weeks (there may still be benefit from starting after 16 weeks and up to 20⁺⁰ weeks for prevention of preterm birth in wāhine/people at risk of preeclampsia but not SGA/FGR).

• Aspirin should be continued to 36⁺⁰ weeks gestation.

• Aspirin should be prescribed by obstetric services whenever possible.

• Midwives or primary care providers may prescribe aspirin to allow commencement within the therapeutic window. It is recommended that midwives make a referral to the local obstetric service (as per Te Whatu Ora Guidelines for Consultation)¹⁷ including identification of the indication for offering aspirin. Written response from the obstetric service should confirm the recommendation for aspirin and this should be included in the wāhine/person’s health record.

• Heparin and low molecular weight are not recommended for the prevention of FGR for wāhine with or without major risk factors.

• Follow the Preterm risk assessment and antenatal surveillance Algorithm adapted from Te Whatu Ora SGA and FGR In Aotearoa New Zealand clinical practice guideline.

• Wāhine/people with no major or ≤2 minor risk factors for FGR should not be offered routine ultrasound for fetal growth assessment.
• All wāhine/people with no major or ≤2 minor risk factors for FGR should have serial fundal height assessment at each antenatal visit, plotted on a customised fundal height chart starting from 26-28 weeks gestation using the GROW-App NZ which is incorporated into the BadgerNet platform where these tools are available. Measurements should be at least two weeks apart.
• If the plotted fundal height is <10^th centile or if fundal height declines >30 centiles, wāhine/people should be referred for ultrasound for fetal growth assessment.

• Wāhine/people with ≥1 risk factor for early-onset FGR should have a monthly ultrasound scan for fetal growth assessment starting at 24-26 weeks gestation until birth.

• Wāhine/people with ≥1 major risk factor for FGR should have a monthly ultrasound scan for fetal growth assessment starting at 28-30 weeks gestation until birth.

• Ultrasound scans for fetal growth assessment should include plotting of fetal biometry measurements on an Australasian Society of Ultrasound Medicine Chart (electronically if possible, as has been incorporated into the BadgerNet platform) and routinely report abdominal circumference (AC) centile.

• Ultrasound scans for fetal growth assessment should include calculation of estimated fetal weight (EFW) using the Hadlock three or four parameter formulae and report a EFW centile, wherever possible this should be customised centile. Reports should state the method of calculation of EFW and centile used (customised or population).

• A customised antenatal centile chart should be supplied to the scan provider by the referrer (included in the referral or carried by the wāhine/person).

• Where possible, electronic plotting is recommended to improve accuracy and reduce transcription errors.

• Where an ultrasound provider does not report a EFW customised centile, it is the lead maternity carer’s responsibility to calculate this.

• When ultrasound growth assessment confirms SGA or FGR is suspected (slowing of growth), the following Doppler waveforms should be performed:

  - Uterine artery Doppler (mean pulsatility index (PI) and presence/absence of diastolic notching). Uterine artery Doppler is only required at the time of diagnosis

  - Umbilical artery Doppler (PI and reported as normal/>95th centile/absent/reversed end diastolic flow [EDF])

  - Middle cerebral artery (MCA) Doppler (PI to allow calculation of cerebroplacental ratio [CPR] but only reporting CPR) if ≥32⁺⁰ weeks gestation.

  - Ductus venosus Doppler (PI and presence/absence/reversal of the ‘a’ wave) if <32⁺⁰ weeks gestation.

• Use the Obstetric Doppler for Preterm SGA/FGR and preeclampsia assessment Standard Operating Procedure adapted from the Wāhi Rua New Zealand Maternal Fetal Medicine Network Obstetric Doppler Guideline 2014⁸, on how to perform uterine artery, umbilical artery, middle cerebral artery and ductus venosus Doppler assessment and calculation of CPR. This includes gestational age specific reference tables.

• Follow the Management of preterm FGR/SGA (<37⁺⁰ weeks) Algorithm adapted from Te Whatu Ora SGA and FGR In Aotearoa New Zealand clinical practice guideline.

The lead maternity carer or primary maternity service provider is responsible for:

• Confirming gestational age. This should be estimated by known last menstrual period and confirmed by ultrasound at 12⁺⁰ to 13⁺⁶ weeks gestation (± seven days). Confirmation of gestational age should form part of first trimester combined screening and an earlier ‘dating’ scan is not routinely required (perform if last menstrual period date is unknown, previous ectopic pregnancy or early pregnancy clinical concerns).

• Considering risk factors for placental-mediated FGR, including those that may have developed during pregnancy.

• Considering non-placental causes for FGR including review of first trimester combined screening, second trimester serum screening and non-invasive prenatal testing (NIPT) if performed and review of fetal anatomy and placental location and morphology report.

• Recommending and making referral for all wāhine/people with SGA/FGR for an obstetric consultation (Consultation referral codes 4048/4049/4051).¹⁷

  - Umbilical artery Doppler with absent or reversed EDF requires same day referral and urgent in-patient management.

  - Umbilical artery Doppler with forward EDF but abnormal PI >95^th centile requires same day referral for specialist review.

  - Normal umbilical artery Doppler waveform but customised EFW <3^rd centile, uterine artery Doppler PI >95^th centile and/or bilateral diastolic notches or CPR <5^th centile if ≥32⁺⁰ weeks requires referral for specialist review within one week.

• Recommending a transfer of clinical responsibility where there is a risk of birth <28⁺⁰ weeks gestation and/or birthweight <1000g (code 4050).¹⁷

• Referring and/or discussing with the local Fetal Medicine service if early onset FGR (<32⁺⁰ weeks) or if FGR is associated with polyhydramnios or fetal malformation regardless of gestation.

Obstetric services are responsible for:

• Further considering causes of FGR (placental and non-placental) including serology for congenital infection in early-onset and severe FGR including cytomegalovirus (CMV) (IgG and IgM), rubella (if non-immune or status unknown), syphilis, and toxoplasmosis (IgG and IgM). Lead maternity carers may be requested to order these tests as part of the referral pathway.
• Developing a plan in consultation with the wahine/person and the Lead Maternity Carer for ongoing surveillance and timing of birth.

Fetal Medicine services are responsible for:

• Detailed consideration of non-placental causes of FGR including assessment for familial genetic conditions, parental consanguinity and infection risk, tertiary level anatomy survey, serology for congenital infection if not already completed.
• Offering amniocentesis for genetic testing by microarray and infection testing by polymerase chain reaction (PCR).
• Guidance as requested by general obstetric services on timing of birth in very early onset FGR <28⁺⁰ weeks.
• Management of FGR resulting from fetal causes, which should be individualised depending on cause (e.g. chromosomal, genetic, infectious).

• Monitoring and surveillance after SGA/FGR is diagnosed depend on severity and gestational age.
• For FGR with absent/reversed EDF umbilical artery Doppler and once the limit of survival is reached – ultrasound for umbilical artery and ductus venosus Doppler and amniotic fluid volume should be performed 2-3 times per week, growth scan every two weeks, CTG (ideally computerised CTG) twice daily.
• For FGR with forward EDF umbilical artery Doppler <32⁺⁰ weeks - ultrasound for umbilical artery Doppler and amniotic fluid volume should be performed at least weekly, growth scan every two weeks.
• For FGR with forward EDF umbilical artery Doppler ≥32⁺⁰ weeks - ultrasound for umbilical artery and MCA Doppler with calculation of CPR and amniotic fluid volume should be performed twice weekly, growth scan every two weeks, CTG (ideally computerised CTG) twice weekly.
• For isolated SGA at all gestations - ultrasound for growth, umbilical artery Doppler, and amniotic fluid volume should be performed every two weeks. At ≥32⁺⁰ weeks MCA Doppler with calculation of CPR should be included.

• Wāhine/people with FGR are also at risk of developing preeclampsia and should have regular blood pressure monitoring included in surveillance.

• Appropriate and timely preparation to optimise outcomes for pēpi should be made when preterm birth is planned or considered likely.
• Wāhine/people with FGR at risk of birth <28⁺⁰ weeks and/or EFW <1000g should be transferred to a hospital with a Level 3 neonatal unit.
• Wāhine/people with FGR at risk of birth 28⁺⁰ – 32⁺⁰ weeks should have transfer to a hospital with a Level 3 neonatal unit discussed (dependent on local level of NICU care).
• Wāhine/people with FGR with absent/reversed EDF umbilical artery Doppler should be managed as in-patients once the limit of survival is reached.
• Antenatal corticosteroids should be administered as for any other preterm birth when gestational age is ≤34⁺⁶ weeks and birth is planned or anticipated within the next seven days, even if birth is likely within 24 hours.
• Indications for corticosteroids in FGR include absent/reversed EDF umbilical artery Doppler, ductus venosus Doppler with absent or reversed ‘a’ wave, or an abnormal CTG.
• FGR with forward EDF umbilical artery Doppler (normal or abnormal PI) is not an indication for corticosteroid use unless there are additional clinical concerns/indication.
• Repeat corticosteroid doses/courses should be administered as for other indications of repeat doses when gestational age is ≤32⁺⁶ weeks, when 7-14 days since previous corticosteroid and preterm birth is anticipated or planned within the next seven days, even if birth is likely within the next 24 hours, to a maximum of three single weekly repeat doses OR one repeat course of two doses.
• Indications for repeat corticosteroid use in FGR include persistent absent/reversed EDF umbilical artery Doppler, ductus venosus Doppler with absent or reversed ‘a’ wave, or an abnormal CTG.
• Magnesium sulphate should be administered as for any other preterm birth when gestational age is <30⁺⁰ weeks and birth is planned for FGR, and is ideally given for at least four hours prior to birth.
• Birth should not be delayed to allow time for corticosteroid or magnesium sulphate administration if the delay would be detrimental to the immediate wellbeing of the wahine/person and/or pēpi.

• Follow the Management of preterm FGR/SGA (<37⁺⁰ weeks) Algorithm adapted from Te Whatu Ora SGA and FGR In Aotearoa New Zealand clinical practice guideline.

• Timing of planned preterm birth is dependent on gestational age, severity of FGR and fetal wellbeing (determined by Doppler waveforms and CTG).

For early-onset FGR <32 weeks, indications to plan preterm birth are:

• Computerised CTG/CTG changes

  - short term variability (STV) <2.6 ms at 26⁺⁰ to 28⁺⁶ weeks

  - STV <3 ms at 29⁺⁰ to 31⁺⁶ weeks

  - persistent spontaneous decelerations at any gestation.

• Ductus venosus changes

  - absent or reversed ‘a’ wave at any gestation.

• Umbilical artery Doppler

  - reversed EDF at ≥32⁺⁰ weeks (consider after 30⁺⁰ weeks)

  - absent EDF at ≥34⁺⁰ weeks (consider after 32⁺⁰ weeks).

• Wahine/person indications including severe preeclampsia and HELLP syndrome.

For late-onset FGR ≥32 weeks indications to plan preterm birth are:

• Any indication for birth with early-onset FGR (see above).

• Umbilical artery Doppler with forward flow but PI >95^th centile may be considered after 36⁺⁰ weeks.

• Computerised CTG/CTG changes

  - STV <3.5 ms at 32⁺⁰ to 33⁺⁶ weeks

  - STV <4.5 ms at 34⁺⁰ to 36⁺⁶ weeks.

• Abnormal CPR and/or abnormal uterine artery Doppler alone are not indications for preterm birth.

• Mode of birth should be individualised depending on the severity of FGR, Doppler waveform indices, amniotic fluid volume and gestational age.

• Caesarean section is recommended when there are severe Doppler waveform abnormalities such absent/reversed EDF in the umbilical artery Doppler, ductus venosus Doppler with absent/reversed ‘a’ wave or an abnormal CTG (low STV or persistent decelerations) (and when at the limits of survival, a plan for survival-focused care has been made).

• The utility of cord blood sampling and placenta investigations should be discussed with wāhine/people and whānau.

• Placental histological examination should be recommended to contribute information that may affect care of the preterm pēpi and/or māmā/person, and for management of future pregnancies, including counselling on the chance of recurrence.

• Placental histopathology should be reported using the Amsterdam Workshop Consensus Criteria²³ to support identification of placental pathologies with high recurrence rates.

• All wāhine/people should be provided with individualised counselling on the chance of recurrence of preterm FGR, FGR (and preeclampsia) with consideration of specific risk factors, severity of FGR, gestational age at birth, any co-existing preeclampsia and placental histopathology results.

• All wāhine/people should be advised on their increased chance of developing longer-term health conditions such as cardiovascular, metabolic and renal disease, throughout life which may be higher after preterm (than term) FGR.

• Primary care providers should offer longer-term health and wellbeing advice and recommend regular lifelong screening for conditions such as hypertension, hypercholesterolaemia and diabetes.

• All pēpi should have calculation of a customised birthweight centile available at GROW-App NZ and incorporated into the BadgerNet platform.

• Assess all pēpi suspected of FGR by reviewing maternal risk factors for FGR and calculating population cross-sectional z-scores for length, head circumference and BMI.

• FGR in the neonate includes one or more of:

  - customised birthweight <3^rd centile.

  - customised birthweight centile from ≥3^rd to <10^th with two or more additional features: BMI z-score ≤1.3, length z-score ≤1.3‡, skin or body fat z-score ≤1.3, antenatal diagnosis of FGR, one or more major wāhine/person risk factors for FGR, evidence of placental insufficiency on histopathology.

  - antenatal diagnosis of FGR and evidence of placental insufficiency (e.g. abnormal Doppler waveform studies) even if the customised birthweight is ≥10^th centile.

• Follow the Te Whatu Ora SGA and FGR in Aotearoa New Zealand clinical practice guideline algorithm for Management of the neonate with FGR.