Higher Order Multiple Pregnancy

Higher order multiple pregnancy is a pregnancy with four or more fetuses (quadruplets, quintuplets and more). It results almost always from ovulation induction or multiple embryo transfer. It is rare with modern practice. It matters because birth is often very preterm, and rates of loss, cerebral palsy, preeclampsia and maternal death are very high.

• Risk factors: ovulation induction with clomifene or gonadotrophins, multiple embryo transfer, family history.
• Fetal reduction to twins improves outcomes.
• Survival of all fetuses is rare without reduction.

Women have severe pregnancy symptoms, a very large uterus, breathlessness, oedema, anaemia and complications such as hypertension. Examination finds many fetal parts and possibly polyhydramnios.

• Fundal height 8 or more cm above dates by 20 weeks.
• Respiratory compromise from uterine size.
• Differential diagnosis: twin or triplet pregnancy, polyhydramnios, molar pregnancy, ovarian hyperstimulation, large fibroid.
• Complications: preterm labour, preeclampsia, severe anaemia, pulmonary oedema, ovarian hyperstimulation, discordant growth, fetal loss, cerebral palsy, postpartum haemorrhage, maternal death.

The approach is early ultrasound to count the fetuses and define placentation, with intensive follow-up.

• Ultrasound at 6 to 8 weeks to count sacs and embryos, and at 11 to 13 weeks for chorionicity and amnionicity, crown rump length and nuchal translucency.
• Scans every 2 weeks from 16 weeks; cervical length every 2 weeks from 16 weeks; growth scans each visit.
• Full blood count monthly; 75 g oral glucose tolerance test at 24 to 28 weeks; blood pressure and urine protein every visit.
• Fetal echocardiography and anomaly scan at 20 to 22 weeks.

The principle is early referral, fetal reduction counselling, intensive maternal care and planned caesarean birth by 30 to 32 weeks.

• Supportive: refer to a tertiary unit at diagnosis; counselling on risks and the option of fetal reduction at 11 to 13 weeks; admission from 24 weeks; high energy and protein diet of 3000 kcal or more; rest; thromboprophylaxis; birth in a unit with neonatal intensive care and one neonatal team per baby.
• Pharmacological: folic acid 400 micrograms oral daily; ferrous sulphate 200 mg oral 8-hourly; aspirin 150 mg oral at night from 12 weeks to 36 weeks; enoxaparin 40 mg subcutaneous daily from admission to 6 weeks postpartum; calcium 1.5 g elemental oral daily where intake is low; betamethasone 12 mg IM twice, 24 hours apart, from 24 weeks to 34 weeks and 6 days; magnesium sulphate 4 g IV over 20 minutes then 1 g per hour until delivery for 24 hours at most before 32 weeks; nifedipine 20 mg oral once then 10 to 20 mg every 6 to 8 hours for up to 48 hours for contractions; cefazolin 2 g IV before caesarean section; oxytocin 10 IU IM at birth then infusion of 20 IU in 1 litre sodium chloride 0.9 percent at 125 mL per hour for 4 hours; carboprost 250 micrograms IM every 15 minutes (maximum 8 doses) for atony, avoided in asthma.
• Procedures: multifetal reduction to twins at 11 to 13 weeks by a fetal medicine team under ultrasound guidance; planned caesarean section at 30 to 32 weeks; cervical cerclage for a short cervix below 25 mm before 24 weeks in selected women; balloon tamponade, compression sutures or hysterectomy for uncontrolled haemorrhage.
• Special groups: women with ovarian hyperstimulation need fluid balance, albumin 20 percent 100 mL IV with furosemide 20 mg IV for ascites, and enoxaparin 40 mg subcutaneous daily.
• Red flags: contractions, short cervix, leaking fluid, blood pressure 140/90 mmHg or more, bleeding, breathlessness at rest, reduced movements of any fetus.
• Follow-up: growth scans every 2 weeks; postnatal haemoglobin and ferrous sulphate 200 mg oral 8-hourly for 3 months; contraception; counselling and psychological support.