See the Green book for guidance. Seronegative women who get chickenpox in pregnancy tend to get pretty unwell, and in the first 20 weeks of pregnancy the fetus is at risk of congenital varicella syndrome (scarring, intracranial calcification, limb deformities), while around the time of delivery the baby may develop disseminated varicella infection because no transplacental antibody transfer can occur. So women who are exposed in the first 20 weeks, or else a week before to a week after birth, should be considered at risk. Exposure is defined as close contact with chickenpox, or someone who develops chickenpox within a week, or exposed zoster (ie on the face). If the woman has definitely had chickenpox herself, then there is no risk to the baby, during the pregnancy or in newborn period. If in doubt, check serology and wait on result: no evidence that delaying treatment for up to 10 days (to wait on antibody status) makes any difference. For high risk contacts, give the mum VZIG – costs £1000 per dose, so make sure it's indicated. Aciclovir is unlicensed for use in pregnancy so not used prophylactically but usually given if the woman actually develops chickenpox. VZIG has been shown to reduce but not prevent infection; however, if infection does occur it tends to be less severe.
Preterm babies are different; even if the mother is seropositive (ie immune), they should be considered vulnerable to infection and given VZIG if exposed.
See CHIVA for guidelines and evidence. Latest summary of recommendations from September 08.
Risk of transmission depends on viral load, obstetric factors, and gestation. Currently 1% in the UK. Factors are:
Viral loads should be checked every 3 months and at week 36, as well as at birth. Also check 2 weeks after starting/changing therapy.
Mono therapy gives a 7-fold reduction, and regimens consisting of 3+ drugs a 10-fold reduction (dual no advantage over mono). Approx half of mothers on combination will achieve undetectable viral loads by delivery. But short term combination increases risk to Mum and fetus of side effects (pre-eclampsia risk is increased, esp with PI) and possibly preterm delivery (1 study, not in others). HIV itself increases risk of adverse pregnancy outcomes but this relates more to IUGR and spontaneous abortion.
HAART in pregnancy is usually ZDV, 3TC plus a boosted PI.
Resistance (genotypic/phenotypic) testing should be done where:
If HAART started for pregnancy rather than maternal reasons (Short Term ART, or START), then it can be discontinued after delivery after confirming viral load <50 cps/ml.
Consider a detailed anomaly ultrasound at 21 weeks for all fetuses exposed to ART during the first trimester.
Avoid invasive monitoring and artificial rupture of the membranes.
Do LSCS at 38 weeks for the first 2; at 39 weeks for women with undetectable levels on HAART (where SVD is also an option).
LSCS is recommended for:
After spontaneous rupture of membranes, risk of transmission increases with each passing hour so at term expedite delivery (difficult decision if preterm).
Threatened preterm delivery - take Mum's bloods for CD4 and viral load if not known, start HAART including NVP (which causes rapid fall in count, crosses placenta rapidly and persists in the baby who may be unable to take oral medication). Consider single dose NVP even if no viraemia esp if under 32/40 and not on an NNRTI. Multidiscipl decision about timing of delivery.
Risk of transmission increases, esp HCV, where combination ART should be given and LSCS should always be considered even if not viraemic. For HBV, give HBIG to the baby if HBcAg pos or high HBV viral loads (as well as their vaccince).
HIV-2 has lower transmission rates, so if symptomatic in mother, treat the same, but otherwise <50 copies probably no treatment required whatsoever. If CD4 >300 then treat as per HIV-1. Barts has lab doing viral loads. HIV-2 is not sensitive to NNRTIs.
ZDV side effects: bone marrow suppression up to 18 months; mitochondrial toxicity (suspect in sick infant); no evidence of increased congenital abnormalities overall, but not enough data to comment on any one particular drug.
ZDV, 3TC and NVP appropriate for infants born to drug naieve women, but for non-naieve mothers other combinations might be required if there is a possibility of resistance. Resistance testing should be carried out in the mother in such a situation and on the first positive sample of any infected infant.
Currently no proven increase in congenital abnormalities, although there have been mitochondrial cytopathies in 3 out of 1000 deliveries.
Exclusive formula feeding is still recommended. HAART extended postnatally, or postnatal infant antiretroviral treatment reduces the risk of postnatal transmission to as low as 1% at 6 months. WHO is to redraft guidelines for breast feeding in developing countries (still unclear whether discontinuing breast feeding at 6 months is worse than continuing it...)
HIVNET 012 - benefit of 2 doses of nevirapine, one to the mother in labour and the second to the neonate age 48-72 hours, cf zidovudine initiated in labour and continued in the neonate for one week. Transmission was reduced by 47% after 3 months follow-up. This was the initial WHO regimen.
See HIV for more clinical information.
The DREAM program in 6 African countries, gave ART in pregnancy (combination) and for 6 months postpartum, and all engaged in exclusive breast-feeding. At 1 month of age, 1.2% of infants were infected, with an additional 0.8% infected by 6 months. So although results are half as good as the UK they do show that such a program is feasible in Africa.
Fetal Alcohol Syndrome (FAS) is the leading cause of non-genetic intellectual disability in the West. No evidence in RCOG review that 1-2 units 1-2 times weekly (old DoH/BMA position) in pregnancy is harmful. But NICE says avoid in first 3 months, and limit to less than 1.5units per day. Advice changed because of increasing problem drinking in young women and evidence that 9% of pregnant women drank more than recommended limit – need for more straightforward advice. US, Canada, France, NZ, Australia all go with abstinence advice. Some evidence for behaviour at age 6yr being affected by low alcohol consumption, with dose-response effect.
Probably appropriate to talk about Fetal Alcohol effects, rather than syndrome, since cases with obvious dysmorphism probably represent the severe end of a spectrum of effects.
Anti-epileptics in pregnancy carry small but definite risk of teratogenicity. Avoid valproate unless no other drug gives satisfactory seizure control. Tonic-clonic seizures pose risk to both mother and child. Folate supplementation (5mg/d) is recommended but no good evidence for effectiveness.
No lower limit on alcohol intake has been defined ie there is no safe drinking limit in pregnancy.
Characteristic facial features:
Other problems:
Lesley's NAS study - Median treatment duration was four days shorter with opiate replacement (8 v 12 days) cf phenobarbitone. Morphine dose is 50 µg/kg four times a day.(Arch Fet 2004)
Lipsitz score -
Methadone concentrations taken from cord blood may identify infants at greater risk of neonatal withdrawal and therefore requiring treatment.
Arch Fet 2004; 89
This work
is licensed under a Creative
Commons Attribution-Noncommercial-Share Alike 2.5 UK: Scotland License.