After all the urging of doctors to be less afraid of opiates and more ready to use them for pain control, it seems the pendulum may be swinging back the other way. It is now thought that opioid use for chronic non-cancer pain may not be effective long-term, and, really, not nearly enough is known about either the effectiveness or the possible harms.
Antivirals in early pregnancy, however, do now appear to have a green light – a huge registry study in Denmark, reported in JAMA, found that in utero exposure to aciclovir or valaciclovir in the first three months was not associated with any increase in birth defects. (Famciclovir likewise came up clean, but was used in so few women that it isn’t really possible to say whether it’s OK or not.) Not surprisingly, aciclovir was by far the most commonly used, and would therefore be the drug of choice.
On to the review articles this week, of which there are several:
Gastro-oesophageal reflux in infants: A passing point of interest is that this is not one of the many conditions of which breastfeeding can reduce the risk – it occurs in breastfed and formula-fed infants with equal prevalence. Cow’s milk allergy can produce similar symptoms – in that case, use of extensively hydrolysed formula, or maternal elimination of cow’s milk protein, can alleviate symptoms, though it may take two to four weeks.
What to do about it? The old advice to add rice cereal to the milk does have something to it – it was shown to be moderately effective in a systematic review, as were various other forms of feed thickener (carob bean gum, corn starch, soy fibre, or some prescribable products – Instant Carobel, Thick & Easy, Thixo-D, and Vitaquick). However, these have various drawbacks: starch-based thickeners can lead to excess calorie intake (and are therefore only recommended in cases of FTT), and parents need to use teats with large holes. A better way of reaching the same end may be to prescribe Enfamil AR or SMA Staydown, both of which are licenced for prescription for significant reflux and which do not require a larger hole in the teat. The big advantage is that you know the calorie intake, osmolality, and the like, is going to be correct.
Another bit of traditional advice, however, is not recommended – elevating the cot while the baby is lying supine. It’s not clear from this review whether this is because of evidence of lack of effect or lack of evidence of effect. However, premature infants with reflux may benefit from lying on their left side, although this does have the drawback that it’s not a stable position for them to stay in and propping them in it with pillows isn’t safe.
My usual approach to babies with reflux is to try some Gaviscon Infant and to refer them to the paeds if that doesn’t work. This is, it seems, quite correct – Gaviscon may be of some help (though trial results are conflicting) and is worth trying, though not at the same time as other feed thickeners, and infants unresponsive to Gaviscon should be referred. In cases where I really feel the need to try something else while a baby is waiting to see the paeds, Ranitidine seems to be my best bet, as it’s licenced for this use. Possible side-effects include diarrhoea, rash, sleepiness, irritability, and head rubbing (assumed headache). The acid suppression may increase rates of gastroenteritis in babies over 4 months and NEC in VLBW babies. I should probably avoid domperidone and metoclopramide – they can cause acute dystonic reactions, domperidone can also cause QT prolongation and one study suggests it may actually make reflux worse, and metoclopramide can cause tardive dyskinesia and may or may not work (evidence is conflicting). Simeticone and sucralfate should not be used. Omeprazole, possibly, but again I think that would be specialist territory.
Hypertensive disorders in pregnancy: First, the thresholds, because I always forget them:
- Mild hypertension – (140 – 149)/(90 – 99)
- Moderate hypertension – (150 – 159)/(100 – 109)
- Severe hypertension – 160 or above/110 or above
And the threshold for proteinuria is >300 mg protein in 24 hours or >30mg/mmol protein:creatinine (I think the local lab tests albumin:creatinine, so I could have done with a threshold for that as well, but I guess I’ll sort that out if and when it comes up).
OK, I think I got that. As for the definitions, it’s chronic hypertension if it shows up any time before 20 weeks and gestational hypertension if it shows up after 20 weeks.
Pre-eclampsia, of course, = gestational hypertension + proteinuria.
Severe pre-eclampsia = severe gestational hypertension + proteinuria, or pre-eclampsia plus symptoms, or pre-eclampsia + abnormal blood results
And the danger symptoms?
- Severe headache
- Visual problems (including blurring/flashing before the eyes)
- Severe pain just below the ribs (I note it doesn’t specify a side)
- Sudden swelling of face, hands, or feet
So, who is at risk? Me, for one (well, I would be if I was actually pregnant – I should clarify that I have no intention whatsoever of this happening, so I think that puts me in the clear). After two entirely uneventful pregnancies I’m a bit surprised at the thought of me being at risk for anything pregnancy-related, but the reason, of course, is that I’m no spring chicken – age over 40 is a moderate risk factor for pre-eclampsia. The other moderate risk factors are, of course, first pregnancy, pregnancy after a gap of >10 years (seems that, after long enough, your body restarts), multiple pregnancy (as the obstetricians who taught me as a medical student said, that just raises your risk for everything), a family history, or a BMI of >35. High risk factors are chronic hypertension, chronic kidney disease, previous gestational hypertension/pre-eclampsia, diabetes, or auto-immune disease. Women with one high-risk factor or two moderate risk factors should take 75 mg of aspirin daily from 12 weeks until the birth. A long list of other things (everything from progesterone to garlic) have been suggested as potential preventatives, but currently all these have either shown no benefit or (in the case of calcium) fall into the ‘contradictory evidence, needs further clarification before we can recommend it’ category; so, in short, don’t give anything other than aspirin as prophylaxis.
What do we do about it once it’s detected? Send the patient off to hospital for the full workover, and then monitor if it’s mild and treat if it’s moderate or severe. Details of recommended monitoring and treatment are given, but I think (hope) that by that stage the hospital would be advising on management anyway. This summary didn’t contain much information about management in the postpartum period, so I’ll check the NICE guidelines themselves when I need to. However, do remember to warn the woman that she is at increased risk of hypertensive problems both in future pregnancies and in later life.
Chronic hypertension would, of course, be something I would be referring to a medical disorders in pregnancy clinic. However, for reference, in treatment I should be aiming for a systolic below 150 and a diastolic between 100 & 80 (why it’s not supposed to go below 80 I’m not sure, but we are specifically warned against this).
Finally, and importantly, the matter of what medications are compatible with pregnancy and with breastfeeding. ACE inhibitors, AIIRAs, and thiazides should be avoided in pregnancy – everything else seems, on limited available evidence, to be OK. (Shouldn’t this rather important information be included in the, um, whatever the hell set of guidelines it is that works on AB/CD? By my calculations, women of childbearing age with hypertension would normally be offered ACEs first-line with thiazides and/or AIIRAs pretty high up the list. Shouldn’t we be taking into account the possible risks of women getting pregnant on these medications?) For breastfeeding, labetalol, atenolol, metoprolol, nifedipine, enalapril, and captopril all seem OK. We don’t have enough information about other ACE inhibitors, amlodipine, and AIIRAs. The article doesn’t say anything about other antihypertensives.
Investigating fatigue: Last but most definitely not least. I was pleased to see this one – I could do with some finessing of how I approach these patients. (‘Any obvious stresses in your life recently? No? Well, we’ll do some bloods and contact you with the results.’)
It seems my approach is OK as far as it goes, but I should ask about more things:
- GI problems
- Weight loss
- Symptoms of diabetes
- Symptoms of sleep apnoea
- Symptoms of depression/stress
- Recent infections
- Joint pains/swellings
- Medication, including OTC
- Alcohol consumption.
Examination should include BP measurement (for postural hypotension, which could indicate Addison’s), and urinalysis (presumably for kidney problems, though it doesn’t say). And don’t forget to check those lymph nodes!
Now, the bloods. Apparently, the only ones from the standard list that I actually should be considering in every case are the FBC, TFTs and plasma viscosity. As for the others:
- Glucose – only if obese or has symptoms of diabetes
- U&Es – only if >60 or has symptoms such as itching or polyuria
- Ferritin – women of menstruating age
- B12/folate – not even mentioned
And some others that I don’t usually do but wondered whether I should:
- LFTs – >60 or alcohol/drug abuse
- Calcium – only if symptoms suggest
- CRP – only if symptoms suggest persistent infection
- Paul Bunnell – only if <40 and recent infection
- Coeliac screen – only if GI symptoms or for consideration as second-line test
Finally, it’s encouraging to note that almost three-quarters of TATT patients do not come back for further consultation. This suggests that, a lot of the time, the problem probably resolves spontaneously.