Ilana Levene & Mark Anthony

Please start by reading Part 1 of this series!

Part 2 is about the ‘Big Three’ in infant crying – that is to say, colic, cows milk protein allergy (CMPA) and reflux.

Any thoughts about diagnosing these conditions in crying babies should be informed by an understanding of how common crying is in normal babies, and evidence-based management strategies that don’t involve drugs or special formula. Remember that both you and parents would like a quick fix, but often chasing a diagnosis just exposes the baby to potential harms, and time is the key management strategy. However if there are clues to cows milk protein allergy, or the crying is severe and doesn’t fit a colic pattern, do an exclusion/re-challenge trial to rule it out.

What about Colic?

Colic follows the same pattern as normal crying but more of it, and with more inconsolable bouts. Parents are good at knowing when their baby’s crying is ‘excessive’, and there is no specific treatment so strict diagnostic criteria are somewhat moot. But if you like numbers, the modified Wessel criteria for colic is a baby crying for at least 3 hours a day for at least 3 days a week. The 90th centile for crying in one systematic review was 3.5 hours per day in the first six weeks, dropping to 2 hours per day by 3 months of age.

Colic is a mysterious entity, associated with pre-existing maternal anxiety and maternal migraine. Babies with colic are also more likely to have migraine later in life. Being born preterm or low birth weight is associated with increased likelihood of colic.

Colic is linked to subsequent parental depression and with non-accidental injury. Potential injury is likely far higher than the clinical presentations we see of ‘shaken baby’ syndrome – in a Dutch study, 6% of parents of normal six-month-old babies reported having shaken, slapped or smothered their baby in response to excessive crying. There is a time delay between peak crying age and peak presentation of ‘shaken baby’, which may be due to escalating events – thus a significant number of parents you see with crying babies may have already shaken or hit their baby in frustration regardless of whether you see any evidence for this. They are extremely unlikely to bring this up, so introducing the fact that parents of crying parents often find it hard to deal with the crying, discussing the possibility of harm and how to reduce this is an essential part of your management for all.

Colic is common, particularly in the UK – 20-30% of babies fit modified Wessel criteria in the first 6 weeks of life, decreasing to 11% by 2 months of age and 0.6% by 3 months. First line treatment for colic in a breastfed baby is expert, face to face breastfeeding support. The rest of your advice is the same as described in part 1 of this series for babies with ‘normal’ crying, with extra emphasis on safety and putting the baby down in a safe place to calm down if the parents need ‘time out’. Encourage parents to get help from family and friends to reduce the pressure on them. Strongly consider information sharing with the health visitor and GP for further support and any parental mental health assessment needed.

There are a lot of treatments marketed for colic, but none have reached a Cochrane/NICE level of evidence to recommend (although there is likely to be a placebo effect to many). Specifically, NICE recommends avoiding simethicone (such as Infacol), lactase drops (such as Colief), any herbal remedies and any manual therapies such as spinal manipulation or cranial osteopathy. There is emerging evidence that probiotic L. reuteri may improve crying time in breastfed babies only, for example reducing crying time by 30 minutes at day 7 and 45 minutes by day 21, compared to placebo. There is at time of writing one over the counter L. reuteri preparation designed for babies that parents can buy online.

Importantly, unless a diagnosis of cows’ milk protein allergy is being proposed, there is insufficient evidence for dietary modification in a breastfeeding mother – so please don’t take away their chocolate! There is also insufficient evidence for switching between formulas, including to those (often more expensive) marketed for this purpose (‘comfort’ partially hydrolysed formula and lactose-free formula), although again placebo effect is common.

What about GORD?

Reflux of stomach contents (also called ‘posseting’ or ‘regurgitation’) is normal in infants, affecting 40% of all babies to a varying extent – as a wise woman once told me, this is a laundry problem, not a medical problem. Physiological reflux tends to start before 8 weeks of age, peaks at 3-4 months and 90% have resolved by 1 year. Gastro-oesophageal reflux disease is the presence of gastro-oesophageal reflux and evidence of harm to the baby, for example “marked distress” or faltering growth. However, when 40% of infants have GOR and 30% of infants have excessive crying, it isn’t hard to see the potential for overdiagnosis!

If GORD is suspected, initial advice is conservative – keeping the baby upright during and for 30 minutes after feeds, avoiding tobacco exposure, and when lying down to use a surface that is angled at 30 degrees rather than flat. Safe sleep messages must not be compromised – babies should sleep on their backs on a firm, even surface. Prone position can only be used when babies are awake and observed.

If GORD is suspected because of ‘marked distress’ and frequent regurgitation, then discuss with parents whether they would like a trial of treatment. To make this decision they need to know the natural history of crying, the natural history of reflux and the potential for treatment side effects. All treatment should be viewed as a trial.

The picture summarises the NICE protocol for GORD treatment. Each trial should be given for 2-4 weeks, and even if successful, all treatments should be stopped at regular intervals to see if they are still needed due to the natural history of resolution with age. Please try to avoid the classic pattern of throwing a new drug at a baby every week around the peak “I don’t think this crying is ever going to stop, I just can’t cope any more” 6 week time point.

Even though drug treatments are recommended as second and third line by NICE, a Cochrane review concluded there was no evidence that ranitidine works, and only weak evidence for PPIs and alginates in infants. Particularly, Systematic review of RCTs has shown no effect of PPIs on reducing crying, fussing or irritability in infants.

What about CMPA?

This is an allergic response to proteins found in cows’ milk, commonly presenting in the first month of life, often with skin and gastrointestinal symptoms. It is either IgE mediated or non-IgE mediated, depending on the speed of reaction seen (take a look at this PaediatricFOAM article on IgE vs non-IgE mediated reactions). Just like GORD, CMPA is easy to over diagnose – up to 15% of infants have symptoms that could be consistent with CMPA, but most are not confirmed by dietary exclusion and re-challenge. Confirmed CMPA only occurs in 2-3% of babies who are partially or fully formula fed, often within days of first exposure to formula, and 0.5% of exclusively breastfed babies.

An incorrect diagnosis of CMPA has serious consequences. A breastfeeding mother will be on a restrictive diet, with risk of calcium deficiency and higher chance of giving up breastfeeding. A formula fed baby is on an expensive prescription only formula (NHS costs for CMPA formula have rocketed in recent years). In both situations there is increased stress when complementary feeds are introduced, with risk of calcium deficiency and further medical appointments for guidance on reintroduction of cows’ milk protein. Therefore it is vital to remember that for most babies (unless the symptoms are particularly severe or clearly IgE mediated), a trial of treatment must be followed by a re-challenge with cows’ milk protein before a diagnosis is made.

What clues might there be to a diagnosis of CMPA? Firstly, it’s more likely in the context of a strongly atopic family history or if the baby has treatment resistant eczema. IgE mediated symptoms occur within 2 hours of ingestion of cows’ milk protein, often within 30 minutes. Symptoms are classically allergic – for example, itching, urticarial or erythematous rash, eczema flare, vomiting, diarrhoea, rhinitis, sneezing, wheeze, cough, shortness of breath and angio-oedema.

Non-IgE mediated symptoms occur several days after ingestion of cows’ milk protein and include itching, erythematous rash, eczema, loose or frequent stools, blood and/or mucous in stools, excessive crying, constipation, feed refusal, cough, wheeze, shortness of breath and pallor. In both types, faltering growth signifies severe CMPA.

If a baby’s crying is not fitting the classic pattern of colic – for example there is no improvement at 3 months or they are still crying excessively at 4 or 5 months of age – it is probably worth trying an exclusion/re-challenge strategy.

If a baby is exclusively breastfed, the trial of treatment is for the mother to exclude all cows’ milk protein from her diet (NOT lactose – all human milk contains lactose, regardless of mother’s diet!) for 2-4 weeks. Advise the mum to take 1000mg calcium daily, or preferably refer her for the holy grail – a dietitian appointment.

If a baby is exclusively formula fed the trial of treatment is an extensively hydrolysed formula for 2-4 weeks. If symptoms are severe and non-IgE mediated then some suggest the most disgusting tasting one of all – amino acid formula.

If a baby is mixed fed, both elements need to be trialled at the same time. However, if a recent introduction of formula has triggered the symptoms, another option is to go back to exclusive breastfeeding. If there were previously no symptoms during breastfeeding the mother can continue a normal diet.

So that’s “The Big Three”. We should think carefully about whether the baby in front of us fits the pattern of these labels, but the potential for overdiagnosis, and the importance of trials of treatment, including rechallenge for a CMPA diagnosis, needs to be discussed with parents so they can make an informed decision whether to go ahead.


Confidence in the patterns and treatment strategies for “The Big 3” will allow you to help families join you in applying them with care and trying to restrain everyone’s desire to “just try everything”, regardless of potential harms. Good luck, and may the babies of the world benefit!

Key Learning Points

There isn’t much you can do for the colicky baby (think about probiotics if breastfed) – but the parents are the ones to focus on

Physiological reflux and excessive crying are both common, think carefully before treating suspected reflux disease and remember that all treatments are a trial

Look for atopic clues for cows milk protein allergy or rule it out when crying is severe and atypical. Exclusion and re-challenge should be your default before making the diagnosis

Remember the possible harms of treatment and discuss them with parents before coming to a shared plan

Resources for parents

Excessive crying:

Cry-sis telephone helpline 0845 122 8669

Gastro-oesophageal Reflux

Cows’ Milk Protein Allergy parent section on CMPA

Conflicts of Interest

Ilana Levene is a paediatric registrar in the Oxford Deanery, with an interest in infant feeding. She is co-chair of the Hospital Infant Feeding Network, a new organisation aiming to promote and facilitate breastfeeding in hospital settings. She is also a trustee of a community breastfeeding support charity.

Mark Anthony is a consultant neonatologist in the Newborn Care Unit at the John Radcliffe Hospital in Oxford. He has written a book for parents called “The Baby Crying Guide” and sees crying babies in private practice.

3 thoughts on “Cry Baby Cry… Part 2 (Colic, CMPA and Reflux)”

  1. I should have mentioned in the resources for parents section that AllergyUK receives funding by manufacturers of CMPA formulas

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