Colic doesn’t have a single, proven cause. Despite decades of research, the intense crying episodes that affect 10% to 40% of infants worldwide remain one of the most frustrating mysteries in pediatrics. What scientists have found is a handful of overlapping biological factors, from gut chemistry to nervous system development, that likely work together to trigger and sustain colic in the first months of life.
What Counts as Colic
Colic is defined as repeated episodes of unexplained crying or irritability in an otherwise healthy infant under five months old. The crying is often accompanied by visible signs of discomfort: leg flexion, back arching, and a visibly distended belly. It typically begins in the first six weeks of life, peaks around six weeks, and resolves on its own by three to four months for most babies. In some cases, it lingers until six months.
The word “unexplained” is key. A baby who cries because of hunger, a wet diaper, or an ear infection doesn’t have colic. Colic is the label for when everything checkable has been checked and the crying continues.
The Serotonin-Melatonin Imbalance
One of the most compelling biological explanations involves two chemicals your baby’s body produces: serotonin and melatonin. Serotonin causes the smooth muscles in the intestines to contract. Melatonin does the opposite, relaxing those same muscles. In adults and older children, these two chemicals balance each other out.
Newborns, however, are born with only serotonin’s daily cycle in place. Melatonin’s cycle doesn’t kick in until around three months of age. That means during the evening hours, when serotonin levels naturally peak, a young baby’s intestines contract without any chemical counterbalance to ease the tension. The result is cramping, and the timing lines up almost perfectly with the classic pattern of colic: worst in the evening, gone by three months. This hypothesis explains both the daily timing and the age at which colic resolves in a way few other theories can.
An Oversensitive Nervous System
Some babies appear to have a lower threshold for sensory input than others. Research on sensory processing in infants has found that babies who cry excessively tend to have what’s called a low neurological threshold, meaning they react strongly to levels of stimulation that wouldn’t bother most infants. A car driving past the house, a dog barking in the next room, or background music that seems harmless to you can register as overwhelming to these babies.
This isn’t a disorder. Sensory sensitivity exists on a spectrum, with most babies in the middle and a smaller number on either end. Babies at the hypersensitive end struggle with self-regulation. Their nervous systems haven’t yet developed the ability to filter out unimportant stimuli, so incoming signals pile up throughout the day. The disorganized response to all that input manifests as crying, fussing, and extreme difficulty settling down, especially by evening when the cumulative load is highest.
Gas: A Symptom, Not a Cause
Parents often notice that their colicky baby burps frequently or passes a lot of gas, which naturally leads to the assumption that trapped gas is driving the distress. But the relationship likely runs in the other direction. Babies swallow air when they cry, and the more intensely and longer they cry, the more air they take in. That air has to go somewhere, which produces the burping and flatulence parents observe.
This distinction matters because it changes how you approach the problem. Gas drops or specialized bottles may provide some comfort, but they’re unlikely to resolve colic if the crying itself is what’s producing the gas in the first place.
Cow’s Milk Protein Sensitivity
Because colic and cow’s milk protein allergy share overlapping symptoms, including abdominal discomfort, frequent spitting up, and distressed crying, milk allergy is frequently suspected in colicky babies. In a small subset of infants, a genuine sensitivity to proteins in cow’s milk (passed through breast milk or present in formula) does contribute to the problem.
However, research has clarified that most colic is not caused by cow’s milk allergy. The non-immune form of milk sensitivity has no reliable lab test, so the only way to confirm it is to remove dairy from the diet and then reintroduce it to see if symptoms return. If your baby has additional red flags beyond crying, such as bloody stools, persistent vomiting, or a skin rash, a milk protein issue becomes more worth investigating. For the majority of colicky infants who are otherwise healthy and growing normally, dairy elimination is unlikely to be the answer.
A Surprising Link to Migraines
One of the more unexpected findings in colic research is a strong statistical connection between infant colic and childhood migraines. A study published in JAMA found that children with migraines were roughly 6.6 times more likely to have had colic as infants compared to children without migraines. Nearly 73% of children in the migraine group had a history of infantile colic, compared to about 27% in the control group.
This doesn’t mean colic is a headache. It suggests the two conditions may share an underlying mechanism, possibly related to how the nervous system processes and responds to stimulation. The connection held for migraines both with and without visual disturbances (aura), reinforcing the idea that something about the way these children’s brains handle sensory input is different from birth. For parents, this finding reframes colic less as a “tummy problem” and more as a neurological pattern that some children eventually outgrow in its infant form but may express differently later in childhood.
Why It Peaks in the Evening
Nearly every parent of a colicky baby reports that the worst crying happens in the late afternoon or evening. Several of the mechanisms described above converge at this time of day. Serotonin peaks in the evening, driving intestinal contractions. Sensory input has accumulated over the course of the day, pushing a hypersensitive nervous system past its limit. And the baby’s capacity for self-soothing, already minimal, is at its lowest when fatigue sets in.
This clustering isn’t a coincidence. It’s the strongest clue researchers have that colic is driven by biology rather than parenting. Babies in calm, quiet households and babies in noisy, busy ones develop colic at similar rates. The evening pattern reflects internal rhythms, not external mistakes.
What the Timeline Looks Like
Colic follows a remarkably predictable arc. It most commonly appears in the first six weeks, intensifies through weeks four to six, and then gradually improves. By three months, the majority of babies have turned a corner. By six months, nearly all have.
The timeline aligns with several developmental milestones. Melatonin’s daily cycle comes online around three months, counterbalancing serotonin’s effect on the gut. The nervous system matures enough to begin filtering sensory input more effectively. The digestive tract grows and adapts. No single switch flips, but the convergence of these changes explains why colic resolves as reliably as it arrives. For parents in the thick of it, the predictability of the timeline is one of the few reassurances available: this is temporary, and there is a biological end point.