Monday, July 29, 2019

Maternal migraine and infant colic

Mothers, but not fathers, with migraine are significantly more likely to have an infant with colic, new research suggests.

In a large cross-sectional study, infants 4 to 8 weeks old were 70% more likely to have colic when born to mothers with migraine compared with babies born to unaffected women.

"There was a clear association no matter how we asked about migraine," lead author Amy Gelfand, MD, University of California, San Francisco, told attendees here at the American Headache Society (AHS) Annual Meeting 2019.

"Infant colic being associated with migraine really opens up a door for us to think what migraine looks like in the developing brain," she said. "People will ask me if these babies are really having a headache. Clearly, they are experiencing distress." 

Gelfand noted that the babies with colic could be inheriting an increased sensitivity to stimuli. 

"They may be experiencing the fundamental migraine [experience] and expressing it in the only way they can," she said.

Previous case-control studies examining an association between migraine and infant colic were limited by "some recall bias," Gelfand said.

Conversations about symptoms sounded very similar when she was a child neurology resident talking to parents of children with colic and when she did a headache rotation and talked to patients with migraine.

As reported by Medscape Medical News, Gelfand conducted a smaller cross-sectional survey study during her residency to find out more. Among the 154 mother–baby pairs, 22 infants had colic and 28 mothers reported migraines.

"We found mothers with migraine were more than 2.5 times as likely to have a baby with colic," she said.

The current study builds on her previous findings. 

The investigators assessed responses to a web-based survey from 827 biologic mothers and 592 biologic fathers of infants 4 to 8 weeks old.

They used the same question to identify infants with colic as the first study: "Has your baby cried for at least 3 hours at least three times in the past week?" A total of 26% of babies met this criterion for colic.

Researchers also asked about migraine in a number of ways, including self-report. Participants were asked if a physician had ever diagnosed them with migraine and through screening using the modified International Classification of Headache Disorders, 3rd edition, criteria.

Of the participating mothers, 33.5% were classified as having migraine or probable migraine.

Results showed that maternal migraine was linked with an increased likelihood of infant colic (odds ratio [OR], 1.7; 95% CI, 1.3 - 2.4). The findings held when the researchers controlled for anxiety and depression as possible confounders.

Gelfand noted a "dose effect" as well. Mothers who reported migraines on 15 days or more per month were even more likely to have an infant with colic (OR, 2.5; 95% CI, 1.2 - 5.3).

In contrast, paternal migraines were not associated with higher odds for infant colic (OR, 1.0; 95% CI, 0.7 - 1.5). A total of 19% of fathers reported migraines.

"Paternal migraine was not associated with infant colic no matter how we looked at it," Gelfand said. "We had enough numbers that if it was there we would have expected to see it."

Experts have proposed many theories of what causes infant colic, including a gastrointestinal etiology, Gelfand said.

However, "there is pretty limited evidence of thinking of colic as a gastrointestinal problem," she noted.

She added that X-rays in a small number of studies have shown no extra-abdominal gas; that simethicone does not seem to improve colic; and whether the baby is fed by breast, bottle, or both does not seem to be related.

"For me, the thing that is most indicative that we are not dealing with a feeding phenomenon is that it peaks in the evening, [whereas] feeding at this age is around the clock," Gelfand said.

"I would like to introduce the concept of infant crying as a neurodevelopment process," she said.

In general, colicky crying peaks at 5 or 6 weeks post gestational age, so it could be something that involves neuronal maturation, Gelfand added.

"Infant crying may be a brain-driven process rather than a belly-driven process," she said.

The mechanism underlying the link between maternal migraine and infant colic remains unknown.

Mitochondrial genetics passed down from a mother is one theory, Gelfand said. It might also be a different epigenetic phenomenon or a social effect, "such as a difference in how mothers perceive crying versus how fathers perceive it."

"Are these babies inheriting genes that make them more sensitive to stimuli? We're now getting into post hoc/exploratory data territory," she said. "For us as a field, this is just a tremendous opportunity moving forward."

In terms of clinical implications, "If you are seeing a woman with migraine who is pregnant or considering pregnancy, I think it is worthwhile to counsel them about increased likelihood of having a baby with colic," Gelfand said. "Assure them it's a time-limited phenomenon."

In addition, "maybe if you have a colic baby you do not need to buy special formula, maybe you need to decrease the stimuli they are encountering," she noted.

The researchers are now conducting a pilot study in 20 babies to measure and report minutes of daily crying.

Commenting for Medscape Medical News, chair of the AHS meeting's Scientific Committee Andrew C. Charles, MD, a neurologist at the University of California, Los Angeles Medical Center, noted that the research is "part of this changing concept of migraine" as a disorder that can present in a variety of different ways at different times of life.

"It's not utterly definitive, but it's strong enough to be provocative," said Charles, who was not involved with the study.

"The other point she makes is that colic has often been assumed to be a gastrointestinal (GI) issue. But there is no evidence for that; it's defined as 'inconsolable crying'," Charles noted.

"So the whole idea that it's a GI problem is just dogma that's been around a long time without any particular evidence," he concluded.

The research earned Gelfand the Harold G. Wolff Award, recognizing the best paper on headache, head, or face pain, or the nature of pain itself. Gelfand and Charles have reported no relevant financial relationships.

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