Nicotine Replacement Therapy During Pregnancy and Infantile Colic in the Offspring

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Infantile colic affects almost 10% of all infants and is characterized by crying and fussing in an otherwise healthy and well-fed infant. Prenatal exposure to tobacco smoking is a risk factor, but it is unclear whether nicotine causes the association.WHAT THIS STUDY ADDS: Infants exposed to nicotine replacement therapy during pregnancy had elevated infantile colic risk of the same magnitude as infants exposed to tobacco smoking. Intrauterine exposure to nicotine may play a causal role in the pathogenesis of infantile colic. abstract OBJECTIVE: To investigate the associations between use of nicotine replacement therapy (NRT) and smoking during pregnancy and infantile colic in the offspring. METHODS:We used data from maternal interviews (from pregnancy and at 6 months post partum) from the Danish National Birth Cohort (1996)(1997)(1998)(1999)(2000)(2001)(2002). We included 63 128 live-born singletons with complete information on nicotine exposure during pregnancy and infantile colic symptoms as recorded at 6 months of age. RESULTS:A total of 46 660 infants (73.9%) were unexposed to nicotine during pregnancy; 207 (0.3%) were exposed to NRT, 15 016 (23.8%) were exposed to smoking, and 1245 (2.0%) to both. A total of 4974 (7.9%) infants fulfilled Wessel' s modified criteria for infantile colic. Prenatal nicotine exposure was associated with elevated risk for infantile colic in the offspring. Compared with the unexposed, NRT users had an adjusted odds ratio (OR) (95% confidence interval) of 1.6 (1.0-2.5; P = .03), smokers had OR = 1.3 (1.2-1.4), and women who both smoked and used NRT had OR = 1.6 (1.3-1.9). Partners' smoking was not associated with infantile colic after adjustment for maternal smoking. CONCLUSIONS:We corroborated the association between smoking and infantile colic after adjustment for several possible confounders in a large cohort study. Moreover, we found that infants exposed to NRT prenatally had an increased risk for infantile colic of the same magnitude as those exposed to tobacco smoke. Thus, nicotine may play a role in the pathogenesis of infantile colic. Pediatrics 2012;129:e652-e658 AUTHORS:

A systematic review of possible serious adverse health effects of nicotine replacement therapy

“…Another study (Dhalwani et al (2015), CAF 9, “fair”) used mother–child primary care records of children born in the UK to relate NRT prescription to incidence of major congenital abnormalities. The remainder (Lassen et al (2010); Milidou et al (2012); Morales-Suarez-Varela et al (2006); Strandberg-Larsen et al (2008); Torp-Pedersen et al (2010); Zhu et al (2014), CAFs 2 to 7, all “good”) derived from the Danish National Birth Cohort, each concerning different endpoints. The analyses all involve births in 1996 to 2003, though the publications vary in inclusion/exclusion criteria, and the comparison groups used for assessing NRT effects, some only reporting risks for women who used NRT and did not smoke.…”

“…a ReferencesComparison b Endpoint c Cases d OR/RR (95 %CI) e 5Torp-Pedersen et al (2010)Any NRT versus no NRTStrabismus61/12391.22 (0.92–1.61) f 6Milidou et al (2012)Any NRT versus no NRTInfantile colic137/14171.15 (0.97–1.37) g 7Zhu et al (2014)Any NRT versus no NRTADHD29/5321.11 (0.75–1.63) h HISNA−0.08 (−0.28 to 0.12) i 11Kapur et al (2001)Nicotine versus placebo patchRapid fetal movements0/10.24 (0.01–5.38) j 12Schroeder et al (2002)Nicotine patchSevere infant morbidity3/−No comparison group13Pollak et al (2007)Any NRT + CBT versus CBT onlyAny serious AE34/101.75 (0.93–3.28) j Placental abnormality4/04.64 (0.25–84.7) j 14Oncken et al (2008)Nicotine versus placebo gumMaternal hospitalization9/81.01 (0.41–2.50) j Spontaneous abortion2/04.49 (0.22–92.19) j Any serious AE24/33…”

“…Possible adverse effects were also noted, with the endpoints varying: overall congenital abnormalities (Morales-Suarez-Varela et al 2006); infantile colic (Milidou et al 2012); attention-deficit/hyperactivity disorder (Zhu et al 2014); low birthweight and preterm birth (Gaither et al 2009); respiratory system abnormalities (Dhalwani et al 2015); rapid fetal movements (Kapur et al 2001); and negative birth outcomes (Pollak et al 2007). However, four of these conclusions (Gaither et al 2009; Milidou et al 2012; Morales-Suarez-Varela et al 2006; Zhu et al 2014) were based on significant differences from non-smokers, no longer significant when comparisons were made within smokers. Furthermore, one conclusion (Kapur et al 2001) was based on a single case of rapid fetal movements in a subject given a placebo patch, while differences noted in the final study (Pollak et al 2007) were not significant.…”

Potential Evolutionary, Neurophysiological, and Developmental Origins of Sudden Infant Death Syndrome and Inconsolable Crying (Colic): Is It About Controlling Breath?

“…An additional question to ask is whether these convergent deficiencies in neural structures place infants at greater risk of exhibiting emotional and behavioral problems at later ages. Toward that end, we note that Milidou, Henriksen, Jensen, Olsen, and Søndergaard () found that children with a history of infantile colic had a slightly increased probability of exhibiting emotional and conduct problems, attention‐deficit/hyperactivity disorder, and difficult relations with peers in comparison to children who did not have a history of colic. That adolescents who had infantile colic demonstrate greater problems controlling and integrating emotions, attention, and self‐regulation could reflect a continuing decrement in functionality at the ACG level although, given the maturity of chemoreceptors as a backup for the reinitiation of breathing, the consequences would no longer be life threatening (SIDS) but find expression in different ways.…”

Multigenerational epigenetic effects of nicotine on lung function

“…This has led some practitioners to advocate the use of nicotine replacement therapy (NRT) as a smoking cessation aid for pregnant women since it may reduce the risk of low birth weight and preterm delivery [8]. However, the clinical community is divided on this recommendation because of continued concerns about efficacy and safety [9,10]. Preclinical investigators have long argued that nicotine is a developmental teratogen and should not be used as a treatment for pregnant smokers [2,11].…”