Impact of Caesarean section on the future health of offspring

The rates of Caesarean section (CS) are rapidly increasing worldwide and, currently, CS is the most common surgical procedure in women of child-bearing age [1]. In some regions, more than 50% of pregnant women – particularly primigravida – are delivered by CS [2]. This new and rapid change in mode of delivery probably reflects the notion that CS is life saving and prevents serious injury to both the mother [3] and her baby [4]. Increasing parental requests for elective CS are also boosted by a worrying increase in fear of childbirth [5,6] and, at the same time, a casual ‘drive-through’ attitude toward surgery, both among the public and professionals.

When addressing a request for CS and discussing the mode of delivery, short-term risks to the pregnant woman herself are the highest priority [7,8]. A clear majority of women and care givers are also concerned regarding the short-term risks for the newborn infant from vaginal delivery. However, only two out of three women are reported to have discussed risks to the infant during CS [7,8], in spite of the fact that CSs at term are associated with increased intrapartum and neonatal mortality, increased risk of admission for neonatal care, a prolonged length of hospital stay and increased probability of respiratory morbidity compared with vaginal delivery [3,9–11].

CS & disease risk in the offspring

While the long-term benefits and harms of CS for the mother are also important issues for discussion and counseling, much less is known regarding the implications of delivery mode and the future health of the offspring. With a rapidly growing population of children and young people who were delivered by CS, this gap in knowledge is now beginning to resolve. Epidemiological studies show an increased risk for autoimmune diseases, such as food allergy [12,13], allergic rhinitis and atopy [14,15] and asthma [16–20], in children delivered by CS. In meta-analyses, the over-risk for childhood asthma associated with CS was estimated to be 20–25% [16,19]. In view of the high and rising prevalence of pediatric asthma, this modest relative increase in risk can be translated into hundreds of thousands of affected children. CS has also been associated with a similar 20% over-risk of childhood-onset Type 1 diabetes [21]. Other morbidities that are associated with CS include childhood leukemia [22] and neuroblastoma [23], as well as testicular germ cell tumors (the most common cancer among young men) [24], although these findings have not been confirmed [25–27]. Finally, CS carries a 36% over-risk for later Legg–Calve’–Perthes disease (ischemic necrosis of the femoral head) in childhood, also after adjusting for malpresentation (breech position) of the fetus at the time of delivery [28].

Is it ‘guilt by association’ or will the current CS epidemic be another medical setback?

In the absence of a plausible underlying mechanism, a causal relationship between CS and later disease may seem far-fetched. One cannot rid oneself of a suspicion of confounding and that disease in childhood after delivery by CS is another case of guilt by association. “CS has always been accused for being the root of all evil,” my friend and colleague in obstetrics reassuringly commented some years ago. However, several of the recently reported associations of later disease risk in young people delivered by CS cannot be explained by known confounders, such as maternal age, parity, family history, socioeconomic status, maternal disease, pregnancy complications or smoking. Today, given the established associations between perinatal exposure and outcomes in adulthood [29,30], it is no longer unintelligible to see how changes in birth-related procedures during the transition from fetal to neonatal life may play a role in future health. CS alters the microbial colonization of the neonatal gut and, thereby, the priming of the neonatal immune system, which is the prevailing hypothesis regarding why the risk for autoimmune and allergic diseases increases after CS [31,32]. The evidence-based recommendation of antibiotic prophylaxis for women undergoing elective CS [33] adds further substance to such an explanation [34]. Different epigenetic programming of the offspring’s immune system can also occur in relation to the mode of delivery [35], which might provide an additional explanation for the increasing disease susceptibility found in children and young adults delivered by CS [36]. Finally, the timing and magnitude of birth stress is altered if delivery is performed via CS. Infants delivered by elective CS are physiologically unprepared for birth and lack the surge of stress hormones and activation of defense systems seen during vaginal delivery [37]. The full significance of this fundamental difference in birth-related stress remains to be studied. However, experimental evidence shows that adverse perinatal stress may permanently alter neuroendocrine and behavioral responses to stress in the adult offspring [38].

Where do we go from here?

Any other phenomenon – even one with the noblest motives – that, after a short exposure or intervention in early life, turns out to exhibit similar over-risks for later childhood and adult diseases (in terms of numbers and severity) as those that we now know to be associated with CS would be scrutinized beyond any doubt and, if necessary, stopped. However, CS is different. It is not all about the healthy baby’s future but also about fetal distress and maternal health in a broad sense. We should not ‘discontinue’ an everyday medical procedure that can be truly life saving in an emergency and, in many circumstances, constitutes a preventive measure with clear and sound cost–benefit ratio. However, it is time to leave the one-sided and sometimes ignorant perspective that seems to drive and justify a considerable proportion of the current epidemic of elective CS. A higher awareness among both professionals and childbearing women regarding the impact of CS on the future health of their offspring is warranted. CS should not be recommended solely on parental request without a clear medical indication, or without an individualized response to such a request, including an evaluation of potential harms and benefits. In such an evaluation, both short- and long-term consequences for the infant and child should carry a greater weight in professional recommendations and the patient’s informed consent.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.