research articles on maternal smoking

An official website of the United States government

Official websites use .gov A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Publications
Account settings
Advanced Search
Journal List

Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn

Mathias mund, frank louwen, doris klingelhoefer, alexander gerber.

Author information
Article notes
Copyright and License information

Author to whom correspondence should be addressed; E-Mail: [email protected] .

Received 2013 Oct 8; Revised 2013 Nov 12; Accepted 2013 Nov 13; Issue date 2013 Dec.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/ ).

Smoking cigarettes throughout pregnancy is one of the single most important avoidable causes of adverse pregnancy outcomes and it represents the first major environmental risk of the unborn. If compared with other risk factors in the perinatal period, exposure to tobacco smoke is considered to be amongst the most harmful and it is associated with high rates of long and short term morbidity and mortality for mother and child. A variety of adverse pregnancy outcomes are linked with cigarette consumption before and during pregnancy. Maternal prenatal cigarette smoke disturbs the equilibrium among the oxidant and antioxidant system, has negative impact on the genetic and cellular level of both mother and fetus and causes a large quantity of diseases in the unborn child. These smoking-induced damages for the unborn offspring manifest themselves at various times in life and for most only a very limited range of causal treatment exists. Education, support and assistance are of high importance to decrease maternal and fetal morbidity and mortality, as there are few other avoidable factors which influence a child’s health that profoundly throughout its life. It is imperative that smoking control should be seen as a public health priority.

Keywords: smoking, pregnancy, pregnant, tobacco, cigarette, prevention, therapy

1. Introduction

The fact that smoking cigarettes throughout pregnancy is one of the single most important avoidable cause of adverse pregnancy outcomes, resulting in severe short- and long-term negative effects for the mother and the unborn child has been proven by many different studies [ 1 , 2 , 3 , 4 ]. It can be regarded as the first major environmental risk factor that can be encountered by the unborn in the developed and undeveloped world. If compared with other risk factors in the perinatal period, exposure to tobacco smoke is considered to be amongst the most harmful. The byproducts of combustion are believed to inflict more damage on the fetus than the nicotine itself, but due to the complexity and number of dangerous substances it is unknown which toxic effect is caused by exactly which product [ 5 ]. This is especially significant as the majority of the smoking-induced harm for the unborn fetus is permanent. Even today modern medicine offers very little or no therapeutic treatments for the long-term negative consequences of being exposed to smoke in-utero [ 6 ]. According to a 2010 study from the USA, one of the most significant behavior changes a future mother can make is the complete cessation of smoking in pregnancy, with numerous health benefits for both the woman and her offspring [ 7 ].

2. Epidemiology and Risk Factors

In 1990 in Germany, a multicenter allergy study surveying 5,395 postpartum women concluded that 28.6% smoked during pregnancy [ 8 ]. These results are supported by a second German study from 2001–2002 investigating the cotinine-concentration in the urine of 323 pregnant women in the second trimester. Approximately one quarter of German future mothers smoked during pregnancy ( Figure 1 ) [ 4 ], although the rate of smokers varies from state to state. From 1998–2000, the highest frequencies in Germany were observed in the states of Mecklenburg-Vorpommern and Hamburg, whereas the lowest rates were found in Saxony, Thuringia and Bavaria ( Figure 2 ) [ 9 ]. In the first years of the new millennium the rate of smoking pregnant women in Germany declined further to approximately 20% [ 10 ].

Written information on smoking behavior of 310 pregnant women in Berlin 2001–2002; with kind permission and modified after [ 4 ].

Smoking behavior of pregnant women in different German states 1998–2000; with kind permission and modified after [ 5 ] .

Indicators of socio-economic status are an independent, reliable correlate of active smoking during pregnancy. Studies from Australia and Texas, USA indicated that low socio-economic status three or more times below the poverty line combined with the absence of health insurance increase the risk for smoking during pregnancy, regardless of ethnicity. The smoking rate among Australian women with low socio-economic position, both Aboriginal and non-Aboriginal, was on both occasions approximately two and a half times that of high socio-economic status Aboriginal and non-Aboriginal women [ 11 , 12 ]. Women exposing their unborn child to tobacco smoke were more likely not to be married to the child’s father [ 11 ]. Furthermore, women educated only up to high school standard were generally more likely to smoke during pregnancy [ 13 , 14 , 15 ]. Women employed in serving-related occupations and food preparation were considerably more likely to continue to smoke during pregnancy. They were at a greater risk for drinking alcohol while being pregnant as well. Additionally, women of this risk group showed tendencies to neglect early prenatal care in comparison to women in different occupational groups (Odds Ratio (OR) 1.8–3.0). Female scientist and managers, businesswomen, female artists and other women with higher education were much less likely to smoke during pregnancy compared to the general population of pregnant women (OR 0.2–0.5) [ 13 ].

Ethnic minorities often have an increased risk of smoking due to a variety of reasons. According to a Canadian study from 2011, 92% of pregnant Inuit women from Arctic Quebec smoked cigarettes [ 16 ]. Roma women in Eastern Europe were 5.2 times more likely ( p < 0.01) to continue smoking during pregnancy instead of quitting (OR 0.32; 95% Confidence Interval (CI) 0.14–0.72) [ 17 ].

3. Decreased Fertility and Pregnancy Complications Due to Smoking

For women of childbearing age, active and passive smoking is linked to reduced fertility [ 18 ]. Several studies agree that smoking women were more likely to have an abortion, with the total rate of abortion increasing up to 33% [ 19 , 20 , 21 , 22 ]. A Japanese case-cohort analysis from 2001 to 2005 involving 180,855 pregnant women concluded that women smoking during pregnancy had statistically considerably elevated risks for various obstetric complications and their rate for stillbirth was estimated by a British study to be increased by 23% ( Table 1 ) [ 23 , 24 ]. For example, a woman who smokes while being pregnant is more than 50% more likely to expose her unborn child to an infection within the womb in comparison to a non-smoker, as the smoker’s Absolute Risk Reduction (ARR) is 1.67 compared to the non-smoker.

Pregnancy complications due to smoking; modified after [ 23 , 24 ].

Even though in this UK study none of the relations with specific congenital abnormalities were significant by themselves, the overall risk of giving birth to a child with a congenital malformation increased by 13% (OR1.13; 95% Confidence interval (CI) 1.01–1.26) [ 24 ].

4. Biochemical Changes and Alterations

The placenta is an important source of hormones, pro-oxidant agents and antioxidant enzymes and in a physiological pregnancy this vital organ is able to control lipid peroxidation [ 10 ]. Several studies concluded that maternal prenatal cigarette smoking disturbs the equilibrium among the oxidant and antioxidant system, thus causing additional oxidative stress and augmenting lipid peroxidation. Smoking during pregnancy increases the free radical damage to the unborn fetus as well as to the mother [ 10 , 25 , 26 ].

5. Smoking and Intrauterine Growth Retardation

Intrauterine growth retardation of the unborn child is the most important smoking-induced pathology [ 6 ]. Two studies from 1999 and 2006 associated maternal smoking with an augmented dose-dependent risk for not only adverse birth outcomes such as small-for-gestational age (SGA) and intra-uterine growth restriction but for preterm birth (Adjusted Odds Ratio (AOR) 1.42; 95% CI 1.27–1.59) for both male and female babies as well [ 2 , 27 ]. These findings are supported by numerous studies, which all concluded that children born to mothers who have smoked during pregnancy had significantly decreased birth weights when compared with offspring of non-smokers [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. A Brazilian study about newborns exposed to tobacco smoke throughout pregnancy presented an average decrease in birth weight of 223.4 g (95% CI 156.7–290.0), a decrease in birth length of 0.94 cm (95% CI 0.60–1.28), and a decrease in head circumference of 0.69 cm (95% CI 0.42–0.95) [ 37 ]. Quitting smoking may have a greater impact on birth weight than refraining from illegal hard drug use, a study by the Quillen College of Medicine, USA examining 265 infants discovered. Among pregnant women who used hard illicit drugs and did not smoke, the adjusted mean birth weight increased 317 g compared to smokers who did not use any illegal drugs [ 6 ].

6. Alterations in the Genetic and Cellular Level

Smoking cigarettes has a tremendous negative impact on the genetic and cellular level of not only the mother but of the fetus as well, as numerous studies have proven. If certain genetic predispositions are present, the adverse effects of smoking during pregnancy are multiplied [ 30 , 32 , 38 ]. Genetic and epigenetic mechanisms in combination with cytogenetic damage are believed by a 2012 study from North Carolina, USA, to play an important role in the pathogenesis of malformations and adverse outcomes associated with smoking and pregnancy. In the study, methylation changes in a set of genes (Cytochrome P450 1A1 (CYP1A1), AHRR and GFI1) were present at birth in offspring whose mothers consumed tobacco during pregnancy. These genes seem to play an important role in the aryl hydrocarbon signaling pathway, which mediates the clearance and detoxification of the poisonous components of tobacco smoke [ 38 ].

In a Dutch study from May 2012 investigating the effects of smoking on the maternal immune system by examining first-trimester decidual tissue and peripheral blood, researchers concluded that mothers smoking during pregnancy have an altered local and systemic immune system. Using real-time reverse transcription-polymerase chain reaction, flow cytometry and immune-histochemical investigations, the study indicated that more natural-killer cells and inflammatory macrophages are present locally if the woman smokes cigarettes. According to the study smoking mothers have lower percentages of regulatory T-cells than pregnant women who do not smoke [ 30 ].

7. Diseases Caused by Smoking during Pregnancy

Cigarettes are legal poisons, which damage not only the health of the mother, but jeopardize the health of the unborn child as well. These smoking-induced damages for the unborn offspring manifest themselves at various times in life, some being clearly visible from birth on, others becoming evident only in the following generation. These diseases have one thing in common: the vast majority of them are permanent and for most only a very limited range of causal treatment exists. For many of these diseases only symptomatic therapeutic treatments are available at best [ 6 ].

7.1. Heart Diseases and Cardiovascular Diseases

The risk of fetal congenital heart defects has been shown by two studies to be at least partially linked to exposure to maternal smoking in early pregnancy or to be directly linked to maternal smoking during pregnancy for some specific subtypes [ 39 , 40 ].

A positive correlation between maternal smoking during pregnancy and the risk for congenital heart defects ( Table 2 ) was observed by a study from Atlanta, GA, USA [ 41 ] and backed up by a British meta-analysis, which also detected a significant positive correlation between maternal cigarette smoking and fetal cardiovascular and heart defects (OR 1.09; 95% CI 1.02–1.17) ( Table 2 ) [ 42 ]. Twelve of 17 subtypes of fetal congenital heart defects have been proven to be more closely associated to maternal cigarette consumption than the other five subtypes. In the study, these twelve subtypes accounted for 71% of fetal congenital heart defects. Fetal septal heart defects as a group were the highest risk for any subtype ( Table 2 ). The incidence of septal defects as a group, atrial septal defects and atrioventricular-septal defects correlated directly with the number of maternal cigarettes smoked [ 43 ].

Smoking and fetal congenital heart defects; modified after [ 41 , 42 , 43 ].

7.2. Hypertension and Kidney Diseases

Maternal cigarette smoking during pregnancy might also affect fetal kidney development. A dose-dependent relationship between the number of cigarettes consumed during pregnancy and fetal kidney volume was observed by a Dutch prospective cohort study of 1,072 children. Researchers found that maternal smoking of ten cigarettes per day correlated with a decreased fetal combined kidney volume compared to women who smoked less than five cigarettes per day ( p = 0.002). This could predispose the offspring to the development of kidney disease and hypertension later in adult life [ 44 ].

7.3. Pulmonary Diseases

A study from Detroit, MI, USA, has shown that smoking and pregnancy is significantly linked with a decrease in pulmonary function in offspring later in life [ 43 ]. An important increase in pediatric hospitalization and mortality because of respiratory infections in early childhood independent of both birth weight and gestational age was associated by a retrospective case-control analyses of infants born in Washington State from 1987–2004 with having been exposed to maternal smoking in-utero (AOR 1.69; 95% CI 1.63–1.76) [ 26 ].

Studies from the New York University School of Medicine, USA and from the Karolinska Institute, Sweden, found that pregnant women who have smoked cigarettes increased the risk of wheezing and asthma for their children. If children have been exposed to maternal smoking in-utero, but not in the first year after birth, the AOR increased for wheeze and asthma. At the age of four to six years the OR increased to 1.39 for wheeze (95% CI 1.08–1.77) and 1.65 for asthma (95% CI 1.18–2.31). The likeliness to suffer from these two diseases in later childhood increased significantly in relation to the amount of exposure to maternal cigarette smoke in-utero during the first trimester of pregnancy [ 37 , 44 ].

7.4. Gastrointestinal Diseases

A Danish follow-up study of singleton infants concluded that maternal smoking during pregnancy increases the risk for infantile colic even after adjustment for factors like maternal age, birth weight, gestational age, breastfeeding and paternal smoking. A two-fold increased risk for infantile colic was observed in offspring of women who smoked at least 15 cigarettes per day during their pregnancy ( Table 3 ) [ 45 ]. These findings are consistent with a study from the UK on non-chromosomal birth defects, which discovered that babies of mothers who have smoked during pregnancy were also at higher risk for gastrointestinal defects, gastroschisis and anal atresia ( Table 3 ) [ 40 ].

Maternal smoking and gastrointestinal diseases in the offspring; modified after [ 42 , 45 ].

8. BMI and Obesity

Multiple studies agree that maternal smoking during pregnancy harms linear growth, promotes increased Body Mass Index (BMI) in children and augments the risk for obesity in childhood and adult life [ 46 , 47 , 48 , 49 ]. Exposure to cigarettes in-utero causes increased mean BMI, pulse rate, waist circumference and waist-hip-ratio. Offspring of mothers who smoked at other times in the child’s life but not during their pregnancy have similar mean risk factors compared to children whose mothers never smoked. Among children of mothers who smoked during pregnancy, the degree of overweight children with an increased BMI is positively correlated with the duration of the maternal smoking, which is due to reduced height and increased amount of body fat [ 47 , 49 , 50 , 51 ].

9. Alterations in Neurology and Psychological Behavior

Early child neurodevelopment plays a key role in the potential of preserving human intelligence and health in the next generation, as stated in a study from the University of Iowa, USA [ 52 ]. Similarly, a review from Providence, RI, USA concluded that the various adverse aspects of long-term in-utero exposure to active and passive smoking on the neurological development of the child and its behavior have become the focus of a few investigations in recent years [ 53 ].

Maternal smoking during pregnancy has been linked to growth restriction and decrease in the size of the fetal brain by numerous studies. It has been proven that the density of important parts of the fetal brain, namely the cerebellum and the corpus callosum is diminished. A decrease in coordination within the different parts of the fetal brain during processing of information and a deceleration in the ability to adequately respond to external stimuli and subtly diminished motor competence predominantly on the non-dominant side have been shown by these studies [ 53 , 54 , 55 ].

In a 2011 Finish cohort study investigating various cognitive functions such as general reasoning, visual-motor integration, verbal competence and language comprehension in 1,019 infants, researchers found a pattern between heavy cigarette consumption prior to pregnancy with poorer cognitive executive function proficiency in the offspring. Interestingly, the results indicated a poorer performance of the offspring even if the woman had ceased smoking before conception. Children of mothers who smoked more than ten cigarettes per day before pregnancy but none during pregnancy scored 12.07 (95% CI 4.07–20.08) age-standardized points less in general reasoning and 11.23 (95% CI 2.81–19.66) age-standardized points less in language comprehension tests compared to children of mothers who never smoked [ 56 ]. Independent of maternal education levels offspring born to smoking mothers were also more probable to achieve less in math (OR 2.78; 95% CI 1.59–4.87) and reading (OR 2.00; 95% CI 1.10–3.63) compared to children of non-smokers [ 57 ].

10. Addiction

Pregnancy functions as a motivator to quit smoking and is a good time to stop smoking since pregnant women are more probable to be in an advanced phase of behavioral change. This was proven by a study from Philadelphia, PA, USA to be true even for pregnant nicotine- and opioid-dependent patients in substance abuse programs [ 58 ]. In a comparative study by the University of Padua, Italy pregnant women reported decreased levels of nicotine use and lower level of self-reported cigarette cravings reaching a statistically significant level in comparison to non-pregnant female patients [ 59 ].

Generally a low uptake of smoking cessation programs among pregnant females has been observed by many different studies. Pregnant females with high levels of nicotine dependence and several occupational groups such as women in serving-related occupations and in food preparation were the most unlikely socio-economic group to give up smoking during pregnancy or to take advantage of smoking cessation interventions [ 13 , 17 , 60 , 61 ]. In particular, smoking cessation programs for pregnant low-income smokers were for the most part unsuccessful, a study from Buffalo, NY, USA discovered [ 62 ].

Several studies indicated that even if the pregnant woman has been able to quit or reduce smoking, the smoking rate increased again after giving birth. During pregnancy, 45% of smoking women were able to quit smoking but at 24 weeks post-delivery only 34.6% of women remained abstinent and almost 80% continued to smoke within one year postpartum [ 3 , 63 , 64 ]. Unfortunately, quitting smoking during pregnancy was proven by a study from Vermont, GA, USA, investigating data from over 40,000 adults, not to be significantly connected to the smoking status three years later [ 65 ].

11. Therapy and Anti-Smoking Programs

Pregnant women who smoke welcome receiving advice on how to quit or reduce smoking from midwives, a comparative study from the UK discovered. Nevertheless, according to the study, they tend to have negative expectations of smoking cessation programs services, even though the experiences of those who have participated are positive [ 66 ]. A South African study on midwives concluded that the way in which medical personal communicate about the issue of smoking and pregnancy is of high importance. The most positive response from pregnant women was obtained by the patient-centered approach which is based on short motivational interviewing and a trusting and cooperative connection between midwife and patient. Medical personal practicing this modern approach was more successful in fulfilling their function in smoking cessation programs [ 67 ].

A comparative study from Italy recommended that smoking cessation campaigns should not only target the smoking future mother. Instead, the social network including partners, roommates, family and friends who smoke should be included as well, especially in postpartum women [ 59 ]. A systematic literature review from Vancouver, BC, Canada attributed a significant role to the male partner’s smoking behavior. Their support for the woman’s efforts to diminish or abstain from smoking cigarettes may impact her success in doing so. Regardless of the significance of partner smoking, there are only a small number of effective anti-smoking programs for pregnant and postpartum females that take male partners into consideration [ 68 ].

In comparison to smoking pregnant women who received only brief routine advice to quit, a US randomized controlled trial discovered that women who were additionally educated by a “Commit to Quit” video, a “Pregnant Woman’s Guide to Quit Smoking” and counseling achieved a significantly higher cessation rate (17.3% vs. 8.8%) [ 69 ].

Unconventional methods can be effective if additionally added to established methods of treatment. A small Japanese study ( n = 48) investigating the effectiveness of an e-learning program which supports pregnant women willing to quit smoking by use of a cell phone internet connection reported a high achievement rate of 71.1%. The maternal carbon monoxide exhalation levels were significantly reduced from 6.43 (±4.5) ppm to 0.29 (±1.08) after three months ( p < 0.001) [ 70 ]. These findings certainly have to be regarded in the context of a technologically highly advanced society, but the very principle should be applicable to a country of the developing world as well.

Two studies from Australia and Italy indicated that in addition to being significantly less likely to smoke cigarettes in general (AOR 0.10; 95% CI 0.02–0.68), women breastfeeding their children were in the short and long term more likely to stay abstinent or smoke less compared to non-breastfeeding women. Breastfeeding in itself may also indirectly support smoking cessation, even without the presence of specific anti-smoking campaigns and should therefore be widely promoted [ 71 , 72 ].

Additionally to high quality educational programs the pharmacological aspect needs to be taken more into consideration [ 73 ]. A Canadian study from 2012 emphasized on the importance of using suitable drugs which include nicotine in different forms as replacement therapy and sustained-release bupropion. In the study, nicotine replacement therapy and bupropion did not seem to augment the prenatal risk of malformations. For an additional drug varenicline, insufficient data has been collected to safely advise its use during pregnancy. Taking into consideration that these pharmacological agents on their own are only marginally successful in smoking cessation, their prescription should at all times be combined with behavioral counseling and education to optimize success rates [ 74 ].

12. Conclusions

The epidemiology, pathogenesis and methods of education and prevention of smoking and pregnancy are of great interest and importance for public health, as there are few other avoidable factors which influence a child’s health that profoundly throughout its life. In 1990 in Germany, 28.6% of women smoke during pregnancy; the highest frequencies are observed in Mecklenburg-Vorpommern and Hamburg, the lowest in Saxony, Thuringia and Bavaria. In the first years of the new millennium the rate declines to approximately 20%. Low socio-economic status, lower education and belonging to an ethnic minority increase the risk for smoking during pregnancy significantly.

Smoking women are up to 33% more likely to have an abortion and suffer from considerably elevated risks for various obstetric complications. For smokers the rate for stillbirth is increased by 23% and the overall risk of giving birth to a child with a congenital malformation increases by 13%. Babies of smokers are more likely to be SGA and suffer from intra-uterine growth restriction as well as to be born before term.

Smoking cigarettes has a negative impact on the maternal and fetal genetic and cellular level; the increase in fetal septal heart defects correlate directly with the number of maternal cigarettes smoked during pregnancy. Maternal cigarette smoking during pregnancy is likely to affect fetal kidney development leading to kidney disease and hypertension later in adult life. Smoking and pregnancy is significantly linked with a decrease in pulmonary function in addition to wheezing, asthma and respiratory infections in offspring later in life. Additionally, an elevated risk for various gastrointestinal defects is observed in offspring of smokers. Smoking during pregnancy harms linear growth, promotes increased BMI in children and augments the risk for obesity in childhood and adult life. Maternal smoking during pregnancy has been linked to decrease in the size of the fetal brain as well as to diminish general reasoning, visual-motor integration, verbal competence and language comprehension in the offspring.

During pregnancy, 45% of smoking women are able to quit smoking, but almost 80% continue to smoke within one year postpartum. A low uptake of smoking cessation programs among pregnant females has been observed in particular among pregnant low-income smokers. Pregnant women who smoke welcome receiving advice on how to quit; the way in which medical personal communicate about the issue of smoking and pregnancy is of high importance. The most positive response is obtained by the patient-centered approach based on short motivational interviewing and a trusting and cooperative connection. For these reasons, medical personal should be specially trained in this highly sensitive task. Smoking cessation campaigns should target the smoking future mother as well as her social network. Male partners, roommates, family and friends should be included, especially in postpartum women. The importance of breastfeeding cannot be emphasized enough. Smoking cessation campaigns should combine these conventional methods with modern building blocks like multimedia, videos, computers and e-learning programs in addition to mobile telephone communication. Another focus should be set on the pharmacological aspect with nicotine replacement therapy and other suitable supporting drugs. Culturally and socio-economically sensitive smoking cessation programs need to be established for the ethnic and socio-economic groups of pregnant women most at risk.

Conflicts of Interest

The authors declare no conflict of interest.

1. Higgins S.T., Washio Y., Heil S.H., Solomon L.J., Gaalema D.E., Higgins T.M., Bernstein I.M. Financial incentives for smoking cessation among pregnant and newly postpartum women. Prev. Med. 2011;55:S33–S40. doi: 10.1016/j.ypmed.2011.12.016. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
2. Bickerstaff M., Beckmann M., Gibbons K., Flenady V. Recent cessation of smoking and its effect on pregnancy outcomes. Aust. N. Z. J. Obstet. Gynaecol. 2012;52:54–58. doi: 10.1111/j.1479-828X.2011.01387.x. [ DOI ] [ PubMed ] [ Google Scholar ]
3. El-Mohandes A.A., El-Khorazaty M.N., Kiely M., Gantz M.G. Smoking cessation and relapse among pregnant African-American smokers in Washington, DC. Matern. Child Health J. 2011;15:S96–S105. doi: 10.1007/s10995-011-0825-6. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
4. Dudenhausen J.W. Rauchen in der Schwangerschaft—Häufigkeit. Urban und Vogel; Munich, Germany: 2009. (in German) [ Google Scholar ]
5. Knut-Olaf H., Groneberg D. Tabakabhängigkeit—Gesundheitliche Schäden durch das Rauchen. Springer Verlag; Berlin, Germany: 2008. (in German) [ Google Scholar ]
6. Thäle V., Schlitt A. Effects of alcohol and smoking in pregnancy. Internist. 2011;52:1185–1190. doi: 10.1007/s00108-011-2826-3. [ DOI ] [ PubMed ] [ Google Scholar ]
7. Simmons V.N., Cruz L.M., Brandon T.H., Quinn G.P. Translation and adaptation of smoking relapse-prevention materials for pregnant and postpartum Hispanic women. J. Health Commun. 2011;16:90–107. doi: 10.1080/10810730.2010.529492. [ DOI ] [ PubMed ] [ Google Scholar ]
8. Rauchen Während Der Schwangerschaft Oder Niedriger Sozialstatus. [(accessed on 5 October 2013)]. Available online: https://www.thieme-connect.com/ejournals/abstract/10.1055/s-2001-18366 .
9. Rauchen in der Schwangerschaft. [(accessed on 5 October 2013)]. Available online: http://www.stern.de/gesundheit/gesundheitsnews/rauchen-in-der-schwangerschaft-gewuerzgurken-und-glimmstaengel-608001.html .
10. Dittrich R., Schibel A., Hoffmann I., Mueller A., Beckmann M.W., Cupisti S. Influence of maternal smoking during pregnancy on oxidant status in amniotic fluid. In Vivo. 2012;26:813–818. [ PubMed ] [ Google Scholar ]
11. Page R.L., Padilla Y.C., Hamilton E.R. Psychosocial factors associated with patterns of smoking surrounding pregnancy in fragile families. Matern. Child Health J. 2012;16:249–257. doi: 10.1007/s10995-010-0735-z. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
12. Thrift A.P., Nancarrow H., Bauman A.E. Maternal smoking during pregnancy among aboriginal women in New South Wales is linked to social gradient. Aust. N. Z. J. Public Health. 2011;35:337–342. doi: 10.1111/j.1753-6405.2011.00728.x. [ DOI ] [ PubMed ] [ Google Scholar ]
13. Agopian A.J., Lupo P.J., Herdt-Losavio M.L., Langlois P.H., Rocheleau C.M., Mitchell L.E., National birth defects prevention study Differences in folic acid use, prenatal care, smoking, and drinking in early pregnancy by occupation. Prev. Med. 2012;55:341–345. doi: 10.1016/j.ypmed.2012.07.015. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
14. Batista J., Albuquerque M.F., Ximenes R.A., Miranda-Filho D.B., Melo H.R., Maruza M., Moura L.V., Ferraz E.J., Rodrigues L.C. Prevalence and socioeconomic factors associated with smoking in people living with HIV by sex, in Recife, Brazil. Rev. Bras. Epidemiol. 2013;16:432–443. doi: 10.1590/S1415-790X2013000200018. [ DOI ] [ PubMed ] [ Google Scholar ]
15. O’Callaghan F.V., O’Callaghan M., Najman J.M., Williams G.M., Bor W., Alati R. Prediction of adolescent smoking from family and social risk factors at 5 years, and maternal smoking in pregnancy and at 5 and 14 years. Addiction. 2006;101:282–290. doi: 10.1111/j.1360-0443.2006.01323.x. [ DOI ] [ PubMed ] [ Google Scholar ]
16. Muckle G., Laflamme D., Gagnon J., Boucher O., Jacobson J.L., Jacobson S.W. Alcohol, smoking, and drug use among Inuit women of childbearing age during pregnancy and the risk to childre. Alcohol. Clin. Exp. Res. 2011;35:1081–1091. doi: 10.1111/j.1530-0277.2011.01441.x. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
17. Foley K.L., Balázs P., Grenczer A., Rákóczi I. Factors associated with quit attempts and quitting among Eastern Hungarian women who smoked at the time of pregnancy. Cent. Eur. J. Public Health. 2011;19:63–66. doi: 10.21101/cejph.a3631. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
18. Murin S., Rafii R., Bilello K. Smoking and smoking cessation in pregnancy. Clin. Chest. Med. 2011;32:75–91. doi: 10.1016/j.ccm.2010.11.004. [ DOI ] [ PubMed ] [ Google Scholar ]
19. Ahluwawalia I.B., Grummer-Strawn L., Scanlon K.S. Exposure to environmental tobacco smoke and birth outcome: Increased effects on pregnant women aged 30 years and older. Am. J. Epidemiol. 1997;146:42–47. doi: 10.1093/oxfordjournals.aje.a009190. [ DOI ] [ PubMed ] [ Google Scholar ]
20. Ananth C.V., Savitz D.A., Luther E.R. Maternal cigarette smoking as a risk factor for placental abruption, placenta previa, and uteine bleeding in pregnancy. Am. J. Epidemiol. 1996;144:881–889. doi: 10.1093/oxfordjournals.aje.a009022. [ DOI ] [ PubMed ] [ Google Scholar ]
21. Cnattingius S., Axelsson O., Eklund G., Lindmark G. Smoking, maternal age, and fetal growth. Obstet. Gynecol. 1985;66:449–452. [ PubMed ] [ Google Scholar ]
22. Wang X., Tager I.B., Van Vunakis H., Speizer F.E., Hanrahan J.P. Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study. Int. J. Epidemiol. 1997;26:978–988. doi: 10.1093/ije/26.5.978. [ DOI ] [ PubMed ] [ Google Scholar ]
23. Hayashi K., Matsuda Y., Kawamichi Y., Shiozaki A., Saito S. Smoking during pregnancy increases risks of various obstetric complications: A case-cohort study of the Japan Perinatal Registry Network database. J. Epidemiol. 2011;21:61–66. doi: 10.2188/jea.JE20100092. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
24. Leonardi-Bee J., Britton J., Venn A. Secondhand smoke and adverse fetal outcomes in nonsmoking pregnant women: A meta-analysis. Pediatrics. 2011;127:734–741. doi: 10.1542/peds.2010-3041. [ DOI ] [ PubMed ] [ Google Scholar ]
25. Chelchowska M., Ambroszkiewicz J., Gajewska J., Laskowska-Klita T., Leibschang J. The effect of tobacco smoking during pregnancy on plasma oxidant and antioxidant status in mother and newborn. Eur. J. Obstet. Gynecol. Reprod. Biol. 2011;155:132–136. doi: 10.1016/j.ejogrb.2010.12.006. [ DOI ] [ PubMed ] [ Google Scholar ]
26. Sahinli A.S., Marakoğlu K., Kiyici A. Evaluation of the levels of oxidative stress factors and ischemia modified albumin in the cord blood of smoker and non-smoker pregnant women. J. Matern. Fetal Neonatal Med. 2012;25:1064–1068. doi: 10.3109/14767058.2011.622001. [ DOI ] [ PubMed ] [ Google Scholar ]
27. Suzuki K., Kondo N., Sato M., Tanaka T., Ando D., Yamagata Z. Gender differences in the association between maternal smoking during pregnancy and childhood growth trajectories: Multilevel analysis. Int. J. Obes. 2011;35:53–59. doi: 10.1038/ijo.2010.198. [ DOI ] [ PubMed ] [ Google Scholar ]
28. Metzger M.J., Halperin A.C., Manhart L.E., Hawes S.E. Association of maternal smoking during pregnancy with infant hospitalization and mortality due to infectious diseases. Pediatr. Infect. Dis. J. 2012;32:e1–e7. doi: 10.1097/INF.0b013e3182704bb5. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
29. Erickson A.C., Arbour L.T. Heavy smoking during pregnancy as a marker for other risk factors of adverse birth outcomes: A population-based study in British Columbia, Canada. BMC Public Health. 2012;12:102. doi: 10.1186/1471-2458-12-102. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
30. Prins J.R., Hylkema M.N., Erwich J.J., Huitema S., Dekkema G.J., Dijkstra F.E., Faas M.M., Melgert B.N. Smoking during pregnancy influences the maternal immune response in mice and humans. Am. J. Obstet. Gynecol. 2012;207:76.e1–76.e14. doi: 10.1016/j.ajog.2012.04.017. [ DOI ] [ PubMed ] [ Google Scholar ]
31. Titova O.E., Ayvazova E.A., Bichkaeva F.A., Brooks S.J., Chumakova G.N., Schiöth H.B., Benedict C. The influence of active and passive smoking during pregnancy on umbilical cord blood levels of vitamins A and E and neonatal anthropometric indices. Br. J. Nutr. 2012;108:1341–1345. doi: 10.1017/S000711451100688X. [ DOI ] [ PubMed ] [ Google Scholar ]
32. Tyrrell J., Huikari V., Christie J.T., Cavadino A., Bakker R., Brion M.J., Geller F., Paternoster L., Myhre R., Potter C., et al. Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight. Hum. Mol. Genet. 2012;21:5344–5358. doi: 10.1093/hmg/dds372. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
33. Chertok I.R., Luo J., Anderson R.H. Association between changes in smoking habits in subsequent pregnancy and infant birth weight in West Virginia. Matern. Child Health J. 2011;15:249–254. doi: 10.1007/s10995-010-0582-y. [ DOI ] [ PubMed ] [ Google Scholar ]
34. Lelong N., Blondel B., Kaminski M. Smoking during pregnancy in France between 1972 to 2003: Results from the national perinatal surveys. J. Gynecol. Obstet. Biol. Reprod. (Paris) 2011;40:42–49. doi: 10.1016/j.jgyn.2010.07.007. [ DOI ] [ PubMed ] [ Google Scholar ]
35. Pavić I., Dodig S., Jurković M., Krmek T., Spanović D. The influence of mother’s active smoking during pregnancy on body mass index of newborns. Coll. Antropol. 2011;35:1149–1154. [ PubMed ] [ Google Scholar ]
36. Lynch C.M., O’Kelly R., Stuart B., Treumann A., Conroy R., Regan C.L. The role of thromboxane A(2) in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy. Prostaglandins Other Lipid Mediat. 2011;95:63–67. doi: 10.1016/j.prostaglandins.2011.06.007. [ DOI ] [ PubMed ] [ Google Scholar ]
37. Zhang L., González-Chica D.A., Cesar J.A., Mendoza-Sassi R.A., Beskow B., Larentis N., Blosfeld T. Maternal smoking during pregnancy and anthropometric measurements of newborns: A population-based study in southern of Brazil. Cad. Saude Publica. 2011;27:1768–1776. doi: 10.1590/S0102-311X2011000900010. [ DOI ] [ PubMed ] [ Google Scholar ]
38. Joubert B.R., Håberg S.E., Nilsen R.M., Wang X., Vollset S.E., Murphy S.K., Huang Z., Hoyo C., Midttun Ø., Cupul-Uicab L.A., et al. 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking During Pregnancy. Environ. Health Perspect. 2012;120:1425–1431. doi: 10.1289/ehp.1205412. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
39. Allina J., Grabowski J., Doherty-Lyons S., Fiel M.I., Jackson C.E., Zelikoff J.T., Odin J.A. Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring. J. Immunotoxicol. 2011;8:258–264. doi: 10.3109/1547691X.2011.589412. [ DOI ] [ PubMed ] [ Google Scholar ]
40. Chehab G., El-Rassi I., Adhami A., Chokor I., Chatila F., Haddad W., Saliba Z. Parental smoking during early pregnancy and congenital heart defects. J. Med. Liban. 2012;60:14–18. [ PubMed ] [ Google Scholar ]
41. Alverson C.J., Strickland M.J., Gilboa S.M., Correa A. Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study. Pediatrics. 2011;127:e647–e653. doi: 10.1542/peds.2010-1399. [ DOI ] [ PubMed ] [ Google Scholar ]
42. Hackshaw A., Rodeck C., Boniface S. Maternal smoking in pregnancy and birth defects: A systematic review based on 173 687 malformed cases and 11.7 million controls. Hum. Reprod. Update. 2011;17:589–604. doi: 10.1093/humupd/dmr022. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
43. Lee L.J., Lupo P.J. Maternal Smoking During Pregnancy and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Metaanalysis. Pediatr. Cardiol. 2012;34:398–407. doi: 10.1007/s00246-012-0470-x. [ DOI ] [ PubMed ] [ Google Scholar ]
44. Taal H.R., Geelhoed J.J., Steegers E.A., Hofman A., Moll H.A., Lequin M., van der Heijden A.J., Jaddoe V.W. Maternal smoking during pregnancy and kidney volume in the offspring: The Generation R Study. Pediatr. Nephrol. 2011;26:1275–1283. doi: 10.1007/s00467-011-1848-3. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
45. Søndergaard C., Henriksen T.B., Obel C., Wisborg K. Smoking during pregnancy and infantile colic. Pediatrics. 2001;108:342–346. doi: 10.1542/peds.108.2.342. [ DOI ] [ PubMed ] [ Google Scholar ]
46. Matijasevich A., Brion M.J., Menezes A.M., Barros A.J., Santos I.S., Barros F.C. Maternal smoking during pregnancy and offspring growth in childhood: 1993 and 2004 Pelotas cohort studies. Arch. Dis. Child. 2011;96:519–525. doi: 10.1136/adc.2010.191098. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
47. Mamun A.A., O’Callaghan M.J., Williams G.M., Najman J.M. Maternal smoking during pregnancy predicts adult offspring cardiovascular risk factors - evidence from a community-based large birth cohort study. PLoS One. 2012;7:e41106. doi: 10.1371/journal.pone.0041106. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
48. Raum E., Küpper-Nybelen J., Lamerz A., Hebebrand J., Herpertz-Dahlmann B., Brenner H. Tobacco smoke exposure before, during, and after pregnancy and risk of overweight at age 6. Obesity. 2011;19:2411–2417. doi: 10.1038/oby.2011.129. [ DOI ] [ PubMed ] [ Google Scholar ]
49. Durmus B., Kruithof C.J., Gillman M.H., Willemsen S.P., Hofman A., Raat H., Eilers P.H., Steegers E.A., Jaddoe V.W. Parental smoking during pregnancy, early growth, and risk of obesity in preschool children: The Generation R Study. Am. J. Clin. Nutr. 2011;94:164–171. doi: 10.3945/ajcn.110.009225. [ DOI ] [ PubMed ] [ Google Scholar ]
50. Ino T., Shibuya T., Saito K., Inaba Y. Relationship between body mass index of offspring and maternal smoking during pregnancy. Int. J. Obes. (Lond) 2012;36:554–558. doi: 10.1038/ijo.2011.255. [ DOI ] [ PubMed ] [ Google Scholar ]
51. Koch S., Vilser C., Groß W., Schleußner E. Smoking during pregnancy: Risk for intrauterine growth retardation and persisting microsomia. Z. Geburtshilfe Neonatol. 2012;216:77–81. doi: 10.1055/s-0032-1308958. [ DOI ] [ PubMed ] [ Google Scholar ]
52. Wehby G.L., Prater K., McCarthy A.M. The Impact of Maternal Smoking during Pregnancy on Early Child Neurodevelopment. J. Hum. Cap. 2011;5:207–254. doi: 10.1086/660885. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
53. Bublitz M.H., Stroud L.R. Maternal smoking during pregnancy and offspring brain structure and function: Review and agenda for future research. Nicotine Tob. Res. 2012;14:388–397. doi: 10.1093/ntr/ntr191. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
54. Cents R.A., Bublitz M.H., Stroud L.R. Maternal smoking during pregnancy and child emotional problems: The relevance of maternal and child 5-HTTLPR genotype. Am. J. Med. Genet. B Neuropsychiatr Genet. 2012;159:289–297. doi: 10.1002/ajmg.b.32026. [ DOI ] [ PubMed ] [ Google Scholar ]
55. Larsson M., Montgomery S.M. Maternal smoking during pregnancy and physical control and coordination among offspring. J. Epidemiol. Community Health. 2011;65:1151–1158. doi: 10.1136/jech.2008.085241. [ DOI ] [ PubMed ] [ Google Scholar ]
56. Heinonen K., Räikkönen K., Pesonen A.K., Andersson S., Kajantie E., Eriksson J.G., Wolke D., Lano A. Longitudinal study of smoking cessation before pregnancy and children’s cognitive abilities at 56 months of age. Early Hum. Dev. 2011;87:353–339. doi: 10.1016/j.earlhumdev.2011.02.002. [ DOI ] [ PubMed ] [ Google Scholar ]
57. Piper B.J., Corbett S.M. Executive function profile in the offspring of women that smoked during pregnancy. Nicotine Tob. Res. 2012;14:191–199. doi: 10.1093/ntr/ntr181. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
58. Holbrook A.M., Kaltenbach K.A. Effectiveness of a smoking cessation intervention for methadone-maintained women: A comparison of pregnant and parenting women. Int. J. Pediatr. 2011;2011:567056. doi: 10.1155/2011/567056. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
59. Buja A., Guarnieri E., Forza G., Tognazzo F., Sandonà P., Zampieron A. Socio-demographic factors and processes associated with stages of change for smoking cessation in pregnant versus non-pregnant women. BMC Womens Health. 2011;11:3. doi: 10.1186/1472-6874-11-3. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
60. Blalock J.A., Nayak N., Wetter D.W., Schreindorfer L., Minnix J.A., Canul J., Cinciripini P.M. The relationship of childhood trauma to nicotine dependence in pregnant smokers. Psychol. Addict. Behav. 2011;25:652–663. doi: 10.1037/a0025529. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
61. Wang C.Y., Kuo S.C. Pregnancy and the struggle to quit smoking. Hu Li Za Zhi. 2011;58:87–92. [ PubMed ] [ Google Scholar ]
62. Eiden R.D., Leonard K.E., Colder C.R., Homish G.G., Schuetze P., Gray T.R., Huestis M.A. Anger, hostility, and aggression as predictors of persistent smoking during pregnancy. J. Stud. Alcohol Drugs. 2011;72:926–932. doi: 10.15288/jsad.2011.72.926. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
63. Nguyen S.N., Von Kohorn I., Schulman-Green D., Colson E.R. The importance of social networks on smoking: Perspectives of women who quit smoking during pregnancy. Matern. Child Health J. 2012;16:1312–1318. doi: 10.1007/s10995-011-0896-4. [ DOI ] [ PubMed ] [ Google Scholar ]
64. Levine M.D., Cheng Y., Marcus M.D., Kalarchian M.A. Relapse to smoking and postpartum weight retention among women who quit smoking during pregnancy. Obesity (Silver Spring) 2012;20:457–459. doi: 10.1038/oby.2011.334. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
65. Grover K.W., Zvolensky M.J., Lemeshow A.R., Galea S., Goodwin R.D. Does quitting smoking during pregnancy have a long-term impact on smoking status? Drug. Alcohol Depend. 2012;123:110–114. doi: 10.1016/j.drugalcdep.2011.10.024. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
66. Herberts C., Sykes C. Midwives’ perceptions of providing stop-smoking advice and pregnant smokers’ perceptions of stop-smoking services within the same deprived area of London. J. Midwifery Womens Health. 2012;57:67–73. doi: 10.1111/j.1542-2011.2011.00072.x. [ DOI ] [ PubMed ] [ Google Scholar ]
67. Everett-Murphy K., Paijmans J., Steyn K., Matthews C., Emmelin M., Peterson Z. Scolders, carers or friends: South African midwives’ contrasting styles of communication when discussing smoking cessation with pregnant women. Midwifery. 2011;27:517–524. doi: 10.1016/j.midw.2010.04.003. [ DOI ] [ PubMed ] [ Google Scholar ]
68. Hemsing N., Greaves L., O’Leary R., Chan K., Okoli C. Partner support for smoking cessation during pregnancy: A systematic review. Nicotine Tob. Res. 2012;14:767–776. doi: 10.1093/ntr/ntr278. [ DOI ] [ PubMed ] [ Google Scholar ]
69. Windsor R., Woodby L., Miller T., Hardin M. Effectiveness of Smoking Cessation and Reduction in Pregnancy Treatment (SCRIPT) methods in Medicaid-supported prenatal care: Trial III. Health Educ. Behav. 2011;38:412–422. doi: 10.1177/1090198110382503. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
70. Fujioka N., Kobayashi T., Turale S. Short-term behavioral changes in pregnant women after a quit-smoking program via e-learning: A descriptive study from Japan. Nurs. Health Sci. 2012;14:304–311. doi: 10.1111/j.1442-2018.2012.00702.x. [ DOI ] [ PubMed ] [ Google Scholar ]
71. Lauria L., Lamberti A., Grandolfo M. Smoking behaviour before, during, and after pregnancy: The effect of breastfeeding. Sci. World J. 2012;2012:154910. doi: 10.1100/2012/154910. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
72. Xu H., Wen L.M., Rissel C., Baur L.A. Smoking Status and Factors Associated with Smoking of First-Time Mothers During Pregnancy and Postpartum: Findings from the Healthy Beginnings Trial. Matern. Child Health J. 2012;17:1151–1157. doi: 10.1007/s10995-012-1108-6. [ DOI ] [ PubMed ] [ Google Scholar ]
73. Filion K.B., Abenhaim H.A., Mottillo S., Joseph L., Gervais A., O’Loughlin J., Paradis G., Pihl R., Pilote L., Rinfret S. The effect of smoking cessation counselling in pregnant women: A meta-analysis of randomised controlled trials. BJOG. 2011;118:1422–1428. doi: 10.1111/j.1471-0528.2011.03065.x. [ DOI ] [ PubMed ] [ Google Scholar ]
74. Cressman A.M., Pupco A., Kim E., Koren G., Bozzo P. Smoking cessation therapy during pregnancy. Can. Fam. Physician. 2012;58:525–527. [ PMC free article ] [ PubMed ] [ Google Scholar ]
View on publisher site
PDF (252.5 KB)
Collections

Add to Collections

Open access
Published: 01 November 2022

Maternal factors during pregnancy influencing maternal, fetal, and childhood outcomes

Louis J. Muglia ORCID: orcid.org/0000-0002-0301-8770 1 , 2 ,
Katrien Benhalima 3 ,
Stephen Tong 4 , 5 &
Susan Ozanne 6

BMC Medicine volume 20 , Article number: 418 ( 2022 ) Cite this article

16k Accesses

25 Citations

36 Altmetric

Metrics details

Enhancing pregnancy health is known to improve the mother’s and offspring’s life-long well-being. The maternal environment, encompassing genetic factors, impacts of social determinants, the nutritional/metabolic milieu, and infections and inflammation, have immediate consequences for the in utero development of the fetus and long-term programming into childhood and adulthood. Moreover, adverse pregnancy outcomes such as preterm birth or preeclampsia, often attributed to the maternal environmental factors listed above, have been associated with poor maternal cardiometabolic health after pregnancy. In this BMC Medicine article collection, we explore a broad spectrum of maternal characteristics across pregnancy and postnatal phenotypes, anticipating substantial cross-fertilization of new understanding and shared mechanisms around diverse outcomes. Advances in the ability to leverage ‘omics across different platforms (genome, transcriptome, proteome, metabolome, microbiome, lipidome), large high-dimensional population databases, and unique cohorts are generating exciting new insights: The first articles in this collection highlight the role of placental biomarkers of preterm birth, metabolic influences on fetal and childhood growth, and the impact of common pre-existing maternal disorders, obesity and smoking on pregnancy outcomes, and the child’s health. As the collection grows, we look forward to seeing the connections emerge across maternal, fetal, and childhood outcomes that will foster new insights and preventative strategies for women.

The extraordinary, foundational months of pregnancy are a time of emergence of a new life for the conceptus and remarkable physiological and psychological adaptation by the mother. The orchestration of mutual communication between the mother and fetus is the driver of long-term health. It is shaped primarily by the maternal environment, with its genetic, physiologic, nutritional, inflammatory/infection, and psychological components. It has been repeatedly recognized that the in utero environment programs the fetus for lifelong health—the Barker Hypothesis—and pregnancy complications such as preeclampsia and preterm birth impact maternal cardiovascular health [ 1 , 2 ].

This special collection of articles by BMC Medicine seeks to synthesize information related to maternal and offspring outcomes associated with in utero exposures across pregnancy phenotypes and complications. Among the most common maternal traits that impact multiple aspects of fetal outcomes are maternal undernutrition and, more often, maternal overnutrition/obesity, associated with complications from development in an obesogenic environment and influences of gestational diabetes mellitus. In addition, the mechanisms leading to abnormalities in gestational duration and an increased risk for adverse outcomes such as preterm birth are central research targets [ 3 ]. The growing opportunity to interrogate “big data” with artificial intelligence or machine learning tools will accelerate this research and help to determine pregnancy interventions that are both safe and effective [ 4 , 5 , 6 , 7 ].

The editors believe that providing novel insights on exposures and outcomes across pregnancy phenotypes will be mutually informative as many driving determinants are shared. In this editorial, we will highlight some initial contributions to this collection and the new information that has been revealed.

Towards better health of mother and child—novel insights and potential pathways for intervention

Revealing underlying mechanisms in preterm birth and potential links to polycystic ovary syndrome.

Adverse pregnancy outcomes are common and have generally been refractory to interventions designed to reduce their incidence. Of all obstetric complications, preterm birth towers above nearly all others as the most severe. Affecting 8–10% of all pregnancies, it is depressingly common and can leave the newborn with a lifelong legacy of health deficits [ 8 ]: from subtle decrements in developmental outcomes for those born “late preterm” to profound disabilities for those born “extremely preterm” (cerebral palsy, chronic lung conditions, major learning problems) [ 9 ].

Spontaneous idiopathic preterm birth has been among the greatest challenges. Until now, there are no generally effective therapeutic interventions, and predictive biomarkers, while beginning to emerge, are limited. The lack of mechanistic insight has resulted in preterm birth being a long-standing leading cause of infant mortality and mortality in children under 5 years of age [ 10 ]. However, research of the underlying mechanisms in preterm birth has been greatly accelerated by using hypothesis-free interrogation of large data sets across ‘omics platforms and medical record information using advanced bioinformatic strategies [ 4 , 5 , 6 , 7 ].

As part of this collection, Tiensuu and colleagues [ 11 ] present new data for a candidate biomarker for preterm birth that may also help unravel the underlying mechanisms and is a potential target for interventions. In this study, the investigators evaluated whether placental proteins associated with spontaneous preterm birth can be identified using proteomics. Intriguingly, protein and mRNA levels of alpha-1 antitrypsin (AAT)/SERPINA1 were found to be downregulated on both the maternal and fetal sides of the placenta. This finding served as a basis to investigate whether damaging genetic DNA variations in AAT were also associated with spontaneous preterm birth through whole exome sequencing—and indeed, they were. After revealing this association, the authors performed functional studies, indicating that the downregulation of AAT affects the actin cytoskeletal pathways and extracellular matrix organization.

Beyond identifying relevant biomarkers, there is a strong need for interventions to prevent adverse pregnancy outcomes. The Tiensuu study moves forward with one strong candidate for such an intervention. Moreover, their approach of utilizing multiple association strategies to provide further evidence for a particular finding can be applied across various disease phenotypes.

Major risk factors for preterm birth have long been elucidated [ 8 , 9 ], such as prior preterm birth, early rupture of membranes, or co-existing medical conditions such as polycystic ovary syndrome (PCOS), as reported by others in this special collection [ 12 ]. Rocha and colleagues address an interesting question: for those in their second pregnancy and birth preterm, do risk factors associated with their preterm birth differ depending on whether or not their first infant was born preterm?

To address this question, the authors examined a large retrospective dataset from Brazil representing 1.7 million births [ 13 ]. They focused on women who had a preterm birth in their second pregnancy and split them according to whether their first pregnancy was delivered at full term (> 37 weeks gestation, “incident preterm birth” cohort) or they previously had a preterm birth (< 37 weeks gestation, “recurrent preterm birth” cohort).

Interestingly, the incident but not the recurrent preterm birth cohort had significant associations with household overcrowding, variations in ethnicity (being black, mixed-race, or indigenous had raised risks), being a younger mother (14–19 years), and having had a prior cesarean section, with odds ratios ranging from 1.04 to 1.34. Both cohorts were associated with reduced prenatal visits with higher odds ratios in the incidence preterm birth cohort. Notably, many of these risk factors likely reflect socioeconomic deprivation, stress, low educational attainment, and smoking—established risk factors for preterm birth [ 8 ].

Surprisingly, in both cohorts, being single or a widow conferred a 10–15% reduced risk of preterm birth compared to those who were married or in a civil union. While interesting, this finding is difficult to explain, and we do not suggest encouraging women to be single is a promising public health strategy to reduce preterm birth rates.

In another contribution to this collection, Subramanian and colleagues [ 12 ] present data indicating a convincing link between preterm birth and PCOS, a condition affecting 10% of women. While defined by a varied constellation of signs and symptoms—cysts on the ovary, biochemical or clinical evidence of androgen excess, oligo/anovulation [ 14 ]—PCOS is, at its heart, a metabolic disorder [ 15 ]. As a chronic condition that never retreats, those affected incur the risk of developing metabolic-related conditions as they age, especially diabetes and obesity [ 15 ].

Given PCOS is the most common endocrine disorder among women of reproductive age, it will invariably intersect with many pregnancies. In their retrospective study, Subramanian et al. examined the link between a pre-specified set of serious obstetric complications, including preterm birth, fetal size, mode of birth and stillbirth, and PCOS based on just under 140,000 pregnancies in the UK, of which 27,586 were affected by PCOS. While the lift in preterm birth risk in women affected by PCOS was modest (an 11% relative rise on the adjusted odds ratio), it could be substantiated by further sub-analyses. These findings concur with a recent study in a Swedish population, indicating an apparent doubling in the risk of extreme preterm birth < 28 weeks gestation in women suffering from PCOS and, thus, an even larger effect size [ 16 ].

But how is the link between PCOS and preterm birth explained? The authors muse over potential causes such as a shared genetic polymorphism between preterm birth and PCOS or a dysregulated hypothalamic-pituitary-adrenal axis tipping off a biological cascade that ends in spontaneous preterm birth. However, as the team did not adjust for important pregnancy-induced complications strongly associated with both PCOS and preterm birth (such as gestational diabetes and hypertensive disorders), more likely, the presence of such complications led to the excess in preterm births. They also found PCOS associated with a modestly increased risk of a cesarean section but no apparent link with stillbirth. While this finding seems reassuring, the study was likely underpowered to explore this outcome.

Finally, there may be a fascinating biological message buried within their apparently plain finding that PCOS is not associated with the birth of babies that are either small or large for gestational age. It suggests placental function may be surprisingly resistant to the multiple metabolic perturbations occurring within the mother, which would be a reassuring finding.

The impact of environmental exposures—metabolic in utero environment, obesity, and smoking during pregnancy

In addition to adverse obstetric outcomes such as preterm birth and associated risk factors, obesity during pregnancy is of great concern. Obesity rates continue to increase across the globe in all age groups in the population, including women of childbearing age [ 17 ]. Consequently, in a growing number of countries, over half of the pregnant women are now either obese or overweight.

Obesity is associated with immediate detrimental consequences for the mother and baby, including increased risk of gestational diabetes, preeclampsia, and the need for a caesarian section [ 18 ]. In addition, it is established that children born to obese women are at increased risk of becoming obese and developing type 2 diabetes and cardiovascular diseases. Furthermore, evidence suggests that at least part of this transmission of poor cardio-metabolic health from mother to child is driven by non-genetic factors. Notably, the latter provides an opportunity for early intervention before disease pathology is established [ 19 ].

Currently, it is not known which children born to obese mothers will follow a higher-than-normal body mass index growth trajectory and become overweight and ultimately obese. In this article collection, Gomes and colleagues address this knowledge deficit using the mother-child cohort study Programming of Enhanced Adiposity Risk in Childhood–Early Screening (PEACHES), which comprised 1671 mothers with pre-conception obesity and without (controls) and their offspring. They identified a “high-risk” subpopulation of offspring born to obese mothers susceptible to early upper deviations from healthy weight gain trajectories present within the first few months of life and progressing to overweight/obesity by 5 years of age. Hence, they established a novel sequential prediction system to allow early-risk stratification and re-evaluation to prevent a “higher-than-normal BMI growth pattern” at a subclinical stage preceding overweight. Maternal smoking and excessive gestational weight gain were the strongest predictors of a higher-than-normal BMI growth pattern by 3 months of age. Importantly, they validated these findings in the independent Perinatal Prevention of Obesity (PEPO) cohort, comprising 11,730 mother-child pairs recruited around 6 years of age. These findings take us a step closer to developing cost-effective and personalized advice and measures, counteracting the risk of early excess weight gain and ultimately preventing childhood obesity.

Several articles in this collection have focused on the metabolic environment in utero and the impact of environmental exposures in pregnancy on the mother’s and offspring’s long-term metabolic health. For example, the large mother-offspring Asian cohort study Growing Up in Singapore Towards healthy Outcomes (GUSTO), consisting of 1247 women from Singapore, studied the changes of 480 lipid species in the plasma of women during pregnancy (antenatal vs postnatal) and their offspring during development (cord blood and 6-year-old child plasma) [ 20 ]. This study demonstrated that around 36% of the profiled lipids increased in circulation during pregnancy, with phosphatidylethanolamine levels changing the most compared to pre-pregnancy. Compared to the gestating mother, the cord blood showed a lower concentration of most lipids, and a higher concentration of lysophospholipids, suggesting the specific developmental needs of the growing fetus. Pre-pregnancy BMI was specifically associated with a decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy, highlighting the importance of managing obesity before pregnancy. Notably, lipid species associated with the child’s BMI were very similar to those associated with the adult’s BMI. This overlapping effect of adiposity, as observed in 6-year-old children and postnatal mothers in this study, may be influenced by the similarities in the diet apart from other factors such as genetics and shared lifestyle. The findings of this study were validated in an independent Caucasian birth cohort and provide an important resource for future research targeting early nutritional interventions to benefit maternal and child metabolic health.

Also focusing on the influencing factors on metabolic health, a Swedish nationwide register-based study investigated the association between maternal smoking during pregnancy and type 1 diabetes in the offspring [ 21 ]. The cohort consisted of nearly three million children born between the years 1983 and 2014, with follow-up until 2020. In addition, a nested case-control study was performed comparing children with type 1 diabetes to their age-matched siblings. A total of 18,617 children developed type 1 diabetes. Interestingly, maternal smoking during pregnancy was associated with a 22% lower risk of offspring type 1 diabetes in the full cohort. Although these data suggest a protective effect of maternal smoking on the risk for offspring to develop type 1 diabetes, mechanistic studies are needed to elucidate the underlying pathways behind this link. Despite these findings, we emphasize that smoking during pregnancy should be strongly advised against since it has severe effects on fetal and childhood health [ 21 ].

For example, a longitudinal study by Howell and colleagues in this collection provides evidence that maternal smoking is also associated with shorter offspring telomere length [ 22 ]. Acting as a mitotic clock to the cell, these hexameric repeat sequences found at the ends of chromosomes shorten with cell division [ 23 ] and, as shown recently, as a consequence of oxidative damage. Therefore, they represent good biomarkers of cellular aging and also exposure to oxidative damage [ 23 ]. Accelerated aging has been suggested as one potential mechanism linking suboptimal in utero exposures to long-term health. However, most evidence has primarily come from studies of suboptimal in utero nutritional exposures [ 24 ].

Howell et al. demonstrated that maternal prenatal smoking predicted greater telomere shortening by measuring the telomere length in buccal cells in infants from 4 to 18 months of age. They also showed that the relationship between maternal prenatal smoking and offspring attention-deficit/hyperactivity disorder (ADHD) was modulated by telomere length. Paradoxically, ADHD was associated with less telomere attrition for children whose mothers smoked. It is not known if these differences in buccal cell telomere length are reflective of the differences in other cell types, such as those in the brain. However, if similar differences are also present in brain tissue, this finding could indicate delayed maturation of cortical cells, which could provide a mechanistic link to ADHD.

Conclusions

As demonstrated by the initial series of articles published in this collection, the ability to utilize now more refined technologies to elucidate the underlying mechanisms that drive adverse pregnancy outcomes, such as preterm birth and metabolic risks for both the mother and fetus, has revealed new insights and potential pathways for intervention. Moreover, a deeper understanding of how these diverse outcomes are influenced by maternal co-morbidities such as maternal PCOS or smoking status is emerging.

However, to have a real impact on public health, these robust, reliable data and their implications need to be implemented in physician practice and be used for therapy development for a historically under-explored and invested group—pregnant women.

It will be essential to figure out how these findings can be used to tackle challenges related to lifestyle factors such as maternal obesity or smoking that have been refractory to preventive strategies and interventions. As the recognition of these influencing factors on maternal, fetal, and childhood outcomes across the lifespan emerges, we are encouraged that it will ultimately benefit the mother’s and child’s health.

We have enjoyed learning from this initial set of articles and look forward to future contributions to this collection.

Availability of data and materials

All data discussed in this editorial are included in this published article.

Parrettini S, Caroli A, Torlone E. Nutrition and metabolic adaptations in physiological and complicated pregnancy: focus on obesity and gestational diabetes. Front Endocrinol (Lausanne). 2020;11:611929.

Article Google Scholar

Sadovsky Y, Mesiano S, Burton GJ, Lampl M, Murray JC, Freathy RM, et al. Advancing human health in the decade ahead: pregnancy as a key window for discovery: a Burroughs Wellcome Fund Pregnancy Think Tank. Am J Obstet Gynecol. 2020;223(3):312–21.

Article PubMed PubMed Central Google Scholar

Jain VG, Monangi N, Zhang G, Muglia LJ. Genetics, epigenetics, and transcriptomics of preterm birth. Am J Reprod Immunol. 2022;88:e13600.

Article PubMed CAS Google Scholar

Tarca AL, Pataki BA, Romero R, Sirota M, Guan Y, Kutum R, et al. Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth. Cell Rep Med. 2021;2(6):100323.

Article PubMed PubMed Central CAS Google Scholar

Espinosa C, Becker M, Marić I, Wong RJ, Shaw GM, Gaudilliere B, et al. Data-driven modeling of pregnancy-related complications. Trends Mol Med. 2021;27(8):762–76.

Marić I, Tsur A, Aghaeepour N, Montanari A, Stevenson DK, Shaw GM, et al. Early prediction of preeclampsia via machine learning. Am J Obstet Gynecol MFM. 2020;2(2):100100.

Article PubMed Google Scholar

Stevenson DK, Wong RJ, Aghaeepour N, Marić I, Angst MS, Contrepois K, et al. Towards personalized medicine in maternal and child health: integrating biologic and social determinants. Pediatr Res. 2021;89(2):252–8.

Frey HA, Klebanoff MA. The epidemiology, etiology, and costs of preterm birth. Semin Fetal Neonatal Med. 2016;21(2):68–73.

Colvin M, McGuire W, Fowlie PW. Neurodevelopmental outcomes after preterm birth. BMJ. 2004;329(7479):1390–3.

Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE. Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–40. https://doi.org/10.1016/S0140-6736(14)61698-6 . Epub 2014 Sep 30.

Tiensuu H, Haapalainen AM, Tissarinen P, Pasanen A, Maatta TA, Huusko JM, et al. Human placental proteomics and exon variant studies link AAT/SERPINA1 with spontaneous preterm birth. BMC Med. 2022;20(1):141.

Subramanian A, Lee SI, Phillips K, Toulis KA, Kempegowda P, O’Reilly MW, et al. Polycystic ovary syndrome and risk of adverse obstetric outcomes: a retrospective population-based matched cohort study in England. BMC Med. 2022;20(1):1–3.

Rocha AS, de Cassia R-SR, Fiaccone RL, Paixao ES, Falcao IR, Alves FJO, et al. Differences in risk factors for incident and recurrent preterm birth: a population-based linkage of 3.5 million births from the CIDACS birth cohort. BMC Med. 2022;20(1):111.

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41–7.

Anagnostis P, Tarlatzis BC, Kauffman RP. Polycystic ovarian syndrome (PCOS): long-term metabolic consequences. Metabolism. 2018;86:33–43.

Valgeirsdottir H, Sundstrom Poromaa I, Kunovac Kallak T, Vanky E, Akhter T, Roos N, et al. Polycystic ovary syndrome and extremely preterm birth: a nationwide register-based study. PLoS One. 2021;16(2):e0246743.

Website of World Obesity. https://www.worldobesity.org/ . Accessed 22 Oct 2022.

Poston, et al. Preconceptional and maternal obesity: epidemiology and health consequences. Lancet Diabetes Endocrinol. 2016;4:1025–36.

Inzani I, Ozanne SE. Programming by maternal obesity: a pathway to poor cardiometabolic health in the offspring. Proc Nutr Soc. 2022;29:1–6.

Mir SA, Chen L, Burugupalli S, Burla B, Ji S, Smith AA, et al. Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study. BMC Med. 2022;20(1):1–8.

Wei Y, Andersson T, Edstorp J, Löfvenborg JE, Talbäck M, Feychting M, Carlsson S. Maternal smoking during pregnancy and type 1 diabetes in the offspring: a nationwide register-based study with family-based designs. BMC Med. 2022;20(1):240. https://doi.org/10.1186/s12916-022-02447-5 .

Salihu HM, Pradhan A, King L, Paothong A, Nwoga C, Marty PJ, et al. impact of intrauterine tobacco exposure on fetal telomere length. Am J Obstet Gynecol. 2015;212(2):205.

Blackburn, et al. Human telomere biology: a contributory and interactive factor in ageing, disease risks and protection. Science. 2015;350:1193–8.

Tarry-Adkins JL, Ozanne SE. The impact of early nutrition on the ageing trajectory. Proc Nutr Soc. 2014;73(2):289–301.

Download references

Acknowledgements

We thank Dr. Susanne Kröncke for her outstanding editorial support.

KB is the recipient of a “Fundamenteel Klinisch Navorserschap FWO Vlaanderen.”

None of the authors received funding for this editorial.

Author information

Authors and affiliations.

Burroughs Wellcome Fund, Research Triangle Park, Durham, NC, USA

Louis J. Muglia

Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium

Katrien Benhalima

University of Melbourne, Melbourne, Australia

Stephen Tong

Mercy Perinatal, Heidelberg, Australia

University of Cambridge, Cambridge, UK

Susan Ozanne

You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally and read and approved the final manuscript.

Corresponding author

Correspondence to Louis J. Muglia .

Ethics declarations

Ethics approval and consent to participate.

Not applicable; individual studies described in this editorial have appropriate ethical approvals.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Muglia, L.J., Benhalima, K., Tong, S. et al. Maternal factors during pregnancy influencing maternal, fetal, and childhood outcomes. BMC Med 20 , 418 (2022). https://doi.org/10.1186/s12916-022-02632-6

Download citation

Received : 22 October 2022

Accepted : 24 October 2022

Published : 01 November 2022

DOI : https://doi.org/10.1186/s12916-022-02632-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

BMC Medicine

ISSN: 1741-7015

General enquiries: [email protected]