Prevention of women's health through structured preconception counseling - medically managed prevention

Since the introduction of maternity care in 1961 as a standardized, comprehensive and freely available measure of preventive medicine, perinatal mortality has fallen by a factor of 10 and maternal mortality has fallen many times more. However, an increase in perinatal and maternal morbidity as well as cesarean section rates can be observed. The question arises to what extent pregnancy outcomes are not also influenced by the woman's health outside of pregnancy. Against this background, the increase in fertility disorders must also be examined, as well as the two main causes of death in women, cardiovascular diseases and carcinomas.

>> Pre- and interconceptional health is an important determinant of fertility (ability to reproduce) and fecundity (number of successful pregnancies per woman), but also of pregnancy progression and its “outcome” [1]. This affects both the immediate perinatal and maternal morbidity and mortality as well as the long-term health of mother and child, because pregnancy is a sensitive and formative phase for both. Preconception Counseling (PCC) aims to identify and resolve individual lifestyle, behavioral, medical and social risks to a woman's health or the success of a pregnancy, in good time before a (further) pregnancy. The concept focuses on primary prevention and intervention, health protection and promotion [2].
In the following, epidemiological data and medical backgrounds of the individual parameters of reproductive health are presented and pathogenetic mechanisms, protective factors and possible measures of active prevention and intervention are highlighted.
Desire to have children, fertility and its limits
According to the 2014 family report from the Federal Ministry for Family, Senior Citizens, Women and Youth, more than 80 percent of 20 to 39 year olds want their own children. However, in the “women's lives 3” study by the Federal Center for Health Education (BZgA), only around a fifth of all women who wanted to have children stated that they wanted to realize this “very soon”; for the majority of women, the desire to have children was of a perspective nature. 17 % of all women had been unintentionally pregnant at least once in their lives, in large part despite using oral hormonal contraceptives or condom contraception. An extensive representative survey conducted by the Federal Center for Health Education in 2011 showed that before consultation with a gynecologist, 26 % were unsure about the contraceptive method that was suitable for them, and after the consultation only 5 % [3].
At the same time, there has been an increase in unwanted childlessness due to fertility problems [4]. Fertility depends on age with a woman's optimal fertility in her 20s, which, according to surveys, is little known among the population [2]. The conception rate within a year decreases with the age of the woman, and the need for reproductive medicine measures increases depending on age. At the same time, success rates are falling, while the incidence of multiple pregnancies is increasing and the health risks for mother and child are increasing [5]. According to the Federal Statistical Office (Destatis), in 2014 the proportion of multiple births among all newborns was higher than ever before.
Both fertility and fecundity are also influenced by lifestyle. An accumulation of negative lifestyle factors such as smoking, alcohol and obesity, in addition to other factors such as psychosocial stress, reduces the probability of conception within one year from approx. 80% to approx. 40%, significantly prolongs the time until pregnancy and increases the probability of subfecundity [6 ]. Obesity reduces fertility through ovulatory dysfunction, which worsens with increasing severity and duration of overweight. Gaps in knowledge about fertility and reproduction, especially in connection with psychological aspects such as depression, can be a reason for risky behavior [4]. Depressive symptoms exist in 8.1% of adults, with women being affected more frequently than men (6.1 %; gender effect). In both sexes, the prevalence is highest among 18 to 29 year olds (Study on Adult Health in Germany (DEGS1) [7].
Other factors influencing fertility are sexually transmitted diseases such as HPV infections. According to the KiGGS study (Child and Adolescent Health Survey), the participation rate of the target group of 14 to 17-year-old girls in the HPV vaccination is only 40 %.
Pregnancy-associated risks for the
Children's health
Even in times of the most modern reproductive medicine technologies, human prenatal development takes place in a woman's body, whose intrauterine environmental conditions have a formative effect on the embryo and fetus. The main aspects of pregnancy-related risks to child health are prematurity, congenital malformations and child obesity. The number of premature births is increasing worldwide, including in industrialized nations, despite increasing diagnostic and therapeutic options. In Germany, the premature birth rate is 9 %, which is one of the highest rates in Europe [8]. On the one hand, prematurity is responsible for 70 % of neonatal deaths and, on the other hand, is associated with a high risk of permanent neurological damage. Despite the low prevalence of 2–4 %, congenital malformations cause 30 % of perinatal morbidity [9]. They are the most common cause of death in childhood and the main cause of lifelong disability. Modifiable external factors play just as important a role in its development as genetic factors. Teratogenetic processes are induced by exposure to noxae at a certain sensitive point in organogenesis, which could be partially prevented by simple measures. For example, at least one in two of the approximately 1,000 annual cases of neural tube defects could be prevented by folic acid prophylaxis that began preconception [10]. There is increasing evidence that the predisposition to obesity and other non-communicable diseases arises in utero, through a type of functional teratogenesis [11; 12]. In 2007, 15 % children and adolescents between the ages of 3 and 17 in Germany were overweight, and more than a third of them (6.3%) suffered from obesity [13]. Table 1 gives an overview of a number of avoidable causes that can be assigned to two categories: disorders that can in some cases be completely avoided through active prophylactic measures, as well as factors that are generally amenable to intervention. A detailed presentation of the topic can be found elsewhere [14].
Pregnancy-associated risk factors for women's health
The main causes of maternal morbidity and mortality are shown in Table 2. The most important risk factors are age, smoking and obesity.

Maternal age
According to a press release from the Federal Statistical Office dated September 3, 2014, almost half of those giving birth in 2012 were older than 30 years. 22 % of all children born in Germany in 2012 had a mother who was 35 years old or older at the time of birth. In 2014, mothers of first-born children were on average 29.5 years old when giving birth and around 32 years old when giving birth to their second child. A particularly strong increase in birth frequency was observed among women between 29 and 38 years of age. Age is the strongest predictor of numerical chromosomal abnormalities and is associated with an increased risk of all causes of maternal morbidity and mortality [reviewed in 5].

Preventable causes of maternal morbidity and mortality
Some of the triggering factors can be avoided through active prevention or primary intervention. This also includes avoiding reproductive medical measures by protecting fertility (see above).
In addition to the health risks for the unborn and newborn child, viral infections during pregnancy are also associated with an increased risk of abortions and premature births and a particularly severe illness in the mother. Since 2003, there has been a significant increase in measles infections, especially among young adults over the age of 20, and there have been consistently high incidences among zero and one-year-olds for years. Measles vaccination is contraindicated in pregnancy, but both age groups could be reached by vaccinating women of childbearing age. Nevertheless, in the National Action Plan 2015 – 2020 to eliminate measles in Germany, women of childbearing age are not named as a “population group with special need for action”. In Germany, around 60,000 women undergo surgery every year for cervical precancer, mostly before and during the family planning phase. Since there is a lifelong increased risk of premature birth after such conization, which is not limited to the first post-interventional delivery [15], primary prevention through timely HPV vaccination should be given high priority.
Another preventable risk factor is smoking, which is associated with an increased risk of abortion, ectopic pregnancy, premature birth and stillbirth, and increases the risk of serious pregnancy complications such as placental abruption. According to the “Study on the Health of Adults in Germany (DEGS1)”, the smoking rate among women is 27 percent, with a high proportion especially among younger adults.
A third of women begin pregnancy with a BMI > 25kg/m2. Obesity is the leading cause of both fetal and maternal morbidity [16]. It is a high-risk factor for gestational diabetes and hypertensive pregnancy complications, which are the leading cause of maternal mortality in Europe [reviewed in 17]. The increase in cesarean section rates caused by obesity also increases the risk of placentation disorders, uterine rupture and resection in a subsequent pregnancy. The risk of maternal and fetal complications increases with the degree of overweight and obesity [18]. A cascade of subsequent developments begins that affects the woman's long-term health, subsequent pregnancies and the next generation, and can even influence the birth weight of the grandchild. In Fig. 1 the individual stages of this cascade are shown as predictors of future undesirable development.
A woman who is underweight or overweight in the first pregnancy increases the risk of complications in a subsequent pregnancy, even if the first pregnancy is uncomplicated or normal weight in the second pregnancy [19]. After gestational diabetes, around half of women develop type 2 diabetes mellitus within the following ten years. Women with a BMI > 30 kg/m2 during pregnancy have an increased all-cause mortality and a significantly increased risk of cardiovascular events later in life [20 ].
Effects unrelated to pregnancy
more modifiable
Lifestyle factors
For years, cardiovascular diseases have been the most common cause of death in both sexes in Germany, and there is a close connection to obesity and the associated metabolic and cardiovascular changes. Cancer is the second leading cause of death. The most common cancer in women is breast cancer, followed by colon and lung cancer. Tobacco consumption is a significant risk factor for bronchial and lung cancer, which in 2014 reduced the age at death of affected women by an average of 10.4 years, according to the Federal Statistical Office. Obesity is a significant risk factor for both (postmenopausal) breast cancer and colon cancer [21]. According to a press release from the Federal Statistical Office dated November 5, 2014, there were 40 % in 2013
of adult women were overweight, 14 % were obese, which corresponds to a significant increase in prevalence in recent years. At the same time, there is a growing number of diabetics (mainly type 2), with affected women suffering a heart attack or stroke more often than men [22] (gender effect). An analysis of data from the NHANES (National Health and Nutrition Examination Survey) indicates that excessive body weight at age 25 increases the risk of grade 3 obesity (BMI > 40 kg/m2) and measurable risk indicators (blood pressure, laboratory parameters). increased after the 35th birthday [23]. This effect is significantly more pronounced for women than for men (gender effect).
Developmental disease disposition and transgenerational effects
The example of adipogenesis
Pregnancy has a key function in the child's body weight development [18], which is largely determined by the intrauterine supply of oxygen and nutrients. A high birth weight predisposes to later obesity [review and meta-analysis in 24]. As part of the Ulm children's study, in which 1,000 children were followed from pregnancy to eight years of age, it was proven that the maternal BMI at the beginning of pregnancy correlated with the child's weight at primary school age [25]. There was also a clear association between pre-gravid maternal obesity and infant plasma insulin concentrations, both at birth and at eight years of age. Girls at the age of 8 had higher insulin concentrations than boys (gender effect).
Intrauterine exposure to maternal obesity and gestational diabetes is a risk factor for childhood and adult obesity; Childhood overweight is the main risk factor for obesity in adulthood [26]. Women with a high birth weight have a greater risk of giving birth to a LGA child during their childbearing years, regardless of their BMI (large for gestational age, [18]).
Increasing maternal blood pressure can lead to intrauterine nutritional deficiencies and the birth of SGA children (small for gestational age) even in prehypertension [27]. SGA children also have a consistently increased risk of obesity and metabolic dysfunction as adults [28]. Premature birth can also promote the development of insulin resistance [29].

Pathogenetic mechanisms
The development of childhood obesity and other predispositions to illness depends to a large extent on the intrauterine metabolic environment. Both intrauterine malnutrition and overnutrition, but also smoking [30] and psychological factors such as stress or depression lead to modifications of the epigenome that change the functioning of genes and have an impact on physiological, structural and metabolic development as well as that of the immune system and behavior . The special sensitivity to these environmental influences during certain developmental windows during pregnancy leads to a lasting, protective (“resilience”, [31]) or harmful imprinting of physiological mechanisms that have effects well into later life.
Intrauterine misprogramming promotes accelerated cell aging and has pathogenic potential with regard to the development of chronic diseases and carcinogenesis. The probability of disease manifestation is higher the more pronounced the pre-pathogenic state is and/or the longer it exists. This is why the spectrum of illnesses shifts from acute to chronic illnesses in childhood [32]. Pregnancy is a stress model for both the cardiovascular and metabolic systems and for the regulation of immunological processes, which can lead to decompensation, ie disease manifestation, in the presence of prepathology [33]. Since reducing the age of women giving birth does not seem realistic, primary prevention and intervention are of crucial importance.
Protective factors
In a prospective cohort study of over 5,000 first-time mothers, normalizing weight, reducing blood pressure, or abstaining from substance abuse in the first trimester were associated with subsequent healthy pregnancies. The observed increase in the risk of complications depending on blood pressure, even within defined normal limits, may explain the additional increase in risk with age despite “normal” RR values [34].
A partial analysis of the prospective Nurses' Health Study II was able to show that a healthy lifestyle (non-smoking, 150 minutes of physical activity per week of moderate to vigorous exertion, a healthy diet, BMI < 25) is associated with a significantly reduced risk of gestational diabetes, which is all taken into account four criteria 83 % was lower [35].
A crucial protective factor is physical activity. Women who are most physically active have the lowest prevalence of gestational diabetes. Regular moderate physical activity before and during pregnancy leads to lower maternal weight gain and lower birth weight of the child, protects against gestational hypertension [36] and reduces the incidence of postpartum weight retention. Physical activity contributes to weight maintenance or loss and improves risk factors for cardiovascular disease. This also applies to overweight women, regardless of whether weight loss occurs. The children of physically active women have a significantly lower risk of postnatal catch-up growth, which promotes chronic diseases later in life [18].
The WHO recommends 150 minutes of physical activity per week for people aged 18-64. This reduces the risk of developing chronic diseases such as diabetes, coronary heart disease, hypertension and breast or colon cancer, which are associated with five million deaths per year worldwide and cost more than 60 billion euros per year [37 ]. However, according to current studies by both the Techniker Krankenkasse (“Beweg Dich, Deutschland”) and the German Health Insurance (DKV), more and more German citizens are affected by the “pandemic of physical inactivity” [37].
Breastfeeding reduces the risk of developing type 2 diabetes mellitus by 40 percent for women with gestational diabetes for more than three months. This protective effect lasts up to 15 years and is based on a favorable influence on disease-relevant metabolic pathways [38].
Pre- and interconceptional health
optimization through qualified individuals
preconception counseling
A concept for pre-conception health optimization includes a whole repertoire of preventatively effective measures relating to reproductive health, which are based on the diverse factors influencing pre- and inter-conception health status (Table 3). Preconception counseling pursues the goals of fertility protection, the reduction of pregnancy-related health risks for mother and child as well as the promotion of women's health independent of pregnancy and consists of the building blocks
• Education/information on (modifiable) factors influencing reproductive health, the chance of (later) healthy pregnancy and children
• Evaluation of health status
• Identification of potential risk factors and prepathological findings
• Targeted advice/health education tailored to the individual situation
• Motivation for active prevention and timely primary intervention.

For most young people, starting a family is an essential part of life planning; the option of having your own child is a strong motivating factor. A prospective randomized study showed that women after PCC had a better level of knowledge about essential aspects of reproductive health and were significantly more likely to make positive changes in their behavior. The rate of unfavorable pregnancy outcomes also fell significantly [39]. A Chinese study of 1,012 migrant women showed positive effects of PCC on the frequency of folic acid prophylaxis and use of better prenatal care [40]. An intervention study for women in pre- and interconception phases of life showed a higher probability of taking a multivitamin preparation containing folic acid, a lower BMI and a lower weight gain in a subsequent pregnancy in the intervention group [41].
Despite these encouraging results, there are obstacles to implementing the concept in practice. Only a few women seek preconception medical advice on their own initiative. Since there is only a limited amount of time available per consultation, other medical measures are prioritized, especially since PCC advice is particularly time-consuming but is not specifically remunerated. In addition, there are currently no sufficient information materials and options from independent sources and no standardized concept [42].
While preventive examinations accompany children and young people in critical development phases (U1 to J2) as well as adults in the prevention or early detection of the most important “common diseases” (health check from the age of 35), there is a gap in prevention in between. In a phase of life that is of crucial importance for women's health and that of the following generation(s), a prevention-oriented health examination is missing in an important target group that could be optimally reached through the invitation program for cancer screening examinations that has already been decided.
Disease management programs (DMP), which were established ten years ago for the structured care of patients with chronic illnesses, have proven to be successful: patients benefit from a better quality of life, fewer complications and higher health literacy, and doctors benefit from performance-related remuneration and a increased intelligence skills, both through improved communication. The cost bearers are demonstrably relieved, among other things by avoiding inpatient stays. At the same time, updates based on guidelines and new research results can be incorporated into the existing concept at any time, such as the access to evaluated tobacco cessation programs for every smoking participant in the DMP COPD (chronic obstructive pulmonary disease), which was just decided by the Federal Joint Committee on June 21, 2016. DMPs have initiated a paradigm shift away from a purely curative objective towards preventative aspects. In gynecology, medical maternity care represents a management program that is also preventative with a focus on identifying and treating risks. In view of the ever longer reproductive period and ever larger pre- and inter-conception periods as well as the far-reaching importance of pre-conception health for women and their offspring, freely available, qualified medical health management not only of pregnancy, but of the entire reproductive phase of life appears to be urgently required as a standard of care (Table 4). According to the theorem of Pythagoras of Samos, “Habit makes man's property the wisdom he has acquired and gives him stability,” healthy habits should be encouraged from the start and healthy developments strengthened. The woman of reproductive age, who often takes on the function of a health guide in her relationship and family, plays a key role. The existing gynecological expertise should be used systematically to strengthen women's health literacy. <<