Piet Hein Jongbloet, Pediatrician

1

Piet Hein Jongbloet, Pediatrician

FOR DISCUSSION

The Recent Epidemics of Common Diseases in Children and Young Adults as Collateral Damage of Widespread Birth Control?

Correspondence address: Beukenlaan,10A, box 2,

B2020 Antwerp, Belgium

email:

tel.0032 (0)3 827 08 65

Keywords: Overripeness ovopathy, epigenetics, chronobiology of reproduction, month-of-birth effect, south-north gradient, sex ratio, socio-economic profiles

The author declares that he has no conflict of interest.

Former Medical Director of Huize Maria Roepaan, Institute for the mentally and physical disabled, Ottersum, The Netherlands (1964-91), and partial affiliations to the Dept Human Genetics, Vrije Universiteit, Amsterdam (1970-91) and the Dept Epidemiology and Biostatistics, Radboud Universiteit, Nijmegen (1990-2007). Retired on 1 July 2007.

FOR DISCUSSION:

The Recent Epidemics of Common Diseases in Children and Young Adults as Collateral Damage of Widespread Birth Control?

Background: In many countries a range of epidemics of common diseases and/or disorders has been reported in children, adolescents and young adults, born since the 1960- and 70ies, e.g. heart failure, cardiomyopathy, valve anomalies, diabetes, morbid adipositas, asthma, as well as autism spectrum disorders [ASD], attention deficit (hyperactivity) disorders [AD(H)D], suicide, etc.. In essence, their appearance is neither familiar nor genetic and they are often associated with comorbidity, geographic south-north gradient, a secondary sex ratio (SSR) shift in male direction, and crowding in low socio-economic profiles. In addition, different signals pointing to a decline in mean intelligence have been reported. Concurrently, the introduction of widespread birth control during the 60- and 70ies, and in particular of hormonal contraception, led to disruption of the universal and centuries-old bimodal ovulatory pattern at the summer- and winter equinoxes and the inherent monthly spread of births (Figure 1).

Methods: In 1935, Wolda correlated the month of conception of neonatal and child mortality, and of patients withmenstrual disorders in sanatoria with both the conception peaks around the winter- and summer solstices, in particular during the adjacent months. Huntington (1938), on the other hand, identified the conceptions of eminent people in the US and Europe coinciding with these conception peaks. Combination of three disregarded concepts from the late-19th and early-20th century, i.e. overripenness ovopathy, chronobiology of reproduction and month-of-birth led to two complementary, seasonally linked hypotheses: the seasonal pre-ovulatory overripe oocytes (SPrOO-) hypothesis, versus the seasonal optimally ripened oocytes (SOptRO-) hypothesis.

Results: The mentioneddistortion of the chronobiologically driven ovulatory pattern since the 1970s and the inherent quenching of SOptRO- directionSPrOO-conceptions explain the aforementioned recent worldwide epidemics and concomitant comorbidity, south-north gradient, SSR shift in male direction and crowding in low socio-economic profiles. The loss of this month-of-birth effect and of the key for epidemiological and etiological research is no longer meaningful, except in the surviving population group born before the 1960s.

Conclusion: In order to restore the chronobiological ovulatory pattern and to avoid the mentioned SPrOO-conceptions, alternative non-hormonal methods for birth control are necessary. The overripeness ovopathy concept may also be of interest for research related to endocrine disrupting chemicals [EDCs].

Introduction

A worldwide increase in common diseases/disorders is observed in children, adolescents and young adults, born after the 1970s. This is accompanied by an equally universal decrease of mean intelligence. A causal relationship between the widespread introduction of family planning can be hypothesised epidemiologically and biopathologically. The question arises if Homo sapiens can ignore with impunity its universal and historical seasonal pattern of reproduction. As is the case with the course of history, science did not always develop progressively, so too family planning will probably have to adapt again and again, albeit under new forms.

A world-wide increase of common diseases and/or disorders since the 1960- and 1970ies

In Doetinchem, 40-year-old men and women born in the 1970s are at greater risk of heart and vascular disease, diabetes and adipositas, than those born in the 1950s (Hulsegge, 2016). The same divergent trend between the young and the elderly was observed in a Swedish national study (1987-2006) for heart failure, coupled with heart disorders and diabetes (Barassa et al., 2014). In 18-years-old recruits, born between 1960 and 1987, a robust increase of morbid obesitas was seen “as predictor of heart failure” (Neovius et al., 2008; Rosengren et al., 2016). Following traditional thought patterns, unhealthy lifestyle and adipositas are quoted as causes for diabetes, heart and vascular disorders. An important question in this regard is whether cause and consequence are not being confused, and whether the comorbidity of adipositas, diabetes, heart failure and other common disorders could be the consequence of an unknown, but common cause.

In the United States [US], between 1995 and 2005, a dramatic increase was reported of diabetes, asthma, but also autism spectrum disorders (ASD) and attention deficit/ hyperactivity disorder [AD(H)D](Latham et al, 2012). In the World Health Organisation [WHO] statistics, the incidence of suicide rose considerably around 1975-85 in 6 European countries and in the US (Neeleman, 2001). The aforementioned divergence between the young and the elderly was also seen in the Netherlands and Belgium: there was a noteworthy increase in the young (aged 15-34 years), while in those older than 55, i.e., born before World War II, the suicide figures remained stable throughout the second half of the last century (Neeleman, 1981; Moens, 2003). In 987,308 Swedish recruits followed for 5 to 26 years (1968-94), the risk of suicide was two to three times higher in those with lowest compared to those with the highest test scores (Gunnell et al., 2004). This observation and the known association with schizophrenia and idiopathic depression indicate comorbidity. These disorders, unlikely to be genetic, are not only typified by the comorbidities present, but also by a south-north or latitude gradient, a shift in the secondary sex ratio [SSR] towards the male gender, and a higher incidence in lower socioeconomic profiles.

A world-wide decrease of mean intelligence

The mean intelligence, tested world-wide in 18-year-old recruits since the 1900s, was seen to increase steadily everywhere until the 1950s, as was first determined by Flynn, and attributed to improved education, nutrition, hygiene and wider exposure to cognitive stimuli, the so-called ‘Flynn effect’ (Flynn, 2013). This increase levelled off in the 1960s, and a linear decrease was observed from the 1970s onwards, by ±2 IQ points per decade (Griffiths, 2014). This decrease was attributed to ‘dysgenic inheritance’, since parents with higher intelligence have smaller families than their less intelligent contemporaries (Woodley et al., 2013).Both concepts strive for primacy and attenuate each other, the ‘Flynn paradox’ (Sundet et al.,2008). In 2008, British 14-year-olds (born in 1994) scored ±2 IQ points lower than their counterparts did 28 years earlier in 1980 (born in 1966). This decrease in IQ was not observed in all categories, but was more pronounced in children in the middle and higher class, namely ±6 IQ points. Over the past 20 years, there is a worrying steady decline in arithmetics in 8-year-olds in primary schools of many European countries, as well as in mathematics and physics in 15-year-olds. These data were gathered by leading research institutes: Trends in International Mathematics and ScienceStudies and Programme for International Student Assessment [PISA] study of the Organisation for Economic Co-operation and Development [OECD]. These results remain a concern for policy makers.

Hormone-disrupting chemicals [EDCs] in the environment

The reported increase in AD(H)D, ASD, obesitas and diabetes, and the decrease in mean intelligence are also the focus of toxicologists, and are being linked to the exposure to hundreds of substances in nutrition, cosmetics, plastics and pesticides. These EDCs are thought to dose-proportionally affect the hormonal balances. In an extensive report of the University of Utrecht, a publication commissioned by the Ministry of Infrastructure in the Netherlands, the conclusion states that with respect to causality, many uncertainties remain and specific points of engagement are lacking (Rijk et al., 2016).

A paradigm shift is needed

Traditional genetics fail to explain an overall increase of common diseases and a decrease in mean intelligence in 1 or 2 generations, especially when taking into account the changing comorbidities, and the associated south-north gradient, the SSR shift and higher incidence in lower socio-economic profiles. With respect to life expectancy: after a full DNA analysis of seventeen 110-year-olds, the American researchers found no indication for the existence of a gene that may have offered the possibility of reaching that age (Gierman et al., 2010). The same holds true for adipositas and the socalled thrifty genes, found frequently in overweight people and less so in thin people: the 115 DNA positions linked to these genes were not found in 14 human populations worldwide (Wang & Speakman, 2016). As to intelligence: of the 74 gene variants affecting school success, not a single gene was able to predict it (Okbay et al., 2016). Frustrations like these compel us to find alternative mechanisms and exogenous factors that can modify gene function through activation or inactivation, as suggested by epigenetics.

After the post-war baby-boom, the widespread introduction of family planning in the 1960s and -70s marked a fundamental change in the Western society: parents choose the most socially desirable birth time for their children, unaware of a worldwide and centuries-old seasonality of conception. In addition, hormonal contraception was introduced in the 1970s, interfering directly with the maturation of the oocyte and with ovulation. This resulted in a radical change in the monthly dispersion of births between 1970-74 and 1980-84 (Figure 1): the birth peak gradually shifted from spring to summer and then to the late summer. These findings stimulate a discussion on the role of planning as a cause of birth seasonality (Haandrikman, 2004).

Figure 1: The disruption of the monthly conception/birth dispersion in 1970-74 compared with 1980-84 as consequence of the widespread birth control in the 1970s in the Netherlands (correction for length of month and Index=100) [Haandrikman, 2004]

Three not well-known lines of research can offer a clue

Three important lines of research, dating from the end of the 19th and the start of the 20th century, have not received the appropriate attention due to the predominance of ‘genetic reductionism’ and/or ‘genetic determinism’ of the second half of the 20th century: (1) the animal experiments into ‘overripeness’ of the oocyte, (2) the chronobiology of reproduction, and (3) the inherent month-of-birth effect. The combination of these can offer a key to construct a causal relationship between the widespread birth control in the 1960s and -70s and the recent epidemics of common diseases and mean intelligence reduction in young people.

1.Fertilisaton of the overripe oocyte and epigenetics

In 1882, a long list of experiments in amphibians and mammals started into the pleiotropic effect of fertilisation of ‘overripe ova’, resulting in a wide range of developmental defects in various organ systems, especially in neurulation. At first, research focussed on gradually postponing insemination after ovulation, resulting in overripeness of the oocyte with increasing unsuitability for fertilisation, i.e. post-ovulatory overripening of the oocyte (PoOO, Pflüger, 1882). Later experiments disrupted the ripening or maturation of the ovum before ovulation through varying doses of (psycho)pharmaca, i.e. the pre-ovulatory overripening of the oocyte (PrOO, Witschi, 1952). Both sets of experiments led to similar results, with or without chromosomal aberrations (Mikamo, 1968). This aspect of chromosomal aberrations is important since non-disjunction of the chromatids in majority, occurs during one of the two meiotic divisions after penetration of the zona pellucida. Observations in children with indistinct genetic congenital disabilities, and especially the related conception anamnesis with the parents, introduced PoOO and PrOO as possible etiologies, also in man (Jongbloet, 1971). PoOO may rather be expected with untimely presence of sperm cells in the oviduct, e.g. in case of low coitus frequency or attempts to avoid conception, such as the calendar method. PrOO can be expected in case of long or irregular menses with inherent non-optimal ripening before ovulation. Delayed ovulation occurs during the transition phases, such as menarche, premenopause, postpartum, unbalanced nutrition or induced by psychotropic substances. They are known to be associated with high-risk pregnancies (Jongbloet, 1971). This line of animal research was recently taken up by G. Horsthemke (Genetic Department, University of Essen, Germany). His hypothesis that PrOO, in analogy with other environmental factors, would lead to deficient DNA/RNA reprogramming during the first or second meiotic division, has been confirmed (Horsthemke & Ludwig, 2005; Kosubek et al., 2010).

2. Chronobiology of human reproduction

The focus here is on conceptions around the winter- and summer solstices, i.e. 21 June and 21 December, when the sun is at its highest and lowest position on the horizon, respectively. In pre-Christian times the months of June and December were festival months, characterised by erotically charged fertility rites (Midsummer night and Stonehenge). These pagan festivals were Christianised into Easter with Easter eggs as a remnant of fertility, and Christmas of the lengthening of the days. Baptismal records from the 16th century show that births were not spread evenly throughout the 12 months of the year, but showed a larger or major peak around February/March, and a smaller or minor peak around September (Wolda, 1946). The bimodal dispersion of conceptions between 1881 and 1920 in all 11 Dutch provinces (Figure 2) corresponds with the summer and winter solstices.

------Figure 2------

These double peaks and troughs were observed in the northern and southern hemisphere, with a 6-month shift between the hemispheres. The greater the distance from the equator, the more pronounced the peaks (Lam & Miron, 1987; Roenneberg & Aschoff, 1990). These conception/birth peaks refer to photoperiodicity and gonadotropic activity, as is observed in reproduction seasons of fish, amphibians, birds and mammals. Ewes are rutted in the autumn, but when they are shipped to Australia, they immediately switch to the local fertility pattern, i.e. to the prevailing chronobiology, as do European migrants and vice versa. There are subtle varieties in the birth peaks and troughs, depending on climatological and/or geographical factors. They are more pronounced during the transition phases of reproduction, menarche and premenopause, particularly more distinct in in lower socioeconomic groups and inrural than urban areas (Wolda, 1935; Lam & Miron, 1987). The stronger profiles in illegitimate births underscore a hormone-steered libido.

Figure 2: The concentration of conceptions (- 9 months) around the summer- and winter solstices, i.e. 21 June and 21 December, in each of the 11 Dutch provinces and sum total, 1881-1920 [original reproduction from Wolda, 1946]

Sociology-minded demographers and historians remain doubtful about the dominant role of chronobiology and upgrade the influential role of behavioural patterns, such as first births related to the month of marriage, hunting and fishing, agriculture, etc. This nature/nurture discussion was further muddled by a fairly recent (around 1900) reversal of the major and minor birth peaks as a mysterious exception in the US, making it the opposite to the pattern in adjacent Canada on the northern hemisphere (Cowgill, 1966; Lam & Miron, 1987; Roenneberg & Aschoff, 1990; Dobblehammer et al., 1999). There are speculations about an ‘American way of life’, but a real explanation is lacking. It is likely that there is a biological adaptation to specific geographical/climatological modifiers in the US, since this reversal also has consequences, as mentioned below. Using computer modelling, climatologists and oceanographers have studied the temperature differences during the winter months between the east and west coast (Seattle and New York), and between the east and west side of the Pacific Ocean (Seager, 2006). On the one hand, these temperature differences would be due to the Rocky Mountains with inherent air compression and decompression, resulting in whirlwinds and predominant west north-west circulation. On the other hand, there is a big contrast between the maritime climate in the west and the continental climate on the east (in spite of the presence of the warm Gulf Stream). The question remains if these recent climatological insights can provide an explanation for this mystery, but further research, especially in other species in their natural surroundings, is hoped-for.

3.The month-of-birth effect

Early in the 20th century G Wolda (1935; 1946), an ornithologist in Wageningen, recognised the analogy between the timing of clutches of birds and the ‘conception optimum’ in humans. He identified the month of conception of stillbirths and infant mortality as “outside the powerful optimum”. He found a similar trend in more than 10,000 patients with tuberculosis in health centres in the Netherlands and in Sweden. This led him to the conclusion that ‘the months with the lowest chance of conception were associated with births with reduced resistance’. He also saw that, outside of these powerful optimums, the menstrual cycles were less regular or even lacking: (my translation) the spring season with highest chance of conception was also the period with the least menstrual disturbances.

In his book ‘Season of birth - Its relation to human abilities’, A. Huntington (1938) pointed out that the concentration of births of eminent individuals coincided with the birth peaks (Figure 3); this concentration was gradually more pronounced if ≤2, 3 to 5 or ≥5 columns were dedicatedto them in ‘WHO is WHO, The Dictionary of American Biography’. In the months adjacent to the birth peaks, fewer of them were born. As was previously reported by Wolda, he also saw that the births of tuberculosis patients showed “apeculiar relationship to the seasons”, as was the case with schizophrenics, manic-depressives and criminals: “Infants born according to the basic animal rhythm are less susceptible than others to the danger of the weather” (pg 281). Later on, divergent monthofbirth effects were reported frequently, in children/individuals with excellent physical condition during the peak months and with mental and/or physical disabilities during the adjacent months.The meaning of this was not