Thyroid dysfunction in pregnancy - a retrospective observational analysis of a Maltese cohort.

BACKGROUND: Thyroid dysfunction is known to adversely affect pregnancy. This study evaluates the prevalence of thyroid disorders and explores their association with pregnancy complications/comorbidities and modes of delivery in the Maltese pregnant population over a ten year period. DESIGN: A population based observational study. METHOD: We analysed data from the National Obstetrics Information Service of the Department of Health Informations and Research (NOIS) for all births delivered in Malta between 2006 and 2016. Cases identified and recorded by NOIS to have had some form of thyroid dysfunction during pregnancy were confirmed by cross-referencing  with laboratory results found in patients' medical records and/or iSOFT® database system. Using the Statistical Package for the Social sciences (SPSS®)  demographic data, past obstetric and medical history and obstetric outcomes were analysed for pregnancies with thyroid dysfunction and compared to data pertaining to pregnancies in euthyroid patients, that is those with no recorded thyroid dysfunction on NOIS. Chi square/Fisher's exact test were used to compare categorical variables while ANOVA/Mann-Whitney U test was used to compare continuous variables. Statistical significance was defined by a two-sided p value <0.05. RESULTS: Data was available for 46,283 women (mean [SD] age = 29.2 [5.4] years). 587 pregnancies (1.3%) suffered from thyroid dysfunction. Of these, 67.3% were hypothyroid, 3.2% had hyperthyroidism, 28.3% had isolated hypothyroxinaemia (IHT) while 1.2% had a history of thyroid carcinoma. Patients with IHT and hypothyroidism were older than euthyroid patients (p < 0.001).  IHT and hypothyroid patients had a statistically significant higher body mass index (BMI) than euthyroid women (p=0.001 for hypothyroid women, p = 0.035 for IHT). Hypothyroid  and IHT women were more likely to have had a previous lower segment caesarean section  (p=0.043,  and 0.006 respectively). Type 1 diabetes and gestational diabetes  p = 0.012) were more common associated comorbidities in hypothyroid pregnancies. Offspring of patients with IHT had a higher birth weight than those born to euthyroid patients (p=0.009). Patients with hyperthyroidism were found to have a significantly increased risk of early preterm delivery before 34 weeks of gestation and were also more likely to have suspected intrauterine growth restriction and low mean birth weight. We report no significant differences in past history of obstetric loss, antenatal complications, mode of delivery, gestational age at delivery and postpartum haemorrhage rates across thyroid categories. CONCLUSIONS: Available evidence suggests that thyroid dysfunction is more likely in the setting of older age, and higher body mass index. Moreover, it impacts on neonatal birth weight, rates of early preterm delivery and intrauterine growth restriction.

Relation of the Mediterranean diet with the incidence of gestational diabetes.

BACKGROUND/OBJECTIVES: Some studies document relationships of the incidence of gestational diabetes mellitus (GDM) with individual components of the diet, but studies exploring relationships with patterns of eating are lacking. This observational study aimed to explore a possible relationship between the incidence of GDM and the Mediterranean diet (MedDiet) pattern of eating. SUBJECTS/METHODS: In 10 Mediterranean countries, 1076 consecutive pregnant women underwent a 75-g OGTT at the 24th-32nd week of gestation, interpreted both by the ADA_2010 and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)_2012 criteria. The dietary habits were assessed by a previously validated questionnaire and a Mediterranean Diet Index (MDI) was computed, reflecting the degree of adherence to the MedDiet pattern of eating: a higher MDI denoting better adherence. RESULTS: After adjustment for age, BMI, diabetes in the family, weight gain and energy intake, subjects with GDM, by either criterion, had lower MDI (ADA_2010, 5.8 vs 6.3, P=0.028; IADPSG_2012, 5.9 vs 6.4, P<0.001). Moreover, the incidence of GDM was lower in subjects with better adherence to the MedDiet (higher tertile of MDI distribution), 8.0% vs 12.3%, OR=0.618, P=0.030 by ADA_2010 and 24.3% vs 32.8%, OR=0.655, P=0.004 by IADPSG_2012 criteria. In subjects without GDM, MDI was negatively correlated with both fasting plasma glucose and AUC glucose, P<0.001 for both. CONCLUSIONS: Adherence to a MedDiet pattern of eating is associated with lower incidence of GDM and better degree of glucose tolerance, even in women without GDM. The possibility to use MedDiet for the prevention of GDM deserves further testing with intervention studies.

Transgenerational metabolic determinants of fetal birth weight.

BACKGROUND: Infants born with a higher birth weight have long been associated with an increased incidence of developing the metabolic syndrome starting from early childhood and persisting into adult life. Such risk factors include genetic tendencies as well as environmental factors. Of these, certain maternal anthropometric characteristics such as obesity or carbohydrate intolerance alter the intrauterine environment to one of nutritional plenty, thus impacting on intrauterine development. This hypernutrition pathway has led to the hypothesis of 'fuel mediated teratogenesis' and an obesogenic environment. AIM: The aim was to identify a relationship across 3 generations relating to body weight and birth weight in order to identify whether a genetic and/or nutritional role are involved in the observed transmission. METHODS/MATERIALS: The study utilized 2 clinical databases. The first consisted of a cohort of 182 women born in 1987 and who delivered a child between 2004-2010 [2nd Generation]. A total of 233 infants were born [3rd Generation]. This was further linked to another database of women who had delivered a child in 1987 [1st Generation]. The birth weight of the 2nd and 3rd generations and the pre-pregnancy body mass index (BMI) of the 1st and 2nd generation were registered as was the development of features of the metabolic syndrome in the 1st generation population. The 1st generation population was subdivided into 2 groups based on the BMI: BMI <25 kg/m2 (n=76) and BMI >=25 kg/m2 (n=106). The mean birth weights and pre-pregnancy BMI of the subsequent generations were compared using the student t-test. RESULTS: There was no direct transgenerational link between the first generation BMI and third generation birth weight. Rather, birth weight was directly linked to maternal BMI. Furthermore in this study we also studied the presence of metabolic syndrome in first generation mothers. The presence or absence of metabolic syndrome did not cause any statistically significant difference in the birth weight of 2nd and 3rd generations. CONCLUSIONS: This study supports previous reports that environmental factors play a key role in determining fetal birth weight. Identifying women with a higher pre-pregnancy BMI and educating them with regards to dietary modification in order to reduce body weight prior to pregnancy would contribute towards less adverse outcomes to the mother and her child in both the short and the long term.

Attitudes towards preconception care in Maltese women with type 1 diabetes mellitus.

INTRODUCTION: The aim of this study was to assess the level of knowledge and awareness related to preconception care among Maltese women of reproductive age with type 1 diabetes mellitus (T1DM). METHODS: Thirty-seven T1DM women, aged 12-30 years, were self-administered a questionnaire related to diabetes self-management and preconception care. The participants then underwent an educational intervention and re-took the same questionnaire. RESULTS: Before the intervention, 26 participants (70%) claimed they did not have any knowledge about the preconception care of diabetes. Of the remaining 11 participants, the main reported source of information about diabetes care was the diabetologist (n = 8; 6.7%). The response rate was 70% (26 out of 37 participants completed the questionnaire after the educational intervention). Six of the participants who initially reported no preconception care knowledge claimed an increased awareness after the event. There was a statistically significant increase in the knowledge scores after the intervention. CONCLUSION: It is evident that there is a lack of awareness of the importance of pre-pregnancy planning to avoid pregnancy-related complications with diabetes. This emphasizes the need for more education and it is imperative for healthcare professionals to address these issues with adolescent female patients.

Terminations of pregnancy in the European Union.

OBJECTIVE: To study the current legislation and trends in terminations of pregnancy in the European Union (EU). DESIGN: Data were collected on legislation and statistics for terminations of pregnancy. SETTING: Population-based statistics from the EU member states. POPULATION: Women in reproductive age in the 27 EU member states. METHODS: Information on legislation was collected for all 27 EU member states. Statistical information until 2008 was compiled from international (n = 24) and national sources (n = 17). Statistical data were not available for Austria, Cyprus and Luxembourg. MAIN OUTCOMES MEASURES: Terminations of pregnancy per 1000 women aged 15-49 years. RESULTS: Ireland, Malta and Poland have restrictive legislation. Luxembourg permits termination of pregnancy on physical and mental health indications; Cyprus, Finland, and the UK further include socio-economic indications. In all other EU member states termination of pregnancy can be performed in early pregnancy on a women's request. In general, the rates of termination of pregnancy have declined in recent years. In total, 10.3 terminations were reported per 1000 women aged 15-49 years in the EU in 2008. The rate was 12.3/1000 for countries requiring a legal indication for termination, and 11.0/1000 for countries allowing termination on request. Northern Europe (10.9/1000) and Central and Eastern Europe (10.8/1000) had higher rates than Southern Europe (8.9/1000). Northern Europe, however, had substantially higher rates of termination of pregnancy among teenagers. CONCLUSION: A more consistent and coherent reporting of terminations of pregnancy is needed in the EU. The large variation of termination rates between countries suggests that termination of pregnancy rates may be reduced in some countries without restricting women's access to termination. Sexual education and provision of access to reliable and affordable contraception are essential to achieve low rates of termination of pregnancy.

Body Mass Index adjustment for sitting height for better assessment of obesity risks in Maltese women.

OBJECTIVE: This study is aimed to assess the influence of body shape on Body Mass Index (BMI) estimations by determining the Sitting Height to Standing height ratio. METHODS: The study population included 291 non-pregnant premenopausal Maltese women aged 20-54 years. These women were assessed using the following anthropometric measurements: Body weight (Kg), standing height (cm) and sitting height (cm). The Sitting-to-Standing Height (SH/S) ratio, the observed BMI (oBMI) based on the standing height, and the SH/S ratio-corrected BMI (cBMI) were calculated. The SPSS package version 18.0 was used for statistical calculations. RESULTS: The average SH/S ratio of the Maltese premenopausal women is 0.44. The mean oBMI is 25.06, while the mean cBMI is 34.49 (P value < 0.001). Applying the linear regression prediction model with either oBMI or cBMI as dependent variables and the SH/S ratio as independent variable proved that the sitting height is a significant predictor of both oBMI and cBMI (P value < 0.00001). CONCLUSIONS: The results suggest that the cohort of this study tend to have long legs relative to torso-length (low SH/S ratio). Thus, the oBMI will underestimate the actual BMI value. The correction of BMI for the sitting height in Maltese population will more correctly identify individuals at greater risk for chronic diseases.

Genetic factors in risk assessment for the development of type 2 diabetes mellitus in a small case series.

OBJECTIVE: This study aimed to investigate the role of genetic biomarkers in assessing risk for the eventual development of type 2 diabetes mellitus (T2DM). METHODS: Three Maltese women with a history of previous severe GDM and with apparent similar clinical risk factors underwent anthropomorphic and metabolic reassessment 4-7 years post-partum. They were further genotyped for four specific genetic single nucleotide polymorphisms (SNPs) using the qPCR technique for the alleles of SLC2A2 (rs5393A/C), FTO (rs9939609A/T), PCK (rs2071023C/G) and CDKAL1 (rs10946398A/C). RESULTS: While the previous obstetric history of all the cases was similar, the biological status was characterized by an increasing degree of obesity correlating to increasing severity of current carbohydrate intolerance. Genotyping showed that all the tested SNPs were homozygous mutant in the T2DM woman and heterozygous in the impaired glucose tolerance woman. The woman with normal glucose tolerance was shown to be wild type for SLC2A2 (rs5393A/C). CONCLUSIONS: There appeared to be an interrelationship between eventual severity of carbohydrate metabolism abnormalities and the genetic allele status. It would appear that the specific allele-scoring can be used to identify further the potential risk of developing T2DM.

Conjoint twinning in the Maltese Islands.

Conjoined twinning is a relatively rare event in any community, with a rate of 1.58 per 100,000 maternities reported in the EUROCAT database. The present study reviews the historical records for conjoined twins born in a closed Central Mediterranean archipelago population with particular reference to the last three decades. While the natural monozygotic twinning rates in the Maltese Islands corresponds to that reported from other communities, the incidence of conjoined twinning in the Maltese Islands has been shown by the present study to be significantly 2.5-times higher than that reported by the remaining EUROCAT contributors. The rate reported from the Maltese Islands by this review is 3.98 per 100,000 maternities.

Metabolic carcinogenesis in the Maltese population.

Endometrial adenocarcinoma has been associated with prolonged oestrogen exposure causing endometrial hyperplasia and adenocarcinoma. Metabolic disorders and nutritional factors may contribute towards obesity and the increased adipose production of oestrogen. The study confirms the association between endometrial carcinoma risk and diabetes mellitus and increased total fat intake. It further relates the malignancy to a prolonged natural oestrogen exposure period and confirms the protective role of past pregnancies.

Hypertensive disorders during pregnancy in gestational diabetic women.

Gestational diabetes is often compounded by hypertensive disease of pregnancy. Women diagnosed as suffering from gestational diabetes were subdivided into two groups: those found to be suffering from some form of hypertension during their pregnancy [n = 78]; and those who did not develop hypertension [n = 345]. The maternal characteristics and perinatal outcome of the two groups were statistically correlated. The results show that obesity was the only statistically significant correlate, and that obstetric outcome more often required planned delivery by induction of labour or caesarean section. The infant was more likely to be delivered prematurely. While the perinatal morbidity did not show any significant differences, this was only because of the more active intervention policy in these women.

Pregnancy in maltese drug-abusers: a socio-biological study.

The use of illicit drugs has increased disturbingly in the last decades, this increase being reflected by an increase in the number of female drug abusers who present in the pregnant state. A total of 47 cases of current or past heroine abuse (0.24% of total maternities) were delivered at the Karin Grech Maternity Unit of St. Luke's Teaching Hospital in Malta. The socio-biological characteristics of these women were assessed and compared to similar parameters in the remaining pregnant population. These women have been shown to be generally of a younger age <25 years and are generally unmarried. The women tend to seek antenatal care late in pregnancy. Their associated medical problems include Hepatitis C infection. There also appeared to be a statistically increased predisposition to pre-existing diabetes. There did not appear to be any statistically significant increased risks to the infant, though there may have been a greater predisposition to low birth weight and prematurity.

Lead and other metals in gestational hypertension.

OBJECTIVES: To identify any effects that lead, calcium, magnesium, and zinc may have on the development of gestational hypertension. METHODS: Third-trimester 110 normotensive and 33 gestational hypertension cases were assayed for various metal levels, using standard techniques, including atomic absorption spectrometry. RESULTS: Gestational hypertension cases showed significantly higher blood lead levels than normotensives. No differences were noticed regarding calcium (ionized and total), magnesium, and zinc levels. Blood lead was significantly related with blood pressure, even after correcting for the body mass indices and age. Blood pressure levels showed no relation to the other analyzed metals. However, the lead:ionized calcium ratio showed a stronger association with blood pressure, than lead alone. Blood lead showed a significant negative relationship with ionized calcium, but none with the other metals. CONCLUSIONS: Blood lead evidently influenced blood pressure increments and gestational hypertension development. This implies that all efforts should be made to reduce the population's exposure.

Secular trends in sex ratios at birth in North America and Europe over the second half of the 20th century.

CONTEXT: A previous study showed that significantly more boys were born in southern latitudes in Europe than in northern latitudes and the converse pattern was observed in North America. OBJECTIVE: This study analyses secular trends in gender ratios for live births over the second half of the 20th century. DESIGN, SETTING, PARTICIPANTS: Analysis was carried out from a World Health Organisation dataset comprising live births over the above period. This included 127034732 North American and 157947117 European live births. MAIN OUTCOME MEASURES: Analysis of trends in gender ratios for countries in both continents. RESULTS: The findings show a highly significant overall decline in male births in both Europe and North America (p<0.0001), particularly in Mexico (p<0.0001). Interestingly, in Europe, male births declined in North European countries (latitude>40 degrees, p<0.0001) while rising in Mediterranean countries (latitude congruent with 35-40 degrees, p<0.0001). These trends produced an overall European male live birth deficit 238693 and a North American deficit of 954714 (total male live birth deficit 1193407). CONCLUSIONS: No reasonable explanation/s for the observed trends have been identified and the causes for these trends may well be multifactorial.

Birth weight influence on the subsequent development of gestational diabetes mellitus.

Epidemiological observations have suggested a relationship between type 2 diabetes and a low or high birth weight. However, there are many confounding variables and problems with retrospective data collection. The study of women with gestational diabetes mellitus (GDM), who are likely to develop type 2 diabetes in the future, may help clarify these observations. Women diagnosed as suffering from GDM (n=162) were included in the study if their own birth weight data were available. The birth-weight distribution of the general population was obtained from published data for the same period. A family history of diabetes prevalence was assessed from medical records for the 162 GDM subjects, and by direct interview of 250 non-diabetic pregnant controls. The birth-weight distribution of women with GDM, when normalized to that of the general population, showed a statistically significant U-shape with a greater proportion of GDM women having low (1000-2000 g) or high (>4500 g) birth weight. Compared to non-diabetic pregnant controls, a statistically higher proportion of GDM women had a maternal family history of diabetes; the mean birth weight of these women was also statistically higher than that of GDM women with no family history of diabetes. No such differences were noted among women with a paternal family history. These data suggest that the intrauterine millieur Interieur, whether one of nutritional deprivation or one of nutritional plenty, results in changes in pancreatic development and peripheral response to insulin that may lead to adult-onset GDM and type 2 diabetes. Genetic predisposition, unless determined by mitrochondrial genetic material, does not apparently have any part in determining birth weight.

Long-term significance of gestational carbohydrate intolerance: a longitudinal study.

Severe forms of GDM have been conclusively associated with significantly increased risk of developing DM later on in life. The long-term significance of GIGT has not yet been definitely elucidated. The study was set up to compare the present carbohydrate metabolism status and anthropomorphic characteristics of women diagnosed as suffering from abnormal carbohydrate tolerance during pregnancy eight years previously with those recorded as having normal glucose tolerance. The prevalence of present abnormal glucose tolerance was significantly higher in women who had been noted to have carbohydrate intolerance during their pregnancy, the prevalence depending on the gestational severity (10.0% in normal glucose tolerance, 36.4% in borderline GIGT; 66.7% in GIGT). Women whose overweight or obese status persists or develops after their pregnancy were statistically more likely to develop abnormal glucose tolerance later on in life (11.9-12.5% in normal-overweight BMI, 38.2% in obese BMI). A maternal and sibling, but not paternal, family history of diabetes was also a statistically significant risk factor. GIGT appears to be a definite risk factor for the development of carbohydrate metabolism problems later on in life, this being related to the severity during pregnancy and the presence or development of obesity. It is proposed that women diagnosed to suffer from GIGT should be regularly monitored after the pregnancy, particularly if other risk factors such as obesity are also present.

Domestic abuse in a central Mediterranean pregnant population.

The Mediterranean region is generally characterized by a patriarchal society that generally predisposes towards a higher prevalence of spouse abuse. The prevalence of domestic spouse abuse in a central Mediterranean closed island community was assessed to approximate 11.7% of the pregnant population. The abuse varied from psychological to physical abuse. There was a strong history of experience of domestic violence/abuse during childhood in both the victim and perpetrator suggesting that a "circle of abuse" may play a role in some cases. The socio-biological characteristics of the victim did not appear to statistically predispose towards a higher risk for domestic abuse, though single mothers were statistically more likely to report a history of domestic abuse. Abused women were more likely to smoke cigarettes during pregnancy than their counterparts. The perpetrator was statistically more likely to be unemployed, and smoke cigarettes and drink alcohol. There were no statistical correlation between a history of spouse abuse and educational level attained by both the victim and perpetrator. A history of domestic abuse appears to have an adverse effect on the pregnancy with a higher risk of premature birth and its attendant complications; although it is difficult to ascertain how much the reported poor obstetric outcome is a direct effect of violence itself or to other associated adverse social or biological co-factors. About a third of the women interviewed were unaware of the domestic violence services being offered in their community emphasizing the need of an information drive. The antenatal period, with the distribution of leaflets and antenatal classes, is an opportune time to promote the support services available in the community.

Risk factors for gestational impaired glucose tolerance in the Maltese population: a cross-sectional study.

Screening criteria for impaired carbohydrate metabolism problems during pregnancy include the use of specified risk factors, which are generally considered to be inadequate. The value of these risk factors in a population characterised by a high prevalence of abnormal carbohydrate metabolism is investigated. The study identified biological characteristics such as a maternal age >35 years, previous early pregnancy loss, a maternal family history of DM/IGT, pre-prandial glucosuria and an operative delivery with resuscitation as significant risk factors for the development of G-IGT. There appeared to be no statistical association with a history of multiparity, previous perinatal loss, congenital anomalies or macrosomia and a parental and grandparent family history of DM/IGT. There appeared to be a statistical difference in fasting blood glucose values, but no difference in glycosated haemoglobin. The risk factors for the development of G-IGT are shown to have a high specificity and negative predictive value, but overall moderate to low sensitivity and positive predictive values when used in isolation. The prevalence of the various identified risk factors was very high, a feature which would require at least a third of the population to be screened with an oral glucose tolerance test. These features suggest that the historical and clinical risk criteria are not ideal screening tools to identify G-IGT and a routine early third-trimester oral glucose tolerance test remains the ideal screening tool to identify these cases.

Declining male births with increasing geographical latitude in Europe.

OBJECTIVE: Demographic studies in various industrialised countries have shown a decline in male births in the latter half of the 20th century from the expected ratio of 0.515 (males/total). This study analyses trends in this ratio over the period 1890 to 1995 in Malta, and also analyses this ratio for Western European countries for the period 1990-1995. DESIGN: Births subdivided by sex were obtained from official Maltese publications. European countries were grouped according to geographical latitude by banding countries into three groups: Northern Mediterranean, Central European and Scandinavian. Births by sex for these countries were also analysed for the period 1990-1995. RESULTS: No decline in the ratio of male births to total births was noted in Malta over the period 1916-1995. However, the ratio was higher than expected (n = 151,766, ratio = 0.517 (95% confidence intervals (95% CI): 0.514, 0.519). Moreover, during the period 1890-1899 (n = 66,874), the ratio was 0.523 (95% CI: 0.519, 0.527), even higher than observed during the 20th century (chi 2 = 8.3, p = 0.004). Analysis of European births showed a much higher ratio of male births in the south of Europe than in the north (chi 2 = 87.2, p < 0.0001). CONCLUSIONS: The findings were unable to explain the higher incidence of male births in the south of Europe, but it is speculated that ambient temperatures may not only affect fertility, but also influence sex ratios at birth.