PERINATAL ASPECTS OF SARS-CoV-2 INFECTION DURING PREGNANCY: A POTENTIAL CAUSE FOR CONCERN.

Ever since the beginning of COVID-19 pandemic, uncertainty regarding clinical presentation and differences among various subpopulations exist. With more than 209,870,000 confirmed cases and more than 4,400,000 deaths worldwide, we are facing the new era of health crisis which will undoubtedly impair global health, economic and social circumstances. In the past year, numerous genetic mutations which code SARS-CoV-2 proteins led to the occurrence of new viral strains, with higher transmission rates. Apart from the implementation of vaccination, the effect of SARS-CoV-2 on pregnancy outcome and maternal fetal transmission remains an important concern. Although neonates diagnosed with COVID-19 were mostly asymptomatic or presented with mild disease, the effect on early pregnancy is yet to be evident. While positive finding of SARS-CoV-2 RNA in some samples such as amniotic fluid, placental tissue, cord blood and breast milk exists, additional research should confirm its association with transplacental transmission.

PREGNANCY OUTCOME IN GESTATIONAL DIABETES COMPARED TO BODY MASS INDEX.

Gestational diabetes involves disorder of glucose metabolism first diagnosed in pregnancy. Obese women undoubtedly have more often complications in reproductive age, such as fertility difficulties, spontaneous and recurrent miscarriages, premature births, and various obstetric and surgical complications related to the course of pregnancy, delivery and puerperium. Children of obese pregnant women are more likely to develop obesity in childhood and adulthood. We analyzed the outcome of 51 pregnancies in obese pregnant women and 50 pregnant women with normal body mass index. All women in both groups were diagnosed with gestational diabetes by the IADPSG criteria. We analyzed gestational age at delivery and mode of delivery, gestational weight gain, presence of concomitant diagnosis of gestational or chronic hypertension, difference in birth weight, and prevalence of hypertrophic newborns. There was no significant difference in gestational age at pregnancy termination and in the mode of delivery. There was a significant difference in gestational weight gain, number of pregnant women with hypertension, neonatal birth weight and number of hypertrophic children. Based on the data presented, we conclude that obesity is an unfavorable factor for pregnancy outcome. It also influences birth weight and fetal hypertrophy, as well as gestational weight gain.

Do Changing Diagnostic Criteria for Gestational Diabetes Influence Pregnancy Outcome?

The incidence of pregnancy related diabetes has been steadily increasing during the past decade. The aim of this retrospective study was to evaluate the type and prevalence of gestational diabetes complications after implementing new diagnostic criteria for gestational diabetes. The incidence of gestational diabetes, maternal age, mode of delivery and birth weight were analyzed. Study patients were divided into three groups. The first group consisted of patients who gave birth during 2005, the second group during 2011 and the third group during 2012. In 2005, the World Health Organization criteria were used on diagnosing gestational diabetes, whereas in 2011 and 2012 the criteria issued by the International Association of Diabetes and Pregnancy Study Groups were considered. There was no statistically significant difference among the groups according to maternal age, birth weight (p=0.203) and mode of delivery (p=0.883). Cesarean section was performed in about 30% of deliveries in all groups combined. There was no significant difference in the number of neonatal hypertrophy (p=0.348), although the distribution of hypertrophy showed a tendency towards higher values in 2005. The incidence of gestational diabetes was 2.2% in 2005, 6.6% in 2011 and 12% in 2012. In conclusion, difference in the incidence of pregnancy related diabetes appeared to have resulted directly from using different diagnostic criteria. The new criteria contributed to a relatively higher incidence of gestational diabetes but also achieved better gestational glycemic control and consequently better fetal growth regulation.

Secular Changes in Education, Urban-rural Living, Menarche and Abortion Rates in Perinatal Population.

Over a 25-year period we examined the anthropological characteristics of mothers and their partners, such as the place of living: urban vs. rural, the degree of education, parity, the time of menarche, and the frequency of intentional abortions. We examined 2 414 mothers and their partners in four periods of time extending from 1985 to 2009 in order to establish changes in the said anthropological characteristics over a period of 25 years. The degree of education of mothers and their partners is on the rise. In the period from 1985 to 1994, the percentage of mothers from the country was on the rise. Women with less education have on average more children, and those with better education the least children. Women from rural areas have on average more children than women from urban areas. The time of menarche dropped by 9 months over the period of 25 years. Girls from urban areas have their first menstrual cycle earlier. Women with higher professional qualifications had their first period earlier. The number of intentional abortions over the 25-year period dropped.

Development and validation of the Prenatal Diagnostic Procedures Anxiety Scale.

OBJECTIVES: As there are currently no specific measures of anxiety due to prenatal diagnostic procedures, the aim of the study was to develop and validate a new measure called the Prenatal Diagnostic Procedure Anxiety Scale (PDPAS). METHODS: Seventy-four pregnant women scheduled for amniocentesis and ultrasound completed the PDPAS, the State-Trait Anxiety Inventory, the Edinburgh Postnatal Depression Scale, and the Perceived Stress Scale before undergoing the diagnostic procedure. Reliability, concurrent validity, factor structure, scale sensitivity, and specificity were analyzed. Differences between amniocentesis and ultrasound groups in the PDPAS score were analyzed with a t-test. RESULTS: The final scale comprised 11 items and two subscales measuring 'fear of procedure' and 'fear of abnormal result'. Concurrent validity analysis showed that the PDPAS is an independent measure of anxiety. At a cut-off score of >11, sensitivity was 75.0% and specificity was 72.01% with moderate accuracy. Fear of procedure was higher in the amniocentesis group, whereas fear of abnormal result was equally present in both amniocentesis and ultrasound groups. CONCLUSION: The PDPAS has good internal consistency and concurrent validity with satisfactory psychometric characteristics. As a short measure of situation-specific anxiety, it can be used as a screening tool in prenatal clinical settings.

The psychological effects of prenatal diagnostic procedures: maternal anxiety before and after invasive and noninvasive procedures.

OBJECTIVES: (1) To examine the change in anxiety before and after prenatal diagnostic procedures in women undergoing invasive (amniocentesis) and noninvasive (ultrasound) procedures; and (2) to examine predictors of anxiety before the diagnostic procedure. METHODS: A short-term follow-up study was conducted on a sample of pregnant women in the second trimester. Questionnaires were administered to women scheduled for amniocentesis (n = 37) and ultrasonography (n = 37) before and immediately after the procedure. The following questionnaires were administered: the State-Trait Anxiety Inventory, the Affect Intensity Measure, the COPE inventory, and the Optimism-Pessimism Scale. RESULTS: Prior to the administration of the prenatal diagnostic procedure, measured anxiety levels were the same in both groups of women (p > 0.05). An interaction effect of a two-way ANOVA revealed that anxiety decreased after the procedure in the ultrasound but not the amniocentesis group (F(1, 72) = 5.01, p = 0.028). Although coping styles and affect intensity were found to be related to anxiety (p < 0.05), they were not significant predictors of anxiety before the diagnostic procedure when controlling for trait anxiety and procedure type. CONCLUSION: Anxiety levels associated with noninvasive but not after invasive, prenatal diagnostics tests decrease immediately following the procedure.

Secular changes in growth and obesity in perinatal population.

The survey was conducted during the last 25 years and included 2414 healthy women who delivered in "Sestre milosrdnice" University Hospital Center in Zagreb, Croatia and their newborns. The aim was to establish the secular trend of some anthropological factors through two generations. Anthropological features such as pre-pregnancy weight, body mass index before pregnancy, height, age, place of residence, educational level, parity and the newborn weight were registered. The study was randomized. The mothers from the city of Zagreb and the surrounding villages, rural areas are examined. The women age was different and also different levels of education and socioeconomic status. The study included women who had not given birth yet, who had delivered once, twice, and three or more times. Maternal height in 25 years increased by 3.1cm. and increases with education. The pre-pregnancy weight increased 2.8 kg and increases with age, parity and rural life. The body mass index (BMI) which the women had before pregnancy was calculated, and according to its value the participants were divided in three groups: with normal weight, overweight and fat. Among the studied periods BMI does not differ significantly, but does differ significantly with respect to the ordinal number of births, parity, age and living environment. Higher BMI was associated with deliveries to heavier children.

Detection of ovarian cancer by determination of CA 125 in different patohistologycal types of tumor according to age.

During the eighteen-year period in "Sestre milosrdnice" University Hospital Center, Zagreb, 271 women with ovarian tumor was studied. 229 women with ovarian cancer and 42 with borderline tumor. The pathohistological types of tumors were different. The age of the patients ranged from 20-83 years. In all patients the value of biochemical marker CA125 was determined. The aim of this study was to determine the usefulness of CA125 measurement in different age groups and in different patohistologycal forms of tumor. CA125 has proven to be positive in 89.1% of women with ovarian cancer and in 62% with neoplasm of low malignant potential. The higher values of CA125 were detected in younger women with low malignant tumor potential. Serous and metastatic tumor types were also associated with higher values of CA125.

Platelet serotonin concentration at term pregnancy and after birth: physiologic values for Croatian population.

The aim of this study was to determine physiological value of platelet serotonin (5-HT) and its variations in the group of women in term pregnancy and after birth. Obtained results were compared to the platelet 5-HT level in nonpregnant women group. Determination of normal level of 5-HT in pregnancy and after could help in its further measurement and evaluation of different psychologic and psychiatric disorders related to pregnant and postpartal period, including better understanding of mood changes after the birth. A total of 137 healthy Croatian women were enrolled in the study--82 of them were pregnant and 55 were not. Their blood was sampled and the platelet serotonin concentration was determined. In pregnant women the blood was sampled twice: at term pregnancy, and soon after birth. The mean value of 5-HT in pregnant women was 1.209 nmol/mg protein, after the delivery 1.045 nmol/mg protein, and in non pregnant 1.088 nmol/ mg protein. The concentrations were significantly different in those three groups. We did not find differences in 5-HT levels in groups divided by age.

Prediction of ovarian tumor malignancy.

Ovarian cancer is the leading cause of mortality among gynecological cancers. The aim of the study was to form the decision rules for distinguishing benign from malignant ovary lesions. The research was conducted on 201 women with ovary tumor. Commonly used specific markers for ovarian cancer (biochemical marker Ca 125, ultrasound and vascular markers) were used. The significant difference in the presence of an ultrasound and vascular markers between benign and malignant ovary changes along with the significantly different level of Ca 125 is confirmed. To a specific marker certain score number was appointed and the scoring system was formed. The incidence of benign/malignant ovary changes was observed in the researched group regarding anthropometric parameters (age, marital and menopausal status and number of deliveries). There is also significant difference in the incidence of benign/malignant ovary tumor regarding these parameters. Based on combination of the scoring system and anthropometric parameters the decision rules for distinguishing benign from malignant ovary tumors were formed. The logistic regression method was used. We proved that this method has higher accuracy in prediction of malignancy in women with ovary tumors than using morphological, Doppler or anthropometric parameters separately.

Male to female birth ratios over a 35-year period.

Aim Along with changes to the human physique recorded over the past decades in certain countries, there are also changes concerning the male-female birth ratio. The aim of this study was to establish the movement of male-female birth ratios and factors affecting the ratio. Methods This retrospective study was conducted in Zagreb, Croatia, in the period from 1985 to 2019 on a sample of 3804 newborns. Results In the 35-year period the ratio of boys and girls at birth did not change significantly. Girls had lower birth weight, and boys had higher birth length. In the war period (1992-1994), a mild increase in the ratio of boys was noted, but not statistically significant. Father's age in the last period examined (2007-2009) showed to be a statistically significant predictor of the child's gender. Namely, the descendants of younger fathers were statistically significantly more frequently girls, while the descendants of older fathers were more frequently boys. Married mothers had higher percentage of male births (51.5%), and a lower percentage (47.1%) by unmarried mothers. Conclusion The changes in birth ratios are particularly pronounced in different age and socioeconomic groups of parents nowadays when the growth of living standards is accompanied by significant changes of the human physique.

Secular trends in parental age in Croatia from 1985-2009.

BACKGROUND: In developed countries general living conditions and living standard have grown, leading to reproductive and other secular changes. During the past decade in Croatia living conditions and living standard have improved. OBJECTIVE: The aim of this study was to determine changes in reproductive secular trend in our country similar to trends in developed countries considering different and improved living conditions in Croatia. METHODS: 2414 parents and their newborns during 25 years were examined. The study was conducted in University Hospital Center "Sisters of mercy", Zagreb, Croatia. The study was randomized and included only healthy singleton pregnancies. The information was taken from medical data. Anthropological parameters of pregnant women regarding the place of residence, educational level, marital status and parity were examined. The results were statistically analyzed using nonparametric tests, parametric tests, and if necessary additional post hoc tests. RESULTS: The age of mothers during the study period significantly increased especially in primiparas and secundiparas. The percentage of highly educated mothers and fathers increased. The age of the fathers also increased. Women living in the cities deliver later. Older women deliver heavier and longer children. The share of under-aged mothers during the 25 year period did not change significantly. In the group of older fathers somewhat more common are boys. The proportion of babies with a specified mass is significantly different regarding the maternal age. The proportion of babies of certain length is significantly different with respect to the maternal age only when all periods are considered. CONCLUSION: Our data show a secular trend in reproductive health similar to developed countries.

Macroprolactinemia: new insights in hyperprolactinemia.

Hypersecretion of prolactin by lactotroph cells of the anterior pituitary may lead to hyperprolactinemia in physiological, pathological and idiopathic conditions. Most patients with idiopathic hyperprolactinemia may have radiologically undetected microprolactinomas, but some may present other causes of hyperprolactinemia described as macroprolactinemia. This condition corresponds to the predominance of higher molecular mass prolactin forms (big-big prolactin, MW > 150 kDa), that have been postulated to represent prolactin monomer complexed with anti-prolactin immunoglobulins or autoantibodies. The prevalence of macroprolactinemia in hyperprolactinemic populations between 15-46% has been reported. In the pathophysiology of macroprolactinemia it seems that pituitary prolactin has antigenicity, leading to the production of anti-prolactin autoantibodies, and these antibodies reduce prolactin bioactivity and delay prolactin clearance. Antibody-bound prolactin is big enough to be confined to vascular spaces, and therefore macroprolactinemia develops due to the delayed clearance of prolactin rather than increased production. Although the clinical symptoms are less frequent in macroprolactinemic patients, they could not be differentiated from true hyperprolactinemic patients, on the basis of clinical features alone. Although gel filtration chromatography (GFC) is known to be the gold standard for detecting macroprolactin, the polyethylene glycol precipitation (PEG) method has offered a simple, cheap, and highly suitable alternative. In conclusion, macroprolactinemia can be considered a benign condition with low incidence of clinical symptoms and therefore hormonal and imaging investigations as well as medical or surgical treatment and prolonged follow-up are not necessary.

Treatment of ectopic pregnancy with methotrexate.

The aim of the present study was to analyze retrospectively the safety and success rates of single- and two-dose methotrexate (MTX) protocols for the treatment of hemodynamically stable cases of ectopic pregnancy at University Department of Gynecology and Obstetrics, Zagreb University Hospital Center, during a five-year period. The study evaluated MTX treatment efficacy in 35 women with ectopic pregnancies in relation to the initial levels of human chorionic gonadotropin (hCG) and progesterone. Successful treatment was recorded in 32/35 women, 24/25 on single dose MTX and 8/10 on double dose MTX, whereas 3/35 patients underwent laparoscopy. The mean initial hCG level in all 35 patients on day 0 was 657.54 +/- 592.4 IU/L; 572.99 +/- 488.10 IU/L in those successfully treated with MTX and 1560.30 +/- 890.70 IU/L in those requiring additional laparoscopy (p < 0.005). The mean initial hCG level was 393.10 +/- 305.9 IU/L in patients successfully treated with a single dose of MTX and 973.5 +/- 722.40 IU/L in those with an additional dose of MTX (p < 0.002). The mean initial progesterone level was 16.36 +/-10.70 nmol/L in 35 MTX-treated ectopic pregnancy patients, 13.64 +/- 8.89 nmol/L in those with treatment success and 28.45 +/- 11.32 nmol/L in cases of treatment failure (p < 0.05). The mean level of progesterone on day 0 was 12.74 +/- 830 nmol/L in patients successfully treated with a single dose of MTX and 26.10 +/- 18.80 nmol/L in patients treated with double-dose MTX (p < 0.006). It is concluded that pretreatment values of hCG and progesterone are inversely related to medicamentous treatment success in selected cases ofhemodynamically stable patients, thus they may be used as an important predictor in the management of ectopic pregnancy treated with MTX.