Volume 32, Issue 4

Alterations of the intrauterine and early postnatal nutritional, metabolic, and hormonal environment may cause predispositions to the development of disorders and diseases in later life. Mechanisms responsible for this perinatally acquired ‘malprogramming’ still remain unclear. It has long been known, however, that hormones are environment-dependent organizers of the developing ‘neuroendocrine-immune network’, which regulates all fundamental processes of life. When present in nonphysiological concentrations during critical ontogenetic periods, hormones can therefore also act as ‘endogenous functional teratogens’. Fetal and neonatal hyperinsulinism is a pathognomic feature in the offspring of diabetic mothers. Perinatal hyperinsulinism also occurs due to early postnatal overfeeding. Data obtained by our group indicate that elevated insulin concentrations during critical periods of perinatal life may induce a lasting ‘malprogramming’ of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism etc. Since mechanisms of early ‘programming’ of obesity, diabetes, and the metabolic syndrome X are unclear, a complex ‘neuroendocrine malprogramming’ of the regulation of body weight and metabolism may provide a general etiopathogenetic concept in this context, exemplarily revealing critical new implications for chances and challenges of perinatal preventive medicine in the future.

Aims: This study compares neonatal and maternal morbidity and mortality between waterbirths and landbirths (spontaneous singleton births in cephalic presentation, vacuum extractions are excluded). Methods: In this observational study covering nine years, standardized questionnaires were used to document 9,518 spontaneous singleton cephalic presentation births, of which 3,617 were waterbirths and 5,901 landbirths. Results: Landbirths show higher rates of episiotomies as well as third and fourth degree perineal lacerations. Waterbirths show a higher rate of births “without injuries”, first and second-degree perineal lacerations, vaginal and labial tears. After a waterbirth, there is an average loss of 5.26 g/l blood; this is significantly less than landbirths where there is an 8.08 g/l blood loss on average. In 69.7% waterbirths required no analgesic, compared to 58.0% for landbirths. Water and landbirths do not differ with respect to maternal and neonatal infections. After landbirths, there was a higher rate of newborn complications with subsequent transfer to an external NICU. During the study, there were neither maternal nor neonatal deaths related to spontaneous labor. Conclusions: Waterbirths are associated with low risks for both mother and child when obstetrical guidelines are followed.

Objective: To investigate and compare the direct effects of compounds used in the treatment of hypertensive disease in pregnancy on human umbilical artery resistance in vitro . Methods: Isometric tension recordings were performed under physiological conditions on human umbilical arterial rings (n=30). The in vitro effects of labetolol, hydralazine, alpha-methyldopa, nifedepine and magnesium sulphate (at concentration ranges from 1 nanomolar to 1 millimolar), and their respective vehicle controls, were measured. Results were expressed as −logEC 50 (pD 2 ) and mean maximal inhibition values for each compound. Results: All compounds investigated, except alpha methyldopa, exerted a significant relaxant effect on umbilical arterial tone. Alpha-methyldopa was significantly less potent when compared to all other compounds (mean maximal inhibition value [20.89±7.99%] versus all other agents [range 63.15±8.70−84.12±3.84%] (P<0.01)). The dose response curve of nifedipine yielded a significantly greater pD 2 value when compared to that of hydralazine, labetalol, and magnesium sulphate (pD 2 value [5.82±0.34] versus the above groups [range 3.10±0.09−3.52±0.14] (P<0.01)). Conclusion: These findings demonstrate that agents commonly used for the treatment of hypertensive disease in pregnancy, excluding alpha-methyldopa, have significant direct effects on the feto-placental circulation. These results suggest that alpha-methyldopa administration during pregnancy is less likely to produce significant direct effects on fetal vasculature then other agents used.

Aim: To determine how the omission of the third hour glucose measurement of the 100 g oral glucose tolerance test (GTT) affects the diagnosis of gestational diabetes mellitus (GDM). Methods: Retrospective chart review of 876 women delivered in a tertiary care hospital in Israel during a three-year period, who underwent a 100 g 3 hour oral GTT following an abnormal 50 g glucose screen. GDM was diagnosed according to the “criterion standard” accepted in the Fourth International Workshop Conference on GDM. The results of the 100 g 3 hour oral GTT were then retrospectively re-evaluated by omission of the third hour plasma glucose measurement from the “criterion standard”. Results: GDM was diagnosed in 28.4% of the study patients, while the omission of the third hour glucose measurement resulted in a 26.4% diagnosis of GDM. The perinatal data of the 18-omitted cases suggests that their exclusion from the GDM group would not have altered substantially the perinatal outcome of the study cohort. Conclusions: A 100 g 2 hour oral GTT is a simple and economic alternative to the 100 g 3 hour oral GTT.

Objective: The relationship between detection of Mycoplasma hominis in mid-trimester amniotic fluid and subsequent pregnancy outcome was investigated. Study design: Amniotic fluids from 456 women of European background who underwent a transabdominal amniocentesis at weeks 15–17 of pregnancy were tested for M. hominis by polymerase chain reaction (PCR). The amplicons were hybridized to an internal probe and detected by ELISA. Pregnancy outcomes and clinical data were subsequently obtained. Results: M. hominis were identified in 29 (6.4%) of the amniotic fluids. The rate of preterm labor in women positive for M. hominis (14.3%) was higher than in the negative women (3.3%) (p=0.01). Similarly, a spontaneous preterm birth with intact membranes occurred in 10.7% of the M. hominis -positive women as opposed to only 1.9% of the negative women (p=0.02). The presence of this mycoplasma was not correlated with fetal chromosomal aberrations, intrauterine growth restriction or preeclampsia. Conclusions: Detection of M. hominis in second-trimester amniotic fluids can identify women at increased risk for subsequent preterm labor and delivery.

Aims: To investigate the changes in the size of maternal inferior vena cava (IVC) during normal pregnancy. Methods: The diameter and the area of IVC were measured in 32 non-pregnant and 214 pregnant women by ultrasonography. They were measured not only in the supine but also in the complete left lateral position when gestation was over 16 weeks. Results: IVC in the 4–7 weeks pregnant group was larger than that in the non-pregnant group, and it decreased as gestation progressed during an early stage of pregnancy. After 16 weeks gestation, it demonstrated no change, at least for depending on the periods when the mother was in the supine position. On the contrary, they increased with the gestational progress as for the maternal left lateral position. Conclusions: The size of IVC at an early stage of pregnancy is enlarged, suggesting an underfilling state of arterial circulation. In the second and third trimesters, it is stationary when the mother is supine. In the left lateral position, it increases as the gestation progresses, reflecting blood volume expansion during pregnancy.

The purpose of this study was to evaluate procalcitonin (PCT) plasma levels in pregnancy complicated by preterm labor and to determine their value in the prediction of preterm delivery and the length of the admission-to-delivery interval. The study population consisted of 53 patients with preterm labor and 31 healthy pregnants. The study patients were divided according to the delivery time and to the admission-to-delivery interval. Plasma PCT concentrations were higher in preterm labor than in healthy pregnants. Although at the onset of preterm labor plasma PCT concentrations in patients who delivered prematurely were higher than in patients who, after tocolytic treatment, delivered at term, the difference was not significant. Also in cases of preterm labor delivered within and after three and seven days of admission no differences were observed. The highest values in the prediction of preterm delivery and the length of admission- to-delivery interval corresponded to a PCT concentration of 1.7 ng/ml. These findings suggest that although preterm labor is associated with increased PCT concentrations in maternal plasma, there is no significant association either between plasma concentration of PCT at the moment of threat and preterm delivery, or the admission- to-delivery interval. The predictive value of plasma PCT determinations is unsatisfactory.

Objective: Determine social factors related to pregnancy among young adolescents. Methods: We obtained socio-demographic data from early adolescent nulliparas aged ≤15 years. Results: During the study period at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil-Ecuador 201 early adolescent nulliparous patients of low socio-economic status were surveyed and compared with 201 low socio-economic nulliparous controls aged 20 to 30. Mean age of adolescents was 14±0.6 years, 58.7% of them were aged 14. Age of menarche and sexual initiation was lower among adolescents (11.8±0.9 vs 12.8±2 years and 12.6±1.1 vs 16.2±5 years, respectively, p<0.05). A higher rate of adolescents initiated sexually before menarche onset (18.4% vs 5%, p<0.05). The rate of those who wanted to become pregnant, had adequate prenatal care and had knowledge of conception, used contraception or had knowledge of any contraceptive method prior to pregnancy was significantly lower in adolescents (16.9% vs 86.5%; 37.3% vs 94.5%; 18% vs 70.1%; 6.5% vs 89.5%; 42.8% vs 84.5%, respectively, p<0.05). Age of sexual partner was lower in the adolescent group (20.4±3.4 vs 30±8 years, p<0.05). Compared to controls, higher rates of adolescents were school dropouts, had problems with the law and were involved in domestic violence (87% vs 9.9%, 7.5% vs 0.5%, 44.7% vs 2.5%, respectively, p<0.05). None of the adolescents were living with mother and father in a complete family structure. Parental illiteracy was higher among adolescents (9% vs 3.5%, p<0.05). Conclusion: In this low socio-economic population, early sexual initiation, poor reproductive health knowledge and the disruption of family structure

Fetal gender has a significant effect on maternal and cord blood hCG levels, particularly during the last trimester of the pregnancy. However, the reason for this difference is obscure. The aim of the present study was to investigate whether term fetal hypophyseal - adrenal - gonadal axis differs between female and male fetuses thereby causing different hCG levels. The study consisted of 60 women with singleton pregnancies in the third trimester. Thirtyone pregnant women were carrying female fetuses, whereas 29 were carrying male. Human chorionic gonadotropin (hCG), estradiol, progesterone, testosterone, dehydro-epiandrosteron-sulfate (DHEAS), prolactin and growth hormone levels were measured in maternal serum and umbilical cord blood. In female bearing pregnancies maternal and cord blood hCG levels were significantly higher than in male bearing pregnancies (P<0.001). Maternal and cord blood estradiol, progesterone, testosterone, DHEAS, prolactin and growth hormone levels were not significantly different in either fetal gender. When all patients were considered as a group there were no correlations between fetal hCG levels and any of the measured hormones. Term fetal DHEAS, estrogen, progesterone, testosterone, growth hormone and prolactin levels do not contribute to different hCG levels between female and male fetuses. It is possible that fetal hypophyseal-adrenal - gonadal axis does not play a central role as the cause of different hCG levels.

Aim: To investigate whether the same behavioral patterns were present pre- and postnatally, and whether there were any differences in the frequency of movements observed in fetal and in early neonatal life. Subjects and methods: Ten out of 37 pregnant women in the third trimester of pregnancy (median gestational age 34 weeks, range 33 to 35 weeks) in the two-month period (from November 1 st to December 31 st , 2003) were enrolled in the investigation. Ten term, appropriate for gestational age newborns (seven born vaginally, three by elective SC, six girls, six first-born) and were enrolled in the study. All 4D examinations were performed on Voluson 730 (Kretztechnik, Zipt, Austria) and Acuvix (Medison, Korea) with transabdominal 5 MHz transducer. After standard assessment in 2D B-mode ultrasound, a 4D mode was switched on and live 3D image was reconstructed by selecting the ideal representative 2D image placed in the region of interest (ROI). The recordings of neonatal behavior were made on the Sony P-612 OHMPL videotape by video camera (Sony Camcoder CC DTRV 318 Hv8) and reviewed on the videocassette recorder (Sony VHS SLV-N 900). The median of newborns' age at the moment of recording was 49 hours (range 4 to 112). During the examination, newborns were lying in the bed, separated from other infants in the nursery, dressed, and lying on their backs in a supine position with unrestrained hands. The temperature in the room was 22 to 24°C. The video recording was performed mainly while the children were actively awake or during alert inactivity. Results: There were no movements observed in fetal life that were not present in neonatal life, while the Moro reflex was present only in neonates. The most frequent fetal and neonatal movements were scowling, eye and mouth opening, and hand to face, hand to eye and hand to head movements. Isolated blinking, mouth to eyelid movement, yawning, tongue expulsion and scowling were more frequent in neonates than in fetuses, although the difference was not statistically significant. Hand to mouth movements were more frequent in neonatal than in fetal life while all other hand movements were less frequent in neonates than in fetuses, although the differences did not reach statistical significance. Spearman rank order correlation reached statistical significance in smiling (R=0.71; t=2.91; P=0.02) and in hand to ear movement (R=0.80; t=3.86; P=0.005), and was almost statistically significant in isolated eye blinking (R=0.61; t=2.17; P=0.06), while the correlations between the rest of the movements were not statistically significant. Conclusions: 4D ultrasonography is a powerful tool in the assessment of fetal behavior, and our study showed that there is a continuity from fetal to neonatal behavior, especially in terms of isolated eye blinking movements, mouth and eyelid opening, yawning, tongue expulsion, smiling, scowling and hand movements directed to other parts of the face.

Introduction: The instillation of surfactant into the airways of patients with respiratory distress syndrome (RDS), especially in the neonatal period, is a proven therapy. The preventive therapy of RDS through intra-amniotic injection of surfactant has been reported recently. It has not been conclusively shown, however, that the surfactant administered in this way actually reaches the fetal pulmonary airways. Objective: To study the distribution in fetal organs of a natural surfactant labeled with technetium-99m and injected through amniocentesis into the amniotic sac of guinea pigs in the last third of pregnancy. Methods: After stimulating fetal respiratory movements with aminophylline 0.3 ml of an aqueous suspension containing 0.75 mg of phospholipids of a natural bovine surfactant labeled with technetium-99m, together with 0.1 ml of the biological dye carmine indigo, were injected into the amniotic sac. One hour later fetuses were delivered by cesarean section. In those that were dye-stained, dosimetric and gammagraphic tests were applied to trachea, lungs, esophagus, stomach, heart, liver, kidneys and placenta. Results: Significant radio isotopic activity was found in both lungs of six treated fetuses, with a dose capture of between 1.0% and 5.3% of total dose. The level of activity in the stomachs was similar to that in the lungs (0.9% to 3.0% dose capture), whereas activity in other organs was negligible except in two placentae. No radio isotopic activity was found in non-injected control fetuses. Conclusions: In the present animal model natural surfactant injected intra-amniotically is aspirated into the lungs within one hour.

Aim: The objective of this study was to evaluate the effects of close and remote phototherapy on serum nitric oxide (NO) and vascular endothelial growth factor (VEGF) levels as well as on body temperature heart rate and blood pressure in neonates of different gestational ages. Patients and method: Term (gestational age ≥37 weeks) and preterm neonates (GA <37 weeks) with hyperbilirubinemia requiring phototherapy were included in the study. All patients except for the ones in incubators were randomized to receive either close phototherapy (15 cm above the patient) or remote phototherapy (30–45 cm above patient). Body temperature, heart rate and blood pressure were measured before treatment, six hours into treatment and one hour after cessation of treatment. Blood samples for NO and VEGF measurements were also taken at the same times. Results: Sixty-one term newborns and 37 preterm newborns were included in the study. Patients were distributed into four groups according to the dose of treatment together with gestational age, i.e. term close and remote photoherapy groups (n=29, n=32, respectively), preterm close and remote photoherapy groups (n=10, n=27, respectively). Body temperature increased significantly with phototherapy in all groups but was not at hyperthermia level. Heart rate increased in all groups except for term newborns in the remote phototherapy group and blood pressure decreased in term infants but was unchanged in preterms. None of these changes were at the level of tachycardia or hypotension for a newborn. Phototherapy did not result in elevation of NO or VEGF levels. Conclusion: This study showed that in our group of patients close or remote phototherapy caused some body temperature, heart rate and blood pressure changes that were not clinically significant and did not result in increased levels of NO or VEGF, which are well known vasodilator mediators.

Reexpansion pulmonary edema (RPE) is rare and usually follows rapid reexpansion of a collapsed lung. We report on a preterm infant who developed pulmonary edema within an hour of surgical ligation of patent ductus arteriosus (PDA). There were no other cardiac anomalies, fluid overload or airway obstruction to explain the change in clinical status. With supportive treatment the patient's condition became stable and was extubated within 48 hours. Lung retraction for better field exposure is often needed when performing PDA ligation in preterm infants. Reinflation of a retracted lung is thought to be the cause of our patient's pulmonary edema. We conclude that RPE, although uncommon, may occur following surgical ductal ligation and that clinicians should be aware of such a possible complication.

Prostaglandin E 1 (PGE 1 ) treatment can be life saving in patients suffering from ductus dependent congenital heart defect. We analyzed the indications and side-effects of PGE 1 therapy over a five-year period. The purpose of the study was also to examine whether a change in serum electrolyte levels could be detected. Forty-nine patients were treated with PGE 1 during this period. PGE 1 treatment was indicated by ductus dependent systemic circulation in 16 cases, ductus dependent pulmonary circulation in 17 cases, transposition of the great arteries in 13 cases and pulmonary hypertension (persistent fetal circulation) in three cases. As early side-effects of the treatment, fever occurred in 27/49 cases while apnoea was observed in 15 patients. In a one-week-old neonate with coarctation of the aorta grade III intraventricular hemorrhage developed. A mild decrease of sodium, potassium and chloride levels and a slight shift of pH levels toward metabolic alkalosis could be detected after one day and one week of PGE 1 treatment. Because of these side-effects of PGE 1 patients should be monitored in an intensive care unit. According to our observations electrolyte levels may exhibit a slight decrease; however, in the case of a short-term therapy extra salt supplementation is not necessary.

We report a case of maternal anaphylaxis following intrapartum chemoprophylaxis. The term fetus developed severe brain damage as a consequence of intrapartum asphyxia. The lesions resulted from maternal hypotension following anaphylaxis. We discuss the feto-maternal risks and the controversial treatment of such a condition. The increasing number of penicillin-treated parturients will result in further cases of maternal anaphylaxis than previously found.

Ultrasonographic demonstration of bowel peristalsis within the fetal scrotum has been described as a pathognomonic sign of inguinoscrotal bowel herniation. We present the sonographic features and neonatal outcome of a fetus with a scrotal mass seen at 34 weeks of gestation in a twin pregnancy. This mass was diagnosed postnatally as a non-reducible inguinoscrotal hernia, in which bowel peristalsis had not been observed by realtime ultrasound in utero .

Polysplenia syndrome is a condition that persists as a defect of lateralisation, the embryonic process by which the site of body organs is determined. The most frequent manifestations of this syndrome, in addition to polysplenia are complex cardiac malformations, situs inversus, and bilobed lungs. Laterality defects have been known to be due to autosomal recessive inheritance. We report a unique case of polysplenia syndrome in association with genital tract duplication anomaly.

Hyperphenylalaninemia in preterm neonates with heterozygosity for phenylketonuria has previously not been described. We report on a very low birth weight infant, born at a gestational age of 27+5 weeks with a birth weight of 1080 g. Due to a positive family history prenatal diagnosis for phenylketonuria was performed, revealing heterozygosity for classic phenylketonuria. Yet the girl showed hyperphenylalaninemia with a maximum serum phenylalanine concentration of 515 μmol/l on the eighth day of life. Phenylalanine-restrictive parenteral and enteral nutrition was kept from the eighth until the 41 st day of life. At term serum phenylalanine concentrations had normalized. We hypothesize that heterozygosity for phenylketonuria may be a risk factor for hyperphenylalaninemia in preterm born infants. Prematurity and the resulting immaturity of liver function with the genetically determined reduced activity of phenylalanine hydroxylase might have caused hyperphenylalaninemia in this girl.