Blood pressure levels but not hypertensive complications have increased in Type 1 diabetes pregnancies during 1989-2010.

AIMS: The pre-pregnancy BMI and the third trimester HbA(1c) levels increased in Finnish parturients with Type 1 diabetes during 1989-2008. The aim of the present study was to investigate whether these trends have been accompanied by increases in blood pressure or hypertensive complications. Hypertension trends were analysed using the definitions of hypertension of both the American College of Obstetricians and Gynecologists and the American Diabetes Association. The associations of hypertension, as defined by the latter criteria, with perinatal complications were also studied. METHODS: The records of a cohort of 1007 consecutive patients with Type 1 diabetes with a singleton live childbirth during 1989-2010 at the Helsinki University Central Hospital were studied. RESULTS: The frequencies of hypertensive pregnancy complications did not change, but the mean diastolic blood pressure increased in normotensive parturients in all trimesters. The proportion of patients with systolic blood pressure > 130 mmHg or diastolic blood pressure > 80 mmHg in the first, second and third trimesters of pregnancy increased from 25 to 33%, from 26 to 35% and from 57 to 71%, respectively. Systolic blood pressure of 131-139 mmHg or diastolic blood pressure of 81-89 mmHg in the third trimester was associated with umbilical artery pH < 7.15. CONCLUSIONS: Blood pressure of patients with Type 1 diabetes during pregnancy is increasing. A growing proportion of women with Type 1 diabetes exceed the American Diabetes Association's definition of hypertension during pregnancy.

Trends in maternal BMI, glycaemic control and perinatal outcome among type 1 diabetic pregnant women in 1989-2008.

AIMS/HYPOTHESIS: Our objective was to examine the trends in prepregnancy BMI and glycaemic control among Finnish type 1 diabetic patients and their relation to delivery mode and perinatal outcome. METHODS: We analysed the obstetric records of 881 type 1 diabetic women with a singleton childbirth during 1989-2008. Maternal prepregnancy weight and height were obtained from the maternity cards, where they are recorded as reported by the mother. RESULTS: Maternal BMI increased significantly during 1989-2008 (p < 0.001). The mean HbA(1c) in the first trimester remained unchanged, but the midpregnancy and the last HbA(1c) before delivery increased (p = 0.009 and 0.005, respectively). Elective Caesarean sections (CS) decreased (p for trend <0.001), while emergency CS increased (p for trend <0.001). The mean umbilical artery (UA) pH decreased in vaginal deliveries (p for trend <0.001). The frequency of UA pH <7.15 and <7.05 increased (p for trend <0.001 and 0.008, respectively). The macrosomia rate remained at 32-40%. Neonatal intensive care unit (NICU) admissions increased (p for trend 0.03) and neonatal hypoglycaemia frequency decreased (p for trend 0.001). In multiple logistic regression analysis, maternal BMI was associated with macrosomia and NICU admission. The last HbA(1c) value before delivery was associated with delivery before 37 weeks' gestation, UA pH <7.15, 1 min Apgar score <7, macrosomia, NICU admission and neonatal hypoglycaemia. CONCLUSIONS/INTERPRETATION: Self-reported pregestational BMI has increased and glycaemic control during the second half of pregnancy has deteriorated. Poor glycaemic control seems to be associated with the observed increases in adverse obstetric and perinatal outcomes.

Prediction of placental abruption by testing for C-reactive protein and chlamydial antibody levels in early pregnancy.

OBJECTIVE: Placental abruption may be a manifestation of acute and chronic inflammatory process. We wanted to assess the association of first-trimester serum C-reactive protein (CRP), Chlamydia pneumoniae antibodies, Chlamydia trachomatis antibodies or chlamydial heat-shock protein 60 (CHSP60) antibodies to placental abruption. DESIGN: Retrospective case-control study. SETTING: University Hospital. POPULATION: A total of 181 women with subsequent placental abruption and 261 control women with normal pregnancy. METHODS: Serum samples collected at first trimester (mean 10.4 gestational weeks) were analysed for CRP levels, C. pneumoniae-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies and C. trachomatis-specific IgG, IgA and CHSP60 antibodies. MAIN OUTCOME MEASURE: Placental abruption. RESULTS: The levels of CRP showed no difference between the cases and the controls (median 2.35 mg/l [interquartile range {IQR} 1.09-5.93] versus 2.28 mg/l [IQR 0.92-5.01], not significant). C. pneumoniae-specific IgG and IgA as well as C. trachomatis-specific IgG, IgA and CHSP60 antibody frequencies were similar between the groups. There was no association between CRP levels and chlamydial antibodies. CONCLUSION: These markers of inflammation in early pregnancy failed to predict subsequent placental abruption.

Hyperinsulinemia and macrosomia in the fetus of the diabetic mother.

OBJECTIVE: To determine 1) whether macrosomia in the fetus of the diabetic mother is related to fetal hyperinsulinemia and 2) whether hyperinsulinemia and macrosomia are related to maternal metabolic control. RESEARCH DESIGN AND METHODS: Normal pregnant women (n = 95) were compared with insulin-treated pregnant women (n = 155), who were subdivided according to White's class, hypertension, and mode of delivery. All women were treated to achieve optimal metabolic control. HbA1c was determined at each visit. At delivery, umbilical plasma was analyzed for glucose, insulin antibodies, total insulin, free insulin, C-peptide, proinsulin components, and total and individual amino acids. RESULTS: Macrosomia, defined as > 2 standard deviation units (97.75%), was found in 10-27% of the diabetic groups. It was not related to maternal mass or size, but was significantly correlated with umbilical total insulin, free insulin, and C-peptide. Proinsulin components were not different among groups. Amino acids also were not different. Glycosylated hemoglobin was a weak predictor of birth weight and fetal hyperinsulinism. CONCLUSIONS: Macrosomia in the fetus of the diabetic mother remains inadequately explained. In a large population of pregnant women with strict metabolic control, macrosomia was mainly independent of glycosylated hemoglobin. Nevertheless, fetal hyperinsulinism remains the driving force for excessive fetal growth. The stimulus for fetal insulin excess in humans remains to be defined.

Objectively measured perinatal exposure to meperidine and benzodiazepines in Finland.

We measured concentrations of meperidine and benzodiazepines in the umbilical serum of all live neonates born in Finland during a single week. Of the neonates, 31.1% were exposed to meperidine or benzodiazepines or both. One hundred twenty-one mothers of the 261 neonates exposed to meperidine were not recorded in the Finnish Medical Birth Registry as having received analgesic drugs. Infants born to primiparous mothers were more likely to be exposed. The exposures were associated with the type of delivery: vacuum extraction with a high proportion of neonates exposed to meperidine and elective caesarean section with a high proportion of neonates exposed to benzodiazepines. The exposures were influenced by the method of obstetric analgesia: epidural blockade was associated with more frequent exposure to meperidine. No significant circadian variation in exposures was detected. Validation of birth registry data is imperative before they are used for pharmacoepidemiologic studies.

Pregnancy and birth in women with epilepsy.

The literature pertinent to obstetric aspects of the pregnancies in women with epilepsy is reviewed. The small risk (1%) of malformations of fetal central nervous system attributed to the use of carbamazepine or valproate during pregnancy should not discourage women who take these drugs from having children since these malformations can be reliably diagnosed (as well as excluded) during the 15th to 19th weeks of pregnancy with alpha-fetoprotein determinations and high-resolution ultrasound scans. Except for the 1.2- to 3-fold increase in perinatal mortality, the course of pregnancy and labor in women with epilepsy is usually uneventful. Most can have a normal vaginal delivery. Cesarean section is warranted only in a select minority of the difficult cases. Counseling, follow-up, and treatment of pregnant women with epilepsy should be provided at centers with the experience and resources to attend to the very specific problems that sometimes develop.

Outcome of children after maternal primary Toxoplasma infection during pregnancy with emphasis on avidity of specific IgG. The Study Group.

Congenital toxoplasmosis results from maternal primary infection during pregnancy. In our serologic screening study 42 of 16,733 pregnant women had findings suggestive of primary infection. Here we document the outcome of their offspring, 37 of 39 liveborn children. After 12 months postnatally, serologically verified congenital toxoplasmosis appeared in 4 children. All these children had persisting IgG at the age of 12 months by both the dye test and the IgG enzyme-linked immunosorbent assay. All the congenitally infected infants had also specific IgM and IgA and showed significant increases in avidity of specific IgG during the 12-month follow-up. One of them had a unilateral retinal scar and intracranial calcifications. An additional 3 infants of the mothers with primary infection during early pregnancy presented with unilateral retinal scars but without seroresponses during the first 12 months of life. Maternal high avidity of IgG during the first trimester is a strong indicator against primary infection during pregnancy; the fetuses of such mothers are at low risk for congenital toxoplasmosis.

Predicting delivery date by ultrasound and last menstrual period in early gestation.

OBJECTIVE: To compare last menstrual period and ultrasonography in predicting delivery date. METHODS: We used ultrasound to scan 17,221 nonselected singleton pregnancies at 8-16 completed weeks. The last menstrual period (LMP) was considered certain in 13,541 and uncertain in 3680 cases. The duration of pregnancy from the scan to the day of spontaneous delivery was predicted by crown-rump length, biparietal diameter (BPD), and femur length (FL) using linear regression models, and the results were compared with estimates based on LMP. RESULTS: At all gestational ages, ultrasound was superior to certain LMP in predicting the day of delivery by at least 1.7 days. When deliveries before 37 weeks were excluded, crown-rump length measurement of 15-60 mm (corresponding to 8-12.5 weeks) had the lowest prediction error of 7.3 days. After that time, BPD (at least 21 mm) showed a similar error (7.3 days) and was more precise than crown-rump length. Femur length was slightly less accurate than crown-rump length or BPD. Regression models using a combination of any two or three ultrasonic variables did not improve accuracy of prediction. When ultrasound was used instead of certain LMP, the number of postterm pregnancies decreased from 10.3% to 2.7% (P <.001). CONCLUSION: Ultrasound was more accurate than LMP in dating, and when it was used the number of postterm pregnancies decreased. Crown-rump length of 15-60 mm was superior to BPD, but then BPD (at least 21 mm) was more precise. Combining more than one ultrasonic measurements did not improve dating accuracy.

Sonographic measurement of uterine cervix at 18-22 weeks' gestation and the risk of preterm delivery.

OBJECTIVE: Premature delivery is difficult to predict and causes considerable neonatal morbidity and mortality. Despite much research, little progress has been made in timely identification of the mothers at risk. We examined the uterine cervix with ultrasonography to discover whether such a procedure would be helpful in determining which women will deliver prematurely. METHODS: We performed transvaginal ultrasound examinations in addition to routine transabdominal ultrasonography at 18 to 22 weeks' gestation in 3694 consecutive pregnant women with live singleton fetuses. We measured the length of the uterine cervix and evaluated the dilatation, if any, of the internal os. The results of cervical ultrasonography were not available to the clinicians. RESULTS: Spontaneous delivery occurred before 37 completed weeks in 88 women (2.4%) and before 35 weeks in 31 (0.8%). The relative risk of delivery before 35 weeks was 8 (95% confidence interval 3, 19) when the cervical length was 29 mm or shorter. When dilatation of the internal cervical os of 5 mm or greater was present, the relative risk of delivery before 35 weeks was 28 (95% confidence interval 12, 67). Either short cervix (29 mm or less) or dilatation of internal cervical os (5 mm or greater) was present in 3.6% of the population; this combination had a sensitivity of 29% in predicting delivery at earlier than 35 weeks. After adjusting for cervical dilatation and length by using multiple logistic regression, nulliparity also remained a risk factor for delivery before 35 weeks (odds ratio 3.6, 95% confidence interval 1.7, 7.5). CONCLUSION: Transvaginal ultrasonography performed as an addition to routine transabdominal ultrasonography at 18 to 22 weeks helps to identify many patients at significant risk for prematurity; however, low sensitivity and low positive predictive value limit its usefulness in screening low-risk obstetric populations.

Diagnosis of placenta previa by transvaginal sonographic screening at 12-16 weeks in a nonselected population.

OBJECTIVE: To evaluate the clinical significance of placenta previa at 12-16 weeks' gestation found by transvaginal sonographic screening. METHODS: An unselected population of 6428 pregnant women was scanned by transvaginal sonography during 1993-1994 to assess the gestational age and to diagnose major fetal anomalies. The location of the placenta was also recorded systematically. If the edge of the placenta extended over the internal cervical os, this distance was measured with electronic calipers. RESULTS: In 156 of 6428 patients (2.4%), the placental edge extended 15 mm or more over the internal cervical os at 12-16 weeks' gestation. Eight of these patients had placenta previa at delivery. Using this criterion at screening, two cases of placenta previa at delivery were missed. The frequency of placenta previa at delivery in this nonselected population was ten of 6428 (0.16%). CONCLUSIONS: The likelihood of placenta previa at delivery is 5.1% (95% confidence interval 2.2, 9.9) if the placenta extends at least 15 mm over the internal cervical os at 12-16 weeks' gestation.

Depression and anxiety in early pregnancy and risk for preeclampsia.

OBJECTIVE: To examine whether depression and anxiety in early pregnancy are associated with preeclampsia in an unselected nulliparous population. METHODS: In this prospective population-based study during pregnancy at outpatient maternity clinics in the Helsinki metropolitan area, depression was assessed by a Finnish modification of the short form of the Beck Depression Inventory and anxiety by one established question. Preeclampsia was defined as elevated blood pressure (BP) (more than 140/100 mmHg) and proteinuria (0.3 g during 24 hours or more). Age, smoking, alcohol consumption, marital status, socioeconomic status, and bacterial vaginosis were analyzed as potentially confounding factors in a multiple logistic regression analysis. RESULTS: Six hundred twenty-three consecutive nulliparous women with singleton pregnancies were studied at ten to 17 (median 12) weeks' gestation and at delivery. Of them, 28 (4.5%) women developed preeclampsia. Depression (mean Beck score 4.5, range 3-17) was observed in 185 (30%), women and anxiety was observed in 99 (16%) in early pregnancy. In multivariate analysis, after adjustment for potentially confounding factors, depression was associated with increased risk (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.1, 5.4) for preeclampsia, as was anxiety (OR 3.2; 95% CI 1.4, 7.4). Either depression or anxiety, or both, were associated with increased risk (OR 3.1; 95% CI 1.4, 6.9) for preeclampsia. Bacterial vaginosis together with depression was associated with increased risk (OR 5.3; 95% CI 1.8, 15.0) for preeclampsia. CONCLUSION: Depression and anxiety in early pregnancy are associated with risk for subsequent preeclampsia, a risk further increased by bacterial vaginosis.

Phosphorylated isoforms of insulin-like growth factor binding protein-1 in the cervix as a predictor of cervical ripeness.

OBJECTIVE: To study the isoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in cervical secretion and to evaluate whether their assessment could serve in prediction of cervical ripeness at term. METHODS: We measured the concentrations of IGFBP-1 in cervical swab samples of 64 women scheduled for labor induction by amniotomy or cervical ripening with prostaglandin E2 gel. Two immunoenzymometric assays were used: a previously described assay 1, which detects the nonphosphorylated and lesser phosphorylated isoforms, and a novel assay 2, which detects the lesser and highly phosphorylated isoforms of IGFBP-1. A set of 39 amniotic fluid (AF) samples also was analyzed to compare the phosphorylation status of IGFBP-1 in cervical secretion with that in AF. RESULTS: In all cervical samples, IGFBP-1 concentration was higher by assay 2 than by assay 1, whereas in all AF samples, the results were the opposite. Initially, the median IGFBP-1 concentration in the ripe cervices (Bishop scores 6 or greater; n = 29) was approximately four times as high as that in the unripe cervices (Bishop scores 5 or less; n = 35). The cervical IGFBP-1 concentrations increased eight-fold in 6 hours after the first application of PGE2. CONCLUSION: Phosphorylated isoforms of IGFBP-1, different from those in AF, are present in the cervical secretion of women with intact fetal membranes and reflect cervical ripeness. A bedside test for those IGFBP-1 isoforms might help in predicting amenability for labor induction.

Head circumference in children of epileptic mothers: contributions of drug exposure and genetic background.

Head circumference after the first year of life was investigated in 144 children of epileptic mothers ('study group'). Fifty-two children had been exposed to phenytoin monotherapy, 19 to carbamazepine monotherapy, 27 to drug combinations including barbiturates, 29 to other drug combinations, and 17 children had not been exposed to antiepileptic drugs (AEDs) during pregnancy. The prevalence of microcephaly (2.1%) was no higher than that in the general population. Head circumference was measured at 5.5 years in 121 of the study group children, in 105 control children, and in the majority of their parents (118 mothers and 89 fathers in the study group, and 103 mothers and 65 fathers in the control group). The sex-adjusted head circumferences of the children showed a significant variation according to exposure subgroup, with the barbiturate and carbamazepine monotherapy exposed children having the lowest mean values. This result is similar to our previous findings in the same children at birth and at 18 months of age. Paternal head circumference was also below average in the same subgroups. After further adjustment for parental head circumference, the significant variation between the subgroups of children disappeared, even though the barbiturate exposed children continued to have the lowest mean value. Genetic causes may thus contribute to the relatively small head circumference in some AED exposed children of epileptic mothers. However, a mild drug effect in the barbiturate and carbamazepine exposed children cannot be excluded.

Maternal antihypertensive therapy with beta-blockers associated with poor outcome in very-low birthweight infants.

The progress of 36 very-low birthweight (less than or equal to 1500 g) infants born to mothers with pregnancy-induced hypertonia or pre-eclampsia was studied. During the first year of life, 7 out of 19 infants died when the mothers' antihypertensive regimen included beta-blockers. Four of the deaths occurred within 15 days. There were no deaths in 16 infants whose mothers were treated with other antihypertensive treatment (P = 0.006). These results suggest that maternal beta-blocker therapy may have adverse effects on the very-low birthweight infants.