Congenital anomaly rate in offspring of mothers with diabetes treated with insulin lispro during pregnancy.

AIM: To determine the rate of major congenital anomalies in offspring of a large group of women with diabetes mellitus treated with insulin lispro (Humalog). METHODS: This multinational, multicentre, retrospective study included mothers with diabetes mellitus (diagnosed prior to conception) who were treated with insulin lispro for at least 1 month before conception and during at least the first trimester of pregnancy. Anomalies were assessed by two independent dysmorphologists not affiliated with the sponsor. RESULTS: The charts of 496 women were reviewed for 533 pregnancies resulting in 542 offspring (500 live births, 31 spontaneous and seven elective abortions, and four stillbirths). Mothers' characteristics: mean (+/- SD) age was 29.9 (+/- 5.2) years, 85.6% were Caucasian and 97.2% had Type 1 diabetes mellitus. Insulin lispro continued to be the main mealtime insulin for more than 96% of the women during the second and third trimester. The dysmorphologists determined that 27 (5.4%) offspring had major congenital anomalies and 2 (0.4%) offspring had minor congenital anomalies. CONCLUSIONS: The rate of major congenital anomalies was 5.4% [95% CI (3.45%, 7.44%)] for offspring of mothers with diabetes mellitus treated with insulin lispro before and during pregnancy. The current published rates of major anomalies in infants born to mothers with diabetes treated with insulin are between 2.1 and 10.9%. This suggests that the anomaly rate with insulin lispro treatment does not differ from the published major congenital anomaly rates for other insulin treatments.

Placenta percreta and uterine rupture associated with prior whole body radiation therapy.

BACKGROUND: Injury to reproductive organs including the uterus is a known complication of ionizing radiation, but the risks to the mother and fetus during subsequent pregnancies are not well defined. CASE: A young woman with a remote history of whole body irradiation for childhood leukemia had uterine rupture at 17 weeks' gestation. Pathologic examination of the supracervical hysterectomy specimen revealed a posterior-fundal placenta percreta with a diffusely thinned myometrium (1-6 mm). The clinicopathologic findings were consistent with prior radiation injury. CONCLUSION: Uterine irradiation may predispose to abnormal placentation and uterine rupture in a subsequent pregnancy.

Relationship of twin zygosity and risk of preeclampsia.

OBJECTIVE: Twin gestations are known to be at higher risk for preeclampsia. One theory suggests that maternal recognition of fetal and trophoblastic tissues as foreign may be a factor. If that hypothesis is true, mothers carrying monozygous (MZ) gestations (ie a single fetal graft) might be predicted to have a lower rate of preeclampsia than those carrying dizygous (DZ) gestations. To evaluate this hypothesis, we compared the rate of preeclampsia in mothers with MZ and DZ twin gestations. STUDY DESIGN: Seven hundred sixty-eight twin deliveries from 1994 to 1999 were reviewed. Placental pathology reports were reviewed to determine the chorionic state of each placenta. Monochorionic placentas were assumed to be MZ. Dichorionic placentas were categorized as DZ if the neonates were of different sexes or different blood types. Maternal and fetal data were abstracted from the medical records. Preeclampsia was defined by standard criteria of the National Institutes of Health Working Group on High Blood Pressure. Our analysis was limited to women with pregnancies reaching at least 30 weeks of gestation where zygosity could be determined. RESULTS: Our analysis included 464 twin pregnancies, 154 MZ and 310 DZ. Among nulliparous women, the rate of preeclampsia was 15% (25/170) for DZ twins versus 20% (15/75) for MZ twins (P =.3). Among multiparous women, the rate was 8% (11/140) for DZ twins and 5% (4/79) for MZ twins (P =.4). In a logistic regression performed to control for confounding by maternal age, gestational age at delivery, assisted reproduction, and male sex, dizygotic state was associated with an odds ratio of 1.4 (95% CI = 0.5-3.9) for developing preeclampsia in nulliparous women and 1.2 in multiparous women (95% CI = 0.3-5.0). CONCLUSIONS: : These results do not support the hypothesis that zygosity affects the rate of preeclampsia in twin gestations, though the number of subjects in our study was too small to allow definitive conclusions. Larger studies are needed to evaluate this finding.

Resolution of fetal goiter after discontinuation of propylthiouracil in a pregnant woman with Graves' hyperthyroidism.

We report a case of Graves' hyperthyroidism in a 34-year-old pregnant woman treated with propylthiouracil (PTU) complicated by the development of a fetal goiter. Because of the fetal goiter and normal maternal thyroid function tests, the PTU was discontinued. Over the next 10 weeks, there was a progressive decrease in the fetal thyroid volume as documented by ultrasonography. The fetal neck returned to a normal flexed position, fetal growth and amniotic fluid remained normal, and the patient remained asymptomatic. A normal infant was delivered at term. This is the first report to demonstrate that noninvasive management may be appropriate for fetuses with goiter caused by antithyroid drug therapy.

Alternative methods of diagnosing gestational diabetes mellitus.

OBJECTIVE: In an attempt to find more efficacious alternatives for the diagnosis of gestational diabetes mellitus, we evaluated whether (1) there is a glucose loading test value above which all glucose tolerance test results are positive, (2) omission of the third-hour plasma glucose measurement of the glucose tolerance test alters the sensitivity of the test, and (3) the presence of a fasting plasma glucose concentration >/=105 mg/dL suffices as a diagnostic standard after an abnormal glucose loading test result. STUDY DESIGN: The charts of 512 patients who underwent 3-hour glucose tolerance tests at our institution between January 1995 and December 1996 were reviewed. Only subjects for whom the glucose loading test yielded plasma glucose levels >/=140 mg/dL were selected. The positive predictive value of a glucose loading test result >/=185 mg/dL was calculated. Results of glucose tolerance tests of subjects with elevated fasting plasma glucose concentrations were then evaluated to determine the positive predictive value for gestational diabetes mellitus of an elevated fasting plasma glucose concentration. RESULTS: Among the subjects who underwent glucose tolerance tests, 22% (114/512) met positive test criteria for gestational diabetes mellitus. The positive predictive value for a glucose loading test result >/=185 mg/dL was 57% (25/44), whereas a glucose loading test result >199 mg/dL showed a positive predictive value of 69% (4/13). Omission of the third-hour glucose tolerance test value yielded a sensitivity of 87% (99/114). Among the 24 women with fasting plasma glucose concentrations >/=105 mg/dL, 96% had positive glucose tolerance test results. An elevated fasting plasma glucose concentration was highly associated with gestational diabetes mellitus necessitating insulin therapy (65%). CONCLUSION: An elevated glucose loading test result was associated with but not highly predictive of gestational diabetes mellitus. Omission of the 3-hour glucose tolerance test measurement resulted in failure to diagnose 13% of gestational diabetes mellitus cases. A fasting plasma glucose concentration >/=105 mg/dL was highly predictive of an abnormal glucose tolerance test result among patients with an elevated glucose loading test value.