Sujata Chandra

Unexplained elevated maternal serum α-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes

OBJECTIVE The study was undertaken to determine the risks of adverse obstetric outcomes in pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) and/or human chorionic gonadotropin (hCG) and to determine whether these risks vary by prepregnancy risk status. STUDY DESIGN All women who underwent double-marker screening (MSAFP+hCG) between 1994 and 2000 and were delivered of an infant in Nova Scotia, Canada, during this period were identified from a hospital serum screening database and a provincial perinatal database. Patients with inaccurate dating, major structural anomalies, or chromosomal abnormalities were excluded. The primary outcomes studied were preeclampsia, abruptio placentae, fetal growth restriction, fetal death, and preterm birth. Women with medical or previous obstetric complications were designated high risk. Logistic regression, controlling for confounding factors, was used to estimate the relative risks (RRs) and 95% CI for elevated levels of MSAFP and/or hCG and each of the outcomes. RESULTS Among the 14,374 women who met the study criteria, 5,789 were designated high risk. Except for abruptio placentae, unexplained elevated MSAFP or elevated hCG levels were independently associated with all the outcomes in both high- and low-risk women. Elevated screening values were associated with increased risk of abruptio placentae among low-risk women only. Particularly large RRs were seen for fetal death in both high- and low-risk women (RR=4.9, 95% CI 2.7-8.7 for elevated MSAFP or hCG in high- and low-risk women combined). CONCLUSION Unexplained elevated levels of MSAFP and/or hCG are associated with an increased risk of most pregnancy complications. Increased antenatal surveillance of these patients is important regardless of prepregnancy risk status.

Relationship between interpregnancy interval and congenital anomalies

OBJECTIVE To assess the association between interpregnancy intervals and congenital anomalies. STUDY DESIGN A retrospective cohort study on women who had 2 consecutive singleton births from 1999-2007 was conducted using a linked dataset from the Alberta Perinatal Health Program, the Alberta Congenital Anomalies Surveillance System, and the Alberta Health and Wellness Database. Interpregnancy interval was calculated as the interval between 2 consecutive deliveries minus the gestational age of the second infant. The primary outcome of congenital anomaly was defined using the International Classification of Diseases. Maternal demographic and obstetric characteristics and interpregnancy intervals were included in multivariable logistic regression models for congenital anomalies. RESULTS The study included 46,243 women, and the overall rate of congenital anomalies was 2.2%. Both short and long interpregnancy intervals were associated with congenital anomalies. The lowest rate was for the 12-17 months category (1.9%, reference category), and increased rates were seen for both short intervals (2.5% for 0-5 months; adjusted odds ratio, 1.32; 95% confidence interval, 1.01-1.72) and long intervals (2.3% for 24-35 months; adjusted odds ratio, 1.25; 95% confidence interval, 1.02-1.52). Statistically significant associations were also observed for folate independent anomalies, but not for folate dependent anomalies. CONCLUSION The risk of congenital anomalies appears to increase with both short and long interpregnancy intervals. This study supports the limited existing studies in the literature, further explores the types of anomalies affected, and has implications for further research and prenatal risk assessment.

Relationship Between Interpregnancy Interval and Adverse Perinatal and Neonatal Outcomes in Northern Alberta

BACKGROUND Birth outcomes are known to be associated with birth spacing, but there are population differences. The purpose of this study was to examine the association between interpregnancy intervals and perinatal and neonatal outcomes in a Canadian population during the era of mandatory folate fortification of food. METHODS We conducted a study of 46 243 women who had two consecutive singleton births in northern Alberta between 1999 and 2007, using a linked provincial dataset. Perinatal outcomes of interest were preterm birth, low birth weight (LBW), small for gestational age, and perinatal death. Neonatal outcomes were low Apgar score, low arterial blood gas pH, need for neonatal resuscitation or admission to NICU, and neonatal death. Multivariable logistic regression was used to control for maternal demographic and obstetrical characteristics. RESULTS The risk of preterm birth was increased for multiple interpregnancy intervals: for an interval of 0 to 5 months, the adjusted odds ratio (aOR) was 1.37 (95% CI 1.18 to 1.59), for 6 to 11 months the aOR was 1.18 (95% CI 1.04 to 1.34), for 24 to 35 months the aOR was 1.16 (95% CI 1.02 to 1.31), and for 36+ months the aOR was 1.36 (95% CI 1.20 to 1.53), compared with the reference interval of 12 to 17 months. The risk of LBW was increased with interpregnancy intervals of 0 to 5 months (aOR 1.48; 95% CI 1.23 to 1.80), 6 to 11 months (aOR 1.21; 95% CI 1.03 to 1.42), 24 to 35 months (aOR 1.21; 95% CI 1.03 to 1.41) and 36+ months (aOR 1.48; 95% CI 1.27 to 1.73). The risk of SGA was increased with intervals 0 to 5 months (aOR 1.29; 95% CI 1.09 to 1.52), 24 to 35 months (aOR 1.15; 95% CI 1.01 to 1.31), and 36+ months (aOR 1.26; 95% CI 1.11 to 1.44). The risk of perinatal death was increased with an interval of 36+ months (aOR 1.60; 95% CI 1.06 to 2.43). Similar associations were also observed for neonatal outcomes. CONCLUSION This study suggests that both short and long interpregnancy intervals are associated with adverse perinatal and neonatal outcomes, and it provides risk estimates for a Canadian population in the era of folate fortification of food.

Transvaginal ultrasonography to predict preterm birth in women with bicornuate or didelphus uterus

Objective: To estimate whether cervical length measured by transvaginal ultrasonography (TVUS) in women with uterine anomalies predicts spontaneous preterm birth (SPTB). Methods: This retrospective cohort study compared women with a uterine anomaly who were pregnant with singleton gestations and delivered August 2000 to April 2008 to a low risk control group. Transvaginal ultrasonographic cervical lengths were measured 16–30 weeks gestation. Primary outcome was cervical length and SPTB less than 35 weeks and the primary exposure variable of interest was cervical length. Secondary outcomes were SPTB less than 37 weeks, less than 32 weeks, low birth weight, maternal and neonatal outcomes. Receiver operating characteristic curves were generated to identify the best cervical length cutoff. Results: Women with a bicornuate uterus (N = 35) had shorter cervical length (3.46 cm) than the low risk control group (N = 122, 4.32 cm, p < 0.0001). Women with a bicornuate or didelphus uterus, compared with low risk women, had higher rates of SPTB less than 35 weeks (8.6% and 30.8% versus 0.8%, p = 0.0007), neonatal intensive care unit admission more than 24 h (26.5% and 41.7% versus 7.5%, p = 0.0021) and composite perinatal morbidity (32.4% and 69.2% versus 8.3%, p < 0.0001). Using a cutoff of 3.0 cm, TVUS cervical length in women with a bicornuate uterus predicted SPTB less than 35 weeks (positive predictive value [PPV] = 37.5% and negative predictive value [NPV] = 100%), birth weight less than 2500 g (PPV = 50.0% and NPV = 96.3%) and respiratory distress syndrome (PPV = 37.5% and NPV = 100%). Conclusion Women with a bicornuate uterus have shorter cervical lengths than low risk controls, and are at higher risk of SPTB less than 35 weeks. Transvaginal ultrasonographic cervical length predicts SPTB less than 35 weeks, low birth weight and perinatal morbidity in these women.

A Case of Alloimmune Thrombocytopenia, Hemorrhagic Anemia-Induced Fetal Hydrops, Maternal Mirror Syndrome, and Human Chorionic Gonadotropin–Induced Thyrotoxicosis

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin–induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.