Prevalence and outcomes of twin pregnancies in Botswana: a national birth outcomes surveillance study

ObjectivesThis study aims to evaluate the prevalence and outcome of twin pregnancies in Botswana.SettingThe Tsepamo Study conducted birth outcomes surveillance at 8 government-run hospitals (~45% of all births in Botswana) from August 2014 to June 2018 and expanded to 18 hospitals (~70% of all births in Botswana) from July 2018 to March 2019.ParticipantsData were collected for all live-born and stillborn in-hospital deliveries with a gestational age (GA) greater than 24 weeks. This analysis included 117 593 singleton and 3718 twin infants (1859 sets (1.6%)) born to 119 477 women between August 2014 and March 2019 and excluded 73 higher order multiples (23 sets of triplets and 1 set of quadruplets).Outcomes measuredOur primary outcomes were preterm delivery (<37 weeks GA), very preterm delivery (<32 weeks GA) and stillbirth (APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of 0, 0, 0).ResultsWomen with twin pregnancies had a similar median number of antenatal care visits (9 vs 10), but were more likely to deliver in a tertiary centre (54.8% vs 45.1%, p<0.001) and more likely to have a cesarean-section (54.6% vs 22.0%, p<0.001) than women with singletons. Compared with singletons, twin pregnancies had a higher risk of preterm delivery (<37 weeks GA) (47.6% vs 16.7%, adjusted risk ratio (aRR) 2.8, 95% CI 2.7 to 2.9) and very preterm delivery (<32 weeks) (11.8% vs 4.0%, aRR 3.0 95% CI 2.6 to 3.4). Among all twin pregnancies, 128 (6.9%) had at least one stillborn infant compared with 2845 (2.4%) stillbirths among singletons (aRR 2.8, 95% CI 2.3 to 3.3).ConclusionAdverse birth outcomes are common among twins in Botswana, and are often severe. Interventions that allow for earlier identification of twin gestation and improved antenatal management of twin pregnancies may improve infant and child survival.

Congenital CMV Infection Presenting with Massive Intracerebral Hemorrhage

Cytomegalovirus (CMV) is among the most common of intrauterine infections against which we have no effective preventative or therapeutic options. The developing nervous system is a frequent target of CMV and while most injuries are subclinical, severe insults leading to microcephaly and migration defects are well known. A 20-week gestational age fetus was found to have several abnormalities on prenatal ultrasound, the most prominent of which was a large echogenic focus in one cerebral hemisphere. Congenital CMV infection was identified by amniocentesis and maternal serology. The pregnancy was ended by early induction of labour for a 368g stillborn infant. Postmortem examination revealed massive intracerebral hemorrhage as the correlate for the sonographic finding. The microscopic examination of the brain was also striking for extensive polymicrogyria, a high burden of CMV and abundant angiocentric CMV pathology. Catastrophic intracerebral hemorrhage has not been previously reported in association with congenital CMV infection. The present case expands the range of potential injuries the developing brain is subject to in the setting of CMV infection and raises the possibility of a direct vascular injury.Learning ObjectivesConsider intracerebral hemorrhage in the range of potential outcomes in congenital CMV infectionDescribe how polymicrogyria may result from an insult during proliferation and migrationDiscuss possible mechanisms of injury to the developing brain by CMV

Congenital Malformation Risk According to Hemoglobin A1c Values in a Contemporary Cohort with Pregestational Diabetes

Objective The study aimed to evaluate the association between hemoglobin A1c values and likelihood of fetal anomalies in women with pregestational diabetes. Study Design Women with pregestational diabetes who delivered at a single institution that serves a nonreferred population from May 1, 2009 to December 31, 2018 were ascertained. Hemoglobin A1c values were obtained at the first prenatal visit. Women who delivered a singleton live- or stillborn infant with a major malformation as defined by European Surveillance of Congenital Anomalies criteria were identified. In infants with multiple system anomalies, each malformation was considered separately. Hemoglobin A1c values were analyzed categorically by using Mantel–Haenszel method and continuously with linear regression for trend for fetal anomalies. Results A total of 1,676 deliveries to women with pregestational diabetes were delivered at our institution, and hemoglobin A1c was assessed in 1,573 deliveries (94%). There were 129 deliveries of an infant with at least one major malformation, an overall anomaly rate of approximately 8%. Mean hemoglobin A1c concentration was significantly higher in pregnancies with anomalous infants, 9.3 ± 2.1% versus 8.0 ± 2.1%, and p <0.001. There was no difference in gestational age at the time hemoglobin A1c was obtained, 13 ± 8.3 versus 14 ± 8.7 weeks. Hemoglobin A1c was associated with increased probability of a congenital malformation. This reached 10% with a hemoglobin A1c concentration of 10%, and 20% with a hemoglobin A1c of 13%. Similar trends were seen when examining risk of anomalies by organ system with increasing hemoglobin A1c levels, with the greatest increase in probability for both cardiac and genitourinary anomalies. Conclusion In women with pregestational diabetes, hemoglobin A1c is strongly associated with fetal anomaly risk. Data from a contemporary cohort may facilitate counseling and also highlight the need for preconceptual care and glycemic optimization prior to entry to obstetric care. Key Points

Number of Risk Factors in Down Syndrome Pregnancies

Objective The objective of this study was to evaluate risk factor prevalence in pregnancies with fetal Down syndrome, in an effort to characterize efficacy of population-based screening. Study Design Retrospective review of singleton pregnancies with delivery of live born or stillborn infant with Down syndrome from 2009 through 2015. Risk factor categories included maternal age ≥35 years, abnormal serum screening, identification of ≥1 ultrasound marker at 16 to 22 weeks (nuchal thickness ≥6 mm, echogenic intracardiac focus, echogenic bowel, renal pelvis dilatation, femur length <third percentile), and detection of a major fetal anomaly. Statistical analyses included χ2 test and Mantel–Haenszel χ2 test. Results Down syndrome infants represented 1:428 singleton births. All risk categories were assessed in 125 pregnancies and included abnormal serum screen in 110 (88%), ≥1 ultrasound marker in 66 (53%), and ≥1 anomaly in 41 (34%). The calculated risk was at least 1:270 in 93% of Down syndrome pregnancies. More pregnancies had multiple risk factors than had a single risk factor, 90 (72%) versus 30 (24%), p < 0.001. An abnormal ultrasound marker or anomaly was identified in >50% of fetuses in women <35 years and in >75% of those 35 years and older. Conclusion In a population-based cohort, sensitivity of second-trimester Down syndrome screening was 93%, with multiple risk factors present in nearly three-fourths of cases.

Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark

Objective:We examined the causes of death amongst full term stillbirths and early neonatal deaths.Methods:Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE).Results:A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20–34 years and with a normal body mass index (BMI).Conclusion:Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

In a Genomic Era, Placental Pathology Still Holds the Key in the Nondysmorphic Stillbirth

Objective To explore the relative utility of genetic testing in contrast to placental pathology in explaining causation of death in the structurally normal stillborn population. Methods A retrospective review of a structurally normal stillborn infant cohort in South East Scotland between 2011 and 2015, defined by death at or after 24 weeks of gestation. We reviewed pathology reports and collected demographic data on cases. This information was collated with genetic test results (quantitative fluorescent polymerase chain reaction and microarray analysis) and placental pathology to create a database for analysis. Primary Results Within the structurally normal population (n = 131), there were 125 genetic tests performed and 11 abnormal results. Sixty-six microarray analyses were performed, and 2 (3%) of the results were thought likely to reflect cause of stillbirth (1 case of incomplete trisomy 4 and 1 case of deletion of chromosome Xp in a female). Analysis was significantly limited in 2 cases as parental samples were not available. The placental pathology was available in a total of 129 cases; significant findings were identified in 100 cases; 79 (61%) showed changes that were considered to have caused death (including cord “accidents”), and a further 21 (16%) showed findings likely to influence the management of subsequent pregnancies. Conclusions We reaffirm the utility of placental examination in the investigation of stillbirth. In cases of nondysmorphic stillbirth where placental pathology does not explain the cause of stillbirth, microarray analysis of fetal DNA can add further diagnostic information in 3% of cases but can add further diagnostic confusion, and it is important that parental bloods are taken to minimize this risk.