Laura Jelliffe-Pawlowski

Abstract

Implementation of dietary and lifestyle interventions prior to and early in pregnancy in high risk women has been shown to reduce the risk of gestational diabetes mellitus (GDM) development later in pregnancy. Although numerous risk factors for GDM have been identified, the ability to accurately identify women before or early in pregnancy who could benefit most from these interventions remains limited. As nulliparous women are an under-screened population with risk profiles that differ from their multiparous counterparts, development of a prediction model tailored to nulliparous women may facilitate timely preventive intervention and improve maternal and infant outcomes. We aimed to develop and validate a model for preconception and early pregnancy prediction of gestational diabetes mellitus based on clinical risk factors for nulliparous women. A risk prediction model was built within a large California birth cohort including singleton live birth records from 2007–2012. Model accuracy was assessed both internally and externally, within a cohort of women who delivered at University of Iowa Hospitals and Clinics between 2009–2017, using discrimination and calibration. Differences in predictive accuracy of the model were assessed within specific racial/ethnic groups. The prediction model included five risk factors: race/ethnicity, age at delivery, pre-pregnancy body mass index, family history of diabetes, and pre-existing hypertension. The area under the curve (AUC) for the California internal validation cohort was 0.732 (95% confidence interval (CI) 0.728, 0.735), and 0.710 (95% CI 0.672, 0.749) for the Iowa external validation cohort. The model performed particularly well in Hispanic (AUC 0.739) and Black women (AUC 0.719). Our findings suggest that estimation of a woman’s risk for GDM through model-based incorporation of risk factors accurately identifies those at high risk (i.e., predicted risk >6%) who could benefit from preventive intervention encouraging prompt incorporation of this tool into preconception and prenatal care.

Abstract

Few studies have examined the relationship between sexually transmitted infections (STIs) and preterm birth (<37 weeks gestation) by subtype (<32 weeks, 32-36 weeks, spontaneous, provider-initiated). Here, we evaluate the odds of preterm (by subtype) and early-term (37 and 38 weeks gestation) birth in women with an STI compared with a propensity score-matched reference population. Methods The sample was selected from California births in 2007 to 2012. Sexually transmitted infection was defined as a maternal diagnosis of chlamydia, gonorrhea, or syphilis in the birth certificate or hospital discharge record. A reference sample of women without an STI was selected using exact propensity score matching on maternal factors. Odds of preterm and early-term birth were calculated. Results Sixteen thousand three hundred twelve women were identified as having an STI during pregnancy and an exact propensity score-matched control was identified for 97.2% (n = 15,860). Women with an indication of syphilis during pregnancy were at 1.6 times higher odds of having a preterm birth and, in particular, at elevated odds of a birth less than 32 weeks due to preterm premature rupture of the membranes or provider-initiated birth (odds ratios 4.0-4.2). Women with gonorrhea were at increased odds of a preterm birth, a birth less than 32 weeks, or an early-term birth (odds ratios 1.2-1.8). Chlamydia did not raise the odds of either a preterm or early-term birth. Conclusions Gonorrhea and syphilis increased the odds of a preterm birth. Gonorrhea also increased the odds of an early-term birth. Chlamydia did not raise the odds of an early birth.

Abstract

Maternal lipid profiles are associated with risk for preterm birth (PTB), although the lipid component and effect size are inconsistent between studies. It is also unclear whether these associations are the result of excessive changes in lipid metabolism during pregnancy or genetic variability in genes controlling basal lipid metabolism. This study investigates the association between genetic risk scores (GRS) for four lipid components (high-density lipoprotein [HDL-C], low-density lipoprotein [LDL-C], triacylglycerols [TAG], and total cholesterol [TC]) with risk for PTB. Subjects included 954 pregnant women from California for whom second trimester serum samples were available, of which 479 gave birth preterm and 475 gave birth at term. We genotyped 96 single-nucleotide polymorphisms, which were selected from genome-wide association studies of lipid levels in adult populations. Lipid-specific GRS were constructed for HDL-C, LDL-C, TAG, and TC. The associations between GRS and PTB were analyzed using logistic regression. A higher HDL-C GRS was associated with increased risk for PTB overall and spontaneous PTB. Higher TAG and TC GRS were associated with decreased risk for PTB overall and spontaneous PTB. This study identifies counter-intuitive associations between lipid GRS and spontaneous PTB. Further replication studies are needed to confirm these findings, but they suggest that our current scientific understanding of the relationship between lipid metabolism, PTB, and genetics is incomplete.

Abstract

We examined the association between gastroschisis and preterm birth (PTB, <37 weeks) by subtype. The sample was drawn from singleton live births in California from 2007 to 2012 contained in a birth cohort file maintained by the California Office of Statewide Health Planning and Development (n = 2,891,965; 1,421 with gastroschisis). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for PTB by gestational age (<34, 34–36, and any <37 weeks) and by type (spontaneous labor with intact membranes, preterm premature rupture of the membranes [PPROM], provider initiated) and were adjusted for maternal characteristics. Over 44.5% of infants with gastroschisis were born preterm because of spontaneous etiologies; notably, 8.4% of infants with gastroschisis were born <34 weeks because of spontaneous etiologies (adjusted RRs 9.1–12.2). Overall, 53.7% of infants with gastroschisis were born preterm compared with only 6.9% of infants without gastroschisis (adjusted RR 15.2, 95% CI 13.6–19.5) and are at particularly high risk of spontaneous PTB. Nearly 9% of infants with gastroschisis delivered <34 weeks, regardless of preterm etiology, indicating that these infants are at great risk for PTB morbidities in addition to the complications from gastroschisis.

Abstract

Objective The objective of this study was to investigate the role of gestational hypertension (gHTN) and chronic hypertension (cHTN) on rates of preterm birth (PTB) among black women. Study Design Singleton live births between 20 and 44 weeks' gestation among black women in California from 2007 to 2012 were used for analysis. Risk of PTB by subtype and gestational age among women with cHTN or gHTN, including preeclampsia, was calculated via Poisson's logistic regression modeling. Risks were adjusted for maternal factors associated with increased risk of PTB. Results A total of 154,950 women met the inclusion criteria. Of the 5,948 women in the sample with cHTN, 26.2% delivered preterm; for the 11,728 women with gHTN, 21.6% delivered preterm. Women with gHTN or cHTN had a higher risk of medically indicated and spontaneous PTB, both at less than 32 and 32 to 36 weeks, when compared with nonhypertensive women (adjusted relative risks [aRRs]: 3.4-11.6). Women with superimposed preeclampsia had higher risks of spontaneous (aRR: 2.8, 95% confidence interval [CI]: 2.3-3.4) and medically indicated PTB (aRR: 2.8, 95% CI: 2.0-3.8), especially PTB < 32 weeks, when compared with women with preeclampsia. Conclusion Among black women, superimposed preeclampsia increased the risk for spontaneous and medically indicated PTB, especially PTB < 32 weeks.

Abstract

Background: Infants with critical congenital heart disease (CCHD) are more likely to be small for gestational age (SGA) or born to mothers with maternal placental syndrome. The objective of this study was to investigate the relationship between maternal placental syndrome, SGA, and gestational age (GA) on 1-year mortality in infants with CCHD. Methods and Results: In a population-based administrative database of all live-born infants in California (2007–2012) we identified all infants with CCHD without chromosomal anomalies. Our primary predictor was an impaired fetal environment (IFE), defined as presence of maternal placental syndrome or SGA. We calculated hazard ratios to quantify the association between different components of IFE and 1-year mortality and conducted a causal mediation analysis to assess GA at birth as a mediator. We identified 6863 infants with CCHD. IFE was present in 25.1%. Infants with IFE were more likely to die than infants without IFE (16.6% versus 11.1%; hazard ratios 1.55, 95% CI 1.34–1.78). Only SGA (hazard ratios 1.76, 95% CI 1.50–2.05) and placental abruption (hazard ratios 1.70, 95% CI 1.17–2.48) were significantly associated with mortality; preeclampsia and gestational hypertension had no significant association with mortality. The mediation analysis showed that 32.8% (95% CI 24.9–47.0%) of the relationship between IFE and mortality is mediated through GA. Conclusions: IFE is a significant contributor to outcomes in the CCHD population. SGA and placental abruption are the main drivers of postnatal mortality while other maternal placental syndrome components had much less of an impact. Only one third of the effect between IFE and mortality is mediated through GA.

Abstract

Objective: This study aims to describe adverse maternal and neonatal outcomes in women diagnosed with anemia in pregnancy. Study design: This was a retrospective cohort study of California live births from 2007–2012, linked to maternal and infant hospital discharge records. Relative risks of adverse maternal and neonatal outcomes were calculated for women with and without anemia. Results: Anemic mothers were more likely to be diagnosed with hypertension, diabetes, placental abruption, or chorioamnionitis, or require a blood transfusion or admission to the intensive care unit (aRRs 1.2–6.8). Infants born to anemic mothers were more likely to be born preterm (8.9% versus 6.5%), but not more likely to suffer morbidities associated with prematurity. Conclusion: In a population-based study, the diagnosis of anemia in pregnancy carries a higher risk of peri-partum, intra-partum, and post-partum complications for the mother, and a higher risk of preterm birth for the infant.

Abstract

Objective: Examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. Methods: The study population was drawn from singleton live births in California from 2007 to 2012 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes linked birth certificate and mother and infant hospital discharge records. The sample was restricted to infants delivered between 20 and 44 weeks gestation. Logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) for factors influencing late entry into prenatal care. Maternal age, education, smoking, drug or alcohol abuse/dependence, mental illness, participation in the Women, Infants and Children’s program and rural residence were evaluated for women entering prenatal care > sixth month of gestation compared with women entering < fourth month. Backwards stepwise logistic regression was used to create final multivariable models of risk and protective factors for late prenatal care entry for each race or ethnicity and insurance payer. Results: The sample included 2,963,888 women. The percent of women with late entry into prenatal care was consistently higher among women with public versus private insurance. Less than 1% of white non-Hispanic and Asian women with private insurance entered prenatal care late versus more than 4% of white non-Hispanic and black women with public insurance. After stratifying by race or ethnicity and insurance status, women less than 18 years of age were more likely to enter prenatal care late, with young Asian women with private insurance at the highest risk (15.6%; adjusted RR 7.4, 95%CI 5.3–10.5). Among all women with private insurance, > 12-year education or age >34 years at term reduced the likelihood of late prenatal care entry (adjusted RRs 0.5–0.7). Drugs and alcohol abuse/dependence and residing in a rural county were associated with increased risk of late prenatal care across all subgroups (adjusted RRs 1.3–3.8). Participation in the Women, Infants, and Children’s program was associated with decreased risk of late prenatal care for women with public insurance (adjusted RRs 0.6–0.7), but increased risk for women with private insurance (adjusted RRs 1.4–2.1). Conclusions: The percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. Participation in the Women, Infants, and Children’s program and maternal age >34 years at delivery increased the likelihood of late prenatal care for some subgroups of women and decreased the likelihood for others. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care. Rationale: Optimal prenatal care includes initiation before the 14th week of gestation. Beginning care in the first trimester provides an opportunity for sonographic pregnancy dating or confirmation with best accuracy, which can later prove critical for management of preterm labor, maternal or fetal complications, or prolonged pregnancy. In order to improve maternal and infant health by increasing the number of women seeking prenatal care in the first trimester, it is important to examine the drivers for late entry. Here, we examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. We found the percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care.

Abstract

Objective: To assess postdischarge mortality and morbidity in infants diagnosed with different etiologies and severities of persistent pulmonary hypertension of the newborn (PPHN), and to identify risk factors for these adverse clinical outcomes. Study design: This was a population-based study using an administrative dataset linking birth and death certificates, hospital discharge and readmissions records from 2005 to 2012 in California. Cases were infants ≥34 weeks' gestational age with International Classification of Diseases, 9th edition, codes consistent with PPHN. The primary outcome was defined as postdischarge mortality or hospital readmission during the first year of life. Crude and adjusted risk ratio (aRR) with 95% CIs were calculated to quantify the risk for the primary outcome and to identify risk factors. Results: Infants with PPHN (n = 7847) had an aRR of 3.5 (95% CI, 3.3-3.7) for the primary outcome compared with infants without PPHN (n = 3 974 536), and infants with only mild PPHN (n = 2477) had an aRR of 2.2 (95% CI, 2.0-2.5). Infants with congenital diaphragmatic hernia as etiology for PPHN had an aRR of 8.6 (95% CI, 7.0-10.6) and infants with meconium aspiration syndrome had an aRR of 4.0 (95% CI, 3.6-4.4) compared with infants without PPHN. Hispanic ethnicity, small for gestational age, severe PPHN, and etiology of PPHN were risk factors for the primary outcome. Conclusions: The postdischarge morbidity burden of infants with PPHN is large. These findings extend to infants with mild PPHN and etiologies with pulmonary vascular changes that are thought to be short term and recoverable. These data could inform counseling of parents.

Abstract

Our objective was to assess the relationship between hyperbilirubinemia with and without kernicterus and metabolic profile at newborn screening. Included were 1,693,658 infants divided into a training or testing subset in a ratio of 3:1. Forty-two metabolites were analyzed using logistic regression (odds ratios (ORs), area under the receiver operating characteristic curve (AUC), 95% confidence intervals (CIs)). Several metabolite patterns remained consistent across gestational age groups for hyperbilirubinemia without kernicterus. Thyroid stimulating hormone (TSH) and C-18:2 were decreased, whereas tyrosine and C-3 were increased in infants across groupings. Increased C-3 was also observed for kernicterus (OR: 3.17; 95% CI: 1.18–8.53). Thirty-one metabolites were associated with hyperbilirubinemia without kernicterus in the training set. Phenylalanine (OR: 1.91; 95% CI: 1.85–1.97), ornithine (OR: 0.76; 95% 0.74–0.77), and isoleucine + leucine (OR: 0.63; 95% CI: 0.61–0.65) were the most strongly associated. This study showed that newborn metabolic function is associated with hyperbilirubinemia with and without kernicterus.