Sarka Lisonkova

A large body of literature has assessed the association between pre-pregnancy body mass index (BMI) and adverse birth outcomes, however, the effects of maternal height, irrespective of BMI, have been understudied. In this thesis I evaluated the association between maternal stature and adverse perinatal outcomes, and whether this association is modified by maternal race/ethnicity. I also examined how maternal stature modifies the association between small- and large-for-gestational age infants (SGA and LGA, respectively) and adverse neonatal outcomes. I conducted two retrospective cohort studies using data on all singleton births in the USA in 2016 and 2017, obtained from the National Center for Health Statistics (NCHS). Short and tall stature were defined as 10th and >90th centile of the maternal height distribution, respectively; maternal race/ethnicity included non-Hispanic White, non-Hispanic Black, American Indian/Alaskan Native, Asian/Pacific Islander, and Hispanic categories. SGA and LGA infant categories were defined using the United States’ reference for fetal growth. Adverse outcomes included, for example, preterm birth, perinatal death, and neonatal morbidity. Regression models were used to adjust for potential confounding and to assess effect modification.Overall, short women had an increased risk while tall women had a decreased risk of adverse perinatal outcomes relative to average stature women. Associations between maternal height and adverse perinatal outcomes were modified by race/ethnicity: the magnitude of the associations between maternal height and adverse perinatal outcomes were larger among some racial/ethnic groups and attenuated in others. When investigating risks of adverse neonatal outcomes among SGA and LGA infants, I found that the association between SGA and adverse neonatal outcomes was weaker in women of short stature, while it was stronger in women of tall stature. These findings raise important questions about the existing SGA/LGA classification since the medical prognosis for these infants also depends on maternal height. The findings of my thesis including various adverse perinatal health outcomes associated with maternal stature, race/ethnicity, and size for gestational age fill gaps in the literature regarding the modifying effects of maternal stature. The results provide health care providers with additional information that can improve risk assessment in pregnant women.

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Preterm birth (PTB; 37 weeks’ gestation) is the leading cause of neonatal mortality and morbidity. After a decade of increase, the PTB rate has declined in the United States since 2006. In Canada, PTB rates have remained stable, despite the rise in clinician-initiated deliveries at late preterm (34-36 weeks) since 2006. I examined temporal trends in the rates of spontaneous and clinician-initiated singleton PTB and assessed concomitant changes in neonatal mortality and severe morbidity.I conducted two retrospective population-based studies included singleton births (24-45 weeks) in Washington State (WA), U.S.A., 2004-2013, using birth certificate data linked to hospitalization records (N=754,763), and in Canada (excluding Quebec), 2009/2010-2015/2016, using national data on all hospital births (N=1,887,362). Primary outcomes were neonatal mortality and a composite outcome including death and/or severe neonatal morbidity (identified by diagnostic codes; definitions varied in both studies). Statistical significance was assessed using the Cochran-Armitage test for trend. Logistic regression yielded adjusted odds ratios (AOR) per 1-year change and 95% confidence intervals (CI). The singleton PTB rate in WA declined from 7.3% in 2004-2006 to 7.0% in 2011-2013 (n=52,014), predominantly due to declines in spontaneous labour and PPROM. The proportion of clinician-initiated PTBs increased from 37.7% to 40.7% in WA (p=0.004). Similarly, clinician-initiated deliveries increased from 31.0% in 2009/2010 to 37.9% in 2015/2016 in Canada (p0.001). The corresponding decrease in spontaneous PTBs resulted in a stable PTB rate (6.2%; n=117,114) across Canada.Overall, neonatal mortality remained unchanged; 1.3% in WA and 1.1% in Canada. In subgroup analysis, neonatal mortality decreased at 32-33 weeks (AOR:0.85, CI:0.74-0.97) and increased at 34-36 weeks (AOR:1.10, CI:1.01-1.20) following clinician-initiated delivery in WA; mortality decreased at 28-33 weeks (AOR:0.91, CI:0.86-0.97) after spontaneous PTB in Canada. The composite outcome of neonatal mortality/severe morbidity increased from 7.9% to 11.9% (AOR:1.06, CI:1.05-1.08) in WA, mainly at 34-36 weeks. Neonatal mortality/severe morbidity decreased from 12.7% to 12.2% (AOR:0.98, CI:0.97-0.99) in Canada, particularly in clinician-initiated late PTB. The endured increase in clinician-initiated PTB was not associated with increased adverse neonatal outcomes in Canada. The increase in adverse neonatal health outcomes in Washington State, particularly at late preterm, warrant further investigation.

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