Congenital hydrocephaly is characterized by excessive fluid accumulation, resulting in abnormally dilated cerebral ventricles at birth (Isaacs et al., 2018). Although congenital hydrocephaly is frequently present among infants with spina bifida, when it occurs without spina bifida the etiologies are different (Gili et al., 2022; Isaacs et al., 2018). Therefore, this study focused on congenital hydrocephaly without spina bifida (hereafter referred to as hydrocephaly, except where otherwise indicated). If left untreated, hydrocephaly leads to chronic morbidity and can be fatal (Gili et al., 2022; Isaacs et al., 2018). Prevalence of hydrocephaly differs worldwide (Isaacs et al., 2018). Total birth prevalence of hydrocephaly in North America is estimated to be approximately 5–6 cases/10,000 live births (Gili et al., 2022; Isaacs et al., 2018). In Texas, prevalence of hydrocephaly appears to be higher than national levels and is estimated to be 8 cases/10,000 live births (Texas Birth Defects Registry, n.d.).

Prior epidemiologic studies (Acakpo-Satchivi et al., 2008; Casey et al., 1997; Fernell et al., 1994; Iskandar et al., 1998; Persson et al., 2005; Vinchon et al., 2012) have reported survival estimates for hydrocephaly based on limited, clinic-based populations (e.g., a single hospital), which are subject to selection bias. A limited number of published population-based studies are available regarding hydrocephaly mortality or survival. In a recent international study, 6% of neonates with hydrocephaly died within 7 days, and infants with syndromic hydrocephaly had approximately a two times higher risk for death (Gili et al., 2022). However, the study did not assess mortality beyond 7 days. Two older studies conducted in the United States provided state-based estimates for survival among infants with hydrocephaly (Nembhard et al., 2001; Wang et al., 2011). In one study investigators reported 75% survival (one-year period) among infants born with hydrocephaly in Texas in 1995–1997. These results were before full implementation of a statewide active ascertainment registry in 1999 (Nembhard et al., 2001). Another study examined data from a passive ascertainment system in New York State. The study showed an overall 25-year survival of 83% among infants with hydrocephaly (Wang et al., 2011). Studies also report that infant survival is influenced by maternal and infant-associated risk factors, such as maternal race and ethnicity, preterm birth, low birth weight, and maternal age (Ely & Driscoll, 2019; Gili et al., 2022; Ratnasiri et al., 2020; Shi et al., 2004), including improvements in care of preterm infants in more recent years (Glinianaia et al., 2020). However, a fuller understanding of mortality risk factors is needed using current information on survival estimates.

The objectives of this study were to (1) describe population-based survival in a statewide cohort of infants born with hydrocephaly, through their first year of life, and (2) to identify independent maternal and infant characteristics that influence survival among these infants, including maternal race and ethnicity.

In total, 5709 infants with hydrocephaly were analyzed for delivery years 1999–2017 (Table 1). In terms of maternal race and ethnicity, 34.78% of mothers of infants were White, 13.37% were Black, 48.48% were Hispanic, and 3.37% were from additional groups. Based on clinical classification, 15.76% of infants had chromosomal or syndromic, 26.69% isolated (no co-occurring birth defects), and 53.56% multiple forms of hydrocephaly. Among infants analyzed, 42.53% were preterm (<37 weeks of gestation) and 41.01% were low birth weight (<2500 grams). In total, 62.67% of infants with hydrocephaly were born before 2012. Distribution of infants born based on maternal education was 28.51%, 30.68%, and 40.81% for <12 years, 12 years, and > 12 years of education, respectively.

Overall, infant survival for hydrocephaly was 82.83% (95% CI: 0.82–0.84) (Table 2, Figure 1). The lowest infant survival rates were observed among infants with hydrocephaly classified as chromosomal and syndromic (66.33%; 95% CI: 63.14–69.32), preterm births (78.91%; 95% CI:77.24–80.48), and low birth weight (76.29%; 95% CI: 74.52–77.96). The highest survival rates were observed among infants with isolated hydrocephaly (92.45%; 95% CI:91.01–93.67). The survival patterns in Kaplan–Meier curve showed the greatest decrease in survival occurring during neonatal period (within the first month), followed by a leveling of the survival estimates in later months (Figure 1).

In the unadjusted Cox proportional hazard model, the following maternal and infant characteristics had an increased risk of infant mortality: maternal race and ethnicity, clinical classification, gestational age, birth weight, birth year period, and maternal education (Table 3). In the multivariable Cox proportional hazards model, racial and ethnic differences in infant survival were observed after adjustment for all maternal and infant characteristics. Infants of Black (HR:1.28, 95% CI: 1.04–1.58) and Hispanic (HR:1.31, 95% CI: 1.12–1.54) women were at approximately 30% increased relative risk for death, compared with White women (Table 4).

This study provides contemporary population-based infant survival estimates for hydrocephaly in Texas from an active ascertainment birth defects surveillance system. Overall survival estimates of 83% appears to be higher than the 75% estimate observed in a previous study conducted in Texas during the 1990s. The difference between the two studies might be the result of the earlier data being from an incomplete surveillance system and with relatively limited frequencies. However, this estimate seems consistent with the survival estimate (83%) provided in a 2011 New York study (1983–2006), based on passively reported data (Nembhard et al., 2001; Wang et al., 2011). Compared with population of all infants born in Texas, the excess mortality among infants with hydrocephaly is considerable (Nembhard et al., 2001).

Studies have shown that mortality is higher among infants and children with birth defects (Agha et al., 2006; Copeland & Kirby, 2007; Kassebaum et al., 2017), compared with those in the general population. An analysis of National Vital Statistics System and the National Linked Birth and Death data from 1915 to 2017 revealed racial and ethnic, socioeconomic, and geographic disparities in infant mortality in the United States (Singh & Stella, 2019). Factors, including maternal race and ethnicity, maternal age, maternal education, gestational age, and birth weight were shown to be associated with mortality and survival among infants with or without birth defects (Almli et al., 2020; Lopez et al., 2018; Nembhard et al., 2010; Oster et al., 2013; Pace et al., 2018; Yang et al., 2006). Early diagnosis and treatment of birth defects such as hydrocephaly and an improved understanding of potential risk factors is crucial for infant survival.

This study provided statewide, population-based survival estimates for infants with hydrocephaly stratified by multiple factors, including maternal race and ethnicity. After accounting for multiple variables, adjusted HRs suggested that infants with hydrocephaly born to Black and Hispanic mothers are approximately 30% more likely to die during infancy, compared with infants born to White mothers. These results appear consistent with typical birth defects survival patterns (Glinianaia et al., 2020). Associations with maternal race and ethnicity might represent the role of many complex factors not included in this study. Although racial and ethnic differences in low birth weight, prematurity, and respiratory distress syndrome are hypothesized to play a role in birth defect mortality (Centers for Disease Control and Prevention [CDC], 1990), the current analyses accounted only for low birth weight and preterm birth. Given the complex landscape of factors associated with maternal race and ethnicity, to reduce infant mortality from birth defects, further work is needed to understand discrepancies that lie within social determinants associated with adverse infant outcomes.

In this study, unadjusted results showed infants with chromosomal or syndromic hydrocephaly had approximately five-times higher hazard of death, compared with infants born with isolated hydrocephaly. This finding is consistent with those from an international study concerning early neonatal hydrocephaly mortality that reported case fatality rates approximately 2.7 times higher among infants with syndromic versus nonsyndromic hydrocephaly (Gili et al., 2022). A previous Texas study also reported 88%, 63%, and 25% survival for infants with hydrocephaly with zero, one, and two co-occurring “life-threatening” defects, respectively, but did not focus on chromosomal or syndromic defects specifically (Nembhard et al., 2001).

Similarly, the unadjusted results showed low birthweight (<2500 grams) was significantly associated with higher mortality. Further, unadjusted preterm birth was associated with infant mortality among this population. Gestational age and birthweight play a crucial role in survival among infants without birth defects and might also be important among those with birth defects. For instance, Benjamin et al. reported that preterm and low birth weight contributed to 10% of deaths among all infants with birth defects in Texas (Benjamin et al., 2021). Similarly, a national-level analysis of linked birth defects and infant death records for infants born to U.S. residents during 2002–2017 reported increased mortality rates among preterm infants with birth defects born at 32–36 weeks (Almli et al., 2020). Prematurity and low-birth weight pose increased health concerns because of conditions such as premature lungs, difficulty with feeding and risk for infection, which might influence mortality hazard in infants with existing hydrocephaly.

Based on unadjusted results, the current study also reported that over the 19 years of the study’s cohort (from 1999 to 2017), infants born before 2012 were at an increased risk for mortality (16% higher), compared with those born in years after 2012. These findings suggest some improvement in clinical care and wraparound services in terms of timely identification and referrals. Examples of potential improvement in prenatal and neonatal clinical care over time include advances in prenatal diagnosis, neonatal care (including intensive care, standard use of antenatal steroids, and surfactant therapy for prevention of neonatal mortality and morbidity in preterm births), early surgical interventions, extracorporeal membrane oxygenation, care centralization, and treatment and transplantation of certain organs or body systems (for those with co-occurring defects) (Glinianaia et al., 2020). Similarly, results of a meta-analyses showed statistically significant improvement in survival over time among infants with spina bifida, esophageal atresia, biliary atresia, congenital heart defects (CHD), gastroschisis, and Down syndrome with CHD, but not with encephalocele, biliary atresia with a native liver or Down syndrome without CHD (Glinianaia et al., 2020).

Strengths of this study include new information for an under published topic, regarding the survival of infants with hydrocephaly in Texas. This analysis used statewide data collected through a large public health surveillance system with active ascertainment of birth defects, accounting for approximately 1 in 10 annual births in the United States (Agha et al., 2006). Finally, this study used a substantial sample size, resulting in relatively precise estimates for survival estimates and HRs.

Study limitations include reliance on state-level vital records, although our prior work suggests that only a limited number of infant deaths might occur out of state for infants with birth defects born in Texas (Nembhard et al., 2001). Assumptions about proportionality of hazards held for main variable of interest (race/ethnicity) and other covariates with exception of gestational age and less than high school category of maternal education. This analysis included some infants who might have had hydrocephaly that developed early in infancy rather than in utero. However, hydrocephaly that was likely secondary to another select documented anomaly was excluded from the analysis. This study did not conduct separate analyses for infant survival and for each confounding maternal and infant characteristics, which might have addressed bias introduced by intermediate variables in the causal pathway. Additional clinical variables that were not available (e.g., full diagnostic details, treatment strategies, and other clinical information) might shed additional light on mortality risk in future studies. In this analysis racial and ethnic groups other than NH White, NH Black, and Hispanic were collapsed into one additional groups category due to small sizes. Therefore, this may not be a full examination of all racial/ethnic differences in infant survival by maternal race/ethnicity. Although research on causal pathways has increased, most cases of hydrocephaly remain genetically unexplained from a clinical diagnosis and treatment standpoint and can play a role in infant survival (Allington et al., 2021; Tully & Dobyns, 2014). Therefore, results of this study should be interpreted cautiously.

This study confirms that mortality continues to be common among infants with hydrocephaly in a Texas cohort, which highlights the need for new avenues to work toward identification of modifiable mortality risk factors among affected infants. As a next step in this direction, the study identified racial and ethnic differences in infant survival for hydrocephaly and potential differences by clinical classification, gestational age, birth weight, birth year, and maternal education. Some of these potential associations might identify candidate risk factors that can be considered for future hypothesis-testing analytic approaches, such as time analyses. Such further research is expected to ultimately help elucidate the underlying causal pathways involved and might translate to clinical strategies for improving infant survival for hydrocephaly.